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Wen H, Qian L, Gao X, Singer A, Xie S, Tang YW, Zhao J. Technical advances in laboratory diagnosis of bloodstream infection. Expert Rev Mol Diagn 2025; 25:67-85. [PMID: 39869103 DOI: 10.1080/14737159.2025.2458467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Revised: 01/17/2025] [Accepted: 01/22/2025] [Indexed: 01/28/2025]
Abstract
INTRODUCTION Rapid and accurate laboratory diagnosis is essential for the effective treatment of bloodstream infection (BSI). AREAS COVERED This review aims to address novel and traditional approaches that exhibit different performance characteristics in the diagnosis of BSI. In particular, the authors will discuss the pros and cons of the blood culture-based phenotypic methods, nucleic acid-targeted molecular methods, and host response-targeted biomarker detection in the diagnosis of BSI. EXPERT OPINION This manuscript summarizes etiologic and host-based techniques in the diagnosis of BSI. Both methods are not mutually exclusive but should be selected based on clinical needs and laboratory conditions to help diagnose BSI more quickly and accurately.
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Affiliation(s)
- Hainan Wen
- Department of Clinical Laboratory, Hebei Key Laboratory of Panvascular Diseases, The Affiliated Hospital of Chengde Medical University, Chengde, Hebei, People's Republic of China
| | - Liu Qian
- Medical Affairs, Danaher Diagnostic Platform/Cepheid (China), Shanghai, People's Republic of China
| | - Xinghui Gao
- Medical Affairs, Danaher Diagnostic Platform/Cepheid (China), Shanghai, People's Republic of China
| | | | - Shuojun Xie
- Department of Clinical Laboratory, Hebei Key Laboratory of Panvascular Diseases, The Affiliated Hospital of Chengde Medical University, Chengde, Hebei, People's Republic of China
| | - Yi-Wei Tang
- Medical Affairs, Danaher Diagnostic Platform/Cepheid (China), Shanghai, People's Republic of China
- College of Public Health, Chongqing Medical University, Chongqing, People's Republic of China
| | - Jianhong Zhao
- Hebei Provincial Center for Clinical Laboratories, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China
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2
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Wu W, Zhang Y, Qu X, Zhang C, Zhang Z. Association between hematocrit-to-albumin ratio and acute kidney injury in patients with acute pancreatitis: a retrospective cohort study. Sci Rep 2024; 14:27113. [PMID: 39511252 PMCID: PMC11544263 DOI: 10.1038/s41598-024-77842-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Accepted: 10/25/2024] [Indexed: 11/15/2024] Open
Abstract
Acute pancreatitis (AP) can result in acute kidney injury (AKI), which is linked to poor outcomes. We aimed to assess the relationship between the hematocrit-to-albumin ratio (HAR) and AKI in this population. This retrospective cohort study included consecutive patients diagnosed with AP and admitted to hospital. Data were systematically extracted from electronic medical records, covering baseline demographic and clinical characteristics. Total 1514 AP patients were enrolled, with 17% (257/1514) developing AKI. Multivariable-adjusted regression analysis, curve fitting, threshold effects analyses, and subgroup analyses were conducted to evaluate the relationship between HAR and AKI incidence in AP patients. Compared to the reference tertile of HAR, the adjusted OR values for the lower and higher tertiles of HAR were 1.25 (95% CI, 0.82-1.91, P = 0.297) and 1.50 (95% CI, 1.03-2.20, P = 0.037), respectively, after adjusting for covariates. The curve fitting results showed a J-shaped relationship between HAR and AKI (non-linear, p = 0.001), with an inflection point of 8.969. Furthermore, validation using the Medical Information Mart for Intensive Care (MIMIC-IV) database AP population revealed a similar relationship with an inflection point at 10.257. Our findings suggest a J-shaped relationship between HAR and AKI in AP patients, indicating higher risk of AKI when HAR exceeds 8.969.
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Affiliation(s)
- Wen Wu
- Department of Critical Care Medicine, Yichang Central People's Hospital, Yichang, 443003, Hubei, China
- The First College of Clinical Medical Science, China Three Gorges University, Yichang, 443003, Hubei, China
| | - Yupei Zhang
- Department of Critical Care Medicine, Yichang Central People's Hospital, Yichang, 443003, Hubei, China
- The First College of Clinical Medical Science, China Three Gorges University, Yichang, 443003, Hubei, China
| | - Xingguang Qu
- Department of Critical Care Medicine, Yichang Central People's Hospital, Yichang, 443003, Hubei, China
- The First College of Clinical Medical Science, China Three Gorges University, Yichang, 443003, Hubei, China
| | - Chunzhen Zhang
- Department of Critical Care Medicine, Yichang Central People's Hospital, Yichang, 443003, Hubei, China
- The First College of Clinical Medical Science, China Three Gorges University, Yichang, 443003, Hubei, China
| | - Zhaohui Zhang
- Department of Critical Care Medicine, Yichang Central People's Hospital, Yichang, 443003, Hubei, China.
- The First College of Clinical Medical Science, China Three Gorges University, Yichang, 443003, Hubei, China.
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Elhassan E, Omolo CA, Gafar MA, Kiruri LW, Ibrahim UH, Ismail EA, Devnarain N, Govender T. Disease-Inspired Design of Biomimetic Tannic Acid-Based Hybrid Nanocarriers for Enhancing the Treatment of Bacterial-Induced Sepsis. Mol Pharm 2024; 21:4924-4946. [PMID: 39214595 DOI: 10.1021/acs.molpharmaceut.4c00048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
This study explored the development of novel biomimetic tannic acid-based hybrid nanocarriers (HNs) for targeted delivery of ciprofloxacin (CIP-loaded TAH-NPs) against bacterial-induced sepsis. The prepared CIP-loaded TAH-NPs exhibited appropriate physicochemical characteristics and demonstrated biocompatibility and nonhemolytic properties. Computational simulations and microscale thermophoresis studies validated the strong binding affinity of tannic acid (TA) and its nanoformulation to human Toll-like receptor 4, surpassing that of the natural substrate lipopolysaccharide (LPS), suggesting a potential competitive inhibition against LPS-induced inflammatory responses. CIP released from TAH-NPs displayed a sustained release profile over 72 h. The in vitro antibacterial activity studies revealed that CIP-loaded TAH-NPs exhibited enhanced antibacterial efficacy and efflux pump inhibitory activity. Specifically, they showed a 3-fold increase in biofilm eradication activity against MRSA and a 2-fold increase against P. aeruginosa compared to bare CIP. Time-killing assays demonstrated complete bacterial clearance within 8 h of treatment with CIP-loaded TAH-NPs. In vitro DPPH scavenging and anti-inflammatory investigations confirmed the ability of the prepared hybrid nanosystem to neutralize reactive oxygen species (ROS) and modulate LPS-induced inflammatory responses. Collectively, these results suggest that CIP-loaded TAH-NPs may serve as an innovative nanocarrier for the effective and targeted delivery of antibiotics against bacterial-induced sepsis.
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Affiliation(s)
- Eman Elhassan
- Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Private Bag Durban X54001, South Africa
| | - Calvin A Omolo
- Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Private Bag Durban X54001, South Africa
- Department of Pharmaceutics and Pharmacy Practice, School of Pharmacy and Health Sciences, United States International University-Africa, P.O. Box 14634-00800, Nairobi 00800, Kenya
| | - Mohammed Ali Gafar
- Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Private Bag Durban X54001, South Africa
- Department of Pharmaceutics, Faculty of Pharmacy, University of Khartoum, Khartoum 11111, Sudan
| | - Lucy W Kiruri
- Department of Chemistry, Kenyatta University, P.O. Box 43844, Nairobi 00100, Kenya
| | - Usri H Ibrahim
- Discipline of Human Physiology, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban 4300, South Africa
| | - Eman A Ismail
- Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Private Bag Durban X54001, South Africa
| | - Nikita Devnarain
- Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Private Bag Durban X54001, South Africa
| | - Thirumala Govender
- Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Private Bag Durban X54001, South Africa
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Porru E, Comito R, Interino N, Cerrato A, Contoli M, Rizzo P, Conti M, Campo G, Spadaro S, Caliceti C, Marini F, Capriotti AL, Laganà A, Roda A. Sulfated Bile Acids in Serum as Potential Biomarkers of Disease Severity and Mortality in COVID-19. Cells 2024; 13:1576. [PMID: 39329758 PMCID: PMC11430696 DOI: 10.3390/cells13181576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 09/11/2024] [Accepted: 09/13/2024] [Indexed: 09/28/2024] Open
Abstract
The fight against coronavirus disease 2019 (COVID-19) continues. Since the pandemic's onset, several biomarkers have been proposed to assess the diagnosis and prognosis of this disease. This research aimed to identify potential disease severity biomarkers in serum samples of patients with COVID-19 during the disease course. Data were collected using untargeted and targeted mass spectrometry methods. The results were interpreted by performing univariate and multivariate analyses. Important metabolite classes were identified by qualitative untargeted metabolomics in 15 serum samples from survivors of COVID-19. Quantitative targeted metabolomics on a larger patient cohort including 15 non-survivors confirmed serum 3-sulfate bile acids (i.e. GLCA-3S) were significantly increased in non-survivors compared to survivors during the early disease stage (p-value < 0.0001). Notably, it was associated with a higher risk of mortality (odds ratio of 26). A principal component analysis showed the ability to discriminate between survivors and non-survivors using the BA concentrations. Furthermore, increased BA-S is highly correlated with known parameters altered in severe clinical conditions.
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Affiliation(s)
- Emanuele Porru
- Occupational Medicine Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy;
| | - Rossana Comito
- Division of Occupational Medicine, “IRCCS” Azienda Ospedaliero—Universitaria di Bologna, 40138 Bologna, Italy;
| | - Nicolò Interino
- Laboratorio di Proteomica Metabolomica e Chimica Bioanalitica, “IRCCS” Istituto delle Scienze Neurologiche di Bologna, 40139 Bologna, Italy;
| | - Andrea Cerrato
- Department of Chemistry, “Sapienza” University of Rome, 00185 Rome, Italy; (A.C.); (F.M.); (A.L.C.); (A.L.)
| | - Marco Contoli
- Respiratory Section, Department of Morphology, Surgery, and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy;
| | - Paola Rizzo
- Laboratory for Technologies of Advanced Therapies “LTTA”, Department of Translaqutional Medicine, University of Ferrara, 44121 Ferrara, Italy;
- Maria Cecilia Hospital, GVM Care & Research, 48022 Cotignola, Italy
| | - Matteo Conti
- Local Unit of Imola, Department of Public Health, Health Service of the Emilia-Romagna Region, 40026 Imola, Italy;
| | - Gianluca Campo
- Cardiovascular Institute, Azienda Ospedaliero, University of Ferrara, 44124 Ferrara, Italy;
| | - Savino Spadaro
- Intensive Care Unit, Department of Morphology, Surgery, and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy;
| | - Cristiana Caliceti
- Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum, University of Bologna, 40123 Bologna, Italy;
- Biostructures and Biosystems National Institute “INBB”, 00136 Rome, Italy
- Interdepartmental Centre for Industrial Agrofood Research-CIRI Agrofood, University of Bologna, 47521 Cesena, Italy
- Interdepartmental Center of Industrial Research “CIRI”-Energy and Environment, Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy
| | - Federico Marini
- Department of Chemistry, “Sapienza” University of Rome, 00185 Rome, Italy; (A.C.); (F.M.); (A.L.C.); (A.L.)
| | - Anna L. Capriotti
- Department of Chemistry, “Sapienza” University of Rome, 00185 Rome, Italy; (A.C.); (F.M.); (A.L.C.); (A.L.)
| | - Aldo Laganà
- Department of Chemistry, “Sapienza” University of Rome, 00185 Rome, Italy; (A.C.); (F.M.); (A.L.C.); (A.L.)
| | - Aldo Roda
- Biostructures and Biosystems National Institute “INBB”, 00136 Rome, Italy
- Department of Chemistry “G. Ciamician”, Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy
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Srdić T, Đurašević S, Lakić I, Ružičić A, Vujović P, Jevđović T, Dakić T, Đorđević J, Tosti T, Glumac S, Todorović Z, Jasnić N. From Molecular Mechanisms to Clinical Therapy: Understanding Sepsis-Induced Multiple Organ Dysfunction. Int J Mol Sci 2024; 25:7770. [PMID: 39063011 PMCID: PMC11277140 DOI: 10.3390/ijms25147770] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Revised: 06/24/2024] [Accepted: 06/30/2024] [Indexed: 07/28/2024] Open
Abstract
Sepsis-induced multiple organ dysfunction arises from the highly complex pathophysiology encompassing the interplay of inflammation, oxidative stress, endothelial dysfunction, mitochondrial damage, cellular energy failure, and dysbiosis. Over the past decades, numerous studies have been dedicated to elucidating the underlying molecular mechanisms of sepsis in order to develop effective treatments. Current research underscores liver and cardiac dysfunction, along with acute lung and kidney injuries, as predominant causes of mortality in sepsis patients. This understanding of sepsis-induced organ failure unveils potential therapeutic targets for sepsis treatment. Various novel therapeutics, including melatonin, metformin, palmitoylethanolamide (PEA), certain herbal extracts, and gut microbiota modulators, have demonstrated efficacy in different sepsis models. In recent years, the research focus has shifted from anti-inflammatory and antioxidative agents to exploring the modulation of energy metabolism and gut microbiota in sepsis. These approaches have shown a significant impact in preventing multiple organ damage and mortality in various animal sepsis models but require further clinical investigation. The accumulation of this knowledge enriches our understanding of sepsis and is anticipated to facilitate the development of effective therapeutic strategies in the future.
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Affiliation(s)
- Tijana Srdić
- Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia; (T.S.); (S.Đ.); (I.L.); (A.R.); (P.V.); (T.J.); (T.D.); (J.Đ.)
| | - Siniša Đurašević
- Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia; (T.S.); (S.Đ.); (I.L.); (A.R.); (P.V.); (T.J.); (T.D.); (J.Đ.)
| | - Iva Lakić
- Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia; (T.S.); (S.Đ.); (I.L.); (A.R.); (P.V.); (T.J.); (T.D.); (J.Đ.)
| | - Aleksandra Ružičić
- Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia; (T.S.); (S.Đ.); (I.L.); (A.R.); (P.V.); (T.J.); (T.D.); (J.Đ.)
| | - Predrag Vujović
- Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia; (T.S.); (S.Đ.); (I.L.); (A.R.); (P.V.); (T.J.); (T.D.); (J.Đ.)
| | - Tanja Jevđović
- Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia; (T.S.); (S.Đ.); (I.L.); (A.R.); (P.V.); (T.J.); (T.D.); (J.Đ.)
| | - Tamara Dakić
- Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia; (T.S.); (S.Đ.); (I.L.); (A.R.); (P.V.); (T.J.); (T.D.); (J.Đ.)
| | - Jelena Đorđević
- Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia; (T.S.); (S.Đ.); (I.L.); (A.R.); (P.V.); (T.J.); (T.D.); (J.Đ.)
| | - Tomislav Tosti
- Institute of Chemistry, Technology and Metallurgy, National Institute of the Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia;
| | - Sofija Glumac
- School of Medicine, University of Belgrade, 11129 Belgrade, Serbia; (S.G.); (Z.T.)
| | - Zoran Todorović
- School of Medicine, University of Belgrade, 11129 Belgrade, Serbia; (S.G.); (Z.T.)
| | - Nebojša Jasnić
- Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia; (T.S.); (S.Đ.); (I.L.); (A.R.); (P.V.); (T.J.); (T.D.); (J.Đ.)
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Toc DA, Costache C, Neculicioiu VS, Rusu IM, Roznovan BV, Botan A, Toc AG, Șchiopu P, Panaitescu PS, Pană AG, Colosi IA. Yokenella regensburgei-Past, Present and Future. Antibiotics (Basel) 2024; 13:589. [PMID: 39061271 PMCID: PMC11273379 DOI: 10.3390/antibiotics13070589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Revised: 06/18/2024] [Accepted: 06/20/2024] [Indexed: 07/28/2024] Open
Abstract
Yokenella regensburgei is a Gram-negative rod part of the Enterobacteriaceae family (order Enterobacterales) and a rare cause of human infections. Although improved diagnostic methods have led to an increase in reports of this elusive pathogen, information remains limited. In order to provide a better understanding of this bacterium, we developed the first comprehensive review of its biology, biochemical profile, antimicrobial resistance pattern, virulence factors, natural reservoir and involvement in various veterinary and human infections. Human infections with this bacterium are scarcely reported, most probably due to constraints regarding its identification and biochemical similarities to Hafnia alvei. Multiple systematic searches revealed 23 cases of human infection, with a seemingly worldwide distribution, mostly in middle-aged or elderly male patients, often associated with immunosuppression. To date, Y. regensburgei has been reported in skin and soft tissue infections, bacteremia and sepsis, osteoarticular infections and in others such as urinary tract and digestive infections. The unique ability of Y. regensburgei to degrade polystyrene presents a novel and promising avenue for addressing plastic pollution in the near future. However, large-scale applications of this bacterium will undoubtedly increase human exposure, highlighting the necessity for comprehensive research into its role in human and veterinary infections, pathogenicity and antibiotic resistance.
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Affiliation(s)
- Dan Alexandru Toc
- Department of Microbiology, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Carmen Costache
- Department of Microbiology, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Vlad Sever Neculicioiu
- Department of Microbiology, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Irina-Maria Rusu
- Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Bogdan-Valentin Roznovan
- Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Alexandru Botan
- Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Adelina Georgiana Toc
- Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Pavel Șchiopu
- Department of Microbiology, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Paul-Stefan Panaitescu
- Department of Microbiology, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Adrian Gabriel Pană
- Department of Microbiology, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Ioana Alina Colosi
- Department of Microbiology, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
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Thatrimontrichai A, Surachat K, Singkhamanan K, Thongsuksai P. Differential Abundances of Bdellovibrio and Rheinheimera in the Oral Microbiota of Neonates With and Without Clinical Sepsis. Pediatr Infect Dis J 2024; 43:e195-e200. [PMID: 38295225 DOI: 10.1097/inf.0000000000004259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2024]
Abstract
BACKGROUND Neonatal sepsis is associated with high rates of morbidity and mortality, long hospital stays and high cost of care, thereby inflicting a burden on health care systems. Oral care with breast milk has been shown to modify the intestinal tract microbiota and immune system. Herein, we attempted to identify probiotics that may be beneficial to prevent or treat neonatal sepsis. METHODS This was a secondary analysis comparing the microbiota during oropharyngeal care in very-low-birth-weight infants with and without clinical sepsis. Oral samples were collected before oral feeding was initiated. The primary outcome was oral microbiota composition including diversity, relative abundance and linear discriminant analysis effect size. RESULTS Sixty-three neonates, including 39 and 24 with and without clinical sepsis, respectively, were enrolled. The medians gestational age and birth weight were 29 (27-30) weeks and 1010 (808-1263) g. Neonates with clinical sepsis had lower gestational age, birth weight (both P < 0.001) and lower rate of oral care with breast milk ( P = 0.03), but higher doses and days of antibiotic exposure (both P < 0.001) compared to neonates without clinical sepsis. No differences in alpha and beta diversities were found between groups and Streptococcus agalactiae was the most common bacteria in both groups. Linear discriminant analysis effect size analysis revealed that neonates without clinical sepsis had significantly higher abundances of order Bdellovibrionales, family Bdellovibrionaceae, genus Bdellovibrio and genus Rheinheimera . CONCLUSIONS Neonates without clinical sepsis had a significantly greater abundance of the Bdellovibrio and Rheinheimera genera.
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Affiliation(s)
| | - Komwit Surachat
- Department of Biomedical Sciences and Biomedical Engineering
| | | | - Paramee Thongsuksai
- Department of Pathology, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand
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Wu J, Sun X, Jiang P. Metabolism-inflammasome crosstalk shapes innate and adaptive immunity. Cell Chem Biol 2024; 31:884-903. [PMID: 38759617 DOI: 10.1016/j.chembiol.2024.04.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 04/08/2024] [Accepted: 04/16/2024] [Indexed: 05/19/2024]
Abstract
Inflammasomes are a central component of innate immunity and play a vital role in regulating innate immune response. Activation of inflammasomes is also indispensable for adaptive immunity, modulating the development and response of adaptive immunity. Recently, increasing studies have shown that metabolic alterations and adaptations strongly influence and regulate the differentiation and function of the immune system. In this review, we will take a holistic view of how inflammasomes bridge innate and adaptive (especially T cell) immunity and how inflammasomes crosstalk with metabolic signals during the immune responses. And, special attention will be paid to the metabolic control of inflammasome-mediated interactions between innate and adaptive immunity in disease. Understanding the metabolic regulatory functions of inflammasomes would provide new insights into future research directions in this area and may help to identify potential targets for inflammasome-associated diseases and broaden therapeutic avenues.
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Affiliation(s)
- Jun Wu
- School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, Fujian, China; State Key Laboratory of Molecular Oncology, School of Life Sciences, Tsinghua University, Beijing 100084, China; Tsinghua-Peking Center for Life Sciences, Beijing 100084, China
| | - Xuan Sun
- State Key Laboratory of Molecular Oncology, School of Life Sciences, Tsinghua University, Beijing 100084, China; Tsinghua-Peking Center for Life Sciences, Beijing 100084, China
| | - Peng Jiang
- State Key Laboratory of Molecular Oncology, School of Life Sciences, Tsinghua University, Beijing 100084, China; Tsinghua-Peking Center for Life Sciences, Beijing 100084, China.
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9
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Alipourfard I, Darvishi M, Khalighfard A, Ghazi F, Mobed A. Nanomaterial-based methods for sepsis management. Enzyme Microb Technol 2024; 174:110380. [PMID: 38147783 DOI: 10.1016/j.enzmictec.2023.110380] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2023] [Revised: 11/26/2023] [Accepted: 12/12/2023] [Indexed: 12/28/2023]
Abstract
Sepsis is a serious disease caused by an impaired host immune response to infection, resulting in organ dysfunction, tissue damage and is responsible for high in-hospital mortality (approximately 20%). Recently, WHO documented sepsis as a global health priority. Nevertheless, there is still no effective and specific therapy for clinically detecting sepsis. Nanomaterial-based approaches have appeared as promising tools for identifying bacterial infections. In this review, recent biosensors are introduced and summarized as nanomaterial-based platforms for sepsis management and severe complications. Biosensors can be used as tools for the diagnosis and treatment of sepsis and as nanocarriers for drug delivery. In general, diagnostic methods for sepsis-associated bacteria, biosensors developed for this purpose are presented in detail, and their strengths and weaknesses are discussed. In other words, readers of this article will gain a comprehensive understanding of biosensors and their applications in sepsis management.
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Affiliation(s)
- Iraj Alipourfard
- Institute of Biology, Biotechnology and Environmental Protection, Faculty of Natural Sciences, University of Silesia, Katowice, Poland
| | - Mohammad Darvishi
- Infectious Diseases and Tropical Medicine Research Center (IDTMRC), Department of Aerospace and Subaquatic Medicine, AJA University of Medical Sciences, Tehran, Iran
| | - Arghavan Khalighfard
- Department of Nursing and Midwifery٫ Faculty of Midwifery٬ Zanjan University of Medical Sciences, Zanjan, Iran
| | - Farhood Ghazi
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz 5154853431, Iran
| | - Ahmad Mobed
- Infectious and Tropical Diseases Research Center, Clinical Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
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Algarni AM, Alfaifi MS, Al Bshabshe AA, Omair OM, Alsultan MA, Alzahrani HM, Alali HE, Alsabaani AA, Alqarni AM, Alghanem SA, Al Mufareh BS, Almemari AM, Sindi AA, Ozturan IU, Alhadhira AA, Shujaa AS, Alotaibi AH, Awladthani MM, Alsaad AA, Almarshed AA, AlQahtani AM, Harris TR, Alyahya BA, Assiri SA, Abuzeyad FH, Kazim SN, Al-Fares AA, Almazroua FY, Marzook NT, Basri AA, Elsafti AM, Alalshaikh AS, Özturan CA, Alawad YI, AlOmari A, Alkhateeb MA, Farooq MM, AlMutairi LA, Alasfour MM, Al Haber MI, Umar UKA, Bokhary NH, Alqahtani SF, Almutairi A, Alyahya HF, Alzahrani WS, Alsalmi F, Omair AM, Alasmari FM, Alfifi SY, Al-Nujimi MS, Foroutan F. Prognostic accuracy of qSOFA score, SIRS criteria, and EWSs for in-hospital mortality among adult patients presenting with suspected infection to the emergency department (PASSEM) Multicenter prospective external validation cohort study protocol. PLoS One 2024; 19:e0281208. [PMID: 38232095 PMCID: PMC10793907 DOI: 10.1371/journal.pone.0281208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Accepted: 01/12/2023] [Indexed: 01/19/2024] Open
Abstract
BACKGROUND Early identification of a patient with infection who may develop sepsis is of utmost importance. Unfortunately, this remains elusive because no single clinical measure or test can reflect complex pathophysiological changes in patients with sepsis. However, multiple clinical and laboratory parameters indicate impending sepsis and organ dysfunction. Screening tools using these parameters can help identify the condition, such as SIRS, quick SOFA (qSOFA), National Early Warning Score (NEWS), or Modified Early Warning Score (MEWS). We aim to externally validate qSOFA, SIRS, and NEWS/NEWS2/MEWS for in-hospital mortality among adult patients with suspected infection who presenting to the emergency department. METHODS AND ANALYSIS PASSEM study is an international prospective external validation cohort study. For 9 months, each participating center will recruit consecutive adult patients who visited the emergency departments with suspected infection and are planned for hospitalization. We will collect patients' demographics, vital signs measured in the triage, initial white blood cell count, and variables required to calculate Charlson Comorbidities Index; and follow patients for 90 days since their inclusion in the study. The primary outcome will be 30-days in-hospital mortality. The secondary outcome will be intensive care unit (ICU) admission, prolonged stay in the ICU (i.e., ≥72 hours), and 30- as well as 90-days all-cause mortality. The study started in December 2021 and planned to enroll 2851 patients to reach 200 in-hospital death. The sample size is adaptive and will be adjusted based on prespecified consecutive interim analyses. DISCUSSION PASSEM study will be the first international multicenter prospective cohort study that designated to externally validate qSOFA score, SIRS criteria, and EWSs for in-hospital mortality among adult patients with suspected infection presenting to the ED in the Middle East region. STUDY REGISTRATION The study is registered at ClinicalTrials.gov (NCT05172479).
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Affiliation(s)
| | - Musa S. Alfaifi
- Emergency Medicine Department, Armed Forces Hospital Southern Region, Khamis Mushait, Saudi Arabia
| | | | - Othman M. Omair
- Emergency Medicine Department, Aseer Central Hospital, Abha, Saudi Arabia
| | | | | | - Hadi E. Alali
- Emergency Medicine Department, Armed Forces Hospital Southern Region, Khamis Mushait, Saudi Arabia
| | | | - Ali M. Alqarni
- Radiology Department, Prince Mashary Bin Saud Hospital, Belgraishi, Saudi Arabia
| | - Salah A. Alghanem
- Emergency Medicine Department, Bahrain Defence Force Hospital, Al Riffa, Bahrain
| | - Bandar S. Al Mufareh
- Emergency Medicine Department, Royal Commission Hospital in Jubail, Jubail, Saudi Arabia
| | - Ayesha M. Almemari
- Emergency Medicine Department, Shaikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates
| | | | - Ibrahim U. Ozturan
- Kocaeli University, Faculty of Medicine, Emergency Medicine Department, Kocaeli, Turkey
| | - Abdullah A. Alhadhira
- Emergency Medicine Department, Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia
| | - Asaad S. Shujaa
- Emergency Medicine Department, Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia
| | - Abdullah H. Alotaibi
- Emergency Medicine Department, King Abdullah University Hospital, Riyadh, Saudi Arabia
| | | | - Ahmed A. Alsaad
- Emergency Medicine Department, King Fahad Specialist Hospital, Dammam, Saudi Arabia
| | | | | | - Tim R. Harris
- Emergency Medicine Department, Hamad Medical Corporation, Doha, Qatar
| | | | - Saad A. Assiri
- Emergency Medicine Department, Sulaiman Al Habib Medical Group, Riyadh, Saudi Arabia
| | - Feras H. Abuzeyad
- Emergency Medicine Department, King Hamad University Hospital, Muharraq, Bahrain
| | - Sara N. Kazim
- Emergency Medicine Department, Rashid Hospital, Dubai, United Arab Emirates
| | | | | | - Naif T. Marzook
- Emergency Medicine Department, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia
| | - Abdullah A. Basri
- Emergency Medicine Department, Bahrain Defence Force Hospital, Al Riffa, Bahrain
| | | | | | - Cansu A. Özturan
- Emergency Medicine Department, Gölcük Necati Çelik State Hospital, Gölcük, Kocaeli, Turkey
| | - Yousef I. Alawad
- Emergency Medicine Administration, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Awad AlOmari
- Critical Care Department, Sulaiman Al Habib Medical Group, Riyadh, Saudi Arabia
| | - Malek A. Alkhateeb
- Emergency Medicine Department, Sulaiman Al Habib Medical Group, Riyadh, Saudi Arabia
| | - Moonis M. Farooq
- Emergency Medicine Department, King Hamad University Hospital, Muharraq, Bahrain
| | | | | | - Mohammad I. Al Haber
- Emergency Medicine Department, Shaikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates
| | - Umma-Kulthum A. Umar
- Emergency Medicine Department, Shaikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates
| | - Nidal H. Bokhary
- College of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Saeed F. Alqahtani
- Emergency Medicine Department, Aseer Central Hospital, Abha, Saudi Arabia
| | | | - Hisham F. Alyahya
- Emergency Medicine Department, King Saud Medical City, Riyadh, Saudi Arabia
| | - Wejdan S. Alzahrani
- Emergency Medicine Department, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia
| | - Fawziah Alsalmi
- Emergency Medicine Department, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia
| | | | | | | | | | - Farid Foroutan
- Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
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Tortora SC, Agurto MG, Martello LA. The oral-gut-circulatory axis: from homeostasis to colon cancer. Front Cell Infect Microbiol 2023; 13:1289452. [PMID: 38029267 PMCID: PMC10663299 DOI: 10.3389/fcimb.2023.1289452] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Accepted: 10/23/2023] [Indexed: 12/01/2023] Open
Abstract
The human microbiota is widely recognized as providing crucial health benefits to its host, specifically by modulating immune homeostasis. Microbial imbalance, known as dysbiosis, is linked to several conditions in the body. The oral cavity and gut host the two largest microbial communities playing a major role in microbial-associated diseases. While the oral-gut axis has been previously explored, our review uniquely highlights the significance of incorporating the circulatory system into this axis. The interaction between immune cells, inflammatory factors, circulating bacteria, and microbial metabolites influences the homeostasis of both the oral and gut microbiota in a bidirectional manner. In this comprehensive review, we aim to describe the bacterial components of the oral-gut-circulatory axis in both health and disease, with a specific focus on colon cancer.
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Affiliation(s)
- Sofia C. Tortora
- Department of Medicine and Division of Gastroenterology & Hepatology, SUNY Downstate Health Sciences University, Brooklyn, NY, United States
| | - Maria Gonzalez Agurto
- Departamento de Rehabilitación Craneofacial Integral, Universidad de Los Andes, Santiago, Chile
| | - Laura A. Martello
- Department of Medicine and Division of Gastroenterology & Hepatology, SUNY Downstate Health Sciences University, Brooklyn, NY, United States
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Zong H, Shang X, Wang X, Chen T, Wang Y, Ren Y, Jiang Y, Li Y, Lv Q, Liu P. Diagnosis of septic shock by serum measurement of human neutrophil lipocalin by a rapid homogeneous assay. J Immunol Methods 2023; 522:113570. [PMID: 37774777 DOI: 10.1016/j.jim.2023.113570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Revised: 09/20/2023] [Accepted: 09/21/2023] [Indexed: 10/01/2023]
Abstract
BACKGROUND Human neutrophil lipocalin (HNL) is a marker of neutrophil activation and has a high efficacy in diagnosing bacterial infections. In this study, we applied the AlphaLISA technique to measure the serum level of HNL, evaluate HNL's efficacy in diagnosing septic shock, and identify any association between HNL level and septic patients' prognosis. METHODS We collected 146 serum samples from the Fifth Medical Center of Chinese PLA General Hospital. HNL was measured by AlphaLISA and results were compared with commercial ELISA kits. We studied 78 patients admitted to the ICU with sepsis and data on their clinical and physiological characteristics were recorded. Blood levels of HNL, procalcitonin (PCT), high-sensitivity C-reactive protein (hs-CRP), and lactate were measured. A receiver operating characteristic (ROC) curve was used to evaluate the performance of each marker. RESULTS The AlphaLISA assay for serum HNL had a detection range from 1.5 ng/mL to 1000 ng/mL, with a detection limit of 1 ng/mL and a detection time of approximately 25 min. The AlphaLISA assay's results were in high agreement with ELISA results (R2 = 0.9413). HNL levels were analyzed in sepsis patients, and HNL was significantly higher in sepsis patients with shock compared to sepsis patients without shock (median 356.47 ng/mL vs 158.93 ng/mL, P < 0.0001) and in the 28-day non-survivor group compared to the 28-day survivor group (median 331.83 ng/mL vs 175.17 ng/mL, P < 0.0001). ROC curve analysis was performed for the biomarkers. In differentiating the diagnosis of septic shock from sepsis patients, HNL was the most effective marker (AUC = 0.857), followed by PCT (AUC = 0.754) and hs-CRP (AUC = 0.627). In predicting the prognosis of septic patients, lactate had the best effect (AUC = 0.805), followed by HNL (AUC = 0.784), PCT (AUC = 0.721), and hs-CRP (AUC = 0.583). CONCLUSIONS As an assessment tool, we found that our AlphaLISA had good consistency with an ELISA and had several other advantages, including requiring a shorter processing time and detecting a wider range of serum HNL concentrations. Monitoring serum HNL levels of patients admitted to the ICU might be useful in distinguishing sepsis patients who have septic shock from other sepsis patients, indicating its value in the prediction of sepsis patient prognosis.
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Affiliation(s)
- Huijun Zong
- State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing 100071, China; The Fifth School of Clinical Medicine, Anhui Medical University, Hefei 230032, China; Department of Critical Care Medicine, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100071, China
| | - Xueyi Shang
- Department of Critical Care Medicine, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100071, China
| | - Xin Wang
- Department of Critical Care Medicine, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100071, China
| | - Ting Chen
- The Fifth School of Clinical Medicine, Anhui Medical University, Hefei 230032, China; Department of Critical Care Medicine, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100071, China
| | - Ye Wang
- State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing 100071, China
| | - Yuhao Ren
- State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing 100071, China
| | - Yongqiang Jiang
- State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing 100071, China
| | - Yan Li
- The Fifth School of Clinical Medicine, Anhui Medical University, Hefei 230032, China; Department of Critical Care Medicine, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100071, China.
| | - Qingyu Lv
- State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing 100071, China.
| | - Peng Liu
- State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing 100071, China.
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Wang M, Feng J, Zhou D, Wang J. Bacterial lipopolysaccharide-induced endothelial activation and dysfunction: a new predictive and therapeutic paradigm for sepsis. Eur J Med Res 2023; 28:339. [PMID: 37700349 PMCID: PMC10498524 DOI: 10.1186/s40001-023-01301-5] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 08/18/2023] [Indexed: 09/14/2023] Open
Abstract
BACKGROUND Lipopolysaccharide, a highly potent endotoxin responsible for severe sepsis, is the major constituent of the outer membrane of gram-negative bacteria. Endothelial cells participate in both innate and adaptive immune responses as the first cell types to detect lipopolysaccharide or other foreign debris in the bloodstream. Endothelial cells are able to recognize the presence of LPS and recruit specific adaptor proteins to the membrane domains of TLR4, thereby initiating an intracellular signaling cascade. However, lipopolysaccharide binding to endothelial cells induces endothelial activation and even damage, manifested by the expression of proinflammatory cytokines and adhesion molecules that lead to sepsis. MAIN FINDINGS LPS is involved in both local and systemic inflammation, activating both innate and adaptive immunity. Translocation of lipopolysaccharide into the circulation causes endotoxemia. Endothelial dysfunction, including exaggerated inflammation, coagulopathy and vascular leakage, may play a central role in the dysregulated host response and pathogenesis of sepsis. By discussing the many strategies used to treat sepsis, this review attempts to provide an overview of how lipopolysaccharide induces the ever more complex syndrome of sepsis and the potential for the development of novel sepsis therapeutics. CONCLUSIONS To reduce patient morbidity and mortality, preservation of endothelial function would be central to the management of sepsis.
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Affiliation(s)
- Min Wang
- Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 JieFang Avenue, Wuhan, 430030, Hubei, People's Republic of China
- Department of Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 JieFang Avenue, Wuhan, 430030, Hubei, People's Republic of China
| | - Jun Feng
- Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 JieFang Avenue, Wuhan, 430030, Hubei, People's Republic of China
- Department of Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 JieFang Avenue, Wuhan, 430030, Hubei, People's Republic of China
| | - Daixing Zhou
- Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 JieFang Avenue, Wuhan, 430030, Hubei, People's Republic of China.
- Department of Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 JieFang Avenue, Wuhan, 430030, Hubei, People's Republic of China.
| | - Junshuai Wang
- Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 JieFang Avenue, Wuhan, 430030, Hubei, People's Republic of China.
- Department of Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 JieFang Avenue, Wuhan, 430030, Hubei, People's Republic of China.
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Krebs I, Zhang Y, Wente N, Leimbach S, Krömker V. Bacteremia in Severe Mastitis of Dairy Cows. Microorganisms 2023; 11:1639. [PMID: 37512812 PMCID: PMC10384933 DOI: 10.3390/microorganisms11071639] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 06/18/2023] [Accepted: 06/21/2023] [Indexed: 07/30/2023] Open
Abstract
The aim of this cross-sectional study was to investigate the occurrence of bacteremia in severe mastitis cases of dairy cows. Milk and corresponding blood samples of 77 cases of severe mastitis were bacteriologically examined. All samples (milk and blood) were incubated aerobically and anaerobically to also investigate the role of obligate anaerobic microorganisms in addition to aerobic microorganisms in severe mastitis. Bacteremia occurred if identical bacterial strains were isolated from milk and blood samples of the same case. In addition, pathogen shedding was examined, and the data of animals and weather were collected to determine associated factors for the occurrence of bacteremia in severe mastitis. If Gram-negative bacteria were detected in milk samples, a Limulus test (detection of endotoxins) was also performed for corresponding blood samples without the growth of Gram-negative bacteria. In 74 cases (96.1%), microbial growth was detected in aerobically incubated milk samples. The most-frequently isolated bacteria in milk samples were Escherichia (E.) coli (48.9%), Streptococcus (S.) spp. (18.1%), and Klebsiella (K.) spp. (16%). Obligatory anaerobic microorganisms were not isolated. In 72 cases (93.5%) of the aerobically examined blood samples, microbial growth was detected. The most-frequently isolated pathogens in blood samples were non-aureus Staphylococci (NaS) (40.6%) and Bacillus spp. (12.3%). The Limulus test was positive for 60.5% of cases, which means a detection of endotoxins in most blood samples without the growth of Gram-negative bacteria. Bacteremia was confirmed in 12 cases (15.5%) for K. pneumoniae (5/12), E. coli (4/12), S. dysgalactiae (2/12), and S. uberis (1/12). The mortality rate (deceased or culled) was 66.6% for cases with bacteremia and 34.1% for cases without bacteremia. High pathogen shedding and high humidity were associated with the occurrence of bacteremia in severe mastitis.
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Affiliation(s)
- Isabel Krebs
- Department of Bioprocess Engineering, Microbiology, Faculty II, Hannover University of Applied Sciences and Arts, 30453 Hannover, Germany
| | - Yanchao Zhang
- Department of Bioprocess Engineering, Microbiology, Faculty II, Hannover University of Applied Sciences and Arts, 30453 Hannover, Germany
| | - Nicole Wente
- Department of Bioprocess Engineering, Microbiology, Faculty II, Hannover University of Applied Sciences and Arts, 30453 Hannover, Germany
| | - Stefanie Leimbach
- Department of Bioprocess Engineering, Microbiology, Faculty II, Hannover University of Applied Sciences and Arts, 30453 Hannover, Germany
| | - Volker Krömker
- Department of Veterinary and Animal Sciences, University of Copenhagen, 1870 Frederiksberg C, Denmark
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Wu Z, Xia Y, Wang C, Lu W, Zuo H, Wu D, Li Y, Guo R, Lu J, Zhang L. Electroacupuncture at Neiguan (PC6) attenuates cardiac dysfunction caused by cecal ligation and puncture via the vagus nerve. Biomed Pharmacother 2023; 162:114600. [PMID: 36996679 DOI: 10.1016/j.biopha.2023.114600] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 03/22/2023] [Accepted: 03/23/2023] [Indexed: 03/30/2023] Open
Abstract
PURPOSE Previous studies proved the benefits of electroacupuncture (EA) on heart in ischemia reperfusion injury and chronic heart failure. However, the role of EA on sepsis-induced cardiac dysfunction has rarely been elucidated before. In this study, we aimed to investigate the effects of EA on cardiac dysfunction in a rat model of sepsis and to speculate the underlying mechanisms. METHODS Sepsis was induced by cecum ligation and puncture in anesthetized rats. EA at the acupoint "Neiguan (PC6)" was applied 0.5 h after the induction of sepsis for 20 min. Heart rate variability was obtained immediately after EA to evaluate autonomic balance. Echocardiography was performed at 6 h and 24 h after sepsis induction in vivo. Measurements of hemodynamics, blood gases, cytokines and biochemistry were collected at 24 h. Cardiac tissue underwent immunofluorescence staining to determine the expression of α7 nicotinic acetylcholine receptor (α7nAChR) on macrophages. RESULTS EA increased vagus nerve activity, prevented the development of hyperlactatemia, attenuated the decline of left ventricle ejection fraction, suppressed systemic and cardiac inflammation and alleviated the histopathological manifestations of heart in sepsis rats. Furthermore, the cardiac tissue from EA treated rats showed increased expressions of α7nAChR on macrophages. The cardio-protective and anti-inflammatory effects of EA were partly or completely prevented in rats with vagotomy. CONCLUSION EA at PC6 attenuates left ventricle dysfunction and decreases inflammation in sepsis-induced cardiac dysfunction. The cardio-protective effects of EA are mediated through vagus nerve mediated cholinergic pathway.
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Affiliation(s)
- Zhiyang Wu
- Department of Critical Care Medicine, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, 758 Hefei Road, Qingdao, Shandong 266035, China.
| | - Yiqiu Xia
- Department of Pathology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, 210023 Nanjing, China; Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Chaofan Wang
- Department of Pathology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, 210023 Nanjing, China; Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, China.
| | - Wenjun Lu
- Department of Pathology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, 210023 Nanjing, China.
| | - Han Zuo
- Department of Pathology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, 210023 Nanjing, China.
| | - Dawei Wu
- Department of Critical Care Medicine, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, 758 Hefei Road, Qingdao, Shandong 266035, China.
| | - Yu Li
- Department of Physiology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, 210023 Nanjing, China.
| | - Rui Guo
- Department of Physiology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, 210023 Nanjing, China.
| | - Jun Lu
- Department of Intensive Care Unit, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China.
| | - Luyao Zhang
- Department of Pathology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, 210023 Nanjing, China.
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Zou Z, Yu J, Huang R, Yu J. Cx43-Delivered miR-181b Negatively Regulates Sirt1/FOXO3a Signalling Pathway-Mediated Apoptosis on Intestinal Injury in Sepsis. Digestion 2023; 104:370-380. [PMID: 37231890 DOI: 10.1159/000529102] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Accepted: 01/09/2023] [Indexed: 05/27/2023]
Abstract
INTRODUCTION Gap junctions can transmit signals between cells, including miRNAs, leading to the amplification of adjacent cell damage. No previous study has addressed gap junctions and miRNAs in sepsis because the internal mechanism of sepsis-induced intestinal injury is complex. Therefore, we studied the relationship between connexin43 (Cx43) and miR-181b and provided a research direction for further study of sepsis. METHODS A mouse caecal ligation and puncture method was used to construct a mouse sepsis model. Firstly, damage to intestinal tissues at different time points was analysed. The levels of Cx43, miR-181b, Sirt1, and FOXO3a in intestinal tissues and the transcription and translation of the apoptosis-related genes Bim and puma, which are downstream of FOXO3a were analysed. Secondly, the effect of Cx43 levels on miR-181b and Sirt1/FOXO3a signalling pathway activity was explored by using the Cx43 inhibitor heptanol. Finally, luciferase assays were used to determine miR-181b binding to the predicted target sequence. RESULTS The results show that during sepsis, intestinal injury becomes increasingly worse with time, and the expression of Cx43 and miR-181b increase. In addition, we found that heptanol could significantly reduce intestinal injury. This finding indicates that inhibiting Cx43 regulates the transfer of miR-181b between adjacent cells, thereby reducing the activity of the Sirt1/FOXO3a signalling pathway and reducing the degree of intestinal injury during sepsis. CONCLUSIONS In sepsis, the enhancement of Cx43 gap junctions leads to an increase in miR-181b intercellular transfer, affects the downstream SIRT1/FOXO3a signalling pathway and causes cell and tissue damage.
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Affiliation(s)
- Zhaowei Zou
- Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Jianyang Yu
- Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Renli Huang
- Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Jinlong Yu
- Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
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Palamim CVC, Boschiero MN, Marson FAL. Epidemiological profile and risk factors associated with death in patients receiving invasive mechanical ventilation in an adult intensive care unit from Brazil: a retrospective study. Front Med (Lausanne) 2023; 10:1064120. [PMID: 37181356 PMCID: PMC10166862 DOI: 10.3389/fmed.2023.1064120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Accepted: 03/28/2023] [Indexed: 05/16/2023] Open
Abstract
Introduction Understanding the epidemiological profile and risk factors associated with invasive mechanical ventilation (IMV) is essential to manage the patients better and to improve health services. Therefore, our objective was to describe the epidemiological profile of adult patients in intensive care that required IMV in-hospital treatment. Also, to evaluate the risks associated with death and the influence of positive end-expiratory pressure (PEEP) and arterial oxygen pressure (PaO2) at admission in the clinical outcome. Methods We conducted an epidemiological study analyzing medical records of inpatients who received IMV from January 2016 to December 2019 prior to the Coronavirus Disease (COVID)-19 pandemic in Brazil. We considered the following characteristics in the statistical analysis: demographic data, diagnostic hypothesis, hospitalization data, and PEEP and PaO2 during IMV. We associated the patients' features with the risk of death using a multivariate binary logistic regression analysis. We adopted an alpha error of 0.05. Results We analyzed 1,443 medical records; out of those, 570 (39.5%) recorded the patients' deaths. The binary logistic regression was significant in predicting the patients' risk of death [X2(9) = 288.335; p < 0.001]. Among predictors, the most significant in relation to death risk were: age [elderly ≥65 years old; OR = 2.226 (95%CI = 1.728-2.867)]; male sex (OR = 0.754; 95%CI = 0.593-0.959); sepsis diagnosis (OR = 1.961; 95%CI = 1.481-2.595); need for elective surgery (OR = 0.469; 95%CI = 0.362-0.608); the presence of cerebrovascular accident (OR = 2.304; 95%CI = 1.502-3.534); time of hospital care (OR = 0.946; 95%CI = 0.935-0.956); hypoxemia at admission (OR = 1.635; 95%CI = 1.024-2.611), and PEEP >8 cmH2O at admission (OR = 2.153; 95%CI = 1.426-3.250). Conclusion The death rate of the studied intensive care unit was equivalent to that of other similar units. Regarding risk predictors, several demographic and clinical characteristics were associated with enhanced mortality in intensive care unit patients under mechanical ventilation, such as diabetes mellitus, systemic arterial hypertension, and older age. The PEEP >8 cmH2O at admission was also associated with increased mortality since this value is a marker of initially severe hypoxia.
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Affiliation(s)
- Camila Vantini Capasso Palamim
- Laboratory of Cell and Molecular Tumor Biology and Bioactive Compounds, São Francisco University, Bragança Paulista, São Paulo, Brazil
- Laboratory of Human and Medical Genetics, Bragança Paulista, São Francisco University, São Paulo, Brazil
| | - Matheus Negri Boschiero
- Laboratory of Cell and Molecular Tumor Biology and Bioactive Compounds, São Francisco University, Bragança Paulista, São Paulo, Brazil
- Laboratory of Human and Medical Genetics, Bragança Paulista, São Francisco University, São Paulo, Brazil
| | - Fernando Augusto Lima Marson
- Laboratory of Cell and Molecular Tumor Biology and Bioactive Compounds, São Francisco University, Bragança Paulista, São Paulo, Brazil
- Laboratory of Human and Medical Genetics, Bragança Paulista, São Francisco University, São Paulo, Brazil
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Zhao X, Wang LY, Tang CY, Li K, Huang YH, Duan YR, Zhang ST, Ke K, Su BH, Yang W. Electro-microenvironment modulated inhibition of endogenous biofilms by piezo implants for ultrasound-localized intestinal perforation disinfection. Biomaterials 2023; 295:122055. [PMID: 36805242 DOI: 10.1016/j.biomaterials.2023.122055] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 02/08/2023] [Accepted: 02/12/2023] [Indexed: 02/16/2023]
Abstract
Endogenous bacterial infections from damaged gastrointestinal (GI) organs have high potential to cause systemic inflammatory responses and life-threatening sepsis. Current treatments, including systemic antibiotic administration and surgical suturing, are difficult in preventing bacterial translocation and further infection. Here, we report a wireless localized stimulator composed of a piezo implant with high piezoelectric output serving as an anti-infective therapy patch, which aims at modulating the electro-microenvironment of biofilm around GI wounds for effective inhibition of bacterial infection if combined with ultrasound (US) treatment from outside the body. The pulsed charges generated by the piezo implant in response to US stimulation transfer into bacterial biofilms, effectively destroying their macromolecular components (e.g., membrane proteins), disrupting the electron transport chain of biofilms, and inhibiting bacterial proliferation, as proven by experimental studies and theoretical calculations. The piezo implant, in combination with US stimulation, also exhibits successful in vivo anti-infection efficacy in a rat cecal ligation and puncture (CLP) model. The proposed strategy, combining piezo implants with controllable US activation, creates a promising pathway for inhibiting endogenous bacterial infection caused by GI perforation.
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Affiliation(s)
- Xing Zhao
- Department of Nephrology, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Li-Ya Wang
- Department of Nephrology, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Chun-Yan Tang
- College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, 610065, Sichuan, China
| | - Kai Li
- Department of Thoracic Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, China
| | - Yan-Hao Huang
- School of Materials Science and Engineering, Chongqing Jiao Tong University, Chongqing, 400074, China
| | - Yan-Ran Duan
- Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Shu-Ting Zhang
- College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, 610065, Sichuan, China
| | - Kai Ke
- College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, 610065, Sichuan, China.
| | - Bai-Hai Su
- Department of Nephrology, West China Hospital, Sichuan University, Chengdu, 610041, China.
| | - Wei Yang
- College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, 610065, Sichuan, China.
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19
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Bezati S, Velliou M, Ventoulis I, Simitsis P, Parissis J, Polyzogopoulou E. Infection as an under-recognized precipitant of acute heart failure: prognostic and therapeutic implications. Heart Fail Rev 2023:10.1007/s10741-023-10303-8. [PMID: 36897491 PMCID: PMC9999079 DOI: 10.1007/s10741-023-10303-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/20/2023] [Indexed: 03/11/2023]
Abstract
As the prevalence of heart failure (HF) continues to rise, prompt diagnosis and management of various medical conditions, which may lead to HF exacerbation and result in poor patient outcomes, are of paramount importance. Infection has been identified as a common, though under-recognized, precipitating factor of acute heart failure (AHF), which can cause rapid development or deterioration of HF signs and symptoms. Available evidence indicates that infection-related hospitalizations of patients with AHF are associated with higher mortality, protracted length of stay, and increased readmission rates. Understanding the intricate interaction of both clinical entities may provide further therapeutic strategies to prevent the occurrence of cardiac complications and improve prognosis of patients with AHF triggered by infection. The purpose of this review is to investigate the incidence of infection as a causative factor in AHF, explore its prognostic implications, elucidate the underlying pathophysiological mechanisms, and highlight the basic principles of the initial diagnostic and therapeutic interventions in the emergency department.
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Affiliation(s)
- Sofia Bezati
- Emergency Medicine Department, Attikon University Hospital, Rimini 1, Chaidari, 12462, Athens, Greece.
| | - Maria Velliou
- Emergency Medicine Department, Attikon University Hospital, Rimini 1, Chaidari, 12462, Athens, Greece
| | - Ioannis Ventoulis
- Department of Occupational Therapy, University of Western Macedonia, Keptse Area, Ptolemaida, 50200, Greece
| | - Panagiotis Simitsis
- National and Kapodistrian University of Athens, 2nd Department of Cardiology, Heart Failure Unit, Attikon University Hospital, Athens, Greece
| | - John Parissis
- Emergency Medicine Department, Attikon University Hospital, Rimini 1, Chaidari, 12462, Athens, Greece.,Emergency Medicine Department, National and Kapodistrian University of Athens, Athens, Greece
| | - Effie Polyzogopoulou
- Emergency Medicine Department, Attikon University Hospital, Rimini 1, Chaidari, 12462, Athens, Greece.,Emergency Medicine Department, National and Kapodistrian University of Athens, Athens, Greece
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20
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Hao X, Wang X, Wei H, Ding H, Zheng S, Wang L, Li Z, Yin H. Development and Validation of the Prediction Model of Sepsis in Patients After Percutaneous Nephrolithotomy and Sepsis Progresses to Septic Shock. J Endourol 2023; 37:377-386. [PMID: 36585859 DOI: 10.1089/end.2022.0384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Background: To study the predictors of sepsis and the progression of sepsis to septic shock in patients after percutaneous nephrolithotomy (PCNL) and to establish and validate predictive models. Methods: The patients were assigned to either the development cohort or the validation cohort depending on their hospital. In the development cohort, univariate and multivariate logistic regression analyses were used to screen independent risk factors for sepsis after PCNL and sepsis progression to septic shock. Nomogram prediction models were established according to the related independent risk factors. Areas under the receiver operating characteristic curves, calibration plots, and decision curve analysis (DCA) were used to estimate the discrimination, calibration, and clinical usefulness of the prediction models, respectively. The two sets of models were further validated on the validation cohort. Results: In the development cohort, the risk factors for sepsis after PCNL were diabetes, urine nitrite, staghorn calculi, HU value, albumin-globulin ratio, and high-sensitivity C-reactive protein/albumin ratio. The pre- and postoperative white blood cell counts were risk factors for the progression of sepsis to septic shock. The area under the ROC curve value for predicting sepsis risk was 0.891 and that for predicting septic shock risk was 0.981 in the development cohort; in the validation cohort, these values were 0.893 and 0.996, respectively. In the development cohort, the calibration test p values in the sepsis and septic shock cohorts were 0.946 and 0.634, respectively; in the validation cohort, these values were 0.739 and 0.208, respectively. DCA of the model in the sepsis and septic shock cohorts showed threshold probabilities of 10%-90% in the development cohort; in the validation cohort, these values were 10%-90%. Conclusion: The individualized nomogram prediction models can help improve the early identification of patients who are at higher risk of developing sepsis after PCNL and the progression of sepsis to septic shock to avoid further damage.
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Affiliation(s)
- Xiaodong Hao
- Department of Urology, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Xiaowei Wang
- Department of Urology, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Hongliang Wei
- Department of Urology, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Hao Ding
- Department of Urology, Liaocheng People s Hospital, Liaocheng, China
| | - Shuo Zheng
- Department of Urology, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Lei Wang
- Department of Urology, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Zhong Li
- Department of Urology, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Haijun Yin
- Department of Urology, The First Hospital of Hebei Medical University, Shijiazhuang, China
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21
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Kamal AHM, Chakrabarty JK, Chowdhury SM. Lipopolysaccharide and statin-mediated immune-responsive protein networks revealed in macrophages through affinity purification spacer-arm controlled cross-linking (AP-SPACC) proteomics. Mol Omics 2023; 19:48-59. [PMID: 36377691 DOI: 10.1039/d2mo00224h] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Toll-like receptor 4 (TLR4), a pattern recognition receptor, is activated by lipopolysaccharides (LPS) and induces the MyD88 pathway, which subsequently produces pro-inflammatory cytokines through activation of transcriptional nuclear factor (NF)-κB. Statins have been widely prescribed to reduce cholesterol synthesis for patients with cardiovascular disease. Statins may have pleiotropic effects, which include anti- and pro-inflammatory effects on cells. The molecular mechanism of the sequential influence of LPS and statin on the innate immune system remains unknown. We employed affinity purification-spacer-arm controlled cross-linking (AP-SPACC) MS-based proteomics analysis to identify the LPS- and statin-LPS-responsive proteins and their networks. LPS-stimulated RAW 264.7 macrophage cells singly and combined with the drug statin used in this study. Two chemical cross-linkers with different spacer chain lengths were utilized to stabilize the weak and transient interactors. Proteomic analysis identified 1631 differentially expressed proteins. We identified 151 immune-response proteins through functional enrichment analysis and visualized their interaction networks. Selected candidate protein-coding genes were validated, specifically squamous cell carcinoma antigens recognized by T cells 3, sphingosine-1-phosphate lyase 1, Ras-related protein Rab-35, and tumor protein D52 protein-coding genes through transcript-level expression analysis. The expressions of those genes were significantly increased upon statin treatment and decreased in LPS-stimulated macrophage cells. Therefore, we presumed that the expression changes of genes occurred due to immune response during activation of inflammation. These results highlight the immune-responsive proteins network, providing a new platform for novel investigations and discovering future therapeutic targets for inflammatory diseases.
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Affiliation(s)
- Abu Hena Mostafa Kamal
- Department of Chemistry and Biochemistry, University of Texas at Arlington, TX, 76019, USA. .,Advanced Technology Cores, Dan L Duncan Comprehensive Cancer Center, Metabolomics Core, Baylor College of Medicine, Houston, TX, 77030, USA.,Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA
| | - Jayanta K Chakrabarty
- Department of Chemistry and Biochemistry, University of Texas at Arlington, TX, 76019, USA. .,Quantitative Proteomics and Metabolomics Center, Columbia University, New York, NY, 10027, USA
| | - Saiful M Chowdhury
- Department of Chemistry and Biochemistry, University of Texas at Arlington, TX, 76019, USA.
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22
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Gao J, Zhao F, Yi S, Li S, Zhu A, Tang Y, Li A. Protective role of crocin against sepsis-induced injury in the liver, kidney and lungs via inhibition of p38 MAPK/NF-κB and Bax/Bcl-2 signalling pathways. PHARMACEUTICAL BIOLOGY 2022; 60:543-552. [PMID: 35225146 PMCID: PMC8890572 DOI: 10.1080/13880209.2022.2042328] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 12/28/2021] [Accepted: 02/09/2022] [Indexed: 06/01/2023]
Abstract
CONTEXT Crocin has been reported to have multiple bioactivities. However, the effect of crocin administration on caecal ligation and puncture (CLP)-induced sepsis remains unknown. OBJECTIVE We investigated the effects of crocin on CLP-induced sepsis in mice and the underlying mechanism of action. MATERIALS AND METHODS Five experimental groups (n = 10) of BALB/c mice were used: control, CLP (normal saline) and CLP + crocin (50, 100 and 250 mg/kg, 30 min prior to CLP). Mice were sacrificed 24 h after CLP. Liver, kidney and lung histopathology, indicator levels, apoptotic status, pro-inflammatory cytokines and relative protein levels were evaluated. RESULTS Compared to the CLP group, crocin treatment significantly increased the survival rate (70%, 80%, 90% vs. 30%). Crocin groups exhibited protection against liver, kidney and lung damage with mild-to-moderate morphological changes and lower indicator levels: liver (2.80 ± 0.45, 2.60 ± 0.55, 1.60 ± 0.55 vs. 5.60 ± 0.55), kidney (3.00 ± 0.71, 2.60 ± 0.55, 1.40 ± 0.55 vs. 6.20 ± 0.84) and lungs (8.00 ± 1.59, 6.80 ± 1.64, 2.80 ± 0.84 vs. 14.80 ± 1.79). The proinflammatory cytokines (IL-1β, TNF-α, IL-6 and IL-10 levels in the crocin groups) were distinctly lower and the apoptotic index showed a significant decrease. Crocin administration significantly suppressed p38 MAPK phosphorylation and inhibited NF-κB/IκBα and Bcl-2/Bax activation. DISCUSSION AND CONCLUSIONS Pre-treatment with crocin confers protective effects against CLP-induced liver, kidney and lung injury, implying it to be a potential therapeutic agent.
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Affiliation(s)
- Jun Gao
- Department of Laboratory Medicine, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China
| | - Feng Zhao
- Department of Nephrology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China
| | - Shaona Yi
- Department of Nephrology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China
| | - Shuhang Li
- Department of Urology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China
| | - Aiqing Zhu
- Department of Dermatology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China
| | - Yingxiu Tang
- Department of Laboratory Medicine, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China
| | - Aiqun Li
- Department of Emergency, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China
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23
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Nüssing S, Sutton VR, Trapani JA, Parish IA. Beyond target cell death - Granzyme serine proteases in health and disease. Mol Aspects Med 2022; 88:101152. [PMID: 36368281 DOI: 10.1016/j.mam.2022.101152] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 10/06/2022] [Accepted: 10/22/2022] [Indexed: 11/09/2022]
Abstract
Granzymes are a family of small (∼32 kDa) serine proteases with a range of substrate specificities that are stored in, and released from, the cytoplasmic secretory vesicles ('granules') of cytotoxic T lymphocytes and natural killer cells. Granzymes are not digestive proteases but finely tuned processing enzymes that target their substrates in specific ways to activate various signalling pathways, or to inactivate viral proteins and other targets. Great emphasis has been placed on studying the pro-apoptotic functions of granzymes, which largely depend on their synergy with the pore-forming protein perforin, on which they rely for penetration into the target cell cytosol to access their substrates. While a critical role for granzyme B in target cell apoptosis is undisputed, both it and the remaining granzymes also influence a variety of other biological processes (including important immunoregulatory functions), which are discussed in this review. This includes the targeting of many extracellular as well as intracellular substrates, and can also lead to deleterious outcomes for the host if granzyme expression or function are dysregulated or abrogated. A final important consideration is that granzyme repertoire, biochemistry and function vary considerably across species, probably resulting from the pressures applied by viruses and other pathogens across evolutionary time. This has implications for the interpretation of granzyme function in preclinical models of disease.
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Affiliation(s)
- Simone Nüssing
- Peter MacCallum Cancer Centre, Melbourne, Victoria, 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, 3052, Australia
| | - Vivien R Sutton
- Peter MacCallum Cancer Centre, Melbourne, Victoria, 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, 3052, Australia
| | - Joseph A Trapani
- Peter MacCallum Cancer Centre, Melbourne, Victoria, 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, 3052, Australia.
| | - Ian A Parish
- Peter MacCallum Cancer Centre, Melbourne, Victoria, 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, 3052, Australia; John Curtin School of Medical Research, ANU, ACT, Australia.
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24
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Son H, Park SC, Kim YM, Lee JK, Park S, Guk T, Yoon AM, Lim HS, Jang MK, Lee JR. Potent Anti-Inflammatory Effects of a Helix-to-Helix Peptide against Pseudomonas aeruginosa Endotoxin-Mediated Sepsis. Antibiotics (Basel) 2022; 11:1675. [PMID: 36421317 PMCID: PMC9686674 DOI: 10.3390/antibiotics11111675] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Revised: 11/16/2022] [Accepted: 11/18/2022] [Indexed: 08/27/2023] Open
Abstract
Although considerable scientific research data is available for sepsis and cytokine storm syndrome, there is a need to develop new treatments or drugs for sepsis management. Antimicrobial peptides (AMPs) possess anti-bacterial and anti-inflammatory activity, neutralizing toxins such as lipopolysaccharides (LPS, endotoxin). Most AMPs have been designed as a substitute for conventional antibiotics, which kill drug-resistant pathogens. The present study aimed to determine the anti-inflammatory potential of 10 designed XIW (X: lysine, arginine, or glutamic acid) α-helical peptides in macrophages and a mouse model in the presence of LPS. Among them, WIKE-14, a peptide with a helix-to-helix structure, having the 12th amino acid substituted with glutamic acid, suppressed pro-inflammatory cytokines in RAW 264.7 macrophages. This reaction was mediated by the inhibition of the binding between LPS and macrophages. In addition, the WIKE-14 peptide exhibited a potent anti-inflammatory activity in mice ears and lungs inflamed using LPS. Thus, our results may provide useful insights for the development of anti-sepsis agents via the sequence and structure information of the WIKE-14 peptide.
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Affiliation(s)
- Hyosuk Son
- Department of Chemical Engineering, Sunchon National University, Suncheon 57922, Republic of Korea
- Department of Exhibition and Education, National Marine Biodiversity Institute of Korea, Seocheon 33662, Republic of Korea
| | - Seong-Cheol Park
- Department of Chemical Engineering, Sunchon National University, Suncheon 57922, Republic of Korea
| | - Young-Min Kim
- Department of Chemical Engineering, Sunchon National University, Suncheon 57922, Republic of Korea
| | - Jong-Kook Lee
- Department of Chemical Engineering, Sunchon National University, Suncheon 57922, Republic of Korea
| | - Soyoung Park
- Department of Chemical Engineering, Sunchon National University, Suncheon 57922, Republic of Korea
| | - Taeuk Guk
- Department of Chemical Engineering, Sunchon National University, Suncheon 57922, Republic of Korea
| | - A-Mi Yoon
- LMO Team, National Institute of Ecology (NIE), Seocheon 33657, Republic of Korea
- Division of Life Sciences, Jeonbuk National University, Jeonju 54896, Republic of Korea
| | - Hye Song Lim
- LMO Team, National Institute of Ecology (NIE), Seocheon 33657, Republic of Korea
| | - Mi-Kyeong Jang
- Department of Chemical Engineering, Sunchon National University, Suncheon 57922, Republic of Korea
| | - Jung Ro Lee
- LMO Team, National Institute of Ecology (NIE), Seocheon 33657, Republic of Korea
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25
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Fan J, Shi S, Qiu Y, Liu M, Shu Q. Analysis of signature genes and association with immune cells infiltration in pediatric septic shock. Front Immunol 2022; 13:1056750. [PMID: 36439140 PMCID: PMC9686439 DOI: 10.3389/fimmu.2022.1056750] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Accepted: 10/26/2022] [Indexed: 08/02/2023] Open
Abstract
Background Early diagnosis of septic shock in children is critical for prognosis. This study committed to investigate the signature genes and their connection with immune cells in pediatric septic shock. Methods We screened a dataset of children with septic shock from the GEO database and analyzed differentially expressed genes (DEGs). Functional enrichment analysis was performed for these DEGs. Weighted gene co-expression network analysis (WCGNA) was used to screen the key modules. Least absolute shrinkage and selection operator (LASSO) and random forest analysis were finally applied to identify the signature genes. Then gene set enrichment analysis (GSEA) was exerted to explore the signaling pathways related to the hub genes. And the immune cells infiltration was subsequently classified via using CIBERSORT. Results A total of 534 DEGs were screened from GSE26440. The data then was clustered into 17 modules via WGCNA, which MEgrey module was significantly related to pediatric septic shock (cor=-0.62, p<0.0001). LASSO and random forest algorithms were applied to select the signature genes, containing UPP1, S100A9, KIF1B, S100A12, SLC26A8. The receiver operating characteristic curve (ROC) of these signature genes was 0.965, 0.977, 0.984, 0.991 and 0.989, respectively, which were verified in the external dataset from GSE13904. GSEA analysis showed these signature genes involve in positively correlated fructose and mannose metabolism and starch and sucrose metabolism signaling pathway. CIBERSORT suggested these signature genes may participate in immune cells infiltration. Conclusion UPP1, S100A9, KIF1B, S100A12, SLC26A8 emerge remarkable diagnostic performance in pediatric septic shock and involved in immune cells infiltration.
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Affiliation(s)
- Jiajie Fan
- Department of Cardiac Intensive Care Unit, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Shanshan Shi
- Department of Cardiac Intensive Care Unit, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Yunxiang Qiu
- Department of Cardiac Intensive Care Unit, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Mingnan Liu
- Department of Cardiac Intensive Care Unit, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Qiang Shu
- Department of Cardiac Surgery, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
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26
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Bonini A, Carota AG, Poma N, Vivaldi FM, Biagini D, Bottai D, Lenzi A, Tavanti A, Di Francesco F, Lomonaco T. Emerging Biosensing Technologies towards Early Sepsis Diagnosis and Management. BIOSENSORS 2022; 12:894. [PMID: 36291031 PMCID: PMC9599348 DOI: 10.3390/bios12100894] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/24/2022] [Revised: 09/28/2022] [Accepted: 10/13/2022] [Indexed: 06/16/2023]
Abstract
Sepsis is defined as a systemic inflammatory dysfunction strictly associated with infectious diseases, which represents an important health issue whose incidence is continuously increasing worldwide. Nowadays, sepsis is considered as one of the main causes of death that mainly affects critically ill patients in clinical settings, with a higher prevalence in low-income countries. Currently, sepsis management still represents an important challenge, since the use of traditional techniques for the diagnosis does not provide a rapid response, which is crucial for an effective infection management. Biosensing systems represent a valid alternative due to their characteristics such as low cost, portability, low response time, ease of use and suitability for point of care/need applications. This review provides an overview of the infectious agents associated with the development of sepsis and the host biomarkers suitable for diagnosis and prognosis. Special focus is given to the new emerging biosensing technologies using electrochemical and optical transduction techniques for sepsis diagnosis and management.
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Affiliation(s)
- Andrea Bonini
- Department of Chemistry and Industrial Chemistry, University of Pisa, Via G. Moruzzi 13, 56124 Pisa, Italy
- Department of Biology, University of Pisa, Via San Zeno 35-39, 56100 Pisa, Italy
| | - Angela Gilda Carota
- Department of Chemistry and Industrial Chemistry, University of Pisa, Via G. Moruzzi 13, 56124 Pisa, Italy
| | - Noemi Poma
- Department of Biology, University of Pisa, Via San Zeno 35-39, 56100 Pisa, Italy
| | - Federico Maria Vivaldi
- Department of Chemistry and Industrial Chemistry, University of Pisa, Via G. Moruzzi 13, 56124 Pisa, Italy
| | - Denise Biagini
- Department of Chemistry and Industrial Chemistry, University of Pisa, Via G. Moruzzi 13, 56124 Pisa, Italy
| | - Daria Bottai
- Department of Biology, University of Pisa, Via San Zeno 35-39, 56100 Pisa, Italy
| | - Alessio Lenzi
- Department of Chemistry and Industrial Chemistry, University of Pisa, Via G. Moruzzi 13, 56124 Pisa, Italy
| | - Arianna Tavanti
- Department of Biology, University of Pisa, Via San Zeno 35-39, 56100 Pisa, Italy
| | - Fabio Di Francesco
- Department of Chemistry and Industrial Chemistry, University of Pisa, Via G. Moruzzi 13, 56124 Pisa, Italy
| | - Tommaso Lomonaco
- Department of Chemistry and Industrial Chemistry, University of Pisa, Via G. Moruzzi 13, 56124 Pisa, Italy
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27
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Hao X, Wang X, Ding H, Zheng S, Li Z, Yin H, Wang L, Luo J, Wei H. A model for sepsis prediction after retrograde intrarenal surgery and the use of the preoperative/postoperative white blood cell ratio to predict progression from sepsis to septic shock. World J Urol 2022; 40:2979-2990. [PMID: 36229701 DOI: 10.1007/s00345-022-04182-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Accepted: 10/05/2022] [Indexed: 11/28/2022] Open
Abstract
OBJECTIVES To study the predictors of sepsis and progression to septic shock after RIRS; to establish and validate predictive models accordingly. METHODS In total, 1220 patients were included in the study during. Eight hundred forty-eight patients were assigned to the development cohort and 372 to the validation cohort according to medical record. Univariate and multivariate logistic regression analyses were used to screen independent risk factors for post-RIRS (Retrograde intrarenal surgery) sepsis and progression to septic shock. Nomogram prediction models were established according to the related independent risk factors. Areas under the receiver operating characteristic curves, calibration plots, and DCA (Decision curve analysis) were used to estimate the discrimination, calibration and clinical usefulness of the prediction model, respectively. RESULTS In the development cohort, sepsis occurred in 59 patients, 16 of whom developed septic shock. Multivariate logistic regression analyses showed that the independent risk factors for sepsis after RIRS were preoperative D-J stent implantation, hydronephrosis > 6.25 HU (Hounsfield units), AGR (Albumin/globulin ratio) < 1.95, hs-CRP/Alb (High-sensitivity C-reactive protein/albumin ratio) > 0.060, operating time > 67.5 min, and urinary nitrite positivity. The preoperative/postoperative WBC ratio > 1.5 was an independent risk factor for progression from sepsis to septic shock. In the development cohort, the AUC (Area under curve) for predicting sepsis risk was 0.845, and the AUC for predicting septic shock risk was 0.896; in the validation cohort, the corresponding values were 0.896 and 0.974, respectively. In the development cohort, the calibration test P values in the sepsis and septic shock cohorts, respectively, were 0.921 and 0.817; in the validation cohort, these values were 0.882 and 0.859. DCA of the model in the sepsis and septic shock cohorts showed threshold probabilities of 10-90% in the development cohort and 10-50% and 10-20% in the validation cohort. CONCLUSION These individualized nomogram prediction models can improve the early identification of patients at risk for developing sepsis after RIRS or progressing from sepsis to septic shock.
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Affiliation(s)
- Xiaodong Hao
- The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Xiaowei Wang
- The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Hao Ding
- Liaocheng People's Hospital, Liaocheng, Shandong, China
| | - Shuo Zheng
- The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Zhong Li
- The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Haijun Yin
- The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Lei Wang
- The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Jie Luo
- The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Hongliang Wei
- The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
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Gupta E, Kumar S, Srivastava VK, Saxena J, Siddiqui AJ, Mehta S, Kaushik S, Jyoti A. Unravelling the Differential Host Immuno-Inflammatory Responses to Staphylococcus aureus and Escherichia coli Infections in Sepsis. Vaccines (Basel) 2022; 10:vaccines10101648. [PMID: 36298513 PMCID: PMC9610428 DOI: 10.3390/vaccines10101648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 09/27/2022] [Accepted: 09/28/2022] [Indexed: 11/16/2022] Open
Abstract
Previous reports from our lab have documented dysregulated host inflammatory reactions in response to bacterial infections in sepsis. Both Gram-negative bacteria (GNB) and Gram-positive bacteria (GPB) play a significant role in the development and progression of sepsis by releasing several virulence factors. During sepsis, host cells produce a range of inflammatory responses including inducible nitric oxide synthase (iNOS) expression, nitrite generation, neutrophil extracellular traps (NETs) release, and pro-inflammatory cytokines production. The current study was conducted to discern the differences in host inflammatory reactions in response to both Escherichia coli and Staphylococcus aureus along with the organ dysfunction parameters in patients of sepsis. We examined 60 ICU sepsis patients identified based on the Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA II) scores. Pathogen identification was carried out using culture-based methods and gene-specific primers by real-time polymerase chain reaction (RT-PCR). Samples of blood from healthy volunteers were spiked with E. coli (GNB) and S. aureus (GPB). The incidence of NETs formation, iNOS expression, total nitrite content, and pro-inflammatory cytokine level was estimated. Prevalence of E. coli, A. baumannii (both GNB), S. aureus, and Enterococcus faecalis (both GPB) was found in sepsis patients. Augmented levels of inflammatory mediators including iNOS expression, total nitrite, the incidence of NETs, and proinflammatory cytokines, during spiking, were found in response to S. aureus infections in comparison with E. coli infections. These inflammatory mediators were found to be positively correlated with organ dysfunction in both GN and GP infections in sepsis patients. Augmented host inflammatory response was generated in S. aureus infections as compared with E. coli.
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Affiliation(s)
- Ena Gupta
- Amity Institute of Biotechnology, Amity University Rajasthan, Amity Education Valley, Kant Kalwar, NH-11C, Jaipur-Delhi Highway, Jaipur 303002, Rajasthan, India
| | - Sanni Kumar
- Amity Institute of Biotechnology, Amity University Rajasthan, Amity Education Valley, Kant Kalwar, NH-11C, Jaipur-Delhi Highway, Jaipur 303002, Rajasthan, India
| | - Vijay Kumar Srivastava
- Amity Institute of Biotechnology, Amity University Rajasthan, Amity Education Valley, Kant Kalwar, NH-11C, Jaipur-Delhi Highway, Jaipur 303002, Rajasthan, India
| | - Juhi Saxena
- Department of Biotechnology, University Institute of Biotechnology, Chandigarh University, S.A.S Nagar 140413, Punjab, India
| | - Arif Jamal Siddiqui
- Department of Biology, College of Science, University of Ha’il, Ha’il P.O. Box 2440, Saudi Arabia
| | - Sudhir Mehta
- Department of Geriatric Medicine, SMS Medical College & Attached Hospitals, J.L.N. Marg, Jaipur 302004, Rajasthan, India
| | - Sanket Kaushik
- Amity Institute of Biotechnology, Amity University Rajasthan, Amity Education Valley, Kant Kalwar, NH-11C, Jaipur-Delhi Highway, Jaipur 303002, Rajasthan, India
- Correspondence: (S.K.); (A.J.)
| | - Anupam Jyoti
- Department of Biotechnology, University Institute of Biotechnology, Chandigarh University, S.A.S Nagar 140413, Punjab, India
- Correspondence: (S.K.); (A.J.)
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Mabeza RM, Chervu N, Hadaya J, Lee C, Park M, MacQueen I, Benharash P. Impact of malnutrition on outcomes following groin hernia repair: Insights from the ACS NSQIP. Surgery 2022; 172:1456-1462. [PMID: 36049899 DOI: 10.1016/j.surg.2022.07.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 06/02/2022] [Accepted: 07/27/2022] [Indexed: 10/31/2022]
Abstract
BACKGROUND The present study examined the association of nutrition status, as defined by preoperative serum albumin, with postoperative outcomes and resource use after groin hernia repair. METHODS The 2006 to 2019 American College of Surgeons National Surgical Quality Improvement Program database was queried for adults (≥18 years) undergoing open or laparoscopic repair of inguinal or femoral hernia. Patients were stratified based on the following preoperative serum albumin levels: <2.5 g/dL (severe hypoalbuminemia), 2.5 to <3.0 (moderate hypoalbuminemia), 3.0 to <3.5 (mild), and ≥3.5 (normal albumin). Multivariable regression models were developed to assess the association of hypoalbuminemia with outcomes of interest, including 30-day mortality, postoperative complications, length of stay, and 30-day readmission. RESULTS Of the 261,052 patients meeting inclusion criteria, 0.3% had severe, 1.1% had moderate, and 7.4% had mild hypoalbuminemia, with 91.2% classified as normal albumin. After risk adjustment, mortality risk was greater for severe (5.8%, 95% confidence interval: 4.1-7.6), moderate (4.4%, 95% confidence interval: 3.4-5.3), and mild hypoalbuminemia (1.5%, 95% confidence interval: 1.2-1.8) relative to normal albumin (0.3%, 95% confidence interval: 0.2-0.3). Decreasing serum albumin levels were associated with a stepwise increase in risk of complications, length of stay, and 30-day readmission. CONCLUSION Decreased preoperative serum albumin is associated with increased mortality and morbidity after open and laparoscopic groin hernia repair. Serum albumin remains a relevant predictor of postsurgical outcomes and can thus be used in shared decision-making and optimization of malnourished patients in need of groin hernia repair.
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Affiliation(s)
- Russyan Mark Mabeza
- Cardiovascular Outcomes Research Laboratories (CORELAB), David Geffen School of Medicine, University of California-Los Angeles, CA. https://twitter.com/RussyanMabeza
| | - Nikhil Chervu
- Cardiovascular Outcomes Research Laboratories (CORELAB), David Geffen School of Medicine, University of California-Los Angeles, CA
| | - Joseph Hadaya
- Cardiovascular Outcomes Research Laboratories (CORELAB), David Geffen School of Medicine, University of California-Los Angeles, CA
| | - Cory Lee
- Cardiovascular Outcomes Research Laboratories (CORELAB), David Geffen School of Medicine, University of California-Los Angeles, CA
| | - Mina Park
- Cardiovascular Outcomes Research Laboratories (CORELAB), David Geffen School of Medicine, University of California-Los Angeles, CA
| | - Ian MacQueen
- Depatment of Surgery, David Geffen School of Medicine, University of California-Los Angeles, CA
| | - Peyman Benharash
- Cardiovascular Outcomes Research Laboratories (CORELAB), David Geffen School of Medicine, University of California-Los Angeles, CA.
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Association between Vitamin C Deficiency and Mortality in Patients with Septic Shock. Biomedicines 2022; 10:biomedicines10092090. [PMID: 36140190 PMCID: PMC9495833 DOI: 10.3390/biomedicines10092090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2022] [Revised: 08/19/2022] [Accepted: 08/22/2022] [Indexed: 12/05/2022] Open
Abstract
The prognostic value of low vitamin C levels has not been well investigated in patients with septic shock. We aimed to evaluate the association of vitamin C deficiency with mortality in patients with septic shock. We conducted a retrospective analysis of 165 patients with septic shock from a prospective multicenter trial and institutional sepsis registry between April 2018 and January 2020. The primary outcome was 28-day mortality. The patients were categorized into vitamin C deficiency and normal groups based on a vitamin C cutoff level of 11.4 mmol/L. Multivariable Cox regression analysis was performed to examine the association between vitamin C levels and 28-day mortality. A total of 165 patients was included for analysis and 77 (46.7%) had vitamin C deficiency. There was no significant difference in the 28-day mortality rate between the vitamin C deficiency group and the normal group (23.4% (n = 18/77) vs. 13.6% (n = 12/88), p = 0.083). Multivariable Cox proportional hazard analysis showed vitamin C deficiency to be associated with increased risk of 28-day mortality (adjusted hazard ratio, 2.65, 95% confidence interval (CI), 1.08–6.45; p = 0.032). Initial vitamin C deficiency was associated with a higher risk of 28-day mortality in patients with septic shock after adjusting for intravenous administration of vitamin C and thiamine, baseline characteristics, laboratory findings, and severity of illness.
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Wang Z, Zhang L, Li S, Xu F, Han D, Wang H, Huang T, Yin H, Lyu J. The relationship between hematocrit and serum albumin levels difference and mortality in elderly sepsis patients in intensive care units-a retrospective study based on two large database. BMC Infect Dis 2022; 22:629. [PMID: 35850582 PMCID: PMC9295343 DOI: 10.1186/s12879-022-07609-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Accepted: 07/12/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Sepsis still threatens the lives of more than 300 million patients annually and elderly patients with sepsis usually have a more complicated condition and a worse prognosis. Existing studies have shown that both Hematocrit (HCT) and albumin (ALB) can be used as potential predictors of sepsis, and their difference HCT-ALB has a significant capacity to diagnose infectious diseases. Currently, there is no relevant research on the relationship between HCT-ALB and the prognosis of elderly sepsis patients. Therefore, this study aims to explore the association between HCT-ALB and mortality in elderly patients with sepsis. METHODS This study was a multi-center retrospective study based on the Medical Information Mart for Intensive Care (MIMIC-IV) database and the eICU Collaborative Research Database (eICU-CRD) in elderly patients with sepsis. The optimal HCT-ALB cut-off point for ICU mortality was calculated by the Youden Index based on the eICU-CRD dataset, and multivariate logistic regressions were conducted to explore the association between HCT-ALB and ICU/hospital mortality in the two databases. Subgroup analyses were performed for different parameters and comorbidity status. RESULTS The number of 16,127 and 3043 elderly sepsis patients were selected from two large intensive care databases (eICU-CRD and MIMIC-IV, respectively) in this study. Depending on the optimal cut-off point, patients in both eICU-CRD and MIMIC-IV were independently divided into low HCT-ALB (< 6.7) and high HCT-ALB (≥ 6.7) groups. The odds ratio (95%confidence interval) [OR (95CI%)] of the high HCT-ALB group were 1.50 (1.36,1.65) and 1.71 (1.58,1.87) for ICU and hospital mortality in the eICU-CRD database after multivariable adjustment. Similar trends in the ICU and hospital mortality [OR (95%CI) 1.41 (1.15,1.72) and 1.27 (1.07,1.51)] were observed in MIMIC-IV database. Subgroup analysis showed an interaction effect with SOFA score in the eICU-CRD database however not in MIMIC-IV dataset. CONCLUSIONS High HCT-ALB (≥ 6.7) is associated with 1.41 and 1.27 times ICU and hospital mortality risk in elderly patients with sepsis. HCT-ALB is simple and easy to obtain and is a promising clinical predictor of early risk stratification for elderly sepsis patients in ICU.
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Affiliation(s)
- Zichen Wang
- Department of Intensive Care Unit, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, 510630, People's Republic of China
- Department of Public Health, University of California, Irvine, CA, USA
| | - Luming Zhang
- Department of Intensive Care Unit, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, 510630, People's Republic of China
- Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China
| | - Shaojin Li
- Department of Orthopaedics, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, 510630, People's Republic of China
| | - Fengshuo Xu
- Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China
| | - Didi Han
- Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China
| | - Hao Wang
- Department of Statistics, Iowa State University, Ames, USA
| | - Tao Huang
- Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China
| | - Haiyan Yin
- Department of Intensive Care Unit, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, 510630, People's Republic of China.
| | - Jun Lyu
- Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
- Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization, Guangzhou, Guangdong, China.
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Wang H, Yang JL, Chen C, Zheng Y, Chen M, Qi J, Tang S, Zhan XY. Identification of Peptoniphilus vaginalis-Like Bacteria, Peptoniphilus septimus sp. nov., From Blood Cultures in a Cervical Cancer Patient Receiving Chemotherapy: Case and Implications. Front Cell Infect Microbiol 2022; 12:954355. [PMID: 35880078 PMCID: PMC9307962 DOI: 10.3389/fcimb.2022.954355] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Accepted: 06/17/2022] [Indexed: 11/17/2022] Open
Abstract
A 39-year-old woman with a 3-year human papillomavirus (HPV) 18 infection history was admitted to the hospital for a 16-day history of vaginal bleeding after sex. She was diagnosed with cervical cancer based on the results of the electronic colposcopy, cervical cytology, microscopy, and magnetic resonance imaging (MRI). Then, she received chemotherapy, with paclitaxel 200 mg (day 1), cisplatin 75 mg (day 2), and bevacizumab 700 mg (day 3) twice with an interval of 27 days. During the examination for the diagnosis and treatment, many invasive operations, including removal of intrauterine device, colposcopy, and ureteral dilatation, were done. After that, the patient was discharged and entered the emergency department about 2.5 months later with a loss of consciousness probably caused by septic shock. The patient finally died of multiple organ failure and bacterial infection, although she has received antimicrobial therapy. The blood cultures showed a monobacterial infection with an anaerobic Gram-positive bacterial strain, designated as SAHP1. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI–TOF MS) indicated that the patient was infected with Peptoniphilus asaccharolyticus, while molecular analysis and genome-based taxonomy confirmed the infection with a novel Peptoniphilus species that has a close genetic relationship with Peptoniphilus vaginalis and proposed provisionally as Peptoniphilus septimus sp. nov., which may also act as a commensal of the human vagina. Genomic features of SAHP1 have been fully described, and comparative genomic analysis reveals the known prokaryote relative of Peptoniphilus septimus sp. nov. in the genus Peptoniphilus. The invasive operations on the genital tract during the diagnosis and treatment of the patient and the tumor tissue damage and bleeding may have a certain role in the bloodstream infection. This study casts a new light on the Peptoniphilus bacteria and prompts clinicians to include anaerobic blood cultures as part of their blood culture procedures, especially on patients with genital tract tumors. Furthermore, due to the incomplete database and unsatisfying resolution of the MALDI–TOF MS for Peptoniphilus species identification, molecular identification, especially whole-genome sequencing, is required for those initially identified as bacteria belonging to Peptoniphilus in the clinical laboratory.
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Affiliation(s)
- Huacheng Wang
- The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Jin-Lei Yang
- The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Chunmei Chen
- The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Ying Zheng
- The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
- School of Clinical Medicine, Guangdong Pharmaceutical University, Guangzhou, China
| | - Mingming Chen
- The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Junhua Qi
- The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Shihuan Tang
- The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Xiao-Yong Zhan
- The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
- *Correspondence: Xiao-Yong Zhan,
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33
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Costa SP, Carvalho CM. Burden of bacterial bloodstream infections and recent advances for diagnosis. Pathog Dis 2022; 80:6631550. [PMID: 35790126 DOI: 10.1093/femspd/ftac027] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 06/07/2022] [Accepted: 07/01/2022] [Indexed: 11/13/2022] Open
Abstract
Bloodstream infections (BSIs) and subsequent organ dysfunction (sepsis and septic shock) are conditions that rank among the top reasons for human mortality and have a great impact on healthcare systems. Their treatment mainly relies on the administration of broad-spectrum antimicrobials since the standard blood culture-based diagnostic methods remain time-consuming for the pathogen's identification. Consequently, the routine use of these antibiotics may lead to downstream antimicrobial resistance and failure in treatment outcomes. Recently, significant advances have been made in improving several methodologies for the identification of pathogens directly in whole blood especially regarding specificity and time to detection. Nevertheless, for the widespread implementation of these novel methods in healthcare facilities, further improvements are still needed concerning the sensitivity and cost-effectiveness to allow a faster and more appropriate antimicrobial therapy. This review is focused on the problem of BSIs and sepsis addressing several aspects like their origin, challenges, and causative agents. Also, it highlights current and emerging diagnostics technologies, discussing their strengths and weaknesses.
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Affiliation(s)
- Susana P Costa
- Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal.,LABBELS - Associate Laboratory, Braga/Guimarães, Portugal.,International Iberian Nanotechnology Laboratory, Av. Mestre José Veiga s/n, 4715-330, Braga, Portugal.,Instituto de Engenharia de Sistemas e Computadores - Microsistemas e Nanotecnologias (INESC MN) and IN - Institute of Nanoscience and Nanotechnology, Rua Alves Redol, 9 1000-029 Lisbon, Portugal
| | - Carla M Carvalho
- International Iberian Nanotechnology Laboratory, Av. Mestre José Veiga s/n, 4715-330, Braga, Portugal
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Andersson U, Yang H. HMGB1 is a critical molecule in the pathogenesis of Gram-negative sepsis. JOURNAL OF INTENSIVE MEDICINE 2022; 2:156-166. [PMID: 36789020 PMCID: PMC9924014 DOI: 10.1016/j.jointm.2022.02.001] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 01/19/2022] [Accepted: 02/06/2022] [Indexed: 04/12/2023]
Abstract
Gram-negative sepsis is a severe clinical syndrome associated with significant morbidity and mortality. Lipopolysaccharide (LPS), expressed on Gram-negative bacteria, is a potent pro-inflammatory toxin that induces inflammation and coagulation via two separate receptor systems. One is Toll-like receptor 4 (TLR4), expressed on cell surfaces and in endosomes, and the other is the cytosolic receptor caspase-11 (caspases-4 and -5 in humans). Extracellular LPS binds to high mobility group box 1 (HMGB1) protein, a cytokine-like molecule. The HMGB1-LPS complex is transported via receptor for advanced glycated end products (RAGE)-endocytosis to the endolysosomal system to reach the cytosolic LPS receptor caspase-11 to induce HMGB1 release, inflammation, and coagulation that may cause multi-organ failure. The insight that LPS needs HMGB1 assistance to generate severe inflammation has led to successful therapeutic results in preclinical Gram-negative sepsis studies targeting HMGB1. However, to date, no clinical studies have been performed based on this strategy. HMGB1 is also actively released by peripheral sensory nerves and this mechanism is fundamental for the initiation and propagation of inflammation during tissue injury. Homeostasis is achieved when other neurons actively restrict the inflammatory response via monitoring by the central nervous system and the vagus nerve through the cholinergic anti-inflammatory pathway. The neuronal control in Gram-negative sepsis needs further studies since a deeper understanding of the interplay between HMGB1 and acetylcholine may have beneficial therapeutic implications. Herein, we review the synergistic overlapping mechanisms of LPS and HMGB1 and discuss future treatment opportunities in Gram-negative sepsis.
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Affiliation(s)
- Ulf Andersson
- Department of Women's and Children's Health, Karolinska Institute at Karolinska University Hospital, Stockholm 17176, Sweden
- Corresponding author: Ulf Andersson, Department of Women's and Children's Health, Karolinska Institute at Karolinska University Hospital, Stockholm 17176, Sweden.
| | - Huan Yang
- Institute for Bioelectronic Medicine, The Feinstein Institutes for Medical Research, Manhasset, NY 11030, United States of America
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Honda TJ, Kazemiparkouhi F, Henry TD, Suh HH. Long-term PM 2.5 exposure and sepsis mortality in a US medicare cohort. BMC Public Health 2022; 22:1214. [PMID: 35717154 PMCID: PMC9206363 DOI: 10.1186/s12889-022-13628-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Accepted: 06/13/2022] [Indexed: 11/10/2022] Open
Abstract
Background Risk factors contributing to sepsis-related mortality include clinical conditions such as cardiovascular disease, chronic lung disease, and diabetes, all of which have also been shown to be associated with air pollution exposure. However, the impact of chronic exposure to air pollution on sepsis-related mortality has been little studied. Methods In a cohort of 53 million Medicare beneficiaries (228,439 sepsis-related deaths) living across the conterminous United States between 2000 and 2008, we examined the association of long-term PM2.5 exposure and sepsis-related mortality. For each Medicare beneficiary (ages 65–120), we estimated the 12-month moving average PM2.5 concentration for the 12 month before death, for their ZIP code of residence using well validated GIS-based spatio-temporal models. Deaths were categorized as sepsis-related if they have ICD-10 codes for bacterial or other sepsis. We used Cox proportional hazard models to assess the association of long-term PM2.5 exposure on sepsis-related mortality. Models included strata for age, sex, race, and ZIP code and controlled for neighborhood socio-economic status (SES). We also evaluated confounding through adjustment of neighborhood behavioral covariates. Results A 10 μg/m3 increase in 12-month moving average PM2.5 was associated with a 9.1% increased risk of sepsis mortality (95% CI: 3.6–14.9) in models adjusted for age, sex, race, ZIP code, and SES. HRs for PM2.5 were higher and statistically significant for older (> 75), Black, and urban beneficiaries. In stratified analyses, null associations were found for younger beneficiaries (65–75), beneficiaries who lived in non-urban ZIP codes, and those residing in low-SES urban ZIP codes. Conclusions Long-term PM2.5 exposure is associated with elevated risks of sepsis-related mortality.
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Affiliation(s)
- Trenton J Honda
- School of Clinical and Rehabilitation Sciences, Northeastern University, 360 Huntington Avenue, Boston, MA, 02115, USA.
| | | | - Trenton D Henry
- Division of Public Health, Department of Family and Preventive Medicine, University of Utah, Salt Lake City, UT, USA
| | - Helen H Suh
- Department of Civil and Environmental Engineering, Tufts University, Medford, MA, USA
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Minasyan H. Oxygen therapy for sepsis and prevention of complications. Acute Crit Care 2022; 37:137-150. [PMID: 35545238 PMCID: PMC9184979 DOI: 10.4266/acc.2021.01200] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Accepted: 12/16/2021] [Indexed: 11/30/2022] Open
Abstract
Patients with sepsis have a wide range of respiratory disorders that can be treated with oxygen therapy. Experimental data in animal sepsis models show that oxygen therapy significantly increases survival, while clinical data on the use of different oxygen therapy protocols are ambiguous. Oxygen therapy, especially hyperbaric oxygenation, in patients with sepsis can aggravate existing oxidative stress and contribute to the development of disseminated intravascular coagulation. The purpose of this article is to compare experimental and clinical data on oxygen therapy in animals and humans, to discuss factors that can influence the results of oxygen therapy for sepsis treatment in humans, and to provide some recommendations for reducing oxidative stress and preventing disseminated intravascular coagulation during oxygen therapy.
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37
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Huang Q, Wang Y, He F. Blood long non-coding RNA intersectin 1-2 is highly expressed and links with increased Th17 cells, inflammation, multiple organ dysfunction, and mortality risk in sepsis patients. J Clin Lab Anal 2022; 36:e24330. [PMID: 35243686 PMCID: PMC8993609 DOI: 10.1002/jcla.24330] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 02/15/2022] [Accepted: 02/23/2022] [Indexed: 12/03/2022] Open
Abstract
Background Long non‐coding RNA intersectin 1–2 (lnc‐ITSN1‐2) exacerbates inflammation and promotes T‐helper (Th) cell differentiation, also serves as a biomarker in critical illness diseases. However, its clinical role in sepsis remains obscure. Hence, the study aimed to explore the relationship of lnc‐ITSN1‐2 with Th cells, inflammation, disease severity, multiple organ dysfunction, and mortality risk in sepsis. Methods Peripheral blood mononuclear cells (PBMC) were isolated from 95 sepsis patients and 50 health controls, followed by lnc‐ITSN1‐2 evaluation using RT‐qPCR. PBMC Th1, Th17 cells and their secreted cytokines in serum were detected by flow cytometry and ELISA, respectively. Results Lnc‐ITSN1‐2 in sepsis patients was higher than it in health controls (Z = −7.328, p < 0.001). Lnc‐ITSN1‐2 correlated with increased interferon‐gamma (p = 0.009), Th17 cells (p = 0.022), and interleukin‐17A (p = 0.006), but not Th1 cells (p = 0.169) in sepsis patients. Moreover, lnc‐ITSN1‐2 had a positive connection with C‐reactive protein (p = 0.001), acute pathologic and chronic health evaluation (APACHE) II (p = 0.024), and sequential organ failure assessment (SOFA) scores (p = 0.022). Regarding SOFA subscales, lnc‐ITSN1‐2 linked with elevated respiratory system score (p = 0.005), cardiovascular system score (p = 0.007), and renal system score (p = 0.004) but no other subscales. Besides, lnc‐ITSN1‐2 had an increasing trend, but no statistical difference, in septic deaths compared to survivors (Z = −1.852, p = 0.064). Conclusion Lnc‐ITSN1‐2 reflects sepsis progression and unfavorable prognosis to some extent, which may serve as a potential biomarker to improve the management of sepsis patients.
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Affiliation(s)
- Qinghe Huang
- Department of Central Intensive Care Unit, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, China
| | - Yibin Wang
- Department of Central Intensive Care Unit, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, China
| | - Fuyun He
- Department of Central Intensive Care Unit, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, China
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Falk GE, Rogers J, Lu L, Ablah E, Okut H, Vindhyal MR. Sepsis, Septic Shock, and Differences in Cardiovascular Event Occurrence. J Intensive Care Med 2022; 37:1528-1534. [PMID: 35236176 DOI: 10.1177/08850666221083644] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Introduction: Mortality estimates from sepsis and septic shock ranged from 18% to 35% and 40% to 60%, respectively, prior to 2014. Sepsis patients who experience subsequent cardiovascular events have increased mortality; however, data are limited among septic shock patients. This study reports in-hospital mortality, incident cardiovascular events, and cardiovascular procedures among sepsis patients with and without subsequent septic shock. Methods: Patients with a primary diagnosis of sepsis with and without a secondary diagnosis of septic shock were identified from the 2016 and 2017 National Readmissions Database. These patients were then evaluated for the occurrence of cardiovascular events and procedures. Results: A total of 2,127,137 patients were included in the study, with a mean age of 66 years. Twenty percent of patients (n = 420,135) developed subsequent septic shock. In-hospital mortality among patients with a primary diagnosis of sepsis was 5.3%, and it was 31.2% for those with subsequent septic shock. Notable cardiovascular events occurring among sepsis patients with and without subsequent septic shock, respectively, included: acute kidney injury (65.1% vs. 32.8%, P < .0001), acute systolic heart failure (9.8% vs. 5.1%, P < .0001), NSTEMI (8.8% vs. 3.2%, P < .0001), and ischemic stroke (2.3% vs. 0.9%, P < .0001). Similarly, the most common cardiovascular procedures between the two groups were: percutaneous coronary intervention (0.37% vs. 0.20%, P < .0001), intra-aortic balloon pump (0.19% vs. 0.02%, P < .0001), and extracorporeal membrane oxygenation (0.18% vs. 0.01%, P < .0001). Conclusions: Sepsis with subsequent septic shock is associated with an increased frequency of in-hospital cardiovascular events and procedures.
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Affiliation(s)
- Grace E Falk
- Medical Students, 8586University of Kansas School of Medicine-Wichita, Wichita, KS, USA
| | - Jerad Rogers
- Medical Students, 8586University of Kansas School of Medicine-Wichita, Wichita, KS, USA
| | - Liuqiang Lu
- Department of Population Health, 8586University of Kansas School of Medicine-Wichita, Wichita, KS, USA
| | - Elizabeth Ablah
- Department of Population Health, 8586University of Kansas School of Medicine-Wichita, Wichita, KS, USA
| | - Hayrettin Okut
- Department of Population Health, 8586University of Kansas School of Medicine-Wichita, Wichita, KS, USA
| | - Mohinder R Vindhyal
- Department of Cardiovascular Disease, 21638Kansas University Medical Center, Kansas City, KS, USA
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Cortes C, Desler C, Mazzoli A, Chen JY, Ferreira VP. The role of properdin and Factor H in disease. Adv Immunol 2022; 153:1-90. [PMID: 35469595 DOI: 10.1016/bs.ai.2021.12.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
The complement system consists of three pathways (alternative, classical, and lectin) that play a fundamental role in immunity and homeostasis. The multifunctional role of the complement system includes direct lysis of pathogens, tagging pathogens for phagocytosis, promotion of inflammatory responses to control infection, regulation of adaptive cellular immune responses, and removal of apoptotic/dead cells and immune complexes from circulation. A tight regulation of the complement system is essential to avoid unwanted complement-mediated damage to the host. This regulation is ensured by a set of proteins called complement regulatory proteins. Deficiencies or malfunction of these regulatory proteins may lead to pro-thrombotic hematological diseases, renal and ocular diseases, and autoimmune diseases, among others. This review focuses on the importance of two complement regulatory proteins of the alternative pathway, Factor H and properdin, and their role in human diseases with an emphasis on: (a) characterizing the main mechanism of action of Factor H and properdin in regulating the complement system and protecting the host from complement-mediated attack, (b) describing the dysregulation of the alternative pathway as a result of deficiencies, or mutations, in Factor H and properdin, (c) outlining the clinical findings, management and treatment of diseases associated with mutations and deficiencies in Factor H, and (d) defining the unwanted and inadequate functioning of properdin in disease, through a discussion of various experimental research findings utilizing in vitro, mouse and human models.
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Affiliation(s)
- Claudio Cortes
- Department of Foundational Medical Studies, Oakland University William Beaumont School of Medicine, Rochester, MI, United States.
| | - Caroline Desler
- Oakland University William Beaumont School of Medicine, Rochester, MI, United States
| | - Amanda Mazzoli
- Oakland University William Beaumont School of Medicine, Rochester, MI, United States
| | - Jin Y Chen
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States
| | - Viviana P Ferreira
- Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United States.
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Wu D, Wang L, Hong D, Zheng C, Zeng Y, Ma H, Lin J, Chen J, Zheng R. Interleukin 35 contributes to immunosuppression by regulating inflammatory cytokines and T cell populations in the acute phase of sepsis. Clin Immunol 2022; 235:108915. [PMID: 34995813 DOI: 10.1016/j.clim.2021.108915] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 02/17/2021] [Accepted: 12/22/2021] [Indexed: 12/30/2022]
Abstract
Cytokines interact closely with each other and play a crucial role in the progression of sepsis. We focused on the associations of a cytokine network with IL-35 in sepsis. First, the retrospective study included 42 patients with sepsis and 23 healthy controls. Blood samples were collected from patients on days 1, 2, 4. Levels of IL-35, IL-1β, IL-4, IL-6, IL-10, IL-17A, TNF-α and IFN-γ were measured. They all increased to various extend on days 1, 2, 4, and strongly associated with markers of disease severity. Network analysis revealed a network formed by IL-35, with IL-6, IL-10, IL-17A, TNF-α and IFN-γ throughout the acute phase of sepsis(days 1, 2 and4). Then, the CLP-induced septic rats were used. The recombinant human IL-35(rIL-35) upregulated the levels of IL-10, but downregulated IL-4, IL-6, IL-17A, TNF-α and IFN-γ, while it had no significant effect on IL-1β, and upregulated the percentages of CD4+CD25+Tregs, and iTR35, but downregulated Teff cells in the peripheral blood. The rIL-35 reduced inflammation damage and improved prognosis of the septic rats. IL-35 forms a network with other cytokines and plays a major role in the immunopathogenesis of sepsis.
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Affiliation(s)
- Dansen Wu
- Department of Critical Care Medicine, Fujian Provincial Hospital, Fujian Provincial Center for Critical Care Medicine, Fujian Medical University, Fuzhou 350001, Fujian, China.
| | - Liming Wang
- Department of Critical Care Medicine, Fujian Provincial Hospital, Fujian Provincial Center for Critical Care Medicine, Fujian Medical University, Fuzhou 350001, Fujian, China
| | - Donghuang Hong
- Department of Critical Care Medicine, Fujian Provincial Hospital, Fujian Provincial Center for Critical Care Medicine, Fujian Medical University, Fuzhou 350001, Fujian, China
| | - Caifa Zheng
- Department of Critical Care Medicine, Fujian Provincial Hospital, Fujian Provincial Center for Critical Care Medicine, Fujian Medical University, Fuzhou 350001, Fujian, China
| | - Yongping Zeng
- Department of Critical Care Medicine, Fujian Provincial Hospital, Fujian Provincial Center for Critical Care Medicine, Fujian Medical University, Fuzhou 350001, Fujian, China
| | - Huolan Ma
- Department of Critical Care Medicine, Fujian Provincial Hospital, Fujian Provincial Center for Critical Care Medicine, Fujian Medical University, Fuzhou 350001, Fujian, China
| | - Jing Lin
- Department of Critical Care Medicine, Fujian Provincial Hospital, Fujian Provincial Center for Critical Care Medicine, Fujian Medical University, Fuzhou 350001, Fujian, China
| | - Jialong Chen
- Department of Critical Care Medicine, Fujian Provincial Hospital, Fujian Provincial Center for Critical Care Medicine, Fujian Medical University, Fuzhou 350001, Fujian, China
| | - Ronghui Zheng
- Department of Critical Care Medicine, Fujian Provincial Hospital, Fujian Provincial Center for Critical Care Medicine, Fujian Medical University, Fuzhou 350001, Fujian, China
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Yu N, Liu X, Shi D, Bai L, Niu T, Liu Y. CD63 and C3AR1: The Potential Molecular Targets in the Progression of Septic Shock. Int J Gen Med 2022; 15:711-728. [PMID: 35082520 PMCID: PMC8784317 DOI: 10.2147/ijgm.s338486] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Accepted: 12/16/2021] [Indexed: 11/23/2022] Open
Abstract
Background The molecular mechanism of septic shock is unknown. We studied the pathogenesis of septic shock and provide a novel strategy for treating and improving the prognosis of septic shock. Methods Gluten-Sensitive Enteropathy (GSE) 131761, GSE119217, GSE26378 datasets were downloaded from the Gene Expression Omnibus (GEO) database. The three datasets included 204 septic shock samples and 48 normal samples. The R packages “affy” and “limma” were employed to identify the differently expressed genes (DEGs) between septic shock and normal samples. Weighted gene co-expression network analysis (WGCNA) was performed to search for modules that play an important role in septic shock. Functional annotation of DEGs and construction and analysis of hub genes were used to explore the pathomechanism of septic shock. The receiver operating characteristic (ROC) curves were obtained using MedCalc software. The drug molecules that could regulate hub genes associated with septic shock were searched for in the CMap database. An animal model of septic shock was constructed to analyze the role of these hub genes. Results The merged series contained 321 up-regulated and 255 down-regulated genes. WGCNA showed the brown module had the highest correlation with the status of septic shock. GO and KEGG enrichment analysis results of the brown module genes showed they were mainly enriched in “leukocyte differentiation”, “Ras-proximate-1 (Rap1) signaling pathway”, and “cytokine–cytokine receptor interaction”. Through construction and analysis of a protein–protein interaction (PPI) network, cluster of differentiation 63 (CD63) and complement component 3a receptor 1 (C3AR1) were identified as hub genes of septic shock. The area under curve (AUC) of C3AR1 for the septic shock is 0.772 (P<0.001), and the AUC of CD63 for the septic shock is 0.871 (P<0.001). Small molecule drugs were filtered by the number of instances (n>3) and P-values <0.05, including “monensin”, “verteporfin”, “ikarugamycin”, “tetrahydroalstonine”, “cefamandole”, “etoposide”. In the animal model, the relative expression levels of interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α), and lactic acid were significantly higher in the septic shock group compared with the control group. Results of Real Time Quantitative PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) analysis for CD63 and C3AR1 showed that their relative expression levels were significantly lower in the septic shock group compared with the control group (P<0.05). Conclusion CD63 and C3AR1 are significant hub genes of septic shock and may represent potential molecular targets for future studies of septic shock.
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Affiliation(s)
- Ning Yu
- Department of Anaesthesiology and Intensive Care, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050004, People’s Republic of China
| | - Xuefang Liu
- Department of Anaesthesiology and Intensive Care, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050004, People’s Republic of China
| | - Dandan Shi
- Department of Anaesthesiology and Intensive Care, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050004, People’s Republic of China
| | - Long Bai
- Department of Anaesthesiology and Intensive Care, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050004, People’s Republic of China
| | - Tianfu Niu
- Department of Anaesthesiology and Intensive Care, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050004, People’s Republic of China
| | - Ya Liu
- Department of Anaesthesiology and Intensive Care, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050004, People’s Republic of China
- Correspondence: Ya Liu, Department of Anaesthesiology and Intensive Care, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050004, People’s Republic of China, Email ;
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Sansores-España LD, Melgar-Rodríguez S, Olivares-Sagredo K, Cafferata EA, Martínez-Aguilar VM, Vernal R, Paula-Lima AC, Díaz-Zúñiga J. Oral-Gut-Brain Axis in Experimental Models of Periodontitis: Associating Gut Dysbiosis With Neurodegenerative Diseases. FRONTIERS IN AGING 2021; 2:781582. [PMID: 35822001 PMCID: PMC9261337 DOI: 10.3389/fragi.2021.781582] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Accepted: 11/08/2021] [Indexed: 12/12/2022]
Abstract
Periodontitis is considered a non-communicable chronic disease caused by a dysbiotic microbiota, which generates a low-grade systemic inflammation that chronically damages the organism. Several studies have associated periodontitis with other chronic non-communicable diseases, such as cardiovascular or neurodegenerative diseases. Besides, the oral bacteria considered a keystone pathogen, Porphyromonas gingivalis, has been detected in the hippocampus and brain cortex. Likewise, gut microbiota dysbiosis triggers a low-grade systemic inflammation, which also favors the risk for both cardiovascular and neurodegenerative diseases. Recently, the existence of an axis of Oral-Gut communication has been proposed, whose possible involvement in the development of neurodegenerative diseases has not been uncovered yet. The present review aims to compile evidence that the dysbiosis of the oral microbiota triggers changes in the gut microbiota, which creates a higher predisposition for the development of neuroinflammatory or neurodegenerative diseases.The Oral-Gut-Brain axis could be defined based on anatomical communications, where the mouth and the intestine are in constant communication. The oral-brain axis is mainly established from the trigeminal nerve and the gut-brain axis from the vagus nerve. The oral-gut communication is defined from an anatomical relation and the constant swallowing of oral bacteria. The gut-brain communication is more complex and due to bacteria-cells, immune and nervous system interactions. Thus, the gut-brain and oral-brain axis are in a bi-directional relationship. Through the qualitative analysis of the selected papers, we conclude that experimental periodontitis could produce both neurodegenerative pathologies and intestinal dysbiosis, and that periodontitis is likely to induce both conditions simultaneously. The severity of the neurodegenerative disease could depend, at least in part, on the effects of periodontitis in the gut microbiota, which could strengthen the immune response and create an injurious inflammatory and dysbiotic cycle. Thus, dementias would have their onset in dysbiotic phenomena that affect the oral cavity or the intestine. The selected studies allow us to speculate that oral-gut-brain communication exists, and bacteria probably get to the brain via trigeminal and vagus nerves.
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Affiliation(s)
- Luis Daniel Sansores-España
- Periodontal Biology Laboratory, Faculty of Dentistry, University of Chile, Santiago, Chile
- Faculty of Dentistry, Autonomous University of Yucatán, Mérida, México
| | | | | | - Emilio A. Cafferata
- Department of Periodontology, School of Dentistry, Universidad Científica Del Sur, Lima, Perú
| | | | - Rolando Vernal
- Periodontal Biology Laboratory, Faculty of Dentistry, University of Chile, Santiago, Chile
| | - Andrea Cristina Paula-Lima
- Biomedical Neuroscience Institute, Faculty of Medicine, Universidad de Chile, Santiago, Chile
- Department of Neuroscience, Faculty of Medicine, Universidad de Chile, Santiago, Chile
- Institute for Research in Dental Sciences, Faculty of Dentistry, Universidad de Chile, Santiago, Chile
| | - Jaime Díaz-Zúñiga
- Periodontal Biology Laboratory, Faculty of Dentistry, University of Chile, Santiago, Chile
- Department of Medicine, Faculty of Medicine, University of Atacama, Copiapó, Chile
- *Correspondence: Jaime Díaz-Zúñiga, ,
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Erythrocyte-enabled immunomodulation for vaccine delivery. J Control Release 2021; 341:314-328. [PMID: 34838929 DOI: 10.1016/j.jconrel.2021.11.035] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Revised: 11/21/2021] [Accepted: 11/22/2021] [Indexed: 12/11/2022]
Abstract
Erythrocytes capture pathogens in circulation and present them to antigen-presenting cells (APCs) in the spleen. Senescent or apoptotic erythrocytes are physiologically eliminated by splenic APCs in a non-inflammatory manner as to not induce an immune reaction, while damaged erythrocytes tend to induce immune activation. The distinct characteristics of erythrocytes in their lifespan or different states inspire the design of targeting splenic APCs for vaccine delivery. Specifically, normal or damaged erythrocyte-driven immune targeting can induce antigen-specific immune activation, whereas senescent or apoptotic erythrocytes can be tailored to achieve antigen-specific immune tolerance. Recent studies have revealed the potential of erythrocyte-based vaccine delivery; however, there is still no in-depth review to describe the latest progress. This review summarizes the characteristics, different immune functions, and diverse vaccine delivery behaviors and biomedical applications of erythrocytes in different states. This review aims to contribute to the rational design and development of erythrocyte-based vaccine delivery systems for treating various infections, tumors, inflammatory diseases, and autoimmune diseases.
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Ding X, Kambara H, Guo R, Kanneganti A, Acosta-Zaldívar M, Li J, Liu F, Bei T, Qi W, Xie X, Han W, Liu N, Zhang C, Zhang X, Yu H, Zhao L, Ma F, Köhler JR, Luo HR. Inflammasome-mediated GSDMD activation facilitates escape of Candida albicans from macrophages. Nat Commun 2021; 12:6699. [PMID: 34795266 PMCID: PMC8602704 DOI: 10.1038/s41467-021-27034-9] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Accepted: 10/25/2021] [Indexed: 12/11/2022] Open
Abstract
Candida albicans is the most common cause of fungal sepsis. Inhibition of inflammasome activity confers resistance to polymicrobial and LPS-induced sepsis; however, inflammasome signaling appears to protect against C. albicans infection, so inflammasome inhibitors are not clinically useful for candidiasis. Here we show disruption of GSDMD, a known inflammasome target and key pyroptotic cell death mediator, paradoxically alleviates candidiasis, improving outcomes and survival of Candida-infected mice. Mechanistically, C. albicans hijacked the canonical inflammasome-GSDMD axis-mediated pyroptosis to promote their escape from macrophages, deploying hyphae and candidalysin, a pore-forming toxin expressed by hyphae. GSDMD inhibition alleviated candidiasis by preventing C. albicans escape from macrophages while maintaining inflammasome-dependent but GSDMD-independent IL-1β production for anti-fungal host defenses. This study demonstrates key functions for GSDMD in Candida's escape from host immunity in vitro and in vivo and suggests that GSDMD may be a potential therapeutic target in C. albicans-induced sepsis.
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Affiliation(s)
- Xionghui Ding
- Department of Pathology, Dana-Farber/Harvard Cancer Center, Harvard Medical School; Department of Laboratory Medicine, Boston Children's Hospital, Enders Research Building, Room 814, Boston, MA, 02115, USA
- Department of Burn and Plastic Surgery, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, 400014, China
| | - Hiroto Kambara
- Department of Pathology, Dana-Farber/Harvard Cancer Center, Harvard Medical School; Department of Laboratory Medicine, Boston Children's Hospital, Enders Research Building, Room 814, Boston, MA, 02115, USA
| | - Rongxia Guo
- Department of Pathology, Dana-Farber/Harvard Cancer Center, Harvard Medical School; Department of Laboratory Medicine, Boston Children's Hospital, Enders Research Building, Room 814, Boston, MA, 02115, USA
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, CAMS Key laboratory for prevention and control of hematological disease treatment related infection, Chinese Academy of Medical Sciences & Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, China
| | - Apurva Kanneganti
- Department of Pathology, Dana-Farber/Harvard Cancer Center, Harvard Medical School; Department of Laboratory Medicine, Boston Children's Hospital, Enders Research Building, Room 814, Boston, MA, 02115, USA
| | - Maikel Acosta-Zaldívar
- Division of Infectious Diseases, Boston Children's Hospital/Harvard Medical School, Boston, MA, 02115, USA
| | - Jiajia Li
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, CAMS Key laboratory for prevention and control of hematological disease treatment related infection, Chinese Academy of Medical Sciences & Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, China
| | - Fei Liu
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, CAMS Key laboratory for prevention and control of hematological disease treatment related infection, Chinese Academy of Medical Sciences & Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, China
| | - Ting Bei
- Department of Pathology, Dana-Farber/Harvard Cancer Center, Harvard Medical School; Department of Laboratory Medicine, Boston Children's Hospital, Enders Research Building, Room 814, Boston, MA, 02115, USA
| | - Wanjun Qi
- Division of Infectious Diseases, Boston Children's Hospital/Harvard Medical School, Boston, MA, 02115, USA
| | - Xuemei Xie
- Department of Pathology, Dana-Farber/Harvard Cancer Center, Harvard Medical School; Department of Laboratory Medicine, Boston Children's Hospital, Enders Research Building, Room 814, Boston, MA, 02115, USA
| | - Wenli Han
- Department of Pathology, Dana-Farber/Harvard Cancer Center, Harvard Medical School; Department of Laboratory Medicine, Boston Children's Hospital, Enders Research Building, Room 814, Boston, MA, 02115, USA
| | - Ningning Liu
- Division of Infectious Diseases, Boston Children's Hospital/Harvard Medical School, Boston, MA, 02115, USA
| | - Cunling Zhang
- Department of Pathology, Dana-Farber/Harvard Cancer Center, Harvard Medical School; Department of Laboratory Medicine, Boston Children's Hospital, Enders Research Building, Room 814, Boston, MA, 02115, USA
| | - Xiaoyu Zhang
- Department of Pathology, Dana-Farber/Harvard Cancer Center, Harvard Medical School; Department of Laboratory Medicine, Boston Children's Hospital, Enders Research Building, Room 814, Boston, MA, 02115, USA
| | - Hongbo Yu
- VA Boston Healthcare System, Department of Pathology and Laboratory Medicine, 1400 VFW Parkway West Roxbury, Boston, MA, 02132, USA
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA
| | - Li Zhao
- Department of Pathology, Dana-Farber/Harvard Cancer Center, Harvard Medical School; Department of Laboratory Medicine, Boston Children's Hospital, Enders Research Building, Room 814, Boston, MA, 02115, USA
| | - Fengxia Ma
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, CAMS Key laboratory for prevention and control of hematological disease treatment related infection, Chinese Academy of Medical Sciences & Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, China
| | - Julia R Köhler
- Division of Infectious Diseases, Boston Children's Hospital/Harvard Medical School, Boston, MA, 02115, USA
| | - Hongbo R Luo
- Department of Pathology, Dana-Farber/Harvard Cancer Center, Harvard Medical School; Department of Laboratory Medicine, Boston Children's Hospital, Enders Research Building, Room 814, Boston, MA, 02115, USA.
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Han Y, Kang L, Liu X, Zhuang Y, Chen X, Li X. Establishment and validation of a logistic regression model for prediction of septic shock severity in children. Hereditas 2021; 158:45. [PMID: 34772470 PMCID: PMC8588704 DOI: 10.1186/s41065-021-00206-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 10/14/2021] [Indexed: 11/10/2022] Open
Abstract
Background Septic shock is the most severe complication of sepsis, and is a major cause of childhood mortality, constituting a heavy public health burden. Methods We analyzed the gene expression profiles of septic shock and control samples from the Gene Expression Omnibus (GEO). Four differentially expressed genes (DEGs) from survivor and control groups, non-survivor and control groups, and survivor and non-survivor groups were selected. We used data about these genes to establish a logistic regression model for predicting the survival of septic shock patients. Results Leave-one-out cross validation and receiver operating characteristic (ROC) analysis indicated that this model had good accuracy. Differential expression and Gene Set Enrichment Analysis (GSEA) between septic shock patients stratified by prediction score indicated that the systemic lupus erythematosus pathway was activated, while the limonene and pinene degradation pathways were inactivated in the high score group. Conclusions Our study provides a novel approach for the prediction of the severity of pathology in septic shock patients, which are significant for personalized treatment as well as prognostic assessment. Supplementary Information The online version contains supplementary material available at 10.1186/s41065-021-00206-9.
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Affiliation(s)
- Yujie Han
- Department of Neonatal, Qilu Children's Hospital of Shandong University, No. 23976, Huaiyin District, Jinan City, 250022, Shandong, People's Republic of China
| | - Lili Kang
- Department of Neonatal, Qilu Children's Hospital of Shandong University, No. 23976, Huaiyin District, Jinan City, 250022, Shandong, People's Republic of China
| | - Xianghong Liu
- Department of Neonatal, Qilu Children's Hospital of Shandong University, No. 23976, Huaiyin District, Jinan City, 250022, Shandong, People's Republic of China
| | - Yuanhua Zhuang
- Department of Neonatal, Qilu Children's Hospital of Shandong University, No. 23976, Huaiyin District, Jinan City, 250022, Shandong, People's Republic of China
| | - Xiao Chen
- Department of Neonatal, Qilu Children's Hospital of Shandong University, No. 23976, Huaiyin District, Jinan City, 250022, Shandong, People's Republic of China
| | - Xiaoying Li
- Department of Neonatal, Qilu Children's Hospital of Shandong University, No. 23976, Huaiyin District, Jinan City, 250022, Shandong, People's Republic of China.
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VEGF-C and podoplanin, as biomarkers of sepsis. An experimental study. REV ROMANA MED LAB 2021. [DOI: 10.2478/rrlm-2021-0030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Abstract
Background: Sepsis is the leading cause of morbidity and mortality in intensive care units. This study explored the possible role of vascular endothelial growth factor-C (VEGF-C) and podoplanin (PDPN) in sepsis.
Methods: 22 Wistar rats were divided into three groups: two experimental (Group A and B, n=8/8) and a control (Group C, n=6). Sepsis was induced with intraperitoneal injection of ESBL (extended-spectrum beta-lactamases)-producing E-coli live bacteria for group A and with lipopolysaccharide for group B. Sterile saline solution was injected for group C. Blood samples were collected after 24 hours to determine the serum level of VEGF-C, and PDPN expression was examined in liver, kidney, and lung tissues. Bacteremia was assessed for group A.
Results: Higher serum levels of VEGF-C were found in Group A vs C (p=0.05) and group B vs. C (p=0.004), respectively.VEGF-C was also increased in animals with negative- vs. positive blood cultures from group A (p=0.04) and from group B vs. those with positive blood cultures from group A (p=0.03). High intensity of PDPN tissue expression was observed in the pulmonary alveolocytes from Group A and epithelium of the proximal renal tubules in groups B and C, compared to group A.
Conclusions: Circulating VEGF-C can be succesfuly used as a biomarker of sepsis with negative blood cultures and high risk of renal failure, whereas PDPN seems to exert a protective role against lung injuries in live bacteria-induced sepsis.
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Suh JW, Kim MJ, Kim JH. Risk factors of septic shock development and thirty-day mortality with a predictive model in adult candidemia patients in intensive care units. Infect Dis (Lond) 2021; 53:908-919. [PMID: 34330205 DOI: 10.1080/23744235.2021.1959052] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
Abstract
BACKGROUND This study aimed to investigate factors associated with septic shock development and 30-day mortality outcome with a prediction model among adult candidemia patients in the intensive care unit (ICU). METHODS A retrospective study was conducted among patients admitted to the ICU from 2009 to 2018 at a tertiary care medical centre. The study subjects included adult patients ≥ 19 years with candidemia treated with antifungal agent for ≥ 3 days. Clinical variables were collected and analysed. RESULTS A total of 126 patients were included in the study. Of these patients, 32 patients (25.4%) had septic shock. Multivariate logistic regression analysis revealed that chronic liver disease was associated with septic shock (odds ratio [OR] 3.372, 95% confidence interval [CI] 1.057 - 10.057). The rate of 30-day mortality was 35.7% and the associated mortality risk factors were malignancy (OR 8.251, 95% CI 2.227 - 30.573), chronic liver disease (OR 3.605, 95% CI 0.913 - 14.227), haemodialysis (OR 8.479, 95% CI 1.801 - 39.924), mycological failure (OR 29.675, 95% CI 7.012 - 125.578), and septic shock (OR 3.980, 95% CI 1.238 - 12.796). A predictive model for 30-day mortality was created based on the mortality risk factor scores, which had an area of 0.862 under the receiver operating characteristic curve. CONCLUSIONS Adult candidemia patients in the ICU who have chronic liver disease may be at higher risk of developing septic shock. Furthermore, our predictive model for 30-day mortality based on the mortality risk factors may be useful for clinical assessment.
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Affiliation(s)
- Jin Woong Suh
- Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Min Ja Kim
- Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Jong Hun Kim
- Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
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Bonini A, Poma N, Vivaldi F, Biagini D, Bottai D, Tavanti A, Di Francesco F. A label-free impedance biosensing assay based on CRISPR/Cas12a collateral activity for bacterial DNA detection. J Pharm Biomed Anal 2021; 204:114268. [PMID: 34298471 DOI: 10.1016/j.jpba.2021.114268] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Revised: 07/10/2021] [Accepted: 07/12/2021] [Indexed: 12/26/2022]
Abstract
The rapid and selective identification in the clinical setting of pathogenic bacteria causing healthcare associated infections (HAIs) and in particular blood stream infections (BSIs) is a major challenge, as the number of people affected worldwide and the associated mortality are on the rise. In fact, traditional laboratory techniques such culture and polymerase chain reaction (PCR)-based methodologies are often associated to long turnaround times, which justify the pressing need for the development of rapid, specific and portable point of care devices. The recently discovered clustered regularly interspaced short palindromic repeat loci (CRISPR) and the new class of programmable endonuclease enzymes called CRISPR associated proteins (Cas) have revolutionised molecular diagnostics. The use of Cas proteins in optical and electrochemical biosensing devices has significantly improved the detection of nucleic acids in clinical samples. In this study, a CRISPR/Cas12a system was coupled with electrochemical impedance spectroscopy (EIS) measurements to develop a label-free biosensing assay for the detection of Escherichia coli and Staphylococcus aureus, two bacterial species commonly associated to BSI infections. The programmable Cas12a endonuclease activity, induced by a specific guide RNA (gRNA), and the triggered collateral activity were assessed in in vitro restriction analyses, and evaluated thanks to impedance measurements using a modified gold electrode. The Cas12a/gRNA system was able to specifically recognize amplicons from different clinical isolates of E. coli and S. aureus with a limit of detection of 3 nM and a short turnaround time approximately of 1.5 h. To the best of our knowledge, this is the first biosensing device based on CRISPR/Cas12a label free impedance assay.
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Affiliation(s)
- Andrea Bonini
- Department of Chemistry and Industrial Chemistry, University of Pisa, Via G. Moruzzi 13, Pisa, Italy.
| | - Noemi Poma
- Department of Chemistry and Industrial Chemistry, University of Pisa, Via G. Moruzzi 13, Pisa, Italy.
| | - Federico Vivaldi
- Department of Chemistry and Industrial Chemistry, University of Pisa, Via G. Moruzzi 13, Pisa, Italy; Institute of Clinical Physiology, National Research Council, Via G. Moruzzi 1, Pisa, Italy.
| | - Denise Biagini
- Department of Chemistry and Industrial Chemistry, University of Pisa, Via G. Moruzzi 13, Pisa, Italy.
| | - Daria Bottai
- Department of Biology, University of Pisa, Via San Zeno 35-39, Pisa, Italy.
| | - Arianna Tavanti
- Department of Biology, University of Pisa, Via San Zeno 35-39, Pisa, Italy.
| | - Fabio Di Francesco
- Department of Chemistry and Industrial Chemistry, University of Pisa, Via G. Moruzzi 13, Pisa, Italy; INSTM, Via G. Giusti 9, Florence, Italy.
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Kim C, Lee S, Kim J. Spinal epidural abscess due to coinfection of bacteria and tuberculosis: A case report. World J Clin Cases 2021; 9:4072-4080. [PMID: 34141768 PMCID: PMC8180206 DOI: 10.12998/wjcc.v9.i16.4072] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Revised: 02/23/2021] [Accepted: 03/24/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Spinal epidural abscess (SEA) is a rare condition that mostly results from infection with either bacteria or tuberculosis. However, coinfection with bacteria and tuberculosis is extremely rare, and it results in delays in diagnosis and antimicrobial treatment causing unfavorable outcomes.
CASE SUMMARY A 75-year-old female visited the hospital with low back pain, and magnetic resonance imaging (MRI) revealed an SEA at the lumbosacral segment. Staphylococcus hominis and methicillin-resistant Staphylococcus epidermidis were identified from preoperative blood culture and intraoperative abscess culture, respectively. Thus, the patient underwent treatment with vancomycin medication for 9 wk after surgical drainage of the SEA. However, the low back pain recurred 2 wk after vancomycin treatment. MRI revealed an aggravated SEA in the same area in addition to erosive destruction of vertebral bodies. Second surgery was performed for SEA removal and spinal instrumentation. The microbiological study and pathological examination confirmed Mycobacterium tuberculosis as the pathogen concurrent with the bacterial SEA. The patient improved completely after 12 mo of antitubercular medication.
CONCLUSION We believe that the identification of a certain pathogen in SEAs does not exclude coinfection with other pathogens. Tubercular coinfection should be suspected if an SEA does not improve despite appropriate antibiotics for the identified pathogen.
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Affiliation(s)
- Choonghyo Kim
- Department of Neurosurgery, Kangwon National University School of Medicine, Chuncheon 24341, Gangwon, South Korea
- Department of Neurosurgery, Kangwon National University Hospital, Chuncheon 24289, Gangwon, South Korea
| | - Seungkoo Lee
- Department of Anatomic Pathology, Kangwon National University School of Medicine, Chuncheon 24341, Gangwon, South Korea
- Department of Anatomic Pathology, Kangwon National University Hospital, Chuncheon 24289, Gangwon, South Korea
| | - Jiha Kim
- Department of Neurosurgery, Kangwon National University School of Medicine, Chuncheon 24341, Gangwon, South Korea
- Department of Neurosurgery, Kangwon National University Hospital, Chuncheon 24289, Gangwon, South Korea
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Du Y, Zhang H, Guo Y, Song K, Zeng L, Chen Y, Xie Z, Li R. CD38 deficiency up-regulated IL-1β and MCP-1 through TLR4/ERK/NF-κB pathway in sepsis pulmonary injury. Microbes Infect 2021; 23:104845. [PMID: 34098107 DOI: 10.1016/j.micinf.2021.104845] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Revised: 05/15/2021] [Accepted: 05/17/2021] [Indexed: 01/14/2023]
Abstract
As a disease with high mortality,many cytokines and signaling pathways are associated with sepsis.The pro-inflammatory cytokines and chemokines are participating in the pathogenesis of sepsis, especially in early stage. Moreover, the releases and expressions of cytokines are regulated by numerous signaling pathways, including TLR4/ERK pathway. But despite many studies have expounded the pathogenesis of sepsis and the regulation of cytokines in sepsis, how CD38 influence the expressions of related molecules in sepsis are still unknown. The aim of this study is illuminating the alteration of cytokines and signaling pathways in CD38-/- mice injected with Escherichia coli.Compared with WT mice, E. coli infection results in more severe pulmonary injuries and higher mRNA expressions of cytokines. Compared with E. coli infected WT mice,CD38 knockout leads to aggravated pulmonary injury, increasedphosphorylated ERK1/2, p38 and NF-κB p65, and enhancedlevels of IL-1β, iNOS and MCP-1.While compared with E. coli infected CD38-/- mice, TLR4 mutation results in alleviated pulmonary injury, down-regulated phosphorylated ERK1/2 and NF-κB p65, and decreased expressions of IL-1β and MCP-1.CD38 deficiency increased the expressions of IL-1β andMCP-1and aggravated pulmonary injury through TLR4/ERK/NF-κB pathway in sepsis.
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Affiliation(s)
- Yuna Du
- Department of Clinical Laboratory and Laboratory of Infection & Immunity, Jiangxi Provincial People's Hospital&People's Hospital Affiliated to Nanchang University, Nanchang 330006, China
| | - Huiqing Zhang
- Department of Clinical Laboratory and Laboratory of Infection & Immunity, Jiangxi Provincial People's Hospital&People's Hospital Affiliated to Nanchang University, Nanchang 330006, China; Department of Medical Microbiology, School of Basic Medical Sciences, Nanchang University, Nanchang 330006, China
| | - Yujie Guo
- Department of Clinical Laboratory and Laboratory of Infection & Immunity, Jiangxi Provincial People's Hospital&People's Hospital Affiliated to Nanchang University, Nanchang 330006, China; Department of Medical Microbiology, School of Basic Medical Sciences, Nanchang University, Nanchang 330006, China
| | - Kuangyu Song
- Department of Medical Microbiology, School of Basic Medical Sciences, Nanchang University, Nanchang 330006, China
| | - Lifeng Zeng
- Department of Clinical Laboratory and Laboratory of Infection & Immunity, Jiangxi Provincial People's Hospital&People's Hospital Affiliated to Nanchang University, Nanchang 330006, China
| | - Yiguo Chen
- Department of Clinical Laboratory and Laboratory of Infection & Immunity, Jiangxi Provincial People's Hospital&People's Hospital Affiliated to Nanchang University, Nanchang 330006, China
| | - Zhengyu Xie
- Department of Clinical Laboratory and Laboratory of Infection & Immunity, Jiangxi Provincial People's Hospital&People's Hospital Affiliated to Nanchang University, Nanchang 330006, China
| | - Rong Li
- Department of Clinical Laboratory and Laboratory of Infection & Immunity, Jiangxi Provincial People's Hospital&People's Hospital Affiliated to Nanchang University, Nanchang 330006, China.
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