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Padilha MDM, Melo FTDV, Laurentino RV, da Silva ANMR, Feitosa RNM. Dysregulation in the microbiota by HBV and HCV infection induces an altered cytokine profile in the pathobiome of infection. Braz J Infect Dis 2025; 29:104468. [PMID: 39608222 PMCID: PMC11636304 DOI: 10.1016/j.bjid.2024.104468] [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: 06/06/2024] [Revised: 10/07/2024] [Accepted: 11/03/2024] [Indexed: 11/30/2024] Open
Abstract
Viral hepatitis is a public health problem, about 1 million people die due to complications of this viral disease, the etiological agents responsible for inducing cirrhosis and cellular hepatocarcinoma are HBV and HCV, both hepatotropic viruses that cause asymptomatic infection in most cases. The regulation of the microbiota performs many physiological functions, which can induce normal intestinal function and produce essential nutrients for the human body. Metabolites derived from gut microbiota or direct regulation of host immunity and metabolism have been reported to profoundly affect tumorigenesis in liver disease. If the microbiota is unbalanced, both exogenous and symbiotic microorganisms can affect a pathological process. It is well understood that the microbiota plays a role in viral diseases and infections, specifically the hepatic portal pathway has been linked to the gut-liver axis. In HBV and HCV infections, the altered bacterial representatives undergo a state of dysbiosis, with subsequent establishment of the pathobiome with overexpression of taxons such as Bacteroides, Clostridium, Lactobacillus, Enterobacter, and Enterococcus. This dysregulated microbiome induces a microenvironment conducive to the development of hepatic complications in patients with acute and chronic HBV and HCV infection, with subsequent dysregulation of cytokines IFN-α/β, TNF-α, IL-1β, TGF-β, IL-6 and IL-10, which alter the dysfunction and damage of the hepatic portal system. In view of the above, this review aimed to correlate the pathophysiological mechanisms in HBV and HCV infection, the dysregulation of the microbiome in patients infected with HBV and HCV, the most altered cytokines in the microbiome, and the most altered bacterial representatives in the pathobiome of infection.
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Affiliation(s)
- Marcos Daniel Mendes Padilha
- Universidade Federal do Pará (UFPA), Instituto de Ciências Biológicas, Laboratório de Virologia, Belém, PA, Brazil.
| | | | - Rogério Valois Laurentino
- Universidade Federal do Pará (UFPA), Instituto de Ciências da Saúde, Health Sciences, Belém, PA, Brazil
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2
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Surve D, Fish A, Debnath M, Pinjari A, Lorenzana A, Piya S, Peyton S, Kulkarni A. Sprayable inflammasome-inhibiting lipid nanorods in a polymeric scaffold for psoriasis therapy. Nat Commun 2024; 15:9035. [PMID: 39426974 PMCID: PMC11490495 DOI: 10.1038/s41467-024-53396-x] [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: 03/03/2024] [Accepted: 10/11/2024] [Indexed: 10/21/2024] Open
Abstract
Localized delivery of inflammasome inhibitors in phagocytic macrophages could be promising for psoriasis treatment. The present work demonstrates the development of non-spherical lipid nanoparticles, mimicking pathogen-like shapes, consisting of an anti-inflammatory inflammasome inhibiting lipid (pyridoxine dipalmitate) as a trojan horse. The nanorods inhibit inflammasome by 3.8- and 4.5-fold compared with nanoellipses and nanospheres, respectively. Nanorods reduce apoptosis-associated speck-like protein and lysosomal rupture, restrain calcium influx, and mitochondrial reactive oxygen species. Dual inflammasome inhibitor (NLRP3/AIM-2-IN-3) loaded nanorods cause synergistic inhibition by 21.5- and 59-folds compared with nanorods and free drug, respectively alongside caspase-1 inhibition. The NLRP3/AIM-2-IN-3 nanorod when transformed into a polymeric scaffold, simultaneously and effectively inhibits RNA levels of NLRP3, AIM2, caspase-1, chemokine ligand-2, gasdermin-D, interleukin-1β, toll-like receptor 7/ 8, and IL-17A by 6.4-, 1.6-, 2.0-, 13.0-, 4.2-, 24.4-, 4.3-, and 1.82-fold, respectively in psoriatic skin in comparison to Imiquimod positive control group in an in-vivo psoriasis-like mice model.
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Affiliation(s)
- Dhanashree Surve
- Department of Chemical Engineering, University of Massachusetts, Amherst, MA, 01003, USA
| | - Adam Fish
- Department of Chemical Engineering, University of Massachusetts, Amherst, MA, 01003, USA
| | - Maharshi Debnath
- Department of Chemical Engineering, University of Massachusetts, Amherst, MA, 01003, USA
| | - Aniruddha Pinjari
- Department of Chemical Engineering, University of Massachusetts, Amherst, MA, 01003, USA
| | - Adrian Lorenzana
- Department of Chemical Engineering, University of Massachusetts, Amherst, MA, 01003, USA
| | - Sumi Piya
- Pathology Department, University of Massachusetts-Chan Medical School, Baystate Medical Center, Springfield, MA, 01199, USA
| | - Shelly Peyton
- Department of Chemical Engineering, University of Massachusetts, Amherst, MA, 01003, USA
| | - Ashish Kulkarni
- Department of Chemical Engineering, University of Massachusetts, Amherst, MA, 01003, USA.
- Center for Bioactive Delivery, Institute for Applied Life Sciences, University of Massachusetts, Amherst, MA, 01003, USA.
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3
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Al Mamun A, Geng P, Wang S, Shao C. Role of Pyroptosis in Endometrial Cancer and Its Therapeutic Regulation. J Inflamm Res 2024; 17:7037-7056. [PMID: 39377044 PMCID: PMC11457779 DOI: 10.2147/jir.s486878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2024] [Accepted: 09/21/2024] [Indexed: 10/09/2024] Open
Abstract
Pyroptosis is an inflammatory cell death induced by inflammasomes that release several pro-inflammatory mediators such as interleukin-18 (IL-18) and interleukin-1β (IL-1β). Pyroptosis, a type of programmed cell death, has recently received increased interest both as a therapeutic and immunological mechanism. Numerous studies have provided substantial evidence supporting the involvement of inflammasomes and pyroptosis in a variety of pathological conditions including cancers, nerve damage, inflammatory diseases and metabolic conditions. Researchers have demonstrated that dysregulation of pyroptosis and inflammasomes contribute to the progression of endometriosis and gynecological malignancies. Current research also indicates that inflammasome and pyroptosis-dependent signaling pathways may further induce the progression of endometrial cancer (EC). More specifically, dysregulation of NLR family pyrin domain 3 (NLRP3) and caspase-1-dependent pyroptosis play a contributory role in the pathogenesis and development of EC. Therefore, pyroptosis-regulated protein gasdermin D (GSDMD) may be an independent prognostic biomarker for the detection of EC. This review presents the molecular mechanisms of pyroptosis-dependent signaling pathways and their contributory role and function in advancing EC. Moreover, this review offers new insights into potential future applications and innovative approaches in utilizing pyroptosis to develop effective anti-cancer therapies.
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Affiliation(s)
- Abdullah Al Mamun
- Key Laboratory of Joint Diagnosis and Treatment of Chronic Liver Disease and Liver Cancer of Lishui, The Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of China
- Molecular Pharmacology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China
| | - Peiwu Geng
- Key Laboratory of Joint Diagnosis and Treatment of Chronic Liver Disease and Liver Cancer of Lishui, The Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of China
| | - Shuanghu Wang
- Key Laboratory of Joint Diagnosis and Treatment of Chronic Liver Disease and Liver Cancer of Lishui, The Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of China
| | - Chuxiao Shao
- Key Laboratory of Joint Diagnosis and Treatment of Chronic Liver Disease and Liver Cancer of Lishui, The Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of China
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4
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Wang M, Zhu Z, Wu X, Cheong K, Li X, Yu W, Yao Y, Wu J, Cao Z. Bioactive Polysaccharides from Gracilaria lemaneiformis: Preparation, Structures, and Therapeutic Insights. Foods 2024; 13:2782. [PMID: 39272547 PMCID: PMC11395005 DOI: 10.3390/foods13172782] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 08/18/2024] [Accepted: 08/29/2024] [Indexed: 09/15/2024] Open
Abstract
Gracilaria lamaneiformis, a red seaweed, is an abundant source of bioactive polysaccharides with significant health-promoting properties. Nevertheless, the broad application of G. lamaneiformis in the nutraceutical and pharmaceutical sectors remains constrained due to the absence of comprehensive data. This review provides a detailed examination of the preparation methods, structural characteristics, and biological activities of G. lamaneiformis polysaccharides (GLPs). We explore both conventional and advanced extraction techniques, highlighting the efficiency and yield improvements achieved through methods such as microwave-, ultrasonic-, and enzyme-assisted extraction. The structural elucidation of GLPs using modern analytical techniques, including high-performance liquid chromatography, gas chromatography, and nuclear magnetic resonance spectroscopy, is discussed, providing comprehensive insights into their molecular composition and configuration. Furthermore, we critically evaluate the diverse biological activities of GLPs, including their antioxidant, anti-inflammatory, antitumor, and gut microbiota modulation properties. This review underscores the therapeutic potential of GLPs and suggests future research directions to fully harness their health benefits.
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Affiliation(s)
- Min Wang
- College of Coastal Agriculture Sciences, Guangdong Ocean University, Zhanjiang 524088, China
| | - Zhen Zhu
- College of Coastal Agriculture Sciences, Guangdong Ocean University, Zhanjiang 524088, China
| | - Xiaocheng Wu
- College of Coastal Agriculture Sciences, Guangdong Ocean University, Zhanjiang 524088, China
| | - Kitleong Cheong
- College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China
| | - Xiaohua Li
- College of Coastal Agriculture Sciences, Guangdong Ocean University, Zhanjiang 524088, China
| | - Wanli Yu
- College of Coastal Agriculture Sciences, Guangdong Ocean University, Zhanjiang 524088, China
| | - Yinlin Yao
- College of Coastal Agriculture Sciences, Guangdong Ocean University, Zhanjiang 524088, China
| | - Jiang Wu
- College of Coastal Agriculture Sciences, Guangdong Ocean University, Zhanjiang 524088, China
| | - Zhanhui Cao
- College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China
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Dahiya R, Sutariya VB, Gupta SV, Pant K, Ali H, Alhadrawi M, Kaur K, Sharma A, Rajput P, Gupta G, Almujri SS, Chinni SV. Harnessing pyroptosis for lung cancer therapy: The impact of NLRP3 inflammasome activation. Pathol Res Pract 2024; 260:155444. [PMID: 38986361 DOI: 10.1016/j.prp.2024.155444] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Revised: 06/22/2024] [Accepted: 06/28/2024] [Indexed: 07/12/2024]
Abstract
Lung cancer is still a global health challenge in terms of high incidence, morbidity, and mortality. Recent scientific studies have determined that pyroptosis, a highly inflammatory form of programmed cell death, can be identified as a potential lung cancer therapeutic target. The NLRP3 inflammasome acts as a critical mediator in this process and, upon activation, activates multiprotein complex formation as well as caspase-1 activation. This process, triggered by a release of pro-inflammatory cytokines, results in pyroptotic cell death. Also, the relationship between the NLRP3 inflammasome and lung cancer was justified by its influence on tumour growth or metastasis. The molecular pathways produce progenitive mediators and remake the tissue. Finally, targeting NLRP3 inflammasome for pyroptosis induction and inhibition of its activation appears to be a promising lung cancer treatment approach. This technique makes cancer treatment more promising and personalized. This review explores the role of NLRP3 inflammasome activation and its possibilities in lung cancer treatment.
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Affiliation(s)
- Rajiv Dahiya
- School of Pharmacy, Faculty of Medical Sciences, The University of the West Indies, St. Augustine, Trinidad & Tobago, West Indies
| | - Vijaykumar B Sutariya
- USF Health Taneja College of Pharmacy, University of South Florida, Tampa, FL 33612, USA
| | - Sheeba Varghese Gupta
- USF Health Taneja College of Pharmacy, University of South Florida, Tampa, FL 33612, USA
| | - Kumud Pant
- Graphic Era (Deemed to be University) Clement Town Dehradun, 248002, India; Graphic Era Hill University Clement Town Dehradun, 248002, India.
| | - Haider Ali
- Centre for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, India; Department of Pharmacology, Kyrgyz State Medical College, Bishkek, Kyrgyzstan
| | - Merwa Alhadrawi
- College of Technical Engineering, The Islamic University, Najaf, Iraq; College of Technical Engineering, The Islamic University of Al Diwaniyah, Al Diwaniyah, Iraq
| | - Kiranjeet Kaur
- Chandigarh Pharmacy College, Chandigarh Group of Colleges, Jhanjeri, Mohali, Punjab 140307, India
| | - Abhishek Sharma
- Department of Medicine, National Institute of Medical Sciences, NIMS University Rajasthan, Jaipur, India
| | - Pranchal Rajput
- School of Applied and Life Sciences, Division of Research and Innovation, Uttaranchal University, Dehradun, India
| | - Gaurav Gupta
- Centre for Research Impact & Outcome-Chitkara College of Pharmacy, Chitkara University, Punjab
| | - Salem Salman Almujri
- Department of Pharmacology, College of Pharmacy, King Khalid University, Abha, Asir 61421, Saudi Arabia
| | - Suresh V Chinni
- Department of Biochemistry, Faculty of Medicine, Bioscience, and Nursing, MAHSA University, Jenjarom, Selangor 42610, Malaysia
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Liu YY, Cai D, Tang XP, Cheng YX. Ganoderma lucidum-Derived Meroterpenoids Show Anti-Inflammatory Activity In Vitro. Molecules 2024; 29:1149. [PMID: 38474661 PMCID: PMC10935275 DOI: 10.3390/molecules29051149] [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: 02/05/2024] [Revised: 02/22/2024] [Accepted: 02/27/2024] [Indexed: 03/14/2024] Open
Abstract
Ganoderma lucidum, known as the "herb of spiritual potency", is used for the treatment and prevention of various diseases, but the responsible constituents for its therapeutic effects are largely unknown. For the purpose of obtaining insight into the chemical and biological profiling of meroterpenoids in G. lucidum, various chromatographic approaches were utilized for the title fungus. As a result, six undescribed meroterpenoids, chizhienes A-F (1-6), containing two pairs of enantiomers (4 and 5), were isolated. Their structures were identified using spectroscopic and computational methods. In addition, the anti-inflammatory activities of all the isolates were evaluated by Western blot analysis in LPS-induced macrophage cells (RAW264.7), showing that 1 and 3 could dose dependently inhibit iNOS but not COX-2 expression. Further, 1 and 3 were found to inhibit nitric oxide (NO) production using the Greiss reagent test. The current study will aid in enriching the structural and biological diversity of Ganoderma-derived meroterpenoids.
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Affiliation(s)
- Yun-Yun Liu
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
- Institute for Inheritance-Based Innovation of Chinese Medicine, School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China
- Marshall Laboratory of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China
| | - Dan Cai
- Institute for Inheritance-Based Innovation of Chinese Medicine, School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China
- Marshall Laboratory of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China
| | - Xin-Ping Tang
- Institute for Inheritance-Based Innovation of Chinese Medicine, School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China
- Marshall Laboratory of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China
| | - Yong-Xian Cheng
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
- Institute for Inheritance-Based Innovation of Chinese Medicine, School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China
- Marshall Laboratory of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China
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7
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Fusco A, Perfetto B, Savio V, Chiaromonte A, Torelli G, Donnarumma G, Baroni A. Regulatory Ability of Lactiplantibacillus plantarum on Human Skin Health by Counteracting In Vitro Malassezia furfur Effects. J Fungi (Basel) 2023; 9:1153. [PMID: 38132754 PMCID: PMC10744525 DOI: 10.3390/jof9121153] [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: 10/03/2023] [Revised: 11/23/2023] [Accepted: 11/28/2023] [Indexed: 12/23/2023] Open
Abstract
The skin serves as the first barrier against pathogen attacks, thanks to its multifunctional microbial community. Malassezia furfur is a commensal organism of normal cutaneous microflora but is also a cause of skin diseases. It acts on different cell pattern recognition receptors (TLRs, AhR, NLRP3 inflammasome) leading to cellular damage, barrier impairment, and inflammatory cytokines production. Lactobacillus spp. Is an endogenous inhabitant of healthy skin, and studies have proven its beneficial role in wound healing, skin inflammation, and protection against pathogen infections. The aim of our study is to demonstrate the ability of live Lactiplantibacillus plantarum to interfere with the harmful effects of the yeast on human keratinocytes (HaCat) in vitro. To enable this, the cells were treated with M. furfur, either alone or in the presence of L. plantarum. To study the inflammasome activation, cells require a stimulus triggering inflammation (LPS) before M. furfur infection, with or without L. plantarum. L. plantarum effectively counteracts all the harmful strategies of yeast, reducing the phospholipase activity, accelerating wound repair, restoring barrier integrity, reducing AhR and NLRP3 inflammasome activation, and, consequently, releasing inflammatory cytokines. Although lactobacilli have a long history of use in fermented foods, it can be speculated that they can also have health-promoting activities when topically applied.
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Affiliation(s)
- Alessandra Fusco
- Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (B.P.); (V.S.); (A.C.); (G.T.)
| | - Brunella Perfetto
- Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (B.P.); (V.S.); (A.C.); (G.T.)
| | - Vittoria Savio
- Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (B.P.); (V.S.); (A.C.); (G.T.)
| | - Adriana Chiaromonte
- Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (B.P.); (V.S.); (A.C.); (G.T.)
| | - Giovanna Torelli
- Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (B.P.); (V.S.); (A.C.); (G.T.)
| | - Giovanna Donnarumma
- Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (B.P.); (V.S.); (A.C.); (G.T.)
| | - Adone Baroni
- Department of Mental and Physical Health and Preventive Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy;
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Chen T, Du H, Zhou H, He Y, Yang J, Li C, Wei C, Yu D, Wan H. Yinhuapinggan granule ameliorates lung injury caused by multidrug-resistant Acinetobacter baumannii via inhibiting NF-κB/NLRP3 pathway. Heliyon 2023; 9:e21871. [PMID: 38027639 PMCID: PMC10661428 DOI: 10.1016/j.heliyon.2023.e21871] [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: 05/11/2023] [Revised: 09/13/2023] [Accepted: 10/30/2023] [Indexed: 12/01/2023] Open
Abstract
Yinhuapinggan granule (YHPG) is a traditional Chinese medicine prescription with rich clinical experience for the treatment of colds and coughs. The aim of this study is to investigate the protective effect of YHPG on multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) infection in vivo and its potential anti-inflammatory mechanism. BALB/c mice were intranasally inoculated with MDR A. baumannii strain to establish the pneumonia infection model, and received intraperitoneally cyclophosphamide to form immunosuppression before attack. YHPG (6, 12 and 18 g/kg) was administered by gavage once a day for 3 consecutive days after infection. The protective effect of YHPG was evaluated by lung index, spleen index, thymus index, pathological changes of lung tissue and inflammatory factors (IL-1β, IL-6 and TNF-α) in serum. The expression of key targets of NF-κB/NLRP3 signaling pathway in vivo was analyzed by immunohistochemistry, immunofluorescence, reverse transcription quantitative PCR (RT-qPCR) and Western blot. The results showed that YHPG improved the lung index and its inhibition rate, immune organ indexes and lung pathological changes in infected mice, and significantly reduced IL-1β, IL-6 and TNF-α levels in serum. In addition, YHPG significantly down-regulated the mRNA and protein expression of NF-κB p65, NLRP3, ASC, Caspase-1, TNF-α, IL-6 and IL-1β in mice lung tissue. The results of the current study demonstrated that YHPG has significant protective effects on mice infected with MDR A.baumannii, which may be related to the regulation of inflammatory factors and NF-κB/NLRP3 signaling pathway, indicating that YHPG has a wide range of clinical application value and provides a theoretical basis for its treatment of MDR A.baumannii infection.
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Affiliation(s)
- Tianhang Chen
- Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Haixia Du
- Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Huifen Zhou
- Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Yu He
- Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Jiehong Yang
- Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Chang Li
- Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Chenxing Wei
- Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China
| | - Daojun Yu
- Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China
| | - Haitong Wan
- Zhejiang Chinese Medical University, Hangzhou, 310053, China
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Umair M, Jabbar S, Zhaoxin L, Jianhao Z, Abid M, Khan KUR, Korma SA, Alghamdi MA, El-Saadony MT, Abd El-Hack ME, Cacciotti I, AbuQamar SF, El-Tarabily KA, Zhao L. Probiotic-Based Bacteriocin: Immunity Supplementation Against Viruses. An Updated Review. Front Microbiol 2022; 13:876058. [PMID: 36033850 PMCID: PMC9402254 DOI: 10.3389/fmicb.2022.876058] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 04/14/2022] [Indexed: 11/13/2022] Open
Abstract
Viral infections are a major cause of severe, fatal diseases worldwide. Recently, these infections have increased due to demanding contextual circumstances, such as environmental changes, increased migration of people and product distribution, rapid demographic changes, and outbreaks of novel viruses, including the COVID-19 outbreak. Internal variables that influence viral immunity have received attention along with these external causes to avert such novel viral outbreaks. The gastrointestinal microbiome (GIM), particularly the present probiotics, plays a vital role in the host immune system by mediating host protective immunity and acting as an immune regulator. Bacteriocins possess numerous health benefits and exhibit antagonistic activity against enteric pathogens and immunobiotics, thereby inhibiting viral infections. Moreover, disrupting the homeostasis of the GIM/host immune system negatively affects viral immunity. The interactions between bacteriocins and infectious viruses, particularly in COVID-19, through improved host immunity and physiology are complex and have not yet been studied, although several studies have proven that bacteriocins influence the outcomes of viral infections. However, the complex transmission to the affected sites and siRNA defense against nuclease digestion lead to challenging clinical trials. Additionally, bacteriocins are well known for their biofunctional properties and underlying mechanisms in the treatment of bacterial and fungal infections. However, few studies have shown the role of probiotics-derived bacteriocin against viral infections. Thus, based on the results of the previous studies, this review lays out a road map for future studies on bacteriocins for treating viral infections.
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Affiliation(s)
- Muhammad Umair
- Department of Food Science and Engineering, College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen, China
- Key Laboratory of Optoelectronic Devices and Systems, College of Physics and Optoelectronic Engineering, Ministry of Education and Guangdong Province, Shenzhen University, Shenzhen, China
| | - Saqib Jabbar
- Food Science Research Institute (FSRI), National Agricultural Research Centre (NARC), Islamabad, Pakistan
| | - Lu Zhaoxin
- College of Food Science and Technology, Nanjing Agricultural University, Nanjing, China
| | - Zhang Jianhao
- College of Food Science and Technology, Nanjing Agricultural University, Nanjing, China
| | - Muhammad Abid
- Institute of Food and Nutritional Sciences, Pir Mehr Ali Shah Arid Agriculture University, Rawalpindi, Pakistan
| | - Kashif-Ur R. Khan
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
| | - Sameh A. Korma
- Department of Food Science, Faculty of Agriculture, Zagazig University, Zagazig, Egypt
| | - Mashail A. Alghamdi
- Department of Biology, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Mohamed T. El-Saadony
- Department of Agricultural Microbiology, Faculty of Agriculture, Zagazig University, Zagazig, Egypt
| | | | - Ilaria Cacciotti
- Department of Engineering, INSTM RU, University of Rome “Niccolò Cusano”, Rome, Italy
| | - Synan F. AbuQamar
- Department of Biology, College of Science, United Arab Emirates University, Al-Ain, United Arab Emirates
| | - Khaled A. El-Tarabily
- Department of Biology, College of Science, United Arab Emirates University, Al-Ain, United Arab Emirates
- Khalifa Center for Genetic Engineering and Biotechnology, United Arab Emirates University, Al-Ain, United Arab Emirates
- Harry Butler Institute, Murdoch University, Murdoch, WA, Australia
| | - Liqing Zhao
- Department of Food Science and Engineering, College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen, China
- Key Laboratory of Optoelectronic Devices and Systems, College of Physics and Optoelectronic Engineering, Ministry of Education and Guangdong Province, Shenzhen University, Shenzhen, China
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10
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Evaluation of different bacterial honey isolates as probiotics and their efficient roles in cholesterol reduction. World J Microbiol Biotechnol 2022; 38:106. [PMID: 35507200 PMCID: PMC9068672 DOI: 10.1007/s11274-022-03259-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Accepted: 02/28/2022] [Indexed: 11/03/2022]
Abstract
Continue to hypothesize that honey is a storehouse of beneficial bacteria, and the majority of these isolates are levansucrase producers. Accordingly, ten bacterial strains were isolated from different honey sources. Four honey isolates that had the highest levansucrase production and levan yield were identified by the partial sequencing of the 16S rRNA gene as Achromobacter sp. (10A), Bacillus paralicheniformis (2M), Bacillus subtilis (9A), and Bacillus paranthracis (13M). The cytotoxicity of the selected isolates showed negative blood hemolysis. Also, they are sensitive to the tested antibiotics (Amoxicillin + Flucloxacillin, Ampicillin, Gentamicin, Benzathine benzylpenicillin, Epicephin, Vancomycin, Amikacin, and Zinol). The isolates had strong alkaline stability (pHs 9, 11) and were resistant to severe acidic conditions (29-100 percent). The tested isolates recorded complete tolerance to both H2O2 and the bile salt (0.3% Oxgall powder) after 24 h incubation. The cell-free supernatant of the examined strains had antifungal activities against C. Albicans with varying degrees. Also, isolates 2M and 13M showed strong activities against S. aureus. The isolates showed strong adhesion and auto-aggregation capacity. Isolate 10A showed the highest antioxidant activity (91.45%) followed by 2M (47.37%). The isolates recorded different catalase and protease activity. All isolates produced cholesterol oxidase and lipase with different levels. Besides, the four isolates reduced LDL (low-density lipoprotein) to different significant values. The cholesterol-reducing ability varied not only for strains but also for the time of incubation. The previous results recommended these isolates be used safely in solving the LDL problem.
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11
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Saudenova M, Promnitz J, Ohrenschall G, Himmerkus N, Böttner M, Kunke M, Bleich M, Theilig F. Behind every smile there's teeth: Cathepsin B's function in health and disease with a kidney view. BIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR CELL RESEARCH 2022; 1869:119190. [PMID: 34968578 DOI: 10.1016/j.bbamcr.2021.119190] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 12/10/2021] [Accepted: 12/13/2021] [Indexed: 06/14/2023]
Abstract
Cathepsin B (CatB) is a very abundant lysosomal protease with endo- and carboxydipeptidase activities and even ligase features. In this review, we will provide a general characterization of CatB and describe structure, structure-derived properties and location-dependent proteolytic actions. We depict CatB action within lysosome and its important roles in lysosomal biogenesis, lysosomal homeostasis and autophagy rendering this protease a key player in orchestrating lysosomal functions. Lysosomal leakage and subsequent escape of CatB into the cytosol lead to harmful actions, e.g. the role in activating the NLPR3 inflammasome, affecting immune responses and cell death. The second focus of this review addresses CatB functions in the kidney, i.e. the glomerulus, the proximal tubule and collecting duct with strong emphasis of its role in pathology of the respective segment. Finally, observations regarding CatB functions that need to be considered in cell culture will be discussed. In conclusion, CatB a physiologically important molecule may, upon aberrant expression in different cellular context, become a harmful player effectively showing its teeth behind its smile.
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Affiliation(s)
- Makhabbat Saudenova
- Institute of Anatomy, Department of Medicine, Christian-Albrechts-University Kiel, Germany
| | - Jessica Promnitz
- Institute of Anatomy, Department of Medicine, Christian-Albrechts-University Kiel, Germany
| | - Gerrit Ohrenschall
- Institute of Anatomy, Department of Medicine, Christian-Albrechts-University Kiel, Germany
| | - Nina Himmerkus
- Institute of Physiology, Department of Medicine, Christian-Albrechts-University Kiel, Germany
| | - Martina Böttner
- Institute of Anatomy, Department of Medicine, Christian-Albrechts-University Kiel, Germany
| | - Madlen Kunke
- Institute of Anatomy, Department of Medicine, Christian-Albrechts-University Kiel, Germany
| | - Markus Bleich
- Institute of Physiology, Department of Medicine, Christian-Albrechts-University Kiel, Germany
| | - Franziska Theilig
- Institute of Anatomy, Department of Medicine, Christian-Albrechts-University Kiel, Germany.
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12
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Neag MA, Mitre AO, Catinean A, Buzoianu AD. Overview of the microbiota in the gut-liver axis in viral B and C hepatitis. World J Gastroenterol 2021; 27:7446-7461. [PMID: 34887642 PMCID: PMC8613744 DOI: 10.3748/wjg.v27.i43.7446] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 08/13/2021] [Accepted: 11/03/2021] [Indexed: 02/06/2023] Open
Abstract
Viral B and C hepatitis are a major current health issue, both diseases having a chronic damaging effect on the liver and its functions. Chronic liver disease can lead to even more severe and life-threatening conditions, such as liver cirrhosis and hepatocellular carcinoma. Recent years have uncovered an important interplay between the liver and the gut microbiome: the gut-liver axis. Hepatitis B and C infections often cause alterations in the gut microbiota by lowering the levels of ‘protective’ gut microorganisms and, by doing so, hinder the microbiota ability to boost the immune response. Treatments aimed at restoring the gut microbiota balance may provide a valuable addition to current practice therapies and may help limit the chronic changes observed in the liver of hepatitis B and C patients. This review aims to summarize the current knowledge on the anato-functional axis between the gut and liver and to highlight the influence that hepatitis B and C viruses have on the microbiota balance, as well as the influence of treatments aimed at restoring the gut microbiota on infected livers and disease progression.
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Affiliation(s)
- Maria Adriana Neag
- Department of Pharmacology, Toxicology and Clinical Pharmacology, Iuliu Hatieganu University of Medicine and Pharmacy of Cluj-Napoca, Cluj-Napoca 400337, Romania
| | - Andrei Otto Mitre
- Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy of Cluj-Napoca, Cluj-Napoca 400012, Romania
| | - Adrian Catinean
- Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy of Cluj-Napoca, Cluj-Napoca 400006, Romania
| | - Anca Dana Buzoianu
- Department of Pharmacology, Toxicology and Clinical Pharmacology, Iuliu Hatieganu University of Medicine and Pharmacy of Cluj-Napoca, Cluj-Napoca 400337, Romania
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13
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McMillan HM, Kuehn MJ. The extracellular vesicle generation paradox: a bacterial point of view. EMBO J 2021; 40:e108174. [PMID: 34636061 PMCID: PMC8561641 DOI: 10.15252/embj.2021108174] [Citation(s) in RCA: 66] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 06/29/2021] [Accepted: 07/28/2021] [Indexed: 12/23/2022] Open
Abstract
All bacteria produce secreted vesicles that carry out a variety of important biological functions. These extracellular vesicles can improve adaptation and survival by relieving bacterial stress and eliminating toxic compounds, as well as by facilitating membrane remodeling and ameliorating inhospitable environments. However, vesicle production comes with a price. It is energetically costly and, in the case of colonizing pathogens, it elicits host immune responses, which reduce bacterial viability. This raises an interesting paradox regarding why bacteria produce vesicles and begs the question as to whether the benefits of producing vesicles outweigh their costs. In this review, we discuss the various advantages and disadvantages associated with Gram-negative and Gram-positive bacterial vesicle production and offer perspective on the ultimate score. We also highlight questions needed to advance the field in determining the role for vesicles in bacterial survival, interkingdom communication, and virulence.
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Affiliation(s)
- Hannah M McMillan
- Department of Molecular Genetics and MicrobiologyDuke UniversityDurhamNCUSA
| | - Meta J Kuehn
- Department of BiochemistryDuke UniversityDurhamNCUSA
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14
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Gut Microbiota, Microbial Metabolites and Human Physical Performance. Metabolites 2021; 11:metabo11110716. [PMID: 34822374 PMCID: PMC8619554 DOI: 10.3390/metabo11110716] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 10/12/2021] [Accepted: 10/16/2021] [Indexed: 01/02/2023] Open
Abstract
Trillions of microbes inhabiting the gut modulate the metabolism of the host. Cross-sectional studies have reported associations between physical performance and the gut microbiota (GM). Physical activity seems to increase GM diversity and the abundance of certain health-beneficial microbes. We reviewed the evidence from longitudinal studies on the connection between physically active lifestyle or long-term exercise interventions and the GM. We made literature searches using databases of Web of Science and PubMed Medline to collect human studies showing or not the associations between the GM and exercise. Many controversies exist in the studies. However, the longitudinal studies show that frequently, medium-intensity endurance exercise has yielded most beneficial effects on the GM, but the results vary depending on the study population and exercise protocol. In addition, the literature shows that certain microbes own the potency to increase physical activity and performance. Generally, a physically active lifestyle and exercise associate with a “healthy” GM. However, in previously sedentary subjects, the exercise-induced improvements in the GM seem to disappear unless the active lifestyle is continued. Unfortunately, several studies are not controlled for the diet. Thus, in the future, more longitudinal studies on the GM and physical performance are needed, with detailed dietary information.
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15
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Masumoto J, Zhou W, Morikawa S, Hosokawa S, Taguchi H, Yamamoto T, Kurata M, Kaneko N. Molecular biology of autoinflammatory diseases. Inflamm Regen 2021; 41:33. [PMID: 34635190 PMCID: PMC8507398 DOI: 10.1186/s41232-021-00181-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 09/09/2021] [Indexed: 12/25/2022] Open
Abstract
The long battle between humans and various physical, chemical, and biological insults that cause cell injury (e.g., products of tissue damage, metabolites, and/or infections) have led to the evolution of various adaptive responses. These responses are triggered by recognition of damage-associated molecular patterns (DAMPs) and/or pathogen-associated molecular patterns (PAMPs), usually by cells of the innate immune system. DAMPs and PAMPs are recognized by pattern recognition receptors (PRRs) expressed by innate immune cells; this recognition triggers inflammation. Autoinflammatory diseases are strongly associated with dysregulation of PRR interactomes, which include inflammasomes, NF-κB-activating signalosomes, type I interferon-inducing signalosomes, and immuno-proteasome; disruptions of regulation of these interactomes leads to inflammasomopathies, relopathies, interferonopathies, and proteasome-associated autoinflammatory syndromes, respectively. In this review, we discuss the currently accepted molecular mechanisms underlying several autoinflammatory diseases.
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Affiliation(s)
- Junya Masumoto
- Department of Pathology, Ehime University Graduate School of Medicine and Proteo-Science Center, Shitsukawa 454, Toon, Ehime, 791-0295, Japan.
| | - Wei Zhou
- Department of Pathology, Ehime University Graduate School of Medicine and Proteo-Science Center, Shitsukawa 454, Toon, Ehime, 791-0295, Japan
| | - Shinnosuke Morikawa
- Department of Pathology, Ehime University Graduate School of Medicine and Proteo-Science Center, Shitsukawa 454, Toon, Ehime, 791-0295, Japan
| | - Sho Hosokawa
- Department of Pathology, Ehime University Graduate School of Medicine and Proteo-Science Center, Shitsukawa 454, Toon, Ehime, 791-0295, Japan
| | - Haruka Taguchi
- Department of Pathology, Ehime University Graduate School of Medicine and Proteo-Science Center, Shitsukawa 454, Toon, Ehime, 791-0295, Japan
| | - Toshihiro Yamamoto
- Department of Pathology, Ehime University Graduate School of Medicine and Proteo-Science Center, Shitsukawa 454, Toon, Ehime, 791-0295, Japan
| | - Mie Kurata
- Department of Pathology, Ehime University Graduate School of Medicine and Proteo-Science Center, Shitsukawa 454, Toon, Ehime, 791-0295, Japan
| | - Naoe Kaneko
- Department of Pathology, Ehime University Graduate School of Medicine and Proteo-Science Center, Shitsukawa 454, Toon, Ehime, 791-0295, Japan
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16
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Balta I, Butucel E, Mohylyuk V, Criste A, Dezmirean DS, Stef L, Pet I, Corcionivoschi N. Novel Insights into the Role of Probiotics in Respiratory Infections, Allergies, Cancer, and Neurological Abnormalities. Diseases 2021; 9:60. [PMID: 34562967 PMCID: PMC8482260 DOI: 10.3390/diseases9030060] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 08/26/2021] [Accepted: 08/31/2021] [Indexed: 12/16/2022] Open
Abstract
In recent years, probiotics have attracted public attention and transformed the social perception of microorganisms, convening a beneficial role/state on human health. With aging, the immune system, body physiology, and intestinal microbiota tend to change unfavorably, resulting in many chronic conditions. The immune-mediated disorders can be linked to intestinal dysbiosis, consequently leading to immune dysfunctions and a cluster of conditions such as asthma, autoimmune diseases, eczema, and various allergies. Probiotic bacteria such as Lactobacillus and Bifidobacterium species are considered probiotic species that have a great immunomodulatory and anti-allergic effect. Moreover, recent scientific and clinical data illustrate that probiotics can regulate the immune system, exert anti-viral and anti-tumoral activity, and shields the host against oxidative stress. Additionally, microbiota programming by probiotic bacteria can reduce and prevent the symptoms of respiratory infections and ameliorate the neurological status in humans. This review describes the most recent clinical findings, including safe probiotic therapies aiming to medicate respiratory infections, allergies, cancer, and neurological disorders due to their physiological interconnection. Subsequently, we will describe the major biological mechanism by which probiotic bacteriotherapy expresses its anti-viral, anti-allergic, anticancer, and neuro-stimulatory effects.
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Affiliation(s)
- Igori Balta
- Bacteriology Branch, Veterinary Sciences Division, Agri-Food and Biosciences Institute, Belfast BT4 3SD, Northern Ireland, UK; (I.B.); (E.B.)
- Faculty of Animal Science and Biotechnologies, University of Agricultural Sciences and Veterinary Medicine, 400372 Cluj-Napoca, Romania; (A.C.); (D.S.D.)
- Faculty of Bioengineering of Animal Resources, Banat University of Animal Sciences and Veterinary Medicine—King Michael I of Romania, 300645 Timisoara, Romania;
| | - Eugenia Butucel
- Bacteriology Branch, Veterinary Sciences Division, Agri-Food and Biosciences Institute, Belfast BT4 3SD, Northern Ireland, UK; (I.B.); (E.B.)
- Faculty of Animal Science and Biotechnologies, University of Agricultural Sciences and Veterinary Medicine, 400372 Cluj-Napoca, Romania; (A.C.); (D.S.D.)
- Faculty of Bioengineering of Animal Resources, Banat University of Animal Sciences and Veterinary Medicine—King Michael I of Romania, 300645 Timisoara, Romania;
| | - Valentyn Mohylyuk
- School of Pharmacy, Queen’s University Belfast, Belfast BT7 1NN, Northern Ireland, UK;
| | - Adriana Criste
- Faculty of Animal Science and Biotechnologies, University of Agricultural Sciences and Veterinary Medicine, 400372 Cluj-Napoca, Romania; (A.C.); (D.S.D.)
| | - Daniel Severus Dezmirean
- Faculty of Animal Science and Biotechnologies, University of Agricultural Sciences and Veterinary Medicine, 400372 Cluj-Napoca, Romania; (A.C.); (D.S.D.)
| | - Lavinia Stef
- Faculty of Bioengineering of Animal Resources, Banat University of Animal Sciences and Veterinary Medicine—King Michael I of Romania, 300645 Timisoara, Romania;
| | - Ioan Pet
- Faculty of Bioengineering of Animal Resources, Banat University of Animal Sciences and Veterinary Medicine—King Michael I of Romania, 300645 Timisoara, Romania;
| | - Nicolae Corcionivoschi
- Bacteriology Branch, Veterinary Sciences Division, Agri-Food and Biosciences Institute, Belfast BT4 3SD, Northern Ireland, UK; (I.B.); (E.B.)
- Faculty of Bioengineering of Animal Resources, Banat University of Animal Sciences and Veterinary Medicine—King Michael I of Romania, 300645 Timisoara, Romania;
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17
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Gusev E, Sarapultsev A, Hu D, Chereshnev V. Problems of Pathogenesis and Pathogenetic Therapy of COVID-19 from the Perspective of the General Theory of Pathological Systems (General Pathological Processes). Int J Mol Sci 2021; 22:7582. [PMID: 34299201 PMCID: PMC8304657 DOI: 10.3390/ijms22147582] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 06/30/2021] [Accepted: 07/12/2021] [Indexed: 01/18/2023] Open
Abstract
The COVID-19 pandemic examines not only the state of actual health care but also the state of fundamental medicine in various countries. Pro-inflammatory processes extend far beyond the classical concepts of inflammation. They manifest themselves in a variety of ways, beginning with extreme physiology, then allostasis at low-grade inflammation, and finally the shockogenic phenomenon of "inflammatory systemic microcirculation". The pathogenetic core of critical situations, including COVID-19, is this phenomenon. Microcirculatory abnormalities, on the other hand, lie at the heart of a specific type of general pathological process known as systemic inflammation (SI). Systemic inflammatory response, cytokine release, cytokine storm, and thrombo-inflammatory syndrome are all terms that refer to different aspects of SI. As a result, the metabolic syndrome model does not adequately reflect the pathophysiology of persistent low-grade systemic inflammation (ChSLGI). Diseases associated with ChSLGI, on the other hand, are risk factors for a severe COVID-19 course. The review examines the role of hypoxia, metabolic dysfunction, scavenger receptors, and pattern-recognition receptors, as well as the processes of the hemophagocytic syndrome, in the systemic alteration and development of SI in COVID-19.
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Affiliation(s)
- Evgenii Gusev
- Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Science, 620049 Ekaterinburg, Russia; (E.G.); (V.C.)
| | - Alexey Sarapultsev
- Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Science, 620049 Ekaterinburg, Russia; (E.G.); (V.C.)
- School of Medical Biology, South Ural State University, 454080 Chelyabinsk, Russia
| | - Desheng Hu
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 200092, China;
| | - Valeriy Chereshnev
- Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Science, 620049 Ekaterinburg, Russia; (E.G.); (V.C.)
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18
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Ye C, Huang Q, Jiang J, Li G, Xu D, Zeng Z, Peng L, Peng Y, Fang R. ATP-dependent activation of NLRP3 inflammasome in primary murine macrophages infected by pseudorabies virus. Vet Microbiol 2021; 259:109130. [PMID: 34052623 DOI: 10.1016/j.vetmic.2021.109130] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Accepted: 05/23/2021] [Indexed: 12/18/2022]
Abstract
Pseudorabies virus (PRV), an alphaherpesvirus, causes respiratory and reproductive diseases in pigs and severe nervous symptom in other susceptible hosts. Previous studies showed that PRV infection induced a systemic inflammatory response in mice, indicating that pro-inflammatory cytokines participated in viral neuropathy in mice. The pro-inflammatory cytokine IL-1β is a key mediator of the inflammatory response and plays an important role in host-response to pathogens. However, the secretion of IL-1β and its relationship with inflammasome activation during PRV infection remains poorly understood. In this study, we found that PRV infection caused significant secretion of several pro-inflammatory cytokines in macrophages and promoted IL-1β secretion in an ATP-dependent manner. Furthermore, the expression of IL-1β can be induced by only PRV infection and depended on NF-κB pathway activation, while the subsequent secretion of IL-1β was mediated by ATP-induced P2 × 7R activation, loss of intracellular K+, and the subsequent NLRP3 inflammasome activation. By using a mouse infection model, we also found that ATP exacerbated clinical signs and death of mice infected by PRV in a NLRP3-dependent manner. These results indicate that ATP facilitates activation of NLRP3 inflammasome and enhances the pathogenicity of PRV in mice during its acute infection.
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Affiliation(s)
- Chao Ye
- Joint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing, 400715, China; Immunology Research Center, Medical Research Institute, Southwest University, Chongqing, 402460, China
| | - Qingyuan Huang
- Joint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing, 400715, China
| | - Jiali Jiang
- Chongqing Animal Disease Prevention and Control Center, Chongqing, 401120, China
| | - Gang Li
- Joint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing, 400715, China
| | - Dongyi Xu
- Joint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing, 400715, China
| | - Zheng Zeng
- Chongqing Animal Disease Prevention and Control Center, Chongqing, 401120, China
| | - Lianci Peng
- Joint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing, 400715, China
| | - Yuanyi Peng
- Joint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing, 400715, China
| | - Rendong Fang
- Joint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing, 400715, China; Immunology Research Center, Medical Research Institute, Southwest University, Chongqing, 402460, China.
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19
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Gedefaw L, Ullah S, Leung PHM, Cai Y, Yip SP, Huang CL. Inflammasome Activation-Induced Hypercoagulopathy: Impact on Cardiovascular Dysfunction Triggered in COVID-19 Patients. Cells 2021; 10:916. [PMID: 33923537 PMCID: PMC8073302 DOI: 10.3390/cells10040916] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 04/09/2021] [Accepted: 04/14/2021] [Indexed: 12/12/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) is the most devastating infectious disease in the 21st century with more than 2 million lives lost in less than a year. The activation of inflammasome in the host infected by SARS-CoV-2 is highly related to cytokine storm and hypercoagulopathy, which significantly contribute to the poor prognosis of COVID-19 patients. Even though many studies have shown the host defense mechanism induced by inflammasome against various viral infections, mechanistic interactions leading to downstream cellular responses and pathogenesis in COVID-19 remain unclear. The SARS-CoV-2 infection has been associated with numerous cardiovascular disorders including acute myocardial injury, myocarditis, arrhythmias, and venous thromboembolism. The inflammatory response triggered by the activation of NLRP3 inflammasome under certain cardiovascular conditions resulted in hyperinflammation or the modulation of angiotensin-converting enzyme 2 signaling pathways. Perturbations of several target cells and tissues have been described in inflammasome activation, including pneumocytes, macrophages, endothelial cells, and dendritic cells. The interplay between inflammasome activation and hypercoagulopathy in COVID-19 patients is an emerging area to be further addressed. Targeted therapeutics to suppress inflammasome activation may have a positive effect on the reduction of hyperinflammation-induced hypercoagulopathy and cardiovascular disorders occurring as COVID-19 complications.
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Affiliation(s)
| | | | | | | | - Shea-Ping Yip
- Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Kowloon, Hong Kong, China; (L.G.); (S.U.); (P.H.M.L.); (Y.C.)
| | - Chien-Ling Huang
- Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Kowloon, Hong Kong, China; (L.G.); (S.U.); (P.H.M.L.); (Y.C.)
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20
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Yang HC, Ma TH, Tjong WY, Stern A, Chiu DTY. G6PD deficiency, redox homeostasis, and viral infections: implications for SARS-CoV-2 (COVID-19). Free Radic Res 2021; 55:364-374. [PMID: 33401987 PMCID: PMC7799378 DOI: 10.1080/10715762.2020.1866757] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Revised: 12/08/2020] [Accepted: 12/10/2020] [Indexed: 02/08/2023]
Abstract
The COVID-19 pandemic has so far affected more than 45 million people and has caused over 1 million deaths worldwide. Infection with SARS-CoV-2, the pathogenic agent, which is associated with an imbalanced redox status, causes hyperinflammation and a cytokine storm, leading to cell death. Glucose-6-phosphate dehydrogenase (G6PD) deficient individuals may experience a hemolytic crisis after being exposed to oxidants or infection. Individuals with G6PD deficiency are more susceptible to coronavirus infection than individuals with normally functioning G6PD. An altered immune response to viral infections is found in individuals with G6PD deficiency. Evidence indicates that G6PD deficiency is a predisposing factor of COVID-19.
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Affiliation(s)
- Hung-Chi Yang
- Department of Medical Laboratory Science and Biotechnology, Yuanpei University of Medical Technology, Hsinchu, Taiwan
| | - Tian-Hsiang Ma
- Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan
| | - Wen-Ye Tjong
- Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan
| | - Arnold Stern
- Grossman School of Medicine, New York University, New York, NY, USA
| | - Daniel Tsun-Yee Chiu
- Research Center for Chinese Herbal Medicine, Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan
- Department of Pediatric Hematology/Oncology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
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Tomczyk M, Tomaszewska-Zaremba D, Bochenek J, Herman A, Herman AP. Anandamide Influences Interleukin-1β Synthesis and IL-1 System Gene Expressions in the Ovine Hypothalamus during Endo-Toxin-Induced Inflammation. Animals (Basel) 2021; 11:ani11020484. [PMID: 33673103 PMCID: PMC7918765 DOI: 10.3390/ani11020484] [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: 01/11/2021] [Revised: 02/09/2021] [Accepted: 02/10/2021] [Indexed: 11/16/2022] Open
Abstract
Simple Summary Pro-inflammatory cytokines are considered to be one of the most important mediators affecting the function of central nervous system during an immune/inflammatory challenge. It was found that in acting on different hypothalamic nuclei, pro-inflammatory cytokines influence the centrally regulated processes including reproduction. Recently, it has been shown that the endocannabinoid system and endogenous cannabinoids may attenuate the inflammatory response. Therefore, in our study we examined the influence of anandamide, one of the earliest known endocannabinoids, on the synthesis of interleukin (IL)-1β and IL-1 system gene expressions in the hypothalamic structures involved in gonadotropin-releasing hormone (GnRH)-ergic activity, and thus the central control of reproduction, during immune stress induced by endotoxin injection. It was found that anandamide inhibited lipopolysaccharide (LPS)-stimulated synthesis of IL-1β in the hypothalamus, likely affecting posttranscriptional levels of this cytokine synthesis. Anti-inflammatory effect of anandamide at the level of central nervous system might also result from its stimulating action on IL-1 antagonist and IL-1 type II receptor gene expression. This study suggests the potential of endocannabinoids and/or their metabolites in the inhibition of inflammatory process at the level of the central nervous system, as well as their usefulness in the therapy of inflammation-induced neuroendocrine disorders, but further detailed research is required to investigate this issue. Abstract This study evaluated the effect of anandamide (AEA) on interleukin (IL)-1β synthesis and gene expression of IL-1β, its type I (IL-1R1) and II (IL-1R2) receptors, and IL-1 receptor antagonist (IL-1RN) in the hypothalamic structures, involved in the central control of reproduction, during inflammation. Animals were intravenously (i.v.) injected with bacterial endotoxin-lipopolysaccharide (LPS) (400 ng/kg) or saline, and two hours after LPS administration., a third group received i.v. injection of AEA (10 μg/kg). Ewes were euthanized one hour later. AEA injection (p < 0.05) suppressed LPS-induced expression of IL-1β protein in the hypothalamus. The gene expression of IL-1β, IL-1RN, and IL-1R2 in the hypothalamic structures was higher (p < 0.05) in animals treated with both LPS and AEA in comparison to other experimental groups. AEA administration did not influence LPS-stimulated IL-1R1 gene expression. Our study shows that AEA suppressed IL-1β synthesis in the hypothalamus, likely affecting posttranscriptional levels of this cytokine synthesis. However, anti-inflammatory effect of AEA might also result from its stimulating action on IL-1RN and IL-1R2 gene expression. These results indicate the potential of endocannabinoids and/or their metabolites in the inhibition of inflammatory process at the level of central nervous system, and therefore their usefulness in the therapy of inflammation-induced neuroendocrine disorders.
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Affiliation(s)
- Monika Tomczyk
- Department of Genetic Engineering, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, 05-110 Jabłonna, Poland; (M.T.); (J.B.)
| | - Dorota Tomaszewska-Zaremba
- Department of Animal Physiology, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, 05-110 Jabłonna, Poland;
| | - Joanna Bochenek
- Department of Genetic Engineering, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, 05-110 Jabłonna, Poland; (M.T.); (J.B.)
| | - Anna Herman
- Faculty of Health Sciences, Warsaw School of Engineering and Health, 02-366 Warsaw, Poland;
| | - Andrzej P. Herman
- Department of Genetic Engineering, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, 05-110 Jabłonna, Poland; (M.T.); (J.B.)
- Correspondence: ; Tel.: +45-22-7653300
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Lopez-Santamarina A, Lamas A, del Carmen Mondragón A, Cardelle-Cobas A, Regal P, Rodriguez-Avila JA, Miranda JM, Franco CM, Cepeda A. Probiotic Effects against Virus Infections: New Weapons for an Old War. Foods 2021; 10:foods10010130. [PMID: 33435315 PMCID: PMC7827890 DOI: 10.3390/foods10010130] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 01/05/2021] [Accepted: 01/07/2021] [Indexed: 12/19/2022] Open
Abstract
This review aimed to gather the available literature investigating the effects of probiotics against the most common viral infections using in vitro trials in cell lines and in vivo clinical trials in both experimental animals and humans. Probiotics were employed to prevent and reduce symptoms of infections caused by common viruses, especially respiratory tract viruses, but also for viral digestive infections (such as rotavirus, coronavirus, or norovirus) and other viral infections (such as viruses that cause hepatitis, human papillomavirus, human immunodeficiency virus, and herpes simplex virus). Different probiotics have been studied to see their possible effect against the abovementioned viruses, among which different Lactobacillus species, Bifidobacterium, Clostridium, Enterococcus, and Streptococcus can be highlighted. In many cases, mixtures of various probiotic strains were used. Although the results obtained did not show similar results, in most cases, probiotic supplementation improved both barrier and biochemical immune responses, decreased susceptibility to viral infections, and enhanced the effects of concomitant vaccines. Works collected in this review show a beneficial effect of probiotics in the prevention and treatment of different viral infections. We found interesting results related to the prevention of viral infections, reduction of the duration of diseases, and decrease of symptoms.
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Affiliation(s)
- Aroa Lopez-Santamarina
- Laboratorio de Higiene Inspección y Control de Alimentos, Departamento de Química Analítica, Nutrición y Bromatología, Universidad de Santiago de Compostela, 27002 Lugo, Spain; (A.L.-S.); (A.L.); (A.d.C.M.); (A.C.-C.); (P.R.); (C.M.F.); (A.C)
| | - Alexandre Lamas
- Laboratorio de Higiene Inspección y Control de Alimentos, Departamento de Química Analítica, Nutrición y Bromatología, Universidad de Santiago de Compostela, 27002 Lugo, Spain; (A.L.-S.); (A.L.); (A.d.C.M.); (A.C.-C.); (P.R.); (C.M.F.); (A.C)
| | - Alicia del Carmen Mondragón
- Laboratorio de Higiene Inspección y Control de Alimentos, Departamento de Química Analítica, Nutrición y Bromatología, Universidad de Santiago de Compostela, 27002 Lugo, Spain; (A.L.-S.); (A.L.); (A.d.C.M.); (A.C.-C.); (P.R.); (C.M.F.); (A.C)
| | - Alejandra Cardelle-Cobas
- Laboratorio de Higiene Inspección y Control de Alimentos, Departamento de Química Analítica, Nutrición y Bromatología, Universidad de Santiago de Compostela, 27002 Lugo, Spain; (A.L.-S.); (A.L.); (A.d.C.M.); (A.C.-C.); (P.R.); (C.M.F.); (A.C)
| | - Patricia Regal
- Laboratorio de Higiene Inspección y Control de Alimentos, Departamento de Química Analítica, Nutrición y Bromatología, Universidad de Santiago de Compostela, 27002 Lugo, Spain; (A.L.-S.); (A.L.); (A.d.C.M.); (A.C.-C.); (P.R.); (C.M.F.); (A.C)
| | - José Antonio Rodriguez-Avila
- Área Académica de Química, Instituto de Ciencias Básicas e Ingeniería, Universidad Autónoma del Estado de Hidalgo, Carretera Pachuca-Tulancingo Km. 4.5, Pachuca 42076, Hidalgo, Mexico;
| | - José Manuel Miranda
- Laboratorio de Higiene Inspección y Control de Alimentos, Departamento de Química Analítica, Nutrición y Bromatología, Universidad de Santiago de Compostela, 27002 Lugo, Spain; (A.L.-S.); (A.L.); (A.d.C.M.); (A.C.-C.); (P.R.); (C.M.F.); (A.C)
- Correspondence:
| | - Carlos Manuel Franco
- Laboratorio de Higiene Inspección y Control de Alimentos, Departamento de Química Analítica, Nutrición y Bromatología, Universidad de Santiago de Compostela, 27002 Lugo, Spain; (A.L.-S.); (A.L.); (A.d.C.M.); (A.C.-C.); (P.R.); (C.M.F.); (A.C)
| | - Alberto Cepeda
- Laboratorio de Higiene Inspección y Control de Alimentos, Departamento de Química Analítica, Nutrición y Bromatología, Universidad de Santiago de Compostela, 27002 Lugo, Spain; (A.L.-S.); (A.L.); (A.d.C.M.); (A.C.-C.); (P.R.); (C.M.F.); (A.C)
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