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1
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Kang SJ, Lee KJ. Association of Proton Pump Inhibitor Use With Gastric Cancer in Regions With High Prevalence of Gastric Cancer: Systematic Review and Meta-analysis. J Neurogastroenterol Motil 2025; 31:178-185. [PMID: 40205895 PMCID: PMC11986659 DOI: 10.5056/jnm24145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Accepted: 02/05/2025] [Indexed: 04/11/2025] Open
Abstract
Background/Aims Although the association between the use of proton pump inhibitors (PPIs) and the risk of gastric cancer has been postulated in casecontrol and cohort studies, it remains still controversial. We aim to evaluate association of PPI use with gastric cancer in regions with high prevalence of gastric cancer, particularly in patients who underwent eradication of Helicobacter pylori, by systemic review and meta-analysis. Methods Comprehensive literature search through the PubMed, Embase, and Cochrane database was performed in October 2023. We used random effects model to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs) between PPI use and gastric cancer. The Cochran Q-statistic and the I2 test were employed for evaluating potential heterogeneity between studies. Results Two case-control and 6 cohort studies were identified. PPI use was significantly associated with the development of gastric cancer (OR, 2.02; 95% CI, 1.35-3.01). In subgroup analysis carried out according to the study design, sample size, and adjustment of confounding factors (age, sex, and H. pylori), such association was significant. A meta-analysis of 4 studies performed in patients with H. pylori eradication history showed that the use of PPIs was significantly associated with an elevated incidence of gastric cancer (OR, 2.10; 95% CI, 1.48-2.97). Conclusions Long-term use of PPIs is associated with an increased risk of gastric cancer in Asian regions with high prevalence of gastric cancer, particularly in subjects who have eradication history of H. pylori. Optimization of long-term PPI use seems to be necessary in regions where gastric cancer is prevalent.
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Affiliation(s)
- Seung Joo Kang
- Department of Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea
| | - Kwang Jae Lee
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Gyeonggi-do, Korea
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2
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Whitmire JM, Windham IH, Makobongo MO, Westland MD, Tran SC, Piñol J, Hui Y, Raheem Alkarkoushi R, Pich OQ, McGee DJ, Piazuelo MB, Melton-Celsa A, Testerman TL, Cover TL, Merrell DS. A unique Helicobacter pylori strain to study gastric cancer development. Microbiol Spectr 2025; 13:e0216324. [PMID: 39641575 PMCID: PMC11705839 DOI: 10.1128/spectrum.02163-24] [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: 08/28/2024] [Accepted: 10/20/2024] [Indexed: 12/07/2024] Open
Abstract
Helicobacter pylori colonizes a majority of the human population worldwide and can trigger development of a variety of gastric diseases. Since the bacterium is classified as a carcinogen, elucidation of the characteristics of H. pylori that influence gastric carcinogenesis is a high priority. To this end, the Mongolian gerbil infection model has proven to be an important tool to study gastric cancer progression. However, only a small number of H. pylori strains have been evaluated in the gerbil model. Thus, to identify additional strains able to colonize and induce disease in this model, several H. pylori strains were used to infect Mongolian gerbils, and stomachs were harvested at multiple timepoints to assess colonization and gastric pathology. The USU101 strain reproducibly colonized Mongolian gerbils and induced gastric inflammation in the majority of the animals 1 month after infection. Adenocarcinoma or dysplasia was observed in the majority of gerbils by 2 months post-infection. To define the contribution of key virulence factors to this process, isogenic strains lacking cagA or vacA, along with restorant strains containing a wild-type (WT) copy of the genes, were studied. The ΔcagA USU101 strain colonized gerbils at levels similar to WT, but did not induce comparable levels of inflammation or disease. In contrast, the ΔvacA USU101 strain did not colonize gerbils, and the stomach pathology resembled that of the mock-infected animals. The restorant USU101 strains expressed the CagA and VacA proteins in vitro, and in vivo experiments with Mongolian gerbils showed a restoration of colonization levels and inflammation scores comparable to those observed in WT USU101. Our studies indicate that the USU101 strain is a valuable tool to study H. pylori-induced disease.IMPORTANCEGastric cancer is the fifth leading cause of cancer-related death globally; the majority of gastric cancers are associated with Helicobacter pylori infection. Infection of Mongolian gerbils with H. pylori has been shown to result in induction of gastric cancer, but few H. pylori strains have been studied in this model; this limits our ability to fully understand gastric cancer pathogenesis in humans because H. pylori strains are notoriously heterogenous. Our studies reveal that USU101 represents a unique H. pylori strain that can be added to our repertoire of strains to study gastric cancer development in the Mongolian gerbil model.
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Affiliation(s)
| | - Ian H. Windham
- Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
| | - Morris O. Makobongo
- Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
- University of South Carolina School of Medicine, Columbia, South Carolina, USA
| | | | | | - Jaume Piñol
- Institut de Biotecnologia i Biomedicina, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain
- Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain
| | - Yvonne Hui
- University of South Carolina School of Medicine, Columbia, South Carolina, USA
| | | | - Oscar Q. Pich
- Institut de Biotecnologia i Biomedicina, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain
- Laboratori de Recerca en Microbiologia i Malalties Infeccioses, Hospital Universitari Parc Taulí, Institut d’Investigació i Innovació Parc Taulí (I3PT-CERCA), Universitat Autònoma de Barcelona, Sabadell, Spain
| | - David J. McGee
- Department of Microbiology and Immunology, LSU Health Sciences Center-Shreveport, Shreveport, Louisiana, USA
| | | | - Angela Melton-Celsa
- Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
| | - Traci L. Testerman
- University of South Carolina School of Medicine, Columbia, South Carolina, USA
| | - Timothy L. Cover
- Vanderbilt University, Nashville, Tennessee, USA
- Vanderbilt University Medical Center, Nashville, Tennessee, USA
- Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee, USA
| | - D. Scott Merrell
- Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
- School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, Arizona, USA
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3
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Sun M, Liu Y, Ni X, Tan R, Wang Y, Jiang Y, Ke D, Du H, Guo G, Liu K. Intranasal immunization with poly I:C and CpG ODN adjuvants enhances the protective efficacy against Helicobacter pylori infection in mice. Microbes Infect 2024:105433. [PMID: 39461584 DOI: 10.1016/j.micinf.2024.105433] [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: 05/14/2024] [Revised: 10/17/2024] [Accepted: 10/19/2024] [Indexed: 10/29/2024]
Abstract
Helicobacter pylori (H. pylori) infection is a serious public health issue, and development of vaccines is a desirable preventive strategy for H. pylori. Toll-like receptor (TLR) ligands have shown potential as vaccine adjuvants that induce immune responses, but polyinosinic-polycytidylic acid (poly I:C), a nucleic acid-based TLR9 ligand, is less well studied in H. pylori vaccine research. Here, we evaluated the effects of poly I:C and CpG oligodeoxynucleotide (CpG ODN), a nucleic acid TLR3 ligand, as adjuvants in combination with the H. pylori recombinant proteins LpoB and UreA to protect against H. pylori infection. For analysis of specific immune responses, the levels of specific antibodies and splenic cytokines were measured in the immunized mice. Compared with CpG ODN, poly I:C could induce mucosal sIgA antibody responses and reduce H. pylori colonization. Additionally, the combination of poly I:C and CpG ODN caused greater immunoprotection and significantly reduced gastritis, exerting synergistic effects. Analysis of splenic cytokines revealed that poly I:C mainly triggered a mixed Th1/Th2/Th17 immune response, whereas the combination of CpG ODN and poly I:C induced a Th1/Th17 immune response. Our findings indicated that increased levels of mucosal sIgA antibodies and a robust splenic Th1/Th17 immune response were associated with reduced H. pylori colonization in vaccinated mice. This study identified a potential TLR ligand adjuvant for developing more effective H. pylori vaccines.
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Affiliation(s)
- Min Sun
- Biopharmaceutical Research Institute, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yu Liu
- Biopharmaceutical Research Institute, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Xiumei Ni
- Biopharmaceutical Research Institute, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Runqing Tan
- Biopharmaceutical Research Institute, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yi Wang
- Biopharmaceutical Research Institute, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yajun Jiang
- Biopharmaceutical Research Institute, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Dingxin Ke
- Biopharmaceutical Research Institute, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Han Du
- Biopharmaceutical Research Institute, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Gang Guo
- Biopharmaceutical Research Institute, West China Hospital, Sichuan University, Chengdu 610041, China.
| | - Kaiyun Liu
- Biopharmaceutical Research Institute, West China Hospital, Sichuan University, Chengdu 610041, China.
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Zhong X, Zheng H, Zhao S, Wang Z, Su Y, Zhong K, Wang M, Shi Y. Effects and mechanisms of Helicobacter pylori on cancers development and immunotherapy. Front Immunol 2024; 15:1469096. [PMID: 39434880 PMCID: PMC11491387 DOI: 10.3389/fimmu.2024.1469096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Accepted: 09/23/2024] [Indexed: 10/23/2024] Open
Abstract
Tumor immunotherapy has been widely used in clinical treatment of various cancers. However, some patients of these cancers do not respond to immunotherapy effectively. And H. pylori infection has been considered to be related to the efficacy of immunotherapy. This review aims to summarize the different effects and mechanisms of H. pylori infection on immunotherapy in different kinds of cancers. We searched the relevant literature on H. pylori and tumor immunotherapy, and summarized to form a review. Generally, H. pylori infection plays a role in affecting kinds of cancers' development, besides gastric cancer. Current evidence suggests that H. pylori infection may reduce the efficacy of immunotherapy for colorectal cancer, non-small cell lung cancer and melanoma, but due to the lack of sufficient evidence, more data is needed to prove that. While for gastric cancer, the effects remain controversial. The H. pylori regulation effects and metabolisms involved in systematic related cancers should be paid attention to. Whether H. pylori should be eradicated when immunotherapy performed may be a critical consideration for some kinds of tumors.
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Affiliation(s)
- Xiaotian Zhong
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, China
- Peking University Health Science Center, Beijing, China
| | - Huiling Zheng
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Shiqing Zhao
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, China
- Peking University Health Science Center, Beijing, China
| | - Ziye Wang
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, China
- Peking University Health Science Center, Beijing, China
| | - Yi Su
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, China
- Peking University Health Science Center, Beijing, China
| | - Kaili Zhong
- Department of Lymphoma, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Mopei Wang
- Department of Tumor Chemotherapy and Radiation Sickness, Peking University Third Hospital, Beijing, China
| | - Yanyan Shi
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, China
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Wang H, Ahn JY, Noh JH, Na HK, Jung KW, Lee JH, Kim DH, Choi KD, Song HJ, Lee GH, Jung HY. Clinical outcomes of argon plasma coagulation for the treatment of gastric low-grade dysplasia. Gastrointest Endosc 2024; 100:221-230.e3. [PMID: 38272278 DOI: 10.1016/j.gie.2024.01.025] [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] [Received: 06/19/2023] [Revised: 12/18/2023] [Accepted: 01/15/2024] [Indexed: 01/27/2024]
Abstract
BACKGROUND AND AIMS Argon plasma coagulation (APC) could be considered a treatment modality for small gastric low-grade dysplasia (LGD) instead of endoscopic resection. Our study investigated the clinical outcomes of APC for treating gastric LGD and associated variables with local recurrence. METHODS This study included 911 patients who underwent APC for gastric neoplasms at the tertiary hospital from July 2007 to March 2022 with a minimal follow-up of 12 months. Of these patients, 112 without any information about Helicobacter pylori infection status, 164 who underwent APC for salvage therapy, 5 with high-grade dysplasia, and 12 with cancer were excluded. Through a retrospective review of medical data, the clinical outcomes and variables associated with the local recurrence were analyzed. RESULTS A total of 618 patients with LGD (median age, 64 years) were followed up for a median of 30 months, and local recurrence has happened in 21 (3.4%) patients. Multivariate analysis showed that lesion size (hazard ratio, 1.06; 95% confidential interval, 1.01-1.12) was associated with the local recurrence. Among 557 lesions smaller than 10 mm, local recurrence was found in 14 (2.6%) cases, and local recurrence was found in 7 (9.5%) cases of 109 tumors larger than 10 mm (P < .004). CONCLUSIONS In gastric LGD smaller than 10 mm without scars, APC is a good treatment modality in place of endoscopic resection. However, when a lesion is larger, APC should be selected carefully with close monitoring.
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Affiliation(s)
- Hoyoung Wang
- Department of Gastroenterology, Ulsan University Hospital, University of Ulsan College of Medicine, Seoul, Korea
| | - Ji Yong Ahn
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jin Hee Noh
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hee Kyoung Na
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kee Wook Jung
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jeong Hoon Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Do Hoon Kim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kee Don Choi
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ho June Song
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gin Hyug Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hwoon-Yong Jung
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Tran VH, Nguyen TMN, Le PTQ, Nguyen THT, Nguyen TCL, Ha TMT. Current status of Helicobacter pylori resistance to clarithromycin and levofloxacin in Vietnam: Results from molecular analysis of gastric biopsy specimens. J Glob Antimicrob Resist 2024; 36:76-82. [PMID: 38160708 DOI: 10.1016/j.jgar.2023.12.026] [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: 06/11/2023] [Revised: 10/13/2023] [Accepted: 12/21/2023] [Indexed: 01/03/2024] Open
Abstract
OBJECTIVES The management of Helicobacter pylori in Vietnam is becoming progressively more difficult due to increasing antibiotic resistance, particularly to clarithromycin (CLR) and levofloxaxin (LVX). In Vietnam, the selection of an H. pylori eradication regimen is predominantly based on empirical evidence. However, molecular analysis aimed at identifying H. pylori antibiotic-resistant genotypes is a promising method in antibiotic susceptibility testing. In this study, we aimed to determine the rates of genotypic H. pylori resistance to CLR and LVX by using DNA strip technology in Vietnam. METHODS We performed DNA-strip technology-based testing on 112 patients with H. pylori-positive gastroduodenal diseases to detect 23S rRNA and gyrA mutations. RESULTS Helicobacter pylori genotypic resistance to CLR and LVX was evident in 81.3% and 53.6% of the patients, respectively, and dual resistance was observed in 48.2%. The 23S rRNA A2142G and A2143G mutations accounted for 1.8% and 79.5% of cases, respectively. The gyrA N87K, D91N, D91G, and D91Y mutations were present in 37.5%, 11.6%, 5.4%, and 5.4% of patients, respectively. All four gyrA mutations were observed in both the naïve and failure patients. We further found an association between the 23S rRNA A2143G mutation and a history of CLR use as well as between the gyrA N87K mutation and a history of LVX use. CONCLUSIONS We found a very high prevalence of H. pylori resistance to CLR and LVX and dual resistance to these antibiotics in Vietnam. The application of molecular assays is feasible and may improve the management of H. pylori infection in Vietnam.
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Affiliation(s)
- Van Huy Tran
- Department of Internal Medicine, University of Medicine and Pharmacy, Hue University, Hue, Vietnam; Gastroenterology and Endoscopy Center, Hospital of University of Medicine and Pharmacy, Hue University, Hue, Vietnam
| | - Thi Mai Ngan Nguyen
- Department of Medical Genetics, University of Medicine and Pharmacy, Hue University, Hue, Vietnam
| | - Phan Tuong Quynh Le
- Department of Medical Genetics, University of Medicine and Pharmacy, Hue University, Hue, Vietnam
| | - Thi Huyen Thuong Nguyen
- Gastroenterology and Endoscopy Center, Hospital of University of Medicine and Pharmacy, Hue University, Hue, Vietnam
| | - Thi Chau Loan Nguyen
- Department of Internal Medicine, University of Medicine and Pharmacy, Hue University, Hue, Vietnam
| | - Thi Minh Thi Ha
- Department of Medical Genetics, University of Medicine and Pharmacy, Hue University, Hue, Vietnam; Institute of Biomedicine, University of Medicine and Pharmacy, Hue University, Hue, Vietnam.
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Zeidan S, Jeh Seng Chang A, Thi Nhat Truong T. Helicobacter pylori-Induced Gastroduodenal Stricture in a Child. ACG Case Rep J 2024; 11:e01227. [PMID: 38162007 PMCID: PMC10754570 DOI: 10.14309/crj.0000000000001227] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Accepted: 11/02/2023] [Indexed: 01/03/2024] Open
Abstract
Helicobacter pylori is a known cause of peptic ulcers, but it has not been reported to cause strictures in children. We present the case of a previously healthy 12-year-old boy with sudden onset of abdominal pain and vomiting, positive stool H. pylori antigen testing, and esophagogastroduodenoscopy revealing a gastroduodenal stricture causing gastric outlet obstruction. Because of medically refractory disease, he ultimately required laparoscopic truncal vagotomy with open pyloroplasty. This is an unusually severe presentation and may warrant H. pylori being on the differential of pediatric gastrointestinal strictures as well as further discussion on other long-term implications.
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Affiliation(s)
- Sofia Zeidan
- Davis School of Medicine, University of California, Sacramento, CA
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Jung MS, Piazuelo MB, Brackman LC, McClain MS, Algood HMS. Essential role of Helicobacter pylori apolipoprotein N-acyltransferase (Lnt) in stomach colonization. Infect Immun 2023; 91:e0036923. [PMID: 37937999 PMCID: PMC10715074 DOI: 10.1128/iai.00369-23] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2023] [Accepted: 10/17/2023] [Indexed: 11/09/2023] Open
Abstract
Bacterial lipoproteins are post-translationally modified with acyl chains, anchoring these proteins to bacterial membranes. In Gram-negative bacteria, three enzymes complete the modifications. Lgt (which adds two acyl chains) and LspA (which removes the signal peptide) are essential. Lnt (which adds a third acyl chain) is not essential in certain bacteria including Francisella tularensis, Neisseria gonorrhoeae, and Acinetobacter baumannii. Deleting lnt results in mild to severe physiologic changes. We previously showed lnt is not essential for Helicobacter pylori growth in vitro. Here, the physiologic consequences of deleting lnt in H. pylori and the role of Lnt in the host response to H. pylori were examined using in vitro and in vivo models. Comparing wild-type, Δlnt, and complemented mutant H. pylori, no changes in growth rates or sensitivity to acid or antibiotics were observed. Since deleting lnt changes the number of acyl chains on lipoproteins and the number of acyl chains on lipoproteins impacts the innate immune response through Toll-like receptor 2 (TLR2) signaling, primary human gastric epithelial cells were treated with a purified lipoprotein from wild-type or lnt mutant H. pylori. Differential gene expression analysis indicated that lipoprotein from the lnt mutant induced a more robust TLR2 response. In a complementary approach, we infected wild-type and Tlr2-/- mice and found that both the wild-type and complemented mutant strains successfully colonized the animals. However, the lnt mutant strain was unable to colonize either mouse strain. These results show that lnt is essential for H. pylori colonization and identifies lipoprotein synthesis as a target for therapeutic intervention.
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Affiliation(s)
- Matthew S. Jung
- Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
| | - M. Blanca Piazuelo
- Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
| | - Lee C. Brackman
- Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
| | - Mark S. McClain
- Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
- Vanderbilt Institute for Infection Immunology and Inflammation, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Holly M. Scott Algood
- Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
- Vanderbilt Institute for Infection Immunology and Inflammation, Vanderbilt University Medical Center, Nashville, Tennessee, USA
- Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
- Vanderbilt Center for Immunobiology, Vanderbilt Medical Center, Nashville, Tennessee, USA
- Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee, USA
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Liu J, Shao N, Qiu H, Zhao J, Chen C, Wan J, He Z, Zhao X, Xu L. Intestinal microbiota: A bridge between intermittent fasting and tumors. Biomed Pharmacother 2023; 167:115484. [PMID: 37708691 DOI: 10.1016/j.biopha.2023.115484] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 09/07/2023] [Accepted: 09/08/2023] [Indexed: 09/16/2023] Open
Abstract
Intestinal microbiota and their metabolites are essential for maintaining intestinal health, regulating inflammatory responses, and enhancing the body's immune function. An increasing number of studies have shown that the intestinal microbiota is tightly tied to tumorigenesis and intervention effects. Intermittent fasting (IF) is a method of cyclic dietary restriction that can improve energy metabolism, prolong lifespan, and reduce the progression of various diseases, including tumors. IF can affect the energy metabolism of tumor cells, inhibit tumor cell growth, improve the function of immune cells, and promote an anti-tumor immune response. Interestingly, recent research has further revealed that the intestinal microbiota can be impacted by IF, in particular by changes in microbial composition and metabolism. These findings suggest the complexity of the IF as a promising tumor intervention strategy, which merits further study to better understand and encourage the development of clinical tumor intervention strategies. In this review, we aimed to outline the characteristics of the intestinal microbiota and its mechanisms in different tumors. Of note, we summarized the impact of IF on intestinal microbiota and discussed its potential association with tumor suppressive effects. Finally, we proposed some key scientific issues that need to be addressed and envision relevant research prospects, which might provide a theoretical basis and be helpful for the application of IF and intestinal microbiota as new strategies for clinical interventions in the future.
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Affiliation(s)
- Jing Liu
- Special Key Laboratory of Gene Detection ＆Therapy of Guizhou Province, Zunyi Medical University, Zunyi, Guizhou 563000, China; Department of Immunology, Zunyi Medical University, Zunyi, Guizhou 563000, China
| | - Nan Shao
- Special Key Laboratory of Gene Detection ＆Therapy of Guizhou Province, Zunyi Medical University, Zunyi, Guizhou 563000, China; Department of Immunology, Zunyi Medical University, Zunyi, Guizhou 563000, China
| | - Hui Qiu
- Special Key Laboratory of Gene Detection ＆Therapy of Guizhou Province, Zunyi Medical University, Zunyi, Guizhou 563000, China; Department of Immunology, Zunyi Medical University, Zunyi, Guizhou 563000, China
| | - Juanjuan Zhao
- Special Key Laboratory of Gene Detection ＆Therapy of Guizhou Province, Zunyi Medical University, Zunyi, Guizhou 563000, China; Department of Immunology, Zunyi Medical University, Zunyi, Guizhou 563000, China
| | - Chao Chen
- Special Key Laboratory of Gene Detection ＆Therapy of Guizhou Province, Zunyi Medical University, Zunyi, Guizhou 563000, China; Department of Immunology, Zunyi Medical University, Zunyi, Guizhou 563000, China
| | - Jiajia Wan
- Special Key Laboratory of Gene Detection ＆Therapy of Guizhou Province, Zunyi Medical University, Zunyi, Guizhou 563000, China; Department of Immunology, Zunyi Medical University, Zunyi, Guizhou 563000, China
| | - Zhixu He
- Special Key Laboratory of Gene Detection ＆Therapy of Guizhou Province, Zunyi Medical University, Zunyi, Guizhou 563000, China; Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical University, Zunyi, Guizhou 563000, China
| | - Xu Zhao
- Special Key Laboratory of Gene Detection ＆Therapy of Guizhou Province, Zunyi Medical University, Zunyi, Guizhou 563000, China; Guizhou University Medical College, Guiyang 550025, Guizhou Province, China.
| | - Lin Xu
- Special Key Laboratory of Gene Detection ＆Therapy of Guizhou Province, Zunyi Medical University, Zunyi, Guizhou 563000, China; Department of Immunology, Zunyi Medical University, Zunyi, Guizhou 563000, China.
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10
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Qyi YZ, Aung HH, Aye SN, Tung WS, Naing C. Toll-like receptor 9 (-1237 T/C, -1486 T/C) and the risk of gastric cancer: a meta-analysis of genetic association studies. BMC Cancer 2023; 23:1027. [PMID: 37875868 PMCID: PMC10594725 DOI: 10.1186/s12885-023-11509-7] [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: 07/06/2023] [Accepted: 10/10/2023] [Indexed: 10/26/2023] Open
Abstract
BACKGROUND Gastric cancer has a complex aetiology including genetic factors. Individual case-control studies of toll like receptor (TLR) 9 (-1237 T/C, -1486 T/C) polymorphisms in the gastric cancer risk were available, and they showed variation in the findings. Therefore, we performed a meta-analysis to synthesize the evidence on the association between polymorphisms of TLR 9 (-1237 T/C, -1486 T/C) and the risk of gastric cancer using data from eligible studies. METHODS This study followed the PRISMA 2020 Checklist. Studies were searched in health-related databases. The methodological quality of studies was evaluated with the use of Newcastle-Ottawa Scale criteria. The summary odds ratio (OR) and its 95% confidence interval (CI) were used to determine the strength of association between each polymorphism and the risk of gastric cancer using five genetic models. Stratification was done by ethnic groups. For the robustness of the analysis, a leave-one-out meta-analysis was performed. RESULTS Eight case-control studies with 3,644 participants (1914 cases, 1730 controls) were conducted across six countries. Half of the studies were conducted in China. In the NOS methodological quality assessment, only three studies received a high-quality rating (i.e., a score of ≥ 7). TLR 9 (-1486 T/C) polymorphism and the risk of gastric cancer were assessed in six studies, four of Asian ethnicity and two of non-Asian. Under the dominant model, only in the Asian ethnic group showed a marginally and significantly increased risk of gastric cancer (overall: OR = 1.22, 95%CI = 0.90-1.67, I2 = 56%; Asian: OR = 1.24, 95%CI = 1.00-1.54, I2 = 0%, non-Asian: OR = 1.25, 95%CI = 0.38-4.09, I2 = 89%). Under the recessive model in the absence of heterogeneity, only the Asian group had a significantly higher risk of developing gastric cancer (overall: OR = 1.4, 95% CI = 0.74-2.64, I2 = 85%; Asian: OR: 1.41, 95% CI = 1.07-1.86, I2 = 0%, non-Asian: OR = 1.18, 95% CI = 0.12-11.76, I2 = 97%). Under the heterozygous model, there was no significant association with the risk of gastric cancer overall or among any ethnic subgroup. Under the homozygous model in the absence of heterogeneity, only the Asian group had a significantly higher risk of gastric cancer (overall, OR = 1.47, 95% CI = 0.76-2.86, I2 = 82%; Asian: OR = 1.54, 95% CI = 1.13-2.1, I2 = 0%; non-Asian: OR = 1.19, 95% CI = 0.1-14.33, I2 = 96%). Under the allele model, a significantly increased risk of gastric cancer was observed only in the Asian group (overall: OR = 1.23, 95% CI = 0.89-1.71, I2 = 84%; Asian: OR = 1.22, 95% CI = 1.05-1.41, I2 = 0%; non-Asian: OR = 1.24, 95% CI = 0.34-4.59, I2 = 97%). Four studies investigated the association between TLR 9 (-1237 T/C) polymorphism and the risk of developing gastric cancer. Under any of the five genetic models, there was no association between TLR 9 (-1237 T/C) and the development of gastric cancer in overall or in any ethnic subgroup. Sensitivity analysis revealed that the effect was unstable. With a small number of studies with a small number of participants, we addressed the issue of insufficient power for drawing conclusions. CONCLUSIONS The findings suggested that TLR9 (-1486 T/C) may play a role in the risk of gastric cancer specific to the Asian ethnic group. To substantiate the findings on the association between these two polymorphisms (TLR9 -1237 T/C, -1486 T/C) and the risk of gastric cancer, future well-designed case-control studies with a sufficient number of participants in multi-ethnic groups are recommended.
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Affiliation(s)
- Yap Zi Qyi
- School of Medicine, International Medical University, Kuala Lumpur, Malaysia
- School of Humanities, Social Sciences and Law, University of Dundee, Dundee, Scotland, UK
| | - Htar Htar Aung
- School of Medicine, International Medical University, Kuala Lumpur, Malaysia.
| | - Saint-Nway Aye
- School of Medicine, International Medical University, Kuala Lumpur, Malaysia
| | - Wong Siew Tung
- School of Medicine, International Medical University, Kuala Lumpur, Malaysia
| | - Cho Naing
- Faculty of Tropical Health and Medicine, James Cook University, Queensland, Australia
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11
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Costache DO, Bejan H, Poenaru M, Costache RS. Skin Cancer Correlations in Psoriatic Patients. Cancers (Basel) 2023; 15:cancers15092451. [PMID: 37173917 PMCID: PMC10177598 DOI: 10.3390/cancers15092451] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Revised: 04/20/2023] [Accepted: 04/24/2023] [Indexed: 05/15/2023] Open
Abstract
Psoriasis is a common chronic, immune-mediated, inflammatory disease with associated comorbidities. Common psoriasis-associated comorbidities include psoriatic arthritis, cardiovascular disease, metabolic syndrome, inflammatory digestive syndromes, and depression. A less studied association is between psoriasis and specific-site cancers. A key cell in the pathophysiology of psoriasis is the myeloid dendritic cell, which links the innate and adaptive immune systems, and therefore is involved in the control of cancer-prevention mechanisms. The relationship between cancer and inflammation is not new, with inflammation being recognized as a key element in the development of neoplastic foci. Infection leads to the development of local chronic inflammation, which further leads to the accumulation of inflammatory cells. Various phagocytes produce reactive oxygen species that cause mutations in cellular DNA and lead to the perpetuation of cells with altered genomes. Therefore, in inflammatory sites, there will be a multiplication of cells with damaged DNA, leading to tumor cells. Over the years, scientists have tried to assess the extent to which psoriasis can increase the risk of developing skin cancer. Our aim is to review the available data and present some information that might help both the patients and the care providers in properly managing psoriatic patients to prevent skin cancer development.
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Affiliation(s)
- Daniel Octavian Costache
- II Dermatology Discipline, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Horia Bejan
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Marcela Poenaru
- Dermatology Department, Carol Davila University Central Emergency Military Hospital, 010825 Bucharest, Romania
| | - Raluca Simona Costache
- Internal Medicine and Gastroenterology Discipline, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
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12
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Xiao S, Zhang L, Wang X, Li W, Wang X. The signal conversion strategy using the lytic transglycosylase Cag4-double nanoporous gold co-catalysis for the rapid screening of drugs against Helicobacter pylori infection. Biosens Bioelectron 2023; 233:115345. [PMID: 37116248 DOI: 10.1016/j.bios.2023.115345] [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: 02/10/2023] [Revised: 04/03/2023] [Accepted: 04/21/2023] [Indexed: 04/30/2023]
Abstract
The cag pathogenicity island (cagPAI) is the main virulence factor of gastric carcinoma induced by Helicobacter pylori (H. pylori). The lytic transglycosylase Cag4 is an important component that assists in the translocation of the bacterial oncoprotein CagA and maintains the peptidoglycan cycle. The allosteric regulation of Cag4 has been preliminarily demonstrated to inhibit H. pylori infection. Unfortunately, a rapid screening technology for allosteric regulators of Cag4 has not been established. In this study, a novel Cag4-double nanoporous gold (NPG) biosensor based on enzyme-inorganic co-catalysis was constructed using the heterologously expressed H. pylori 26695 Cag4 as the biological recognition element for screening Cag4 allosteric regulators. The results showed that chitosan or carboxymethyl chitosan was a mixed Cag4 inhibitor combining non-competition with uncompetition. The inhibition constants were Ki' Chitosan = 0.88909 mg/mL and Ki' Carboxymethyl chitosan = 1.13480 mg/mL, respectively. Surprisingly, D-(+)-cellobiose showed the activation effect of Cag4 on E. coli MG1655 cell wall lysis by decreasing the Ka value by 29.7% and increasing the Vmax value by 71.3%. In addition, molecular docking revealed the importance of the polarity of the C2 substituent group with glucose as the main structure in the Cag4 allosteric regulator. This study provides a fast and useful platform for screening potential new drugs based on the Cag4 allosteric regulator.
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Affiliation(s)
- Sa Xiao
- State Key Laboratory of Microbial Technology, Shandong University, Qingdao, 266237, PR China
| | - Lei Zhang
- State Key Laboratory of Microbial Technology, Shandong University, Qingdao, 266237, PR China
| | - Xiaolei Wang
- State Key Laboratory of Microbial Technology, Shandong University, Qingdao, 266237, PR China
| | - Wenjuan Li
- Key Laboratory for Experimental Teratology of Chinese Ministry of Education, The Shandong Provincial Key Laboratory of Infection and Immunology, Department of Microbiology, School of Basic Medical Sciences, Shandong University, Jinan, 250012, PR China.
| | - Xia Wang
- State Key Laboratory of Microbial Technology, Shandong University, Qingdao, 266237, PR China.
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Shrestha AB, Pokharel P, Sapkota UH, Shrestha S, Mohamed SA, Khanal S, Jha SK, Mohanty A, Padhi BK, Asija A, Sedhai YR, Rijal R, Singh K, Chattu VK, Rodriguez-Morales AJ, Barboza JJ, Sah R. Drug Resistance Patterns of Commonly Used Antibiotics for the Treatment of Helicobacter pylori Infection among South Asian Countries: A Systematic Review and Meta-Analysis. Trop Med Infect Dis 2023; 8:tropicalmed8030172. [PMID: 36977173 PMCID: PMC10051479 DOI: 10.3390/tropicalmed8030172] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 02/17/2023] [Accepted: 02/24/2023] [Indexed: 03/18/2023] Open
Abstract
Background: In South Asia, resistance to commonly used antibiotics for the treatment of Helicobacter pylori infection is increasing. Despite this, accurate estimates of overall antibiotic resistance are missing. Thus, this review aims to analyze the resistance rates of commonly used antibiotics for the treatment of H. pylori in South Asia. Methods: The systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. We searched five medical databases for relevant studies from inception to September 2022. A random effect model with a 95% confidence interval (CI) was used to calculate the pooled prevalence of antibiotic resistance. Results: This systematic review and meta-analysis included 23 articles, 6357 patients, 3294 Helicobacter pylori isolates, and 2192 samples for antibiotic resistance. The prevalences of antibiotic resistance to common antibiotics were clarithromycin: 27% (95%CI: 0.17–0.38), metronidazole: 69% (95%CI: 0.62–0.76), tetracycline: 16% (95%CI: 0.06–0.25), amoxicillin: 23% (95%CI: 0.15–0.30), ciprofloxacin: 12% (95%CI: 0.04–0.23), levofloxacin: 34% (95%CI: 0.22–0.47), and furazolidone: 14% (95%CI: 0.06–0.22). Subgroup analysis showed antibiotic resistances were more prevalent in Pakistan, India, and Bangladesh. Furthermore, a ten-year trend analysis showed the increasing resistance prevalence for clarithromycin (21% to 30%), ciprofloxacin (3% to 16%), and tetracycline (5% to 20%) from 2003 to 2022. Conclusion: This meta-analysis showed a high prevalence of resistance among the commonly used antibiotics for H. pylori in South Asian countries. Furthermore, antibiotic resistance has been increasing over the time of 20 years. In order to tackle this situation, a robust surveillance system, and strict adherence to antibiotic stewardship are required.
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Affiliation(s)
| | - Pashupati Pokharel
- Department of Medicine, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Kathmandu 1524, Nepal
| | | | - Sajina Shrestha
- Department of Internal Medicine, KIST Medical College, Imadol, Patan 284128, Nepal
| | - Shueb A. Mohamed
- School of Medicine, Alexandria University, Alexandria 21568, Egypt
| | - Surakshya Khanal
- Department of Medicine, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Kathmandu 1524, Nepal
| | - Saroj Kumar Jha
- Department of Medicine, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Kathmandu 1524, Nepal
| | - Aroop Mohanty
- Department of Microbiology, All India Institute of Medical Sciences, Gorakhpur 273008, India
| | - Bijaya Kumar Padhi
- Department of Community Medicine and School of Public Health, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Ankush Asija
- School of Medicine, West Virginia University, Morgantown, WV 26506, USA
| | - Yub Raj Sedhai
- Division of Pulmonary Disease and Critical Care Medicine, University of Kentucky College of Medicine, Bowling Green, KY 42101, USA
| | - Rishikesh Rijal
- Division of infectious Diseases, University of Louisville, Louisville, KY 40208, USA
| | - Karan Singh
- Division of Pulmonary Disease and Critical Care Medicine, University of Kentucky College of Medicine, Bowling Green, KY 42101, USA
| | - Vijay Kumar Chattu
- Department of Occupational Science and Occupational Therapy, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5R 0A3, Canada
- Center for Transdisciplinary Research, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai 600077, India
- Department of Community Medicine, Faculty of Medicine, Datta Meghe Institute of Medical Sciences, Wardha 442107, India
| | - Alfonso J. Rodriguez-Morales
- Grupo de Investigación Biomedicina, Faculty of Medicine, Fundación Universitaria Autónoma de las Américas, Pereira 660003, Colombia
- Master’s Program in Clinical Epidemiology and Biostatistics, Universidad Cientifica del Sur, Lima 15846, Peru
- Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Beirut 1101, Lebanon
| | - Joshuan J. Barboza
- Escuela de Medicina, Universidad Cesar Vallejo, Trujillo 13007, Peru
- Correspondence: (J.J.B.); (R.S.)
| | - Ranjit Sah
- Department of Medicine, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Kathmandu 1524, Nepal
- Department of Microbiology, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth, Pune 411018, India
- Department of Public Health Dentistry, Dr. D.Y. Patil Dental College and Hospital, Dr. D.Y. Patil Vidyapeeth, Pune 411018, India
- Correspondence: (J.J.B.); (R.S.)
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Pathways Affected by Falcarinol-Type Polyacetylenes and Implications for Their Anti-Inflammatory Function and Potential in Cancer Chemoprevention. Foods 2023; 12:foods12061192. [PMID: 36981118 PMCID: PMC10048309 DOI: 10.3390/foods12061192] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 03/05/2023] [Accepted: 03/08/2023] [Indexed: 03/14/2023] Open
Abstract
Polyacetylene phytochemicals are emerging as potentially responsible for the chemoprotective effects of consuming apiaceous vegetables. There is some evidence suggesting that polyacetylenes (PAs) impact carcinogenesis by influencing a wide variety of signalling pathways, which are important in regulating inflammation, apoptosis, cell cycle regulation, etc. Studies have shown a correlation between human dietary intake of PA-rich vegetables with a reduced risk of inflammation and cancer. PA supplementation can influence cell growth, gene expression and immunological responses, and has been shown to reduce the tumour number in rat and mouse models. Cancer chemoprevention by dietary PAs involves several mechanisms, including effects on inflammatory cytokines, the NF-κB pathway, antioxidant response elements, unfolded protein response (UPR) pathway, growth factor signalling, cell cycle progression and apoptosis. This review summarises the published research on falcarinol-type PA compounds and their mechanisms of action regarding cancer chemoprevention and also identifies some gaps in our current understanding of the health benefits of these PAs.
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15
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Helicobacter pylori and Gastric Cancer: Pathogenetic Mechanisms. Int J Mol Sci 2023; 24:ijms24032895. [PMID: 36769214 PMCID: PMC9917787 DOI: 10.3390/ijms24032895] [Citation(s) in RCA: 95] [Impact Index Per Article: 47.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 01/27/2023] [Accepted: 01/31/2023] [Indexed: 02/05/2023] Open
Abstract
Gastric cancer is the sixth most commonly diagnosed cancer and the fourth leading cause of cancer death worldwide. Helicobacter pylori (H. pylori) is one of the main risk factors for this type of neoplasia. Carcinogenetic mechanisms associated with H. pylori are based, on the one hand, on the onset of chronic inflammation and, on the other hand, on bacterial-specific virulence factors that can damage the DNA of gastric epithelial cells and promote genomic instability. Here, we review and discuss the major pathogenetic mechanisms by which H. pylori infection contributes to the onset and development of gastric cancer.
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16
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Anang V, Singh A, Kottarath SK, Verma C. Receptors of immune cells mediates recognition for tumors. PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE 2023; 194:219-267. [PMID: 36631194 DOI: 10.1016/bs.pmbts.2022.09.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Over the last few decades, the immune system has been steered toward eradication of cancer cells with the help of cancer immunotherapy. T cells, B cells, monocytes/macrophages, dendritic cells, T-reg cells, and natural killer (NK) cells are some of the numerous immune cell types that play a significant part in cancer cell detection and reduction of inflammation, and the antitumor response. Briefly stated, chimeric antigen receptors, adoptive transfer and immune checkpoint modulators are currently the subjects of research focus for successful immunotherapy-based treatments for a variety of cancers. This chapter discusses ongoing investigations on the mechanisms and recent developments by which receptors of immune cells especially that of lymphocytes and monocytes/macrophages regulate the detection of immune system leading to malignancies. We will also be looking into the treatment strategies based on these mechanisms.
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Affiliation(s)
- Vandana Anang
- International Center for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India
| | | | - Sarat Kumar Kottarath
- Department of Experimental Therapeutics, MD Anderson Cancer Center, Huston, TX, United States.
| | - Chaitenya Verma
- Department of Pathology, Wexner Medical Center, Ohio State University, Columbus, OH, United States.
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Shimamura M, Kamijo SI, Illarionov P. C-type lectin Mincle-dependent and -independent activation of invariant NKT cells by exposure to Helicobacter pylori α-cholesteryl glucosides. FEBS J 2023; 290:134-147. [PMID: 35920835 DOI: 10.1111/febs.16588] [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: 02/23/2022] [Revised: 07/01/2022] [Accepted: 08/03/2022] [Indexed: 01/14/2023]
Abstract
Helicobacter pylori extracts cholesterol from the host and converts it to its glycosides. We found that cholesteryl 6'-O-acyl α-glucoside (ChAcαG) produced by H. pylori is recognised by both invariant Vα14+ NKT (iNKT) cells and a C-type lectin receptor Mincle (Clec4e). However, it is unclear how these duplicated recognitions cooperate and contribute to host defence against H. pylori. Among T cell populations in the liver, iNKT cells predominantly expressed the T cell activation marker CD69 just after stimulation with ChAcαG. The production of IFN-γ and IL-4 was strictly dependent on both CD1d and Jα18 expressions, indicating the necessity of iNKT cell activation for the initiation of immune responses. Production of IFN-γ by iNKT cells was markedly reduced by the Mincle deficiency on antigen-presenting cells (APCs), while IL-4 production was not significantly influenced. IL-2 production by iNKT cell hybridomas was also diminished by the Mincle deficiency upon stimulation with APCs previously loaded with ChAcαG. Here, the immune responses of iNKT cell hybridomas stimulated with wild-type APCs were reduced by the addition of anti-IL-12 blocking antibody to the level stimulated with Mincle-deficient APCs. Collectively, these results suggest that iNKT cells can be activated with the cholesteryl glycosides via a Mincle-dependent, IL-12 signal-dependent pathway and a Mincle-independent, invariant TCR signal-dominant pathway. iNKT cells activated via the Mincle-dependent pathway produce IFN-γ-dominant cytokines; hence, they may contribute to enhancing proinflammatory responses against H. pylori infection.
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Affiliation(s)
- Michio Shimamura
- Tsukuba Research Center for Interdisciplinary Materials Science, University of Tsukuba, Japan.,Mitsubishi Kagaku Institute of Life Sciences, Tokyo, Japan.,School of Science and Technology, Meiji University, Kawasaki, Japan
| | - Shin-Ichi Kamijo
- Mitsubishi Kagaku Institute of Life Sciences, Tokyo, Japan.,LifeWill Corporation, Tokyo, Japan
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Ndlovu KS, Moloto MJ, Sekhosana KE, Nkambule TTI, Managa M. Porphyrins developed for photoinactivation of microbes in wastewater. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2023; 30:11210-11225. [PMID: 36515881 DOI: 10.1007/s11356-022-24644-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Accepted: 12/04/2022] [Indexed: 06/17/2023]
Abstract
Photodynamic antimicrobial chemotherapy (PACT) is extensively studied as a strategic method to inactivate pathogenic microbes in wastewater for addressing the limitations associated with chlorination, ozonation, and ultraviolet irradiation as disinfection methods, which generally promote the development of resistant genes and harmful by-products such as trihalomethanes. PACT is dependent on photons, oxygen, and a photosensitizer to induce cytotoxic effects on various microbes by generating reactive oxygen species. Photosensitizers such as porphyrins have demonstrated significant microbial inactivation through PACT, hence now explored for wastewater phototreatment. This review aims to evaluate the efficacy of porphyrins and porphyrin-conjugates as photosensitizers for wastewater photoinactivation. Concerns relating to the application of photosensitizers in water treatment are also evaluated. This includes recovery and reuse of the photosensitizer when immobilized on solid supports.
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Affiliation(s)
- Knowledge Siyabonga Ndlovu
- Institute for Nanotechnology and Water Sustainability (iNanoWS), Florida Campus, College of Science, Engineering and Technology, University of South Africa, Johannesburg, 1710, South Africa
| | - Makwena Justice Moloto
- Institute for Nanotechnology and Water Sustainability (iNanoWS), Florida Campus, College of Science, Engineering and Technology, University of South Africa, Johannesburg, 1710, South Africa
| | - Kutloano Edward Sekhosana
- Institute for Nanotechnology and Water Sustainability (iNanoWS), Florida Campus, College of Science, Engineering and Technology, University of South Africa, Johannesburg, 1710, South Africa
| | - Thabo Thokozani Innocent Nkambule
- Institute for Nanotechnology and Water Sustainability (iNanoWS), Florida Campus, College of Science, Engineering and Technology, University of South Africa, Johannesburg, 1710, South Africa
| | - Muthumuni Managa
- Institute for Nanotechnology and Water Sustainability (iNanoWS), Florida Campus, College of Science, Engineering and Technology, University of South Africa, Johannesburg, 1710, South Africa.
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Abstract
BACKGROUND Metformin has good anti-hyperglycemic effectiveness, but does not induce hypoglycemia，is very safe, and has become the preferred drug for the treatment of type 2 diabetes. Recently, the other effects of metformin, such as being anti-inflammatory and delaying aging, have also attracted increased attention. METHODS AND RESULTS The relevant literatures on pubmed and other websites for reading, classification and sorting, and did not involve any animal experiments. CONCLUSION Metformin has anti-inflammatory effects through multiple routes, which provides potential therapeutic targets for certain inflammatory diseases, such as neuroinflammation and rheumatoid arthritis. In addition, inflammation is a key component of tumor occurrence and development ; thus, targeted inflammatory intervention is a significant benefit for both cancer prevention and treatment. Therefore, metformin may have further potential for inflammation-related disease prevention and treatmen. However, the inflammatory mechanism is complex; various molecules are connected and influence each other. For example, metformin significantly inhibits p65 nuclear translocation, but pretreatment with compound C, an AMPK inhibitor, abolishes this effect, and silencing of HMGB1 inhibits NF-κB activation . SIRT1 deacetylates FoxO, increasing its transcriptional activity . mTOR in dendritic cells regulates FoxO1 via AKT. The interactions among various molecules should be further explored to clarify their specific mechanisms and provide more direction for the treatment of inflammatory diseases, as well as cancer.
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Yousuf S, Liu H, Yingshu Z, Zahid D, Ghayas H, Li M, Ding Y, Li W. Ginsenoside Rg1 modulates intestinal microbiota and supports re-generation of immune cells in dexamethasone-treated mice. Acta Microbiol Immunol Hung 2022; 69:259-269. [PMID: 36342667 DOI: 10.1556/030.2022.01881] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2022] [Accepted: 10/17/2022] [Indexed: 11/13/2022]
Abstract
Ginsenoside Rg1 is one of the major ginsenosides found in roots of Panax ginseng and Panax notoginseng. Ginsenoside Rg1 is known to possess various biological activities including immunity enhancement activity. However, it is not clear whether the regulation of immune function by Rg1 is related to the intestinal microbiota. In the present study, the immuno-modulatory and gut microbiota-reshaping effects of ginsenoside Rg1 were evaluated. Ginsenoside Rg1 acts as an immune-enhancing agent to increase spleen index and the number of T, B and dendritic cells in dexamethasone (Dex)-treated mice. Ginsenoside Rg1 also increased the production of sIgA and regulated the expression of interleukin 2 (IL-2), IL-4, IL-10 and IFN-γ. Meanwhile, Rg1 administration regulated the structure of intestinal microbiota. The relative abundance of mouse intestinal microbial groups, such as Alistipes, Ruminococcaceae, Lachnospiraceae, and Roseburia were increased by Rg1 administration, whereas a decrease in the potential pathogens like Helicobacteraceae, Dubosiella, Mycoplasma, Alloprevotella, Allobaculum was observed. Moreover, Rg1 metabolites of Lachnospiraceae bacterium enhanced the proliferation of CD4+ T cells and T regulatory (Treg) cells. Ginsenoside Rg1 improved the inflammatory condition of the colonic tissue and repaired the destructed mucosal barrier. This study suggested that Rg1 strengthens immunity with regulating the homeostasis of intestinal microbiota in mice.
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Affiliation(s)
- Sabiha Yousuf
- College of Basic Medical Sciences, Dalian Medical University, 9-Western Section, Lvshun South Road, Dalian, Liaoning, 116044, China
| | - He Liu
- College of Basic Medical Sciences, Dalian Medical University, 9-Western Section, Lvshun South Road, Dalian, Liaoning, 116044, China
| | - Zhang Yingshu
- College of Basic Medical Sciences, Dalian Medical University, 9-Western Section, Lvshun South Road, Dalian, Liaoning, 116044, China
| | - Danish Zahid
- College of Basic Medical Sciences, Dalian Medical University, 9-Western Section, Lvshun South Road, Dalian, Liaoning, 116044, China
| | - Hassan Ghayas
- Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning, 116044, China
| | - Ming Li
- College of Basic Medical Sciences, Dalian Medical University, 9-Western Section, Lvshun South Road, Dalian, Liaoning, 116044, China
| | - Yan Ding
- School of Food Science and Technology, Dalian Polytechnic University, Dalian, Liaoning, 116034, China
| | - Wenzhe Li
- Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, Guangdong, 515041, China
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Prichard A, Khuu L, Whitmore LC, Irimia D, Allen LAH. Helicobacter pylori-infected human neutrophils exhibit impaired chemotaxis and a uropod retraction defect. Front Immunol 2022; 13:1038349. [PMID: 36341418 PMCID: PMC9630475 DOI: 10.3389/fimmu.2022.1038349] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Accepted: 10/05/2022] [Indexed: 11/17/2022] Open
Abstract
Helicobacter pylori is a major human pathogen that colonizes the gastric mucosa and plays a causative role in development of peptic ulcers and gastric cancer. Neutrophils are heavily infected with this organism in vivo and play a prominent role in tissue destruction and disease. Recently, we demonstrated that H. pylori exploits neutrophil plasticity as part of its virulence strategy eliciting N1-like subtype differentiation that is notable for profound nuclear hypersegmentation. We undertook this study to test the hypothesis that hypersegmentation may enhance neutrophil migratory capacity. However, EZ-TAXIScan™ video imaging revealed a previously unappreciated and progressive chemotaxis defect that was apparent prior to hypersegmentation onset. Cell speed and directionality were significantly impaired to fMLF as well as C5a and IL-8. Infected cells oriented normally in chemotactic gradients, but speed and direction were impaired because of a uropod retraction defect that led to cell elongation, nuclear lobe trapping in the contracted rear and progressive narrowing of the leading edge. In contrast, chemotactic receptor abundance, adhesion, phagocytosis and other aspects of cell function were unchanged. At the molecular level, H. pylori phenocopied the effects of Blebbistatin as indicated by aberrant accumulation of F-actin and actin spikes at the uropod together with enhanced ROCKII-mediated phosphorylation of myosin IIA regulatory light chains at S19. At the same time, RhoA and ROCKII disappeared from the cell rear and accumulated at the leading edge whereas myosin IIA was enriched at both cell poles. These data suggest that H. pylori inhibits the dynamic changes in myosin IIA contractility and front-to-back polarity that are essential for chemotaxis. Taken together, our data advance understanding of PMN plasticity and H. pylori pathogenesis.
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Affiliation(s)
- Allan Prichard
- Department of Microbiology and Immunology, University of Iowa, Iowa City, IA, United States
- Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO, United States
| | - Lisa Khuu
- Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO, United States
| | - Laura C. Whitmore
- Department of Medicine, Division of Infectious Diseases, University of Iowa, Iowa City, IA, United States
| | - Daniel Irimia
- Department of Surgery, BioMEMS Resource Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - Lee-Ann H. Allen
- Department of Microbiology and Immunology, University of Iowa, Iowa City, IA, United States
- Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO, United States
- Department of Medicine, Division of Infectious Diseases, University of Iowa, Iowa City, IA, United States
- Iowa City VA Healthcare System, Iowa City, IA, United States
- Harry S. Truman Memorial VA Hospital, Columbia, MO, United States
- *Correspondence: Lee-Ann H. Allen,
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22
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Mun SJ, Cho E, Kim JS, Yang CS. Pathogen-derived peptides in drug targeting and its therapeutic approach. J Control Release 2022; 350:716-733. [PMID: 36030988 DOI: 10.1016/j.jconrel.2022.08.041] [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: 07/13/2022] [Revised: 08/18/2022] [Accepted: 08/21/2022] [Indexed: 02/06/2023]
Abstract
Peptides, short stretches of amino acids or small proteins that occupy a strategic position between proteins and amino acids, are readily accessible by chemical and biological methods. With ideal properties for forming high-affinity and specific interactions with host target proteins, they have established an important niche in the drug development spectrum complementing small molecule and biological therapeutics. Among the most successful biomedicines in use today, peptide-based drugs show great promise. This, coupled with recent advances in synthetic and nanochemical biology, has led to the creation of tailor-made peptide therapeutics for improved biocompatibility. This review presents an overview of the latest research on pathogen-derived, host-cell-interacting peptides. It also highlights strategies for using peptide-based therapeutics that address cellular transport challenges through the introduction of nanoparticles that serve as platforms to facilitate the delivery of peptide biologics and therapeutics for treating various inflammatory diseases. Finally, this paper describes future perspectives, specific pathogen-based peptides that can enhance specificity, efficiency, and capacity in functional peptide-based therapeutics, which are in the spotlight as new treatment alternatives for various diseases, and also presents verified sequences and targets that can increase chemical and pharmacological value.
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Affiliation(s)
- Seok-Jun Mun
- Department of Bionano Technology, Hanyang University, Seoul 04673, Republic of Korea; Center for Bionano Intelligence Education and Research, Ansan 15588, Republic of Korea
| | - Euni Cho
- Department of Bionano Technology, Hanyang University, Seoul 04673, Republic of Korea; Center for Bionano Intelligence Education and Research, Ansan 15588, Republic of Korea
| | - Jae-Sung Kim
- Department of Bionano Technology, Hanyang University, Seoul 04673, Republic of Korea; Institute of Natural Science & Technology, Hanyang University, Ansan 15588, Republic of Korea
| | - Chul-Su Yang
- Center for Bionano Intelligence Education and Research, Ansan 15588, Republic of Korea; Department of Molecular and Life Science, Hanyang University, Ansan 15588, Republic of Korea.
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Zhang G, Wang J, Zhao Z, Xin T, Fan X, Shen Q, Raheem A, Lee CR, Jiang H, Ding J. Regulated necrosis, a proinflammatory cell death, potentially counteracts pathogenic infections. Cell Death Dis 2022; 13:637. [PMID: 35869043 PMCID: PMC9307826 DOI: 10.1038/s41419-022-05066-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 06/29/2022] [Accepted: 07/04/2022] [Indexed: 02/07/2023]
Abstract
Since the discovery of cell apoptosis, other gene-regulated cell deaths are gradually appreciated, including pyroptosis, ferroptosis, and necroptosis. Necroptosis is, so far, one of the best-characterized regulated necrosis. In response to diverse stimuli (death receptor or toll-like receptor stimulation, pathogenic infection, or other factors), necroptosis is initiated and precisely regulated by the receptor-interacting protein kinase 3 (RIPK3) with the involvement of its partners (RIPK1, TRIF, DAI, or others), ultimately leading to the activation of its downstream substrate, mixed lineage kinase domain-like (MLKL). Necroptosis plays a significant role in the host's defense against pathogenic infections. Although much has been recognized regarding modulatory mechanisms of necroptosis during pathogenic infection, the exact role of necroptosis at different stages of infectious diseases is still being unveiled, e.g., how and when pathogens utilize or evade necroptosis to facilitate their invasion and how hosts manipulate necroptosis to counteract these detrimental effects brought by pathogenic infections and further eliminate the encroaching pathogens. In this review, we summarize and discuss the recent progress in the role of necroptosis during a series of viral, bacterial, and parasitic infections with zoonotic potentials, aiming to provide references and directions for the prevention and control of infectious diseases of both human and animals.
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Affiliation(s)
- Guangzhi Zhang
- grid.464332.4Institute of Animal Sciences of Chinese Academy of Agricultural Sciences, Beijing, 100193 China
| | - Jinyong Wang
- grid.508381.70000 0004 0647 272XShenzhen Bay Laboratory, Institute of Infectious Diseases, Shenzhen, 518000 China ,grid.258164.c0000 0004 1790 3548Institute of Respiratory Diseases, Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University, Shenzhen, 518020 Guangdong China
| | - Zhanran Zhao
- grid.47840.3f0000 0001 2181 7878Department of Molecular and Cell Biology and Cancer Research Laboratory, University of California, Berkeley, CA 94720-3200 USA
| | - Ting Xin
- grid.464332.4Institute of Animal Sciences of Chinese Academy of Agricultural Sciences, Beijing, 100193 China
| | - Xuezheng Fan
- grid.464332.4Institute of Animal Sciences of Chinese Academy of Agricultural Sciences, Beijing, 100193 China
| | - Qingchun Shen
- grid.464332.4Institute of Animal Sciences of Chinese Academy of Agricultural Sciences, Beijing, 100193 China
| | - Abdul Raheem
- grid.464332.4Institute of Animal Sciences of Chinese Academy of Agricultural Sciences, Beijing, 100193 China ,grid.35155.370000 0004 1790 4137Present Address: Huazhong Agricultural University, Wuhan, China
| | - Chae Rhim Lee
- grid.47840.3f0000 0001 2181 7878Department of Molecular and Cell Biology and Cancer Research Laboratory, University of California, Berkeley, CA 94720-3200 USA ,grid.266093.80000 0001 0668 7243Present Address: University of California, Irvine, CA USA
| | - Hui Jiang
- grid.464332.4Institute of Animal Sciences of Chinese Academy of Agricultural Sciences, Beijing, 100193 China
| | - Jiabo Ding
- grid.464332.4Institute of Animal Sciences of Chinese Academy of Agricultural Sciences, Beijing, 100193 China
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Pop R, Tăbăran AF, Ungur AP, Negoescu A, Cătoi C. Helicobacter Pylori-Induced Gastric Infections: From Pathogenesis to Novel Therapeutic Approaches Using Silver Nanoparticles. Pharmaceutics 2022; 14:pharmaceutics14071463. [PMID: 35890358 PMCID: PMC9318142 DOI: 10.3390/pharmaceutics14071463] [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: 06/02/2022] [Revised: 06/29/2022] [Accepted: 07/11/2022] [Indexed: 02/01/2023] Open
Abstract
Helicobacter pylori is the first formally recognized bacterial carcinogen and the most important single digestive pathogen responsible for the induction of gastroduodenal diseases such as gastritis, peptic ulcer, and, finally, gastric neoplasia. The recently reported high rates of antimicrobial drug resistance hamper the current therapies of H. pylori, with therapeutic failure reaching up to 40% of patients. In this context, new treatment options and strategies are urgently needed, but the successful development of these new therapeutic tools is conditioned by the understanding of the high adaptability of H. pylori to the gastric acidic environment and the complex pathogenic mechanism. Due to several advantages, including good antibacterial efficiency, possible targeted delivery, and long tissular persistence, silver nanoparticles (AgNPs) offer the opportunity of exploring new strategies to improve the H. pylori therapy. A new paradigm in the therapy of H. pylori gastric infections using AgNPs has the potential to overcome the current medical limitations imposed by the H. pylori drug resistance, which is reported for most of the current organic antibiotics employed in the classical therapies. This manuscript provides an extensive overview of the pathology of H. pylori-induced gastritis, gastric cancer, and extradigestive diseases and highlights the possible benefits and limitations of employing AgNPs in the therapeutic strategies against H. pylori infections.
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A rapid anti-Helicobacter pylori biofilm drug screening biosensor based on AlpB outer membrane protein and colloidal gold/nanoporous gold framework. Biosens Bioelectron 2022; 215:114599. [DOI: 10.1016/j.bios.2022.114599] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 06/23/2022] [Accepted: 07/23/2022] [Indexed: 12/26/2022]
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Zhang X, Sang S, Guan Q, Tao H, Wang Y, Liu C. Oral Administration of a Shigella 2aT32-Based Vaccine Expressing UreB-HspA Fusion Antigen With and Without Parenteral rUreB-HspA Boost Confers Protection Against Helicobacter pylori in Mice Model. Front Immunol 2022; 13:894206. [PMID: 35769459 PMCID: PMC9234132 DOI: 10.3389/fimmu.2022.894206] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Accepted: 05/18/2022] [Indexed: 11/13/2022] Open
Abstract
Helicobacter pylori (H. pylori) is a gram-negative pathogen classified as a class I carcinogen. The H. pylori urease B subunit (UreB) and heat shock protein A (HspA) are two important vaccine candidate antigens. In this study, we evaluated the immunogenicity and immunoprotective effect of the attenuated Shigella vector vaccine SH02 expressing the UreB-HspA fusion protein of H. pylori in a mouse model. Oral SH02 with or without subcutaneous injection of rUreB-HspA induced antigen-specific serum IgG, mucosal sIgA, and T cells immune response. Subcutaneous injection of the candidate antigen rUreB-HspA enhanced the level of serum antigen-specific IgG antibodies (p < 0.0001) and the levels of IgG1/IgG2a/IgG2b subtypes. In addition, injection boost also increased the proportion of spleen antigen-specific CD4+CD154+ T cells (p < 0.001), and the proportion of CD4+CD154+ T cells that secrete IFN-γ and IL-17A. Following the H. pylori challenge, the levels of H. pylori colonization in the two experimental groups (Groups A and B) significantly reduced compared with the control group (p < 0.001), indicating that the candidate vaccine yielded a preventive effect of anti-H.pylori infection. Compared with the non-subcutaneous booster injection group (Group A), the subcutaneous booster injection group (Group B) exhibited less gastric inflammation, but there was no significant difference in the level of colonization (p > 0.05). These results lay a foundation for the development of a vaccine against H. pylori and the optimization of immunization methods and procedures to prevent H. pylori infection.
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Affiliation(s)
- Xin Zhang
- State Key Laboratory of Pathogen and Biosecurity, Institute of Biotechnology, Academy of Military Medical Sciences, Beijing, China
- Department of Pharmacy, Medical Supplies Center, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Shuli Sang
- State Key Laboratory of Pathogen and Biosecurity, Institute of Biotechnology, Academy of Military Medical Sciences, Beijing, China
| | - Qing Guan
- State Key Laboratory of Pathogen and Biosecurity, Institute of Biotechnology, Academy of Military Medical Sciences, Beijing, China
| | - Haoxia Tao
- State Key Laboratory of Pathogen and Biosecurity, Institute of Biotechnology, Academy of Military Medical Sciences, Beijing, China
| | - Yanchun Wang
- State Key Laboratory of Pathogen and Biosecurity, Institute of Biotechnology, Academy of Military Medical Sciences, Beijing, China
- *Correspondence: Chunjie Liu, ; Yanchun Wang,
| | - Chunjie Liu
- State Key Laboratory of Pathogen and Biosecurity, Institute of Biotechnology, Academy of Military Medical Sciences, Beijing, China
- *Correspondence: Chunjie Liu, ; Yanchun Wang,
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27
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Alkhaldi NK, Alghamdi WK, Alharbi MH, Almutairi AS, Alghamdi FT. The Association Between Oral Helicobacter pylori and Gastric Complications: A Comprehensive Review. Cureus 2022; 14:e24703. [PMID: 35663643 PMCID: PMC9162906 DOI: 10.7759/cureus.24703] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/26/2022] [Indexed: 12/13/2022] Open
Abstract
Helicobacter pylori (H. pylori) is linked to chronic gastritis, duodenal or gastric ulcers, and gastric cancer (GC). Because the oral cavity is the first component of the gastrointestinal tract (GIT) and the entrance point for H. pylori, it has been proposed as a possible reservoir of H. pylori. As a result, a putative oral-oral transmission pathway of H. pylori poses the possibility of whether personal contact, such as kissing or sharing a meal, might trigger H. pylori transmission. As a result, several investigations have been done on this issue using various approaches for detecting H. pylori in oral and stomach samples. Furthermore, the relationship between H. pylori and gastrointestinal disorders has yet to be studied. The evidence for the association between H. pylori and gastric diseases and their complications is still a controversial subject due to the existing literature in this review. The goal of this comprehensive review was to collect all available published articles and critically evaluate existing investigations looking into the relationship between oral H. pylori contamination and the danger of gastric complications. Few studies indicated an association between H. pylori and gastric diseases. Furthermore, more longitudinal randomized clinical studies to further investigate the association between H. pylori and gastric diseases are warranted.
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Affiliation(s)
- Njoud K Alkhaldi
- General Medicine and Surgery, College of Medicine, Princess Nourah bint Abdulrahman University, Riyadh, SAU
| | - Waad K Alghamdi
- General Medicine and Surgery, College of Medicine, Princess Nourah bint Abdulrahman University, Riyadh, SAU
| | - Maryam H Alharbi
- General Medicine and Surgery, College of Medicine, Princess Nourah bint Abdulrahman University, Riyadh, SAU
| | - Albandri S Almutairi
- General Medicine and Surgery, College of Medicine, Princess Nourah bint Abdulrahman University, Riyadh, SAU
| | - Faisal T Alghamdi
- Department of Oral Biology, Faculty of Dentistry, King Abdulaziz University, Jeddah, SAU
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28
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Uberti AF, Callai-Silva N, Grahl MVC, Piovesan AR, Nachtigall EG, Furini CRG, Carlini CR. Helicobacter pylori Urease: Potential Contributions to Alzheimer’s Disease. Int J Mol Sci 2022; 23:ijms23063091. [PMID: 35328512 PMCID: PMC8949269 DOI: 10.3390/ijms23063091] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2021] [Revised: 03/09/2022] [Accepted: 03/10/2022] [Indexed: 11/24/2022] Open
Abstract
Alzheimer’s disease (AD) causes dementia and memory loss in the elderly. Deposits of beta-amyloid peptide and hyperphosphorylated tau protein are present in a brain with AD. A filtrate of Helicobacter pylori’s culture was previously found to induce hyperphosphorylation of tau in vivo, suggesting that bacterial exotoxins could permeate the blood–brain barrier and directly induce tau’s phosphorylation. H. pylori, which infects ~60% of the world population and causes gastritis and gastric cancer, produces a pro-inflammatory urease (HPU). Here, the neurotoxic potential of HPU was investigated in cultured cells and in rats. SH-SY5Y neuroblastoma cells exposed to HPU (50–300 nM) produced reactive oxygen species (ROS) and had an increased [Ca2+]i. HPU-treated BV-2 microglial cells produced ROS, cytokines IL-1β and TNF-α, and showed reduced viability. Rats received daily i.p., HPU (5 µg) for 7 days. Hyperphosphorylation of tau at Ser199, Thr205 and Ser396 sites, with no alterations in total tau or GSK-3β levels, and overexpression of Iba1, a marker of microglial activation, were seen in hippocampal homogenates. HPU was not detected in the brain homogenates. Behavioral tests were performed to assess cognitive impairments. Our findings support previous data suggesting an association between infection by H. pylori and tauopathies such as AD, possibly mediated by its urease.
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Affiliation(s)
- Augusto F. Uberti
- Laboratory of Neurotoxins, Brain Institute of Rio Grande do Sul (BRAINS) and Graduate Program in Medicine and Health Sciences, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre CEP 90610-000, RS, Brazil; (A.F.U.); (N.C.-S.); (M.V.C.G.)
| | - Natalia Callai-Silva
- Laboratory of Neurotoxins, Brain Institute of Rio Grande do Sul (BRAINS) and Graduate Program in Medicine and Health Sciences, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre CEP 90610-000, RS, Brazil; (A.F.U.); (N.C.-S.); (M.V.C.G.)
| | - Matheus V. C. Grahl
- Laboratory of Neurotoxins, Brain Institute of Rio Grande do Sul (BRAINS) and Graduate Program in Medicine and Health Sciences, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre CEP 90610-000, RS, Brazil; (A.F.U.); (N.C.-S.); (M.V.C.G.)
| | - Angela R. Piovesan
- Center of Biotechnology, Graduate Program in Cellular and Molecular Biology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre CEP 91501-970, RS, Brazil;
| | - Eduarda G. Nachtigall
- Laboratory of Cognition and Memory Neurobiology, Brain Institute of Rio Grande do Sul (BRAINS) and Graduate Program in Biomedical Gerontology, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre CEP 90610-000, RS, Brazil; (E.G.N.); (C.R.G.F.)
| | - Cristiane R. G. Furini
- Laboratory of Cognition and Memory Neurobiology, Brain Institute of Rio Grande do Sul (BRAINS) and Graduate Program in Biomedical Gerontology, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre CEP 90610-000, RS, Brazil; (E.G.N.); (C.R.G.F.)
| | - Celia Regina Carlini
- Laboratory of Neurotoxins, Brain Institute of Rio Grande do Sul (BRAINS) and Graduate Program in Medicine and Health Sciences, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre CEP 90610-000, RS, Brazil; (A.F.U.); (N.C.-S.); (M.V.C.G.)
- Correspondence: ; Tel.: +55-51-3320-5986
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Fernandez-Yague MA, Hymel LA, Olingy CE, McClain C, Ogle ME, García JR, Minshew D, Vyshnya S, Lim HS, Qiu P, García AJ, Botchwey EA. Analyzing immune response to engineered hydrogels by hierarchical clustering of inflammatory cell subsets. SCIENCE ADVANCES 2022; 8:eabd8056. [PMID: 35213226 PMCID: PMC8880784 DOI: 10.1126/sciadv.abd8056] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Accepted: 12/31/2021] [Indexed: 06/14/2023]
Abstract
Understanding the immune response to hydrogel implantation is critical for the design of immunomodulatory biomaterials. To study the progression of inflammation around poly(ethylene glycol) hydrogels presenting Arg-Gly-Asp (RGD) peptides and vascular endothelial growth factor, we used temporal analysis of high-dimensional flow cytometry data paired with intravital imaging, immunohistochemistry, and multiplexed proteomic profiling. RGD-presenting hydrogels created a reparative microenvironment promoting CD206+ cellular infiltration and revascularization in wounded dorsal skin tissue. Unbiased clustering algorithms (SPADE) revealed significant phenotypic transition shifts as a function of the cell-adhesion hydrogel properties. SPADE identified an intermediate macrophage subset functionally regulating in vivo cytokine secretion that was preferentially recruited for RGD-presenting hydrogels, whereas dendritic cell subsets were preferentially recruited to RDG-presenting hydrogels. Last, RGD-presenting hydrogels controlled macrophage functional cytokine secretion to direct polarization and vascularization. Our studies show that unbiased clustering of single-cell data provides unbiased insights into the underlying immune response to engineered materials.
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Affiliation(s)
- Marc A. Fernandez-Yague
- The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA
- Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA
| | - Lauren A. Hymel
- The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA
- Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA
| | - Claire E. Olingy
- The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA
- Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA
| | - Claire McClain
- The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA
- Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA
| | - Molly E. Ogle
- The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA
- Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA
| | - José R. García
- Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA
- Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA
| | - Dustin Minshew
- The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA
| | - Sofiya Vyshnya
- The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA
| | - Hong Seo Lim
- The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA
| | - Peng Qiu
- The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA
| | - Andrés J. García
- Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA
- Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA
| | - Edward A. Botchwey
- The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA
- Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA
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Sun H, He T, Wu Y, Yuan H, Ning J, Zhang Z, Deng X, Li B, Wu C. Cytotoxin-Associated Gene A-Negative Helicobacter pylori Promotes Gastric Mucosal CX3CR1+CD4+ Effector Memory T Cell Recruitment in Mice. Front Microbiol 2022; 13:813774. [PMID: 35154057 PMCID: PMC8829513 DOI: 10.3389/fmicb.2022.813774] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Accepted: 01/07/2022] [Indexed: 11/13/2022] Open
Abstract
Background Helicobacter pylori can cause many kinds of gastric disorders, ranging from gastritis to gastric cancer. Cytotoxin-associated gene A (CagA)+H. pylori is more likely to cause gastric histopathologic damage than CagA–H. pylori. However, the underlying mechanism needs to be further investigated. Materials and methods Mice were intragastrically administered equal amounts of CagA+ or CagA–H. pylori. Four weeks later, 24 chemokines in stomachs were measured using a mouse chemokine array, and the phenotypes of the recruited gastric CD4+ T cells were analyzed. The migration pathway was evaluated. Finally, the correlation between each pair among the recruited CD4+ T cell sub-population, H. pylori colonization level, and histopathologic damage score were determined by Pearson correlation analysis. Results The concentration of chemokines, CCL3 and CX3CL1, were significantly elevated in CagA–H. pylori-infected gastric mucosa than in CagA+H. pylori-infected gastric mucosa. Among them, CX3CL1 secreted by gastric epithelial cells, which was elicited more effectively by CagA–H. pylori than by the CagA+ strain, dramatically promoted mucosal CD4+ T cell migration. The expression of CX3CR1, the only known receptor of CX3CL1, was upregulated on the surface of gastric CD4+ T cells in CagA–H. pylori-infected stomach. In addition, most of the CX3CR1-positive gastric CD4+ T cells were CD44+CD69–CCR7– effector memory T cells (Tem). Pearson correlation analysis showed that the recruited CX3CR1+CD4+ Tem cell population was negatively correlated with H. pylori colonization level and histopathologic damage score. Conclusion CagA–H. pylori promotes gastric mucosal CX3CR1+CD4+ Tem recruitment in mice.
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Affiliation(s)
- Heqiang Sun
- Department of Laboratory Medicine, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
| | - Taojun He
- Department of Laboratory Medicine, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Yanan Wu
- Peking University People’s Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
| | - Hanmei Yuan
- Department of Laboratory Medicine, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Jie Ning
- Department of Laboratory Medicine, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Zhenhua Zhang
- Department of Gastroenterology of the 305 Hospital of Chinese People’s Liberation Army, Beijing, China
| | - Xinli Deng
- Department of Laboratory Medicine, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
| | - Bin Li
- Department of Laboratory Medicine, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
- Bin Li,
| | - Chao Wu
- Department of Laboratory Medicine, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
- *Correspondence: Chao Wu,
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Harris RB, Brown HE, Begay RL, Sanderson PR, Chief C, Monroy FP, Oren E. Helicobacter pylori Prevalence and Risk Factors in Three Rural Indigenous Communities of Northern Arizona. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19020797. [PMID: 35055622 PMCID: PMC8775467 DOI: 10.3390/ijerph19020797] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 12/31/2021] [Accepted: 01/05/2022] [Indexed: 02/07/2023]
Abstract
Helicobacter pylori (H. pylori) is one of the most common bacterial stomach infections and is implicated in a majority of non-cardia gastric cancer. While gastric cancer has decreased in the United States (US), the incidence in the Navajo Nation is nearly four times higher than surrounding Non-Hispanic White populations. Little is known about H. pylori prevalence in this population or other Indigenous communities in the lower 48 states. In this cross-sectional study, 101 adults representing 73 households from three Navajo Nation chapter communities completed surveys and a urea breath test for active H. pylori. Accounting for intrahousehold correlation, H. pylori prevalence was 56.4% (95% CI, 45.4–66.8) and 72% of households had at least one infected person. The odds of having an active infection in households using unregulated water were 8.85 (95% CI, 1.50–53.38) that of the use of regulated water, and males had 3.26 (95% CI, 1.05–10.07) higher odds than female. The prevalence of H. pylori in Navajo is similar to that seen in Alaska Natives. Further investigation into factors associated with prevention of infection is needed as well as understanding barriers to screening and treatment.
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Affiliation(s)
- Robin B. Harris
- Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, 1295 N. Martin Ave., Tucson, AZ 85724, USA; (H.E.B.); (R.L.B.)
- Correspondence:
| | - Heidi E. Brown
- Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, 1295 N. Martin Ave., Tucson, AZ 85724, USA; (H.E.B.); (R.L.B.)
| | - Rachelle L. Begay
- Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, 1295 N. Martin Ave., Tucson, AZ 85724, USA; (H.E.B.); (R.L.B.)
| | - Priscilla R. Sanderson
- Department of Health Sciences, College of Health and Human Services, Northern Arizona University, SAS (Bldg 60), 1100 S. Beaver St., POB 15095, Flagstaff, AZ 86011, USA;
| | - Carmenlita Chief
- Center for Health Equity Research, College of Health and Human Services, Northern Arizona University, 1395 South Knoles Drive, POB 4065, Flagstaff, AZ 86011, USA;
| | - Fernando P. Monroy
- Department of Biological Sciences, College of the Environment, Forestry and Natural Sciences, Northern Arizona University, 617 S. Beaver St., Flagstaff, AZ 86011, USA;
| | - Eyal Oren
- Division of Epidemiology & Biostatistics, School of Public Health, San Diego State University, 5500 Campanile Drive, San Diego, CA 92182, USA;
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32
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Bai L, Yan XL, Lu YX, Meng Q, Rong YM, Ye LF, Pan ZZ, Xing BC, Wang DS. Circulating Lipid- and Inflammation-Based Risk (CLIR) Score: A Promising New Model for Predicting Outcomes in Complete Colorectal Liver Metastases Resection. Ann Surg Oncol 2022; 29:10.1245/s10434-021-11234-0. [PMID: 35254582 PMCID: PMC9174322 DOI: 10.1245/s10434-021-11234-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Accepted: 12/08/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Colorectal cancer liver metastasis (CRLM) is a determining factor affecting the survival of colorectal cancer (CRC) patients. This study aims at developing a novel prognostic stratification tool for CRLM resection. METHODS In this retrospective study, 666 CRC patients who underwent complete CRLM resection from two Chinese medical institutions between 2001 and 2016 were classified into the training (341 patients) and validation (325 patients) cohorts. The primary endpoint was overall survival (OS). Associations between clinicopathological variables, circulating lipid and inflammation biomarkers, and OS were explored. The five most significant prognostic factors were incorporated into the Circulating Lipid- and Inflammation-based Risk (CLIR) score. The predictive ability of the CLIR score and Fong's Clinical Risk Score (CRS) was compared by time-dependent receiver operating characteristic (ROC) analysis. RESULTS Five independent predictors associated with worse OS were identified in the training cohort: number of CRLMs >4, maximum diameter of CRLM >4.4 cm, primary lymph node-positive, serum lactate dehydrogenase (LDH) level >250.5 U/L, and serum low-density lipoprotein-cholesterol (LDL-C)/high-density lipoprotein-cholesterol (HDL-C) ratio >2.9. These predictors were included in the CLIR score and each factor was assigned one point. Median OS for the low (score 0-1)-, intermediate (score 2-3)-, and high (score 4-5)-risk groups was 134.0 months, 39.9 months, and 18.7 months in the pooled cohort. The CLIR score outperformed the Fong score with superior discriminatory capacities for OS and RFS, both in the training and validation cohorts. CONCLUSIONS The CLIR score demonstrated a promising ability to predict the long-term survival of CRC patients after complete hepatic resection.
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Affiliation(s)
- Long Bai
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China
- Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, 510060, People's Republic of China
- Department of VIP Region, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China
| | - Xiao-Luan Yan
- Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing), Beijing, 100142, People's Republic of China
- Hepatopancreatobiliary Surgery Department I, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China
| | - Yun-Xin Lu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China
- Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, 510060, People's Republic of China
- Department of Medical Oncology, Sun Yat-sen University Cancer Center/Cancer Hospital, Guangzhou, People's Republic of China
| | - Qi Meng
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China
- Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, 510060, People's Republic of China
- Department of Medical Oncology, Sun Yat-sen University Cancer Center/Cancer Hospital, Guangzhou, People's Republic of China
| | - Yu-Ming Rong
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China
- Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, 510060, People's Republic of China
- Department of VIP Region, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China
| | - Liu-Fang Ye
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China
- Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, 510060, People's Republic of China
- Department of Medical Oncology, Sun Yat-sen University Cancer Center/Cancer Hospital, Guangzhou, People's Republic of China
| | - Zhi-Zhong Pan
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China.
- Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, 510060, People's Republic of China.
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center/Cancer Hospital, Guangzhou, Guangdong, 510060, People's Republic of China.
| | - Bao-Cai Xing
- Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing), Beijing, 100142, People's Republic of China.
- Hepatopancreatobiliary Surgery Department I, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China.
| | - De-Shen Wang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China.
- Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, 510060, People's Republic of China.
- Department of Medical Oncology, Sun Yat-sen University Cancer Center/Cancer Hospital, Guangzhou, People's Republic of China.
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Tamrakar A, Singh R, Kumar A, Makde RD, Ashish, Kodgire P. Biophysical characterization of the homodimers of HomA and HomB, outer membrane proteins of Helicobacter pylori. Sci Rep 2021; 11:24471. [PMID: 34963695 PMCID: PMC8714817 DOI: 10.1038/s41598-021-04039-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Accepted: 11/24/2021] [Indexed: 12/16/2022] Open
Abstract
Helicobacter pylori is a Gram-negative bacterium that causes chronic inflammations in the stomach area and is involved in ulcers, which can develop into gastric malignancies. H. pylori attaches and colonizes to the human epithelium using some of their outer membrane proteins (OMPs). HomB and HomA are the most studied OMPs from H. pylori as they play a crucial role in adherence, hyper biofilm formation, antibiotic resistance and are also associated with severe gastric malignancies. The role of HomA and HomB in pathogenesis concerning their structure and function has not been evaluated yet. In the present study, we explored the structural aspect of HomA and HomB proteins using various computational, biophysical and small-angle X-ray scattering (SAXS) techniques. Interestingly, the in-silico analysis revealed that HomA/B consists of 8 discontinuous N and C terminal β-strands forming a small β-barrel, along with a large surface-exposed globular domain. Further, biophysical experiments suggested that HomA and HomB are dimeric and most likely the cysteine residues present on surface-exposed loops participate in protein-protein interactions. Our study provides essential structural information of unexplored proteins of the Hom family that can help in a better understanding of H. pylori pathogenesis.
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Affiliation(s)
- Anubhav Tamrakar
- Discipline of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, Madhya Pradesh, 453 552, India
| | - Rahul Singh
- High Pressure and Synchrotron Radiation Physics Division, Bhabha Atomic Research Center, Trombay, Mumbai, India
| | - Amit Kumar
- Discipline of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, Madhya Pradesh, 453 552, India
| | - Ravindra D Makde
- High Pressure and Synchrotron Radiation Physics Division, Bhabha Atomic Research Center, Trombay, Mumbai, India
| | - Ashish
- Protein Science and Engineering Division, CSIR-Institute of Microbial Technology, Chandigarh, India
| | - Prashant Kodgire
- Discipline of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, Madhya Pradesh, 453 552, India.
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Yuan S, Wu Q, Wang Z, Che Y, Zheng S, Chen Y, Zhong X, Shi F. miR-223: An Immune Regulator in Infectious Disorders. Front Immunol 2021; 12:781815. [PMID: 34956210 PMCID: PMC8702553 DOI: 10.3389/fimmu.2021.781815] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Accepted: 11/24/2021] [Indexed: 12/12/2022] Open
Abstract
MicroRNAs (miRNAs) are diminutive noncoding RNAs that can influence disease development and progression by post-transcriptionally regulating gene expression. The anti-inflammatory miRNA, miR-223, was first identified as a regulator of myelopoietic differentiation in 2003. This miR-223 exhibits multiple regulatory functions in the immune response, and abnormal expression of miR-223 is shown to be associated with multiple infectious diseases, including viral hepatitis, human immunodeficiency virus type 1 (HIV-1), and tuberculosis (TB) by influencing neutrophil infiltration, macrophage function, dendritic cell (DC) maturation and inflammasome activation. This review summarizes the current understanding of miR-223 physiopathology and highlights the molecular mechanism by which miR-223 regulates immune responses to infectious diseases and how it may be targeted for diagnosis and treatment.
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Affiliation(s)
- Shun Yuan
- Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Qi Wu
- Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Zhiwei Wang
- Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Yanjia Che
- Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Sihao Zheng
- Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Yuanyang Chen
- Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Xiaohan Zhong
- Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Feng Shi
- Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan, China
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35
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Wu SE, Chen WL. Detrimental relevance of Helicobacter pylori infection with sarcopenia. Gut Pathog 2021; 13:67. [PMID: 34782007 PMCID: PMC8591825 DOI: 10.1186/s13099-021-00464-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 11/09/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori), Gram negative microaerophilic bacteria, is a well-known pathogen of many gastrointestinal diseases. But several emerging evidences suggest it role in numerous other extra-gastric diseases. The current study investigates the relationship between H. pylori infection and sarcopenia, a clinical condition characterized by the loss of mass and function of skeletal muscle. A total of 3453 eligible participants from the Third National Health and Nutrition Examination Survey (NHANES III), the United States, were enrolled. Based on the serum laboratory results, subjects were categorized into three groups: normal (without evidence of any H. pylori infection), anti-H. pylori IgG positive [H. pylori (+)], and concurrent anti-H. pylori IgG and anti-cytotoxin-associated gene A IgG positive [CagA (+)]. Sarcopenia was determined as having a skeletal muscle index (SMI) value that is more than 1 standard deviation away from the mean value of sex-specific, healthy young adults between 20 and 39 years old. Risk of sarcopenia and its components are compared between subgroups. RESULTS Odds ratios (OR) for confirmed diagnosis of sarcopenia were higher in H. pylori (+) (OR = 2.052, 95% CI 1.697-2.481, p < 0.001) and CagA (+) (OR = 1.585, 95% CI 1.278-1.965, p < 0.001) groups. Moreover, negative beta regression coefficient of SMI were shown in H. pylori (+) (β: - 0.023, p < 0.001) and CagA (+) (β: - 0.017, p < 0.001). Sub-analyses which categorized participants by gender revealed that absolute value of beta regression coefficient for SMI were higher in female in H. pylori (+) subgroup (β: - 1.745 in male and - 2.942 in female, p were both < 0.001), and the CagA (+) subgroup (β: - 1.407 in male and - 2.159 in female, p were both < 0.001). CONCLUSIONS Positive serum H. pylori infectious markers including anti-H. pylori antibody and CagA seropositivity are correlated with sarcopenia and low muscle quantity. Therefore, H. pylori eradication therapy may bring benefits to sarcopenia patients with concurrent active H. pylori infection.
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Affiliation(s)
- Shou-En Wu
- Department of Dermatology, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China
- Division of Family Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China
- Division of Geriatric Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Number 325, Section 2, Chang-gong Rd, Nei-Hu District, Taipei, 114, Taiwan, Republic of China
| | - Wei-Liang Chen
- Division of Family Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China.
- Division of Geriatric Medicine, Department of Family and Community Medicine, Tri-Service General Hospital; and School of Medicine, National Defense Medical Center, Number 325, Section 2, Chang-gong Rd, Nei-Hu District, Taipei, 114, Taiwan, Republic of China.
- Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan, Republic of China.
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Saad MR, Han HS, Yoon YS, Cho JY, Lee JS, Shehta A. Impact of Acute Inflammation on the Survival Outcomes of Patients with Resected Pancreatic Ductal Adenocarcinoma. Dig Surg 2021; 38:343-351. [PMID: 34731855 DOI: 10.1159/000520063] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Accepted: 09/30/2021] [Indexed: 12/11/2022]
Abstract
INTRODUCTION The impact of acute inflammation on cancer progression is still not well elucidated. Pancreatic head cancer is occasionally associated with acute cholangitis. C-reactive protein (CRP) is a biomarker that indicates presence of acute inflammation. METHODS We reviewed the patients' data with pancreatic ductal adenocarcinoma (PDAC) who underwent pancreaticoduodenectomy between 2004 and 2018. RESULTS Two hundred ninety-one patients were included. Median preoperative CRP was 0.45 mg/dL (0-18.9). Median follow-up duration was 22 months (4-152). The 1-, 3-, and 5-year overall survival (OS) rates were 76.4%, 32.2%, and 22.9%, respectively. Recurrence occurred in 168 cases (57.7%). The 1-, 3-, and 5-year disease-free survival (DFS) rates were 53.9%, 27.1%, and 21.9%, respectively. The median OS was higher in normal CRP patients (27 months) than those with elevated CRP (18 months) (log-rank 0.038). The median DFS was higher in normal CRP patients (17 months) than those with elevated CRP (9 months) (log-rank < 0.001). Predictive factors for OS included BMI, CRP, adjuvant therapy, positive lymph nodes, and microvascular invasion. Predictive factors for DFS included CRP, positive lymph nodes, and microvascular invasion. CONCLUSION Preoperative CRP was an independent poor prognostic factor for OS and DFS of patients with resected PDAC.
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Affiliation(s)
- Mohamed Rabie Saad
- Department of Surgery, Faculty of Medicine, Aswan University Hospital, Aswan, Egypt.,Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ho-Seong Han
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yoo-Seok Yoon
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jai Young Cho
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jun Suh Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ahmed Shehta
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea, .,Department of Surgery, Gastrointestinal Surgery Center, College of Medicine, Mansoura University, Mansoura, Egypt,
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Roda N, Blandano G, Pelicci PG. Blood Vessels and Peripheral Nerves as Key Players in Cancer Progression and Therapy Resistance. Cancers (Basel) 2021; 13:cancers13174471. [PMID: 34503281 PMCID: PMC8431382 DOI: 10.3390/cancers13174471] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Revised: 08/31/2021] [Accepted: 09/02/2021] [Indexed: 12/12/2022] Open
Abstract
Simple Summary The interactions between cancer cells and the surrounding blood vessels and peripheral nerves are critical in all the phases of tumor development. Accordingly, therapies that specifically target vessels and nerves represent promising anticancer approaches. The first aim of this review is to document the importance of blood vessels and peripheral nerves in both cancer onset and local or distant growth of tumoral cells. We then focus on the state-of-the-art therapies that limit cancer progression through the impairment of blood vessels and peripheral nerves. The mentioned literature is helpful for the scientific community to appreciate the recent advances in these two fundamental components of tumors. Abstract Cancer cells continuously interact with the tumor microenvironment (TME), a heterogeneous milieu that surrounds the tumor mass and impinges on its phenotype. Among the components of the TME, blood vessels and peripheral nerves have been extensively studied in recent years for their prominent role in tumor development from tumor initiation. Cancer cells were shown to actively promote their own vascularization and innervation through the processes of angiogenesis and axonogenesis. Indeed, sprouting vessels and axons deliver several factors needed by cancer cells to survive and proliferate, including nutrients, oxygen, and growth signals, to the expanding tumor mass. Nerves and vessels are also fundamental for the process of metastatic spreading, as they provide both the pro-metastatic signals to the tumor and the scaffold through which cancer cells can reach distant organs. Not surprisingly, continuously growing attention is devoted to the development of therapies specifically targeting these structures, with promising initial results. In this review, we summarize the latest evidence that supports the importance of blood vessels and peripheral nerves in cancer pathogenesis, therapy resistance, and innovative treatments.
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Affiliation(s)
- Niccolò Roda
- Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, 20139 Milan, Italy; (N.R.); (G.B.)
| | - Giada Blandano
- Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, 20139 Milan, Italy; (N.R.); (G.B.)
| | - Pier Giuseppe Pelicci
- Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, 20139 Milan, Italy; (N.R.); (G.B.)
- Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy
- Correspondence:
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38
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Jiang X, Xu Z, Zhang T, Li Y, Li W, Tan H. Whole-Genome-Based Helicobacter pylori Geographic Surveillance: A Visualized and Expandable Webtool. Front Microbiol 2021; 12:687259. [PMID: 34408729 PMCID: PMC8366602 DOI: 10.3389/fmicb.2021.687259] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 06/07/2021] [Indexed: 01/08/2023] Open
Abstract
Helicobacter pylori exhibit specific geographic distributions that are related to clinical outcomes. Despite the high infection rate of H. pylori throughout the world, the genetic epidemiology surveillance of H. pylori still needs to be improved. This study used the single nucleotide polymorphisms (SNPs) profiling approach based on whole genome sequencing (WGS) to facilitate genomic population analyses of H. pylori and encourage the dissemination of microbial genotyping strategies worldwide. A total number of 1,211 public H. pylori genomes were downloaded and used to construct the typing tool, named HpTT (H. pylori Typing Tool). Combined with the metadata, we developed two levels of genomic typing, including a continent-scale and a country scale that nested in the continent scale. Results showed that Asia was the largest isolate source in our dataset, while isolates from Europe and Oceania were comparatively more widespread. More specifically, Switzerland and Australia are the main sources of widespread isolates in their corresponding continents. To integrate all the typing information and enable researchers to compare their dataset against the existing global database easily and rapidly, a user-friendly website (https://db.cngb.org/HPTT/) was developed with both genomic typing tools and visualization tools. To further confirm the validity of the website, ten newly assembled genomes were downloaded and tested precisely located on the branch as we expected. In summary, the H. pylori typing tool (HpTT) is a novel genomic epidemiological tool that can achieve high-resolution analysis of genomic typing and visualizing simultaneously, providing insights into the genetic population structure, evolution analysis, and epidemiological surveillance of H. pylori.
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Affiliation(s)
- Xiaosen Jiang
- BGI-Shenzhen, Shenzhen, China.,BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, China.,College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Zheng Xu
- BGI-Shenzhen, Shenzhen, China.,Shenzhen Key Laboratory of Unknown Pathogen Identification, BGI-Shenzhen, Shenzhen, China
| | | | - Yuan Li
- BGI-Shenzhen, Shenzhen, China
| | - Wei Li
- BGI-Shenzhen, Shenzhen, China.,BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, China.,College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China
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Choi MS, Ze EY, Park JY, Shin TS, Kim JG. Helicobacter pylori-derived outer membrane vesicles stimulate interleukin 8 secretion through nuclear factor kappa B activation. Korean J Intern Med 2021; 36:854-867. [PMID: 33242939 PMCID: PMC8273812 DOI: 10.3904/kjim.2019.432] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2019] [Accepted: 03/19/2020] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND/AIMS Bacteria-derived outer membrane vesicles (OMVs) are commonly associated with various biological activities and functions. Helicobacter pylori-derived OMVs are thought to contribute to pathogenesis. This study aimed to investigate the effects of H. pylori-derived OMVs. METHODS H. pylori strains were isolated from patients with gastritis, gastric ulcer, or gastric cancer using endoscopic biopsy. The U-937, AGS, and MKN-45 cell lines were exposed to H. pylori and H. pylori-derived OMVs. The expression of interleukin 8 (IL-8) messenger RNA (mRNA) was assessed using reverse transcription-polymerase chain reaction (RT-PCR) and real-time RT-PCR, and IL-8 secretion was analyzed using enzyme-linked immunosorbent assay. Nuclear factor kappa B (NF-κB) activation was evaluated by Western blotting. RESULTS H. pylori and H. pylori-derived OMVs induced the expression of IL-8 mRNA and protein. Importantly, the bacteria induced higher IL-8 mRNA and protein expression than the OMVs. IL-8 expression was induced to different levels in response to H. pylori-derived OMVs from hosts with different gastric diseases. Western blotting revealed the increased phosphorylation and reduced degradation of inhibitor of NF-κB alpha in cells exposed to OMVs. CONCLUSION H. pylori-derived OMVs may aid the development of various gastric diseases by inducing IL-8 production and NF-κB activation.
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Affiliation(s)
- Mun Sun Choi
- Division of Gastroenterology, Department of Internal Medicine, Armed Forces Capital Hospital, Seongnam,
Korea
| | - Eun Young Ze
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul,
Korea
| | - Jae Yong Park
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul,
Korea
| | - Tae-Seop Shin
- Research Institute, Chung-Ang University, Seoul,
Korea
| | - Jae Gyu Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul,
Korea
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Outer Membrane Vesicle Production by Helicobacter pylori Represents an Approach for the Delivery of Virulence Factors CagA, VacA and UreA into Human Gastric Adenocarcinoma (AGS) Cells. Int J Mol Sci 2021; 22:ijms22083942. [PMID: 33920443 PMCID: PMC8069053 DOI: 10.3390/ijms22083942] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 04/07/2021] [Accepted: 04/09/2021] [Indexed: 01/18/2023] Open
Abstract
Helicobacter pylori infection is the etiology of several gastric-related diseases including gastric cancer. Cytotoxin associated gene A (CagA), vacuolating cytotoxin A (VacA) and α-subunit of urease (UreA) are three major virulence factors of H. pylori, and each of them has a distinct entry pathway and pathogenic mechanism during bacterial infection. H. pylori can shed outer membrane vesicles (OMVs). Therefore, it would be interesting to explore the production kinetics of H. pylori OMVs and its connection with the entry of key virulence factors into host cells. Here, we isolated OMVs from H. pylori 26,695 strain and characterized their properties and interaction kinetics with human gastric adenocarcinoma (AGS) cells. We found that the generation of OMVs and the presence of CagA, VacA and UreA in OMVs were a lasting event throughout different phases of bacterial growth. H. pylori OMVs entered AGS cells mainly through macropinocytosis/phagocytosis. Furthermore, CagA, VacA and UreA could enter AGS cells via OMVs and the treatment with H. pylori OMVs would cause cell death. Comparison of H. pylori 26,695 and clinical strains suggested that the production and characteristics of OMVs are not only limited to laboratory strains commonly in use, but a general phenomenon to most H. pylori strains.
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Structure, metabolism and biological functions of steryl glycosides in mammals. Biochem J 2021; 477:4243-4261. [PMID: 33186452 PMCID: PMC7666875 DOI: 10.1042/bcj20200532] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 10/09/2020] [Accepted: 10/21/2020] [Indexed: 12/20/2022]
Abstract
Steryl glycosides (SGs) are sterols glycosylated at their 3β-hydroxy group. They are widely distributed in plants, algae, and fungi, but are relatively rare in bacteria and animals. Glycosylation of sterols, resulting in important components of the cell membrane SGs, alters their biophysical properties and confers resistance against stress by freezing or heat shock to cells. Besides, many biological functions in animals have been suggested from the observations of SG administration. Recently, cholesteryl glucosides synthesized via the transglycosidation by glucocerebrosidases (GBAs) were found in the central nervous system of animals. Identification of patients with congenital mutations in GBA genes or availability of respective animal models will enable investigation of the function of such endogenously synthesized cholesteryl glycosides by genetic approaches. In addition, mechanisms of the host immune responses against pathogenic bacterial SGs have partially been resolved. This review is focused on the biological functions of SGs in mammals taking into consideration their therapeutic applications in the future.
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Banga Ndzouboukou JL, Lei Q, Ullah N, Zhang Y, Hao L, Fan X. Helicobacter pylori adhesins: HpaA a potential antigen in experimental vaccines for H. pylori. Helicobacter 2021; 26:e12758. [PMID: 33259676 DOI: 10.1111/hel.12758] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Revised: 08/14/2020] [Accepted: 09/01/2020] [Indexed: 12/19/2022]
Abstract
BACKGROUND Helicobacter pylori is a gram-negative bacterium involved in many gastric pathologies such as ulcers and cancers. Although the treatment for this infection has existed for several years, the development of a vaccine is nevertheless necessary to reduce the severe forms of the disease. For more than three decades, many advances have been made particularly in the understanding of virulence factors as well as the pathogenesis of gastric diseases caused by H. pylori. Among these key virulence factors, specific antigens have been identified: Urease, Vacuolating cytotoxin A (VacA), Cytotoxin-associated gene A (CagA), Blood group antigen-binding adhesin (BabA), H. pylori adhesin A (HpaA), and others. OBJECTIVES This review will focus on H. pylori adhesins, in particular, on HpaA and on the current knowledge of H. pylori vaccines. METHODS All of the information included in this review was retrieved from published studies on H. pylori adhesins in H. pylori infections. RESULTS These proteins, used in their native or recombinant forms, induce protection against H. pylori in experimental animal models. CONCLUSION H. pylori adhesins are known to be promising candidate vaccines against H. pylori. Future research should be carried out on adhesins, in particular, on HpaA.
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Affiliation(s)
- Jo-Lewis Banga Ndzouboukou
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qing Lei
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Nadeem Ullah
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yandi Zhang
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ling Hao
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xionglin Fan
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Abstract
Alternate remedies with natural products provides unlimited opportunities for new drug development. These can be either as pure compounds or as standardized set of compounds. The phytochemicals and secondary metabolites are in great demand for screening bioactive compounds and plays an important role towards drug development. Natural products have many advantages over to synthetic chemical drugs. Helicobacter pylori (H. pylori) a Gram-negative bacteria has been classified as Class I carcinogen by World Health Organization in 1994. Current treatment regimens for H. pylori is ‘triple therapy’ administrated for two weeks which includes a combination of two antibiotics like Amoxicillin and Clarithromycin and a proton pump inhibitor (PPI) like Lansoprazole, and for ‘quadruple therapy’ in addition to antibiotics and a PPI, Bismuth is used. Antibiotic resistance can be named as the main factor for failure of treatment of H. pylori infection. The need of the hour is to develop a herbal remedy that could combat the growth of H. pylori. Probiotics can also be used as ‘feasible’ tool for H. pylori infection management. Present review is an attempt to briefly discuss about the pathogenicity, genetic predisposition, perturbation of gut microbiota due to antibiotic treatment and restoration of healthy gut microbiota with phytochemicals and probiotics.
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Yaw ACK, Chan EWL, Yap JKY, Mai CW. The effects of NLRP3 inflammasome inhibition by MCC950 on LPS-induced pancreatic adenocarcinoma inflammation. J Cancer Res Clin Oncol 2020; 146:2219-2229. [PMID: 32507974 DOI: 10.1007/s00432-020-03274-y] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Accepted: 05/23/2020] [Indexed: 02/05/2023]
Abstract
PURPOSE Pancreatic cancer is a lethal form of cancer that can be triggered by prolonged or acute inflammation of the pancreas. Inflammation have been shown to be regulated by a group of key protein molecules known as the inflammasomes. The NLRP3 inflammasome is the most studied inflammasome and have been strongly implicated to regulate cancer cell proliferation. Therefore, this study aimed to examine the regulation of NLRP3 inflammasome under LPS-induced inflammation and its role in modulating cell proliferation in a panel of pancreatic cancer cells. METHODS The effects of LPS-induced NLRP3 activation in the presence or absence of MCC950, NLRP3-specific inhibitor, was tested on a panel of three pancreatic cancer cell lines (SW1990, PANC1 and Panc10.05). Western blotting, cell viability kits and ELISA kits were used to examine the effects of LPS-induced NLRP3 activation and inhibition by MCC950 on NLRP3 expression, cell viability, caspase-1 activity and cytokine IL-1β, respectively. RESULTS LPS-induced inflammation in the presence of ATP activates NLRP3 that subsequently increases pancreatic cancer cell proliferation by increasing caspase-1 activity leading to overall production of IL-1β. The inhibition of the NLRP3 inflammasome activation via the specific NLRP3 antagonist MCC950 was able to reduce the cell viability of pancreatic cancer cells. However, the efficacy of MCC950 varies between cell types which is most probably due to the difference in ASC expressions which have a different role in inflammasome activation. CONCLUSION There is a dynamic interaction between inflammasome that regulates inflammasome-mediated inflammation in pancreatic adenocarcinoma cells.
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Affiliation(s)
- Alan Cheuk Keong Yaw
- School of Postgraduate Studies, International Medical University, Jalan Jalil Perkasa 19, Bukit Jalil, 57000, Kuala Lumpur, Malaysia
| | - Elaine Wan Ling Chan
- Institute for Research, Development and Innovation, International Medical University, Jalan Jalil Perkasa 19, 126 Jalan 19/155B, Bukit Jalil, 57000, Kuala Lumpur, Malaysia.
| | - Jeremy Kean Yi Yap
- School of Postgraduate Studies, International Medical University, Jalan Jalil Perkasa 19, Bukit Jalil, 57000, Kuala Lumpur, Malaysia
| | - Chun Wai Mai
- Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, Jalan Jalil Perkasa 19, Bukit Jalil, 57000, Kuala Lumpur, Malaysia
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Seib KL, Srikhanta YN, Atack JM, Jennings MP. Epigenetic Regulation of Virulence and Immunoevasion by Phase-Variable Restriction-Modification Systems in Bacterial Pathogens. Annu Rev Microbiol 2020; 74:655-671. [PMID: 32689914 DOI: 10.1146/annurev-micro-090817-062346] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Human-adapted bacterial pathogens use a mechanism called phase variation to randomly switch the expression of individual genes to generate a phenotypically diverse population to adapt to challenges within and between human hosts. There are increasing reports of restriction-modification systems that exhibit phase-variable expression. The outcome of phase variation of these systems is global changes in DNA methylation. Analysis of phase-variable Type I and Type III restriction-modification systems in multiple human-adapted bacterial pathogens has demonstrated that global changes in methylation regulate the expression of multiple genes. These systems are called phasevarions (phase-variable regulons). Phasevarion switching alters virulence phenotypes and facilitates evasion of host immune responses. This review describes the characteristics of phasevarions and implications for pathogenesis and immune evasion. We present and discuss examples of phasevarion systems in the major human pathogens Haemophilus influenzae, Neisseria meningitidis, Neisseria gonorrhoeae, Helicobacter pylori, Moraxella catarrhalis, and Streptococcus pneumoniae.
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Affiliation(s)
- Kate L Seib
- Institute for Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia; ,
| | - Yogitha N Srikhanta
- Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia
| | - John M Atack
- Institute for Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia; ,
| | - Michael P Jennings
- Institute for Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia; ,
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Identification of new regulatory genes through expression pattern analysis of a global RNA-seq dataset from a Helicobacter pylori co-culture system. Sci Rep 2020; 10:11506. [PMID: 32661418 PMCID: PMC7359330 DOI: 10.1038/s41598-020-68439-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Accepted: 06/22/2020] [Indexed: 02/07/2023] Open
Abstract
Helicobacter pylori is a gram-negative bacterium that persistently colonizes the human stomach by inducing immunoregulatory responses. We have used a novel platform that integrates a bone marrow-derived macrophage and live H. pylori co-culture with global time-course transcriptomics analysis to identify new regulatory genes based on expression patterns resembling those of genes with known regulatory function. We have used filtering criteria based on cellular location and novelty parameters to select 5 top lead candidate targets. Of these, Plexin domain containing 2 (Plxdc2) was selected as the top lead immunoregulatory target. Loss of function studies with in vivo models of H. pylori infection as well as a chemically-induced model of colitis, confirmed its predicted regulatory function and significant impact on modulation of the host immune response. Our integrated bioinformatics analyses and experimental validation platform has enabled the discovery of new immunoregulatory genes. This pipeline can be used for the identification of genes with therapeutic applications for treating infectious, inflammatory, and autoimmune diseases.
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Yin H, Chu A, Liu S, Yuan Y, Gong Y. Identification of DEGs and transcription factors involved in H. pylori-associated inflammation and their relevance with gastric cancer. PeerJ 2020; 8:e9223. [PMID: 32547867 PMCID: PMC7275685 DOI: 10.7717/peerj.9223] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Accepted: 04/29/2020] [Indexed: 12/16/2022] Open
Abstract
Background Previous studies have indicated that chronic inflammation linked to H. pylori infection is the leading causes for gastric cancer (GC). However, the exact mechanism is not entirely clear until now. Purpose To identify the key molecules and TFs involved in H. pylori infection and to provide new insights into H. pylori-associated carcinogenesis and lay the groundwork for the prevention of GC. Results GO and KEGG analysis revealed that the DEGs of Hp+-NAG were mainly associated with the immune response, chemokine activity, extracellular region and rheumatoid arthritis pathway. The DEGs of Hp+-AG-IM were related to the apical plasma membrane, intestinal cholesterol absorption, transporter activity and fat digestion and absorption pathway. In Hp+-NAG network, the expression of TNF, CXCL8, MMP9, CXCL9, CXCL1, CCL20, CTLA4, CXCL2, C3, SAA1 and FOXP3, JUN had statistical significance between normal and cancer in TCGA database. In Hp+-AG-IM network the expression of APOA4, GCG, CYP3A4, XPNPEP2 and FOXP3, JUN were statistically different in the comparison of normal and cancer in TCGA database. FOXP3 were negatively associated with overall survival, and the association for JUN was positive. Conclusion The current study identified key DEGs and their transcriptional regulatory networks involved in H. pylori-associated NAG, AG-IM and GC and found that patients with higher expressed FOXP3 or lower expressed JUN had shorter overall survival time. Our study provided new directions for inflammation-associated oncogenic transformation involved in H. pylori infection.
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Affiliation(s)
- Honghao Yin
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, Shenyang, LiaoNing, China.,Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department, the First Hospital of China Medical University, Shenyang, LiaoNing, China.,Key Laboratory of GI Cancer Etiology and Prevention in Liaoning Province, the First Hospital of China Medical University, Shenyang, LiaoNing, China
| | - Aining Chu
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, Shenyang, LiaoNing, China.,Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department, the First Hospital of China Medical University, Shenyang, LiaoNing, China.,Key Laboratory of GI Cancer Etiology and Prevention in Liaoning Province, the First Hospital of China Medical University, Shenyang, LiaoNing, China
| | - Songyi Liu
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, Shenyang, LiaoNing, China.,Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department, the First Hospital of China Medical University, Shenyang, LiaoNing, China.,Key Laboratory of GI Cancer Etiology and Prevention in Liaoning Province, the First Hospital of China Medical University, Shenyang, LiaoNing, China
| | - Yuan Yuan
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, Shenyang, LiaoNing, China.,Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department, the First Hospital of China Medical University, Shenyang, LiaoNing, China.,Key Laboratory of GI Cancer Etiology and Prevention in Liaoning Province, the First Hospital of China Medical University, Shenyang, LiaoNing, China
| | - Yuehua Gong
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, Shenyang, LiaoNing, China.,Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department, the First Hospital of China Medical University, Shenyang, LiaoNing, China.,Key Laboratory of GI Cancer Etiology and Prevention in Liaoning Province, the First Hospital of China Medical University, Shenyang, LiaoNing, China
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Schacher K, Spotts H, Correia C, Walelign S, Tesfaye M, Desta K, Tsegaye A, Taye B. Individual and household correlates of Helicobacter pylori infection among Young Ethiopian children in Ziway, Central Ethiopia. BMC Infect Dis 2020; 20:310. [PMID: 32334539 PMCID: PMC7183626 DOI: 10.1186/s12879-020-05043-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Accepted: 04/16/2020] [Indexed: 01/17/2023] Open
Abstract
Background Investigating distinct individual- and household-level risk factors for acquiring Helicobacter pylori (H. pylori) infection can inform disease prevention efforts and implicate possible routes of transmission. This study determined the magnitude of H. pylori infection among schoolchildren in Ziway, central Ethiopia and identified personal and household correlates of H. pylori infection in young Ethiopian children. Methods A total of 434 schoolchildren participated in this cross-sectional study. Infection status was assessed using antigen and antibody rapid tests. Demographic and lifestyle information was obtained from parents via an interviewer-led questionnaire. Univariate and multivariate logistic regressions were performed to assess the relationships between potential individual- and household-level risk factors and H. pylori infection. Results The prevalence of H. pylori infection was 65.7% (285/434). Of the personal variables assessed, the age group 10–14 years was found to be significantly associated with higher odds of H. pylori infection in univariate analysis (COR = 2.22, 95% CI: 1.06–4.66, p = 0.03) and remained positively correlated after adjusting for confounding factors. Of the household-level factors explored, having a traditional pit or no toilet was found to be significantly associated with 3.93-fold higher odds of H. pylori infection (AOR = 3.93, 95% CI: 1.51–10.3, p = 0.01), while the presence of smokers in the household was associated with 68% lower odds of infection (AOR = 0.32, 95% CI: 0.11–0.89, p = 0.03). Conclusion This study from a developing country provides additional evidence for older age as a personal risk factor for H. pylori infection and identifies correlations between socioeconomic and sanitation household factors and positive childhood infection status. The associations reported here support the hypothesized fecal-oralroute of transmission for H. pylori.
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Affiliation(s)
- Kayla Schacher
- Department of Biology, Colgate University, 214 Olin Hall, 13 Oak Dr., Hamilton, NY, 13346, USA
| | - Hannah Spotts
- Department of Biology, Colgate University, 214 Olin Hall, 13 Oak Dr., Hamilton, NY, 13346, USA
| | - Caroline Correia
- Department of Biology, Colgate University, 214 Olin Hall, 13 Oak Dr., Hamilton, NY, 13346, USA
| | - Sosina Walelign
- Addis Ababa University, College of Health Sciences, Department of Medical Laboratory Science, Addis Ababa, Ethiopia
| | - Mehret Tesfaye
- Addis Ababa University, College of Health Sciences, Department of Medical Laboratory Science, Addis Ababa, Ethiopia
| | - Kassu Desta
- Addis Ababa University, College of Health Sciences, Department of Medical Laboratory Science, Addis Ababa, Ethiopia
| | - Aster Tsegaye
- Addis Ababa University, College of Health Sciences, Department of Medical Laboratory Science, Addis Ababa, Ethiopia
| | - Bineyam Taye
- Department of Biology, Colgate University, 214 Olin Hall, 13 Oak Dr., Hamilton, NY, 13346, USA.
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In vitro Anti-Helicobacter pylori Activity of Capsaicin. JOURNAL OF PURE AND APPLIED MICROBIOLOGY 2020. [DOI: 10.22207/jpam.14.1.29] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
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Prinz C, Weber D. MicroRNA (miR) dysregulation during Helicobacter pylori-induced gastric inflammation and cancer development: critical importance of miR-155. Oncotarget 2020; 11:894-904. [PMID: 32206186 PMCID: PMC7075464 DOI: 10.18632/oncotarget.27520] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Accepted: 02/06/2020] [Indexed: 02/03/2023] Open
Abstract
Dysregulation of noncoding microRNA molecules has been associated with immune cell activation in the context of Helicobacter pylori induced gastric inflammation as well as carcinogenesis, but also with downregulation of mismatch repair genes, and may interfere with immune checkpoint proteins that lead to the overexpression of antigens on gastric tumor cells. Numerous miR-molecules have been described as important tools and markers in gastric inflammation and cancer development -including miR-21, miR-143, miR-145, miR-201, and miR-335- all of which are downregulated in gastric tumors, and involved in cell cycle growth or tumor invasion. Among the many microRNAs involved in gastric inflammation, adenocarcinoma development and immune checkpoint regulation, miR-155 is notable in that its upregulation is considered a key marker of chronic gastric inflammation that predisposes a patient to gastric carcinogenesis. Among various other miRs, miR-155 is highly expressed in activated B and T cells and in monocytes/macrophages present in chronic gastric inflammation. Notably, miR-155 was shown to downregulate the expression of certain MMR genes, such as MLH1, MSH2, and MSH6. In tumor-infiltrating miR-155-deficient CD8+ T cells, antibodies against immune checkpoint proteins restored the expression of several derepressed miR-155 targets, suggesting that miR-155 may regulate overlapping pathways to promote antitumor immunity. It may thus be of high clinical impact that gastric pathologies mediated by miR-155 result from its overexpression. This suggests that it may be possible to therapeutically attenuate miR-155 levels for gastric cancer treatment and/or to prevent the progression of chronic gastric inflammation into cancer.
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Affiliation(s)
- Christian Prinz
- Lehrstuhl für Innere Medizin1, University of Witten gGmbH, Helios Universitätsklinikum, D-42283 Wuppertal, Germany
| | - David Weber
- Lehrstuhl für Innere Medizin1, University of Witten gGmbH, Helios Universitätsklinikum, D-42283 Wuppertal, Germany
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