Background &Aims: Proinflammatory interleukin (IL)-1 gene polymorphisms asso ciated with high levels of IL-1βactivity increase the risk for hypochlorhydria and distal gastric carcinoma. The aim of this study was ...Background &Aims: Proinflammatory interleukin (IL)-1 gene polymorphisms asso ciated with high levels of IL-1βactivity increase the risk for hypochlorhydria and distal gastric carcinoma. The aim of this study was to evaluate whether car riers of these polymorphic genes are protected against gastroesophageal reflux d isease (GERD). TNFA-308 polymorphisms were also studied. Methods: We prospectiv ely evaluated 385 patients without gastric cancer and peptic ulcer. Of these pat ients,383 (98 with GERD and 285 controls) were successfully genotyped for all cy tokines studied. The cagA status of Helicobacter pylori isolates was determined by polymerase chain reaction (PCR). IL1B-511/-31, IL1RN, and TNFA-308 polymor phisms were genotyped by PCR, PCR/restriction fragment length polymorphism, or PCR/confronting 2-pair primers. Histologic g astritis was assessed according to the updated Sydney system. The role of the pr oinflammatory cytokine genotypes in the genesis of GERD was evaluated before and after stratification by H. pylori status in logistic regression models controll ing for confounding factors. Results: IL1B-31 (a near-complete linkage disequi librium between polymorphism at -31 and -511 was found) and IL1RN*2 allele po lymorphisms were associated with GERD. After stratification, in the group of H. pylori-positive patients, cagA-positive status,IL1B-31 polymorphic alleles, I L1RN*2 alleles, and the degree of corpus gastritis were negatively associated w ith GERD. In the H. pylori-negative group, IL1B-31C/C genotype was inversely a ssociated with GERD even after adjustment for age and sex. Conclusions: This stu dy provides evidence supporting the independent protective role of cagA-positiv e H.pylori status and IL1B and ILRN allele polymorphisms against GERD.展开更多
Objective:The objective of this study was to determine the level of methotrexate(MTX)toxicity in the intestines of mice and to evaluate the protective effect of probiotics composed of Streptococcus,Bifidobacterium,and...Objective:The objective of this study was to determine the level of methotrexate(MTX)toxicity in the intestines of mice and to evaluate the protective effect of probiotics composed of Streptococcus,Bifidobacterium,and Lactobacillus species on intestinal cells during MTX treatment.Methods:Mice were divided into three groups:control,MTX group(received MTX injections),and MTX+probiotics group(received MTX injections along with a diet containing probiotics).Morphological and histological changes,the level of mitochondrial DNA(mtDNA)damage,the level of lipid peroxidation products,and gene expression in the mice’s small intestine were assessed.Results:We demonstrated that intraperitoneal MTX injections significantly increased mtDNA damage in the liver(p<0.001),small intestine(p<0.001),and blood of mice(p<0.01).MTX elevated the quantity of lipid peroxidation products in the liver and small intestine,indicating its strong prooxidative properties.MTX induced structural changes in the mice’s intestines,characterized by leukocytic infiltration of tissues.Probiotic therapy in mice partially mitigated the morphological and histological changes in the small intestine induced by MTX,reduced oxidative stress,and promoted increased expression of quinone oxidoreductase 1(Nqo1),which participates in both cell protection against oxidative stress and drug/xenobiotic detoxification.Probiotics prevented the upregulation of the proinflammatory cytokine IL-1b in the small intestine and induced increased expression of genes associated with the Nuclear factor erythroid 2-related factor 2/Antioxidant response element(Nrf2/ARE)pathway,an important mechanism of cell protection.Conclusions:Probiotics can be considered an effective approach to reducing the toxicity of MTX during psoriasis or cancer treatment.展开更多
Background: Triple-negative breast cancer(TNBC), which is so called because of the lack of estrogen receptors(ER), progesterone receptors(PR), and human epidermal growth factor receptor 2(HER2) receptors on the cancer...Background: Triple-negative breast cancer(TNBC), which is so called because of the lack of estrogen receptors(ER), progesterone receptors(PR), and human epidermal growth factor receptor 2(HER2) receptors on the cancer cells, accounts for 10%–15% of all breast cancers. The heterogeneity of the tumor microenvironment is high.However, the role of plasma cells controlling the tumor migration progression in TNBC is still not fully understood.Methods: We analyzed single-cell RNA sequencing data from five HER2 positive, 12ER positive/PR positive, and nine TNBC samples. The potential targets were validated by immunohistochemistry.Results: Plasma cells were enriched in TNBC samples, which was consistent with validation using data from The Cancer Genome Atlas. Cell communication analysis revealed that plasma cells interact with T cells through the intercellular adhesion molecule 2–integrin–aLb2 complex, and then release interleukin 1 beta(IL1B), as verified by immunohistochemistry, ultimately promoting tumor growth.Conclusion: Our results revealed the role of plasma cells in TNBC and identified IL1B as a new prognostic marker for TNBC.展开更多
Rheumatoid arthritis (RA) is an immune-mediated chronic inflammatory disease that causes huge destruction to human body. IL1B encodes key mediator IL-1β protein, which plays an important role in the pathogenesis of i...Rheumatoid arthritis (RA) is an immune-mediated chronic inflammatory disease that causes huge destruction to human body. IL1B encodes key mediator IL-1β protein, which plays an important role in the pathogenesis of inflammatory syndromes. The aim of this study was to evaluate the association between IL1B polymorphisms and RA. A meta-analysis was performed on the association between three IL1B polymorphisms (IL1B-31: rs1143627;IL1B-511: rs16944;IL1B + 3954: rs1143634) and RA. A trend of significant association was observed between IL1B + 3954 and RA (p = 0.06, odd ratio (OR) = 1.19, 95% confidential interval (CI) = 1.00-1.42). A significant association was found in Europeans under the dominant model between IL1B-511T and RA (p = 0.03, OR = 0.89, 95% CI = 0.81-0.99). Our meta-analysis indicated that IL1B ? 511-T played a protective role against RA in Europeans, and that IL1B + 3954-T had the potential to increase the risk of RA. Future large-scale studies should be considered to confirm the association between IL1B polymorphisms and RA.展开更多
The pandemic of COVID-19 caused by SARS-CoV-2 has made serious threats to the public health.Antibodies have been considered as promising therapeutics for the prevention and treatment of pathogens.So far,effectors that...The pandemic of COVID-19 caused by SARS-CoV-2 has made serious threats to the public health.Antibodies have been considered as promising therapeutics for the prevention and treatment of pathogens.So far,effectors that can influence the sustainability of SARS-CoV-2 specific antibodies in COVID-19 patients are still unclear.In this paper,we attempted to find potential key factors correlated with SARS-CoV-2 specific antibodies.Transcriptional analysis with the peripheral blood mononuclear cells(PBMCs)revealed proportional changes of immune cell subsets in COVID-19 convalescent patients,including a substantial decrease of monocytes and evident increase of dendritic cells(DCs).Moreover,we found that the gene expressions of chemokines associated with monocyte/macrophage were significantly up-regulated during the COVID-19 recovery phase.Most importantly,we found a set of 27 immune genes corresponding to a comparatively lower amount of SARS-CoV-2 specific antibodies,and identified two hub genes,IL1βand IL6,the protein expressions of which exhibited negative correlation with the immunoglobulin G(IgG)levels in COVID-19 convalescent sera.In addition,we found that high expressions of these 2 hub genes during the convalescent stage were negatively associated with the plasma cell marker CD138.Our study presented two key inflammatory factors correlated to the low level of SARS-CoV-2 specific antibodies,which indicated the potential regulatory process of plasmatic antibodies levels in some COVID-19 convalescent patients.展开更多
文摘IL1B（Interleukin 1 beta）是一种对抗感染的前炎症因子，在肿瘤的发生发展中起着重要的作用。IL1B基因启动子区-31C／T多态性位点通过影响IL1B的转录参与癌症的发生。针对已有的研究存在结论不一致的现状，为了阐明两者之间的关系，我们对47篇发表的病例对照研究进行meta分析，其中包括11125病例和14415例对照。比值比（Odds Ratio，OR）和95％可信区间（CI）用来评估多态性位点与癌症风险的关联程度。在所有的对比中没有发现此多态性位点与所有癌症相关联。通过分层分析发现，携带C等位基因的个体比不带C等位基因的个体患肝癌的风险低（CCVS TT：OR=0．87，95％CI：0．77—0．98，Phetermgrenty=0．103；TC vs TT：OR=0．77，95％CI：0．62-0．95，Phetermgrenty=0．734；TC＋CC vs TT：OR=0．74，95％CI：0．61～0．91，Phetermgrenty=0．472）。同样，C／C基因型个体相比T，T基因型个体患胃癌风险低（OR=0．87，95％CI：0．77-0．98，Rhetermgrenty=0．103）。运用隐性模型，患胃癌的风险显著下降（OR=0．88，95％CI：0．80～0．97，Phetermgrenty=0．158），在欧洲人群（OR=0．84，95％CI：0．73-0．97,Phetermgrenty=0．070）和感染-配埘研究（OR=0．75，95％CI：0．60～0．94，Phetermgrenty=0．220）中都发现有显著下降的风险；在乳腺癌中有显著增加的风险（OR=1．34，95％CI：1．18～1．61，Phetermgrenty=0．116）。虽然一些适度偏倚不能消除，此meta分析显示IL1B-3IC基因型是癌症发生的保护因素，特别是在感染人群中。
文摘Background &Aims: Proinflammatory interleukin (IL)-1 gene polymorphisms asso ciated with high levels of IL-1βactivity increase the risk for hypochlorhydria and distal gastric carcinoma. The aim of this study was to evaluate whether car riers of these polymorphic genes are protected against gastroesophageal reflux d isease (GERD). TNFA-308 polymorphisms were also studied. Methods: We prospectiv ely evaluated 385 patients without gastric cancer and peptic ulcer. Of these pat ients,383 (98 with GERD and 285 controls) were successfully genotyped for all cy tokines studied. The cagA status of Helicobacter pylori isolates was determined by polymerase chain reaction (PCR). IL1B-511/-31, IL1RN, and TNFA-308 polymor phisms were genotyped by PCR, PCR/restriction fragment length polymorphism, or PCR/confronting 2-pair primers. Histologic g astritis was assessed according to the updated Sydney system. The role of the pr oinflammatory cytokine genotypes in the genesis of GERD was evaluated before and after stratification by H. pylori status in logistic regression models controll ing for confounding factors. Results: IL1B-31 (a near-complete linkage disequi librium between polymorphism at -31 and -511 was found) and IL1RN*2 allele po lymorphisms were associated with GERD. After stratification, in the group of H. pylori-positive patients, cagA-positive status,IL1B-31 polymorphic alleles, I L1RN*2 alleles, and the degree of corpus gastritis were negatively associated w ith GERD. In the H. pylori-negative group, IL1B-31C/C genotype was inversely a ssociated with GERD even after adjustment for age and sex. Conclusions: This stu dy provides evidence supporting the independent protective role of cagA-positiv e H.pylori status and IL1B and ILRN allele polymorphisms against GERD.
基金This research was carried out within the State Assignment of the Ministry of Science and Higher Education of the Russian Federation(project FZGW-2024-0003).
文摘Objective:The objective of this study was to determine the level of methotrexate(MTX)toxicity in the intestines of mice and to evaluate the protective effect of probiotics composed of Streptococcus,Bifidobacterium,and Lactobacillus species on intestinal cells during MTX treatment.Methods:Mice were divided into three groups:control,MTX group(received MTX injections),and MTX+probiotics group(received MTX injections along with a diet containing probiotics).Morphological and histological changes,the level of mitochondrial DNA(mtDNA)damage,the level of lipid peroxidation products,and gene expression in the mice’s small intestine were assessed.Results:We demonstrated that intraperitoneal MTX injections significantly increased mtDNA damage in the liver(p<0.001),small intestine(p<0.001),and blood of mice(p<0.01).MTX elevated the quantity of lipid peroxidation products in the liver and small intestine,indicating its strong prooxidative properties.MTX induced structural changes in the mice’s intestines,characterized by leukocytic infiltration of tissues.Probiotic therapy in mice partially mitigated the morphological and histological changes in the small intestine induced by MTX,reduced oxidative stress,and promoted increased expression of quinone oxidoreductase 1(Nqo1),which participates in both cell protection against oxidative stress and drug/xenobiotic detoxification.Probiotics prevented the upregulation of the proinflammatory cytokine IL-1b in the small intestine and induced increased expression of genes associated with the Nuclear factor erythroid 2-related factor 2/Antioxidant response element(Nrf2/ARE)pathway,an important mechanism of cell protection.Conclusions:Probiotics can be considered an effective approach to reducing the toxicity of MTX during psoriasis or cancer treatment.
基金funded by Young Elite Scientists Sponsorship Program by Beijing Association for science and technology(Grant No.BYESS2023226)。
文摘Background: Triple-negative breast cancer(TNBC), which is so called because of the lack of estrogen receptors(ER), progesterone receptors(PR), and human epidermal growth factor receptor 2(HER2) receptors on the cancer cells, accounts for 10%–15% of all breast cancers. The heterogeneity of the tumor microenvironment is high.However, the role of plasma cells controlling the tumor migration progression in TNBC is still not fully understood.Methods: We analyzed single-cell RNA sequencing data from five HER2 positive, 12ER positive/PR positive, and nine TNBC samples. The potential targets were validated by immunohistochemistry.Results: Plasma cells were enriched in TNBC samples, which was consistent with validation using data from The Cancer Genome Atlas. Cell communication analysis revealed that plasma cells interact with T cells through the intercellular adhesion molecule 2–integrin–aLb2 complex, and then release interleukin 1 beta(IL1B), as verified by immunohistochemistry, ultimately promoting tumor growth.Conclusion: Our results revealed the role of plasma cells in TNBC and identified IL1B as a new prognostic marker for TNBC.
文摘Rheumatoid arthritis (RA) is an immune-mediated chronic inflammatory disease that causes huge destruction to human body. IL1B encodes key mediator IL-1β protein, which plays an important role in the pathogenesis of inflammatory syndromes. The aim of this study was to evaluate the association between IL1B polymorphisms and RA. A meta-analysis was performed on the association between three IL1B polymorphisms (IL1B-31: rs1143627;IL1B-511: rs16944;IL1B + 3954: rs1143634) and RA. A trend of significant association was observed between IL1B + 3954 and RA (p = 0.06, odd ratio (OR) = 1.19, 95% confidential interval (CI) = 1.00-1.42). A significant association was found in Europeans under the dominant model between IL1B-511T and RA (p = 0.03, OR = 0.89, 95% CI = 0.81-0.99). Our meta-analysis indicated that IL1B ? 511-T played a protective role against RA in Europeans, and that IL1B + 3954-T had the potential to increase the risk of RA. Future large-scale studies should be considered to confirm the association between IL1B polymorphisms and RA.
基金This study was sponsored by Natural Science Foundation of Chongqing,China(No.cstc2020jcyj-bshX0027),with the donation from Mr Yuling Feng.
文摘The pandemic of COVID-19 caused by SARS-CoV-2 has made serious threats to the public health.Antibodies have been considered as promising therapeutics for the prevention and treatment of pathogens.So far,effectors that can influence the sustainability of SARS-CoV-2 specific antibodies in COVID-19 patients are still unclear.In this paper,we attempted to find potential key factors correlated with SARS-CoV-2 specific antibodies.Transcriptional analysis with the peripheral blood mononuclear cells(PBMCs)revealed proportional changes of immune cell subsets in COVID-19 convalescent patients,including a substantial decrease of monocytes and evident increase of dendritic cells(DCs).Moreover,we found that the gene expressions of chemokines associated with monocyte/macrophage were significantly up-regulated during the COVID-19 recovery phase.Most importantly,we found a set of 27 immune genes corresponding to a comparatively lower amount of SARS-CoV-2 specific antibodies,and identified two hub genes,IL1βand IL6,the protein expressions of which exhibited negative correlation with the immunoglobulin G(IgG)levels in COVID-19 convalescent sera.In addition,we found that high expressions of these 2 hub genes during the convalescent stage were negatively associated with the plasma cell marker CD138.Our study presented two key inflammatory factors correlated to the low level of SARS-CoV-2 specific antibodies,which indicated the potential regulatory process of plasmatic antibodies levels in some COVID-19 convalescent patients.
