BACKGROUND The mucosal barrier's immune-brain interactions,pivotal for neural development and function,are increasingly recognized for their potential causal and therapeutic relevance to irritable bowel syndrome(I...BACKGROUND The mucosal barrier's immune-brain interactions,pivotal for neural development and function,are increasingly recognized for their potential causal and therapeutic relevance to irritable bowel syndrome(IBS).Prior studies linking immune inflammation with IBS have been inconsistent.To further elucidate this relationship,we conducted a Mendelian randomization(MR)analysis of 731 immune cell markers to dissect the influence of various immune phenotypes on IBS.Our goal was to deepen our understanding of the disrupted brain-gut axis in IBS and to identify novel therapeutic targets.AIM To leverage publicly available data to perform MR analysis on 731 immune cell markers and explore their impact on IBS.We aimed to uncover immunophenotypic associations with IBS that could inform future drug development and therapeutic strategies.METHODS We performed a comprehensive two-sample MR analysis to evaluate the causal relationship between immune cell markers and IBS.By utilizing genetic data from public databases,we examined the causal associations between 731 immune cell markers,encompassing median fluorescence intensity,relative cell abundance,absolute cell count,and morphological parameters,with IBS susceptibility.Sensitivity analyses were conducted to validate our findings and address potential heterogeneity and pleiotropy.RESULTS Bidirectional false discovery rate correction indicated no significant influence of IBS on immunophenotypes.However,our analysis revealed a causal impact of IBS on 30 out of 731 immune phenotypes(P<0.05).Nine immune phenotypes demonstrated a protective effect against IBS[inverse variance weighting(IVW)<0.05,odd ratio(OR)<1],while 21 others were associated with an increased risk of IBS onset(IVW≥0.05,OR≥1).CONCLUSION Our findings underscore a substantial genetic correlation between immune cell phenotypes and IBS,providing valuable insights into the pathophysiology of the condition.These results pave the way for the development of more precise biomarkers and targeted therapies for IBS.Furthermore,this research enriches our comprehension of immune cell roles in IBS pathogenesis,offering a foundation for more effective,personalized treatment approaches.These advancements hold promise for improving IBS patient quality of life and reducing the disease burden on individuals and their families.展开更多
As a large group of cells in a central nervous system, astrocytes have a great influence on ion and energy metabolism in a nervous system. Disorders of neuronal ion and energy metabolism caused by impaired astrocytes ...As a large group of cells in a central nervous system, astrocytes have a great influence on ion and energy metabolism in a nervous system. Disorders of neuronal ion and energy metabolism caused by impaired astrocytes play a key role in the pathogenesis of epilepsy. This paper reviews the existing computational models of epileptogenesis resulting from impaired astrocytes and presents several open perspectives with regard to ion and energy metabolism-induced epileptogenesis in a neuron-astrocyte-capillary coupled model.展开更多
BACKGROUND Food antigens have been shown to participate in the etiopathogenesis of inflammatory bowel disease (IBD),but their clinical value in IBD is still unclear.AIM To analyze the levels of specific immunoglobulin...BACKGROUND Food antigens have been shown to participate in the etiopathogenesis of inflammatory bowel disease (IBD),but their clinical value in IBD is still unclear.AIM To analyze the levels of specific immunoglobulin G (IgG) and E (IgE) antibodies against food antigens in IBD patients and to determine their clinical value in the pathogenesis of IBD.METHODS We performed a retrospective study based on patients who visited the First Affiliated Hospital of Nanjing Medical University between August 2016 and January 2018.A total of 137 IBD patients,including 40 patients with ulcerative colitis (UC) and 97 patients with Crohn’s disease (CD),and 50 healthy controls (HCs),were recruited.Serum food-specific IgG antibodies were detected by semiquantitative enzyme-linked immunosorbent assay,and serum food-specific IgE antibodies were measured by Western blot.The value of food-specific IgG antibodies was compared among different groups,and potent factors related to these antibodies were explored by binary logistic regression.RESULTS Food-specific IgG antibodies were detected in 57.5% of UC patients,in 90.72% of CD patients and in 42% of HCs.A significantly high prevalence and titer of foodspecific IgG antibodies were observed in CD patients compared to UC patients and HCs.The number of IgG-positive foods was greater in CD and UC patients than in HCs (CD vs HCs,P = 0.000;UC vs HCs,P = 0.029).The top five food antigens that caused positive specific IgG antibodies in CD patients were tomato (80.68%),corn (69.32%),egg (63.64%),rice (61.36%),and soybean (46.59%).The foods that caused positive specific IgG antibodies in UC patients were egg (60.87%),corn (47.83%),tomato (47.83%),rice (26.09%),and soybean (21.74%).Significantly higher levels of total food-specific IgG were detected in IBD patients treated with anti-TNFα therapy compared to patients receiving steroids and immunosuppressants (anti-TNFα vs steroids,P = 0.000;anti-TNFα vs immunosuppressants,P = 0.000;anti-TNFα vs steroids + immunosuppressants,P = 0.003).A decrease in food-specific IgG levels was detected in IBD patients after receiving anti-TNFα therapy (P = 0.007).Patients who smoked and CD patients were prone to developing serum food-specific IgG antibodies [Smoke: OR (95%CI): 17.6 (1.91-162.26),P = 0.011;CD patients: OR (95%CI): 12.48 (3.45-45.09),P = 0.000].There was no difference in the prevalence of food-specific IgE antibodies among CD patients (57.1%),UC patients (65.2%) and HCs (60%)(P = 0.831).CONCLUSION CD patients have a higher prevalence of food-specific IgG antibodies than UC patients and HCs.IBD patients are prone to rice,corn,tomato and soybean intolerance.Smoking may be a risk factor in the occurrence of food-specific IgG antibodies.Food-specific IgG antibodies may be a potential method in the diagnosis and management of food intolerance in IBD.展开更多
Hepatocellular carcinoma(HCC)is one of the most prevalent malignant cancers worldwide.Epithelialmesenchymal transition(EMT),which endows epithelial cells with mesenchymal properties,plays an important role in the earl...Hepatocellular carcinoma(HCC)is one of the most prevalent malignant cancers worldwide.Epithelialmesenchymal transition(EMT),which endows epithelial cells with mesenchymal properties,plays an important role in the early stages of metastasis.Conventional cancer therapies have promising effects,but issues remain,such as high rates of metastasis and drug resistance.Thus,exploring and evaluating new therapies is an urgent need.Traditional Chinese medicines(TCMs)have been acknowledged for their multi-target and coordinated intervention effects against HCC.Accumulating evidence indicates that TCM can inhibit the malignancy of cells and the progression of EMT in HCC.However,studies on the effects of TCM on EMT in HCC are scarce.In this review,we summarized recent developments in anti-EMT TCMs and formulae,focusing on their underlying pharmacological mechanisms,to provide a foundation for further research on the exact mechanisms through which TCM affects EMT in HCC.展开更多
To the Editor:Sepsis is defined as the life-threatening organ dysfunction caused by dysregulated host response to infection,eventually leading to multiple organ dysfunction syndrome.The gut,which is considered to play...To the Editor:Sepsis is defined as the life-threatening organ dysfunction caused by dysregulated host response to infection,eventually leading to multiple organ dysfunction syndrome.The gut,which is considered to play a significant role during sepsis,is defined as the motor of sepsis.展开更多
Traditional Chinese medicine,as a complementary and alternative medicine,has been practiced for thousands of years in China and possesses remarkable clinical efficacy.Thus,systematic analysis and examination of the me...Traditional Chinese medicine,as a complementary and alternative medicine,has been practiced for thousands of years in China and possesses remarkable clinical efficacy.Thus,systematic analysis and examination of the mechanistic links between Chinese herbal medicine(CHM)and the complex human body can benefit contemporary understandings by carrying out qualitative and quantitative analysis.With increasing attention,the approach of network pharmacology has begun to unveil the mystery of CHM by constructing the heterogeneous network relationship of“herb-compound-target-pathway,”which corresponds to the holistic mechanisms of CHM.By integrating computational techniques into network pharmacology,the efficiency and accuracy of active compound screening and target fishing have been improved at an unprecedented pace.This review dissects the core innovations to the network pharmacology approach that were developed in the years since 2015 and highlights how this tool has been applied to understanding the coronavirus disease 2019 and refining the clinical use of CHM to combat it.展开更多
文摘BACKGROUND The mucosal barrier's immune-brain interactions,pivotal for neural development and function,are increasingly recognized for their potential causal and therapeutic relevance to irritable bowel syndrome(IBS).Prior studies linking immune inflammation with IBS have been inconsistent.To further elucidate this relationship,we conducted a Mendelian randomization(MR)analysis of 731 immune cell markers to dissect the influence of various immune phenotypes on IBS.Our goal was to deepen our understanding of the disrupted brain-gut axis in IBS and to identify novel therapeutic targets.AIM To leverage publicly available data to perform MR analysis on 731 immune cell markers and explore their impact on IBS.We aimed to uncover immunophenotypic associations with IBS that could inform future drug development and therapeutic strategies.METHODS We performed a comprehensive two-sample MR analysis to evaluate the causal relationship between immune cell markers and IBS.By utilizing genetic data from public databases,we examined the causal associations between 731 immune cell markers,encompassing median fluorescence intensity,relative cell abundance,absolute cell count,and morphological parameters,with IBS susceptibility.Sensitivity analyses were conducted to validate our findings and address potential heterogeneity and pleiotropy.RESULTS Bidirectional false discovery rate correction indicated no significant influence of IBS on immunophenotypes.However,our analysis revealed a causal impact of IBS on 30 out of 731 immune phenotypes(P<0.05).Nine immune phenotypes demonstrated a protective effect against IBS[inverse variance weighting(IVW)<0.05,odd ratio(OR)<1],while 21 others were associated with an increased risk of IBS onset(IVW≥0.05,OR≥1).CONCLUSION Our findings underscore a substantial genetic correlation between immune cell phenotypes and IBS,providing valuable insights into the pathophysiology of the condition.These results pave the way for the development of more precise biomarkers and targeted therapies for IBS.Furthermore,this research enriches our comprehension of immune cell roles in IBS pathogenesis,offering a foundation for more effective,personalized treatment approaches.These advancements hold promise for improving IBS patient quality of life and reducing the disease burden on individuals and their families.
基金Project supported by the National Natural Science Foundation of China(Grant No.11772242)。
文摘As a large group of cells in a central nervous system, astrocytes have a great influence on ion and energy metabolism in a nervous system. Disorders of neuronal ion and energy metabolism caused by impaired astrocytes play a key role in the pathogenesis of epilepsy. This paper reviews the existing computational models of epileptogenesis resulting from impaired astrocytes and presents several open perspectives with regard to ion and energy metabolism-induced epileptogenesis in a neuron-astrocyte-capillary coupled model.
基金Supported by the National Natural Science Foundation of China,No.81770553Science and Technology Development Fund of Nanjing Medical University,No.NMUB2018291
文摘BACKGROUND Food antigens have been shown to participate in the etiopathogenesis of inflammatory bowel disease (IBD),but their clinical value in IBD is still unclear.AIM To analyze the levels of specific immunoglobulin G (IgG) and E (IgE) antibodies against food antigens in IBD patients and to determine their clinical value in the pathogenesis of IBD.METHODS We performed a retrospective study based on patients who visited the First Affiliated Hospital of Nanjing Medical University between August 2016 and January 2018.A total of 137 IBD patients,including 40 patients with ulcerative colitis (UC) and 97 patients with Crohn’s disease (CD),and 50 healthy controls (HCs),were recruited.Serum food-specific IgG antibodies were detected by semiquantitative enzyme-linked immunosorbent assay,and serum food-specific IgE antibodies were measured by Western blot.The value of food-specific IgG antibodies was compared among different groups,and potent factors related to these antibodies were explored by binary logistic regression.RESULTS Food-specific IgG antibodies were detected in 57.5% of UC patients,in 90.72% of CD patients and in 42% of HCs.A significantly high prevalence and titer of foodspecific IgG antibodies were observed in CD patients compared to UC patients and HCs.The number of IgG-positive foods was greater in CD and UC patients than in HCs (CD vs HCs,P = 0.000;UC vs HCs,P = 0.029).The top five food antigens that caused positive specific IgG antibodies in CD patients were tomato (80.68%),corn (69.32%),egg (63.64%),rice (61.36%),and soybean (46.59%).The foods that caused positive specific IgG antibodies in UC patients were egg (60.87%),corn (47.83%),tomato (47.83%),rice (26.09%),and soybean (21.74%).Significantly higher levels of total food-specific IgG were detected in IBD patients treated with anti-TNFα therapy compared to patients receiving steroids and immunosuppressants (anti-TNFα vs steroids,P = 0.000;anti-TNFα vs immunosuppressants,P = 0.000;anti-TNFα vs steroids + immunosuppressants,P = 0.003).A decrease in food-specific IgG levels was detected in IBD patients after receiving anti-TNFα therapy (P = 0.007).Patients who smoked and CD patients were prone to developing serum food-specific IgG antibodies [Smoke: OR (95%CI): 17.6 (1.91-162.26),P = 0.011;CD patients: OR (95%CI): 12.48 (3.45-45.09),P = 0.000].There was no difference in the prevalence of food-specific IgE antibodies among CD patients (57.1%),UC patients (65.2%) and HCs (60%)(P = 0.831).CONCLUSION CD patients have a higher prevalence of food-specific IgG antibodies than UC patients and HCs.IBD patients are prone to rice,corn,tomato and soybean intolerance.Smoking may be a risk factor in the occurrence of food-specific IgG antibodies.Food-specific IgG antibodies may be a potential method in the diagnosis and management of food intolerance in IBD.
基金supported by Natural Science Foundation of Shanghai Minhang District(No.2019MHZ062)Shanghai Key Specialty Construction Project of Clinical Pharmacy(Minhang District,No.2018YXZDZK)+1 种基金National Natural Science Foundation of China(No.81700065)the Talent Development Special Funds(leading talent)project of Shanghai Minhang District。
文摘Hepatocellular carcinoma(HCC)is one of the most prevalent malignant cancers worldwide.Epithelialmesenchymal transition(EMT),which endows epithelial cells with mesenchymal properties,plays an important role in the early stages of metastasis.Conventional cancer therapies have promising effects,but issues remain,such as high rates of metastasis and drug resistance.Thus,exploring and evaluating new therapies is an urgent need.Traditional Chinese medicines(TCMs)have been acknowledged for their multi-target and coordinated intervention effects against HCC.Accumulating evidence indicates that TCM can inhibit the malignancy of cells and the progression of EMT in HCC.However,studies on the effects of TCM on EMT in HCC are scarce.In this review,we summarized recent developments in anti-EMT TCMs and formulae,focusing on their underlying pharmacological mechanisms,to provide a foundation for further research on the exact mechanisms through which TCM affects EMT in HCC.
基金grants from the Anhui Province Natural Science Foundation for Youth(No.1908085QH360)the"Peak”Training Program for Scientific Research of Yijishan Hospital,Wannan Medical College(Nos.GF2019J03 and GF2019G08).
文摘To the Editor:Sepsis is defined as the life-threatening organ dysfunction caused by dysregulated host response to infection,eventually leading to multiple organ dysfunction syndrome.The gut,which is considered to play a significant role during sepsis,is defined as the motor of sepsis.
基金supported by grants from the National Natural Science Foundation of China(No.81903786)the Shaanxi Natural Science Foundation of China(No.2021JQ-731)Subject Innovation Team of Shaanxi University of Chinese Medicine(No.2019-YL10)。
文摘Traditional Chinese medicine,as a complementary and alternative medicine,has been practiced for thousands of years in China and possesses remarkable clinical efficacy.Thus,systematic analysis and examination of the mechanistic links between Chinese herbal medicine(CHM)and the complex human body can benefit contemporary understandings by carrying out qualitative and quantitative analysis.With increasing attention,the approach of network pharmacology has begun to unveil the mystery of CHM by constructing the heterogeneous network relationship of“herb-compound-target-pathway,”which corresponds to the holistic mechanisms of CHM.By integrating computational techniques into network pharmacology,the efficiency and accuracy of active compound screening and target fishing have been improved at an unprecedented pace.This review dissects the core innovations to the network pharmacology approach that were developed in the years since 2015 and highlights how this tool has been applied to understanding the coronavirus disease 2019 and refining the clinical use of CHM to combat it.
