OBJECTIVE:To explore the therapeutic effect and target of atractylenolide I(AT-I)on post-infectious irritable bowel syndrome(PI-IBS)rats.METHODS:Therefore,the preliminarily mechanism of AT-I in anti-PI-IBS were first ...OBJECTIVE:To explore the therapeutic effect and target of atractylenolide I(AT-I)on post-infectious irritable bowel syndrome(PI-IBS)rats.METHODS:Therefore,the preliminarily mechanism of AT-I in anti-PI-IBS were first predicted by network pharmacology and molecular docking,then the possible signaling pathways were systematically analyzed.Finally,the potential therapeutic targets and possible signaling pathways of AT-I on PI-IBS in Sprague-Dawley(SD)rat model were verified by experiments.RESULTS:AT-I could alleviate PI-IBS symptoms and reduce the expression of tumor necrosis factorα,interleukin-6 and Interferon-gamma in PI-IBS SD rat model and inhibit the c-Jun N-terminal kinase/inducible nitric oxide synthase(JNK/iNOS)pathway.Notably,AT-I treatment could inhibit the overexpression of polymeraseⅠand transcript release factor(PTRF).CONCLUSION:AT-I could alleviate PI-IBS symptoms through downregulation of PTRF and inhibiting the JNK/iNOS pathway.This study not only provides a scientific basis to clarify the anti-PI-IBS effect of AT-I and its mechanism but also suggests a novel promising therapeutic strategy to treat the PI-IBS.展开更多
Irritable bowel syndrome(IBS)is a commonly encountered chronic functional gastrointestinal(GI)disorder.Approximately 10%of IBS patients can trace the onset of their symptoms to a previous a bout of infectious dysenter...Irritable bowel syndrome(IBS)is a commonly encountered chronic functional gastrointestinal(GI)disorder.Approximately 10%of IBS patients can trace the onset of their symptoms to a previous a bout of infectious dysentery.The appearance of new IBS symptoms following an infectious event is defined as post-infectiousIBS.Indeed,with the World Health Organization estimating between 2 and 4 billion cases annually,infectious diarrheal disease represents an incredible international healthcare burden.Additionally,compounding evidence suggests many commonly encountered enteropathogens as unique triggers behind IBS symptom generation and underlying pathophysiological features.A growing body of work provides evidence supporting a role for pathogen-mediated modifications in the resident intestinal microbiota,epithelial barrier integrity,effector cell functions,and innate and adaptive immune features,all proposed physiological manifestations that can underlie GI abnormalities in IBS.Enteric pathogens must employ a vast array of machinery to evade host protective immune mechanisms,and illicit successful infections.Consequently,the impact of infectious events on host physiology can be multidimensional in terms of anatomical location,functional scope,and duration.This review offers a unique discussion of the mechanisms employed by many commonly encountered enteric pathogens that cause acute disease,but may also lead to the establishment of chronic GI dysfunction compatible with IBS.展开更多
AIM:To investigate the interstitial cells of Cajal(ICC) number using a new rat model.METHODS:Sprague-Dawley rats were assigned to two groups.The first group received gavage with Campylobacter jejuni(C.jejuni) 81-176.T...AIM:To investigate the interstitial cells of Cajal(ICC) number using a new rat model.METHODS:Sprague-Dawley rats were assigned to two groups.The first group received gavage with Campylobacter jejuni(C.jejuni) 81-176.The second group was gavaged with placebo.Three months after clearance of Campylobacter from the stool,precise segments of duodenum,jejunum,and ileum were ligated in self-contained loops of bowel that were preserved in anaerobic bags.Deep muscular plexus ICC(DMP-ICC) were quantified by two blinded readers assessing the tissue in a random,coded order.The number of ICC per villus was compared among controls,Campylobacter recovered rats without small intestinal bacterial overgrowth(SIBO),and Campylobacter recovered rats with SIBO.RESULTS:Three months after recovery,27% of rats gavaged with C.jejuni had SIBO.The rats with SIBO had a lower number of DMP-ICC than controls in the jejunum and ileum.Additionally there appeared to be a density threshold of 0.12 DMP-ICC/villus that was associated with SIBO.If ileal density of DMP-ICC was < 0.12 ICC/villus,54% of rats had SIBO compared to 9% among ileal sections with > 0.12(P<0.05).If the density of ICC was < 0.12 DMP-ICC/villus in more than one location of the bowel,88% of these had SIBO compared to 6% in those who did not(P<0.001).CONCLUSION:In this post-infectious rat model,the development of SIBO appears to be associated with a reduction in DMP-ICC.Further study of this rat model might help understand the pathophysiology of postinfectious irritable bowel syndrome.展开更多
BACKGROUND Post-infectious irritable bowel syndrome(PI-IBS)is generally regarded as a functional disease.Several recent studies have reported the involvement of lowgrade inflammation and immunological dysfunction in P...BACKGROUND Post-infectious irritable bowel syndrome(PI-IBS)is generally regarded as a functional disease.Several recent studies have reported the involvement of lowgrade inflammation and immunological dysfunction in PI-IBS.T helper 17(Th17)polarization occurs in IBS.Adenosine and its receptors participate in intestinal inflammation and immune regulation.AIM To investigate the role of Th17 polarization of CD4+T cells regulated by adenosine 2A receptor(A2AR)in PI-IBS.METHODS A PI-IBS model was established by infecting mice with Trichinella spiralis.The intestinal A2AR and CD4+T lymphocytes were detected by immunohistochemistry,and the inflammatory cytokines were detected by enzyme-linked immunoassay.CD4+T lymphocytes present in the animal’s spleen were separated and cultured with or without A2AR agonist and antagonist.Western blotting and real-time quantitative polymerase chain reaction were performed to determine the effect of A2AR on the cells and intestinal tissue.Cytokine production was determined.The protein and mRNA levels of A2AR associated signaling pathway molecules were also evaluated.Furthermore,A2AR agonist and antagonist were injected into the mouse model and the clinical features were observed.RESULTS The PI-IBS mouse model showed increased expression of ATP and A2AR(P<0.05),and inhibition of A2AR improved the clinical features in PI-IBS,including the abdominal withdrawal reflex and colon transportation test(P<0.05).The number of intestinal CD4+T cells and interleukin-17(IL-17)protein levels increased during PI-IBS,which was reversed by administration of the A2AR antagonist(P<0.05).CD4+T cells expressed A2AR and produced IL-17 in vitro,which was regulated by the A2AR agonist and antagonist.The A2AR antagonist increased the production of IL-17 by CD4+T cells via the Janus kinase-signal transducer and activator of transcriptionreceptor-related orphan receptorγsignaling pathway.CONCLUSION The results of the present study suggested that the upregulation of A2AR increases PI-IBS by promoting the Th17 polarization of CD4+T cells.展开更多
One-hundred years have passed since the original description of the commonly described phenomenon of persistent abdominal symptoms being triggered by an acute enteric infection. This first account was generated out of...One-hundred years have passed since the original description of the commonly described phenomenon of persistent abdominal symptoms being triggered by an acute enteric infection. This first account was generated out of astute observations by Sir Arthur Hurst in World War I. Additional descriptions followed from military and non-military practitioners adding the evidence which has transitioned this recognized condition from association to causation. While mechanistic understanding is an area of active pursuit, this historical accounting of a centuries progress highlights important advances and contributions of military medicine and scientists to advances benefiting global populations.展开更多
The application of traditional Chinese medicines(TCMs)has a history of more than 2000 years,which have the characteristics of multi-component,multi-target,and high safety.Post-infectious cough(PIC)is a respiratory dis...The application of traditional Chinese medicines(TCMs)has a history of more than 2000 years,which have the characteristics of multi-component,multi-target,and high safety.Post-infectious cough(PIC)is a respiratory disease with high incidence.It belongs to subacute cough and accounts for as much as40%–50%.Cough is the main clinical manifestation of PIC.PIC seriously affects people’s life quality because of complex etiology,long-term course of disease,treatment difficulties and other characteristics.Western medicines are based on the principle of symptomatic treatment,so they are often difficult to control PIC fundamentally.These factors could due to that PIC is prolonged and unable to heal repeatedly.TCMs have obvious advantages in treating PIC,with accurate curative effects,less side effects and adverse reactions and are effective in improving PIC-related symptoms and indicators,enhancing patients’life quality and reducing pain.TCMs,guided by holistic concept and syndrome differentiation,advocate determine treatment on the basis of pattern types,and have remarkable clinical treatment effects.As for TCMs etiology,pathogenesis and syndrome types of PIC,TCM scholars have not yet reached a unified standard.However,most of them think that wind pathogen can cause PIC alone,or it can be combined with other evils,which might be the main mechanism of PIC.This paper discusses the advantages and limitations of TCMs in PIC treatment from etiology,pathogenesis,distribution of syndrome types and treatment of TCMs.This article focuses on the treatment methods and pharmacodynamic material basis of wind pathogen,providing ideas in treating PIC of TCMs clinically and innovative drug development.展开更多
Irritable bowel syndrome(IBS) is a common and troublesome disorder in children with an increasing prevalence noted during the past two decades. It has a significant effect on the lives of affected children and their f...Irritable bowel syndrome(IBS) is a common and troublesome disorder in children with an increasing prevalence noted during the past two decades. It has a significant effect on the lives of affected children and their families and poses a significant burden on healthcare systems. Standard symptom-based criteria for diagnosis of pediatric IBS have changed several times during the past two decades and there are some differences in interpreting symptoms between different cultures. This has posed a problem when using them to diagnose IBS in clinical practice. A number of potential patho-physiological mechanisms have been described, but so far the exact underlying etiology of IBS is unclear. A few potential therapeutic modalities have been tested in children and only a small number of them have shown some benefit. In addition, most of the described patho-physiological mechanisms and treatment options are based on adult studies. These have surfaced as challenges when dealing with pediatric IBS and they need to be overcome for effective management of children with IBS. Recently suggested top-down and bottom-up models help integrating reported patho-physiological mechanisms and will provide an opportunity for better understanding of the diseases process. Treatment trials targeting single treatment modalities are unlikely to have clinically meaningful therapeutic effects on IBS with multiple integrating patho-physiologies. Trials focusing on multiple combined pharmacological and non-pharmacological therapies are likely to yield more benefit. In addition to treatment, in the future, attention should be paid for possible prevention strategies for IBS.展开更多
Giardiasis is the most common waterborne parasitic infection of the human intestine worldwide.The etiological agent,Giardia duodenalis(syn.G.intestinalis,G.lamblia),is a flagellated,binucleated protozoan parasite whic...Giardiasis is the most common waterborne parasitic infection of the human intestine worldwide.The etiological agent,Giardia duodenalis(syn.G.intestinalis,G.lamblia),is a flagellated,binucleated protozoan parasite which infects a wide array of mammalian hosts.Human giardiasis is a true cosmopolitan pathogen,with highest prevalence in developing countries.Giardiasis can present with a broad range of clinical manifestations from asymptomatic,to acute or chronic diarrheal disease associated with abdominal pain and nausea.Most infections are self-limiting,although re-infection and chronic infection can occur.Recent evidence indicating that Giardia may cause chronic post-infectious gastrointestinal complications have made it a topic of intense research.The causes of the post-infectious clinical manifestations due to Giardia,even after complete elimination of the parasite,remain obscure.This review offers a state-of-the-art discussion on the long-term consequences of Giardia infections,from extra-intestinal manifestations,growth and cognitive deficiencies,to post-infectious irritable bowel syndrome.The discussion also sheds light on some of the novel mechanisms recently implicated in the production of these postinfectious manifestations.展开更多
Objective:To investigate the impact of the preinduced intestinal heat shock protein 70(HSP70)on the visceral hypersensitivity and abnormal intestinal motility in a post-infectious irritable bowel syndrome(PI-IBS) mous...Objective:To investigate the impact of the preinduced intestinal heat shock protein 70(HSP70)on the visceral hypersensitivity and abnormal intestinal motility in a post-infectious irritable bowel syndrome(PI-IBS) mouse model.Methods:Eighty-four female C57BL/6 mice were randomly assigned to four groups:control group(n=21) and induction+PI-IBS group(n=21),PI-IBS group(n=21) and induction group(n=21).The mice in PI-IBS group were infected in vivo with trichinella spiralis by oral administration.The visceral hypersensitivity and intestinal motility were evaluated respectively with abdominal withdrawal reflex and colon transportation test.The intestinal HSP70 protein and mRNA level was measured by Western blot and realtime PCR.Meanwhile,the intestinal proinflammatory cytokines IL-10 and TNF-α level was detected by ELISA.Results:Compared with their counterparts in PI-IBS group,the animals in the Induction+PI-IBS group show significantly increased intestinal level of HSP70 and obviously ameliorative clinical tigurcs.including abdominal withdrawal reflex score,intestine transportation time and Bristol scores(P<0.05).Meanwhile,the intestinal post-inflammatory cytokines remarkably changed,including increased IL-10 level and decreased TNF-αlevel(P<0.05).Conclusions:Intestinal IISP70 may play a potential protective role through improving the imbalance between the intestinal post-inflammatory and anti-inflammatory cytokines in PI-IBS.展开更多
The Autoimmune Brain1 explains I-Cubed, a shorthand for post-infectious autoimmunity that results from the multiplier effect of infection, immunity and inflammation, when protective immunity becomes the source of auto...The Autoimmune Brain1 explains I-Cubed, a shorthand for post-infectious autoimmunity that results from the multiplier effect of infection, immunity and inflammation, when protective immunity becomes the source of autoimmunity, conditioned by applicable environmental and genetic predisposing factors. In keeping with the post-infectious autoimmune nature of I-Cubed, neurologic and psychiatric symptoms evolve beyond a standard of care course of antibiotic therapy. Extensive serologic, electrophysiological and neuroradiographic diagnostic testing provides clues to areas of central, peripheral and autonomic nervous system, and systemic involvement that guide therapy. A multimodality therapeutic approach employing immune modulatory (Ig) therapy that addresses the underlying mechanisms and not just the symptoms of Cubed disorders is most effective. Representative cases of post-infectious autoimmunity associated with Lyme disease and PANDAS are presented.展开更多
BACKGROUND Immunological dysfunction-induced low-grade inflammation is regarded as one of the predominant pathogenetic mechanisms in post-infectious irritable bowel syndrome(PI-IBS).γδT cells play a crucial role in ...BACKGROUND Immunological dysfunction-induced low-grade inflammation is regarded as one of the predominant pathogenetic mechanisms in post-infectious irritable bowel syndrome(PI-IBS).γδT cells play a crucial role in innate and adaptive immunity.Adenosine receptors expressed on the surface ofγδT cells participate in intestinal inflammation and immunity regulation.AIM To investigate the role ofγδT cell regulated by adenosine 2A receptor(A2AR)in PI-IBS.METHODS The PI-IBS mouse model has been established with Trichinella spiralis(T.spiralis)infection.The intestinal A2AR and A2AR inγδT cells were detected by immunohistochemistry,and the inflammatory cytokines were measured by western blot.The role of A2AR on the isolatedγδT cells,including proliferation,apoptosis,and cytokine production,were evaluated in vitro.Their A2AR expression was measured by western blot and reverse transcription polymerase chain reaction(RT-PCR).The animals were administered with A2AR agonist,or A2AR antagonist.Besides,γδT cells were also injected back into the animals,and the parameters described above were examined,as well as the clinical features.Furthermore,the A2AR-associated signaling pathway molecules were assessed by western blot and RT-PCR.RESULTS PI-IBS mice exhibited elevated ATP content and A2AR expression(P<0.05),and suppression of A2AR enhanced PI-IBS clinical characteristics,indicated by the abdominal withdrawal reflex and colon transportation test.PI-IBS was associated with an increase in intestinal T cells,and cytokine levels of interleukin-1(IL-1),IL-6,IL-17A,and interferon-α(IFN-α).Also,γδT cells expressed A2AR in vitro and generated IL-1,IL-6,IL-17A,and IFN-α,which can be controlled by A2AR agonist and antagonist.Mechanistic studies demonstrated that the A2AR antagonist improved the function ofγδT cells through the PKA/CREB/NF-κB signaling pathway.CONCLUSION Our results revealed that A2AR contributes to the facilitation of PI-IBS by regulating the function ofγδT cells via the PKA/CREB/NF-κB signaling pathway.展开更多
<div style="text-align:justify;"> <span style="font-family:Verdana;"><strong>Background:</strong> Chikungunya fever is an infectious disease that can evolve to a subacute or...<div style="text-align:justify;"> <span style="font-family:Verdana;"><strong>Background:</strong> Chikungunya fever is an infectious disease that can evolve to a subacute or chronic condition, with changes in the daily activities of patients. Drugs that aim to reduce these symptoms are used, such as corticoids (acute phase) and disease-modifying anti-rheumatic drugs (chronic phase). <strong>Objective: </strong>To evaluate the clinical response to drug therapy in the subacute and chronic phase of infection by the Chikungunya virus. <strong>Methodology:</strong> A prospective and a retrospective study with patients with subacute and chronic Chikungunya infection, out at the infection and autoimmunity outpatient clinic at the Nucleus of Tropical Medicine, from January 2016 to December 2019, in the morning of Thursdays. The patient was observed in the Baseline, first and second return, and drugs were introduced according to the stage of the disease with subsequent reassessment. The Visual Analogue Scale (VAS) was applied to all evaluation moments. <strong>Results:</strong> 101 patients were evaluated, and arthralgia was the predominant symptom in the three evaluated moments. According to the VAS, moderate baseline pain was observed in 58.1% and 58.6% of subacute and chronic cases, respectively. On the first return, moderate pain still predominated in 46.2% in subacute cases and 43% in chronic cases. In the second visit, all patients were in the chronic phase of the disease, 43.8% had VAS with no pain. Regarding the number of compromised joints in the Baseline, polyarticular involvement predominated in both subacute (79%) and chronic (74.1%) cases, in the first return, oligoarticular involvement predominated in 53.8% of subacute cases and 54.7% in chronic cases and, the second return, 40.6% of the patients had oligoarticular involvement and 43.8% had no joint involvement. As for the use of medications in the Baseline, 33.4% of subacute cases used antiinflammatory drugs, and 40% of chronic cases used corticosteroids. At the first visit, 25% of chronic patients were already using combined corticosteroids and methotrexate and 15% were using only methotrexate. In the second return, 35.1% used combined methotrexate and corticosteroids, and 64.9% used only methotrexate. Safety in the use of methotrexate was observed in the context of CHIKV treatment, as the number of adverse reactions was minimal (three patients) and the medication was well tolerated. <strong>Conclusion:</strong> It was observed that with the adjustment of the medications, there was a reduction in joint impairment, VAS showed mild pain indexes and in some cases with no pain, showing the benefit of using therapy in subacute and chronic cases and improving quality of life of these users.</span> </div>展开更多
Background Limited data are available in relation to the clinical features of PIBO undergoing prolonged nebulization treat-ment with budesonide, terbutaline and ipratropium bromide. This retrospective study aimed to o...Background Limited data are available in relation to the clinical features of PIBO undergoing prolonged nebulization treat-ment with budesonide, terbutaline and ipratropium bromide. This retrospective study aimed to outline the features of clini-cal, high-resolution computed tomography (HRCT) and pulmonary function test (PFT) of PIBO, undergoing maintenance therapy utilizing a triple nebulization treatment and to determine the factors associated with prognosis. Methods Children diagnosed with PIBO were followed up between April 2014 and March 2017. The clinical features after maintenance nebulization treatment for 12 months were thereafter summarized. Results Thirty patients, 21 boys and 9 girls, were enrolled in the study. The median age of patients was 17.4 months, with a range between 3.0 and 33 months. Persistent coughing and wheezing were detected whilst wheezing and crackles were the common manifestations presented. HRCT scans revealed patchy ground and glass opacity, while PFT showed fixed airway obstruction in all patients. Four patients were lost during follow-up. After treatment, the clinical symptoms were improved greatly in all patients (P<0.01). The mean increase in the percentage of TPEF%TE and VPEF%VE were improved greatly (P < 0.01). Images of the HRCT scan indicated marked improvements in 18 patients (81.8%) in comparison with scans obtained pre-treatment. Conclusions Our data suggest a potential role of long-term nebulization treatment of budesonide, terbutaline, ipratropium bromide on PIBO, due to its efficacy as indicated in the improved clinical symptoms, pulmonary functions and CT manifesta-tions identified in the children. New prospective and controlled studies are required to confirm this proposition.展开更多
Previous reviews have highlighted complementary and alternative medicine therapies that are used to treat irritable bowel syndrome（IBS） based on published clinical trial data.Here the author describes and comments o...Previous reviews have highlighted complementary and alternative medicine therapies that are used to treat irritable bowel syndrome（IBS） based on published clinical trial data.Here the author describes and comments on a number of potentially relevant factors that have been commonly emphasized by practitioners who treat IBS and patients who have the disease.They include gluten and other food allergies,the Candida syndrome and biofilm,interference fields and post-infectious IBS, as well as mind-body factors.展开更多
基金The University Collaborative Innovation Project of Anhui:Creation of a Combined Animal Model of Coronary Heart Disease based on the Theory of Xin'an Medicine(No.GXXT-2020-024)Start-up Funding for Doctoral Research at Wannan Medical College(WYRCQD2018009)Horizontal Project of South Anhui Medical College(H202003)。
文摘OBJECTIVE:To explore the therapeutic effect and target of atractylenolide I(AT-I)on post-infectious irritable bowel syndrome(PI-IBS)rats.METHODS:Therefore,the preliminarily mechanism of AT-I in anti-PI-IBS were first predicted by network pharmacology and molecular docking,then the possible signaling pathways were systematically analyzed.Finally,the potential therapeutic targets and possible signaling pathways of AT-I on PI-IBS in Sprague-Dawley(SD)rat model were verified by experiments.RESULTS:AT-I could alleviate PI-IBS symptoms and reduce the expression of tumor necrosis factorα,interleukin-6 and Interferon-gamma in PI-IBS SD rat model and inhibit the c-Jun N-terminal kinase/inducible nitric oxide synthase(JNK/iNOS)pathway.Notably,AT-I treatment could inhibit the overexpression of polymeraseⅠand transcript release factor(PTRF).CONCLUSION:AT-I could alleviate PI-IBS symptoms through downregulation of PTRF and inhibiting the JNK/iNOS pathway.This study not only provides a scientific basis to clarify the anti-PI-IBS effect of AT-I and its mechanism but also suggests a novel promising therapeutic strategy to treat the PI-IBS.
基金Supported by Natural Sciences and Engineering Research Council of Canada(individual operating and CREATE)
文摘Irritable bowel syndrome(IBS)is a commonly encountered chronic functional gastrointestinal(GI)disorder.Approximately 10%of IBS patients can trace the onset of their symptoms to a previous a bout of infectious dysentery.The appearance of new IBS symptoms following an infectious event is defined as post-infectiousIBS.Indeed,with the World Health Organization estimating between 2 and 4 billion cases annually,infectious diarrheal disease represents an incredible international healthcare burden.Additionally,compounding evidence suggests many commonly encountered enteropathogens as unique triggers behind IBS symptom generation and underlying pathophysiological features.A growing body of work provides evidence supporting a role for pathogen-mediated modifications in the resident intestinal microbiota,epithelial barrier integrity,effector cell functions,and innate and adaptive immune features,all proposed physiological manifestations that can underlie GI abnormalities in IBS.Enteric pathogens must employ a vast array of machinery to evade host protective immune mechanisms,and illicit successful infections.Consequently,the impact of infectious events on host physiology can be multidimensional in terms of anatomical location,functional scope,and duration.This review offers a unique discussion of the mechanisms employed by many commonly encountered enteric pathogens that cause acute disease,but may also lead to the establishment of chronic GI dysfunction compatible with IBS.
基金Supported by A grant from Beatrice and Samuel A Seaver Foundation as well as the Shoolman Foundation
文摘AIM:To investigate the interstitial cells of Cajal(ICC) number using a new rat model.METHODS:Sprague-Dawley rats were assigned to two groups.The first group received gavage with Campylobacter jejuni(C.jejuni) 81-176.The second group was gavaged with placebo.Three months after clearance of Campylobacter from the stool,precise segments of duodenum,jejunum,and ileum were ligated in self-contained loops of bowel that were preserved in anaerobic bags.Deep muscular plexus ICC(DMP-ICC) were quantified by two blinded readers assessing the tissue in a random,coded order.The number of ICC per villus was compared among controls,Campylobacter recovered rats without small intestinal bacterial overgrowth(SIBO),and Campylobacter recovered rats with SIBO.RESULTS:Three months after recovery,27% of rats gavaged with C.jejuni had SIBO.The rats with SIBO had a lower number of DMP-ICC than controls in the jejunum and ileum.Additionally there appeared to be a density threshold of 0.12 DMP-ICC/villus that was associated with SIBO.If ileal density of DMP-ICC was < 0.12 ICC/villus,54% of rats had SIBO compared to 9% among ileal sections with > 0.12(P<0.05).If the density of ICC was < 0.12 DMP-ICC/villus in more than one location of the bowel,88% of these had SIBO compared to 6% in those who did not(P<0.001).CONCLUSION:In this post-infectious rat model,the development of SIBO appears to be associated with a reduction in DMP-ICC.Further study of this rat model might help understand the pathophysiology of postinfectious irritable bowel syndrome.
基金Supported by National Natural Science Foundation of China,No.81160057,No.81860102,and No.82060102.
文摘BACKGROUND Post-infectious irritable bowel syndrome(PI-IBS)is generally regarded as a functional disease.Several recent studies have reported the involvement of lowgrade inflammation and immunological dysfunction in PI-IBS.T helper 17(Th17)polarization occurs in IBS.Adenosine and its receptors participate in intestinal inflammation and immune regulation.AIM To investigate the role of Th17 polarization of CD4+T cells regulated by adenosine 2A receptor(A2AR)in PI-IBS.METHODS A PI-IBS model was established by infecting mice with Trichinella spiralis.The intestinal A2AR and CD4+T lymphocytes were detected by immunohistochemistry,and the inflammatory cytokines were detected by enzyme-linked immunoassay.CD4+T lymphocytes present in the animal’s spleen were separated and cultured with or without A2AR agonist and antagonist.Western blotting and real-time quantitative polymerase chain reaction were performed to determine the effect of A2AR on the cells and intestinal tissue.Cytokine production was determined.The protein and mRNA levels of A2AR associated signaling pathway molecules were also evaluated.Furthermore,A2AR agonist and antagonist were injected into the mouse model and the clinical features were observed.RESULTS The PI-IBS mouse model showed increased expression of ATP and A2AR(P<0.05),and inhibition of A2AR improved the clinical features in PI-IBS,including the abdominal withdrawal reflex and colon transportation test(P<0.05).The number of intestinal CD4+T cells and interleukin-17(IL-17)protein levels increased during PI-IBS,which was reversed by administration of the A2AR antagonist(P<0.05).CD4+T cells expressed A2AR and produced IL-17 in vitro,which was regulated by the A2AR agonist and antagonist.The A2AR antagonist increased the production of IL-17 by CD4+T cells via the Janus kinase-signal transducer and activator of transcriptionreceptor-related orphan receptorγsignaling pathway.CONCLUSION The results of the present study suggested that the upregulation of A2AR increases PI-IBS by promoting the Th17 polarization of CD4+T cells.
文摘One-hundred years have passed since the original description of the commonly described phenomenon of persistent abdominal symptoms being triggered by an acute enteric infection. This first account was generated out of astute observations by Sir Arthur Hurst in World War I. Additional descriptions followed from military and non-military practitioners adding the evidence which has transitioned this recognized condition from association to causation. While mechanistic understanding is an area of active pursuit, this historical accounting of a centuries progress highlights important advances and contributions of military medicine and scientists to advances benefiting global populations.
基金financially supported by National Natural Science Foundation of China(Grant No.U1903122,81872768,82003630)Liaoning Revitalization Talents Program(XLYC1807118)+4 种基金Liaoning BaiQianWanShenyang Young Scientific and Technological Innovators Program(RC200408)Doctoral Scientific Research Foundation of Liaoning Province(2020-BS-129)Postdoctoral Scienceof China(2020M671384)Special Fund of Research Institute of Drug Regulatory Science Research Shenyang Pharmaceutical University(2021jgkx010)。
文摘The application of traditional Chinese medicines(TCMs)has a history of more than 2000 years,which have the characteristics of multi-component,multi-target,and high safety.Post-infectious cough(PIC)is a respiratory disease with high incidence.It belongs to subacute cough and accounts for as much as40%–50%.Cough is the main clinical manifestation of PIC.PIC seriously affects people’s life quality because of complex etiology,long-term course of disease,treatment difficulties and other characteristics.Western medicines are based on the principle of symptomatic treatment,so they are often difficult to control PIC fundamentally.These factors could due to that PIC is prolonged and unable to heal repeatedly.TCMs have obvious advantages in treating PIC,with accurate curative effects,less side effects and adverse reactions and are effective in improving PIC-related symptoms and indicators,enhancing patients’life quality and reducing pain.TCMs,guided by holistic concept and syndrome differentiation,advocate determine treatment on the basis of pattern types,and have remarkable clinical treatment effects.As for TCMs etiology,pathogenesis and syndrome types of PIC,TCM scholars have not yet reached a unified standard.However,most of them think that wind pathogen can cause PIC alone,or it can be combined with other evils,which might be the main mechanism of PIC.This paper discusses the advantages and limitations of TCMs in PIC treatment from etiology,pathogenesis,distribution of syndrome types and treatment of TCMs.This article focuses on the treatment methods and pharmacodynamic material basis of wind pathogen,providing ideas in treating PIC of TCMs clinically and innovative drug development.
文摘Irritable bowel syndrome(IBS) is a common and troublesome disorder in children with an increasing prevalence noted during the past two decades. It has a significant effect on the lives of affected children and their families and poses a significant burden on healthcare systems. Standard symptom-based criteria for diagnosis of pediatric IBS have changed several times during the past two decades and there are some differences in interpreting symptoms between different cultures. This has posed a problem when using them to diagnose IBS in clinical practice. A number of potential patho-physiological mechanisms have been described, but so far the exact underlying etiology of IBS is unclear. A few potential therapeutic modalities have been tested in children and only a small number of them have shown some benefit. In addition, most of the described patho-physiological mechanisms and treatment options are based on adult studies. These have surfaced as challenges when dealing with pediatric IBS and they need to be overcome for effective management of children with IBS. Recently suggested top-down and bottom-up models help integrating reported patho-physiological mechanisms and will provide an opportunity for better understanding of the diseases process. Treatment trials targeting single treatment modalities are unlikely to have clinically meaningful therapeutic effects on IBS with multiple integrating patho-physiologies. Trials focusing on multiple combined pharmacological and non-pharmacological therapies are likely to yield more benefit. In addition to treatment, in the future, attention should be paid for possible prevention strategies for IBS.
基金Supported by Grants from the Natural Sciences and Engineering Research Council of Canada(individual operating and CREATE),the France-Canada Research Fundthe"Ministère de l’enseignement supérieur et de la recherche",French Ministry of Secondary Education and Research
文摘Giardiasis is the most common waterborne parasitic infection of the human intestine worldwide.The etiological agent,Giardia duodenalis(syn.G.intestinalis,G.lamblia),is a flagellated,binucleated protozoan parasite which infects a wide array of mammalian hosts.Human giardiasis is a true cosmopolitan pathogen,with highest prevalence in developing countries.Giardiasis can present with a broad range of clinical manifestations from asymptomatic,to acute or chronic diarrheal disease associated with abdominal pain and nausea.Most infections are self-limiting,although re-infection and chronic infection can occur.Recent evidence indicating that Giardia may cause chronic post-infectious gastrointestinal complications have made it a topic of intense research.The causes of the post-infectious clinical manifestations due to Giardia,even after complete elimination of the parasite,remain obscure.This review offers a state-of-the-art discussion on the long-term consequences of Giardia infections,from extra-intestinal manifestations,growth and cognitive deficiencies,to post-infectious irritable bowel syndrome.The discussion also sheds light on some of the novel mechanisms recently implicated in the production of these postinfectious manifestations.
基金supported by Natural Science Foundation of China Grant(No.81160057):International Science and Technique Corporation Foundation of Hainan Province Grant(No.KJHZ2013-14)
文摘Objective:To investigate the impact of the preinduced intestinal heat shock protein 70(HSP70)on the visceral hypersensitivity and abnormal intestinal motility in a post-infectious irritable bowel syndrome(PI-IBS) mouse model.Methods:Eighty-four female C57BL/6 mice were randomly assigned to four groups:control group(n=21) and induction+PI-IBS group(n=21),PI-IBS group(n=21) and induction group(n=21).The mice in PI-IBS group were infected in vivo with trichinella spiralis by oral administration.The visceral hypersensitivity and intestinal motility were evaluated respectively with abdominal withdrawal reflex and colon transportation test.The intestinal HSP70 protein and mRNA level was measured by Western blot and realtime PCR.Meanwhile,the intestinal proinflammatory cytokines IL-10 and TNF-α level was detected by ELISA.Results:Compared with their counterparts in PI-IBS group,the animals in the Induction+PI-IBS group show significantly increased intestinal level of HSP70 and obviously ameliorative clinical tigurcs.including abdominal withdrawal reflex score,intestine transportation time and Bristol scores(P<0.05).Meanwhile,the intestinal post-inflammatory cytokines remarkably changed,including increased IL-10 level and decreased TNF-αlevel(P<0.05).Conclusions:Intestinal IISP70 may play a potential protective role through improving the imbalance between the intestinal post-inflammatory and anti-inflammatory cytokines in PI-IBS.
文摘The Autoimmune Brain1 explains I-Cubed, a shorthand for post-infectious autoimmunity that results from the multiplier effect of infection, immunity and inflammation, when protective immunity becomes the source of autoimmunity, conditioned by applicable environmental and genetic predisposing factors. In keeping with the post-infectious autoimmune nature of I-Cubed, neurologic and psychiatric symptoms evolve beyond a standard of care course of antibiotic therapy. Extensive serologic, electrophysiological and neuroradiographic diagnostic testing provides clues to areas of central, peripheral and autonomic nervous system, and systemic involvement that guide therapy. A multimodality therapeutic approach employing immune modulatory (Ig) therapy that addresses the underlying mechanisms and not just the symptoms of Cubed disorders is most effective. Representative cases of post-infectious autoimmunity associated with Lyme disease and PANDAS are presented.
基金Supported by National Natural Science Foundation of China,No.81160057,No.81860102,and No.82060102Natural Science Foundation of Hainan Province,High-level Personnel Program,No.821RC1116+1 种基金Research Project of Health Industry in Hainan Province,No.20A200066Hainan Provincial Clinical Medical Center.
文摘BACKGROUND Immunological dysfunction-induced low-grade inflammation is regarded as one of the predominant pathogenetic mechanisms in post-infectious irritable bowel syndrome(PI-IBS).γδT cells play a crucial role in innate and adaptive immunity.Adenosine receptors expressed on the surface ofγδT cells participate in intestinal inflammation and immunity regulation.AIM To investigate the role ofγδT cell regulated by adenosine 2A receptor(A2AR)in PI-IBS.METHODS The PI-IBS mouse model has been established with Trichinella spiralis(T.spiralis)infection.The intestinal A2AR and A2AR inγδT cells were detected by immunohistochemistry,and the inflammatory cytokines were measured by western blot.The role of A2AR on the isolatedγδT cells,including proliferation,apoptosis,and cytokine production,were evaluated in vitro.Their A2AR expression was measured by western blot and reverse transcription polymerase chain reaction(RT-PCR).The animals were administered with A2AR agonist,or A2AR antagonist.Besides,γδT cells were also injected back into the animals,and the parameters described above were examined,as well as the clinical features.Furthermore,the A2AR-associated signaling pathway molecules were assessed by western blot and RT-PCR.RESULTS PI-IBS mice exhibited elevated ATP content and A2AR expression(P<0.05),and suppression of A2AR enhanced PI-IBS clinical characteristics,indicated by the abdominal withdrawal reflex and colon transportation test.PI-IBS was associated with an increase in intestinal T cells,and cytokine levels of interleukin-1(IL-1),IL-6,IL-17A,and interferon-α(IFN-α).Also,γδT cells expressed A2AR in vitro and generated IL-1,IL-6,IL-17A,and IFN-α,which can be controlled by A2AR agonist and antagonist.Mechanistic studies demonstrated that the A2AR antagonist improved the function ofγδT cells through the PKA/CREB/NF-κB signaling pathway.CONCLUSION Our results revealed that A2AR contributes to the facilitation of PI-IBS by regulating the function ofγδT cells via the PKA/CREB/NF-κB signaling pathway.
文摘<div style="text-align:justify;"> <span style="font-family:Verdana;"><strong>Background:</strong> Chikungunya fever is an infectious disease that can evolve to a subacute or chronic condition, with changes in the daily activities of patients. Drugs that aim to reduce these symptoms are used, such as corticoids (acute phase) and disease-modifying anti-rheumatic drugs (chronic phase). <strong>Objective: </strong>To evaluate the clinical response to drug therapy in the subacute and chronic phase of infection by the Chikungunya virus. <strong>Methodology:</strong> A prospective and a retrospective study with patients with subacute and chronic Chikungunya infection, out at the infection and autoimmunity outpatient clinic at the Nucleus of Tropical Medicine, from January 2016 to December 2019, in the morning of Thursdays. The patient was observed in the Baseline, first and second return, and drugs were introduced according to the stage of the disease with subsequent reassessment. The Visual Analogue Scale (VAS) was applied to all evaluation moments. <strong>Results:</strong> 101 patients were evaluated, and arthralgia was the predominant symptom in the three evaluated moments. According to the VAS, moderate baseline pain was observed in 58.1% and 58.6% of subacute and chronic cases, respectively. On the first return, moderate pain still predominated in 46.2% in subacute cases and 43% in chronic cases. In the second visit, all patients were in the chronic phase of the disease, 43.8% had VAS with no pain. Regarding the number of compromised joints in the Baseline, polyarticular involvement predominated in both subacute (79%) and chronic (74.1%) cases, in the first return, oligoarticular involvement predominated in 53.8% of subacute cases and 54.7% in chronic cases and, the second return, 40.6% of the patients had oligoarticular involvement and 43.8% had no joint involvement. As for the use of medications in the Baseline, 33.4% of subacute cases used antiinflammatory drugs, and 40% of chronic cases used corticosteroids. At the first visit, 25% of chronic patients were already using combined corticosteroids and methotrexate and 15% were using only methotrexate. In the second return, 35.1% used combined methotrexate and corticosteroids, and 64.9% used only methotrexate. Safety in the use of methotrexate was observed in the context of CHIKV treatment, as the number of adverse reactions was minimal (three patients) and the medication was well tolerated. <strong>Conclusion:</strong> It was observed that with the adjustment of the medications, there was a reduction in joint impairment, VAS showed mild pain indexes and in some cases with no pain, showing the benefit of using therapy in subacute and chronic cases and improving quality of life of these users.</span> </div>
文摘Background Limited data are available in relation to the clinical features of PIBO undergoing prolonged nebulization treat-ment with budesonide, terbutaline and ipratropium bromide. This retrospective study aimed to outline the features of clini-cal, high-resolution computed tomography (HRCT) and pulmonary function test (PFT) of PIBO, undergoing maintenance therapy utilizing a triple nebulization treatment and to determine the factors associated with prognosis. Methods Children diagnosed with PIBO were followed up between April 2014 and March 2017. The clinical features after maintenance nebulization treatment for 12 months were thereafter summarized. Results Thirty patients, 21 boys and 9 girls, were enrolled in the study. The median age of patients was 17.4 months, with a range between 3.0 and 33 months. Persistent coughing and wheezing were detected whilst wheezing and crackles were the common manifestations presented. HRCT scans revealed patchy ground and glass opacity, while PFT showed fixed airway obstruction in all patients. Four patients were lost during follow-up. After treatment, the clinical symptoms were improved greatly in all patients (P<0.01). The mean increase in the percentage of TPEF%TE and VPEF%VE were improved greatly (P < 0.01). Images of the HRCT scan indicated marked improvements in 18 patients (81.8%) in comparison with scans obtained pre-treatment. Conclusions Our data suggest a potential role of long-term nebulization treatment of budesonide, terbutaline, ipratropium bromide on PIBO, due to its efficacy as indicated in the improved clinical symptoms, pulmonary functions and CT manifesta-tions identified in the children. New prospective and controlled studies are required to confirm this proposition.
文摘Previous reviews have highlighted complementary and alternative medicine therapies that are used to treat irritable bowel syndrome（IBS） based on published clinical trial data.Here the author describes and comments on a number of potentially relevant factors that have been commonly emphasized by practitioners who treat IBS and patients who have the disease.They include gluten and other food allergies,the Candida syndrome and biofilm,interference fields and post-infectious IBS, as well as mind-body factors.
