The wealth of DNA data generated by the human genome project coupling with recently invented high-throughput gene expression profiling techniques has dramatically sped up the process for biomedical researchers on eluc...The wealth of DNA data generated by the human genome project coupling with recently invented high-throughput gene expression profiling techniques has dramatically sped up the process for biomedical researchers on elucidating the role of genes in human diseases. One powerful method to reveal insight into gene functions is the systematic analysis of gene expression. Two popular high-throughput gene expression technologies, microarray and Serial Analysis of Gene Expression (SAGE) are capable of producing large amounts of gene expression data with the potential of providing novel insights into fundamental disease processes, especially complex syndromes such as cardiovascular disease, whose etiologies are due to multiple genetic factors and their interplay with the environment. Microarray and SAGE have already been used to examine gene expression patterns of cell-culture, animal and human tissues models of cardiovascular diseases. In this review, we will first give a brief introduction of microarray and SAGE technologies and point out their limitations. We will then discuss the major discoveries and the new biological insightsthat have emerged from their applications to cardiovascular diseases. Finally we will touch upon potential challenges and future developments in this area.展开更多
Gut microbiota are involved in the development or prevention of various diseases such as type 2 diabetes,fatty liver, and malignancy such as colorectal cancer,breast cancer and hepatocellular carcinoma. Alzheimer'...Gut microbiota are involved in the development or prevention of various diseases such as type 2 diabetes,fatty liver, and malignancy such as colorectal cancer,breast cancer and hepatocellular carcinoma. Alzheimer'sdisease, osteoporosis, sarcopenia, atherosclerotic stroke and cardiovascular disease are major diseases associated with decreased activities of daily living(ADL), especially in elderly people. Recent analyses have revealed the importance of gut microbiota in the control of these diseases. The composition or diversity of these microbiota is different between patients with these conditions and healthy controls, and administration of probiotics or prebiotics has been shown effective in the treatment of these diseases. Gut microbiota may affect distant organs through mechanisms that include regulating the absorption of nutrients and/or the production of microbial metabolites, regulating and interacting with the systemic immune system, and translocating bacteria/bacterial products through disrupted mucosal barriers.Thus, the gut microbiota may be important regulators in the development of diseases that affect ADL. Although adequate exercise and proper diet are important for preventing these diseases, their combination with interventions that manipulate the composition and/or diversity of gut microbiota could be a promising strategy for maintaining health condition and preserving ADL. This review thus summarizes current understanding of the role of gut microbiota in the development or prevention of diseases closely associated with the maintenance of ADL.展开更多
Pulmonary abnormalities are not frequently encountered in patients with inflammatory bowel diseases.However,lung toxicity can be induced by conventional medications used to maintain remission,and similar evidence is a...Pulmonary abnormalities are not frequently encountered in patients with inflammatory bowel diseases.However,lung toxicity can be induced by conventional medications used to maintain remission,and similar evidence is also emerging for biologics.We present the case of a young woman affected by colonic Crohn’s disease who was treated with oral mesalamine and became steroid-dependent and refractory to azathioprine and adalimumab.She was referred to our clinic with a severe relapse and was treated with infliximab,an antitumor necrosis factor α(TNF-α)antibody,to induce remission.After an initial benefit,with decreases in bowel movements,rectal bleeding and C-reactive protein levels,she experienced shortness of breath after the 5thinfusion.Noninfectious interstitial lung disease was diagnosed.Both mesalamine and infliximab were discontinued,and steroids were introduced with slow but progressive improvement of symptoms,radiology and functional tests.This represents a rare case of interstitial lung disease associated with infliximab therapy and the effect of drug withdrawal on these lung alterations.Given the increasing use of anti-TNF-α therapies and the increasing reports of pulmonary abnormalities in patients with inflammatory bowel diseases,this case underlines the importance of a careful evaluation of respiratory symptoms in patients undergoing infliximab therapy.展开更多
Obesity, especially at mid-life, is a major risk factor for atherosclerosis, insulin resistance and the metabolic syndrome, which in turn contribute to coronary artery disease (CAD), Type 2 diabetes and Alzheimer’s d...Obesity, especially at mid-life, is a major risk factor for atherosclerosis, insulin resistance and the metabolic syndrome, which in turn contribute to coronary artery disease (CAD), Type 2 diabetes and Alzheimer’s disease (AD). The rise in overweight and obesity in all societies is prompting intense research into the causes and effects of the condition. Obesity disrupts many body systems including glucose and lipid metabolism, circadian rhythms and liver function. It also causes or increases inflammation and oxidative stress. Within cells, the endoplasmic reticulum (ER) appears to be particularly susceptible to such metabolic disruption. Sirtuin 1?(Sirt1) and leptin have received attention recently as they are central regulatory factors for the body’s metabolic pathways which interact at particular levels, for example lipid and Abeta metabolism. This mini-review discusses recent findings concerning obesity, lipid metabolism and the role of Sirtuin 1 and how all influence the ER. A greater understanding of obesity and its effects on metabolic control systems of the body are required, to develop pharmacological, dietary and lifestyle changes that will reduce the incidence of CAD, Type 2 diabetes and AD.展开更多
Abundant scientific evidence supporting an association between inflammatory bowel disease(IBD) and venous thromboembolic events, caused by an IBD related hypercoagulability, is acknowledged and thromboprophylactic tre...Abundant scientific evidence supporting an association between inflammatory bowel disease(IBD) and venous thromboembolic events, caused by an IBD related hypercoagulability, is acknowledged and thromboprophylactic treatment strategies are now implemented in the management of IBD patients. In contrary, the risk of arterial thromboembolic disease, as ischemic heart disease, cerebrovascular events, and mesenteric ischemia in patients with IBD remains uncertain and the magnitude of a potentially increased risk is continuously debated, with ambiguous risk estimates among studies. The evident role of inflammation in the pathogenesis of atherosclerosis forms the basis of a biological plausible link; the chronic systemic inflammation in IBD patients increases the risk of atherosclerosis and thereby the risk of thrombotic events. Further, studies have shown that the burden of traditional risk factors for atherosclerosis, such as obesity, diabetes mellitus, and dyslipidemia is lower in IBD populations, thus further strengthen the role of non-traditional risk factors, as chronic inflammation in the linking of the two disease entities. Likewise, mortality from cardiovascular disease in IBD remains questioned. The aim of the current review is to give an up-date on the existing evidence of the possible association between IBD and cardiovascular disease and to discuss traditional and non-traditional risk factors.展开更多
Purpose: The purpose of this systematic review of the literature is to examine the cerebrovascular and cardiovascular effects on cognition in persons with Parkinson’s disease. Relevance: Physical therapy treatment of...Purpose: The purpose of this systematic review of the literature is to examine the cerebrovascular and cardiovascular effects on cognition in persons with Parkinson’s disease. Relevance: Physical therapy treatment of persons with Parkinson’s disease (PD) has traditionally focused on lessening the impact of disease severity by improving quality of life and functional capacity. Research has shown that quality of life in persons with PD is not only significantly affected by motor symptoms, but also by the presence of defined non-motor symptoms such as cerebrovascular perfusion, cardiovascular dysfunction, and cognitive impairment. This study seeks to determine a causative effect among these non-motor symptoms with the intention to better manage cognitive impairment in persons with PD. Methods: A literature search was conducted utilizing the following databases: Scopus, PubMed, and CINAHL. After evaluating and grading studies using the Downs and Black Checklist, a total of seven studies remained for the final review. Results: Five common domains of cognition emerged throughout the seven studies: executive function, attention, verbal memory and fluency, visual memory, and working memory. Considering the articles reviewed, a relationship between cerebrovascular and cardiovascular deficiency and cognitive impairment in persons with PD was established. Conclusions: Persons with PD and certain cerebrovascular and cardiovascular risk factors, including orthostatic hypotension and systemic hypertension, should be referred to appropriate professionals for comprehensive neuropsychological testing secondary to an increased risk for more severe cognitive deficit.展开更多
CASTLEMAN'S disease(CD),a rare lymphoproliferative disorder of unknown etiology, was first described in 1956 as a benign mass in the mediastinum. Although CD can present anywhere in the body, 70% of the cases are ...CASTLEMAN'S disease(CD),a rare lymphoproliferative disorder of unknown etiology, was first described in 1956 as a benign mass in the mediastinum. Although CD can present anywhere in the body, 70% of the cases are in the chest along the tracheobronchial tree or hilum of the lung in the middle mediastinum; however, they can also occur in the anterior or posterior compartments. CD is classi-fied as unicentric (UCD) or multicentric (MCD) based on the anatomical distribution, and histologically as hya-line-vascular, plasma cell, or mixed subtypes.1 Although MCD is less common than UCD, it can be rapidly pro-gressive and often fatal.展开更多
Since the worldwide outbreak of coronavirus disease 2019,angiotensin-converting enzyme 2(ACE2)has received widespread attention as the cell receptor of the severe acute respiratory syndrome coronavirus 2 virus.At the ...Since the worldwide outbreak of coronavirus disease 2019,angiotensin-converting enzyme 2(ACE2)has received widespread attention as the cell receptor of the severe acute respiratory syndrome coronavirus 2 virus.At the same time,as a key enzyme in the renin-angiotensin-system,ACE2 is considered to be an endogenous negative regulator of vasoconstriction,proliferation,fibrosis,and proinflammation caused by the ACE-angiotensin II-angiotensin type 1 receptor axis.ACE2 is now implicated as being closely connected to diabetes,cardiovascular,kidney,and lung diseases,and so on.This review covers the available information on the host factors regulating ACE2 and discusses its role in a variety of pathophysiological conditions in animal models and humans.展开更多
Background: The prevention of cardiovascular disease (CVD) can substantially contribute to reducing the mortality rate across countries. The level of interest in cholesterol among experts increases when the subjects a...Background: The prevention of cardiovascular disease (CVD) can substantially contribute to reducing the mortality rate across countries. The level of interest in cholesterol among experts increases when the subjects are elderly and obese individuals. However, specialists do not recommend that children should receive the cholesterol test. The objective of this study was to investigate the distribution of cholesterol levels among the children of public school and their parents’ lifestyles that are associated with cholesterol levels, and to assess the need for and utility of cholesterol testing in school settings. Methods: The study investigated a group of 226 fourth-grade public school children aged between 9 and 10 years and guardians in Akitakatacity of Hiroshima Prefecture, Japan. Multiple regression analyses were performed with the logarithmic value of cholesterol levels as a response variable, awareness about lifestyles and health of children as an explanatory variable, and child’s sex and body mass index (BMI) as moderating variables. Using questionnaires about lifestyles, the step-down procedure was applied in multiple regression analyses to narrow down relevant lifestyle variables. Results: The percentage of children with the high total cholesterol (TC) value was about 15 and with low-density lipoprotein (LDL) cholesterol value was about 10. Children with low high-density lipoprotein (HDL) cholesterol value were 5%. Treatment was not required according to the comprehensive assessment. Cholesterol levels were associated with the situation of the children and their guardians as follows, guardian need to consider the food, and child has the correct knowledge about food like how to eat snacks. Conclusions: Children had poor cholesterol levels. From childhood, along with the parents, there is a need to learn about appropriate level of cholesterol for CVD prevention.展开更多
BACKGROUND While extensive information exists relating cigarette smoking to the risk of lung cancer,chronic obstructive pulmonary disease(COPD),ischaemic heart disease(IHD)or acute myocardial infarction(AMI),and strok...BACKGROUND While extensive information exists relating cigarette smoking to the risk of lung cancer,chronic obstructive pulmonary disease(COPD),ischaemic heart disease(IHD)or acute myocardial infarction(AMI),and stroke,far less information is available on risks from moist snuff(“snus”)or smokeless tobacco(ST)in United States/Canada,Europe or Japan.AIM To summarize data from the selected countries on risks of the four diseases associated with current ST or snus use.METHODS Publications in English in 1990-2020 were considered that,based on epidemiological studies in North America,Europe or Japan,estimated risks of lung cancer,COPD,IHD/AMI,or stroke according to use of ST or snus.The studies should involve at least 100 cases of the disease considered,and not be restricted to those with specific other diseases.Medline literature searches were conducted,selecting papers initially from examination of titles and abstracts,and then from full texts.Further papers were sought from reference lists in selected papers,reviews and meta-analyses.For each disease,relative risk estimates adjusted at least for age were extracted relating ST or snus use to risk,and combined using random-effects meta-analysis.The estimates were mainly for current vs.never or non-current use,but results for ever vs never use were also considered.RESULTS Seven publications reported results for ST use from six United States studies.The most useful results came from four studies which provided results for current vs.never use.Random-effects meta-analyses of these results showed an increased risk for each disease,clearest for lung cancer(relative risk 1.59,95%confidence interval 1.06-2.39,based on 4 estimates)and COPD(1.57,1.09-2.26,n=3),but also significant(at P<0.05)for IHD(1.26,1.10-1.45,n=4)and stroke(1.27,1.03-1.57,n=4).Also including results for ever vs.never use from two other studies increased the lung cancer estimate to 1.80(1.23-2.64,n=6),but had little effect on the other estimates.For snus,16 publications described results from 12 studies,one in Norway and the rest in Sweden.There were no results for COPD,and only three for lung cancer,with these reporting a relative risk of 0.80(0.40-1.30)for current vs never use.More extensive data were available for IHD/AMI and stroke.Using the latest results from each study,combined estimates for current vs.never use were 1.00(0.91-1.11,n=5)for IHD/AMI and 1.05(0.95-1.17,n=2)for stroke,while for current vs.non-current use they were 1.10(0.92-1.33,n=9)for IHD/AMI and 1.12(0.86-1.45,n=9)for stroke.Meta-analyses including earlier results from some studies also showed no significant association between snus use and IHD/AMI or stroke.No relevant results were found for Japan.CONCLUSION Risks of smoking-related diseases from snus use in Scandinavia are not demonstrated,while those from ST use in the United States are less than from smoking.展开更多
Interstitial lung disease(ILD) is an important mani-festation of collagen vascular diseases. It is a common feature of scleroderma, and also occurs in dermatomyositis and polymyositis, mixed connective tissue disease,...Interstitial lung disease(ILD) is an important mani-festation of collagen vascular diseases. It is a common feature of scleroderma, and also occurs in dermatomyositis and polymyositis, mixed connective tissue disease, Sjogren's syndrome, rheumatoid arthritis, systemic lupus erythematosus, and Antineutrophil cytoplasmic antibody-associated vasculitis. When present, it is associated with increased morbidity and mortality, thus making early diagnosis important. In fact, in many patients, ILD may be the first manifestation of a collagen vascular disease. The most common symptoms are cough and dyspnea. The diagnosis is made based on pulmonary function tests showing restrictive lung disease and impaired oxygen diffusion and chest imaging showing ground glass infiltrates, interstitial thickening, and/or fibrosis. The most common histologic finding on lung biopsy is non-specific interstitial pneumonia, though organizing pneumonia and usual interstitial pneumonia may also be seen. Treatment is focused on addressing the underlying collagen vascular disease with immunosuppression, either with corticosteroids or a steroid-sparing agent such as cyclophosphamide, azathioprine, or mycophenolate, although the optimal agent and duration of therapy is not known. There are few clinical trials to guide therapy that focus specifically on the progression of ILD. The exception is in the case of scleroderma-associated ILD, where cyclophosphamide has been shown to be effective.展开更多
AIM:To determine the relationship of pulmonary abnormalities and bowel disease activity in inflammatory bowel disease(IBD).METHODS:Thirty ulcerative colitis(UC)and nine Crohn's disease patients,and 20 control subj...AIM:To determine the relationship of pulmonary abnormalities and bowel disease activity in inflammatory bowel disease(IBD).METHODS:Thirty ulcerative colitis(UC)and nine Crohn's disease patients,and 20 control subjects were enrolled in this prospective study.Detailed clinical information was obtained.Extent and activity of the bowel disease were established endoscopically.Each patient underwent pulmonary function tests and high-resolution computed tomography(HRCT).Blood samples for measurement of C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),angiotensin converting enzyme and total IgE were delivered by the patients.RESULTS:Ten(25.6%)patients had respiratory symptoms.A pulmonary function abnormality was present in 22 of 39 patients.Among all patients,the most prevalent abnormalities in lung functions were a decrease in forced expiratory volume in 1 s(FEV1),FEV1/forced vital capacity(FVC),forced expiratory flow(FEF)25%-75%,transfer coefficient for carbon monoxide(DLCO),DLCO/alveolar volume.Increased respiratory symptoms score was associated with high endoscopic activity index in UC patients.Endoscopic and clinical activities in UC patients were correlated with FEV1,FEV1/FVC,and FEF 25%-75%.Smoking status,duration of disease and medication were not correlated with pulmonary physiological test results,HRCT abnormalities,clinical/endoscopic disease activity,CRP,ESR or total IgE level or body mass index.CONCLUSION:It is important that respiratory manifestations are recognized and treated early in IBD.Otherwise,they can lead to destructive and irreversible changes in the airway wall.展开更多
Extraintestinal manifestations of inflammatory bowel disease(IBD) are a systemic illness that may affect up to half of all patients. Among the extraintestinal manifestations of IBD, those involving the lungs are relat...Extraintestinal manifestations of inflammatory bowel disease(IBD) are a systemic illness that may affect up to half of all patients. Among the extraintestinal manifestations of IBD, those involving the lungs are relatively rare and often overlooked. However, there is a wide array of such manifestations, spanning from airway disease to lung parenchymal disease, thromboembolic disease, pleural disease, enteric-pulmonary fistulas, pulmonary function test abnormalities, and adverse drug reactions. The spectrum of IBD manifestations in the chest is broad, and the manifestations may mimic other diseases. Although infrequent, physicians dealing with IBD must be aware of these conditions, which are sometimes life-threatening, to avoid further health impairment of the patients and to alleviate their symptoms by prompt recognition and treatment. Knowledge of these manifestations in conjunction with pertinent clinical data is essential for establishing the correct diagnosis and treatment. The treatment of IBD-related respiratory disorders depends on the specific pattern of involvement, and in most patients, steroids are required in the initial management. Corticosteroids, both systemic and aerosolized, are the mainstay therapeutic approach, while antibiotics must also be administered inthe case of infectious and suppurative processes, whose sequelae sometimes require surgical intervention.展开更多
BACKGROUND Patients with inflammatory bowel disease(IBD)are associated with increased cardiovascular risk and have increased overall cardiovascular burden.On the other hand,urotensin II(UII)is one of the most potent v...BACKGROUND Patients with inflammatory bowel disease(IBD)are associated with increased cardiovascular risk and have increased overall cardiovascular burden.On the other hand,urotensin II(UII)is one of the most potent vascular constrictors with immunomodulatory effect that is connected with a number of different cardiometabolic disorders as well.Furthermore,patients with ulcerative colitis have shown increased expression of urotensin II receptor in comparison to healthy controls.Since the features of IBD includes chronic inflammation and endothelial dysfunction as well,it is plausible to assume that there is connection between increased cardiac risk in IBD and UII.AIM To determine serum UII levels in patients with IBD and to compare them to control subjects,as well as investigate possible associations with relevant clinical and biochemical parameters.METHODS This cross sectional study consecutively enrolled 50 adult IBD patients(26 with Crohn’s disease and 24 with ulcerative colitis)and 50 age and gender matched controls.Clinical assessment was performed by the same experienced gastroenterologist according to the latest guidelines.Ulcerative Colitis Endoscopic Index of Severity and Simple Endoscopic Score for Crohn’s Disease were used for endoscopic evaluation.Serum levels of UII were determined using the enzyme immunoassay kit for human UII,according to the manufacturer’s instructions.RESULTS IBD patients have significantly higher concentrations of UII when compared to control subjects(7.57±1.41 vs 1.98±0.69 ng/mL,P<0.001),while there were no significant differences between Crohn’s disease and ulcerative colitis patients(7.49±1.42 vs 7.65±1.41 ng/mL,P=0.689).There was a significant positive correlation between serum UII levels and high sensitivity C reactive peptide levels(r=0.491,P<0.001)and a significant negative correlation between serum UII levels and total proteins(r=-0.306,P=0.032).Additionally,there was a significant positive correlation between serum UII levels with both systolic(r=0.387,P=0.005)and diastolic(r=0.352,P=0.012)blood pressure.Moreover,serum UII levels had a significant positive correlation with Ulcerative Colitis Endoscopic Index of Severity(r=0.425,P=0.048)and Simple Endoscopic Score for Crohn’s Disease(r=0.466,P=0.028)scores.Multiple linear regression analysis showed that serum UII levels retained significant association with high sensitivity C reactive peptide(β±standard error,0.262±0.076,P<0.001)and systolic blood pressure(0.040±0.017,P=0.030).CONCLUSION It is possible that UII is involved in the complex pathophysiology of cardiovascular complications in IBD patients,and its purpose should be investigated in further studies.展开更多
Crohn’s disease (CD) is a systemic illness with a constellation of extraintestinal manifestations affecting various organs. Of these extraintestinal manifestations of CD, those involving the lung are relat...Crohn’s disease (CD) is a systemic illness with a constellation of extraintestinal manifestations affecting various organs. Of these extraintestinal manifestations of CD, those involving the lung are relatively rare. However, there is a wide array of lung manifestations, ranging from subclinical alterations, airway diseases and lung parenchymal diseases to pleural diseases and drug-related diseases. The most frequent manifestation is bronchial inflammation and suppuration with or without bronchiectasis. Bronchoalveolar lavage findings show an increased percentage of neutrophils. Drug-related pulmonary abnormalities include disorders which are directly induced by sulfasalazine, mesalamine and methotrexate, and opportunistic lung infections due to immunosuppressive treatment. In most patients, the development of pulmonary disease parallels that of intestinal disease activity. Although infrequent, clinicians dealing with CD must be aware of these, sometimes life-threatening, conditions to avoid further impairment of health status and to alleviate patient symptoms by prompt recognition and treatment. The treatment of CD-related respiratory disorders depends on the specific pattern of involvement, and in most patients, steroids are required in the initial management.展开更多
Crohn's disease is a granulomatous systemic disorder of unknown etiology. Obvious pulmonary involvement is exceptional. Tracheal involvement in Crohn's disease is even more unusual, only a few cases have been ...Crohn's disease is a granulomatous systemic disorder of unknown etiology. Obvious pulmonary involvement is exceptional. Tracheal involvement in Crohn's disease is even more unusual, only a few cases have been report-ed to date. We herein report a rare case of tracheobron-chial nodules and pulmonary infiltrates in both lungs as a complication of Crohn's disease. A 42-year-old man underwent pancolectomy for multiple broken colon caused by Crohn's disease. Forty days later pulmonary symptoms and radiologic abnormalities were noted. A search for bacterial (including mycobacteria) and fungal in the repeated sputum proved negative. The treatment consisted of intravenous antimicrobials for one month, but there was no improvement in pyrexia or cough and radiologic abnormalities. Fibreoptic bronchoscopy (FOB) was performed and revealed nodes in the trachea and the right upper lobe opening. Histopathology of tracheo-bronchial nodules and bronchial mucosa biopsy specimen both showed granulomatous inflammation with proliferation of capillaries and inflammatory cells. Oral steroid and salicylazosulfapyridine were commenced and led to marked improvement in symptoms and an almost complete resolution of his chest radiograph. Repeated FOB showed that nodes in the trachea disappeared and the ones in the right upper lobe opening diminished obviously. Crohn's disease can be associated with several respiratory manifestations. The form of tracheal and bronchopulmonary involvement in Crohn's disease is rare and responded well to steroids.展开更多
Pneumoconiosis (PNC) is a major occupational disease that develops as a result of occupational exposure to dust via inhalation. In addition to its harmful effects on the respiratory system, PNC can increase vulnerabil...Pneumoconiosis (PNC) is a major occupational disease that develops as a result of occupational exposure to dust via inhalation. In addition to its harmful effects on the respiratory system, PNC can increase vulnerability to coronary heart disease (CHD)—the leading cause of death in the United States and in the world. Currently, two types of cardiovascular intervention procedures for CHD treatment are percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). The objective of this study was to investigate comparative effectiveness of the two major cardiovascular intervention procedures—PCI and CABG—in PNC patients with CHD. Data from 1094 hospitalizations of adult patients with PNC and CHD (CHD-PNC patients) and 534,120 hospi-talizations of CHD patients without PNC (CHD-nonPNC) were investigated. Adjusted odds ratios for in-hospital death in relation to the type of procedure, adjusted for patient socio-demographic and clinical characteristics and hospital characteristics, were calculated using multivariable logistic regression. Men constituted 97.8% of CHD-PNC patients and 68.6% of CHD-nonPNC patients. Within the CHD-PNC group, crude (unadjusted) in-hospital mortality after CABG and PCI did not differ significantly (1.35% vs. 2.00%, p = 0.425) and remained insignificant in the multivariable analysis, adjusted for patient and hospital characteristics (adjusted OR = 0.714, 95% CI 0.220 - 2.323, p = 0.576). But in the CHD-nonPNC group, in-hospital mortality after CABG was significantly higher than after PCI both in crude analysis (2.83% vs. 1.28%,展开更多
BACKGROUND Obesity is associated with an increased risk of developing Crohn’s disease(CD),higher disease activity,and comparatively worse clinical outcomes.AIM To investigate the role of mesenteric adipose tissue-der...BACKGROUND Obesity is associated with an increased risk of developing Crohn’s disease(CD),higher disease activity,and comparatively worse clinical outcomes.AIM To investigate the role of mesenteric adipose tissue-derived exosomes in the pathogenesis of CD aggravation in obese individuals.METHODS First,we induced colitis in mice initiated on high-fat and normal diets and compared the severity of colitis.We then extracted and identified exosomes from mesenteric adipose tissue and determined the levels of metastasis-associated lung adenocarcinoma transcript 1(MALAT1)in mesenteric adipose tissue-derived exosomes and the colon.Next,we demonstrated an interaction between MALAT1 and the miR-15a-5p/activating transcription factor 6(ATF6)axis.Finally,we explored the effects of mesenteric adipose tissue-derived exosomes extracted from mice fed a high-fat or normal diet on the severity of 2,4,6-trinitrobe-nzenesulfonic acid(TNBS)-induced colitis and ATF6-related endoplasmic reticulum stress pathways.RESULTS High-fat diet was found to aggravate TNBS-induced colitis in mice.The expression of MALAT1 in mesenteric adipose tissue-derived exosomes of high-fat diet-fed mice increased.The increased expression of MALAT1 in colon tissue exacerbated TNBS-induced colitis and activated the ATF6 endoplasmic reticulum stress pathway.This effect was partially reversed by the reduced expression of MALAT1 and overexpression of miR-15a-5p.CONCLUSION Mesenteric adipose tissue-derived exosome-encapsulated long noncoding RNAs MALAT1 targets the colon and aggravates TNBS-induced colitis in obese mice,which may potentially act on the miR-15a-5p/ATF6 axis and activate endoplasmic reticulum stress.展开更多
基金Part of studies cited in this review was in partsupported by Johns Hopkins Institutional ResearchGrant(Ye,SQ),a pilot project(Ye,SQ)in The Hop-kins DK Center for the Analysis of Gene Expres-sion(R24DK58757-01,NIDDK)and Dorothy WallisWagner Charitable Tru
文摘The wealth of DNA data generated by the human genome project coupling with recently invented high-throughput gene expression profiling techniques has dramatically sped up the process for biomedical researchers on elucidating the role of genes in human diseases. One powerful method to reveal insight into gene functions is the systematic analysis of gene expression. Two popular high-throughput gene expression technologies, microarray and Serial Analysis of Gene Expression (SAGE) are capable of producing large amounts of gene expression data with the potential of providing novel insights into fundamental disease processes, especially complex syndromes such as cardiovascular disease, whose etiologies are due to multiple genetic factors and their interplay with the environment. Microarray and SAGE have already been used to examine gene expression patterns of cell-culture, animal and human tissues models of cardiovascular diseases. In this review, we will first give a brief introduction of microarray and SAGE technologies and point out their limitations. We will then discuss the major discoveries and the new biological insightsthat have emerged from their applications to cardiovascular diseases. Finally we will touch upon potential challenges and future developments in this area.
文摘Gut microbiota are involved in the development or prevention of various diseases such as type 2 diabetes,fatty liver, and malignancy such as colorectal cancer,breast cancer and hepatocellular carcinoma. Alzheimer'sdisease, osteoporosis, sarcopenia, atherosclerotic stroke and cardiovascular disease are major diseases associated with decreased activities of daily living(ADL), especially in elderly people. Recent analyses have revealed the importance of gut microbiota in the control of these diseases. The composition or diversity of these microbiota is different between patients with these conditions and healthy controls, and administration of probiotics or prebiotics has been shown effective in the treatment of these diseases. Gut microbiota may affect distant organs through mechanisms that include regulating the absorption of nutrients and/or the production of microbial metabolites, regulating and interacting with the systemic immune system, and translocating bacteria/bacterial products through disrupted mucosal barriers.Thus, the gut microbiota may be important regulators in the development of diseases that affect ADL. Although adequate exercise and proper diet are important for preventing these diseases, their combination with interventions that manipulate the composition and/or diversity of gut microbiota could be a promising strategy for maintaining health condition and preserving ADL. This review thus summarizes current understanding of the role of gut microbiota in the development or prevention of diseases closely associated with the maintenance of ADL.
文摘Pulmonary abnormalities are not frequently encountered in patients with inflammatory bowel diseases.However,lung toxicity can be induced by conventional medications used to maintain remission,and similar evidence is also emerging for biologics.We present the case of a young woman affected by colonic Crohn’s disease who was treated with oral mesalamine and became steroid-dependent and refractory to azathioprine and adalimumab.She was referred to our clinic with a severe relapse and was treated with infliximab,an antitumor necrosis factor α(TNF-α)antibody,to induce remission.After an initial benefit,with decreases in bowel movements,rectal bleeding and C-reactive protein levels,she experienced shortness of breath after the 5thinfusion.Noninfectious interstitial lung disease was diagnosed.Both mesalamine and infliximab were discontinued,and steroids were introduced with slow but progressive improvement of symptoms,radiology and functional tests.This represents a rare case of interstitial lung disease associated with infliximab therapy and the effect of drug withdrawal on these lung alterations.Given the increasing use of anti-TNF-α therapies and the increasing reports of pulmonary abnormalities in patients with inflammatory bowel diseases,this case underlines the importance of a careful evaluation of respiratory symptoms in patients undergoing infliximab therapy.
文摘Obesity, especially at mid-life, is a major risk factor for atherosclerosis, insulin resistance and the metabolic syndrome, which in turn contribute to coronary artery disease (CAD), Type 2 diabetes and Alzheimer’s disease (AD). The rise in overweight and obesity in all societies is prompting intense research into the causes and effects of the condition. Obesity disrupts many body systems including glucose and lipid metabolism, circadian rhythms and liver function. It also causes or increases inflammation and oxidative stress. Within cells, the endoplasmic reticulum (ER) appears to be particularly susceptible to such metabolic disruption. Sirtuin 1?(Sirt1) and leptin have received attention recently as they are central regulatory factors for the body’s metabolic pathways which interact at particular levels, for example lipid and Abeta metabolism. This mini-review discusses recent findings concerning obesity, lipid metabolism and the role of Sirtuin 1 and how all influence the ER. A greater understanding of obesity and its effects on metabolic control systems of the body are required, to develop pharmacological, dietary and lifestyle changes that will reduce the incidence of CAD, Type 2 diabetes and AD.
文摘Abundant scientific evidence supporting an association between inflammatory bowel disease(IBD) and venous thromboembolic events, caused by an IBD related hypercoagulability, is acknowledged and thromboprophylactic treatment strategies are now implemented in the management of IBD patients. In contrary, the risk of arterial thromboembolic disease, as ischemic heart disease, cerebrovascular events, and mesenteric ischemia in patients with IBD remains uncertain and the magnitude of a potentially increased risk is continuously debated, with ambiguous risk estimates among studies. The evident role of inflammation in the pathogenesis of atherosclerosis forms the basis of a biological plausible link; the chronic systemic inflammation in IBD patients increases the risk of atherosclerosis and thereby the risk of thrombotic events. Further, studies have shown that the burden of traditional risk factors for atherosclerosis, such as obesity, diabetes mellitus, and dyslipidemia is lower in IBD populations, thus further strengthen the role of non-traditional risk factors, as chronic inflammation in the linking of the two disease entities. Likewise, mortality from cardiovascular disease in IBD remains questioned. The aim of the current review is to give an up-date on the existing evidence of the possible association between IBD and cardiovascular disease and to discuss traditional and non-traditional risk factors.
文摘Purpose: The purpose of this systematic review of the literature is to examine the cerebrovascular and cardiovascular effects on cognition in persons with Parkinson’s disease. Relevance: Physical therapy treatment of persons with Parkinson’s disease (PD) has traditionally focused on lessening the impact of disease severity by improving quality of life and functional capacity. Research has shown that quality of life in persons with PD is not only significantly affected by motor symptoms, but also by the presence of defined non-motor symptoms such as cerebrovascular perfusion, cardiovascular dysfunction, and cognitive impairment. This study seeks to determine a causative effect among these non-motor symptoms with the intention to better manage cognitive impairment in persons with PD. Methods: A literature search was conducted utilizing the following databases: Scopus, PubMed, and CINAHL. After evaluating and grading studies using the Downs and Black Checklist, a total of seven studies remained for the final review. Results: Five common domains of cognition emerged throughout the seven studies: executive function, attention, verbal memory and fluency, visual memory, and working memory. Considering the articles reviewed, a relationship between cerebrovascular and cardiovascular deficiency and cognitive impairment in persons with PD was established. Conclusions: Persons with PD and certain cerebrovascular and cardiovascular risk factors, including orthostatic hypotension and systemic hypertension, should be referred to appropriate professionals for comprehensive neuropsychological testing secondary to an increased risk for more severe cognitive deficit.
文摘CASTLEMAN'S disease(CD),a rare lymphoproliferative disorder of unknown etiology, was first described in 1956 as a benign mass in the mediastinum. Although CD can present anywhere in the body, 70% of the cases are in the chest along the tracheobronchial tree or hilum of the lung in the middle mediastinum; however, they can also occur in the anterior or posterior compartments. CD is classi-fied as unicentric (UCD) or multicentric (MCD) based on the anatomical distribution, and histologically as hya-line-vascular, plasma cell, or mixed subtypes.1 Although MCD is less common than UCD, it can be rapidly pro-gressive and often fatal.
基金National Natural Science Foundation of China,No.81873861and Key Grant of Research and Development in Hunan Province,No.2020DK2002.
文摘Since the worldwide outbreak of coronavirus disease 2019,angiotensin-converting enzyme 2(ACE2)has received widespread attention as the cell receptor of the severe acute respiratory syndrome coronavirus 2 virus.At the same time,as a key enzyme in the renin-angiotensin-system,ACE2 is considered to be an endogenous negative regulator of vasoconstriction,proliferation,fibrosis,and proinflammation caused by the ACE-angiotensin II-angiotensin type 1 receptor axis.ACE2 is now implicated as being closely connected to diabetes,cardiovascular,kidney,and lung diseases,and so on.This review covers the available information on the host factors regulating ACE2 and discusses its role in a variety of pathophysiological conditions in animal models and humans.
文摘Background: The prevention of cardiovascular disease (CVD) can substantially contribute to reducing the mortality rate across countries. The level of interest in cholesterol among experts increases when the subjects are elderly and obese individuals. However, specialists do not recommend that children should receive the cholesterol test. The objective of this study was to investigate the distribution of cholesterol levels among the children of public school and their parents’ lifestyles that are associated with cholesterol levels, and to assess the need for and utility of cholesterol testing in school settings. Methods: The study investigated a group of 226 fourth-grade public school children aged between 9 and 10 years and guardians in Akitakatacity of Hiroshima Prefecture, Japan. Multiple regression analyses were performed with the logarithmic value of cholesterol levels as a response variable, awareness about lifestyles and health of children as an explanatory variable, and child’s sex and body mass index (BMI) as moderating variables. Using questionnaires about lifestyles, the step-down procedure was applied in multiple regression analyses to narrow down relevant lifestyle variables. Results: The percentage of children with the high total cholesterol (TC) value was about 15 and with low-density lipoprotein (LDL) cholesterol value was about 10. Children with low high-density lipoprotein (HDL) cholesterol value were 5%. Treatment was not required according to the comprehensive assessment. Cholesterol levels were associated with the situation of the children and their guardians as follows, guardian need to consider the food, and child has the correct knowledge about food like how to eat snacks. Conclusions: Children had poor cholesterol levels. From childhood, along with the parents, there is a need to learn about appropriate level of cholesterol for CVD prevention.
文摘BACKGROUND While extensive information exists relating cigarette smoking to the risk of lung cancer,chronic obstructive pulmonary disease(COPD),ischaemic heart disease(IHD)or acute myocardial infarction(AMI),and stroke,far less information is available on risks from moist snuff(“snus”)or smokeless tobacco(ST)in United States/Canada,Europe or Japan.AIM To summarize data from the selected countries on risks of the four diseases associated with current ST or snus use.METHODS Publications in English in 1990-2020 were considered that,based on epidemiological studies in North America,Europe or Japan,estimated risks of lung cancer,COPD,IHD/AMI,or stroke according to use of ST or snus.The studies should involve at least 100 cases of the disease considered,and not be restricted to those with specific other diseases.Medline literature searches were conducted,selecting papers initially from examination of titles and abstracts,and then from full texts.Further papers were sought from reference lists in selected papers,reviews and meta-analyses.For each disease,relative risk estimates adjusted at least for age were extracted relating ST or snus use to risk,and combined using random-effects meta-analysis.The estimates were mainly for current vs.never or non-current use,but results for ever vs never use were also considered.RESULTS Seven publications reported results for ST use from six United States studies.The most useful results came from four studies which provided results for current vs.never use.Random-effects meta-analyses of these results showed an increased risk for each disease,clearest for lung cancer(relative risk 1.59,95%confidence interval 1.06-2.39,based on 4 estimates)and COPD(1.57,1.09-2.26,n=3),but also significant(at P<0.05)for IHD(1.26,1.10-1.45,n=4)and stroke(1.27,1.03-1.57,n=4).Also including results for ever vs.never use from two other studies increased the lung cancer estimate to 1.80(1.23-2.64,n=6),but had little effect on the other estimates.For snus,16 publications described results from 12 studies,one in Norway and the rest in Sweden.There were no results for COPD,and only three for lung cancer,with these reporting a relative risk of 0.80(0.40-1.30)for current vs never use.More extensive data were available for IHD/AMI and stroke.Using the latest results from each study,combined estimates for current vs.never use were 1.00(0.91-1.11,n=5)for IHD/AMI and 1.05(0.95-1.17,n=2)for stroke,while for current vs.non-current use they were 1.10(0.92-1.33,n=9)for IHD/AMI and 1.12(0.86-1.45,n=9)for stroke.Meta-analyses including earlier results from some studies also showed no significant association between snus use and IHD/AMI or stroke.No relevant results were found for Japan.CONCLUSION Risks of smoking-related diseases from snus use in Scandinavia are not demonstrated,while those from ST use in the United States are less than from smoking.
文摘Interstitial lung disease(ILD) is an important mani-festation of collagen vascular diseases. It is a common feature of scleroderma, and also occurs in dermatomyositis and polymyositis, mixed connective tissue disease, Sjogren's syndrome, rheumatoid arthritis, systemic lupus erythematosus, and Antineutrophil cytoplasmic antibody-associated vasculitis. When present, it is associated with increased morbidity and mortality, thus making early diagnosis important. In fact, in many patients, ILD may be the first manifestation of a collagen vascular disease. The most common symptoms are cough and dyspnea. The diagnosis is made based on pulmonary function tests showing restrictive lung disease and impaired oxygen diffusion and chest imaging showing ground glass infiltrates, interstitial thickening, and/or fibrosis. The most common histologic finding on lung biopsy is non-specific interstitial pneumonia, though organizing pneumonia and usual interstitial pneumonia may also be seen. Treatment is focused on addressing the underlying collagen vascular disease with immunosuppression, either with corticosteroids or a steroid-sparing agent such as cyclophosphamide, azathioprine, or mycophenolate, although the optimal agent and duration of therapy is not known. There are few clinical trials to guide therapy that focus specifically on the progression of ILD. The exception is in the case of scleroderma-associated ILD, where cyclophosphamide has been shown to be effective.
文摘AIM:To determine the relationship of pulmonary abnormalities and bowel disease activity in inflammatory bowel disease(IBD).METHODS:Thirty ulcerative colitis(UC)and nine Crohn's disease patients,and 20 control subjects were enrolled in this prospective study.Detailed clinical information was obtained.Extent and activity of the bowel disease were established endoscopically.Each patient underwent pulmonary function tests and high-resolution computed tomography(HRCT).Blood samples for measurement of C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),angiotensin converting enzyme and total IgE were delivered by the patients.RESULTS:Ten(25.6%)patients had respiratory symptoms.A pulmonary function abnormality was present in 22 of 39 patients.Among all patients,the most prevalent abnormalities in lung functions were a decrease in forced expiratory volume in 1 s(FEV1),FEV1/forced vital capacity(FVC),forced expiratory flow(FEF)25%-75%,transfer coefficient for carbon monoxide(DLCO),DLCO/alveolar volume.Increased respiratory symptoms score was associated with high endoscopic activity index in UC patients.Endoscopic and clinical activities in UC patients were correlated with FEV1,FEV1/FVC,and FEF 25%-75%.Smoking status,duration of disease and medication were not correlated with pulmonary physiological test results,HRCT abnormalities,clinical/endoscopic disease activity,CRP,ESR or total IgE level or body mass index.CONCLUSION:It is important that respiratory manifestations are recognized and treated early in IBD.Otherwise,they can lead to destructive and irreversible changes in the airway wall.
文摘Extraintestinal manifestations of inflammatory bowel disease(IBD) are a systemic illness that may affect up to half of all patients. Among the extraintestinal manifestations of IBD, those involving the lungs are relatively rare and often overlooked. However, there is a wide array of such manifestations, spanning from airway disease to lung parenchymal disease, thromboembolic disease, pleural disease, enteric-pulmonary fistulas, pulmonary function test abnormalities, and adverse drug reactions. The spectrum of IBD manifestations in the chest is broad, and the manifestations may mimic other diseases. Although infrequent, physicians dealing with IBD must be aware of these conditions, which are sometimes life-threatening, to avoid further health impairment of the patients and to alleviate their symptoms by prompt recognition and treatment. Knowledge of these manifestations in conjunction with pertinent clinical data is essential for establishing the correct diagnosis and treatment. The treatment of IBD-related respiratory disorders depends on the specific pattern of involvement, and in most patients, steroids are required in the initial management. Corticosteroids, both systemic and aerosolized, are the mainstay therapeutic approach, while antibiotics must also be administered inthe case of infectious and suppurative processes, whose sequelae sometimes require surgical intervention.
文摘BACKGROUND Patients with inflammatory bowel disease(IBD)are associated with increased cardiovascular risk and have increased overall cardiovascular burden.On the other hand,urotensin II(UII)is one of the most potent vascular constrictors with immunomodulatory effect that is connected with a number of different cardiometabolic disorders as well.Furthermore,patients with ulcerative colitis have shown increased expression of urotensin II receptor in comparison to healthy controls.Since the features of IBD includes chronic inflammation and endothelial dysfunction as well,it is plausible to assume that there is connection between increased cardiac risk in IBD and UII.AIM To determine serum UII levels in patients with IBD and to compare them to control subjects,as well as investigate possible associations with relevant clinical and biochemical parameters.METHODS This cross sectional study consecutively enrolled 50 adult IBD patients(26 with Crohn’s disease and 24 with ulcerative colitis)and 50 age and gender matched controls.Clinical assessment was performed by the same experienced gastroenterologist according to the latest guidelines.Ulcerative Colitis Endoscopic Index of Severity and Simple Endoscopic Score for Crohn’s Disease were used for endoscopic evaluation.Serum levels of UII were determined using the enzyme immunoassay kit for human UII,according to the manufacturer’s instructions.RESULTS IBD patients have significantly higher concentrations of UII when compared to control subjects(7.57±1.41 vs 1.98±0.69 ng/mL,P<0.001),while there were no significant differences between Crohn’s disease and ulcerative colitis patients(7.49±1.42 vs 7.65±1.41 ng/mL,P=0.689).There was a significant positive correlation between serum UII levels and high sensitivity C reactive peptide levels(r=0.491,P<0.001)and a significant negative correlation between serum UII levels and total proteins(r=-0.306,P=0.032).Additionally,there was a significant positive correlation between serum UII levels with both systolic(r=0.387,P=0.005)and diastolic(r=0.352,P=0.012)blood pressure.Moreover,serum UII levels had a significant positive correlation with Ulcerative Colitis Endoscopic Index of Severity(r=0.425,P=0.048)and Simple Endoscopic Score for Crohn’s Disease(r=0.466,P=0.028)scores.Multiple linear regression analysis showed that serum UII levels retained significant association with high sensitivity C reactive peptide(β±standard error,0.262±0.076,P<0.001)and systolic blood pressure(0.040±0.017,P=0.030).CONCLUSION It is possible that UII is involved in the complex pathophysiology of cardiovascular complications in IBD patients,and its purpose should be investigated in further studies.
文摘Crohn’s disease (CD) is a systemic illness with a constellation of extraintestinal manifestations affecting various organs. Of these extraintestinal manifestations of CD, those involving the lung are relatively rare. However, there is a wide array of lung manifestations, ranging from subclinical alterations, airway diseases and lung parenchymal diseases to pleural diseases and drug-related diseases. The most frequent manifestation is bronchial inflammation and suppuration with or without bronchiectasis. Bronchoalveolar lavage findings show an increased percentage of neutrophils. Drug-related pulmonary abnormalities include disorders which are directly induced by sulfasalazine, mesalamine and methotrexate, and opportunistic lung infections due to immunosuppressive treatment. In most patients, the development of pulmonary disease parallels that of intestinal disease activity. Although infrequent, clinicians dealing with CD must be aware of these, sometimes life-threatening, conditions to avoid further impairment of health status and to alleviate patient symptoms by prompt recognition and treatment. The treatment of CD-related respiratory disorders depends on the specific pattern of involvement, and in most patients, steroids are required in the initial management.
文摘Crohn's disease is a granulomatous systemic disorder of unknown etiology. Obvious pulmonary involvement is exceptional. Tracheal involvement in Crohn's disease is even more unusual, only a few cases have been report-ed to date. We herein report a rare case of tracheobron-chial nodules and pulmonary infiltrates in both lungs as a complication of Crohn's disease. A 42-year-old man underwent pancolectomy for multiple broken colon caused by Crohn's disease. Forty days later pulmonary symptoms and radiologic abnormalities were noted. A search for bacterial (including mycobacteria) and fungal in the repeated sputum proved negative. The treatment consisted of intravenous antimicrobials for one month, but there was no improvement in pyrexia or cough and radiologic abnormalities. Fibreoptic bronchoscopy (FOB) was performed and revealed nodes in the trachea and the right upper lobe opening. Histopathology of tracheo-bronchial nodules and bronchial mucosa biopsy specimen both showed granulomatous inflammation with proliferation of capillaries and inflammatory cells. Oral steroid and salicylazosulfapyridine were commenced and led to marked improvement in symptoms and an almost complete resolution of his chest radiograph. Repeated FOB showed that nodes in the trachea disappeared and the ones in the right upper lobe opening diminished obviously. Crohn's disease can be associated with several respiratory manifestations. The form of tracheal and bronchopulmonary involvement in Crohn's disease is rare and responded well to steroids.
文摘Pneumoconiosis (PNC) is a major occupational disease that develops as a result of occupational exposure to dust via inhalation. In addition to its harmful effects on the respiratory system, PNC can increase vulnerability to coronary heart disease (CHD)—the leading cause of death in the United States and in the world. Currently, two types of cardiovascular intervention procedures for CHD treatment are percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). The objective of this study was to investigate comparative effectiveness of the two major cardiovascular intervention procedures—PCI and CABG—in PNC patients with CHD. Data from 1094 hospitalizations of adult patients with PNC and CHD (CHD-PNC patients) and 534,120 hospi-talizations of CHD patients without PNC (CHD-nonPNC) were investigated. Adjusted odds ratios for in-hospital death in relation to the type of procedure, adjusted for patient socio-demographic and clinical characteristics and hospital characteristics, were calculated using multivariable logistic regression. Men constituted 97.8% of CHD-PNC patients and 68.6% of CHD-nonPNC patients. Within the CHD-PNC group, crude (unadjusted) in-hospital mortality after CABG and PCI did not differ significantly (1.35% vs. 2.00%, p = 0.425) and remained insignificant in the multivariable analysis, adjusted for patient and hospital characteristics (adjusted OR = 0.714, 95% CI 0.220 - 2.323, p = 0.576). But in the CHD-nonPNC group, in-hospital mortality after CABG was significantly higher than after PCI both in crude analysis (2.83% vs. 1.28%,
基金Supported by the National Natural Science Foundation of China,No.81770574the Natural Science Foundation of Zhejiang Province,No.LZ21H030002 and No.LY21H030005.
文摘BACKGROUND Obesity is associated with an increased risk of developing Crohn’s disease(CD),higher disease activity,and comparatively worse clinical outcomes.AIM To investigate the role of mesenteric adipose tissue-derived exosomes in the pathogenesis of CD aggravation in obese individuals.METHODS First,we induced colitis in mice initiated on high-fat and normal diets and compared the severity of colitis.We then extracted and identified exosomes from mesenteric adipose tissue and determined the levels of metastasis-associated lung adenocarcinoma transcript 1(MALAT1)in mesenteric adipose tissue-derived exosomes and the colon.Next,we demonstrated an interaction between MALAT1 and the miR-15a-5p/activating transcription factor 6(ATF6)axis.Finally,we explored the effects of mesenteric adipose tissue-derived exosomes extracted from mice fed a high-fat or normal diet on the severity of 2,4,6-trinitrobe-nzenesulfonic acid(TNBS)-induced colitis and ATF6-related endoplasmic reticulum stress pathways.RESULTS High-fat diet was found to aggravate TNBS-induced colitis in mice.The expression of MALAT1 in mesenteric adipose tissue-derived exosomes of high-fat diet-fed mice increased.The increased expression of MALAT1 in colon tissue exacerbated TNBS-induced colitis and activated the ATF6 endoplasmic reticulum stress pathway.This effect was partially reversed by the reduced expression of MALAT1 and overexpression of miR-15a-5p.CONCLUSION Mesenteric adipose tissue-derived exosome-encapsulated long noncoding RNAs MALAT1 targets the colon and aggravates TNBS-induced colitis in obese mice,which may potentially act on the miR-15a-5p/ATF6 axis and activate endoplasmic reticulum stress.