High-fat diet aggravates colitis via mesenteric adipose tissue derived exosome metastasis-associated lung adenocarcinoma transcript 1

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.

Antagonizing adipose tissue-derived exosome miR-103-hepatocyte phosphatase and tensin homolog pathway alleviates autophagy in non-alcoholic steatohepatitis:A trans-cellular crosstalk

BACKGROUND Obesity plays a vital role in the occurrence and development of non-alcoholic steatohepatitis(NASH).However,the underlining mechanism is still unclear,where adipose tissue(AT)derived exosomes may actively participate.MicroRNAs(miRNAs)are commonly secreted from exosomes for cell communication.Though the regulation of miR-103 on insulin sensitivity has been reported,the specific role of AT-derived exosomes miR-103 in NASH is still vague and further investigation may provide novel therapeutic choices.AIM To determine the specific role of AT-derived exosomes miR-103 in developing NASH through various methods.METHODS The expression levels of miR-103 in the AT-derived exosomes and livers were detected and compared between NASH mice and control.The effect of miR-103 on NASH progression was also explored by antagonizing miR-103,including steatosis and inflammation degree changes.The interaction between miR-103 and the autophagy-related gene phosphatase and tensin homolog(PTEN)was confirmed by dual-luciferase reporter assay.The role of the interaction between miR-103 and PTEN on autophagy was verified in NASH-like cells.Finally,the effects of miR-103 from adipose-derived exosomes on NASH and autophagy were analyzed through animal experiments.RESULTS The expression of miR-103 was increased in NASH mice,compared to the control,and inhibition of miR-103 could alleviate NASH.The results of the dual-luciferase reporter assay showed miR-103 could interact with PTEN.MiR-103-anta decreased p-AMPKa,p-mammalian target of rapamycin(mTOR),and p62 but increased the protein levels of PTEN and LC3-II/I and the number of autophagosomes in NASH mice.Similar results were also observed in NASH-like cells,and further experiments showed PTEN silencing inhibited the effect of miR-103-anta.AT derivedexosome miR-103 aggravated NASH and increased the expressions of p-AMPKa,p-mTOR,and p62 but decreased the protein levels of PTEN and LC3-II/I and the number of autophagosomes in mice.CONCLUSION AT derived-exosome increased the levels of miR-103 in the liver,and miR-103 aggravated NASH.Mechanically,miR-103 could interact with PTEN and inhibit autophagy.

Crohn’s disease as the intestinal manifestation of pan-lymphatic dysfunction:An exploratory proposal based on basic and clinical data

Crohn’s disease(CD)is caused by immune,environmental,and genetic factors.It can involve the entire gastrointestinal tract,and although its prevalence is rapidly increasing its etiology remains unclear.Emerging biological and small-molecule drugs have advanced the treatment of CD;however,a considerable proportion of patients are non-responsive to all known drugs.To achieve a breakthrough in this field,innovations that could guide the further development of effective therapies are of utmost urgency.In this review,we first propose the innovative concept of pan-lymphatic dysfunction for the general distribution of lymphatic dysfunction in various diseases,and suggest that CD is the intestinal manifestation of pan-lymphatic dysfunction based on basic and clinical preliminary data.The supporting evidence is fully summarized,including the existence of lymphatic system dysfunction,recognition of the inside-out model,disorders of immune cells,changes in cell plasticity,partial overlap of the underlying mechanisms,and common gut-derived fatty and bile acid metabolism.Another benefit of this novel concept is that it proposes adopting the zebrafish model for studying intestinal diseases,especially CD,as this model is good at presenting and mimicking lymphatic dysfunction.More importantly,the ensuing focus on improving lymphatic function may lead to novel and promising therapeutic strategies for CD.

Exposure to different severities of famine and subsequent risk of sarcopenia in old age

Background:Poor nutritional status is closely related to the development of sarcopenia and possible sarcopenia.Limited articles have evaluated the impact of undernutrition at different stages of life on the development of sarcopenia or possible sarcopenia in old age.The 1959–1962 Chinese famine provided the possibility for large-scale population studies on the effects of long-term undernutrition or inad-equate intake on various health problems.In this study,we aimed to investigate the effects of long-term reduction of food intake(expo-sure to the 1959–1962 Chinese famine)in early life on the development of sarcopenia and possible sarcopenia in later life.Methods:We used data from the China Health and Retirement Longitudinal Survey(CHARLS)2015 and obtained information on whether participants had experienced famine from the 2014 Life Course Survey of Chinese Residents.After data integration and cleaning,we divided the included participants into five age-exposure cohorts based on birthdate,including cohorts exposed to famine during preschool,midchildhood,young teenage years,teenage years,and adulthood to analyze the long-term effects of exposure to famine on the development of sarcopenia and possible sarcopenia.Results:Exposure to moderate or severe famine did not significantly increase the risk of possible sarcopenia(P>0.05).In a further stratified analysis,moderate famine exposure in adulthood significantly increased the risk of possible sarcopenia(1.475 times;95%CI:1.104–1.969,P=0.009).However,there was no significant association between famine exposure and possible sarcopenia in the preschool,midchildhood,young teenage,or teenage exposure cohorts(P>0.05).Conclusions:Exposure to famine in preadulthood did not increase the risk of possible sarcopenia in older adults.However,the risk of possible sarcopenia in later life was increased about 50%among participants who were exposed to moderate famine in adulthood.

Palmitoylation in Crohn’s disease:Current status and future directions

S-palmitoylation is one of the most common post-translational modifications in nature;however,its importance has been overlooked for decades.Crohn’s disease(CD),a subtype of inflammatory bowel disease(IBD),is an autoimmune disease characterized by chronic inflammation involving the entire gastrointestinal tract.Bowel damage and subsequent disabilities caused by CD are a growing global health issue.Well-acknowledged risk factors for CD include genetic susceptibility,environmental factors,such as a westernized lifestyle,and altered gut microbiota.However,the pathophysiological mechanisms of this disorder are not yet comprehensively understood.With the rapidly increasing global prevalence of CD and the evident role of S-palmitoylation in CD,as recently reported,there is a need to investigate the relationship between CD and S-palmitoylation.In this review,we summarize the concept,detection,and function of S-palmitoylation as well as its potential effects on CD,and provide novel insights into the pathogenesis and treatment of CD.

Structural Evolution in Flowing Immiscible Blends in the Presence of Rough Particles:Dependence of Shear Rate and Blend Ratio

The influence of polystyrene particles with different nanoscale roughnesses on the morphology of polyisobutylene/poly-dimethylsiloxane blends was studied under shear flow by using confocal laser scanning microscopy.It was found that the surface roughness of particles strongly affected their diffusion and distribution behaviors,thereby determining the size and spatial arrangement of droplets in the blends.The roughness effect of particles was found to possess a strong dependence on both the blend ratio and the shear rate.The result suggested that the particle roughness can serve as a new parameter to control the structure-property correlation in particle-filled polymer blends,especially under slow flow.