Mucosal healing(MH)is vital in maintaining homeostasis within the gut and protecting against injury and infections.Multiple factors and signaling pathways contribute in a dynamic and coordinated manner to maintain int...Mucosal healing(MH)is vital in maintaining homeostasis within the gut and protecting against injury and infections.Multiple factors and signaling pathways contribute in a dynamic and coordinated manner to maintain intestinal homeostasis and mucosal regeneration/repair.However,when intestinal homeostasis becomes chronically disturbed and an inflammatory immune response is constitutively active due to impairment of the intestinal epithelial barrier autoimmune disease results,particularly inflammatory bowel disease(IBD).Many proteins and signaling pathways become dysregulated or impaired during these pathological conditions,with the mechanisms of regulation just beginning to be understood.Consequently,there remains a relative lack of broadly effective therapeutics that can restore MH due to the complexity of both the disease and healing processes,so tissue damage in the gastrointestinal tract of patients,even those in clinical remission,persists.With increased understanding of the molecular mechanisms of IBD and MH,tissue damage from autoimmune disease may in the future be ameliorated by developing therapeutics that enhance the body’s own healing response.In this review,we introduce the concept of mucosal healing and its relevance in IBD as well as discuss the mechanisms of IBD and potential strategies for altering these processes and inducing MH.展开更多
Non-alcoholic fatty liver disease (NAFLD), a further expression of metabolic syndrome, strictly linked to obesity and diabetes mellitus, is characterized by insulin resistance (IR), elevated serum levels of free fatty...Non-alcoholic fatty liver disease (NAFLD), a further expression of metabolic syndrome, strictly linked to obesity and diabetes mellitus, is characterized by insulin resistance (IR), elevated serum levels of free fatty acids and fatty infi ltration of the liver, which is known as hepatic steatosis. Hepatocyte apoptosis is a key feature of this disease and correlates with its severity. Free-fatty-acidinduced toxicity represents one of mechanisms for the pathogenesis of NAFLD and hormones, growth factors and adipokines influence also play a key role. This review highlights the various pathways that contribute to the development of hepatic steatosis. Circulating concentrations of inflammatory cytokines are reckoned to be the most important factor in causing and maintaining IR. Low-grade chronic inflammation is fundamental in the progression of NAFLD toward higher risk cirrhotic states.展开更多
Independent of the cause and location,inflammation-even when minimal-has clear effects on gastrointestinal morphology and function.These result in altered digestion,absorption and barrier function.There is evidence of...Independent of the cause and location,inflammation-even when minimal-has clear effects on gastrointestinal morphology and function.These result in altered digestion,absorption and barrier function.There is evidence of reduced villus height and crypt depth,increased permeability,as well as altered sugar and peptide absorption in the small intestine after induction of inflammation in experimental models,which is supported by some clinical data.Identification of inflammatory factors which may promote the process of gastrointestinal dysfunction as well as clinical research to verify experimental observations of inflammatory modulation of gastrointestinal function are required.Moreover,nutritional strategies to support functional restitution are needed.展开更多
BACKGROUND Studies have demonstrated a potential role for fecal biomarkers such as fecal calprotectin(FC)and fecal lactoferrin(FL)in monitoring inflammatory bowel diseases(IBD)-Crohn's disease(CD)and ulcerative co...BACKGROUND Studies have demonstrated a potential role for fecal biomarkers such as fecal calprotectin(FC)and fecal lactoferrin(FL)in monitoring inflammatory bowel diseases(IBD)-Crohn's disease(CD)and ulcerative colitis(UC).However,their correlation to endoscopic scores,disease severity and affected intestinal surface has not been extensively investigated.AIM To correlate FL,and for comparison white blood cell(WBC)and C-reactive protein(CRP),with endoscopic scores,disease extent and location in CD and UC.METHODS Retrospective analysis in 188 patients who had FL,CRP and WBC determined within 30 d of endoscopy.Disease location,disease extent(number of intestinal segments involved),disease severity(determined by endoscopic scores),timing of FL testing in relation to colonoscopy,as well as the use of effective fast acting medications(steroids and biologics)between colonoscopy and FL measurement,were recorded.RESULTS In 131 CD and 57 UC patients,both CRP and FL-but not WBC-distinguished disease severity(inactive,mild,moderate,severe).In patients receiving fastacting(steroids or biologics)treatment in between FL and colonoscopy,FL showed a higher correlation to endoscopic scores when tested before vs after the procedure(r=0.596,P<0.001,vs r=0.285,P=0.15 for the Simple Endoscopic Score for CD;and r=0.402,P=0.01 vs r=0.054 P=0.84 for Disease Activity Index).Finally,FL was significantly correlated with the diseased mucosal surface(colon-ileocolon>small bowel)and the number of inflamed colon segments.CONCLUSION FL and CRP separated disease severity categories with FL showing lower discriminating P-values.FL showed a close correlation with the involved mucosal surface and with disease extent and was more closely correlated to endoscopy when determined before the procedure–this indicating that inflammatory activity changes associated with therapy might be rapidly reflected by FL levels.FL can accurately and timely characterize intestinal inflammation in IBD.展开更多
Objective:To investigate the protective effect of Dahuang Fuzi Decoction(DHFZD),a traditional Chinese prescription,at alleviating sepsis-induced inflammation and gut barrier damage in rats.Methods:Forty clean-grade ma...Objective:To investigate the protective effect of Dahuang Fuzi Decoction(DHFZD),a traditional Chinese prescription,at alleviating sepsis-induced inflammation and gut barrier damage in rats.Methods:Forty clean-grade male Sprague-Dawley rats were divided randomly into three groups:normal control group(NCG,n?10),model control group(MCG,n?15)and DHFZD-treated group(DHFZDG,n?15).NCG rats were sham operated on and used as the controls,whereas MCG and DHFZDG rats were used to replicate the rat sepsis model using cecal ligation and puncture(CLP).The DHFZDG rats received DHFZD by gavage(4.5 mg/g of body weight)2 h prior to CLP and after its successful induction,while the NCG and MCG rats received equivalent amounts of sterilized water by gavage.All rat groups were starved and had free access to water.At 24 h post-experimental set up,the mortality of rats in each group was recorded,and peritoneal inflammation assessment and pathological changes related to the intestinal mucosal injury index(IMII)in the surviving rats were evaluated.D-lactic acid,tumor necrosis factor(TNF)-a,interleukin(IL)-6 and IL-10 peripheral blood concentrations,along with secretory immunoglobulin A(sIgA)in the intestinal mucosa were evaluated by enzyme-linked immunosorbent assays.Gut microbes were detected using 16S rRNA gene sequencing.Results:DHFZD reduced sepsis-related mortality in the rats.Moreover,it alleviated peritoneal inflammation and pathological changes according to the IMII.DHFZD reduced serum procalcitonin,TNF-a and IL-6 concentrations,but not the IL-10 concentration.It also reduced serum D-lactic acid and increased sIgA concentrations in intestinal mucosa.Notably,DHFZDG restored gut microbiota diversity and regulated the decrease in Bacteroidetes induced by sepsis,compared with the MCG rats.Conclusion:DHFZDG may play a protective role in sepsis by alleviating sepsis-induced inflammation and gut barrier damage in rats.展开更多
More and more evidence suggests that puerarin,a potential remedy for gut inflammation,may have an ameliorative effect on sleep disturbances.However,the relationship between puerarin and sleep disruption has not been e...More and more evidence suggests that puerarin,a potential remedy for gut inflammation,may have an ameliorative effect on sleep disturbances.However,the relationship between puerarin and sleep disruption has not been extensively researched.This study aims to explore the role and mechanisms of puerarin in improving sleep disorders.We established a light-induced sleep disorder model in mice and assessed the effects of puerarin on cognitive behavior using open field and water maze tests.Pathological detection demonstrated that sleep disturbances resulted in observable damage to the liver,lung,and kidney.Puerarin reversed multi-organ damage and inflammation.Further,puerarin activated paneth cells,resulting in increased lysozyme and TGF-βproduction,and stimulating intestinal stem cell proliferation.Puerarin also effectively inhibited the expression of F4/80,iNOS,TNF-α,and IL-1βin the small intestine,while it increased Chil3,CD206,and Arg-1 levels.Moreover,puerarin treatment significantly decreased P-P65,TLR4,Bcl-xl,and cleaved caspase-3 protein levels while increasing barrier protein levels,including ZO-1,Occludin,Claudin 1 and E-cadherin suggesting a reduction in inflammation and apoptosis in the gut.Overall,puerarin diminished systemic inflammation,particularly intestinal inflammation,and enhanced intestinal barrier integrity in mice with sleep disorders.Our findings suggest a potential new therapeutic pathway for sleep disorders.展开更多
Ulcerative colitis(UC)is a chronic inflammatory bowel disease characterized by persistent inflammation of the colon and disrupted intestinal function.Ramulus mori(Sangzhi)alkaloids(SZ-A),derived from twigs of mulberry...Ulcerative colitis(UC)is a chronic inflammatory bowel disease characterized by persistent inflammation of the colon and disrupted intestinal function.Ramulus mori(Sangzhi)alkaloids(SZ-A),derived from twigs of mulberry,were approved by the National Medical Products Administration in 2020 for treating type 2 diabetes mellitus.Accumulated evidence has confirmed that SZ-A also alleviates non-alcoholic fatty liver disease and ameliorates inflammation,indicating its potential to address inflammation in UC.However,the treatment of UC faces challenges due to low drug delivery efficiency and short retention time.To overcome these challenges,an injectable and adherent in-situ thermo-sensitive hydrogel containing SZ-A was developed for rectal drug delivery,utilizing the thermo-sensitive polymers Poloxamer 407and 188.The thermo-sensitive hydrogel system was designed with a moderate gelation temperature of 32±0.5℃,a short gelation time of 64 s,a p H range of 7-10,high moisturizing capability exceeding 90%,and moderate mechanical strength of 4-5 s.In a rat model with UC,the in situ thermo-sensitive hydrogel significantly extended the retention time at the colonic site and enabled sustained release after rectal administration.Symptoms of UC were markedly reduced following rectal administration of SZ-A thermosensitive hydrogel.Furthermore,the release of inflammatory factors,such as interleukin-1β(IL-1β),IL-6,IL-18,tumor necrosis factor-α(TNF-α),and transforming growth factor-β1(TGF-β1),significantly decreased in the SZ-A thermo-sensitive hydrogel group.The integrity of the colonic mucosal barrier was significantly enhanced following the application of SZ-A thermo-sensitive hydrogel.In conclusion,rectal administration of SZ-A in situ thermo-sensitive hydrogel effectively alleviated UC symptoms,inhibited the secretion of inflammatory factors,and promoted the repair of the colonic mucosal barrier.This approach holds promise as a potential treatment for UC.展开更多
Although gastroesophageal reflux disease(GERD)is a common disorder in Western countries,with a significant impact on quality of life and healthcare costs,the mechanisms involved in the pathogenesis of symptoms remain ...Although gastroesophageal reflux disease(GERD)is a common disorder in Western countries,with a significant impact on quality of life and healthcare costs,the mechanisms involved in the pathogenesis of symptoms remain to be fully elucidated.GERD symptoms and complications may result from a multifactorial mechanism,in which acid and acid-pepsin are the important noxious factors involved.Prolonged contact of the esophageal mucosa with the refluxed content,probably caused by a defective anti-reflux barrier and luminal clearance mechanisms,would appear to be responsible for macroscopically detectable injury to the esophageal squamous epithelium.Receptors on acid-sensitive nerve endings may play a role in nociception and esophageal sensitivity,as suggested in animal models of chronic acid exposure.Meanwhile,specific cytokine and chemokine profiles would appear to underlie the various esophageal phenotypes of GERD,explaining,in part,the genesis of esophagitis in a subset of patients.Despite these findings,which show a significant production of inflammatory mediators and neurotransmitters in the pathogenesis of GERD,the relationship between the hypersensitivity and esophageal inflammation is not clear.Moreover,the large majority of GERD patients(up to 70%)do not develop esophageal erosions,a variant of the condition called non-erosive reflux disease.This summary aims to explore the inflammatory pathway involved in GERD pathogenesis,to better understand the possible distinction between erosive and non-erosive reflux disease patients and to provide new therapeutic approaches.展开更多
AIM To investigate the effects of orally gavaged aqueous rhubarb extract(RE) on 5-fluorouracil(5-FU)-induced intestinal mucositis in rats. METHODS Female Dark Agouti rats(n = 8/group) were gavaged daily(1 mL) with wat...AIM To investigate the effects of orally gavaged aqueous rhubarb extract(RE) on 5-fluorouracil(5-FU)-induced intestinal mucositis in rats. METHODS Female Dark Agouti rats(n = 8/group) were gavaged daily(1 mL) with water, high-dose RE(HDR; 200 mg/kg) or low-dose RE(LDR; 20mg/kg) for eight days. Intestinal mucositis was induced(day 5) with 5-FU(150 mg/kg) via intraperitoneal injection. Intestinal tissue samples were collected for myeloperoxidase(MPO) activity and histological examination. Xenopus oocytes expressing aquaporin 4 water channels were prepared to examine the effect of aqueous RE on cell volume, indicating a potential mechanism responsible for modulating net fluid absorption and secretion in the gastrointestinal tract. Statistical significance was assumed at P < 0.05 by one-way ANOVA. RESULTS B o d y w e i g h t w a s s i g n i f i c a n t l y r e d u c e d i n r a t s administered 5-FU compared to healthy controls(P < 0.01). Rats administered 5-FU significantly increased intestinal MPO levels(≥ 307%; P < 0.001), compared to healthy controls. However, LDR attenuated this effect in 5-FU treated rats, significantly decreasing ileal MPO activity(by 45%; P < 0.05), as compared to 5-FU controls. 5-FU significantly reduced intestinal mucosal thickness(by ≥ 29% P < 0.001) as compared to healthy controls. LDR significantly increased ileal mucosal thickness in 5-FU treated rats(19%; P < 0.05) relative to 5-FU controls. In xenopus oocytes expressing AQP4 water channels, RE selectively blocked water influx into the cell, induced by a decrease in external osmotic pressure. As water efflux was unaltered by the presence of extracellular RE, the directional flow of water across the epithelial barrier, in the presence of extracellular RE, indicated that RE may alleviate water loss across the epithelial barrier and promote intestinal health in chemotherapy-induced intestinal mucositis.CONCLUSION In summary, low dose RE improves selected parameters of mucosal integrity and reduces ileal inflammation, manifesting from 5-FU-induced intestinal mucositis.展开更多
BACKGROUND Intestinal mucosal barrier dysfunction plays an important role in the pathogenesis of ulcerative colitis(UC).Recent studies have revealed that impaired autophagy is associated with intestinal mucosal dysfun...BACKGROUND Intestinal mucosal barrier dysfunction plays an important role in the pathogenesis of ulcerative colitis(UC).Recent studies have revealed that impaired autophagy is associated with intestinal mucosal dysfunction in the mucosa of colitis mice.Resveratrol exerts anti-inflammatory functions by regulating autophagy.AIM To investigate the effect and mechanism of resveratrol on protecting the integrity of the intestinal mucosal barrier and anti-inflammation in dextran sulfate sodium(DSS)-induced ulcerative colitis mice.METHODS Male C57BL/6 mice were divided into four groups:negative control group,DSS model group,DSS+resveratrol group,and DSS+5-aminosalicylic acid group.The severity of colitis was assessed by the disease activity index,serum inflammatory cytokines were detected by enzyme-linked immunosorbent assay.Colon tissues were stained with haematoxylin and eosin,and mucosal damage was evaluated by mean histological score.The expression of occludin and ZO-1 in colon tissue was evaluated using immunohistochemical analysis.In addition,the expression of autophagy-related genes was determined using reverse transcription-polymerase chain reaction and Western-blot,and morphology of autophagy was observed by transmission electron microscopy.RESULTS The resveratrol treatment group showed a 1.72-fold decrease in disease activity index scores and 1.42,3.81,and 1.65-fold decrease in the production of the inflammatory cytokine tumor necrosis factor-α,interleukin-6 and interleukin-1β,respectively,in DSS-induced colitis mice compared with DSS group(P<0.05).The expressions of the tight junction proteins occludin and ZO-1 in DSS model group were decreased,and were increased in resveratrol-treated colitis group.Resveratrol also increased the levels of LC3B(by 1.39-fold compared with DSS group)and Beclin-1(by 1.49-fold compared with DSS group)(P<0.05),as well as the number of autophagosomes,which implies that the resveratrol may alleviate intestinal mucosal barrier dysfunction in DSS-induced UC mice by enhancing autophagy.CONCLUSION Resveratrol treatment decreased the expression of inflammatory factors,increased the expression of tight junction proteins and alleviated UC intestinal mucosal barrier dysfunction;this effect may be achieved by enhancing autophagy in intestinal epithelial cells.展开更多
Ulcerative colitis(UC) is a chronic inflammatory bowel condition characterised by a relapsing and remitting course. Symptom control has been the traditional mainstay of medical treatment. It is well known that histolo...Ulcerative colitis(UC) is a chronic inflammatory bowel condition characterised by a relapsing and remitting course. Symptom control has been the traditional mainstay of medical treatment. It is well known that histological inflammatory activity persists despite adequate symptom control and absence of endoscopic inflammation. Current evidence suggests that presence of histological inflammation poses a greater risk of disease relapse and subsequent colorectal cancer risk. New endoscopic technologies hold promise for developing endoscopic markers of mucosal inflammation. Achieving endoscopic and histological remission appears be the future aim of medical treatments for UC. This review article aims to evaluate the use of endoscopy as a tool in assessment of mucosal inflammation UC and its correlation with disease outcomes.展开更多
Stress ulceration is single or multiple mucosal defects with/without bleeding from the gastric mucosa during the physiologic stress. Oxidative stress (OS) is a key pathogenic factor in psychogenic stress-induced acute...Stress ulceration is single or multiple mucosal defects with/without bleeding from the gastric mucosa during the physiologic stress. Oxidative stress (OS) is a key pathogenic factor in psychogenic stress-induced acute gastric mucosal lesion (AGML). Fermented papaya preparation (FPP) is reported to have oxygen radical scavenging activity and is effective in OS-related diseases. Here, we investigated the protective effects and the mechanism of action of FPP on stress-induced AGML in rats, induced by water immersion restraint stress (WIRS). Exposure of rats to 6-hour WIRS resulted in the appearance of splinter hemorrhages and mucosal lesions in the stomach. WIRS induced significant increase in lipid peroxidation and decrease in superoxide dismutase-like activity in both the plasma and gastric mucosa. WIRS also significantly increased myeloperoxidase activity together with Nuclear factor-kappaB (NF-kB) activation in gastric mucosa. FPP reduced all the above changes. The results suggest that oral administration of FPP provides protection against WIRS-induced acute gastric mucosal lesions through its anti-oxidative and anti-inflammatory properties.展开更多
三萜类化合物是一类富含多种异戊二烯单元的天然产物,其具有抗炎、抗氧化等生物活性,并在缓解肠道炎症方面具有潜在的治疗效果。首先,三萜类化合物可通过抑制炎性介质(白细胞介素、前列腺素、肿瘤坏死因子)及其相关信号通路来减少炎性...三萜类化合物是一类富含多种异戊二烯单元的天然产物,其具有抗炎、抗氧化等生物活性,并在缓解肠道炎症方面具有潜在的治疗效果。首先,三萜类化合物可通过抑制炎性介质(白细胞介素、前列腺素、肿瘤坏死因子)及其相关信号通路来减少炎性因子的分泌,起到抗肠道炎症的作用;其次,三萜类化合物通过改善活性氧的产生,平衡氧化还原系统,降低氧化应激损伤,达到抗炎的作用;再次,三萜类化合物也能通过调节NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain associated protein 3,NLRP3)炎性小体、多条信号通路(NF-κB/MAPK/Nrf2信号通路)来改善免疫球蛋白和补体水平含量达到免疫平衡作用;第四,三萜类化合物还可通过促进紧密连接蛋白表达,修复损伤的肠道黏膜上皮,提高肠道屏障功能,减少刺激性物质的渗透来抑制肠道炎症;另外,三萜类化合物与肠道菌群间具有紧密联系,能维持肠道微生物稳定,保持肠道上皮屏障的完整性,减少肠道炎症的发生。综上,三萜类化合物通过调控炎症、氧化应激、免疫平衡、黏膜屏障、肠道微生物5个途径,发挥对肠道炎症的保护作用。目前对于三萜类化合物的研究还存在一些限制和挑战,本综述为进一步探索、开发和利用三萜类化合物提供了重要参考,为其在肠道炎症治疗领域的应用提供了新的思路。展开更多
文摘Mucosal healing(MH)is vital in maintaining homeostasis within the gut and protecting against injury and infections.Multiple factors and signaling pathways contribute in a dynamic and coordinated manner to maintain intestinal homeostasis and mucosal regeneration/repair.However,when intestinal homeostasis becomes chronically disturbed and an inflammatory immune response is constitutively active due to impairment of the intestinal epithelial barrier autoimmune disease results,particularly inflammatory bowel disease(IBD).Many proteins and signaling pathways become dysregulated or impaired during these pathological conditions,with the mechanisms of regulation just beginning to be understood.Consequently,there remains a relative lack of broadly effective therapeutics that can restore MH due to the complexity of both the disease and healing processes,so tissue damage in the gastrointestinal tract of patients,even those in clinical remission,persists.With increased understanding of the molecular mechanisms of IBD and MH,tissue damage from autoimmune disease may in the future be ameliorated by developing therapeutics that enhance the body’s own healing response.In this review,we introduce the concept of mucosal healing and its relevance in IBD as well as discuss the mechanisms of IBD and potential strategies for altering these processes and inducing MH.
文摘Non-alcoholic fatty liver disease (NAFLD), a further expression of metabolic syndrome, strictly linked to obesity and diabetes mellitus, is characterized by insulin resistance (IR), elevated serum levels of free fatty acids and fatty infi ltration of the liver, which is known as hepatic steatosis. Hepatocyte apoptosis is a key feature of this disease and correlates with its severity. Free-fatty-acidinduced toxicity represents one of mechanisms for the pathogenesis of NAFLD and hormones, growth factors and adipokines influence also play a key role. This review highlights the various pathways that contribute to the development of hepatic steatosis. Circulating concentrations of inflammatory cytokines are reckoned to be the most important factor in causing and maintaining IR. Low-grade chronic inflammation is fundamental in the progression of NAFLD toward higher risk cirrhotic states.
文摘Independent of the cause and location,inflammation-even when minimal-has clear effects on gastrointestinal morphology and function.These result in altered digestion,absorption and barrier function.There is evidence of reduced villus height and crypt depth,increased permeability,as well as altered sugar and peptide absorption in the small intestine after induction of inflammation in experimental models,which is supported by some clinical data.Identification of inflammatory factors which may promote the process of gastrointestinal dysfunction as well as clinical research to verify experimental observations of inflammatory modulation of gastrointestinal function are required.Moreover,nutritional strategies to support functional restitution are needed.
基金Supported by an unrestricted research grant from Tech Lab,Blacksburg,VA,United States
文摘BACKGROUND Studies have demonstrated a potential role for fecal biomarkers such as fecal calprotectin(FC)and fecal lactoferrin(FL)in monitoring inflammatory bowel diseases(IBD)-Crohn's disease(CD)and ulcerative colitis(UC).However,their correlation to endoscopic scores,disease severity and affected intestinal surface has not been extensively investigated.AIM To correlate FL,and for comparison white blood cell(WBC)and C-reactive protein(CRP),with endoscopic scores,disease extent and location in CD and UC.METHODS Retrospective analysis in 188 patients who had FL,CRP and WBC determined within 30 d of endoscopy.Disease location,disease extent(number of intestinal segments involved),disease severity(determined by endoscopic scores),timing of FL testing in relation to colonoscopy,as well as the use of effective fast acting medications(steroids and biologics)between colonoscopy and FL measurement,were recorded.RESULTS In 131 CD and 57 UC patients,both CRP and FL-but not WBC-distinguished disease severity(inactive,mild,moderate,severe).In patients receiving fastacting(steroids or biologics)treatment in between FL and colonoscopy,FL showed a higher correlation to endoscopic scores when tested before vs after the procedure(r=0.596,P<0.001,vs r=0.285,P=0.15 for the Simple Endoscopic Score for CD;and r=0.402,P=0.01 vs r=0.054 P=0.84 for Disease Activity Index).Finally,FL was significantly correlated with the diseased mucosal surface(colon-ileocolon>small bowel)and the number of inflamed colon segments.CONCLUSION FL and CRP separated disease severity categories with FL showing lower discriminating P-values.FL showed a close correlation with the involved mucosal surface and with disease extent and was more closely correlated to endoscopy when determined before the procedure–this indicating that inflammatory activity changes associated with therapy might be rapidly reflected by FL levels.FL can accurately and timely characterize intestinal inflammation in IBD.
基金This work was supported by Chinese Natural Science Foundation Grants(81630080)the Fundamental Research Funds for the Central Universities of China(NO:2017-JYB-JS-101,2018-JYBZZ-JS075,2019-JYB-JSPYGD-011).
文摘Objective:To investigate the protective effect of Dahuang Fuzi Decoction(DHFZD),a traditional Chinese prescription,at alleviating sepsis-induced inflammation and gut barrier damage in rats.Methods:Forty clean-grade male Sprague-Dawley rats were divided randomly into three groups:normal control group(NCG,n?10),model control group(MCG,n?15)and DHFZD-treated group(DHFZDG,n?15).NCG rats were sham operated on and used as the controls,whereas MCG and DHFZDG rats were used to replicate the rat sepsis model using cecal ligation and puncture(CLP).The DHFZDG rats received DHFZD by gavage(4.5 mg/g of body weight)2 h prior to CLP and after its successful induction,while the NCG and MCG rats received equivalent amounts of sterilized water by gavage.All rat groups were starved and had free access to water.At 24 h post-experimental set up,the mortality of rats in each group was recorded,and peritoneal inflammation assessment and pathological changes related to the intestinal mucosal injury index(IMII)in the surviving rats were evaluated.D-lactic acid,tumor necrosis factor(TNF)-a,interleukin(IL)-6 and IL-10 peripheral blood concentrations,along with secretory immunoglobulin A(sIgA)in the intestinal mucosa were evaluated by enzyme-linked immunosorbent assays.Gut microbes were detected using 16S rRNA gene sequencing.Results:DHFZD reduced sepsis-related mortality in the rats.Moreover,it alleviated peritoneal inflammation and pathological changes according to the IMII.DHFZD reduced serum procalcitonin,TNF-a and IL-6 concentrations,but not the IL-10 concentration.It also reduced serum D-lactic acid and increased sIgA concentrations in intestinal mucosa.Notably,DHFZDG restored gut microbiota diversity and regulated the decrease in Bacteroidetes induced by sepsis,compared with the MCG rats.Conclusion:DHFZDG may play a protective role in sepsis by alleviating sepsis-induced inflammation and gut barrier damage in rats.
基金the National Key Research and Development Program of China(No:2020YFC2005300,No:2021YFC2009101)Open/Independent Project of the Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine,Medical School of Nanjing University,and Jiangsu Province Postgraduate Scientific Research Innovation Project(KYCX22-0183).
文摘More and more evidence suggests that puerarin,a potential remedy for gut inflammation,may have an ameliorative effect on sleep disturbances.However,the relationship between puerarin and sleep disruption has not been extensively researched.This study aims to explore the role and mechanisms of puerarin in improving sleep disorders.We established a light-induced sleep disorder model in mice and assessed the effects of puerarin on cognitive behavior using open field and water maze tests.Pathological detection demonstrated that sleep disturbances resulted in observable damage to the liver,lung,and kidney.Puerarin reversed multi-organ damage and inflammation.Further,puerarin activated paneth cells,resulting in increased lysozyme and TGF-βproduction,and stimulating intestinal stem cell proliferation.Puerarin also effectively inhibited the expression of F4/80,iNOS,TNF-α,and IL-1βin the small intestine,while it increased Chil3,CD206,and Arg-1 levels.Moreover,puerarin treatment significantly decreased P-P65,TLR4,Bcl-xl,and cleaved caspase-3 protein levels while increasing barrier protein levels,including ZO-1,Occludin,Claudin 1 and E-cadherin suggesting a reduction in inflammation and apoptosis in the gut.Overall,puerarin diminished systemic inflammation,particularly intestinal inflammation,and enhanced intestinal barrier integrity in mice with sleep disorders.Our findings suggest a potential new therapeutic pathway for sleep disorders.
基金financially supported by the National Natural Science Foundation(No.82304393,China)Beijing Nova Program(Nos.Z211100002121127 and 20220484219,China)+1 种基金Beijing Natural Science Foundation(No.L212059,China)CAMS Innovation Fund for Medical Sciences(No.2021-I2M-1-028,China)。
文摘Ulcerative colitis(UC)is a chronic inflammatory bowel disease characterized by persistent inflammation of the colon and disrupted intestinal function.Ramulus mori(Sangzhi)alkaloids(SZ-A),derived from twigs of mulberry,were approved by the National Medical Products Administration in 2020 for treating type 2 diabetes mellitus.Accumulated evidence has confirmed that SZ-A also alleviates non-alcoholic fatty liver disease and ameliorates inflammation,indicating its potential to address inflammation in UC.However,the treatment of UC faces challenges due to low drug delivery efficiency and short retention time.To overcome these challenges,an injectable and adherent in-situ thermo-sensitive hydrogel containing SZ-A was developed for rectal drug delivery,utilizing the thermo-sensitive polymers Poloxamer 407and 188.The thermo-sensitive hydrogel system was designed with a moderate gelation temperature of 32±0.5℃,a short gelation time of 64 s,a p H range of 7-10,high moisturizing capability exceeding 90%,and moderate mechanical strength of 4-5 s.In a rat model with UC,the in situ thermo-sensitive hydrogel significantly extended the retention time at the colonic site and enabled sustained release after rectal administration.Symptoms of UC were markedly reduced following rectal administration of SZ-A thermosensitive hydrogel.Furthermore,the release of inflammatory factors,such as interleukin-1β(IL-1β),IL-6,IL-18,tumor necrosis factor-α(TNF-α),and transforming growth factor-β1(TGF-β1),significantly decreased in the SZ-A thermo-sensitive hydrogel group.The integrity of the colonic mucosal barrier was significantly enhanced following the application of SZ-A thermo-sensitive hydrogel.In conclusion,rectal administration of SZ-A in situ thermo-sensitive hydrogel effectively alleviated UC symptoms,inhibited the secretion of inflammatory factors,and promoted the repair of the colonic mucosal barrier.This approach holds promise as a potential treatment for UC.
文摘Although gastroesophageal reflux disease(GERD)is a common disorder in Western countries,with a significant impact on quality of life and healthcare costs,the mechanisms involved in the pathogenesis of symptoms remain to be fully elucidated.GERD symptoms and complications may result from a multifactorial mechanism,in which acid and acid-pepsin are the important noxious factors involved.Prolonged contact of the esophageal mucosa with the refluxed content,probably caused by a defective anti-reflux barrier and luminal clearance mechanisms,would appear to be responsible for macroscopically detectable injury to the esophageal squamous epithelium.Receptors on acid-sensitive nerve endings may play a role in nociception and esophageal sensitivity,as suggested in animal models of chronic acid exposure.Meanwhile,specific cytokine and chemokine profiles would appear to underlie the various esophageal phenotypes of GERD,explaining,in part,the genesis of esophagitis in a subset of patients.Despite these findings,which show a significant production of inflammatory mediators and neurotransmitters in the pathogenesis of GERD,the relationship between the hypersensitivity and esophageal inflammation is not clear.Moreover,the large majority of GERD patients(up to 70%)do not develop esophageal erosions,a variant of the condition called non-erosive reflux disease.This summary aims to explore the inflammatory pathway involved in GERD pathogenesis,to better understand the possible distinction between erosive and non-erosive reflux disease patients and to provide new therapeutic approaches.
文摘AIM To investigate the effects of orally gavaged aqueous rhubarb extract(RE) on 5-fluorouracil(5-FU)-induced intestinal mucositis in rats. METHODS Female Dark Agouti rats(n = 8/group) were gavaged daily(1 mL) with water, high-dose RE(HDR; 200 mg/kg) or low-dose RE(LDR; 20mg/kg) for eight days. Intestinal mucositis was induced(day 5) with 5-FU(150 mg/kg) via intraperitoneal injection. Intestinal tissue samples were collected for myeloperoxidase(MPO) activity and histological examination. Xenopus oocytes expressing aquaporin 4 water channels were prepared to examine the effect of aqueous RE on cell volume, indicating a potential mechanism responsible for modulating net fluid absorption and secretion in the gastrointestinal tract. Statistical significance was assumed at P < 0.05 by one-way ANOVA. RESULTS B o d y w e i g h t w a s s i g n i f i c a n t l y r e d u c e d i n r a t s administered 5-FU compared to healthy controls(P < 0.01). Rats administered 5-FU significantly increased intestinal MPO levels(≥ 307%; P < 0.001), compared to healthy controls. However, LDR attenuated this effect in 5-FU treated rats, significantly decreasing ileal MPO activity(by 45%; P < 0.05), as compared to 5-FU controls. 5-FU significantly reduced intestinal mucosal thickness(by ≥ 29% P < 0.001) as compared to healthy controls. LDR significantly increased ileal mucosal thickness in 5-FU treated rats(19%; P < 0.05) relative to 5-FU controls. In xenopus oocytes expressing AQP4 water channels, RE selectively blocked water influx into the cell, induced by a decrease in external osmotic pressure. As water efflux was unaltered by the presence of extracellular RE, the directional flow of water across the epithelial barrier, in the presence of extracellular RE, indicated that RE may alleviate water loss across the epithelial barrier and promote intestinal health in chemotherapy-induced intestinal mucositis.CONCLUSION In summary, low dose RE improves selected parameters of mucosal integrity and reduces ileal inflammation, manifesting from 5-FU-induced intestinal mucositis.
基金Supported by the National Natural Science Foundation of China,No.81600414Medical Health Science and Technology Project of Zhejiang Provincial Health Commission,No.2018255969Zhejiang TCM Science and Technology Project,No.2016ZA123 and No.2018ZA013.
文摘BACKGROUND Intestinal mucosal barrier dysfunction plays an important role in the pathogenesis of ulcerative colitis(UC).Recent studies have revealed that impaired autophagy is associated with intestinal mucosal dysfunction in the mucosa of colitis mice.Resveratrol exerts anti-inflammatory functions by regulating autophagy.AIM To investigate the effect and mechanism of resveratrol on protecting the integrity of the intestinal mucosal barrier and anti-inflammation in dextran sulfate sodium(DSS)-induced ulcerative colitis mice.METHODS Male C57BL/6 mice were divided into four groups:negative control group,DSS model group,DSS+resveratrol group,and DSS+5-aminosalicylic acid group.The severity of colitis was assessed by the disease activity index,serum inflammatory cytokines were detected by enzyme-linked immunosorbent assay.Colon tissues were stained with haematoxylin and eosin,and mucosal damage was evaluated by mean histological score.The expression of occludin and ZO-1 in colon tissue was evaluated using immunohistochemical analysis.In addition,the expression of autophagy-related genes was determined using reverse transcription-polymerase chain reaction and Western-blot,and morphology of autophagy was observed by transmission electron microscopy.RESULTS The resveratrol treatment group showed a 1.72-fold decrease in disease activity index scores and 1.42,3.81,and 1.65-fold decrease in the production of the inflammatory cytokine tumor necrosis factor-α,interleukin-6 and interleukin-1β,respectively,in DSS-induced colitis mice compared with DSS group(P<0.05).The expressions of the tight junction proteins occludin and ZO-1 in DSS model group were decreased,and were increased in resveratrol-treated colitis group.Resveratrol also increased the levels of LC3B(by 1.39-fold compared with DSS group)and Beclin-1(by 1.49-fold compared with DSS group)(P<0.05),as well as the number of autophagosomes,which implies that the resveratrol may alleviate intestinal mucosal barrier dysfunction in DSS-induced UC mice by enhancing autophagy.CONCLUSION Resveratrol treatment decreased the expression of inflammatory factors,increased the expression of tight junction proteins and alleviated UC intestinal mucosal barrier dysfunction;this effect may be achieved by enhancing autophagy in intestinal epithelial cells.
文摘Ulcerative colitis(UC) is a chronic inflammatory bowel condition characterised by a relapsing and remitting course. Symptom control has been the traditional mainstay of medical treatment. It is well known that histological inflammatory activity persists despite adequate symptom control and absence of endoscopic inflammation. Current evidence suggests that presence of histological inflammation poses a greater risk of disease relapse and subsequent colorectal cancer risk. New endoscopic technologies hold promise for developing endoscopic markers of mucosal inflammation. Achieving endoscopic and histological remission appears be the future aim of medical treatments for UC. This review article aims to evaluate the use of endoscopy as a tool in assessment of mucosal inflammation UC and its correlation with disease outcomes.
文摘Stress ulceration is single or multiple mucosal defects with/without bleeding from the gastric mucosa during the physiologic stress. Oxidative stress (OS) is a key pathogenic factor in psychogenic stress-induced acute gastric mucosal lesion (AGML). Fermented papaya preparation (FPP) is reported to have oxygen radical scavenging activity and is effective in OS-related diseases. Here, we investigated the protective effects and the mechanism of action of FPP on stress-induced AGML in rats, induced by water immersion restraint stress (WIRS). Exposure of rats to 6-hour WIRS resulted in the appearance of splinter hemorrhages and mucosal lesions in the stomach. WIRS induced significant increase in lipid peroxidation and decrease in superoxide dismutase-like activity in both the plasma and gastric mucosa. WIRS also significantly increased myeloperoxidase activity together with Nuclear factor-kappaB (NF-kB) activation in gastric mucosa. FPP reduced all the above changes. The results suggest that oral administration of FPP provides protection against WIRS-induced acute gastric mucosal lesions through its anti-oxidative and anti-inflammatory properties.
文摘三萜类化合物是一类富含多种异戊二烯单元的天然产物,其具有抗炎、抗氧化等生物活性,并在缓解肠道炎症方面具有潜在的治疗效果。首先,三萜类化合物可通过抑制炎性介质(白细胞介素、前列腺素、肿瘤坏死因子)及其相关信号通路来减少炎性因子的分泌,起到抗肠道炎症的作用;其次,三萜类化合物通过改善活性氧的产生,平衡氧化还原系统,降低氧化应激损伤,达到抗炎的作用;再次,三萜类化合物也能通过调节NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain associated protein 3,NLRP3)炎性小体、多条信号通路(NF-κB/MAPK/Nrf2信号通路)来改善免疫球蛋白和补体水平含量达到免疫平衡作用;第四,三萜类化合物还可通过促进紧密连接蛋白表达,修复损伤的肠道黏膜上皮,提高肠道屏障功能,减少刺激性物质的渗透来抑制肠道炎症;另外,三萜类化合物与肠道菌群间具有紧密联系,能维持肠道微生物稳定,保持肠道上皮屏障的完整性,减少肠道炎症的发生。综上,三萜类化合物通过调控炎症、氧化应激、免疫平衡、黏膜屏障、肠道微生物5个途径,发挥对肠道炎症的保护作用。目前对于三萜类化合物的研究还存在一些限制和挑战,本综述为进一步探索、开发和利用三萜类化合物提供了重要参考,为其在肠道炎症治疗领域的应用提供了新的思路。