Mucosal healing and inflammatory bowel disease:Therapeutic implications and new targets

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.

Hepatic steatosis,low-grade chronic inflammation and hormone/growth factor/adipokine imbalance

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.

Even low-grade inflammation impacts on small intestinal function

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.

Fecal lactoferrin accurately reflects mucosal inflammation in inflammatory bowel disease

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.

Dahuang Fuzi decoction reduces inflammation levels and alleviates intestinal mucosal barrier damage in septic rats

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.

Puerarin alleviates sleep disorders in aged mice related to repairing intestinal mucosal barrier

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.

Simple and versatile in situ thermo-sensitive hydrogel for rectal administration of SZ-A to alleviate inflammation and repair mucosal barrier in ulcerative colitis

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.

Gastroesophageal reflux disease: Update on inflammation and symptom perception

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.

Rhubarb extract partially improves mucosal integrity in chemotherapy-induced intestinal mucositis

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.

Resveratrol alleviates intestinal mucosal barrier dysfunction in dextran sulfate sodium-induced colitis mice by enhancing autophagy

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.

Clinical relevance of endoscopic assessment of inflammation in ulcerative colitis: Can endoscopic evaluation predict outcomes?

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.

Protective effect of fermented papaya preparation on stress-induced acute gastric mucosal lesion

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.

辛麻颗粒对慢性哮喘小鼠呼吸道黏膜免疫功能的影响

【目的】探讨辛麻颗粒对慢性哮喘小鼠呼吸道黏膜免疫功能的影响。【方法】将50只雌性BALB/C小鼠随机分成正常组、模型组、辛麻颗粒低剂量组、辛麻颗粒高剂量组、地塞米松组,每组10只。除正常组,其余各组小鼠采用卵清白蛋白(OVA)致敏和激发法建立慢性哮喘模型。给予相应干预后,采用酶联免疫吸附分析(ELISA)测定支气管灌洗液分泌型免疫球蛋白A(sIgA)、免疫球蛋白E(IgE)水平,苏木素-伊红(HE)染色法观察肺组织病理学改变,Western Blot法检测肺组织E钙黏蛋白(E-cadherin)表达。【结果】HE染色可见哮喘小鼠明显气道炎症。模型组小鼠支气管灌洗液sIgA浓度低于正常组(P<0.05);辛麻颗粒高、低剂量组及地塞米松组sIgA浓度高于模型组(P<0.05)。模型组小鼠支气管灌洗液IgE浓度高于正常组(P<0.05);辛麻颗粒高、低剂量组及地塞米松组IgE浓度低于模型组(P<0.05)。模型组小鼠肺组织E-cadherin蛋白相对表达量低于正常组(P<0.05);辛麻颗粒高、低剂量组及地塞米松组小鼠肺组织中E-cadherin蛋白相对表达量高于模型组(P<0.05)。辛麻颗粒高剂量组和地塞米松组各指标改善效果优于辛麻颗粒低剂量组(P<0.05),且2组比较,差异无统计学意义(P>0.05)。【结论】辛麻颗粒可能通过改善气道炎症、增高呼吸道sIgA浓度、增强呼吸道E-cadherin蛋白的表达,提高哮喘小鼠呼吸道黏膜免疫功能。

中医药改善慢性鼻窦炎内镜术后鼻黏膜重塑研究进展

中医药改善慢性鼻窦炎内镜术后鼻黏膜重塑是有效预防术腔黏膜发生新病变及复发的关键。本文综述慢性鼻窦炎内镜术后鼻黏膜重塑的机制及中医药治疗的独特优势。虚、痰、瘀三者互为因果导致“肺失治节”是鼻黏膜重塑迁延不愈的主要原因。治疗以“补虚祛痰,益气活血”为原则,针药并用、内外兼治以调节Th17/Treg平衡,减少炎症浸润;阻断MAPK和NF-κB途径的磷酸化抑制TGF-β1诱导的肌成纤维细胞,减少胶原沉积及抑制其重塑等,促进黏膜上皮化进程,可为中医药防治鼻黏膜重塑进程的理论和临床治疗研究提供思路。

AOM/DSS结肠癌模型优化及其肠道菌群变化探究

目的优化氧化偶氮甲烷(azoxymethane,AOM)联合葡聚糖硫酸钠(dextran sodium sulfate,DSS)造模结肠炎相关性结肠癌(colitis-associated colorectal cancer,CAC)方法并探究肠道菌群在CAC中的发病机制。方法通过AOM不同注射次数联合自由饮用DSS的方法建立A(AOM 1次注射)和B(AOM 2次注射)模型组,正常组采用腹腔注射生理盐水联合饮用纯净水,每组10只。造模结束后通过DAI评分、结肠长度、成瘤率及死亡率等指标综合评估,选择最佳的造模方案。然后对B模型组小鼠进行实验,取血清以ELISA法检测白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)及肿瘤标志物CA199、CEA、CA724含量;同时进行HE染色观察结肠病变;并对小鼠粪便进行16S rDNA高通量基因测序法分析,以探究CAC小鼠肠道菌群的变化。结果单次和加强AOM注射联合DSS均能诱导CAC小鼠模型。但与A模型组相比,B模型组小鼠结肠内增生物较大,排列紧密且形态大小较一致,成瘤率达到100%。与正常组相比,B模型组IL-6显著升高(P<0.05),TNF-α含量升高(P>0.05);肿瘤标志物除CA724外,CA199和CEA含量均明显升高(P<0.05);HE病理结肠内炎性细胞的浸润,并伴有管腔表面显示出高级别上皮内肿瘤样改变。菌群结果显示,与正常组相比,CAC小鼠肠道菌群物种多样性及丰度降低,疣微菌门和放线菌门增多(P<0.05),拟杆菌门和弯曲菌门减少(P<0.05)。阿克曼菌、普雷沃菌、瘤胃球菌、双歧杆菌等显著增多(P<0.05);罗氏菌属、Muribaculaceae、理研菌属、厌氧原体属等显著减少(P<0.05)。结论AOM 2次注射联合自由饮用1.5%(1.5 g/100 mL)DSS诱导的CAC模型小鼠结肠成瘤率高、肿瘤形态大小均一、死亡率低,可作为药效学实验评价的优选造模方案。多种肠道菌群紊乱或功能失调,造成的通透性增高,肠黏膜屏障功能破坏,进而诱发肠源性内毒素释放,导致持续的炎症反应或是诱发CAC发病的间接或直接原因。

英夫利西单抗联合美沙拉嗪对溃疡性结肠炎患者炎症因子、结肠黏膜屏障指标、炎症相关蛋白的影响

目的:探讨英夫利西单抗联合美沙拉嗪对溃疡性结肠炎(UC)患者炎症因子、结肠黏膜屏障指标及炎症相关蛋白的影响。方法:选取2021年8月~2023年10月期间于某院治疗的84例UC患者作为研究对象,采用随机数字表法分为对照组和观察组,每组42例。两组患者均给予补液、营养支持等常规治疗,对照组患者在常规治疗基础上加用美沙拉嗪肠溶片,观察组患者在对照组治疗基础上加用注射用英夫利西单抗。比较两组患者炎症因子[白介素-6(IL-6)、C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)]、结肠黏膜屏障指标[二胺氧化酶(DAO)、D-乳酸]、炎症相关蛋白[粪便钙卫蛋白(FC)、GATA结合蛋白-3(GATA-3)]、临床疗效及不良反应发生情况。结果:治疗后,两组患者血清IL-6、CRP、TNF-α水平均降低(P<0.05),且观察组低于对照组(P<0.05);血清DAO、D-乳酸水平均降低(P<0.05),且观察组低于对照组(P<0.05);FC、血清GATA-3水平均降低(P<0.05),且观察组低于对照组(P<0.05)。观察组患者治疗总有效率(85.71%)高于对照组(61.90%,P<0.05)。两组患者治疗期间皮疹、头晕、恶心呕吐等不良反应发生情况比较无统计学差异(P>0.05)。结论:英夫利西单抗联合美沙拉嗪治疗UC患者临床疗效较好,可有效抑制炎症因子,增强结肠黏膜屏障功能,改善FC、血清GATA-3水平,且不会增加不良反应的发生风险。

三萜类化合物对肠道炎症的药理作用

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。

放化疗所致口腔黏膜炎疼痛电生理机制研究进展

放化疗后普遍出现的口腔黏膜炎(oral mucositis,OM)是头颈癌患者治疗过程中出现的最常见的不良反应之一,表现为口腔黏膜充血、水肿以及溃疡等,其引发的疼痛会严重影响患者的生活质量,干扰治疗进程。放化疗所致OM的发病机制复杂,涉及多种炎症因子及多条信号通路,而有关其疼痛的电生理机制的研究相对较少。黏膜损伤处的急性疼痛和炎症环境下的持续性疼痛,导致离子通道重构,产生中枢及外周的敏化。本研究从离子通道角度对OM的致痛机制进行探讨,通过类比其他炎性疼痛的研究结果,重点关注瞬时受体电位通道、钠通道和钾通道在OM及其他疾病所致疼痛中的变化,推测OM致痛可能的电生理机制。离子通道作为重要的药物靶点,针对性的开放剂和拮抗剂可有效缓解疼痛,结合目前放化疗所致OM主要治的疗方式,以期为OM疼痛管理提供新的思路。

基于细胞自噬调控的中药治疗溃疡性结肠炎药理机制研究进展

自噬是由溶酶体介导的程序化细胞降解途径,通过降解和重吸收作用,在维持细胞稳态、清除细胞内有毒物质、平衡代谢能量等方面发挥着重要作用。自噬参与了溃疡性结肠炎诸多环节,研究显示自噬可以改善肠道黏膜屏障功能,调节免疫炎症反应,调节肠道菌群,减轻氧化应激损伤,目前,通过干预自噬靶向治疗溃疡性结肠炎已成为研究的前沿方向。据报道,多种对溃疡性结肠炎具有确切疗效的中药单体(或其活性成分)及复方通过对自噬相关蛋白、自噬相关基因、自噬信号通路、细胞因子及其他方面的调控参与了自噬的调节。

反示教法对血液病化疗口腔黏膜炎的预防价值

目的 探讨反示教法对血液病化疗口腔黏膜炎的预防价值。方法 选取2022年3月—2023年3月厦门大学附属第一医院收治的100例血液病患者,将2022年3—8月收治的50例患者作为对照组,2022年9月—2023年3月收治的50例患者作为观察组。对照组采用常规护理,而观察组接受反示教法,比较2组患者对口腔健康知信行情况,口腔黏膜炎症严重程度以及患者对护理的满意度。结果 干预后,2组口腔健康知信行问卷知识层面、信念层面、行为层面评分均上升(P <0.05);观察组口腔健康知信行问卷知识层面、信念层面、行为层面评分高于对照组(P <0.05);干预后,观察组口腔黏膜炎总发生率为18.00%(9/50),低于对照组的52.00%(26/50)(P <0.05);干预后,观察组中国医院住院患者体验和满意监测量表(Chinese hospital patient experience and satisfaction monitor,CHPESMS)可及入院、投诉与意见管理以及环境与后勤管理评分与对照组比较,差异无统计学意义(P> 0.05);但观察组一般住院服务、治疗服务以及出院指导维度评分高于对照组,差异有统计学意义(P <0.05)。结论 反示教法相较于常规护理,不仅能增长血液病化疗患者口腔相关卫生知识,强化信念,提升口腔相关卫生健康行为,还能降低口腔黏膜炎症发生率,提升患者对一般住院服务、治疗服务以及出院指导服务的满意度。