Effect of ageing on colonic mucosal regeneration

The physiologic and pathologic cellular and molecular changes occurring with age in the human colon affect both the inflammatory process leading to mucosal injury and the regenerative capacity of the epithelium.On the one hand,age-related telomere shortening and inflamm-ageing may lead to the development of colonic inflammation,which results in epithelial damage.On the other hand,the altered migration and function of regenerative stem cells,the age-related methylation of mucosal healing-associated genes,together with the alterations of growth factor signaling with age,may be involved in delayed mucosal regeneration.The connections of these alterations to the process of ageing are not fully known.The understanding and customtailored modification of these mechanisms are of great clinical importance with regard to disease prevention and modern therapeutic strategies.Here,we aim to summarize the age-related microscopic and molecular changes of the human colon,as well as their role in altered mucosal healing.

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.

Isolated lymphoid follicles in colon: Switch points between inflammation and colorectal cancer?

Gut-associated lymphoid tissue is supposed to play a central role in both the organization of colonic repair mechanisms and colorectal carcinogenesis. In inflammatory conditions, the number, diameter and density of isolated lymphoid follicles (ILFs) increases. They are not only involved in immune surveillance, but their presence is also indispensable in normal mucosal regeneration of the colon. In carcinogenesis, ILFs may play a dual role. On the one hand they may support tumor growth and the metastatic process by vascular endothelial growth factor receptor signaling and producing a specific cytokine and cellular milieu, but on the other hand their presence is sometimes associated with a better prognosis. The relation of ILFs to bone marrow derived stem cells, follicular dendritic cells, subepithelial myofibroblasts or crypt formation, which are all involved in mucosal repair and carcinogenesis, has not been directly studied. Data about the putative organizer role of ILFs is scattered in scientific literature.

An antibiotic-free platform for eliminating persistent Helicobacter pylori infection without disrupting gut microbiota

Helicobacter pylori(H.pylori)infection remains the leading cause of gastric adenocarcinoma,and its eradication primarily relies on the prolonged and intensive use of two antibiotics.However,antibiotic resistance has become a compelling health issue,leading to H.pylori eradication treatment failure worldwide.Additionally,the powerlessness of antibiotics against biofilms,as well as intracellular H.pylori and the long-term damage of antibiotics to the intestinal microbiota,have also created an urgent demand for antibiotic-free approaches.Herein,we describe an antibiotic-free,multifunctional copperorganic framework(HKUST-1)platform encased in a lipid layer comprising phosphatidic acid(PA),rhamnolipid(RHL),and cholesterol(CHOL),enveloped in chitosan(CS),and loaded in an ascorbyl palmitate(AP)hydrogel:AP@CS@Lip@HKUST-1.This platform targets inflammatory sites where H.pylori aggregates through electrostatic attraction.Then,hydrolysis by matrix metalloproteinases(MMPs)releases CS-encased nanoparticles,disrupting bacterial urease activity and membrane integrity.Additionally,RHL disperses biofilms,while PA promotes lysosomal acidification and activates host autophagy,enabling clearance of intracellular H.pylori.Furthermore,AP@CS@Lip@HKUST-1 alleviates inflammation and enhances mucosal repair through delayed Cu^(2+) release while preserving the intestinal microbiota.Collectively,this platform presents an advanced therapeutic strategy for eradicating persistent H.pylori infection without inducing drug resistance.