Barrier Repair Research Articles

Enhanced Anti-Inflammatory and Skin Barrier Repair Effects of Nanoemulsions Supplemented with Boesenbergia rotunda for Atopic Dermatitis

Enhanced Anti-Inflammatory and Skin Barrier Repair Effects of Nanoemulsions Supplemented with <i>Boesenbergia rotunda</i> for Atopic Dermatitis

Lipid extract from Black Soldier Fly larvae: A high value excipient for solid lipid nanoparticles tailored to tackle atopic dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin disorder with a complex pathogenesis involving epidermal barrier dysfunction and aberrant lipid composition, particularly ceramides and fatty acids (FA). Conventional management options, such as topical glucocorticoids (GC), often lead to adverse effects upon prolonged usage, prompting the exploration of alternative therapeutic strategies. The lipid extract from Black Soldier Fly larvae (BSFL) biomass, holding a rich blend of FA, holds substantial potential as a novel ingredient to tackle skin barrier impairment. This study aimed to achieve proof-of-concept validation of innovative nanotechnology-based formulations tailored to enhance the topical management of AD. Specifically, solid lipid nanoparticles (SLNs) with BSFL lipid extract were developed to perform both as a carrier for dexamethasone (DEX), a representative GC, and as skin barrier repair adjuvants. Through systematic optimization using Box-Behnken Design, BSFL lipid extract-based SLNs demonstrated favorable physicochemical properties for topical application and satisfactory stability over 2 months. Notably, these SLNs exhibited favorable drug release kinetics, delivering the total DEX payload within a therapeutically relevant timeframe. Furthermore, these nanocarriers showed the ability to permeate human keratinocytes without pronounced toxicity, suggesting their potential utility in enhancing drug delivery and cellular uptake. Overall, these findings suggest that BSFL lipid extract is a promising natural and sustainable ingredient for the development of nanotechnology-driven approaches to AD management, offering a potential avenue for addressing the unmet needs in this challenging dermatologic condition.

194 Filaggrin status modulates gene transcription, DNA damage and epidermal barrier repair during clinical response to methotrexate in atopic eczema

194 Filaggrin status modulates gene transcription, DNA damage and epidermal barrier repair during clinical response to methotrexate in atopic eczema

Effect of bioactive compounds in processed Camellia sinensis tea on the intestinal barrier

The human intestinal tract plays a pivotal role in safeguarding the body against noxious substances and microbial pathogens by functioning as a barrier. This barrier function is achieved through the combined action of physical, chemical, microbial, and immune components.Tea (Camellia sinensis) is the most widely consumed beverage in the world. Tea is consumed and appreciated in a multitude of regions across the globe. Tea can be classified into various categories, including green, white, yellow, oolong, black, and dark teas, based on the specific processing methods employed. In recent times, there has been a notable surge in scientific investigation into the various types of tea. The recent surge in research on tea can be attributed to the plethora of bioactive compounds it contains, including polyphenols, polysaccharides, pigments, and theanine. The processing of different teas affects the active ingredients to varying degrees, resulting in a range of chemical reactions and the formation of different types and quantities of ingredients. The bioactive compounds present in tea are of great importance for the maintenance of the integrity of the intestinal barrier, operating through a variety of mechanisms. This literature review synthesizes scientific studies on the impact of the primary bioactive compounds and different processing methods of tea on the intestinal barrier function. This review places particular emphasis on the exploration of the barrier repair and regulatory effects of these compounds, including the mitigation of damage to different barriers following intestinal diseases. Specifically, the active ingredients in tea can alleviate damage to physical barriers and also alleviate damage to chemical barriers by regulating barrier protein expression. At the same time, they can also maintain the stability of immune and biological barriers by regulating the expression of inflammatory factors and the metabolism of intestinal flora. This investigation can establish a strong theoretical foundation for the future development of innovative tea products.

Investigating bacteria-induced inflammatory responses using novel endometrial epithelial gland organoid models.

The endometrium plays a crucial role in early human pregnancy, particularly in embryo implantation, survival, and growth. However, invasion and infection by pathogens can lead to endometritis, infertility, and poor reproductive outcomes. Understanding the mechanisms of endometritis and its impact on fertility remains limited. An infection model using patient-derived endometrial epithelial gland organoids (EEGOs) was established to advance in vitro studies on endometritis and related infertility. An EEGOs infection model was constructed and characterized from human endometrium, treating the organoids with estrogen and progesterone to observe changes in the proliferative and secretory phases. The organoids were infected with E. coli, and the release of inflammatory cytokines in the supernatant was detected using ELISA. RNA-seq was employed to analyze the differences before and after E. coli treatment, and differential gene mRNA expression was validated using real-time quantitative PCR. Additionally, the effect of E2 in alleviating inflammation was assessed through markers of receptivity (PAEP, LIF, ITGβ), proliferation (Ki67), and barrier repair (ZO-1). The constructed human EEGOs exhibited long-term expansion capability, genetic stability, and characteristic hormonal responses, strongly expressing epithelial markers (MUC1, E-Cadherin). After E. coli infection, the expression levels of inflammatory cytokines TNF-α, IL-8, and IFN-γ increased significantly (P < 0.05). RNA-seq indicated that the MAPK signaling pathway was activated post-infection, with increased expression levels of heat shock proteins and transcription factor mRNA. E2 treatment post-infection significantly decreased the mRNA expression of inflammatory genes IL-1β, IL8, IL6 and TNF-α compared to the E. coli infected group (P < 0.05). Additionally, the expression of genes related to receptivity, proliferation, and barrier repair was enhanced in the E2-treated organoids. Our findings demonstrate that patient-derived EEGOs are responsive to bacterial infection and are effective models for studying host-pathogen interactions in bacterial infections. These organoids revealed the anti-inflammatory potential of E2 in alleviating E. coli-induced inflammation, providing insights into the mechanisms of endometritis and its impact on infertility. The study supports the use of EEGOs as valuable tools for understanding endometrial health and developing targeted treatments.

Probiotic-derived extracellular vesicles alleviate AFB1-induced intestinal injury by modulating the gut microbiota and AHR activation

BackgroundAflatoxin B1 (AFB1) is a mycotoxin that widely found in the environment and mouldy foods. AFB1 initially targets the intestine, and AFB1-induced intestinal injury cannot be ignored. Lactobacillus amylovorus (LA), a predominant species of Lactobacillus, plays a role in carbohydrate metabolism. Extracellular vesicles (EVs), small lipid membrane vesicles, are widely involved in diverse cellular processes. However, the mechanism by which Lactobacillus amylovorus-QC1H-derived EVs (LA.EVs) protect against AFB1-induced intestinal injury remains unclear.ResultsIn our study, a new strain named Lactobacillus amylovorus-QC1H (LA-QC1H) was isolated from pig faeces. Then, EVs derived from LA-QC1H were extracted via ultracentrifugation. Our results showed that LA.EVs significantly alleviated AFB1-induced intestinal injury by inhibiting the production of proinflammatory cytokines, decreasing intestinal permeability and increasing the expression of tight junction proteins. Moreover, 16 S rRNA analysis revealed that LA.EVs modulated AFB1-induced gut dysbiosis in mice. However, LA.EVs did not exert beneficial effects in antibiotic-treated mice. LA.EVs treatment increased intestinal levels of indole-3-acetic acid (IAA) and activated intestinal aryl hydrocarbon receptor (AHR)/interleukin-22 (IL-22) signalling in AFB1-exposed mice. Inhibition of intestinal AHR signalling markedly weakened the protective effect of LA.EVs in AFB1-exposed mice.ConclusionsLA.EVs alleviated AFB1-induced intestinal injury by modulating the gut microbiota, activating the intestinal AHR/IL-22 signalling, reducing the inflammatory response and promoting intestinal barrier repair in mice.

Mesenchymal stem cells: a novel therapeutic approach for feline inflammatory bowel disease

BackgroundInflammatory bowel disease (IBD) poses a significant and growing global health challenge, affecting both humans and domestic cats. Research on feline IBD has not kept pace with its widespread prevalence in human populations. This study aimed to develop a model of feline IBD by incorporating dextran sulfate sodium (DSS) to evaluate the therapeutic potential of MSCs and to elucidate the mechanisms that enhance their action.MethodsWe conducted a comprehensive clinical assessment, including magnetic resonance imaging (MRI), endoscopy, and histopathological examination. Additionally, alterations in intestinal microbiota were characterized by 16 S rDNA sequencing, and the influence of MSCs on IBD-related gene expression was investigated through transcriptome analysis.ResultsAccording to our findings, MSC treatment significantly mitigated DSS-induced clinical manifestations, reduced inflammatory cell infiltration, decreased the production of inflammatory mediators, and promoted mucosal repair. Regarding the intestinal microbiota, MSC intervention effectively corrected the DSS-induced dysbiosis, increasing the presence of beneficial bacteria and suppressing the proliferation of harmful bacteria. Transcriptome analysis revealed the ability of MSCs to modulate various inflammatory and immune-related signaling pathways, including cytokine-cytokine receptor interactions, TLR signaling pathways, and NF-κB pathways.ConclusionThe collective findings indicate that MSCs exert multifaceted therapeutic effects on IBD, including the regulation of intestinal microbiota balance, suppression of inflammatory responses, enhancement of intestinal barrier repair, and modulation of immune responses. These insights provide a solid scientific foundation for employing MSCs as an innovative therapeutic strategy for IBD and pave the way for future clinical explorations.

Retinol (Vitamin A) and Its Derivatives: Synthesis and Applications

This paper systematically reviews the synthesis methods of retinol (Vitamin A) and its derivatives, along with their applications in skincare and pharmaceuticals. By examining traditional chemical synthesis pathways such as the Roche, BASF, and Rhone-Poulenc routes, as well as modern biological synthesis pathways, the paper highlights the advantages and limitations of each method, particularly in terms of improving synthesis efficiency, reducing production costs, and minimizing environmental impact. The paper also analyzes the application of retinol derivatives in skincare, including their roles in anti-aging, skin barrier repair, skin whitening, and even tone. Additionally, the paper discusses methods to enhance the stability and bioactivity of retinol. Future directions include further innovation in synthesis techniques, the development of new derivatives, and new pharmaceutical applications of retinol. The paper concludes that retinol and its derivatives hold great promise in the beauty and health sectors, though further research is needed to overcome current challenges and promote wider application.

Elegant approach to intervention of homogalacturonan from the fruits of Ficus pumila L. in colitis: Unraveling the role of methyl esters and acetyl groups.

Oral administration of homogalacturonan (HG) has shown significant potential in anti-colitis activity, yet the therapeutic efficacy of naturally sourced HG still requires enhancement. Herein, HG from the fruits of Ficus pumila L. was modified by chemical methods and the intervention effect of modified HG with different degrees of methyl-esterification (DM) and acetylation (DA) on dextran sulfate sodium-induced colitis in mice was explored. Our results indicated that low-DM HG (DM3 and DM25) primarily mitigated colitis by reducing inflammation (TNF-α, IL-1β, IL-17, and IL-6), while high-DM HG (DM54 and DM94) primarily repaired the intestinal barrier. These effects may be attributed to the differential regulation of gut microbiota by HG with varying DM, such as Lachnospiraceae_NK4A136_group, Lactobacillus, Mucispirillum, Escherichia-Shigella, Bifidobacterium, and Bacteroides. Increased DA reduced the solubility of HG, showing limited anti-inflammatory response but unique advantages in intestinal barrier repair and microbiome regulation (Bifidobacterium, Candidatus_Saccharimonas, Lachnospiraceae_NK4A136_group, Mucispirillum, and Escherichia-Shigella). Furthermore, various structural parameters and substitution degrees showed no significant impact on HG's regulation of oxidative stress reactions. This study emphasized the importance of substituent effect in determining HG's functional role, providing a robust foundation for the design and development of functional polysaccharides for the prevention of intestinal inflammation and other related conditions.

Luteolin ameliorates ulcerative colitis in mice via reducing the depletion of NCR+ILC3 through Notch signaling pathway

The disorder of group 3 innate lymphoid cells (ILC3) subgroup, such as the predominance of NCR-ILC3 but the depletion of NCR+ILC3, is unfavorable to damaged intestinal barrier repair, which leads to the prolongations and obstinacy of ulcerative colitis (UC). Our previous studies had shown that luteolin promoted NCR−ILC3 differentitating into NCR+ILC3 to improving the depletion of NCR+ILC3 in UC mice, while the mechanism is unclear. This article aimed to explore the underlying mechanism of luteolin enhancing the proportion NCR+ILC3. UC mice model was established with 2% DSS and Notch signaling was blocked, then luteolin was used to intervene. The results showed that the effect of luteolin on ameliorating disease symptoms in UC mice, including inhibiting the weight loss, reducing the pathological damage of colon mucosa, etc., was diminished with blocking Notch signaling pathway. In addition, luteolin increased the proportion of NCR+ILC3, NCR+MNK3 and IL-22+ILC3, decreased intestinal permeability, promoted mucin secretion, and promoted ZO-1 and Occludin expression, the above effect of luteolin was neutralized by Notch inhibitor LY-411575. Luteolin activated the abnormally blocked Notch signaling pathway in UC mice. And molecular docking predicted the affinity of luteolin for RBPJ to be −7.5 kcal·mol−1 in mouse, respectively; the affinity of luteolin for Notch1 and RBPJ was respectively scored to be −6.4 kcal·mol−1 and −7.7 kcal·mol−1 homo sapiens. These results proved that luteolin is positive for enhancing the proportion of NCR+ILC3 via Notch signaling, and it provides a basis for targeting NCR+ILC3 for restoring intestinal barrier function to alleviating ulcerative colitis.

Skin barrier repair efficacy and safety evaluation of an extract from Gardenia jasminoides J.Ellis

Gardenia jasminoides J.Ellis, a well-known traditional Chinese medicine, has been widely used in Asian countries for centuries. This study presented the skin barrier repair efficacy and safety evaluation of an extract from G. jasminoides. The results showed that GarPepair was primarily composed of geniposide and genipin-1-β-D-gentiobioside with concentrations of 3.39 and 1.03 mg/mL, respectively. GarPepair (1.25%, w/w), geniposide (50 μg/mL), and genipin-1-β-D-gentiobioside (50 μg/mL) showed no cytotoxicity but could significantly up-regulate mRNA level (82.5%, 54.4%, and 99.4%, respectively) and protein expression (68.7%, 57.1%, and 92.6%, respectively) of ZO-1 in HaCat cells induced by lipopolysaccharide. Moreover, GarPepair showed low acute toxicity on zebrafish with an IC50 value of 5.91% (w/w), indicating that GarPepair had high safety. In summary, we can conclude that GarPepair and its active ingredients (geniposide and genipin-1-β-D-gentiobioside) had significant skin barrier repair efficacy with high safety, making it suitable for use as an active substance in cosmetics.

Mask wearing impacts skin barrier function and microbiome profile in sensitive skin

Mask-wearing behavior, common in the post-COVID-19 era, raises concerns for sensitive skin. This split-face study investigated mask-related changes in skin barrier function and microbiome composition among 30 female volunteers with sensitive skin and assessed the mitigating effects of a moisturizer containing biological lipids and probiotics. Skin physiological indicators (transepidermal water loss, erythema index, stratum corneum hydration, pH, temperature) of masked and unmasked areas were collected at baseline, after three hours of mask-wearing, post-tape stripping, and after 24 h, respectively. Microbiome samples collected from the masked areas before and after wearing a medical mask were analyzed with bioinformatics methods. Mask-wearing significantly weakened barrier function in both masked and adjacent unmasked areas, while reducing bacterial diversity. It was also associated with an increase in Cutibacterium (P = 0.110) and decreases in Streptococcus (P = 0.032) and Prevotella (P = 0.026) abundance. Moisturizer application prior to mask-wearing significantly reduced transepidermal water loss and erythema (both P < 0.001) and further improved erythema after 24 h (P = 0.048). These findings demonstrate that mask-wearing can disrupt the skin barrier and microbiome in individuals with sensitive skin and applying a moisturizer beforehand can mitigate mask-related discomforts by aiding barrier repair and reducing sensitivity.

Intestinal Barrier Impairment, Preservation, and Repair: An Update.

Our objective was to review published studies of the intestinal barrier and permeability, the deleterious effects of dietary components (particularly fat), the impact of altered intestinal permeability in disease models and human diseases, the role of the microbiome and epigenomics in control of barrier function, and the opportunities to restore normal barrier function with dietary interventions and products of the microbiota. We conducted a literature review including the following keywords alone or in combination: intestinal barrier, permeability, microbiome, epigenomics, diet, irritable bowel syndrome, inflammatory bowel disease, probiotics. Intestinal permeability is modified by a diet including fat, which increases permeability, and nutrients such as fiber, glutamine, zinc, vitamin D, polyphenols, emulsifiers, and anthocyanins, which decrease permeability. There is significant interaction of the microbiome and barrier function, including the inflammatory of luminal/bacterial antigens, and anti-inflammatory effects of commensals or probiotics and their products, including short-chain fatty acids. Epigenomic modification of barrier functions are best illustrated by effects on junction proteins or inflammation. Detailed documentation of the protective effects of diet, probiotics, prebiotics, and microbiota is provided. intestinal permeability is a critical factor in protection against gastrointestinal diseases and is impacted by nutrients that preserve or heal and repair the barrier and nurture anti-inflammatory effects.

Human Amniotic Epithelial Stem Cells Promote Colonic Recovery in Experimental Colitis via Exosomal MiR-23a-TNFR1-NF-κB Signaling.

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, manifests as chronic intestinal inflammation with debilitating symptoms, posing a significant burden on global healthcare. Moreover, current therapies primarily targeting inflammation can lead to immunosuppression-related complications. Human amniotic epithelial stem cells (hAESCs), which exhibit low immunogenicity and ethical acceptability, have gained attention as potential therapeutics. In this study, it is demonstrated that their encapsulation in a hydrogel and administration via anal injection enhanced the colonic mucosal barrier repair in a murine colitis model induced by dextran sodium sulfate during the recovery phase. The underlying mechanism involved the release of exosomes from hAESCs enriched with microRNA-23a-3p, which post-transcriptionally reduced tumor necrosis factor receptor 1 expression, suppressing the nuclear factor-κB pathway in colonic epithelial cells, thus played a key role in inflammation. The novel approach shows potential for IBD treatment by restoring intestinal epithelial homeostasis without the immunosuppressive therapy-associated risks. Furthermore, the approach provides an alternative strategy to target the key molecular pathways involved in inflammation and promotes intestinal barrier function using hAESCs and their secreted exosomes. Overall, this study provides key insights to effectively treat IBD, addresses the unmet needs of patients, and reduces related healthcare burden.

Trehalose Prevents IL-4/IL-13–Induced Skin Barrier Impairment by Suppressing IL-33 Expression and Increasing NRF2 Activation in Human Keratinocytes In Vitro

Skin barrier dysfunction initiates or deteriorates various cutaneous problems, such as atopic dermatitis (AD). At high concentrations, the nonreducing disaccharide α-d-glucopyranosyl α-d-glucopyranoside (trehalose) induces a transient senescence-like state in fibroblasts and promotes wound repair. Here, we investigated the effect of trehalose on normal human keratinocytes (KCs) and demonstrated its specific role in the skin barrier. RNA-seq analysis revealed that trehalose regulates the expression of many skin-barrier-associated genes. T helper 2 (Th2) cytokines interleukin (IL)-4/IL-13 were observed to downregulate several differentiation markers (FLG, LOR, K1, and K10) and epidermal antimicrobial proteins in monolayer-cultured KCs and living skin equivalents (LSE), and impaired skin barrier function in LSE, all of which were significantly upregulated or restored by trehalose. Trehalose inhibited IL-33 expression and reduced nuclear IL-33 levels by activating MEK5-extracellular signal-regulated kinase 5 (ERK5) and suppressing MEK1/2-ERK pathway. It also increased nuclear factor erythroid 2-related factor 2 (Nrf2) activation to trigger antioxidant enzyme production via c-Jun N-terminal kinase (JNK), thus, neutralizing IL-4/IL-13-mediated oxidative stress. Trehalose prevented IL-4/IL-13-mediated signal transducer and activator of transcription (STAT)3/STAT6 activation and restored IL-4/IL-13-suppressed skin barrier molecules via IL-33 downregulation and Nrf2 activation. This study demonstrated that trehalose may play a role in skin barrier repair in AD.

Ternary inulin hydrogel with long-term intestinal retention for simultaneously reversing IBD and its fibrotic complication.

Excessive accumulation of reactive oxygen and nitrogen species (RONS) and dysbiosis of intestinal microbiota are pivotal symptoms for inflammatory bowel disease (IBD) and its associated complications, such as intestinal fibrosis. This research introduces a probiotic inulin hydrogel loaded with polypyrrole (PPy) nanozymes and antifibrotic drug pirfenidone (PFD) (PPy/PFD@Inulin gel) designed for the concurrent amelioration of IBD and its fibrotic complication. Upon oral administration, the inulin gel matrix could extend the gastrointestinal residence time of PPy nanozymes and PFD, facilitating the efficient reduction of pro-inflammatory cytokine levels and enhancement of the intestinal epithelial barrier repair as well as the suppression of intestinal fibrosis through sustained RONS scavenging, modulation of gut microbiota and attenuation of the TGF-β/Smad signaling pathway to inhibit fibroblast proliferation. Notably, the PPy/PFD@Inulin gel demonstrated significant prophylactic and therapeutic efficacy in acute and chronic colitis as well as intestinal fibrosis induced by dextran sodium sulfate (DSS) in mouse models. Thus, the engineered ternary PPy/PFD@Inulin gel offered a pioneered paradigm for simultaneous reversal of IBD and its associated complications, such as intestinal fibrosis, in a single therapeutic regimen.

Sukralfat as a Therapy for Reducing Itching and Repairing the Skin Barrier: A Systematic Review

Sucralate is an aluminum salt from sucrose octasulfate that is known for its anti-ulcer activity, mucosal protection, and anti-mucositis potential. Recently, sucralfat has been used topically for the healing of various epithelial wounds, including ulcers, inflammatory dermatitis, mucositis, and burns. This systematic review aimed to evaluate the effectiveness of sucralfat as a topical therapy in reducing itching (pruritus) and improving the skin barrier. The analysis method used is Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA). A literature search was conducted on studies from 2004 to 2024 using keywords such as "sucralfate", "pruritus", "dermatitis", and "skin barrier" on PubMed, ProQuest, Science Direct, and Scopus databases. Inclusion criteria include topic relevance, research design, human subjects, and United Kingdom-speaking studies. Of the 141 articles found, 7 articles met the inclusion criteria. These studies involved a total of 605 subjects from different countries and used clinical trial methods and randomized controlled trials. The results showed that topical sucralfat was effective in reducing itching and improving the skin barrier in various skin conditions such as diaper dermatitis, chronic ulcers, and postoperative wounds. Sukralfat shows great potential in wound healing and skin barrier repair through the mechanism of protective layer formation, increased expression of epidermal growth factors, and anti-inflammatory properties. This effect indirectly helps reduce pruritus which often occurs due to damage to the skin barrier. Topical succulthate is effective in reducing itching and repairing the skin barrier, making it a promising therapy for a variety of inflammatory and ulcerative skin conditions.

Functional Ginger-Derived Extracellular Vesicles-Coated ZIF-8 Containing TNF-α siRNA for Ulcerative Colitis Therapy by Modulating Gut Microbiota.

Tumor necrosis factor-α (TNF-α) plays a causal role in the pathogenesis of ulcerative colitis (UC), and anti-TNF-α siRNA shows great promise in UC therapy. However, delivering siRNA with site-targeted stability and therapeutic efficacy is still challenging due to the complex and dynamic intestinal microenvironment. Here, based on the functional plant-derived ginger extracellular vesicles (EVs) and porous ZIF-8 nanoparticles, we propose a novel TNF-α siRNA delivery strategy (EVs@ZIF-8@siRNA) for UC targeted therapy. Ginger EVs show strong colon and macrophage targeting, as well as robust resistance to acidic degradation in the stomach. Moreover, 6-shogaol in ginger-derived EVs displays anti-inflammatory effects, which enhance the treatment efficiency by cooperation with TNF-α siRNA. In vitro experiments reveal that ZIF-8 nanoparticles have high TNF-α siRNA loading capacity and promote siRNA escape from cellular lysosomes. In vivo experiments show that the TNF-α level is reduced more significantly in colonic tissue than other nontargeted inflammation related factors, showing a good targeting of this composite nanoparticle. Furthermore, gut microbiota sequencing results demonstrate that the nanoparticles can promote intestinal barrier repair by regulating the intestinal microbial balance and restoring the intestinal health of UC mice. Therefore, the developed EVs@ZIF-8@siRNA nanoparticles may represent a novel colon-targeted oral drug, providing a promising therapeutic strategy for UC therapy.

Xylan acetate ester ameliorates ulcerative colitis through intestinal barrier repair and inflammation inhibition via regulation of macrophage M1 polarization

Ulcerative colitis (UC) is a chronic inflammatory disease resulting from abnormal immune response to gut microflora translocating through damaged intestinal barrier. Xylan acetate ester (XylA) can increase colon short-chain fatty acids (SCFAs) levels and alleviate kidney disease by inhibiting inflammation through the G protein-coupled receptor pathway. Here, we synthesized and purified XylA, and then the effects and mechanisms of XylA on dextran sodium sulfate-induced UC in mice were investigated. The results showed that in mice, similar to the positive drug 5-aminosalicylic acid, oral administration of XylA significantly alleviated all UC symptoms, including weight loss, diarrhea, and hematochezia. Further mechanism studies revealed that XylA could repair the damaged colon structure and intestinal barrier function by increasing the expression of tight junction protein zonula occludens 1 and occludin, thus reducing LPS penetration. Moreover, XylA could also restrain intestinal inflammation via inhibiting LPS-TLR4 pathway, downregulating M1 macrophage polarization, and reducing proinflammatory cytokines expression, and in vitro cell experiments showed that these effects may be mediated by XylA derived SCFAs, particularly acetates, propionates and butyrates. All these results suggested that XylA may be a potential improving agent for UC treatment, and natural polysaccharides may represent a novel avenue for drug development of UC.

Exploring skin barrier repair as a novel therapeutic strategy for CKD-associated pruritus.

Exploring skin barrier repair as a novel therapeutic strategy for CKD-associated pruritus.