Mucosal Cells Research Articles

The Potential Effectiveness of an Ancient Chinese Herbal Formula Yupingfeng-San for Prevention of COVID-19: A Systematic Review

The COVID-19 has been spreading all over the world, and human health is at stake. Conventional medicine played an important role in the treatment and syndrome relief, while there is limited research evidence to support any prevention or antiviral treatment for COVID-19. YupingfengSan is a classic formula with the effect of replenishing qi, consolidating exterior, and arresting sweating. YupingfengSan has been widely used to treat various diseases in China and Southeast Asia for hundreds of years. Accumulating evidence suggests that YPFS has both immune-regulatory and anti-virus effects clinically, but leaving the mechanism elusive. In this paper, we reviewed the recent progress of YupingfengSan in immune-regulatory and anti-virus activities, including the effect on mucosal immunity, biological antagonism, macrophages, adaptive immunity, and NK cells. From this systematic review, we speculate that YPFS can play an effective role in the prevention of SARS-CoV-2, but further experimental studies are expected to investigate the specific mechanisms. This review suggests an alternative direction for the prevention of COVID-19.

Bitter taste receptors as sensors of gut luminal contents.

Taste is important in the selection of food and is orchestrated by a group of distinct receptors, the taste G protein-coupled receptors (GPCRs). Taste 1 receptors (Tas1rs in mice and TAS1Rs in humans; also known as T1Rs) detect sweet and umami tastes, and taste 2 receptors (Tas2rs in mice and TAS2Rs in humans; also known as T2Rs) detect bitterness. These receptors are also expressed in extraoral sites, including the gastrointestinal mucosa. Tas2rs/TAS2Rs have gained interest as potential targets to prevent or treat metabolic disorders. These bitter taste receptors are expressed in functionally distinct types of gastrointestinal mucosal cells, including enteroendocrine cells, which, upon stimulation, increase intracellular Ca2+ and release signalling molecules that regulate gut chemosensory processes critical for digestion and absorption of nutrients, for neutralization and expulsion of harmful substances, and for metabolic regulation. Expression of Tas2rs/TAS2Rs in gut mucosa is upregulated by high-fat diets, and intraluminal bitter 'tastants' affect gastrointestinal functions and ingestive behaviour through local and gut-brain axis signalling. Tas2rs/TAS2Rs are also found in Paneth and goblet cells, which release antimicrobial peptides and glycoproteins, and in tuft cells, which trigger type 2 immune response against parasites, thus providing a direct line of defence against pathogens. This Review will focus on gut Tas2r/TAS2R distribution, signalling and regulation in enteroendocrine cells, supporting their role as chemosensors of luminal content that serve distinct functions as regulators of body homeostasis and immune response.

Expression and localization of Uhrf1 in the major reproductive organs of yaks during different reproductive cycles

Uhrf1 is a multi-domain and multifunctional epigenetic regulator playing key roles in DNA methylation, cell metabolism, and cell proliferation. To investigate the role of Uhrf1 in the reproductive physiology of female yaks, we collected three reproductive organs (ovaries, oviducts, and uteri) from healthy yaks during three reproductive phases (follicular, luteal, and gestational phases), with a total of nine groups. Real-time fluorescence quantitative PCR (RT-qPCR), Western blotting, and immunohistochemistry (IHC) were employed to determine the expression levels of Uhrf1 and the subcellular localization of this protein. RT-qPCR and Western blotting results showed that Uhrf1 was expressed highest in the oviduct during the follicular phase, moderate expression in the uterus during the gestational phase, and the lowest expression in the uterus during the luteal phase (P < 0.05). IHC results showed that Uhrf1 was mainly expressed in the ovarian germinal epithelium, theca follicular, follicular granulosa, luteal cells, oviduct mucosal epithelial cells, and uterine glands (UG) of yaks. In conclusion, Uhrf1 was differentially expressed in the major reproductive organs during the reproductive cycle of female yaks, indicating its important regulatory role in the reproductive physiology of yaks.

Mucosal Addressin Cell Adhesion Molecule-1 Mediates T Cell Migration into Pancreas-Draining Lymph Nodes for Initiation of the Autoimmune Response in Type 1 Diabetes.

Type 1 diabetes (T1D) is an autoimmune disease that is caused by autoreactive T cell-mediated destruction of insulin-producing β cells in the pancreatic islets. Although naive autoreactive T cells are initially primed by islet antigens in pancreas-draining lymph nodes (pan-LNs), the adhesion molecules that recruit T cells into pan-LNs are unknown. We show that high endothelial venules in pan-LNs of young nonobese diabetic mice have a unique adhesion molecule profile that includes strong expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1). Anti-MAdCAM-1 antibody blocked more than 80% of the migration of naive autoreactive CD4+ T cells from blood vessels into pan-LNs. Transient blockade of MAdCAM-1 in young nonobese diabetic mice led to increased numbers of autoreactive regulatory CD4+ T cells in pan-LNs and pancreas and to long-lasting protection from T1D. These results indicate the importance of MAdCAM-1 in the development of T1D and suggest MAdCAM-1 as a potential therapeutic target for treating T1D.

Loss of HIV candidate vaccine efficacy in male macaques by mucosal nanoparticle immunization rescued by V2-specific response

Systemic vaccination of macaques with V1-deleted (ΔV1) envelope immunogens reduce the risk of SIVmac251 acquisition by approximately 60%, with protective roles played by V2-specific ADCC and envelope-specific mucosal IL-17+NKp44+ innate lymphoid cells (ILCs). We investigated whether increased mucosal responses to V2 benefit vaccine efficacy by delivering oral nanoparticles (NPs) that release V2-scaffolded on Typhoid Toxin B (TTB) to the large intestine. Strikingly, mucosal immunization of male macaques abrogated vaccine efficacy with control TTB or empty NPs, but vaccine efficacy of up to 47.6% was preserved with V2-TTB NPs. The deleterious effects of NPs were linked to preferential recruitment of mucosal plasmacytoid dendritic cells (pDCs), reduction of protective mucosal NKp44+ ILCs, increased non-protective mucosal PMA/Ionomycin-induced IFN-γ+NKG2A-NKp44-ILCs, and increased levels of mucosal activated Ki67+CD4+ T cells, a potential target for virus infection. V2-TTB NP mucosal boosting rescued vaccine efficacy, likely via high avidity V2-specific antibodies mediating ADCC, and higher frequencies of mucosal NKp44+ ILCs and of ∆V1gp120 binding antibody-secreting B cells in the rectal mucosa. These findings emphasize the central role of systemic immunization and mucosal V2-specific antibodies in the protection afforded by ΔV1 envelope immunogens and encourage careful evaluation of vaccine delivery platforms to avoid inducing immune responses favorable to HIV transmission.

Valproic acid alleviates total-body irradiation-induced small intestinal mucositis in mice

Purpose Gastrointestinal (GI) injury is one of the serious problems of total-body irradiation (TBI). However, no fundamental treatment for TBI and other radiation-induced GI injury has yet been established. Valproic acid (VPA) administration reduces mortality in mice subjected to total-body irradiation (TBI) with X-rays. This study aimed to evaluate the effects of VPA on GI injury induced by TBI in mice. Materials and methods Mice were subjected to TBI with X-rays to induce GI injury. Changes in survival and weight were observed after VPA administration. The small intestine was then sampled at 0, 1, 3, 7, and 10 d after irradiation for histological and immunohistological evaluation and measurement of myeloperoxidase (MPO) activity and inflammatory cytokine levels (IL-1β). Results VPA (200 and 600 mg/kg) increased survival rate and reduced weight loss in model mice. IL-1β expression 1 d after irradiation was significantly lower in the VPA group than that in the vehicle group. Furthermore, the increase in MPO activity at 3 and 7 d after irradiation was significantly suppressed by VPA administration. Histological examination (hematoxylin and eosin staining) revealed that 600 mg/kg VPA inhibited inflammatory cell infiltration. Immunostaining for the proliferating cell nuclear antigen involved in cell proliferation showed that VPA suppressed the irradiation-induced decrease in cell proliferative capacity. Conclusions Treatment with VPA in mice with GI injury caused by TBI suppressed inflammatory responses in small intestinal mucosal cells. These results suggest that VPA may be a useful therapeutic agent against TBI-induced small intestinal mucositis.

Gut microbiome impact on childhood allergic rhinitis and house dust mite IgE responses.

The correlation between the gut microbiota and airway inflammation in childhood allergic rhinitis (AR), particularly concerning allergen exposure, remains insufficiently explored. This study aimed to link gut microbiota changes with house dust mite (HDM)-specific IgE responses in pediatric AR. Using metagenomic shotgun sequencing, we compared the fecal microbiota of 60 children with HDM-AR to 48 healthy controls (HC), analyzing the link to IgE reactions. We examined the effects of oral Escherichia (E.) fergusonii treatment in mice sensitized with ovalbumin and HDM on allergic symptoms, mucosal cell infiltration, Th1/Th2/Tregs balance in the spleen, serum cytokine levels, and E. fergusonii presence in feces. Children with HDM-AR have a less diverse gut microbiome and lower levels of E. fergusonii compared to controls, with a negative correlation between E. fergusonii abundance and HDM-specific IgE levels. In mice sensitized with OVA and HDM, oral administration of E. fergusonii improved allergic symptoms, reduced nasal eosinophils/mast cells infiltration and adjusted Th cell populations towards a non-allergic profile in splenic lymphocytes with exception of IFN-γ change in serum. These findings underline the potential of targeting gut microbiota, particularly E. fergusonii, in managing childhood HDM-AR, suggesting a promising approach for future interventions. The composition and distribution of gut microbiota in children with HDM-AR are significant changed. The abundance of Escherichia genus is decreased in HDM-AR children. HDM-specific IgE levels are strongly negatively associated with E. fergusonii abundance. Oral administration of E. fergusonii effectively suppresses allergic responses in murine model. These findings offer novel insights into the diagnosis and treatment of HDM-AR, which suggested that E. fergusonii holds promise as a potential therapeutic avenue for managing HDM-AR.

The Impact of Genetic Polymorphisms for Detecting Genotoxicity in Workers Occupationally Exposed to Metals: A Systematic Review.

The present study aims to provide a systematic review of studies on the essential and nonessential metal exposure at occupational level, genotoxicity, and polymorphisms and to answer the following questions: Are genetic polymorphisms involved in metal-induced genotoxicity? In this study, 14 publications were carefully analyzed in this setting. Our results pointed out an association between polymorphism and genotoxicity in individuals exposed to metals, because 13 studies (out of 14) revealed positive relations between genotoxicity and polymorphisms in xenobiotics metabolizing and DNA repair genes. Regarding the quality of these findings, they can be considered reliable, as the vast majority of the studies (12 out of 14) were categorized as strong or moderate in the quality assessment. Taken as a whole, occupational exposure to metals (essentials or not) induces genotoxicity in peripheral blood or oral mucosa cells. Additionally, professional individuals with certain genotypes may present higher or lower DNA damage as well as DNA repair potential, which will certainly impact the level of DNA damage in the occupational environment.

The Effects of Ghrelin on Spike Activity of the Suprachiasmatic Nucleus Neurones of the Rat

In one of the most important non-photic mechanisms of the circadian biological clock synchronization with environmental geophysical 24 h rhythm, information on feeding schedule, composition and calorie content of food is used. Hormone ghrelin, a product of the neuroendocrine oxyntic cells of the gastric mucosa to be a signal molecule within this mechanism. In experiments on sagittal hypothalamic slices of male Wistar rats, the effects of 25 nM ghrelin on spike activity and parameters of spike information coding were investigated. Application of ghrelin induced an increase in spike frequency and a decrease in entropy of interspike interval distribution in 32.1% of the neurones recorded. In 29.6% of the cells, opposite responses in the form of a reduction of activity and an increase in the entropy of interspike interval distribution were observed. Parameters of spike activity of the reminder 38.3% neurones of the suprachiasmatic nucleus did not change. The observed responses of the entropy of interspike interval distribution indicate the appropriate changes in a degree of irregularity of interspike interval induced by ghrelin. Application of selective high-affinity antagonist of GHS-R1a receptor, JMV 2959 (100 nM) did not induce responses of the investigated parameters of spike activity but completely prevented changes of both, spike frequency and entropy of interspike interval distribution observed in the presence of ghrelin. The obtained data show that hormone ghrelin by a direct influence on the suprachiasmatic nucleus in vitro modulates the activity level and spike code of relatively numerous population of neurones of the nucleus, wherein the effects of ghrelin are implemented via GHS-R1a receptors. The results of the current study provide additional evidence in favour of the hypothesis on the involvement of ghrelin in mechanisms of non-photic entrainment of the circadian biological clock in accordance with severity of food motivation and level of metabolism.

Effect of Probiotic Supplementation in Diet on Egg Production, Egg Quality, Intestinal Morphology and Bacterial Population in Caecum of Laying Hens

The objective of this study was to study the effect of probiotic supplementation in diet on egg production, egg quality, intestinal morphology, and bacterial population in caecum of laying hens. A total of 768 Lohmann Brown-Classic laying hens, aged 42 - 54 weeks, were used. The laying hens were divided into 3 groups, each with 8 subgroups of 32 birds each. The experiment was planned to use a completely randomized design method. The 3 experimental groups were classified based on their dietary treatment as follows: 1) Basal diet (without probiotic supplementation), 2) Basal diet with probiotic 0.01 and 0.02 % in 3, respectively. Data was collected for 12 weeks. Adding probiotic in the diet was no significant difference on egg production, egg quality, and bacterial population in caecum. However, probiotic supplementation in the diet increased villi height of the duodenum significantly improved (p &lt; 0.02), villi height per depth crypt of the duodenum significantly improved (p &lt; 0.05), villi height per depth crypt of the jejunum significantly improved (p &lt; 0.01), and villi height per depth crypt of the ileum significantly improved (p &lt; 0.02). Therefore, studies have shown that dietary probiotic supplementation can improved small intestinal morphology are the most important indexes for measuring the digestive and absorption function of the small intestine are more efficient. HIGHLIGHTS Probiotic (Bacillus subtilis) is a gram-positive, non-pathogenic bacterium that can inhibit digestive enzymes such as protease, amylase, and lipase. These enzymes help increase the efficiency of digestion and absorption of nutrients. As a result of the working mechanism of Bacillus subtilis, it helps strengthen the intestinal wall, eliminates pathogenic microorganisms, reduces damaged intestinal mucosal cells, and improves intestinal absorption, resulting in increased production. Effect of probiotic (Bacillus subtilis) supplementation in laying hen diets on total bacterial load in appendix. No difference was found in the load of total bacteria and Escherichia coli (P &gt; 0.05). Its beneficial properties stimulate the growth of beneficial bacteria in the intestines, such as Bifidobacteria sp. and Lactobacillus sp., causing the production of lactic acid, which makes the colon more acidic, resulting in inhibition of the growth of pathogenic microorganisms. GRAPHICAL ABSTRACT

Study of the relationships among known virulence genes, coccoid transformation and cytotoxicity of Helicobacter pylori in different clinical diseases

ABSTRACT Background Helicobacter pylori (H. pylori) has infected approximately 4.4 billion individuals worldwide. The known virulence genes and the existing H. pylori typing methods have not been shown to have a recognized correlation with its infectivity. The aim of this study was to elucidate the relationships among known important virulence genes, coccoid transformation, and cytotoxicity of H. pylori isolated from individuals with different clinical diseases to provide guidance for the development of new virulence typing methods for H. pylori. Methods The known important virulence genes of 35 H. pylori strains were identified by whole-gene next-generation sequencing (WGS) and polymerase chain reaction (PCR). The chronological changes in the proportion of coccoid forms of H. pylori and their ultramicroscopic structures were observed chronologically using transmission electron microscopy. Human gastric mucosal epithelial cells (GES-1) w Results There were no significant correlations among the known important virulence genes, coccoid transformation and cytotoxicity of H. pylori isolated from patients with different clinical diseases. We developed a new virulence classification based on the defensive and offensive abilities of H. pylori. Conclusions Coccoid transformation and virulence are two independent characteristics of H. pylori that reflect its defensive and offensive abilities, respectively. These two abilities work synergistically, warranting the construction of a new virulence typing method for H. pylori. However, the correlation between the new virulence classification and pathogenic ability still needs to be further ver

The influence of professional oral hygiene on the indicators of local immunity

Professional oral hygiene is an important part of measures aimed at preventing and maintaining the patient’s health. Local immune response is the first barrier of immune protection capable of preventing infection diseases. The aim of the study - the influence of professional hygiene on the indicators of local immunity has been studied. The study involved two groups of patients: the first group included 19 individuals with chronic caries of varying depths (class I), and the second group comprised 15 individuals with moderate periodontal disease. To evaluate nonspecific oral protection, the index of natural colonization of the buccal epithelium and the activity of microbial adsorption by oral mucosal cells were assessed. Specific immunity was evaluated by measuring the concentration of immunoglobulins in unstimulated saliva. All indicators were recorded both before and after professional oral hygiene procedures. When studying the index of natural colonization of the buccal epithelium, it was found that professional cleaning in both groups led to normalization of the spectrum of bacteria adhered to the epithelium: there was a decrease in the amount of gram-negative microflora, atypical for this biotope, while maintaining a high adhesion index of gram-positive cocci. In persons with caries, before sanation, “unsatisfactory” resistance of oral mucosa was revealed in a third of the examined, after sanation, the number of such patients decreased by 3 times, with “satisfactory” resistance increased by 2 times. In the group with periodontal disease, all patients exhibited “unsatisfactory” mucosal resistance before the hygiene procedures. After sanitation, 20 % “unsatisfactory” resistance persisted. In the majority of patients (80 %), the resistance of the oral mucosa improved to “satisfactory”. The concentration of all classes of immunoglobulins in both groups before sanitation was significantly below the norm, after the measures taken, the indicators increased significantly and reached the level typical for healthy individuals. Carrying out professional cleaning of the teeth leads to the normalization of local immune status even without additional medical immunocorrection.

Intestinal Epithelial Cell Brush Border Membrane Cl:HCO3 Exchanger Regulation by Mast Cells in Chronic Ileitis.

Malabsorption of NaCl is the primary cause of diarrhea in inflammatory bowel disease (IBD). Coupled NaCl absorption occurs via the dual operation of Na:H and Cl:HCO3 exchange in the brush border membrane (BBM) of villus cells. Cl:HCO3 exchange is mediated by BBM transporters DRA (downregulated in adenoma) and PAT1 (putative anion transporter 1) in the mammalian small intestine. DRA/PAT1-mediated Cl:HCO3 exchange was significantly downregulated in the BBM of villus cells in a rabbit model of chronic ileitis, while Na:H exchange was unaffected. The inhibition of Cl:HCO3 exchange was restored in the rabbits when treated with a broad-spectrum immunomodulator, i.e. a glucocorticoid, indicating that the downregulation of DRA/PAT1 is likely to be immune-mediated during chronic enteritis. Mucosal mast cells are one type of key immune cells that are known to proliferate and release immune inflammatory mediators, thus playing a significant role in the pathogenesis of IBD. However, how mast cells may regulate DRA- and PAT1-mediated Cl:HCO3 exchange in a rabbit model of chronic ileitis is unknown. In this study, treatment of rabbits with chronic intestinal inflammation with the mast cell stabilizer ketotifen did not affect the mucosal architecture of the inflamed intestine. However, ketotifen treatment reversed the inhibition of Cl:HCO3 activity in the BBM of villus cells. This restoration of Cl:HCO3 activity to normal levels by ketotifen was found to be secondary to restoring the affinity of the exchangers for its substrate chloride. This observation was consistent with molecular studies, where the mRNA and BBM protein expressions of DRA and PAT1 remained unaffected in the villus cells under all experimental conditions. Thus, this study indicates that mast cells mediated the inhibition of coupled NaCl absorption by inhibiting Cl:HCO3 exchange in a rabbit model of chronic enteritis.

In vitro determination of genotoxicity and cytotoxicity induced by stainless steel brackets with and without surface coating in cultures of oral mucosal cells

BackgroundOrthodontics is a speciality of dentistry that uses a plethora of devices made from myriad materials to manage various malocclusions. Prolonged contact of orthodontic appliances with oral tissues can lead to cellular damage, highlighting the need for biocompatible materials to mitigate health risks.ObjectivesTo analyze the genotoxicity and cytotoxicity produced by metal brackets and coated metallic brackets with polymeric and nanoparticle coatings in oral mucosal cells.Materials & methodsThe current study compares the toxicity of 3 different types of orthodontic brackets with control groups of oral mucosal cells. Each of the three treatment groups consisted of 10 samples of orthodontic brackets: stainless steel brackets(Group 1), nanoparticle-coated brackets(Group 2), and polymeric-coated brackets(Group 3) exposed to corrosion eluates employing an oral biomimicry model. Two types of oral mucosal cells- Human Gingival Fibroblasts and Buccal Epithelial Cells were used to study the cytotoxic and/or genotoxic effects of the elutes. Intergroup comparisons were conducted using one-way analysis of variance, while scanning electron microscopy evaluated surface characteristic.ResultsThe interaction between metal ions and oral mucosal cells showed no statistically significant difference for toxicity assays between the three groups(p > 0.005). However, polymeric and nanoparticle-coated groups showed reduced cellular differentiation when compared with conventional stainless-steel brackets.ConclusionThis in-vitro study shows that polymeric or nanoparticle coating of conventional metal brackets aids in enhancing corrosion-resistant characteristics of orthodontic appliances and reduces the toxic oral environment created by metal release in the oral cavity.

Appendiceal Mucosal Schwann Cell Proliferation Associated with Incidentally Detected Goblet Cell Adenocarcinoma of Appendix in a Case of Invasive Adenocarcinoma of Sigmoid Colon- A Case Report

Abstract Introduction/Objective Appendiceal mucosal Schwann cell proliferation has been suggested to be a putative histologic marker of appendiceal diverticular disease. Appendiceal Goblet cell adenocarcinoma, (GCA) is amongst the most rare appendiceal tumors with a reported incidence of 0.05 cases per 100,000 population per year in United States. They have features of both neuroendocrine tumors and adenocarcinomas, but behave more similarly to adenocarcinomas. Methods/Case Report Herein, we report a case of appendiceal mucosal schwann cell proliferation associated with incidentally detected Goblet cell adenocarcinoma of appendix in a known case of invasive adenocarcinoma of sigmoid colon. A 75-year-old female presented with sigmoid colon obstruction. Intraoperatively, she was found to have gangrenous and perforated colon, as well as a large obstructing sigmoid mass, and underwent total abdominal colectomy with end-ileostomy. On gross examination, a tan bosselated tumor (up to 3.5 cm) was seen in proximal sigmoid colon. Microscopic examination showed Invasive adenocarcinoma, moderately-differentiated. Appendix was unremarkable on gross examination. Incidentally, the appendix microscopically demonstrated “Goblet cell adenocarcinoma”, histologic grade 1 out of 3 (pathologic stage pTis pN0), present in multiple foci within lamina propria of the distal third of appendix over an area measuring 1.5 cm. Additionally, there were foci of SOX10-positive bland- looking spindle cell proliferation in lamina propria of the appendix. This proliferation is rendered as “Schwann cell proliferation”. Results (if a Case Study enter NA) NA Conclusion One study found that “Schwann cell proliferation” is seen in 42% of appendiceal diverticula cases. It has never been reported in association with “Appendiceal GCA” before. Here we report an intriguing case of Schwann cell proliferation associated with this rare entity of GCA for the first time in literature. Therefore, awareness of such coexistence of these pathologic entities in the same appendix is essential to alert the pathologist to look for GCA, whenever Schwann cell proliferation is encountered in random section of an appendix. This case also emphasizes the importance of being vigilant of the possible presence of other tumors in a specimen with a known tumor.

GBP2 Regulates Lipid Metabolism by Inhibiting the HIF-1 Pathway to Alleviate the Progression of Allergic Rhinitis.

Allergic rhinitis (AR) is a prevalent allergic disorder instigated by a variety of allergenic stimuli. The study aims to elucidate the mechanistic underpinnings of Guanylate-binding protein 2 (GBP2) in modulating AR. Bioinformatics analysis was used to identify hub genes in AR, and GBP2 was identified. Mice were injected with ovalbumin (OVA) to create AR model. The pathological changes of the nasal mucosa were observed by hematoxylin-eosin staining. ELISA and western blot demonstrated that in OVA-induced AR mice, high IgE and IgG1 levels, inflammation (increased TNF-α, IL-5 and IFN-γ), oxidative stress (high ROS, low TAOC and GSH) and abnormal lipid metabolism (increased TC and LDL-C, decreased HLD-C) were observed. Mouse nasal mucosal epithelial cells (MNECs) were treated with TNF-α to simulate AR. Cell viability and apoptosis were evaluated by CCK-8 assay and flow cytometer, respectively. In vitro assay revealed that GBP2 inhibited total IgE, OVA-IgE and IgG1 levels and suppressed abnormal lipid metabolism, inflammation and oxidative stress to alleviate AR. Furthermore, HIF-1 pathway was screened as the downstream pathway of GBP2. GBP2 inhibited the HIF-1 pathway, and Fenbendazole-d3, the activator of HIF-1 pathway, weakened the inhibitory effects of GBP2 on apoptosis, inflammation, oxidative stress and abnormal lipid metabolism in vitro. In summary, GBP2 alleviated abnormal lipid metabolism, inflammation and oxidative stress by inhibiting the HIF-1 pathway, providing a direction for the treatment of AR.

Clostridium sporogenes-derived metabolites protect mice against colonic inflammation

ABSTRACT Gut microbiota-derived metabolites play a pivotal role in the maintenance of intestinal immune homeostasis. Here, we demonstrate that the human commensal Clostridium sporogenes possesses a specific metabolic fingerprint, consisting predominantly of the tryptophan catabolite indole-3-propionic acid (IPA), the branched-chain acids (BCFAs) isobutyrate and isovalerate and the short-chain fatty acids (SCFAs) acetate and propionate. Mono-colonization of germ-free mice with C. sporogenes (CS mice) affected colonic mucosal immune cell phenotypes, including up-regulation of Il22 gene expression, and increased abundance of transcriptionally active colonic tuft cells and Foxp3+ regulatory T cells (Tregs). In DSS-induced colitis, conventional mice suffered severe inflammation accompanied by loss of colonic crypts. These symptoms were absent in CS mice. In conventional, but not CS mice, bulk RNAseq analysis of the colon revealed an increase in inflammatory and Th17-related gene signatures. C. sporogenes-derived IPA reduced IL-17A protein expression by suppressing mTOR activity and by altering ribosome-related pathways in Th17 cells. Additionally, BCFAs and SCFAs generated by C. sporogenes enhanced the activity of Tregs and increased the production of IL-22, which led to protection from colitis. Collectively, we identified C. sporogenes as a therapeutically relevant probiotic bacterium that might be employed in patients with inflammatory bowel disease (IBD).

Features of the nasal microbiota in patients with allergic rhinitis: A review

The article analyzes the data of modern literature on the microbiota of ENT organs in normal and pathological conditions. The microbiota plays an important role in maintaining homeostasis by influencing metabolism, the immune system and human physiology. This complex of microorganisms includes bacteria, viruses and fungi that form the biofilm of otolaryngological organs, which prevents the penetration of pathogenic microorganisms. Different parts of the human upper respiratory tract have similar types of bacteria, but it differs dramatically at the level of families and genera. In addition, the balance of microbial flora depends on the immune system status, environmental factors, medication intake, age, race, lifestyle, as well as the health of other ENT organs. Changes in the nasal mucosa in allergic rhinitis are often associated with an increase in the content of bacteria. For example, Staphylococcus aureus can cause more severe nasal congestion in conjunction with protracted rhinitis and sinusitis. The production of bacterial proteinases contributes to easier penetration of allergens and activation of mucosal cells. The absence of microbiota can increase the response of the immune system and reduce the number of cells that contribute to the regulation of inflammation. This review presents an analysis of the composition of the normal microflora of otolaryngological organs and its effect on the occurrence of allergic rhinitis.

Oleanolic acid 28-O-β-D-glucopyranoside: A novel therapeutic agent against ulcerative colitis via anti-inflammatory, barrier-preservation, and gut microbiota-modulation

Ulcerative colitis (UC), an incurable and recurrent inflammatory bowel disease, presents a significant threat to health and highlights the need for novel therapeutic strategies. Oleanolic acid 28-O-β-D-glucopyranoside (OAG) is a naturally occurring pentacyclic triterpenoid found in ginseng. In this study, we demonstrated that OAG exhibited remarkable anti-UC activity in LPS-induced Caco-2 cells and DSS-induced model mice. First, OAG alleviated the symptoms of UC by mitigating weight loss, reducing the DAI score, and increasing colon length. Second, the inflammatory response was inhibited after OAG intervention, evidenced decreases in the spleen coefficient, cytokine levels, and inflammatory cell infiltration in colon tissue. Thirdly, OAG also enhanced intestinal epithelial barrier function, as evidenced by elevated TEER values, increased expression of tight junction proteins, diminished bacterial translocation, and maintained intact ultrastructure of colonic mucosal cells. Notably, compared with 5-aminosalicylic acid, OAG demonstrated superior efficacy in enhancing mucosal barrier function. Fourth, OAG increased microbial diversity, promoted the abundance of beneficial bacteria, reduced the abundance of harmful bacteria, and rebalanced the gut microbiome. Finally, the PI3K-AKT and MAPK signaling pathways were identified as crucial mechanisms underlying the therapeutic effects of OAG against UC through multi-omics. In summary, we identified OAG as a novel therapeutic agent against UC, demonstrating anti-inflammatory, barrier-preserving, and gut microbiota-modulating effects, highlighting its promising potential as a candidate UC drug.

Expression and role of methyltransferase 3 in oral malignant transformation

ObjectiveTo investigate the expression and role of methyltransferase 3 (METTL3) in oral malignant transformation. Materials and methodsImmunohistochemical method was used to investigate the expression of METTL3 in the human oral malignant transformation. Bioinformatics analysis was used to explore the role of METTL3 in oral malignant transformation. Oral cancer animal model was used to verify the expression trend of METTL3 in oral malignant transformation. Knockdown of METTL3 expression in human oral mucosal precancerous lesion cells was performed to explore the METTL3 effect on proliferation, migration, apoptosis, and cell cycle. ResultsMETTL3 expression was significantly up-regulated in the human oral malignant transformation. Moreover, METTL3 was related to the pathway of “Neuroactive ligand-receptor interaction.” In addition, METTL3 expression was also significantly up-regulated in the hamster oral malignant transformation. Finally, the proliferation and migration abilities of human oral mucosal precancerous lesion cells were inhibited after METTL3 knockdown. ConclusionsIn conclusion, we found that METTL3 was up-regulated in oral malignant transformation, and the role may relate to the pathway of “Neuroactive ligand-receptor interaction.”