Mucosal Alterations Research Articles

Potential of Fiber and Probiotics to Fight Against the Effects of PhIP + DSS-Induced Carcinogenic Process of the Large Intestine.

We determined the in vivo counteracting effect of fiber and probiotic supplementation on colonic mucosal damage and alterations in gut microbiota caused by 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP) and sodium dextran sulfate (DSS). Male Fischer-344 rats were randomly divided into 4 groups: control (standard diet), PhIP + DSS group (standard diet + PhIP + DSS), fiber (fiber diet + PhIP + DSS), and probiotic (probiotic diet + PhIP + DSS). The intake of PhIP + DSS for 3 weeks induced colonic mucosal erosion, crypt loss, and inflammation, and the distal colon was more severely damaged. Fiber alleviated colonic mucosal damage by reducing crypt loss and inflammation, while the probiotic increased colon length. The intake of PhIP + DSS increased the fecal relative abundance of Clostridia UCG014 along the intervention, in contrast to the lower abundances of these taxa found after PhIP + DSS administration in the rats supplemented with probiotics or fiber. Fiber supplementation mitigated the histological damage caused by PhIP + DSS shifting the gut microbiota toward a reduction of pro-inflammatory taxa.

A Description of the THRIVE (“The Study of Host-Bacterial Relationships in Different Vaginal Environments”) Bacterial Vaginosis Observational Study

ObjectivesBacterial vaginosis (BV) contributes to poor reproductive health and is characterized by a displacement of Lactobacillus in the vaginal microbiome. However, treatment for BV is limited to antibiotics and half of the women treated experience recurrence within a year. THRIVE is a prospective study in XXXXX, which is designed to capture the daily variation of the microbiome and host mucosal immunity during treatment. The objective of this study is to identify host and bacterial factors that associate with vaginal microbiome stability to better inform therapeutic interventions. MethodsWomen treated for BV, and controls, are followed for 6 months collecting daily vaginal swabs and monthly questionnaires. Comprehensive mucosal sampling, including swabs, cytobrushes, biopsies, and blood are collected at baseline, months 1 and 6 post-enrolment. ResultsWe performed analysis on the first 52 participants, (19 BV+, 33 BV–). Molecular profiling by 16s RNA sequencing showed 20 women with non-Lactobacillus-dominant microbiomes and 32 with Lactobacillus-dominant microbiomes, with increased microbial diversity in non-Lactobacillus-dominant microbiomes (P = 3.1E-05). A pilot analysis in 2 participants demonstrates that multi-omics profiling of self-collected daily swabs provides high-quality data identifying 73 bacterial species, 1773 mucosal proteins and 117 metabolites. Initial flow cytometry analysis showed an increased cluster of differentiation (CD)4+ T cells and neutrophil activation (CD11b+CD62Lneg/dim) in the positive participant at baseline, while after treatment these shifted and resembled the control participant. ConclusionsThis study provides a framework to comprehensively investigate the kinetics of vaginal mucosal microbiome alterations, providing further insight into host and molecular features predicting BV recurrence.

Single cell sequencing reveals cellular landscape alterations in the airway mucosa of patients with pulmonary long COVID.

To elucidate the important cellular and molecular drivers of pulmonary long COVID, we generated a single-cell transcriptomic map of the airway mucosa using bronchial brushings from patients with long COVID who reported persistent pulmonary symptoms.Adults with and without long COVID were recruited from the general community in Greater Vancouver, Canada. The cohort was divided into those with pulmonary long COVID (PLC), which was defined as persons with new or worsening respiratory symptoms following at least one year from their initial acute SARS-CoV-2 infection (N=9); and control subjects defined as SARS-CoV-2 infected persons whose acute respiratory symptoms had fully resolved or individuals who had no history of acute COVID-19 (N=9). These participants underwent bronchoscopy from which a single cell suspension was created from bronchial brush samples and then sequenced.A total of 56 906 cells were recovered for the downstream analysis, with 34 840 cells belonging to the PLC group, which strikingly showed a unique cluster of neutrophils in the PLC group (p<0.05). Ingenuity Pathway Analysis revealed that the neutrophil degranulation pathway was enriched across epithelial cell clusters. Differential gene expression analysis between the PLC and control groups demonstrated upregulation of inflammatory chemokines and epithelial barrier dysfunction across epithelial cell clusters, as well as over-expression of mucin genes across secretory cell clusters.In conclusion, a single-cell transcriptomic landscape of the small airways suggest that neutrophils may play a significant role in mediating the chronic small airway inflammation driving pulmonary symptoms of long COVID.

Review: Food-induced mucosal alterations visualized using endomicroscopy.

Confocal laser endomicroscopy (CLE) is a novel technique allowing real time invivo microscopy during standard endoscopy. Recently, acute mucosal alterations after food administration visualized by CLE have been linked to symptoms in irritable bowel syndrome (IBS). Interestingly, the observed reactions occurred in subjects without demonstrable allergic sensitization to food-this is in line with mechanistic research showing local but not systemic allergic sensitization to foods in an animal model for IBS. Here, European experts conducting CLE with food administration provide a narrative review of the available literature and propose practical guidance on the use of this technique. CLE allows physicians to observe acute mucosal reactions after the application of food to the duodenal mucosa in patients with functional gastrointestinal disorders. Some open-label interventions show a symptomatic benefit when patients exclude the nutrient that triggered an acute mucosal reaction. However, many technical, mechanistic, and clinical questions remain unanswered to date. Technically, the interobserver variability and learning curve requires systematic evaluation and criteria or cutoffs for alterations require validation. Mechanistic studies are needed to enhance our understanding of the mechanisms underlying observed alterations. Finally, rigorous blinded controlled studies are needed to assess a link of these observed alterations with symptom generation. CLE offers a platform allowing scientific insights related to food induced acute mucosal alterations. However, many questions remain unanswered, and more research is warranted to understand the role of acute mucosal alterations visualized upon food administration in IBS pathophysiology and treatment.

Mucosal microbiota characterization in gastric cancer identifies immune-activated-related transcripts relevant gastric microbiome signatures.

Tumor microenvironment (TME) immune cells and gastric mucosal microbiome constitute two vital elements of tumor tissue. Increasing evidence has elucidated their clinicopathological significance in predicting outcomes and therapeutic efficacy. However, comprehensive characterization of immune cell-associated microbiome signatures in the TME is still in the early stages of development. Here, we characterized the gastric mucosa microbiome and its associations with immune-activated related transcripts (IATs) in 170 GC tumor tissues and matched non-tumor tissues using 16s rRNA gene sequencing and quantitative reverse transcription-PCR. Microbial diversity and richness were significantly higher in GC tumor tissues than in non-tumor tissues. Differences in microbial composition between the groups were evident, with Firmicutes, Proteobacteria, Bacteroidota, Campilobacterota, Actinobacteria, Fusobacteriota, Verrucomicrobiota, Acidobacteriota, and Cyanobacteria being the dominant phyla in the gastric mucosal microbiota. Microbial interaction network analysis revealed distinctive centralities of oral bacteria (such as Fusobacterium, Porphyromonas, Prevotella, etc.) in both tumor and normal mucosae networks, suggesting their significant influence on GC microbial ecology. Furthermore, we analyzed the expression of IATs (CXCL9, CXCL10, GZMA, GZMB, PRF1, CD8A, IFNG, TBX2, and TNF) and characterized IAT-relevant gastric microbiome signatures in GC patients. Our results showed that the expression of CXCL9, CXCL10, GZMA, GZMB, PRF1 and IFNG was significantly higher in tumor tissues than in adjacent normal tissues in GC patients. Notably, high expression of IATs in tumor tissues was associated with improved survival in GC patients and could serve as a powerful predictor for disease-free survival. Additionally, analysis of IAT levels and mucosal microbiota diversity revealed a correlation between higher IAT expression and increased microbiota richness and evenness in the IATs high group, suggesting potential interactions between mucosal microbiota and tumor immunopathology. Spearman correlation analysis showed positive associations between IAT expression and specific mucosal bacterial species. Notably, Akkermansia muciniphila demonstrated potential involvement in modulating GZMB expression in the GC mucosal microenvironment. These findings underscore the importance of mucosal microbiota alterations in GC and suggest potential therapeutic targets focusing on modulating the tumor microbiota for improved clinical outcomes. The detailed characterization of these elements has profound implications for both treatment and survival prediction in GC. We observed that microbial diversity and richness were significantly higher in GC tumor tissues compared to non-tumor tissues. These differences highlight the unique microbial landscape of GC tumors and suggest that the microbiome could influence tumor development and progression. Importantly, our study demonstrated that high expression levels of IATs in GC tumor tissues were associated with improved patient survival. This suggests that IATs not only reflect immune activation but also serve as valuable biomarkers for predicting disease-free survival. The potential of IATs as predictive markers underscores their utility in guiding therapeutic strategies and personalizing treatment approaches. Moreover, the correlation between higher IAT expression and increased microbiota richness and evenness suggests that a diverse and balanced microbiome may enhance immune responses and contribute to better clinical outcomes. These findings highlight the critical need to consider mucosal microbiota alterations in GC management. Targeting the tumor microbiota could emerge as a promising therapeutic strategy, potentially leading to more effective treatments and improved patient outcomes. Understanding and modulating the microbiome's role in GC opens new avenues for innovative therapeutic interventions and personalized medicine.

Gut mucosa alterations after kidney transplantation: a cross sectional study.

Kidney transplant recipients (KTRs) rely on immunosuppressants like mycophenolate to prevent organ rejection. However, mycophenolate often causes intestinal symptoms and inflammation in various organs, including the skin and the colon. While KTRs have an increased risk for skin cancer, the risk of colorectal cancer is not increased. Elucidating the histological alterations in the colon of KTRs and comparing these changes with known skin alterations would help understand how immunosuppressants influence cancer development and progression. Whole slide images from gut biopsies (Non-transplanted subjects n = 35, KTRs n = 49) were analyzed using the ImageJ and R programming environment. A total of 22,035 epithelial cells, 38,870 interstitial cells, 3465 epithelial cell mitoses, and 7477 endothelial cells, each characterized by multiple microscopy parameters, from a total of 1788 glands were analyzed. The large database was subsequently analyzed to verify the changes of inflammatory milieu in KTRs and in cancer. KTRs without colon-cancer showed a significantly higher density of interstitial cells in the colon compared to non-transplanted patients. Moreover, the increase in interstitial cell number was accompanied by subtle modifications in the architecture of the colon glands, without altering the epithelial cell density. We could not identify significant structural modifications in cancer samples between KTRs and non-transplanted patients. Our findings demonstrate an increased number of resident interstitial cells in the colon of KTRs, as in other patients treated with mycophenolate. These changes are associated with subtle alterations in the architecture of colon glands.

Enteric glial NLRP3 inflammasome contributes to gut mucosal barrier alterations in a mouse model of diet-induced obesity.

In the present study, we investigated the involvement of NLRP3 inflammasome in the intestinal epithelial barrier (IEB) changes associated with obesity, and its role in the interplay between enteric glia and intestinal epithelial cells (IECs). Wild-type C57BL/6J and NLRP3-KO (-/-) mice were fed with high-fat diet (HFD) or standard diet for 8 weeks. Colonic IEB integrity and inflammasome activation were assessed. Immunolocalization of colonic mucosal GFAP- and NLRP3-positive cells along with invitro coculture experiments with enteric glial cells (EGCs) and IECs allowed to investigate the potential link between altered IEB, enteric gliosis, and NLRP3 activation. HFD mice showed increased body weight, altered IEB integrity, increased GFAP-positive glial cells, and NLRP3 inflammasome hyperactivation. HFD-NLRP3-/- mice showed a lower increase in body weight, an improvement in IEB integrity and an absence of enteric gliosis. Coculture experiments showed that palmitate and lipopolysaccharide contribute to IEB damage and promote enteric gliosis with consequent hyperactivation of enteric glial NLRP3/caspase-1/IL-1β signaling. Enteric glial-derived IL-1β release exacerbates the IEB alterations. Such an effect was abrogated upon incubation with anakinra (IL-1β receptor antagonist) and with conditioned medium derived from silenced-NLRP3 glial cells. HFD intake elicits mucosal enteric gliotic processes characterized by a hyperactivation of NLRP3/caspase-1/IL-1β signaling pathway, that contributes to further exacerbate the disruption of intestinal mucosal barrier integrity. However, we cannot rule out the contribution of NLRP3 inflammasome activation from other cells, such as immune cells, in IEB alterations associated with obesity. Overall, our results suggest that enteric glial NLRP3 inflammasome might represent an interesting molecular target for the development of novel pharmacological approaches aimed at managing the enteric inflammation and intestinal mucosal dysfunctions associated with obesity.

Huopuxialing Decoction: A Promising Candidate for Precancerous Lesions of Gastric Cancer Treatment Based on Bioinformatics and Experimental Verification.

The Precancerous Lesion of Gastric Cancer (PLGC) is an early stage in the development of gastric cancer. The clinical application of HPXLD has been found to be effective in treating PLGC, but the mechanism of how HPXLD acts on PLGC is still unclear. The objectives of this study were to reveal the molecular mechanism of how HPXLD can be used to treat PLGC and investigate this mechanism through bioinformatics and experimental validation. PLGC-associated target genes were identified through bioinformatics analysis. A rat model of PLGC was induced using N-methyl-N'-nitro-N-nitrosoquanidine (MNNG) in combination with ranitidine, hot saline, ethanol, and intermittent fasting, with interventions by HPXLD. The pathological alterations in gastric mucosa were assessed through Hematoxylin-eosin staining (HE). Immunohistochemistry (IHC) and Western blot analyses were employed to evaluate the changes in expression levels of inflammation-related proteins. After conducting bioinformatics analysis, it was found that there were 23 HPXLDPLGC crossover genes, which were significantly enriched in the IL-17 signaling pathway, TNF signaling pathway, and NF-kappa B signaling pathway. The results of HE showed that HPXLD was effective in improving gastric mucosal histopathological changes. Additionally, the IHC results demonstrated that HPXLD was able to downregulate the expression of IL-6, COX-2, MCP- 1, and MMP-9. Furthermore, Western blot analysis revealed that HPXLD was able to downregulate the expressions of IL-6, IL-17RA, ACT1, NF-κB, and TNF-α. HPXLD has been shown to improve PLGC by reducing the expression of inflammation- related proteins. This suggests that HPXLD may potentially be a treatment option for PLGC.

Lectin histochemistry in the small intestines of piglets naturally infected with porcine epidemic diarrhea virus.

Porcine epidemic diarrhea virus (PEDV) binds to particular cell surface receptors to penetrate cells. The virus specifically identifies certain carbohydrate structures present on the surface of the cell to facilitate the binding process. Nevertheless, the influence of viral infections on specific alterations of glycoconjugates in the small intestines remains unexplored. This work aimed to examine the alterations in glycoconjugates in the small intestines of piglets naturally infected with PEDV using lectin histochemistry. Six piglets including three PEDV-infected and three non-infected piglets were evaluated. Small intestinal samples were histopathologically examined, and lectin histochemistry was performed. Piglets infected with PEDV had significant histological abnormalities in their small intestines, such as pronounced villous atrophy, varying degrees of villous fusion, and diverse mucosal alterations. Specific regions of the duodenum, jejunum, and ileum showed discernible variations in glycoconjugate distribution, as determined by lectin histochemistry. Compared with the controls, the PEDV-infected piglets showed significant changes in N-acetylglucosamine- and galactose-binding lectins (particularly wheat germ agglutinin and Arachis hypogaea (peanut) agglutinin) in multiple intestinal regions. These findings can enhance understanding of how viruses such as PEDV impact the glycoconjugate composition of the small intestines and emphasize the potential connection between the pathogenesis of PEDV and glycoconjugate.

Linking GERD and the Peptide Bombesin: A New Therapeutic Strategy to Modulate Inflammatory, Oxidative Stress and Clinical Biochemistry Parameters.

Gastroesophageal reflux disease (GERD) represents one of the most prevalent foregut illnesses, affecting a large portion of individuals worldwide. Recent research has shown that inflammatory mediators such as cytokines, chemokines, and enzymes are crucial for causing esophageal mucosa alterations in GERD patients. It seems likely that the expression of various cytokines in the esophageal mucosa also induces oxidative stress by increasing the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS). As humoral agents and peptidergic neurotransmitters that may support the enterogastric axis, bombesin and its related bombesin-like peptide, GRP (gastrin releasing peptide), have not been fully investigated. Therefore, considering all these assumptions, this study aimed to evaluate the influence of bombesin in reestablishing biochemical markers linked with inflammation and oxidative/nitrosative stress in GERD pathological settings. C57BL/6 mice were alternatively overfed and fasted for 56 days to induce GERD and then treated with bombesin (0.1, 0.5, and 1 mg/kg intraperitoneally) once daily for 7 days, and omeprazole was used as the positive control. After 7 days of treatment, gastric pain and inflammatory markers were evaluated. Abdominal pain was significantly reduced following bombesin administration, which was also successful in diminishing inflammatory and oxidative/nitrosative stress markers in a manner overlapping with omeprazole. Moreover, bombesin was also able to appreciably modulate gastric pH as a result of the restoration of gastric homeostasis. Overall, these observations indicated that the upregulation of bombesin and interconnected peptides is a promising alternative approach to treat GERD patients.

Endoscopic Features of Chronic Rhinosinusitis in Patients with Gastroesophageal Reflux Disease.

Chronic rhinosinusitis (CRS) is a complex inflammatory condition affecting the nasal and paranasal sinus mucosa. Gastroesophageal reflux disease (GERD) has been implicated as a potential exacerbating factor in CRS, but the specific endoscopic features of nasopharyngeal pathology in this context remain poorly understood. Background and Objectives: Chronic rhinosinusitis is a multifactorial disease with various underlying etiologies, including inflammation, anatomical factors, and environmental triggers. While gastroesophageal reflux disease has been suggested as a potential contributor to chronic rhinosinusitis, the specific endoscopic features indicative of nasopharyngeal pathology in CRS patients with GERD symptoms have not been clearly elucidated. Our aim is to identify specific endoscopic features of nasopharyngeal pathology in patients with CRS associated with GERD symptoms and to propose a method for assessing the influence of gastroesophageal reflux disease on the mucosal layer of the nose and nasopharynx. Materials and Methods: We conducted a cross-sectional observational study involving 521 adult patients presenting with symptoms suggestive of CRS. From this cohort, 95 patients with the highest scores on the Reflux Symptom Index (RSI) and Reflux Symptom Score-12 (RSS-12) questionnaires were selected as the main group. Endoscopic examinations were performed to assess the nasal and nasopharyngeal mucosa. Results: Our study revealed significant alterations in the nasopharyngeal mucosa of patients with CRS associated with GERD symptoms. Increased vascularity of the nasopharyngeal mucosa was observed in 91 patients (95.7%), while hypertrophy was noted in 83 patients (87.4%). Mucus was present in the nasopharynx of 77 patients (81.1%), exhibiting varying characteristics of color and consistency. Asymmetric hypertrophy of the oropharyngeal mucosa was noted in 62 patients (65.3%). Conclusions: We propose a method for assessing the influence of gastroesophageal reflux disease on the mucosal layer of the nose and nasopharynx, which may aid in diagnostic and management decisions. Further research is warranted to explore the potential impact of GERD symptoms on the course and severity of CRS exacerbations.

Melatonin as a preventive treatment of tongue mucosa alterations in an animal model of orofacial radiation

Melatonin as a preventive treatment of tongue mucosa alterations in an animal model of orofacial radiation

Role of mucosal-associated invariant T cells dynamics in pathogenesis of Sjögren syndrome

Sjögren syndrome (SS) is an autoimmune disease characterized by chronic inflammatory infiltrates in the salivary and lacrimal glands. Mucosal-associated invariant T (MAIT) cells are a subset of innate-like T-cells, predominantly found in mucosal tissues with crucial role in epithelial homeostasis. Thus, MAIT cells may be implicated in mucosal alterations of SS patients. Activation markers, inflammatory and cytotoxic cytokines were examined in 23 SS patients and compared to 23 healthy controls (HC). Tissular MAIT cells in salivary gland (SG) biopsies were also analyzed. Circulating MAIT cells were decreased in SS patients with a higher expression of CD69 and a higher CD4/CD8 ratio of MAIT cells. MAIT cells showed a higher production of IFNγ, TNFα and GzB in SS compare to HC. Tissular MAIT cells were present within inflamed SG of SS patients, while they were absent in SG of HC. Overall, circulating MAIT cells are decreased in the peripheral blood of SS albeit producing higher amounts of IFNγ, TNFα, and GzB. Tissular MAIT cells are detected in salivary glands from SS with a proinflammatory tissular cytokine environment. MAIT cells with abnormal phenotype, functions and tissular homeostasis may contribute to epithelial damage in SS.

Pre-housing fasting and diet physical form impact broiler chicks’ gastrointestinal development along the first week of housing

This study aimed to evaluate body and gastrointestinal development in broilers chicks subjected or not to pre-housing fasting and different diet physical forms during the first week of housing. Nine hundred chicks were distributed into a completely randomized design in a 3×3 factorial arrangement: 0, 24 and 48 hours(h) of fasting; mashed (MM), crushed (CC) and micropelletized (MP) physical forms. For each fasting period, 300 animals were housed in protection circles with 100 chicks each. On days 1, 3, 5 and 7 of feeding, six animals were randomly selected, previously weighed and euthanized to obtain organs biometrical and histological data. Chicks fasted for 24 h and 48 h were lighter compared to the 0 h group and the 24-h fasting x MP interaction had a positive impact on body weight at d7 (P<0.05). Although fasted chicks presented lower body weight, small intestine, liver and gizzard were heavier, and presented greater yolk sac consumption (YSC; P<0.05). There were no alterations in the duodenal mucosa (DM) in pre-housing fasting animals (P>0.05). Despite the diet physical form and pre-housing fasting interactions for villus height (VH) and absorptive area (AA) on d1, only diet physical form affected DM, where greater VH and AA on d7 were observed in CC and MP groups (P<0.05). Animals fed MP after 48 h fasting presented smaller VH and AA compared to chicks fed the same diet after 24 h and were similar to the 0 h group (P<0.05). On d1, YSC was similar among groups of the same diet, but for those fed with MP(P<0.05). The 48 h-fasted group presented heavier intestines relative weights (IRW) at d1(P<0.05). Furthermore, the 0 h group fed with CC presented higher IRW, whereas MP showed the lowest IRW over the first week (P<0.05). The DM development (kinetics) showed an increase in VH and AA overtime in all groups, which was more pronounced in 48 h-fasting chicks throughout the first week, showing the highest increase in VH when fed with MP (P<0.05). VH:CD ratio was similar along the first week in MP groups, regardless of the fasting period but more pronounced in the 24 h group fed MM and CC (P<0.05). Therefore, 24 h fasting associated to MP diet may be the most efficient management practice. Collectively, these findings suggest pre-housing fasting is strongly associated with diet physical form at the first week of housing and should be considered to achieve greater performance in broilers.

The Spectrum of Sarcina Colonization in the Gastrointestinal Tract of Pediatric and Adolescent Patients.

Introduction. Sarcina organisms are rare, gram-positive, sugar-fermenting cocci, identifiable in tissues only by histologic examination or molecular testing. Since its discovery, the pathogenicity and relevance of Sarcina in the human gastrointestinal tract has remained ill-defined. A recent literature review of 66 reported examples demonstrated the potential for severe complications such as emphysematous gastritis and gastric perforation. In pediatrics, colonization is associated with mucosal alterations and/or gastrointestinal dysmotility/obstruction with variable outcomes, including death secondary to gastric perforation. Yet, the features of Sarcina colonization within the gastrointestinal tract of adolescents are poorly understood and rarely reported. Methods. We present the gastrointestinal histopathological findings and the complete history of 4 pediatric patients with Sarcina colonization at our institution. Additionally a literature review with focus in the keywords "Sarcina" and "gastrointestinal' was performed, and the clinical and histopathological features of all previously reported examples of Sarcina in the gastrointestinal tract of pediatric patients were summarized. Results. All 4 patients had delayed gastric emptying, 3 of them due to neurologic disease, and one with pyloric obstruction due to duodenal ulceration with Helicobacter gastritis. In the 3 patients with available esophageal biopsies, it was associated to esophagitis with increased intraepithelial eosinophils. Conclusion. The potential pathogenicity of Sarcina colonization in the gastrointestinal tract of pediatric patients needs to be reevaluated. Due to potential serious complications, the identification of these organisms in the gastrointestinal tract sample should be reported and warrants further evaluation for possible gastrointestinal dysmotility or other mucosal alterations.

Transcriptome analysis suggests broad jejunal alterations in Linghu’s obesity-diarrhea syndrome: A pilot study

BACKGROUND Obesity is associated with a significantly increased risk for chronic diarrhea, which has been proposed as Linghu’s obesity-diarrhea syndrome (ODS); however, its molecular mechanisms are largely unknown. AIM To reveal the transcriptomic changes in the jejunum involved in ODS. METHODS In a cohort of 6 ODS patients (JOD group), 6 obese people without diarrhea (JO group), and 6 healthy controls (JC group), high-throughput sequencing and bioinformatics analyses were performed to identify jejunal mucosal mRNA expression alterations and dysfunctional biological processes. In another cohort of 16 ODS patients (SOD group), 16 obese people without diarrhea (SO group), and 16 healthy controls (SC group), serum diamine oxidase (DAO) and D-lactate (D-LA) concentrations were detected to assess changes in intestinal barrier function. RESULTS The gene expression profiles of jejunal mucosa in the JO and JC groups were similar, with only 1 differentially expressed gene (DEG). The gene expression profile of the JOD group was significantly changed, with 411 DEGs compared with the JO group and 211 DEGs compared with the JC group, 129 of which overlapped. The enrichment analysis of these DEGs showed that the biological processes such as digestion, absorption, and transport of nutrients (especially lipids) tended to be up-regulated in the JOD group, while the biological processes such as rRNA processing, mitochondrial translation, antimicrobial humoral response, DNA replication, and DNA repair tended to be down-regulated in the JOD group. Eight DEGs (CDT1 , NHP2 , EXOSC5 , EPN3 , NME1 , REG3A , PLA2G2A , and PRSS2 ) may play a key regulatory role in the pathological process of ODS, and their expression levels were significantly decreased in ODS patients (P &lt; 0.001). In the second cohort, compared with healthy controls, the levels of serum intestinal barrier function markers (DAO and D-LA) were significantly increased in all obese individuals (P &lt; 0.01), but were higher in the SOD group than in the SO group (P &lt; 0.001). CONCLUSION Compared with healthy controls and obese individuals without diarrhea, patients with Linghu’s ODS had extensive transcriptomic changes in the jejunal mucosa, likely affecting intestinal barrier function and thus contributing to the obesity and chronic diarrhea phenotypes.

Clinical aspects of oral cancer and potentially malignant disorders in South and Southeast Asia.

Oral cancer and Oral Potentially Malignant Disorders (OPMD) are major health problems in South and Southeast Asia. To describe and discuss the clinical aspects of Oral Cancer and OPMD in South and Southeast Asia. Literature review of concepts and data over the last four decades. Asian countries account for about two-thirds of new cases of oral cancer (OC) globally, with the highest burden in the South and Southeast Asian countries, including Pakistan and India. Habits, dietary patterns, socioeconomic status, and access to routine dental care play a crucial role in defining the demographics and clinical presentation of OC in these regions and significantly influence the morbidity and mortality of the disease. This region sees the use of different types of tobacco with or without areca nut (AN), such as pan masala, gutka, gul, snuff, mawa, and mishri. Tobacco use is high among men in Sri Lanka, Myanmar, Maldives, Bangladesh, Nepal, India and Bhutan. Areca nut is the fourth most common addictive substance globally and is frequently used in South and Southeast Asian countries, including Southeast China, Hainan Island, India, Taiwan, and the Pacific Islands, and immigrants from these regions in Africa, Europe, and North America. The use of these products results in mucosal alterations with varied clinical presentation of Oral Potentially Malignant Disorders (OPMDs) and OC. We discuss here the different types of OPMD and OC, the diagnostic aids and their relevance in clinical practice, and factors that influence their prognosis.

Air pollution and rhinitis.

Rhinitis arises from either allergic or non-allergic inflammation of the nasal mucosa, characterized by the infiltration of inflammatory cells into the tissue and nasal secretions, along with structural alterations in the nasal mucosa. The pathways through which air pollution affects rhinitis may diverge from those affecting asthma. This article aims to review the effects of diverse air pollutants on the nose, the correlation of climate change and pollution, and how they aggravate the symptoms of patients with rhinitis.

Exploring the Link between Helicobacter pylori, Gastric Microbiota and Gastric Cancer.

Gastric cancer (GC) still represents one of the leading causes of cancer-related mortality and is a major public health issue worldwide. Understanding the etiopathogenetic mechanisms behind GC development holds immense potential to revolutionize patients' treatment and prognosis. Within the complex web of genetic predispositions and environmental factors, the connection between Helicobacter pylori (H. pylori) and gastric microbiota emerges as a focus of intense research investigation. According to the most recent hypotheses, H. pylori triggers inflammatory responses and molecular alterations in gastric mucosa, while non-Helicobacter microbiota modulates disease progression. In this review, we analyze the current state of the literature on the relationship between H. pylori and non-Helicobacter gastric microbiota in gastric carcinogenesis, highlighting the mechanisms by which microecological dysbiosis can contribute to the malignant transformation of the mucosa.

Endoscopic evaluation of gastric mucosal alterations in patients with chronic heart failure II-III nyha functional class utilizing advanced endoscopic techniques

Objective: To assess the alterations of gastric mucosa, its pathomorphological and functional characteristics in patients with complete erosions suffering from chronic heart failure II-III NYHA functional class. Materials and Methods: 185 patients with complete erosions comprised the main group, while the control group consisted of 183 patients with incomplete erosions of the stomach. Patients in both groups had chronic heart failure II-III NYHA functional class. All patients underwent esophagogastroduodenoscopy with white light imaging (WLI), narrow-band imaging (NBI), and ZOOM modes, as well as biopsy sampling followed by pathomorphological examination, determination of Helicobacter pylori presence, and endoscopic pH-metry. The diagnosis of chronic heart failure was established based on anamnestic data and the results of instrumental and functional diagnostic methods, including electrocardiography (ECG), echocardiography, Holter monitoring of ECG, stress echocardiography, and coronary angiography. Results: The study utilized the classification of gastric erosive lesions by K. Toljamo (2012), according to which in the main group, mature erosions subtype Ia were detected in 83.8% of cases, while immature extensive erosions subtype Ib were found in 16.2%. In combination with haemorrhagic erosions (type III), complete erosions were detected in 12.6% of cases, while with incomplete erosions of type II, they were found in 11.4%. The combination of complete erosions with erosive prepyloric changes (type IV) was identified in 8.7%. In the control group, gastric erosive lesions were mainly represented by type III (41%) and type IV (38.8%). Based on the analysis of endoscopic changes in the gastric mucosa using WLI, NBI, and ZOOM modes, the most characteristic visual changes were identified for each type and subtype of erosive gastric mucosa alterations. In patients with chronic heart failure II-III NYHA functional class, gastritis was noted in 75.1% of cases in the main group and in 58.5% in the control group. Helicobacter pylori infection of weak degree was determined in 40.5% in the main group and 37.7% in the control group. Evaluation of endoscopic pH-metry showed predominantly hypochlorhydria in both groups - 70.8% in the main group and 48.6% in the control group. Conclusion: By comparing the macroscopic features of various gastric erosive lesions in WLI, NBI, and ZOOM modes according to the classification by K. Toljamo (2012), the most characteristic signs for each type and subtype were identified. High prevalence of gastritis was established among patients with chronic heart failure II-III NYHA functional class.