Search Results (27)

Background: Chronic atrophic gastritis precancerous lesions (PL-CAG) are characterized by the atrophy of gastric mucosal glands, often accompanied by intestinal metaplasia or dysplasia. Timely intervention and treatment can effectively reverse its malignant progression and prevent the onset of gastric cancer. Bombyx Batryticatus (BB) exhibits a range of pharmacological effects, including anticoagulation, antiepileptic properties, anticancer activity, and antibacterial effects. However, the pharmacological basis and mechanisms underlying BB’s efficacy in treating PL-CAG remain unclear. Methods: A three-factor modeling approach was implemented to develop a rat PL-CAG model, while the MNNG-induced PLGC (precancerous lesions of gastric cancer) cell model was served as a cell PL-CAG model. UPLC-QE-Orbitrap-MS/MS (Ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry) was utilized to perform an in-depth analysis of the components in the plasma extract of BB. Leveraging network pharmacology, molecular docking analyses, and experimental validation, we initially elucidated the potential mechanisms through which BB mediates its therapeutic effects on PL-CAG at both in vivo and in vitro levels. Results: Prototype compounds of 42 blood-entering components were identified by UPLC-QE-Orbitrap-MS/MS analysis. Network pharmacology analysis and molecular docking studies indicate that the core targets are primarily enriched in the PI3K-Akt signaling pathway, and the key components, including Nepitrin, Quercetin 3-O-neohesperidoside, Rutin, and others, exhibited stable docking conformations with the first eleven pivotal targets. Both in vivo and in vitro experiments validated that BB may effectively treat PL-CAG via modulation of the PI3K-Akt signaling pathway. Conclusions: The therapeutic efficacy of BB in the management of PL-CAG may be achieved through the synergistic interaction of multiple components and targets, which may be more closely related to the inhibition of the PI3K/AKT signaling pathway. This approach will establish a solid experimental foundation and provide essential data for the clinical application of BB in treating PL-CAG, while also facilitating further research initiatives. Full article

Ulcerative colitis (UC) is a chronic inflammation disease with severe impact on quality of life, with limited treatment options. Ramulus Mori alkaloids (SZ-A) from Morus alba show promise for UC treatment due to their safety and pharmacological effects, including anti-inflammation and barrier repair. However, their clinical use has been limited by gastrointestinal flatulence as a side effect due to their pharmacological action as an α-glucosidase inhibitor targeting the small intestine following oral administration. Therefore, constructing a colon-targeted formulation to deliver SZ-A is an advantageous strategy to improve UC therapy. In this study, we used the complex formed by thiolated hyaluronic acid, which has mucosal adhesion and inflammation-targeting properties, and SZ-A as an intermediate carrier and prepared sodium alginate-modified PLGA microspheres (SZ-A@MSs) with the double emulsion method to achieve efficient encapsulation of SZ-A. Specifically, sodium alginate serves as a gastric acid protectant and microbiota-responsive material, enabling the precise and responsive release of microspheres in the colonic region. SZ-A@MSs have a particle size of about 30 µm, a drug loading of about 12.0%, and an encapsulation efficiency of about 31.7% and function through intestinal adhesion to and targeting of inflammatory sites. SZ-A@MSs showed antioxidant and anti-inflammatory abilities in Raw264.7 cells. In vivo imaging results suggest that SZ-A@MSs have good colon site retention and sustained-release effect. Pharmacodynamic results show that SZ-A@MSs display good efficacy, including the ability to inhibit weight loss, inhibit colonic atrophy, and inhibit the secretion of inflammatory factors. In conclusion, SZ-A@MSs have good colon-targeting properties, can improve therapeutic effects, and provide a potential treatment method for UC. Full article

Sanghuang (Sanghuangporus sanghuang, SS) is a medicinal fungus with multiple pharmacological effects, including antioxidant, anti-inflammatory, immune-boosting, and anti-cancer activities. 5-fluorouracil (5-FU) is a commonly used chemotherapeutic agent for the treatment of colorectal cancer. It primarily exerts its antitumor effect by inhibiting DNA and RNA synthesis, leading to cell apoptosis. However, it frequently induces adverse effects These issues limit the clinical application of 5-FU. This research aims to determine the potential of SS as a therapeutic agent in reducing 5-FU-induced intestinal mucositis in a mouse model. The results indicated that 5-FU administration significantly increased diarrhea severity, reduced colon length, caused small intestinal villus atrophy, disrupted intestinal architecture, led to insufficient crypt cell proliferation, and resulted in weight loss. It also significantly upregulated inflammatory responses, apoptosis, oxidative stress, and epithelial–mesenchymal transition (EMT) pathways, and disrupted the integrity of intestinal mucosal tight junction, while elevating pro-inflammatory cytokines and reducing antioxidant capacity. However, SS significantly ameliorating alleviating the adverse impacts of the chemotherapeutic agent on the intestinal mucosa. In conclusion, this investigation provides the first evidence of the protective effects of SS on 5-FU-induced mucositis. These findings suggest SS as a potential therapeutic application, offering a promising strategy for reducing the adverse effects of 5-FU chemotherapy and improving the treatment and quality of life for colorectal cancer patients. Full article

Background and Clinical significance: Plummer–Vinson (PV) syndrome is a rare medical entity diagnosed when iron-deficiency anemia, dysphagia, and esophageal webs occur in the same patient. PV syndrome has been associated with different autoimmune diseases, such as celiac disease (CD). CD is a chronic multisystemic disorder affecting the small intestine, but it is recognized as having a plethora of clinical manifestations secondary to the malabsorption syndrome that accompanies the majority of cases. However, similar to PV syndrome, a high percentage of CD patients are asymptomatic, and those who are symptomatic may present with a wide variety of gastrointestinal and extraintestinal symptoms, including iron-deficiency anemia, making the diagnosis challenging. Case presentation: We present the case of a 43-year-old Caucasian female patient with a 7-year history of iron-deficiency anemia and increased bowel movements (3–4 stools/day). Upper endoscopy demonstrated a narrowing at the proximal cervical esophagus from a tight esophageal stricture caused by a smooth mucosal diaphragm. A 36F Savary–Gilliard dilator was used to manage the stenosis. The distal esophagus and stomach were normal, but scalloping of the duodenal folds was noted, and CD was confirmed by villous atrophy and positive tissue transglutaminase antibodies. Dysphagia was immediately resolved, and a glute-free diet was implemented. Conclusions: The relationship between PV syndrome and CD is still a matter of debate. Some might argue that PV syndrome is a complication of an undiagnosed CD. In cases of PV syndrome, a CD diagnosis should be considered even in the absence of typical symptoms of malabsorption. Full article

Background/Objectives: Although Helicobacter pylori (H. pylori) eradication therapy is important for preventing gastric cancer (GC), the occurrence of GC after H. pylori eradication remains a problem. In this study, the aim was to identify risk factors for GC after H. pylori eradication by comparing long-term histological, endoscopic, and serological evaluations of patients with and without GC. Methods: Patients who underwent H. pylori eradication therapy at Oita University Hospital between June 1997 and August 2013 and were followed for at least 3 years with long-term endoscopy, histology, and serum biochemical tests were included, and the GC (215 cases) and non-GC (11 cases) groups were compared. Results: The GC group was older than the non-GC group at the time of eradication, had lower serum pepsinogen I/II levels, had severe endoscopic atrophic changes, had higher activity at the antrum, and inflammation and intestinal metaplasia (IM) at the corpus on updated Sydney system scoring. On long-term follow-up after eradication, the GC group had a wider range of endoscopic mucosal atrophy and a lower serum pepsinogen I/II ratio at any time point. Conclusions: Endoscopic mucosal atrophy and the serum pepsinogen I/II ratio are useful predictors of GC in patients post H. pylori eradication at any time point. Full article

(1) Background: Weaning is a challenging and stressful event in the pig’s life, which disrupts physiological balance and induces oxidative stress. Microbiota play a significant role during the weaning process in piglets. Therefore, this study aimed to investigate key gut microbiota and metabolites associated with weaning stress in piglets. (2) Methods: A total of ten newborn piglet littermates were randomly assigned to two groups: S (suckling normally) and W (weaned at 21 d; all euthanized at 23 d). Specimens of the cecum were dehydrated with ethanol, cleared with xylene, embedded in paraffin, and cut into 4 mm thick serial sections. After deparaffinization, the sections were stained with hematoxylin and eosin (H&E) for morphometric analysis. Cecal metagenomic and liver LC-MS-based metabolomics were employed in this study. Statistical comparisons were performed by a two-tailed Student’s t-test, and p < 0.05 indicated statistical significance. (3) Results: The results showed that weaning led to intestinal morphological damage in piglets. The intestinal villi of suckling piglets were intact, closely arranged in an orderly manner, and finger-shaped, with clear contours of columnar epithelial cells. In contrast, the intestines of weaned piglets showed villous atrophy and shedding, as well as mucosal bleeding. Metagenomics and metabolomics analyses showed significant differences in composition and function between suckling and weaned piglets. The W piglets showed a decrease and increase in the relative abundance of Bacteroidetes and Proteobacteria (p < 0.05), respectively. The core cecal flora in W piglets were Campylobacter and Clostridium, while those in S piglets were Prevotella and Lactobacillus. At the phylum level, the relative abundance of Bacteroidetes significantly decreased (p < 0.05) in weaned piglets, while Proteobacteria significantly increased (p < 0.05). Significant inter-group differences were observed in pathways and glycoside hydrolases in databases, such as the KEGG and CAZymes, including fructose and mannose metabolism, salmonella infection, antifolate resistance, GH135, GH16, GH32, and GH84. We identified 757 differential metabolites between the groups through metabolomic analyses—350 upregulated and 407 downregulated (screened in positive ion mode). In negative ion mode, 541 differential metabolites were identified, with 270 upregulated and 271 downregulated. Major differential metabolites included glycerophospholipids, histidine, nitrogen metabolism, glycine, serine, threonine, β-alanine, and primary bile acid biosynthesis. The significant differences in glycine, serine, and threonine metabolites may be potentially related to dysbiosis caused by weaning stress. Taken together, the identification of microbiome and metabolome signatures of suckling and weaned piglets has paved the way for developing health-promoting nutritional strategies, focusing on enhancing bacterial metabolite production in early life stages. Full article

Inflammatory bowel diseases (IBDs) represent multifactorial chronic inflammatory conditions of the gastrointestinal tract. The main IBDs are Crohn’s disease (CD) and ulcerative colitis (UC). CD may cause perforation, stricture or transmural inflammation, which can occur discontinuously in the entire gastrointestinal tract (GIT). UC leads to mucosal inflammation as well as mucosal atrophy in the rectum and the colon. Innate immunity is considered the first line of defense against microbial invasion; among Toll-like receptors, TLR2 is the most important for defense against mycobacterial infection. TLR2 has been reported to have a lot of functions in infectious diseases and in other pathologies, such as chronic and acute inflammatory diseases. Alfa-Smooth Muscle Actin (α-SMA) is an important biomarker in IBDs. All myofibroblasts express α-SMA, which has been found to be upregulated in CD and UC. Paraformaldehyde-fixed intestinal tissues, from patients with CD and patients with UC, were analyzed by immunostaining for TLR2 and α-SMA. Our results showed that, in the samples obtained from UC patients with inflamed mucosa, TLR2-positive epithelial cells concentrated on the mucosal surface and scattered immune cells in the connective tissue; furthermore, numerous α-SMA-positive cells (subepithelial myofibroblasts) were detected in the lamina propria and around glands, while some myofibroblasts co-localizing with α-SMA and TLR2 could be inflammatory macrophages. In CD patients, TLR2-positive enterocytes and α-SMA-positive myofibroblasts in the lamina propria of the villus have been observed. In control samples, a low positivity to α-SMA and TLR2 was observed in subepithelial myofibroblasts and scattered immune cells of the lamina propria. These data showed the recall of α-SMA-positive myofibroblasts during the inflammatory state; in addition, TLR2 expression has been observed to change in the intestinal epithelium in IBDs, demonstrating that alterations in the innate system response may contribute to the pathogenesis of these diseases. Full article

Background. Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS) is an autosomal dominant autoinflammatory disorder stemming from mutations in the TNFRSF1A gene affecting the tumor necrosis factor receptor (TNFR)-1. These mutations lead to dysregulated inflammatory responses, primarily mediated by augmented interleukin (IL)-1β release. Case Presentation. We present the case of a 29-year-old woman with a history of recurrent febrile episodes, abdominal pain, and joint manifestations, eventually diagnosed with TRAPS following genetic testing revealing a heterozygous R92Q mutation in TNFRSF1A. Further genetic examinations unveiled additional clinically significant mutations, complicating the clinical picture. Our patient exhibited delayed colonic transit time and right colonic amyloidosis, a rare complication. Surgical intervention was required for overwhelming intestinal obstruction, revealing mucosal atrophy and dense lymphocytic infiltrates on histological examination. Discussion. Gastrointestinal involvement in TRAPS is common but can present diagnostic challenges. Following colon resection, histological examination revealed amyloid deposition, underscoring the importance of a comprehensive evaluation of these patients. Isolated colic amyloidosis has significant diagnostic and prognostic implications, warranting cautious monitoring and tailored management strategies. Treatment of TRAPS typically involves anti-inflammatory agents such as IL-1 inhibitors, with our patient experiencing clinical improvement on anakinra and canakinumab. Conclusion. This case report emphasizes the diverse manifestations of TRAPS and the importance of recognizing gastrointestinal complications, particularly isolated colic amyloidosis. Comprehensive evaluation, including histological examination, is crucial for identifying atypical disease presentations and guiding management decisions. Continued research is needed to elucidate the underlying mechanisms and optimize treatment strategies for TRAPS and its associated complications. Full article

Type 2 diabetes mellitus (T2DM) is a burgeoning public health challenge worldwide. Individuals with T2DM are at increased risk for skeletal muscle atrophy, a serious complication that significantly compromises quality of life and for which effective prevention measures are currently inadequate. Emerging evidence indicates that systemic and local inflammation stemming from the compromised intestinal barrier is one of the crucial mechanisms contributing to skeletal muscle atrophy in T2DM patients. Notably, natural plant polysaccharides were found to be capable of enhancing intestinal barrier function and mitigating secondary inflammation in some diseases. Herein, we hypothesized that Grifola frondosa polysaccharide (GFP), one of the major plant polysaccharides, could prevent skeletal muscle atrophy in T2DM via regulating intestinal barrier function and inhibiting systemic and local inflammation. Using a well-established T2DM rat model, we demonstrated that GFP was able to not only prevent hyperglycemia and insulin resistance but also repair intestinal mucosal barrier damage and subsequent inflammation, thereby alleviating the skeletal muscle atrophy in the T2DM rat model. Additionally, the binding free energy analysis and molecular docking of monosaccharides constituting GFP were further expanded for related targets to uncover more potential mechanisms. These results provide a novel preventative and therapeutic strategy for T2DM patients. Full article

The COVID-19 pandemic, which emerged in early 2020, has had a profound and lasting impact on global health, resulting in over 7.0 million deaths and persistent challenges. In addition to acute concerns, there is growing attention being given to the long COVID health consequences for survivors of COVID-19 with documented cases of cardiovascular abnormalities, liver disturbances, lung complications, kidney issues, and noticeable cognitive deficits. Recent studies have investigated the physiological changes in various organs following prolonged exposure to murine hepatitis virus-1 (MHV-1), a coronavirus, in mouse models. One significant finding relates to the effects on the gastrointestinal tract, an area previously understudied regarding the long-lasting effects of COVID-19. This research sheds light on important observations in the intestines during both the acute and the prolonged phases following MHV-1 infection, which parallel specific changes seen in humans after exposure to SARS-CoV-2. Our study investigates the histopathological alterations in the small intestine following MHV-1 infection in murine models, revealing significant changes reminiscent of inflammatory bowel disease (IBD), celiac disease. Notable findings include mucosal inflammation, lymphoid hyperplasia, goblet cell hyperplasia, and immune cell infiltration, mirroring pathological features observed in IBD. Additionally, MHV-1 infection induces villous atrophy, altered epithelial integrity, and inflammatory responses akin to celiac disease and IBD. SPIKENET (SPK) treatment effectively mitigates intestinal damage caused by MHV-1 infection, restoring tissue architecture and ameliorating inflammatory responses. Furthermore, investigation into long COVID reveals intricate inflammatory profiles, highlighting the potential of SPK to modulate intestinal responses and restore tissue homeostasis. Understanding these histopathological alterations provides valuable insights into the pathogenesis of COVID-induced gastrointestinal complications and informs the development of targeted therapeutic strategies. Full article

Background: Malnutrition is usual in patients referred for endoscopic gastrostomy (PEG). Refeeding syndrome is rarely observed in PEG-fed patients, which could possibly be associated with reduced absorption induced by prolonged starvation. Objective: In patients submitted to PEG after a significant period of fasting, the present study aims to: 1. evaluate the histological/ultrastructural initial changes in the intestinal mucosa, potentially associated with reduced absorption, and 2. assess if these changes could reverse with enteral refeeding. Methods: The present study is an observational, prospective, controlled study. Adult patients with ingestion below 50% of daily needs for at least one month and/or diagnosis of malnutrition were enrolled. Duodenal biopsies were taken at baseline and after 3–6 months of PEG feeding, which then underwent histological/ultrastructural analysis. Random healthy individuals were used as controls. Results: A total of 30 patients (16 men/14 women) aged 67.1 ± 13.5 years were included. Malnutrition was found in 40% of patients. Approximately 14 patients completed follow-up during both periods (46.7%). At baseline: duodenal mucosal atrophy was evident in three patients (10%); the median villi length (MVL) was 0.4 mm (0.25–0.6 mm), with it being shorter than the controls, which was 0.6 mm (0.4–0.7 mm) (p = 0.006); ultrastructural changes included focal shortening, bending, and disruption of enterocyte microvilli, the presence of citoplasmatic autophagic vacuoles, dilation and vesiculation of the smooth endoplasmic reticulum, and the presence of dilated intercellular spaces with basement membrane detachment. After refeeding, most patients displayed normal histology (92.9%) and increase MVL (p < 0.001), ultrastructural changes disappeared, and enterocytes resumed a normal appearance, although retaining scarce, small, dense bodies in apical regions from the evolution of previous autophagy. Conclusions: Prolonged fasting induces histological and ultrastructural changes in the intestinal mucosa that may reflect impaired absorption in the early post-PEG period. These changes were reverted after refeeding with enteral nutrition. Full article

This study aimed to investigate the effects of oral administration with L. plantarum CAM6 on the hematological profile, relative weight of digestive organs, and cecal traits in growing pigs. A total of 36 castrated male pigs [(Landrace × Pietrain) × Duroc] aged 49 to 139 days old were randomly assigned to 3 experimental groups with 12 animals per treatment. The treatments included a control diet without additives (CTRL), a positive control with subtherapeutic antibiotics (TRT1), and CTRL supplemented with 5 mL Lactobacillus plantarum CAM6 preparation providing 10⁹ CFU/pig/day (TRT2). The TRT2 group showed a higher (p ≤ 0.05) small intestine length and the cecum relative weight compared to the CTRL group. Moreover, L. plantarum CAM6 supplementation promoted (p ≤ 0.05) increased thickness of the muscular and mucosal layers, as well as enhanced depth and width of the cecal crypts. The TRT2 group also showed well-defined crypts without lesions, while the CTRL and TRT1 groups exhibited congestion, lymphocytic infiltration in the crypt, and intestinal-associated lymphoid tissue atrophy, respectively. Additionally, TRT2 stimulated (p ≤ 0.05) the growth of the autochthonous cecal microbiota compared to other experimental groups. Overall, the results indicate that oral administration of L. plantarum CAM6 improved intestinal health and enhanced the growth of autochthonous cecal lactic acid bacteria and had no impact on the complete blood count in growing pigs. Full article

The clinical examination of patients often includes the observation of the existence of a close relationship between the ingestion of certain foods and the appearance of various symptoms. Until now, the occurrence of these events has been loosely defined as food intolerance. Instead, these conditions should be more properly defined as adverse food reactions (AFRs), which can consist of the presentation of a wide variety of symptoms which are commonly identified as irritable bowel syndrome (IBS). In addition, systemic manifestations such as neurological, dermatological, joint, and respiratory disorders may also occur in affected patients. Although the etiology and pathogenesis of some of them are already known, others, such as non-celiac gluten sensitivity and adverse reactions to nickel-containing foods, are not yet fully defined. The study aimed to evaluate the relationship between the ingestion of some foods and the appearance of some symptoms and clinical improvements and detectable immunohistochemical alterations after a specific exclusion diet. One hundred and six consecutive patients suffering from meteorism, dyspepsia, and nausea following the ingestion of foods containing gluten or nickel were subjected to the GSRS questionnaire which was modified according to the “Salerno experts’ criteria”. All patients underwent detection of IgA antibodies to tissue transglutaminase, oral mucosal patch tests with gluten and nickel (OMPT), and EGDS, including biopsies. Our data show that GSRS and OMPT, the use of APERIO CS2 software, and the endothelial marker CD34 could be suggested as useful tools in the diagnostic procedure of these new pathologies. Larger, multi-center clinical trials could be helpful in defining these emerging clinical problems. Full article

Introduction and aim: Usually, adherence to the gluten-free diet (GFD) in celiac patients is indirectly assessed through serological analysis, questionnaires, or invasive methods such as intestinal biopsy. The detection of gluten immunogenic peptides in urine (urinary gluten immunogenic peptides—uGIP) is a novel technique that directly evaluates the ingestion of gluten. The aim of this study was to evaluate the clinical efficacy of uGIP in the follow-up of celiac disease (CD). Methods: From April 2019 to February 2020, CD patients reporting complete adherence to the GFD were prospectively enrolled but were unaware of the reason for the tests. Urinary GIP, the celiac dietary adherence test (CDAT), symptomatic visual analog scales (VAS), and tissue transglutaminase antibodies (tTGA) titres were evaluated. Duodenal histology and capsule endoscopy (CE) were performed when indicated. Results: A total of 280 patients were enrolled. Thirty-two (11.4%) had a positive uGIP test (uGIP+). uGIP+ patients did not show significant differences in demographic parameters, CDAT, or VAS scores. The tTGA+ titre was not related to the positivity of uGIP (14.4% vs. 10.9% in patients with tTGA+ and tTGA−). Regarding histology, 66.7% of the GIP+ patients had atrophy compared to 32.7% of the GIP patients (p-value 0.01). However, the presence of atrophy did not correlate with tTGA. Mucosal atrophy was detected in 29 (47.5%) out of 61 patients by CE. With this method, no noticeable dependence on uGIP results (24 GIP− vs. 5 GIP+) was observed. Conclusions: The single uGIP test was positive in 11% of CD cases referring a correct GFD adherence. Furthermore, uGIP results significantly correlated with the duodenal biopsy, formerly considered the gold standard for assessing CD activity. Full article

Parenteral nutrition (PN) is a life-saving therapy providing nutritional support in patients with digestive tract complications, particularly in preterm neonates due to their gut immaturity during the first postnatal weeks. Despite this, PN can also result in several gastrointestinal complications that are the cause or consequence of gut mucosal atrophy and gut microbiota dysbiosis, which may further aggravate gastrointestinal disorders. Consequently, the use of PN presents many unique challenges, notably in terms of the potential role of the gut microbiota on the functional and clinical outcomes associated with the long-term use of PN. In this review, we synthesize the current evidence on the effects of PN on gut microbiome in infants and children suffering from diverse gastrointestinal diseases, including necrotizing enterocolitis (NEC), short bowel syndrome (SBS) and subsequent intestinal failure, liver disease and inflammatory bowel disease (IBD). Moreover, we discuss the potential use of pre-, pro- and/or synbiotics as promising therapeutic strategies to reduce the risk of severe gastrointestinal disorders and mortality. The findings discussed here highlight the need for more well-designed studies, and harmonize the methods and its interpretation, which are critical to better understand the role of the gut microbiota in PN-related diseases and the development of efficient and personalized approaches based on pro- and/or prebiotics. Full article