Search Results (138)

Claudin-18.2 (CLDN18.2) is an isoform of a tight junction protein and has emerged as a promising therapeutic target in gastric cancer (GC). CLDN18.2 is responsible for gastric homeostasis and protects epithelial cells from low pH conditions. Interestingly, CLDN18.2 expression is strictly restricted to the stomach, making it an ideal tumor marker. This narrative review presents the characterization and role of claudin 18.2 (CLDN18.2) as a promising biomarker in GC and a target for clinical therapies, more specifically CLDN18.2-targeted drugs and therapies including mABs (e.g., Zolbetuximab, Osemitamab, ZL-1211), bsAB, and CAR-T cell-based immunotherapies. We also summarize numerous ongoing worldwide clinical trials that are evaluating CLDN18.2 as a target for GC treatment. What seems to be crucial is that preclinical and clinical data indicate their high efficacy and safety. Full article

Helicobacter pylori infection causes inflammation in the gastric mucosa, and this has been reported to disrupt the gastric microbiota. Serotonin (5-HT) is a key neurotransmitter in the gut–brain axis and plays key roles in intestinal homeostasis and immune function. We investigated gastric serotonin release in H. pylori-infected mice and observed increased release in vaccinated, challenged mice compared to sham vaccinated controls. We investigated the effects of 5-HT on epithelial responses in an in vitro human gastric cancer cell line model (AGS), as well as inflammatory responses and the gastric microbiota in a C57BL/6 mouse model of H. pylori infection. HTR1A was upregulated in the stomachs of mice chronically infected with H. pylori SS1 (3 weeks) compared to uninfected controls, whereas HTR2B was upregulated only in acutely infected mice (3 days), consistent with a role for 5-HT signalling in the development of gastritis. Exposure to 5-HT did not affect NF-κB activation in H. pylori-exposed AGS cells but did inhibit extracellular signal-regulated kinase 1 (ERK1) translocation. Analysis of the gastric microbiota revealed that while vaccination did not significantly affect the diversity of the microbiota, vaccinated animals had increased abundance of Lactobacilli. Our results suggest that local inflammation caused by H. pylori is responsible for increased 5-HT release. Full article

Notoginsenoside Rb1 (Rb1), a bioactive saponin from Panax notoginseng, exerts cardio-cerebrovascular protective, anti-inflammatory, antioxidant, and glucose homeostasis-regulating effects. However, its oral bioavailability is limited by gastric degradation and poor intestinal permeability. This study presents a food-grade bigel system for encapsulating Rb1 to enhance its stability and controlled-release performance. Oleogels were structured using monoglycerides (8%, w/w) in soybean oil. Rb1-loaded binary hydrogels (gellan gum/xanthan gum, 12:1 w/w) were emulsified in 10% Tween-80 (w/w). Bigels were formulated at varying hydrogel-to-oleogel ratios, and a ratio of 4:6 was identified as optimal. Stress-sweep rheological analysis revealed a dense gel structure with a peak storage modulus (G′) of 290.64 Pa—the highest among all tested ratios—indicating superior structural integrity. Confocal microscopy confirmed homogeneous encapsulation of Rb1 within the continuous hydrogel phase, effectively preventing payload leakage. Differential scanning calorimetry (DSC) analysis detected a distinct endothermic transition at 55 °C (ΔH = 6.25 J/g), signifying energy absorption that enables thermal buffering during food processing. The system achieved an encapsulation efficiency of 99.91% and retains both water and oil retention. Effective acid protection and colon-targeted delivery were observed in the digestion test. Effective acid protection and colon-targeted delivery were observed in the digestion test. Less than 5% of Rb1 was released in the gastric phase, and over 90% sustained intestinal release occurred at 4 h. The optimized bigel effectively protected Rb1 from gastric degradation and enabled sustained intestinal release. Its food-grade composition, thermal stability, and tunable rheology offer significant potential for use in functional foods and nutraceuticals. Full article

Background: Short-chain fatty acids (SCFAs), microbial metabolites also known as postbiotics, are essential for maintaining gut health. However, their antiproliferative effects on gastric cancer cells and potential interactions with conventional therapies remain underexplored. This study aimed to investigate the effects of three SCFA salts—magnesium acetate (A), sodium propionate (P), and sodium butyrate (B)—individually and in combination (APB), as well as in combination with dexamethasone (Dex), on AGS gastric adenocarcinoma cells. Methods: AGS cells were treated with PB, AP, AB, APB, Dex, and APB+Dex. Cell viability was assessed to determine antiproliferative effects, and the IC₅₀ of APB was calculated. Flow cytometry was used to evaluate apoptosis and necrosis. Reactive oxygen species (ROS) levels were measured to assess oxidative stress. Proteomic analysis via LC-MS was performed to identify differential protein expression and related pathways impacted by the treatments. Results: SCFA salts showed significant antiproliferative effects on AGS cells, with APB exhibiting a combined IC₅₀ of 568.33 μg/mL. The APB+Dex combination demonstrated strong synergy (combination index = 0.76) and significantly enhanced growth inhibition. Both APB and APB+Dex induced substantial apoptosis (p < 0.0001) with minimal necrosis. APB alone significantly increased ROS levels (p < 0.0001), while Dex moderated this effect in the combination group APB+Dex (p < 0.0001). Notably, the APB+Dex treatment synergistically targeted multiple tumour-promoting mechanisms, including the impairment of redox homeostasis through SLC7A11 suppression, and inhibition of the haemostasis, platelet activation network and NF-κB signalling pathway via downregulation of NFKB1 (−1.34), exemplified by increased expression of SERPINE1 (1.99) within the “Response to elevated platelet cytosolic Ca²⁺” pathway. Conclusions: These findings showed a multifaceted anticancer mechanism by APB+Dex that may collectively impair cell proliferation, survival signalling, immune modulation, and tumour microenvironment support in gastric cancer. Full article

Background: Constipation is a common gastrointestinal disorder with a significant impact on quality of life. Methods: Constipation was induced in male ICR mice via 25% cotrimoxazole gavage (20 mL/kg/day for 7 days). Mice were divided into prevention (pre-MBSFL), treatment (MBSFL), and control groups. MBSFL was prepared by fermenting mung bean starch with Lactobacillus plantarum (1:3 w/v ratio, 37 °C for 48 h), and administered via daily oral gavage (250 mg/kg bw) for 14 days. Fecal parameters (water content and first black stool latency), gastrointestinal motility (gastric emptying and small intestinal propulsion), serum biomarkers (NO, VIP, SP, and 5-HT), and intestinal gene expression (5HTR₄, SERT, and MAO_A) were analyzed. Results: MBSFL intervention restored fecal water content by 38%, reduced first black stool latency from 6.2 h to 3.1 h, and improved small intestinal propulsion by 64%. Additionally, it downregulated serum NO (25%) and VIP (32%) while upregulating SP (49%) and 5-HT (78%) levels. Intestinal 5HTR4 and SERT expression increased by 78% and 71%, respectively, with MAOA suppression (25%). Microbial analysis revealed a 140% increase in Dubosiella and 49% in Lactobacillus abundance, alongside a 62% reduction in Mucispirillum. MBSFL contained polysaccharides (12.3% w/w) and organic acids, including hydroxy butyric acid (4.2 mg/mL). Conclusions: MBSFL alleviates constipation through dual mechanisms: modulating 5-HT pathway activity and restoring gut microbiota homeostasis. Full article

Background: The oral microbiome differs in obese patients compared to normal-weight subjects. Microbiologic shifts very often appear after surgical interventions such as bariatric surgery (BS) and in immunocompromised patients. However, the oral microbiome composition and load in subjects after bariatric surgery are unclear. Aim: The aim of this review is to summarize the current state of the art related to the oral microbiome shift induced by bariatric surgery and to discuss its implications on oral cavity health. Methods: Electronic databases: PubMed/Medline, Web of Science, and Cochrane Library were searched for articles published up to March 30, 2025, describing prospective studies focused on changes in the oral microbiota of patients who underwent bariatric surgery. Results: Eight studies measuring the oral microbiome with different approaches—16S ribosomal RNA (16S rRNA) sequencing, polymerase chain reaction (PCR), culture, and matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI TOF MS)—were included in this review. The following bariatric techniques were used: sleeve gastrectomy, Roux-en-Y gastric bypass, Omega loop gastric bypass, and laparoscopic gastric plication. The follow-up period ranged from 3 to 12 months. The results of microbiologic studies were unequivocal. There was an increment in Streptococcus mutans reported, high levels of Candida species, and increased rates of some periodontitis-associated bacteria (Porphyromonas gingivalis) in the post-bariatric surgery period, though some studies suggested a shift towards non-pathogenic composition of the oral microbiome in prospective observations. Conclusions: The local oral microbial homeostasis becomes strongly impacted by the bariatric surgical treatment itself as well as its consequences in the further post-operative period. Therefore, obese patients undergoing BS require very careful dental observation. Full article

Glucagon-like peptide-1 (GLP-1) has emerged as a pivotal regulator in the management of glucose homeostasis, glycogen metabolism, and energy balance, positioning it as a critical therapeutic target for addressing obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM). GLP-1 receptor agonists (GLP-1RAs) have shown promise for improving glycemic control and reducing weight through appetite regulation, delayed gastric emptying, and energy expenditure modulation. This narrative review explores the mechanisms of GLP-1-mediated glycogen metabolism and energy expenditure, particularly in key tissues—pancreas, liver, skeletal muscle, and adipose tissue. In the pancreas, GLP-1 enhances insulin secretion and beta-cell function. In the liver, it promotes glycogen synthesis via insulin-dependent and potential insulin-independent pathways, involving protein kinase B (AKT) and AMP-activated protein kinase (AMPK) signaling. Skeletal muscle benefits from GLP-1 through increased glucose uptake, AMPK activation, and mitochondrial function, facilitating glycogen storage. In adipose tissue, GLP-1 stimulates brown adipose tissue (BAT) thermogenesis and energy expenditure, contributing to weight loss. This increase in energy expenditure, along with enhanced glycogen metabolism, is a plausible mechanism for the weight loss observed with GLP-1RAs. Despite these advances, significant knowledge gaps remain, particularly regarding the direct hepatic effects of GLP-1, the extent to which it modulates glycogen metabolism in vivo, and its impact on thermogenesis in humans. Future research focusing on both the tissue-specific actions of GLP-1 and its systemic role in energy homeostasis and metabolic regulation will be essential for optimizing its therapeutic potential. Full article

The essential micronutrient zinc is known to inhibit gastric acid secretion (GAS), where its homeostasis is strictly regulated. We hypothesized that the gastric bitter taste receptors, TAS2Rs, regulate the following: (i) zinc-modulated proton secretory activity (PSA) as a key mechanism of GAS and (ii) zinc homeostasis in immortalized parietal cells. To confirm this hypothesis, human gastric tumor cells (HGT-1) were exposed to 100–1000 µM of zinc salts for 30 min in order to quantitate their TAS2R-dependent PSA and intracellular zinc concentration using a fluorescence-based pH sensor and ICP-MS, respectively. Thereby, we identified TAS2R43 as a key player in parietal cell PSA and zinc homeostasis, with both conclusions being verified by a CRISPR-Cas9 knockout approach. Moreover, by regulating the zinc importer protein ZIP14, TAS2R43 proved to perform a protective role against excessive zinc accumulation in immortalized parietal cells. Full article

Helicobacter pylori (H. pylori) is a Gram-negative bacterium that colonizes the human stomach and is associated with several gastric diseases, including gastritis, peptic ulcer disease, and gastric cancer. The bacterium’s ability to thrive in the harsh gastric environment is due, to some extent, to its stress response mechanisms, with its heat shock proteins (HSPs) playing a putative, yet not fully understood, role in these adaptive processes. HSPs are a family of molecules, highly conserved throughout phylogenesis, that assist in protein folding, prevent aggregation, and ensure cellular homeostasis under stressful conditions. In H. pylori, HSPs contribute to survival in the stomach’s acidic environment and oxidative stress. Furthermore, they aid in the bacterium’s ability to adhere to gastric epithelial cells, modulate the host immune response, and form biofilms, all contributing to chronic infection and pathogenicity. The role of microbial HSPs in antibiotic resistance has also emerged as a critical area of research, as these proteins help stabilize efflux pumps, protect essential proteins targeted by antibiotics, and promote biofilm formation, thereby reducing the efficacy of antimicrobial treatments. Among bacterial HSPs, GroEL and DnaK are probably the major proteins that control most of the H. pylori’s functioning. Indeed, both proteins possess remarkable acid resistance, high substrate affinity, and dual roles in protein homeostasis and host interaction. These features make them critical for H. pylori’s adaptation, persistence, and pathogenicity in the gastric niche. In addition, recent findings have also highlighted the involvement of HSPs in the crosstalk between H. pylori and gastric epithelial cells mediated by the release of bacterial outer membrane vesicles and host-derived exosomes, both of these extracellular vesicles being part of the muco-microbiotic layer of the stomach and influencing cellular signalling and immune modulation. Considering their critical role in the survival and persistence of bacteria, microbial HSPs also represent potential therapeutic targets. Strategies aimed at inhibiting microbial HSP function, combined with conventional antibiotics or developing vaccines targeting microbial HSPs, could provide new avenues for the treatment of H. pylori infections and combat antibiotic resistance. This review explores the multifaceted roles of microbial HSPs in the pathogenesis of H. pylori, highlighting their contributions to bacterial adhesion, immune evasion, stress response, and antibiotic resistance. Full article

NKX3-2, a transcriptional repressor factor belonging to the NK family of homeobox-containing proteins, has been widely studied for its role in promoting chondrogenic differentiation and homeostasis. NKX3-2 is upregulated in chemoresistant ovarian tumors and metastatic gastric cancer cells; however, its prognostic role and mechanistic involvement in cancer cell biology remain to be elucidated. By interrogating the TCGA database, we found that cancer patients with high NKX3-2 expression had a shorter overall survival rate than patients with low expression. In ovarian cancer patients, NKX3-2 negatively correlates with P53. Given the prominent role of the latter oncosuppressor in controlling DNA repair and cell death, here we investigate the molecular mechanism involved in this negative correlation in several ovarian cancer cell lines expressing different levels of the two proteins. We found that the high expression of endogenous or ectopic P53 reduced NKX3-2 protein expression, while its knockdown increased it. In contrast, the genetic manipulation of NKX3-2 expression did not affect P53 expression. Mechanistically, P53-mediated downregulation of NKX3-2 does not entail transcriptional activity or proteasomal clearance but occurs via P53–NKX3-2 protein–protein interaction, which in turn results in P53-induced NKX3-2 degradation via the autophagy–lysosome pathway. Remarkably, patients bearing a tumor characterized by low NKX3-2 and high MAP1LC3B expression (indicative of active autophagy) display a better prognosis. Taken together, our data indicate that NKX3-2 represents a negative prognostic factor under P53 control in ovarian cancer. From a translational point of view, identifying this novel mechanism may represent a new molecular signature capable of predicting the clinical outcome of patients, a crucial aspect of developing personalized therapeutic approaches. Full article

Inflammatory bowel disease (IBD) represents a chronic inflammatory disorder of the gastrointestinal tract with a multifactorial etiology that remains incompletely elucidated. Accumulating evidence implicates dysregulation of the intestinal micro-ecosystem, aberrant neuroimmune interactions, and compromised epithelial barrier integrity as key contributors to IBD pathogenesis. While oral administration remains the predominant therapeutic approach, the acidic gastric milieu and enzymatic catabolism markedly compromise drug efficacy. Consequently, selecting an optimal drug delivery method has become a pressing issue in IBD management. As a drug delivery platform, hydrogels, distinguished by their favorable biocompatibility, biodegradability, and injectability, can shield drugs from the harsh gastrointestinal environment. This review offers an innovative and comprehensive analysis of the interactions among various hydrogel application forms, delivery routes, and loaded substances, summarizing the advantages of different types of hydrogels in terms of their anti-inflammatory properties and maintenance of intestinal flora homeostasis, as well as discussing the limitations of current hydrogel deliver systems and looking to the future. Full article

Objectives: This study engineered a colon-targeted drug delivery system (CTDS) using the dual pharmaceutical and edible properties of Pueraria lobata to encapsulate Lactobacillus paracasei for Type 2 diabetes mellitus (T2DM) therapy. Methods: The CTDS was designed as a core–shell composite through microwave–hydrothermal engineering, comprising the following: (1) a retrograded starch shell with acid/enzyme-resistant crystallinity to protect probiotics from gastric degradation; (2) a porous cellulose core derived from Pueraria lobata’s natural microstructure, serving as a colonization scaffold for probiotics. Results: Structural characterization confirmed the shell’s resistance to acidic/pancreatic conditions and the core’s hierarchical porosity for bacterial encapsulation. pH/enzyme-responsive release kinetics were validated via fluorescence imaging, demonstrating targeted probiotic delivery to the colon with minimal gastric leakage. In diabetic models, the CTDS significantly reduced fasting blood glucose and improved dyslipidemia, while histopathological analysis revealed restored hepatic and pancreatic tissue architecture. Pharmacologically, the system acted as both a probiotic delivery vehicle and a microbiota modulator, selectively enriching Allobaculum and other short-chain fatty acid (SCFA)-producing bacteria to enhance SCFA biosynthesis and metabolic homeostasis. The CTDS further exhibited direct compression compatibility, enabling its translation into scalable oral dosage forms (e.g., tablets). Conclusions: By integrating natural material engineering, microbiota-targeted delivery, and tissue repair, this platform bridges the gap between pharmaceutical-grade probiotic protection and metabolic intervention in T2DM. Full article

Ghrelin, a gastric-derived peptide, regulates appetite, food intake, and energy homeostasis. Body weight plays a crucial role in modulating circulating ghrelin levels. Since exercise training is one of the most valuable tools for controlling body weight, it is relevant to consider whether exercise can influence total ghrelin secretion. This study aims to perform a systematic review of the effect of acute/chronic exercise on plasma ghrelin levels. An extensive literature search was carried out on various databases, including PubMed, ScienceDirect, and Google Scholar. The search was conducted using English keywords such as acute-exercise, transient-exercise, exercise, chronic-exercise, training, physical-activity, physical-training, exercise training, and total-ghrelin, ghrelin, appetite-related-peptides, gastrointestinal-peptides, gastrointestinal-hormones, and appetite-regulating-hormone. Initially, 2104 studies were identified. After evaluating study quality, data from 61 relevant studies were extracted for inclusion in this review. Most studies indicated that short-term acute aerobic exercise did not affect total ghrelin levels regardless of exercise intensity, characteristics, or growth hormone (GH) secretion. However, long and very-long aerobic/chronic exercise increased total ghrelin levels, mainly in overweight/obese individuals. Acute/chronic exercise may differentially influence total ghrelin secretion. Short-term acute aerobic exercise induces stable plasma ghrelin concentrations, independent of GH secretion. Long-term aerobic training increased its levels mainly in overweight/obese individuals through body composition and oxidative stress reduction. Additionally, total ghrelin secretion is more sensitive to exercise/training duration than exercise/training intensity. Full article

The human gastrointestinal tract is estimated to be populated by 38 trillion bacteria from almost 1000 different species. The dominant phyla are Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria. However, the diversity and amount of gut microbiota depends on various factors. The importance of gut microbiota is increasingly noticed due to the influence of bacteria on energy homeostasis, the immune system, general health, and metabolism. Bariatric surgery is the mainstay treatment for patients with obesity. Two of the most common mechanisms are reducing gastric volume and decreasing ghrelin secretion. This literature review aims to depict the diverse impact of different bariatric procedures on gut microbiota. The original research papers were collected from the PubMed, Cochrane, and Elsevier databases. This literature review is focused on human studies. However, several references include animal models, specifically rats and germ-free mice. The findings suggest that bariatric surgery causes changes in the diversity of gut microbiota. However, the specificity of the changes depends on the type of bariatric surgery. The Firmicutes/Bacteroidetes ratio is elevated in the groups of patients with obesity compared to lean individuals. Bariatric surgery lowers the ratios impact on metabolism and energy absorption. Gut microbiota produces short-chain fatty acids, of which butyrate is responsible for strengthening the gut barrier, and acetate is correlated with fat deposition and lipogenesis. Moreover, changes in short-chain fatty acids influence insulin resistance and inflammation. In conclusion, bariatric surgery impacts gut microbiota, resulting in metabolic changes in patients, and the need for further study regarding long-term microbiota alterations post-operation is notable. Full article

Background: Roux-en-Y gastric bypass (RYGB) surgery results in weight reduction and decreased energy intake and can ameliorate type 2 diabetes. These beneficial effects are usually attributed to changes in hunger and satiety and relatively rapid improvements in glycemic control, but these effects may depend on dietary adherence. The aim of this study is to investigate the relatively early effects of RYGB surgery on weight reduction (by focusing on eating patterns) and glycemic control in rats subjected to a healthy maintenance diet or an unhealthy Western-style diet. Methods: Rats were fed a high-fat diet with added sucrose (HF/S) or a low-fat (LF) diet. Body weight, high-resolution tracking of meal-related parameters, and glucose regulation after overnight fasting and during a mixed meal tolerance test (MMTT; 2 mL sweet/condensed milk) were measured before and after RYGB (RYGB+) or sham surgery (RYGB−). Results: HF/S feeding led to an increased body weight just before RYGB surgery, but it also caused enhanced weight loss following RYGB, which led to similar body weights in the HF/S and LF diet groups twenty-four days post-operatively. RYGB surgery and diet dependently and independently influenced meal-related parameter outcomes, where both RYGB+ and HF/S feeding resulted in shorter meal duration (p < 0.01), higher ingestion rates (p < 0.001), and increased satiety ratio (p < 0.05), especially in the HF/S diet group subjected to RYGB. While RYGB surgery generally improved baseline glycemic parameters including HOMA-IR (p < 0.01), it often interacted with diet to affect MMTT-induced hyperglycemia (p < 0.05), beta-cell sensitivity (p < 0.01), and the insulinogenic index (p < 0.01), with the LF rats overall maintaining better glycemic control than the HF/S-fed rats. Conclusions: This study shows the importance of controlling diet after RYGB surgery, as diet type significantly influences ingestive behavior, post-prandial glucose regulation, beta-cell sensitivity, and glucose tolerance after RYGB. Full article