Search Results (471)

Polysaccharide-based hydrogels for gastric retention face the inherent challenge of achieving effective retention through swelling while avoiding mechanical failure. Here, we introduce a strategy by incorporating curdlan into chitosan/sodium polyacrylate interpenetrating networks to reinforce the hydrogel and regulate swelling-induced transport behavior. Curdlan-reinforced chitosan/polyacrylate (CS/CUR/PAAS) hydrogels with varying curdlan content (0–4 wt.%) were synthesized and characterized. Optimal reinforcement was achieved with 2 wt.% curdlan, yielding an indentation hardness of ~80 kPa and an elastic modulus of ~63 kPa without compromising swelling capacity. Under acidic conditions (pH 1.2), the hydrogel swelled rapidly (~50-fold at 3 h; ~140-fold at 8 h) while maintaining structural integrity. Using a dynamic in vitro human stomach simulator (DHSI-IV), the optimized hydrogel demonstrated gastric retention for up to 5 h, with ~60% of the initial mass retained at 6 h. Metformin hydrochloride release followed diffusion-controlled kinetics (~69% over 8 h), governed primarily by pH with secondary shear modulation. Microstructural and rheological analyses revealed that acidic conditions regulated network expansion, viscoelastic relaxation, and pore formation, which in turn controlled transport pathways and drug release. The findings highlight that curdlan reinforcement stabilizes swelling behavior under acidic conditions, offering a robust and pH-responsive strategy for designing mechanically stable, gastric-retentive hydrogels. Full article

Background and Objectives: Gastric cancer remains a leading cause of cancer-related mortality worldwide and develops through complex interactions between environmental factors, microbial dysbiosis, and host molecular pathways. Although Helicobacter pylori infection is a well-established risk factor, emerging evidence suggests that broader alterations in the gastric microbiome may also contribute to carcinogenesis. However, the associations between gastric cancer-associated microbial taxa and host gene expression profiles remain insufficiently characterized. This study aimed to identify host gene signatures associated with gastric cancer-related microbial taxa through a descriptive analysis integrating microbiome-derived taxa with transcriptome data. Materials and Methods: Microbial taxa associated with gastric cancer were systematically retrieved from the Disbiome database. Taxon set enrichment analysis (TSEA) was performed using the MicrobiomeAnalyst platform to identify host genes associated with gastric cancer-associated taxa. Importantly, TSEA relies on healthy reference data from the Human Microbiome Project and does not establish gastric cancer-specific interactions or causal relationships. Gene expression levels were subsequently evaluated using The Cancer Genome Atlas (TCGA) PanCancer stomach adenocarcinoma (STAD) dataset by comparing tumor and matched normal gastric tissues. Gene interaction network and transcription factor (TF) enrichment analyses were conducted to explore predicted regulatory relationships. Results: Among 64 microbial taxa associated with gastric cancer, 43 were reported as elevated. After removing overlapping taxa across studies, 37 elevated and 21 reduced taxa were retained for analysis. TSEA identified 11 host genes associated with gastric cancer-related microbial taxa. Transcriptomic analysis demonstrated significant downregulation of DPP6 and DLG2, while KDM4D, USP34, and VDR were significantly upregulated in gastric cancer tissues compared with normal controls. Network and TF enrichment analyses revealed predicted co-expression and co-localization patterns among these genes, suggesting their potential involvement in immune-related processes, epigenetic regulation, and cellular organization. Conclusions: This descriptive study identifies distinct host gene expression signatures associated with gastric cancer-associated microbial dysbiosis. This study is purely associative and hypothesis-generating; no causal or mechanistic inferences are made. TSEA used healthy reference data and therefore does not reflect gastric cancer-specific host–microbe interactions. The findings provide a basis for future hypothesis-driven research but require validation in independent cohorts. Full article

Corn, paddy, wheat, sorghum, and cassava serve as the primary energy sources in both human and animal diets. This study aimed to evaluate their nutrient release patterns in a simulated gastrointestinal environment and to assess the in vitro biological activity of the metabolites produced during digestion. The results showed that wheat exhibited the highest dry matter degradation in the stomach–jejunum–ileum digestion stage, while wheat and paddy showed the highest crude protein degradation compared with the other starch sources. In addition, wheat had a higher total free sugar concentration than paddy, sorghum, and cassava. Among the individual free sugars, such as D-sorbitol and D-(+)-trehalose, were found to have the highest concentrations in wheat, whereas cassava had the highest D(−)-fructose concentration. Several differential metabolites, including valeric acid, caproic acid, octanoic acid, and azelaic acid were highly released in paddy, whereas glucaric acid, threonic acid, phenylacetic acid, and shikimic acid were highly released in cassava, and 4-hydroxycinnamic acid was highly released in paddy and sorghum. Four unique metabolites were identified during the digestion process of five starch sources. Particularly, isocitric acid and trans-Cinnamic acid were released only from cassava; caffeic acid was released only from sorghum and corn; and pimelic acid was released only from paddy and wheat. Furthermore, cassava was distinct from the other starch sources, displaying a higher abundance of differential metabolites within the glucagon signaling pathway as mapped in KEGG pathway analysis. In summary, compared with other starch sources, wheat provides more dry matter, protein, and sugars for the body. Cassava is unlikely to offer any advantage in glycemic regulation, while paddy and cassava possess stronger biological activity in terms of differential metabolites. Full article

Limited data exist on the prevalence of human epidermal growth factor receptor 2 (ERBB2/HER2) amplification in patients with all types of solid tumors. This retrospective, observational study (UMIN ID: UMIN000057382) analyzed the prevalence of HER2 amplification across all solid tumors using comprehensive genomic profiling (CGP) data from the Center for Cancer Genomics and Advanced Therapeutics database in Japan. We analyzed 89,374 eligible patients with solid tumors: HER2 amplification was detected in 5119 patients (5.7%). The highest rates of HER2 amplification were observed in patients with tumors of the esophagus/stomach (12.9%), followed by tumors of the bladder/urinary tract (10.6%), breast (9.5%), biliary tract (8.4%), and uterus (8.4%). Among the five assay platforms, FoundationOne CDx accounted for 69.7% of all CGP tests and had an HER2 amplification detection rate of 7.4%, compared to the other four platforms (range: 1.9–15.4% of all CGP tests [detection rates: 1.5–2.3%]). Substantial differences were observed in the mutation frequencies of multiple genes between HER2 amplified and HER2 non-amplified tumors. The results highlight that HER2 amplification extends beyond conventional tumor types and enables the identification, via CGP testing, of non-traditional tumor subsets (cancers other than breast and gastric cancer), including rare cancers, that could be candidates for HER2-targeting therapy such as trastuzumab deruxtecan in Japan. Full article

Exposure of healthy tissue to ionizing radiation (IR) occurs due to nuclear accidents and terrorism, as well as radiotherapy. The vascular endothelium is a key target of IR, and microvascular endothelial cells (ECs) are particularly vulnerable to radiation. IR induces EC activation leading to endothelial cell injury. Human ghrelin is a stomach-derived peptide with pleiotropic effects, including protection against inflammation. We hypothesize that human ghrelin improves survival in total body irradiation (TBI) and that ghrelin’s protective effect could be mediated by attenuating endothelial cell injury. To test this, mice were exposed to TBI and after 24 h were treated subcutaneously with human ghrelin once daily for 4 days and monitored for 30 days. The survival rate of the human ghrelin-treated group was significantly higher than that of the vehicle group. Subsequently, human ghrelin treatment showed an effective dose modification factor of 1.0681. On day 4 after TBI, human ghrelin significantly attenuated EC permeability in the lungs and improved tight junction protein ZO-1 expression. Human ghrelin also improved ZO-1 and Claudin5 expression in primary mouse lung vascular endothelial cells. Taken together, these results indicate that human ghrelin improves survival after TBI, and its survival benefit is in part due to the attenuation of EC permeability and microvascular barrier dysfunction. Full article

TFF1 is a secretory polypeptide that is typical of mucous epithelia belonging to the trefoil factor family (TFF) of lectins. Originally, TFF1 was discovered as an estrogen-responsive gene in breast cancer cell lines. However, its major physiological expression site is the stomach where it exists mainly in a monomeric form, with minor amounts of homodimeric as well as heterodimeric forms, such as a high-molecular-mass complex with IgG Fc binding protein (FCGBP). For the first time, we characterized different low-molecular-mass forms of TFF1 in human post-menopausal vaginal specimens, i.e., monomeric and dimeric forms. Attempts to identify high-molecular-mass forms of TFF1, such as TFF1-FCGBP, failed. Based on its known anti-inflammatory effects, TFF1 could play an important role in the homeostasis of vaginal microbiota, which is normally predominated by Lactobacillus spp. Due to its lectin activity, TFF1 might also be capable of binding to members of the vaginal microbiota or to vaginal fungal pathogens. This points to a potential role for TFF1 in the vagina’s innate immune defence and could be of clinical relevance particularly after menopause, e.g., for the treatment of bacterial vaginosis or vulvovaginal candidiasis, as here vaginal dysbiosis is often observed as a consequence of estrogen deficiency. Full article

The appearance of antibiotic-resistant strains of Helicobacter pylori (H. pylori) is leading to a decreased eradication rate of H. pylori infection. There is an urgent need to find new agents with antimicrobial mechanisms different from those of antibiotics, with therapeutic potential to clear colonization of H. pylori in the stomach. Some antimicrobial peptides (AMPs) possess bactericidal activity by enhancing the permeability of the outer membrane and damaging the integrity of the cell membrane. Bacteria are not susceptible to drug resistance through this antimicrobial mechanism. In this study, 28 short peptides containing 12 amino acid residues were designed based on nine amino acid fragments (KRIVQRIKD) from human cathelicidin LL-37, which is stable in gastric juice, and 3 amino acids were added at the C-terminus of the peptide. These designed peptides were not digested and degraded by pepsin at low pH values. The peptides were predicted using the online tool platform. Then, the strongest antimicrobial peptide, named SAMP-12aa (KRIVQRIKDVIR), was screened from 28 short peptides. Further studies found that SAMP-12aa retained anti-H. pylori activity after incubation in simulated gastric juice. The MIC and MBC of SAMP-12aa were 8 μg/mL and 32 μg/mL, respectively. SAMP-12aa showed good bactericidal kinetics. SAMP-12aa was found to have cell selectivity, penetrating and damaging bacterial cell membranes and exhibiting almost no toxicity to human cells at a relatively high concentration (128 μg/mL). Regulatory T (Treg) cells express CD25^High with immunosuppressive activity that induces immune tolerance in response to H. pylori. Molecular docking prediction revealed that SAMP-12aa could target the active center of Foxp3. Flow cytometry analysis revealed that SAMP-12aa can inhibit Foxp3 activity and downregulate CD25 protein expression on CD4⁺ T cells, thereby reducing the development and differentiation of CD4⁺Foxp3⁺CD25^High Treg cells with immunosuppressive effects. Further research revealed that the levels of the cytokine interferon-γ (IFN-γ), which activates CD8⁺ T-cell activity, were significantly elevated, and the levels of transforming growth factor-β (TGF-β), which inhibits CD8⁺ T-cell activity, were significantly reduced. The results of this study reveal that SAMP-12aa not only possesses antibacterial activity but also has immunomodulatory effects. Full article

Bile acids are widely distributed in the human gastrointestinal tract. A literature review indicates that bile acids may have a role in initiating cancers in every organ of the digestive system. The estimated number of new digestive system cancers world-wide in 2022 was about 5 million. In the particular case of colon cancer, secondary bile acids produced in response to a high fat diet disrupt colonic epithelial cell mitochondrial membranes. This disruption leads to the release of oxidative free radicals that damage DNA, potentially leading to carcinogenic mutations. High levels of colonic bile acids may also alter the gut microbiome, with some bacteria causing inflammation and increased reactive oxygen species leading to DNA damage. Also, bile acids taken up by receptors on the surface of gastrointestinal tract cells can activate NF-kB. In turn, NF-kB may activate a super-enhancer at an oncogene. Bile acid reflux also plays a significant role in esophageal adenocarcinoma, stomach cancer and small intestine carcinogenesis. In addition, cancers of the pancreas, liver, and biliary tract can be caused by the constriction of the common bile duct leading to reflux of bile acids back into these organs. Gastroesophageal reflux involving bile acids may also contribute to hypopharyngeal squamous cell carcinogenesis. Thus, bile acids are a likely major contributory cause of cancer throughout the digestive tract. Full article

Background: Once considered a sterile organ, the human stomach is now known to harbor a diverse microbial community that may influence both gastric homeostasis and disease. While extensive research has been conducted worldwide, regional variation in the gastric microbiome remains insufficiently characterized. This study aimed to describe the gastric antrum microbiome of Helicobacter pylori-negative Greek adults using 16S rRNA next-generation sequencing (NGS). Methods: Samples of gastric biopsies were obtained from patients undergoing gastroscopy at a tertiary hospital in Greece. H. pylori infection was excluded through a combination of bacterial culture and patient medical history. The final study group consisted of 9 subjects. Following DNA extraction, the 16S rRNA gene was sequenced on the Ion Torrent™ platform. Bioinformatic processing and statistical analyses were performed using the phyloseq, vegan, and ggplot2 R packages. Microbial composition, relative abundance, and alpha diversity (Shannon and Inverse Simpson indices) were evaluated at the genus level. Results: The gastric microbiome comprised 19 phyla, 150 families, 213 genera, and 391 species. The predominant phyla were Proteobacteria (36.92%), Firmicutes (34.21%), and Bacteroidetes (12.97%). The most prevalent families were Streptococcaceae, Helicobacteraceae, Prevotellaceae, and Pasteurellaceae. At the genus level, Streptococcus (21.71%), Helicobacter (18.39%), and Prevotella (9.99%) accounted for nearly half of the total relative abundance. Alpha diversity indices indicated moderate richness and evenness across samples. Conclusions: The gastric antrum microbiome of H. pylori-negative Greek individuals exhibits substantial taxonomic diversity dominated by Proteobacteria and Firmicutes. The microbial community structure aligns closely with profiles reported in other global populations. These findings provide a reference baseline for future comparative analyses involving H. pylori-positive individuals to better understand microbiome shifts associated with colonization and gastric disease. Full article

Objective: This study assessed the ability of capsule formulations to improve the oral delivery and retain activity of an acid-sensitive enzyme during gastrointestinal transit. Methods: The dissolution characteristics of five capsule formulations—single DRcaps^® [DR], single Vcaps^® Plus [VCP], and three DUOCAP^® capsule-in-capsule combinations, DRcaps^® inside DRcaps^® (DR-in-DR), DRcaps^® inside Vcaps^® Plus (DR-in-VCP), and Vcaps^® Plus inside DRcaps^® (VCP-in-DR)—were evaluated in an in vitro simulation of a healthy human upper gastrointestinal tract under fasting and fed conditions using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME)^® platform. Capsules contained caffeine as a marker of capsule dissolution, and pancreatin as an active ingredient for which activity was determined by the conversion of tributyrin. Readouts included visual capsule scoring, the analysis of caffeine release, and the quantification of tributyrin-to-butyrate conversion at the end of each gastrointestinal tract segment. Results: The single VCP capsules had a high level of caffeine release at the end of the stomach incubation with low butyrate recovery (16–21%), suggesting the rapid release and gastric degradation of the unprotected enzyme. The single DR, DR-in-VCP, and VCP-in-DR formulations showed caffeine release at the end of the duodenum and/or jejunum and had high butyrate recovery, ranging from 53% to 87%. The DR-in-DR formulation had the most delayed release, with incomplete caffeine release and low-to-moderate butyrate recovery (10–36%). Conclusions: Fast capsule dissolution led to the reduced enzymatic activity of the active ingredient, while delayed dissolution resulted in inadequate time for the enzymatic conversion of tributyrin to butyrate. These results highlight that capsule selection should align with the intended use and targeted nutrient delivery, with DUOCAP^® formulations being best suited for small intestinal (VCP-in-DR and DR-in-VCP) and colonic (DR-in-DR) delivery. Full article

Human African Trypanosomiasis (HAT) and Malaria are serious infectious diseases endemic in tropical regions, caused by protozoan parasites, and necessitating an urgent development of new antiprotozoal drugs. As part of our ongoing search for new antiprotozoal steroidal alkaloids from plants, we investigated the methanolic stem bark extract of Holarrhena pubescens (Apocynaceae). H. pubescens is a tropical tree that some Kenyan coastal communities have long used to treat various ailments, including fever and stomach pain. The crude extract, alkaloid fraction, and 16 subfractions acquired through centrifugal partition chromatography (CPC) displayed promising in vitro antiprotozoal activity against Trypanosoma brucei rhodesiense (Tbr) and Plasmodium falciparum (Pf). Partial least squares (PLS) regression modeling of UHPLC/+ESI QqTOF-MS data and the antiprotozoal activity data of the crude extract and its fractions was performed to predict compounds that may be responsible for the observed antiplasmodial activity. Chromatographic separation of the alkaloid fraction afforded one new steroidal alkaloid (5), along with 18 known compounds (1, 2, 4, 6–20), and one artifact (3) that was presumably formed during the acid–base extraction process. The structural characterization of the isolated compounds was accomplished using UHPLC/+ESI-QqTOF-MS/MS and NMR spectroscopy. The isolated compounds were tested for their in vitro antiprotozoal properties against the two aforementioned pathogens, as well as for their cytotoxicity against mammalian cells (L6 cell line). Compounds 2 and 16 (IC₅₀ = 0.2 μmol/L) demonstrated the highest antitrypanosomal activity, with compound 2 showing the highest selectivity (SI = 127). The new compound 5 exhibited the strongest antiplasmodial activity and selectivity against Pf (IC₅₀ = 0.7 μmol/L, SI = 43). Our findings provide further promising antiprotozoal leads for HAT and Malaria. Full article

Background: Altered glycosphingolipidome in cancerous tissues and cells reflects the circulatory glycosphingolipid (GSL) profiles, which is advantageous for establishing cancer biomarkers and/or unravelling GSL-associated mechanisms of immunity in cancer. Methods: Here, we combined a microscale extraction of GSLs with multiple overlay TLC assays and IR-MALDI-o-TOF MS and implemented it for the first time in serum analysis of CD75s-, CD15s-, and iso-CD75s-containing sialylated GSLs of ganglio- and neolacto-series. Results: This sensitive antigen-specific targeted GSL workflow enabled the identification of 80 sialylated GSLs containing the specific antigens in human sera and was applied for the investigation of clinical serum samples from gastric/stomach cancer patients (n = 40), pancreatic cancer patients (n = 40), and a cancer-free control group (n = 20). The CD75s-, CD15s-, and iso-CD75s-containing GSL series encompassing complex monosialylated and fucosylated GSLs of neolacto-series, with up to pentadecasaccharide chains, were detected in both cancer types, while differential semi-quantitative analysis indicates a tumor type-specific associated GSL profile. Both cancer types share a drop in the complex fucosylated neolacto-gangliosides during tumor progression, implying a decreased synthesis of long-chain neolacto-series. Conclusions: This drop suggesting a role of these highly polar complex ganglioside species in evading humoral tumor immune response in the early tumor stages. Full article

Helicobacter pylori (H. pylori) is recognized as one of the most widespread and persistent bacterial infections globally, with a remarkable ability to colonize the human stomach. This pathogen is a major contributor to the development of gastric diseases, including gastric lymphoma and adenocarcinoma. The H. pylori infection triggers a complex pathogenic cascade within the gastric environment, characterized by prolonged inflammation and heightened oxidative stress, which fosters a milieu of immune dysregulation, where both innate and adaptive immune cells become activated inappropriately, thereby leading to epithelial injury and subsequent remodeling of the gastric tissue. As the infection persists, repeated cycles of inflammation and epithelial damage contribute to the development of epigenetic alterations, including changes in DNA methylation, histone modifications, and non-coding RNA expression, all of which render the gastric epithelium more susceptible to further aberrations, including dysplasia and cancer. In this article, we review the latest advances in understanding the molecular mechanisms of H. pylori-induced gastritis and its role in the progression of gastric cancer, offering new perspectives on the complex biology of this infection and its potential therapeutic implications for preventing the development of gastric malignancies. Full article

Human milk oligosaccharides (HMOs) are the third most abundant solid component in human milk and play crucial roles in shaping the gut microbiome and promoting infant health. Although their functions during infancy are well established, emerging evidence suggests that HMOs exert region-specific effects throughout the gastrointestinal tract, extending their benefits beyond early life. This review summarizes current findings on HMO activity in the oral cavity, stomach, small intestine, and large intestine, focusing on their microbiota-modulating, barrier-enhancing, and immunoregulatory effects. In the oral cavity, HMOs inhibit pathogen adhesion and biofilm formation, maintaining oral homeostasis. In the stomach, fucosylated and sialylated HMOs act as soluble decoy receptors, preventing Helicobacter pylori infection. In the small intestine, HMOs strengthen epithelial integrity, regulate inflammation, and promote nutrient absorption. In the large intestine, they serve as selective prebiotics for beneficial microbes, enhancing short-chain fatty acid production and improving barrier function. Although preclinical and clinical studies demonstrate their safety and efficacy, further research is required to elucidate their mechanisms in adults. Overall, HMOs represent multifunctional bioactive glycans with promising applications for gastrointestinal health across all ages. Full article

Background: The separation between oral and systemic health is increasingly challenged. Globally prevalent inflammatory diseases such as gastritis, often caused by Helicobacter pylori (H. pylori), and oral pathologies like periodontitis may be interconnected through microbial and inflammatory pathways. Objective: This review synthesizes evidence on the dental-gastric link, examining mechanistic pathways and clinical implications. Methods: A structured literature search identified key studies from 2000 to 2025, prioritizing systematic reviews and high-quality human research. Findings: Three key mechanistic pathways link oral dysbiosis with gastric pathology: (1) the direct translocation of oral pathogens to the stomach, including H. pylori and the broader dysbiotic oral microbiome; (2) the systemic inflammatory spillover from the periodontium, which primes the host immune system and exacerbates gastric inflammation; and (3) ancillary mechanisms such as the disruption of beneficial nitrate-nitrite-nitric oxide metabolism. Epidemiological studies show strong associations, and initial interventional trials indicate periodontal therapy may improve H. pylori eradication rates and reduce recurrence. However, the evidence is tempered by methodological limitations, including profound confounding by shared risk factors (e.g., smoking, socioeconomic status), the challenge of reverse causality, and inconsistent results from interventional studies. Conclusion: While confounding factors require consideration, oral health is a promising modifiable risk factor for gastritis. Interdisciplinary collaboration between dentistry and gastroenterology is essential to advance research and integrate oral care into gastrointestinal disease management. Full article