Microbiome signatures associated with clinical stages of gastric Cancer: whole metagenome shotgun sequencing study.

BACKGROUND: Gastric cancer is one of the global health concerns. A series of studies on the stomach have confirmed the role of the microbiome in shaping gastrointestinal diseases. Delineation of microbiome signatures to distinguish chronic gastritis from gastric cancer will provide a non-invasive preventative and treatment strategy. In this study, we performed whole metagenome shotgun sequencing of fecal samples to enhance the detection of rare bacterial species and increase genome sequence coverage. Additionally, we employed multiple bioinformatics approaches to investigate the potential targets of the microbiome as an indicator of differentiating gastric cancer from chronic gastritis. RESULTS: A total of 65 patients were enrolled, comprising 33 individuals with chronic gastritis and 32 with gastric cancer. Within each group, the chronic gastritis group was sub-grouped into intestinal metaplasia (n = 15) and non-intestinal metaplasia (n = 18); the gastric cancer group, early stage (stages 1 and 2, n = 13) and late stage (stages 3 and 4, n = 19) cancer. No significant differences in alpha and beta diversities were detected among the patient groups. However, in a two-group univariate comparison, higher Fusobacteria abundance was identified in phylum; Fusobacteria presented higher abundance in gastric cancer (LDA scored 4.27, q = 0.041 in LEfSe). Age and sex-adjusted MaAsLin and Random Forest variable of importance (VIMP) analysis in species provided meaningful features; Bacteria_caccae was the most contributing species toward gastric cancer and late-stage cancer (beta:2.43, se:0.891, p:0.008, VIMP score:2.543). In contrast, Bifidobacterium_longum significantly contributed to chronic gastritis (beta:-1.8, se:0.699, p:0.009, VIMP score:1.988). Age, sex, and BMI-adjusted MasAsLin on metabolic pathway analysis showed that GLCMANNANAUT-PWY degradation was higher in gastric cancer and one of the contributing species was Fusobacterium_varium. CONCLUSION: Microbiomes belonging to the pathogenic phylum Fusobacteria and species Bacteroides_caccae and Streptococcus_anginosus can be significant targets for monitoring the progression of gastric cancer. Whereas Bifidobacterium_longum and Lachnospiraceae_bacterium_5_1_63FAA might be protection biomarkers against gastric cancer.

Possible Strategies to Reduce the Tumorigenic Risk of Reprogrammed Normal and Cancer Cells.

The reprogramming of somatic cells to pluripotent stem cells has immense potential for use in regenerating or redeveloping tissues for transplantation, and the future application of this method is one of the most important research topics in regenerative medicine. These cells are generated from normal cells, adult stem cells, or neoplastic cancer cells. They express embryonic stem cell markers, such as OCT4, SOX2, and NANOG, and can differentiate into all tissue types in adults, both in vitro and in vivo. However, tumorigenicity, immunogenicity, and heterogeneity of cell populations may hamper the use of this method in medical therapeutics. The risk of cancer formation is dependent on mutations of these stemness genes during the transformation of pluripotent stem cells to cancer cells and on the alteration of the microenvironments of stem cell niches at genetic and epigenetic levels. Recent reports have shown that the generation of induced pluripotent stem cells (iPSCs) derived from human fibroblasts could be induced using chemicals, which is a safe, easy, and clinical-grade manufacturing strategy for modifying the cell fate of human cells required for regeneration therapies. This strategy is one of the future routes for the clinical application of reprogramming therapy. Therefore, this review highlights the recent progress in research focused on decreasing the tumorigenic risk of iPSCs or iPSC-derived organoids and increasing the safety of iPSC cell preparation and their application for therapeutic benefits.

Endothelial Mitochondria Transfer to Melanoma Induces M2-Type Macrophage Polarization and Promotes Tumor Growth by the Nrf2/HO-1-Mediated Pathway.

Gynecologic tract melanoma is a malignant tumor with poor prognosis. Because of the low survival rate and the lack of a standard treatment protocol related to this condition, the investigation of the mechanisms underlying melanoma progression is crucial to achieve advancements in the relevant gynecological surgery and treatment. Mitochondrial transfer between adjacent cells in the tumor microenvironment regulates tumor progression. This study investigated the effects of endothelial mitochondria on the growth of melanoma cells and the activation of specific signal transduction pathways following mitochondrial transplantation. Mitochondria were isolated from endothelial cells (ECs) and transplanted into B16F10 melanoma cells, resulting in the upregulation of proteins associated with tumor growth. Furthermore, enhanced antioxidation and mitochondrial homeostasis mediated by the Sirt1-PGC-1α-Nrf2-HO-1 pathway were observed, along with the inhibition of apoptotic protein caspase-3. Finally, the transplantation of endothelial mitochondria into B16F10 cells promoted tumor growth and increased M2-type macrophages through Nrf2/HO-1-mediated pathways in a xenograft animal model. In summary, the introduction of exogenous mitochondria from ECs into melanoma cells promoted tumor growth, indicating the role of mitochondrial transfer by stromal cells in modulating a tumor's phenotype. These results provide valuable insights into the role of mitochondrial transfer and provide potential targets for gynecological melanoma treatment.

Rapid identification of mushroom toxins by direct electrospray probe mass spectrometry for emergency care.

Mushroom poisoning occurs frequently after the ingestion of toxic wild mushrooms misidentified as edible species. The goal of this study is to develop a mass spectrometric platform to bypass the need for morphological recognition of poisonous mushrooms by experts and rapidly identify the toxins in the mushrooms for emergency care. Trace mushroom toxins were collected by penetrating and removing the mushrooms surface for 3 mm with a direct electrospray probe (DEP). The analytes on the DEP were then dissolved in the solution (70% isopropanol containing 0.1% acetic acid) flowing out of a solvent reservoir on the DEP. Electrospray ionization was induced from the sample solution as a high electric field was generated between the DEP and MS inlet. The obtaining mass spectrometric results were further analyzed with principal component analysis (PCA) to classify mushroom toxins. The mass spectrometric platform for detecting mushroom toxins was assessed for its sensitivity, precision, and efficiency by determining its limit-of-detection (LOD), repeatability, and turnaround time, respectively. As a result, the LODs of the mushroom toxins in pure methanol and spiked in human vomitus by DEP/MS were within 0.001-0.5 ng/µL and 0.01-1 ng/µL, respectively. Linear responses of the mushroom toxins in pure methanol with concentrations between 0.01 and 5 ng/µL (R2 between 0.9922 and 0.998) were obtained. The repeatability of the approach (n = 10) was shown in the low relative standard deviation value (<15%) from ten repeat analysis of mushroom toxins standard solution. The corresponding toxic compounds were identified through matching of the obtained mass spectrometric data with those provided by its companion database library of mushroom toxins. Since no time-consuming pretreatment of the samples is required, identification of mushroom toxins with DEP/MS was complete within 1 min. This will be helpful for the emergency physicians to make correct clinical judgment and prescribe appropriate medical treatment in a timely manner.

Di-n-butyl phthalate promotes the neural differentiation of mouse embryonic stem cells through neurogenic differentiation 1.

An understanding of the risk of gene deletion and mutation posed by endocrine-disrupting chemicals (EDCs) is necessary for the identification of etiological reagents for many human diseases. Therefore, the characterization of the genetic traits caused by developmental exposure to EDCs is an important research subject. A new regenerative approach using embryonic stem cells (ESCs) holds promise for the development of stem-cell-based therapies and the identification of novel therapeutic agents against human diseases. Here, we focused on the characterization of the genetic traits and alterations in pluripotency/stemness triggered by phthalate ester derivatives. Regarding their in vitro effects, we reported the abilities of ESCs regarding proliferation, cell-cycle control, and neural ectoderm differentiation. The expression of their stemness-related genes and their genetic changes toward neural differentiation were examined, which led to the observation that the tumor suppressor gene product p53/retinoblastoma protein 1 and its related cascades play critical functions in cell-cycle progression, cell death, and neural differentiation. In addition, the expression of neurogenic differentiation 1 was affected by exposure to di-n-butyl phthalate in the context of cell differentiation into neural lineages. The nervous system is one of the most sensitive tissues to exposure to phthalate ester derivatives. The present screening system provides a good tool for studying the mechanisms underlying the effects of EDCs on the developmental regulation of humans and rodents, especially on the neuronal development of ESCs.

Transplanting mitochondria from gastric epithelial cells reduces the malignancy of gastric cancer.

Mitochondria are essential for energy supplementation and metabolic homeostasis of cancer cells. Using mitochondria transplantation to reduce the malignancy of gastric cancer (GC) cells is herein proposed. In our study normal human gastric mucous epithelium cell line (GES-1) showed a lower mitochondrial membrane potential (MMP) compared to immortalized human vascular endothelial cell line (EAhy 926) and human gastric adenocarcinoma cell line (AGS). The transplantation of GES-1 mitochondria to AGS were confirmed both by confocal microscopy and flow cytometry. After transplanting GES-1 mitochondria, the AGS showed a reduced cell migration, and invasion without affecting cell viability and apoptosis. Investigating the expression of proteins involved in epithelial-mesenchymal-transition (EMT), transplanted GES-1 mitochondria reduced the expression of mesenchymal markers α-SMA, MMP-9, snail, vimentin and N-cadherin, whereas the epithelial markers E-cadherin and clauding-1 were not changed. The proteins implicated in the cell cycle such as cyclin B1 and D1 were decreased. In mice, inoculation with AGS carrying the transplanted GES-1 mitochondria resulted in smaller sized tumors. Further investigating the mitochondrial balance, the transplanted GES-1 mitochondria were more stably preserved compared to endogenous AGS mitochondria. The MMP, ATP production and mitochondrial mass decreased in GES-1 mitochondria and the mitophagic proteins LC3 II and PINK1 were up-regulated. In conclusion the decreased malignancy of AGS was a result of exogenous GES-1 mitochondria transplantation. This suggests for a therapy with low efficiency mitochondria transplantation in the treatment of cancer cells.

Risk Perception, Acceptance, and Trust of Using AI in Gastroenterology Practice in the Asia-Pacific Region: Web-Based Survey Study.

BACKGROUND: The use of artificial intelligence (AI) can revolutionize health care, but this raises risk concerns. It is therefore crucial to understand how clinicians trust and accept AI technology. Gastroenterology, by its nature of being an image-based and intervention-heavy specialty, is an area where AI-assisted diagnosis and management can be applied extensively. OBJECTIVE: This study aimed to study how gastroenterologists or gastrointestinal surgeons accept and trust the use of AI in computer-aided detection (CADe), computer-aided characterization (CADx), and computer-aided intervention (CADi) of colorectal polyps in colonoscopy. METHODS: We conducted a web-based questionnaire from November 2022 to January 2023, involving 5 countries or areas in the Asia-Pacific region. The questionnaire included variables such as background and demography of users; intention to use AI, perceived risk; acceptance; and trust in AI-assisted detection, characterization, and intervention. We presented participants with 3 AI scenarios related to colonoscopy and the management of colorectal polyps. These scenarios reflect existing AI applications in colonoscopy, namely the detection of polyps (CADe), characterization of polyps (CADx), and AI-assisted polypectomy (CADi). RESULTS: In total, 165 gastroenterologists and gastrointestinal surgeons responded to a web-based survey using the structured questionnaire designed by experts in medical communications. Participants had a mean age of 44 (SD 9.65) years, were mostly male (n=116, 70.3%), and mostly worked in publicly funded hospitals (n=110, 66.67%). Participants reported relatively high exposure to AI, with 111 (67.27%) reporting having used AI for clinical diagnosis or treatment of digestive diseases. Gastroenterologists are highly interested to use AI in diagnosis but show different levels of reservations in risk prediction and acceptance of AI. Most participants (n=112, 72.72%) also expressed interest to use AI in their future practice. CADe was accepted by 83.03% (n=137) of respondents, CADx was accepted by 78.79% (n=130), and CADi was accepted by 72.12% (n=119). CADe and CADx were trusted by 85.45% (n=141) of respondents and CADi was trusted by 72.12% (n=119). There were no application-specific differences in risk perceptions, but more experienced clinicians gave lesser risk ratings. CONCLUSIONS: Gastroenterologists reported overall high acceptance and trust levels of using AI-assisted colonoscopy in the management of colorectal polyps. However, this level of trust depends on the application scenario. Moreover, the relationship among risk perception, acceptance, and trust in using AI in gastroenterology practice is not straightforward.

Management of Crohn's disease in Taiwan: consensus guideline of the Taiwan Society of Inflammatory Bowel Disease updated in 2023.

Crohn's disease (CD) is a chronic, fluctuating inflammatory condition that primarily affects the gastrointestinal tract. Although the incidence of CD in Taiwan is lower than that in Western countries, the severity of CD presentation appears to be similar between Asia and the West. This observation indicates the urgency for devising revised guidelines tailored to the unique reimbursement system, and patient requirements in Taiwan. The core objectives of these updated guidelines include the updated treatment choices and the integration of the treat-to-target strategy into CD management, promoting the achievement of deep remission to mitigate complications and enhance the overall quality of life. Given the diversity in disease prevalence, severity, insurance policies, and access to medical treatments in Taiwan, a customized approach is imperative for formulating these guidelines. Such tailored strategies ensure that international standards are not only adapted but also optimized to local contexts. Since the inception of its initial guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease (TSIBD) has acknowledged the importance of continuous revisions for incorporating new therapeutic options and evolving disease management practices. The latest update leverages international standards and recent research findings focused on practical implementation within the Taiwanese healthcare system.

Management of ulcerative colitis in Taiwan: consensus guideline of the Taiwan Society of Inflammatory Bowel Disease updated in 2023.

Ulcerative colitis (UC) is a chronic inflammation of the gastrointestinal tract and is characterized by alternating periods of inflammation and remission. Although UC incidence is lower in Taiwan than in Western countries, its impact remains considerable, demanding updated guidelines for addressing local healthcare challenges and patient needs. The revised guidelines employ international standards and recent research, emphasizing practical implementation within the Taiwanese healthcare system. Since the inception of the guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease has acknowledged the need for ongoing revisions to incorporate emerging therapeutic options and evolving disease management practices. This updated guideline aims to align UC management with local contexts, ensuring comprehensive and context-specific recommendations, thereby raising the standard of care for UC patients in Taiwan. By adapting and optimizing international protocols for local relevance, these efforts seek to enhance health outcomes for patients with UC.

Development of a Genetically Engineered Mouse Model Recapitulating LKB1 and PTEN Deficiency in Gastric Cancer Pathogenesis.

The LKB1 and PTEN genes are critical in gastric cancer (G.C.) development. LKB1, a robust tumor suppressor gene, encodes a serine/threonine kinase that directly triggers the activation of AMPK-an integral cellular metabolic kinase. The role of the LKB1 pathway extends to maintaining the stability of epithelial junctions by regulating E-cadherin expression. Conversely, PTEN, a frequently mutated tumor suppressor gene in various human cancers, emerges as a pivotal negative regulator of the phosphoinositide 3-kinase (PI3K) signaling pathway. This study is set to leverage the H+/K+ ATPase Cre transgene strain to precisely target Cre recombinase expression at parietal cells within the stomach. This strategic maneuver seeks to selectively nullify the functions of both LKB1 and PTEN in a manner specific to the stomach, thereby instigating the development of G.C. in a fashion akin to human gastric adenocarcinoma. Moreover, this study endeavors to dissect the intricate ways in which these alterations contribute to the histopathologic advancement of gastric tumors, their potential for invasiveness and metastasis, their angiogenesis, and the evolving tumor stromal microenvironment. Our results show that conditional deletion of PTEN and LKB1 provides an ideal cancer microenvironment for G.C. tumorigenesis by promoting cancer cell proliferation, angiogenesis, and metastasis.

Independent Risk Factors Predicting Eradication Failure of Hybrid Therapy for the First-Line Treatment of Helicobacter pylori Infection.

Hybrid therapy is a recommended first-line anti-H. pylori treatment option in the American College of Gastroenterology guidelines, the Bangkok Consensus Report on H. pylori management, and the Taiwan H. pylori Consensus Report. However, the cure rates of eradication therapy in some countries are suboptimal, and the factors affecting the treatment efficacy of hybrid therapy remain unclear. The aim of this study is to identify the independent risk factors predicting eradication failure of hybrid therapy in the first-line treatment of H. pylori infection. A retrospective cohort study was conducted on 589 H. pylori-infected patients who received 14-day hybrid therapy between September 2008 and December 2021 in ten hospitals in Taiwan. The patients received a hybrid therapy containing a dual regimen with a proton pump inhibitor (PPI) plus amoxicillin for an initial 7 days and a quadruple regimen with a PPI plus amoxicillin, metronidazole and clarithromycin for a final 7 days. Post-treatment H. pylori status was assessed at least 4 weeks after completion of treatment. The relationships between eradication rate and 13 host and bacterial factors were investigated via univariate and multivariate analyses. In total, 589 patients infected with H. pylori infection were included in the study. The eradication rates of hybrid therapy were determined as 93.0% (95% confidence interval (CI): 90.9-95.1%), 94.4% (95% CI: 93.8-97.2%) and 95.5%% (95% CI: 93.8-97.2%) by intention-to-treat, modified intention-to-treat and per-protocol analyses, respectively. Univariate analysis showed that the eradication rate of clarithromycin-resistant strains was lower than that of clarithromcyin-susceptible strains (83.3% (45/54) vs. 97.6%% (280/287); p < 0.001). Subjects with poor drug adherence had a lower cure rate than those with good adherence (73.3% (11/15) vs. 95.5% (534/559); p = 0.005). Other factors such as smoking, alcohol drinking, coffee consumption, tea consumption and type of PPI were not significantly associated with cure rate. Multivariate analysis revealed that clarithromcyin resistance of H. pylori and poor drug adherence were independent risk factors related to eradication failure of hybrid therapy with odds ratios of 4.8 (95% CI: 1.5 to 16.1; p = 0.009) and 8.2 (95% CI: 1.5 to 43.5; p = 0.013), respectively. A 14-day hybrid therapy has a high eradication rate for H. pylori infection in Taiwan, while clarithromycin resistance of H. pylori and poor drug adherence are independent risk factors predicting eradication failure of hybrid therapy.