Therapeutic targets for gastrointestinal diseases: proteome-wide Mendelian randomization and colocalization analyses.

PURPOSE: This study was aimed to identify serum proteins linked with gastrointestinal diseases by proteome-wide Mendelian randomization analysis. METHODS: We determined the casual relationship between 732 kinds of circulating proteins and the 24 kinds of gastrointestinal diseases via Mendelian randomization analysis. RESULTS: Four circulating proteins (FCGR3B, IL-12B, MAPKAPK2, and IL-23R) were associated with the occurrence of ulcerative colitis (UC), and IL23R was also correlated with risk of Crohn's disease (CD). Genetically predicted levels of IL23R were strongly correlated with the risk of UC and CD based on the high supporting evidence of colocalization analysis. Five circulating proteins (NOV, EFEMP1, ADGRE2, LCT, and SEMA3G) were associated with the risk of diverticulosis disease. With high supporting evidence of colocalization, genetically predicted levels of NOV and SEMA3G were inversely correlated with the risk of diverticulosis disease. Five circulating proteins (FUT3, FUT5, CRHBP, SULT2A1, and QPCTL) were associated with the occurrence of cholelithiasis. With high supporting evidence of colocalization, genetically predicted levels of FUT3 and CRHBP were inversely correlated with the risk of cholelithiasis. CONCLUSIONS: The proteome-wide Mendelian randomization investigation identified several circulating proteins associated with the risk of UC, CD, diverticular disease and cholelithiasis, which reinforced the understanding of molecular pathogenesis and design of therapeutic targets.

Traditional clinical symptoms and signs: Kampo pattern diagnosis in modern gastrointestinal disease.

Introduction: In traditional Japanese Kampo medicine, a profound anamnesis is completed by clinical examination. The resulting clinical image forms the basis of the patient's diagnosis pattern, including the recent mental, physical, and social contexts. Kampo questionnaires support pattern diagnosis and bridge traditional and Western medicine diagnoses. Aims of the study: Traditional Kampo therapy is tailored to a specific body constitution, while Western medicine treatment is tailored to a specific disease. The aims of this study were to analyze whether traditional Kampo diagnosis is applicable to German patients and whether specific symptom patterns are characteristic for defined diseases. Material and methods: This study validates for the first time a Kampo questionnaire adapted for German patients. The analysis focuses on patients with gastrointestinal diseases, the main field for Kampo medicines. Results: In total, we prospectively included 251 participants; of those, 58 were cancer patients (23.1%), 35 had Crohn's disease (13.9%), 18 had ulcerative colitis (7.2%), 17 had irritable bowel syndrome (6.8%), and 103 had other abdominal diseases (41%), as well as 20 German controls (8%). The patient population consisted of 144 female (57.4%) and 107 male (42.6%) participants. The median age was 65 years. The disease duration (average: 211 months) varied from 1 month (cancer patient) to 540 months (patient with Crohn's disease). The scores for questions on the state of mind were significantly higher in patients with inflammatory bowel disease (IBD) as well as irritable bowel syndrome (IBS)-in comparison to the tumor and control groups. This was reflected in questions about abdominal discomfort, appetite, fecal habits, and cold sensation. Accordingly, symptoms of Qi (i.e., vital energy) deficiency were mostly observed in patients with chronic diseases such as Crohn's disease and ulcerative colitis. Defined symptom combinations did not reflect conventional Western diagnosis. Conclusion: Our study results show that symptom patterns are independent of the underlying disease. They rather depict the individual patient within an individual time frame. Traditional Kampo questionnaires were found to be valid for the analysis of a patients' body constitution (sho) and serve as a guide for Kampo treatment. We propose that individual pattern diagnosis should be taken into account to help treatment individualization.

Patterns of upper gastrointestinal diseases among patients undergoing esophagogastroduodenoscopy at three hospitals in Asella town, Southeast Ethiopia.

Upper gastrointestinal (UGI) symptoms are among the common complaints among patients visiting health facilities. Because of the scarcity of gastrointestinal endoscopy services and gastroenterologists, the pattern of common upper gastrointestinal diseases has not been well studied in the study setting. This study aimed to determine the pattern of upper gastrointestinal diseases among patients undergoing esophagogastroduodenoscopy (EGD). An institution-based cross-sectional study was conducted at three hospitals in Asella town, southeast Ethiopia. A total of 279 study subjects were included in the study. Three-fourths (74%) of the study participants had abnormal endoscopic findings. The clinical indications for endoscopic examination were dyspepsia (32.6%), peptic ulcer disease (PUD) (27.2%), suspicion of gastric cancer (13.3%), and suspicion of esophageal cancer (11.5%). The abnormal endoscopic findings were esophageal cancer (10.4%), gastric cancer (10%), duodenal ulcer (DU) (9.3%), and gastritis (8.6%). The abnormal biopsy findings were esophageal cancer (7.5%), gastric adenocarcinoma (6.4%), and gastritis (3.9%). Dyspepsia, peptic ulcer disease, and suspicion of UGI malignancies were the most common clinical indications for endoscopic examination, while esophageal cancer and gastric cancer were the most common abnormal endoscopic findings. The most common abnormal biopsy results were esophageal squamous cell carcinoma and gastric adenocarcinoma. It is advised to have a high index of suspicion for esophageal cancer and gastric cancer for patients who present with alarming upper gastrointestinal symptoms in the study setting.

Extracted Plasma Cell-Free DNA Concentrations Are Elevated in Colic Patients with Systemic Inflammation.

Colic is a common and potentially life-threatening condition in horses; in many cases, it remains challenging for clinicians to determine the cause, appropriate treatment, and prognosis. One approach that could improve patient care and outcomes is identification of novel diagnostic and prognostic biomarkers. Plasma cell-free DNA (cfDNA) is a biomarker that shows promise for characterizing disease severity and predicting survival in humans with acute abdominal pain or requiring emergency abdominal surgery. In horses, we recently determined that extracted plasma cfDNA concentrations are elevated in colic patients compared to healthy controls. For this current study, we hypothesized that extracted plasma cfDNA concentrations would be significantly higher in horses with strangulating or inflammatory colic lesions, in colic patients with systemic inflammatory response syndrome (SIRS), and in non-survivors. Cell-free DNA concentrations were measured in extracted plasma samples using a compact, portable Qubit fluorometer. Colic patients that met published criteria for equine SIRS had significantly higher median extracted plasma cfDNA compared to non-SIRS colic patients. There were no significant differences in extracted plasma cfDNA concentrations between other groups of interest. Our data offer early evidence that extracted plasma cfDNA concentration may provide information about systemic inflammation in colic patients, and additional research is warranted to expand on these findings.

Study on the Therapeutic Effects and Mechanisms of Gintonin in Irritable Bowel Syndrome and Its Relationship with TRPV1, TRPV4, and NaV1.5.

Irritable bowel syndrome (IBS) is a gastrointestinal (GI) disease accompanied by changes in bowel habits without any specific cause. Gintonin is a newly isolated glycoprotein from ginseng that is a lysophosphatidic acid (LPA) receptor ligand. To investigate the efficacy and mechanisms of action of gintonin in IBS, we developed a zymosan-induced IBS murine model. In addition, electrophysiological experiments were conducted to confirm the relevance of various ion channels. In mice, gintonin restored colon length and weight to normal and decreased stool scores, whilst food intake remained constant. Colon mucosal thickness and inflammation-related tumor necrosis factor-α levels were decreased by gintonin, along with a reduction in pain-related behaviors. In addition, the fecal microbiota from gintonin-treated mice had relatively more Lactobacillaceae and Lachnospiraceae and less Bacteroidaceae than microbiota from the control mice. Moreover, gintonin inhibited transient receptor potential vanilloid (TRPV) 1 and TRPV4 associated with visceral hypersensitivity and voltage-gated Na+ 1.5 channels associated with GI function. These results suggest that gintonin may be one of the effective components in the treatment of IBS.

Increased Mortality in a Nationwide Study of Gastrointestinal Hospitalizations in the United States During the 2020 Coronavirus Pandemic.

Background The impact of the coronavirus disease-2019 (COVID-19) pandemic on patients with acute gastrointestinal (GI) presentations including acute pancreatitis, diverticulitis, and GI bleeding, requiring hospitalization, has not been fully characterized at the population level in the United States. Aims We used the National Inpatient Sample to describe inpatient gastroenterology outcomes in the United States during the first year of the pandemic (2020), using 2018 and 2019 as comparator years. Methods Using the National Inpatient Sample, we explored year-to-year and month-to-month trends in hospitalizations, length of stay, and inpatient mortality for GI presentations, including luminal, biliary, infectious, inflammatory, and pancreatic diseases, with regression modeling. Relative change was used to compare time periods. Results We observed significantly lower rates of hospitalization for most acute GI conditions in 2020 relative to 2019. Despite this, we noted an increase in all-cause mortality (0.9% in 2019 and 1.1% in 2020, p<0.001) and hospital costs for patients hospitalized with acute presentations of GI-related conditions in 2020 relative to 2019. Importantly, we also observed increased mortality among COVID-19-positive patients who were hospitalized for acute pancreatitis (OR 2.56; 95% CI 1.37-6.53), variceal upper GI bleeding (OR 2.88; 95% CI 1.29-3.84), ulcerative colitis (OR 4.50; 95% CI 1.14-7.74), and acute cholangitis (OR 2.43; 95% CI 1.14-4.93). In 2020, the lowest number of admissions for all conditions occurred in April, coinciding with lockdowns ordered by most state governments. Conclusions Acute GI-related hospitalizations, in general, decreased in 2020 but this was associated with higher hospital costs and all-cause mortality increased compared with the pre-pandemic period.

Rosacea and Gastrointestinal Diseases: A Case-Control Study in the All of Us Database.

INTRODUCTION: Recent reports have suggested a link between rosacea and several gastrointestinal diseases, although the evidence has largely been limited to European and Asian populations. This study seeks to confirm and expand upon the connection between rosacea and gastrointestinal conditions using the diverse All of Us database. METHODS: We identified 8,319 rosacea patients and selected 4:1 controls matched (n = 33,276) based on age, race, gender, smoking status, insurance status, annual income, education, and alcohol use. Conditional logistic regression was then performed on the matched cohort to assess the relationship between rosacea and Crohn's disease (CD), microscopic colitis, ulcerative colitis (UC), celiac disease (CED), irritable bowel syndrome (IBS), Helicobacter-associated disease, and gastroesophageal reflux disease (GERD). RESULTS: On logistic regression, rosacea patients were significantly more likely than matched controls to be diagnosed with IBS (odds ratio [OR]: 2.35, 95% confidence interval [CI]: 2.18-2.53, p < 0.001), CD (OR: 1.82, 95% CI: 1.53-2.15, p < 0.001), UC (OR: 1.70, 95% CI: 1.44-2.02, p < 0.001), CED (OR: 1.93, 95% CI: 1.59-2.34, p < 0.001), Helicobacter-associated disease (OR: 1.79, 95% CI: 1.50-2.14, p < 0.001), and GERD (OR: 2.07, 95% CI: 1.97-2.18, p < 0.001). However, there was no statistically significant association between rosacea and microscopic colitis (OR: 1.47, 95% CI: 0.91-2.37, p = 0.12). CONCLUSION: This study highlights the presence of notable gastrointestinal comorbidities among individuals with rosacea in a diverse cohort. Consequently, more targeted monitoring of gastrointestinal diseases in rosacea patients may be warranted, as well as potential further investigation into the gut-skin axis in terms of rosacea pathophysiology.

Video capsule endoscopy findings in dogs with chronic enteropathy and in healthy dogs.

BACKGROUND: Video capsule endoscopy is a noninvasive technique for evaluation of the gastrointestinal tract. OBJECTIVE: To investigate the safety of using the video capsule ALICAM in dogs with chronic enteropathy (CE) >10 kg, and to compare macroscopic gastrointestinal morphology between CE dogs and healthy controls (HC). ANIMALS: Fifteen CE dogs and 15 similarly breed, age and body weight matched HC. METHODS: All dogs underwent a clinical work up including blood analyses, fecal samples, abdominal ultrasonographic examination, and blood pressure measurement. The dogs were withheld from food for 16 hours before and 8 hours after they PO received an ALICAM. All recordings were quality assessed, and blindly evaluated by 2 trained observers. RESULTS: The median age of CE dogs and HC was 3.3 (interquartile range [IQR] 2.5-5.9) years and 4.7 (IQR 3.3-5.6) years, respectively. The median body weight in the CE dogs and HC was 25.9 (IQR 20.6-30.9) kg, and 29 (IQR 16.2-30.5) kg, respectively. Complete recordings of the gastrointestinal tract were obtained from all dogs without complications. No significant differences were found between groups regarding number of abnormalities such as irregular mucosa, erythema, nonbleeding erosions, bleeding erosions, and dilated lacteals, as well as severity and extent of the abnormalities. CONCLUSIONS AND CLINICAL IMPORTANCE: The use of ALICAM for evaluation of the gastrointestinal tract in CE dogs and HC seems safe and feasible regarding gastrointestinal transit and macroscopic morphology assessment in dogs >10 kg. Abnormalities were found in similar proportions in CE dogs and HC.

Navigating Through the Rare and Accepting the New Shift: Laparoscopic Gastro-Jejunostomy for Gastric Outlet Obstruction Secondary to Eosinophilic Gastritis in a Pediatric Patient.

Eosinophilic gastritis, a rare variant of gastritis, presents with inflammation of the stomach lining due to eosinophil infiltration. This case report describes a complex presentation of eosinophilic gastritis in a 12-year-old boy, highlighting the challenges encountered in management. A 12-year-old male presented with symptoms consistent with gastritis, including abdominal pain, nausea, and vomiting. Despite extensive medical workup to identify potential etiologies (parasitic infections, autoimmune conditions), the diagnosis of eosinophilic gastritis was established. Unfortunately, the patient exhibited persistent symptoms despite aggressive medical management. The case was further complicated by pyloric stenosis, a narrowing of the stomach outlet. Laparoscopic intervention, a minimally invasive surgical approach, was initially attempted but deemed challenging due to the patient's specific condition. The presence of metabolic abnormalities added further complexity. Alternative approaches, such as endoscopic dilatation, were considered but ultimately deemed unsuitable due to the severity of the stenosis and the desire for a minimally invasive solution compared to laparotomy. This case exemplifies the challenges associated with managing rare gastrointestinal conditions like eosinophilic gastritis, particularly in pediatric patients. The report emphasizes the importance of a multidisciplinary approach, involving collaboration between gastroenterologists, surgeons, and potentially other specialists depending on the specific complications, to achieve optimal outcomes. This case highlights the complexities in managing this patient, especially when accompanied by complications like pyloric stenosis. It underscores the crucial role of a multidisciplinary team in navigating challenging presentations and exploring minimally invasive surgical options when feasible.

Risk of Serious Adverse Gastrointestinal Events with Potassium Binders in Hospitalized Patients: A National Study.

BACKGROUND: Concerns about serious adverse gastrointestinal (GI) events with sodium polystyrene sulfonate (SPS) led to development of two new potassium binders, patiromer and sodium zirconium cyclosilicate (SZC), for treatment of hyperkalemia. OBJECTIVE: To compare risk of intestinal ischemia/thrombosis or other serious GI events associated with SPS, patiromer, or SZC in hospitalized patients. DESIGN: Retrospective cohort study. PARTICIPANTS: National sample of 3,144,960 veterans hospitalized 2016-2022 in the U.S. Department of Veterans Affairs Healthcare System. MAIN MEASURES: Demographics, comorbidities, medications and outcomes were ascertained from the VA Corporate Data Warehouse. Exposures were SPS, patiromer, SZC. Outcomes were 30-day intestinal ischemia/thrombosis, and a composite of intestinal ischemia/thrombosis, peptic ulcer/perforation or bowel resection/ostomy. KEY RESULTS: Potassium binders were used during 39,270 (1.3%) hospitalizations: SPS = 30,040 (1.0%), patiromer = 3,750 (0.1%), and SZC = 5,520 (0.2%). Intestinal ischemia/thrombosis occurred with 106/30,040 (0.4%) SPS, 12/3750 (0.3%) patiromer and 24/5520 (0.4%) SZC, vs. 6998/3,105,650 (0.2%) without potassium binder. Adjusted odds ratios (aOR) were 1.40 [95% CI, 1.16 to 1.69] with SPS, 1.36 [CI, 0.79 to 2.36] with patiromer, and 1.78 [CI, 1.21 to 2.63] with SZC exposures. Composite GI adverse events occurred with 754/30,040 (2.5%) SPS, 96/3750 (2.6%) patiromer, 2.6% SZC, vs. 144/5520 (2.4%) without binder; aOR were 1.00 [CI, 0.94 to 1.08] with SPS, 1.08 [CI, 0.89 to 1.32] with patiromer, and 1.08 [CI, 0.93 to 1.27] with SZC exposures. No statistical difference in intestinal ischemia/thrombosis between each new agent and SPS was seen (p = 0.274 for SPS vs. SZC; p = 0.916 for SPS vs. patiromer). CONCLUSION: Risk of intestinal ischemia/thrombosis or other serious adverse GI events was low and did not differ across three potassium-binding drugs.

Enteroendocrine cells regulate intestinal homeostasis and epithelial function.

Enteroendocrine cells (EECs) are well-known for their systemic hormonal effects, especially in the regulation of appetite and glycemia. Much less is known about how the products made by EECs regulate their local environment within the intestine. Here, we focus on paracrine interactions between EECs and other intestinal cells as they regulate three essential aspects of intestinal homeostasis and physiology: 1) intestinal stem cell function and proliferation; 2) nutrient absorption; and 3) mucosal barrier function. We also discuss the ability of EECs to express multiple hormones, describe in vitro and in vivo models to study EECs, and consider how EECs are altered in GI disease.

Different processing methods and pharmacological effects of Atractylodis Rhizoma.

Atractylodis Rhizoma, a traditional Chinese medicine with an extensive history of treating gastrointestinal disorders and other diseases, undergoes various processing methods in China to enhance its therapeutic efficacy for specific conditions. However, a comprehensive report detailing the changes in chemical composition and pharmacological effects due to these processing methods is currently lacking. This article provides a systematic review of the commonly employed processing techniques for Atractylodis Rhizoma, including raw Atractylodis Rhizoma (SCZ), bran-fried Atractylodis Rhizoma (FCZ), deep-fried Atractylodis Rhizoma (JCZ), and rice water-processed Atractylodis Rhizoma (MCZ). It examines the alterations in chemical constituents and pharmacological activities resulting from these processes and elucidates the mechanisms of action of the primary components in the various processed forms of Atractylodis Rhizoma in the treatment of gastrointestinal diseases.

Obstructive sleep apnea and 19 gastrointestinal diseases: a Mendelian randomization study.

Background: Alterations gastrointestinal diseases (GDs) were reported in individuals with obstructive sleep apnea (OSA), however, the genetic background between OSA and GDs is still unclear. Methods: This investigation employed Mendelian randomization (MR) analyses to evaluate the causal effect between OSA and 19 types of GDs (gastroesophageal reflux disease (GERD), ulcerative colitis, celiac disease, Crohn's disease, chronic gastritis, irritable bowel syndrome, primary biliary cholangitis, diverticular disease, gastroduodenal ulcer, acute pancreatitis, non-alcoholic fatty liver disease, primary sclerosing cholangitis, cirrhosis, calculus of bile duct, calculus of gallbladder, pancreatic cancer, gastric cancer, colorectal cancer, and esophageal cancer). The inverse-variance weighted (IVW) method was used to evaluate the main effects model of causality. Results: This MR study suggests that OSA may play a causal role inflammation-related GDs (GERD, PIVW=5.94×10-9; gastroduodenal ulcer, PIVW=1×10-4; chronic gastritis, PIVW=0.0214; ulcerative colitis, PIVW=0.0296), and gallstones (calculi of the gallbladder, PIVW=0.0429; calculi of the bile duct, PIVW=0.0068). After accounting for obesity, type 2 diabetes, smoking, and alcohol consumption, the multivariate MR (MVMR) analysis identified that OSA is an independent risk factor for GERD, gastroduodenal ulcer, and calculus of the bile duct. The reverse MVMR analysis showed a causal effect of GERD on OSA. Besides, we did not find that the predisposition to OSA was associated with 4 cancers. Conclusion: This MR analysis provides compelling evidence of an independent causal relationship between genetically predicted OSA and an elevated risk of inflammation-related GDs. Besides, no causal association was observed between OSA and cancers. Further studies should be carried out to verify our findings.

Long-term gastrointestinal and hepatobiliary outcomes of COVID-19: a multi-nationwide cohort study from South Korea, Japan, and the UK.

Background/Aims: Considering emerging evidence on long COVID, comprehensive analyses of the post-acute complications of long COVID in the gastrointestinal and hepatobiliary systems are needed. We aimed to investigate the impact of COVID-19 on the long-term risk of gastrointestinal and hepatobiliary outcomes and other digestive abnormalities in various follow-up periods. Methods: We used three large-scale population-based cohorts: the Korean cohort (discovery cohort), the Japanese cohort (validation cohort-A), and the UK Biobank (validation cohort-B). 10,027,506 Korean, 12,218,680 Japanese, and 468,617 UK patients aged ≥20 years, including those with SARS-CoV-2 infection between 2020 and 2021 matched to non-infected control patients. Seventeen gastrointestinal and eight hepatobiliary outcomes as well as nine other digestive abnormalities following SARS-CoV-2 infection were identified and compared with contemporary controls. Results: The discovery cohort, consisting of 10,027,506 individuals (mean age 48.4 years; 49.9% female), revealed heightened risks of gastrointestinal diseases (HR: 1.15; 95% CI: 1.08-1.22), hepatobiliary diseases (1.30; 1.09-1.55), and other digestive abnormalities (1.05; 1.01-1.10) beyond the first 30 days after infection, following exposure-driven propensity score-matching. These results indicate a pronounced association as the severity of COVID-19 increases. The SARS-CoV-2 vaccination was found to lower the risk of gastrointestinal diseases but did not affect hepatobiliary diseases and other digestive disorders. The results derived from validation cohorts were consistent. Over time, the risk profile was most pronounced during the initial 3 months; however, it persisted for >6 months in validation cohorts, but not in the discovery cohort. Conclusions: The incidences of gastrointestinal disease, hepatobiliary disease, and other digestive abnormalities increased in patients with SARS-CoV-2 infection during the post-acute phase.

Advances and ongoing challenges in eosinophilic gastrointestinal disorders presented at the CEGIR/TIGERs Symposium at the 2024 American Academy of Allergy, Asthma & Immunology meeting.

The Consortium of Eosinophilic Gastrointestinal disease Researchers (CEGIR) and The International Gastrointestinal Eosinophil Researchers (TIGERs) organized a daylong symposium at the 2024 annual meeting of the American Academy of Allergy, Asthma & Immunology. The symposium featured new discoveries in basic and translational research as well as debates on the mechanisms and management of eosinophilic gastrointestinal diseases. Updates on recent clinical trials and consensus guidelines were also presented. We summarize the updates on eosinophilic gastrointestinal diseases presented at the symposium.

Eosinophils, Eosinophilic Gastrointestinal Diseases, and Inflammatory Bowel Disease: A Critical Review.

BACKGROUND/OBJECTIVES: Inflammatory bowel disease (IBD) and eosinophilic gastrointestinal diseases (EGIDs) are complex, multifactorial chronic inflammatory disorders affecting the gastrointestinal tract. Their epidemiology, particularly for eosinophilic esophagitis (EoE), is increasing worldwide, with a rise in the co-diagnosis of IBD and EGIDs. Both disorders share common risk factors, such as early exposure to antibiotics or specific dietary habits. Moreover, from a molecular perspective, eosinophilic infiltration is crucial in the diagnosis of eosinophilic disorders, and it also plays a pivotal role in IBD histological diagnosis. Indeed, recent evidence highlights the significant role of eosinophils in the health of the intestinal mucosal barrier and as mediators between innate and acquired immunity, even indicating a potential role in IBD pathogenesis. This narrative review aims to summarize the current evidence regarding the common clinical and molecular aspects of EGIDs and IBD and the current state of knowledge regarding overlap conditions and their pathogenesis. METHODS: Pubmed was searched until May 2023 to assess relevant studies describing the epidemiology, pathophysiology, and therapy of EGIDs in IBD. RESULTS: The immune pathways and mechanisms underlying both EGIDs and IBD remain partially known. An improved understanding of the role of eosinophils in overlapping conditions could lead to enhanced diagnostic precision, the development of more effective future therapeutic strategies, and a more accurate prediction of patient response. Consequently, the identification of red flags indicative of an eosinophilic disorder in IBD patients is of paramount importance and must be evaluated on a case-by-case basis.

Acupuncture influences multiple diseases by regulating gut microbiota.

Acupuncture, an important green and side effect-free therapy in traditional Chinese medicine, is widely use both domestically and internationally. Acupuncture can interact with the gut microbiota and influence various diseases, including metabolic diseases, gastrointestinal diseases, mental disorders, nervous system diseases, and other diseases. This review presents a thorough analysis of these interactions and their impacts and examines the alterations in the gut microbiota and the potential clinical outcomes following acupuncture intervention to establish a basis for the future utilization of acupuncture in clinical treatments.

The Role of DNA Methylation in Gastrointestinal Disease: An Expanded Review of Malignant and Nonmalignant Gastrointestinal Diseases.

Esophageal, colorectal, pancreatic, hepatocellular, and gastric cancer together impact millions of patients worldwide each year, with high overall mortality rates, and are increasing in incidence. Additionally, premalignant gastrointestinal diseases, such as Barrett's esophagus and inflammatory bowel disease, are also increasing in incidence. However, involvement of aberrant DNA methylation in these diseases is incompletely understood, especially given recent research advancements in this field. Here, we review knowledge of this epigenetic mechanism in gastrointestinal preneoplasia and neoplasia, considering mechanisms of action, genetic and environmental factors, and 5'-C-phosphate-G-3' island methylator phenotype. We also highlight developments in translational research, focusing on genomic-wide database data, methylation-based biomarkers and diagnostic tests, machine learning, and therapeutic epigenetic strategies.

The Horizons of Medical Mineralogy: Structure-Bioactivity Relationship and Biomedical Applications of Halloysite Nanoclay.

Medical mineralogy explores the interactions between natural minerals and living organisms such as cells, tissues, and organs and develops therapeutic and diagnostic applications in drug delivery, medical devices, and healthcare materials. Many minerals (especially clays) have been recognized for pharmacological activities and therapeutic potential. Halloysite clay (Chinese medicine name: Chishizhi), manifested as one-dimensional aluminum silicate nanotubes (halloysite nanotubes, HNTs), has gained applications in hemostasis, wound repair, gastrointestinal diseases, tissue engineering, detection and sensing, cosmetics, and daily chemicals formulations. Various biomedical applications of HNTs are derived from hollow tubular structures, high mechanical strength, good biocompatibility, bioactivity, and unique surface characteristics. This natural nanomaterial is safe, abundantly available, and may be processed with environmentally safe green chemistry methods. This review describes the structure and physicochemical properties of HNTs relative to bioactivity. We discuss surface area, porosity and surface defects, hydrophilicity, heterogeneity and charge of external and internal surfaces, as well as biosafety. The paper provides comprehensive guidance for the development of this tubule nanoclay and its advanced biomedical applications for clinical diagnosis and therapy.