Introduction Gastrointestinal complications (GICs) are common after kidney transplantation (KT) and may compromise graft function. Our study aimed to determine the prevalence of acute GICs, identify the associated risk factors, and evaluate their impact on graft survival. Methods We conducted a retrospective study including patients who experienced an acute GIC defined as any acute digestive event lasting less than 14 days after KT. We included infectious or drug-induced diarrhea, gastrointestinal bleeding, and surgical abdominal complications. Patients with chronic gastrointestinal or hepatic diseases were excluded. As multiple GICs could occur in the same patient, the analysis was performed at the event level. A logistic regression analysis was conducted to identify factors associated with graft dysfunction, defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m² at three months following a GIC. Results Fifty-three patients experienced at least one GIC, corresponding to a prevalence of 46.9%, with a total of 84 events recorded. The mean age was 50 ± 13.3 years, with a male-to-female ratio of 1.52. The mean time to onset was 34.5 ± 46.1 months. Acute diarrhea was the most frequent complication (85.71%), which was of infectious origin in 79% and drug-related in 21%. Hemorrhagic complications accounted for 10%, including five cases of hematemesis and four cases of rectal bleeding. Three surgical complications were identified: appendicitis, colonic obstruction, and cholecystitis. From a renal perspective, 47% of patients developed acute kidney injury (AKI), and 20% progressed to graft dysfunction. The occurrence of AKI had a significant impact on six-year graft survival (p = 0.002). In univariate analysis, AKI (OR = 18.75, 95% CI = 3.60-97.5, p < 0.001) and recurrent diarrhea (OR = 2.91, 95% CI = 1.29-6.55, p = 0.010) were significantly associated with graft dysfunction. In multivariate analysis, both AKI (adjusted OR = 41.69, 95% CI = 4.75-365.82, p < 0.001) and recurrent diarrhea (adjusted OR = 3.62, 95% CI = 1.01-13.04, p = 0.049) remained independent predictors of graft dysfunction following GIC episodes. Conclusion Infectious diarrhea is the most common GIC after KT. AKI is the main determinant of graft dysfunction and graft survival.
Postoperative delirium (POD) is a common and severe complication in elderly patients following gastrointestinal oncologic surgery, associated with prolonged hospitalization, increased morbidity and mortality, and substantial healthcare costs. The stellate ganglion block (SGB), a sympathetic nerve block with anti-inflammatory and autonomic-modulating effects, has shown promise in improving perioperative outcomes. However, high-quality randomized controlled trials evaluating its efficacy in preventing POD in this older population are lacking. This is a single-center, prospective, randomized, double-blind (participants and outcome assessors), sham- controlled trial. A total of 174 elderly patients (≥60 years) scheduled for elective radical gastrointestinal cancer surgery will be randomized in a 1:1 ratio to receive either two ultrasound-guided SGBs (one on the afternoon before surgery and one 30 min before anesthesia induction) with 0.375% ropivacaine (3-5 mL each) or a sham block with normal saline (3-5 mL). All patients, surgeons, and outcome assessors will be blinded to group assignment. A standardized anesthesia protocol and a multicomponent delirium- prevention bundle will be applied to all participants. The primary outcome is the cumulative incidence of POD within postoperative days 1-3, assessed twice daily using the 3-Minute Diagnostic Interview for CAM-defined Delirium (3D-CAM). Secondary outcomes include delirium severity and duration, postoperative recovery (Quality of Recovery-15 score), inflammatory biomarkers (procalcitonin, C-reactive protein (CRP), interleukin-6 (IL-6), lymphocyte-to-monocyte ratio [LMR], neutrophil-to-lymphocyte ratio [NLR]), pain trajectories, opioid consumption, and length of hospital stay. We hypothesize that preoperative SGB will reduce the incidence and severity of POD compared to a sham block. This study will provide preliminary evidence on the feasibility and efficacy of SGB as a targeted intervention for high-risk older surgical oncology patients, while acknowledging that the assumed effect size may be optimistic. https://www.chictr.org.cn/showproj.html?proj=302103, identifier: ChiCTR2600118223.
Gastrointestinal stromal tumors (GISTs), the most common gastrointestinal sarcomas, experience a high rate of resistance to standard treatment tyrosine kinase inhibitor (TKI) imatinib, leading to tumor progression. Identifying non-responders and offering precise alternatives are crucial, however, multi-omics studies of GIST are limited, which hinders GIST biology understanding and novel drug development. We performed whole-exome and transcriptomic sequencing on 106 primary GIST patients. Subtype-specific molecular features and therapeutic responses were further validated in vitro and in vivo. Unsupervised clustering analysis of RNA data classified them into four subtypes, including immune (G1), stromal (G2), proliferative (G3), and metabolic (G4) subtypes. The G4 subtype had more patients with primary non-gastric tumors, a poor response to neoadjuvant imatinib treatment and synchronous metastasis, with an overall poor prognosis. Notably, G4 subtype exhibited significantly enhanced aerobic metabolism. Moreover, G4 subtype harbored homologous recombination repair deficiency (HRD) signatures, with significantly reduced homologous recombination activity and upregulation of non-homologous repair pathways. By stratifying GIST cell lines into subtypes, we confirmed that the HRD-targeting poly ADP-ribose polymerase (PARP) inhibitor Olaparib suppressed tumor growth in the G4 subtype-representative GIST882 cell line. In vivo experiments demonstrated that Olaparib monotherapy significantly reduced tumor burden in GIST882 xenograft-bearing mice and synergized with imatinib. We systematically deconstructed the molecular subtypes of primary GISTs by integrated genomic and transcriptomic analysis. A specific GIST subtype characterized by poor treatment responses and prognosis, marked by the activation of aerobic metabolism and HRD features, may be a potential candidate for PARP inhibitors.
Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms, with rectal GISTs making up less than 5% of cases. An 80-year-old woman presented with an incidental rectal mass on magnetic resonance imaging and failure to pass stool. Endoscopic ultrasound with fine needle biopsy confirmed a 3.1 cm multilobulated rectal GIST. This case highlights the diagnostic challenges and variability in managing rectal GISTs. A literature review of rectal GISTs from the past 5 years was conducted, summarizing tumor size, neoadjuvant or adjuvant imatinib use, surgical management, and outcomes to better characterize current treatment patterns for this rare malignancy.
Although upper gastrointestinal (GI) endoscopy is a crucial diagnostic tool for evaluating lesions of the upper GI tract, its findings are not always definitive, necessitating histopathological confirmation. This retrospective study aimed to assess the spectrum of histopathological lesions and their correlation with endoscopic impressions at Methodist Hospital, Wenchi, Ghana. A retrospective observational study was conducted on patients who underwent upper GI endoscopy with biopsy between August 2024 and September 2025. Out of 513 patients who underwent upper GI endoscopy, 176 were biopsied, but 46 were excluded due to missing histopathology reports, leaving 130 patients for analysis. Endoscopic impressions were compared with histopathological diagnoses across different GI tract sites (esophagus, stomach, and duodenum). Diagnostic accuracy was calculated with sensitivity, specificity, and 95% confidence intervals (CIs). Agreement was assessed using Cohen's Kappa and prevalence-adjusted bias-adjusted Kappa (PABAK). Of the 130 patients, 97.7% of lesions were benign (predominantly chronic gastritis), and 2.3% were malignant. Endoscopy demonstrated a sensitivity of 100% (95% CI: 29.2-100) and specificity of 99.2% (95% CI: 95.8-100) for malignant lesions. Cohen's Kappa was 0.796, indicating substantial agreement, while PABAK was 0.966, reflecting near-perfect concordance after adjusting for prevalence. Upper GI endoscopy showed high diagnostic accuracy and substantial concordance with histopathology for benign lesions such as gastritis. These findings suggest that clinicians in resource-deprived areas where histopathology is not readily available or may be associated with long turnaround times can safely commence targeted treatments for benign upper GI conditions based primarily on endoscopic findings.
Cadherin-17 (CDH17) is a cell-adhesion molecule physiologically expressed along the intestinal epithelial tight junctions. Aberrant overexpression of CDH17 in gastrointestinal (GI) cancers promotes tumor growth and metastasis and is associated with poor patient prognosis. Due to its restricted expression in normal tissues and strong association with malignancy, CDH17 represents an emerging therapeutic target for GI tract cancers. A high-affinity anti-CDH17 monoclonal antibody (TAVO307) was generated and conjugated with auristatin-derived cytotoxic payloads to obtain CDH17-directed antibody-drug conjugates (ADCs). In parallel, a VHH antibody capable of activating γδ T cell receptors from both Vδ1 and Vδ2 subsets was identified and combined with the anti-CDH17 antibody to generate CDH17-targeted T cell engager (TCE) to recruit γδ T cells, which are abundant in the intestinal mucosa and play a critical role in tumor immunosurveillance. An attenuated interleukin-15 (IL-15) fused with the IL-15 receptor α sushi domain was further incorporated on TCE to enhance γδ T cell expansion and activation. CDH17-based ADCs exhibited potent and selective cytotoxicity in multiple GI cancer cell lines and significant tumor regression in xenograft models. The CDH17 γδ TCE induced tumor antigen-dependent γδ T cell degranulation and redirected both Vδ1 and Vδ2 T cells to effectively kill CDH17-expressing cancer cells. IL-15 fusion further augmented γδ T cell expansion and activation. Both CDH17-targeted ADCs and γδ TCEs demonstrated promising potency and efficacy to control GI cancers. They could offer complementary therapeutic options that could be used in combination therapy.
Gastrointestinal (GI) perforation, as an acute digestive condition, is difficult to heal spontaneously and requires prompt surgical intervention or bioactive adhesives to promote wound closure. Among various types of tissue adhesives, hydrogel adhesives have attracted tremendous attention and have been used in the clinic due to their atraumatic nature, good biocompatibility, and tunable physicochemical properties. Despite their promise, the bioadhesive applications with engineered hydrogels still face challenges in the wet and acidic gastric environment. This review outlines the mainstream design approaches of hydrogel adhesives through covalent and noncovalent molecular interactions, illustrating the underlying adhesive mechanisms and material properties. Representative GI applications of hydrogel adhesives are also summarized. Finally, we discuss future perspectives on the clinical translations of hydrogel adhesives in the management of GI perforations.
Gallstone ileus is a rare complication of cholelithiasis. Its diagnosis is challenging due to a nonspecific presentation and high morbidity and mortality related to age and comorbidities. An 87-year-old female with a history of hypertension presented with obstructive abdominal pain, hyporexia, and "coffee-ground" emesis. Upon admission, she showed hemodynamic instability [blood pressure (BP) 83/51 mmHg] and acute renal failure [Creatinine (Cr) 1.34 mg/dL]. Computed tomography revealed Rigler's triad, consisting of small bowel obstruction, neumobilia, and an ectopic gallstone. Exploratory laparotomy identified a stone impacted 140 cm from the Treitz ligament. A "milking" maneuver and simple enterolithotomy were performed, extracting a 2.5 cm gallstone. The patient had a favorable recovery and was discharged on the sixth postoperative day. Gallstone ileus should be suspected in geriatric patients with obstructive symptoms, even when presenting with atypical gastrointestinal bleeding. In extremely frail or hemodynamically unstable patients, simple enterolithotomy remains the gold standard to reduce surgical time and intraoperative complications.
Gastrointestinal cancer (GIC) remains a major clinical burden, and readily available biomarkers are needed to improve preoperative prognostic assessment and risk stratification. The present study aimed to evaluate the prognostic significance of the preoperative lactate dehydrogenase-to-albumin ratio (LAR) in patients with GIC. A comprehensive search was performed in PubMed, Embase and the Cochrane Library to identify relevant studies published from the date of database inception to March 20, 2025. The extracted outcomes included hazard ratios (HRs) for overall survival (OS) and recurrence-free survival (RFS) and odds ratios (ORs) for major postoperative complications. A total of five independent studies involving 6,379 patients were included in the present meta-analysis. A higher preoperative LAR was significantly associated with poorer OS [HR=1.90; 95% confidence interval (CI), 1.63-2.21; P<0.001]. Subgroup analysis confirmed the robustness of this association across analytical models, cancer types, countries and LAR cut-off values. A higher LAR was also associated with poorer RFS (HR=1.83; 95% CI, 1.52-2.20; P<0.001) and a higher risk of major postoperative complications (OR=2.36; 95% CI, 1.49-3.74; P<0.001). In conclusion, preoperative LAR may serve as a useful prognostic biomarker for survival outcomes in patients with GIC. Incorporating this readily available and low-cost biomarker into routine preoperative assessment may help improve perioperative risk stratification and guide postoperative management.
Non-vitamin K antagonist oral anticoagulants (NOACs) are widely prescribed for stroke prevention in atrial fibrillation (AF). Although they reduce intracranial hemorrhage compared with warfarin, gastrointestinal bleeding (GIB), particularly upper GIB (UGIB), remains a clinically significant complication. Proton pump inhibitors (PPIs) are frequently co-prescribed for gastroprotection, yet the available evidence remains largely observational and subject to methodological heterogeneity and confounding by indication. We conducted a structured narrative review of nationwide cohort studies, multi-database analyses, randomized trials, and meta-analyses evaluating PPI co-therapy in NOAC-treated populations, with emphasis on clinically adjudicated UGIB outcomes and methodological considerations including confounding by indication and endpoint variability. A large Korean nationwide cohort demonstrated that PPI co-therapy in NOAC-treated AF patients was associated with reduced risks of UGIB hospitalization (weighted HR 0.825) and transfusion-requiring UGIB (weighted HR 0.798), particularly in high-risk subgroups. A meta-analysis of approximately 1.97 million oral anticoagulant users reported lower odds of total and major GIB with PPI use (OR ∼0.67-0.68). Randomized evidence suggests biological plausibility for reduction of gastroduodenal bleeding but highlights endpoint specificity. However, heterogeneity across analytic designs underscores persistent residual confounding. PPI co-therapy may represent a clinically pragmatic strategy pending dedicated randomized evidence in high-risk NOAC-treated patients. A pragmatic, risk-stratified approach appears most appropriate while awaiting confirmation from dedicated randomized trials.
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The Kirsten rat sarcoma viral oncogene homolog (KRAS) is one of the most frequently mutated oncogenes and is associated with poor prognosis. Long considered an undruggable target, KRAS has recently become actionable with the development of direct inhibitors, particularly against the G12C mutation. Our group previously reported promising efficacy and safety results for glecirasib (JAB-21822), a novel KRASG12C inhibitor, in phase I/II trials involving solid tumors harboring KRASG12C mutations (ClinicalTrials.gov NCT05009329, NCT05194995). Nevertheless, primary (5.61%) and acquired (9.64%) resistance were observed. This study analyzed 18 patients with advanced solid tumors harboring the KRASG12C mutation from the JAB-21822 cohort. Longitudinal blood samples (N = 45) were collected at baseline, during partial response or stable disease, and at disease progression. Circulating tumor cells (CTCs) were isolated via a microfluidics platform (CTC100, Cellomics) and categorized into epithelial (E-CTCs), mesenchymal (M-CTCs), and epithelial/mesenchymal mixed (E/M-CTCs) subtypes. At progression, the proportion of E-CTCs showed a decreased trend, while that of E/M-CTCs increased significantly (p = 0.03). In long-term responders, the inflection points of declining M-CTC levels correlated with clinical progression and were consistent with radiographic outcomes. Baseline CTC counts > 1 were associated with shorter progression-free survival (PFS; p = 0.046). E-CTC ≤ 1 correlated with longer PFS (p = 0.025), and M-CTC ≤ 1 with longer overall survival (OS; p = 0.033). E/M-CTC ≤ 1 showed a trend toward improved OS (p = 0.086). In addition, patients with > 1 CTC who received local radiotherapy for progressive lesions after glecirasib targeted therapy had significantly prolonged PFS and OS compared to those who did not (p < 0.05).
Gastrointestinal mucormycosis is a rare but life-threatening invasive fungal infection carrying mortality rates approaching 85%. We report 3 cases of gastric mucormycosis managed at our institution. Two patients presented atypically-one with refractory seizures and another with severe respiratory distress-resulting in diagnostic delays and subsequent fatal outcomes despite antifungal therapy. A third patient, diagnosed promptly following early esophagogastroduodenoscopy and biopsy, achieved complete clinical recovery. Rapid disease progression demonstrated the aggressive nature of this condition, but early diagnosis greatly improved outcomes. These cases collectively highlight the critical importance of maintaining a high index of clinical suspicion, pursuing early endoscopic biopsy of atypical gastric ulcerations, and initiating timely antifungal therapy to optimize patient prognosis.
Obesity has emerged as one of the leading global drivers of gastrointestinal and metabolic disease, contributing substantially to the burden of metabolic dysfunction-associated steatotic liver disease (MASLD), gastroesophageal reflux disease (GERD), Barrett's esophagus, pancreatitis, colorectal neoplasia, and obesity-associated malignancies. Simultaneously, the rapid expansion of glucagon-like peptide-1 (GLP-1) receptor agonists and minimally invasive bariatric endoscopic interventions has transformed the therapeutic landscape of obesity management and increasingly positioned gastroenterologists at the intersection of obesity medicine, hepatology, therapeutic endoscopy, nutrition, and metabolic care. This narrative review evaluates the evolving role of gastroenterologists in obesity medicine and discusses the integration of pharmacologic, endoscopic, metabolic, and hepatologic approaches into modern gastrointestinal practice. A focused literature review was conducted by searching PubMed and Google Scholar, prioritizing peer-reviewed publications from 2015 to 2026, with inclusion of landmark earlier studies where relevant. Articles were selected based on clinical relevance, methodological quality, and applicability to the evolving role of gastroenterologists in metabolic care. The role of gastroenterologists is expanding beyond traditional luminal and procedural practice into longitudinal metabolic disease management. The emergence of GLP-1 receptor agonists, dual incretin therapies, and endobariatric procedures has accelerated GI involvement in obesity treatment and preventive metabolic care. In parallel, the increasing prevalence of MASLD and obesity-related gastrointestinal disorders has reinforced the importance of comprehensive obesity management strategies involving gastroenterologists within multidisciplinary care teams. Integration of obesity medicine into gastroenterology training programs and metabolic clinics may further redefine the future scope of GI practice. Modern gastroenterology is undergoing a transition toward obesity-focused and metabolic care. As pharmacologic and endoscopic obesity therapies continue to evolve, gastroenterologists are uniquely positioned to play a central role in the multidisciplinary management of obesity-associated gastrointestinal disease.
Incretin-based pharmacotherapies, including GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists, have transformed obesity management by producing substantial weight loss through appetite suppression, reduced energy intake, and gastrointestinal effects. These mechanisms may also modify dietary intake, gastrointestinal physiology, and weight-loss-related metabolic adaptations, raising concern about micronutrient disturbances during long-term treatment. This narrative clinical review synthesizes evidence on mechanistic pathways, clinical signals, and monitoring considerations related to micronutrient risk during incretin-based obesity pharmacotherapy. Evidence was integrated from dietary studies, observational cohorts, mechanistic investigations, clinical trials, pharmacovigilance reports, and literature on obesity-related micronutrient physiology. Micronutrient vulnerability appears to arise from the interaction between reduced food intake, lower dietary diversity, gastrointestinal intolerance, delayed gastric emptying, rapid weight loss, and baseline nutritional risk. The most relevant signals involve hematologic, fat-soluble, bone-related, trace element, and electrolyte domains, particularly iron, vitamin B12, vitamin D, calcium, magnesium, zinc, with additional context-dependent concerns involving thiamine, folate, vitamin A, other fat-soluble vitamins and potassium. Most abnormalities reported to date are subclinical or indirect, but clinically meaningful consequences may occur in susceptible individuals, including those with prior bariatric surgery, gastrointestinal disorders, poor baseline diet quality, older age, or prolonged nausea and vomiting. Micronutrient risk during incretin-based obesity pharmacotherapy is likely multifactorial and patient-specific. Individualized nutritional assessment and targeted laboratory monitoring should be considered for high-risk patients, while prospective studies are needed to define incidence, clinical relevance, and evidence-based monitoring strategies.
To compare the real-world weight loss effectiveness and safety of tirzepatide and semaglutide in patients treated for obesity, including those with prior obesity medication (OM) use. This retrospective, multicenter study analyzed adults prescribed tirzepatide or semaglutide for weight loss across multiple US health care centers from January 1, 2021, through May 1, 2024. Total body weight loss percentage (TBWL%) was assessed at 3, 6, 9, and 12 months. Subgroup analyses were conducted by diabetes status, medication dose, and prior OM use. Safety was evaluated based on reported gastrointestinal side effects. Among 511 patients (n= 469; 91.8% White, n= 382; 74.8% female, mean body mass index 40.0 kg/m2), tirzepatide (n=207) was associated with greater 12-month TBWL% than semaglutide (n=304) (16.6% ± 8.6% vs 13.4% ± 8.0%; P<.01). More tirzepatide users achieved greater than or equal to 15% (56.8% vs 40.7%; P=.03) and greater than or equal to 20% TBWL% (39.0% vs 22.1%; P<.01). Among patients without diabetes, tirzepatide led to significantly greater weight loss than semaglutide (18.5% ± 8.2% vs 14.2% ± 8.6%; P<.01). Prior OM use was associated with reduced weight loss in both groups (semaglutide: 10.4% vs 14.4%, tirzepatide: 16.1% vs 17.1%; P<.01). Semaglutide users reported more gastrointestinal side effects than tirzepatide users (50.7% vs 28.5%; P<.01). In this large, real-world cohort, tirzepatide resulted in greater weight loss than semaglutide, including in patients with prior OM exposure. Both agents were generally well tolerated, although gastrointestinal side effects were more frequent with semaglutide. Further studies in more diverse populations are warranted.
Understanding what matters most to patients is central to person-centered care, particularly in surgical oncology, where decisions often involve significant tradeoffs. We explored how surgeons elicit, integrate, document, and support patient values in cancer-related decision-making. This qualitative descriptive study involved semi-structured interviews with surgical oncologists (June-September 2025). Participants were purposively sampled from a prior international survey to ensure variation in demographics. Interviews were recorded, transcribed, and analyzed using thematic analysis. Participant characteristics were summarized descriptively. Fourteen surgeons participated. Most were male (71%), White (86%), and early-career (43%), practicing primarily in gastrointestinal or hepatobiliary surgery (each 43%) at academic centers (57%) in the U.S. South or Midwest (each 36%). Surgeons described various approaches to eliciting values, including inferring values from contextual clues and clarifying tradeoffs between survival and quality-of-life. Values elicitation was largely situational, occurring in high-risk or preference-sensitive contexts. When values conflicted with recommendations, surgeons adapted plans within oncologic safety. Documentation varied and was shaped by relevance, medicolegal concerns, and workflow. Barriers included time limitations, emotional distress, family dynamics, and limited training. Values elicitation was inconsistent and situational rather than routine. More structured, earlier approaches and system-level support may better align surgical decisions with patient values.
IntroductionCholecystectomy is considered the gold standard treatment for symptomatic gallstone disease. In certain cases, due to technical difficulties, a subtotal cholecystectomy may be performed. Between 1998 and 2015, a total of 1 423 080 laparoscopic cholecystectomies were performed. 10 162 patients who underwent completion cholecystectomy were identified and stratified by age (<50 vs. ≥50 years). This study examines outcomes and risk factors associated with completion cholecystectomy following partial (subtotal) cholecystectomy, with a focus on age and comorbidity burden.ResultsOlder patients demonstrated significantly higher comorbidity burdens, as reflected by Charlson Comorbidity Index scores. Overall complication rates were substantial (26.3%), including gastrointestinal, infectious, and cardiopulmonary events. Mortality was 2.5% overall but markedly higher in patients aged ≥50 years (3.3% vs 0.6%). Length of stay was also longer in older patients.ConclusionsWorse outcomes in older individuals correlated strongly with increased comorbidities rather than age alone. Completion cholecystectomy is frequently performed in complex surgical settings with distorted anatomy, contributing to higher complication rates. However, variability in outcomes across studies suggests that patient selection, operative approach, and baseline health status are key determinants. The study highlights the diagnostic challenge of post-subtotal cholecystectomy cholecystitis and underscores the importance of clinical vigilance. It concludes that careful preoperative risk stratification and patient selection are critical to improving outcomes, as procedural risk is closely tied to underlying health status and case complexity rather than the surgery itself.
Supplements are commonly used by osteoarthritis (OA) patients, and eggshell membrane (ESM) proteins are widely advertised as natural bioactive compounds for joint health. Here, we evaluated the solubility, digestibility, and immunomodulatory potential of commercial ESM supplements under physiologically relevant conditions to assess their plausibility as anti-inflammatory agents. We analyzed three commercial ESM formulations (NEM®, Torolis®, and Biova®) using standardized extraction protocols. Protein solubility was assessed in physiological saline and under simulated gastric (pH 2) and intestinal (pH 5.8) conditions with controlled temperature, agitation, and digestive enzyme exposure. We examined the role of disulfide-crosslinked proteins in insolubility using dithiothreitol (DTT) and evaluated digestibility of proteins by SDS-PAGE after treatment with pepsin, pancrelipase (Creon®), or sequential digestion. Released peptides were identified by MALDI-TOF mass spectrometry, and immunomodulatory effects were tested using human peripheral blood mononuclear cells (PBMC) by measuring cytokine release after stimulation with lipopolysaccharide or Phorbol 12-myristate 13-acetate/Ionomycin, in the presence or absence of Biova®. NEM® and Torolis® showed extremely low solubility (< 0.3%) and remained insoluble under all conditions, including after DTT treatment. Although Biova® was highly soluble (~ 90%), simulated gastrointestinal digestion produced minimal peptide generation. Only non-physiological extraction yielded sporadic trace peptides, most lacking known anti-inflammatory relevance. In PBMC assays, Biova® increased IL-6 after lipopolysaccharide stimulation, showed a non-significant TNFα reduction, and had no effect on IL-17 A or granzyme B. Together, commercial ESM supplements are largely insoluble, resistant to digestion, and show no meaningful anti-inflammatory activity in human immune cells. These findings challenge the plausibility of orally administered ESM as a therapeutic intervention for osteoarthritis.
The application of tea polyphenols (TP) is constrained by their inherent chemical instability. In this study, a nanocarrier delivery system for TP was fabricated via electrostatic self-assembly between a natural pomelo peel extract (PP) and quaternary ammonium chitosan (QAC). PP was characterized as a protein-pectin complex, containing 60.1% protein and 23.2% polysaccharides, of which 75.6% was galacturonic acid. PP formed stable complexes with QAC at pH ∼4, achieving a TP encapsulation efficiency of 39.6%. The QAC-PP nanocarrier significantly improved TP stability under simulated gastrointestinal conditions, retaining 96.3% of TP after 1 h of gastric digestion and 59.5% after a subsequent 2 h of intestinal digestion. Furthermore, after 12 h of UV irradiation, 58.9% of encapsulated TP remained, substantially higher than the 43.0% retention observed for free TP. This work successfully valorizes pomelo peel waste into an effective nanocarrier, presenting a viable strategy to enhance the stability of TP.