Cyclooxygenase-1 (COX-1), an essential enzyme in the synthesis of pro-inflammatory prostanoids from arachidonic acid, is widely expressed in the brain, primarily in microglia. Previous studies from our laboratory found that the novel positron emission tomography (PET) radioligand [11C]PS13 has excellent in vivo selectivity for constitutively expressed COX-1 in human brain. This study sought to further evaluate the effects of age and sex on levels of constitutive COX-1 expression in the brains of 56 healthy volunteers. COX-1 density in the brain measured by [11C]PS13 PET showed a significant positive correlation with age in the whole brain, as well as in regions with the highest COX-1 expression, such as the hippocampus, lateral occipital cortex, and pericentral cortex. No significant sex differences were observed in any regions. Consistent findings were observed regardless of partial volume correction (PVC), while overall statistical significance was enhanced with PVC. In conclusion, the present study found that constitutive COX-1 binding in the brain, which is associated with microglial density, increased with age with no significant sex differences. The physiological roles of COX-1 in these regions and its potential contributions to the aging process remain largely unknown, and further investigation is warranted. Clinical trial registration information: NCT03324646; NCT04396873 in ClinicalTrials.gov.

A recent change in terminology proposed by scientific societies replaces the term NAFLD (non-alcoholic fatty liver disease) with the term MASLD (metabolic dysfunction associated steatotic liver disease). The prevalence of metabolic steatosis in France is 18.2%, higher among at-risk individuals (obese, diabetic, or with elevated transaminases). Among patients with MASLD, approximately 25% have liver inflammation with hepatocyte damage, now referred to as MASH (Metabolic dysfunction Associated Steatohepatitis), replacing the former name NASH (Non Alcoholic Steatohepatitis). MASH is associated with a significant increase in overall mortality, related to the severity of histological lesions, particularly cirrhosis. Cirrhosis develops in 15% to 30% of patients with MASH, usually at an older age than in other chronic liver diseases, due to a slower progression rate of fibrosis. Closely related to metabolic syndrome and insulin resistance, the disease progression involves the liver (progression of fibrosis, development of cirrhosis) but also exposes individuals to a significant risk of extrahepatic complications, such as cardiovascular, metabolic, and neoplastic diseases.

The epidemic of metabolic dysfunction-associated steatotic liver disease (MASLD), amplified by shifting dietary habits and increasing sedentary lifestyles, has elevated metabolic dysfunction-associated steatohepatitis (MASH) to a major public health challenge, burdened by the threat of cirrhosis and hepatocellular carcinoma.In this alarming context, bariatric surgery has progressively established itself as a key therapeutic solution, transforming the prognosis for patients with severe forms of the disease. Its efficacy extends beyond simple weight loss: it improves metabolism, reduces hepatic steatosis, inflammation, and, above all, fibrosis. Recent data confirm its impact on long-term survival, with a significant reduction in cardiovascular morbimortality and an overall improvement in life expectancy.However, this approach remains reserved for carefully selected patients. Its integration into therapeutic algorithms raises crucial questions, particularly with the emergence of new pharmacological therapies or less invasive endoscopic approaches.

Although the core pathophysiological pathways of chronic urticaria (CU) are increasingly understood, the upstream triggers and factors contributing to disease chronicity remain poorly understood. Emerging evidence suggests that gut microbiota dysbiosis represents a potentially modifiable upstream factor, which has been predominantly investigated in patients with chronic spontaneous urticaria (CSU). Multi-omics and Mendelian randomization studies have provided convergent evidence linking gut dysbiosis to systemic inflammation and mast cell instability. This is characterized primarily by the depletion of short-chain fatty acid (SCFA)-producing taxa (e.g., Faecalibacterium, Roseburia and Bifidobacterium) and the relative enrichment of pro-inflammatory Proteobacteria (particularly Enterobacteriaceae). Mechanistically, these alterations may lower the mast cell activation threshold and promote systemic immune dysregulation through specific metabolic shifts, such as the depletion of SCFAs and unsaturated fatty acids, and the translocation of endotoxins (e.g., lipopolysaccharide) due to compromised intestinal barrier function. In this review, we discuss how the use of Mendelian randomization (MR) and germ-free mouse models can advance the gut-urticaria axis (with a primary focus on CSU) from mere correlation to causation, while highlighting the crucial need to account for clinical confounders. Finally, we evaluate the clinical translational potential and associated challenges of microbiome-targeted interventions (e.g., probiotics, faecal microbiota transplantation) as novel adjuvant therapies.

Hyperuricemia (HUA), a metabolic disorder characterized by elevated serum uric acid (UA) levels, is closely linked to various chronic diseases. Galangin (GAL), a natural polyphenol abundant in Alpinia officinarum and propolis, has been reported to alleviate HUA by inhibiting hepatic UA production and promoting renal UA excretion. However, its impact on intestinal UA elimination is poorly understood. This study investigated GAL's protective role in HUA mice, focusing on intestinal UA transport, inflammatory response, and barrier integrity. Our findings demonstrate that GAL suppressed xanthine oxidase activity in the serum, jejunum, and ileum, attenuated intestinal morphological damage and oxidative stress, and enhanced expression of ABCG2 and GLUT9 in the small intestine. GAL also upregulated the tight junction proteins Occludin and ZO-1 while inhibiting MAPK/NF-κB pathway in the intestine. Collectively, GAL ameliorates HUA by modulating intestinal UA metabolism and repairing intestinal injury, highlighting its potential as a nutraceutical for UA-lowering therapy.

Aging is driven by progressive cellular damage, dysfunction, and senescence, a therapeutically actionable contributor to chronic inflammation, tissue degeneration, and age-related disease. However, senolytic and senomorphic translation remains constrained by senescent-cell heterogeneity, narrow therapeutic windows, inconsistent exposure, limited tissue penetration, uncertain nanoparticle accumulation in poorly perfused aged organs, and the absence of definitive clinical efficacy. Nanomedicine should therefore be viewed not as generic drug packaging, but as a strategy to improve the senolytic index through controlled exposure, multi-step selectivity, intracellular delivery, and context-responsive release. This review critically evaluates lipid-based, polymeric, hybrid, and biomimetic nanoplatforms by asking whether they improve target engagement, functional recovery, and safety over free drugs, rather than merely increasing encapsulation efficiency or in vitro cytotoxicity. Emphasis is placed on assay-aware interpretation of quantitative claims, limitations of single-marker targeting, variability of EPR-like behavior in aging tissues, manufacturability, and regulatory readiness. Overall, nanomedicine-based senotherapy is highly promising but not yet clinically de-risked; meaningful progress will require disciplined biology-to-design integration, human-tissue validation, and rigorous benchmarking against clinically relevant outcomes.

Inflammation-driven diseases are characterized by localized oxidative stress, acidosis, and hyperthermia-microenvironmental features that often compromise the effectiveness of conventional anti-inflammatory therapies due to poor site selectivity and uncontrolled systemic exposure. In this context, the present study provides an exclusively in silico investigation of an inflammation-responsive drug delivery concept based on β-cyclodextrin (β-CD) encapsulation of a redox-active vanadium complex, VO-INAP-tryptophan. Leveraging the supramolecular host-guest properties of β-CD, the computational model explores a system designed to remain stable under physiological conditions while undergoing selective destabilization within the pathological microenvironment of inflamed tissues. Two plausible inclusion modes of the vanadium complex within the β-CD cavity were systematically evaluated under simulated inflammatory conditions, including acidic pH, increased dielectric constant, and elevated temperature. Frontier molecular orbital analysis and global reactivity descriptors were used to examine how variations in electronic structure, thermodynamic stability, and chemical reactivity influence encapsulation strength and release propensity. The results identify a specific inclusion conformation particularly susceptible to solvent competition and electronic destabilization, indicating a favorable pathway for site-selective release. Component-resolved electronic analysis highlights the complementary roles of the vanadium center and the tryptophan ligand in modulating redox behavior and potential anti-inflammatory activity. Overall, this study provides computational insights that may inform a mechanistic framework for designing inflammation-responsive supramolecular delivery systems and suggests the potential of β-cyclodextrin architectures for optimizing the therapeutic performance of redox-active metal complexes, pending experimental validation.

IntroductionImmune checkpoint inhibitors (ICIs) are standard therapy for metastatic non-small cell lung cancer (NSCLC). Blood transfusions, particularly erythrocyte suspension (ES) transfusions, may induce immunomodulatory effects and potentially influence cancer outcomes. This study investigated the association between transfusions and survival in NSCLC patients treated with nivolumab.MethodsWe retrospectively reviewed 88 patients with metastatic NSCLC who received nivolumab between January 2018 and December 2023. Transfusion status, baseline inflammatory markers, progression-free survival (PFS), and overall survival (OS) were evaluated. Survival outcomes were assessed using Kaplan-Meier analysis and univariable statistical methods.ResultsThe median patient age was 64 years (range, 41-76). Median PFS was 5.93 months (95% Confidence Interval [CI], 3.72-8.14), and median OS was 8.23 months (95% CI, 6.19-10.27). Patients who received ES transfusions during nivolumab therapy experienced shorter PFS (p=0.033) and OS (p=0.039), predominantly driven by the non-squamous subgroup (PFS: p=0.002; OS: p=0.008). In univariable analyses, nivolumab cycle count, pre-treatment hemoglobin, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein-to-albumin ratio (CAR), and systemic immune-inflammation index were associated with PFS, while programmed cell death ligand-1 (PD-L1) status, treatment line, number of cycles, pre-treatment hemoglobin, NLR, CAR, and prognostic nutritional index were associated with OS (all p< 0.05).ConclusionES transfusions administered during nivolumab therapy were associated with poorer PFS and OS in patients with metastatic NSCLC, particularly in those with non-squamous histology. Given the retrospective design and limited number of transfused patients, these findings should be interpreted with caution and considered hypothesis-generating. Larger, prospective multicenter studies are warranted to further clarify the relationship between transfusion exposure and ICI outcomes.

Background Laparoscopic cholecystectomy is the accepted standard treatment for symptomatic gallstone disease. However, severe inflammation, fibrosis, adhesions, or anatomical distortion can obscure critical landmarks and increase the risk of bile duct injury. In such cases, timely recognition of operative difficulty and appropriate modification of technique are essential to ensure patient safety. Methods This prospective case series was conducted at a tertiary care center, R L Jalappa Hospital & Research Center, Tamaka, Karnataka, India, in 2024 and included seven adult patients whose intraoperative findings met predefined criteria for difficult laparoscopic cholecystectomy. Demographic data, operative challenges, technical adaptations, postoperative outcomes, and 30-day follow-up findings were documented and analyzed descriptively. Results Operative difficulty was associated with a frozen Calot's triangle, dense omental or bowel adhesions, a mucocele with impacted stones, a short cystic duct, severe fibrosis, and vascular anomalies. Structured bailout strategies were employed based on intraoperative findings. These included fundus-first (dome-down) dissection, fenestrating subtotal cholecystectomy, selective partial cystic ductotomy for impacted stone retrieval, endoloop ligation of the cystic duct stump, and judicious drain placement. In one patient, transient postoperative jaundice resolved spontaneously without intervention. No bile duct injuries or major postoperative complications occurred. All patients recovered satisfactorily, and no delayed morbidity was identified at the 30-day follow-up. Conclusion Difficult laparoscopic cholecystectomy requires vigilance, thorough anatomical knowledge, and the readiness to adapt the operative plan. Familiarity with bailout techniques and individualized intraoperative decision-making can prevent major biliary injuries and enable the safe completion of surgery, even in challenging operative fields.

Intestinal tuberculosis is an uncommon but clinically significant manifestation of tuberculosis that often presents with nonspecific gastrointestinal symptoms. Although the ileocecal region is most frequently involved, overt gastrointestinal bleeding is an unusual presentation, particularly in elderly patients who may lack classic constitutional symptoms. An elderly man presented to a community hospital in Guam with hematochezia one week after the diagnosis of pulmonary tuberculosis and initiation of rifampin, isoniazid, pyrazinamide, and ethambutol. Colonoscopy revealed a large semi-circumferential ulcer in the terminal ileum with a non-bleeding visible vessel. Histopathologic evaluation demonstrated necrotizing granulomatous inflammation, and acid-fast bacilli staining confirmed mycobacterial infection, establishing the diagnosis of intestinal tuberculosis. Despite appropriate anti-tuberculous therapy, the presence of concurrent pulmonary and intestinal disease reflected an advanced disease burden and poor prognosis. Given advanced frailty and clinical status, the patient and his family elected to pursue comfort-focused care. This case highlights intestinal tuberculosis as an uncommon cause of gastrointestinal bleeding and emphasizes its diagnostic overlap with conditions such as Crohn's disease. It underscores the importance of biopsy in granulomatous ileal disease and the need to maintain clinical suspicion for tuberculosis, particularly in patients from endemic regions or with relevant epidemiologic risk factors.

Crohn's disease (CD) is a chronic, systemic disease characterized by transmural inflammation of the gastrointestinal (GI) tract. Patients can present with a range of GI and extraintestinal features depending on the areas involved. Esophageal involvement can be a direct result of Crohn's or other co-existing diseases. Determining the cause of esophagitis in CD is important as it affects management and prognosis. Lymphocytic esophagitis (LE) is an example of a disease that can cause esophagitis on a background of CD. Patients presenting with the two conditions simultaneously are relatively rare. We present a case of LE and CD in a young male patient.