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Background/aim: Insulin secretion deficiency is one of the factors that cause onset and progression of type 2 diabetes, and pancreatic β-cell mass is also reduced in patients with type 2 diabetes. Some anti-diabetic drugs act directly on the pancreas to promote insulin secretion. Although such drugs provide good glycemic control, there are concerns regarding secondary failure during long-term treatment. Therefore, we aimed to investigate the effects of the sodium-glucose cotransporter 2 (SGLT2) inhibitor, dapagliflozin, which does not act directly on the pancreas, using obese type 2 diabetic mice.

Materials and methods: Six-week-old db/db mice were administered dapagliflozin at doses equivalent to 0.3 or 1 mg/kg in their diet for nine weeks.

Results: Dapagliflozin treatment increased blood insulin levels and improved hyperglycemia. Histological analysis showed an increase in islet areas and improved islet irregularity and fibrosis in a dose-dependent manner. Immunostaining also showed a dose-dependent increase in β-cell positive areas and decrease in the ratio of α-cell positive area/β-cell positive area. Furthermore, dapagliflozin treatment suppressed the expression of CD44 (an inflammation- and fibrosis-related factor) around the pancreatic islets.

Conclusion: Treatment with dapagliflozin for nine weeks increases insulin secretion and preserves β-cell areas in type 2 diabetic mice, suggesting that long-term administration of dapagliflozin may have a protective effect on pancreas affected by diabetes.

Background/aim: Candidemia is a life-threatening fungal infection associated with high mortality and significant morbidity, particularly among older adults. Few studies have addressed mortality in this population. This study aimed to identify the risk factors for mortality in older patients with candidemia.

Patients and methods: We conducted a retrospective study to identify the risk factors for mortality in older patients with candidemia using the Medical Information Mart for Intensive Care-IV database. The clinical characteristics and risk factors for mortality in patients younger or older than 65 years of age were determined. We also evaluated the effects of early antifungal therapy on outcomes in these patients.

Results: Among patients with candidemia, advanced age, congestive heart failure, cardiac arrhythmia, smoking habits, leukocytosis, and thrombocytopenia were significantly associated with in-hospital mortality. The early administration of antifungal therapy was related to improved survival in all age groups. Among older individuals who died during hospitalization, a higher prevalence of congestive heart failure, pulmonary vascular diseases, and smoking habit was observed. In contrast, the younger patients who died had a higher incidence of underlying metastatic cancer, coagulopathy, and cardiac arrhythmia.

Conclusion: Older patients with candidemia had higher in-hospital mortality rates than those of younger patients. Thrombocytopenia was found to be an independent risk factor, and early fungal therapy was associated with lower in-hospital mortality. Early identification of patients with candidemia and appropriate antifungal therapy are important for its treatment.

Background/aim: Chronic low-dose pesticide exposure through high fruit and vegetable consumption is an underappreciated risk factor for metabolic dysfunction. While plant-based diets provide antioxidants and polyphenols, co-exposure to pesticide residues and heavy metals may induce subtle but clinically relevant biochemical disruptions.

Materials and methods: We analyzed the detailed metabolomic organic acid profiles from 26 individuals reporting high intake of conventionally grown fruits and vegetables. Dietary modeling was performed to estimate daily polyphenol intake, while metabolomic data were evaluated for markers of detoxification stress, oxidative damage, mitochondrial function, gut dysbiosis, and heavy metal burden.

Results: Both profiles revealed reproducible patterns of metabolic disturbance, including elevated methylmalonic acid, formiminoglutamic acid, and xanthurenic acid (suggestive of methylation and B-vitamin deficits); increased lipid peroxides and 8-OHdG (indicative of systemic oxidative stress); raised Krebs cycle intermediates and β-hydroxybutyrate (suggesting mitochondrial dysfunction); mild to moderate dysbiosis markers and evidence of fungal overgrowth; and elevated mercury levels exceeding reference thresholds. Despite estimated high polyphenol intake (2.5-3.5 g/day), antioxidant biomarkers remained elevated, supporting the hypothesis of pesticide-induced oxidative burden.

Conclusion: These findings suggest that chronic dietary pesticide exposure - even at regulatory-compliant levels - may produce a consistent metabolomic signature, particularly when at least five different pesticide, herbicide, or fungicide residues are simultaneously detected, highlighting the potential for cumulative biological effects characterized by oxidative stress, detoxification pathway strain, gut microbiome disruption, and mitochondrial impairment. This underscores the need for integrated dietary strategies to reduce contaminant intake and highlights the importance of further cohort studies to clarify health impacts and guide nutritional interventions.

Background/aim: Cancer cachexia is a complication that emerges in approximately 50-80% of patients with advanced cancer, characterized by symptoms such as lipoatrophy, skeletal muscle loss, metabolic abnormalities, and anorexia. While UCP1, a mitochondrial uncoupling protein, is implicated in lipolysis associated with cancer cachexia, the involvement of other thermogenic proteins remains unclear. In this exploratory study, we examined the expression of thermogenic genes in a mouse model of cancer cachexia.

Materials and methods: Tumor-bearing mice were generated by injecting Colon-26 cells (C26) into the right flank of male BALB/c mice. The body weight and temperature, tumor volume, and food intake of these mice were recorded three times a week. After 46 days of C26 administration, the adipose tissue, muscle, tumor, and blood were isolated from the mice and analyzed for thermogenic gene expression and biochemical parameters.

Results: Quantitative reverse transcription PCR analysis revealed increased expression of Serca2b, a gene associated with Ucp1 independent thermogenesis, in adipose tissue of C26-bearing mice. A positive correlation between Serca2b and Ucp1 mRNA levels was observed. In addition, Serca2b expression was not responsive to norepinephrine in differentiated 3T3-L1 adipocytes.

Conclusion: Although the functional relevance of Serca2b up-regulation remains to be elucidated, these findings suggest a potential role for SERCA2b in adipose tissue remodeling during cachexia. This preliminary observation may serve as a foundation for future studies investigating calcium cycling and non-canonical thermogenesis in the pathophysiology of cancer cachexia.

Background/aim: Hyperlipidemia is a major risk factor for cardiovascular diseases. Pharmacological treatment and lifestyle modifications are the main therapeutic approaches; however, some patients respond poorly or have limited tolerance. Intravenous laser irradiation of blood (ILIB) has recently been proposed as a potential adjunctive therapy, but its clinical efficacy remains unclear. The aim of this study was to evaluate the effects of ILIB therapy on lipid profiles and glycemic parameters in patients with chronic diseases.

Patients and methods: This retrospective single-group study included 60 patients with chronic diseases who received ILIB therapy at the Chang Bing Show Chwan Memorial Hospital between July 2022 and February 2024. Laboratory parameters before and after treatment, including total cholesterol, triglycerides (TG), LDL-C, fasting glucose, and HbA1c, were descriptively compared to demonstrate absolute and percentage changes. Paired t-test and Wilcoxon signed-rank test were used, with p<0.05 considered statistically significant.

Results: After treatment, only TG showed a significant reduction (167.8 mg/dl vs. 118.8 mg/dl, p=0.001). Subgroup analysis revealed that patients with TG >150 mg/dL, LDL>130 mg/dl, and total cholesterol >200 mg/dl all demonstrated significant decreases after ILIB therapy (p<0.05), while no significant changes were observed in patients with normal baseline values. Fasting glucose and HbA1c showed no significant changes in any subgroup.

Conclusion: ILIB demonstrated significant lipid-lowering effects in patients with dyslipidemia, particularly in those with elevated TG, LDL, and total cholesterol. No changes were observed in patients with normal lipid levels, suggesting a "normalizing" rather than broadly "lowering" effect. ILIB shows promise as an adjunctive therapy for hyperlipidemia, though larger randomized controlled trials are warranted to confirm these findings.

Background/aim: This study aimed to quantitatively analyze and compare aqueous humor concentrations of vascular endothelial growth factor-C (VEGF-C) in patients with primary open-angle glaucoma (POAG) versus non-glaucomatous controls while evaluating potential significant correlations.

Patients and methods: We conducted an observational cross-sectional study. At surgery initiation, anterior chamber paracentesis was performed under sterile conditions, and 50-100 μl of aqueous humor samples were collected. VEGF-C quantification employed a multiplex magnetic bead immunoassay platform.

Results: The study involved the collection of aqueous humor samples from 76 participants: 39 samples were collected from the POAG group and 37 from the control group (age-related cataract). Quantitative analysis revealed mean VEGF-C concentrations of 26.41±26.016 pg/ml in POAG eyes compared to 16.70±8.60 pg/ml in controls (p=0.277), demonstrating no statistically significant difference. Receiver operating characteristic (ROC) curve analysis showed limited prognostic ability for POAG detection (AUC=0.60; p=0.278).

Conclusion: This study represents the first large-scale evaluation of aqueous humor VEGF-C levels in patients with POAG. Our results provide evidence against VEGF-C up-regulation in POAG.

Background/aim: Mesenchymal stem cells (MSCs) are used to treat various degenerative diseases. However, their therapeutic potential is limited by cellular aging during in vitro cultivation. This study aimed to explore whether cannabidiol (CBD) can delay MSC aging by enhancing the expression of Sirtuin 1 (SIRT1) and autophagy, two key anti-aging regulators.

Materials and methods: CBD, the most important non-psychotomimetic phytocannabinoid derived from the Cannabis sativa plant, was used to up-regulate SIRT1 and autophagy in order to maintain MSC stemness. MSCs were treated with CBD and assessed for cell viability, doubling time, key gene/protein expression, relative senescence-associated β-galactosidase (SA-β-gal) assay, relative telomere length, and telomerase expression.

Results: CBD significantly increased the expression of SIRT1 and autophagy-related markers in MSCs. Furthermore, CBD preserved MSC stemness by promoting the deacetylation of SRY-box transcription factor 2 (SOX2) through SIRT1, and delayed cellular senescence by enhancing autophagy, reducing SA-β-gal activity, maintaining proliferation capacity, and supporting telomere function.

Conclusion: CBD promotes MSC stemness and delays cellular senescence, potentially through the activation of SIRT1 and autophagy. These findings suggest that CBD may serve as a promising agent for preserving MSC function in regenerative medicine.

Background/aim: In hepatocellular carcinoma (HCC), portal hypertension (PHT) during the advanced stages of cirrhosis leads to splenomegaly. Additionally, the immune environment is an important factor in HCC treatment. Splenectomy and partial splenic embolization (PSE) are expected to improve this condition; however, data on the effects of PSE on immune function are limited. Therefore, we investigated the effects of PSE on the immune environment and hepatic function in patients with PHT-related cirrhosis.

Patients and methods: The study included 117 of 238 patients who underwent PSE for PHT at our Department between 2011 and 2024 and were followed-up for more than 12 months, excluding those who underwent additional procedures concurrent with PSE. Changes in blood cell counts, hepatic function and immunological parameters including the neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio, were examined.

Results: The mean splenic volume, mean splenic infarction volume, and splenic infarction rate were 396.64 ml, 222.8 ml, and 58.6%, respectively. The preoperative splenic volume was inversely correlated with platelet and lymphocyte counts. The platelet count increased from 7.3 to 10.4 at 1 year; the platelet-albumin-bilirubin score improved from -2.38 to -2.49 (p<0.01); the fibrosis-4 index improved from 6.02 to 4.69 (p<0.01); the albumin-bilirubin score improved from -2.10 to -2.27 (p<0.01); and the NLR improved from 2.49 to 2.25 (p=0.028). Additionally, analysis of the background liver revealed improvements in platelet count and NLR.

Conclusion: PSE not only improved platelet counts, but also increased lymphocyte counts and improved the NLR. PSE-induced improvements in the immune environment may be useful for introducing combination immunotherapy for HCC.

Background/aim: The hypothesis that elimination of cigarette smoke-derived acetaldehyde in the saliva by slow-release L-cysteine would eliminate acetaldehyde-enhanced nicotine addiction among smokers has been tested in two randomized controlled trials (RCT) using Acetium^® lozenge (Biohit Oyj, Helsinki, Finland). Both RCTs showed a similar direction and magnitude of the effect size, but only the larger study was adequately powered to reach statistical significance.

Materials and methods: The two published RCTs on Acetium^® in smoking intervention included in this formal meta-analysis include: a cohort of 423 cigarette smokers, randomly allocated to intervention (n=212) and placebo arms (n =211) in Study 1, as well as a cohort of 1,998 smokers, with 996 and 1,002 subjects in the intervention and placebo arms, respectively, in Study 2. Both studies analyzed the results for intention-to-treat (ITT) and per protocol (PP) compliance groups. Random-effects (RE) meta-analysis was used to compute the summary effect size.

Results: In the ITT group of Study 1, Acetium^® was more effective than placebo, with OR=1.48 (95% CI=0.87-2.54), and in Study 2, the respective OR=1.26 (95% CI=0.99-1.59). In the PP groups, the success rates in both studies were better: OR=1.65 (95% CI=0.75-3.62) and OR=1.51 (95% CI=1.12-2.02), respectively. In RE meta-analysis, the summary estimates of Acetium^® efficacy were statistically significant in both the ITT (n=2,421) and PP (n=863) analysis: OR=1.29 (95% CI=1.04-1.60, p=0.018) and OR=1.53 (95% CI=1.16-2.01, p=0.0025), respectively.

Conclusion: Although meta-analyses with a limited number of studies should be interpreted with caution, these data provide clear support to the concept that Acetium^® lozenge significantly (1.5-fold) increases the likelihood of successful smoking cessation as compared to placebo.

Background/aim: Autologous platelet-derived growth factors such as platelet rich fibrin (PRF) are receiving increasing attention in the context of different medical situations such as soft-tissue wound healing or bone regeneration in patients with cancer suffering from therapy-associated osteonecrosis. PRF has been observed to support the colonization and differentiation of osteoblasts, thereby improving the wound healing process. In the recent past, fruit extracts from the tropical plant Morinda citrifolia have been associated with improved intestinal health and anti-inflammatory therapeutic effects. The aim of this study was to investigate the influence of Morinda citrifolia-derived noni juice on clinical blood parameters and the composition of human PRF.

Materials and methods: Forty healthy volunteers participated in a prospective, single-blinded, placebo-controlled, cross-over study. Participants consumed either noni juice (2 ml/kg/day) or placebo for four weeks, separated by a four-week washout. Blood samples were collected, and PRF was prepared by centrifugation. Clinical blood values were analyzed, and PRF samples were examined for growth factors, structural proteins, and cytokines using ELISA and cytokine arrays.

Results: Noni juice consumption led to significant changes in blood calcium, ALAT, and γ-GT levels. PRF analysis revealed elevated interleukin-11 (IL-11), macrophage colony-stimulating factor (M-CSF), and chemokine CCL7, indicating that noni juice alters the molecular profile of PRF.

Conclusion: Regular intake of noni juice influences PRF composition and modulates hepatic enzymes. These findings highlight the potential of dietary factors to impact regenerative biomaterials and warrant further targeted investigations.