Bosnian Journal of Basic Medical Sciences (BJBMS)
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Association between triglyceride-glucose (TyG) index and risk of depression in middle-aged and elderly Chinese adults: Evidence from a large national cohort study
Full text linkInsulin resistance (IR) has been proposed as a contributing factor to major depressive disorder (MDD), with previous studies reporting a positive correlation between triglyceride-glucose (TyG) a proxy indicator of IR and MDD. However, limited information is available regarding their longitudinal association. This study aimed to clarify the connection between TyG levels and depression risk, as well as explore its predictive potential. A total of 3021 participants without a prior history of depression were recruited from the China Health and Retirement Longitudinal Study and followed for seven years. Participants were categorized into tertiles based on their TyG levels. The cumulative hazard of depression was analyzed using Kaplan–Meier curves, while cox regression analyses and multivariable-adjusted restricted cubic spline (RCS) curves were employed to assess the relationship between TyG levels and depression risk. Stratified analyses across various subgroups were also conducted to confirm the robustness of the conclusions. Over the follow-up period, 1782 participants (58.9%) developed depression, with incidence rates of 30.2%, 34.0%, and 35.8% in tertiles 1, 2, and 3, respectively. After adjusting for confounding factors, each 1-unit increase in TyG was associated with a significantly higher risk of depression. RCS curve analysis revealed a compelling dose-response relationship between TyG levels and depression susceptibility. These findings indicate that elevated TyG levels are strongly associated with an increased risk of depression and could serve as a reliable biomarker for assessing depression risk. These insights provide valuable guidance for developing more effective strategies for the prevention and treatment of depressive disorders
The molecular mechanisms of cuproptosis and its relevance to atherosclerosis
Full text linkAtherosclerosis (AS) is a chronic inflammatory disease associated with lipid deposition in the vascular intima. Copper is a vital trace element implicated in the onset and progression of AS. Excessive intracellular copper accumulation induces a unique form of cell death termed “cuproptosis.” The emergence of the concept of cuproptosis has highlighted the potential role of copper in AS. This review explores the regulatory mechanisms of copper metabolism and cuproptosis, summarizes recent findings on the link between copper excess and AS, and examines how cuproptosis may influence AS progression. The goal is to propose novel diagnostic and therapeutic strategies for AS through the lens of cuproptosis
Methylene blue mitigates lung injury in HCA rats by regulating macrophage pyroptosis via Nrf2/HO-1 and NLRP3 pathways
Full text linkMethylene blue (MB) has antioxidant properties, yet its role in acute lung injury (ALI) induced by hypothermic circulatory arrest (HCA) remains unexplored. This study investigates MB’s effects and underlying regulatory mechanisms in an HCA rat model. Rats received an intravenous bolus of MB (1 mg/kg) 15 min before HCA induction. Physiological parameters were monitored, and bronchoalveolar lavage fluid (BALF) was collected 2 h postoperatively to assess total protein levels, inflammatory cells, and cytokines. Histopathological lung damage was evaluated using hematoxylin–eosin (H&E) and TUNEL staining. Inflammatory markers and oxidative stress indicators were measured via ELISA and dihydroethidium (DHE) staining. Alveolar macrophages (AMs) were isolated to analyze polarization using flow cytometry and immunofluorescence double staining. Pyroptosis in AMs was detected with Yo-Pro-1 and Hoechst 33342 staining. Additionally, Western blotting was performed to examine the nuclear factor erythroid-2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway, Nod-like receptor protein 3 (NLRP3) inflammasome, and pyroptosis-related proteins. Following HCA, rats exhibited significant blood gas abnormalities, structural lung damage, increased pathological scores, and higher apoptosis rates. However, MB mitigated these effects, improving physiological parameters and reducing lung histopathology scores. MB also lowered proinflammatory cytokine levels, increased SOD and GSH-Px activity, promoted AM polarization toward the M2 phenotype, and decreased pyroptosis. Mechanistically, MB activated the Nrf2/HO-1 pathway while inhibiting NLRP3 inflammasome activation. Notably, Nrf2 inhibitors and NLRP3 agonists weakened MB’s protective effects by promoting inflammasome activation and pyroptosis, whereas Nrf2 agonists and NLRP3 inhibitors enhanced MB’s beneficial impact. In conclusion, MB attenuates HCA-induced ALI by modulating AM polarization and pyroptosis via Nrf2/HO-1 pathway activation and NLRP3 inflammasome inhibition
Integrative PANoptosis gene profiling reveals prognostic and therapeutic insights in prostate cancer
Full text linkProstate cancer (PCa) remains a significant global health challenge, representing the most common solid tumor in men and the fifth leading cause of cancer-related death. Despite therapeutic advances, achieving a definitive cure remains difficult. Early diagnosis and personalized treatment strategies are crucial for improving patient outcomes. Programmed cell death—particularly PANoptosis, an inflammatory pathway that integrates pyroptosis, apoptosis, and necroptosis—has emerged as a promising therapeutic target in oncology.In this study, individuals with PCa were categorized into PANoptosis-high and PANoptosis-low subgroups based on the expression levels of 45 PANoptosis-related genes. Differential gene expression analysis and subsequent enrichment analyses were conducted to explore the biological pathways associated with each subgroup. A four-gene risk signature (CASP7, ADAR, DNM1L, and NAIP) was identified, showing strong predictive value for overall survival (OS) in both training and validation cohorts. This signature was independently associated with OS and showed meaningful correlations with the tumor microenvironment, particularly immune cell infiltration and immunotherapy responsiveness. These findings suggest that the PANoptosis-related gene signature may serve as a valuable prognostic biomarker and inform immunotherapeutic strategies in PCa management
Adefovir anticancer potential: Network pharmacology, anti-proliferative and apoptotic effects in HeLa cells
Full text linkCervical cancer presents a significant healthcare challenge due to recurrent disease and drug resistance, highlighting the urgent need for novel therapeutic strategies. Network pharmacology facilitates drug repurposing by elucidating multi-target mechanisms of action. Adefovir, an acyclic nucleotide analog, has shown promising potential in cervical cancer treatment, particularly in HeLa cells. In vitro studies have demonstrated that adefovir inhibits HeLa cell proliferation by enhancing apoptosis while maintaining a low cytotoxicity profile at therapeutic concentrations, making it an attractive candidate for further exploration. A combined network pharmacology and in vitro study was conducted to investigate the molecular mechanism of adefovir against cervical cancer. Potential gene targets for adefovir and cervical cancer were predicted using database analysis. Hub targets were identified, and protein-protein interaction (PPI) networks were constructed. Molecular docking assessed adefovir\u27s binding affinity to key targets. In vitro cytotoxic assays, including 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and crystal violet assays, were performed using 96-well plates to evaluate anti-proliferative effects in HeLa cells. Apoptosis was assessed via p53 immunocytochemistry Enzyme-Linked Immunosorbent Assay (ELISA), while Vascular Endothelial Growth Factor ELISA (VEGF ELISA) was used to measure cell proliferation. Venn analysis identified 144 common targets between adefovir and cervical cancer. Network analysis revealed key hub targets involved in oncogenic pathways. Molecular docking demonstrated strong binding between adefovir and Mitogen-Activated Protein Kinase 3 (MAPK3) and SRC proteins. In vitro, adefovir significantly suppressed HeLa cell viability, with an Inhibitory Concentration 50 (IC50) of 7.8 µM, outperforming 5-Fluorouracil (5-FU). Additionally, it induced apoptosis via p53 activation and inhibited cell proliferation through VEGF suppression. These integrated computational and experimental findings suggest that adefovir exerts multi-targeted effects against cervical cancer. Its promising preclinical efficacy warrants further investigation as a potential alternative therapy
Anti-Müllerian hormone in PCOS: Molecular regulation and emerging therapeutic strategies
Full text linkAnti-Müllerian hormone (AMH), a glycoprotein belonging to the transforming growth factor-beta (TGF-β) superfamily, is a key regulator of ovarian folliculogenesis. Dysregulated AMH expression is a hallmark of polycystic ovary syndrome (PCOS), a common endocrine and metabolic disorder characterized by hyperandrogenism, anovulation, and polycystic ovarian morphology. Elevated AMH levels in PCOS impair follicle-stimulating hormone (FSH) sensitivity, disrupt follicular maturation, and contribute to androgen excess—creating a feedback loop that exacerbates ovarian dysfunction. This review explores the complex regulatory mechanisms governing AMH expression, including transcriptional, post-transcriptional, and post-translational processes. It highlights the interplay between AMH, FSH, and androgen signaling pathways, emphasizing their roles in the pathophysiology of PCOS. Particular attention is given to the downstream SMAD-dependent signaling cascade, which mediates many of AMH’s biological effects. Additionally, we summarize emerging therapeutic strategies targeting AMH signaling, such as AMHR2 (anti-Müllerian hormone receptor type 2) antagonists, GnRH (gonadotropin-releasing hormone) antagonists, and aromatase inhibitors. A deeper understanding of AMH regulation and signaling provides critical insights into its role in PCOS progression and supports the development of novel, targeted treatments aimed at alleviating both reproductive and metabolic symptoms
Drug-coated balloon treatment for tasc c/d infrapopliteal disease: Two-year matched cohort outcomes
Full text linkAs the most common form of peripheral arterial disease, lower extremity arterial disease—caused by atherosclerotic stenosis or occlusion—has led to widespread concern due to the high risk of postoperative restenosis. This study aimed to evaluate the effectiveness of drug-coated balloon (DCB) angioplasty in treating severe infrapopliteal artery (IPA) lesions. Plain old balloon (POB) angioplasty served as the control. Patients who underwent procedures at our center for Trans-Atlantic Inter-Society Consensus (TASC) C/D IPA lesions between June 2020 and June 2022 and met the inclusion criteria were enrolled in this retrospective cohort study, which used the propensity score matching (PSM) method. The primary outcomes were the 2-year cumulative rates and survival trends of primary patency (PP) and target lesion revascularization (TLR), based on the treated lesions. Secondary outcomes included limb-based major amputation (MA) and patient-based all-cause death (ACD). A total of 278 target lesions were initially included, with significant differences (p < 0.05) observed in some non-outcome variables. After PSM, analyses were conducted on 240 target lesions, 221 limbs, and 195 patients. The PSM models satisfied both the common support and parallel trend assumptions. In terms of PP, the 2-year cumulative rate in the DCB group was significantly higher than in the POB group (48.0% vs. 22.9%, p < 0.001). The log-rank test yielded a p-value of &lt; 0.001, and the adjusted hazard ratio (HR) from Cox regression analysis was 2.303 [95% confidence interval (CI): 1.518–3.495]. However, there was no statistically significant difference in TLR between the two groups: the 2-year cumulative rates were 25.0% vs. 27.1% (p = 0.767), the log-rank test p-value was 0.563, and the adjusted HR was 0.956 (95% CI: 0.523–1.747). Similarly, no significant differences were found between groups in MA or ACD (p > 0.05). Based on these findings, the study concludes that for severe IPA lesions such as TASC C/D, DCB angioplasty is superior to POB angioplasty in maintaining primary patency over a 2-year period, without any inferiority in other clinical outcomes
Cutaneous inflammation alters nociceptor electrophysiology in guinea pigs but not rats
Full text linkInflammatory pain hypersensitivity is believed to result, in part, from increased excitability of nociceptive dorsal root ganglion (DRG) neurons. We previously demonstrated in guinea pigs that hindlimb inflammation induces electrophysiological changes in these neurons, including faster action potential (AP) and afterhyperpolarization (AHP) kinetics. Given that rats and guinea pigs are distinct species with notable differences in genetic composition and physiology, we hypothesized that cutaneous inflammation would have different effects on the electrophysiological properties of nociceptive DRG neurons in rats—the predominant rodent model for pain research. To test this hypothesis, we performed intracellular voltage recordings from DRG neurons (n = 430) in deeply anesthetized, untreated (control) and complete Freund’s adjuvant (CFA)-treated rats and guinea pigs. C-, Aδ-, and Aβ-nociceptors were identified based on their dorsal root conduction velocities (CVs) and responses to natural noxious stimuli. Consistent with our hypothesis, we observed no significant changes in any electrophysiological variables in rat nociceptive neurons four days after CFA-induced hindlimb inflammation. In contrast, guinea pig nociceptors exhibited a significant increase in CV and significant decreases in both AP and AHP durations. The inflammation-induced shortening of absolute and relative refractory periods likely contributes to increased firing frequency in nociceptive nerve fibers, thereby promoting inflammatory pain hypersensitivity. These findings suggest species-specific differences in peripheral neuronal mechanisms underlying inflammatory pain, potentially due to variation in ion channel expression and/or function in DRG neurons between rats and guinea pigs. Given the genetic and metabolic similarities between guinea pigs and humans, further research is warranted to determine whether guinea pigs may serve as a more accurate model of chronic inflammatory pain than rats
Vitamin D supplementation for tuberculosis prevention: A meta-analysis
Full text linkVitamin D plays an important role in immune regulation, prompting interest in its potential for preventing tuberculosis. However, clinical findings regarding its protective effects against tuberculosis infection and disease remain inconsistent. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the impact of vitamin D supplementation on the prevention of tuberculosis infection and the progression to active tuberculosis. We searched PubMed, Embase, Cochrane Library, and Web of Science databases through January 2025. Eligible studies involved participants without active tuberculosis at baseline and reported outcomes related to tuberculosis. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup and sensitivity analyses were conducted, and the certainty of evidence was evaluated using the GRADE approach. Six RCTs, involving 15,677 participants, met our inclusion criteria. Compared to placebo, vitamin D supplementation did not significantly reduce the risk of tuberculosis infection (5 RCTs; OR: 0.95; 95% CI: 0.79–1.14; p = 0.55) or the development of active tuberculosis (4 RCTs; OR: 0.77; 95% CI: 0.56–1.05; p = 0.10). The certainty of evidence was moderate for both outcomes. Subgroup analyses based on baseline vitamin D levels and duration of follow-up yielded consistent results. The incidence of serious adverse events was comparable between the vitamin D and placebo groups (OR: 1.02; 95% CI: 0.76–1.38; p = 0.87), and none of the serious events were attributed to vitamin D supplementation. In conclusion, vitamin D supplementation does not significantly reduce the risk of tuberculosis infection or progression to active tuberculosis, although it is safe and well tolerated
Development of a novel clinical prediction model for sepsis related mortality by combining NEWS, PIRO and lactate
Full text linkPrognostic assessment plays a crucial role in guiding therapeutic decision-making for patients with sepsis, particularly in intensive care settings. This study aimed to develop a multivariable model to predict 28-day mortality among intensive care unit (ICU) patients with sepsis by integrating serum lactate levels, the National Early Warning Score (NEWS), and the Predisposition, Infection, Response, and Organ Dysfunction (PIRO) score. Demographic information, clinical characteristics, and laboratory findings routinely collected at ICU admission were used to calculate the NEWS and PIRO scores for each patient. Patients were categorized as survivors or non-survivors based on their outcome. Both logistic regression and Cox proportional hazards models were applied for mortality prediction analysis. The final analysis included 205 patients diagnosed with sepsis (mean age: 73.6 ± 13.2 years; 53.2% male), of whom 109 died during hospitalization. Logistic regression analysis revealed that lactate, NEWS, and PIRO scores were independently associated with 28-day mortality. Combining lactate levels with NEWS and PIRO significantly enhanced mortality prediction, with the greatest accuracy observed when all three parameters were integrated. Pairwise analyses demonstrated that adding lactate to the base model significantly improved predictive accuracy (DBA: −0.103, p = 0.003), and incorporating lactate into a model already including NEWS further enhanced its predictive value (DBA: −0.042, p = 0.037). In conclusion, serum lactate measured at initial ICU admission provides valuable prognostic information for predicting 28-day mortality in sepsis patients. Furthermore, combining lactate levels with NEWS and PIRO scores substantially enhances the accuracy of mortality prediction in these patients