Tag: nevin manimala

Front Endocrinol (Lausanne). 2026 Aug 6;17:1876045. doi: 10.3389/fendo.2026.1876045. eCollection 2026.

ABSTRACT

BACKGROUND: Fasting induces coordinated metabolic and endocrine adaptations, yet its effects on thyroid hormone dynamics remain incompletely characterized. This systematic review and meta-analysis aimed to evaluate the effects of fasting on thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), and total triiodothyronine (total T3).

METHODS: PubMed, Web of Science, and Scopus were searched for peer-reviewed original research articles published in English between January 2000 and June 2026. Human studies examining fasting interventions lasting ≥ 24 h and reporting pre-post thyroid hormone data in adults were included. Standardized mean changes were calculated as Hedges’ g and pooled using random-effects models. Sensitivity analyses were performed using assumed pre-post correlations of r = 0.3, 0.5, and 0.7. To preserve statistical independence, one effect estimate per study (corresponding to the longest eligible fasting duration) was retained in the primary analysis. Subgroup analyses compared fasting durations of ≤ 3 days and > 3 days, and random-effects meta-regression examined fasting duration as a continuous moderator.

RESULTS: Fifteen studies were included in the systematic review. Fasting was associated with significant reductions in FT3 (k = 7; g = -1.979, 95% CI [-3.054, -0.905], p < 0.001), TSH (k = 10; g = -0.581, 95% CI [-0.882, -0.280], p < 0.001), and total T3 (k = 4; g = -1.337, 95% CI [-1.866, -0.807], p < 0.001). No significant change was observed in FT4 (k = 7; g = 0.073, 95% CI [-0.237, 0.382], p = 0.644). Heterogeneity was considerable for FT3, moderate for TSH and FT4, and low to moderate for total T3. Sensitivity analyses produced comparable estimates. Subgroup analysis indicated a larger FT3 reduction after fasting > 3 days, whereas duration subgroup differences were not significant for TSH, FT4, or total T3. Meta-regression showed no significant linear association between fasting duration and any thyroid outcome.

CONCLUSIONS: Fasting produces a biomarker-specific thyroid response characterized by pronounced reductions in FT3 and total T3, a moderate decrease in TSH, and relative stability of FT4. This pattern is more consistent with altered peripheral thyroid hormone metabolism and reduced T4-to-T3 conversion than with a uniform suppression of thyroid hormone production.

PMID:42625622 | PMC:PMC13489877 | DOI:10.3389/fendo.2026.1876045

Front Oncol. 2026 Aug 6;16:1903503. doi: 10.3389/fonc.2026.1903503. eCollection 2026.

ABSTRACT

BACKGROUND: The prognostic significance of glycemic status in pancreatic ductal adenocarcinoma (PDAC) remains controversial, largely due to heterogeneity in the exposure definitions (new-onset vs. long-standing diabetes, metformin use, and single fasting glucose measurement). This meta-analysis aimed to clarify the association of four distinct glycemic exposures with overall survival (OS) in patients with PDAC.

METHODS: We systematically searched Web of Science, PubMed, and EMBASE from 1 January 2010 to 1 June 2026. Cohort studies reporting hazard ratios (HRs) for OS were included and categorized into four subgroups: 1) new-onset diabetes (NOD) vs. non-diabetes; 2) long-standing diabetes (LSD) vs. non-diabetes; 3) metformin use vs. non-use; and 4) hyperglycemia (elevated preoperative fasting glucose or poor glycemic control) vs. normoglycemia. Random-effects meta-analyses were performed. Heterogeneity was assessed using I ², and publication bias was evaluated via funnel plots and the trim-and-fill method.

RESULTS: A total of 21 studies (six for NOD, four for LSD, six for metformin, and eight for hyperglycemia) were included. NOD was significantly associated with worse OS (pooled HR = 1.33, 95%CI = 1.13-1.57, I ² = 72.5%). LSD showed no significant association (HR = 1.21, 95%CI = 0.98-1.49, I ² = 70.1%). Metformin use was associated with a 33% reduction in mortality (HR = 0.67, 95%CI = 0.53-0.84, I ² = 70.5%). Preoperative hyperglycemia or poor glycemic control consistently predicted worse OS (HR = 1.45, 95%CI = 1.29-1.62, I ² = 25.7%). No substantial publication bias was detected (trim-and-fill added zero studies for all subgroups).

CONCLUSIONS: NOD and preoperative hyperglycemia are independent negative prognostic factors in PDAC, whereas LSD did not show a statistically significant association. An indirect comparison between NOD and LSD yielded a null result, suggesting that diabetes duration may not be the key determinant of prognosis. The potential mediating role of hyperglycemia requires further investigation. Metformin use was associated with a marked survival benefit, particularly in patients with resectable tumors. These findings highlight the need to differentiate diabetes subtypes and optimize glycemic control, while clinical decisions regarding antidiabetic agents should be made with caution.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=261415381, identifier CRD420261415381.

PMID:42625611 | PMC:PMC13489918 | DOI:10.3389/fonc.2026.1903503

Front Immunol. 2026 Aug 6;17:1873001. doi: 10.3389/fimmu.2026.1873001. eCollection 2026.

ABSTRACT

BACKGROUND: Dupilumab is an effective treatment for moderate-to-severe atopic dermatitis (AD), yet a substantial proportion of patients develop ocular complications collectively termed dupilumab-associated ocular surface disease (DAOSD). Despite multiple proposed mechanisms – including goblet cell depletion, mucin deficiency, Th1/Th17 immune shifts, and microbiome alterations – no upstream epithelial cytokine marker has been clearly identified.

OBJECTIVE: To evaluate whether plasma cytokines differ between AD patients treated with dupilumab who develop ocular complications and those without ocular involvement.

METHODS: Complex dermatological examination was performed in adult AD patients receiving dupilumab for ≥24 months. Plasma cytokines (IFN-γ, TNF-α, IL-23, IL-2, IL-31, IL-6, IL-17A, IL-17E, IL-12p70, TSLP, IL-4, IL-5, IL-13, IL-10, IL-33) were quantified under unstimulated and PMA/ionomycin-stimulated conditions in winter and summer seasons. Differences between groups were assessed using non-parametric tests (Mann-Whitney U test and Kolmogorov-Smirnov test). To account for multiple comparisons across the large number of tested cytokines, false discovery rate (FDR) correction was performed using the Benjamini-Hochberg procedure with a significance threshold of q = 0.05. Receiver operating characteristic (ROC) analysis was performed to evaluate biomarker potential to explore potential discriminative performance. AUC values were calculated using empirical (non-parametric) ROC analysis.

RESULTS: During the summer period, stimulated thymic stromal lymphopoietin (TSLP) levels were nominally higher in patients with ocular complications compared with those without (p = 0.045). However, this difference did not remain statistically significant after FDR correction. In winter, stimulated TSLP showed a non-significant trend toward higher levels (p = 0.088). No other cytokines differed between groups. ROC analysis demonstrated moderate discriminative ability of stimulated TSLP (AUC 0.81 in summer; 0.70 in winter), although confidence intervals were wide.

CONCLUSION: Stimulated TSLP may represent a preliminary observation requiring confirmation in dupilumab-treated AD patients with ocular complications.

PMID:42625606 | PMC:PMC13489922 | DOI:10.3389/fimmu.2026.1873001

Front Oncol. 2026 Aug 6;16:1912193. doi: 10.3389/fonc.2026.1912193. eCollection 2026.

ABSTRACT

INTRODUCTION: Head and neck cancer (HNC) is characterized by substantial immune heterogeneity and limited availability of clinically actionable molecular targets. Here, we developed an integrative single-cell eQTL-driven multi-omics framework to identify immune cell-specific causal genes and prioritize drug-repurposing candidates for HNC.

METHODS: Single-cell eQTL data from the OneK1K cohort were integrated with European HNC GWAS summary statistics through two-sample Mendelian randomization, followed by transcriptomic differential expression analysis and weighted gene co-expression network analysis. Candidate targets were further evaluated using diagnostic modeling, immune infiltration analysis, single-cell and spatial transcriptomics, Bayesian colocalization, Western blot validation, molecular docking, molecular dynamics simulations, and FAERS-based safety profiling.

RESULTS: We identified 494 immune cell-specific eGenes causally associated with HNC risk. Multi-layered target prioritization highlighted AIM1 and ANXA1 as protective immune-related genes, both of which were downregulated in HNC tissues and showed cell-type-preferential expression in T cells and monocytes, respectively. A dual-gene diagnostic model achieved strong discrimination performance with an AUC of 0.917. Colocalization analysis supported shared genetic signals between AIM1 or ANXA1 loci and HNC susceptibility, while Western blotting confirmed reduced AIM1 and ANXA1 protein expression in SCC-9 cells compared with normal HOK cells. Drug screening and molecular docking identified topotecan as a candidate ligand for AIM1 and terbutaline as a candidate ligand for ANXA1. Subsequent molecular dynamics simulations demonstrated stable drug-target complexes with favorable binding free energies. FAERS analysis further characterized the adverse-event spectrum and potential safety considerations for both compounds.

DISCUSSION: Collectively, this study provides a single-cell genetic and pharmacological framework for defining immune-related causal targets in HNC and supports AIM1 and ANXA1 as promising biomarkers and therapeutic entry points for precision drug development.

PMID:42625604 | PMC:PMC13489846 | DOI:10.3389/fonc.2026.1912193

Front Med (Lausanne). 2026 Aug 6;13:1899303. doi: 10.3389/fmed.2026.1899303. eCollection 2026.

ABSTRACT

BACKGROUND: Postoperative deep vein thrombosis (DVT) is an important complication in older patients undergoing transurethral resection of the prostate (TURP). Although associations between geriatric vulnerability and thrombosis are established, these domains are not routinely integrated into TURP-specific risk assessment. We therefore evaluated whether preoperative geriatric assessment (GA) domains add predictive information to age-adjusted D-dimer in this setting.

METHODS: In this retrospective single-center cohort (n = 420; 294 development and 126 internal validation), an exploratory two-stage procedure comprising univariable screening followed by LASSO regression identified four predictors: preoperative age-adjusted D-dimer positivity, serum albumin, Activities of Daily Living (ADL) score, and Mini-Mental State Examination (MMSE) score. An unweighted logistic regression model was used as the primary integrated model. Discrimination, calibration, precision-recall performance, and decision-curve analysis were assessed. Logistic regression (LR), random forest (RF), and support vector machine (SVM) were additionally compared using the same development-set cross-validated sigmoid calibration framework.

RESULTS: The perioperative DVT incidence was 11.19% (47/420). In the internal validation cohort, the primary integrated LR model achieved an AUC of 0.750 (95% CI: 0.557-0.903), a precision-recall AUC of 0.457, and a Brier score of 0.081. Compared with the D-dimer-only clinical model, the integrated model showed improvements in NRI (0.893, 95% CI: 0.360-1.345; P < 0.001) and IDI (0.078, 95% CI: 0.020-0.145; P = 0.015). At a prespecified probability threshold of 0.20, sensitivity was 0.571 and specificity was 0.911. In the uniformly calibrated algorithm comparison, SVM had the highest AUC point estimate (0.796), but its difference from LR (0.751) was not statistically conclusive (bootstrap difference 0.045, 95% CI: -0.004 to 0.102; P = 0.071).

CONCLUSIONS: A TURP-specific model combining preoperative age-adjusted D-dimer with geriatric assessment domains showed preliminary value for postoperative DVT risk stratification. Because the study was retrospective, single-center, and based on only 47 events, the findings should be considered exploratory and require prospective external validation before clinical implementation.

PMID:42625599 | PMC:PMC13489928 | DOI:10.3389/fmed.2026.1899303

Front Pharmacol. 2026 Aug 6;17:1902928. doi: 10.3389/fphar.2026.1902928. eCollection 2026.

ABSTRACT

BACKGROUND: Exposure to fine particulate matter (PM2.5) is a well-established risk factor for lung inflammation and injury. Macrophages are key innate immune cells in the lung and play critical roles in maintaining pulmonary immune homeostasis and orchestrating inflammatory responses following environmental insults. However, the precise mechanisms by which PM2.5 modulates macrophage function and contributes to lung injury remain incompletely understood. This study aimed to investigate the role of macrophage phenotypic polarization in PM2.5-induced lung injury and the underlying molecular mechanisms.

METHODS: A subacute exposure (21-day) PM2.5 mouse model and bone marrow-derived macrophages (BMDMs) were used in vivo and in vitro to evaluate the effects of PM2.5 on pulmonary inflammation, macrophage polarization, mitochondrial injury, and cGAS-STING signaling activation. Pharmacological inhibition of cGAS was performed using RU.521 to assess the functional role of the cGAS-STING pathway in PM2.5-induced macrophage activation and lung injury. Statistical analyses were conducted to compare differences between experimental groups.

RESULTS: PM2.5 exposure triggered pulmonary inflammation and tissue injury, accompanied by increased pulmonary macrophage accumulation and polarization toward the pro-inflammatory M1 phenotype. Mechanistically, PM2.5 induced mitochondrial damage in macrophages, leading to mtDNA release and subsequent activation of cGAS-STING signaling. Pharmacological inhibition of cGAS with RU.521 attenuated STING pathway activation, macrophage M1 polarization, and PM2.5-induced pulmonary inflammation and lung injury in mice.

CONCLUSIONS: Our study indicates that PM2.5 promotes lung injury by driving macrophage M1 polarization through an mtDNA-cGAS-STING axis, highlighting cGAS-STING signaling as a potential therapeutic target for PM2.5-related lung injury.

PMID:42625593 | PMC:PMC13489883 | DOI:10.3389/fphar.2026.1902928

Front Physiol. 2026 Aug 6;17:1888004. doi: 10.3389/fphys.2026.1888004. eCollection 2026.

ABSTRACT

INTRODUCTION: Neuropathic pain arises from lesions or dysfunction within the somatosensory system, leading to chronic disability and scarce effective therapies. The NAD⁺-dependent deacetylase SIRT6 participates in aging and inflammatory responses, yet its involvement in neuropathic pain has remained unexplored. Using two selective SIRT6 activators-UBCS039 and MDL-800-in a rat model of chronic constriction injury (CCI), we asked whether pharmacological SIRT6 activation could ameliorate pain behaviors and, if so, through what molecular route.

METHODS: CCI surgery was performed in male Sprague-Dawley rats, and SIRT6 expression in the spinal dorsal horn was assessed post-operatively. From day 3 to day 9 after injury, rats received daily intraperitoneal injections of UBCS039 (20 mg/kg) or MDL-800 (10 mg/kg). On day 10, paw withdrawal thresholds (PWT) and paw withdrawal latencies (PWL) were measured. Spinal cord tissues were harvested for assessment of oxidative stress markers (TBARS, SOD, GSH-Px), pro-inflammatory cytokines (IL-1β, IL-18), NLRP3 inflammasome components (NLRP3, ASC, cleaved caspase-1), and Nrf2/HO-1 protein levels. An additional cohort received the Nrf2 inhibitor ML385 (30 mg/kg) 30 minutes before each MDL-800 dose to verify pathway specificity.

RESULTS: CCI markedly reduced SIRT6 mRNA and protein levels in the spinal dorsal horn (n=6 per group, P<0.001). Both UBCS039 and MDL-800 significantly elevated PWT and PWL (n=8, P<0.001), reduced TBARS content, restored SOD and GSH-Px activities (n=6, P<0.01), and suppressed IL-1β and IL-18 production at both transcript and protein levels. Western blotting revealed that SIRT6 activation inhibited NLRP3, ASC, and cleaved caspase-1 expression while reversing the CCI-induced decline of Nrf2 and HO-1. Co-administration of ML385 abolished these protective effects, rendering all measured parameters-including NLRP3 protein, cytokine levels, and pain thresholds-statistically indistinguishable from the untreated CCI group (P>0.05).

CONCLUSION: Activating SIRT6 dampens neuropathic pain and NLRP3 inflammasome activation by restoring Nrf2 signaling. This positions SIRT6 as a previously unrecognized therapeutic target for neuropathic pain.

PMID:42625583 | PMC:PMC13489838 | DOI:10.3389/fphys.2026.1888004

Front Plant Sci. 2026 Aug 6;17:1880606. doi: 10.3389/fpls.2026.1880606. eCollection 2026.

ABSTRACT

INTRODUCTION: This study assessed the agronomic performance, grain composition, and mineral traits of six maize genotypes grown under Black Sea conditions in Türkiye during the 2020 and 2021 growing seasons.

METHODS: The experiment took place in Samsun-Bafra using a randomized complete block design with four replications. Agronomic and morphological traits included days to pollen shedding, plant height, ear height, grain moisture, and grain yield, while grain quality was evaluated through compositional traits (ash, fat, protein, cellulose, and starch) and mineral concentrations (Fe, Cu, Mn, Ca, and Mg). Data were analyzed using linear mixed-effects models, while correlation and principal component analyses were used only as exploratory descriptive tools to visualize general trait relationships and genotype-year tendencies.

RESULTS: Significant effects of genotype and year were observed for days to pollen shedding, plant height, and ear height. Grain moisture was significantly influenced by year and the interaction between genotype and year, whereas grain yield was primarily affected by genotype. Among the tested genotypes, P2088 yielded the highest average grain yield (14.50 t ha^-1), while KALUMET showed the latest flowering and the tallest plants. Protein content was the only compositional trait significantly impacted by genotype, with DKC6680 showing the highest average protein content (10.33%) and P2088 the lowest (9.16%). Conversely, mineral traits remained statistically stable across genotypes and years.

DISCUSSION: Overall, the findings provide preliminary information on the regional performance of six maize genotypes under Black Sea ecological conditions and may support further multi-location testing before cultivar recommendation.

PMID:42625576 | PMC:PMC13489869 | DOI:10.3389/fpls.2026.1880606

Front Psychol. 2026 Aug 6;17:1911170. doi: 10.3389/fpsyg.2026.1911170. eCollection 2026.

ABSTRACT

Elite sport increasingly requires athletes to manage large volumes of competition-relevant information under conditions characterized by uncertainty, time pressure, and continuous adaptation. Although previous research has identified important perceptual, cognitive, and motivational foundations of athletic expertise, less attention has been given to how supportive coaching environments are associated with athletes’ ability to organize and use competition-relevant information. Drawing on Information Scaffolding Theory, this cross-sectional study examined whether perceived coach support is linked to competitive information processing through regulatory information management capability, and whether competitive pressure functions as a boundary condition. Survey data were collected from 500 Chinese competitive athletes from elite university, provincial elite, and national elite sport settings. Structural equation modeling indicated that perceived coach support was positively associated with regulatory information management capability and competitive information processing. Regulatory information management capability showed a positive indirect association between perceived coach support and competitive information processing. Conditional indirect effects were statistically significant at low, mean, and high levels of competitive pressure; however, the index of moderated mediation was not significant, indicating that the hypothesized moderation by competitive pressure was not supported. The findings are consistent with a statistical mediation model in which coach support and self-regulatory information management are linked with competitive information processing. Because the design is cross-sectional and based on self-report data, the results should be interpreted as associative rather than causal.

PMID:42625568 | PMC:PMC13489832 | DOI:10.3389/fpsyg.2026.1911170

Health Psychol Rep. 2025 Aug 28;14(3):280-292. doi: 10.5114/hpr/203960. eCollection 2026.

ABSTRACT

BACKGROUND: Research indicates that narcissistic traits negatively correlate with empathy and may significantly predict interpersonal behaviors. Narcissism is also associated with a higher risk of addiction and mental health issues, making its analysis among future healthcare workers particularly important.

PARTICIPANTS AND PROCEDURE: A cross-sectional study was conducted using a quantitative method with the computer-assisted web interview (CAWI) technique on a group of 1,092 medical and psychology students in Poland and France. The NPI-40 test was used to analyze narcissism. The study was fully anonymous and voluntary. Students were invited to participate through university mailing systems and information posted on social media platforms.

RESULTS: Our study found differences in NPI-40 scores based on gender, country, and field of study. Men scored higher than women in both France (M = 10.60, SD = 6.00) and Poland (M = 12.90, SD = 6.60), with a statistically significant gender effect. While medical students had slightly higher scores than psychology students, the difference was not significant. However, gender-field interactions varied by country: in France, male medical students scored higher than male psychology students, whereas in Poland, psychology students had higher scores than medical students. Despite these findings, the models explained only 5% of the variance in France and 3% in Poland, suggesting that other factors contribute to narcissism levels in this studied population.

CONCLUSIONS: These results may prove important in designing programs that support students’ mental health and interventions aimed at improving interpersonal relationships, especially in the case of Polish medical students.

PMID:42625564 | PMC:PMC13489825 | DOI:10.5114/hpr/203960