Nevin Manimala

Cell Commun Signal. 2025 Dec 11. doi: 10.1186/s12964-025-02573-6. Online ahead of print.

ABSTRACT

BACKGROUND: Given the role of metabolism in brain health and disease, the investigation of the role of insulin (INS) and insulin-like growth factors (IGFs) as potential therapeutic strategies for neurodegenerative diseases is currently underway. Yet, the signaling pathways associated with INS and IGFs in the brain remain elusive, particularly for the human brain. Unraveling these pathways is critical for harnessing their therapeutic potential in metabolism-associated brain disorders.

METHODS: This study employed phosphoproteomics using a human neuroblastoma cell line, SH-SY5Y, to unravel the signaling networks of INS, IGF-1, and IGF-2. Briefly, cells were stimulated for 10 and 60-minutes with the ligands, followed by protein extraction, trypsin digestion, tandem mass tag (TMT) labelling and phosphopeptide enrichment using an immobilized metal affinity chromatography (IMAC) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The data were processed using R statistical software. Protein annotations were obtained from the UniprotKB database, and pathway enrichment analysis was performed using Ingenuity Pathway Analysis (IPA).

RESULTS: Phosphoproteomics performed at 10 and 60 min identified 34,358 phosphosites, of which 3,284 were significant at 10 min and 2,374 at 60 min (p.adj < 0.05) across all three ligands. Ligand stimulation induced modulation in phosphorylation at both the receptor level and downstream targets at serine (S), threonine (T), and tyrosine (Y) residues. LIMA1-Y229, a regulator of actin-cytoskeletal function, was the most prominent Y phosphosite across all ligands. IPA identified Rho GTPase as the most significantly enriched pathway, with IGF-1 predominantly driving phosphorylation of Rho GTPase effectors such as Rho guanine nucleotide exchange factors (ARHGEFs), Rho GTPase activating proteins (ARHGAPs) and CDC42. Myocardin-related transcription factor A (MRTFA), a transcriptional target of Rho GTPase, was increased in ligand-stimulated cells at 10 min, and inhibition of the Rho/SRF pathway and PI3K by CCG1423 and wortmannin, respectively, prevented nuclear localization of IGF-1-induced MRTFA.

CONCLUSIONS: This study demonstrates that INS, IGF-1, and IGF-2 regulate Rho GTPase and MRTFA activation, thereby contributing to the control of actin cytoskeletal dynamics in neuronal cells. Given the role of INS and IGFs in neuronal survival and neurodegenerative conditions, elucidating these mechanisms is of critical importance, as it offers insights into disease pathogenesis and potential therapeutic targets.

PMID:41382216 | DOI:10.1186/s12964-025-02573-6

Diabetol Metab Syndr. 2025 Dec 11. doi: 10.1186/s13098-025-02052-5. Online ahead of print.

ABSTRACT

BACKGROUND: Metabolic syndrome (MS) poses a growing threat to adolescent health, yet its sex-specific patterns remain inadequately characterized. This study aimed to investigate sex differences in MS prevalence, risk factor clustering, and metabolic phenotypes among U.S. adolescents.

METHODS: We analyzed cross-sectional data from 6,989 adolescents aged 12-19 years, representing 30.97 million U.S. adolescents, from the National Health and Nutrition Examination Survey (1999-2020). MS was defined based on abdominal obesity, elevated blood pressure, hyperglycemia, and dyslipidemia, using weighted analyses to account for complex survey design.

RESULTS: The overall MS prevalence was 5.1%, with a significantly higher prevalence in males than in females (6.1% vs. 4.1%, P = 0.017). Critically, no significant temporal trends in MS prevalence were observed over the 20-year period for either sex. Males accumulated more metabolic risk factors than females, showing higher rates of elevated BP (5.9% vs. 0.9%), fasting glucose (22.7% vs. 10.4%), and triglycerides (8.8% vs. 6.4%), whereas, females had higher prevalences of abdominal obesity (25.9% vs. 12.6%) and low HDL-C (22.8% vs. 18.8%). Moreover, metabolically unhealthy obesity was more common in males (13.7% vs. 10.0%). Subgroup analyses showed significant sex disparities persisted among ages 12-15, obese, non-Hispanic White, and high-income subgroups. Sensitivity analyses using alternative definitions, including waist-to-height ratio for abdominal obesity, robustly confirmed the male predominance in MS prevalence.

CONCLUSION: Male U.S. adolescents exhibited a higher MS prevalence and a more unfavorable aggregation of metabolic risk factors than females. The stability of MS prevalence over the two-decade period highlighted the need for sex-specific and developmentally targeted interventions, especially within identified high-disparity subgroups.

PMID:41382204 | DOI:10.1186/s13098-025-02052-5

Indian Dermatol Online J. 2025 Dec 11. doi: 10.4103/idoj.idoj_983_24. Online ahead of print.

ABSTRACT

BACKGROUND: Age-related decline in skin moisture affects many older adults and is exacerbated by factors such as sun exposure and lifestyle habits. Recent research has explored the potential of exercise to improve skin moisture; however, the optimal activity levels remain unclear. This study investigated the link between exercise habits and skin moisture to inform clinical preventive strategies.

PATIENTS AND METHODS: In this cross-sectional study, we investigated the relationship between stratum corneum (SC) hydration and lifestyle habits in older adults using the International Physical Activity Questionnaire (IPAQ) short version and a self-administered questionnaire. Participants were recruited from community spaces and local elderly facilities. Data were collected between September 1 and December 31, 2023. Based on the IPAQ responses, physical activity levels were classified as low, moderate, or high, and SC hydration was measured on the right forearm. Statistical analyses were conducted using t-tests.

RESULTS: A total of 124 participants were included, with a mean age of 84.3 ± 9.2 years. Among them, 69.4% were female. The participants were belonged to low (57) and moderate/high (67) activity-level groups, with significant differences in SC hydration (P = 0.001) between the groups.

LIMITATIONS: Cross-sectional design, restricted sample, and potential unmeasured confounding may limit interpretation.

CONCLUSIONS: The results suggested a significant difference in horny skin water content between the low-and moderate/high-activity groups, indicating that exercise habits may enhance skin moisturization, possibly via increased skin blood flow, stress reduction, improved sleep, and increased collagen production. Exercise regimens may mitigate age-related decline in skin function, potentially offering a preventive strategy for skin dryness and related conditions in older adults.

PMID:41382199 | DOI:10.4103/idoj.idoj_983_24

Eur J Med Res. 2025 Dec 11. doi: 10.1186/s40001-025-03639-4. Online ahead of print.

ABSTRACT

BACKGROUND: Vestibular migraine (VM) is often considered a subtype of migraine, but the pathogenesis of both has not been fully elucidated. The aim of this study is to integrate clinical data systems through transcriptome sequencing to explore the similarities and differences between the two in terms of pathogenesis and clinical manifestations and predict therapeutic drugs.

METHODS: This study included 9 cases of VM, 6 cases of migraine only (MO), and 14 healthy controls (HC). Detailed records were kept of each participants basic information and clinical characteristics related to their onset of illness, with statistical analysis conducted using R. Additionally, peripheral blood mononuclear cells (PBMCs) from each participant were collected for high-throughput RNA sequencing. Next, DEseq2 packages were used to identify differentially expressed genes (DEGs) between MO/HC, VM/HC, and VM/MO. Pearson correlation was used to calculate co-expressed genes between MO/HC and VM/HC, and gene sets were functional annotation and pathway enrichment analysis. Furthermore, hub genes were screened using protein interaction and Cytoscapes Degree algorithm, and further evaluation was conducted using transcriptome data. Finally, common therapeutic drugs were predicted using DGIdb, Drugbank, and ClinicalTricals.

RESULTS: Compared to HC, both VM and MO patients exhibited higher incidences of anxiety, depression, and sleep disorders, with overlapping triggers and symptoms. However, VM patients demonstrated higher headache frequency, longer attack duration, and a higher prevalence of abnormal vestibular function tests. Transcriptomic analysis revealed significant activation of neutrophil activation and cholesterol metabolism pathways in MO, while Interleukin-17 (IL-17) signaling, calcium signaling, and estrogen-related pathways were prominent in VM. Co-expression analysis identified IL-17 signaling as a key pathway, more activated in VM than MO, potentially explaining VM’s higher attack frequency and delayed onset (average 9 years after migraine diagnosis). C-X-C motif chemokine ligand 8 (CXCL8) was validated as a common biomarker for both conditions. Drug prediction identified 55 potential therapeutic agents, including nonsteroidal antiinflammatory drugs (NSAIDs), vitamin A, and verapamil.

CONCLUSION: VM and MO share overlapping clinical and pathogenic features, particularly inflammation and metabolic dysregulation. CXCL8 serves as a shared biomarker, and NSAIDs, vitamin A, and verapamil may offer therapeutic benefits. The heightened inflammatory activation in VM suggests it could represent an advanced stage of MO, emphasizing the importance of early intervention in migraine progression.

PMID:41382196 | DOI:10.1186/s40001-025-03639-4

Eur J Med Res. 2025 Dec 11. doi: 10.1186/s40001-025-03599-9. Online ahead of print.

ABSTRACT

OBJECTIVES: To develop a nomogram-based risk prediction model utilizing patients’ clinical characteristics for post-endoscopic submucosal dissection hemorrhage, and to evaluate its clinical utility.

METHODS: A total of 250 patients who developed postprocedural hemorrhage after endoscopic submucosal dissection (ESD) for gastrointestinal tumors at our institution (2022-2024) were enrolled. Enrichment criteria included at least one high-risk factor for complications (e.g., lesion size > 10 mm, antithrombotic medication use, or comorbid diabetes/hypertension) or early post-ESD symptoms suggestive of complications. Patients were randomly divided into a training set (n = 175) and a validation set (n = 75) at a 7:3 ratio. In the training set, multivariate logistic regression identified independent prognostic risk factors to construct the nomogram. Model performance was assessed via receiver operating characteristic (ROC) curves and calibration plots, with external validation performed in the validation set.

RESULTS: Hemorrhage occurred in 70/175 cases (40.00%) in the training set and 28/75 (37.33%) in the validation set, with no statistically significant intergroup differences in incidence or baseline characteristics (P > 0.05). Univariate analysis revealed significant disparities between hemorrhage and non-hemorrhage groups in age, hemoglobin, white blood cell count, platelet count, prothrombin time, activated partial thromboplastin time, and fibrinogen (P < 0.05). Multivariate analysis confirmed age, hemoglobin, white blood cell count, platelet count, prothrombin time, activated partial thromboplastin time, and fibrinogen were independent risk factors (P < 0.05). The nomogram demonstrated C-index were 0.861 and 0.841 (validation), and mean absolute errors were 0.151 and 0.171, respectively. AUC values were 0.849 (95% CI 0.778-0.920) and 0.824 (95% CI 0.707-0.941), indicating high predictive accuracy.

CONCLUSIONS: The clinical feature-based nomogram exhibits good predictive performance and reliability in both training and validation cohorts, serving as a valuable tool for prognostic evaluation in gastrointestinal tumor patients who experience post-ESD hemorrhage.

PMID:41382183 | DOI:10.1186/s40001-025-03599-9

BMC Psychol. 2025 Dec 11. doi: 10.1186/s40359-025-03808-4. Online ahead of print.

ABSTRACT

BACKGROUND: In today’s volatile, uncertain, complex and ambiguous (VUCA) environment, organizations expect employees to change from passively accepting task requests to actively pursuing improvement. Feedback-seeking behavior has gained widespread attention. The study aims to adopt Conservation of Resources Theory to examine the influence mechanism and boundary condition of performance pressure and time pressure on employee feedback-seeking behavior.

METHODS: To investigate the mediating role of work rumination and the moderating role of competitive climate on the relationship between performance pressure, time pressure and employee feedback-seeking behavior, data were collected from 410 Chinese employees through a two-wave survey distributed via WJX.cn. Statistical analyses were performed with Spss 26, Amos 26 and Process 4.0.

RESULTS: The findings indicate that work rumination mediates the relationship between performance pressure, time pressure and employee feedback-seeking behavior. The impact of performance pressure is stronger than that of time pressure. Competitive climate positively moderates the indirect influence of performance pressure and time pressure on employee feedback-seeking behavior through work rumination.

CONCLUSION: The study deepens the understanding of how diverse workplace stressors shape employees’ feedback-seeking behavior. Particularly in competitive work environments, organizations can foster a culture of healthy competition by implementing well-designed performance requirements and reasonable time expectations, thereby motivating employees to transform work pressures into proactive feedback-seeking for professional growth.

PMID:41382169 | DOI:10.1186/s40359-025-03808-4

J Surg Res. 2025 Dec 10;317:173-180. doi: 10.1016/j.jss.2025.11.018. Online ahead of print.

ABSTRACT

INTRODUCTION: Pediatric gunshot wounds to the head (GSWH) are among the most devastating injuries, with mortality rates ranging from 20% to 65%. Prognostic tools such as the St. Louis Score (SLS) and Rotterdam computed tomography (CT) Score have been studied, but data specific to pediatric populations are limited. This study aimed to identify factors predictive of mortality and functional outcomes in pediatric GSWH and evaluate the predictive accuracy of existing scoring systems.

METHODS: We retrospectively reviewed all 14 pediatric patients (≤18 y old) with GSWH at an urban, level 1 trauma center between 2010 and 2023. Patient demographics, injury characteristics, imaging findings, and outcomes were analyzed. Predictive tools were evaluated using receiver operator curve analysis, and statistical comparisons were conducted between survivors and nonsurvivors and between favorable (Glasgow Outcome Score ≥ 4) and unfavorable outcomes.

RESULTS: The overall mortality rate was 65%. Survivors had significantly higher admission Glasgow Coma Scale (11 versus 4, P = 0.008), lower international normalized ratio (1.1 versus 1.7, P = 0.015), lower serum glucose (138 versus 225, P = 0.021), and lower Rotterdam CT Scores (3 versus 5, P = 0.038). SLS and Rotterdam CT Score demonstrated poor predictive accuracy for mortality.

CONCLUSIONS: Survivors of pediatric GSWH exhibited distinct clinical and laboratory profiles on admission, including higher Glasgow Coma Scale and lower international normalized ratio and glucose levels. While the Rotterdam CT Score performed better than the SLS, both prognostic tools were suboptimal to predict favorable outcomes for this cohort. Larger studies are needed to refine predictive models and improve management strategies in pediatric GSWH.

PMID:41380225 | DOI:10.1016/j.jss.2025.11.018

Sleep Med. 2025 Dec 6;138:108708. doi: 10.1016/j.sleep.2025.108708. Online ahead of print.

ABSTRACT

Although sodium-glucose transporter 2 inhibitors (SGLT2is) are recommended medications for the treatment of type 2 diabetes mellitus (T2DM), conclusive evidence suggesting that they could alleviate the common complication of obstructive sleep apnea (OSA) in T2DM is lacking at present. Our objective is to systematically summarize the clinical evidence of SGLT2is for OSA in patients with T2DM by searching 12 databases and registers from the establishment to July 25, 2025. We included randomized controlled trials (RCTs) and non-randomized studies evaluating the use of SGLT2is for OSA in participants with T2DM. This analysis was registered on the PROSPERO website (CRD42024576637) and performed in accordance of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Data were extracted by two investigators separately, and the meta-analysis of sleep-disordered breathing parameters, metabolic parameters, and adverse events outcomes was conducted using Review Manager 5.4 and Stata 15.0. Nine studies, including six RCTs and three non-RCTs, were included. The results demonstrated that the efficacy of SGLT2is in reducing the apnea-hypopnea index (AHI) (mean difference [MD] = -12.57, 95 % confidence interval [CI]: [-21.47, -3.66], P = 0.006, I² = 87 %) and increasing the lowest oxygen saturation (lowest SpO₂) was superior to that of the control interventions with other hypoglycemic drugs. Patients with T2DM showed a 50 % relative risk reduction for incident OSA when receiving SGLT2is in comparison with placebo. Furthermore, the adverse event rate in the SGLT2i group was comparable to that in the control group. Considering of the risk reduction for incident OSA and the enhanced metabolic parameters observed with SGLT2i administration, these drugs may be recommended as useful medication for the management of T2DM and OSA. However, Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) assessments rated the evidence quality as low to moderate because of inconsistency and indirectness. Given the weak strength of the evidence, further trials with sufficient statistical power are still needed to confirm efficacy and safety.

PMID:41380220 | DOI:10.1016/j.sleep.2025.108708

Burns. 2025 Dec 3;52(1):107819. doi: 10.1016/j.burns.2025.107819. Online ahead of print.

ABSTRACT

BACKGROUND: Hypertrophic scarring (HTS) is a major concern after burns. While conservative therapy is standard for superficial partial thickness burns and debridement for deep burns, the optimal treatment for intermediate depth burns remains unclear. This retrospective study assesses whether enzymatic debridement with Nexobrid® (EDNX) can reduce HTS in intermediate depth burns.

METHODS: Patients with intermediate depth burns (healing potential (HP) 14-21 days), assessed by laser Doppler imaging (LDI), were retrospectively analysed for HTS following conservative therapy or EDNX. Regions of interest (ROIs) were analysed for flux values, surface area, and wound closure time. HTS within ROIs was evaluated at 3-6, 6-12, and 12-24 months post-injury, independently by two burn specialists.

RESULTS: In total, 87 ROIs were analyzed in 62 patients, with 44 ROIs treated conservatively and 43 ROIs treated with EDNX. HTS was still present after 12 months in 13.6 % (6/44) of ROIs in the conservative group and 9.3 % (4/43) in the EDNX group, showing no statistically significant difference between the two groups (p = 0.186). The conservative group and EDNX group were comparable, with no statistically significant difference in flux values (346.41 ± 22.90 vs. 340.19 ± 20.75, p = 0.275) or wound closure time (22.70 ± 7.90 vs. 23.42 ± 7.47, p = 0.862). A statistically significant correlation was found between HTS formation and wound closure time (p = 0.001); however, no significant correlation was observed between HTS formation and flux values (p = 0.262).

CONCLUSION: The overall incidence of HTS after scar maturation was low in both the conservative group (13.6 %) and in the EDNX group (9.3 %). A small, but in significant difference was observed in HTS prevalence between intermediate depth burns treated conservatively and those treated with EDNX. These findings support conservative management through local wound care as the preferred approach for intermediate depth burns.

PMID:41380209 | DOI:10.1016/j.burns.2025.107819

Drug Alcohol Depend. 2025 Dec 5;278:112995. doi: 10.1016/j.drugalcdep.2025.112995. Online ahead of print.

ABSTRACT

BACKGROUND: Primary care settings tailored for persons with experience of homelessness (PEH) could enhance opioid use disorder treatment delivery, but evidence is lacking.

OBJECTIVE: To examine medication treatment for opioid use disorder (MOUD) among PEH who received homeless-tailored primary care in the Department of Veterans Affairs (VA).

METHODS: Receipt of MOUD was assessed from electronic health records among VA primary care patients with experience of homelessness and OUD in 2016-2020. We estimated the proportion who received MOUD over time and applied mixed effect Poisson models with entropy balance weighting to estimate differences in MOUD by primary care type (homeless-tailored vs. mainstream). Secondary analyses examined the consistency of findings across 18VA service regions.

FINDINGS: The percentage of eligible PEH (n = 45,864) receiving any MOUD rose from 42.1 % to 51.0 % over time. Half (51.3 %) of those initiating MOUD received > 30 days MOUD over one year. In unadjusted models, the proportion receiving MOUD was slightly higher in homeless-tailored primary care, compared to mainstream primary care (48.8 % vs 46.4 %, Unadjusted Incidence Rate Ratio=1.09, 95 % CI=1.03-1.16). After covariate adjustment, there was no statistical difference between groups (Adjusted IRR=0.97, CI=0.92-1.02). This proved broadly consistent across VA service regions.

CONCLUSIONS: Concomitant with a national VA initiative to tailor primary care services for PEH, half of diagnosed patients received MOUD. Yet evidence of durable treatment was low, and the homeless-tailored clinics did not outperform mainstream clinics. Efforts to tailor primary care for PEH may require specialized addiction staffing and implementation support to improve MOUD care in these settings.

PMID:41380198 | DOI:10.1016/j.drugalcdep.2025.112995