Obesity is characterized by chronic low-grade inflammation and oxidative stress, conditions that disrupt metabolic homeostasis and promote vascular endothelial growth factor (VEGF) expression. While hypoxia and fatty acid-induced oxidative stress are known regulators of VEGF, the contribution of endoplasmic reticulum (ER) stress in monocytic cells remains unclear. In this study, we investigated the interplay between ER stress and metabolic stress in regulating VEGF expression using THP-1 monocytic cells. Metabolic stress was induced by palmitic acid (PA) and ER stress by thapsigargin (TG). Co-treatment with PA and TG significantly increased VEGF mRNA and protein levels compared to PA alone. This effect was accompanied by enhanced reactive oxygen species (ROS) production and upregulation of ER stress markers, including CHOP, ATF6, and IRE1. Pretreatment with the antioxidant curcumin markedly reduced VEGF expression and ROS levels, indicating a ROS-dependent mechanism. Additionally, PA+TG co-treatment elevated transcripts of antioxidant defense genes such as SOD2 and NRF2, suggesting a compensatory cellular response to oxidative stress. These findings demonstrate that ER stress amplifies VEGF induction in monocytic cells under lipotoxic conditions through ROS-mediated pathways, highlighting a potential mechanism linking metabolic stress, inflammation, and angiogenesis in obesity-related disorders.

Introduction: This study presents the first systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating the efficacy and safety of oral clonidine in spinal surgery to guide clinical practice and inform future research. Methods: RCTs were identified through four databases (PubMed, Scopus, Web of Science, Cochrane Central) up to August 2025. Risk of bias was assessed, and intraoperative and postoperative outcomes were extracted. Data were pooled using mean differences (MD) or risk ratios (RR) with 95% confidence intervals. Results: Eight RCTs with 474 patients (237 clonidine, 237 control) were included. Four studies had a low risk of bias, while two had some concerns, and two had a high risk. Clonidine had no impact on surgery duration but significantly reduced blood loss (MD = −177.76 mL), mean arterial pressure (MD = −11.33 mmHg), and heart rate (MD = −21.18 bpm). Regarding postoperative outcomes, clonidine was associated with improved analgesia, including lower pain scores up to 12 h and a longer time to first analgesic request, with no significant difference in pain scores at 24 h or total postoperative opioid consumption. No significant increase in postoperative complications, including bradycardia, dizziness, headache, or visual disturbances, was observed. Surgeon satisfaction was higher in the clonidine group. Despite high heterogeneity in some outcomes, sensitivity analyses confirmed the robustness of most findings. Conclusions: Prophylactic oral clonidine in spinal surgery significantly reduces blood loss, heart rate, and mean arterial pressure, with added analgesic benefits and good tolerability. Further high-quality RCTs are needed to confirm these results in broader patient populations.

Background/Objectives: Rotator cuff disease (RCD) is one of the most common causes of shoulder dysfunction, often resulting in pain, limited range of motion (ROM), and reduced function. Mulligan Mobilization with Movement (MWM) has been proposed as an effective adjunct to conventional therapy by correcting positional faults and improving joint mechanics. However, the overall evidence in RCD remains inconclusive. This meta-analysis aimed to evaluate the efficacy of Mulligan mobilization combined with conventional therapy versus conventional therapy alone on pain, functionality, ROM, joint position sense, and quality of life (QoL) in patients with RCD. Methods: A comprehensive literature search was carried out in PubMed, Web of Science, Scopus, and the Cochrane Library from database inception to 12 October 2025, with no restrictions on publication year. We included randomized controlled trials (RCTs) that compared Mulligan mobilization combined with conventional therapy against conventional therapy alone in individuals with rotator cuff-related pain. The predefined outcomes were pain intensity, range of motion (ROM), quality of life (QoL), joint position sense, and functional performance. All statistical analyses were conducted using R version 4.3.1. Heterogeneity was assessed using the I² statistic and the Cochrane Q test. Pooled mean differences (MDs) were calculated using the Inverse Variance approach with a restricted maximum-likelihood (REML) random-effects model. The review protocol was prospectively registered in PROSPERO (ID: CRD420251166854). Results: Four RCTs met the eligibility criteria and were included in the meta-analysis, comprising a total of 160 participants. Of these, 80 (50%) received Mulligan mobilization in combination with conventional therapy (mean age: 51 years; mean proportion of females: 45%). In the pooled analysis, Mulligan mobilization significantly improved pain at rest (MD −1.19; 95% CI [−1.64; −0.74]; p = 0.01; I² = 0%), pain during activity (MD −2.25; 95% CI [−3.18; −1.31]; p = 0.01; I² = 67%), functionality (MD −14.71; 95% CI [−20.10; −9.33]; p = 0.01; I² = 51%), ROM (MD 19.92; 95% CI [11.25; 28.39]; p = 0.01; I² = 58%), and joint position sense (MD −3.31; 95% CI [−6.22; −0.40]; p = 0.03; I² = 80%) compared with conventional therapy alone. No significant difference was observed for QoL (MD 10.58; 95% CI [−3.18; 24.34]; p = 0.13; I² = 76%). Conclusions: Mulligan mobilization combined with conventional therapy provides significant improvements in pain, functionality, ROM, and joint position sense in RCD. However, no statistically significant differences were observed in QoL between the groups. Integration of this technique into rehabilitation protocols may enhance clinical outcomes and functional recovery.

Background: Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are commonly performed procedures, but post-operative recovery is often complicated by significant pain, opioid-related side effects, and psychological distress. Esketamine has been proposed as an adjunct due to its analgesic and antidepressant properties, but its efficacy and safety remain unclear.