Notoginsenoside R1 improves intestinal microvascular functioning in sepsis by targeting Drp1-mediated mitochondrial quality imbalance.

CONTEXT: Sepsis can result in critical organ failure, and notoginsenoside R1 (NGR1) offers mitochondrial protection. OBJECTIVE: To determine whether NGR1 improves organ function and prognosis after sepsis by protecting mitochondrial quality. MATERIALS AND METHODS: A sepsis model was established in C57BL/6 mice using cecum ligation puncture (CLP) and an in vitro model with lipopolysaccharide (LPS, 10 µg/mL)-stimulated primary intestinal microvascular endothelial cells (IMVECs) and then determine NGR1's safe dosage. Groups for each model were: in vivo-a control group, a CLP-induced sepsis group, and a CLP + NGR1 treatment group (30 mg/kg/d for 3 d); in vitro-a control group, a LPS-induced sepsis group, and a LPS + NGR1 treatment group (4 µM for 30 min). NGR1's effects on survival, intestinal function, mitochondrial quality, and mitochondrial dynamic-related protein (Drp1) were evaluated. RESULTS: Sepsis resulted in approximately 60% mortality within 7 days post-CLP, with significant reductions in intestinal microvascular perfusion and increases in vascular leakage. Severe mitochondrial quality imbalance was observed in IMVECs. NGR1 (IC50 is 854.1 µM at 30 min) targeted Drp1, inhibiting mitochondrial translocation, preventing mitochondrial fragmentation and restoring IMVEC morphology and function, thus protecting against intestinal barrier dysfunction, vascular permeability, microcirculatory flow, and improving sepsis prognosis. DISCUSSION AND CONCLUSIONS: Drp1-mediated mitochondrial quality imbalance is a potential therapeutic target for sepsis. Small molecule natural drugs like NGR1 targeting Drp1 may offer new directions for organ protection following sepsis. Future research should focus on clinical trials to evaluate NGR1's efficacy across various patient populations, potentially leading to novel treatments for sepsis.

Neuropsychological rehabilitation and psychotherapy of adult traumatic brain injury patients with depression: a systematic review and meta-analysis.

INTRODUCTION: There is still insufficient appreciation whether neuropsychological rehabilitation and psychotherapy are effective in attenuating depression following traumatic brain injury (TBI). This knowledge gap was addressed in the present systematic review and meta-analysis of the literature. EVIDENCE ACQUISITION: We conducted electronic database (Medline, PsychINFO, Scopus) searches (time frame: January 1st, 2005 to December 31st, 2015) for clinical studies that had tested neuropsychological rehabilitation and psychotherapy in adult TBI survivors with depression. The studies were to have experimental or quasi-experimental study design, and to include survivors from non-military TBI. Quantitative assessment of qualifying studies was done using the random effects model. We calculated the pooled size effect using standardized mean difference (SMD) as the main effect measure. EVIDENCE SYNTHESIS: We identified three studies, totaling 231 participants, which tested cognitive behavioral therapy or mindfulness-based cognitive therapy as interventions to attenuate post-TBI depression. The analysis revealed a small and non-significant decrease in depression symptoms due to intervention (SMD=-0.23 [95% CI: -050, 0.03; z=1.73, P=0.08]). Testing for publication bias was not feasible due to low number of identified studies. CONCLUSIONS: Current evidence indicates only a small therapeutic effect of psychotherapy in attenuating post-TBI depression.