Background: It is widely accepted that mitochondria have a direct impact on neuronal function and survival. Oxidative stress caused by mitochondrial abnormalities play an important role in the pathophysiology of lipopolysaccharide (LPS)-induced memory impairment. Elamipretide (SS-31) is a novel mitochondrion-targeted antioxidant. However, the impact of elamipretide on the cognitive sequelae of inflammatory and oxidative stress is unknown. Methods: We utilized MWM and contextual fear conditioning test to assess hippocampus-related learning and memory performance. Molecular biology techniques and ELISA were used to examine mitochondrial function, oxidative stress, and the inflammatory response. TUNEL and Golgi-staining was used to detect neural cell apoptosis and the density of dendritic spines in the mouse hippocampus. Results: Mice treated with LPS exhibited mitochondrial dysfunction, oxidative stress, an inflammatory response, neural cell apoptosis, and loss of dendritic spines in the hippocampus, leading to impaired hippocampus-related learning and memory performance in the MWM and contextual fear conditioning test. Treatment with elamipretide significantly ameliorated LPS-induced learning and memory impairment during behavioral tests. Notably, elamipretide not only provided protective effects against mitochondrial dysfunction and oxidative stress but also facilitated the regulation of brain-derived neurotrophic factor (BDNF) signaling, including the reversal of important synaptic-signaling proteins and increased synaptic structural complexity. Conclusion: These findings indicate that LPS-induced memory impairment can be attenuated by the mitochondrion-targeted antioxidant elamipretide. Consequently, elamipretide may have a therapeutic potential in preventing damage from the oxidative stress and neuroinflammation that contribute to perioperative neurocognitive disorders (PND), which makes mitochondria a potential target for treatment strategies for PND.

Introduction: The mechanisms underlying sleep deprivation‐induced memory impairments and relevant compensatory signaling pathways remain elusive. We tested the hypothesis that increased brain‐derived neurotrophic factor (BDNF) expression in the basal forebrain following acute sleep deprivation was a compensatory mechanism to maintain fear memory performance.Methods: Adult male Wistar rats were deprived of 6‐hr total sleep from the beginning of the light cycle. The effects of sleep deprivation on BDNF protein expression and activation of downstream tropomyosin receptor kinase B (TrkB)/phospholipase C‐γ1 (PLCγ1) signaling in the basal forebrain and fear memory consolidation were examined. BDNF or selective downstream TrkB receptor antagonist ANA‐12 was further injected into the basal forebrain bilaterally to observe the changes in fear memory consolidation in response to modulation of the BDNF/TrkB signaling.Results: Six hours of sleep deprivation‐induced both short‐ and long‐term fear memory impairments. Increased BDNF protein expression and TrkB and PLCγ1 phosphorylation in the basal forebrain were observed after sleep deprivation. Microinjection of BDNF into the basal forebrain partly reversed fear memory deficits caused by sleep deprivation, which were accompanied by increased BDNF protein levels and TrkB/PLCγ1 activation. After ANA‐12 microinjection, sleep deprivation‐induced activation of the BDNF/TrkB pathway was inhibited and impairments of fear memory consolidation were further aggravated.Conclusions: Acute sleep deprivation induces compensatory increase of BDNF expression in the basal forebrain. Microinjection of BDNF into the basal forebrain mitigates the fear memory impairments caused by sleep deprivation by activating TrkB/PLCγ1 signaling.

Kangqianling decoction (KQL), the modified formulation of a classical Chinese prescription named Taohongsiwu decoction, was clinically employed to treat renal fibrosis in chronic renal failure. The present study was designed to examine whether KQL has a protective effect on renal function in association with transforming growth factor-beta (TGF-beta), angiotensin II (Ang II), tumor necrosis factor-alpha (TNF-alpha), nuclear factor-kappaB (NF-kappaB) in rats with 5/6 renal ablation (Nx)-induced chronic renal failure. In renal function deterioration progression, the high expression of serum creatinine (Scr), 24-h urine protein and systolic blood pressure were markedly (P<0.05 or P<0.01) restored by KQL, respectively, at 4 and 8 weeks. The increasing expressions of renal Ang II (P<0.05), angiotensin II1-receptor (AT1R) (P<0.05), TNF-alpha (P<0.05), NF-kappaB (P<0.001) and urine TGF-beta1 (P<0.05) were reduced by the treatment of KQL. Immunohistochemical study further confirmed the nephro-protective activity of KQL as compared to the control and Sham group. The results indicate that KQL is able to protect renal function via ameliorating experimental rat renal failure as found in these renal functional parameters.

Little evidence on the association between geriatric nutritional risk index (GNRI) with prognosis and postoperative complications was observed. This study examined the potential prognostic value of GNRI in elderly patients undergoing non-cardiac surgery. This retrospective analysis was data retried from the Chinese elderly patients’ perioperative database (CEPPD), a multicenter registry, from June 1st, 2012 to August 15th, 2019. Patients were categorized into at-risk group (GNRI ≤ 98) and no-risk group (GNRI > 98). Kaplan–Meier analysis and multivariate Cox proportional hazard regression were used to explore the association between GNRI and overall survival (OS). Multivariate logistic regression and linear regression were used to explore the association of the GNRI with postoperative complications. A propensity score matching (PSM) analysis was also conducted at a 1:1 ratio using the greedy nearest-neighbor method. The final analysis included 28,762 elderly patients undergoing non-cardiac surgery. The PSM cohort included 7,063 patients in each group. The 1-year OS rate was 90.2% in the at-risk group vs. 96.3% in the no-risk group (P < 0.001). In Kaplan-Meier analysis, OS was significantly shorter in the at-risk group (P < 0.001 for both before matching and PSM). In multivariable Cox regression, at-risk GNRI was independently associated with OS in both the overall analysis (HR: 1.682; 95% CI: 1.502–1.882; P < 0.001) and the PSM cohort (HR: 1.501; 95% CI: 1.316–1.711; P < 0.001). At-risk GNRI was also independently associated with postoperative heart injury, acute renal injury, pulmonary infection, surgical site infection, intensive care unit (ICU) admission, longer ICU length of stay (LOS), and longer postoperative LOS. Preoperative at-risk GNRI was associated with poor survival outcome and higher risk of postoperative complications in elderly patients undergoing non-cardiac surgery.