Therapeutic implication of targeting mitochondrial drugs designed for efferocytosis dysfunction.

Efferocytosis refers to the process by which phagocytes remove apoptotic cells and related apoptotic products. It is essential for the growth and development of the body, the repair of damaged or inflamed tissues, and the balance of the immune system. Damaged efferocytosis will cause a variety of chronic inflammation and immune system diseases. Many studies show that efferocytosis is a process mediated by mitochondria. Mitochondrial metabolism, mitochondrial dynamics, and communication between mitochondria and other organelles can all affect phagocytes' clearance of apoptotic cells. Therefore, targeting mitochondria to modulate phagocyte efferocytosis is an anticipated strategy to prevent and treat chronic inflammatory diseases and autoimmune diseases. In this review, we introduced the mechanism of efferocytosis and the pivoted role of mitochondria in efferocytosis. In addition, we focused on the therapeutic implication of drugs targeting mitochondria in diseases related to efferocytosis dysfunction.

Dexmedetomidine and acute kidney injury after non-cardiac surgery: A meta-analysis with trial sequential analysis.

BACKGROUND: Acute kidney injury (AKI) is a common complication after surgery and is associated with detrimental outcomes. This systematic review and meta-analysis evaluated perioperative dexmedetomidine on AKI and renal function after non-cardiac surgery. METHODS: PubMed, Embase, and Cochrane Library databases were searched until August 2023 for randomised trials comparing dexmedetomidine with normal saline on AKI and renal function in adults undergoing non-cardiac surgery. The primary outcome was the incidence of AKI (according to Kidney Disease Improving Global Outcomes or Acute Kidney Injury Network criteria). Meta-analysis was performed using a random-effect model. We conducted sensitivity analysis, trial sequential analysis (TSA), and Grading of Recommendations Assessment, Development and Evaluation level of evidence. RESULTS: Twenty-three trials involving 2440 patients were included. Dexmedetomidine administration, as compared to normal saline, significantly reduced the incidence of AKI (7.4% vs. 13.2%; risk ratio = 0.57, 95% CI = 0.40-0.83, P = 0.003, I2 = 0%; a high level of evidence); TSA and sensitivity analyses suggested the robustness of this outcome. For the renal function and inflammation parameters, dexmedetomidine decreased serum creatinine, blood urea nitrogen, cystatin C, tumour necrosis factor-α, and interleukin-6, and increased urine output and estimated glomerular filtration rate. Additionally, dexmedetomidine reduced postoperative nausea and vomiting and length of hospital stay. Dexmedetomidine was associated with an increased rate of bradycardia, but not hypotension. CONCLUSION: Dexmedetomidine administration reduced the incidence of AKI and improved renal function after non-cardiac surgery. Based on a high level of evidence, dexmedetomidine is recommended as a component of perioperative renoprotection. REGISTRATION: International Prospective Register of Systematic Reviews; Registration number: CRD42022299252.

Dexmedetomidine Infusion Versus Placebo During Light or Deep Anesthesia on Postoperative Delirium in Older Patients Undergoing Major Noncardiac Surgery: A Pilot Randomized Factorial Trial.

BACKGROUND: Postoperative delirium (POD) is common among older surgical patients and may be affected by dexmedetomidine and depth of anesthesia. We designed this pilot study to assess the feasibility of comparing dexmedetomidine with normal saline during light versus deep anesthesia on POD in older patients undergoing major noncardiac surgery. METHODS: In this pilot randomized factorial study, 80 patients aged 60 years or older undergoing major noncardiac surgery were randomized (1:1:1:1) to receive dexmedetomidine infusion 0.5 µg/kg/h or normal saline placebo during light (bispectral index [BIS] target 55) or deep (BIS target 40) anesthesia. Feasibility end points included consent rate and dropout rate, timely enrollment, blinded study drug administration throughout surgery, no inadvertent unmasking, achieving BIS target throughout >70% of surgery duration, and the process of twice-daily POD screening. In addition, we estimated the POD incidences in the 2 control groups (placebo and deep anesthesia) and treatment effects of dexmedetomidine and light anesthesia. RESULTS: Between November 1, 2021, and June 30, 2022, 78 patients completed the trial (mean [standard deviation, SD] age, 69.6 [4.6] years; 48 male patients [62%]; dexmedetomidine-deep, n = 19; dexmedetomidine-light, n = 20; placebo-deep, n = 19; placebo-light, n = 20). This study had a high consent rate (86%) and a low dropout rate (2.5%). Average recruitment was 5 patients at each center per month. Dexmedetomidine and normal saline were administered in a blinded fashion in all patients. Unmasking did not occur in either group. Approximately 99% of patients received the scheduled study drug infusion throughout the surgery. Approximately 81% of patients achieved the BIS targets throughout >70% of the surgery duration. The scheduled twice-daily POD screening was completed without exception. Overall, 10 of the 78 patients (13%; 95% confidence interval [CI], 7%-22%) developed POD. For the 2 reference groups, POD was observed in 7 of the 39 patients (17.9%; 95% CI, 9%-32.7%) in the placebo group and 7 of the 38 patients (18.4%; 95% CI, 9.2%-33.4%) in the deep anesthesia group. Regarding the treatment effects on POD, the estimated between-group difference was -10% (95% CI, -28% to 7%) for dexmedetomidine versus placebo, and -11% (95% CI, -28% to 6%) for light versus deep anesthesia. CONCLUSIONS: The findings of this pilot study demonstrate the feasibility of assessing dexmedetomidine versus placebo during light versus deep anesthesia on POD among older patients undergoing major noncardiac surgery, and justify a multicenter randomized factorial trial.

Effects of traditional Chinese exercises and general aerobic exercises on older adults with sleep disorders: A systematic review and meta-analysis.

BACKGROUND: Sleep disorders are common in older adults and have a negative influence on their physical and mental health. General aerobic exercises (GAEs) have long been used in the treatment of sleep disorders as a non-pharmacological measure. However, there is no consensus on the efficacy of traditional Chinese exercises (TCEs) for treating sleep disorders in older adults and the difference between TCEs and GAEs. OBJECTIVE: This study assessed the effects of TCEs and GAEs on the sleep quality of older adults and the differences between these two interventions. SEARCH STRATEGY: PubMed, Embase, Cochrane Library, Web of Science, China Biology Medicine disc, China National Knowledge Infrastructure, China Science Journal Database and Wanfang Data were searched from their inception to August 2020. INCLUSION CRITERIA: Randomized controlled trials (RCTs) that evaluated the effects of TCEs and GAEs on older adults with sleep disorders were included. DATA EXTRACTION AND ANALYSIS: Data were extracted by two researchers working independently. The risk bias of included studies was assessed using the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0 and the quality of evidence was assessed using the Grades of Recommendation, Assessment, Development and Evaluation approach. The Pittsburgh Sleep Quality Index (PSQI) was used to estimate sleep quality. Meta-analyses were performed to assess the total PSQI score of the exercise intervention as the primary outcome, and the scores of subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, use of sleep medication and daytime dysfunction were assessed as secondary outcomes. Subgroup, sensitivity, and meta-regression analyses were conducted to assess the contribution of covariables to heterogeneity. RESULTS: A total of 22 RCTs (including 1747 participants) were included in the meta-analysis. The results indicated that TCEs (weighted mean difference [WMD] = -2.14, 95% confidence interval [CI] [-2.82, -1.46], P < 0.001; heterogeneity: P < 0.001, I2 = 82%; 15 studies, n = 1063) and GAEs (WMD = -2.88, 95% CI [-5.22, -0.55], P < 0.001; heterogeneity: P < 0.001, I2 = 98%; 5 studies, n = 500) significantly improved total sleep quality, having favorable effects on subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, use of sleep medication and daytime dysfunction. Subgroup analysis showed that TCEs demonstrated superiority after 12 weeks (WMD = -2.77, 95% CI [-4.26, -1.28], P < 0.001; heterogeneity: P < 0.001, I2 = 85%; 5 studies, n = 420) and Qigong had a greater intervention effect for improving the sleep quality of older adults than Tai Chi (WMD = -3.37, 95% CI [-4.38, -2.35], P < 0.001; heterogeneity: P = 0.04, I2 = 63%; 4 studies, n = 321). Meta-regression revealed that the year of publication, sample size, mean age of participants, and percentage of females in the primary studies did not account for the overall heterogeneity. CONCLUSION: Current evidence shows that both TCEs and GAEs, as complementary and non-pharmacological approaches, help to improve the sleep quality in older adults with potentially clinical implications; however, there was not enough evidence to conclude the difference between them. More rigorous and high-quality RCTs are needed to arrive at reliable conclusions.

Comparison of cyanobacterial communities in temperate deserts: A cue for artificial inoculation of biological soil crusts.

The topsoil cyanobacteria in biological soil crusts (BSCs) play a vital role in stabilizing soil surface of disturbed habitats in water and nutrient-poor ecosystems. Currently, artificial inoculation of BSCs is considered as an effective approach to restore habitats and accelerate ecosystem regeneration. Understanding the character of cyanobacterial communities is the necessary prerequisite to explore the artificial inoculation of BSCs. For this reason, cyanobacterial communities in BSCs were compared between two mid-latitute temperate deserts with distinct precipitation patterns. The results showed that Oscillatoriales and Nostocales dominated crusts in the Tengger desert with majority of rainfall in summer and early autumn while Oscillatoriales dominated crusts in the Kyzyl kum desert with more rainfall in winter and early spring. Moreover, filamentous Microcoleus vaginatus overwhelmingly dominated all the crusts in both deserts with Mastigocladopsis sp. and Chroococcidiopsis spp. as the dominant heterocystous cyanobacteria. Of note, genus Wilmottia kept a relative stable and high abundance in both deserts. The top two abundantly shared cyanobacteria (> 1% of total sequences) were M. vaginatus and Mastigocladopsis sp. in both deserts, while 16 genera with significant variances were found between the two deserts (P <0.05). Total variations of cyanobacterial communities across the deserts were largely explained by a combination of biotic factors (microbial biomass C and N) and abiotic factors (soil pH, soil water content, soil water holding capacity, and soil available potassium). Compared to better-developed crusts, cyanobacterial abundance was higher in cyanobacterial crusts. BSC type and/or geographic location significantly affected cyanobacterial Shannon diversity without significantly influencing species richness. Our data suggest that the basic and major groups (e.g. M. vaginatus, Wilmottia spp., Mastigocladopsis sp., and Chroococcidiopsis spp.), and the abundantly shared phylotypes which showed significant difference in cyanobacterial communities between deserts, should be focused on to further explore the artificial inoculation of BSCs in temperate drylands.

An Accurate and Effective Method for Measuring Osimertinib by UPLC-TOF-MS and Its Pharmacokinetic Study in Rats.

Osimertinib, a new-generation inhibitor of the epidermal growth factor, has been used for the clinical treatment of advanced T790M mutation-positive tumors. In this research, an original analysis method was established for the quantification of osimertinib by ultra-performance liquid chromatography with time of flight mass spectrometry (UPLC-TOF-MS) in rat plasma. After protein precipitation with acetonitrile and sorafinib (internal standard, IS), they were chromatographed through a Waters XTerra MS C18 column. The mobile phase was acetonitrile and water (including 0.1% ammonia). The relative standard deviation (RSD) of the intra- and inter-day results ranged from 5.38 to 9.76% and from 6.02 to 9.46%, respectively, and the extraction recovery and matrix effects were calculated to range from 84.31 to 96.14% and from 91.46 to 97.18%, respectively. The results illustrated that the analysis method had sufficient specificity, accuracy and precision. Meanwhile, the UPLC-TOF-MS method for osimertinib was successfully applied into the pharmacokinetics of SD rats.