Secreted phosphoprotein 1 exacerbates renal ischemia-reperfusion injury by inhibiting PI3K/AKT signaling pathway.

BACKGROUND: Renal ischemia-reperfusion injury (IRI) is a prevalent reason for acute kidney injury and a key clinical issue for patients under anesthesia and about to have surgery. We aim to investigate the Secreted phosphoprotein 1 (SPP1) role in renal IRI and the underlying mechanisms. METHODS: Using Gene Expression Omnibus (GEO) database helped in analyzing the SPP1 expression in renal IRI. We established two models, a mouse renal ischemia-reperfusion (I/R) besides a hypoxia-reoxygenation (H/R) HK-2 cell. Renal tubular lesions were measured using H&E staining. Depending on the TUNEL assay, immunohistochemistry, qRT-PCR, as well as western blot, we applied the assessment of apoptosis and apoptosis-associated protein levels. At the same time, a western blot was performed for assessing PI3K/AKT pathway-associated proteins. RESULTS: GEO data and experimental validation revealed elevated SPP1 content in the kidney tissues of renal I/R mice more than in sham mice. In vitro and in vivo studies revealed an increase in cell apoptosis due to SPP1 overexpression, but the opposite is true when SPP1 is silenced. SPP1 downregulation led to high p-PI3K and p-AKT protein levels, and the LY294002 application inhibited SPP1 inhibition-mediated anti-apoptotic effect CONCLUSION: Taken together, SPP1 exacerbates renal IRI in vivo and in vitro via promoting programmed cell death by inhibiting PI3K/AKT signaling pathway.

Efficacy and safety of remimazolam for procedural sedation during ultrasound-guided transversus abdominis plane block and rectus sheath block in patients undergoing abdominal tumor surgery: a single-center randomized controlled trial.

BACKGROUND: To explore the efficacy and safety of remimazolam for procedural sedation during ultrasound-guided nerve block administration in patients undergoing abdominal tumor surgery, in order to improve and optimize remimazolam use in procedural sedation and clinical anesthesia. METHODS: The enrolled patients were randomly divided into three groups: 50 patients in the remimazolam group (R group), 50 patients in the dexmedetomidine group (D group), and 50 patients in the midazolam group (M group). Before administering an ultrasound-guided nerve block, all patients received sufentanil AND remimazolam or midazolam or dexmedetomidine. Remimazolam 5 mg was administered intravenously in group R, dexmedetomidine 0.6 µg/kg was administered intravenously in group D, and midazolam 0.025 mg/kg was administered intravenously in group M. Sedation was evaluated by the Modified Observer's Assessment of Alertness and Sedation scale.When the Modified Observer's Alertness/Sedation (MOAA/S) score was ≤ 2, block operation was started. If the target sedation level was not reached, rescue sedatives of remimazolam 2.5 mg may be intravenously given in group R, dexmedetomidine 0.4 µg/kg be intravenously given in group D, 0.01 mg/kg midazolam may be intravenously given in Group M. Hemodynamic indicators (systolic and diastolic blood pressure, heart rate), pulse oxygen saturation, depth of anesthesia (Narcotrend), MOAA/S,and the incidences of hypoxemia, injection pain, bradycardia and requirement for rescue sedatives were monitored and recorded. RESULTS: Compared with the control groups (midazolam and dexmedetomidine groups), the Narcotrend index and MOAA/S decreased more in the remimazolam group (P < 0.01). Compared with the control groups, the incidence of hypoxemia and injection pain was slightly higher in the remimazolam group, but the difference was not statistically significant (P > 0.05). Compared with the dexmedetomidine group, the incidence of bradycardia was significantly lower in the remimazolam group. CONCLUSION: Remimazolam can be used safely for procedural sedation during ultrasound-guided nerve block administration in patients undergoing abdominal tumor surgery. The sedation effect is better than that with either midazolam or dexmedetomidine, and sedation can be achieved quickly without obvious hemodynamic fluctuations. Remimazolam is associated with better heart rate stability, and slightly higher incidences of hypoxemia and injection pain than are midazolam and dexmedetomidine (no statistically significant difference). The higher incidence of hypoxemia with remimazolam may be related to enhanced sufentanil opioid analgesia, and the mechanism of injection pain with remimazolam must be studied further and clarified. TRIAL REGISTRATION: This study was approved by the Ethics Committee of Anhui Provincial Cancer Hospital (Ethical Review 2021, No. 23) and registered at https://www.chictr.org.cn  (ChiCTR2000035388). The pre-registration time of this experiment is 09/08/2020, due to ethical committee of the hospital met irregularly,the ethical approval time is 21/06/2021. The recruitment of patients began after the ethical approval (21/06/2021) and registration update (06/07/2021).The study protocol followed the CONSORT guidelines. The study protocol was performed in the relevant guidelines.

The DNA methylation-regulated MCTP1 activates the drug-resistance of esophageal cancer cells.

Accumulating studies have demonstrated that drug-resistance remains a great obstacle for the effective treatment of cancers. Esophageal cancer is still one of the most common cancers worldwide, which also suffers from the drug-resistance during clinical treatment. Here we performed drug-resistance profiling assays and identified several drug-resistant and drug-sensitive esophageal cancer cell lines. The following methylation sequencing showed that the MCTP1 gene is hypermethylated in the drug-resistant esophageal cancer cells. As a result, the expression of MCTP1 is down-regulated in the drug-resistant esophageal cancer cells. Down-regulation of MCTP1 also affects the migration and apoptosis of esophageal cancer cells, as revealed by the wound-healing and apoptosis assays. Further investigations proposed two signaling pathways that might involve in the MCTP1-mediated drug-resistance of esophageal cancer cells. All these results suggested that MCTP1 activates the drug-resistance of esophageal cancer cells, which has implications for further design of new biomarker of esophageal cancer treatment.

Association between CD24 Ala/Val polymorphism and multiple sclerosis risk: A meta analysis.

BACKGROUND: The aim of this study was to explore the association between CD24 Ala/Val polymorphism and susceptibility of multiple sclerosis (MS). METHODS: A comprehensive literature search for relevant studies was performed on google scholar, PubMed, Web of science, Embase, the Chinese National Knowledge Infrastructure and the Chinese Biology Medicine. This meta-analysis was conducted using the STATA 11.0 software and the pooled odds ratio with 95% confidence interval was calculated. RESULTS: Seven case-control studies were included in this meta-analysis. The results showed significant association between CD24 Ala/Val polymorphism and susceptibility to MS. Stratified analysis by areas also showed significant association in Asians. However, no association was found in Europeans. CONCLUSION: This study suggested that the CD24 Val allele was associated with an increased risk of MS and larger-scale studies of populations are needed to explore the role of CD24 Ala/Val polymorphism during the pathogenesis of MS.

Ribosomal protein small subunit 15A (RPS15A) inhibits the apoptosis of breast cancer MDA-MB-231 cells via upregulating phosphorylated ERK1/2, Bad, and Chk1.

AIM: To detect the expression and identify the role of Ribosomal protein S15A (RPS15A) in human breast cancer (BC). METHODS: Immunohistochemistry (IHC) was carried out for detecting the levels of RPS15A protein. Quantitative PCR was used to evaluate the mRNA level of RPS15A in one normal breast and three BC cell lines. Lentivirus-mediated shRNA targeting RPS15A was designed to investigate the impact of silencing RPS15A in MDA-MB-231 cell. RESULTS: Higher RPS15A expression was detected in tumor tissues than in para-cancer tissues, and higher RPS15A expression was related to larger tumor size and higher TNM stage. Also, RPS15A mRNA expression in all three BC cell lines was higher than that in normal breast cell (all P < .005). Further, RPS15A knockdown significantly suppressed MDA-MB-231 cell proliferation and induced apoptosis. Moreover, RPS15A knockdown increased the caspase-3/-7 activity, and suppressed the phosphorylated levels of ERK1/2, Bad, and Chk1 (all P < .01). CONCLUSION: RPS15A inhibits apoptosis via upregulating phosphorylated ERK1/2, Bad, and Chk1 in MDA-MB-231 cell line.

Effect of dexmedetomidine on postoperative cognitive dysfunction and inflammation in patients after general anaesthesia: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: Neuroprotective effects of dexmedetomidine are reported in preclinical and clinical studies but evidence regarding the postoperative neurocognitive function is still unclear. This study performed a meta-analysis on outcomes of studies which examined neurocognitive performance and inflammatory factors to investigate the effects of dexmedetomidine on postoperative cognitive dysfunction (POCD) and inflammation in patients after general anaesthesia. METHODS: Literatures were searched in several electronic databases and studies were selected by following precise inclusion criteria. We searched PubMed, EMBASE, the Cochrane Library, China Academic Journals full-text database (CNKI), and Google Scholar to find randomized controlled trials (RCTs) of the influence of dexmedetomidine on POCD and inflammation in patients who had undergone general anaesthesia. Two researchers independently screened the literature, extracted data, and evaluated quality of methodology against inclusion and exclusion criteria. Meta-analyses of pooled ORs of POCD incidences and mean differences in neurocognitive assessment scores and inflammation levels were carried out and subgroup analyses were performed. Stata 12.0 was used to conduct our meta-analysis. RESULTS: Twenty-six RCTs were included. Compared with controls, perioperative dexmedetomidine treatment significantly reduced the incidence of POCD (pooled ORs = 0.59, 95% confidence interval (CI) 0.45-2.95) and improved Mini-Mental State Examination (MMSE) score (standardized mean difference (SMD) = 1.74, 95% CI 0.43-3.05) on the first postoperative day. Furthermore, perioperative dexmedetomidine treatment significantly decreased IL-6 (SMD = -1.31, 95% CI -1.87-0.75, P < .001) and TNF-α (SMD = -2.14, 95% CI -3.14-1.14, P < .001) compared to saline/comparators treatment. In the stratified analysis by surgical type, age, type of control, and study region, the differences were also significant between dexmedetomidine- and saline-treated patients. CONCLUSION: Perioperative dexmedetomidine treatment is associated with significantly reduced incidence of POCD and inflammation and better neurocognitive function postoperatively in comparison with both saline controls and comparator anaesthetics.

miR-193a-3p Promotes Radio-Resistance of Nasopharyngeal Cancer Cells by Targeting SRSF2 Gene and Hypoxia Signaling Pathway.

BACKGROUND Radio-resistance is an important barrier in nasopharyngeal carcinoma treatment. MicroRNAs are gene expression core regulators in various biological procedures containing cancer radio-resistance. Nevertheless, the clinical association between nasopharyngeal carcinoma and miR-193a-3p/SRSF2 remains unclear. MATERIAL AND METHODS We examined the miR-193a-3p level in radio-sensitive CNE-2 and radio-resistant CNE-1 NPC cell lines, and, based on a literature review, predicted SRSF2 to be the target gene of miR-193a-3p. We explored the expression of SRSF2 at protein and mRNA levels by transfecting either miR-193a-3p-mimic or antagomiR. Finally, we performed signaling pathway analysis to assess the possible role of miR-193a-3p/SRSF2 in signaling pathways. RESULTS miR-193a-3p promotes NPC radio-resistance, and the SRSF2 gene is the direct target for miR-193a-3p in NPC, and thus is negatively correlated with NPC radio-resistance. The hypoxia signaling pathway activity is strongly affected, and it is possible to use the downstream activity of the SRSF2 gene to show the effect of miR-193a-3p on radio-resistance in NPC cells. CONCLUSIONS miR-193a-3p mediates promotion of NPC radio-resistance.