The purpose of this study was to explore the role and mechanism of the PI3K/AKT/mTOR signaling pathway in painful diabetic neuropathy (PDN). The diabetes mellitus (DM) model was established by intraperitoneal injection of streptozocin into SD rats. After 3 weeks of modeling, the DM + LY group was treated with PI3K inhibitor, the DM + vehicle group was treated with DMSO, and the DM group was untreated. The paw mechanical withdrawal thresholds (MWT) was measured by Von Frey filaments, and the expression of PI3K/AKT/mTOR pathway-related proteins and autophagy marker proteins were analyzed by Western blotting. We found that 3 weeks after modeling, the MWT values of diabetic rats were significantly reduced, p-PI3K, p-AKT and p-mTOR proteins expression in the spinal cord was increased, and Beclin1 and LC3-II expressions were reduced (P < 0.05). After administration of PI3K inhibitor, the MWT values in DM + LY group were improved, and the expressions of p-PI3K, p-AKT and p-mTOR proteins in the spinal cord were decreased significantly, and the expressions of Beclin1 and LC3-II were increased (P < 0.05). However, there were no significant changes in the DM + vehicle group compared with the DM group (P > 0.05). Therefore, we conclude that activation of the PI3K/AKT/mTOR pathway and impaired autophagy may be key factors that cause PDN. Inhibition of the PI3K/AKT/mTOR pathway could promote autophagy activity and alleviate PDN.
Previous studies have suggested that microRNAs (miRNAs) are associated with the progression of myocardial ischemic reperfusion (I/R) injury. However, inconsistent results have been obtained due to the differences in sequencing platform, control selection, and filtering conditions. To explore the key miRNAs in the pathogenesis of myocardial I/R injury and develop miRNA diagnostic biomarkers for myocardial I/R injury prevention, we performed a systematic analysis of publicly available myocardial I/R injury miRNA expression data and investigated the function of the signature miRNA. A total of 17 representative myocardial I/R injury miRNA datasets were extracted from the Google Scholar website and a systematic bioinformatics analysis was done. TargetScan software was used to predict the miRNA target genes, and functional enrichment and transcription factor binding analyses were performed on the target genes using the DAVID and Tfacts databases. In this study, a total of 10 signature miRNAs associated with myocardial I/R injury were identified, which included eight significantly upregulated miRNAs (miR‐let‐7b‐3p, miR‐let‐7c‐3p, miR‐15b‐3p, miR‐195‐3p, miR‐21‐5p, miR‐214‐5p, miR‐24‐3p, and miR‐320a) and two significantly downregulated miRNAs (miR‐126‐5p and miR‐499a‐5p). They had different influences on myocardial I/R injury. The upregulated target gene‐expressing signature messenger RNAs (mRNAs) were mainly involved in the transcriptional regulation process of GO: 0000122, negative regulation of transcription from RNA polymerase II promoter, and so on, while downregulated expression of signature mRNAs was mainly involved in GO:0070534, protein K63‐linked ubiquitination, and so forth. To summarize, 10 signature miRNAs of myocardial I/R injury pathogenesis were identified and their target genes and transcription factors were revealed, suggesting the potential novel therapeutic targets for myocardial I/R injury.
Purpose: Pectoral nerve block I (PECS I) and serratus-intercostal plane block (SIPB) can anesthetize the majority mammary region, while parasternal intercostal block (PSI) targets the internal area during breast resection surgery. The aim of this study was to determine whether including PSI with PECS I and SIPB is more effective compared to PECS I and SIPB alone. Patients and Methods: Sixty-two adult females undergoing unilateral modified radical mastectomy (MRM) were randomly assigned to receive either PECS I and SIPB (PS group, n=31) or a combination of PECS I, SIPB, and PSI (PSP group, n=31). The outcomes were measured with a numerical rating scale (NRS) score, and in terms of opioid consumption and anesthesia-related complications within 48 h after surgery. Results: Although there were no differences in the NRS scores between the two groups during the inactive periods, the combination of three nerve blocks significantly reduced the NRS scores during movement. In addition, morphine equivalent consumption was lower in the PSP group compared to the PS group. Postoperative adverse events were similar in both groups in terms of regional anesthesia-related complications. Conclusion: The combination of PECS I block, SIPB, and PSI block provides superior pain relief and postoperative recovery for patients undergoing MRM.
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