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Tumor necrosis factor receptor-associated protein 1 (TRAP1), a member of the heat shock protein 90 (Hsp90) chaperone family, protects cells against oxidative stress and maintains mitochondrial integrity. To date, numerous studies have focused on understanding the relationship between aberrant TRAP1 expression and tumorigenesis. Mitochondrial TRAP1 is a key regulatory factor involved in metabolic reprogramming in tumor cells that favors the metabolic switch of tumor cells toward the Warburg phenotype. In addition, TRAP1 is involved in dual regulation of the mitochondrial apoptotic pathway and exerts an antiapoptotic effect on tumor cells. Furthermore, TRAP1 is involved in many cellular pathways by disrupting the cell cycle, increasing cell motility, and promoting tumor cell invasion and metastasis. Thus, TRAP1 is a very important therapeutic target, and treatment with TRAP1 inhibitors combined with chemotherapeutic agents may become a new therapeutic strategy for cancer. This review discusses the molecular mechanisms by which TRAP1 regulates tumor progression, considers its role in apoptosis, and summarizes recent advances in the development of selective, targeted TRAP1 and Hsp90 inhibitors.

Objective The aim of the current meta-analysis was to assess the effect of dexmedetomidine on emergence agitation (EA) and the recovery outcomes after general anesthesia in adults. Methods We searched the PubMed, the Cochrane Central Register of Controlled Trials, Embase, Web of Science and clinicaltrials.gov for relevant randomized controlled trials (RCTs) investigating the effects of dexmedetomidine on the EA in adults after general anesthesia compared with placebo. The primary outcome was the incidence of EA. Secondary outcomes included other recovery outcomes after general anesthesia. Results Twelve RCTs (842 participants) met the eligibility criteria. A conventional random-effects meta-analysis demonstrated that peri-operative intravenous dexmedetomidine could be effective for the prevention of EA [risk ratio (RR) 0.49, Trial Sequential Analysis (TSA)-adjusted 95% confidence interval (CI) 0.35–0.68, P <0.00001]. In addition, the TSA indicated that the meta-analysis for the incidence of EA reached the required information size (370). Lower number of patients receiving dexmedetomidine required analgesia ( P =0.0009). Extubation time was longer ( P =0.03) and hypotension ( P =0.03) was more common with dexmedetomidine. Moreover, no difference was found in the other outcomes. Conclusion Dexmedetomidine was shown to effectively decrease the incidence of EA and to reduce postoperative analgesic requirements. Yet, other recovery outcomes including extubation time, length of PACU stay, postoperative residual sedation, hypotension, bradycardia as well as postoperative nausea and vomiting provided no data that could be used to form final conclusions.

This retrospective cohort study aimed to investigate the association between intraoperative dexmedetomidine infusion and emergence agitation (EA), and recovery profiles after lung surgery in adult patients. It was hypothesized that dexmedetomidine was associated with reduced EA and improved recovery profiles. Patients and methods: A single-center chart review was conducted on elective lung surgeries in adults between January and December 2016. The primary outcome was the incidence of EA in postanesthesia care units (PACUs). The secondary outcomes included rescue analgesia, shivering, time to extubation, residual sedation, postoperative pulmonary events, duration of PACU stay, length of hospital stay, and intraoperative hemodynamic changes. Univariate and multivariate regression analyses were used to analyze data. Results: Among 2,468 patients, 814 received an intraoperative dexmedetomidine infusion. Intraoperative dexmedetomidine infusion was associated with a lower incidence of EA (10.9% vs 15.0%; adjusted OR, 0.67; 95% CI, 0.51-0.87; P=0.003), rescue analgesia (7.6% vs 12.2%; adjusted OR, 0.63; 95% CI, 0.47-0.86; P=0.003), shivering (4.2% vs 6.6%; adjusted OR, 0.58; 95% CI, 0.38-0.88; P=0.010), and intraoperative bradycardia (18.6% vs 12.6%; adjusted OR, 1.51; 95% CI, 1.19-1.92; P=0.001). No differences were observed in residual sedation, duration of PACU stay, postoperative pulmonary events, and length of hospital stay between the groups. Conclusion: This retrospective study suggested that intraoperative dexmedetomidine infusion was associated with a lower incidence of EA, rescue analgesia, and shivering in adults after lung surgery. Intraoperative bradycardia was the main side effect.

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