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Isoflurane is one of the most popular inhalation anesthetics in the clinical practice but presenting an increased risk of neuronal injury. Hsp90 has been indicated to present an important role for maintaining neuronal homeostasis under the stress. However, the effect of hsp90 during isoflurane exposure is poorly understood. Here in this study, we aimed to observe the protect effect of hsp90 inhibition, and investigate the potential regulatory mechanism after isoflurane exposure. We found that hsp90 inhibitor, 17AAG, showed a great protective effect in maintaining isoflurane-induced ferroptosis of mice hippocampus and cultured neuronal cells. We focus on the crucial protein GPX4 activity in ferroptosis, and found that the 17 AAG contributed its protect effect to preserve physiological level of GPX4 activity under isoflurane exposure, although 17AAG could restored the protein level of GPX4. Further, we observed CMA pathway was activated and then mediated GPX4 degradation under isoflurane exposure. And 17AAG could interfere the complex between hsp90 and lamp2a to inhibit CMA activity, followed by blocking GPX4 degradation, which further affected the isoflurane-induced ferroptosis. Based on these findings, we proposed that hsp90 inhibition as a protective mechanism against isoflurane-induced ferroptosis in neurons.

Background HSP90 has been shown to play an important role in maintaining neuronal homeostasis under stressful conditions. However, the effect of HSP90 during isoflurane exposure is unknown. This study aimed to investigate the protective effect of HSP 90 inhibition following isoflurane exposure and elucidate the potential regulatory mechanisms in vivo and in vitro. Methods Isoflurane-induced hippocampal neuron injury model was established in aged male C57BL/6 mice. After pretreatment with HSP90 inhibitor 17 AAG, the mice were administrated to isoflurane inhalation. Human neuroblastoma SH-SY5Y cells were pretreated with 17AAG and exposed to isoflurane. The hippocampal neuronal injury in mice were examined by HE staining and immunofluorescent staining. Cell viability in SH-SY5Y cells was examined by CCK8 assay and trypan blue staining. Ferroptosis biomarkers were investigated by transmission electron microscopy, flow cytometry, and western blot. We also detected the CMA signaling pathway to test the effect of HSP90 in isoflurane-induced neurotoxicity. Results The HSP90 inhibitor, 17 AAG, reduced isoflurane-induced ferroptosis in the mouse hippocampus and cultured neuronal cells. Isoflurane activated the CMA pathway, which then mediated GPX4 degradation. 17 AAG contributed to the preservation of GPX4 activity at physiological levels under isoflurane exposure. In addition, 17 AAG inhibits CMA activity and GPX4 degradation by preventing the formation of complexes between HSP90 and LAMP2A, thereby affecting isoflurane-induced ferroptosis. Conclusions HSP90 inhibition protects against isoflurane-induced neurotoxicity in vivo and vitro via inhibition of CMA pathway and GPX4 degradation, which induced ferroptosis and thus neuronal cell death.

SUMMARY: The establishment of primary keloid fibroblast culture has always been a fundamental measure for studying mechanisms of keloid disease. The quality of the primary cell culture can directly affect the results of further experiments. This study was performed to investigate the optimal growth conditions, including the optimal storage time and collagenase treatment time, for in vitro cell culture models and the suitable methods for epidermis-dermis separation in different tissues. Keloid tissues, keloid-surrounding tissues, and normal skin tissues were collected from patients, for primary fibroblast culture. Two methods, tissue explant and collagenase digestion, were deployed and compared. Expression levels of the keloid-related genes α -SMA, Col1, and Col3 were assessed in cells cultured using both methods, to verify the qualities of the primary cells. A comparative analysis was conducted between the two methods and among the three different tissues used. Bacterial and lipid contamination was immediately minimized after the samples were processed. Different methods of epidermis removal and different durations of collagenase digestion were required in different tissues to generate optimal results. Real-time PCR results showed that the mRNA expression levels of keloid-related genes in cultured fibroblasts correlated to their in vivo expression profile, as previously reported in other studies. The results of this study have revealed several key points in the culture of primary keloid fibroblasts and demonstrated the correlation in gene expression between in vivo keloid fibroblasts and in vitro primary keloid fibroblasts.

The widely used inhalation anesthetic, isoflurane, potentially induces neuronal injury in clinical practice. Previous studies showed multiple forms of cell death that resulted from isoflurane-induced cytotoxicity, but the precise underlying mechanism remains poorly understood. Ferroptosis has recently been identified as a non-apoptotic form of regulated cell death. Here, we found that ferroptosis inhibitors, ferrostatin-1 and deferoxamine mesylate (DFOM), showed great efficiency in maintaining cell viability in SH-SY5Y neuroblastoma cells exposed to a high concentration of isoflurane for 24 h. We also observed that cellular chelatable iron and lipid peroxidation were increased in a concentration-dependent manner in response to isoflurane. In addition, isoflurane upregulated Beclin1 phosphorylation, followed by the formation of a Beclin1-solute carrier family 7 member 11 (SLC7A11) complex, which affected the activity of cystine/glutamate antipoter and further regulated ferroptotic cell death. Accordingly, Beclin1 overexpression aggravated isoflurane-induced cell damage by upregulating ferroptosis. This phenomenon was significantly attenuated by silencing of Beclin1 in SH-SY5Y cells. These findings indicate that Beclin1 may regulate ferroptosis in a manner involving inhibition of glutamate exchange activity of system xc(-), which is implicated in isoflurane-induced toxicity. In particular, when isoflurane is administrated at high concentrations and for an extended duration, ferroptosis is more likely to play a crucial role in isoflurane-induced toxicity.

Background Surgical stress induces the release of neuroendocrine mediators and cytokines during perioperative period, which may have adverse effects on cancer patients. While the surgical stress responsse can be affected by anesthetic technique. Therefore, we designed this study to assess whether subcostal transversus abdominis plane (TAP) block can affect perioperative neuroendocrine stress response, postoperative analgesia and postoperative recovery in patients undergoing radical gastrectomy under general anesthesia. Methods Sixty-five patients were recruited. Patients randomly received general anesthesia (control group), or general anesthesia combined with TAP block (40 mL of 0.375% ropivacaine) (TAP group). The primary outcome was neuroendocrine levels including norepinephrine (NE), epinephrine (E), cortisol (Cor), glucose (Glu), interleukin (IL)-6 and IL-10 during 48 h after surgery. Secondary outcomes included pain score, hemodynamic variables and recovery characteristics. Results Data from 61 of 65 patients were analyzed. The levels of NE, E, Cor, and Glu were blunt by TAP block during perioperative period. The levels of IL-6 and IL-10 were significantly lower in TAP group than in control group. TAP block efficiently relieved postoperative acute pain up to 12 h postoperatively with more stable perioperative hemodynamics compared with control group. Conclusions Subcostal TAP block blunts perioperative stress response and provides efficient analgesia, with good hemodynamic stability and minimal adverse effects.

Background: This study aimed to assess the effect of subcostal transversus abdominis plane (TAP) block on perioperative neuroendocrine stress response, postoperative analgesia, and recovery profiles in patients undergoing radical gastrectomy with general anesthesia. Methods: Sixty-five patients were recruited. Patients randomly received general anesthesia (control group), or general anesthesia combined with TAP block (40 mL of 0.375% ropivacaine) (TAP group). The primary endpoint was neuroendocrine levels including norepinephrine (NE), epinephrine (E), cortisol (Cor), glucose (Glu), interleukin (IL)-6 and IL-10 during 48 h after surgery. Secondary endpoints included pain score, hemodynamic variables and recovery characteristics. Results: Data from 61 of 65 patients were analyzed. The levels of NE, E, Cor, and Glu were blunt by TAP block during perioperative period. The levels of IL-6 and IL-10 were significantly lower in TAP group than in control group. TAP block efficiently relieved postoperative acute pain up to 12 h postoperatively with more stable perioperative hemodynamics compared with control group. Conclusions: Subcostal TAP block blunts perioperative stress response and provides efficient analgesia, with good hemodynamic stability and minimal adverse effects. Trial registration The trial was registered prior to patient enrollment at clinicaltrials.gov (NCT03035916, principal investigator: Guoqing Zhao, Ruizhu Liu, Kai Li, date of registration: 01/27/2017).

Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases and is considered to be the main cause of cognitive impairment in elderly people. The major symptom of AD is progressive dementia that eventually results in dysfunction of daily life. Due to the fact that AD has a long period of incubation before clinical symptoms emerge, the available therapeutic treatments can only improve the symptoms but not delay the progression of AD. Therefore, there is an urgent need to explore effective diagnostic approaches to catch and better treat the disease before clinical symptoms appear. Recent research revealed that abnormal expression of certain miRNA could have a crucial role in the pathological process of neurodegenerative disease including AD. Furthermore, given that AD patients show increased level of miRNAs in the blood and cerebrospinal fluid, miRNAs are considered promising non-invasive candidates for AD diagnosis and prognosis. Here, we reviewed the current research related to implications of miRNAs during the development of AD, summarized of actively used approaches to identifying potential miRNA biomarkers in body fluids, and discussed the diagnostic potential of microRNAs as biomarkers for AD.

Rationale Negative pressure pulmonary edema (NPPE) is a dangerous clinical complication and potentially life-threatening emergency without prompt diagnosis and intervention during recovery period after anesthetic extubation. Patient concerns A 25-year-old woman has undergone endoscopic thyroidectomy. After extubation, the patient developed acute respiratory distress with high airway resistance accompanied with wheezing, oxyhemoglobin saturation (SpO2) decreased to 70%. With positive pressure mask ventilation, her condition was stable, SpO2 99%. However, the patient developed pink frothy sputum with diffuse bilateral rales 30 min later after transported to surgical intensive care unit (SICU). Diagnoses Negative pressure pulmonary edema. Interventions The patient was undergone assisted ventilation with continuous positive airway pressure (CPAP) and furosemide 20 mg was given intravenously. Outcomes Postoperative day (POD) 2 her condition became stable, computed tomography (CT) scan indicated the pulmonary edema disappeared. The patient was discharged 6 days later. No abnormalities were observed during following 4 weeks. Lessons Although usually the onset of NPPE is rapid, with individual differences NPPE is still challenging. Increased vigilance in monitoring, diagnosis, and treatment are essential to prevent aggravation and further complication.

To evaluate the effect of subcostal transversus abdominis plane (TAP) block on postoperative analgesia and short-term prognosis. Forty patients were divided into T and N groups. Ultrasound-guided bilateral subcostal TAP block was performed by injection of ropivacaine or normal saline using patient-controlled intravenous analgesia pump. Postoperative hypoalgesia plane was T6-T10 in T group. Postoperative time to press PCIA pump time was (175.85±8.99) min and (64.10±27.37) min in N group. Sufentanil consumption at postoperative 0-12 h and 12-24 h and total sufentanil consumption were significantly lower than N group. Patients had significantly higher degree of satisfaction than N group. Off-bed time was (30.28±2.01) h and (39.55±2.56) h and the first flatus time was (48.95±3.83) h and (64.40±4.58) h in N group. It can offer 6 h analgesia time, enhance analgesic effect within postoperative 24 h, decrease the dosage of opiod drugs and promote intestinal tract function and mobility of recovery. Introduction For patients undergoing open radical gastrectomy, the analgesic effect of single intravenous injection was poor. acute upper abdomen pain after surgery severely reduced the comfortableness and affected respiration, off-bed time and the first flatus time and even progressed into neuropathic pain. In 2001, Rafi et al proposed the concept of transversus abdominis plane (TAP) block based upon dissection knowledge, which has been widely applied in the analgesia of lower abdominal operation[1]. Hebbard et al suggested that subcostal TAP was efficacious for upper abdominal operation[2]. Our preliminary experiment validated the good compound analgesic effect of subcostal TAP during surgery[3]. However, whether subcostal TAP could effectively supplement the postoperative intravenous analgesia and affect the quality of postoperative recovery remain unstudied, which is the starting point of this study. International Conference on Biomedical and Biological Engineering (BBE 2016) © 2016. The authors Published by Atlantis Press 258 Materials and Methods