Dexmedetomidine Might Exacerbate Acute Kidney Injury, While Midazolam Might Have a Postconditioning Effect: A Rat Model of Lipopolysaccharide-Induced Acute Kidney Injury.

BACKGROUND: The preconditioning effects of dexmedetomidine and propofol on septic acute kidney injury (AKI) have been reported, but the postconditioning effects remain unknown. This study investigated the postconditioning effects of dexmedetomidine, midazolam, and propofol on septic AKI. METHODS: Forty-eight male Wistar rats were intraperitoneally administered lipopolysaccharide (LPS; 8.3 mg kg-1) or normal saline. Twenty-four hours later, rats were allocated to specific anesthetic groups (n=6 each) and exposed for 6 h, as follows: C, control (no anesthetic); D, dexmedetomidine (5 µg kg-1 h-1); M, midazolam (0.6 mg kg-1 h-1); or P, propofol (10 mg kg-1 h-1). Serum creatinine (Cr) and cystatin C (CysC) were measured at the end of anesthesia. Western blot and immunofluorescent analyses of kidney samples were performed. RESULTS: Among LPS-treated groups, D group showed worsened renal dysfunction (L-C vs L-D: Cr, P=0.002, effect size (η2) =0.83; CysC, P=0.004, η2=0.71), whereas M group showed improved renal function (L-C vs L-M: Cr, P=0.009, η2=0.55). In immunofluorescent analysis of renal tubules, D group showed increased expression of nuclear factor κB (NFκΒ) (L-C vs L-D: NFκΒ, P=0.002, η2=0.75; phospho-NFκΒ, P=0.018, η2=0.66) and inhibitor of κ light polypeptide gene enhancer in B-cell kinase ß (IKKß) (L-C vs L-D: IKKß, P=0.002, η2=0.59; phospho-IKKα/ß, P=0.004, η2=0.59), whereas M group showed decreased NFκB expression (L-C vs L-M: NFκB, P=0.003, η2=0.55; phospho-NFκB, P=0.013, η2=0.46). CONCLUSIONS: Dexmedetomidine administration might worsen septic AKI, while midazolam might preserve kidney function via the NFκΒ pathway.

"Anti-cancer" effect of ketamine in comparison with MK801 on neuroglioma and lung cancer cells.

Ketamine, a N-methyl-D-aspartate (NMDA) receptor antagonist, is commonly used to induce anaesthesia during cancer surgery and relieve neuropathic and cancer pain. This study was conducted to assess whether ketamine has any inhibiting effects on neuroglioma (H4) and lung cancer cells (A549) in vitro. The cultured H4 and A549 cells were treated with ketamine and MK801 (0.1, 1, 10, 100, or 1000 µM) for 24 h. The expressions of glutamate receptors on both types of cancer cells were assessed with qRT-PCR. In addition, cell proliferation and migration were assessed with cell counting Kit-8 and wound healing assays. Cyclin D1, matrix metalloproteinase 9 (MMP9), phosphorylation of extracellular signal-regulated kinase (pERK), and cleaved-caspase-3 expression together with reactive oxygen species (ROS) were also assessed with Western blot, immunostaining, and/or flowcytometry. NMDA and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors were expressed on both H4 and A549 cells. Ketamine inhibited cancer cell proliferation and migration in a dose-dependent manner by suppressing the cell cycle and inducing apoptosis. Ketamine decreased cyclin D1, pERK, and MMP9 expression. In addition, ketamine increased ROS and cleaved caspase-3 expression and induced apoptosis. The anti-cancer effect of ketamine was more pronounced in A549 cells when compared with H4 cells. MK801 showed similar effects to those of ketamine. Ketamine suppressed cell proliferation and migration in both neuroglioma and lung cancer cells, likely through the antagonization of NMDA receptors.

The differential cancer growth associated with anaesthetics in a cancer xenograft model of mice: mechanisms and implications of postoperative cancer recurrence.

Anaesthetics may modify colorectal cancer cell biology which potentially affects long-term survival. This study aims to compare propofol and sevoflurane regarding with the direct anaesthetic effects on cancer malignancy and the indirect effects on host immunity in a cancer xenograft mode of mice. Cultured colon cancer cell (Caco-2) was injected subcutaneously to nude mice (day 1). Mice were exposed to either 1.5% sevoflurane for 1.5 h or propofol (20 µg g-1; ip injection) with or without 4 µg g-1 lipopolysaccharide (LPS; ip) from days 15 to 17, compared with those without anaesthetic exposure as controls. The clinical endpoints including tumour volumes over 70 mm3 were closely monitored up to day 28. Tumour samples from the other cohorts were collected on day 18 for PCR array, qRT-PCR, western blotting and immunofluorescent assessment. Propofol treatment reduced tumour size (mean ± SD; 23.0 ± 6.2mm3) when compared to sevoflurane (36.0 ± 0.3mm3) (p = 0.008) or control (23.6 ± 4.7mm3). Propofol decreased hypoxia inducible factor 1α (HIF1α), interleukin 1ß (IL1ß), and hepatocyte growth factor (HGF) gene expressions and increased tissue inhibitor of metalloproteinases 2 (TIMP-2) gene and protein expression in comparison to sevoflurane in the tumour tissue. LPS suppressed tumour growth in any conditions whilst increased TIMP-2 and anti-cancer neutrophil marker expressions and decreased macrophage marker expressions compared to those in the LPS-untreated groups. Our data indicated that sevoflurane increased cancer development when compared with propofol in vivo under non-surgical condition. Anaesthetics tested in this study did not alter the effects of LPS as an immune modulator in changing immunocyte phenotype and suppressing cancer development.

The neutrophil to lymphocyte ratio and serum albumin as predictors of acute kidney injury after coronary artery bypass grafting.

Postoperative acute kidney injury (AKI) is a highly prevalent and serious complication after cardiac surgery. The aim of this study is to identify the predictors of AKI and the cut-off values after isolated off-pump coronary artery bypass grafting (OPCAB). A total of 329 adult patients, who underwent isolated OPCAB between December 2008 and February 2021, were retrospectively analyzed. The patients were divided into three groups: non-AKI, early AKI and late AKI groups. The early AKI group or the late AKI group were defined as 'having AKI that occurred before or after 48 h postoperatively', respectively. Multivariate logistic regression analysis was performed to identify the predictors of AKI. Receiver operating characteristic (ROC) curve analysis was used to evaluate the cutoff value, the sensitivity, and the specificity of the predictors. On the multivariate analysis, the emergency surgery, the preoperative serum albumin, and the postoperative day 1 neutrophil to lymphocyte ratio (NL ratio) were identified as the independent predictors of AKI. However, neither albumin nor the NL ratio predicted late AKI. The present study showed the preoperative albumin and the postoperative day 1 NL ratio were the robust and independent predictors of postoperative early AKI in isolated OPCAB.

Worse ECOG-PS Is Associated with Increased 30-Day Mortality among Adults Older than 90 Years Undergoing Non-Cardiac Surgery: A Single-Center Retrospective Study.

BACKGROUND: A growing number of older patients are undergoing surgeries. However, reliable preoperative predictors of surgical mortality among older patients have not been identified. This study compared predictive factors for 30-day survival in patients older than 90 years after non-cardiac surgery. METHODS: This retrospective study at Nippon Medical School Hospital investigated the records of patients aged >90 years who underwent non-cardiac surgeries between 2010 and 2020. The data collected included age, gender, American Society of Anesthesiologists physical status (ASA-PS), preoperative Charlson score, preoperative fall risk assessment, Eastern Cooperative Oncology Group performance status (ECOG-PS), modified 5-item frailty index (mFI-5), need for intraoperative transfusion, postoperative complications, and 30-day survival after surgery. RESULTS: A total of 327 cases of elective surgery and 149 cases of emergency surgery were examined. Nonsurvivors (n=20, 4.2%) had significantly worse preoperative ASA-PS (for emergency cases) (nonsurvivors vs. survivors, 2.8 [2-3] vs. 2.3 [1-4], p=0.045), ECOG-PS (3.0 [2-4] vs. 1.0 [0-4], p<0.001), and mFI-5 values (3.0 [1-4] vs. 1.0 [0-3], p<0.001), more emergency cases (75.0% vs. 36.2%, p=0.004), and a greater need for intraoperative transfusion (55.0% vs. 13.4%, p<0.001). Among frailty assessment methods, ECOG-PS was the most strongly associated with 30-day mortality (area under the curve, ECOG-PS: 0.98, p<0.001; mFI-5: 0.86, p<0.001; Charlson score: 0.53, p=0.71; fall risk assessment: 0.55, p=0.44). Kaplan-Maier curves and multivariate logistic regression analysis demonstrated that an ECOG-PS of >3 was significantly associated with 30-day mortality (ECOG-PS: Kaplan-Maier curve, p<0.001, Log-rank test; odds ratio 1.71, 95% confidence interval: 1.35-2.16, p<0.001). CONCLUSIONS: An ECOG-PS of >3 was significantly correlated with 30-day mortality after non-cardiac surgery in patients older than 90 years.

Lung but not brain cancer cell malignancy inhibited by commonly used anesthetic propofol during surgery: Implication of reducing cancer recurrence risk.

Introduction: Intravenous anesthesia with propofol was reported to improve cancer surgical outcomes when compared with inhalational anesthesia. However, the underlying molecular mechanisms largely remain unknown. Objectives: The anti-tumor effects of propofol and the possible underlying mechanism including altered metabolic and signaling pathways were studied in the current study. Methods: The cell viability, proliferation, migration, and invasion of cancer cells were analyzed with CCK-8, Ki-67 staining, wound healing, and Transwell assay, respectively. The protein changes were analyzed with Western blot and immunofluorescent staining. The metabolomics alteration was studied with 1H-NMR spectroscopy. The gene expression regulations were analyzed with PCR gene array and qRT-PCR experiments. Results: In this study, we found that propofol reduced cell viability and inhibited cell proliferation, migration and invasion of lung cancer cells, but not neuroglioma cells. In lung cancer cells, propofol downregulated glucose transporter 1 (GLUT1), mitochondrial pyruvate carrier 1 (MPC1), p-Akt, p-Erk1/2, and hypoxia- inducible factor 1 alpha (HIF-1 α ) expressions and upregulated pigment epithelium-derived factor (PEDF) expression. Propofol increased intracellular glutamate and glycine but decreased acetate and formate whilst increased glucose, lactate, glutamine, succinate, pyruvate, arginine, valine, isoleucine, and leucine and glycerol, and decreased acetate, ethanol, isopropanol in the culture media of lung cancer cells. Furthermore, VEGFA, CTBP1, CST7, CTSK, CXCL12, and CXCR4 gene expressions were downregulated, while NR4A3, RB1, NME1, MTSS1, NME4, SYK, APC, and FAT1 were upregulated following the propofol treatment. Consistent with the phenotypical changes, these molecular and metabolic changes were not found in the neuroglioma cells. Conclusion: Our findings indicated anti-tumor effects of propofol on the lung cancer but not brain cancer, through the regulation of tumor metastasis-related genes, multi-cellular signaling and cellular metabolism.

Inhalational Anesthetics Inhibit Neuroglioma Cell Proliferation and Migration via miR-138, -210 and -335.

Inhalational anesthetics was previously reported to suppress glioma cell malignancy but underlying mechanisms remain unclear. The present study aims to investigate the effects of sevoflurane and desflurane on glioma cell malignancy changes via microRNA (miRNA) modulation. The cultured H4 cells were exposed to 3.6% sevoflurane or 10.3% desflurane for 2 h. The miR-138, -210 and -335 expression were determined with qRT-PCR. Cell proliferation and migration were assessed with wound healing assay, Ki67 staining and cell count kit 8 (CCK8) assay with/without miR-138/-210/-335 inhibitor transfections. The miRNA downstream proteins, hypoxia inducible factor-1α (HIF-1α) and matrix metalloproteinase 9 (MMP9), were also determined with immunofluorescent staining. Sevoflurane and desflurane exposure to glioma cells inhibited their proliferation and migration. Sevoflurane exposure increased miR-210 expression whereas desflurane exposure upregulated both miR-138 and miR-335 expressions. The administration of inhibitor of miR-138, -210 or -335 inhibited the suppressing effects of sevoflurane or desflurane on cell proliferation and migration, in line with the HIF-1α and MMP9 expression changes. These data indicated that inhalational anesthetics, sevoflurane and desflurane, inhibited glioma cell malignancy via miRNAs upregulation and their downstream effectors, HIF-1α and MMP9, downregulation. The implication of the current study warrants further study.

Sevoflurane and Desflurane Exposure Enhanced Cell Proliferation and Migration in Ovarian Cancer Cells via miR-210 and miR-138 Downregulation.

Inhalational anaesthetics were previously reported to promote ovarian cancer malignancy, but underlying mechanisms remain unclear. The present study aims to investigate the role of sevoflurane- or desflurane-induced microRNA (miRNA) changes on ovarian cancer cell behaviour. The cultured SKOV3 cells were exposed to 3.6% sevoflurane or 10.3% desflurane for 2 h. Expression of miR-138, -210 and -335 was determined with qRT-PCR. Cell proliferation and migration were assessed with wound healing assay, Ki67 staining and Cell Counting Kit-8 (CCK8) assay with or without mimic miR-138/-210 transfections. The miRNA downstream effector, hypoxia inducible factor-1α (HIF-1α), was also analysed with immunofluorescent staining. Sevoflurane or desflurane exposure to cancer cells enhanced their proliferation and migration. miR-138 expression was suppressed by both sevoflurane and desflurane, while miR-210 expression was suppressed only by sevoflurane. miR-335 expression was not changed by either sevoflurane or desflurane exposure. The administration of mimic miR-138 or -210 reduced the promoting effects of sevoflurane and desflurane on cancer cell proliferation and migration, in line with the HIF-1α expression changes. These data indicated that inhalational agents sevoflurane and desflurane enhanced ovarian cancer cell malignancy via miRNA deactivation and HIF-1α. The translational value of this work needs further study.

Anesthetics may modulate cancer surgical outcome: a possible role of miRNAs regulation.

BACKGROUND: microRNAs (miRNAs) are single-stranded and noncoding RNA molecules that control post-transcriptional gene regulation. miRNAs can be tumor suppressors or oncogenes through various mechanism including cancer cell biology, cell-to-cell communication, and anti-cancer immunity. MAIN BODY: Anesthetics can affect cell biology through miRNA-mediated regulation of messenger RNA (mRNA). Indeed, sevoflurane was reported to upregulate miR-203 and suppresses breast cancer cell proliferation. Propofol reduces matrix metalloproteinase expression through its impact on miRNAs, leading to anti-cancer microenvironmental changes. Propofol also modifies miRNA expression profile in circulating extracellular vesicles with their subsequent anti-cancer effects via modulating cell-to-cell communication. CONCLUSION: Inhalational and intravenous anesthetics can alter cancer cell biology through various cellular signaling pathways induced by miRNAs' modification. However, this area of research is insufficient and further study is needed to figure out optimal anesthesia regimens for cancer patients.

Inflammation Triggered by SARS-CoV-2 and ACE2 Augment Drives Multiple Organ Failure of Severe COVID-19: Molecular Mechanisms and Implications.

The widespread occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a pandemic of coronavirus disease 2019 (COVID-19). The S spike protein of SARS-CoV-2 binds with angiotensin-converting enzyme 2 (ACE2) as a functional "receptor" and then enters into host cells to replicate and damage host cells and organs. ACE2 plays a pivotal role in the inflammation, and its downregulation may aggravate COVID-19 via the renin-angiotensin system, including by promoting pathological changes in lung injury and involving inflammatory responses. Severe patients of COVID-19 often develop acute respiratory distress syndrome and multiple organ dysfunction/failure with high mortality that may be closely related to the hyper-proinflammatory status called the "cytokine storm." Massive cytokines including interleukin-6, nuclear factor kappa B (NFκB), and tumor necrosis factor alpha (TNFα) released from SARS-CoV-2-infected macrophages and monocytes lead inflammation-derived injurious cascades causing multi-organ injury/failure. This review summarizes the current evidence and understanding of the underlying mechanisms of SARS-CoV-2, ACE2 and inflammation co-mediated multi-organ injury or failure in COVID-19 patients.

Effect of Perioperative Lidocaine, Propofol and Steroids on Pulmonary Metastasis in a Murine Model of Breast Cancer Surgery.

Addressing the hypothesis that anaesthetic-analgesic technique during cancer surgery might influence recurrence or metastatic spread is a research priority. Propofol, which has anti-inflammatory properties in vitro, is clinically associated with reduced risk of cancer recurrence compared with sevoflurane anaesthesia in retrospective studies. Amide local anaesthetics, such as lidocaine, have cancer inhibiting effects in vitro. Steroids have anti-inflammatory and immunosuppressive effects and are associated with improved recovery after major non-cancer surgery. We compared the effects of propofol, lidocaine and methylprednisolone on postoperative metastasis in a murine model of breast cancer surgery under sevoflurane anaesthesia. 4T1 tumour cells were introduced into the mammary fat-pad of female BALB/c mice and the resulting tumour resected seven days later under general anaesthesia with sevoflurane. Mice (n = 72) were randomized to four treatment groups: Sevoflurane alone (control); Propofol group received 5 mg.kg-1; Lidocaine group received 1.5 mg.kg-1 followed by 2 mg.kg-1.h-1 infusion; Methylprednisolone group received 30 mg.kg-1 methylprednisolone. The primary outcome measure was pulmonary metastasis colony count, as assessed by in-vitro proliferation, two weeks post-operatively. This was achieved by treating the post-mortem lung tissue with collagenase IV, straining and culturing for 14 days prior to colony count. Compared with control, lidocaine and propofol each individually reduced pulmonary metastasis colonies; mean (SD) 846 (±581) vs. 88 (±52) vs. 34 (±44) respectively, (p = 0.0001 and p = 0.0001). Methylprednisolone increased lung metastasis, 2555 (±609) vs. 846 (±581), p = 0.0001. Post-operative hepatic metastatic disease and serum interleukin-6 and vascular endothelial growth factor levels were similar in all groups. In conclusion, in a murine model of breast cancer surgery during sevoflurane anaesthesia, propofol and lidocaine each decreased pulmonary metastasis, while methylprednisolone increased it.

Anesthetic Considerations of Intraoperative Neuromonitoring in Thyroidectomy.

BACKGROUND: Intraoperative neuromonitoring (IONM) might reduce the incidence of injury to the recurrent laryngeal nerve (RLN) during thyroidectomy. Although dislocation of endotracheal tube surface electrodes can lead to false-positive IONM results (loss of signal), the risk factors for dislocation and the effects of muscle relaxants are unclear. Therefore, to identify factors that affect IONM results, we examined the frequency and risk factors for tube dislocation after cervical extension before surgery, the effect of sugammadex administration, and the correlation between IONM results and postoperative RLN palsy. METHODS: Thirty-nine patients scheduled for thyroidectomy from October 2016 to April 2017 were enrolled. All patients underwent standard IONM and pre- and postoperative laryngoscopy. Differences in patient characteristics in the tube dislocation group and non-dislocation group, and differences in amplitude during vagal stimulation before and after sugammadex administration, were assessed by the Mann-Whitney test or Fisher's exact test. RESULTS: Tube dislocation occurred in 27 patients (69%). Sterno-cricoid distance was significantly shorter in the dislocation group (n=27) than in the non-dislocation group (n=12) (43.88 [32.2-55.91] mm vs 49.46 [40.66-55.91] mm, respectively; p=0.048). Without sugammadex, amplitude during vagal stimulation was sufficient for monitoring. Nine patients had new-onset RLN palsy, which was transient in all patients. The sensitivity of IONM was 100%, the positive predictive value was 60%, and the negative predictive value was 100%. CONCLUSIONS: The present findings suggest that anesthesiologists should use video laryngoscopy to correct tube dislocation and that a rocuronium dose of 0.6 mg/kg, without sugammadex, is adequate for IONM.

Effect of Perioperative Lidocaine and Cisplatin on Metastasis in a Murine Model of Breast Cancer Surgery.

BACKGROUND/AIM: Mortality from breast cancer is usually attributable to metastasis. In vitro data suggest that amide local anaesthetics, e.g. lidocaine, inhibit metastasis by multiple mechanisms and recent in vivo data support this. Experimental data also suggest that opioids may inhibit cisplatin chemotherapy. Whether lidocaine would influence cisplatin chemotherapy has not been evaluated. MATERIALS AND METHODS: 4T1 cells were injected into the mammary gland of immunocompetent female BALB/c mice, with resection of the tumour under sevoflurane anaesthesia one week later. Mice (n=45) were randomized into one of three groups: The cisplatin group received 3 mg.kg-1 cisplatin; cisplatin and lidocaine group received 3 mg.kg-1 cisplatin and lidocaine bolus of 1.5 mg.kg-1 followed by an infusion of 2 mg.kg-1.h-1 The control group received sevoflurane only. All agents were given perioperatively. After 14 postoperative days, post-mortem lung, serum and liver samples were collected. Primary outcome measure was lung metastasis colony count. RESULTS: During sevoflurane anaesthesia, the addition of lidocaine to cisplatin significantly decreased metastatic lung colony count [(mean±SD) (157±87)] compared to control [846±581, (p=0.001)], and cisplatin alone [580±383, (p=0.018)]. However, liver metastasis colony count was not reduced with the combination of cisplatin and lidocaine (9.3±13.9) when compared to control (74.7±257.3), p=0.78 or to cisplatin alone (110±388.8), p=0.569. Serum VEGF and interleukin-6 concentrations were not significantly different. CONCLUSION: In a 4T1 murine model of breast cancer surgery, under sevoflurane anaesthesia, lidocaine enhanced the metastasis-inhibiting action of cisplatin. Clinical evaluation of the hypothesis that co-administration of systemic lidocaine during cisplatin chemotherapy seems warranted.

Volatile anaesthetics enhance the metastasis related cellular signalling including CXCR2 of ovarian cancer cells.

The majority of ovarian cancer patients relapse after surgical resection. Evidence is accumulating regarding the role of surgery in disseminating cancer cells; in particular anaesthesia may have an impact on cancer re-occurrence. Here, we have investigated the metastatic potential of volatile anaesthetics isoflurane, sevoflurane and desflurane on ovarian cancer cells. Human ovarian carcinoma cells (SKOV3) were exposed to isoflurane (2%), sevoflurane (3.6%) or desflurane (10.3%) for 2 hours. Metastatic related gene expression profiles were measured using the Tumour Metastasis PCR Array and qRT-PCR. Subsequently vascular endothelial growth factor A (VEGF-A), matrix metalloproteinase 11 (MMP11), transforming growth factor beta-1 (TGF-ß1) and chemokine (C-X-C motif) receptor 2 (CXCR2) proteins expression were determined using immunofluorescent staining. The migratory capacities of SK-OV3 cells were assessed with a scratch assay and the potential role of CXCR2 in mediating the effects of volatile anaesthetics on cancer cell biology were further investigated with CXCR2 knockdown by siRNA. All three volatile anaesthetics altered expression of 70 out of 81 metastasic related genes with significant increases in VEGF-A, MMP-11, CXCR2 and TGF-ß genes and protein expression with a magnitude order of desflurane (greatest), sevoflurane and isoflurane. Scratch analysis revealed that exposure to these anesthetics increased migration, which was abolished by CXCR2 knockdown. Volatile anaesthetics at clinically relevant concentrations have strong effects on cancer cell biology which in turn could enhance ovarian cancer metastatic potential. This work raises the urgency for further in vivo studies and clinical trials before any conclusions can be made in term of the alteration of clinical practice.

Anesthesia, surgical stress, and "long-term" outcomes.

An increasing body of evidence shows that the choice of anesthetic can strongly influence more than simply the quality of anesthesia. Regional and general anesthesia have often been compared to ascertain whether one provides benefits through dampening the stress response or harms by accelerating cancer progression. Regional anesthesia offers considerable advantages, by suppressing cortisol and catecholamine levels and reducing muscle breakdown postoperatively. It also has less immunosuppressive effect and potentially reduces the proinflammatory cytokine response. As such, vital organ functions (e.g., brain and kidney) may be better preserved with regional anesthetics, however, further study is needed. Volatile general anesthetics appear to promote cancer malignancy in comparison to regional and intravenous general anesthetics, and reduce the body's ability to act against cancer cells by suppression of natural killer cell activity. There is not sufficient evidence to support an alteration of current clinical practice, however, further research into this area is warranted due to the potential implications elicited by current studies.

Hypoxia-inducible factor-1: a possible link between inhalational anesthetics and tumor progression?

Cancer remains one of the major causes of death worldwide, and the global burden of the disease is rising continuously. Clinical retrospective data suggested that inhalational anesthetics might affect the prognosis of cancer patients, but the underlying molecular mechanism remained unknown. Hypoxia-inducible factor-1 (HIF-1) is a dimeric transcription factor and mediates various cellular responses to hypoxia, including metabolism, cell death and survival, angiogenesis, oxygen delivery, immune evasion, and genomic adaptation. HIF-1 system has been shown to be the driving force of solid tumor progression and substantially contributes to the malignancy of cancer. Inhalational anesthetics such as isoflurane have been demonstrated to confer cytoprotection in a HIF-1-dependent manner in various vital organs. In addition, a recent study has demonstrated the pivotal involvement of HIF-1 in the impact of inhalational anesthetics on cancer cells. This review provides critical insights into the new understanding of cancer sensing of inhalational anesthetics and examines the recent understanding of the underlying molecular mechanisms. However, this area of research is just beginning and warrants further studies preclinically and clinically prior to making any conclusions that inhalational anesthetics may affect cancer outcomes. In addition, it is important to note that there is not enough evidence to support any change in the current clinical practice.

Differential expression of rat hippocampal microRNAs in two rat models of chronic pain.

The two most common forms of chronic pain are inflammatory pain and neuropathic pain. Nevertheless, the underlying mechanisms of these pain conditions and their therapeutic responses are poorly understood. MicroRNAs (miRNAs) negatively regulate cell genes, and thus control cell proliferation, inflammation and metabolism. In the present study, we examined gene expression in the hippocampus of rats in two models of chronic pain. In addition, we used the left hindpaw procedure to identify differences in the bilateral hippocampus. We divided the rats into the 4 following groups: the group with chronic constriction injury (CCI), the sham-operated group, the group injected with complete Freund's adjuvant (CFA) and the group injected with normal saline. miRNA expression profiles were analyzed using TaqMan low-density array (TLDA). We observed 54 miRNAs (22.7%) in the rats with CCI rats that were differentially expressed, including 7 miRNAs that were downregulated compared with the sham-operated rats. In the CFA-injected rats, 40 miRNAs (16.8%) were differentially expressed, including 8 miRNAs that were downregulated compared with the normal saline-injected rats. Pearson's correlation co-efficient for all detected miRNAs in the rat hippocampus failed to identify differences between the hippocampi bilaterally. An unsupervised cluster analysis produced separate clusters between the control and experimental groups. In this study, we demonstrate the differential expression of hippocampal miRNAs in two rat models of chronic pain; however, no significant differences were observed bilaterally in hippocampal miRNA expression. Further research is required to determine the correlation among miRNAs, messenger RNAs (mRNAs) and proteins.