Effects of Glutathione Tablets on Ferroptosis Pathway and Oxidative Stress-Related Indexes in Serum of Patients Undergoing Sevoflurane Inhalation General Anesthesia and Its Clinical Significance.

Objective: To explore the effect of glutathione on serum oxidative stress, inflammatory reaction, and brain injury in patients with Sevoflurane inhalation general anesthesia based on iron metabolism pathway. Methods: From January 2018 to January 2023, 120 patients undergoing Sevoflurane inhalation anesthesia in Xingtai Third Hospital were divided into a control group and an observation group. The control group was given routine treatment, and the observation group patients were given oral glutathione tablets 2 weeks before anesthesia based on the control group. Relevant basic data of patients were collected 3 days before operation (T0), 1 day after the operation (T1), 3 days (T2), and 7 days (T3) respectively, and the serum oxidative stress indicators of patients in each group were measured by ELISA: SOD, MDA, GSH, Hif-1α, ferroptosis related indicators: SIRT3, GPX4; related inflammatory indicators: IL-1ß, TGF-ß, IL-33; neuronal injury related proteins: MBP, NGF, and statistical analysis of the data. Results: There was no significant difference in general conditions and operation time between the two groups (P > .05). Compared with the control group, the observation group showed significant differences in oxidative stress indicators: SOD in the observation group at T1, SOD, and Hif-1α in the observation group at T2, and SOD, MDA, GSH and Hif-1α in the observation group at T3. 1α, there were significant differences compared with the indicators of the control group at the same time (P < .001). In terms of inflammatory factor indicators, compared with the control group, there were significant differences in IL-1ß at T1, TGF-ß, and IL-33 at T2, and IL-1ß, TGF-ß and IL-33 at T3. (P < .001). In terms of ferroptosis indicators, compared with the control group, there were significant differences in SIRT3 at T1, SIRT3, and GPX4 at T2, and SIRT3 and GPX4 at T3 (P < .001). In terms of nerve injury-related proteins, in patients, MBP levels were negatively correlated with SIRT3 (r=-0.8979, P < .0001), MBP levels were positively correlated with GPX4 (r=0.528, P < .0001), and NGF levels were positively correlated with SIRT3 (r=0.8979, P < .0001), NGF level was negatively correlated with GPX4 (r=0.528, P < .0001). Conclusion: Glutathione tablets can alleviate sevoflurane-induced ferroptosis and oxidative stress by elevating GPX4 protein levels, and glutathione tablets have an ameliorative effect on brain injury in patients with sevoflurane inhalation anesthesia.

Efficacy of Adjunctive Chlorhexidine in non-surgical treatment of Peri-Implantitis/Peri-Implant Mucositis: An updated systematic review and meta-analysis.

Objective: The current review aimed to assess the efficacy of adjunctive chlorhexidine (CHX) in the non-surgical treatment of peri-implantitis/peri-implant mucositis. Methods: PubMed, Embase, Science Direct, CENTRAL, and Google Scholar databases were searched up to 10th March 2022 for relevant randomized controlled trials or controlled clinical trials. Results: Fourteen studies were included. Meta-analysis revealed significantly lower probing depths in peri-implant mucositis patients using CHX adjuncts as compared to controls (SMD: -1.49 95% CI: -2.56, -0.42 I2=95% p=0.006). However, the same effect was not noted in peri-implantitis (SMD: -1.18 95% CI: -0.04, 2.40 I2=96% p=0.06). CHX was not found to improve bleeding of probing in peri-implant mucositis while sufficient data was unavailable for peri-implantitis. Results on other outcome variables were conflicting. Conclusion: Evidence on the efficacy of adjunctive CHX for peri-implant mucositis is conflicting. Similarly, strong conclusions on the effect of CHX for peri-implantitis cannot be drawn due to limited number of studies. Overall, there seems to be a trend of non-significant impact of CHX on outcomes of peri-implant mucositis as well as peri-implantitis.

Immediate vs Conventional Loading of Mandibular Overdentures: A Comprehensive Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Clinicians treating overdenture patients need to know if immediate loading and conventional loading results in similar outcomes. This study aimed to perform a systematic literature search of studies comparing immediate and conventional loading of mandibular overdentures irrespective of the number of implants and conduct a meta-analysis of implant failure and marginal bone loss (MBL). A literature search of PubMed, ScienceDirect, Ovoid, Springer, and Google Scholar databases was performed for randomized controlled trials (RCTs) comparing immediate vs conventional loading of mandibular overdentures. The primary outcome was implant failure and the secondary outcome was marginal bine loss (MBL). A descriptive analysis was performed for other outcomes. Thirteen trials were included. Only one trial compared the immediate and delayed loading of single implant-supported overdenture. Seven trials used 2 implants, 1 trial used 3 implants while 4 trials used 4 implants. Meta-analysis indicated no statistically significant difference in implant failure and MBL between immediate and conventional loading of 2- and 4-implant supported overdentures. Descriptive analysis indicated no difference in peri-implant tissue indices, implant stability, and quality of life outcomes between the 2 loading protocols. There may be no difference in implant failure and MBL with immediate loading or conventional loading of 2- and 4-implant supported mandibular overdentures. Literature review indicates that there may be no difference in peri-implant tissue indices, implant stability, and quality of life outcomes between the 2 loading protocols. The overall quality of evidence is moderate. Further, adequately powered RCTs are required to strengthen the evidence.

Salvianolic acid B improved insulin resistance through suppression of hepatic ER stress in ob/ob mice.

Impaired insulin sensitivity of insulin-sensitive tissues plays a major role in the pathogenesis of type 2 diabetes, salvianolic acid B (SalB), a natural antioxidant usually treated various cardiovascular diseases was also reported potential utility on diabetes and dyslipidemia. Based on these, we aimed to explored whether the antioxidant effect of SalB play a pivotal role in the molecular mechanisms leading to insulin resistance. We found that SalB improved glucose tolerance and insulin sensitivity, decreased serum ALT, AST and ALP levels of ob/ob mice. Also, transcription of Bip and CHOP, phosphorylation of PERK and IRE1 for endoplasmic reticulum stress (ER) and phosphorylation of IRS-1 for insulin sensitivity in the liver of ob/ob mice were relieved by SalB. Further, SalB decreased phosphorylation of PERK, IRE1 and IRS1 and transcription of Bip and CHOP stimulated by palmitate of hepatic cells HL7702, but did not reversed phosphorylation of JNK and IRS1 and transcription of Bip and CHOP when ER stress was stimulated by tunicamycin. These data shows that SalB improved insulin resistance of ob/ob mice through suppression of hepatic ER stress.

The pressure-temperature phase diagram of pure Co based on first-principles calculations.

We optimized the high pressure-temperature phase diagram of pure Co up to the liquidus temperature and 120 GPa, based on thermodynamic properties calculated using first-principles. The Gibbs energy for each phase was evaluated in the framework of a quasiharmonic approximation, with a consideration of the thermal electronic contribution at finite temperatures. Particularly, the liquidus temperature, as a function of pressure, was determined using classical Molecular Dynamics simulations. Our results in this work successfully integrated experimental observations and the previous theoretical predictions. The critical solid phase transitions of ε → γf and ε → ß were clarified using the Gibbs energy as a function of pressure and temperature. In addition, the magnetism of ß above 70 GPa was verified to be nonmagnetic. The difference between γp and ß, which was unclear before, has been illustrated to be associated with the magnetic transformation from the paramagnetic state of the γp phase to the nonmagnetic state of the ß phase rather than the structural transformation.

Long-term outcome after surgical resection for cholangiocarcinoma and prognostic index value.

OBJECTIVE: To investigate the prognostic factors of patients with cholangiocarcinoma and establish a prognostic model to evaluate the prognosis. METHODS: 169 cases of cholangiocarcinoma were analyzed retrospectively. Clinicopathological factors were evaluated using univariate and multivariate analysis. Prognostic index (PI) was calculated based on the results of multivariate analysis. Patients with different PI were divided into 3 groups in order to compare the survival rate of each group and draw the survival curves. Individual expected survival rate was calculated based on the prognostic Cox model and PI. The PI equation was built that included all significant variables and coefficients as follow formula: PI = (ß1 × lymph node metastasis) + (ß2 × CEA level) - (ß3 × surgical margin). RESULTS: Univariate analysis showed that CEA, lymph node metastasis, surgical margin, AJCC staging, tumor differentiation and adjuvant chemotherapy were prognostic impacts. The difference was statistically significant (p < 0.05). Cox multivariate analysis showed that CEA, lymph node metastasis and surgical margin are three separate prognostic factors. According to different PI, patients were divided into high-risk group, middle-risk group and low-risk group and three groups were statistically significant difference in survival rate (P < 0.05). CONCLUSION: Racical resection is the key to improve the long-term survival rate of cholangiocarcinoma. By using prognostic Cox model and the PI, the prognosis of patients could be estimated and individualized clinical treatment could be conducted.

Blockade of store-operated calcium entry alleviates ethanol-induced hepatotoxicity via inhibiting apoptosis.

Extracellular Ca(2+) influx has been suggested to play a role in ethanol-induced hepatocyte apoptosis and necrosis. Previous studies indicated that store-operated Ca(2+) entry (SOCE) was involved in liver injury induced by ethanol in HepG2 cells. However, the mechanisms underlying liver injury caused by SOCE remain unclear. We aimed to investigate the effects and mechanism of SOCE inhibition on liver injury induced by ethanol in BRL cells and Sprague-Dawley rats. Our data demonstrated that ethanol (0-400mM) dose-dependently increased hepatocyte injury and 100mM ethanol significantly upregulated the mRNA and protein expression of SOC for at least 72h in BRL cells. Blockade of SOCE by pharmacological inhibitors and sh-RNA knockdown of STIM1 and Orai1 attenuated intracellular Ca(2+) overload, restored the mitochondrial membrane potential (MMP), decreased cytochrome C release and inhibited ethanol-induced apoptosis. STIM1 and Orai1 expression was greater in ethanol-treated than control rats, and the SOCE inhibitor corosolic acid ameliorated the histopathological findings and alanine transaminase and aspartate transaminase activity as well as decreased cytochrome C release and inhibited alcohol-induced cell apoptosis. These findings suggest that SOCE blockade could alleviate alcohol-induced hepatotoxicity via inhibiting apoptosis. SOCE might be a useful therapeutic target in alcoholic liver diseases.

[The impact of non-alcoholic fatty liver disease on islet function in type 2 diabetes].

OBJECTIVE: To analyze the influence of hepatosteatosis on pancreatic P-cell function in type 2 diabetes mellitus (22DM). METHODS: A total of 213 subjects with T2DM from Metabolic Disease Hospital, Tianjin Medical University from January 2013 to December 2013 were included in the study. Non-alcoholic fatty liver disease (NAFLD) was diagnosed with abdominal ultrasonography. Patients were divided into two groups: 22DM with NAFLD and 22DM without NAFLD. ALT, AST, gamma-glutamyltransferase, serum lipid, glycosylated hemoglobin A1c ( HbA1c), fructosamine, fasting glucose, insulin and 2 hours plasma glucose, insulin after 75g glucoseload were detected. The insulin resistance and P-cell function were assessed by HOMA-IR and HOMA-P. RESULTS: Among the 213 22DM subjects, 51% (108 cases) were with NAFLD. The HOMA-IR [4.76(2.83,7.21) vs. 2.79 (1.76, 4.37),P <0.05] and HOMA-P [49.18 (37.78, 85.09) vs. 29.50 (18.09, 45.54), P < 0.05] were significantly higher in 22DM with NAFLD than those in 22DM alone. Within subjects with 22DM and NAFLD,the HOMA-IR [6.28 (2.87, 8.17) vs. 2.95 (2.07, 3.66)P <0. 05] and HOMA-P [59.18 (37.78, 85.09) vs. 30.59 (28.56, 34.49), P < 0.05] levels were higher in subjects with normal liver function than those with abnormal liver function. CONCLUSIONS: T2DM patients with NAFLD have severer insulin resistance than those without NAFLD. The P-cell function of those patients was compensatory increased, which was decreased in subjects with abnormal liver function.

[The efficacy and safety of human glucagon-like peptide-1 analogue liraglutide in newly diagnosed type 2 diabetes with glycosylated hemoglobin A1c > 9].

OBJECTIVE: To evaluate the efficacy and safety of human glucagon-like peptide-1 analogue liraglutide in newly diagnosed type 2 diabetes mellitus (T2DM) with glycosylated hemoglobin A1c (HbA1c) > 9%. METHODS: This was an open-labelled, randomized, parallel-group, treat-to-target trial. Newly diagnosed T2DM patients with HbA1c > 9% were enrolled. These patients were treated with metformin with repaglinide and randomized to receive once-daily liraglutide (LIRA, n=25) or the insulin glargine (IGla, n=24) at bedtime. Efficacy and safety were assessed and compared after 18-month treatment. RESULTS: (1) Compared with the baseline, patients with LIRA had significantly reduced mean body weight,BMI and waist circumference (P < 0.01), whereas, the above indexes were increased (P < 0.01) in patients treated with IGla. (2) After 18 months of treatment, fasting plasma glucose (FPG), 2-hour plasma glucose after a 75g oral glucose load (2hPG) and HbA1c were significantly improved in all patients (P < 0.01), with 2hPG, mean blood glucose (MBG), the largest amplitude of glycemic excursions (LAGE), mean amplitude of glycemic excursions (MAGE) were significantly lower in LIRA group than in IGla group (all P < 0.05). (3) HOMA-IR decreased in both groups (P < 0.05). However, ΔI30/ΔG30, AUCCP180 and Matsuda index were only significantly increased in patients treated with LIRA (respectively, 4.88 ± 1.55 vs 7.60±1.91, 9.23 ± 2.66 vs 13.18 ± 2.72, 39.28 ± 20.35 vs 54.64 ± 23.34, all P < 0.01), while HOMA-IR reduced (4.41 ± 1.58 vs 3.52 ± 1.44, P < 0.05). But in IGla group only HOMA-IR was reduced (4.92 ± 1.84 vs 4.57 ± 1.80, P < 0.05). The index of ΔI30/ΔG30, AUCCP180 and Matsuda index in LIRA group are higher than those of indexes in IGla group(respectively, 7.60 ± 1.91 vs 4.18 ± 1.00, 13.18 ± 2.72 vs 10.53 ± 2.68,54.64 ± 23.34 vs 41.65 ± 17.84, all P < 0.05), while HOMA-IR is lower (3.52 ± 1.44 vs 4.57 ± 1.80, P< 0.05). (4) The rate of HbA1c ≤ 6.5% and the dosages of oral anti-diabetic drugs in LIRA group were significantly better than that in IGla group. (5) No significant differences were observed in hypoglycemic episodes and adverse events between two groups. CONCLUSION: It seems that liraglutide is superior to insulin glargine in newly diagnosed T2DM patients with HbA1c > 9% in improving beta-cell function, insulin sensitivity and glucose homeostasis.

Angiotensin II promotes cardiac differentiation of embryonic stem cells via angiotensin type 1 receptor.

As embryonic stem cells (ESCs) represent an attractive candidate cell source for obtaining cardiomyocytes to be used in cell replacement therapy, it is thus of considerable importance to understand the mechanism by which cardiac differentiation is regulated. In previous studies, we have shown that angiotensin type 1 receptor (AT1R) expressed in cardiomyocytes derived from mouse embryonic stem cells. However, little is known about the role of AT1R in cardiac differentiation, which plays a key role in cardiac physiology and pharmacology. In the present study, we demonstrated that AT1R agonist significantly enhanced cardiac differentiation as determined by increased percentage of beating embryoid bodies and a higher expression level of cardiac markers. On the contrary, AT1R agonist stimulated differentiation was reversed in the presence of AT1R antagonist. In addition, by administering selective inhibitors we found that the effect of AT1R was driven via extracellular-signal regulated kinase, c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase pathways. These findings suggest that AT1R signaling plays a key role in cardiac differentiation of ESCs.

[Low concentration of iodixanol used in CT angiography of lower extremity arteriosclerosis obliterans].

OBJECTIVE: To evaluate the clinical diagnostic value of low concentration of iodixanol used in CT angiography (CTA) of lower extremity arteriosclerosis obliterans (LEASO). METHODS: 42 patients which were suspect diagnosed with LEASO were divided to A group (270 mgI/ml iodixanol, tube voltage 100 kV) and B group (350 mgI/ml iohexol, tube voltage 120 kV), 21 patients in each group. Measure the body mass index (BMI) before the CTA of lower extremity. CTA results were analyzed with the digital subtraction angiography (DSA) as the "gold standard". RESULTS: There were no statistical difference of age, gender, BMI and CT value of the bifurcation of profunda femoral artery and superficial femoral artery, upper segment of anterior tibial artery and posterior tibial artery between A and B group. The diagnostic sensitivity and specificity of A and B groups of CTA were 97.0%, 99.1% and 98.3%, 99.5% for occlusion. Regard artery more than moderate stenosis (include moderate stenosis) as the overall statistics, the diagnostic sensitivity and specificity of A and B groups of CTA were 99.2%, 99.3% and 99.1%, 99.3%, the accuracy were 92.9% and 93.0%, the positive predictive and negative predictive value were 96.9%, 99.3% and 96.6%, 99.3%, respectively. The kappa value of A and B groups of CTA and DSA consistency test were 0.930 and 0.927, respectively. CONCLUSION: The CTA with low concentration of iodixanol combine with low tube voltage can achieve superior conventional scanning imaging features, and has great clinical value in the diagnosis of LEASO, also is an effective method for the inspection, evaluation and follow-up.

Genetically predicted major depression causally increases the risk of temporomandibular joint disorders.

Objective: Observational studies have reported that mental disorders are comorbid with temporomandibular joint disorder (TMD). However, the causal relationship remains uncertain. To clarify the causal relationship between three common mental illnesses and TMD, we conduct this Mendelian Randomization (MR) study. Methods: The large-scale genome-wide association studies data of major depression, bipolar disorder and schizophrenia were retrieved from the Psychiatric Genomics Consortium. The summary data of TMD was obtained from the Finn-Gen consortium, including 211,023 subjects of European descent (5,668 cases and 205,355 controls). The main approach utilized was inverse variance weighting (IVW) to evaluate the causal association between the three mental disorders and TMD. Five sensitivity analyses including MR-Egger, Maximum Likelihood, Weighted median, MR. RAPS and MR-PRESSO were used as supplements. We conducted heterogeneity tests and pleiotropic tests to ensure the robustness. Results: As shown by the IVW method, genetically determined major depression was associated with a 1.65-fold risk of TMD (95% CI = 1.10-2.47, p < 0.05). The direction and effect size remained consistent with sensitivity analyses. The odds ratios (ORs) were 1.51 (95% CI = 0.24-9.41, p > 0.05) for MR-Egger, 1.60 (95% CI = 0.98-2.61, p > 0.05) for Weighted median, 1.68 (95% CI = 1.19-2.38, p < 0.05) for Maximum likelihood, 1.56 (95% CI = 1.05-2.33, p < 0.05) for MR. RAPS, and 1.65 (95% CI = 1.10-2.47, p < 0.05) for MR-PRESSO, respectively. No pleiotropy was observed (both P for MR-Egger intercept and Global test >0.05). In addition, the IVW method identified no significant correlation between bipolar disorder, schizophrenia and TMD. Conclusion: Genetic evidence supports a causal relationship between major depression and TMD, instead of bipolar disorder and schizophrenia. These findings emphasize the importance of assessing a patient's depressive status in clinical settings.

[Role of store-operated Ca2+ channels in ethanol-induced intracellular Ca2+ increase in HepG2 cells].

OBJECTIVE: To investigate the mechanism of ethanol-induced calcium overload in hepatocytes and the related role of store-operated calcium channels (SOCs). METHODS: HepG2 cells were treated an ethanol concentration gradient with or without intervention treatment with the extracellular calcium chelator EGTA or the SOCs inhibitor 2-aminoethoxydiphenyl borate (2-APB). Effects on cell viability were assessed by the CCK8 assay. Effects on leakage of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined by automatic biochemical analyzer measurements of the culture supernatants. Effects on cytoplasmic free Ca2+ concentration ([Ca2+]i) were accessed by detecting fluorescence intensity of the calcium indicator Fluo-3/AM with a flow cytometer. Effects on mRNA and protein expression levels of SOCs, stromal interacting factor 1 (STIM1), and calcium release-activated calcium channel protein 1 (Orai1) were evaluated by qPCR and western blotting. RESULTS: The ethanol treatment produced dose-dependent reduction in cell viability (r = -0.985, P less than 0.01) and increases in leakage of ALT (F = 15.286, P less than 0.01) and AST (F = 39.674, P less than 0.01). Compared to untreated controls, the ethanol treatments of 25, 50, 100, 200 and 400 mM induced significant increases in [Ca2+]i level (1.25+/-0.36, 1.31+/-0.15, 1.41+/-0.18, 2.29+/-0.25, 2.58+/-0.19; F = 15.286, P less than 0.01). Both intervention treatments, EGTA and 2-APB, significantly reduced the 200 mM ethanol treatment-induced [Ca2+]i increase (2.32+/-0.08 reduced to 1.79+/-0.15 (t = 7.201, P less than 0.01) and 1.86+/-0.09 (t = 8.183, P less than 0.01) respectively). EGTA and 2-APB also increased the ethanol-treated cells' viability and reduced the ALT and AST leakage. The 200 mM ethanol treatment stimulated both gene and protein expression of STIM1 and Orai1, and the up-regulation effect lasted at least 72 h after treatment. CONCLUSION: Ethanol-induced dysregulation of SOCs may be an important molecular mechanism of ethanol-induced [Ca2+]i rise in hepatocytes and the related liver cell injury.

A Review of Metamaterials in Wireless Power Transfer.

Wireless power transfer (WPT) is a technology that enables energy transmission without physical contact, utilizing magnetic and electric fields as soft media. While WPT has numerous applications, the increasing power transfer distance often results in a decrease in transmission efficiency, as well as the urgent need for addressing safety concerns. Metamaterials offer a promising way for improving efficiency and reducing the flux density in WPT systems. This paper provides an overview of the current status and technical challenges of metamaterial-based WPT systems. The basic principles of magnetic coupling resonant wireless power transfer (MCR-WPT) are presented, followed by a detailed description of the metamaterial design theory and its application in WPT. The paper then reviews the metamaterial-based wireless energy transmission system from three perspectives: transmission efficiency, misalignment tolerance, and electromagnetic shielding. Finally, the paper summarizes the development trends and technical challenges of metamaterial-based WPT systems.

Seasonal variations of cave dripwater hydrogeochemical parameters and δ13CDIC in the subtropical monsoon region and links to regional hydroclimate.

Stalagmites are considered natural archives of climate proxies. However, under the combined effects of atmospheric circulation patterns, precipitation, and karst environments, drip hydrogeochemical processes can be coupled and linked to each other to control cave sediment record information. Therefore, the evolution of chemistry and factors controlling the isotopic composition of the dripwater during regional precipitation migration from the surface to caves need to be evaluated. In this study, hydrogeochemical characteristics and the isotopic composition of the dripwater in the Mahuang Cave in Guizhou Province, Southwest China, including stable isotope (δ13CDIC) and trace element ratios, were monitored from August 2018 to December 2020. The results showed seasonal variations in the δ13CDIC, Mg/Ca, and Sr/Ca values of the dripwater in dry and wet seasons under the control of water-gas-rock reactions, such as soil CO2 concentrations and carbonate rock dissolution. In addition, the five monitored dripwater points in the Mahuang Cave showed fast and slow seepage due to the complex cave fractures and stratigraphy, reflecting the effects of precipitation variations to different degrees. Indeed, the δ13CDIC were more sensitive to the recharge changes from extreme precipitation and drought events. Therefore, dripwater δ13CDIC is a reliable indicator of the recorded hydrological signal in the southwest monsoon region.

Emulsified isoflurane induces postconditioning against myocardial infarction via JAK-STAT pathway.

BACKGROUND: The authors investigated the cardioprotection afforded by postconditioning with intravenous infusion of emulsified isoflurane in a rat model in vivo and determined the role of Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway in such procedure. MATERIALS AND METHODS: Rats were subjected to a 30-min coronary artery occlusion followed by a 120-min reperfusion. Postconditioning was achieved by inhalation of 1 minimum alveolar concentration isoflurane or intravenous infusion of emulsified isoflurane (8% vol/vol) during the last 3 min of coronary artery occlusion and the first 5 min of reperfusion. AG490 was used to inhibit the activity of JAK2. Infarct size was determined by triphenyltetrazolium chloride staining. Expressions of JAK2, STAT1, and STAT3 were measured by Western blot. RESULTS: Infarct size was significantly reduced from 51.6% ± 7.6% in the control group to 29.8% ± 7.0% in rats postconditioned with inhalation of isoflurane (P < 0.01). A powerful infarct-sparing effect was also induced by postconditioning with intravenous infusion of emulsified isoflurane (33.7% ± 5.6% versus control group, P < 0.01). Pretreatment with AG490 abolished the anti-infarct effects conducted by either inhalation of isoflurane (44.1% ± 7.1% versus control group, P > 0.05) or intravenous infusion of emulsified isoflurane (51.4% ± 6.8% versus control group, P > 0.05). Compared with the control group, postconditioning with inhalation of isoflurane or infusion of emulsified isoflurane remarkably enhanced the expression of phosphorylation of JAK2 Tyr(1007)/Tyr(1008) and STAT3 Tyr(705), but not phosphorylation of STAT1 Tyr(701). CONCLUSIONS: Postconditioning with intravenous infusion of emulsified isoflurane induces powerful cardioprotection, which is mediated, at least in part, by activating JAK-STAT pathway.

Diabetes abolishes the cardioprotection induced by sevoflurane postconditioning in the rat heart in vivo: roles of glycogen synthase kinase-3ß and its upstream pathways.

BACKGROUND: We measured the cardioprotection afforded by sevoflurane postconditioning in streptozotocin-induced diabetic rats (DRs) and determined the roles of glycogen synthase kinase (GSK), phosphatidylinositol-3-kinase/Akt, and extracellular signal-regulated kinase (ERK1/2) in such a procedure. METHODS: DRs and nondiabetic rats (NDRs) were subjected to a 30-min coronary artery occlusion followed by a 120-min reperfusion. Postconditioning was achieved by inhalation of 1 minimum alveolar concentration sevoflurane at the first 5 min of reperfusion. The infarct size was determined by triphenyltetrazolium chloride staining. Expressions of GSK-3ß, Akt, and ERK1/2 were measured using Western blotting. RESULTS: In NDRs, the infarct size was significantly decreased from 53.4% ± 7.6% to 34.9% ± 5.6% by sevoflurane postconditioning (P < 0.01). Such an anti-infarct effect was abolished completely in the DRs, as evidenced by a similar infarct size observed between the sevoflurane-treated and untreated DRs (49.3% ± 8.6% and 49.6% ± 9.3%, respectively, P > 0.05). Direct inhibition of GSK-3ß by injection of SB216763 just before the start of reperfusion induced equivalent infarct-sparing effects in both NDRs (37.8% ± 3.9% and 53.4% ± 7.6% in SB216763-treated and untreated NDRs, respectively; P < 0.01) and DRs (38.8% ± 3.2% and 49.3% ± 8.6% in SB216763-treated and untreated DRs, respectively; P < 0.05). Sevoflurane postconditioning remarkably enhanced the phosphorylation of GSK-3ß Ser(9), Akt Ser(473), and ERK1/2 in NDRs, which were blocked in DRs. CONCLUSIONS: The cardioprotection induced by sevoflurane postconditioning is abolished by diabetes. This might be due to the impairment of phosphorylation of GSK-3ß and its upstream signaling pathways of phosphatidylinositol-3-kinase/Akt and ERK1/2 in the presence of diabetes.

Beta-adrenergic signals regulate cardiac differentiation of mouse embryonic stem cells via mitogen-activated protein kinase pathways.

As embryonic stem cell-derived cardiomyocytes (ESC-CMs) have the potential to be used in cell replacement therapy, an understanding of the signaling mechanisms that regulate their terminal differentiation is imperative. In previous studies, we discovered the presence of adrenergic and muscarinic receptors in mouse embryonic stem cells (ESCs). However, little is known about the role of these receptors in cardiac differentiation and development, which is critically important in cardiac physiology and pharmacology. Here, we demonstrated that a ß-adrenergic receptor (ß-AR) agonist significantly enhanced cardiac differentiation as indicated by a higher percentage of beating embryoid bodies and a higher expression level of cardiac markers. Application of ß1-AR and ß2-AR antagonists partly abolished the effect of the ß-AR agonist. In addition, by administering selective inhibitors we found that the effect of ß-AR was driven via p38 mitogen-activated protein kinase and extracellular-signal regulated kinase pathway. These findings suggest that ESCs are also a target for ß-adrenergic regulation and ß-adrenergic signaling plays a role in ESC cardiac differentiation.