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.

MicroRNA-132-3p alleviates neuron apoptosis and impairments of learning and memory abilities in Alzheimer's disease by downregulation of HNRNPU stabilized BACE1.

Alzheimer's disease (AD) is a progressive neuro-degenerative disease characterized by dementia. MicroRNAs (miRNAs) are involved in many diseases, including AD. MiR-132-3p has been identified to be downregulated in AD. In this study, we explored the effects of miR-132-3p on neuron apoptosis and impairments of learning and memory abilities. Aß1-42-stimulated SH-SY5Y cells were used as in vitro models of AD. An AD-like homocysteine (Hcy) rat model was established to evaluate the effects of miR-132-3p on AD pathogenesis in vivo. RIP, RNA pull down and luciferase reporter assays were conducted to investigate the relationship between miR-132-3p and its downstream target genes. The viability and apoptosis of SH-SY5Y cells were measured by CCK-8 and TUNEL assays. The rat spatial learning and memory abilities were accessed using Morris water maze test. Results indicated that miR-132-3p was downregulated in SH-SY5Y cells after Aß1-42 treatment and promoted cell apoptosis. Mechanistically, miR-132-3p targeted heterogeneous nuclear ribonucleoprotein U (HNRNPU). HNRNPU acted as an RNA binding protein (RBP) to regulate the mRNA stability of ß-site amyloid precursor protein cleaving enzyme 1 (BACE1). Overexpression of HNRNPU or BACE1 reversed the effects of miR-132-3p overexpression on the viability and apoptosis of Aß1-42-treated SH-SY5Y cells. In vivo experiments revealed the downregulation of miR-132-3p in the hippocampus of Hcy-treated rats. MiR-132-3p suppressed levels of apoptotic genes in hippocampus and reduced impairments of learning and memory abilities in Hcy-treated rats. In conclusion, miR-132-3p reduces apoptosis of SH-SY5Y cells and alleviates impairments of learning and memory abilities in AD rats by modulating the HNRNPU/BACE1 axis.

Study of TCM Syndrome Identification Modes for Patients with Type 2 Diabetes Mellitus Based on Data Mining.

OBJECTIVE: To establish the diagnosis model for syndromes of type 2 diabetes mellitus (T2-DM) and explore symptoms, the pulse and tongue signs, and laboratory indexes related to syndromes of T2-DM. METHODS: A syndromatologic and laboratory investigation was conducted in 554 T2-DM patients with 58 symptoms, 14 tongue signs, 6 pulse signs, and 12 laboratory indexes. The clinical data on the syndrome were collected and analyzed by using logistic regression analysis, decision tree, and K-nearest neighbor to establish a diagnostic model for effectively distinguishing the typical syndromes in T2-DM patients. RESULTS: The most typical syndromes revealed in T2-DM were stomach heat flourishing (SHF) syndrome (261 patients, accounting for 47.1%) and Qi-Yin deficiency (QYD) syndrome (293 patients, 52.9%). According to the clinical data of the patients with these two syndromes, variables including 6 symptoms and signs, 2 pulse signs, 1 tongue sign, and 2 laboratory indicators were introduced into the logistic regression model. All of them were statistically significant. Then, a diagnostic model constructed by QUEST and CHAID algorithms of the decision tree for identifying the two syndromes was proved to have an accurate diagnostic rate of 85.2%. It was found that the following sign and symptoms were effective to differentiate these two syndromes: odor in the mouth, polyphagia, vulnerability to starvation, burning sensation in the stomach, fatigue, limb weakness, slippery and replete pulse, weak pulse, pink tongue, oral glucose tolerance test, and hemoglobin A1C. A classification model constructed by the K-nearest neighbor method to identify the two syndromes showed an accurate diagnostic rate of 88.3%. Three major statistically significant predictors included in the model were slippery and replete pulse, polyphagia, and weak pulse (P < 0.05). CONCLUSION: A model for distinguishing the two typical syndromes (SHF syndrome and QYD syndrome) in T2-DM patients was effectively established. This model could help to provide methodological support for the standardization of traditional Chinese medicine (TCM) syndrome differentiation methods.

3D­printed Ti6Al4V scaffolds combined with pulse electromagnetic fields enhance osseointegration in osteoporosis.

The loosening and displacement of prostheses after dental implantation and arthroplasty is a substantial medical burden due to the complex correction surgery. Three­dimensional (3D)­printed porous titanium (pTi) alloy scaffolds are characterized by low stiffness, are beneficial to bone ingrowth, and may be used in orthopedic applications. However, for the bio­inert nature between host bone and implants, titanium alloy remains poorly compatible with osseointegration, especially in disease conditions, such as osteoporosis. In the present study, 3D­printed pTi scaffolds with ideal pore size and porosity matching the bone tissue, were combined with pulse electromagnetic fields (PEMF), an exogenous osteogenic induction stimulation, to evaluate osseointegration in osteoporosis. In vitro, external PEMF significantly improved osteoporosis­derived bone marrow mesenchymal stem cell proliferation and osteogenic differentiation on the surface of pTi scaffolds by enhancing the expression of alkaline phosphatase, runt­related transcription factor­2, osteocalcin, and bone morphogenetic protein­2. In vivo, Microcomputed tomography analysis and histological evaluation indicated the external PEMF markedly enhanced bone regeneration and osseointegration. This novel therapeutic strategy has potential to promote osseointegration of dental implants or artificial prostheses for patients with osteoporosis.

Gabapentin for phantom limb pain after amputation in pediatric oncology: a systematic review protocol.

BACKGROUND: Phantom limb pain (PLP) is a prevalent problem for children after amputation because of the chemotherapy treatment. Gabapentin is a potential option to manage PLP after amputation in pediatric oncology. However, no systematic review specifically investigated this topic. Thus, this study aims to appraise the efficacy and safety of gabapentin for post-amputation PLP in pediatric oncology. METHODS: Electronic databases (Cochrane Library, MEDLINE, EMBASE, Web of Science, CINAHL, PsychINFO, Scopus, WANGFANG, and Chinese Biomedical Literature Database) will be systematically searched from the beginning to the present without limitations to publication status and language. Primary outcome is pain intensity. Secondary outcomes are analgesic drug consumption, sleep quality, depression, anxiety, health-related quality of life, and adverse events. The treatment effect of all dichotomous outcome data will be estimated as risk ratio and 95% confidence intervals (CIs) and that of continuous outcome data will be calculated as mean difference or standardized mean difference and 95% CIs. Methodological quality of randomized controlled trials (RCTs) will be assessed using Cochrane risk of bias tool and that of case-controlled studies (CCSs) will be appraised using Newcastle-Ottawa Tool. Statistical analysis will be conducted using RevMan 5.3 software. DISCUSSION: This study will summarize up-to-date high-quality RCTs and CCSs to assess the efficacy and safety of gabapentin for PLP after amputation in pediatric oncology. The findings of this study will help to determine whether or not gabapentin is effective and safe for children with PLP after amputation. SYSTEMATIC REVIEW REGISTRATION: INPLASY202060090.

miR-183-5p acts as a potential prognostic biomarker in gastric cancer and regulates cell functions by modulating EEF2.

BACKGROUND: Gastric cancer (GC) is the fourth most prevalent malignant tumor and the second leading cause of cancer-related death around the world. Aberrant proliferation and metastasis are the mainspring of death in patients with GC. However, the specific mechanism of gastric cancer is far from being fully elucidated. Accumulating evidence revealed that miRNA played a significant role in the tumorigenesis and development. METHODS: The level of miR-183-5p was detected in 102 GC patients by using qRT-PCR. The prognostic value of miR-183-5p in GC was evaluated. Cell function assays (CCK-8 and transwell assays) were conducted to assess the role of miR-183-5p in proliferation and metastasis in GC. Dual luciferase report assay and western blot were performed to validate this potential target regulated by miR-183-5p in GC. RESULTS: miR-183-5p was down-regulated in GC tissues and cell lines. Remarkable pertinence was obtained between miR-183-5p level and TNM stage, tumor size, invasion depth, and lymph node metastasis. TNM stage, differentiation and miR-183-5p level were independent causes impacting on the overall survival in GC in multivariate analysis. GC individuals with high miR-183-5p level would experience a relatively better survival prognosis. Upregulation of miR-183-5p restrained GC cell proliferation and migration. EEF2 may be a potential target gene regulated by miR-183-5p in GC. CONCLUSION: miR-183-5p acts as a potential prognostic biomarker in gastric cancer and regulates cell functions by modulating EEF2.

Inhibition of MicroRNA-204 Conducts Neuroprotection Against Spinal Cord Ischemia.

BACKGROUND: MicroRNA(miR)-204 is an autophagy- and apoptosis-related gene. Neuroprotection by the inhibition of miR-204 against spinal cord ischemia was evaluated, and the roles of neuronal autophagy and apoptosis were investigated. METHODS: Spinal cord ischemia was conducted in rats by cross-clamping the descending aorta for 14 minutes. Inhibition of miR-204 was induced by intrathecal injection of lentivirus vectors containing antagomiR-204. Hind-limb motor function was assessed with the motor deficit index. Lumbar spinal cords were harvested for histologic examinations and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling staining. Autophagy was evaluated by the LC3-II/LC3-I ratio and beclin-1 expression. Expressions of LC3-I, LC3-II, beclin-1, B-cell lymphoma-2 (BCL-2), caspase-3, and miR-204 were measured by Western blot and quantitative real-time polymerase chain reaction. Autophagy was blocked by 3-methyladenine. RESULTS: Transient ischemia enhanced miR-204 expression and the LC3-II/LC3-I ratio and downregulated BCL-2 expression in spinal cords in a time-dependent manner. AntagomiR-204 significantly reduced expressions of miR-204 and caspase-3, dramatically upregulated expressions of beclin-1 and BCL-2 and the LC3-II/LC3-I ratio in spinal cords after reperfusion. Compared with controls, inhibition of miR-204 markedly decreased the motor deficit index scores at 6, 12, 24, and 48 hours after reperfusion; increased the number of viable motor neurons; and decreased the number of apoptotic neurons. 3-Methyladenine completely abolished enhancements of the LC3-II/LC3-I ratio and beclin-1 expression induced by antagomiR-204 and inhibited the protective effect on hind-limb motor function. CONCLUSIONS: Inhibition of miR-204 exerts spinal cord protection against ischemia-reperfusion injury, possibly via promotion of autophagy and antiapoptotic effects.

Inhibition of SphK2 Stimulated Hepatic Gluconeogenesis Associated with Dephosphorylation and Deacetylation of STAT3.

BACKGROUND: Sphingosine kinase (SphK) is considered as a potential target for developing novel therapeutics of cancer and other diseases including diabetes. As the major SphK isoform in the liver, much less is known the role of SphK2 involved in regulating hepatic glucose metabolism. METHOD: In this study, RNA interference, real time RT-PCR, western blot and immunoprecipitation method was used to investigate the regulation of SphK2 in hepatic glucose metabolism. RESULTS: Both siRNA and SphK2 inhibitor ABC294640 stimulated expression of gluconeogenetic gene PEPCK and G6Pase but not enzymes of hepatic glycogenolysis, glycolysis and glycogen synthesis. Inhibition of SphK2 also prevented insulin repressed PEPCK and G6Pase expression as well as glucose production levels. Furtherly, inhibition of SphK2 inactivated STAT3 by decreasing both phosphorylation on Tyr705 and acetylation on lysine residue, and led to stimulation of PEPCK and G6Pase expression. Inhibition of SphK2 also prevented IL-6 dependent activation of STAT3 and suppression of PEPCK and G6pase expression both in vitro and in vivo. CONCLUSION: Our study suggests that SphK2 participates in hepatic glucose metabolism related to activation of STAT3.

Acquired inhibition of microRNA-124 protects against spinal cord ischemia-reperfusion injury partially through a mitophagy-dependent pathway.

OBJECTIVE: Mitophagy results in selective clearance of damaged mitochondria. We investigated whether mitophagy was involved in the neuroprotection by inhibiting microRNA (miRNA)-124 on ischemic spinal cords. METHODS: Inhibition of miRNA-124 was conducted by intrathecal injection of lentivirus vectors containing antagomiR-124. Spinal cord ischemia was induced in rats by crossclamping the descending aorta just distal to the left subclavian artery for 14 minutes. Hind-limb motor function was assessed with the motor deficit index (MDI). Lumbar spinal cords were harvested for ultrastructural, histologic examinations, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling staining. Mitophagy was evaluated by expressions of beclin-1 and LC3-II in mitochondria. Expressions of inhibitory member of the apoptosis-stimulating proteins of p53 family, p53, beclin-1, LC3-II, and miRNA-124 were measured by Western blot and quantitative real-time polymerase chain reaction. Mitophagy was inhibited by the antagonist of 3-methyladenine. RESULTS: Compared with control animals, antagomiR-124 significantly inhibited expressions of miRNA-124 (P < .01) and p53 (P < .05) and enhanced expressions of inhibitory member of the apoptosis-stimulating proteins of p53 family, becline-1 and LC3-II (P < .01, respectively) in spinal cords. MDI at 6, 12, 24, and 48 hours after reperfusion were markedly lower in antagomiR-124 group (P < .01, vs control group, respectively). More motor neurons and less apoptotic cells were detected in lumbar spinal cords of antagomiR-124 group (P < .01 vs control group). Administration of 3-methyladenine completely abolished enhancements of mitochondrial becline-1 and LC3-II by antagomiR-124 (P < .01 vs antagomiR-124 group) and partially inhibited effects of antagomiR-124 on MDI, number of motor neurons, and apoptotic cells (P < .01 or < .05 vs control group and antagomiR-124 group, respectively). CONCLUSIONS: Inhibition of miRNA-124 exerts neuroprotection on spinal cords against ischemia-reperfusion injury, possibly by induction of mitophagy and antiapoptotic effects.

Overexpression of microRNA-21 protects spinal cords against transient ischemia.

OBJECTIVE: MicroRNA (miRNA) molecules are involved in the response of the central nervous system to ischemia and reperfusion. We sought to test the hypothesis that overexpression of miRNA-21 can induce neuroprotection on spinal cords against transient ischemia. METHODS: Overexpression of miRNA-21 in vivo was conducted by means of intrathecal injection of lentivirus vectors containing pre-miRNA-21. The vehicle or control lentivirus vectors were given to the control group and the control vector group, respectively. Five days later, spinal cord ischemia was accomplished in rats by crossclamping the descending aorta just distal to the left subclavian artery for 14 minutes. Hind-limb motor function was assessed during 48 hours after ischemia using the Motor Deficit Index, and histologic examination was performed. Expressions of caspase-3, Fas ligand (Faslg), programmed cell death 4 (PDCD4), and miRNA-21 in the spinal cord were evaluated by quantitative real-time polymerase chain reaction and western blot analysis. RESULTS: Transfection of pre-miRNA-21 significantly enhanced expression of miRNA-21 in the spinal cord (P < .01 vs the control group) and dramatically downregulated expressions of caspase-3, Faslg, and PDCD4 (P < .01 vs the control group). Compared with the control group, Motor Deficit Index scores at 6, 12, 24, and 48 hours after reperfusion were markedly lower in rats with overexpression of miRNA-21 (P < .01). Histologic examination showed that many more intact motor neurons were preserved in the lumbar spinal cord of rats with overexpression of miRNA-21 (P < .01 vs the control group). CONCLUSIONS: Overexpression of miRNA-21 exerts neuroprotective effects on spinal cords against ischemia-reperfusion injury, possibly by inhibition of the proapoptotic proteins Faslg and PDCD4.

Inhibition of the Let-7 Family MicroRNAs Induces Cardioprotection Against Ischemia-Reperfusion Injury in Diabetic Rats.

BACKGROUND: The expression of the let-7 family microRNAs in the myocardium of streptozotocin-induced diabetic rats was measured, and the cardioprotection of inhibition of let-7 microRNAs against ischemia-reperfusion injury was investigated. METHODS: The diabetic rats and nondiabetic rats were subjected to 30 minutes of coronary artery occlusion followed by 120 minutes of reperfusion. The infarct size was determined by triphenyltetrazolium chloride staining. The expression of let-7 was measured by quantitative real-time polymerase chain reaction, and expressions of insulin receptor (InsR), insulin-like growth factor-1 receptor (IGF-1R), glucose transporter type 4 (GLUT4), and the phosphorylation states of Akt and the mammalian target of rapamycin (mTOR) were analyzed using Western blot. Inhibition of let-7 was performed by local transfection of lentivirus gene transfer vectors containing let-7 antimiR. RESULTS: Compared with nondiabetic rats, the expression of let-7 was enhanced in the myocardium of diabetic rats (p = 0.029), whereas expressions of InsR, IGF-1R, and GLUT4 were decreased after ischemia-reperfusion (p < 0.01). Local transfection of the let-7 antimiR markedly inhibited the expression of let-7 (p = 0.038) and improved expressions of InsR, IGF-1R, and GLUT4 in the myocardium of diabetic rats (p < 0.01). The infarct size of diabetic rats was much higher than that of nondiabetic rats (p < 0.0001). Transfection of the let-7 antimiR significantly reduced the infarct size of diabetic rats (p < 0.0001), and such an antiinfarct effect was abolished completely by pretreatment of Akt inhibitor LY294002 or mTOR inhibitor rapamycin. CONCLUSIONS: Inhibition of the let-7 family microRNAs improves glucose uptake and insulin resistance in the diabetic myocardium and induces cardioprotection against ischemia-reperfusion injury through Akt and mTOR pathways.

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.

Inhibition of micro-ribonucleic acid-320 attenuates neurologic injuries after spinal cord ischemia.

OBJECTIVE: Micro ribonucleic acids (miRNAs) are involved in a wide range of biological functions, in multiple tissues, including the central nervous system. We investigated a novel neuroprotective strategy of down-regulation of miR-320 in the spinal cord under the condition of transient ischemia. METHODS: Spinal cord ischemia was induced in rats by cross-clamping the descending aorta for 14 minutes. Lentivirus vectors containing antisense oligonucleotides of rat miR-320 (antagomiR-320) were transfected into the experimental rats by means of intrathecal injection, 5 days before spinal cord ischemia. Control lentivirus vectors, or the vehicle, were given to the control animals. Hind-limb motor function was assessed during 48 hours after ischemia, using the Motor Deficit Index (MDI), and histologic examination was performed. In parallel experiments, expressions of miR-320, and the phosphorylation state of heat-shock protein 20 (phospho-Hsp20) in the spinal cord were evaluated by quantitative real-time polymerase chain reaction and western blot analysis. RESULTS: The time courses of expressions of miR-320 and phospho-Hsp20 in the spinal cord, after the transient ischemia, indicated that expression of phospho-Hsp20 was negatively correlated with expression of miR-320. Transfection of antagomiR-320 significantly reduced expression of miR-320 in the spinal cord and dramatically up-regulated expression of phospho-Hsp20. Compared with controls, inhibition of miR-320 markedly improved hind-limb motor function, as evidenced by lower MDI scores, at 6, 12, 24, and 48 hours after reperfusion, and increased the number of intact motor neurons in the lumbar spinal cord. CONCLUSIONS: Inhibition of miR-320 induces neuroprotection in the spinal cord, against ischemia-reperfusion injury, possibly via up-regulation of phospho-Hsp20.

[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.

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.