Activated PKB/GSK-3β synergizes with PKC-δ signaling in attenuating myocardial ischemia/reperfusion injury via potentiation of NRF2 activity: Therapeutic efficacy of dihydrotanshinone-I

@#Disrupted redox status primarily contributes to myocardial ischemia/reperfusion injury (MIRI). NRF2, the endogenous antioxidant regulator, might provide therapeutic benefits. Dihydrotanshinone-I (DT) is an active component in Salvia miltiorrhiza with NRF2 induction potency. This study seeks to validate functional links between NRF2 and cardioprotection of DT and to investigate the molecular mechanism particularly emphasizing on NRF2 cytoplasmic/nuclear translocation. DT potently induced NRF2 nuclear accumulation, ameliorating post-reperfusion injuries via redox alterations. Abrogated cardioprotection in NRF2-deficient mice and cardiomyocytes strongly supports NRF2-dependent cardioprotection of DT. Mechanistically, DT phosphorylated NRF2 at Ser40, rendering its nuclear-import by dissociating from KEAP1 and inhibiting degradation. Importantly, we identified PKC-δ-(Thr505) phosphorylation as primary upstream event triggering NRF2-(Ser40) phosphorylation. Knockdown of PKC-δ dramatically retained NRF2 in cytoplasm, convincing its pivotal role in mediating NRF2 nuclear-import. NRF2 activity was further enhanced by activated PKB/GSK-3β signaling via nuclear-export signal blockage independent of PKC-δ activation. By demonstrating independent modulation of PKC-δ and PKB/GSK-3β/Fyn signaling, we highlight the ability of DT to exploit both nuclear import and export regulation of NRF2 in treating reperfusion injury harboring redox homeostasis alterations. Coactivation of PKC and PKB phenocopied cardioprotection of DT in vitro and in vivo, further supporting the potential applicability of this rationale. Graphical abstract

The Role of PI3K / AKT / FOXO Signaling Pathway-mediated Autophagy in Diabetes-associated Cognitive Dysfunction / 中国生物化学与分子生物学报

Diabetes‚ a metabolic disease characterized by hyperglycemia‚ can cause central nerve system damage‚ lead to alteration of the neuronal structure and function‚ and consequently induce cognitive dysfunction. Recently‚ diabetes-associated cognitive dysfunction (DACD) and its molecular mechanism have become a research frontier. The phospoinositide 3 kinase/ protein kinase B/ Forkhead box O (PI3K/ PKB/ FOXO) signaling pathway is an important upstream regulatory mechanism for autophagy. Here we review the role of the PI3K/ AKT/ FOXO signaling pathway in the regulation of Gs‚ Bnip3 and Spk2 gene expressions. GS regulates the Gln-mTORC1 pathway and thus activates autophagy; BNIP3 enhances LC3 expression and promotes autophagy. Moreover‚ the AMPK-FOXO3a-mTORC1 signaling pathway is also an important pathway that involved in the regulation of autophagy. These studies suggest that FOXO3a may be a key target for the treatment of DACD. This review aims to provide a theoretical basis and molecular target for the clinical treatment of DACD and it related drug development.

Effects of cistanche phenylethanol glycosides on the cardiac hypertrophy and PI3K/PKB signaling pathway in rats with pressure overload / 中国药理学通报

Aim To investigate the inhibitory effect of cistanche phenylethanol glycosides (CPhGs) on cardiac hypertrophy in rats caused by pressure overload and its related mechanism. Methods Male SD rats(n =70) were randomly divided into control group (Con), sham operation group (Sham), model group (Mod), positive control group (Vst), and different CPhGs dosage (125, 250, 500 mg • kg-1) groups. Cardiac ultrasound indexes, heart-weight to body-weight index (HWI), cardiac histopathological changes, and the area of myocardical cells (AMC) were detected. Plasma ET-1 and BNP levels were detected by Elisa, and protein expressions of phosphorylated PI3K(p-PI3K), PI3K, phosphorylated PKB (p-pKB) and PKB were detected by Western blot. Results Compared with Mod group, LVPWT, HWI, plasma ET-1, BNP and AMC decreased to different degrees. LVEDD, LVEF, LVFS, the protein expressions of myocardial tissues pPI3K and p-PKB increased to different degrees in CPhGs groups. Moreover, the indexes of CPhGs 250 and 500 mg • kg-1 groups were significantly improved compared to those of Mod group (P < 0. 05 or 0. 01). Compared with Vst group, there were no significant difference in CPhGs 500 mg • kg-1 group. Conclusions CPhGs could inhibit cardiac hypertrophy in rats induced by pressure overload, which might be related to the activation of PI3K/PKB signaling pathway.

RICTOR/mTORC2 affects tumorigenesis and therapeutic efficacy of mTOR inhibitors in esophageal squamous cell carcinoma

Dysregulation of mTORC1/mTORC2 pathway is observed in many cancers and mTORC1 inhibitors have been used clinically in many tumor types; however, the mechanism of mTORC2 in tumorigenesis is still obscure. Here, we mainly explored the potential role of mTORC2 in esophageal squamous cell carcinoma (ESCC) and its effects on the sensitivity of cells to mTOR inhibitors. We demonstrated that RICTOR, the key factor of mTORC2, and p-AKT (Ser473) were excessively activated in ESCC and their overexpression is related to lymph node metastasis and the tumor-node-metastasis (TNM) phase of ESCC patients. Furthermore, we found that mTORC1/ mTORC2 inhibitor PP242 exhibited more efficacious anti-proliferative effect on ESCC cells than mTORC1 inhibitor RAD001 due to RAD001-triggered feedback activation of AKT signal. Another, we demonstrated that down-regulating expression of RICTOR in ECa109 and EC9706 cells inhibited proliferation and migration as well as induced cell cycle arrest and apoptosis. Noteworthy, knocking-down stably RICTOR significantly suppresses RAD001-induced feedback activation of AKT/PRAS40 signaling, and enhances inhibition efficacy of PP242 on the phosphorylation of AKT and PRAS40, thus potentiates the antitumor effect of RAD001 and PP242 both and . Our findings highlight that selective targeting mTORC2 could be a promising therapeutic strategy for future treatment of ESCC.

Effect of the PI3K/AKT signaling pathway regulated by HMGCS1 on drug sensitivity of HL-60 cells / 上海交通大学学报（医学版）

Objective: To explore the mechanism of 3-hydroxymethyl-3-methylglutaryl-CoA synthase 1 (HMGCS1) on drug sensitivity of acute myelocytic leukemia (AML) HL-60 cells. Methods: HL-60 cells were cultured. The negative control group and the HMGCS1 overexpressed group were constructed by infecting the negative control lentivirus and HMGCS1 lentivirus,and the untreated HL-60 cells were set as the blank control group. Real-time quantitative PCR (qPCR) was used to detect the expression of HMGCS1 mRNA in the 3 groups,and to verify whether the cell lines of the HMGCS1 overexpressed group were successfully constructed. The effect of HMGCS1 on the expression of AKT and phosphorylated AKT (p-AKT) in phosphatidylinositol 3 kinase (PI3K) / protein kinase B (PKB / AKT) signaling pathway was detected by Western blotting. CCK8 method was used to detect the effects of HMGCS1 and PI3K/AKT signaling pathway inhibitor LY29400 on the activity of HL-60 cells. The effect of LY29400 on HMGCS1 expression was detected by qPCR and Western blotting. Results: Compared with the negative control group,the HMGCS1 mRNA expression was increased significantly in the HMGCS1 overexpressed group (P=0.000). Compared with the blank control group and the negative control group,the p-AKT protein level in the HMGCS1 overexpression group was significantly increased,while the AKT expression of the 3 groups was not significantly different. CCK8 method showed that compared with the blank control group and the negative control group,HMGCS1 could reduce the effect of adriamycin on cell viability in the HMGCS1 overexpressed group (P=0.003,P=0.006),while LY294002 could inhibit the effect produced by HMGCS1 (P=0.000). The intervention of LY294002 could reduce the expression levels of HMGCS1 and p-AKT protein and HMGCS1 mRNA (both P=0.000) in the negative control group and the blank control group. Conclusion: HMGCS1 can reduce the sensitivity of HL-60 cells to chemotherapy drug adriamycin,while PI3K/AKT signaling pathway inhibitor LY294002 can restore its sensitivity.

Regulation on intercross effect between Cdk5 mediated apoptosis and autophagy after cerebral ischemia / 中国药理学通报

Cyclin-dependent kinase 5 (Cdk5),as a key neuro-nal regulator,has received extensively attention. In our previous experiments, we have preliminary confirmed the importance of the regulation on neuronal apoptosis after cerebral ischemia by Cdk5 signal path. According to the documents reported, we found that there were signal transductions between apoptosis and autophagy, which acted the"rapier"position after cerebral is-chemia. Furthermore,Cdk5 could mediate protein kinase B(Akt or PKB) to play bidirectional regulation on the intercross be-tween apoptosis and autophagy. So,there would be of great sig-nificance to reveal the signal transduction relationship between apoptosis and autophagy mediated by Cdk5. Owing to the impor-tance of the intercross-effect between the two programmed cell death paths,we aimed at the imparity viewpoints between apop-tosis and autophagy after cerebral ischemia, raising the sugges-tions as follows:it is appropriate to reveal the effects of Cdk5 on Akt kinase dynamically, and discuss the double regulation mechanism of co-regulators between apoptosis and autophagy af-ter cerebral ischemia, which would provide references for the following researches.

Inhibition of Akt/PKB signaling pathway promotes hypoxia-induced apoptosis of human periodontal ligament fibroblasts / 实用口腔医学杂志

Objective: To investigate the effects of the Akt/PKB signaling pathway on hypoxia-induced apoptosis. Methods: The cell proliferation, apoptosis, Akt/PKB signaling pathway and HIF-1α expression in periodontal ligament fibroblasts(hPDLFs) under normoxic and hypoxic conditions were evaluated by MTT assay, flowoytometry, qRT-PCR, Western blot and Lipofectamin 2000 transfection respectively. Results: The cell proliferation and the Akt/PKB pathway in hPDLFs were inhibited by hypoxia. Hypoxia promoted apoptosis and increased the levels of HIF-1α of hPDLFs. Akt/PKB signaling pathway inhibition inhibited cell proliferation and promoted hypoxia-induced apoptosis of hPDLFs. Conclusion: The inhibition of Akt/PKB signaling pathway may promote hypoxia-induced apoptosis of hPDLFs under hyoxia condtition.

PKB/Akt regulates the aggregation of actin by Girdin in mouse fertilized eggs / 生物工程学报

The purpose of this study is to reveal the role of Girdin in regulating the aggregation of actin filaments by studying the relationship between PKB/Akt and Girdin. First we used Scansite software (http://scansite.mit.edu) to predict relevant target sites of PKB/Akt on mouse Girdin. To gain insight into the role of phosphorylation of Girdin by PKB/Akt, we assessed the location of phosphorylated Girdin in fertilized eggs by staining with anti-P-Girdin 1 417 Ab. We detected a distinct increase in the fluorescence signal of F-actin and P-Girdin 1 417 after microinjection of Akt WT and myr-Akt. The addition of myr-Akt induced phosphorylation of Girdin in mouse fertilized eggs. In addition, siRNA-mediated Akt-knockdown blocked phosphorylation of Girdin. The distribution of actin filaments was obviously scattered. These results strongly suggest that PKB/Akt could directly phosphorylate Girdin on Ser1 417 and promote its function in mouse fertilized eggs.

The RAS/PI3K Pathway is Involved in the Impairment of Long-term Potentiation Induced by Acute Aluminum Treatment in Rats / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To explore the role of RAS/PI3K pathway in the impairment of long-term potentiation (LTP) induced by acute aluminum (Al) treatment in rats in vivo.</p><p><b>METHODS</b>First, different dosages of aluminum-maltolate complex [Al(mal)3] were given to rats via acute intracerebroventricular (i.c.v.) injection. Following Al exposure, the RAS activity of rat hippocampus were detected by ELISA assay after the hippocampal LTP recording by field potentiation technique in vivo. Second, the antagonism on the aluminum-induced suppression of hippocampal LTP was observed after the treatment of the RAS activator epidermal growth factor (EGF). Finally, the antagonism on the downstream molecules (PKB activity and the phosphorylation of GluR1 S831 and S845) were tested by ELISA and West-blot assays at the same time.</p><p><b>RESULTS</b>With the increasing aluminum dosage, a gradually decreasing in RAS activity of the rat hippocampus was produced after a gradually suppressing on LTP. The aluminum-induced early suppression of hippocampal LTP was antagonized by the RAS activator epidermal growth factor (EGF). And the EGF treatment produced changes similar to those observed for LTP between the groups on PKB activity as well as the phosphorylation of GluR1 S831 and S845.</p><p><b>CONCLUSION</b>The RAS→PI3K/PKB→GluR1 S831 and S845 signal transduction pathway may be involved in the inhibition of hippocampal LTP by aluminum exposure in rats. However, the mechanisms underlying this observation need further investigation.</p>

Advances in the non-genetic regulation of PTEN tumour suppressor activity / 基础医学与临床

Mutations and deletions of the tumour suppressor PTEN are frequently involved in the development of cancer.However, PTEN is also tightly controlled by various non-genomic mechanisms,such as the epigenetic silen-cing of PTEN, post-transcriptional regulation by non-coding RNAs and post-translational modification.

Bile acids and sphingosine-1-phosphate receptor 2 in hepatic lipid metabolism

The liver is the central organ involved in lipid metabolism. Dyslipidemia and its related disorders, including non-alcoholic fatty liver disease (NAFLD), obesity and other metabolic diseases, are of increasing public health concern due to their increasing prevalence in the population. Besides their well-characterized functions in cholesterol homoeostasis and nutrient absorption, bile acids are also important metabolic regulators and function as signaling hormones by activating specific nuclear receptors, G-protein coupled receptors, and multiple signaling pathways. Recent studies identified a new signaling pathway by which conjugated bile acids (CBA) activate the extracellular regulated protein kinases (ERK1/2) and protein kinase B (AKT) signaling pathway via sphingosine-1-phosphate receptor 2 (S1PR2). CBA-induced activation of S1PR2 is a key regulator of sphingosine kinase 2 (SphK2) and hepatic gene expression. This review focuses on recent findings related to the role of bile acids/S1PR2-mediated signaling pathways in regulating hepatic lipid metabolism.

Effects of PI3K/PKB signaling pathway on expression of osteopontin in human hepatic stellate cells induced by transforming growth factor-β1 / 中国病理生理杂志

AIM:To investigate the regulatory effects of phosphatylinositol 3-kinase/protein kinase B (PI3K/PKB) signaling pathway on the expression of osteopontin ( OPN) in transforming growth factor-β1 ( TGF-β1 )-induced hu-man hepatic stellate cells .METHODS:Human hepatic stellate cell line LX-2 was cultured in DMEM and stimulated by TGF-β1 at the final concentration of 2.5, 5, 10 and 20 μg/L for 24 h or at final concentration of 10 μg/L for 12 h, 24 h and 48 h.LX-2 cells were pretreated with wortmannin , a specific inhibitor of PI3K/PKB signaling pathway , at final con-centration of 0.1 μmol/L for 1 h, followed by incubation with TGF-β1 at final concentration of 10μg/L for 24 h.The cells were collected.The expression of OPN was detected by real-time PCR and Western blotting .RESULTS: In LX-2 cells, the expression of OPN was apparently elevated when incubated with TGF-β1 .With the increase in TGF-β1 concentration or the extension of incubation hours , the expression of OPN was increased gradually in a dose-and time-dependent manner with certain limits.LX-2 cells pretreated with wortmannin and incubated with TGF-β1 had a significant decrease in the OPN expression as compared with control group (P<0.01).CONCLUSION:The expression of OPN in TGF-β1-induced LX-2 cells is regulated by the PI3K/PKB signaling pathway.

Effect of Gymnema Sylvestre on Protein Kinase B in Adipose Tissues of Insulin Resistance Mice / 世界科学技术-中医药现代化

This article was aimed to study effects and mechanisms of Gymnema sylvestre on protein kinase B (PKB) and its phosphorylation in adipose tissues of KKAy mice which were mainly characterized by insulin resistance (IR). A total of 18 KKAy mice were randomly divided into the diabetes model (DM) group and Gymnema sylvestre (GS) group according to body weight levels. And 9 normal C57BL/6J mice were used as the normal control (NC) group. Intragastric administration of medication was given to mice for 8 weeks. At the end of the experiment, all animals were tested for fasting plasma glucose (FPG) and fasting insulin level (Fins) for evaluation of insulin sensitivity index (ISI). Expressions of phosphoinositide-dependent kinase-1 (PDK1), PKB, P-PKB (Ser473), P-PKB (Thr 308) in adi-pose tissues of epididymis were determined. The expression of phosphatase and tensin homolog (PTEN) mRNA was also determined. The results showed that compared with the DM group, the GS group showed lower FPG and Fins, higher ISI. The expression of P-PKB (Ser473) phosphorylation and P-PKB (Thr 308) were increased, and the PDK1 and PTEN mRNA were decreased. It was concluded that GS can improve insulin sensitivity of KKAy mice through activating PKB by up-regulate the expression of P- PKB (Ser473) and its phosphorylation ratio and P- PKB (Thr 308) in adipose tissues.

The mechanism of improving insulin resistance of skeletal muscles by ghrelin / 中华内分泌外科杂志

Objective To investigate the effects of acyl and deacyl ghrelin on the expressions of PI3Kp85α,Akt/PKB and GLUT4,the key factors in insulin receptor signaling pathway of insulin resistance in skeletal muscle cells.Methods Insulin resistance models were made by palmitic acid induced rat L6 myoblasts.Successful models were divided into acyl ghrelin group,deacyl ghrelin group,PI3K inhibitor(LY) + acyl ghrelin group,LY + deacyl ghrelin group and control group with corresponding interventions for 24h.The glucose uptake of all group was measured through laser confocal microscopy and flow cytometry.Expressions of phosphorated/total PI3Kp85α,phosphorated/total Akt and cell membrane/total GLUT4 of skeletal muscle cells were measured by Western blot,and PI3Kp85α,Akt,GLUT4 mRNA expression were detected by real-time PCR.Results Induced L6 myoblasts differentiation and insulin resistance model were successfully established.Acyl and deacyl ghrelin could increase glucose uptake for 1.25 and 1.28 folds compared to control group,and the phosphorated and total PI3Kp85α expressions were 1.78 and 1.89 folds to control group,and phosphorylated/total Akt and cell membrane/total GLUT4 were 1.84 and 1.80 folds to control group.The PI3Kp85α,Akt/PKB and GLUT4 mRNA expression were also upregulated compared to control group.The above indexes of LY + acyl or deacyl ghrelin group decreased significantly compared to acyl and deacyl ghrelin group without LY.Conclusions Acyl and deacyl ghrelin can both improve insulin resistance in skeletal muscle cells,increasing the glucose uptake under insulin-stimulation,and up-regulated the phosphorated PI3Kp85α,phosphorated Akt/PKB,and cell membrane GLUT4 relative protein expressions and mRNA expressions.PI3K inhibitor,LY294002,can inhibit the above improvement effect of acyl and decyl ghrelin.

Cardiovascular protection by curcumin: Molecular aspects.

Curcumin is the active component in turmeric — a spice that has been extensively used as a culinary agent and a home remedy to prevent and treat many diseases in India and other countries for hundreds of years. However, systematic studies to understand the molecular basis of disease preventing or therapeutic properties of curcumin began to appear in the scientific literature only during the last 40 years. As a result of these studies, substantial evidence has accumulated to suggest that curcumin can affect signaling pathways linked to cellular growth, proliferation, survival, inflammation and transcription. In addition, curcumin has also been shown to exert anti-atherosclerotic, anti-cancer, anti-diabetic, anti-inflammatory and anti-oxidative properties in animal models of various diseases and in human subjects. In this article, we highlight the cardiovascular protective role of curcumin with an emphasis on the molecular basis of this effect.

Role of AKT / mTORC1 pathway in pancreatic β - cell proliferation / Participación de la vía de señalización AKT/mTORC1 en la proliferación de las células β del páncreas

Growth factors, insulin signaling and nutrients are important regulators of β-cell mass and function. The events linking these signals to regulation of β-cell mass are not completely understood. Recent findings indicate that mTOR pathway integrates signals from growth factors and nutrients with transcription, translation, cell size, cytoskeleton remodeling and mitochondrial metabolism. mTOR is a part of two distinct complexes; mTORC1 and mTORC2. The mammalian TORC1 is sensitive to rapamycin and contains Raptor, deptor, PRAS40 and the G protein β-subunit-like protein (GβL). mTORC1 activates key regulators of protein translation; ribosomal S6 kinase (S6K) and eukaryote initiation factor 4E-binding protein 1. This review summarizes current findings about the role of AKT/mTORC1 signaling in regulation of pancreatic β cell mass and proliferation. mTORC1 is a major regulator of β-cell cycle progression by modulation of cyclins D2, D3 and cdk4/cyclin D activity. These studies uncovered key novel pathways controlling cell cycle progression in β-cells in vivo. This information can be used to develop alternative approaches to expand β-cell mass in vivo and in vitro without the risk of oncogenic transformation. The acquisition of such knowledge is critical for the design of improved therapeutic strategies for the treatment and cure of diabetes as well as to understand the effects of mTOR inhibitors in β-cell function.

Factores de crecimiento y nutrientes son reguladores muy importantes de la masa y función de las células β, pero las vías de señalización que unen estas señales a estos procesos no han sido completamente elucidadas. Estudios recientes han demostrado que la proteína mTOR integra señales provenientes de factores de crecimiento y disponibilidad de nutrientes con procesos celulares como transcripción, traducción, organización del citoesqueleto y metabolismo mitocondrial. mTOR puede hacer parte de dos complejos diferentes, mTORC1 y mTORC2. En el complejo mTORC1, la proteina mTOR la cual es sensible a rapamicina y se encuentra asociada a las proteínas Raptor, G β L, deptor y PRAS40, activa reguladores claves en la síntesis de proteínas, tales como la proteína cinasa ribosomal S6 (S6K) y la proteína de unión al factor eucariótico de iniciación 4E. El presente trabajo recopila información reciente sobre la participación de la vía de señalización AKT/mTORC1 en la regulación de la proliferación y masa de las células β del páncreas. mTORC1 regula la progresión del ciclo celular en células β, mediante la modulación de los niveles de las ciclinas D2 y D3 y la actividad del complejo Cdk4/ ciclina D. Estos estudios que revelan nuevos puntos de control del ciclo celular en células β, pueden ser utilizados en el desarrollo de nuevos enfoques para expandir la masa de células β, sin el riesgo de inducir una transformación oncogénica. Los resultados relacionados en el presente trabajo aportan información muy valiosa para el desarrollo de nuevas estrategias terapéuticas para el tratamiento la diabetes tipo 2.

Analgesia effects of intrathecally coadministered dexamethasone and Alt inhibitors on chronic dorsal root ganglion compression-induced pain in mouse / 中华行为医学与脑科学杂志

Objective To investigate the analgesic effects of intrathecal dexamethasone injection on pain induced by chronic compression of dorsal root ganglion in mouse.Methods Using rat model of radicular pain induced by chronic compression of dorsal root ganglion ( CCD), 40 male SD rats successfully received intrathecal catheter implantation and without motor dysfunction were randomly divided into 5 groups:Sham-operation group ( Sham group, n = 8 ), Control group ( CCD group, n = 8), Dexamethasone group ( D group, n = 8), Akt inhibitor V group (A group, n = 8 ) and Dexamethasone plus Akt inhibitor Ⅳ group (DA group, n = 8 ).Rats in D group, A group or DA group were intrathecally treated with dexamethasone (100μg/kg) ,Akt inhibitor Ⅳ (0.6μg/10μl) or dexamethasone ( 100 μg/kg) plus Akt inhibitor Ⅳ (0.6 μg/10 μl) on Day 3,13 after CCD respectively, while rats in C and Sham group received Vehicle (10% DMSO).Paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were tested on 3 d before and 3 d,4 d,7 d,10 d,13 d,14 d and 15 d after operation.Results Compared with Sham group,both PWMT (P＜0.01) and PWTL (P＜0.01) were significantly decreased after CCD surgery on the ipsilateral side.After dexamethasone and Akt inhibitor were respectively intrathecally injected at 3 postoperative day,PWMT (7.33 ± 1.03 ) g, (5.67 ± 1.03 ) g, (2.67 ± 1.03 ) g (P ＜0.01 ) ,PWTL( 16.47 ±0.46)s, ( 14.48 ±0.84) s, ( 10.82 ±2.21 ) s(P＜0.01 ) ,then decreased gradually,and intrathecally injected again at 13 postoperative day, PWMT ( 7.33 ± 1.03 ) g, ( 5.67 ± 1.03 ) g, (2.33 ± 0.81 ) g (P ＜0.01 ), PWTL( 16.44 ±0.90) s, ( 14.01 ±0.82)s, ( 10.22 ± 1.28)s (P＜0.01).Coadministration dexamethasone and Akt inhibitor exhibit significant synergies, postoperative 4 d PWMT( 10.83 ± 2.04)g, (2.67 ± 1.03 )g (P ＜0.01),PWTL(19.11 ±2.01)s,(10.82 ±2.21)s (P＜0.01);14 d PWMT (7 ±0.82)g,(2.33 ±0.81)g (P ＜ 0.01 ), PWTL( 17.16 ± 1.14)s, ( 10.22 ± 1.28 ) s (P ＜ 0.01 ).Conclusion Intrathecal high-dose dexamethas one or PKB / Akt inhibitors can effectively improve pain behavior response induced by chronic compression of dorsal root ganglia,combination of these two drugs could generate significant synergies, and the effection is more obvious, more durable.

Melatonin Protects N2a against Ischemia/Reperfusion Injury through Autophagy Enhancement / 华中科技大学学报（医学）（英德文版）

Researches have shown that melatonin is neuroprotectant in ischemia/reperfusion-mediated injury.Although melatonin is known as an effective antioxidant,the mechanism of the protection cannot be explained merely by antioxidation.This study was devoted to explore other existing mechanisms by investigating whether melatonin protects ischemia/reperfusion-injured neurons through elevating autophagy,since autophagy has been frequently suggested to play a crucial role in neuron survival.To find it out,an ischemia/reperfusion model in N2a cells was established for examinations.The results showed that autophagy was significantly enhanced in N2a cells treated with melatonin at reper-fusion onset following ischemia and greatly promoted cell survival,while autophagy blockage by 3-MA led to the shortened N2a cell survival as assessed by MTT,transmission electron microscopy,and laser confocal scanning microscopy.Besides,the protein levels of LC311 and Beclinl were remarkably increased in ischemia/reperfusion-injured N2a in the presence of melatonin,whereas the expression of p-PKB,key kinase in PI3K/PKB signaling pathway,showed a decrease when compared with untreated subjects as accessed by immunoblotting.Taken together these data suggest that autophagy is possibly one of the mechanisms underlying neuroprotection of melatonin.

Effect of exercise on expression of protein kinase B in adipose tissue of rats / 中国康复理论与实践

@#ObjectiveTo observe the effect of exercise on expression of protein kinase B (PKB) in adipose tissue of insulin resistant rats fed by high fat diet.Methods30 male Wistar rats were randomly divided into the control group (n=10),given basic diet; the model group (n=20), given fat diet. After 4 weeks, the model group was randomly divided into 2 subgroups, the insulin resistant group was continually given high fat diet, the exercise treated group accepted high fat food and swimming training. After 6 week intervention, the expression of PKB stimulated by insulin in adipose tissue was determined with Western blotting at the end of experiment.ResultsAfter long term high fat diet, expression of PKB in adipose tissue of the insulin resistant group decreased by 23.5% comparing with the control group (P<0.01). After 6 weeks swimming training, the expression of PKB of the exercise treated group was increased by 19.2% comparing with the insulin resistant group (P<0.01).ConclusionExercise treatment can significantly elevate the expression of PKB and ameliorate the state of insulin resistance.

Influence of estrogen on the proliferation of MCF7, a human breast carcinoma cell line / 中国癌症杂志

Purpose: To study the influence of estrogen on the proliferation of human carcinoma cells. Methods: Treated with different concentrations of estrogen, the influence of estrogen on MCF7 was detected by MTT test. Several proteins related with cell cycle, tumor suppressor, proliferation and apoptosis were detected by the method of Western blot. Results: MTT test showed that estrogen could promote the proliferation of MCF7. Cyclin Dl was increased at the same time. But the protein level of PTEN, a tumor suppressor gene, was not changed by estrogen. Furthermore, as an anti -apoptotic protein, PKB protein level was also unchanged. Conclusions: Estrogen can promote the proliferation of human carcinoma cells by certain pathways including cyclin Dl, but not including PKB.