[ ABSTRACT] AIM:To study the influence of insulin resistance on fatty liver in the mice fed with high-fat diet (HFD).METHODS:Male 8-week-old C57BL/6J mice were randomly divided into HFD group (with 60% calories by high saturated fatty acid) and control group (with chow diet).The mice in both groups were fed for 12 weeks.The body weight, liver weight, serum triglyceride (TG) and total cholesterol (TC), and blood glucose and insulin levels were meas-ured.Hyperinsulinemic euglycemic clamp experiment was applied to reflect insulin sensitivity .The lipid deposition in the liver was analyzed by HE staining , Sudan IV staining and measurement of liver fat content .The phosphorylation levels of IRS1 and Akt, and the protein levels of SREBP-1 and FAS were determined by Western blot to reflect the activities of insu-lin signaling and lipid synthesis .RESULTS:Compared with control group , the body weight and liver weight were signifi-cantly increased in HFD group .TG and TC contents in serum and liver tissues were remarkably increased in HFD group . High-fat diet induced insulin resistance , as evidenced by increased serum insulin levels , reduced glucose infusion rate and decreases in IRS1 and Akt phosphorylation levels .In livers of HFD group, HE staining showed that the cytoplasm of hepa-tocytes was filled with vacuoles .Sudan IV staining also displayed that many different sizes of red lipid drops existed in the hepatocytes , and the protein levels of SREBP-1 and FAS were significantly increased .In primary normal hepatocytes with exogenous oleic acid intervention for 48 h, the phosphorylation levels of IRS 1 and Akt were reduced , and the protein ex-pression of SREBP-1 and FAS was significantly increased in a dose-dependent manner .CONCLUSION: Feeding with HFD leads to insulin resistance , resulting in activation of lipid synthesis and accumulation of lipid deposition in the liver , thus inducing fatty liver .

[ ABSTRACT] AIM:To observe the effect of endogenous nitric oxide synthase ( NOS) inhibitor asymmetric dimeth-ylarginine ( ADMA ) and its signaling pathways on NO levels and skeletal muscle contractility in 4-week running rats. METHODS:The 4 weeks running rat model was established.The twitch tension, tetanic tension and the fatigue test of sole-us muscle induced by electrical stimulation ex vivo were detected.The ATP content, mitochondrial DNA levels and the mR-NA expression of peroxisome proliferator-activated receptor γcoactivator-1α(PGC-1α), nuclear respiratory factor (NRF) were measured to reflect the mitochondrial function and biosynthesis in the skeletal muscle.Serum ADMA concentration was detected by high performance liquid chromatography.The endogenous ADMA enzymes PRMT1 and 2 subtypes of ADMA me-tabolism enzyme DDAH, 3 subtypes of NOS protein expression in the skeletal muscle were determined by Western blot.NOS activity and nitric oxide ( NO) content were analyzed by colorimetric method.RESULTS: Compared with normal control group, the twitch tension, tetanic tension and the anti-fatigue capability of soleus muscle in running group were significantly enhanced, ATP content, mitochondrial DNA content and the mRNA expression of PGC-1αand NRF were significantly in-creased (P<0.01).In addition, the protein expression of constitute type NOS (cNOS) and NOS activity were significantly increased (P<0.01), but the increase in NO content was relatively smaller in soleus muscle in exercise group (P<0.05). Moreover, serum ADMA concentration in running group was increased, while the DDAH2 expression in skeletal muscle was decreased.CONCLUSION:Short-term endurance exercise enhances the twitch tension, tetanic tension and fatigue resist-
ance of soleus muscle.The mechanism may be that increased cNOS expression feedbacks to increase ADMA concentration, thus maintaining the increase in NO synthesis at a relatively low level, and resulting in promoting skeletal muscle mitochon-dria biosynthesis and mitochondrial function.

AIM:To investigate the influence of calorie restriction ( CR) on contractility and mitochondrial bi-osynthesis in different types of rat skeletal muscles .METHODS:CR rat model was set up by feeding 60%normal food in-take of control rat every day for 8 weeks.Soleus (SOL) and extensor digitorum longus (EDL) were isolated under anesthe-sia.The twitch tension, titanic tension and fatigue resistance of SOL and EDL in response to electrical stimulation were measured to reflect the contractile function of the muscles .The copy number ratio of mitochondrial gene cytochrome C oxi-dase subunit I ( COX I) to nuclear gene β-actin was determined to evaluate the mitochondrial biosynthesis .ATP content was measured to mirror mitochondrial function .RESULTS:Compared with control group , CR for 8 weeks significantly in-creased twitch tension and titanic tension of both SOL and EDL , but only improved fatigue resistance in SOL .Markedly in-crease in ATP content in both skeletal muscles by CR intervention was observed , especially in SOL .Although CR activated AMP-activated protein kinase (AMPK) in both 2 muscles, up-regulation of mitochondrial biosynthesis and transcription of mitochondrial regulatory genes peroxisome proliferator-activated receptor γcoactivator 1α( PGC-1α) and nuclear respirato-ry factor ( NRF) was only observed in SOL .CONCLUSION:CR for 8 weeks enhanced the contractility of both rat SOL and EDL in response to electrical stimulation , especially in SOL composed of slow-twitch fibers.The mechanisms may be related to the activation of AMPK and the promotion of mitochondrial biosynthesis in SOL .

Aim This study was aimed to explore the influence and mechanism of the long-term exercise on skeletal muscle contraction and mitochondrial biosyn-thesis in different muscle fibers.Methods Soleus (SOL)and extensor digitorum longus (EDL)were i-solated from SD male rats with platform running train-ing for eight weeks.The changes of contractility under different electrical stimulation were observed, mito-chondrial biosynthesis,including ATP content,mito-chondrial DNA,the gene expression of PGC-1αand NRF were also detected.Results Long-term endur-ance exercise can improve twitch tension and titanic tension of SOL and EDL ,but only enhanced the fa-tigue resistance in SOL.ATP contents were significant-ly increased in the two types of muscles,but mtDNA content,PGC-1αexpression and NRF translation were only obviously enhanced in SOL,in accompanied with an increase in p-AMPK/AMPK protein ratio.Conclu-sion Long-term endurance exercise increased skeletal muscle contractility and improved the anti-fatigue abili-ty in SOL,which may be associated with increase in mitochondrial biosynthesis via activated AMPK-PGC-1αaxis.

Objective The purpose of this study was to use diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rs-fMRI) alone or in combination to observe the distribution of white matter lesions and cortical malfunctional areas in human immunodeficiency virus (HIV) infected patients with mild cognitive decline and to explore the relationship between the DTI and the rs-fMRI methods.Methods Twenty-six HIV infected patients with mild cognitive impairment and 30 healthy volunteers were selected by Montreal Cognitive Asessment (MoCA) scale evaluation.DTI data and rs-fMRI data were obtained,fractional anisotropy (FA) value images were obtained with voxel based analysis and the resting-state default mode network (DMN),functional connectivity images were obtained with cingulate gyrus as a seed point.Overlay images were obtained with FA,DMN and Ch2 standard images.Results Compared with the control group,the white matter FA values were significantly decreased in the left precuneus(t=4.0499,P＜0.005) and right precuneus (t=5.1553,P＜0.005),right superior frontal gyrus(t=5.1517,5.1484,P＜0.005),right middle frontal gyrus (t=4.1444,P＜0.005),right precentral gyrus (t=3.7395,P＜0.005),right occipital lobe (t=7.2236,P＜0.005),and right inferior parietal lobule (t=4.1450,P＜0.005) in acquired immunodeficiency syndrome (AIDS) patients.In resting-state default mode network,areas significantly related to cingulate gyrus seed point included the left cingulate gyrus (t =32.78,P＜0.005),left precuneus (t =4.51,P＜0.005),left superior frontal gyrus (t =14.33,4.53,P＜0.005),left middle temporal gyrus (t =10.01,5.72,P＜ 0.005),left inferior temporal gyrus (t =5.99,P＜0.005),left parahippocampal gyrus (t =7.63,P＜0.005),right posterior cingulate (t =34.81,P＜0.005),right precuneus (t=32.09,P＜0.005),right superior frontal gyrus(t =14.12,P＜0.005),right middle frontal gyrus (t=17.71,P＜0.005),right superior temporal gyrus (t=14.59,P＜0.005),and right middle temporal gyrus (t=11.83,P＜0.005); while areas not significantly related to the cingulate gyrus seed point included the left precuneus (t =5.39,P＜0.01),left anterior cingulate gyrus (t =3.66,P＜0.01),left cerebellar tonsils (t =7.51,P＜0.01),right superior parietal lobule (t=4.44,P＜0.01),right parahippocampa gyrus (t =3.69,P＜0.01),and right cerebellar tonsil (t=6.15,P＜0.01).Overlayed images showed that the white matter FA value of the left precuneus were decreased and the functional activitis of the corresponding cortex were significantly decreased; while the white matter FA values of the left precuneus,right precuneus,right superior frontal gyrus,right middle frontal gyrus were decreased without affection of the functional activity of the corresponding cortex in AIDS patients.Conclusion White matter nerve fiber disconnection of multiple brain regions and its corresponding cortical function decline with compensatory activity co-participated in the pathogenesis of AIDS mild cognitive decline.

Objective To analyze the antimicrobial susceptibility of Mycoplasma isolates for rational antimicrobial therapy. Methods BioM?rieux IST kit was used for identification and susceptibility testing of Mycoplasma strains.Results Mycoplasma was positive in 49.5% of the specimens tested.Of the Mycoplasma detected,Ureaplasma urealyticum(Uu)alone accounted for 74.7%,Mycoplasma huminis(Mh)alone accounted for 18.1%,and Uu+Mh was identified in 7.2% of the patients.The results of antimicrobial susceptibility testing showed that the Mycoplasma isolates were most susceptible to doxycycline (98.1%).Ciprofloxacin was the least active (17.3%).Conclusions Doxyeycline,josamycin,and clarithromycin can be used in the treatment of urinary tract infections caused by Mycoplasma.

Fragile X syndrome (FXS) is one of the most prevalent mental retardations. It is mainly caused by the loss of fragile X mental retardation protein (FMRP). FMRP is an RNA binding protein and can regulate the translation of its binding RNA, thus regulate several signaling pathways. Many FXS patients show high susceptibility to epilepsy. Epilepsy is a chronic neurological disorder which is characterized by the recurrent appearance of spontaneous seizures due to neuronal hyperactivity in the brain. Both the abnormal activation of several signaling pathway and morphological abnormality that are caused by the loss of FMRP can lead to a high susceptibility to epilepsy. Combining with the research progresses on both FXS and epilepsy, we outlined the possible mechanisms of high susceptibility to epilepsy in FXS and tried to give a prospect on the future research on the mechanism of epilepsy that happened in other mental retardations.
Brain ; physiopathology ; Epilepsy ; etiology ; genetics ; pathology ; Fragile X Mental Retardation Protein ; genetics ; metabolism ; Fragile X Syndrome ; complications ; genetics ; Humans ; RNA-Binding Proteins ; metabolism

With whole-cell variant patch-clamp and laser scanning confocal microscope technique, we examined the effect of ginkgolide B (GB) from ginkgo leaves on L-type calcium current and cytosolic [Ca(2+)](i) in guinea pig ischemic ventricular myocytes. The results showed that under normal conditions, at a test voltage of 0 mV, GB had no significant effect on I(Ca,L); and during ischemia, the peak Ca(2+) current reduced by 37.71%, and the I-V curve of I(Ca,L) was shifted upward. 1 micromol/L GB reversed the change induced by ischemia, a result being significantly different from those of the ishemia group (P<0.05).Under control condition, 0.1,1,10 micromol/L GB decreased intracellular calcium concentration by 10.58%, 17.27% and 16.35% (n=12, 12, 10, P<0.01-0.001), respectively. With perfusion of ischemic solution for 12 min, intracellular calcium concentration increased by 20.15%. After a 12 min-perfusion of ischemic solution containing 1 micromol/L nifedipine or 5 mmol/L NiCl2, intracellular calcium concentration increased by 18.18% (P>0.05 vs ischemia) and 11% (P<0.05 vs ischemia), respectively. After 12 min of perfusion with ischemic solution containing 1 micromol/L GB, intracellular calcium concentration increased by 9.6% (P<0.05 vs ischemia). It is shown that GB could reverse the decrease of I(Ca,L) and partially inhibit calcium overload during ischemia.
Animals ; Calcium ; metabolism ; Calcium Channels, L-Type ; drug effects ; Cell Hypoxia ; Cytosol ; metabolism ; Ginkgolides ; pharmacology ; Guinea Pigs ; Heart Ventricles ; cytology ; Lactones ; pharmacology ; Male ; Myocardial Ischemia ; metabolism ; physiopathology ; Myocytes, Cardiac ; drug effects ; metabolism ; Patch-Clamp Techniques ; Plant Extracts ; pharmacology

Objective To establish a method for studying molecular mechanism of Rhubarb inhibiting anti-Yersinia pesti based on DNA microarray.Methods A whole genome DN A microarray containing 4005 annotated genes of Yersiniapesti Was used.The minimal inhibitory concentration(MIC)of Rhubarb to Yersiniapestiwas determined by liquid dilution method.The gene expression profile of Yersinia pesti was performed after the exposure to Rhubarb at a concentration of 10×MIC for 30 minutes.The total RNA extracted and purified from Yersinia pesti Was reversely transfected to cDNA and labeled by Cy3-Cy5 dye.The labeled probes were hybridized to the microarray anti the results were obtained by a laser scanner and the microarray data was confirmed by real-time quantitative RT-PCR.Results The platform of the DNA microarray-based bacteria transcriptional profile was established.A total of 498 genes of Yersinia pesti changed significantly in response to Rhubarb.Among them.358 genes were up-regulated,140 down-reguated.Conclusions The whole genome DNA microarray can be used in the studying of molecular anti-Yersinia pesti mechanism of Rhubarb.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Chromosome Aberrations ; Chromosomes, Human, Pair 8 ; Female ; Fibromatosis, Aggressive ; genetics ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Middle Aged