Research progress of traditional external preparations and novel nanoformulations of Arnebiae Radix / 中国药房

Arnebiae Radix is used widely in TCM external treatment. It has obvious curative effect on skin diseases， wound infection and local inflammation， and is used to treat water and fire burns， skin ulcers， eczema， psoriasis， vitiligo and atopic dermatitis， etc. The clinical and commercial preparations mainly include ointment， liniment and suppository. Modern research has proved that microcapsules， nano-micelles， nanofiber membranes， nanogels and other novel nanoformulations can significantly improve the stability of drug-effective substances， improve local drug concentration and targeting， and perform sound drug release properties in vitro. This paper reviews the variety and application of Arnebiae Radix traditional preparations for external use and the research progress of novel nanoformulations of Arnebiae Radix， from which we prospect to provide some valuable references for the future application and development of Arnebiae Radix external preparations.

Sagittaria sagittifolia polysaccharides regulates Nrf2/HO-1 to relieve liver injury caused by multiple heavy metals in vivo and in vitro / 中国中药杂志

This study explored whether Sagittaria sagittifolia polysaccharides(SSP) activates the nuclear factor erythroid-2-related factor2(Nrf2)/heme oxygenase-1(HO-1) signaling pathway to protect against liver damage jointly induced by multiple heavy metals. First, based on the proportion of dietary intake of six heavy metals in rice available in Beijing market, a heavy metal mixture was prepared for inducing mouse liver injury and HepG2 cell injury. Forty male Kunming mice were divided into five groups: control group, model group, glutathione positive control group, and low-and high-dose SSP groups, with eight mice in each group. After 30 days of intragastric administration, the liver injury in mice was observed by HE staining. In the in vitro experiment, MTT assay was conducted to detect the effects of SSP at 0.25, 0.5, 1, and 2 mg·mL~(-1) on HepG2 cell survival at different time points. The content of alanine transaminase(ALT) and aspartate aminotransferase(AST) in the 48-h cell culture fluid was measured using micro-plate cultivation method, followed by the detection of the change in reactive oxygen species(ROS) content by flow cytometry. The mRNA expression levels of Nrf2 and HO-1 in cells were determined by RT-PCR, and their protein expression by Western blot. HE staining results showed that compared with the model group, the SSP administration groups exhibited significantly alleviated inflammatory cell infiltration and fatty infiltration in the liver, with better outcomes observed in the high-dose SSP group. In the in vitro MTT assay, compared with the model group, SSP at four concentrations all significantly increased the cell survival rate, decreased the ALT, AST, and ROS content(P<0.05), and down-regulated Nrf2 and HO-1 mRNA and protein expression(P<0.05). SSP significantly improves inflammatory infiltration in the liver tissue of mice exposed to a variety of heavy metals and corrects the liver fat degeneration, which may be related to its regulation of the Nrf2/HO-1 signaling pathway, reduction of ROS, and alleviation of oxidative damage.

Formulation regularity and thinking of adjuvant sleep-improving Chinese medicinal health products / 中国中药杂志

To summarize and analyze the current adjuvant sleep-improving Chinese medicinal health products,this study retrieved the information on health products with the sleep-improving effect published by the Department of Special Food Safety Supervision and Management,State Administration for Market Regulation( SMAR),which was statistically analyzed with Microsoft Excel and TCMISS for the characteristics of formulations. A total of 435 sleep-improving health products were collected,including 344 ones containing Chinese herbal medicines. Among them,413 health products were not suitable for adolescents,neither 194 for pregnant women. Ten Chinese herbal medicines showed a frequency of use ≥40,with 1 095 times( 73. 1%) in use. Through unsupervised hierarchical entropy-based clustering of the above Chinese herbal medicines of health products( degree of support of 45 and confidence coefficient of0. 7),12 new formulas were obtained. The composition of Chinese herbal medicines was consistent with the principles of improving sleep in traditional Chinese medicine( TCM) theories,i. e.,replenishing the heart and spleen,nourishing blood,calming the nerves,nourishing Yin,reducing internal heat,communicating the heart and kidney,replenishing Qi,relieving convulsions,clearing heat,resolving phlegm,regulating the middle warmer,soothing the liver,relieving heat,and calming the heart. According to TCM theories,syndrome differentiation was performed based on the existing sleep-improving health products,followed by data mining and analysis according to the formulation regularity,aiming to provide new ideas for the development of new Chinese medicinal health products. In particular,attention should be attached to the requirements of special populations to provide a basis for follow-up studies,exert the advantages of TCM,and lay a foundation for Chinese medicinal health products to service the public.

Recommendations for public health protection against flood disaster / 中华预防医学杂志

Flood disaster is one of the most serious natural disasters in the world, and it could pose an inestimable impact on the affected people. Based on existing laws, regulations, and emergency manuals in China, extensive literature review, epidemiological and related protection evidence, and expert consultation, this study analyzed different health risk factors of flood disaster and proposed a multi-stage, multi-population, and multi-phase comprehensive protection measures for the public in the perspective of pre-event prevention, in-event intervention and post-event rescue strategy, which could provide a scientific basis for improving the level of public health protection against the flood disaster and corresponding health outcomes.

GL-V9 reverses adriamycin resistance in hepatocellular carcinoma cells by affecting JNK2-related autophagy / 中国天然药物

Adriamycin resistance in HCC seriously hinders the treatment of patients, it is necessary to investigate the mechanisms. Autophagy is involved in adriamycin resistance and JNK2 is related to autophagy. However, whether JNK2 inducing drug resistance though autophagy is unknown. GL-V9, a new synthesized flavonoid derivative, has been proved of its anti-tumor effects. The aim of the study is to explore the role of JNK2-related autophagy on adriamycin-induced drug resistance and the effects of GL-V9 on reversing adriamycin resistance. We concluded that JNK2 played an important role in drug resistance induced by adriamycin. The high expression of JNK2 activated protective autophagy in Hep G2-DOXR cells under non-stress condition, which protected cells from drug attacking. Furthermore, we found that GL-V9 reversed adriamycin resistance by blocking the JNK2-related protective autophagy in HCC.

Recommendations for public health protection against flood disaster / 中华预防医学杂志

Flood disaster is one of the most serious natural disasters in the world, and it could pose an inestimable impact on the affected people. Based on existing laws, regulations, and emergency manuals in China, extensive literature review, epidemiological and related protection evidence, and expert consultation, this study analyzed different health risk factors of flood disaster and proposed a multi-stage, multi-population, and multi-phase comprehensive protection measures for the public in the perspective of pre-event prevention, in-event intervention and post-event rescue strategy, which could provide a scientific basis for improving the level of public health protection against the flood disaster and corresponding health outcomes.

Extremely low frequency electromagnetic radiation enhanced energy metabolism and induced oxidative stress in Caenorhabditis elegans / 生理学报

The aim of this study was to determine the effects of extremely low frequency electromagnetic field (ELF-EMF) on energy metabolism and oxidative stress in Caenorhabditis elegans (C. elegans). Worms in three adult stages (young adult stage, egg-laying stage and peak egg-laying stage) were investigated under 50 Hz, 3 mT ELF-EMF exposure. ATP levels, ATP synthase activity in vivo, reactive oxygen species (ROS) content, and changes of total antioxidant capacity (TAC) were detected, and worms' oxidative stress responses were also evaluated under ELF-EMF exposure. The results showed that ATP levels were significantly increased under this ELF-EMF exposure, and mitochondrial ATP synthase activity was upregulated simultaneously. In young adult stage, worms' ROS level was significantly elevated, together with upregulated TAC but with a decreased ROS-TAC score indicated by principal component analysis. ROS level and TAC of worms had no significant changes in egg-laying and peak egg-laying stages. Based on these results, we concluded that ELF-EMF can enhance worm energy metabolism and elicit oxidative stress, mainly manifesting as ATP and ROS level elevation together with ATP synthase upregulation and ROS-TAC score decrease in young adult C. elegans.

Forming Technology Optimization of Zuojin Concentrated Pills by Orthogonal Test / 中国药师

Objective:To optimize the forming technology of Zuojin concentrated pills. Methods: Single factor test was used to optimize the types of excipients and wetting agents with the shaping result as the index. Orthogonal test was used to optimize the forming technology taking the dissolution time,shaping rate and appearance quality as the evaluation indices,and the proportion of excipients, the rate of drugs to excipients and wetting agent amount as the investigation factors. Results: The best forming technology of Zuojin concentrated pills was as follows:MCC and PVP-K30 were used as the excipients with the ratio of 3:1,the ratio of drugs to excipients was 1:1,5% water was used as the wetting agent to obtain the damp mass,and then Zuojin concentrated pills were prepared in a pill machine. Conclusion:The optimized forming technology is stable with good reproducibility,and the pills are round and smooth with u-niform color,whose quality meets the requirements described in Chinese Pharmacopoeia(2015 edition,partⅣ,page 0108 for concen-trated pills). The study provides reference for the further study.

Improving qualified rate of cleaning of loaner orthopedic surgery instruments by application of quality control circle / 中国感染控制杂志

Objective To improve the qualified rate of cleaning of loaner orthopedic surgery instruments by application of quality control circle(QCC).Methods QCC activity was carried out in a hospital from May to October 2016, on-site assessment of cleaning quality was performed by two circle members, causes of unqualified cleaning result of loaner orthopedic surgery instruments were recorded, the qualified result of loaner orthopedic surgery instruments before QCC activity(May-June 2016)and after QCC activity(September-October 2016)was compared. Results Before QCC activity, there were 1 667 packages of loaner instruments, 1 415 were qualified for cleaning, qualified rate was 84.88％;after activity, there were 1 673 packages of loaner instruments, 1 655 were qualified for cleaning, qualified rate was 98.92％, difference was statistically significant between two groups(P＜0.01), qualified rate increased to 14.04％, target achievement rate was 116％.Conclusion Application of the scientific tool of QCC can improve the qualified rate of cleaning of loaner orthopedic surgery instruments.

Developing the infusion soft bag for transfusion safety / 中国实用护理杂志

Objective To provide a kind of infusion soft bag with double-pouch that avoids the compatibility reaction between medicinal fluids and improves the safety of transfusion. Methors By consulting the literature, clinical research, developed a safe infusion bag. Researching the volume and the method of tube flushing in vitro simulation experiments, observation of the experimental process, data collection, input, analysis, processing, in order to determine the capacity of the fluid structure to compare the operation time of the two methods of flushing tube. Results In vitro simulation showed that the volume of fluid needed for irrigation infusion tube was 30-50 ml. The time spent on each infusion tube when using the developed safety infusion bag and existing infusion bag was (2.81±0.18) s and (13.63±0.36) s respectively, the difference was statistically significant (t=-146.15,P<0.05). Conclusion The size of the main bag of the safe transfusion soft bag can be set according to the clinical need. The recommended storage capacity of the bag for flushing is 50 ml for the strong solution and 30 ml for the ordinary solution. Safety infusion soft bag is high safety, easy to use, reducing nurse′s workload and the risk of infection, it is worth the clinical promotion.

The Influence of Sex in Stroke Thrombolysis: A Systematic Review and Meta-Analysis

BACKGROUND AND PURPOSE: There is increasing recognition of the importance of stroke in females to both clinical and public health. The natural course of stroke is worse in females than in males, but the evidence regarding sex disparities in the responses to thrombolysis in stroke patents is still controversial. We compared outcomes after thrombolysis treatment between females and males. METHODS: Clinical trials reported in the Embase, PubMed, and Cochrane Library electronic databases up to March 13, 2017 were included in this analysis. Two reviewers independently extracted the data and conducted quality assessments. Statistical tests were performed to check for heterogeneity and publication bias. Sensitivity analysis was also performed to evaluate the stability of the conclusions. RESULTS: Sixteen reports involving 60,159 patients were available for analysis. The female patients were a 0.89-fold [95% confidence interval (CI)=0.87–0.90, p < 0.001], 0.89-fold (95% CI=0.87–0.91, p < 0.001), and 1.24-fold (95% CI=1.11–1.36, p < 0.001) more likely to obtain good, excellent, and poor functional outcomes, respectively, with no significant difference in the complications of symptomatic intracranial hemorrhage among the sexes [risk ratios (RR)=0.99, 95% CI=0.92–1.07, p=0.81] after thrombolysis treatment. In addition, the prevalence of a good functional outcome did not differ significantly between females and males in the intra-arterial thrombolysis (IAT) group (RR=1.05, 95% CI=0.85–1.29, p=0.67) in a subgroup analysis. CONCLUSIONS: This study has demonstrated that females often exhibit a worse outcome than males after intravenous thrombolysis (IVT), whereas no relevant sex differences were found in outcome or recanalization after IAT, with safety regarding hemorrhage complications from thrombolysis being the same for the sexes. However, IVT should not be withheld from female stroke patients solely based on their sex before the findings are confirmed in further large-scale research.

Glomerular Filtration Rate is Associated with Hemorrhagic Transformation in Acute Ischemic Stroke Patients without Thrombolytic Therapy / 中华医学杂志(英文版)

<p><b>Background</b>Whether there is a relationship between glomerular filtration rate (GFR) and hemorrhagic transformation (HT) after acute ischemic stroke (AIS) is still under debate. The aim of our study was to determine whether the GFR level is a predictor of HT in AIS patients without thrombolytic therapy (TT).</p><p><b>Methods</b>Consecutive AIS patients without TT were included in this prospective study from January 2014 to December 2016 in the First Affiliated Hospital of Chongqing Medical University. We divided them into two groups (HT and non-HT group) and meticulously collected baseline characteristics and laboratory and imaging data of interested individuals. Multivariate regression analysis was performed to assess the correlation between GFR and HT in stroke patients without TT.</p><p><b>Results</b>Among 426 consecutive patients, 74 (17.3%) presented HT (mean age: 65 ± 12 years, number of male patients: 47) on the follow-up scans. In multivariate regression analysis, HT was significantly associated with low GFR (odds ratio [OR] = 3.708, confidence interval [CI] = 1.326-10.693, P = 0.013), atrial fibrillation (AF; OR = 2.444, CI = 1.087-5.356, P = 0.027), large cerebral infarction (OR = 2.583, CI = 1.236-5.262, P = 0.010), and hypoalbuminemia (HA; OR = 4.814, CI = 1.054-22.153, P = 0.037) for AIS patients without TT.</p><p><b>Conclusions</b>The present study strongly showed that lower GFR is an independently predictor of HT; in addition, large infarct volume, AF, and HA are also important risks of HT for AIS patients without TT, which offered a practical information that risk factors should be paid attention or eliminated to prevent HT for stroke patients though the level of evidence seems to be unstable.</p>

Claudin-3 expression in colorectal carcinoma and its significance / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expression of claudin-3 in colorectal carcinoma and its association with the occurrence, progression and prognosis of colorectal cancer.</p><p><b>METHODS</b>Forty surgical specimens of colorectal carcinoma and 22 adjacent normal tissues resected between October, 2010 and January, 2013 at Nanfang Hospital were examined for claudin-3 expression using immunohistochemistry, which was analyzed in association with the clinicopathological parameters and the survival of the patients.</p><p><b>RESULTS</b>Claudin-3 was expressed mainly on the cell membrane, and its positivity rate was significantly higher in cancer tissues than in normal tissues (92.50% vs 59.09%, P<0.05). In 13 cases claudin-3 expression was detected in both the cancer tissues and adjacent normal tissues with average expression scores of 4.538 and 3.269, respectively (P<0.05). In the cancer tissues, the strongly positive expression rate was significantly higher in poorly differentiated tissues (85.71%) than in well (21.43%) and moderately (36.48%) differentiated tissues (P<0.05), and was higher in cases with lymph node metastasis than in those without (61.11% vs 22.72%, P<0.05). The strongly positive expression rate of claudin-3 was not correlated with the patients'age, gender, tumor location or tumor size (P>0.05). Of the 33 cancer patients followed up, 14 had a postoperative survival time no longer than 3 years and 19 had longer survival time, and their average expression scores differed significantly (4.50 vs 3.526, P<0.05).</p><p><b>CONCLUSION</b>Claudin-3 is over-expressed in colorectal cancer tissues, and its high expression may promote the occurrence and progression of colorectal cancer. Claudin-3 may serve as a molecular biomarker for early diagnosis and prognostic evaluation.</p>

Protective effects and mechanism of SIRT1 for the regulation of p38 MAPK pathway on retinal ganglion cells in rats with diabetic retinopathy / 眼科新进展

Objective To investigate the effect of silment information regulator factor related enzymes 1 (SIRT1) on the apoptosis of retinal ganglion cells (RGCs) in rats with diabetic retinopathy and its downstream molecular mechanisms.Methods Together 60 healthy male Sprague-Dawley rats were collected and randomly divided into normal group,diabetic group,SIRTI activator-resveratrol treatment group (treatment group),and diabetic rat model was induced by intraperitoneal injection of streptozotocin at 60 mg · kg-1 in the latter two group rats,while the normal group was injected with sodium citrate buffer at 60 mg · kg-1.Then,after 72 h,rats with blood glucose ＞ 16.7 mmol · L-1 were designated as diabetic rats by blood glucose test.Then each rat in the treatment group was treated with SIRT1 activator-resveratrol at 20 g · kg-1 once a day at the 2nd day after the success of the model,and the normal group and diabetic group were given methylene chloride.Finally,after immunohistochemical staining for retina,TUNEL assay was used to evaluate the apoptosis of RGCs,while the expression of SIRTI,p38 MAPK and Caspase-3 protein was detected by Western blot.Results The apoptotic index of RGCs in the normal group,diabetic group and treatment group was (0.848+0.131)％,(19.038 + 1.327)％,(10.461 + 1.089)％ respectively at 8 weeks,and the difference among the three groups was statistically significant (F =670.497,P =0.000),while the differences between each two groups were also statistically significant (all P =0.000).Furthermore,when compared with the normal group (0.132 ± 0.043),the expression of SIRT1 protein in the diabetic group (0.060 ± 0.028) and the treatment group (0.073 ± 0.026) was significantly decreased,and the overall difference among the three groups was statistically significant (F =1 310.663,P =0.000),while the differences between each two groups were also statistically significant (all P =0.000).The expression levels of p38 MAPK and Caspase-3 were increased in diabetic group (1.121 ± 0.082,0.266 ± 0.005) and treatment group (0.574 ± 0.012,0.190 ±0.060) respectively,and the overall difference and pairwise comparison in the three groups approached statistically significance (all P =0.000,0.000).Conelusion Up-regulation of SIRT1,can inhibit the apoptosis of RGCs,and protect RGCs against apoptosis in rat model of diabetic retinopathy,which may be correlated with the downregulation of p38 MAPK signal pathway.

Relationship between Apolipoprotein Superfamily and Parkinson's Disease / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>Parkinson's disease (PD) is featured with motor disorder and nonmotor manifestations including psychological symptoms, autonomic nervous system dysfunction, and paresthesia, which results in great inconvenience to the patients' life. The apolipoprotein (Apo) superfamily, as a group of potentially modifiable biomarkers in clinical practice, is of increasing significance in the diagnosis, evaluation, and prognosis of PD. The present review summarized the current understanding and emerging findings of the relationship between Apo superfamily and PD.</p><p><b>DATA SOURCES</b>All literatures were identified by systematically searching PubMed, Embase, and Cochrane electronic databases with terms "Parkinson disease," "apolipoprotein," and their synonyms until May 2017.</p><p><b>STUDY SELECTION</b>We have thoroughly examined titles and abstracts of all the literatures that met our search strategy and the full text if the research is identified or not so definite. Reference lists of retrieved articles were also scrutinized for additional relevant studies.</p><p><b>RESULTS</b>The levels of plasma ApoA1 are inversely correlated with the risk of PD and the lower levels of ApoA1 trend toward association with poorer motor performance. Higher ApoD expression in neurons represents more puissant protection against PD, which is critical in delaying the neurodegeneration process of PD. It is suggested that APOE alleles are related to development and progression of cognitive decline and age of PD onset, but conclusions are not completely identical, which may be attributed to different ApoE isoforms. APOJ gene expressions are upregulated in PD patients and it is possible that high ApoJ level is an indicator of PD dementia and correlates with specific phenotypic variations in PD.</p><p><b>CONCLUSIONS</b>The Apo superfamily has been proved to be closely involved in the initiation, progression, and prognosis of PD. Apos and their genes are of great value in predicting the susceptibility of PD and hopeful to become the target of medical intervention to prevent the onset of PD or slow down the progress. Therefore, further large-scale studies are warranted to elucidate the precise mechanisms of Apos in PD.</p>

Primary Study on the Synthesis of Active Ingredients of Ophiocordyceps xuefengensis by Submerged Fer-mentation Method / 中国药房

OBJECTIVE:To explore basic technology for synthesis of active ingredients of Ophiocordyceps xuefengensis,and provide necessary technical support for comprehensive development of O. xuefengensis sourse. METHODS:Submerged fermenta-tion method was used to cultivate the mycelium,achieving efficient synthesis of active ingredients by controlling medium composi-tion and cultivation conditions. Using the bacteria as starting strain,the effects of different carbon sources (sucrose,glucose and soluble starch),different nitrogen sources (peptone,yeast extract powder,yeast extract,sodium nitrate,potassium nitrate and urea),different vitamin B(vitamin B1 and vitamin B complex)and different initial pH(pH was set at 4,5,6,7,8 and 9,re-spectively)on mycelial growth,extracellular and intracellular polysaccharide synthesis,cordycepin synthesis and intracellular triter-penoid synthesis were investigated to screen the optimal medium composition. RESULTS:The optimal carbon source,nitrogen source,vitamin B and initial pH were sucrose,yeast extract powder,vitamin B1 and 8,respectively. High biomass and metabolite accumulation levels can be obtained when carbon source was sucrose,nitrogen source was yeast extract powder,adding 0.1 g/L vi-tamin B1 with initial pH of 8. CONCLUSIONS:O. xuefengensis can efficiently accumulate metabolites,and achieve the optimiza-tion of strain cell growth and synthesis of active metabolite by optimizing and controlling the fermentation process.

Bacterial carriage and influencing factors of mobile phones used by health care workers in municipal hospitals in a city / 中国感染控制杂志

Objective To understand the status of mobile phone use and bacterial carriage on surface of mobile phones used by health care workers(HCWs) in municipal hospitals in a city,explore the influencing factors of mobile phone use behavior and bacterial carriage status.Methods In April-June,2016,111 HCWs in 24 hospitals in a city were performed questionnaire survey,on-site observation,and sampling of mobile phone surface.Results A total of 111 (100.00％) available questionnaires were distributed and returned.The average age of the respondents were (32.00 ± 9.03)years old,female and nurses were predominant.95.50％ of respondents used touch screen mobile phones,24.32％ used mobile phones during diagnosis and treatment,65.77％ used mobile phone ＞2 hours every day,93.69％ cleaned and disinfected mobile phones,98.20％ thought that pathogenic microorganisms exited on the surface of mobile phones.A total of 111 mobile phone surface specimens were collected,the qualified rate was 80.18％,contamination rate was 95.50％,average colony number was 2.90 CFU/cm2,the maximum bacterial content was 111.60 CFU/cm2.Among 44 specimens of mobile phone surface,55 strains of 18 species of pathogenic bacteria or opportunistic pathogenic bacteria were detected.Age,gender,and occupation were the influencing factors of mobile phone use behavior and attitude;qualified rates were all significantly different among mobile phones used by HCWs of different gender,occupation,and duration of mobile phone use (all P＜0.05);bacterial contamination on the surface of mobile phones used by HCWs of different age,gender,occupation,duration of mobile phone use,and whether to use the phone shell/set were significantly different respectively(all P＜0.05).Conclusion Potential pathogens on the surface of mobile phones may cause healthcare-associated infection through the use of mobile phones by HCWs during the process of medical diagnosis and treatment.

Losartan inhibits LPS-induced GFAP expression via AMPK activation in mouse hippocampus / 中国病理生理杂志

AIM:To investigate the effects of losartan on lipopolysaccharide (LPS)-induced glial fibrillary acidic protein (GFAP) expression,and to determine whether adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) activation is involved in the mechanism.METHODS:Adult male KM mice were divided into control group,LPS model group,losartan treatment group,and losartan and Compound C co-treatment group.To establish a model of central nervous system inflammation,the mice received daily intracerebroventricular injection of LPS (24 μg/d) for 2 d.Daily losartan administration (0.5,1 or 5 mg · kg-1 · d-1,ip) initiated at 14 d prior to LPS injection.Compound C (10 mg/kg,ip),a selective AMPK inhibitor,started to be injected daily at 2 d prior to LPS injection.The hippocampal tissues in each group were isolated at 3 d after the last LPS injection,and then the protein levels of GFAP,AMPK,p-AMPK,mammalian target of rapamycin (mTOR) and p-mTOR were determined by Western blot.RESULTS:Twice LPS injections significantly increased the expression of GFAP in the hippocampus (P ＜ 0.01).Losartan inhibited LPS-induced GFAP expression in a concentration-dependent way,and losartan at 5 mg· kg-1 · d-1 significantly inhibited GFAP expression and AMPK activation (P ＜ 0.05),but it had no obvious effect on mTOR activation.Furthermore,Compound C significantly reversed the effect of losartan treatment on LPS-induced GFAP expression and AMPK phosphorylation (P ＜ 0.05).CONCLUSION:Losartan inhibits LPS-induced GFAP expression in the mouse hippocampus,and AMPK activation but not mTOR,is involved in the mechanism.

Losartan inhibits LPS-induced GFAP expression via AMPK activation in mouse hippocampus / 中国病理生理杂志

AIM:To investigate the effects of losartan on lipopolysaccharide (LPS)-induced glial fibrillary acidic protein (GFAP) expression,and to determine whether adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) activation is involved in the mechanism.METHODS:Adult male KM mice were divided into control group,LPS model group,losartan treatment group,and losartan and Compound C co-treatment group.To establish a model of central nervous system inflammation,the mice received daily intracerebroventricular injection of LPS (24 μg/d) for 2 d.Daily losartan administration (0.5,1 or 5 mg · kg-1 · d-1,ip) initiated at 14 d prior to LPS injection.Compound C (10 mg/kg,ip),a selective AMPK inhibitor,started to be injected daily at 2 d prior to LPS injection.The hippocampal tissues in each group were isolated at 3 d after the last LPS injection,and then the protein levels of GFAP,AMPK,p-AMPK,mammalian target of rapamycin (mTOR) and p-mTOR were determined by Western blot.RESULTS:Twice LPS injections significantly increased the expression of GFAP in the hippocampus (P ＜ 0.01).Losartan inhibited LPS-induced GFAP expression in a concentration-dependent way,and losartan at 5 mg· kg-1 · d-1 significantly inhibited GFAP expression and AMPK activation (P ＜ 0.05),but it had no obvious effect on mTOR activation.Furthermore,Compound C significantly reversed the effect of losartan treatment on LPS-induced GFAP expression and AMPK phosphorylation (P ＜ 0.05).CONCLUSION:Losartan inhibits LPS-induced GFAP expression in the mouse hippocampus,and AMPK activation but not mTOR,is involved in the mechanism.

Protective effects and mechanism of SIRT1 for the regulation of p38 MAPK pathway on retinal ganglion cells in rats with diabetic retinopathy / 眼科新进展

Objective To investigate the effect of silment information regulator factor related enzymes 1 (SIRT1) on the apoptosis of retinal ganglion cells (RGCs) in rats with diabetic retinopathy and its downstream molecular mechanisms.Methods Together 60 healthy male Sprague-Dawley rats were collected and randomly divided into normal group,diabetic group,SIRTI activator-resveratrol treatment group (treatment group),and diabetic rat model was induced by intraperitoneal injection of streptozotocin at 60 mg · kg-1 in the latter two group rats,while the normal group was injected with sodium citrate buffer at 60 mg · kg-1.Then,after 72 h,rats with blood glucose ＞ 16.7 mmol · L-1 were designated as diabetic rats by blood glucose test.Then each rat in the treatment group was treated with SIRT1 activator-resveratrol at 20 g · kg-1 once a day at the 2nd day after the success of the model,and the normal group and diabetic group were given methylene chloride.Finally,after immunohistochemical staining for retina,TUNEL assay was used to evaluate the apoptosis of RGCs,while the expression of SIRTI,p38 MAPK and Caspase-3 protein was detected by Western blot.Results The apoptotic index of RGCs in the normal group,diabetic group and treatment group was (0.848+0.131)％,(19.038 + 1.327)％,(10.461 + 1.089)％ respectively at 8 weeks,and the difference among the three groups was statistically significant (F =670.497,P =0.000),while the differences between each two groups were also statistically significant (all P =0.000).Furthermore,when compared with the normal group (0.132 ± 0.043),the expression of SIRT1 protein in the diabetic group (0.060 ± 0.028) and the treatment group (0.073 ± 0.026) was significantly decreased,and the overall difference among the three groups was statistically significant (F =1 310.663,P =0.000),while the differences between each two groups were also statistically significant (all P =0.000).The expression levels of p38 MAPK and Caspase-3 were increased in diabetic group (1.121 ± 0.082,0.266 ± 0.005) and treatment group (0.574 ± 0.012,0.190 ±0.060) respectively,and the overall difference and pairwise comparison in the three groups approached statistically significance (all P =0.000,0.000).Conelusion Up-regulation of SIRT1,can inhibit the apoptosis of RGCs,and protect RGCs against apoptosis in rat model of diabetic retinopathy,which may be correlated with the downregulation of p38 MAPK signal pathway.