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Parkinson's disease (PD) is the most common neurodegenerative movement disease. It is featured by abnormal alpha-synuclein (α-syn) aggregation in dopaminergic neurons in the substantia nigra. Macroautophagy (autophagy) is an evolutionarily conserved cellular process for degradation of cellular contents, including protein aggregates, to maintain cellular homeostasis. Corynoxine B (Cory B), a natural alkaloid isolated from Uncaria rhynchophylla (Miq.) Jacks., has been reported to promote the clearance of α-syn in cell models by inducing autophagy. However, the molecular mechanism by which Cory B induces autophagy is not known, and the α-syn-lowering activity of Cory B has not been verified in animal models. Here, we report that Cory B enhanced the activity of Beclin 1/VPS34 complex and increased autophagy by promoting the interaction between Beclin 1 and HMGB1/2. Depletion of HMGB1/2 impaired Cory B-induced autophagy. We showed for the first time that, similar to HMGB1, HMGB2 is also required for autophagy and depletion of HMGB2 decreased autophagy levels and phosphatidylinositol 3-kinase III activity both under basal and stimulated conditions. By applying cellular thermal shift assay, surface plasmon resonance, and molecular docking, we confirmed that Cory B directly binds to HMGB1/2 near the C106 site. Furthermore, in vivo studies with a wild-type α-syn transgenic drosophila model of PD and an A53T α-syn transgenic mouse model of PD, Cory B enhanced autophagy, promoted α-syn clearance and improved behavioral abnormalities. Taken together, the results of this study reveal that Cory B enhances phosphatidylinositol 3-kinase III activity/autophagy by binding to HMGB1/2 and that this enhancement is neuroprotective against PD.
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Objective:To investigate the diagnostic efficacy of serum N-terminal B-type brain natriuretic peptide (NT-proBNP) and D-dimer for cardiogenic cerebral embolism (CE) based on population in southern Sichuan.Methods:We selected the clinical data of 313 patients with acute cerebral infarction (ACI) for the first time, 34 patients with simple atrial fibrillation (AF) and 30 healthy people who were admitted to the Affiliated Hospital of Southwest Medical University from June 2019 to April 2021. The patients with ACI were divided into four subgroups according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) typing: large artery atherosclerosis (LAA), CE, small artery occlusion (SAO), and indeterminate subtype (UT). The differences in clinical data in the groups were compared. At the same time, the differences of NT-proBNP and D-dimer in serum in CE group, AF group and healthy group were compared; The risk factors of CE were analyzed by binary logistic regression, and the diagnostic efficacy of serum NT-proBNP and D-dimer for CE was evaluated by receiver operating characteristic (ROC) curve.Results:The prevalence of hypertension, diabetes, systolic blood pressure (SBP) and diastolic blood pressure (DBP) at admission, prothrombin time (PT), international normalized ratio (INR), fibrinogen (FIB), D-dimer, fibrinogen degradation products (FDP), National Institutes of Health Stroke Scale (NIHSS) score at admission, NT-proBNP and AF rate were significantly different among ACI subgroups (all P<0.05); There was no significant difference in PT and NIHSS score at admission between LAA group and CE group (all P>0.05). The prevalence of D-dimer, NT-proBNP and AF rate in CE group was significantly higher than those in other three groups (all P<0.05). The D-dimer, NT-proBNP, FDP and SBP level in CE group were significantly higher than those in AF group and healthy group (all P<0.05). Binary logistic regression analysis showed that D-dimer and NT-proBNP were independent risk factors for CE (both P<0.05). When the optimal cut-off value of serum D-dimer was 1.015 mg/L, the area under the ROC curve (AUC) was 0.896 (95% CI: 0.856-0.935, P<0.01); the sensitivity and specificity were 0.878 and 0.833, respectively; the positive predictive value and the negative predictive value were 0.705 and 0.953, respectively. When the best cut-off value of serum NT-proBNP was 657.145 ng/L, the AUC was 0.987 (95% CI: 0.977-0.998, P<0.01); the sensitivity and specificity were 0.959 and 0.963, respectively; the positive predictive value and the negative predictive value were 0.922 and 0.981, respectively. The accuracy of the combined detection of serum D-dimer and NT-proBNP in the diagnosis of CE was higher, and the AUC was 0.988 (95% CI: 0.978-0.998, P<0.01), sensitivity of 0.960, specificity of 0.977, positive predictive value of 0.950, negative predictive value of 0.982. Conclusions:The serum levels of NT-proBNP and D-dimer in CE patients increased significantly; NT-proBNP and D-dimer are important predictors of CE and have higher diagnostic efficacy for CE. The combination of them has a higher specificity for diagnosis.
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Aim To explore the anti-inflammatory effect of taurolithocholic acid (TLCA) through network pharmacology-based analyses, to verify with in vitro macrophage study and to reveal the possible mechanisms. Methods The potential targets of TLCA were acquired from public database, and then the protein-protein interaction (PPI) networks against inflammation were constructed and visualized by using Cytoscape. Gene ontology (GO) analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed. The binding activity of TLCA and its target (TGR5) was evaluated through molecular docking analysis. Lastly, the results of the network analysis were confirmed by lipopolysaccharide and interferon-γ induced RAW264.7 cells. Results There were 87 anti-inflammatory potential targets were screened. GO analysis revealed gene functions were mainly involved in regulation of inflammatory response, membrane raft and protein tyrosine kinase. The results of KEGG pathway analysis suggested that PI3K-Akt signaling pathway, human cytomegalovirus infection might be the critical pathways of TLCA against inflammation. The results of in vitro experiments showed that TLCA decreased the LPS and IFN-γ induced inflammatory response in RAW 264.7 macrophages. Furthermore, the expression of TGR5 protein increased after TLCA treatment. Conclusions The potential therapeutic targets of TLCA against inflammation are revealed through network pharmacology analysis. Our results indicate that TLCA might regulate key inflammatory markers through the membrane receptor TGR5.
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Zika virus (ZIKV) is an emerging mosquito-borne virus that is associated with severe congenital brain malformations in the fetus and Guillain-Barré syndrome in adults. However, there are currently no drugs or preventive vaccines approved for ZIKV infection. Here, ciclesonide has been found significantly against ZIKV activity by plaque and cytotoxicity assays in vitro, and its 50% effective concentration (EC50) to ZIKV SZ01 and MR766 are (0.40 ± 0.22) and (1.59 ± 1.08) μmol·L-1, respectively. Its 50% cytotoxic concentration (CC50) to Vero cells are (64.70 ± 7.33) μmol·L-1; Virus yield reduction and Western blot assays showed that ciclesonide can inhibit replication of ZIKV. In addition, ciclesonide can also inhibit the replication of ZIKV in A549 cells; the results of time of drug addition analysis indicated that ciclesonide mainly acts on the ZIKV RNA synthesis stage. Ciclesonide can also inhibit the internalization of ZIKV. These results indicated that ciclesonide is a potential drug against ZIKV.
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ObjectiveThere are few reports on the correlation between blood glucose fluctuation and body mass index(BMI) in patients with type 2 diabetes mellitus (T2DM). This study aims to evaluate the correlation between the two by comparing the differences of glucose fluctuation in T2DM patients with different BMI.MethodsA total of 672 patients with T2DM admitted to the General Hospital of Eastern Theater Command from June 2017 to October 2018 were selected as subjects. They were divided into 4 groups according to the quartile of BMI. The age, height, weight, course of diabetes, hemoglobin, uric acid, glycosylated hemoglobin, HOMA-IR (insulin resistance index) and HOMA-β (islet β cell function index) were collected. The blood glucose of the patients was continuously monitored within 3 days by wearing a continuous glucose monitor (CGMS). The standard deviation of daily blood glucose (SBDG), the mean of daily differences (MODD) and the mean amplitude of glycemic excursion(MAGE) were calculated to analyze the effect of BMI on blood glucose fluctuation.ResultsThe index of blood glucose fluctuation was negatively correlated with BMI, HbA1c and HOMA-β, but positively with HOMA-IR. Compared with the 1st and 2nd quartiles of BMI, the fluctuation level of patients in the 3rd and 4th quartiles was lower. Multivariate logistic regression analysis showed that after adjustment of age, sex, cholesterol, triglyceride and hemoglobin, the risk of hyperglycemia fluctuation in the fourth quartile group was lower than that in the first quartile group (OR=0.594, 95%CI: 1.825~2.062).ConclusionThe fluctuation of blood glucose in patients with higher BMI is lower than that in patients with lower BMI.
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OBJECTIVE: To extract microamounts of animal-derived DNA from the products of Colla Corii Asini boiled at high temperature, establish and optimize a rapid identification method of donkey-derived components in Colla Corii Asini by polymerase chain reaction(PCR), and establish a new molecular biological method for assessing the quality of Colla Corii Asini. METHODS: The donkey-derived genomic DNA was extracted by DNA purification column instead of phenol, chloroform and other toxic organic solvents in SDS-PK method, and the SDS-PK method was optimized with the donkey-derived genomic DNA. RESULTS: The optimum sample size of Colla Corii Asini was 0.20 g. High quality genomic DNA of Colla Corii Asini could be obtained quickly after digestion in water bath for 1 h and then purified by DNA purification column. The purity ranged from 1.70 to 1.80, and the concentration of Colla Corii Asini could reach (187.8±0.56)ng•μL-1. PCR amplification, cloning, and sequencing were performed using specific primers, and the similarity to GenBank's registered Donkey species (MG931481.1) was 100%. CONCLUSION: This study provides animal-derived genomic DNA fragments from deep-processed Colla Corii Asini and Colla Corii Asini products within 90 min. The purity and concentration of extracted DNA can meet the requirements of molecular biological identification of Colla Corii Asini. The established PCR method can quickly identify the scorpion-derived components in Colla Corii Asini. The cloned donkey specific gene fragment can be used as a standard positive control to identify the authenticity of Colla Corii Asini. It is expected that it will be widely used in the quality supervision of Colla Corii Asini and related products.
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Objective The alterations of gut microbiota is closely related to metabolic diseases. The aim of this study was to analyze the effects of antibiotics on glucose metabolism and gut microbiota in mice, and to further explore the mechanism of gut microbiota in reducing blood glucose in db/db diabetic mice by broad-spectrum antibiotics. Methods 16 C57BL/KsJ-db/db mice were randomly divided into antibiotic group and control group with 8 mice in each group. Antibiotic group: broad-spectrum antibiotics(vancomycin 10mg/(kg·d), carbenicillin 50mg/(kg·d), metronidazole 50mg/(kg·d), neomycin 30mg/(kg·d)); Control group: 1% cellulose sodium solution as placebo treatment. Fasting blood glucose and body weights were recorded once a week during the study. At the same time, feces were collected for 16S rDNA gene sequencing analysis. The changes of fasting blood glucose, body weight, the relative abundance of microbiota, Shannon index, Simpson index and GLP-1 were compared between the two groups. Results After 5 weeks of treatment with broad-spectrum antibiotics (Vancomycin , Carbenicillin , Metronidazole , and Neomycin ), fasting blood glucose levels in db/db diabetic mice were significantly decreased (9.59±4.49mmol/L vs 19.71±8.74mmol/L,P=0.016). At the same time, antibiotics can also affect the gut microbiota of mice. The relative abundance of Proteobacteria in mice treated with antibiotics was significantly higher than that in control group (0.471±0.12 vs 0.177±0.12, P<0.05), and the OTUs of Proteobacteria, Enterobacteriaceae, Gamma-proteobacteria, and Enterobacteriales increased in mice treated with antibiotics compared with controls. In addition, we also showed antibiotics could change the diversity of gut microbiota, and the diversity of gut microbiota in antibiotic treated mice decreased significantly (Shannon index 3.135 vs 5.359, P<0.01); Simpson index 0.794 vs 0.946, P<0.01). Conclusion Broad-spectrum antibiotics can significantly reduce the fasting blood glucose level and the diversity of gut microbiota of db / db diabetic mice, and the alterations of gut microbiota may play an essential role in the process of reducing blood glucose by broad-spectrum antibiotics.
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Tenofovir disoproxil fumarate (TDF) is a nucleoside analogue that has been widely used for clinical treatment of human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infection. The aim of this study was to investigate whether TDF has anti-Zika virus (ZIKV) activity in vitro. The inhibitory effect of TDF on ZIKV was detected by plaque reduction assay. Then, the anti-ZIKV activity of TDF at RNA level and protein level was verified by real time quantitative PCR and Western blot. Finally, MTT assay was used to determine the cytotoxicity of TDF. Our results showed that TDF not only reduced the formation of plaque after ZIKV infection, but also inhibited the replication of ZIKV RNA or expression of ZIKV NS2B protein. The 50% effective concentration (EC50) of TDF in inhibition of ZIKV replication were 14.96-27.47 μmol·L-1, while that of ribavirin was 56.01 ± 12.16 μmol·L-1, which served as the positive control. The cytotoxicity of TDF and ribavirin in Vero cells were very low, with their 50% cytotoxic concentration (CC50) values being greater than 500 μmol·L-1. The therapeutic index of TDF calculated by CC50/EC50 was greater than 18.20, which was significantly higher than that of ribavirin. The results suggest that TDF has good anti-ZIKV activity in vitro and is expected to become a candidate drug for anti-ZIKV therapy.
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Objective To observe the effects of Crk-SH3 domain guanine exchange factor(C3G)overexpression on the pro-liferation and apoptosis of high glucose-induced H9C2 cardiomyocytes.Methods H9C2 cardiomyocytes were transiently transfected with pCXN2-Flag(empty plasmid)and pCXN2-Flag-hC3G(human C3G mRNA)plasmids,then conducted high glucose(HG)in-tervention.The experiment was divided into the blank group,empty vector group,C3G overexpression group,blank + HG group, empty vector + HG group and C3G overexpression+ HG group.The C3G protein expressions,apoptosis and proliferation rate were respectively detected in each H9C2 cardiomyocytes groups.Results The proliferation rate in the blank+ HG group and empty vec-tor+ HG group were significantly decreased compared with the blank group and empty vector group,while the apoptosis rate was significantly increased.Compared with blank group and empty vector group,blank + HG and empty vector + HG group,the C3G protein expression and proliferation rate in the C3G overexpression group and C3G overexpression+ HG group were increased sig-nificantly,while the apoptosis rate was decreased significantly.Conclusion High glucose inhibits H9C2 myocardial cell proliferation and promots its apoptosis;furthermore,C3G overexpression can reversed the decrease of high glucose-induced H9C2 cardiomyocyte prolifer-ation rate and apoptosis increase.C3G overexpression can promote the survivability of high glucose-induced H9C2 cardiomyocytes.
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AIM:To investigate the effects of 3-phosphoinositide-dependent protein-1(PDK1)on the biologi-cal characteristics of non-small-cell lung cancer cell line A549 and the underlying mechanisms.METHODS:The expres-sion levels of PDK1 in lung normal epithelial cell line BEAS-2B and different lung cancer cell lines H 460, SPCA1 and A549 were determined by Western blot and real-time PCR.Small interfering RNA was used to down-regulated PDK1 ex-pression in the A549 cells,and then cell viability and apoptosis were measured by CCK-8 assay and flow cytometry,respec-tively.The expression of cell cycle-and apoptosis-related molecules at protein level and the activation of Akt /FoxO1 path-way were measured by Western blot.Insulin-like growth factor-1(IGF-1,one of the most potent Akt activators)was used to evaluate the interaction between PDK 1 and Akt/FoxO1 pathway.RESULTS:Compared with lung normal epithelial cell line BEAS-2B,PDK1 expression in the lung cancer cell lines was obviously increased(P<0.05).Knockdown of PDK1 suppressed cell viability and cell cycle,but promoted the apoptosis of the A 549 cells.The results of Western blot showed that the protein levels of cyclin D1,CDK4,p-Rb,Bcl-2,p-Akt and cytoplasmic p-FoxO1 were significantly decreased after knockdown of PDK1,with increases in the protein levels of P27, cleaved caspase-3 and nuclear FoxO1.Pre-incubation with IGF-1 partly reversed the effect of PDK1 knockdown on Akt/FoxO1 pathway and increased the viability of A 549 cells. CONCLUSION:In human non-small-cell lung cancer A549 cells,knockdown of PDK1 suppresses cell viability and pro-motes cell apoptosis by regulating the expression of cell cycle-and apoptosis-related molecules via Akt/FoxO1 pathway, suggesting that PDK1 may be a potential target for diagnosis and theatment of lung cancer.
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Objective Diabetes mellitus (DM) is often complicated by thyroid hormone abnormality. The aim of this study was to investigate the relationship between the thyroid hormone level and glycemic fluctuation in patients with euthyroid type 2 DM (T2DM).Methods A total of 143 euthyroid T2DM patients were treated in the Department of Endocrinology of Nanjing General Hospital from January 2014 to December 2015. The continuous blood glucose monitoring system was used for 72-hour continuous monitoring of blood glucose fluctuation indexes, including the standard deviation (SD) of the glucose level, the mean amplitude of glycemic excursions (MAGE), and the absolute mean of daily differences (MODD). According to the percentile of the MAGE level, the patients were divided into groups Q1 (MAGE<4.1864, n=35), Q2 (4.1864≤MAGE<5.3764, n=37), Q3 (5.3764≤MAGE<6.8484, n=35), and Q4 (MAGE≥6.8484, n=36), compared the thyroid hormone level and such thyroid function parameters as serum free triiodothyronine (FT3), triiodothyronine (T3), free thyroxine (FT4) and FT3/FT4 among the four groups, and analyzed the correlation between the thyroid hormone level and glycemic indexes.Results The levels of serum FT3, T3 and FT3/FT4 were decreased with the increase of MAGE (P<0.05), and those of FT3 and FT3/FT4 were 4.11±0.77 and 0.38±0.37 in group Q1, 4.06±0.55 and 0.34±0.37 in Q2, 3.49±0.57 and 0.33±0.06 in Q3, and 3.68±0.65 and 0.31±0.09 in Q4, with statistically significant differences between any two groups (P<0.05). There were also statistically significant differences among the four groups (P<0.05) in the T3 and FT4 levels (P<0.05). The levels of FT3 and T3 were correlated negatively with SD, MODD and MAGE (P<0.05), and so was that of FT3/FT4 with MAGE (r=-0.243, P<0.05).Conclusion MAGE reduces the levels of FT3 and FT3/FT4 in patients with euthyroid T2DM probably by inhibiting the conversion of T4 to T3.
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The present study aims to investigate the effects of Xuesaitong (XST)injection on inflammation induced by OGD/reoxygenation in BV2 microglia cell and explore the underlying mechanisms.The effects of XST injection were evaluated in terms of cell viability, secretion of TNF-α, IL-1β, IL-6 and IL-10 into culture media, protein expression of p-ERK1/2, p-JNK and p-p38, and nuclear translocation of NF-κB p65. The results showed that XST injection significantly increased cell viability, suppressed release of TNF-α, IL-1β, IL-6 and IL-10 and down-regulated p-JNK1/2 and p-p38 MAPK expression in BV2 microglia cells induced by OGD/R injury, whereas it had no effect on p-ERK1/2 expression. Furthermore, XST injection suppressed nuclear translocation of NF-κB p65 in BV2 microglia after OGD/R injury. These data indicate that the neuroprotective effects of XST injection on OGD/R injury are associated with its inhibition of pro-inflammatory mediator production, down-regulation of JNK1/2 and p38 MAPK activation, and suppression of NF-κB p65 nuclear translocation in BV2 microglia cells.
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Objective To design a data acquisition and monitoring system to facilitate the maintenance of the ventilator.Methods The system was composed of two modules of data acquisition and monitoring.The data acquisition module used MSP430F149 SCM as the master control chip to realize real-time acquisition and storage of operation data,and the monitoring module adopted STM32 SCM as the master control chip to implement equipment monitoring,server serial port conversion and data communication.Wireless data transmission between the two modules was executed with wireless NRF24L01 module.Results The system realized real-time acquisition and storage of the ventilator log,and transmitted acquired data to the server.Conclusion The system eliminates the deficiencies of manual operation and implements basic risk analysis,and facilitates the engineer to monitor and maintain the ventilator.
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Objective To investigate the effects of DL-3-n-Butylphthalide(NBP)on proliferation and apoptosis of 1-methyl-4-phenyl-pyridinium (MPP +)-induced SH-SY5Y cells, and mechanisms via mixed lineage kinase 3 (MLK3) signaling pathway. Methods The SH-SY5Y cells were divided into control group,MPP+group,NBP group and URMC-099 group,that cultured normally,with 1 mmol/L MPP+for 24 hours,with 10μmol/L NBP for 3 hours and then with MPP+for 24 hours,and with 200 nmol/L MLK3 inhibitor URMC-099 for 3 hours and then with MPP+for 24 hours,respectively.The morphology of SH-SY5Y cells was observed under inverted phase contrast mi-croscope and the survival rate was measured with 3-(4,5-Cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assays.The apoptosis was quantified under flow cytometry with Annexin V/PI fluorescence staining,and the nuclear morphology was observed with Hoechst 33342 staining.The expression of phosphorylated protein of MLK3(p-MLK3),c-Jun N-terminal kinase(p-JNK),extra cellular regulated protein ki-nases(p-ERK1/2)were detected with Western blotting.Results Compared with the control group,the survival rate reduced and apoptosis in-creased in MPP+group(P<0.05),with the increase of p-MLK3 and p-JNK and decrease of p-ERK1/2 d(P<0.05).Compared with MPP+group,the survival rate increased and apoptosis reduced in both NBP and URMC-099 groups(P<0.05),with the decrease of p-MLK3 and p-JNK and increase of p-ERK1/2(P<0.05).Conclusion NBP can decrease the apoptosis and promote the proliferation of SH-SY5Y cells in-duced by MPP+,which may be associated with inhibiting MLK3 signaling pathway,and regulating the downstream p-JNK and p-ERK1/2.
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Objective To design a data acquisition and monitoring system to facilitate the maintenance of the ventilator.Methods The system was composed of two modules of data acquisition and monitoring.The data acquisition module used MSP430F149 SCM as the master control chip to realize real-time acquisition and storage of operation data,and the monitoring module adopted STM32 SCM as the master control chip to implement equipment monitoring,server serial port conversion and data communication.Wireless data transmission between the two modules was executed with wireless NRF24L01 module.Results The system realized real-time acquisition and storage of the ventilator log,and transmitted acquired data to the server.Conclusion The system eliminates the deficiencies of manual operation and implements basic risk analysis,and facilitates the engineer to monitor and maintain the ventilator.
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Objective To analyze the quality of life status and its influencing factors of drug addicts with methadone maintenance treatment (MMT) in Wenzhou, in order to provide a basis for developing health service measures to improve their quality of life. Methods A total of 199 drug addicts with MMT in Wenzhou were investigated by the Quality of Life for Drug Addicts (QOL-DA) and Self-made questionnaire, influencing factors on quality of life were analyzed by multiple linear regression analysis. Results Most of 199 drug addicts with MMT were male, middle aged, local residents, lower educational level, and unemployed. Most of them used traditional drugs such as heroin by intravenous injection, and the proportion of who continually used drugs more than 10 years was 78.39%. The majority of them had abandoned drug habits many times. The proportions of abandoning drug habits more than 12 months this time and self-reported involving drug abuse related diseases were 77.39%, 61.81%, respectively. Scores of physical function and hunger sensory (PH), psychological spirit and self-esteem (PS), withdrawal syndrome and toxic effects (ST), social support and operational capability (SO) were 32.96±6.75, 33.03±5.96, 47.61±8.51 and 38.42±6.86, respectively. The total score of QOL-DA was 152.01±23.55. Marital status, occupation, age of first using drug, time of drug use and drug abuse related diseases were its influencing factors. Conclusion The quality of life of drug addicts with MMT is lower. Comprehensive health service measures for influencing factors should be taken to improve their quality of life.
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Ribavirin is a broad-spectrum antiviral agent and glycyrrhizin has activities of anti-inflammation, immunoregulation and anti-viral infections. To enhance antiviral efficacy and weaken side-effects of ribavirin, antiviral effects of the combination of glycyrrhizin and ribavirin were studied in the present study. Firstly, a mouse model of viral pneumonia was established by inoculation of influenza H1N1 virus. Protective effects of glycyrrhizin and ribavirin used alone or in combination against H1N1 virus infection in mice were evaluated based on the survival rate, lung index and virus titer in lungs of mice. Results showed that the combination of glycyrrhizin and ribavirin significantly inhibited the lung consolidation with a 36% inhibition ratio on the lung swell of infected mice. The combination of the two drugs exhibited synergetic effects on survival of infected mice. The combination of 50 mg · kg(-1) · d(-1) glycyrrhizin and 40 mg · kg(-1) · d(-1) ribavirin resulted a 100% protection for infected mice with a synergetic value of 36, which was significantly higher than the control group and each drug alone. This combination also resulted a significant drop of lung virus titer (P < 0.01), as well as inhibition on the production of proinflammatory cytokines IL-6 (P < 0.01), TNF-α (P < 0.01) and IL-1β (P < 0.05) induced by virus infection compared to the control. The treatment of ribavirin plus glycyrrhizin was more effective in influenza A infection in mice than either compound used alone, which suggested a potential clinical value of the combination of the two agents.
Subject(s)
Animals , Mice , Antiviral Agents , Pharmacology , Disease Models, Animal , Drug Synergism , Drug Therapy, Combination , Glycyrrhizic Acid , Pharmacology , Inflammation , Allergy and Immunology , Influenza A Virus, H1N1 Subtype , Interleukin-1beta , Allergy and Immunology , Interleukin-6 , Allergy and Immunology , Lung , Allergy and Immunology , Virology , Orthomyxoviridae Infections , Drug Therapy , Pneumonia, Viral , Drug Therapy , Ribavirin , Pharmacology , Tumor Necrosis Factor-alpha , Allergy and ImmunologyABSTRACT
Endophytic bacteria which was producing indoleacetic acid was screened from Panax ginseng by using the Salkowski method. The active strain was also tested for its ability of nitrogen fixation by using the Ashby agar plates, the PKV plates and quantitative analysis of Mo-Sb-Ascrobiology acid colorimetry was used to measure its ability of phosphate solubilization, for its ability of potassium solubilization the silicate medium and flame spectrophotometry was used, for its ability of producing siderophores the method detecting CAS was used, for its ability of producing ACC deaminase the Alpha ketone butyric acid method was applied. And the effect on promoting growth of seed by active strain was tested. The results showed that the indoleacetic acid producing strain of JJ5-2 was obtained from 118 endophytes, which the content of indoleacetic acid was 10.2 mg x L(-1). The JJ5-2 strain also had characteristics of phosphate and potassium solubilization, nitrogen fixation, producing siderophores traits, and the promoting germination of ginseng seeds. The JJ5-2 strain was identified as Bacillus thuringiensis by analyzing morphology, physiological and biochemical properties and 16S rRNA gene sequences.
Subject(s)
Bacteria , Metabolism , Endophytes , Metabolism , Indoleacetic Acids , Metabolism , Panax , MicrobiologyABSTRACT
Objective To investigate the etiology and risk factors of stroke in young adults from Southern Sichuan, China to provide a basis for prevention and treatment of stroke. Methods The data of 398 young patients with first-ever stroke (aged 18 to 44) admitted to department of Neurology, the Affiliated Hospital of Luzhou Medical College from 2009 to 2013 was retrospectively analyzed. Four hundred twenty-five cases of stroke (aged greater than or equal to 45) were re?cruited by stratified random sampling to analyze its causes and risk factors in the same period. Results ① Young stroke accounted for 6.09% of all hospitalized stroke patients in which 78.39% of young stroke was ischemic, 64.57%was male and 58.04% aged from 40 to 44. ② According to TOAST etiology classification group, the percentage of large-artery atherosclerosis, small-vessel, cardioembolism, other determined and undetermined reasons were 56.09%, 17.95%, 9.93%, 10.90% and 5.13% in young stroke, respectively. Compared with the elderly group, other determined and undetermined reasons were higher, and the small-vessel was lower in young stroke (P0.05).③ Risk factors analysis revealed that the constituent ratio of smoking (34.92%), hyper?lipidemia (31.41%), alcohol (20.10%), obesity (13.07%), rheumatic heart disease (6.03%) in youth group were higher whereas hypertension(66.12%), diabetes(20.47%)and coronary heart disease(10.82%)were lower in young stroke com?pared with the elderly group (P<0.05). Conclusion ①Large-artery atherosclerosis is the most common etiology of youth ischemic stroke. ② Hypertensive cerebral hemorrhage is the most frequent type in Hemorrhagic stroke. ③ Hyperten?sion, smoking and hyperlipidemia are the most common risk factors to stroke.
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<p><b>OBJECTIVE</b>To detect expression of Slit2 and Robo4 in mouse ventricular muscle blood vessel and explore the impact of exogenous Slit2 on proliferation and migrate of mouse cardiac microvascular endothelial cells.</p><p><b>METHODS</b>Slit2 and Robo4 expression in mouse ventricular muscle blood vessel was detected by immunohistochemistry. Slit2 and Robo4 expression in cardiac microvascular endothelial cells isolated from mouse ventricular muscle were detected by euzymelinked immunosorbent assay and immunofluorescence, respectively. The effects of various concentrations exogenous Slit2 on proliferation of mouse cardiac microvascular endothelial cells was examined by CCK-8 cell proliferation kit. Transwell chamber was used to detect migration of mouse cardiac microvascular endothelial cells treated with 800 µl M199 culture medium containing 20%FBS (negative control), 10 ng/ml VEGF(positive control), 100 ng/ml Slit2(Slit2) and 100 ng/ml Slit2+10 ng/ml VEGF (Slit2+VEGF) and incubated for 18 h at 37 °C and 5%CO(2).</p><p><b>RESULTS</b>Both Slit2 and Robo4 protein expressions were detected in ventricular muscle blood vessel. Slit2 protein expression was detected in mouse microvascular endothelial cells. Protein and mRNA Robo4 expressions were also evidenced in mouse microvascular endothelial cells. Proliferation of mouse cardiac microvascular endothelial cells was not affected by exogenous Slit2. Migration of mouse cardiac microvascular endothelial cells was not affected by exogenous Slit2 (22.1 ± 2.8 vs. 23.2 ± 3.8 in negative control, P > 0.05) and significantly enhanced by VEGF (65.3 ± 3.8, P < 0.05 vs. Slip2 and negative control), this effect could be blocked by cotreatment with Slip2 (29.2 ± 3.4 in Slip2+VEGF, P < 0.05 vs.</p><p><b>VEGF) CONCLUSION</b>Slit2 and Robo4 are expressed in mouse ventricular muscle blood vessels and cardiac microvascular endothelial cells. Exogenous Slit2 has no impact on the proliferation of mouse cardiac microvascular endothelial cells but could inhibit VEGF-induced mouse cardiac microvascular endothelial cell migration.</p>