Animals ; China ; Elapidae ; Humans ; Male ; Snake Bites ; Snake Venoms ; poisoning ; Young Adult

AIMTo study the pharmacokinetics of genistein at different doses in Beagle dogs.

METHODSSuspended in 0.5% CMC-Na solution, genistein was orally administered to Beagle dogs at doses of 2.67, 5.34 and 10.68 mg.kg(-1). At various time intervals, 1.5 mL of blood was drawn from the femoral vein of dogs in their front legs. The plasma was treated with beta-glucuronidase. The genistein in plasma was extracted twice by vortexing with 2.0 mL mixture of methyl tert-tubtyl ether and pentane (v/v = 8:2). The organic phase was removed into the tubes and then evaporated in ventilation cabinet. The residue was dissolved in 50 microL of methanol. 20 microL solution was drawn and detected by high-performance liquid chromatography. The pharmacokinetic parameters were calculated by 3P97 software.

RESULTSThe plasma drug concentration-time data were fitted to the two-compartment model. When the dose was 2.67 mg.kg(-1), the MRT and AUC of parent compound were 52.9 min and 6.7 mg.min. L(-1), respectively. When the dose rose to 5.34 mg.kg(-1), the MRT and AUC of parent compound became 224.8 min and 26.1 mg.min.L(-1), respectively. However, when the dose increased to 10.68 mg .kg(-1), the MRT and AUC of parent compound increased to 267.7 min and 33.2 mg.min L(-1), respectively. The AUC of glucuronidated genistein was 33.9, 70.1 and 140.5 mg.min.L(-1) at the dose of 2.67, 5.34 and 10.68 mg.kg(-1), respectively.

CONCLUSIONDue to significant first pass metabolism, the drug was mainly existed in the form of glucuronidated genistein in the plasma. With the increase of dose, the absorption of genistein became saturated and the half life prolonged.

Animals ; Anticarcinogenic Agents ; administration & dosage ; blood ; pharmacokinetics ; Area Under Curve ; Dogs ; Dose-Response Relationship, Drug ; Female ; Genistein ; administration & dosage ; blood ; pharmacokinetics ; Glucuronides ; blood ; pharmacokinetics ; Male

We predicted the anti-hepatitis B virus (HBV) active components and mechanism of Salvia miltiorrhiza based on network pharmacology. The active components of S. miltiorrhiza were obtained through TCMSP, PubChem database and literature research. The potential targets of the active components and HBV infection were predicted by SwissTargetPrediction and GeneCards databases, respectively. The protein-protein interaction (PPI) network was constructed by String database. Cytoscape software was adopted to construct a visual network of active component-disease target and perform topological analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using DAVID platform. The molecular docking of key components and core targets was carried out by AutoDock Vina software. We screened out a total of 38 active components and 178 disease-component overlapping targets. Enrichment analyses obtained 405 related GO items and 68 signaling pathways, such as T/B cell receptor signaling pathways, PI3K/AKT signaling pathway, and mTOR signaling pathway. According to the results of molecular docking, most characteristic components of S. miltiorrhiza (miltionone Ⅱ, miltirone, protocatechuic acid, lithospermic acid, protocatechualdehyde) showed good affinity with the key targets (PIK3CA, APP, STAT3,AKT1 and mTOR). Furthermore, the anti-HBV activity of lithospermic acid, the representative active component of S. miltiorrhiza, and its regulation on PI3K/AKT and mTOR signaling pathways were investigated in an HBV replicating mouse model. Animal welfare and experimental procedures follow the regulations of the Animal Ethics and Welfare Committee of Hubei University. The results showed that lithospermic acid significantly inhibited HBV DNA replication, reduced serum HBsAg and HBeAg levels, and decreased the phosphorylation protein expression levels of AKT and mTOR in liver, indicating that lithospermic acid might exert the anti-HBV activity by regulating PI3K/AKT and mTOR signaling pathways.

Objective To know the requirement of medication safety of patients during hospital stay, to direct the clinical nursing work, and to provide the scientific basis for clinical service. Methods The requirements of medication safety of 103 inpatients were surveyed through the convenience sampling method and using a self-designed questionnaire. The surveyed contents included 12 aspects such as the name of medicine, pharmacological effect and storage method, and so on. Results The inpatients hoped to know the knowledge of safety medication, especially paying attention to the special medication method (86.9%), the pharmacological effect (84.6%), the adverse effect of medicine (82.3%) and the factors influencing the effect of medicine (83.8%). There were statistical meanings in the 12 aspects among the patients with different education levels (P<0.05). There were statistical meanings in the period of medicine validity and pharmacological effect among patients with different gender. There were statistical meanings in the period of medicine validity among patients with different ages and patients without past medical history. Whether the patients took the medicine or not had statistical meaning in the period of medicine treatment. Conclusions To know the requirement of medication safety of inpatients can help the nurses adopt the corresponding measures and provide the pertinent nursing service to patients, thereby improving the quality of nursing service.

Aim To evaluate the effects of salvianolic acid B ( Sal B ) on bone metabolism and its potential mechanism in high fat diet ( HFD) mice.Methods Thirty C57BL/6J male mice were divided into three groups with 10 mice each, namely normal , HFD and HFD+Sal B.HFD and HFD+Sal B mice were treated with HFD, and HFD+Sal B group mice were also with Sal B (125 mg· kg -1· d-1).After 12 weeks' treat-ment, femurs were harvested .The effects of Sal B on biomechanical strength were evaluated by biomechani-cal tests, and the effects of Sal B on bone microstruc-ture were evaluated by Safranin O/fast green staining and hematoxylin and eosin staining .The expression of nuclear factor-kappa B ( NF-κB)-p65 and NADPH ox-idase 4 ( Nox4 ) and cathepsin K in femurs was deter-mined by immunohistochemical staining . Results Maximum load and elastic load significantly decreased ,and the trabeculae became thinner and irregular in the femurs of HFD mice , while Sal B treatment could re-verse the descending biomechanical strength and the disorganized femurs bone micro-structures in HFD mice.In addition, the expressions of Nox4, NF-κB-p65 and cathepsin Kmarkedly increased in HFD mice , and Sal B possessed the ability to down-regulate the ex-pression of Nox4, NF-κB-p65, and cathepsin K in the femurs triggered by HFD .Conclusions Sal B treat-ment improves bone metabolism via regulating Nox 4/NF-κB/cathepsin K signaling pathway in HFD mice . The findings contribute to the understanding and exten-sion of the applications of Salvia miltiorrhiza and its constituents on osteoporosis .

Our previous results have demonstrated that insulin reduces myocardial ischemia/reperfusion (MI/R) injury and increases the postischemic myocardial functions via activating the cellular survival signaling, i.e., phosphatidylinositol 3-kinase (PI3-K)-Akt-endothelial nitric oxide synthase (eNOS)-nitric oxide (NO) cascade. However, it remains largely controversial whether c-Jun NH2-terminal kinase (JNK) is involved in the effects of insulin on MI/R injury. Therefore, the aims of the present study were to investigate the role of JNK, especially the cross-talk between JNK and previously expatiated Akt signaling, in the protective effect of insulin on I/R myocardium. Isolated hearts from adult Sprague-Dawley rats were subjected to 30 min of regional ischemia and followed by 2 or 4 h of reperfusion (n=6). The hearts were pretreated with PI3-K inhibitor LY294002, or phosphorylated-JNK inhibitor SP600125, respectively, then perfused retrogradely with insulin, and the mechanical functions of hearts, including the heart rate (HR), left ventricular developed pressure (LVDP) and instantaneous first derivation of left ventricular pressure (+/-LVdp/dt(max)) were measured. At the end of reperfusion, the infarct size (IS) and apoptotic index (AI) were examined. MI/R caused significant cardiac dysfunction and myocardial apoptosis (strong TUNEL-positive staining). Compared with the control group, insulin treatment in MI/R rats exerted protective effects as evidenced by reduced myocardial IS [(28.9 +/- 2.0)% vs (45.0 +/- 4.0) %, n=6, P<0.01], inhibited cardiomyocyte apoptosis [decreased AI: (16.0 +/- 0.7) % vs (27.6 +/- 1.3) %, n=6, P<0.01] and improved recovery of cardiac systolic/diastolic function (including LVDP and +/-LVdp/dt(max)) at the end of reperfusion. Moreover, insulin resulted in 1.7-fold and 1.5-fold increases in Akt and JNK phosphorylation in I/R myocardium, respectively (n=6, P<0.05). Inhibition of Akt activation with LY294002 abolished, and inhibition of JNK activation with SP600125 enhanced the cardioprotection by insulin, respectively. And the abolishment by LY294002 could be partly converted by SP600125 pretreatment. In addition, SP600125 also decreased the Akt phosphorylation (n=6, P<0.05). These results demonstrate that insulin simultaneously activates both Akt and JNK, and the latter further increases the phosphorylation of Akt which attenuates MI/R injury and improves heart function; this cross-talk between Akt and JNK in the insulin signaling is involved in insulin-induced cardioprotective effect.
Animals ; Apoptosis ; Heart ; Insulin ; metabolism ; JNK Mitogen-Activated Protein Kinases ; MAP Kinase Signaling System ; Myocardial Infarction ; Myocardial Ischemia ; Myocardial Reperfusion Injury ; Myocardium ; Myocytes, Cardiac ; Nitric Oxide Synthase Type III ; Phosphatidylinositol 3-Kinase ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-akt ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; Signal Transduction

Objective To observe effects on fumigation with Chinese medicine treatment of cervical 9 step in cervical spondylosis patients. Methods 136 patients were randomly divided into 56 cases in the observation group and 80 cases in control group. The control group was treated with conventional methods, the observation group on this basis with fumigation with Chinese medicine treatment of cervical 9 steps. After three treatments periods, the effects between the two groups were compared. Results The efficacy rate in observation and control group were 93.75% and 78.57% respectively and the difference has reached the statistical significance (u = 8. 658 ,P < 0. 05) ; Three months after treatment, The efficacy rate in observation and control group were 91.25% and 76.78% respectively and the observation group was better than control group ( u =7. 232,P < 0. 05 ). Conclusions Fumigation with Chinese medicine treatment of cervical 9 step in cervical Spendylosis was an effective method.

OBJECTIVE: To compare the correlation between musculoskeletal ultrasound features, dysfunction and X-ray findings in patients with knee osteoarthritis, and to analyze the pathological mechanism of soft tissue inflammation in knee osteoarthritis. METHODS: Cross-sectional method was performed in this research (Evidence level: III). The patients with knee osteoarthritis were collected according to the screening criteria from September 2016 to January 2017 in Orthopedic clinic in our hospital. Musculoskeletal ultrasound and X-ray images were obtained and measured, knee function was measured by Lysholm scale. Pearson coefficient, t test and Wilcoxon were applied to analyze the correlation between soft tissue inflammation, knee dysfunction and X-ray features. RESULTS: Total 123 patients with knee osteoarthritis were recruited in this research. Soft tissue inflammation around knee had a high incidence in patients with knee osteoarthritis (infrapatellar fat pad inflammation 81%), and the synovial membrane thickness, joint effusion depth and meniscus bulging were beyond the normal range. Correlation analysis showed that the about Lysholm score and joint effusion depth had negative correlations with "Squat" score(=-0.21, =0.02). and Medial meniscus bulging had negative correlations with "Sustain" score(=-0.26, <0.01) and Lysholm total score (=-0.19, =0.04). Lateral meniscus bulging had a negative correlation with "Unstable" score (=-0.22, =0.02). The X-ray features, and medial joint space narrow had negative correlations with joint effusion depth(=-0.27, <0.01) and synovial membrane thickness(=-0.17, =0.007), and had a positive correlation with medial meniscus bulging. Medial joint space narrow was significantly correlated with patellar ligament inflammation and fat pad inflammation(<0.05). Lateral joint space narrow was significantly correlated with patellar ligament inflammation(=0.02). CONCLUSIONS Soft tissue inflammation around the knee-a major pathological manifestation of knee osteoarthritis, has significant correlations with knee dysfunction and bony structure lesions, and affects the progression of knee osteoarthritis by damaging knee joint function and promoting the destruction of articular cartilage.
Cartilage, Articular ; Cross-Sectional Studies ; Humans ; Knee Joint ; Menisci, Tibial ; Osteoarthritis, Knee

OBJECTIVETo investigate expression features and correlation of genes expression on MyD88-dependent signaling pathway in synovial membrane (SM) of progression of knee osteoarthritis (OA).

METHODSSixty Wistar rats were randomly divided into 6 groups, including blank group (N), false surgical group, model groups[2 weeks (2W), 4 weeks (4W), 8 weeks (8W) and 12 weeks (12W)], with 10 rats in each group. The models were established by using Hulth method. Control group was experienced no surgery, while false surgical group was only opened joint cavity and sutured. The SM samples was collected according to the time designed above. The relative expression quantity of MyD88, TLR4 and NF-κB was detected by Real-time PCR after the extraction of the total RNA and reverse transcription. The correlation analysis was obtained by SPSS.

RESULTSThere was no significant difference in each gene mRNA expression between false surgical and blank group(> 0.05), while enhanced expression was found in the model groups(<0.05). The correlation index among MyD88, TLR4 and NF-κB was 0.91 and 0.86 respectively, and had significant difference among them.

CONCLUSIONSPositively relative among MyD88, TLR4 and NF-κB played main role in TLR4/NF-κB signal passway, and could predicate the expression of other genes in the passway. It also could further provide the basis for clarify the pathologic mechanism of knee OA.