Objective To investigate the expression of phosphodiesterase 5 (PDE5) in clitoral corpus cavernosum and effect of icariin on cyclic GMP (cGMP) levels in vitro. Methods The presence of mRNA coding for PDE5 in clitoral corpus cavernosum was detected by means of RT PCR analysis.The effect of icariin with various concentrations on cGMP levels,which is the target of PDE5 in vivo,was measured by 125 I radioimmunoassay with sildenafil as positive control. EC 50 of icarrin and sildenafil was calculated. Results There was a lane around 800 bp on the agar electrophoresis of the production of RT PCR,which was as long as we designed according to cDNA sequence of PDE5.In the presence of SNP,icariin increased cGMP concentrations in rabbit clitoral corpus cavernosum with increasing dose. Conclusions The results support the proposal that icariin may influence cGMP level by NO cGMP signaling pathway as an inhibitor of PDE5.

Adolescent ; Child ; Child, Preschool ; Female ; Fructose ; analogs & derivatives ; therapeutic use ; Humans ; Infant ; Male ; Tourette Syndrome ; drug therapy

ObjectiveTo study the mechanism of differentiation of mesenchymal stem cells(MSCs) into neuron-like cells in vitro.MethodsMSCs of Wistar rats were separated and cultured, and then induced with DMSO and BHA in vitro. The specific marking proteins of neurons, glia and neural stem cells were detected before preinduction, at 24h after preinduction, at 6h, 24h, and 48h after neuronal induction.ResultsAfter the inducement, many MSCs turned into bipolar,multipolar and taper,and then intersected as network structure. Nestin was strong positive at 6h after neuronal induction, and decreased at 24h, 48h after the induction. NeuN was present at 6 h after neuronal induction, and increased at 24h, 48h after the induction.ConclusionMSCs can be induced into neural stem cells(NSCs) at first, and then differentiate into neuron-like cells in vitro.

Identification and validation of a new target is one of the most important steps for new antituberculosis (TB) drug discovery. Researches have shown that Mycobacterium tuberculosis (Mtb) encodes 20 CYP450 enzymes which play important roles in the synthesis and metabolism of lipid, cholesterol utilization, and the electron transport of respiratory chain in Mtb. With the critical roles within the organism as well as the protein structures of six Mtb CYP450 enzymes being clarified, some of them have been highlighted as potential anti-tuberculosis targets. In this paper, the phylogenetic analysis, the structural features, and the enzymatic functions of Mtb CYPs, as well as the mechanism of interactions with selective inhibitors such as azole antifungal agents for the CYPs have been reviewed and summarized. The druggability of the CYPs has also been analyzed for their further utility as targets in high throughput screening and rational design of more selective inhibitors.
Antitubercular Agents ; chemistry ; pharmacology ; Azoles ; chemistry ; pharmacology ; Cytochrome P-450 Enzyme Inhibitors ; chemistry ; pharmacology ; Cytochrome P-450 Enzyme System ; genetics ; metabolism ; Drug Delivery Systems ; methods ; Drug Discovery ; Humans ; Mycobacterium tuberculosis ; drug effects ; enzymology ; genetics ; Phylogeny ; Tuberculosis ; drug therapy ; microbiology

BACKGROUND:Meta-analysis results have shown that Duhuojisheng Decoction can improve the symptoms and relieve the pain of patients with knee osteoarthritis, but the mechanism and pathway are not very clear.OBJECTIVE:To further verify the curative effect of Duhuojisheng Decoction for primary knee osteoarthritis in macaca fascicularis. METHODS: Under natural conditions, 6 clean young macaca fascicularis (aged 3-5 years, normal group) and 6 elderly macaca fascicularis (aged more than 20 years, model group) were selected from 24 macaca fascicularis. The models of primary knee osteoarthritis were established in the model group,then aged animals were randomly divided into control and intervention(given the treatment of Duhuojisheng Decoction) groups. The number of whole blood leukocytes, C-reactive protein, erythrocyte sedimentation rate, properties of the joint fluid and expression level of tumor necrosis factor-α were compared between the control and intervention groups. RESULTS AND CONCLUSION: The aged macaca fascicularis was characterized by a typical osteoarthritis similar to human. Treatment with Duhuojisheng Decoction significantly down-regulated the expression level of tumor necrosis factor-α and significantly reduced the levels of whole blood leukocytes, and C-reactive protein. Our results suggest that the aged macaca fascicularis model of primary knee osteoarthritis is an effective animal model to simulate the occurrence and development of human primary knee osteoarthritis.Duhuojisheng decoction alleviates the progression of primary knee osteoarthritis probably by inhibiting the expression level of tumor necrosis factor-α and decreasing the levels of inflammatory factors in the articular cartilage. Additionally, the levels of whole blood leukocytes and C-reactive protein are important parameters for the prediction of curative effects.

AIM To investigate the effect of Icarrin on penile erection and cyclic GMP levels in rabbit corpus cavernosum(RCC). METHODS Effects of various concentration of Icariin on cGMP level in RCC were measured by 125 I radioimmunoassay procedure with Sildenafil and papaverine as the positive controls RESULTS In the presence of SNP, Icariin increased cGMP concentration in rabbit corpus cavernosum in a dose dependent manner ( P

0.05).Conclusion Febrile seizures seldomly cause severe neurological damage.

Zanthoxyli Radix is a traditional Chinese medicine. It can be used for the treatment of wind-cold-dampness arthralgia, muscle and bone pain, fall fracture, hernia, sore throat, toothache and other diseases. Due to possessing many excellent and mild pharmacological properties, there are lots of reports about Zanthoxyli Radix worldwide. At present, more than 100 bioactive components have been extracted and purified from Zanthoxyli Radix. Nitidine chloride (NC), one of the most important alkaloids in Zanthoxyli Radix, has the activities of anti-tumor, anti-inflammation, anti-bacteria, etc. In this review, we summarize the chemical components of Zanthoxyli Radix, pharmacological activity and mechanism of action of NC to provide references for further research and utilization of Zanthoxyli Radix.

Objective To improve the level of early detection and treatment of pyonephrosis. Methods This study included 41 cases(17 men and 24 women;mean age,49 years)of pyonephrosis.A variety of examinations,including urinary analysis,blood analysis,kidney nuclear medicine scan,ultrasonog- raphy,intravenous urography(IVU),and CT were used for the early diagnosis of pyonephrosis.Pereutaneous nephrostomy(PCN)drainage was done for the interim management of pyonephrosis,then phase 2 operation was performed in 28 cases.The double-J tube was placed in ureter by ureteroscope for drainage,and then phase 2 operation was done in 2 cases.Emergency operation was done in 10 cases.The remaining 1 case un- derwent ESWL after anti-infective therapy.Results Definite diagnosis of pyonephrosis before operation was made by invasive examinations in 31 cases(75.6%),and by percutaneous drainage in 4 cases;the other 6 cases were detected during operation.Only 6 cases(14.6%)underwent nephrectomy;the other 35 cases (85.4%)underwent kidney-sparing operation.Follow-up of 3 months to 9 years was available in 37 cases. No nephrectomy was needed in 33 cases with spared kidney.Serum creatinine was normal in the 4 cases un- dergoing nephrectomy.Conclusions The key to the treatment of pyonephrosis by kidney-sparing surgery is early diagnosis,timely drainage and relief of obstruction.Ultrasonography plays an important role in the early diagnosis of pyonephrosis,and CT has a high sensibility in the diagnosis.Pereutaneons nephrolithotomy (PCNL)secondary to drainage through pereutaneous nephrostomy was beneficial to the patients with kidney stones or upper ureter stones.

Placentation,which is critical for maternal-fetal exchange of nutrients and gases,is a complicated process comprising stepwise vasculogenesis and angiogenesis.Hypoxia caused by impairedtrophoblast invasion may cause various angiogenic abnormalities in human placenta.The Notchl signaling pathway plays an important role in the regulation of angiogenesis.The angiogenesis of human umbilical vein endothelial cells (HUVECs) under normal/hypoxic conditions and the mRNA/protein level of Notchl/Dell4/Jaggedl were investigated in this study.The effects of DAPT/JAG-1 on the migration of HUVECs were also assessed by cell wound healing assay,so as to discover the possible role of notchl signaling pathway in the angiogenesis of human placenta.The results showed that angiogenic ability of HUVECs was seriously reduced under hypoxic conditions.The mRNA and protein levels of Notchl/Dell4/Jaggedl were decreased in the hypoxic group compared to the control one.In addition,the migration capability of HUVECs was significantly obstructed when treated with DAPT and under hopoxic condition,but promoted when treated with JAG-1.The above results demonstrate that hypoxia downregulates the angiogenesis in human placenta via Notch 1 signaling pathway.