Abnormal cell signal transduction is associated with the occurrence and development of human diseases. Some virus pathogenicity and infection mechanism are due to virus antigen protein acting on the host cell signal transduction pathway, leading to host cell signal transduction disorder. Hepatitis C virus (HCV) is a major pathogen of chronic hepatitis C, which causes cirrhosis and hepatocellular carcinoma. But the pathogenesis of HCV and persistent infection mechanism remain far from clear. HCV pathogenesis may be related to the HCV protein expression interfering host cell signal transduction pathways. The studies of hepatitis C virus proteins acting on host cell signal transduction pathways, not only help to clarify the impact of its pathogenic mechanisms, but also benefit to new drug design and development for new treatment methods. This article summarizes the recent progress in research on the effect of hepatitis C virus protein in cell signal transduction pathways in the past few years.

The Sonic hedgehog (SHH) signaling pathway plays a pivotal role in neurogenesis and brain damage repair. Our previous work demonstrated that the SHH signaling pathway was involved in the neuroprotection of cortical neurons against oxidative stress. The present study was aimed to further examine the underlying mechanism. The cortical neurons were obtained from one-day old Sprague-Dawley neonate rats. Hydrogen peroxide (H(2)O(2), 100 μmol/L) was used to treat neurons for 24 h to induce oxidative stress. Exogenous SHH (3 μg/mL) was employed to activate the SHH pathway, and cyclopamine (20 μmol/L), a specific SHH signal inhibitor, to block SHH pathway. LY294002 (20 μmol/L) were used to pre-treat the neurons 30 min before H(2)O(2) treatment and selectively inhibit the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. The cell viability was measured by MTT and apoptosis rate by flow cytometry analysis. The expression of p38, p-p38, ERK, p-ERK, Akt, p-Akt, Bcl-2, and Bax in neurons was detected by immunoblotting. The results showed that as compared with H(2)O(2) treatment, exogenous SHH could increase the expression of p-Akt by 20% and decrease the expression of p-ERK by 33%. SHH exerted no significant effect on p38 mitogen-activated protein kinase (p38 MAPK) pathway. Blockade of PI3K/Akt pathway by LY294002 decreased the cell viability by 17% and increased the cell apoptosis rate by 2-fold. LY294002 treatment could up-regulate the expression of the pro-apoptotic gene Bax by 12% and down-regulate the expression of the anti-apoptotic gene Bcl-2 by 54%. In conclusion, SHH pathway may activate PI3K/Akt pathway and inhibit the activation of the ERK pathway in neurons under oxidative stress. The PI3K/Akt pathway plays a key role in the neuroprotection of SHH. SHH/PI3K/Bcl-2 pathway may be implicated in the protection of neurons against H(2)O(2)-induced apoptosis.

0.05).Coincidence both of them in subtypes of ADHD diagnosed by 2 different ways were lower than 50% in the 6.0-6.9 and over 10.0 years old groups,but coincidence both of them were higher than 60% in 7.0-7.9,8.0-8.9,9.0-9.9 years old groups.What's more,there were significant differences though ?2 variance analysis in subtypes of ADHD by 2 different ways(Pa

Objective To isolate and identify the potential binding partners of LRRK2,a gene linked to both dominant familial form and sporadic form of Parkinson's disease,thus to further our knowledge of its function.Methods We used a sequence containing full-length of COR domain and part of ROC and MAPKKK domain as bait.The bait amplified by polymerase chain reaction(PCR) was then cloned into a yeast expression plasmid pGBKT7.After being sequenced and analyzed,pGBKT7-bait was transformed into the yeast strain AH109.Western blot was performed to confirm the expression of pGBKT7-bait in AH109 yeast strain.Then human fetal brain cDNA library was trarnsformed into that yeast strain.which could express pGBKT7-bait fusion protein.The yeast strain which contained pGBKT7-bait and human fetal brain cDNA library was plated on quadruple dropout medium (SD/-Trp/-Leu/-His/-Ade)containing X-a-gal.We retested these positive colonies using 2 independent yeast strains AH109 contained pGBKT7-bait or pGBKT7,respectively.At last,these plasmids isolated from these true positive colonies were analyzed by bioinformatics.Results We obtained 9 true positive colonies,these colonies were sequenced, and we performed sequence Blast in GenBank.Three colonies of the 9 positive colonies were not in open reading-frames.Among other 6 colonies,there were known proteins including spermatid perinuclear RNA-binding protein(STRBP)and BCL2-associated athanogene 5 isoform b(BAG5),as well as unknown proteins including tyrosine phosphatase non-receptor type(PTPN23),1(3)mbt-like 3 isoform b(L3 MBTL3),RALY RNA binding protein-like isoform 1(RALYL),and Homo sapiens mRNA for KIAA1783 protein,partial cds(KIAA 1783).Conclusion True positive colonies of LRRK2 are successfully obtained by the yeast 2-hybrid.Our screened proteins may provide a new research clue for revealing biological functions of LRRK2,pathogenesis of Parkinson's disease,and other neurodegerations.

Objective To evaluate the clinical efficacy and safty of le-vocarnitine combined with alprostadil in the treatment of diabetic ne-phropathy.Methods A total of 68 patients with diabetic nephropathy were randomly divided into control group ( n=34 ) and treatment group (n=34).Control group was given alprostadil 1 mL, qd by intravenous drip.Treatment group was received levocarnitine 1 g, qd by intravenous drip on the basis of control group .The course of two groups was 28 d. The clinical efficacy , biochemical indexes before and after treatment and the incidence of adverse drug reactions were compared between two groups.Results After treatment , the total effective rate of control group was significantly lower than that of treatment group ( 67.65% vs 94.12%, P<0.05).After treatment, the levels of serum 24 h urinary protein , urinary microglobulin , urea nitrogen , cystatin C , homocysteine , glycosylated hemoglobin , transforming growth factor -β1 ,Ⅳcollagen in two groups were significantly decreased ( P<0.05 ) , and those indexes of treatment group after treatment were significantly lower than those of control group (P<0.05).After treatment, the levels of serum of serum creatinine , 25 -hydroxy vitamin D 3 in two groups were decreased with significant difference ( P <0.05 ) , and the treatment group was more obvious ( P<0.05 ).The incidence of adverse drug reactions in control group was significantly higher than that in treat -ment group (23.53%vs 8.82%,P<0.05 ) .Conclusion Levocarnitine combined with alprostadil have a definitive clinical efficacy and safety for the treatment of diabetic nephropathy .

OBJECTIVESome research has shown that there may be memory/caution (M/C) defects in children with primary nocturnal enuresis (PNE). This study aimed to investigate whether the defects affect the intelligence level and the intelligence structure in PNE children.

METHODSIntelligence tests were performed by means of Wechsler Young Children Scales of Intelligence (C-WISC) in 40 children with PNE and 40 age-matched normal children.

RESULTSThe full intelligence quotient (FIQ), verbal IQ (VIQ) and performances IQ (PIQ) in the PNE group were in a normal range and did not different from the control group. There were significant differences in the scores for digit extent, decipher, knowledge and arithmetics between the PNE and the control groups (P < 0.05). M/C factor in the PNE group was statistically lower than in the control group (93.44 +/-11.27 vs 100.03 +/-11.79; P < 0.05).

CONCLUSIONSThe total intelligence level of children with PNE was normal, but the M/C factor in the intelligence structure had some defects, suggesting that PNE may be related to the abnormity of executive function in the frontal lobe.

Adolescent ; Attention Deficit Disorder with Hyperactivity ; psychology ; Child ; Female ; Humans ; Intelligence ; Male ; Nocturnal Enuresis ; psychology

Adolescent ; Anti-Glomerular Basement Membrane Disease ; pathology ; Diagnosis, Differential ; Granulomatosis with Polyangiitis ; pathology ; Humans ; Kidney ; pathology ; Lung ; pathology ; Lupus Erythematosus, Systemic ; pathology ; Male

Fourteen compounds were isolated from Dalbergia odoriferae and purified by repeated column chromatography on silica and sephadex LH-20 gel and structurally identified by spectral analysis. These compounds were identified as 4, 9-dimethoxy-3-hydroxypterocarpan (1), medicarpin (2), 2', 4', 5-trihydroxy-7-methoxyisoflavone (3), 2', 3', 7-trihydroxy-4'-methoxyisoflavan (4), formononetin (5), 3, 8-dihydroxy-9-methoxypterocarpan (6), koparin (7), 3-hydroxy-9-methoxypterocarp-6a-ene (8), 2'-hydroxyformononetin (9), stevenin (10), 2', 7-dihydroxy-4', 5'-dimethoxyisoflavone (11), lyoniresinol (12), 2, 4-dihydroxy-5-methoxy-benzophenone (13) and neokhriol A (14). Compounds 1, 3, 4, 6, 8, 12 and 14 were isolated from this plant for the first time. Antibacterial activity assay showed that compound 4 had inhibitory effect on Ralstonia solanacearum.
Anisoles ; chemistry ; isolation & purification ; pharmacology ; Anti-Bacterial Agents ; chemistry ; isolation & purification ; pharmacology ; Benzophenones ; chemistry ; isolation & purification ; pharmacology ; Chromatography ; methods ; Dalbergia ; chemistry ; Dextrans ; Gels ; Isoflavones ; chemistry ; isolation & purification ; pharmacology ; Microbial Sensitivity Tests ; Naphthalenes ; chemistry ; isolation & purification ; pharmacology ; Plant Extracts ; chemistry ; isolation & purification ; pharmacology ; Pterocarpans ; chemistry ; isolation & purification ; pharmacology ; Ralstonia solanacearum ; drug effects ; growth & development ; Silica Gel

Objective To study and observe the effects of cold knife excision by hysteroscopy for the local microcirculation and inflammatory reaction of patients with hysteromyoma.Methods 86 patients with hysteromyoma admitted in our hospital from March 2016 to July 2017 were selected as the research objects,and the patients were divided into control group with 43 cases and observation group with 43 cases according to the method of random number table.The control group were treated with monopolar electric knife excision by hysteroscopy,while the observation group treated with cold knife excision by hysteroscopy.Then the local microcirculation and inflammatory reaction indexes of two groups at different time before and after the operation were detected.Results The local microcirculation and inflammatory reaction indexes of two groups before the operation were compare,no significant differences found (P＞0.05);the local microcirculation indexes of observation group after the operation were significantly better than those of the control group,the inflammatory reaction indexes were significantly lower than those of the control group,both with statistical significance (P＜0.05) .Conclusion The cold knife excision by hysteroscopy has better clinical effects in the control of local microcirculation and inflammatory reaction in patients with hysteromyoma,so it has higher application value in the patients with hysteromyoma.

OBJECTIVEMethylphenidate is recommended as a first-line modality for treating attention deficit hyperactivity disorder (ADHD). In the past, immediate release methylphenidate (IR-MPH) was used for ADHD. Now oral osmotic-methylphenidate (OROS-MPH) is used for ADHD in China. This study was designed to investigate the efficacy and safety of OROS-MPH for treatment of ADHD in children.

METHODSNinety-nine children with ADHD were randomly administered with OROS-MPH (18 mg/time, once daily) and IR-MPH (5 mg/ time, twice or three times per day). After 6 weeks of treatment, the therapeutic effects were evaluated by the SNAP-IV and the IVA-CPT.

RESULTSFifty patients completed the 6-week treatment. The effective rate (83.3% vs 75%) and the complete remission rate (44% vs 25%) in the OROS-MPH treatment group were higher than that in the IR-MPH treatment group. There were statistically significant differences in the SNAP-IV and IVA-CPT scores before and after treatment in the two groups (P<0.01). The two groups had a similar incidence of side effects during treatment.

CONCLUSIONSOROS-MPH for the treatment of ADHD is effective and safe in children, and its once-daily administration is more convenient.

Administration, Oral ; Adolescent ; Attention Deficit Disorder with Hyperactivity ; drug therapy ; Child ; Female ; Humans ; Male ; Methylphenidate ; administration & dosage ; adverse effects