Erectile dysfunction (ED), as a common male disease, seriously affects the patients' sexual life quality. Most ED patients benefit from phosphodiesterase type 5 (PDE5) inhibitors, but some refractory ED sufferers fail to respond to them. With the rapid development of molecular biology, the relevant molecular signaling pathways of penile erection and molecular pathogenesis of ED have been gradually clarified, and attempts have been made at a better management or a complete cure of ED with advanced molecular biological methods such as the gene therapy. This article presents an overview on the research progress in the molecular signaling pathways, molecular pathogenesis, and gene therapy of ED.
Biomedical Research ; Erectile Dysfunction ; genetics ; therapy ; Genetic Therapy ; Humans ; Male ; Penile Erection ; genetics ; Phosphodiesterase 5 Inhibitors ; therapeutic use ; Quality of Life ; Signal Transduction

OBJECTIVE: To study the influence of PD173074 on proliferation and apoptosis of nasopharyngeal carcinoma. METHOD: With immunoblotting and RT-PCR, FGFR1 expression was detected in CNE, PONE1 and C666-1 cell lines. With MTT assay,the time-effect and dose-effect correlation between PD173074 and inhibition of CNE proliferation was evaluated. After PD173074 stimulation, the phosphorylation level of FGFR1 and AKT was detected with immunoblotting assay. Furthermore, influence of PD173074 on the activation of Caspase3 and Caspase9 was detected to study the underlying mechanism of why PD173074 could inhibit CNE proliferation. RESULT: FGFR1 has the highest expression in CNE cell line. Under incubation of 10 nmol/L PD173074 stimulation for 36 hours to 72 hours, the phosphorylation of FGFR1 and AKT was impaired significantly, which further reduced the proliferation of CNE. Moreover, PD173074 can activate the intrinsic apoptotic pathway by stimulating Caspase9,which activated Caspase3 and induced the apoptosis. CONCLUSION PD173074 could inhibit proliferation of nasopharyngeal carcinoma cell through reducing the phosphorylation of FGFR1 and AKT. Additionally, PD173074 can induce CNE apoptosis by activating intrinsic apoptotic pathway via cleaving Caspase9 and Caspase3.
Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Carcinoma ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms ; drug therapy ; pathology ; Pyrimidines ; pharmacology

Objective To investigate the relationship between subclinical cervical HPV infection and recurrence of condyloma acuminatum (CA) in patients. Methods Cervical swabs were collected from 52 patients with frequently recurrent CA, 55 patients with infrequently recurrent CA, and 65 normal human controls. The Cenechip method was performed to detect the presence and type of HPV in cervical swabs followed by a statistical analysis. Results HPV was found in 67.3% (35/52) of swabs from patients with frequently recurrent CA, 5% (19/55) from patients with infrequently recurrent CA, and 4.6% (3/65) in the controls. There was a statistical difference among the three groups in the detection rate of HPV. Conclusion The subclinical cervical HPV infection may contribute to the recurrence of CA.

Objective To observe the expressions of vascular endothelial growth factor(VEGF) and cyclooxygenase-2(COX-2) in the cerebral tissue following hypoxic-ischemic encephalopathy(HIE) in newborn rats and explore the machanism of inosine in protecting against hypoxic-ischemic brain damage(HIBD).Methods Sixty-six newborn rats aged 7 days were divided into sham,control and experimental groups.HIE models were made by clamping the right cervical artery and making hypoxia for 2 hours.The rats in experimental group began injecting inosine,at 1 day before experiment,and the rats in the sham and control groups saline solution with same dose.The samples were made at the given time,and expressions of VEGF and COX-2 were investigated by immunohistochemical technique.Results The cerebral tissue had no expression of VEGF and COX-2 in sham group.From 2 hours on cortex and striatum after HIE in control and experimental groups,expressions of VEGF and COX-2 increased rapidly,peaking at 12-24 hours,and then decreased gradually.Expressions of VEGF and COX-2 were higher in experimental group(All P

Objective To observe the vasodilation effect of extract of Jasminum samba (EJs), a kind of traditional Chinese medicine, on ex vivo rat thoracic aortic rings, and to investigate its mechanism. Methods On ex vivo aortic ring perfusion device, influence of EJs on contraction of the aorta induced by phenylephrine (PE) or potassium chloride (KCl) was observed. Influence of N-nitro-L-arginine-methylester ( L-NAME ), barium chloride ( BaCl2 ), glibenclamide ( Gli ) on vasodilating effect of EJs (0. 5, 1, 2, 4, 8 g·L-1 ) was detected. Effect of EJs on the contraction of calcium chloride (CaCl2 ) and PE in Ca2+-free medium was detected. [ Ca2+ ] i in vascular smooth muscle cells was determined by using laser scanning confocal microscope (LSCM). Results In blood vessels with intact endothelium, EJs concentration-dependently decreased PE- or KCl-induced vasoconstriction, the maximum dilating effect being (105. 0±3. 2)% and (78. 0±6. 5)% , respectively; L-NAME affected the vasodilatory effect of EJs on thoracic aorta rings ( P<0. 01), the maximum dilatory effect being (58. 0 ± 6. 9)% . BaCl2 and Gli had significant influence on vasodilation of EJs, and the contraction was obviously attenuated (P<0. 01), the maximum dilatory effect being (37. 0±5. 2)% and (78. 0±10. 0)% , respectively. EJs significantly inhibited contracting effect of PE on thoracic aorta rings in Ca2+-free medium (P<0. 01). The maximum contraction effect was (70. 0±6. 3)% . EJs inhibited CaCl2-induced vasoconstriction (0. 5-8 mmol·L-1 ), and vasoconstriction was decreased by (65. 0±3. 2)% . LSCM recorded that Fmax / F0 of 4 and 8 g·L-1 EJs was (2. 0±0. 2) and (1. 5±0. 2), respectively. Conclusion EJs exerted a dose-dependent vasodilating effect on rat isolated aorta rings. The mechanism might be related to promoting NO release, activating K+channels and decreasing the concentration of cytoplasmic Ca2+.

Objective　To explore the development of endogenous CO and its mechanisms in asthma.Methods　50 guinea pigs were equally separated 5 groups.After the models of asthmatic guinea pigs were established in 4 groups,3 groups of them were treated with dexamethasone,the specific stimulator(hemin)and inhibitor(Sn-PP)of HO-1 respectively.The rest of groups were asthmatic one and normal control one(NCG).From all tested animals,the COHb in blood and lung HO-1 activity were examined,the lung tissues were pathologically observed and immunohistochemically stained.Results　In asthmatic and hemin stimulated groups,the levels of COHb with enhanced expression of lung HO-1 and their activity were significantly increased compared with NCG(t=4.43～9.97,P＜0.01).For example,the lung HO-1 activities in asthmatic group were (881±361)pmol/(mg*pro*h),COHb (4.94±2.15)% respectively.In dexamethason prevented and Sn-PP inhibited groups,however,all determined levels were markedly reduced compared with asthmatic group(P＜0.01).Conclusion　The increased HO-1 had resulted in the growth of endogenous CO in asthma.

Objective To report filaminopathy with novel insertion mutation in a Chinese family.Methods Total 19 patients from successive 5 generations involved in an autosomal dominant family. The detailed clinical manifestations had been described (Chinese Journal of Neurology, 2008, 41:751-755).The filamin C gene sequencing was performed in 3 patients, 5 family members without symptoms and 50 normal persons. The amplified fragments of the exon 18 in filamin C gene were cloned into pBluesripts vectors, then sequenced and identified with capillary electrophoresis. Results 18-nucleotide deletion and 6-nucleotide insertion were identified in the exon 18 of filamin C gene. The mutation caused the disturbance of the seventh immunoglobulin-like domain in filamin C, leading to the instability of dimmers of filamin C.Another 2 patients in the family had same mutation while 5 family members without symptoms and 50 normal controls were normal. Conclusion The novel nucleotide deletion-insertion in exon 18 of filamin C gene causes filaminopathy. This disease can appear in non-Nordic race.

Objective To study the protective effects of choline on myocardial ischemia rat heart and its potential mecha -nisms .Methods Ischemia hypoxia environment was simulated with low value of pH (pH 6 .8) and lack of oxygen .Calcium currents were recorded by whole cell patch under the voltage clamp configuration .The alternations in[Ca2 + ]induced by KCl was detected by laser scanning confocal microscope in ventricular myocytes ,then disccuss the effects of choline on calcium and calcium store in cells . Results The normalized peak currents of ICa-L in ventricular myocytes were larger in pH 6 .8 group than those in pH 7 .4 group , which can be attenuated by choline .The(Ca2 + )i induced by KCl in ventricular myocytes were significantly increased in pH 6 .8 Ty-rode solution and its increasing can be suppressed by choline .4-DAMP can inhibit the suppressing effect of choline .Conclusion The possible mechanism of M 3 receptor involved in the protection of ischemic myocardium by inhibiting myocardial cells in ICa-L ,in-hibiting intracellular calcium overload .

Objective To explore the relationship between the levels of leptin and leptin receptor in placental and intrauterine growth retardation.Methods Eighty seven newborns were studied .Auxological data(birth weight, length and biceps, triceps, subscapular and iliac skinfold thickness) were obtained and recorded.According to birth weight ,the subjects were divided into :the small for gestational age(SGA)group and the appropriate for gestational age (AGA) group.The levels of leptin and leptin receptor mRNA in 87 placental tissue were assayed by reverse transcription-polymerase chain reaction(RT-PCR).Results 1. The level of leptin receptor mRNA in placental was 0.894?0.291, which was positively related to the birth weight and body fat content (r=0.651,0.581,both P

Objective To investigate the association of gene polymorphism of methylenetetrahydrofolate reductase (MTHFR), and the level of homocysteine (Hcy) in patients with cerebral thrombosis in Chinese population Methods MTHFR genotype and allele frequency in 75 patients with cerebral thrombosis and 62 control subjects were measured by polymerase chain reaction and restriction fragment length polymorphism (PCR RFLP) Concentration of plasma Hcy was measured by reverse phase high performance liquid chromatography in a subgroup Results In patients and control subjects, the frequencies of T allele were 0 41 and 0 31, respectively The frequencies of CC, CT, TT genotype of cerebral thrombosis patients were 0 41, 0 35, 0 24, respectively Meanwhile those of the controls were 0 58, 0 23, 0 19 Neither the genotype ( P =0 137) nor the allele frequency ( P =0 067) was significantly different between patients and control subjects Furthermore, plasma Hcy level of the patients was (18 3?7 2) ?mol/L, which differed significantly from that of the controls, which was (13 6?5 8) ?mol/L ( P