ABSTRACT
The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.
ABSTRACT
Sodium-glucose linked transporter 2 inhibitors（SGLT2i） are novel oral hypoglycaemic agents and are widely used for hypoglycemic therapy in patients with type 2 diabetes mellitus， but differences in the genetic backgrounds of patients often lead to variable responsiveness to drug therapy. By summarizing the pharmacogenomic studies of SGLT2i， the article found that the genetic variants of UGT1A9， UGT2B4， SLC5A2， ABCB1， PNPLA3 and WFS1 may influence the pharmacokinetics of SGLT2i and the external hypoglycemic effects of SGLT2i in improving non-alcoholic fatty liver disease， weight loss and so on， but there is no clinical evidence that genetic polymorphisms affect the hypoglycemic efficacy of SGLT2i.
ABSTRACT
OBJECTIVE:To investigate the effects of NOS1AP rs12742393 A/C gene polymorphism on lipid-regulating re-sponse of rosuvastatin calcium. METHODS:Two hundred and tuirty six patients with coronary heart disease(CHD)were selected from cardiology department of our hospital during Jan. 2014-Jun. 2015,and then given rosuvastatin calcium and other symptomatic treatment for 12 weeks. Polymorphism of NOS1AP rs12742393 A/C was detected by PCR-RFLP. The levels of TG,TC,HDL-C and LDL-C were detected by photoelectric colorimetry before treatment and 4,12 weeks after treatment. The serum relationship of genotype with the level of blood lipid was analyzed. RESULTS:Among 236 CHD patients,there were 131 cases of AA genotype (55.5%),98 cases of AC genotype(41.5%) and 7 cases of CC genotype(3.0%);genotype and allele frequencies met the Har-dy-Weinberg balance(P>0.05). There were 132 patients with normal blood lipid and 104 patients with hypercholesterolemia;there was statistical significance in genotype and allele frequencies (P0.05). 4th and 12th week after treatment,the levels of TG,TC and LDL-C in different genotypes were all de-creased significantly;4th week after treatment,the level of LDL-C in AC+CC genotype was significantly lower than AA genotype, and the change compared to before treatment was significantly more than AA genotype,with statistical significance (P0.05). CONCLUSIONS:NOS1AP rs12742393 A/C gene polymorphism is associated with CHD complicated with hypercholesterolemia;the C allele of NOS1AP rs12742393 may strengthen the response of CHD patients with hy-percholesterolemia to rosuvastatin calcium through influencing the level of LDL-C.