Medications regulate autophagy for treatment of Alzheimer's disease / 药学学报

Alzheimer's disease (AD) is characterized clinically as irreversible cognitive dysfunction. Although a significant progress has been made in the study of AD pathogenesis, the effective measures to block AD progress have not been satisfactory. Abnormal autophagy is thought to be involved in the pathogenesis of AD, and regulation of autophagy may become a new strategy for AD treatment. Some medicines, which regulate autophagy by mTOR-dependent and independent (Bcl-2/Beclin-1, GSK-3β, and p-AKT) pathways, have shown excellent effects in alleviating AD symptoms. In addition, certain compounds extracted from plants have also been reported to regulate autophagy and prevent AD progression through multiple pathways and multiple targets. This article reviews the recent advances in the regulation of autophagy and AD treatment. It provides a new theoretical basis for clinical treatment of AD.

NO donor V-PYRRO/NO inhibits expression of leukotriene C4 synthase in early stage of hepatic ischemia/reperfusion injury in rats / 基础医学与临床

Objective To explore the mechanism underlying a selective liver nitric oxide donor V-PYRRO/NO effects on the gene expression of LTC4 synthase(LTC4S) during hepatic ischemia reperfusion(I/R).Methods Adult male SD rats were divided into 3 groups:control group(sham),ischemic-reperfusion group(I/R) and V-PYRRO/NO group. Liver subjected to 1 hour of partial hepatic ischemia followed by 5 hours of reperfusion, saline or V-PYRRO/NO[1.06 mmol/(kg·h)] administered intravenously. The mRNA expression of LTC4S in rat liver was examined by RT-PCR method,the protein expressions of NF-κB p65,p50 and IκB in liver cell lysates and nu-clear extracts were detected by Western blot analysis. Results Hepatic mRNA expression of LTC4S in I/R group was higher than that in sham group(P<0.05), whereas it was lower in V-PYRRO/NO group than that in I/R group(P<0.05). Moreover,compared with sham group,the protein expressions of NF-κB p65 and p50 in nucleus extract were markedly increased(P<0.01) but significantly decreased in cytoplasm(P<0.01) in I/R group. V-PYRRO/NO reversed completely the increase of these protein expressions in nucleus extract (P<0.05) and the decrease of them in cytoplasm(P<0.01,P<0.05) during hepatic I/R injury.However,IκB protein in three groups did not change. Immunohistochemistry staining revealed that no marked positive staining for NF-κB p65 was found in sham liver,I/R liver exhibited strong cytoplasmic and nuclear positive staining for NF-κB p65,but V-PYRRO/NO I/R group liver presented slight cytoplasmic and nuclear staining. Conclusions V-PYRRO/NO may down-regulate LTC4S mRNA expression by inhibiting NF-κB activation independent of IκB during hepatic I/R injury.

Shenfu injection protects human ECV304 cells from hydrogen peroxide via its anti-apoptosis way.

ETHNOPHARMACOLOGICAL RELEVANCE: The pathogenesis of thromboangiitis obliterans (TAO) has not been fully elucidated until now. Shenfu injection (SFI), a traditional Chinese formula has been widely used clinically for the treatment of cardiovascular diseases for more than two decade. Our previous results first suggested that SFI can cause a significant therapeutic effect on experimental TAO model rats. This experiment was designed to further investigate the protective effect of SFI on VEC damaged by hydrogen peroxide (H2O2) oxidative stress in vitro. METERIALS AND METHODS: The cell viability was evaluated by the MTT assay, the activities of SOD and GSH-PX and the content of MDA in the supernatants of the cultured ECV304 cells were evaluated by a colorimetry method, cell apoptosis was detected by flow cytometry and an AO/EB double staining method. The protein expressions of Bcl2, Bax and caspase-3 were examined by Western blotting. RESULTS: When compared with control group, lower survival rate of ECV304 cells was observed in H2O2 group (p<0.01) ; 20µl/ml, 30µl/ml and 40µl/ml SFI increased the survival rate of ECV304 cells under H2O2 oxidative stress (p<0.05 and p<0.01). The activities of SOD and GSH-PX were higher and MDA level was lower in H2O2 group than those in control group. These effects of H2O2 on SOD, GSH-PX activities and MDA content were reversed by SFI in concentration-dependent way (p<0.05 and p<0.01). Flow cytometry and AO-EB double staining discovered that SFI pretreatment inhibited the ECV304 cells apoptosis. The protein expression of caspase3 in 30µl/ml and 40µl/ml SFI groups significantly decreased whereas Bcl2 protein expressions in 20µl/ml, 30µl/ml and 40µl/ml SFI groups were higher than H2O2 group, with Bax protein expression much lower than H2O2 group (p<0.05 and p<0.01). CONCLUSIONS: Our findings suggest that SFI could prevent the ECV304 cells against H2O2 oxidative-stress by enhancing antioxidant enzyme activities, reducing the membrane lipid peroxidation, as well as upregulating antiapoptotic and downregulating apoptosis protein expressions.

Relationship between anogenital distance and cryptorchidism in human newborns / 中华男科学杂志

<p><b>OBJECTIVE</b>To explore the relation of the anogenital distance (AGD) with cryptorchidism in male newborns.</p><p><b>METHODS</b>This study included 350 male infants delivered in two community hospitals between September 2013 and September 2014. Within 24 hours after birth, a pediatric surgeon measured the AGD of the neonates and determined whether they had cryptorchidism. According to the testicular position, we divided the undescended testes into three types: upper scrotal, inguinal, and non-palpable.</p><p><b>RESULTS</b>Totally 39 cases of cryptorchidism were found in the 350 newborns. The AGD of the cryptorchidism infants was significantly shorter than that of the normal neonates ([2.01 ± 0.22] vs [2.35 ± 0.19] cm, P < 0.01), and statistically significant differences remained even when preterm and low birth-weight infants were excluded ([2.32 ± 0.14] vs [2.06 ± 0.19] cm; (2.37 ± 0.17) cm vs (2.12 ± 0.12) cm, all P < 0.01). The newborns with higher-position cryptorchidism had a shorter AGD, though with no significant difference (F = 0.434, P > 0.05). No significant differences were observed in the AGD between unilateral and bilateral cryptorchidism ([1.96 ± 0.13] vs [2.02 ± 0.17] cm, P > 0.05).</p><p><b>CONCLUSION</b>Shorter AGD is associated with a higher incidence of cryptorchidism in male newborns. AGD could serve as a potential biomarker for disruption of androgen action during the male programming window period.</p>

Interaction between opioid receptor and adrenoceptor signaling in ischemia reperfusion of the isolated rat heart / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the interaction between opioid receptor (OR) stimulation and adrenergic receptor (AR) stimulation in the isolated ischaemia/reperfusion (I-R) rat heart.</p><p><b>METHODS</b>Male Sprague-Dawley rats were used for Langendoff isolated heart perfusion. Myocardial ischemia for 20 min was followed by 30 min of reperfusion, during which the kappa-OR agonist U50488h and beta(1)-AR agonist norepinephrine (NE) were administered.</p><p><b>RESULTS</b>(1) 50488h antagonized the effect of NE in rising left ventricular systolic pressure (LVSP) in the early phase of myocardial ischemia at 10, 20, 30 min of reperfusion. (2) Arrhythmia scores in the I-R+NE+U50488h group were markedly lower than those in the I-R group during the 10 - 20 min reperfusion period. No significant differences in arrhythmia scores were found in either I-R+U50488h or I-R+NE group when compared with I-R group. (3) Compared with the I-R group, U50488h alone or plus NE decreased reperfusion heart rates after myocardial ischemia while NE alone showed no effect.</p><p><b>CONCLUSION</b>It is suggested that the interaction in the signaling pathway between kappa-OR and beta(1)-AR occurred during myocardial I-R of rat heart.</p>