Neurodegenerative disease is characterized by progressive loss of neurons in specific brain regions that results in neuronal dysfunction of the central nervous system. Although the pathological mechanism is not fully established, the activation of glial cells mediated neuroinflammation appears to be involved. Heat shock protein 70 (HSP70) is originally described as intracellular chaperone, which plays an important role in protein quality control in cells. However, recent study showed that up-regulation of HSP70 had anti-inflammatory effects in the brain. HSP70 protected neurons from damage and improved neurological function by decreasing inflammatory response as indicated by inactivation of glial cells and inhibition of pro-inflammatory cytokine release. So it is of great significance to find new compounds targeting at HSP70 as neuroprotective agents to delay the progress of neurodegenerative disease. This review will focus on the role of HSP70 in neuroinflammation and the recent advances in using HSP70 as a target for the treatment of neurodegenerative disease.
Brain ; physiopathology ; Cytokines ; HSP70 Heat-Shock Proteins ; physiology ; Humans ; Inflammation ; pathology ; Neurodegenerative Diseases ; physiopathology ; Neurons ; pathology ; Neuroprotection ; Up-Regulation

Danshen is one of the traditional Chinese herbal medicines and nas a long history or being used clinically in the treatment of cardiovascular and cerebrovascular conditions such as coronary heart disease and angina pectoris. Tanshinone IIA is a derivative of phenanthrene-quinone isolated from Danshen. It has been reported to be the major bioactive compound of Danshen and has diverse biological effects. Recent studies demonstrated that tanshinone IIA had neuroprotective effects on experimental ischemic stroke through its antiinflammatory, anti-oxidant, anti-apoptosis effects and its inhibitory effect on excitatory amino acid toxicity. In this review, we summarized all the recent progresses on the protective effect of tanshinone IIA on cerebral ischemic stroke. Hopefully, this article will throw some light on further study and application of tanshinone IIA.
Antioxidants ; therapeutic use ; Apoptosis ; Diterpenes, Abietane ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Salvia miltiorrhiza ; chemistry ; Stroke ; drug therapy

OBJECTIVETo explore various factors affecting the clinical pregnancy outcomes of artificial insemination with donor sperm (AID).

METHODSWe retrospectively analyzed 15,744 cycles of AID in 6302 women and investigated the association of the clinical pregnancy outcomes of AID with the treatment protocols, the times of insemination per cycle, the age of the infertile women, the status of the oviduct, and the number of AID cycles.

RESULTSThe pregnancy rate of AID was higher in the chlomiphene-treated women than in those of the natural cycle group (P = 0.003) but showed no significant differences either between the chloramiphene and human menopause gonadotropin (HMG) or between the HMG and natural cycle groups (P > 0.05), and so was it in the women that had received AID twice per cycle before and after ovulation (26.3%) than in those that had undergone only once before (7.0%) or after ovulation (23.7%) (P < 0.05). However, the pregnancy rate was remarkably lower in the women aged 35-40 years (16.5%), especially in those over 40 years (1.2%), than in those under 35 years (26.0%) (P < 0.05). There was no significant difference in the success rate of AID between the women with oviductal adhesion and those without (27.4% vs. 28.1%, P > 0.05). The pregnancy rate of the first cycle of AID (27.6%) was markedly higher than those of the second (24.7%), third (23.9%), and fourth (23.1%) (P < 0.01), but with no significant differences among the latter three cycles (P > 0.05), while that of the fifth cycle (19.0%) was remarkably lower than those of the first four (P < 0.01).

CONCLUSIONThe age of the infertile women is an important factor affecting the success rate of AID. AID twice per cycle is better than once only. For those without oviductal factors, at least 4 cycles of AID are required before in vitro fertilization.

Adult ; Age Factors ; Female ; Fertilization in Vitro ; Humans ; Infertility, Female ; Insemination, Artificial ; Insemination, Artificial, Heterologous ; Ovulation ; Ovulation Induction ; Pregnancy ; Pregnancy Outcome ; Pregnancy Rate ; Retrospective Studies

The quality and integrity of clinical trials and associated data are not only derived from accuracy of trial data analyses, but also closely embodied to the authenticity and integrity of those data and data documents as well as the compliant procedures obtaining those data and relevant files in the life cycle of clinical trials. The compliances of good clinical practices and standards suggest the reliability, complete and accuracy of data and data documents, which is constructing the convincible foundation of drug efficacy and safety validated via clinical trials. Therefore, the monitoring and auditing on clinical trials and associated data quality keep eyes on not only verifications of reliability and correctness on the data analytic outcomes, but also validation of science and compliance of the trial management procedure and documentations in the process of data collections.
Clinical Trials as Topic ; standards ; Data Accuracy ; Reproducibility of Results

Abatacept ; Case-Control Studies ; Chromosomes, Human, Pair 2 ; Diabetes, Gestational ; genetics ; Exons ; Female ; Genetic Predisposition to Disease ; Glucokinase ; genetics ; Humans ; Immunoconjugates ; genetics ; Mutation ; Pregnancy ; Promoter Regions, Genetic

Sphingolipids, especially ceramide and S1P, are structural components of biological membranes and bioactive molecules which participate in diverse cellular activities such as cell division, differentiation, gene expression and apoptosis. Emerging evidence demonstrates the role of sphingolipids in hepatocellular death, which contributes to the progression of several liver diseases including ischaemia-reperfusion liver injury, steatohepatitis or hepatocarcinogenesis. Furthermore, some data indicate that the accumulation of some sphingolipids contributes to the hepatic dysfunctions. Hence, understanding of sphingolipid may open up a novel therapeutic avenue to liver diseases. This review focuses on the progress in the sphingolipid metabolic pathway with a focus on hepatic diseases and drugs targeting the sphingolipid pathway.
Apoptosis ; Ceramides ; metabolism ; Fatty Liver ; metabolism ; physiopathology ; Humans ; Liver Diseases ; metabolism ; physiopathology ; Lysophospholipids ; metabolism ; Reperfusion Injury ; metabolism ; physiopathology ; Sphingolipids ; metabolism ; Sphingosine ; analogs & derivatives ; metabolism

Objective To explore the effects of stimulating vagus nerve with pulse current on peripheral blood CD4+T lymphocyte of rats with collagen induced arthritis and its mechanism.Methods To duplicate model rats of experimental arthritis(EA)by intradermal injection of Ⅱtype collagen,divide the rats into 2 groups:vagus nerve stimulation(VNS)group and sham operated group.Rats in VNS group were stimulated at the left cervical vagus nerves for 30 minutes a day with constant square wave,pulse current with intra train of 16 Hz,pulse duration of 1.0 ms,train duration of 10 s,interstimulus interval of 1.5 min and intensities of 3.0 mA.Then flow cytometry and immunofluorescence methods were used to detect the activation of CD4+T lymphocytes(expressing CD71)and the expression of nicotinic acetylcholine receptors alpha 7(nAChR?7)and choline acetyltransferase(ChAT)in peripheral blood CD4+T lymphocytes.Results In VNS group,the expression of nAChR?7 and ChAT were significantly raised in CD4+ T cells at 1st weekend(Pa

OBJECTIVETo investigate the inhibition effect of curcumin on the proliferation of the human esophageal carcinoma cell line Ec109 and its impact on PEN/PI3K/Akt signaling pathway.

METHODSEsophageal carcinoma Ec109 cells were cultured in vitro conventionally and were treated with curcumin at different concentrations. The cell proliferation level was examined by MIT colorimetry, the ultrastructure of curcumin-treated Ec109 cells were detected with transmission electron microscope (TEM) and cell apoptosis was observed by FCM with AnnexinV-FITC/PI double staining. The protein levels of PTEN, Akt, GSK3P and Caspase 3 of curcumin-treated Ec109 cells were detected by Western blot.

RESULTSMTT test showed that curcumin could inhibit the proliferation of Ec109 cells in a time and concentration-dependent manner. TEM examination indicated that curcumin could induce Ec109 cell apoptosis. FCM detection showed that Ec109 cell apoptotic rate increased significantly with the increase of drug concentration. On the other hand, curcumin could promote the expression of PTEN, GSK3beta and Caspase 3 yet reduce the expression of Akt.

CONCLUSIONCurcumin could obviously up-regulate the expression of PTEN, GSK3beta and Caspase 3, surpress PI3K/Akt signaling pathway and hence inhibit the proliferation of Ec109 cells.

Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Curcumin ; pharmacology ; Glycogen Synthase Kinase 3 ; metabolism ; Glycogen Synthase Kinase 3 beta ; Humans ; Oncogene Protein v-akt ; metabolism ; PTEN Phosphohydrolase ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Signal Transduction ; drug effects

AIMTo study the chemical constituents in the mycelia of Hypomyces sp..

METHODSSilica gel column chromatography was employed for the isolation and purification. Chemical and spectral methods were used to determine the structures of the isolated compounds.

RESULTSTwo compounds were isolated and identified as: hypomycin C (I) and hypomycin D (II).

CONCLUSIONCompounds I and II are new compounds.

Chromatography, Gel ; methods ; Fermentation ; Hypocreales ; chemistry ; Molecular Conformation ; Molecular Structure ; Mycelium ; chemistry ; Perylene ; analogs & derivatives ; chemistry ; isolation & purification ; Quinones ; chemistry ; isolation & purification

Objective To investigate the characteristics of renal hemodynamic and the esoteric prostacyclin(PGI2),thromboxane A2(TXA2)level in children with early Henoch-Schonlein purpura(HSP),and study the function of TXB_2/6-Keto-prostaglandin F(6-Keto-PGF_(1?))(T/K)numerus in early changes of kidney injury.Methods Children involved in the experiment were dicided into 3 groups.Thirty-one patients with HSP,divided into 2 groups according to routine urianlysis:children with HSP without renal damage group(n=16)and Henoch-Schonlein purpura nephritis(HSPN)group(n=15).Control group with 16 healthy children,their age and sex match with the other 2 groups.The urine of all children,including the children in control group,was sampled in 24 hours.The urinary production of the samples were kept in the freezer at-20 ℃.The radioimmunoassay was applied to determine the 6-Keto-PGF_(1?),TXB_2 quantitatively,and calculate the number of T/K.In the early morning the children accept the Doppler arteria renalis sonography with an empty stomach to determine the Vmax of the period of contraction of the arteria renalis the Vmin of diastolic phase and the resistent index(RI).SPSS 13.0 software was used to analyze the data.Results 1.The renal hemodynamic indicated a change of high velocity and resistance,the masculine rate(83.9%)was ob-viously higher than that in routine urinalysis(48.4%)(?2=5.79 P0.05).The RI in the former group(0.798?0.165)was much higher than that in the other one(0.637?0.116)(t=4.02 P