Cardiovascular diseases (CVDs) and metabolic disorders are major components of noncommunicable diseases, causing an enormous health and economic burden worldwide. There are common risk factors and developmental mechanisms among them, indicating the far-reaching significance in exploring the corresponding therapeutic targets. MST1/2 kinases are well-established proapoptotic effectors that also bidirectionally regulate autophagic activity. Recent studies have demonstrated that MST1/2 influence the outcome of cardiovascular and metabolic diseases by regulating immune inflammation. In addition, drug development against them is in full swing. In this review, we mainly describe the roles and mechanisms of MST1/2 in apoptosis and autophagy in cardiovascular and metabolic events as well as emphasis on the existing evidence for their involvement in immune inflammation. Moreover, we summarize the latest progress of pharmacotherapy targeting MST1/2 and propose a new mode of drug combination therapy, which may be beneficial to seek more effective strategies to prevent and treat CVDs and metabolic disorders.

Mesp family proteins comprise two members named mesodermal posterior 1 (Mesp1) and mesodermal posterior 2 (Mesp2). Both Mesp1 and Mesp2 are transcription factors and they share an almost identical basic helix-loop-helix motif. They have been shown to play critical regulating roles in mammalian heart and somite development. Mesp1 sits in the core of the complicated regulatory network for generation of cardiovascular progenitors while Mesp2 is central for somitogenesis. Here we summarize the similarities and differences in their molecular functions during mammalian early mesodermal development and discuss possible future research directions for further study of the functions of Mesp1 and Mesp2. A comprehensive knowledge of molecular functions of Mesp family proteins will eventually help us better understand mammalian heart development and somitogenesis as well as improve the production of specific cell types from pluripotent stem cells for future regenerative therapies.
Amino Acid Sequence ; Animals ; Basic Helix-Loop-Helix Transcription Factors ; genetics ; Cell Differentiation ; genetics ; Gene Expression Regulation, Developmental ; Mesoderm ; embryology ; metabolism ; Mice, Knockout ; Molecular Sequence Data ; Pluripotent Stem Cells ; metabolism ; Sequence Homology, Amino Acid

Objective To investigate the application value of the self-rated health measurement scale (SRHMS) in health check-up.Method A total of 8 083 health check-up receivers frow Fujian Province underwent SRHMS self-assessment,and the results of the assessment were analyzed by Chi-square test.Result The results of the survey showed that the total prevalence rate of chronic disease was 57.8％ top five were stomach/duodenum diseases (14.57％),hypertension (11.58％),mammary gland disease (8.04％),abnormal blood lipid (7.16％) and prostate disease (6.54％).The proportion of these five kinds of illness was 43.38％.A positive correlation between the prevalence rate of chronic disease and age was found.The difference of the prevalence rate of chronic diseases between each age group was statistically significant (x2=863.816,P=0.000).Those with family history of chronic diseases accounted for 69.27％ and those with history of present illness accounted for 57.83％ (4 674/8 083).Bodily pain,dietary preferences,refined grain intake,lack of exercise,and alcohol drinking was found in 75.03％,60.15％,54.84％,46.07％ and 41.50％ participants.Conclusion The SRHMS could reflect the chronic disease incidence and unhealthy daily habits.

Objective To investigate the effect of different concentrations of methotrexate (MTX) on IL-17 from peripheral blood mononuclear cells(PBMCs) and To clarify the active mechanisms of MTX on RA. Methods PBMCs were isolated from heparinized blood of healthy donors or patients with RA using Ficoll-Hypaque density gradient centrifugation. The cells were pretreated with various concentrations of MTX and then stimulated by anti-human CD3/anti-human CD28 at 37℃5%CO2. The IL-17 mRAN level was detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). The supernatants were harvested and the protein level of IL-17 was tested by ELISA kit. The percentage of CD4+IL-17+cells in PBMCs was detected by flow cytometry. Results For the four different concentrations of MTX groups (0.1,1.0, 5, 25μg/ml), the IL-17 mRNA/GAPDH ratio(0.58±0.09,0.48±0.11, 0.50±0.09, 0.51±0.14) were lower than those of the non-drug group(0.76±0.08). Paired-t test or independent-samplet test showed significant difference between the MTX treatment group and the non-drug group(P＜0.01). The level of IL-17 of the four MTX groups was(121±54)pg/ml and(104±45)pg/ml and(90±36)pg/ml and(115±41)pg/ml, which was lower than the non-drug group(370±187)pg/ml(P＜0.01). The average C D4+IL-17+cell ratio was reduced, but had no statistically signficant differences(P＞0.05). Conclusion MTX can decrease Th17 cells differentiation and suppress IL-17 production of PBMCs, but no association can be found between its effect on the expression of IL-17 and the concentration of MTX.

Objective To detect steroidogenic acute regulatory protein (StAR) expression in apolipoprotein E-deficient mice at different ages and serum lipid levels. Methods Nighty-six C57BL/6J and apoE-/- mice were enrolled, which were divided into 16 groups with 6 mice per group according to age (1 day, 1, 3, 5 months), sex and genotype (C57BL/6J and apoE-/-). The serum lipid levels in C57BL/6J and apoE-/- mice were detected by commercial kits. StAR mRNA and protein expressions in liver were detected by Real-time PCR and Western blot respectively. Results ApoE-/- mice had higher LDL-cholesterol and lower HDL-cholesterol compared with C57BL/6J mice of the same age and sex. StAR mRNA and protein expressions were decreased following with aging in C57BL/6J mice. However, in apoE-/- mice with higher lipid levels, StAR mRNA and protein expressions were changed with the lipid levels other than ages. StAR mRNA and protein increased in the early stage, and then decreased with the increasement of lipids levels. Conclusions StAR could affect lipids levels and may be an effective regulator for atherosclerosis and other cardiovascular diseases.

Objective By using percutaneous endovascular microcatheter technique to establish an animal model of coronary microembolization in mini-swine which is suitable for long-term observation.Methods Coronary microembolization was established in 10 mini-swine by infusing 15 × 10~4 microspheres (φ45μm) selectively into the left anterior descending artery (n = 10). Coronary flow reserve (CFR) was measured by Doppler wire and left ventricular eject fraction (EF) was assessed by echocardiography.Hematoxylin and eosin (HE) staining and nitroblue tetrazolium (NBT) dye were used to demonstrate the presence of microembolization after the procedure of coronary microembolization. The ultra-structures of cardiomyocyte were observed by transmission electron microscopy (TEM). Before sacrifice, the CFR measurement and coronary angiography were performed again in survival animals. Results The coronary microvascular integrity (CFR < 2.0) and left ventricular function (EF < 50% ) were damaged by coronary microembolization. One month after the procedure, all the 10 animals survived and were able to receive the angiography and CFR measurement again. HE staining and NBT dye could demonstrate the presence of microembolization. The edema and fibrosis of cardiomyocytes could be revealed with TEM. Conclusion The animal model of coronary microembolization can be established in mini-swine by using percutaneous endovascular microcatheter technique. The model is suitable for long-term observation, the preparation is technically-simple and minimally-invasive with very low mortality. Therefore, this kind of animal model is an ideal experimental form for studying the mechanism of coronary microembolization.

Objective To explore the content and gene expression of endothelial nitric-oxide synthase (eNOS) in heart of hyperlipidemia apoE-/- mice. Methods apoE-/- mice were fed with high fat diet as high-fat diet group (n= 7) and normal fat diet as control group (n = 6) for 12 weeks. Serum lipid profiles including total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL) and low density lipoprotein (LDL) were detected, eNOS mRNA expression in heart were determined by Real-Time RT-PCR, as well as protein expression by immunohistochemistry. Results Levels of serum TC, TG and LDL clearly increased in high fat diet group, while HDL decreased (P< 0. 01). mRNA and protein expression of eNOS in heart reduced in high fat diet group(P<0.01). Conclusions High fat diet may lead to hyperlipidemia in apoE-/- mice, which may down-regulate eNOS expression and decrease eNOS content in heart.

In the report of the definition and classification subcommittee of the International Dry Eye WorkShop (2007), inflammation was emphasized specially, and anti-inflammation therapy was also included in the treatment recommendations by severity level. Inflammation has been highly valued in the pathogenesis of dry eye recently. The management of dry eye through anti-inflammation therapy is also a hot point in recent years. What is the role of inflammation in the development of dry eye? This article mainly reviews the advancement of the study about their relevance in recent years.

OBJECTIVETo investigate the antitumor and anti-metastatic effect of in situ transduction of adenovirus encoding cytosine deaminase (AdCD) followed by the systemic use of 5-fluorocytosine (5-FC) in the orthotopic (o.t.) prostate cancer mouse model.

METHODSThe o.t. prostate cancer model of C57BL/6 mouse was developed by o.t. inoculation of RM-1 cells to the subcapsular area of the prostate gland. In situ transduction of the CD gene, followed by systemic use of 5-FC at a daily dosage of 300 mg/kg for 14 days, was performed two days later.

RESULTSCompared with mice treated with Adbeta-gal/5-FC, 5-FC and PBS, mice of the o.t. model receiving in situ treatment of AdCD/5-FC had significant prolongation of survival and suppression of local tumor growth. More importantly, pathological observations showed that metastatic activity occurred in all mice of the PBS, 5-FC and Adbeta-gal groups including metastasis to the iliac lymph node (10/10, 10/10, 10/10) and the lung (8/10, 7/10, 7/10). However, only two out of ten had iliac lymphatic metastasis in the AdCD/5-FC group with no systemic or preaotic lymphatic metastasis, suggesting a strong metastatic inhibitory effect.

CONCLUSIONSIn situ transduction of AdCD followed by systemic use of 5-FC leads to the inhibitory effect on tumor growth and metastatic activity in the o.t. mouse model of prostate cancer. Clinically, it may be possible to treat metastatic or recurrent prostate cancer with a novel gene therapy using in situ injection techniques in future.

Adenoviridae ; genetics ; Animals ; Cell Division ; drug effects ; genetics ; Cytosine Deaminase ; Disease Models, Animal ; Flucytosine ; pharmacology ; Lymphatic Metastasis ; genetics ; pathology ; prevention & control ; Male ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; Nucleoside Deaminases ; genetics ; Prostatic Neoplasms ; genetics ; mortality ; prevention & control ; Survival Rate ; Transfection ; Tumor Cells, Cultured

Objective To study the inhibitory effect of CD/5 FC system on the prostate cancer cell DU145,RM 1 in vitro. Methods In vitro prostate cancer cells DU145 and RM 1 were infected by recombinant adenoviral vector and then the inhibitory effect and the bystander effect of CD/5 FC system were observed. Results CD/5 FC system had a remarkable inhibitory effect on prostate cancer cell DU145 and RM 1 in vitro, the inhibition rates being higher than 97% when infected by AdCMVCD after 4 days added with 15.5mmol/L 5 FC. A strong bystander effect could also be observed, more than 75% tumor cells being killed when only 10% were infected. Conclusions CD/5 FC system may serve as an effective gene therapeutic method.The existence of bystander effect makes itself available in the use of tumor treatment in vivo.