Glucagon-like peptide-1 is an endogenous 30-amino acid gut peptide,which binds at the GLP-1 receptor coupled to the cyclic AMP second messenger pathway.Stimulation of neuronal GLP-1 receptors plays an important role in regulating neuronal plasticity and cell survival.GLP-1 has been documented to induce neurite outgrowth and to protect against excitotoxic cell death and oxidative injury in cultured neuronal cells.Moreover,GLP-1 and Exendin-4,a naturally occuring more stable analogue of GLP-1 that likewise binds at the GLP-1 receptor,were shown to reduce levels of ?-amyloid precusor protein(?APP) in neurons.Treatment with GLP-1 or a related peptide beneficially affects a number of the therapeutic targets associated with Alzheimers disease(AD).This review will consider the potential therapeutic relevance of GLP-1 to AD.

Adenosine deaminase (ADA)plays an important role in the regulation of normal immune system.The altered activ-ity of serum ADA could associate with some autoimmune diseases(AID).Various studies abroad have found the elevated ac-tivity of serum ADA compared with healthy controls in many kinds of AID such as systemic lupus erythematosus (SLE), rheumatoid arthritis(RA),et al (P<0.05).Many studies foused on the correlation of altered activity of serum ADA with the disease severity,but there is still controversy.To explore the diagnostic value of serum ADA in AID,make a review a-bout the application research progress of ADA in several AID.

Objective To investigate the mutual effect between G protein-coupled receptors(GPCR)including C5a receptor(C5aR),C5a like receptor 2(C5L2)and chemotaxis inhibitory protein(CHIPs)secreted by Staphylococcus aureus.Methods The purified CHIPs was incubated with HEK 293T cells overexpressing C5aR,C5L2 and C-X-C chemokine receptor type 3(CXCR3).Binding signal was detected by Western blot.Results HEK 293T cells overexpressing C5aR can efficiently bind to CHIPs.No apparent relation between CHIPs and C5L2 or CXCR3 was identified.Conclusion C5aR but not C5L2 is a membrane receptor for binding CHIPs,suggesting a difference between C5aR and C5L2 in association with binding CHIPs.

Aim To investigate the estrogenic activities of four components from pregnant mare’s urine extract. Methods The estrogenic activities of four components were assessed using two in vitro tests:the MCF-7 cell proliferation assay (E-screen test)and the luciferase transfected CHO cell gene reporter assay.In the lucifer-ase reporter gene assay,the reporter gene plasmids PGM-ERE-Luc and ERαor ERβand a control plasmid (pRL-cmv)were transiently co-transfected into CHO cells to establish an ERα-or ERβ-cell screening system which was used to measure estrogenic activity of four compounds.Results MCF-7 cells treated with HP, DHP,PT and HA significantly proliferated,thereby of-fering in vitro evidence for the estrogenic activities of HP,DHP,PT and HA,and they showed dose-depend-ent activities.Compared EC50 of PE and RPE with that of E2 ,HP,DHP,PT and HA exerted relatively weak estrogenic activities.The in vitro ER-mediated reporter gene assay revealed that HP,DHP,PT and HA dis-played estrogenic activities mediated by ERβor ERα. Compared with the EC50 of E2 ,HP,DHP,PT and HA exhibited lower estrogenic potencies.Conclusion HP, DHP,PT and HA possess weaker estrogenic activities than E2 .

To screen potential hamster chymase 2 inhibitors, a high-throughput screening (HTS) model was established. Recombinant hamster chymase 2 with active form was cloned and expressed in E. coli. The HTS model with total volume of 50 microL in 384-well microplate was based on fluorescence analysis and was proved sensitive as well as specific (Z' = 0.84). A total of 40 080 samples (including 28 060 compounds and 12 020 natural products) were screened, and 613 samples with inhibition greater than 90% were selected for further rescreening. Finally, compounds J16647 and J16648 were identified with high inhibitory activity on chymase 2, and whose IC50 values were 0.823 and 0.690 micromol x L(-1), respectively.

To study in vitro anti-influenza viral activities of Chinese traditional patent medicines for influenza prevention and treatment, neuraminidase (NA) activity assay was used to examine NA inhibitory activity of 33 Chinese traditional patent medicines through fluorimetric assay, and influenza virus induced cytopathic effect (CPE) inhibition assay was used to verify their anti-influenza viral activities in vitro. The assay results showed that most liquid preparations displayed relatively high NA inhibitory activities, such as Shuanghuanglian oral liquid, Qingkailing oral liquid, Qingre Jiedu oral liquid, and Reduning injection. Among liquid preparations, Shuanghuanglian oral liquid not only displayed the highest NA inhibitory effect, but also exhibited obvious in vitro anti-viral activity in CPE experiment. Among solid preparations, Shuanghuanglian powder for injection showed the highest activity on NA inhibition, and Fufang Yuxingcao tablet showed relatively strong anti-influenza viral activity in CPE cells. From the results, it can be concluded that most Chinese traditional patent medicines possessed NA inhibitory activity, but only a few of them displayed significant in vitro anti-influenza viral activities. These results will provide important information for the isolation of active constituents, and for the clinical uses of Chinese traditional patent medicines for influenza treatment and prevention.

Parkinson′s disease(PD),the second neurodegenerative disease in the world,is characterized by a combination of motor symptoms(rest tremor,bradykinesia,rigidity,postural instability,stooped posture and freezing of gait)and non-motor symp?toms(including psychiatric and cognitive disorders). The core neuropathological features of PD are the loss of dopaminergic neurons in the substantia nigra and the deposition of iron and cytoplasmic protein aggregates(Lewy bodies)inside neurons. Currently,clinical treatment for PD is symptomatic and there is no effective treatment to restore neuronal degeneration. In the PD therapy ,medication re?mains dominant. Anti-PD drugs are mainly based on the critical signal pathways or some specific targets which play a key role in the pathogenesis of PD to relieve the symptoms of PD. Research and development in novel drugs to prevent or treat PD have been a crucial subject,and some novel candidates are under development. In this paper,we summarize and analyze the anti-PD drugs,and make a brief discussion about its pharmacological targets.

Objective:To study preoperative MRI imaging and its enhanced mode on tumor features in predicting microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC).Methods:The clinical data of patients with a solitary HCC who underwent MRI examination followed by surgical resection at the General Hospital of Ningxia Medical University from January 2017 to June 2019 were studied. The patients were divided into the MVI (+ ) and MVI (-) groups according to the findings on postoperative pathological diagnosis. The relationship between the rates of MVI and MRI tumor features including diffusion weighted imaging (DWI) signal, enhancement mode, enhancement type and other imaging characteristics were analysed.Results:Of 84 patients with HCC enrolled into this study, there were 65 males and 19 females. Their age (Mean±SD) was (54.94±11.51) years. MVI (+ ) was found in 46 patients and MVI (-) in 38 patients. The maximum tumor diameters (Mean±SD) of the two groups were (7.08±3.45) cm and (4.28±2.47) cm ( P<0.01). Single-factor analysis and comparison of imaging characteristics of the two groups of patients showed tumor DWI signal, tumor encapsulation, enhancement mode, tumor edge smoothness, abnormal enhancement around tumors, and intratumoral arteries were significantly different ( P<0.05); There were no significant differences in T 1WI signals, T 2WI signals, tumor periphery, and enhancement types between groups. After inputting MVI(+ ) as a risk factor into the logistic regression model, tumor maximum diameters >6.33 cm, type 3/4 enhancement mode, and unsmoothness of tumor edge were independent risk factors (all P<0.05). Through combined diagnosis using ROC curve analysis with a cut-off value of 0.53, the area under the curve was 0.881, the sensitivity 0.870, specificity 0.789, and the Youden index 0.659. Conclusion:The multivariate logistic regression model and combined diagnosis using ROC curve analysis improved the diagnostic efficacy of MVI in its prediction of HCC on imaging studies. The risk predictors were easy to use and to promote in clinical practice.

This study is to investigate the effect of total flavonoids of Uygur medicine bugloss (BTF) on rats with myocardial ischemia/reperfusion injury, and to explore the mechanisms by which it acts. Left anterior descending (LAD) coronary artery in rats was occluded for 30 min followed by 4 h reperfusion. Meanwhile, BTF dissolved in saline was administered intraperitoneally at dosage of 10, 30 and 50 mg x kg(-1). Electrocardiograph, infarction index, serum myocardial enzymes and heart function were determined to evaluate the effect of BTF. Some other observations were carried out to explore whether inhibiting inflammation and apoptosis is involved in the mechanisms underlying BTF. Our results showed that in ischemia/reperfusion injured rats BTF could dose-dependently reduce myocardial infarction index and myocardial enzyme leakage, and enhance heart function, indicating that it possesses significant cardio protection. ELISA analysis showed that BTF could decrease the content of myocardial inflammatory cytokines such as IL-1beta, IL-6 and TNF-alpha. Western-blotting confirmed that BTF could increase the expression of anti-apoptotic protein Bcl-2 and reduce the expression of proapoptosis protein Bax. Further more, the phosphorylation level of PI3K and Akt was upregulated by BTF treatment. BTF can protect rat against myocardial ischemia/reperfusion injury. Anti-inflammation and inhibition of apoptosis through upregulating PI3K/Akt signal pathway may contribute to the protective effect of BTF.

This study examined the change of p16(INK4a) and PNCA protein expression in myocardium after injection of hIGF-1 gene modified skeletal myoblasts into post-infarction rats. HIGF-1 gene modified skeletal myoblasts (hIGF-1-myoblasts) were injected into hind limb muscles of 18 post-infraction rats (experimental group). Primary-myoblasts were injected into 18 post-infraction rats (control group) and 12 non-infarction rats (sham group). Expression of p16(INK4a) and PCNA protein in myocardiums were separately detected immunocytochemically 1, 2 and 4 weeks after the inuection. The level of hIGF-1 and rIGF-1 protein in serum and myocardium were detected by enzyme-linked immunosorbent assay (ELISA). Compared with the sham group, the percentage of p16(INK4a) and PCNA positive cells reached a peak after 1 week in the control group and the experimental group (P<0.01). Moreover, the percentage of p16(INK4a)-positive cells in the experimental group was lower than in control group whereas the percentage of PCNA-positive cells was lower in the control group than in the experimental group (P<0.01). The percentage of p16(INK4a)-positive cells in the experimental group and the percentage of PCNA-positive cells in the control group were close to that in the sham group from the 2nd week (P>0.05). ELISA analysis disclosed that the myocardium level of rIGF-1 protein increased gradually in the controls and especially in the experimental group (P<0.01). The serum level of rIGF-1 decreased significantly in post-infraction rats, but these conditions were improved in the experimental group (P<0.01). The hIGF-1 protein in serum and myocardium were detected from the 1st week to the 4th week in the experimental group. Statistical analysis revealed significant associations of myocardium level of hIGF-1 protein with expression of p16(INK4a) and PCNA protein (r=-0.323, P<0.05; r=0.647, P<0.01). It is concluded that genetically hIGF-1-myoblast provides a means for constant synthesis and release of hIGF-1. It could not only improve the expression of rIGF-1 and PCNA protein in myocardium, but also suppress the expression of p16(INK4a) protein for 30 days in post-infraction rats. Myoblasts-mediated IGF-1 gene therapy may provide a new alternative for the clinical treatment of heart failure.