Objective To detect the plasma macrophage inflammatory protein (MIP) levels in patients with early Parkinson' s disease (PD) and to investigate whether plasma MIP was associated with motor and non-motor symptoms in early PD.Methods Fifty-nine patients with early idiopathic PD (Hoehn-Yahr Staging Scale from 1.0 to 2.5) treated in our hospital from January 28,2013 to September 30,2013 and 54 healthy controls were recruited.Plasma MIP-1α and MIP-1β levels were measured by enzyme-linked immunosorbent assay.Motor function was assessed by Unified Parkinson' s Disease Rating Scale Part Ⅲ and Hoehn-Yahr Staging Scale during “on” period.Total non-motor symptoms were assessed by Non-motor Symptoms Questionnaire.Cognitive dysfunction was assessed by Mini Mental State Examination.Autonotic dysfunction was assessed by Scales for Outcomes in Parkinson' s disease-Autonomic.Depression was assessed by Hamilton Depressive Scale (HAMD).Rapid eye movement (REM) sleep behavior disorder was assessed by REM sleep behavior disorder screening questionnaire (RBDSQ).Correlation between plasma MIP levels and scale scores was analyzed by Spearman rank correlation.Results Plasma MIP-1o and MIP-1β levels were not significantly different between early PD patients and healthy controls.However,plasma MIP-1 α level negatively correlated with depression (HAMD score,r =-0.520,P =0.027) and rapid eye movement sleep behavior disorder (RBDSQ score,r =-0.537,P =0.039).Conclusion MIP-1 α may be correlated with depression and RBD in early PD.

Objective To study the killing effects of fractional proteins from Microtus fortis (Mf) serum on schistosomula of Schistosoma japonicum. Methods Mf serum proteins were separated into albumin and globulin by means of salt out of ammonium sulfamate. The globulin was then separated into 4 big and 12 small fractional proteins through Sephacryl S-300 column chromatography and electrophoresis elution. The killing effects were observed in vitro in cultivation in which the purified fractional proteins and schistosomula of S. japonicum were incubated together for 48 h. Results The mortality rate of schistosomula acted by Mf globulin was 59.2% and when added with complements was 68.4%. The killing effects of the 2nd and 3rd big fractional proteins were the same as that of Mf globulin. Three small fractional proteins (3.2, 3.3, 3.4) showed the higher killing effects which made the mortality rate of schistosomula 45.1%, 57.6% and 67.2%, respectively. The fractional protein of 100-135 kDa also showed the same killing effect as that of Mf globulin. Globulin from BALB/c mice sera had no significant effect on schistosomula. There was no significant difference in the mortality rate of schistosomula acted by both albumins. Conclusions Mf globulin has significant killing effects on schistosomula of S.japonicum in vitro and 100-135 kDa fractional protein may be an important effective molecule.

Maturity-onset diabetes of the young (MODY)is a heterogeneous monogenic diabetes, in which MODY1, MODY2, and MODY3 are the most common subtypes. In recent years, new hypoglycemic drugs such as glucagon-like peptide-1 receptor agonists (GLP-1RA), dipeptidyl peptidase-4 inhibitors (DPP-4i), sodium-glucose co-transporter 2 inhibitors (SGLT2i), and glucokinase activators (GKA)have made good progress in the treatment of diabetes. Based on the latest basic and clinical evidence, the article reviews the pathogenesis, clinical features, diagnosis and treatment progress of new hypoglycemic drugs of the above three types of MODY, aiming to develop safer and more effective new ways for the diagnosis and treatment of MODY.

Objective To develop a rapid kit applied to the field for detection of antibody to schistosome in human sera. Methods A new kit for rapid detection of antibody to schistosome was developed through improving the dot immunogold filtration assay (DIGFA). A total of 100 cases of sera from chronic schistosomiasis patients and 140 from healthy people, HBV patients and the people infected with other parasites were detected by the kit. The sensitivity, specificity, Youden's index and Kappa value were utilized as the evaluation standard. Results The sensitivity of detecting antibody to schistosome, specificity, Youden's index and Kappa value were 92% , 95.08% , 0.87 and 0.87, respectively. The cross reaction to patients with clonorchiasis was 5%. Conclusion DICFA kit is practical for antibody to schistosome detection in the field because of its advantages such as smaller serum needed and faster in reaction.

Objective To evaluate effects of tea polyphenols on the mRNA and nucleoprotein expression of Nrf2/Bach1 in human skin fibroblasts (HSFs).Methods Some HSFs were incubated with tea polyphenols at different concentrations of 0,2.5,5,10,20 and 40 mg/L for 24 hours.Methyl thiazolyl tetrazolium (MTT) assay was conducted to evaluate the proliferative activity of HSFs to screen the optimal concentration of tea polyphenols.Then,some other HSFs were treated with tea polyphenols at this optimal concentration for 24 hours.Real-time quantitative PCR (RT-qPCR) was performed to determine mRNA expression of Nrf2 and Bach1,Western blot analysis to measure nuclear expression of Nrf2 and Bach1 proteins,and immunofluorescence assay to determine the distribution of Nrf2 and Bach1 protein in the cell nucleus.Results MTT assay showed that 5 mg/L tea polyphenols had no obvious effects on the proliferation of HSFs,so 5 mg/L was chosen as the optimal concentration of tea polyphenols for subsequent experiments.HSFs cultured without tea polyphenols served as control group.After the treatment,the 5-mg/L tea polyphenol group showed significantly decreased mRNA and nuclear protein expression of Bach 1 (mRNA:0.629 ± 0.077 vs.0.940 ± 0.033,t =6.397,P ＜ 0.05;protein:1.424 ± 0.171 vs.16.966 ± 1.702,t =15.730,P ＜ 0.05),but significantly increased mRNA and nuclear protein expression of Nrf2 (mRNA:1.467 ± 0.076 vs.0.977 ± 0.091,t =7.133,P ＜ 0.05;protein:6.929 ± 0.121 vs.3.537 ± 0.126,t =33.636,P ＜ 0.05) compared with the control group.Immunofluorescence assay showed increased accumulation of Nrf2 protein,but decreased accumulation of Bach1 protein in the nucleus.Conclusion Tea polyphenols can promote the mRNA and nuclear protein expression as well as nuclear distribution of Nrf2,but suppress the mRNA and nuclear protein expression as well as nuclear distribution of Bach 1,finally exerting antioxidative effects.

OBJECTIVETo evaluate the agreement and correlation between hepatic vein pressure gradient (HVPG) and portal vein pressure (PVP) in patients with portal hypertension,and explore their clinical value.

METHODSA total of 46 patients with portal hypertension were directly measured the free hepatic pressure, wedged hepatic pressure, portal vein pressure before and after TIPS therapy. The agreement and correlation of HVPG and PVP were analyzed, and explore their clinical value.

RESULTSThere is no significant agreement or correlation between HVPG and PVP in 5 patients, whose third hilar have large communicating branches between portal vein and Inferior vena cava, or with obvious umbilical vein opened. The HVPGs were significantly agreed with portal vein pressure in other 41 patients. There is no significant difference of HVPG or PVP between earlyTIPS and not early-TIPS groups. In addition, the portal vein pressures after TIPS were significantly decreased compared with that before TIPS.

CONCLUSIONThe HVPG can well show the PVP except these with obvious communicating branches between portal vein and Inferior vena cava in third hilar, and TIPS can effectively decrease the portal vein pressure in patients with portal hypertension.

Hepatic Veins ; Humans ; Hypertension, Portal ; Portal Vein ; Vena Cava, Inferior ; Venous Pressure

OBJECTIVETo investigate the antineoplastic effects of 2-Deoxy-D-glucose (2-DG) combined with Taxol on orthotopically transplanted breast cancer in C3H mice and explore the mechanism.

METHODSC3H mice bearing orthotopically transplanted breast cancer xenograft were randomly divided into 4 groups, namely the control group, 2-DG group, Taxol group, and 2-DG+Taxol group. The corresponding drugs were administered intraperitoneally every 3 days for 18 consecutive days, and the tumor volume was measured every 3 days to draw the tumor growth curve. The mice were then sacrificed to measure the tumor weight on day 19 and examine tumor cell apoptosis with TUNEL assay and VEGF expression using immunohistochemistry.

RESULTS2-DG combined with Taxol obviously suppressed the tumor growth with a tumor inhibition rate of 66.06% as compared to the rate of 36.97% in Taxol group. The combined treatment also caused more obvious cell apoptosis and significantly reduced VEGF expression in the tumor cells as compared with the other groups.

CONCLUSION2-DG can enhance the inhibitory effect of Taxol on orthotopically transplanted breast cancer xenograft in C3H mice probably by inducing tumor cell apoptosis and lowering VEGF expressions.

Animals ; Antineoplastic Agents ; pharmacology ; therapeutic use ; Apoptosis ; Breast Neoplasms ; drug therapy ; pathology ; Cell Line, Tumor ; Deoxyglucose ; pharmacology ; therapeutic use ; Drug Synergism ; Female ; Mice ; Mice, Inbred C3H ; Paclitaxel ; pharmacology ; therapeutic use ; Vascular Endothelial Growth Factor A ; metabolism ; Xenograft Model Antitumor Assays

OBJECTIVETo study the effect of glycolysis inhibitor 3-bromopyruvate (3-BrPA) in inducing apoptosis of human breast carcinoma cells SK-BR-3 and the possible mechanism.

METHODSMTT assay was used to detect the growth inhibition induced by 3-BrPA in breast cancer cells SK-BR-3. The apoptotic cells were detected by flow cytometry with propidium iodide (PI). ATP levels in the cells were detected by ATP assay kit, and DHE fluorescent probe technique was used to determine superoxide anion levels; the mitochondrial membrane potential was assessed using JC-1 staining assay.

RESULTSMTT assay showed that the proliferation of SK-BR-3 cells was inhibited by 3-BrPA in a time- and concentration-dependent manner. Exposure to 80, 160, and 320 µmol·L(-1) 3-BrPA for 24 h resulted in cell apoptosis rates of 6.7%, 22.3%, and 79.6%, respectively, and the intracellular ATP levels of SK-BR-3 cells treated with 80, 160, 320 µmol·L(-1) 3-BrPA for 5 h were 87.7%, 60.6%, and 23.7% of the control levels. 3-BrPA at 160 µmol·L(-1) increased reactive oxygen levels and lowered mitochondrial membrane potential of SK-BR-3 cells.

CONCLUSION3-BrPA can inhibit cell proliferation, reduce the mitochondrial membrane potential and induce apoptosis in SK-BR-3 cells, the mechanism of which may involve a reduced ATP level by inhibiting glycolysis and increasing the reactive oxygen level in the cells.

Apoptosis ; drug effects ; Cell Line, Tumor ; Female ; Glycolysis ; Humans ; Membrane Potential, Mitochondrial ; drug effects ; Pyruvates ; pharmacology ; Reactive Oxygen Species ; metabolism

Intervertebral disc degeneration is one of the common causes of chronic low back pain. As a common spinal disease， its clinical symptoms are mainly low back pain and limited function， which seriously affects physical and psychological health. Because of its complex and unclear pathogenesis， the treatment of intervertebral disc degeneration has been the focus of scientific researchers and clinical workers. At present， the treatment of intervertebral disc degeneration mainly includes non-surgical therapy and surgical therapy， which can alleviate the clinical symptoms of patients to a certain extent， but easily induce new complications， and it is difficult to restore the normal physiological function of the intervertebral disc. In recent years， along with the advanced research on matrix metalloproteinases （MMPs） in the tissues of intervertebral disc degeneration， it has been found that MMPs can be used as molecular therapeutic targets. The expression of MMPs in the intervertebral disc tissues can be regulated by reducing the content and composition of the extracellular matrix of the intervertebral disc， so as to slow down intervertebral disc degeneration and even reverse the occurrence of intervertebral disc degeneration. This treatment is expected to delay intervertebral disc degeneration caused by changes in extracellular matrix composition or content. In recent years， with the continuous development of network pharmacology and bioinformatics research， a large number of researchers have explored the treatment of intervertebral disc degeneration by traditional Chinese medicine （TCM） and found that TCM can reduce the degradation of extracellular matrix by inhibiting the expression of MMPs， thus alleviating the symptoms of intervertebral disc degeneration and slowing down the progression of intervertebral disc degeneration. This paper reviewed the research progress of TCM intervention in MMP expression in the treatment of intervertebral disc degeneration， aiming at providing references for the application of TCM in the prevention and treatment of intervertebral disc degeneration.

Osteoporosis is a chronic skeletal disease characterized by low bone mass， destruction of bone tissue microarchitecture， and imbalance of bone homeostasis， leading to increased bone fragility and increased risk of fractures. Oxidative stress caused by the disruption of the balance between excess reactive oxygen species （ROS） and the anti-oxidative system is an important factor in the occurrence and progression of osteoporosis. Nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） is an important anti-oxidative stress pathway. Nrf2 is a primary factor in regulating cellular oxidative stress. Activating Nrf2 can stimulate the expression of HO-1. HO-1 is a key enzyme whose metabolites are bile green Oxygen， carbon monoxide， and free iron. The metabolites can scavenge ROS， thereby exerting an antioxidant effect in cells. At present， domestic and foreign scholars have reported that the Nrf2/HO-1 signaling pathway is closely related to the occurrence and development of osteoporosis and the mechanism of drugs. Chinese medicine can effectively solve the insufficiency of western medicine with multi-target， multi-channel， and multi-level advantages. Chinese medicine can resist oxidative stress， inflammatory response， and apoptosis by regulating the Nrf2/HO-1 signaling pathway， thus treating osteoporosis. This article reviewed the relationship between Nrf2/HO-1 signaling pathway and its key target protein factors and osteoporosis， to clarify the important role of the Nrf2/HO-1 signaling pathway in osteoporosis. At the same time， a systematic summary of Chinese medicines targeting and regulating the Nrf2/HO-1 signaling pathway for the treatment of osteoporosis was conducted， to provide a theoretical basis for further precise treatment of osteoporosis.