Objective: To study the effect of a potent angiogenic in hi bitor TNP-470 on the growth of sarcoma. Methods:1?10 6 sarcom a S-180 cells 0.1 ml were inoculated into submandibular region in each of 40 K M mice. The mice were divided into control and treatment groups with 10 in each group. Treatment was started 8 hours after inoculation. TNP-40 at 10 mg/kg, 30 mg/kg and 100 mg/kg was given subcutaneously every other day in the 3 treatment groups,total 6 times. On the 12th day, the mice were sacrificed, tumor and mice were weighted. Apoptosis of tumor cells was observed by TUNEL method and transmi ssion microscope. Express of VEGF, bFGF were detected by immunohistochemical sta ining. Results:Sarcoma was developed in all of the mice. The sa rcoma cells invaded deep into adjacent organs and tissues such as muscle, subman dibular gland, parotid and facial nerve. 10 mg/kg, 30 mg/kg and 100 mg/kg TNP- 470 inhibited the growth of the tumor by 27.62%,63.81% and 85.71% respective ly, increased the apoptosis cell number by 54.46%,156.69% and 432.48% respect ively (P

Adult ; China ; epidemiology ; Cross-Sectional Studies ; Diabetes Mellitus ; diagnosis ; epidemiology ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Risk Factors ; Rural Population ; Sensitivity and Specificity

OBJECTIVETo investigate the promotive effect of transplantation of bone morphogenetic protein-2 (BMP-2) gene transfected bone mesenchymal stem cells (BMSCs) compounded with injectable bone tissue engineering scaffold material Pluronic F-127 on bone regeneration in rabbit mandibular distraction osteogenesis(DO).

METHODSForty-eight New Zealand's white rabbits were randomized into four groups with twelve in each. All the objects were prepared into DO surgical model. On the 2nd day of consolidation, group A, B, C and D were injected with the same amount of 200 microL of the compound of BMP-2 gene transfected BMSCs with Pluronic F-127, the solution with BMP-2 gene transfected BMSCs, the solution of BMSCs and physiological saline at distraction zone, respectively. Two halves of the objects of all groups were sacrificed at the end of 2nd and 6th week consolidation, respectively. And the specimens of right mandible were prepared for radiological, histomorphological and immunohistochemical examinations to evaluate bone regeneration.

RESULTSBoth radiological and immunohistochemical images were analyzed and processed with professional software. At the end of 2nd and 6th week consolidation, the bone mineral density and the expression of BMP-2 protein in distraction area of group A were significantly higher than those of B, C, D group (P<0.01). Group B was significantly higher than that in group C and D (P<0.01). There was no significant difference between group C and D (P>0.05). And the regeneration quality of distraction zone in group A and B were better than those in group C and D, just as that of group A better than group B. Conclusion The transplantation of BMP-2 gene transfected BMSCs compound with Pluronic F-127 could effectively promote bone regeneration in rabbit mandibular DO.

Animals ; Bone Density ; Bone Morphogenetic Proteins ; Bone Regeneration ; Mandible ; Mesenchymal Stromal Cells ; Osteogenesis ; Osteogenesis, Distraction ; Poloxamer ; Rabbits ; Tissue Engineering ; Tissue Scaffolds ; Transfection

OBJECTIVETo study the effect of angiogenesis inhibitor and its combine with chemical drug in suppressing the growth of adenoid cystic carcinoma (ACC).

METHODSAcc-M cells were inoculated subcutaneous into BABL/C nu/nu mice. The mice were divided into control, different dose of TNP-470 treatment groups, 5-Fu treatment group and TNP-470 plus 5-Fu treatment group. Treatments were given 48 hours after inoculation. The mice were sacrificed on the 22nd day and excised tumors were weighted. Tumors were also investigated by immunohistochemistry and ultrastructural observations.

RESULTSTNP-470 100 mg/kg/qod efficiently inhibited the growth of Acc-M tumors. TNP-470 30 mg/kg/qod combined with 50 mg/kg/week 5-Fu also resulted in significant growth inhibit of the tumors. TNP-470 suppressed tumor growth by inhibiting neovascularization, therefore inducing apoptosis of Acc-M cells. All experimental groups had different degrees of VEGF and bFGF express.

CONCLUSIONSince ACC is a slow developing tumor, blood supply is not so sufficient as sarcomas. Angiogensis inhibitor may inhibit its growth in high dosage. Combining medium dosage of angiogensis inhibitor with chemical drug may have synergistic result in inhibiting ACC growth.

Angiogenesis Inhibitors ; pharmacology ; Animals ; Apoptosis ; Carcinoma, Adenoid Cystic ; drug therapy ; Cell Line, Tumor ; Cyclohexanes ; pharmacology ; Fluorouracil ; pharmacology ; Humans ; Mice, Inbred BALB C ; Mice, Nude ; Sesquiterpenes ; pharmacology

Objective: To explore the lipid-lowering effect and potential mechanism of the couplet medicines of Flastem Milkvetch Seed and Tribulus terrestris on hyperlipidemia rats. Methods: Forty-eight Sprague-Dawley rats were randomly divided into 6 groups, normal control group, high-fat model group, simvastatin group, Tribulus terrestris group, Flastem Milkvetch Seed group, and couplet medicines of Flastem Milkvetch Seed and Tribulus terrestris group, with 8 rats in each group. The normal control group was fed with basal diet, and the other groups were fed with high-fat diet to establish a hyperlipidemia rat model. At the same time, different group rats were treated with different drug respectively. 6 weeks later, the body weight and visceral index of the rats were measured. Levels of serum cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) were detected by automatic biochemical analyzer. The mRNA and protein expression of HMG coenzyme A reductase (HMGCR), cholesterol 7-alpha hydroxy-lase (CYP7A1) and low density lipoprotein receptor (LDL-R) were detected by RT-PCR and western blot. Results: Compared with model group, the serum levels of TC, TG, and LDL-C were significantly decreased in all Chinese medicine groups, and the serum level of HDL-C was significantly increased in Flastem Milkvetch Seed group and couplet medicines of Flastem Milkvetch Seed and Tribulus terrestris group. Moreover, the mRNA and protein expression of HMGCR, CYP7A1, and LDL-R in rat liver also significantly increased in all Chinese medicine treatment groups. And couplet medicines of Flastem Milkvetch Seed and Tribulus terrestris group shows more significantly effect. Conclusion: Couplet medicines of Flastem Milkvetch Seed and Tribulus terrestris significantly regulate the serum lipid levels on hyperlipidemia rat model, and its mechanism may be related to the regulating expressions of HMGCR, CYP7A1, LDL-R gene.

OBJECTIVETo study the effect of Shexiang Baoxin pill (SBP) on the vascular endothelial function in patients with diabetes mellitus type 2 (DM2) complicated with angina pectoris.

METHODSTwo weeks after runin, according to the randomizing table, 111 patients were divided into two groups, the XBP group (56 patients) and the control group (55 patients, treated with delayed-released isosorbide mononitrate, DRIM), they were treated for 6 months. In the treatment period, the episodes of angina attack and condition of rescue medication were recorded in the daily card, and brachial arterial changes of endothelium-dependent relaxing function before and after treatment were measured by B-ultrasonography.

RESULTSComparison between the two groups in episodes of angina attack and rescue medication were insignificantly different. In the control group, the basal value of brachial arterial inner diameter before and after treatment was 3.68 +/- 0.56 mm and 3.70 +/- 0.58 mm respectively, those before and after responsive congestion was 5.44 +/- 0.81% vs 5.68 +/- 0.83%, and those before and after taking nitroglycerin was 19.8 +/- 4.9% vs 20. +/- 5.2%, all showed insignificant difference (P > 0.05). In the SBP group, the corresponding basal value was 3.73 +/- 0.62 mm vs 3.71 +/- 0.59 mm, and those after taking nitroglycerin 18.8 +/- 4.5 % vs 19.2 +/- 5.8%, also showed insignificant difference, but those before and after responsive congestion (5.69 +/- 0.79 % vs 9.56 +/- 3.82 %) did show significant difference (P < 0.01).

CONCLUSIONXBP could improve the vascular endothelial function in patients with DM2 complicated with angina pectoris.

Aged ; Angina Pectoris ; complications ; drug therapy ; Angioplasty, Balloon, Coronary ; Diabetes Mellitus, Type 2 ; complications ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Endothelium, Vascular ; drug effects ; physiopathology ; Female ; Humans ; Male ; Middle Aged ; Phytotherapy

Objective To identify related factors for hypoglycemic episodes in patients with type 2 diabetes mellitus(T2DM)through continuous glucose monitoring(CGM). Methods The included 147 patients with T2DM were those who had undergone CGM for 5 days in our ward of Department of Endocrinology and Metabolism,Huashan Hospital from Dec 2018 to Oct 2019. The general information, laboratory parameters and CGM parameters of the patients were collected. According to whether there wasan episode of hypoglycemia during the monitoring period,the patients were divided into non-hypoglycemia group and hypoglycemic group. A single hypoglycemia episode was defined as a sensor monitoring blood glucose of less than 3.9 mmol/L and lasting for more than 15 minutes.CGM parameters included the mean blood glucose(MBG),standard deviation(SD),coefficient of variation(CV),the differences between maximum and minimum blood glucose (BG) levels (ΔBG),mean amplitude of glycemic excursions (MAGE)and the percentage of time in range(％TIR)of BG at <3.9 mmol/L,3.9-7.8 mmol/L,>7.8 mmol/L,3.9-10.0 mmol/L,and >10.0 mmol/L. Results Logistic regression analysis showed that lower estimated glomerular filtration rate(eGFR)levels,increased use of insulin and its analogs and lower MBG levels were associated with hypoglycemic episodes. Spearman correlation analysis showed that the MBG level and the ％TIR of BG>7.8 mmol/L and BG>10.0 mmol/L were negatively associated while glycemic variability(GV)levels(SD,CV,ΔBG,MAGE)and ％ TIR of BG at 3.9-7.8 mmol/L were positively associated with hypoglycemic episodes. Pearson correlation analysis showed that the duration of hypoglycemic episodes was positively correlated with the use of sulfonylureas and CV levels. Conclusion Lower eGFR levels,increased treatment with insulin and its analogs and lower MBG levels were related factors for hypoglycemic episodes in patients with T2DM.

OBJECTIVETo investigate the prevalence and risk factors of diabetic retinopathy (DR) among type 2 diabetic patients aged over 30 in Shanghai central area.

METHODS1039 patients diagnosed with type 2 diabetes mellitus (DM) aged over 30 were investigated by randomized cluster sampling in Shanghai central area and data from 767 of those patients were analyzed.

RESULTS(1) Among all of the 1534 digital ocular fundus images from 767 patients, 87.6% of the images from 672 patients were gradable. (2) Among all of the 672 patients with gradable ocular fundus images, the prevalence of non-proliferative diabetic retinopathy (NPDR) was 21.6%, while proliferative diabetic retinopathy (PDR) was 1.3%. The rates of mild, moderate and severe NPDR were 8.8%, 11.2% and 1.6% respectively. (3) DR patients were characterized with elder age, higher HbA1c, urea nitrogen and serum creatinine. DM duration and the level of fasting plasma glucose were risk factors for DR.

CONCLUSIONThe overall prevalence of DR in type 2 diabetic patients aged over 30 in Shanghai central area was 22.9% and the DR risk factors were found to include duration of diabetes and fasting plasma glucose level.

Aged ; China ; epidemiology ; Cluster Analysis ; Diabetes Mellitus, Type 2 ; complications ; Diabetic Retinopathy ; epidemiology ; Epidemiologic Studies ; Female ; Humans ; Male ; Middle Aged ; Prevalence ; Risk Factors

Objective To explore the influence of extracellular matrix protein ABI-interactor 3-binding protein(ABI3BP)on vesicular stomatitis virus(VSV)genome replication and innate immune signaling pathway. Methods The small interfering RNA(siRNA)was transfected to knock down ABI3BP gene in human skin fibroblast BJ-5ta cells.VSV-green fluorescent protein(VSV-GFP)-infected cell model was established.The morphological changes and F-actin stress fiber formation were detected on ABI3BP knockdown cells by phalloidin immunofluorescence staining.The mRNA level of virus replication was detected by RT-qPCR in BJ-5ta cells after VSV-GFP infection;western blotting was performed to detect the changes in interferon regulatory factor 3(IRF3)andTANK-binding kinase 1(TBK1)phosphorylation levels. Results The VSV-GFP-infected BJ-5ta cell model was successfully established.Efficient knockdown of ABI3BP in BJ-5ta cells was achieved.Phalloidin immunofluorescence staining revealed structural rearrangement of intracellular F-actin after ABI3BP gene knockdown.Compared with the control group,the gene copy number of VSV-GFP in ABI3BP knockdown cells increased by 2.2-3.5 times(P＜0.01)and 2.2-4.0 times(P＜0.01)respectively when infected with VSV of multiplicity of infection 0.1 and 1.The expression of viral protein significantly increased in ABI3BP knockdown cells after virus infection.The activation of type-Ⅰ interferon pathway,as determined by phosphorylated IRF3 and phosphorylated TBK1,was significantly decreased in ABI3BP knockdown cells after VSV-GFP infection. Conclusions Extracellular matrix protein ABI3BP plays an important role in maintaining the formation and rearrangement of actin structure.ABI3BP gene deletion promotes RNA virus replication,and ABI3BP is an important molecule that maintains the integrity of type Ⅰ interferon pathway.

The capacity for thermal tolerance is critical for industrial enzyme. In the past decade, great efforts have been made to endow wild-type enzymes with higher catalytic activity or thermostability using gene engineering and protein engineering strategies. In this study, a recently developed SpyTag/SpyCatcher system, mediated by isopeptide bond-ligation, was used to modify a rumen microbiota-derived xylanase XYN11-6 as cyclized and stable enzyme C-XYN11-6. After incubation at 60, 70 or 80 ℃ for 10 min, the residual activities of C-XYN11-6 were 81.53%, 73.98% or 64.41%, which were 1.48, 2.92 or 3.98-fold of linear enzyme L-XYN11-6, respectively. After exposure to 60-90°C for 10 min, the C-XYN11-6 remained as soluble in suspension, while L-XYN11-6 showed severely aggregation. Intrinsic and 8-anilino-1-naphthalenesulfonic acid (ANS)-binding fluorescence analysis revealed that C-XYN11-6 was more capable of maintaining its conformation during heat challenge, compared with L-XYN11-6. Interestingly, molecular cyclization also conferred C-XYN11-6 with improved resilience to 0.1-50 mmol/L Ca²⁺ or 0.1 mmol/L Cu²⁺ treatment. In summary, we generated a thermal- and ion-stable cyclized enzyme using SpyTag/SpyCatcher system, which will be of particular interest in engineering of enzymes for industrial application.
Animals ; Cyclization ; Endo-1,4-beta Xylanases ; chemistry ; metabolism ; Enzyme Stability ; Industrial Microbiology ; methods ; Microbiota ; Protein Engineering ; Rumen ; enzymology ; microbiology ; Temperature