OBJECTIVETo explore anti-cancer effect and mechanism of green tea extract (GTE) in three human oral squamous carcinoma cell lines (CAL-27, SCC-25 and KB).

METHODSThe cell lines were in vitro cultured and its growth inhibition was detected by MTT. After screening most sensitive cell line, effect of GTE on CAL-27 cell cycle was analyzed by flow cytometry. The protein expression of GTE on CAL-27 cell strain was determined by protein chip technique. The protein expression of CDK4, CDK6, and p-PDK1 was verified by using Western blot.

RESULTSCompared with the control group, the inhibition rate on CAL-27 increased significantly after treated by 50, 100, 200, and 400 μg/mL GTE; the inhibition rate on KB increased after treated by 100, 200, and 400 μg/mL GTE; the inhibition rate on SCC-25 increased after treated by 25, 50, 100, 200, and 400 μg/mL GTE, all with statistical difference and in dose dependant manner (P < 0.01). Flow cytometric analysis showed that, when compared with the control group, 50 μg/mL GTE arrested CAL-27 cells in the G2/M phase (P < 0.05), and 100 μg/mL GTE arrested CAL-27 cells in the G2/M phase with concurrent decreased cells in the G0/G1 phase (P < 0.01). Totally 107 proteins were analyzed by protein chip technique. After treated by GTE, a total of 13 proteins significantly changed in CAL-27 cell line. Western blot showed that 25, 50, and 100 μg/mL GTE inhibited the expression of phopho-phosphoinositide-dependent protein kinase 1 (p-PDK1), cyclin-dependent kinase 4 (CDK4), and CDK6 of CAL-27 cell line with statistical difference (P < 0.05). The higher the drug concentration, the higher the inhibition rate (P < 0.05).

CONCLUSIONSGTE could inhibit the proliferation of different human oral squamous carcinoma cell lines. CAL-27 is a sensitive cell line. GTE significantly affected EGFR and Notch signal network, and influenced changes of cell cycle related protein expression levels through the aforesaid channels, resulting in cell cycle arrest in S and G2/M phases.

Antineoplastic Agents, Phytogenic ; pharmacology ; therapeutic use ; Antioxidants ; Carcinoma, Squamous Cell ; Cell Cycle ; Cell Line, Tumor ; Cyclin-Dependent Kinase 4 ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; G1 Phase ; Humans ; Mouth Neoplasms ; Tea

BACKGROUNDDiffusion weighted imaging (DWI), with the applying of intravoxel incoherent motion model, has showed promising results in obtaining additional information about microperfusion and tubular flow associated with morphologic changes in chronic kidney diseases. The study aims to evaluate the potential of T2-weighted signal intensity (SI) and DWI with mono- and bi-exponential models to reflect the serial changes on cisplatin (CP) induced rat renal fibrosis models.

METHODSMagnetic resonance exams were performed prior to and 2 nd day, 4 th day, 6 th day, 8 th day, 2 nd week, 3 rd week and 4 th week after CP injection at a 3.0T with an animal coil. Besides T2-weighted images (T2WI), DWI of 13 b values from 0 to 1500 s/mm 2 was acquired. Apparent diffusion coefficient (ADC), fluid fraction f, pure diffusivity D and pseudodiffusivity DFNx01 values were calculated. The regions of interest were placed on cortex (CO), outer stripe of the outer medulla (OM) and inner stripe of the outer medulla (OM), parameters were measured and compared among different time points. Five rats were scarified at each time point for pathological examination.

RESULTSOM revealed remarkable hyperintense and broadened before it became an obscure thread, while CO demonstrated moderate hyperintense and IM didn't show significant change on T2WI. On all three stripes, ADC values decreased firstly then kept increasing since the 4 th day; f values decreased on all stripes; D values had a tendency to increase with fluctuations but the changes didn't achieve statistical significance; DFNx01 values increased at the 2 nd day then tended to be steady thereafter. Pathological findings revealed tubules epitheliums swelling followed by inflammation cells infiltration, interstitial fibrosis was observed since the 2 nd week.

CONCLUSIONSAll of T2-weighted SI, ADC, and biexponential models parameters vary during fibrotic process; biexponential model is superior to monoexponential model in separating changes of microperfusion together with tubular flow from pure diffusion.

Animals ; Cisplatin ; therapeutic use ; Diffusion Magnetic Resonance Imaging ; methods ; Disease Progression ; Fibrosis ; diagnosis ; Kidney Diseases ; diagnosis ; Male ; Models, Animal ; Rats ; Rats, Sprague-Dawley ; Renal Insufficiency, Chronic ; diagnosis

Objective To explore the association between total cholesterol and type 2 diabetes ( T2DM) ． Methods Non－diabetic people who aged 20 to 90 years at the baseline and who had physical examination more than 2 times were screened． Comparisons of the baseline characteristics were conducted with Student－t test or Pearson chi－square test． Generalized estimating equation ( GEE) was used to analyze the effect of total cholesterol of quantiles groups ( 2．10－ mmol /L，4．16－ mmol /L，4．76－ mmol /L and 5．42 －13．29 mmol /L) to type 2 diabetes． Results The cohort with an average age of 3．53 years per person in- cluded 12 928 subjects and 45 626 person－years． During the follow－up，447 cases of new－onset diabetes occurred and the incidence density was 9. 80‰． The high incidence of type 2 diabetes increased with the increase of total cholesterol． After adjusting the factors including age，high density lipoprotein，hypertension and obesity，based on the 2. 10－ mmol /L group，the relative risk ( RR) of the 4. 16－ mmol /L，4. 76－ mmol/L and 5. 42－13. 29 mmol /L group were 1. 24( 95% CI: 0. 83－1. 86) ，1. 75 ( 95% CI: 1. 19－2. 56) and 3. 60( 95% CI: 2. 51－5. 17) ，respectively． Conclusions Total cholesterol is associated with type 2 diabetes，and as the total cholesterol increases，the risk of developing type 2 diabetes increases．

Hypoxia is a common pathophysiological state especially in the processing inflammatory tissues cells due to hypoxia partial pressure caused by excessive oxygen consumption or insufficient oxygen supply. Hypoxia inducible factor(HIF) that regulates the transcription of downstream target genes in order to cope with the hypoxia environments is induced by various mechanisms in hypoxic state. Studies have demonstrated that HIF-α plays essential roles in the inflammatory response. This paper reviews the recent research that the roles and mechanisms of HIF-α in inflammation-associated diseases mediated by innate immune cells.

AIMTo design and synthesize new phenyloxyisobutyric acid analogues as antidiabetic compounds.

METHODSEight new target compounds were synthesized by combination of lipophilic moieties and acidic moiety with nucleophilic replacement or Mitsunobu condensation. The eight compounds were confirmed by 1H NMR, 13C NMR, IR and MS.

RESULTSIn vitro insulin-sensitizing activity (3T3-L1 adipocyte) demonstrated, that the cultured glucose concentration of up-clear solution detected with GOD-POD assay were 5.942, 6.339, 6.226 and 6.512 mmol x L(-1), respectively, when rosiglitazone, pioglitazone, compounds A and B were added to the insulin-resistant system.

CONCLUSIONIn vitro insulin-sensitizing activity of target compound A is in between that of rosiglitazone and pioglitazone, and activity of target compound B is slightly less than that of pioglitazone.

3T3-L1 Cells ; Adipocytes ; drug effects ; Animals ; Butyrates ; chemical synthesis ; chemistry ; pharmacology ; Hypoglycemic Agents ; chemical synthesis ; chemistry ; pharmacology ; Insulin ; pharmacology ; Mice ; Molecular Structure ; PPAR gamma ; agonists ; pharmacology

OBJECTIVETo explore whether MG-132 could enhance the anti-tumor activity of obatoclax against esophageal cancer cell line CaES-17.

METHODSMTT assay was used to determine the cytotoxicity of obatoclax and MG-132 in CaES-17 cells. The IC(50) of obatoclax and MG-132 were used to determine the molar ratio (1:2.4) of the two drugs for combined treatment of the cells. The concentrations of obatoclax and MG-132 ranged from 1/8 IC(50) to 4 IC(50) after serial dilution, and their combination index (CI) was calculated using CompuSyn software. The expression of ubiquitin and the cleavage of PARP, caspase-9, phospho-histone H3 and phospho-aurora A/B/C in the exposed cells were examined with Western blotting; the cell apoptosis was measured by flow cytometry with Annexin V staining, and the percentage of cells in each cell cycle phase was also determined by flow cytometry.

RESULTSThe CI of obatoclax and MG-132 was 0.296 for a 50% inhibition of Caes-17 cells and was 0.104 for a 95% inhibition. The cells treated with obatoclax or MG-132 alone showed increased expression of ubiquitin and cleavage of PARP and caspase-9. Compared with the cells treated with obatoclax or MG-132 alone, the cells with a combined treatment exhibited significantly increased expression of ubiquitin, cleavage of PARP and caspase-9, and expression of phospho-Histone H3 (P<0.05). The combined treatment of the cells also resulted in significantly increased expression of phospho-Aurora A/B/C compared with obatoclax treatment alone. The cells with the combined treatment showed significantly higher percentages of apoptotic cells and cells in sub-G(1) and G(2)/M phases compared with the cells treated with either of the drugs (P<0.05).

CONCLUSIONObatoclax combined with MG-132 shows a significant synergistic anti-tumor effect against esophageal cancer CaES-17 cells by inducing apoptosis and cell cycle arrest.

Apoptosis ; Caspase 9 ; metabolism ; Cell Cycle Checkpoints ; Cell Line, Tumor ; drug effects ; Esophageal Neoplasms ; pathology ; Histones ; metabolism ; Humans ; Leupeptins ; pharmacology ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerases ; metabolism ; Pyrroles ; pharmacology

Adult ; Female ; Heart Neoplasms ; pathology ; Hemangioendothelioma ; pathology ; Humans ; Immunohistochemistry

OBJECTIVETo investigate the effects of neuropeptide Y (NPY) Y1 receptor antagonist PD160170 in promoting osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and accelerating healing of femoral defect in rats.

METHODSThe third generation of rat BMSCs were treated with PBS (control) or 10, 10, or 10 mol/L NPY Y1 receptor antagonist PD160170. After 7 and 14 days of treatment, the cells were examined for osteogenic differentiation with alkaline phosphatase (ALP) and alizarin red staining. At 7 and 21 days of treatment, the mRNA and protein expressions of collagen type I (COLI), osteocalcin (OCN) and Runt-related transcription factor 2 (Runx2) in the cells were detected using q-PCR and Westem Blotting. In a male SD rat model (body weight 300∓20 g) of bilateral femoral condyle defects (2.5 mm in diameter), the effect of daily local injection of 0.2 mL PD160170 (10 and 10 mol/L, for 28 consecutive days) in promoting bone defect repair was evaluated with micro-CT scans.

RESULTSALP and alizarin red staining showed that the BMSCs treated with PD160170, at the optimal concentration of 10 mol/L, contained more intracellular cytoplasmic brown particles and mineralized nodules in extracellular matrix than PBS-treated cells. PD160170 (10 mol/L) significantly up-regulated the mRNA and protein expressions of COLI at day 7 and those of OCN and Runx2 at day 21 (P<0.05). In the rat models of femoral bone defect, the volume/tissue volume ratio, bone mineral density and the number of bone trabeculae were significantly greater in 10 mol/L PD160170 group than in the control group (P<0.05), but the bone trabecular thickness (P=0.07) and bone volume (P=0.35) were similar between the two groups.

CONCLUSIONNPY Y1 receptor antagonist PD160170 can promote osteogenic differentiation of BMSCs and healing of femoral defects in rats, suggesting the potential of therapeutic strategies targeting NPY Y1 receptor signaling in the prevention and treatment of bone fracture and osteoporosis.

In order to learn from the advanced experience of postgraduate education in foreign first-class universities, Harvard University, Johns Hopkins University and London School of Hygiene and Tropical Medicine were selected as the objects in this study to analyze and compare the advantages and characteristics of their postgraduate training model, curriculum setting and teaching resources, thereby providing suggestions for the reform and development in the cultivation of master of public health and preventive medicine in China.

Depression is a common affective disorder. The application of antidepressants can significantly alleviate the symptoms of depression, which is the most important way to treat depression in clinical practice. Due to the complex etiology, wide variety, as well as diversity and severity of serious concomitant symptoms, rational addition of other drugs into antidepressants can significantly improve the cure rates of depression, reduce adverse reactions, and improve patient compliances. Therefore, the combined applications of differential drugs have been commonly used in clinic. In this paper, more than 600 literatures about depression from 2010 to 2019 were collected based on the key words of antidepressant, depression, combined medication, synergism and increase efficiency. Based on this, by summarizing and classifying the existing combinations of antidepressant drugs, this paper systematically expounds the current combined applications of antidepressant drugs in three categories, i.e. western medicines combined with western medicines, western medicines combined with traditional Chinese medicines, and traditional Chinese medicines combined with traditional Chinese medicines, in the expectation of providing the direction and basis for the selection of rational combinations of antidepressant drugs in clinic.
Antidepressive Agents ; Drug Interactions ; Humans ; Medicine, Chinese Traditional