A GWAS-supported variant interacting with diabetes predicts risk of atherothrombotic stroke in Han Chinese population.

BACKGROUND: A recent genome-wide association study has identified that rs4376531 variant conferred risk of atherothrombotic stroke (AS) in a Japanese population. This study was to explore the association in Han Chinese population. METHODS: A total of 1036 cases and 643 healthy controls were enrolled. We genotyped rs4376531 variant with SNPscan. Multivariate logistic regression analysis was used to determine the association of genetic variation with risk of AS. Interaction analysis was examined by SNPStats web tool. RESULTS: After adjusting for gender, age, body mass index (BMI), hypertension, diabetes and smoking, compared with CC genotype, we observed that GC and GG/GC genotypes were associated with a significantly decreased risk of AS (OR = 0.76, 95% CI = 0.58-0.99 and OR = 0.76, 95% CI = 0.58-0.98, respectively). The decreased risk was more obvious among subgroups with high BMI (OR = 0.63, 95% CI = 0.45-0.88), no hypertension (OR = 0.66, 95% CI = 0.46-0.94), diabetes (OR = 0.33, 95% CI = 0.17-0.64), and smoking (OR = 0.65, 95% CI = 0.44-0.95) in the dominant model (GG/GC vs CC). Interaction analysis also revealed that compared with non-diabetic patients with CC genotype, diabetic patients with CC genotype had a 4.48-fold (OR = 4.48; 95% CI = 2.98-6.72) increased risk of AS. CONCLUSION: Our data suggested that GC and GG/GC of rs4376531 contributed to a decreased risk of AS while CC genotype, interacting with diabetes, increased the stroke risk in Han Chinese population.

[Efficacy and safety of lycopene in the treatment of benign prostatic hyperplasia with lower urinary tract symptoms].

OBJECTIVE: To investigate the efficacy and safety of lycopene in the treatment of BPH with lower urinary tract symptoms (LUTS). METHODS: Totally, 127 BPH patients with LUTS were treated with oral lycopene tablets at 500 mg bid in the Department of Andrology of Jinling Hospital from January 2018 to January 2019. At 8 and 16 weeks of medication, we compared the IPSS, quality of life (QOL) score, prostate volume, PSA level, maximum urinary flow rate (Qmax), postvoid residual urine volume (PVR) and the incidence of adverse reactions before and after treatment. RESULTS: A total of 120 patients completed the treatment. Compared with the baseline, significant improvement was observed after 8 weeks of medication in the IPSS (ï¼»18.42 ± 4.59ï¼½ vs ï¼»14.13 ± 4.51ï¼½, P < 0.01) and QOL score (ï¼»4.34 ± 1.37ï¼½ vs ï¼»3.14 ± 1.25ï¼½, P < 0.01), and even more significant at 16 weeks in the IPSS (ï¼»18.42 ± 4.59ï¼½ vs ï¼»10.29 ± 3.61ï¼½, P< 0.01), QOL score (ï¼»4.34 ± 1.37ï¼½ vs ï¼»2.17 ± 1.35ï¼½, P < 0.01), PSA (ï¼»3.87 ± 3.14ï¼½ vs ï¼»2.90 ± 3.07ï¼½ µg/L, P < 0.01), Qmax (ï¼»10.62 ± 2.08ï¼½ vs ï¼»14.15 ± 3.66ï¼½ ml/s, P < 0.01) and PVR (ï¼»35.88 ± 15.33ï¼½ vs ï¼»18.36 ± 13.09ï¼½ ml, P < 0.01), but there was no statistically significant difference in the prostate volume before and after treatment (ï¼»39.85 ± 10.22ï¼½ vs ï¼»38.16 ± 10.12ï¼½ ml, P > 0.05), and no adverse reactions in any of the patients. CONCLUSIONS: Lycopene has a good therapeutic effect on BPH with LUTS, which can significantly improve the patients' quality of life without causing adverse reactions.

[Knockdown of Grb7 inhibits growth of oral squamous cell carcinoma, cell proliferation and promoted apoptosis through ERK/FOXM1 pathway].

PURPOSE: To investigate the effect of growth factor receptor-bound 7 (Grb7) on oral squamous cell carcinoma growth and tumor xenografts. METHODS: Cal27 and hNOK cells were cultivated, real-time PCR and Western blotting were used to detect the expression of Grb7 in hNOK and Cal27. Cal27 was transfected with Grb7 siRNA for 48 h, cell proliferation was assayed using MTT. Flow cytometry was used to determine the cell cycle and apoptosis. Western blot was used to evaluate the expression of caspase3, Bax, bcl-2, Cyclin D1, Rb, E2F1, ERK and FOXM1. Grb7 siRNA and negative control were designed and injected subcutaneously into the mice, tumor volume and weight were measured. Statistical analysis was performed using SPSS 11.0 software package. RESULTS: Grb7 was highly expressed in Cal27 compared with hNOK. Depletion of Grb7 significantly inhibited cell proliferation, blocked G1/S phase transition, promoted cell apoptosis. Knockdown of Grb7 suppressed the expression of Cyclin D1 and Rb, upregulated E2F1 expression. Moreover, c-caspase 3 and Bax was also reduced after inhibition of Grb7. ERK/FOXM1 signaling pathway was also inhibited by Grb7. In addition, the volume and weight of tumor xenografts were reduced by siGrb7. CONCLUSIONS: Depletion of Grb7 inhibits cell proliferation, promotes apoptosis and reduces tumor xenografts through ERK/FOXM1 pathway.

In vitro cell proliferation evaluation of porous nano-zirconia scaffolds with different porosity for bone tissue engineering.

The selection of scaffold materials and the optimization of scaffold morphological and mechanical properties are critical for successful bone tissue engineering. We fabricated porous scaffolds of nano-sized zirconia using a replication technique. The study aimed to explore the relationship between porosity, pore size, mechanical strength, cell adhesion, and cell proliferation in the zirconia scaffolds. Macro- and micro-structures and compressive strength were comparatively tested. Beagle bone marrow stromal cells were seeded onto the scaffolds to evaluate cell seeding efficiency and cell proliferation profile over 14 d of incubation. The zirconia scaffolds presented a complex porous structure with good interconnectivity of pores. By increasing the sinter cycles, the porosity and pore size of the scaffolds decreased, with mean values ranging from 92.7-68.0% and 830-577 µm, respectively, accompanied by increased compressive strengths of 0.6-4.4 MPa. Cell seeding efficiency and cell proliferation over the first 7 d of incubation increased when the porosity decreased, with cell viability highest in the scaffold with a porosity of 75.2%. After 7 d of incubation, the cell proliferation increased when the porosity increased, highest in the scaffolds with a porosity of 92.7%. These results showed that the zirconia scaffold with a porosity of 75.2% possesses favorable mechanical and biological properties for future applications in bone tissue engineering.

Clinicopathological significance of Polo-like kinase 1 (PLK1) expression in human malignant glioma.

Polo-like kinase 1 (PLK1), a variety of serine/threonine-protein kinase, has been reported to play important roles in malignant transformation. The purpose of this study was to investigate the clinicopathological significance of PLK1 expression in malignant glioma. A semi-quantitative RT-PCR assay was performed to detect the expression of PLK1 mRNA in 68 cases of glioma tissues and corresponding non-cancerous brain tissues. Additionally, the correlation of PLK1 mRNA expression with clinicopathological factors or prognosis of glioma patients was statistically analyzed. Multivariate analysis of prognostic factors was performed using the Cox proportional hazard model. Small interfering RNA was used to knockdown PLK1 expression in a glioma cell line and analyze the effects of PLK1 inhibition on growth, cell cycle, apoptosis and chemo- or radiosensitivity of glioma cells. Results showed that the expression of PLK1 mRNA was significantly higher in glioma tissues than in corresponding normal brain tissues. The expression of PLK1 mRNA was closely correlated with WHO grade, KPS and tumor recurrence of glioma patients (P=0.022, 0.030 and 0.041, respectively). Meanwhile, the disease-free and overall survival rates of patients with high PLK1 mRNA expression were obviously lower than those of patients with low PLK1 mRNA expression. Multivariate analysis showed that high PLK1 mRNA expression was a poor prognostic factor for glioma patients (P=0.028). The expression of PLK1 mRNA and protein was significantly down-regulated in stably transfected U251-S cells. PLK1 down-regulation could inhibit growth, induce cell arrest in G2/M phase of cell cycle and apoptosis enhancement in glioma cells. Further, PLK1 down-regulation could enhance the sensitivity of glioma cells to cisplatin or irradiation. Thus, the status of PLK1 mRNA expression might be an independent prognostic factor for glioma patients and targeting PLK1 could be a novel strategy for chemo- or radiosensitization of human malignant gliomas.

Enantioselective alpha-arylation of ketones with aryl triflates catalyzed by difluorphos complexes of palladium and nickel.

The asymmetric alpha-arylation of ketones with aryl triflates is described, and the use of this electrophile with nickel and palladium catalysts containing a segphos derivative increases substantially the scope of highly enantioselective arylations of ketone enolates. The combination of aryl triflates as reactant, difluorphos as ligand, palladium catalysts for reactions of electron-neutral or electron-rich aryl triflates, and nickel catalysts for reactions of electron-poor aryl triflates led to a series of alpha-arylations of tetralone, indanone, cyclopentanone, and cyclohexanone derivatives. Enantioselectivities ranged from 70% to 98% with 10 examples over 90%. Systematic studies on these alpha-arylations have revealed a number of factors that affect enantioselectivity. Ligands containing biaryl backbones with smaller dihedral angles generate catalysts that react with higher enantioselectivity than related ligands with larger dihedral angles. In addition, faster rates for reactions of aryl triflates versus those for reactions of aryl bromides allow the alpha-arylations of aryl triflates to be conducted at lower temperatures, and this lower temperature improves enantioselectivity. Finally, studies that compare the enantioselectivities of catalytic reactions to those of stoichiometric reactions of isolated [(segphos)Pd(Ar)(Br)], [(segphos)Pd(Ar)(I)], and [(segphos)Ni(C6H4-4-CN)Br] suggest that catalyst decomposition affects enantioselectivity.

Chromium(III) catalysed ethylene tetramerization promoted by bis(phosphino)amines with an N-functionalized pendant.

Several N-functionalized bis(phosphino)amine ligands with ether, thioether and pyridyl tethers [(R'')2PN(R')P(R'')2=PNP] () have been synthesized. They react with CrCl3(THF)3 in CH2Cl2 to give dinuclear chloro bridged Cr2(micro-Cl)2Cl4(PNP)2 () which converts to the corresponding mononuclear solvento complexes fac-CrCl3(PNP)(NCR) (). The structures of the ligand with R'=-(CH2)3SCH3 and R''=Ph, and the complexes with R=CH3 () and C2H5 (), R'=-(CH2)3SCH3 and R''=Ph) have been established by single-crystal X-ray crystallography. All ligands are active towards ethylene tetramerization in the presence of Cr(III) and excess MAO at 80 degrees C in toluene. The ligand with thioether pendant Et2PN(CH2CH2CH2SCH3)PEt2 () shows the highest selectivity (55% weight in liquid product distribution) towards 1-octene. Complexes and are active towards ethylene polymerization under thermal conditions.

A structurally characterized Ni-Al methyl-bridged complex with catalytic ethylene oligomerization activity.

A bimetallic Ni-Al (2.5087(15) A) complex with an agostic alpha-C-H, [eta-C5H4CH=N(C6F5)]Fe[eta-C5H4PPh2]Ni(AlMe3), has been isolated and crystallographically established. The complex is active towards ethylene oligomerization/polymerization under moderate conditions.