Zinc finger protein X-linked (ZFX) is a highly conservative mammalian gene with related functions in cell survival and proliferation. However, there are limited reports on regulation of ZFX as a therapeutic target in cancer treatment. In this study, the expression of ZFX in prostate cancer with matched normal adjacent tissues (n ¼ 45) and benign prostatic hyperplasia (BPH) tissues (n ¼ 16) were observed by immunohistochemical analysis. The effect of lentiviral siRNA (small interference RNA)-mediated dysfunction of ZFX on the proliferation of prostate cancer cells was studied. ZFX mRNA and protein expression levels in prostate cancer cells (PC-3 and DU145) were analyzed by western blotting and real-time polymerase chain reaction (RT-PCR). The effects of siRNA targeting ZFX on growth, cell cycle and apoptosis of PC-3 cells were evaluated by MTT assay and flow cytometry. We also investigated the effect of ZFX deletion on the activation of caspase-1, -3 and -9 by western blotting and colorimetric assay. Prostate cancer specimens appeared significantly higher (42.2% of cases being positive) than that observed in normal adjacent tissues (11.8% of cases being positive) and BPH tissues (12.5% of cases being positive). Repression of ZFX in the prostate cancer cells effectively suppressed the cellular proliferation and colony-formation ability, and led to G1 phase cell cycle arrest. Moreover, inhibition of ZFX-induced cell apoptosis by activating caspase-1, -3 and -9. In conclusion, ZFX represents the prominent role in the progression of prostate cancer and may be a promising therapy target for prostate cancer.

These findings show that ILC2s play a proinflammatory role in the murine AR model, and also highlight ILC2s as a new target in the future AR therapy.

The superconducting magnet with a high magnetic force field can levitate diamagnetic materials. In this study, a specially designed superconducting magnet with large gradient high magnetic field (LGHMF), which provides three apparent gravity levels (μg, 1 g, and 2 g), was used to study its influence on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation from preosteoclast cell line RAW264.7. The effects of LGHMF on the viability, nitric oxide (NO) production, morphology in RAW264.7 cells were detected by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method, the Griess method, and the immunofluorescence staining, respectively. The changes induced by LGHMF in osteoclast formation, mRNA expression, and bone resorption were determined by tartrate-resistant acid phosphatase staining, semiquantity PCR, and bone resorption test, respectively. The results showed that: 1) LGHMF had no lethal effect on osteoclast precursors but attenuated NO release in RAW264.7 cells. 2) Diamagnetic levitation (μg) enhanced both the formation and bone resorption capacity of osteoclast. Moreover, diamagnetic levitation up-regulated mRNA expression of RANK, Cathepsin K, MMP-9, and NFATc1, while down-regulated RunX2 in comparison with controls. Furthermore, diamagnetic levitation induced obvious morphological alterations in osteoclast, including active cytoplasmic peripheral pseudopodial expansion, formation of pedosome belt, and aggregation of actin ring. 3) Magnetic field produced by LGHMF attenuated osteoclast resorption activity. Collectively, LGHMF with combined effects has multiple effects on osteoclast, which attenuated osteoclast resorption with magnetic field, whereas promoted osteoclast differentiation with diamagnetic levitation. Therefore, these findings indicate that diamagnetic levitation could be used as a novel ground-based microgravity simulator, which facilitates bone cell research of weightlessness condition.

Background Methazolamide (MTZ) has been occasionally linked to the lethal Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which are associated with HLA‐B*59:01. However, some MTZ‐induced SJS/TEN (MTZ‐SJS/TEN) cases are negative for HLA‐B*59:01, implying that other genetic factors besides HLA‐B*59:01 are contributing to MTZ‐SJS/TEN. Objectives To comprehensively identify HLA and non‐HLA genetic susceptibility to MTZ‐SJS/TEN in Han Chinese. Methods Eighteen patients with MTZ‐SJS/TEN, 806 subjects of the population control and 74 MTZ‐tolerant individuals were enrolled in this study. Both exome‐wide and HLA‐based association studies were conducted. Molecular docking analysis was employed to simulate the interactions between MTZ and risk HLA proteins. Results We found a strong signal in the major histocompatibility complex region on chromosome 6 with 22 SNPs reaching exome‐wide significance. Compared with MTZ‐tolerant controls, a significant association of HLA‐B*59:01 with MTZ‐SJS/TEN was validated [odds ratio (OR) = 146.00, 95% confidence interval (CI): 16.12–1321.98; P = 6.19 × 10−10]. Moreover, 66.7% of MTZ‐SJS/TEN patients negative for HLA‐B*59:01 were carriers of HLA‐B*55:02, whilst 2.7% of the tolerant individuals were observed with HLA‐B*55:02 (OR = 71.00, 95% CI: 7.84–643.10; P = 1.43 × 10−4). Within HLA‐B protein, the E45‐L116 motif could completely explain the association of HLA‐B*59:01 and HLA‐B*55:02 with MTZ‐SJS/TEN (OR = 119.33, 95% CI: 29.19–1227.96; P = 4.36 × 10−13). Molecular docking analysis indicated that MTZ binds more stably to the pocket of HLA‐B*59:01 and HLA‐B*55:02 than to that of non‐risk alleles of HLA‐B*40:01 and HLA‐C*01:02. Conclusions This study confirmed the association of HLA‐B*59:01 with MTZ‐SJS/TEN and identified HLA‐B*55:02 as a novel risk allele in Han Chinese with the largest sample size to date. Notably, the rs41562914(A)‐rs12697944(A) haplotype, encoding E45‐L116, is capable of serving as a powerful genetic predictor for MTZ‐SJS/TEN with a sensitivity of 89% and specificity of 96%.