Protein regulator of cytokinesis 1 overexpression predicts biochemical recurrence in men with prostate cancer

BackgroundProtein regulator of cytokinesis 1 (PRC1) has been reported to be implicated into the completion of cytokinesis and is dys-regulated in a cancer-specific manner. However, it roles in human prostate cancer (PCa) remain unclear. In the current study, we aimed to investigate the expression pattern of PRC1 and its clinical significance in this malignancy.Materials and methodsPRC1 protein expression in human PCa and non-cancerous prostate tissues was detected by immunohistochemistry, which was validated by microarray-based Taylor data at mRNA level. Then, the associations of PRC1 expression with clinicopathological features and clinical outcome of PCa patients were statistically analyzed.ResultsPRC1 expression in PCa tissues, at both mRNA and protein levels, were significantly higher than those in non-cancerous prostate tissues. In addition, the PCa patients with PRC1 overexpression more frequently had high Gleason score, advanced pathological stage, positive metastasis, short overall survival time and positive PSA failure than those with low Gleason score, early pathological stage, negative metastasis, long overall survival time and negative PSA failure (all P < 0.05). Moreover, PRC1 expression was identified as an unfavorable prognostic factor of biochemical recurrence-free survival in PCa patients (P < 0.001).ConclusionThese findings suggest that the aberrant expression of PRC1 may predict biochemical recurrence in men with PCa highlighting its potential as a prognostic marker of this malignancy.     

Distinguishing between halogenated alkanes containing the same halogen based on the reaction kinetic parameter using negative ion mobility spectrometry at atmospheric pressure

Electron adsorption ionization ion mobility spectrometry can be used to detect halogen-containing volatile organic compounds with high sensitivity. However, this traditional electron attachment detection method cannot distinguish between volatile organic compounds containing the same halogen. For different organic compounds containing the same halogen, the product ions formed by the dissociation electron attachment process are the same. In this article, we propose a novel negative corona discharge ion mobility spectrometry method to distinguish between and detect halogenated alkanes containing the same halogen according to the different electron attachment rates and reaction kinetic parameters of the different halogenated alkanes. Although these halogenated alkanes, which contain the same halogen, produce the same type of ions through the electron attachment process, their electron attachment rates are different from each other. In this work, the kinetic information is used as the fingerprint information for the tested samples to distinguish different halogenated alkanes. Five halogenated alkanes were successfully detected using this method. The results show that the method based on the electron attachment rate constant is feasible for the determination of halogenated alkanes containing the same halogen.

Electron attachment ionization ion mobility spectrometry can be used to detect halogen-containing volatile organic compounds with high sensitivity.     

A combination of Sinomenine and Methotrexate reduces joint damage of collagen induced arthritis in rats by modulating osteoclast-related cytokines

ObjectiveTo analyze the combination therapy of Sinomenine (SIN) and Methotrexate (MTX) in rheumatoid arthritis (RA), we herein demonstrated the combination effect of SIN and MTX on collagen-induced arthritis (CIA) in rats through their modulation on osteoclast-related cytokines.MethodsCIA was induced by the immunization of type II collagen (CII) in SD rats. SIN and MTX were administrated alone or in combination after the onset of arthritis. Arthritis index and histological analysis were used to evaluate the effect of treatments. Effects of SIN and MTX on expression of receptor activator of NF-κB ligand (RANKL) and osteopontin (OPN) in synovial tissues were assayed by immunohistochemistry. RANKL, osteoprotegerin (OPG), IL-6, IL-17 and matrix metalloproteinases (MMPs) in rat serum were measured by ELISA. The expression of osteoclast-related cytokines in fibroblast-like synoviocytes (FLS) from RA patients was assayed by RT-PCR.ResultsSIN and MTX combination additively reduced the inflammatory symptoms and joint damage in CIA. Combination of SIN and MTX significantly repressed synovial RANKL and OPN production. SIN and MTX exhibited complementary and synergistic effect upon down-regulating RANKL, IL-6, IL-17 and MMPs in rat serum. SIN and MTX also modulated the expression of RANKL and OPG in RA-FLS.ConclusionSIN and MTX have additive effects, decreasing inflammation and joint damage in CIA rats by modulating osteoclast-related cytokines. These results are indicative of the combined effect of SIN and MTX for anti-arthritic treatment in RA.     

The molecular mechanisms of XBP-1 gene silencing on IRE1α-TRAF2-ASK1-JNK pathways in oral squamous cell carcinoma under endoplasmic reticulum stress

BackgroundProteasome inhibitor Carbobenzoxy-Leu-Leu-leucinal (MG132) induces the unfolded protein response (UPR) in oral squamous cell carcinoma (OSCC). X-box binding protein 1 (XBP1) is a key UPR component that regulates endoplasmic reticulum stress (ER) homeostasis. This study was aimed to investigate the activation of IRE1α-TRAF2-ASK1-JNK pathway by silencing the XBP1 expression in an OSCC cell line.MethodsThe XBP1 specific short hairpin RNA (shRNA) plasmid vector was constructed and then transfected into the Tca-8113 cells. The effect of XBP-1 gene silencing on IRE1α-TRAF2-ASK1-JNK pathway under MG132 induced endoplasmic reticulum stress in Tca-8113 were investigated by real-time RT-PCR or western blot. Cell apoptosis was detected by flow cytometry.ResultsXBP1 expression was reduced in transfected groups and MG132 groups. shRNA-XBP1 induces IRE1α-TRAF2-ASK1 signaling activation to activate pro-apoptotic ASK1-JNK signaling. Moreover, combined shRNA-XBP1 with MG132 further enhanced downregulated XBP1 expression and upregulated activation of ASK1-JNK signaling.ConclusionsSilencing XBP1 expression under MG132 induced ER stress block the XBP1 survival pathway and synergism with MG132 to promote Tca8113 cell apoptosis. These findings provide a therapeutic option in oral squamous cell carcinoma by inhibition of proteasome and XBP1 splicing.     

Prediction model for malignant pulmonary nodules based on cfMeDIP-seq and machine learning

Cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq) is a new bisulfite-free technique, which can detect the whole-genome methylation of blood cell-free DNA (cfDNA). Using this technique, we identified differentially methylated regions (DMR) of cfDNA between lung tumors and normal controls. Based on the top 300 DMR, we built a random forest prediction model, which was able to distinguish malignant lung tumors from normal controls with high sensitivity and specificity of 91.0% and 93.3% (AUROC curve of 0.963). In summary, we reported a non–invasive prediction model that had good ability to distinguish malignant pulmonary nodules.     

Transforming brain signals related to value evaluation and self‐control into behavioral choices

The processes involved in value evaluation and self‐control are critical when making behavioral choices. However, the evidence linking these two types of processes to behavioral choices in intertemporal decision‐making remains elusive. As the ventromedial prefrontal cortex (vmPFC), striatum, and dorsolateral prefrontal cortex (dlPFC) have been associated with these two processes, we focused on these three regions. We employed functional magnetic resonance imaging during a delayed discounting task (DDT) using a relatively large sample size, three independent samples. We evaluated how much information about a specific choice could be decoded from local patterns in each brain area using multivoxel pattern analysis (MVPA). To investigate the relationship between the dlPFC and vmPFC/striatum regions, we performed a psychophysiological interaction (PPI) analysis. In Experiment I, we found that the vmPFC and dlPFC, but not the striatum, could determine choices in healthy participants. Furthermore, we found that the dlPFC showed significant functional connectivity with the vmPFC, but not the striatum, when making decisions. These results could be replicated in Experiment II with an independent sample of healthy participants. In Experiment III, the choice‐decoding accuracy in the vmPFC and dlPFC was lower in patients with addiction (smokers and participants with Internet gaming disorder) than in healthy participants, and decoding accuracy in the dlPFC was related to impulsivity in addicts. Taken together, our findings may provide neural evidence supporting the hypothesis that value evaluation and self‐control processes both guide the intertemporal choices, and might provide potential neural targets for the diagnosis and treatment of impulsivity‐related brain disorders.     

在XiO计划系统中构建虚拟治疗床的必要性评估

目的 基于XiO计划系统研究加速器碳素纤维治疗床对放射治疗剂量分布的影响,并通过在XiO计划系统中构建虚拟治疗床来模拟加速器治疗床对剂量的衰减。方法 使用大孔径螺旋CT扫描加速器治疗床的延长板,勾画轮廓并保存为床模型。将固体水模置于治疗床的中心,测量不同机架角度（100°~180°）下等中心处的吸收剂量,并在XiO计划系统中加与不加床模型的情况下分别进行剂量计算,得到治疗床的剂量衰减系数。通过不断调整外层碳素纤维（CF）和内层填充泡沫（FC）的相对电子密度（RED）值,得到能最好模拟治疗床剂量衰减的CF和FC的RED值。选取10例肺癌患者计划,使用Octavius 4D模体进行剂量验证,评估在剂量计算中考虑治疗床对计划通过率的改善。结果 CF和FC的最优化RED分别为0.75和0.10 g/cm³。不考虑治疗床,计算值的偏差在120°达到最大值4.84%;考虑治疗床后,误差由（2.54±1.48）%降至（-0.04±0.36）%,差异有统计学意义（Z=-3.621,P<0.05）。三维剂量验证的γ通过率（3 mm/3%标准）由（91.79±1.25）%提高至（94.74±1.69）%,差异有统计学意义（t=6.027,P<0.05）。结论 治疗床对剂量的衰减不应被忽略,在XiO计划系统中构建虚拟治疗床可以很好地模拟衰减,提高剂量计算的准确性。     

Di(2-ethylhexyl) phthalate exacerbates non-alcoholic fatty liver in rats and its potential mechanisms

Di(2-ethylhexyl) phthalate (DEHP) may be responsible for inducing alterations similar to those encountered in nonalcoholic fatty liver disease (NAFLD). The aim of the present study was to investigate the detrimental effects and possible mechanisms of DEHP on fatty liver rats directly through triggering the disorder of liver lipid metabolism or indirectly by hepatotoxic effect. Considering these effects, DEHP may play a significant role in the pathogenesis of NAFLD. In this study, high-fat diet was used to induce NAFLD in rats for eight weeks. DEHP treated groups received (0.05, 5, 500 mg/kg daily, respectively) dose by gavage during the whole experiment period. Our results indicated that the detrimental effects of DEHP on high-fat diet induced NAFLDs were mediated via increasing lipid accumulation in the liver and causing lipid peroxidation and inflammation.