Vitamin D Compounds PRI-2191 and PRI-2205 Enhance Anastrozole Activity in Human Breast Cancer Models

1,25-Dihydroxycholecalciferol, the hormonally active vitamin D₃ metabolite, is known to exhibit therapeutic effects against breast cancer, mainly by lowering the expression of estrogen receptors and aromatase activity. Previously, the safety of the vitamin D active metabolite (24R)-1,24-dihydroxycholecalciferol (PRI-2191) and 1,25(OH)₂D₃ analog PRI-2205 was tested, and the in vitro activity of these analogs against different cancer cell lines was studied. We determined the effect of the two vitamin D compounds on anastrozole (An) activity against breast cancer based on antiproliferative activity, ELISA, flow cytometry, enzyme inhibition potency, PCR, and xenograft study. Both the vitamin D active metabolite and synthetic analog regulated the growth of not only estrogen receptor-positive cells (T47D and MCF-7, in vitro and in vivo), but also hormone-independent cancer cells such as SKBR-3 (HER-2-positive) and MDA-MB-231 (triple-negative), despite their relatively low VDR expression. Combined with An, PRI-2191 and PRI-2205 significantly inhibited the tumor growth of MCF-7 cells. Potentiation of the antitumor activity in combined treatment of MCF-7 tumor-bearing mice is related to the reduced activity of aromatase by both An (enzyme inhibition) and vitamin D compounds (switched off/decreased aromatase gene expression, decreased expression of other genes related to estrogen signaling) and by regulation of the expression of the estrogen receptor ERα and VDR.     

Synthesis of Benzophenones and in vitro Evaluation of Their Anticancer Potential in Breast and Prostate Cancer Cells

Breast and prostate cancers are frequently treated with chemotherapy. Several novel chemicals are being reported for this purpose, particularly synthetic and natural benzophenones. This work reports the synthesis of substituted 2-hydroxybenzophenones through 1,4-conjugate addition/intramolecular cycloaddition/dehydration of nitromethane on key intermediate chromones. Structures were extensively studied by means of 2D NMR spectroscopy and single-crystal XRD. Their cytotoxicity was evaluated in vitro in two breast cancer cell lines (MDA-MB-231 and T47-D) and one prostate cancer cell line (PC3). The most potent compound exhibited good cytotoxic effects against the three cancer cell lines (IC₅₀ values ranging from 12.09 to 26.49 μm ) and induced cell-cycle retardation only on prostate cancer cells, which suggested that it might exert cell-type-specific effects.     

The biological mechanisms of butanol tolerance and the application of solvent-tolerant bacteria for environmental protection

Toxicity caused by the accumulation of butanol in fermentation media is an important factor limiting the concentration of butanol. There is currently no systematic research in place investigating the butanol tolerance mechanism of bacteria such as Clostridium acetobutylicum, which adapts to butanol stress and regulates its growth and metabolism. Here, research results related to the butanol tolerance of C. acetobutylicum are reviewed to understand the molecular basis of changes in butanol-tolerant strains. Organic solvent-tolerant bacteria play an important role in the fields of biofuel production, enzyme preparation and bioremediation. An analysis of limitations of the application of organic solvent-tolerant bacteria has revealed that future research should focus on combining the microbial tolerance phenotype with specific utilization to achieve an optimal balance between organic solvent tolerance and production. This review serves as a reference for the improvement and engineering of strains that tolerate organic solvents. © 2019 Society of Chemical Industry     

Damage mechanism at different transpassive potentials of solution-annealed 316 and 316l stainless steels

Electrochemical impedance spectroscopy (EIS), anodic polarization and scanning electron microscopy techniques were used to investigate the damage mechanism in the transpassive potential region of AISI ...     

基于关键路径延时检测的自适应电压缩减技术

为了减小传统的最差情况设计方法引入的电压裕量,提出了一种变化可知的自适应电压缩减(AVS)技术,通过调整电源电压来降低电路功耗.自适应电压缩减技术基于检测关键路径的延时变化,基于此设计了一款预错误原位延时检测电路,可以检测关键路径延时并输出预错误信号,进而控制单元可根据反馈回的预错误信号的个数调整系统电压.本芯片采用SMIC180 nm工艺设计验证,仿真分析表明,采用自适应电压缩减技术后,4个目标验证电路分别节省功耗12.4％,11.3％,10.4％和11.6％.     

Filtered adaptive constrained sampled-data control for uncertain multivariable nonlinear systems

A filtered adaptive constrained sampled-data controller for uncertain multivariable nonlinear systems in the presence of various constraints is synthesized in this paper. A piecewise constant adaptive law drives that estimation error dynamics to zero at each sampling time instant yields adaptive parameters. The filtered control scheme consists of two components. Based on an estimation/cancellation strategy, a disturbance rejection control law is designed to compensate the nonlinear uncertainties within the bandwidth of low-pass filters, whereas a constraint violation avoidance control law is designed to solve an online constrained optimization problem. Although a reduced sampling time helps to minimize the estimation error caused by the neglect of unknowns, the resulting aggressive signals put more restrictions on the control law. Greater sacrifice of tracking performance is required to satisfy the constraints. The constraints violation avoidance control law is in favor of a larger sampling time. Sufficient conditions are given to guarantee the stability of the closed-loop system with the sampled-data controller, where the input/output signals are held constant over the sampling period. Numerical examples are provided to validate the theoretical results, comparisons between the constrained sampled-data controller and unconstrained adaptive controller with the implementation of different sampling times are carried out.     

PROfound研究——前列腺癌精准治疗新希望

转移性去势抵抗性前列腺癌（metastatic castrate-resistant prostate cancer,mCRPC）是前列腺癌发展的终末阶段。患者生存预后很差。尽管不断地有新的治疗手段出现，比如新型内分泌治疗以及紫杉醇类化疗，mCRPC患者的生存期依然很有限。奥拉帕利是一款聚腺苷酸二磷酸核糖基聚合酶（poly ADP-ribose polymerase,PARP）抑制剂，PARP酶在DNA修复中扮演着重要的角色。奥拉帕利已经获批用于卵巢癌和乳腺癌的治疗。目前，奥拉帕利用于mCRPC治疗的III期临床研究PROfound的结果在2019年的欧洲肿瘤内科学会（ESMO）年会与2020年的美国临床肿瘤学会-泌尿生殖系统肿瘤研讨会（ASCO-GU）已经发布。本文将带来PROfound研究的结果以及最新的结果更新。     

The Gut Microbiota: A Potential Gateway to Improved Health Outcomes in Breast Cancer Treatment and Survivorship

Breast cancer is the most frequently diagnosed cancer in women worldwide. The disease and its treatments exert profound effects on an individual’s physical and mental health. There are many factors that impact an individual’s risk of developing breast cancer, their response to treatments, and their risk of recurrence. The community of microorganisms inhabiting the gastrointestinal tract, the gut microbiota, affects human health through metabolic, neural, and endocrine signaling, and immune activity. It is through these mechanisms that the gut microbiota appears to influence breast cancer risk, response to treatment, and recurrence. A disrupted gut microbiota or state of ‘dysbiosis’ can contribute to a biological environment associated with higher risk for cancer development as well as contribute to negative treatment side-effects. Many cancer treatments have been shown to shift the gut microbiota toward dysbiosis; however, the microbiota can also be positively manipulated through diet, prebiotic and probiotic supplementation, and exercise. The objective of this review is to provide an overview of the current understanding of the relationship between the gut microbiota and breast cancer and to highlight potential strategies for modulation of the gut microbiota that could lead to improved clinical outcomes and overall health in this population.     

Superior foetal electrocardiogram signal elicitation using a novel artificial intelligent Bayesian methodology

Innumerable casualties due to intrauterine hypoxia are a major worry during prenatal phase besides advanced patient monitoring with latest science and technology. Hence, the analysis of foetal electrocardiogram (fECG) signals is very vital in order to evaluate the foetal heart status for timely recognition of cardiac abnormalities. Regrettably, the latest technology in the cutting edge field of biomedical signal processing does not seem to yield the desired quality of fECG signals required by physicians, which is the major cause for the pathetic condition. The focus of this work is to extort non-invasive fECG signal with highest possible quality with a motive to support physicians in utilizing the methodology for the latest intrapartum monitoring technique called STAN (ST analysis) for forecasting intrapartum foetal hypoxia. However, the critical quandary is that the non-invasive fECG signals recorded from the maternal abdomen are affected by several interferences like power line interference, baseline drift interference, electrode motion interference, muscle movement interference and the maternal electrocardiogram (mECG) being the dominant interference. A novel hybrid methodology called BANFIS (Bayesian adaptive neuro fuzzy inference system) is proposed. The BANFIS includes a Bayesian filter and an adaptive neuro fuzzy filter for mECG elimination and non-linear artefacts removal to yield high quality fECG signal. Kalman filtering frame work has been utilized to estimate the nonlinear transformed mECG component in the abdominal electrocardiogram (aECG). The adaptive neuro fuzzy filter is employed to discover the nonlinearity of the nonlinear transformed version of mECG and to align the estimated mECG signal with the maternal component in the aECG signal for annulment. The outcomes of the investigation by the proposed BANFIS system proved valuable for STAN system for efficient prediction of foetal hypoxia.