Androgen receptor inhibition increases MHC Class I expression and improves immune response in prostate cancer.

Tumors escape immune detection and elimination through a variety of mechanisms. Here, we used prostate cancer as a model to examine how androgen-dependent tumors undergo immune evasion through downregulation of the major histocompatibility complex class I (MHCI). We report that response to immunotherapy in late-stage prostate cancer is associated with elevated MHC expression.

Evaluating ATP testing for distribution system monitoring: comparison to HPC, impact of chlorine quenching, and hold time dependency.

Adenosine triphosphate (ATP) assays have a faster turnaround time and higher sensitivity than traditional cultivation methods for microbial monitoring. Challenges implementing ATP testing include incompatibility with chlorine quenching agents and hold time sensitivity, which are not well-studied. Chlorinated distribution system samples were collected from two Canadian utilities, Metro Vancouver (n = 40 samples) and Halifax Water (n = 283).

Ginkgolide A improves the pleiotropic function and reinforces the neuroprotective effects by mesenchymal stem cell-derived exosomes in 6-OHDA-induced cell model of Parkinson's disease.

Parkinson's disease (PD) is a common disorder attributed to the loss of midbrain dopamine (mDA) neurons and reduced dopamine secretion. Currently, the treatment regimes for PD comprise deep brain stimulations, however, it attenuates the PD progression marginally and does not improve neuronal cell death. We investigated the function of Ginkgolide A (GA) to reinforce Wharton's Jelly-derived mesenchymal stem cells (WJMSCs) for treating the model of PD.

Estimating the impact of drug addiction causes heart damage.

To date, few studies have investigated the toxicological effects of the combined use of amphetamine and heroin in the heart. Hence, the aim of this study was to identify indicators for clinical evaluation and prevention of cardiac injury induced by the combined use of amphetamine and heroin. Four different groups were analyzed: (1) normal group (＝25；average age＝35 ± 6.

Neuroprotective Effects of Probiotic Lactobacillus reuteri GMNL-263 in the Hippocampus of Streptozotocin-Induced Diabetic Rats.

Diabetes-related brain complications have been reported in clinical patients and experimental models. The objective of the present study was to investigate the neuroprotective mechanisms of Lactobacillus reuteri GMNL-263 in streptozotocin (STZ)-induced diabetic rats. In this study, three different groups, namely control group, STZ-induced (55 mg/kg streptozotocin intraperitoneally) diabetic rats (DM), and DM rats treated with Lactobacillus reuteri GMNL-263 (1 × 10 CFU/rat/day), were utilized to study the protective effect of GMNL-263 in the hippocampus of STZ-induced diabetic rats.

Glycyrrhiza uralensis root extract ameliorates high glucose-induced renal proximal tubular fibrosis by attenuating tubular epithelial-myofibroblast transdifferentiation by targeting TGF-β1/Smad/Stat3 pathway.

Growing evidences indicate that high glucose toxicity-associated fibrotic effects play a pivotal role in diabetic nephropathy (DN). Tubular epithelial-myofibroblast transdifferentiation is a major hallmark of renal fibrosis event under diabetic stress. Roots of Glycyrrhiza uralensis (Radix glycyrrhizae) used as a sweetener and traditional Chinese medicine possess high potential for renal protection.

Perturbed ER homeostasis by IGF-IIRα promotes cardiac damage under stresses.

The heart is a very dynamic pumping organ working perpetually to maintain a constant blood supply to the whole body to transport oxygen and nutrients. Unfortunately, it is also subjected to various stresses based on physiological or pathological conditions, particularly more vulnerable to damages caused by oxidative stress. In this study, we investigate the molecular mechanism and contribution of IGF-IIRα in endoplasmic reticulum stress induction in the heart under doxorubicin-induced cardiotoxicity.

Predicting cancer drug TARGETS - TreAtment Response Generalized Elastic-neT Signatures.

We are now in an era of molecular medicine, where specific DNA alterations can be used to identify patients who will respond to specific drugs. However, there are only a handful of clinically used predictive biomarkers in oncology. Herein, we describe an approach utilizing in vitro DNA and RNA sequencing and drug response data to create TreAtment Response Generalized Elastic-neT Signatures (TARGETS).

An integrated functional and clinical genomics approach reveals genes driving aggressive metastatic prostate cancer.

Genomic sequencing of thousands of tumors has revealed many genes associated with specific types of cancer. Similarly, large scale CRISPR functional genomics efforts have mapped genes required for cancer cell proliferation or survival in hundreds of cell lines. Despite this, for specific disease subtypes, such as metastatic prostate cancer, there are likely a number of undiscovered tumor specific driver genes that may represent potential drug targets.

IGF IIRα-triggered pathological manifestations in the heart aggravate renal inflammation in STZ-induced type-I diabetes rats.

Pathological manifestations in either heart or kidney impact the function of the other and form the basis for the development of cardiorenal syndrome. However, the mechanism or factors involved in such scenario are not completely elucidated. In our study, to find the correlation between late fetal gene expression in diabetic hearts and their influence on diabetic nephropathy, we created a rat model with cardiac specific overexpression of IGF-IIRα, which is an alternative splicing variant of IGFIIR, expressed in pathological hearts.

Autoantibody Landscape in Patients with Advanced Prostate Cancer.

Purpose: Autoantibody responses in cancer are of great interest, as they may be concordant with T-cell responses to cancer antigens or predictive of response to cancer immunotherapies. Thus, we sought to characterize the antibody landscape of metastatic castration-resistant prostate cancer (mCRPC).

Experimental Design: Serum antibody epitope repertoire analysis (SERA) was performed on patient serum to identify tumor-specific neoepitopes.

Epigallocatechin-3-gallate preconditioned Adipose-derived Stem Cells confer Neuroprotection in aging rat brain.

Aging is the most important current issue and is usually accompanied by complications, such as cardiovascular disorders and neurodegenerative diseases, which are the leading causes of death worldwide and the second major cause of death in Taiwan. In this study, we have investigated the protective effect of adipose-derived mesenchymal stem cells (ADSCs) and the role of epigallocatechin gallate (EGCG) in enhancing this effect in aging cerebral cortex of rats. Further, we attempted to elucidate the molecular mechanism through which EGCG influences the protective effects of ADSC.

Copy Number Loss of 17q22 Is Associated with Enzalutamide Resistance and Poor Prognosis in Metastatic Castration-Resistant Prostate Cancer.

Purpose: The purpose of this study was to measure genomic changes that emerge with enzalutamide treatment using analyses of whole-genome sequencing and RNA sequencing.

Experimental Design: One hundred and one tumors from men with metastatic castration-resistant prostate cancer (mCRPC) who had not been treated with enzalutamide ( = 64) or who had enzalutamide-resistant mCRPC ( = 37) underwent whole genome sequencing. Ninety-nine of these tumors also underwent RNA sequencing.

The DNA methylation landscape of advanced prostate cancer.

Although DNA methylation is a key regulator of gene expression, the comprehensive methylation landscape of metastatic cancer has never been defined. Through whole-genome bisulfite sequencing paired with deep whole-genome and transcriptome sequencing of 100 castration-resistant prostate metastases, we discovered alterations affecting driver genes that were detectable only with integrated whole-genome approaches. Notably, we observed that 22% of tumors exhibited a novel epigenomic subtype associated with hypermethylation and somatic mutations in TET2, DNMT3B, IDH1 and BRAF.

Down-regulation of ADRB2 expression is associated with small cell neuroendocrine prostate cancer and adverse clinical outcomes in castration-resistant prostate cancer.

Objectives: The net oncogenic effect of β2-adrenergic receptor ADRB2, whose downstream elements induce neuroendocrine differentiation and whose expression is regulated by EZH2, is unclear. ADRB2 expression and associated clinical outcomes in metastatic castration-resistant prostate cancer (mCRPC) are unknown.

Methods And Materials: This was a retrospective analysis of a multi-center, prospectively enrolled cohort of mCRPC patients.

Swimming exercise stimulates IGF1/ PI3K/Akt and AMPK/SIRT1/PGC1α survival signaling to suppress apoptosis and inflammation in aging hippocampus.

Hippocampus is one of the most vulnerable brain regions in terms of age-related pathological change. Exercise is presumed to delay the aging process and promote health because it seems to improve the function of most of the aging mechanisms. The purpose of this study is to evaluate the effects of swimming exercise training on brain inflammation, apoptotic and survival pathways in the hippocampus of D-galactose-induced aging in SD rats.

Uncovering axes of variation among single-cell cancer specimens.

While several tools have been developed to map axes of variation among individual cells, no analogous approaches exist for identifying axes of variation among multicellular biospecimens profiled at single-cell resolution. For this purpose, we developed 'phenotypic earth mover's distance' (PhEMD). PhEMD is a general method for embedding a 'manifold of manifolds', in which each datapoint in the higher-level manifold (of biospecimens) represents a collection of points that span a lower-level manifold (of cells).