Proteasome-associated deubiquitinase ubiquitin-specific protease 14 regulates prostate cancer proliferation by deubiquitinating and stabilizing androgen receptor.

Androgen receptor (AR) is frequently over-expressed and plays a critical role in the growth and progression of human prostate cancer. The therapy attempting to target AR signalling was established in decades ago but the treatment of prostate cancer is far from being satisfactory. The assignable cause is that our understanding of the mechanism of AR regulation and re-activation remains incomplete.

Repurposing an antidandruff agent to treating cancer: zinc pyrithione inhibits tumor growth via targeting proteasome-associated deubiquitinases.

The ubiquitin-proteasome system (UPS) plays a central role in various cellular processes through selectively degrading proteins involved in critical cellular functions. Targeting UPS has been validated as a novel strategy for treating human cancer, as inhibitors of the 20S proteasome catalytic activity are currently in clinical use for treatment of multiple myeloma and other cancers, and the deubiquitinase activity associated with the proteasome is also a valid target for anticancer agents. Recent studies suggested that zinc pyrithione, an FDA-approved antidandruff agent, may have antitumor activity, but the detailed molecular mechanisms remain unclear.

Assessment of murine colorectal cancer by micro-ultrasound using three dimensional reconstruction and non-linear contrast imaging.

The relatively low success rates of current colorectal cancer (CRC) therapies have led investigators to search for more specific treatments. Vertebrate models of colorectal cancer are essential tools for the verification of new therapeutic avenues such as gene therapy. The evaluation of colorectal cancer in mouse models has been limited due to the lack of an accurate quantitative and longitudinal noninvasive method.

Nickel pyrithione induces apoptosis in chronic myeloid leukemia cells resistant to imatinib via both Bcr/Abl-dependent and Bcr/Abl-independent mechanisms.

Background: Acquired imatinib (IM) resistance is frequently characterized by Bcr-Abl mutations that affect IM binding and kinase inhibition in patients with chronic myelogenous leukemia (CML). Bcr-Abl-T315I mutation is the predominant mechanism of the acquired resistance to IM. Therefore, it is urgent to search for additional approaches and targeting strategies to overcome IM resistance.

Severe mortality impact of the 1957 influenza pandemic in Chile.

Introduction: Epidemiological studies of the 1957 influenza pandemic are scarce, particularly from lower-income settings.

Methods: We analyzed the spatial-temporal mortality patterns of the 1957 influenza pandemic in Chile, including detailed age-specific mortality data from a large city, and investigated risk factors for severe mortality impact across regions.

Results: Chile exhibited two waves of excess mortality in winter 1957 and 1959 with a cumulative excess mortality rate of 12 per 10 000, and a ~10-fold mortality difference across provinces.

Sex-related differences in reactivity of cerebral arterioles during moderate exercise training.

Objective: Our goals were to determine the influence of sex on reactivity of cerebral arterioles and whether MExT could influence sex-related differences in reactivity of cerebral arterioles.

Materials And Methods: Responses of cerebral arterioles were measured in Sed and MExT adult male and female Sprague-Dawley rats to eNOS-dependent (ADP), nNOS-dependent (NMDA), and NOS-independent (nitroglycerin) agonists before and following L-NMMA. In addition, protein expression for eNOS and nNOS was determined.

SUSD2 expression in high-grade serous ovarian cancer correlates with increased patient survival and defective mesothelial clearance.

The cause of death among the majority of epithelial ovarian cancer (EOC) patients involves passive dissemination of cancer cells within the peritoneal cavity and subsequent implantation of cancer spheroids into adjacent organs. Thus, it is important to identify the factors that mediate EOC metastasis and implantation, including clearance of the mesothelium. Sushi domain containing 2 (SUSD2) encodes a type I transmembrane protein containing several functional domains inherent to adhesion molecules.

Sexual dimorphism of cardiopulmonary regulation in the arcuate nucleus of the hypothalamus.

The arcuate nucleus of the hypothalamus (ANH) interacts with other hypothalamic nuclei, forebrain regions, and downstream brain sites to affect autonomic nervous system outflow, energy balance, temperature regulation, sleep, arousal, neuroendocrine function, reproduction, and cardiopulmonary regulation. Compared to studies of other ANH functions, how the ANH regulates cardiopulmonary function is less understood. Importantly, the ANH exhibits structural and functional sexually dimorphic characteristics and contains numerous neuroactive substances and receptors including leptin, neuropeptide Y, glutamate, acetylcholine, endorphins, orexin, kisspeptin, insulin, Agouti-related protein, cocaine and amphetamine-regulated transcript, dopamine, somatostatin, components of renin-angiotensin system and gamma amino butyric acid that modulate physiological functions.

A novel mouse model for the identification of thioredoxin-1 protein interactions.

Thiol switches are important regulators of cellular signaling and are coordinated by several redox enzyme systems including thioredoxins, peroxiredoxins, and glutathione. Thioredoxin-1 (Trx1), in particular, is an important signaling molecule not only in response to redox perturbations, but also in cellular growth, regulation of gene expression, and apoptosis. The active site of this enzyme is a highly conserved C-G-P-C motif and the redox mechanism of Trx1 is rapid which presents a challenge in determining specific substrates.

UBXD Proteins: A Family of Proteins with Diverse Functions in Cancer.

The UBXD family is a diverse group of UBX (ubiquitin-regulatory X) domain-containing proteins in mammalian cells. Members of this family contain a UBX domain typically located at the carboxyl-terminal of the protein. In contrast to the UBX domain shared by all members of UBXD family, the amino-terminal domains are diverse and appear to carry out different roles in a subcellular localization-dependent manner.

The effect of social networking sites on the relationship between perceived social support and depression.

This study examined whether Social Networking Sites (SNSs) have a negative moderator effect on the established relationship between perceived social support and depression in psychiatric inpatients. Survey instruments assessing for depression, perceived social support, and SNS use, were filled out by 301 psychiatric inpatients. Additional data on age, gender, and primary psychiatric diagnosis were collected.

Red blood cell PUFAs reflect the phospholipid PUFA composition of major organs.

Numerous clinical trials examining the use of omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFAs) on various health outcomes have been conducted, and fish oil remains one of the most widely used nutritional supplements. More recently, studies have begun to utilize the omega-3 index, defined as the sum of EPA+DHA in red blood cells (RBCs), as both a biomarker of n-3 LCPUFA exposure and a potential risk factor for coronary heart disease (CHD). Considerably less research evaluates whether RBC phospholipid fatty acids reflect the phospholipid fatty acid composition of other tissues across increasing intakes of n-3 LCPUFAs.

PTSD, alcohol dependence, and conduct problems: Distinct pathways via lability and disinhibition.

This study tested the role of affect lability and disinhibition in mediating associations between PTSD symptoms and two forms of alcohol-related problems, dependence syndrome symptoms (e.g., impaired control over consumption) and conduct problems (e.

Current Issues with Hysterectomy.

Hysterectomy is one of the most common gynecologic surgeries. Early adoption of surgical advancements in hysterectomies has raised concerns over safety, quality, and costs. The risk of potential leiomyosarcoma in women undergoing minimally invasive hysterectomy led the US Food and Drug Administration to discourage the use of electronic power morcellator.

A Decision Tree to Identify Children Affected by Prenatal Alcohol Exposure.

Objective: To develop and validate a hierarchical decision tree model that combines neurobehavioral and physical measures to identify children affected by prenatal alcohol exposure even when facial dysmorphology is not present.

Study Design: Data were collected as part of a multisite study across the US. The model was developed after we evaluated more than 1000 neurobehavioral and dysmorphology variables collected from 434 children (8-16 years of age) with prenatal alcohol exposure, with and without fetal alcohol syndrome, and nonexposed control subjects, with and without other clinically-relevant behavioral or cognitive concerns.

Identification of Redox and Glucose-Dependent Txnip Protein Interactions.

Thioredoxin-interacting protein (Txnip) acts as a negative regulator of thioredoxin function and is a critical modulator of several diseases including, but not limited to, diabetes, ischemia-reperfusion cardiac injury, and carcinogenesis. Therefore, Txnip has become an attractive therapeutic target to alleviate disease pathologies. Although Txnip has been implicated with numerous cellular processes such as proliferation, fatty acid and glucose metabolism, inflammation, and apoptosis, the molecular mechanisms underlying these processes are largely unknown.

Platinum-containing compound platinum pyrithione is stronger and safer than cisplatin in cancer therapy.

DNA is the well-known molecular target of current platinum-based anticancer drugs; consequently, their clinical use is severely restricted by their systemic toxicities and drug resistance originating from non-selective DNA damage. Various strategies have been developed to circumvent the shortcomings of platinum-based chemotherapy but the inherent problem remains unsolved. Here we report that platinum pyrithione (PtPT), a chemically well-characterized synthetic complex of platinum, inhibits proteasome function and thereby exhibits greater and more selective cytotoxicity to multiple cancer cells than cisplatin, without showing discernible DNA damage both in vitro and in vivo.

Heat Shock Protein 70s as Potential Molecular Targets for Colon Cancer Therapeutics.

Background: Targeted drugs modulate selective pathways activated or repressed only in cancer cells, resulting in a higher response to chemotherapy with less severe side effects. The use of a selected member of the heat shock protein 70 family (HSP70) as an effective therapeutic target in the treatment of colorectal cancer (CRC) will be the focus of this review.

Methods: We generated two main questions for this study: 1) What are the current and potential future molecular therapies in CRC? 2) Can selective members of the HSP70 family advance drug design and drug discovery for treatment of CRC patients? We discuss related articles based on their significance and translational contributions to the existing literature.

Macrophage responses to 316L stainless steel and cobalt chromium alloys with different surface topographies.

The surface topography of a biomaterial plays a vital role in determining macrophage interactions and influencing immune response. In this study, we investigated the effect of smooth and microrough topographies of commonly used metallic biomaterials such as 316 L stainless steel (SS) and cobalt-chromium (CoCr) alloys on macrophage interactions. The macrophage adhesion was greater on CoCr compared to SS, irrespective of their topographies.

Correlates of Receipt of Colorectal Cancer Screening among American Indians in the Northern Plains.

Research has consistently documented lower colorectal cancer (CRC) screening rates for racial and ethnic minority populations, with the lowest screening rates among American Indians (AIs). Given the low CRC screening rates among AIs residing in the Northern Plains region, the objective of this research was to identify CRC screening correlates for Northern Plains AIs. With a sample of 181 AIs age 50 years or older, the authors used Andersen's behavioral model to examine the following factors related to receipt of CRC screening: (a) predisposing factors-age, education, marital status, and gender; (b) need factors-personal and family history of cancer; and (c) enabling factors-having a particular place to receive medical care, annual health checkup, awareness of the availability of CRC screening, knowledge of CRC, and self-efficacy of CRC.

Fetal alcohol spectrum disorders and assessment of maxillary and mandibular arc measurements.

Fetal alcohol spectrum disorders (FASD) comprise a range of physical differences and neurologic deficits from prenatal alcohol exposure. Previous studies suggest that relative maxillary growth deficiency can accompany FASD. Using the Fetal Alcohol Syndrome Epidemiologic Research (FASER) database, we investigated how maxillary and mandibular arcs and the ratio between them differ between FASD and non-FASD individuals.

Vaginal cuff dehiscence: a randomized trial comparing robotic vaginal cuff closure methods.

The purpose of this study is to compare the rate of vaginal cuff dehiscence between two different methods of closure in patients undergoing robotic-assisted total laparoscopic hysterectomy and explore variables related to postoperative breakdown. This was a prospective, randomized controlled study with two arms. The control group (Arm 1) underwent single-layer continuous closure while the study group (Arm 2) had three additional imbricating figure-of-X sutures placed in addition to the standard protocol.

Mifepristone increases mRNA translation rate, triggers the unfolded protein response, increases autophagic flux, and kills ovarian cancer cells in combination with proteasome or lysosome inhibitors.

The synthetic steroid mifepristone blocks the growth of ovarian cancer cells, yet the mechanism driving such effect is not entirely understood. Unbiased genomic and proteomic screenings using ovarian cancer cell lines of different genetic backgrounds and sensitivities to platinum led to the identification of two key genes upregulated by mifepristone and involved in the unfolded protein response (UPR): the master chaperone of the endoplasmic reticulum (ER), glucose regulated protein (GRP) of 78 kDa, and the CCAAT/enhancer binding protein homologous transcription factor (CHOP). GRP78 and CHOP were upregulated by mifepristone in ovarian cancer cells regardless of p53 status and platinum sensitivity.

Emergency Department Utilization for Mental Health in American Indian Children.

Objectives: To examine emergency department (ED) visits for mental health concerns by American Indian children in a multicenter cohort. To analyze demographic and clinical factors, the types of mental health concerns, and repeat mental health visits.

Study Design: Cross-sectional study of children 5-18 years old who visited 1 of 6 EDs in the Upper Midwest from June 2011 to May 2012 and self-identified as white or American Indian.

Responses of endothelial cells, smooth muscle cells, and platelets dependent on the surface topography of polytetrafluoroethylene.

In this study, the effect of different structures (flat, expanded, and electrospun) of polytetrafluoroethylene (PTFE) on the interactions of endothelial cells (ECs), smooth muscle cells (SMCs), and platelets was investigated. In addition, the mechanisms that govern the interactions between ECs, SMCs, and platelets with different structures of PTFE were discussed. The surface characterizations showed that the different structures of PTFE have the same surface chemistry, similar surface wettability and zeta potential, but uniquely different surface topography.