ROR1 regulates chemoresistance in Breast Cancer via modulation of drug efflux pump ABCB1.

Chemoresistance is one of the leading causes of mortality in breast cancer (BC). Understanding the molecules regulating chemoresistance is critical in order to combat chemoresistant BC. Drug efflux pump ABCB1 is overexpressed in chemoresistant neoplasms where it effluxes various chemotherapeutic agents from cells.

The Validity, Reliability, Measurement Error, and Minimum Detectable Change of the 30-Second Fast-Paced Walk Test in Persons with Knee Osteoarthritis: A Novel Test of Short-Distance Walking Ability.

Objective: To develop and establish the reliability, validity, measurement error, and minimum detectable change of a novel 30-second fast-paced walk test (30SFW) in persons with knee osteoarthritis (OA) that is easy to administer and can quantify walking performance in persons of all abilities.

Methods: Twenty females with symptomatic knee OA (mean age [SD] 58.30 [8.

Discovery of a potential positive allosteric modulator of glucagon-like peptide 1 receptor through virtual screening and experimental study.

The Glucagon-like peptide 1 receptor (GLP-1R) is a well-established target for the treatment of type 2 diabetes and GLP-1R agonist-based therapies represent an effective approach which results in several GLP-1 analog drugs. However, the development of nonpeptidic agonist drugs targeting GLP-1R remains unsuccessful. A promising strategy aims to develop orally bioavailable, small-molecule positive allosteric modulators of GLP1-1R.

Intracellular trafficking and cytotoxicity of a gelatine-doxorubicin conjugate in two breast cancer cell lines.

Details of intracellular pathways of cytotoxicity remain unclear for doxorubicin conjugates being studied to treat breast cancer tumours. A high molecular weight gelatine-doxorubicin conjugate was investigated with an emphasis on lysosome participation. The conjugate was synthesised and characterised.

Synthesis and Antimicrobial Evaluation of γ-Borono Phosphonate Compounds in and .

Drug resistance in bacteria is a serious threat, and drugs with novel modes of action are constantly needed. Fosmidomycin is a naturally occurring antibiotic that inhibits the nonmevalonate pathway via inhibition of the enzyme 1-deoxylulose-5-phosphate reductoisomerase (DXR). This work is the first report in which a boronic acid is evaluated as an isostere of the retrohydroxamate moiety of fosmidomycin.

Clotrimazole Loaded Ufosomes for Topical Delivery: Formulation Development and In-Vitro Studies.

Global incidence of superficial fungal infections caused by dermatophytes is high and affects around 40 million people. It is the fourth most common cause of infection. Clotrimazole, a broad spectrum imidazole antifungal agent is widely used to treat fungal infections.

Structural Modeling and in Silico Screening of Potential Small-Molecule Allosteric Agonists of a Glucagon-like Peptide 1 Receptor.

The glucagon-like peptide 1 receptor (GLP-1R) belongs to the pharmaceutically important class B family of G-protein-coupled receptors (GPCRs), and its incretin peptide ligand GLP-1 analogs are adopted drugs for the treatment of type 2 diabetes. Despite remarkable antidiabetic effects, GLP-1 peptide-based drugs are limited by the need of injection. On the other hand, developing nonpeptidic small-molecule drugs targeting GLP-1R remains elusive.

Decreased liver triglyceride content in adult rats exposed to protein restriction during gestation and lactation: roles of hepatic lipogenesis and lipid utilization in muscle and adipose tissue.

Protein restriction throughout pregnancy and lactation reduces liver triglyceride (TG) content in adult male rat offspring. The study determined the contribution of hepatic lipogenesis to the reduction in liver TG content. Rats received either control or protein-restricted diets throughout pregnancy and lactation.

Strictinin, a novel ROR1-inhibitor, represses triple negative breast cancer survival and migration via modulation of PI3K/AKT/GSK3ß activity.

Triple Negative Breast Cancer (TNBC), the most aggressive subtype of breast cancer, is characterized by the absence of hormone receptors usually targeted by hormone therapies like Tamoxifen. Because therapy success and survival rates for TNBC lag far behind other breast cancer subtypes, there is significant interest in developing novel anti-TNBC agents that can target TNBC specifically, with minimal effects on non-malignant tissue. To this aim, our study describes the anti-TNBC effect of strictinin, an ellagitanin previously isolated from Myrothamnus flabellifolius.

Grading and baseline characteristics of meibomian glands in meibography images and their clinical associations in the Dry Eye Assessment and Management (DREAM) study.

Purpose: To describe and evaluate a comprehensive grading system for meibomian gland (MG) digital infrared images developed for the Dry Eye Assessment and Management (DREAM) Study.

Methods: Cross-sectional study. Reading Center (RC) certified readers independently evaluated MG features of both lids from meibography images of dry eye disease subjects.

Assessment of pre-operative psychosocial function among people receiving left ventricular assist devices: A national survey of US LVAD programs.

Background: The International Society for Heart & Lung Transplantation (ISHLT) guidelines for Mechanical Circulatory Support (MCS) includes assessment of four elements of psychosocial functioning prior to Left Ventricular Assist Device (LVAD) implantation. Information about the practices and impact of assessments of psychosocial functioning are limited.

Objective: To describe the psychosocial function assessment practices used within US LVAD programs and the influence of psychosocial assessment results on clinical decisions for LVAD patient selection.

Pharmaceutical feasibility and flow characteristics of polymeric non-spherical particles.

Last decade has seen emergence of particle shape as a critical design parameter to overcome several long standing problems associated with particulate drug delivery- non-specific drug effects, RES uptake, poor bioavailability, achieving controlled release profiles, predictable degradation profiles, longer circulation time and zero order release kinetics to name a few. Non-spherical particles have been synthesized by techniques ranging from classical solvent evaporation to specialized techniques like film stretching and PRINT®. Non-spherical particles tend to show a difference in macrophage uptake, adhesion to target cells and distribution in vivo.

Bicycloheptylamine-Doxorubicin Conjugate: Synthesis and Anticancer Activities in σ2 Receptor-Expressing Cell Lines.

Background: Novel bicycloheptylamines were designed and synthesized. These compounds were found to be selective for sigma-2 receptors. These receptors have been found to be up to 10 fold over-expressed in certain cancer cell lines, leading to investigation of possible uses as a biomarker in diagnosis and/or treatment especially in cancers with poor prognosis.

PML is recruited to heterochromatin during S phase and represses DAXX-mediated histone H3.3 chromatin assembly.

The incorporation of the histone H3 variant, H3.3, into chromatin by the H3.3-specific chaperone DAXX and the ATP-dependent chromatin remodeling factor ATRX is a critical mechanism for silencing repetitive DNA.

CPAP Adherence May Slow 1-Year Cognitive Decline in Older Adults with Mild Cognitive Impairment and Apnea.

Background/objectives: Obstructive sleep apnea (OSA) has been linked to an increased risk for Alzheimer's disease (AD), but little prospective evidence exists on the effects of OSA treatment in preclinical AD. The objective was to determine if continuous positive airway pressure (CPAP) treatment adherence, controlling for baseline differences, predicts cognitive and everyday function after 1 year in older adults with mild cognitive impairment (MCI) and to determine effect sizes for a larger trial.

Design: Quasi-experimental pilot clinical trial with CPAP adherence defined as CPAP use 4 hours or more per night over 1 year.

Reciprocal control of motility and biofilm formation by the PdhS2 two-component sensor kinase of Agrobacterium tumefaciens.

A core regulatory pathway that directs developmental transitions and cellular asymmetries in Agrobacterium tumefaciens involves two overlapping, integrated phosphorelays. One of these phosphorelays putatively includes four histidine sensor kinase homologues, DivJ, PleC, PdhS1 and PdhS2, and two response regulators, DivK and PleD. In several different alphaproteobacteria, this pathway influences a conserved downstream phosphorelay that ultimately controls the phosphorylation state of the CtrA master response regulator.

Administration of Fenofibrate Markedly Elevates Fabp3 in Rat Liver and Plasma and Confounds Its Use as a Preclinical Biomarker of Cardiac and Muscle Toxicity.

Proteins involved in lipid homeostasis are often regulated through the nuclear peroxisome proliferator-activated receptors (PPAR). PPARα is the target for the fibrate-class of drugs. Fenofibrate has been approved for its lipid-lowering effects in patients with hypercholesterolemia and hypertriglyceridemia.

Correction to: Accelerating evidence gathering and approval of precision medicine therapies: the FDA takes aim at rare mutations.

In the original version of this Article, the affiliation details for Personalized Medicine & Targeted Therapeutics, USA were incorrectly given as Personalized Medicine & Targeted Therapeutics, University of the Sciences in Philadelphia, Philadelphia, Pennsylvania, USA. This has now been corrected in both the PDF and HTML versions of the Article.

Intramolecular Natural Energy Decomposition Analysis: Applications to the Rational Design of Foldamers.

We describe an intramolecular version of the natural energy decomposition analysis (NEDA), with the aim of evaluating interactions between molecular fragments across covalent bonds. The electronic energy in intramolecular natural energy decomposition analysis (INEDA) is divided into electrical, core, and charge transfer components. The INEDA method describes the fragments using the nonfragmented electronic density, and, therefore, there are no limitations in how to choose the boundary orbital.

Rpp29 regulates histone H3.3 chromatin assembly through transcriptional mechanisms.

The histone H3 variant H3.3 is a highly conserved and dynamic regulator of chromatin organization. Therefore, fully elucidating its nucleosome incorporation mechanisms is essential to understanding its functions in epigenetic inheritance.

Cardiotoxic effects of chemotherapy: A review of both cytotoxic and molecular targeted oncology therapies and their effect on the cardiovascular system.

Cardiotoxic effects of chemotherapy and targeted drugs are ubiquitous and challenging in the field of oncology therapeutics. The broad spectrum of toxicities ranging from ischemic, hypertensive, cardiomyopathic, and arrhythmic complications can present as a significant challenge for clinicians treating cancer patients. If early diagnosis and intervention of cardiotoxic complications is missed, this can lead to delay or abrogation of planned treatment, which can potentially culminate to significant morbidity due to not only the cardiotoxic complications but also the progression of cancer.

Correction: Fevers in Adult Lupus Patients.

[This corrects the article DOI: 10.7759/cureus.2098.

Protection of the Benzoxaborole Moiety: Synthesis and Functionalization of Zwitterionic Benzoxaborole Complexes.

The synthesis and utility of three benzoxaborole protecting groups are reported. These protecting groups improve organic solubility and allow otherwise incompatible reactions (oxidations, substitutions, and mild reductions) to be achieved in the presence of the benzoxaborole moiety. 3-( N, N-Dimethylamino)-1-propanol was determined to be useful in one-step sequences and is readily cleaved upon workup.

A cell surface display fluorescent biosensor for measuring MMP14 activity in real-time.

Despite numerous recent advances in imaging technologies, one continuing challenge for cell biologists and microscopists is the visualization and measurement of endogenous proteins as they function within living cells. Achieving this goal will provide a tool that investigators can use to associate cellular outcomes with the behavior and activity of many well-studied target proteins. Here, we describe the development of a plasmid-based fluorescent biosensor engineered to measure the location and activity of matrix metalloprotease-14 (MMP14).