Enhancing the Therapeutic Efficacy of Bortezomib in Cancer Therapy Using Polymeric Nanostructures.

Bortezomib (VELCADE®) is a boronate peptide and first-in-class proteasome inhibitor serving an important role in degenerating several intracellular proteins. It is a reversible inhibitor of the 26S proteasome, with antitumor activity and antiproliferative properties. This agent principally exerts its antineoplastic effects by inhibiting key players in the nuclear factor κB (NFκB) pathway involved in cell proliferation, apoptosis, and angiogenesis.

Parenteral systems for statin delivery: a review.

The oral route of drug administration is the most common and convenient route for dosing statin drugs, and, in fact, most medications, because of ease of drug delivery, patient compliance, and cost-effectiveness. However, the oral administration of statin drugs has disadvantages such as hepatic first-pass metabolism and degradation within the gastrointestinal tract that limit their overall bioavailability. This review introduces several diverse non-oral delivery methods for the administration of statins.

The trophic niche of sculpins Cottus spp. in forage fish assemblages of boreal lakes.

We compared the trophic niches of freshwater sculpins Cottus spp. with those of other co-habiting forage fishes in two groups of boreal lakes with distinct habitats and fish communities. Near North Lakes (45° 00' to 47° 30' N) were deeper, stratified and contained lake trout Salvelinus namaycush as the apex piscivore, whereas Far North Lakes (51° 10' to 52° 20' N) were shallower, did not stratify and contained pike Esox lucius and walleye Sander vitreus as the apex piscivores.

A new approach to the diagnosis and treatment of atherosclerosis: the era of the liposome.

The consequences of atherosclerotic cardiovascular disease (ASCVD) include myocardial infarction, ischemic stroke, and angina pectoris, which are major causes of mortality and morbidity worldwide. Despite current therapeutic strategies to reduce risk, patients still experience the consequences of ASCVD. Consequently, a current goal is to enhance visualization of early atherosclerotic lesions to improve residual ASCVD risk.

Bone Mineral Density Testing in Spinal Cord Injury: 2019 ISCD Official Position.

Spinal cord injury (SCI) causes rapid osteoporosis that is most severe below the level of injury. More than half of those with motor complete SCI will experience an osteoporotic fracture at some point following their injury, with most fractures occurring at the distal femur and proximal tibia. These fractures have devastating consequences, including delayed union or nonunion, cellulitis, skin breakdown, lower extremity amputation, and premature death.

The Role of Mesenchymal Stem Cells in Atherosclerosis: Prospects for Therapy via the Modulation of Inflammatory Milieu.

Atherosclerosis is a chronic, inflammatory disease that mainly affects the arterial intima. The disease is more prevalent in middle-age and older individuals with one or more cardiovascular risk factors, including dyslipidemia, hypertension, diabetes, smoking, obesity, and others. The beginning and development of atherosclerosis has been associated with several immune components, including infiltration of inflammatory cells, monocyte/macrophage-derived foam cells, and inflammatory cytokines and chemokines.

A general approach for predicting protein epitopes targeted by antibody repertoires using whole proteomes.

Antibodies are essential to functional immunity, yet the epitopes targeted by antibody repertoires remain largely uncharacterized. To aid in characterization, we developed a generalizable strategy to predict antibody-binding epitopes within individual proteins and entire proteomes. Specifically, we selected antibody-binding peptides for 273 distinct sera out of a random library and identified the peptides using next-generation sequencing.

Unfolded protein response-mediated modulation of mesenchymal stem cells.

The endoplasmic reticulum (ER) receives unfolded proteins predestined for the secretory pathway or to be incorporated as transmembrane proteins. The ER has to accommodate the proper folding and glycosylation of these proteins and also to properly incorporate transmembrane proteins. However, under various circumstances, the proteins shuttling through the ER can be misfolded and undergo aggregation, which causes activation of the unfolded protein response (UPR).

Poly(alkyl glycidyl ether) hydrogels for harnessing the bioactivity of engineered microbes.

Herein, we describe a method to produce yeast-laden hydrogel inks for the direct-write 3D printing of cuboidal lattices for immobilized whole-cell catalysis. A poly(alkyl glycidyl ether)-based triblock copolymer was designed to have three important features for this application: (1) a temperature response, which allowed for facile processing of the material; (2) a shear response, which facilitated the extrusion of the material through a nozzle; and (3) UV light induced polymerization, which enabled the post-extrusion chemical crosslinking of network chains, and the fabrication of robust printed objects. These three key stimuli responses were confirmed via rheometrical characterization.

Efferocytosis and Atherosclerosis: Regulation of Phagocyte Function by MicroRNAs.

There is evidence of the critical role of efferocytosis, the clearance of apoptotic cells (ACs) by phagocytes, in vascular cell homeostasis and protection against atherosclerosis. Specific microRNAs (miRs) can regulate atherogenesis by controlling the accumulation of professional phagocytes (e.g.

Erratum: Mesothelioma subtypes of the tunica vaginalis: a rare case report and review of histological criteria.

[This corrects the article DOI: 10.1093/jscr/rjz040.].

Should a colonoscopy be offered routinely to patients with CT proven acute diverticulitis? A retrospective cohort study and meta-analysis of best available evidence.

Background: The current guidelines suggest that patients should undergo endoscopic evaluation of the colonic lumen after an episode of computed tomography (CT) proven acute diverticulitis to rule out malignancy. The usefulness of routine endoscopic evaluation of CT proven diverticulitis remains unknown.

Aim: To establish whether routine colonoscopy should be offered to patients after an episode of diverticulitis.

An experimental study of a virtual reality counselling paradigm using embodied self-dialogue.

When faced with a personal problem people typically give better advice to others than to themselves. A previous study showed how it is possible to enact internal dialogue in virtual reality (VR) through participants alternately occupying two different virtual bodies - one representing themselves and the other Sigmund Freud. They could maintain a self-conversation by explaining their problem to the virtual Freud and then from the embodied perspective of Freud see and hear the explanation by their virtual doppelganger, and then give some advice.

Demethoxycurcumin: A naturally occurring curcumin analogue for treating non-cancerous diseases.

Turmeric extracts contain three primary compounds, which are commonly referred to as curcuminoids. They are curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin. While curcumin has been the most extensively studied of the curcuminoids, it suffers from low overall oral bioavailability due to extremely low absorption as a result of low water solubility and instability at acidic pH, as well as rapid metabolism and clearance from the body.

Crocin Improves Oxidative Stress by Potentiating Intrinsic Anti-Oxidant Defense Systems in Pancreatic Cells During Uncontrolled Hyperglycemia.

Introduction: Oxidative stress (OS) during uncontrolled hyperglycemia has a pivotal role in pancreatic dysfunction. Our study aimed to demonstrate that crocin can potentiate anti-oxidant defense systems of pancreatic cells to improve oxidative stress.

Methods: Male Wistar rats were divided randomly into four groups: a normal group, a normal-treated group, a diabetic group and a diabetic-treated group (n = 6 rats per group).

Developing a Protein Scaffolding System for Rapid Enzyme Immobilization and Optimization of Enzyme Functions for Biocatalysis.

Immobilization of enzymes is required for most biocatalytic processes, but chemistries used in enzyme immobilization are limited and can be challenging. Genetically encoded protein-based biomaterials could provide easy-to-use immobilization platforms for biocatalysts. We recently developed a self-assembling protein scaffold that covalently immobilized SpyTagged enzymes by engineering the bacterial microcompartment protein EutM from with a SpyCatcher domain.

Measurements of Ion Binding to Lipid-Hosted Ionophores by Affinity Chromatography.

The binding affinity between antibiotic ionophores and alkali ions within supported lipid bilayers was evaluated using affinity chromatography. We used zonal elution and frontal analysis methods in nanovolume liquid chromatography to characterize the binding selectivity of the carrier and channel ionophores valinomycin and gramicidin A within different phosphatidylcholine bilayers. Distinct binding sensitivity to the lipid phase, both in affinity and selectivity, is observed for valinomycin, whereas gramicidin is less sensitive to changes in a membrane environment, behavior that is consistent with ion binding occurring within the interior of an established channel.

Isolation and characterization of high exopolysaccharide-producing Weissella confusa VP30 from young children's feces.

Background: Lactic acid bacteria (LAB) are known to have a significant ability to colonize the human intestinal tract and adhere to the surface of intestinal epithelial cells. Among the various lactic acid bacteria, exopolysaccharide (EPS) producing strains are known to provide a variety of health benefits for their hosts (e.g.

The role of protein SUMOylation in rheumatoid arthritis.

Small ubiquitin-like modifier (SUMO) proteins, as a subgroup of post-translational modifiers, act to change the function of proteins. Through their interactions with different targets, immune pathways, and the responses they elicit, can be affected by these SUMO conjugations. Thus, both a change to protein function and involvement in immune pathways has the potential to promote an efficient immune response to either a pathogenic challenge, or the development of an imbalance that could lead to an autoimmune-based disease.

Colon cancer stem cells: Potential target for the treatment of colorectal cancer.

Despite incessant research, colon cancer still is one of the most common causes of fatalities in both men and women worldwide. Also, nearly 50% of patients with colorectal cancer show tumor recurrence. Recent investigations have highlighted the involvement of colon cancer stem cells (CCSCs) in cancer relapse and chemoresistance.

Biological properties of metal complexes of curcumin.

Curcumin, a naturally occurring phenolic compound isolated from Curcuma longa, has different pharmacological effects, including antiinflammatory, antimicrobial, antioxidant, and anticancer properties. However, curcumin has been found to have a limited bioavailability because of its hydrophobic nature, low-intestinal absorption, and rapid metabolism. Therefore, there is a need for enhancing the bioavailability and its solubility in water in order to increase the pharmacological effects of this bioactive compound.

2018 ACC/HRS/NASCI/SCAI/SCCT Expert Consensus Document on Optimal Use of Ionizing Radiation in Cardiovascular Imaging: Best Practices for Safety and Effectiveness-A Review for the Cardiac Anesthesiologist.

The American College of Cardiology, in collaboration with the American Society of Nuclear Cardiology, Heart Rhythm Society, Mended Hearts, North American Society for Cardiovascular Imaging, Society for Cardiovascular Angiography and Interventions, Society for Cardiovascular Computed Tomography, and Society of Nuclear Medicine and Molecular Imaging, recently published a consensus document recommending best practices for the use of ionizing radiation in cardiovascular medicine. With the increase in number and complexity of catheter-based cardiovascular interventions, cardiothoracic anesthesiologists are being requested to consult and provide care for these patients. This review summarizes the salient portions of the consensus document as it pertains to the anesthesiologist.

Beneficial Effects of Trehalose on Striatal Dopaminergic Deficits in Rodent and Primate Models of Synucleinopathy in Parkinson's Disease.

Disease modification in Parkinson's disease (PD) is an unmet medical need. In the current study, we evaluated trehalose, a safe and well-tolerated disaccharide that has previously demonstrated efficacy in rodent models of neurodegenerative diseases, including PD. In a rat model of PD, based on delivery of adeno-associated virus serotype 1/2 containing the mutated human A53T -synuclein gene (AAV1/2-hourA53T-aSyn) to the substantia nigra (SN), we showed that rats administered trehalose (2.

Clinical validity assessment of genes for inclusion in multi-gene panel testing: A systematic approach.

Background: Advances in sequencing technology have led to expanded use of multi-gene panel tests (MGPTs) for clinical diagnostics. Well-designed MGPTs must balance increased detection of clinically significant findings while mitigating the increase in variants of uncertain significance (VUS). To maximize clinical utililty, design of such panels should include comprehensive gene vetting using a standardized clinical validity (CV) scoring system.