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Παρασκευή 23 Αυγούστου 2019


Advances in encapsulated dermal formulations in chemoprevention of melanoma: An overview
Abstract Background The three forms of skin cancer are cutaneous malignant melanoma, basal cell carcinoma, and squamous cell carcinoma. Melanoma skin cancer is an aggressive type and one of the most chemotherapy‐resistant malignancies. Conventional topical products are beset with limitations, leading to lower efficacy. There is a growing need to develop topical formulations encapsulated in polymeric and lipid nanoparticles, nanoemulsions, dendrimers, and liposomes exhibiting enhanced skin penetration...
Journal of Cosmetic Dermatology
19m
Cutaneous necrotic lesion: A wonderful delay adverse effect of interferon beta‐1b injection for multiple sclerosis treatment
Abstract Multiple sclerosis (MS) is a chronic and inflammatory autoimmune disease. These patients may manifest severe inflammatory cutaneous reactions after using interferon beta‐1b. This article describes a 55‐year‐old man with severe injection site reactions after 10 years administration of interferon beta‐1b. The biopsy specimens revealed skin and subcutaneous tissue necrosis. Histologic evaluation revealed nonspecific inflammatory reactions with no evidence of vasculitis or granulomatous reactions....
Journal of Cosmetic Dermatology
19m
Lactic acid 5% mouth wash vs Kenalog in Orabase 0.1% for treatment and prophylaxis of recurrent aphthous ulcer
Abstract Background The outcomes of most therapeutic modalities for recurrent aphthous ulcer (RAU) are still unsatisfactory. Aim To evaluate lactic acid 5% mouth wash vs Kenalog in Orabase for treatment and prophylaxis of RAU. Patients/Methods Forty cases with early‐onset idiopathic RAU were enrolled in this study. Patients were divided into two equal groups; group A patients had used Kenalog in Orabase twice daily, and group B patients had used lactic acid 5% mouth wash 3 times daily....
Journal of Cosmetic Dermatology
20h
Cyclic di-GMP co-activates the two-component transcriptional regulator DevR in Mycobacterium smegmatis in response to oxidative stress [Gene Regulation]
Cyclic di-GMP (c-di-GMP) is an important second messenger in bacteria, and its regulatory network has been extensively studied. However, information regarding the activation mechanisms of its receptors remains limited. In this study, we characterized the two-component regulator DevR as a new c-di-GMP receptor and further uncovered a novel co-activation mechanism for effective regulation of DevR in mycobacteria. We show that high c-di-GMP levels induce the expression of the devR operon in Mycobacterium...
Journal of Biological Chemistry current issue
20m
Recombinant mussel protein Pvfp-5{beta}: A potential tissue bioadhesive [Molecular Biophysics]
During their lifecycle, many marine organisms rely on natural adhesives to attach to wet surfaces for movement and self-defense in aqueous tidal environments. Adhesive proteins from mussels are biocompatible and elicit only minimal immune responses in humans. Therefore these proteins have received increased attention for their potential applications in medicine, biomaterials, and biotechnology. The Asian green mussel Perna viridis secretes several byssal plaque proteins, molecules that help anchoring...
Journal of Biological Chemistry current issue
20m
Sweet rescue or surrender of the failing heart? [Molecular Bases of Disease]
Natriuretic peptides (NPs) are hormones involved in maintaining heart health that undergo proteolytic cleavage to become activated. Previous work has shown that O-GalNAc glycans affect their processing and activation. Here, Goetze, Schjoldager, and colleagues now provide comprehensive characterization of O-glycosylation of NPs, revealing that all members of the NP family can be modified by O-GalNAc glycans. Intriguingly, the study discovers glycans in the receptor-binding region of the A-type natriuretic...
Journal of Biological Chemistry current issue
20m
CD44 inhibits {alpha}-SMA gene expression via a novel G-actin/MRTF-mediated pathway that intersects with TGF{beta}R/p38MAPK signaling in murine skin fibroblasts [Cell Biology]
Well-regulated differentiation of fibroblasts into myofibroblasts (MF) is critical for skin wound healing. Neoexpression of α-smooth muscle actin (α-SMA), an established marker for MF differentiation, is driven by TGFβ receptor (TGFβR)–mediated signaling. Hyaluronan (HA) and its receptor CD44 may also participate in this process. To further understand this process, primary mouse skin fibroblasts were isolated and treated in vitro with recombinant TGF-β1 (rTGF-β1) to induce α-SMA expression. CD44...
Journal of Biological Chemistry current issue
20m
In vivo stabilization of OPA1 in hepatocytes potentiates mitochondrial respiration and gluconeogenesis in a prohibitin-dependent way [Cell Biology]
Patients with fatty liver diseases present altered mitochondrial morphology and impaired metabolic function. Mitochondrial dynamics and related cell function require the uncleaved form of the dynamin-like GTPase OPA1. Stabilization of OPA1 might then confer a protective mechanism against stress-induced tissue damages. To study the putative role of hepatic mitochondrial morphology in a sick liver, we expressed a cleavage-resistant long form of OPA1 (L-OPA1Δ) in the liver of a mouse model with mitochondrial...
Journal of Biological Chemistry current issue
20m
Discovery of O-glycans on atrial natriuretic peptide (ANP) that affect both its proteolytic degradation and potency at its cognate receptor [Molecular Bases of Disease]
Atrial natriuretic peptide (ANP) is a peptide hormone that in response to atrial stretch is secreted from atrial myocytes into the circulation, where it stimulates vasodilatation and natriuresis. ANP is an important biomarker of heart failure where low plasma concentrations exclude cardiac dysfunction. ANP is a member of the natriuretic peptide (NP) family, which also includes the B-type natriuretic peptide (BNP) and the C-type natriuretic peptide. The proforms of these hormones undergo processing...
Journal of Biological Chemistry current issue
20m
Nanoscale dynamics of cholesterol in the cell membrane [Lipids]
Cholesterol constitutes ∼30–40% of the mammalian plasma membrane, a larger fraction than of any other single component. It is a major player in numerous signaling processes as well as in shaping molecular membrane architecture. However, our knowledge of the dynamics of cholesterol in the plasma membrane is limited, restricting our understanding of the mechanisms regulating its involvement in cell signaling. Here, we applied advanced fluorescence imaging and spectroscopy approaches on in vitro (model...
Journal of Biological Chemistry current issue
20m
Humanization of the entire murine Mapt gene provides a murine model of pathological human tau propagation [Molecular Bases of Disease]
In cortical regions of brains from individuals with preclinical or clinical Alzheimer's disease (AD), extracellular β-amyloid (Aβ) deposition precedes the aggregation of pathological intracellular tau (the product of the gene microtubule-associated protein tau (MAPT)). To our knowledge, current mouse models of tauopathy reconstitute tau pathology by overexpressing mutant human tau protein. Here, through a homologous recombination approach that replaced the entire murine Mapt gene with the human ortholog,...
Journal of Biological Chemistry current issue
20m
Human ATG4 autophagy proteases counteract attachment of ubiquitin-like LC3/GABARAP proteins to other cellular proteins [Protein Synthesis and Degradation]
Microtubule-associated protein 1 light chain 3 α (LC3)/GABA type A receptor-associated protein (GABARAP) comprises a family of ubiquitin-like proteins involved in (macro)autophagy, an important intracellular degradation pathway that delivers cytoplasmic material to lysosomes via double-membrane vesicles called autophagosomes. The only currently known cellular molecules covalently modified by LC3/GABARAP are membrane phospholipids such as phosphatidylethanolamine in the autophagosome membrane. Autophagy-related...
Journal of Biological Chemistry current issue
20m
The N-terminal domain of an archaeal multidrug and toxin extrusion (MATE) transporter mediates proton coupling required for prokaryotic drug resistance [Molecular Biophysics]
As a contributor to multidrug resistance, the family of multidrug and toxin extrusion (MATE) transporters couples the efflux of chemically dissimilar compounds to electrochemical ion gradients. Although divergent transport mechanisms have been proposed for these transporters, previous structural and functional analyses of members of the MATE subfamily DinF suggest that the N-terminal domain (NTD) supports substrate and ion binding. In this report, we investigated the relationship of ligand binding...
Journal of Biological Chemistry current issue
20m
Peptides come to the rescue of pancreatic {beta} cells [Cell Biology]
IntroductionInsulin and glucagon are well-known peptide hormones that keep glucose levels within a healthy range in the body. But they are only part of a complex network that controls concentrations of this ubiquitous sugar in blood and tissues. Other molecules regulate glucose by controlling insulin secretion from the pancreas or protecting pancreatic β cells against stresses that lead to cellular dysfunction or cell death (1).One of these protective regulators is glucagon-like peptide 1 (GLP-1),...
Journal of Biological Chemistry current issue
20m
Inflammasome inhibition blocks cardiac glycoside cell toxicity [Molecular Bases of Disease]
Chronic heart failure and cardiac arrhythmias have high morbidity and mortality, and drugs for the prevention and management of these diseases are a large part of the pharmaceutical market. Among these drugs are plant-derived cardiac glycosides, which have been used by various cultures over millennia as both medicines and poisons. We report that digoxin and related compounds activate the NLRP3 inflammasome in macrophages and cardiomyocytes at concentrations achievable during clinical use. Inflammasome...
Journal of Biological Chemistry current issue
20m
A temperature-dependent conformational shift in p38{alpha} MAPK substrate-binding region associated with changes in substrate phosphorylation profile [Protein Structure and Folding]
Febrile-range hyperthermia worsens and hypothermia mitigates lung injury, and temperature dependence of lung injury is blunted by inhibitors of p38 mitogen-activated protein kinase (MAPK). Of the two predominant p38 isoforms, p38α is proinflammatory and p38β is cytoprotective. Here, we analyzed the temperature dependence of p38 MAPK activation, substrate interaction, and tertiary structure. Incubating HeLa cells at 39.5 °C stimulated modest p38 activation, but did not alter tumor necrosis factor-α...
Journal of Biological Chemistry current issue
20m
Stable calcium-free myocilin olfactomedin domain variants reveal challenges in differentiating between benign and glaucoma-causing mutations [Molecular Biophysics]
Nonsynonymous gene mutations can be beneficial, neutral, or detrimental to the stability, structure, and biological function of the encoded protein, but the effects of these mutations are often not readily predictable. For example, the β-propeller olfactomedin domain of myocilin (mOLF) exhibits a complex interrelationship among structure(s), stability, and aggregation. Numerous mutations within mOLF are linked to glaucoma; the resulting variants are less stable, aggregation-prone, and sequestered...
Journal of Biological Chemistry current issue
20m
A positive feedback loop involving nuclear factor IB and calpain 1 suppresses glioblastoma cell migration [Molecular Bases of Disease]
Glioblastoma (GBM) is a brain tumor that remains largely incurable because of its highly-infiltrative properties. Nuclear factor I (NFI)-type transcription factors regulate genes associated with GBM cell migration and infiltration. We have previously shown that NFI activity depends on the NFI phosphorylation state and that calcineurin phosphatase dephosphorylates and activates NFI. Calcineurin is cleaved and activated by calpain proteases whose activity is, in turn, regulated by an endogenous inhibitor,...
Journal of Biological Chemistry current issue
20m
Lipogenic SREBP-1a/c transcription factors activate expression of the iron regulator hepcidin, revealing cross-talk between lipid and iron metabolisms [Metabolism]
The sterol regulatory element-binding proteins (SREBPs) are a family of transcription factors best known for stimulating the expression of genes encoding key lipogenic enzymes. However, SREBP functions beyond lipid metabolism are less understood. Here, we show that hepcidin antimicrobial peptide (Hamp), encoding the hormone hepcidin essential for iron homeostasis and regulated by dietary iron and inflammation, is a target gene of the two SREBP isoforms SREBP-1a/c. We found that in tissue culture,...
Journal of Biological Chemistry current issue
20m
Transmembrane insertases and N-glycosylation critically determine synthesis, trafficking, and activity of the nonselective cation channel TRPC6 [Protein Synthesis and Degradation]
Transient receptor potential cation channel subfamily C member 6 (TRPC6) is a widely expressed ion channel. Gain–of–function mutations in the human TRPC6 channel cause autosomal-dominant focal segmental glomerulosclerosis, but the molecular components involved in disease development remain unclear. Here, we found that overexpression of gain–of–function TRPC6 channel variants is cytotoxic in cultured cells. Exploiting this phenotype in a genome-wide CRISPR/Cas screen for genes whose inactivation rescues...
Journal of Biological Chemistry current issue
20m
Phosphomimetic substitution at Ser-33 of the chloroquine resistance transporter PfCRT reconstitutes drug responses in Plasmodium falciparum [Cell Biology]
The chloroquine resistance transporter PfCRT of the human malaria parasite Plasmodium falciparum confers resistance to the former first-line antimalarial drug chloroquine, and it modulates the responsiveness to a wide range of quinoline and quinoline-like compounds. PfCRT is post-translationally modified by phosphorylation, palmitoylation, and, possibly, ubiquitination. However, the impact of these post-translational modifications on P. falciparum biology and, in particular, the drug resistance–conferring...
Journal of Biological Chemistry current issue
21m
Two complementary {alpha}-fucosidases from Streptococcus pneumoniae promote complete degradation of host-derived carbohydrate antigens [Enzymology]
An important aspect of the interaction between the opportunistic bacterial pathogen Streptococcus pneumoniae and its human host is its ability to harvest host glycans. The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae. Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated...
Journal of Biological Chemistry current issue
21m
Streptococcus pneumoniae inhibits purinergic signaling and promotes purinergic receptor P2Y2 internalization in alveolar epithelial cells [Cell Biology]
Bacterial pneumonia is a global health challenge that causes up to 2 million deaths each year. Purinergic signaling plays a pivotal role in healthy alveolar epithelium. Here, we used fluorophore-based analysis and live-cell calcium imaging to address the question of whether the bacterial pathogen Streptococcus pneumoniae directly interferes with purinergic signaling in alveolar epithelial cells. Disturbed purinergic signaling might result in pathophysiologic changes like edema formation and atelectasis,...
Journal of Biological Chemistry current issue
21m
The mitophagy receptor Bcl-2-like protein 13 stimulates adipogenesis by regulating mitochondrial oxidative phosphorylation and apoptosis in mice [Metabolism]
Metabolic programming of bone marrow stromal cells (BMSCs) could influence the function of progenitor osteoblasts or adipocytes and hence determine skeletal phenotypes. Adipocytes predominantly utilize oxidative phosphorylation, whereas osteoblasts use glycolysis to meet ATP demand. Here, we compared progenitor differentiation from the marrow of two inbred mouse strains, C3H/HeJ (C3H) and C57BL6J (B6). These strains differ in both skeletal mass and bone marrow adiposity. We hypothesized that genetic...
Journal of Biological Chemistry current issue
21m
The domain architecture of the protozoan protein J-DNA-binding protein 1 suggests synergy between base J DNA binding and thymidine hydroxylase activity [DNA and Chromosomes]
J-DNA–binding protein 1 (JBP1) contributes to the biosynthesis and maintenance of base J (β-d-glucosyl-hydroxymethyluracil), an epigenetic modification of thymidine (T) confined to pathogenic protozoa such as Trypanosoma and Leishmania. JBP1 has two known functional domains: an N-terminal T hydroxylase (TH) homologous to the 5-methylcytosine hydroxylase domain in TET proteins and a J-DNA–binding domain (JDBD) that resides in the middle of JBP1. Here, we show that removing JDBD from JBP1 results in...
Journal of Biological Chemistry current issue
21m
Dysregulation of histone H3 lysine 27 trimethylation in transforming growth factor-{beta}1-induced gene expression in mesangial cells and diabetic kidney [Gene Regulation]
Transforming growth factor-β1 (TGF-β)-induced fibrotic and inflammatory genes in renal mesangial cells (MCs) play important roles in glomerular dysfunction associated with diabetic nephropathy (DN). TGF-β regulates gene expression in MCs by altering key chromatin histone modifications at target gene promoters. However, the role of the repressive histone H3 lysine 27 trimethylation (H3K27me3) modification is unclear. Here we show that TGF-β reduces H3K27me3 at the Ctgf, Serpine1, and Ccl2 gene promoters...
Journal of Biological Chemistry current issue
21m
Focal adhesion kinase-dependent activation of the early endocytic protein Rab5 is associated with cell migration [Signal Transduction]
Focal adhesion kinase (FAK) is a central regulator of integrin-dependent cell adhesion and migration and has recently been shown to co-localize with endosomal proteins. The early endocytic protein Rab5 controls integrin trafficking, focal adhesion disassembly, and cell migration and has been shown to be activated upon integrin engagement by mechanisms that remain unclear. Because FAK is a critical regulator of integrin-dependent signaling and Rab5 recapitulates FAK-mediated effects, we evaluated...
Journal of Biological Chemistry current issue
21m
Glutathione-glutaredoxin is an efficient electron donor system for mammalian p53R2-R1-dependent ribonucleotide reductase [DNA and Chromosomes]
Deoxyribonucleotides are DNA building blocks and are produced de novo by reduction of ribose to deoxyribose. This reduction is catalyzed by ribonucleotide reductase (RNR), a heterodimeric tetramer enzyme in mammalian cells, having one of two free radical-containing subunits called R2 and p53R2. R2 is S-phase specific and used for DNA replication, whereas p53R2 functions in DNA repair and mitochondrial DNA synthesis. The larger RNR subunit, R1, has catalytically active cysteine thiols in its buried...
Journal of Biological Chemistry current issue
21m
A cysteinyl-tRNA synthetase variant confers resistance against selenite toxicity and decreases selenocysteine misincorporation [Enzymology]
Selenocysteine (Sec) is the 21st genetically encoded amino acid in organisms across all domains of life. Although structurally similar to cysteine (Cys), the Sec selenol group has unique properties that are attractive for protein engineering and biotechnology applications. Production of designer proteins with Sec (selenoproteins) at desired positions is now possible with engineered translation systems in Escherichia coli. However, obtaining pure selenoproteins at high yields is limited by the accumulation...
Journal of Biological Chemistry current issue
21m
Ready for the journey: a comparative proteome profiling of porcine cauda epididymal fluid and spermatozoa
Abstract In the present study, we describe the proteome of porcine cauda epididymis fluid and spermatozoa by means of Multidimensional Protein Identification Technology (MudPIT). Ten sexually mature healthy boars were surgically castrated and epididymides were dissected to obtain the cauda epididymal content. Polled protein extracts of cauda epididymal fluid (CEF) and spermatozoa (CESperm) were loaded in an Agilent 1100 quaternary HPLC and peptides eluted from the microcapillary...
Latest Results for Cell and Tissue Research
22m
Effect of pharmacy‐led medication reconciliation in emergency departments: A systematic review and meta‐analysis
This meta‐analysis investigated the impact of pharmacy‐led medication reconciliation on medication discrepancies and potential adverse drug events in the ED. Pharmacy‐led medication reconciliation significantly reduced the proportion of patients with medication discrepancies and the number of medication discrepancy events. Abstract What is known and objective Medication reconciliation is recommended to be performed at every transition of medical care to prevent medication errors or adverse drug...
Journal of Clinical Pharmacy and Therapeutics
22m
Economic evaluations on the use of aripiprazole for patients with schizophrenia: A systematic review
A trend favouring olanzapine, lurasidone and paliperidone could be observed, whereas aripiprazole was extensively described as a dominated alternative. However, notably, 93% of the industry‐funded studies presented results favouring their sponsors, only two of them being the manufacturer of aripiprazole. Abstract What is known and objectives Schizophrenia is a serious mental disorder and is associated with substantial economic and social burden. Cost‐effectiveness analysis is important to assess...
Journal of Clinical Pharmacy and Therapeutics
22m
Re‐elevation of serum amlodipine level after lipid emulsion therapy in an overdose case
Re‐elevation of serum amlodipine level was observed after single bolus of ILE therapy. It is deemed desirable to perform ILE infusion following its bolus in a case of amlodipine overdose. Abstract What is known and objective Amlodipine overdose is common; however, the dose and timing of intravenous lipid emulsion (ILE) therapy as a management strategy remain debatable. Case description A 73‐year‐old man received a single bolus (1.5 mL/kg) of ILE therapy following massive ingestion of multiple...
Journal of Clinical Pharmacy and Therapeutics
22m
Pharmacists practising in family medicine groups: What are their activities and needs?
Pharmacists’ responsibilities and practices have expanded over the years to be more clinical. Working in other settings and collaborating with other healthcare professionals can lead to new needs that are unmet by actual training. This study describes the characteristics and practices of pharmacists working in family medicine groups (FMGs) and assesses their needs to develop a practice‐based network fostering best practices. Abstract What is known and objective Pharmacists' responsibilities...
Journal of Clinical Pharmacy and Therapeutics
22m
Pharmacogenetics of statins treatment: Efficacy and safety
The main objective of this narrative review is to summarize the updated progress of correlation between gene polymorphisms and the efficacy/safety of statins, including SNPs of SLCO1B1, ABCB1, ABCC2, ABCG2, APOE, APOA5, CYP3A4, CYP3A5, CYP2C9, CYP2D6, KIF6, HMGCR, LPA, LDLR, PCSK9, COQ2, CETP, etc. The summary of the roles of the gene polymorphisms might be helpful for the research or individualized application of statins. Abstract What is known and objective Statins are widely used worldwide...
Journal of Clinical Pharmacy and Therapeutics
22m
Fornix-Region Deep Brain Stimulation–Induced Memory Flashbacks in Alzheimer’s Disease
To the Editor: In a randomized trial involving 42 patients, we assessed deep brain stimulation targeting the fornix to improve cognition in patients with Alzheimer’s disease (ClinicalTrials.gov number, NCT01608061; the protocol for the trial is available with the published article). Although the…
The New England Journal of Medicine: Search Results in Neurology\Neurosurgery
22m
The Comfort of the Ordinary — On Dying as We’ve Lived
Years ago, I heard about the death of an old family friend whom I’d loved as a child for her eccentric cooking habits, feeding her parakeets saliva-soaked crumbs from her lips, and letting me rap my knuckles on her wooden leg. Although I wasn’t with her at the end of her colorful life, I can almost…
The New England Journal of Medicine: Search Results in Geriatrics\Aging
23m
Swiss make clinical use of cinematic rendering
The highly detailed, photorealistic appearance of cinematic rendering reconstructions...Read more on AuntMinnieEurope.comRelated Reading: Cinematic rendering illuminates postmortem CTA How can cinematic rendering expand its role in medicine? Research shines spotlight on cinematic rendering
AuntMinnieEurope.com Headlines
24m
RSNA to launch new global learning program
The RSNA plans to launch a new Global Learning Centers program in 2020 to improve...Read more on AuntMinnieEurope.comRelated Reading: RSNA R&E Foundation OKs grant money RSNA 2018 sees flat registration numbers, boost in exhibits Allez la France: 1,200 delegates show talents at RSNA 2018 SERAM provides grants to attend RSNA 2018 RSNA brings AI course to Paris
AuntMinnieEurope.com Headlines
14h

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