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Probiotics-rich emulsion improves insulin signalling in Palmitate/Oleate-challenged human hepatocarcinoma cells through the modulation of Fetuin-A/TLR4-JNK-NF-κB pathway.

Biomed Pharmacother 2021 Apr 8;139:111560. Epub 2021 Apr 8.

Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Norwida 27B, 50-375 Wrocław, Poland; International Institute of Translational Medicine, Jesionowa, 11, Malin, 55-114 Wisznia Mała, Poland. Electronic address:

Background: Fetuin-A, also known as α2-Heremans-Schmid glycoprotein (AHSG), is an abundant plasmatic serum protein synthesized predominantly in liver and adipose tissue. This glycoprotein is known to negatively regulate insulin signaling through the inhibition of insulin receptor (IR) autophosphorylation and tyrosine kinase activity, which participates in insulin resistance (IR) and metabolic syndrome development. Recent studies demonstrated that IR and associated metabolic disorders, are closely related to the gut microbiota and modulating it by probiotics could be effective in metabolic diseases management. Read More

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Essential Role of Somatic Kv2 Channels in High-Frequency Firing in Cartwheel Cells of the Dorsal Cochlear Nucleus.

Authors:
Tomohiko Irie

eNeuro 2021 Apr 8. Epub 2021 Apr 8.

Division of Pharmacology, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki City, Kanagawa, 210-9501, Japan

Among all voltage-gated potassium (Kv) channels, Kv2 channels are the most widely expressed in the mammalian brain. However, studying Kv2 in neurons has been challenging due to a lack of high-selective blockers. Recently, a peptide toxin, guangxitoxin-1E, has been identified as a specific inhibitor of Kv2, thus facilitating the study of Kv2 in neurons. Read More

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CD169+ Subcapsular Macrophage Role in Antigen Adjuvant Activity.

Front Immunol 2021 18;12:624197. Epub 2021 Mar 18.

Section of Infectious Diseases, Department of Medicine, Boston Medical Center, Boston, MA, United States.

Vaccines have played a pivotal role in improving public health, however, many infectious diseases lack an effective vaccine. Controlling the spread of infectious diseases requires continuing studies to develop new and improved vaccines. Our laboratory has been investigating the immune enhancing mechanisms of Toll-like receptor (TLR) ligand-based adjuvants, including the TLR2 ligand Neisseria meningitidis outer membrane protein, PorB. Read More

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Effect of Acetylation on Physicochemical and Functional Properties of Commercial Pumpkin Protein Concentrate.

Molecules 2021 Mar 12;26(6). Epub 2021 Mar 12.

Department of Food Storage and Technology, Wroclaw University of Environmental and Life Sciences, 37 Chelmonskiego Street, 51-630 Wrocław, Poland.

The purpose of the present study was to determine the effects of acetylation with different doses of acetic anhydride on the chemical composition and chosen functional properties of commercial pumpkin protein concentrate (PPC). The total protein content decreased as compared to unmodified samples. Electrophoretic analysis revealed that in the acetylated pumpkin protein, the content of the heaviest protein (35 kDa) decreased in line with increasing concentrations of modifying reagent. Read More

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Effective Treatment of Neurological Symptoms with Normal Doses of Botulinum Neurotoxin in Wilson's Disease: Six Cases and Literature Review.

Toxins (Basel) 2021 Mar 29;13(4). Epub 2021 Mar 29.

Department of Neurology, University Hospital of Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf, Germany.

Background: Recent cell-based and animal experiments have demonstrated an effective reduction in botulinum neurotoxin A (BoNT/A) by copper.

Aim: We aimed to analyze whether the successful symptomatic BoNT/A treatment of patients with Wilson's disease (WD) corresponds with unusually high doses per session.

Methods: Among the 156 WD patients regularly seen at the outpatient department of the university hospital in Düsseldorf (Germany), only 6 patients had been treated with BoNT/A during the past 5 years. Read More

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Trace Element Concentration and Stable Isotope Ratio Analysis in Blueberries and Bilberries: A Tool for Quality and Authenticity Control.

Foods 2021 Mar 9;10(3). Epub 2021 Mar 9.

Department of Environmental Science, University of Latvia, LV-1004 Riga, Latvia.

genus berries-wild bilberries ( L.) and cultivated highbush blueberries ( L.)-are consumed worldwide, and their consumption has a trend of stable increase. Read More

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Agroindustrial Wastes as a Support for the Immobilization of Lipase from : Synthesis of Hexyl Laurate.

Biomolecules 2021 Mar 17;11(3). Epub 2021 Mar 17.

School of Chemistry, Department of Biochemical Engineering, Federal University of Rio de Janeiro, Rio de Janeiro 21941-909, Brazil.

As a consequence of intense industrialization in the last few decades, the amount of agro-industrial wastes has increasing, where new forms of valorization are crucial. In this work, five residual biomasses from Maranhão (Brazil) were investigated as supports for immobilization of lipase from (TLL). The new biocatalysts BM-TLL (babaçu mesocarp) and RH-TLL (rice husk) showed immobilization efficiencies >98% and hydrolytic activities of 5. Read More

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IgGs-Abzymes from the Sera of Patients with Multiple Sclerosis Recognize and Hydrolyze miRNAs.

Int J Mol Sci 2021 Mar 10;22(6). Epub 2021 Mar 10.

Institute of Chemical Biology and Fundamental Medicine, Siberian Division of Russian Academy of Sciences, 8 Lavrentiev Ave, 630090 Novosibirsk, Russia.

Autoantibodies-abzymes hydrolyzing DNA, myelin basic protein, and oligosaccharides have been revealed in the sera of patients with multiple sclerosis (MS). In MS, specific microRNAs are found in blood and cerebrospinal fluid, which are characterized by increased expression. Autoantibodies, specifically hydrolyzing four different miRNAs, were first detected in the blood of schizophrenia patients. Read More

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Correlation between cytologic features and histologic grades in cutaneous and subcutaneous soft tissue sarcomas in dogs-A pilot study.

Vet Clin Pathol 2021 Apr 2. Epub 2021 Apr 2.

Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.

Currently, canine soft tissue sarcoma (STS) grading is based on histopathology. In humans, several studies have demonstrated concordance between cytologic grading systems for STS and histologic grade. The aim of this study was to correlate several cytologic parameters (smear cellularity, anisokaryosis, nucleolar malignancy score, multinucleation, and the number of mitotic figures per 200 cells) that form part of a human STS cytologic grading system, with histologic grades of canine cutaneous and subcutaneous STS. Read More

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Biosimilar recombinant follitropin alfa preparations versus the reference product (Gonal-F®) in couples undergoing assisted reproductive technology treatment: a systematic review and meta-analysis.

Reprod Biol Endocrinol 2021 Apr 2;19(1):51. Epub 2021 Apr 2.

Global Medical Affairs Fertility, Research and Development, Merck KGaA, F135/002, Darmstadt, 64293, Germany.

Background: Live birth has increasingly been identified as the standard clinical approach to measure the success of medically assisted reproduction (MAR). However, previous analyses comparing biosimilar preparations of follitropin alfa versus the reference product (GONAL-f®, Merck KGaA, Darmstadt, Germany or GONAL-f® RFF; EMD Serono, Inc., Rockland, MA), have had insufficient power to detect differences in clinically meaningful outcomes such as live birth. Read More

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SERCA2a stimulation by istaroxime improves intracellular Ca2+ handling and diastolic dysfunction in a model of diabetic cardiomyopathy.

Cardiovasc Res 2021 Apr 1. Epub 2021 Apr 1.

Department of Biotechnology and Biosciences, Università degli Studi di Milano-Bicocca, Milan, Italy.

Aims: Diabetic cardiomyopathy is a multifactorial disease characterized by an early onset of diastolic dysfunction (DD) that precedes the development of systolic impairment. Mechanisms that can restore cardiac relaxation improving intracellular Ca2+ dynamics represent a promising therapeutic approach for cardiovascular diseases associated to DD. Istaroxime has the dual properties to accelerate Ca2+ uptake into sarcoplasmic reticulum (SR) through the SR Ca2+ pump (SERCA2a) stimulation and to inhibit Na+/K+ ATPase (NKA). Read More

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Detection of Microbial Agents in Oropharyngeal and Nasopharyngeal Samples of SARS-CoV-2 Patients.

Front Microbiol 2021 9;12:637202. Epub 2021 Mar 9.

Department of Otorhinolaryngology-Head and Neck Surgery, and Microbiology, The Tumor Virology Program, Abramson Comprehensive Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.

The novel coronavirus outbreak started in December 2019 and rapidly spread around the globe, leading to a global pandemic. Here we reported the association of microbial agents identified in oropharyngeal and nasopharyngeal samples from patients with SARS-CoV-2 infection, using a Pan-microarray based technology referred to as PathoChIP. To validate the efficiency of PathoChIP, reference viral genomes obtained from BEI resource and 25 SARS-CoV-2 positive clinical samples were tested. Read More

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Randomized and dose-escalation trials of recombinant human serum albumin /granulocyte colony-stimulating factor in patients with breast cancer receiving anthracycline-containing chemotherapy.

BMC Cancer 2021 Mar 31;21(1):341. Epub 2021 Mar 31.

Department of Medical Oncology, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China.

Background: To evaluate the efficacy and safety of recombinant human serum albumin /granulocyte colony-stimulating factor (rHSA/G-CSF) in breast cancer following receipt of cytotoxic agents.

Methods: The phase 1b trial assessed the pharmacokinetics, pharmacodynamics, and safety of dose-escalation, ranging from rHSA/G-CSF 1800 μg, 2100 μg, and 2400 μg. Randomized controlled phase 2b trial was further conducted to ensure the comparative efficacy and safety of rHSA/G-CSF 2400 μg and rhG-CSF 5 μg/kg. Read More

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Feasibility and efficacy of modified fixed citrate concentration protocol using only commercial preparations in critically ill patients: a prospective cohort study with a historical control group.

BMC Anesthesiol 2021 Mar 30;21(1):96. Epub 2021 Mar 30.

Department of medical ICU, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, 1 Shuai Fu Yuan, Dongcheng District, Beijing, 100730, China.

Background: The cumbersome program and the shortage of commercial solution hindered the regular application of regional citrate anticoagulation (RCA). It is urgent to simplify the protocol using only commercial preparations. The aim of this study was to explore the feasibility and efficacy of the modified protocol for continuous veno-venous hemofiltration (CVVH) in unselected critically ill patients. Read More

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Safety and tolerability of eptinezumab in patients with migraine: a pooled analysis of 5 clinical trials.

J Headache Pain 2021 Mar 30;22(1):16. Epub 2021 Mar 30.

Lundbeck Seattle BioPharmaceuticals, Inc., Seattle, WA, USA.

Background: The humanized anti-CGRP monoclonal antibody eptinezumab has been evaluated in five large-scale clinical trials conducted in patients with migraine. This integrated analysis was conducted to evaluate the comprehensive safety and tolerability of eptinezumab in patients with migraine across these studies.

Methods: Data were pooled from four randomized, double-blind, placebo-controlled studies and the first year of one open-label study. Read More

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Commercial α1-antitrypsin preparations markedly differ in their potential to inhibit the ATP-induced release of monocytic interleukin-1β.

Pulm Pharmacol Ther 2021 Mar 25;68:102020. Epub 2021 Mar 25.

Laboratory of Experimental Surgery, Department of General and Thoracic Surgery, Justus-Liebig-University, Giessen, Germany; Member of the German Centre for Lung Research (DZL), Germany. Electronic address:

The acute phase protein α1-antitrypsin (AAT) inhibits numerous proteases, specifically neutrophil elastase. Patients with an AAT deficiency due to mutations frequently develop early onset emphysema. The commercial preparations of human plasma AAT are clinically used as biopharmaceuticals to protect the lung tissue of AAT-deficient patients from damage caused by neutrophil elastase. Read More

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Effects of change in temperature on the cardiac contractility of broad-snouted caiman (Caiman latirostris) during digestion.

J Exp Zool A Ecol Integr Physiol 2021 Apr 26;335(4):417-425. Epub 2021 Mar 26.

Department of Physiological Sciences, Federal University of São Carlos, São Carlos, São Paulo, Brazil.

In many reptiles, digestion has been associated with the selection of higher body temperatures, the so-called post-prandial thermophilic response. This study aimed to investigate the excitation-contraction (E-C) coupling in postprandial broad-snouted caimans (Caiman latirostris) in response to acute warming within a preferred body temperature range of crocodiles. Isometric preparations subjected to a temperature transition from 25°C to 30°C were used to investigate myocardial contractility of postprandial caimans, that is, 48 h after the animals ingested a rodent meal corresponding to 15% of body mass. Read More

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Repetitive optogenetic stimulation of glutamatergic neurons: An alternative to NMDA treatment for generating locomotor activity in spinalized zebrafish larvae.

Physiol Rep 2021 Mar;9(6):e14774

Department of Neuroscience, University of Minnesota, Minneapolis, MN, USA.

N-methyl-d-aspartate (NMDA) application has conventionally been used to activate spinal networks to induce locomotion in spinalized animals. We recently described an alternative approach in which application of continuous blue light activates channelrhodopsin-2 in vesicular glutamate transporter 2a (vglut2a)-expressing spinal neurons to produce organized, rhythmic locomotor activity in spinally-transected larval zebrafish. This technique arguably enhances research validity, because endogenous glutamate is released into existing synapses instead of activating only a subset of glutamatergic (NMDA) receptors with an exogenous compound. Read More

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ZIMIR Imaging of Mouse Pancreatic Islet Cells Shows Oscillatory Insulin Secretion.

Front Endocrinol (Lausanne) 2021 9;12:613964. Epub 2021 Mar 9.

Departments of Cell Biology and of Biochemistry, University of Texas Southwestern Medical, Dallas, TX, United States.

Appropriate insulin secretion is essential for maintaining euglycemia, and impairment or loss of insulin release represents a causal event leading to diabetes. There have been extensive efforts of studying insulin secretion and its regulation using a variety of biological preparations, yet it remains challenging to monitor the dynamics of insulin secretion at the cellular level in the intact pancreas of living animals, where islet cells are supplied with physiological blood circulation and oxygenation, nerve innervation, and tissue support of surrounding exocrine cells. Herein we presented our pilot efforts of ZIMIR imaging in pancreatic islet cells in a living mouse. Read More

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Degradation of insulin amyloid by antibiotic minocycline and formation of toxic intermediates.

Sci Rep 2021 Mar 25;11(1):6857. Epub 2021 Mar 25.

Department of Chemistry and Biology, Graduate School of Science and Engineering, Ehime University, Ehime, 790-8577, Japan.

Insulin balls, localized insulin amyloids formed at subcutaneous insulin-injection sites in patients with diabetes, cause poor glycemic control owing to impairments in insulin absorption. Our previous study has shown that some insulin balls are cytotoxic, but others are not, implying amyloid polymorphism. Interestingly, the patient with toxic insulin balls had been treated with antibiotic minocycline, suggesting a possible relationship between toxicity of insulin balls and minocycline. Read More

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Voltage-gated calcium channels regulate K transport in the Malpighian tubules of the larval cabbage looper, Trichoplusia ni.

J Insect Physiol 2021 Mar 23;131:104230. Epub 2021 Mar 23.

Department of Biology, McMaster University, 1280 Main St West, Hamilton, Ontario L8S4K1, Canada.

Transporting epithelia are tissues that specialize in the directional movements of ions and water and are typically either secretory or reabsorptive. Recent work on the Malpighian tubule of larval lepidopterans (caterpillars) demonstrated that the distal ileac plexus segment of this epithelium is capable of rapidly switching between ion secretion and reabsorption. Subsequent transcriptomic studies suggested expression of voltage-gated ion channels in the lepidopteran MTs (which are not contractile and not innervated). Read More

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Oversulfated dermatan sulfate and heparinoid in the starfish Lysastrosoma anthosticta: Structures and anticoagulant activity.

Carbohydr Polym 2021 Jun 25;261:117867. Epub 2021 Feb 25.

N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect 47, Moscow 119991, Russia. Electronic address:

Crude anionic polysaccharides extracted from the Pacific starfish Lysastrosoma anthosticta were separated by anion-exchange chromatography into fractions LA-F1 and LA-F2. The main fraction LA-F1 was solvolytically desulfated giving rise to preparation LA-F1-DS with a structure of dermatan core [→3)-β-d-GalNAc-(1→4)-α-l-IdoA-(1→]. Reduction of LA-F1 afforded preparation LA-F1-RED composed mainly of the repeating disaccharide units →3)-β-d-GalNAc4R-(1→4)-α-l-Ido2S3S-(1→, where R was SO- or H. Read More

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Optical coherence tomography for elucidation of flow-diversion phenomena: The concept of endothelized mural thrombus behind reversible in-stent stenosis in flow-diverters.

Interv Neuroradiol 2021 Mar 22:15910199211003432. Epub 2021 Mar 22.

Department of Neurosurgery, Advocate Aurora Health, Chicago, IL, USA.

Purpose: Flow-diverters have revolutionized the endovascular treatment of intracranial aneurysms, offering a durable solution to aneurysms with high recurrence rates after conventional stent-assisted coiling. Events that occur after treatment with flow-diversion, such as in-stent stenosis (ISS) are not well understood and require further assessment. After assessing an animal model with Optical Coherence Tomography (OCT), we propose a concept that could explain the mechanism causing reversible ISS after treatment of intracranial aneurysms with flow-diverters. Read More

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Bittersweet: infective complications of drug-induced glycosuria in patients with diabetes mellitus on SGLT2-inhibitors: two case reports.

BMC Infect Dis 2021 Mar 20;21(1):284. Epub 2021 Mar 20.

Department of Infectious Diseases, Barwon Health, Geelong, Victoria, Australia.

Background: Sodium-glucose co-transporter 2 (SGLT2) inhibitors are novel hypoglycemic agents which reduce reabsorption of glucose at the renal proximal tubule, resulting in significant glycosuria and increased risk of genital mycotic infections (GMI). These infections are typically not severe as reported in large systematic reviews and meta-analyses of the medications. These reviews have also demonstrated significant cardiovascular benefits through other mechanisms of action, making them attractive options for the management of Type 2 diabetes mellitus (T2DM). Read More

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Transcranial Random Noise Stimulation acutely lowers the response threshold of human motor circuits.

J Neurosci 2021 Mar 16. Epub 2021 Mar 16.

Neural Control of Movement Lab, Department of Health Sciences and Technology, Zurich, Switzerland

Transcranial random noise stimulation (tRNS) over cortical areas has been shown to acutely improve performance in sensory detection tasks. One explanation for this behavioural effect is stochastic resonance, a mechanism that explains how signal processing in non-linear systems can benefit from added noise. While acute noise benefits of electrical random noise stimulation have been demonstrated at the behavioural level as well as in preparations of neural tissue, it is currently largely unknown whether similar effects can be shown at the neural population level using neurophysiological readouts of human cortex. Read More

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Activation of MrgprA3 and MrgprC11 on bladder-innervating afferents induces peripheral and central hypersensitivity to bladder distension.

J Neurosci 2021 Mar 16. Epub 2021 Mar 16.

Visceral Pain Research Group, College of Medicine and Public Health, Flinders Health and Medical Research Institute (FHMRI), Flinders University, Bedford Park, South Australia, 5042, AUSTRALIA.

Understanding the sensory mechanisms innervating the bladder is paramount to developing efficacious treatments for chronic bladder hypersensitivity conditions. The contribution of Mas-gene-related G protein-coupled receptors (Mrgpr) to bladder signalling is currently unknown. Using male and female mice, we show with single-cell RT-PCR that sub-populations of dorsal root ganglion (DRG) neurons innervating the mouse bladder express (14%) and either individually or in combination, with high levels of co-expression with (81-89%). Read More

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Unveiling the mechanism of action behind the anti-cancer properties of cannabinoids in ER breast cancer cells: Impact on aromatase and steroid receptors.

J Steroid Biochem Mol Biol 2021 Mar 17;210:105876. Epub 2021 Mar 17.

UCIBIO.REQUIMTE, Laboratory of Biochemistry, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal. Electronic address:

Breast cancer is the leading cause of cancer-related death in women worldwide. In the last years, cannabinoids have gained attention in the clinical setting and clinical trials with cannabinoid-based preparations are underway. However, contradictory anti-tumour properties have also been reported. Read More

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Mesoporous Graphitized Carbon Column for Efficient Isomeric Separation of Permethylated Glycans.

Anal Chem 2021 03 15;93(12):5061-5070. Epub 2021 Mar 15.

Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas 79409-1061, United States.

Post-translational modifications are vital aspects of functional proteins. Therefore, it is critical to understand their roles in biological processes. Glycosylation is particularly challenging to study among these modifications due to the heterogeneity displayed by the glycans in terms of their isomers. Read More

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