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Optimized BMSC-derived osteoinductive exosomes immobilized in hierarchical scaffold via lyophilization for bone repair through Bmpr2/Acvr2b competitive receptor-activated Smad pathway.

Biomaterials 2021 Mar 27;272:120718. Epub 2021 Mar 27.

Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, 200011, PR China; Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China. Electronic address:

Mesenchymal stem cell-derived exosomes (MSC-exos), with its inherent capacity to modulate cellular behavior, are emerging as a novel cell-free therapy for bone regeneration. Herein, focusing on practical applying problems, the osteoinductivity of MSC-exos produced by different stem cell sources (rBMSCs/rASCs) and culture conditions (osteoinductive/common) were systematically compared to screen out an optimized osteogenic exosome (BMSC-OI-exo). Via bioinformatic analyses by miRNA microarray and in vitro pathway verification by gene silencing and miRNA transfection, we first revealed that the osteoinductivity of BMSC-OI-exo was attributed to multi-component exosomal miRNAs (let-7a-5p, let-7c-5p, miR-328a-5p and miR-31a-5p). Read More

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Sustained IKKβ phosphorylation and NF-κB activation by superoxide-induced peroxynitrite-mediated nitrotyrosine modification of B56γ3 and PP2A inactivation.

Redox Biol 2020 Dec 18;41:101834. Epub 2020 Dec 18.

National University Cancer Institute, National University Health System, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, NUS, Singapore; Integrative Science and Engineering Programme, NUS Graduate School, NUS, Singapore; Faculté de Medicine, University of Paris, Paris, France. Electronic address:

Apart from its physiological role in inflammation and immunity, the nuclear factor-kappa B (NF-κB) protein complex has been implicated in tumorigenesis and its progression. Here, we provide evidence that a pro-oxidant milieu is an upstream effector of oncogenic NF-κB signaling. Through pharmacological or genetic inhibition of SOD1, we show that elevated intracellular superoxide (O) mediates sustained IKK phosphorylation, and induces downstream degradation of IκBα, leading to the nuclear localization and transcriptional activation of NF-κB. Read More

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December 2020

Effectiveness and tolerability of netarsudil in combination with other ocular hypotensive agents.

Ophthalmol Glaucoma 2021 Apr 7. Epub 2021 Apr 7.

Department of Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, Illinois USA. Electronic address:

Purpose: To evaluate the effectiveness of netarsudil in combination with other ocular hypotensive agents in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT).

Design: Retrospective cohort study.

Subjects: All patients with OAG or OHT with netarsudil added to a regimen of at least one other ocular hypotensive agent between March 2018 to March 2019. Read More

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A functional outside-in signaling network of proteoglycans and matrix molecules regulating autophagy.

Matrix Biol 2021 Apr 7. Epub 2021 Apr 7.

Department of Pathology, Anatomy, and Cell Biology, and the Translational Cellular Oncology Program, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania, USA. Electronic address:

Proteoglycans and selected extracellular matrix constituents are emerging as intrinsic and critical regulators of evolutionarily conversed, intracellular catabolic pathways. Often, these secreted molecules evoke sustained autophagy in a variety of cell types, tissues, and model systems. The unique properties of proteoglycans have ushered in a paradigmatic shift to broaden our understanding of matrix-mediated signaling cascades. Read More

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Nanocomposite sponges for enhancing intestinal residence time following oral administration.

J Control Release 2021 Apr 7. Epub 2021 Apr 7.

Univ Lyon, Université Claude Bernard Lyon 1, CNRS, LAGEPP UMR 5007, 43 Boulevard du 11 Novembre 1918, F-69622 Villeurbanne, France. Electronic address:

In this work, nanocomposites that combine mucopenetrating and mucoadhesive properties in a single system are proposed as innovative strategy to increase drug residence time in the intestine following oral administration. To this aim, novel mucoadhesive chitosan (CH) sponges loaded with mucopenetrating nanoemulsions (NE) were developed via freeze-casting technique. The NE mucopenetration ability was determined studying the surface affinity and thermodynamic binding of the nanosystem with mucins. Read More

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Is SARS-CoV-2 Spike glycoprotein impairing macrophage function via α7-nicotinic acetylcholine receptors?

Food Chem Toxicol 2021 Apr 7:112184. Epub 2021 Apr 7.

Laboratory of Molecular Biology and Immunology, Department of Pharmacy, University of Patras, Panepistimiopolis, 26500 Rio-Patras, Greece. Electronic address:

The innate immune cells play an important role in handling early infections, and can eliminate them completely up to a certain threshold. Beyond that threshold they take up their role in "The Resolution of Inflammation". The recognition of the SARS-CoV-2 antigen triggers an eicosanoid storm and initiates a robust inflammatory response. Read More

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Effect of muscle fatigue on brain activity in healthy individuals.

Brain Res 2021 Apr 7:147469. Epub 2021 Apr 7.

Department of Rehabilitation, Faculty of Health Science, Fukui Health Science University, Fukui-city, Fukui, Japan.

Fatigue is affected by both peripheral and central factors. However, the interrelationship between muscle fatigue and brain activity has not yet been clarified. This study aimed to clarify the effect of muscle fatigue due to sustained pinch movement on brain activity in healthy individuals using functional near-infrared spectroscopy (fNIRS). Read More

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Understanding the elements of a quality rural/remote interprofessional education activity: A rough guide.

Aust J Rural Health 2021 Apr 10. Epub 2021 Apr 10.

Western Australian Centre for Rural Health, Faculty of Medicine and Health Sciences, University of Western Australia, Geraldton, WA, Australia.

Aims: To offer a rough guide to a quality rural/remote interprofessional educational activity.

Context: Australian remote and rural interprofessional undergraduate placements offered in Modified Monash Model 3-6 locations.

Approach: Biggs' triple P framework from the interprofessional educational literature and Allport's contact hypothesis are used to describe map, and explore the educational dimensions and positive elements, of a quality rural/remote interprofessional educational activity. Read More

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Influence of soil variation on diosgenin content profile in Costus speciosus (Koen. Ex Retz) from Indo-Gangetic plains.

Chem Biodivers 2021 Apr 10. Epub 2021 Apr 10.

CSIR-National Botanical Research Institute, PHARMACOGNOSY, RANAPRATAP MARG, Not Available, 226001, LUCKNOW, INDIA.

Costus speciosus is a rich source of commercially important compound Diosgenin, distributed in different regions of India. The present investigation was aimed to quantify diosgenin through High Performance Thin Layer Chromatography in 34 germplasms of Costus speciosus  and also to identify the superior sources and to correlate the macronutrients of rhizospheric soil.             The starch content varied in microscopic examination and correlated inversely (r= -0. Read More

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Prednisone-induced sustained remission in a patient with familial fibronectin glomerulopathy (GFND).

CEN Case Rep 2021 Apr 10. Epub 2021 Apr 10.

Nephrology Division, Department of Medicine, University of Rochester, 601 Elmwood Avenue, Box 675, Rochester, NY, 14642, USA.

Glomerulopathy with Fibronectin Deposits (GFND) is a rare, autosomal dominant disease characterized by proteinuria, hematuria and progressive renal failure associated with glomerular deposition of fibronectin, frequently resulting in end-stage renal disease (ESRD). There is no established treatment for this condition beyond conservative measures such as blood pressure control and the use of angiotensin-converting enzyme (ACE) inhibitors. We present a case of GFND associated with progressive chronic kidney disease (CKD) and nephrotic range proteinuria showing a sustained response to prednisone treatment. Read More

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Time to Failure on Oral Glucose-Lowering Agents for Patients with Type 2 Diabetes: A Retrospective Cohort Study.

Diabetes Ther 2021 Apr 10. Epub 2021 Apr 10.

Eli Lilly Polska Sp. z o.o (Eli Lilly and Company), u.l. Żwirki I Wigury 18a, 02-092, Warsaw, Poland.

Introduction: Research has shown that glycemic control is associated with lower rates of microvascular and long-term cardiovascular complications. In the analyses reported here, we examined treatment failure on oral glucose-lowering agents (GLAs), defined as having sustained hemoglobin A1c (HbA1c) ≥  7%.

Methods: This study utilized the IBM® MarketScan® Claims and Laboratory Data from 1 January 2012 through 30 June 2018. Read More

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Long-term Impacts and Benefit-Cost Analysis of the Communities That Care Prevention System at Age 23, 12 Years After Baseline.

Prev Sci 2021 Apr 10. Epub 2021 Apr 10.

Social Development Research Group, School of Social Work, University of Washington, 9725 Third Avenue NE, Suite 401, Seattle, WA, 98115 , USA.

This study estimated sustained impacts and long-term benefits and costs of the Communities That Care (CTC) prevention system, implemented and evaluated in a longitudinal cluster-randomized trial involving 24 communities in seven states. Analyses utilized reports from a longitudinal panel of 4407 participants, followed since the study's baseline in grade 5, with most recent follow-up 12 years later at age 23. Impacts on lifetime abstinence from primary outcomes of substance use and antisocial behavior were estimated using generalized linear mixed Poisson regression analysis, adjusted for individual and community-level covariates. Read More

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COVID-19-Related Occupational Burnout and Moral Distress among Nurses: A Rapid Scoping Review.

Nurs Leadersh (Tor Ont) 2021 Mar;34(1):7-19

Policy Advisor, Policy and Government Relations, Canadian Nurses Association, Ottawa, ON.

Background: The COVID-19 pandemic is placing unprecedented pressure on a nursing workforce that is already under considerable mental strain due to an overloaded system. Convergent evidence from the current and previous pandemics indicates that nurses experience the highest levels of psychological distress compared with other health professionals. Nurse leaders face particular challenges in mitigating risk and supporting nursing staff to negotiate moral distress and fatigue during large-scale, sustained crises. Read More

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Sublingual immunotherapy for 4 years increased the number of Foxp3 Treg cells, which correlated with clinical effects.

Inflamm Res 2021 Apr 9. Epub 2021 Apr 9.

Laboratory of Immunopharmacology, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka, Japan.

Objective: At least 3 years of sublingual immunotherapy (SLIT) is required to achieve long-term clinical tolerance for allergens. However, immunological changes with more than 3 years of SLIT have not yet been elucidated in detail. The present study investigated whether the numbers of regulatory T (Treg) cells and regulatory B (Breg) cells increased with 4 years of SLIT and if these increases correlated with clinical effects for pollinosis. Read More

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Modelling intensive care unit capacity under different epidemiological scenarios of the COVID-19 pandemic in three Western European countries.

Int J Epidemiol 2021 Apr 9. Epub 2021 Apr 9.

MRC Centre for Global Infectious Disease Analysis & WHO Collaborating Centre for Infectious Disease Modelling, Abdul Latif Jameel Institute for Disease and Emergency Analytics, Imperial College London, St Mary's Campus, Norfolk Place, London, UK.

Background: The coronavirus disease 2019 (COVID-19) pandemic has placed enormous strain on intensive care units (ICUs) in Europe. Ensuring access to care, irrespective of COVID-19 status, in winter 2020-2021 is essential.

Methods: An integrated model of hospital capacity planning and epidemiological projections of COVID-19 patients is used to estimate the demand for and resultant spare capacity of ICU beds, staff and ventilators under different epidemic scenarios in France, Germany and Italy across the 2020-2021 winter period. Read More

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A study of endothelial and platelet microvesicles across different hypertension phenotypes.

J Hum Hypertens 2021 Apr 9. Epub 2021 Apr 9.

3rd Department of Internal Medicine, Papageorgiou Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Rather than being mere biomarkers reflecting generalized vascular injury, endothelial- (EMVs) and platelet-derived (PMVs) microvesicles have emerged as potent regulators of intercellular communication with significant biologic effects in vascular homeostasis and several pathophysiological responses including inflammation and thrombosis. So far, studies in hypertension are scarce, whereas no studies exist in masked hypertension (MH). We measured EMVs and PMVs in untreated, newly diagnosed hypertensives (HTs) and MHs compared to normotensive controls (NTs), and associated them with various cardiovascular risk factors. Read More

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Input-specific modulation of murine nucleus accumbens differentially regulates hedonic feeding.

Nat Commun 2021 Apr 9;12(1):2135. Epub 2021 Apr 9.

Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.

Hedonic feeding is driven by the "pleasure" derived from consuming palatable food and occurs in the absence of metabolic need. It plays a critical role in the excessive feeding that underlies obesity. Compared to other pathological motivated behaviors, little is known about the neural circuit mechanisms mediating excessive hedonic feeding. 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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Maternal finger-prick allogenic blood for persistent corneal epithelial defects.

BMJ Case Rep 2021 Apr 9;14(4). Epub 2021 Apr 9.

Department of Ophthalmology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.

This is a case of a 17-year-old patient with aniridia-related keratopathy and persistent epithelial defect (PED) treated successfully using maternal finger-prick blood (FPB). Maternal allogenic FPB treatment was initiated to the patient who was non-compliant with the use of autologous FPB. The PED was successfully managed with maternal FPB treatment with rapid and complete closure of the epithelial defect. Read More

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Hydroxyzine-induced priapism: A case report.

Am J Emerg Med 2021 Mar 24. Epub 2021 Mar 24.

Jesse Brown VA Medical Center, 820 South Damen Avenue, Chicago, IL 60612, United States of America.

Priapism is a severe urologic condition requiring emergency management. Ischemic priapism is the most common subtype which is characterized by a long-lasting, painful, and rigid erection which can be caused by medications with alpha-adrenergic properties such as hydroxyzine. Typically, medication-induced priapism is reported at therapeutic doses and few case reports exist implicating medication overdose as the cause. Read More

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Synovial fluid neutrophils in oligoarticular juvenile idiopathic arthritis have an altered phenotype and impaired effector functions.

Arthritis Res Ther 2021 Apr 9;23(1):109. Epub 2021 Apr 9.

Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden.

Background: Neutrophils are the most prevalent immune cells in the synovial fluid in inflamed joints of children with oligoarticular juvenile idiopathic arthritis (JIA). Despite this, little is known about neutrophil function at the site of inflammation in JIA and how local neutrophils contribute to disease pathogenesis. This study aimed to characterize the phenotype and function of synovial fluid neutrophils in oligoarticular JIA. Read More

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Central composite design for the development of carvedilol-loaded transdermal ethosomal hydrogel for extended and enhanced anti-hypertensive effect.

J Nanobiotechnology 2021 Apr 9;19(1):100. Epub 2021 Apr 9.

Department of Biomedical Science & Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon, 24341, Republic of Korea.

Background: Carvedilol, the anti-hypertensive drug, has poor bioavailability when administered orally. Ethosomes-mediated transdermal delivery is considered a potential route of administration to increase the bioavailability of carvedilol. The central composite design could be used as a tool to optimize ethosomal formulation. Read More

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DNMT1 maintains metabolic fitness of adipocytes through acting as an epigenetic safeguard of mitochondrial dynamics.

Proc Natl Acad Sci U S A 2021 Mar;118(11)

National Creative Research Initiatives Center for Adipocyte Structure and Function, Seoul National University, Seoul 08826, South Korea;

White adipose tissue (WAT) is a key regulator of systemic energy metabolism, and impaired WAT plasticity characterized by enlargement of preexisting adipocytes associates with WAT dysfunction, obesity, and metabolic complications. However, the mechanisms that retain proper adipose tissue plasticity required for metabolic fitness are unclear. Here, we comprehensively showed that adipocyte-specific DNA methylation, manifested in enhancers and CTCF sites, directs distal enhancer-mediated transcriptomic features required to conserve metabolic functions of white adipocytes. Read More

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Noninvasive scalp recording of the middle latency responses and cortical auditory evoked potentials in the alert common marmoset.

Hear Res 2021 Mar 27;405:108229. Epub 2021 Mar 27.

Cognitive Neuroscience Section, Primate Research Institute, Kyoto University, 41-2, Kanrin, Inuyama, Aichi, 484-8506, Japan.

The common marmoset (Callithrix jacchus), a New World monkey, serves as a useful animal model in clinical and basic neuroscience. The present study recorded scalp auditory evoked potentials (AEP) in non-sedated common marmoset monkeys (n = 4) using a noninvasive method similar to that used in humans, and aimed to identify nonhuman primate correlates of the human AEP components. A pure tone stimulus was presented while electroencephalograms were recorded using up to 16 disk electrodes placed on the scalp and earlobes. Read More

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A self-sustained nanoplatform reverses TRAIL-resistance of pancreatic cancer through coactivating of exogenous and endogenous apoptotic pathway.

Biomaterials 2021 Apr 1;272:120795. Epub 2021 Apr 1.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China. Electronic address:

Since the 5-year survival rate of pancreatic cancer is only 10.0%, new therapies are urgently needed. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis specifically on tumor cells, nevertheless its clinical application was seriously restricted by resistance and short in vivo half-life. Read More

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Muscarinic M1, but not M4, receptor antagonism impairs divided attention in male rats.

Pharmacol Biochem Behav 2021 Apr 6;205:173184. Epub 2021 Apr 6.

Department of Psychology, Edinboro University of Pennsylvania, Edinboro, PA 16444, USA. Electronic address:

Divided attention may be more important than ever to comprehend, given ubiquitous distractors in modern living. In humans, concern has been expressed about the negative impact of distraction in education, the home, and the workplace. While acetylcholine supports divided attention, in part via muscarinic receptors, little is known about the specific muscarinic subtypes that may contribute. Read More

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Chitosan derivatives-based films as pH-sensitive drug delivery systems with enhanced antioxidant and antibacterial properties.

Int J Biol Macromol 2021 Apr 6. Epub 2021 Apr 6.

Laboratory of Enzyme Engineering and Microbiology, National School of Engineering of Sfax (ENIS), University of Sfax, P.O. Box 1173, Sfax 3038, Tunisia; Department of Life Sciences, Faculty of Science of Gabes, Omar Ibn Khattab Street, Gabes 6029, Tunisia. Electronic address:

The purpose of this study was to develop and characterize chitosan (Ch)-based films incorporated with varying molecular weight (Mw) and acetylation degree (AD) chitosan-depolymerization-products (CDP), to be applied as drug delivery materials. As compared to Ch-film, optical and antioxidant potentials of Ch/CDP-based films were improved, particularly using low Mw and AD-CDP. Whereas, films water resistance, mechanical and antibacterial properties increased as CDP-Mw increased and AD decreased. Read More

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A real-life study of the positive response to DAA-based therapies for hepatitis C in Brazil.

Braz J Infect Dis 2021 Apr 6:101573. Epub 2021 Apr 6.

University of Brasília (UnB), Faculty of Medicine, Center for Tropical Medicine, Brasília, DF, Brazil; National Institute for Science and Technology for Health Technology Assessment, Porto Alegre, RS, Brazil; University of Brasília (UnB), Faculty of Ceilândia, Brasília, DF, Brazil.

A retrospective cohort of 11,308 chronic hepatitis C infected patients treated with regimens that included Sofosbuvir (SOF), Daclatasvir (DCV), Simeprevir (SMV), or an association of Ombitasvir, Veruprevir/Ritonavir and Dasabuvir (3D) with or without Ribavirin (RBV) were assessed for sustained virologic response (SVR) or viral cure after a 12-week treatment. Logistic regression analyses were used to identify factors independently associated with positive response to direct-acting antivirals (DAA)-based therapies. Overall 57. Read More

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A small molecule inhibitor of the chloride channel TMEM16A blocks vascular smooth muscle contraction and lowers blood pressure in spontaneously hypertensive rats.

Kidney Int 2021 Apr 6. Epub 2021 Apr 6.

Departments of Medicine and Physiology, University of California San Francisco, CA, USA.

Hypertension is a major cause of cardiovascular morbidity and mortality, despite the availability of antihypertensive drugs with different targets and mechanisms of action. Here, we provide evidence that pharmacological inhibition of TMEM16A (ANO1), a calcium-activated chloride channel expressed in vascular smooth muscle cells, blocks calcium-activated chloride currents and contraction in vascular smooth muscle in vitro and decreases blood pressure in spontaneously hypertensive rats. The acylaminocycloalkylthiophene TMinh-23 fully inhibited calcium-activated TMEM16A chloride current with nanomolar potency in Fischer rat thyroid cells expressing TMEM16A, and in primary cultures of rat vascular smooth muscle cells. Read More

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