769,509 results match your criteria Critical Reviews in Clinical Laboratory Sciences [Journal]


Alpha and omega in potassium-channel opening.

Authors:
Fredrik Elinder

Acta Physiol (Oxf) 2018 Dec 16:e13240. Epub 2018 Dec 16.

Department of Clinical and Experimental Medicine, Linköping University, Sweden.

In this issue of Acta Physiologica, a study from the laboratory of Peter Larsson shows that the distance between the carboxyl group and the first double bond of polyunsaturated fatty acids (PUFAs) is critical for the affinity of the PUFA molecule to a voltage-gated potassium channel found in the heart . A shorter distance increases the affinity, and the bound PUFA alters the channel's voltage dependence and thereby opens the channel. The efficacy, that is the channel-opening effect of a bound PUFA molecule, partly depends on the distance between the last double bond and the end of the hydrophobic tail. Read More

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December 2018

In vitro and in vivo evidence of tyrosinase inhibitory activity of a synthesized (Z)-5-(3-hydroxy-4-methoxybenzylidene)-2-thioxothiazolidin-4-one (5-HMT).

Exp Dermatol 2018 Dec 15. Epub 2018 Dec 15.

Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan, 46241, Republic of Korea.

Tyrosinase is a key enzyme that catalyzes the initial rate-limiting steps of melanin synthesis. Due to its critical role in melanogenesis, various attempts were made to find potent tyrosinase inhibitors although many were not safe and effective in vivo. We evaluated tyrosinase inhibitory activity of six compounds. Read More

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December 2018
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A Comparison of the Shielding Effectiveness of Silicone Oil Vitreous Substitutes when used with Palladium-103 and Iodine-125 Eye Plaques.

Med Phys 2018 Dec 16. Epub 2018 Dec 16.

200 Medical Plaza Ste B265, Los Angeles, CA, 90095.

Purpose: Epi-scleral eye plaques provide excellent local control of ocular melanoma, but vision sparing remains a significant problem with 30% or more of patients experiencing significant visual acuity degradation. The use of silicone oil shielding with Iodine-125 plaques has previously been reported to improve critical structure sparing. We hypothesized that the use of Palliadium-103 would improve the shielding effectiveness of silicone oil due to the strong energy dependence of the photoelectric effect. Read More

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December 2018

Quorum sensing between Gram-negative bacteria responsible for methane production in a complex waste sewage sludge consortium.

Appl Microbiol Biotechnol 2018 Dec 15. Epub 2018 Dec 15.

Department of Biological Functions Engineering, Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, 2-4 Hibikino, Wakamatsu, Kitakyushu, 808-0196, Japan.

Quorum sensing (QS) plays a key role in activating bacterial functions through small molecules called autoinducers. In this study, the QS of Gram-negative bacteria in waste sewage sludge (WSS) was downregulated by adding the quorum quenching enzyme, AiiM lactonase, which cleaved the acyl-homoserine lactone (AHL) autoinducer signals from Gram-negative bacteria, and subsequently methane production was inhibited by over 400%. The pH was lowered after 2 days in the anaerobic fermentation whereas protease activity at the hydrolysis step was almost the same with or without AiiM. Read More

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December 2018

Functional roles of Grainyhead-like transcription factors in renal development and disease.

Pediatr Nephrol 2018 Dec 15. Epub 2018 Dec 15.

Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125, Berlin, Germany.

Proper renal function relies on the tightly regulated development of nephrons and collecting ducts. This process, known as tubulogenesis, involves dynamic cellular and molecular changes that instruct cells to form highly organized tubes of epithelial cells which compartmentalize the renal interstitium and tubular lumen via assembly of a selective barrier. The integrity and diversity of the various renal epithelia is achieved via formation of intercellular protein complexes along the apical-basal axis of the epithelial cells. Read More

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December 2018
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Photoplethysmographic characterization of vascular tone mediated changes in arterial pressure: an observational study.

J Clin Monit Comput 2018 Dec 15. Epub 2018 Dec 15.

Hedenstierna Laboratory, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.

To determine whether a classification based on the contour of the photoplethysmography signal (PPGc) can detect changes in systolic arterial blood pressure (SAP) and vascular tone. Episodes of normotension (SAP 90-140 mmHg), hypertension (SAP > 140 mmHg) and hypotension (SAP < 90 mmHg) were analyzed in 15 cardiac surgery patients. SAP and two surrogates of the vascular tone, systemic vascular resistance (SVR) and vascular compliance (Cvasc = stroke volume/pulse pressure) were compared with PPGc. Read More

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December 2018
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The Role of Adaptive Behavior and Parent Expectations in Predicting Post-School Outcomes for Young Adults with Intellectual Disability.

J Autism Dev Disord 2018 Dec 15. Epub 2018 Dec 15.

Nisonger Center, The Ohio State University, 1581 Dodd Drive, McCampbell Hall 357, Columbus, OH, 43210, USA.

This study examined the role of parent expectations and adaptive behavior in predicting outcomes for youth with intellectual disability. A sample of students with intellectual disability were drawn from the National Longitudinal Transition Study-2 for inclusion in this study. Four latent variables were created: demographic factors, adaptive behavior, parent expectations, and post-school outcomes. Read More

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December 2018

Efficacy and Safety of CFTR Corrector and Potentiator Combination Therapy in Patients with Cystic Fibrosis for the F508del-CFTR Homozygous Mutation: A Systematic Review and Meta-analysis.

Adv Ther 2018 Dec 15. Epub 2018 Dec 15.

Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China.

Introduction: Cystic fibrosis (CF) is a progressive, genetic disease that causes persistent lung infections and limits the ability to breathe over time. The combination of a cystic fibrosis transmembrane conductance regulator (CFTR) corrector and potentiator has provided a benefit by decreasing sweat chloride concentration in CF for the F508del-CFTR homozygous mutation, but it remains controversial in lung function, nutritional status, clinical score and safety.

Methods: The authors performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of combination therapy on lung function, nutritional status, clinical score and safety in CF for the F508del-CFTR homozygous mutation. Read More

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December 2018
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Immune aspects of the bi-directional neuroimmune facilitator TRPV1.

Mol Biol Rep 2018 Dec 15. Epub 2018 Dec 15.

School of Arts and Sciences, St. Bonaventure University, St. Bonaventure, New York, 14778, USA.

A rapidly growing area of interest in biomedical science involves the reciprocal crosstalk between the sensory nervous and immune systems. Both of these systems are highly integrated, detecting potential environmental harms and restoring homeostasis. Many different cytokines, receptors, neuropeptides, and other proteins are involved in this bidirectional communication that are common to both systems. Read More

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December 2018

The maternal reward system in postpartum depression.

Arch Womens Ment Health 2018 Dec 15. Epub 2018 Dec 15.

Department of Psychology, The Ohio State University, 1835 Neil Avenue, Columbus, OH, USA.

The experience of motherhood is most often emotionally positive and rewarding, but for many new mothers suffering from postpartum depression (PPD), this is not the case. Preclinical and clinical research has sought to uncover brain changes underlying PPD in order to gain a better understanding of how this disorder develops. This review focuses on the mesolimbic dopamine system, particularly the ventral tegmental area-nucleus accumbens pathway which has been implicated in the regulation of critical functions disrupted in PPD including mood, motivation, and mothering. Read More

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December 2018

The perception of psychosocial risks through the HSE questionnaire of a population of neurophysiology technicians: a cross-sectional study.

Clin Ter 2018 Nov-Dec;169(6):e281-e286

Department of Public Health and Infectious Diseases, University of Rome "Sapienza", Rome, Italy.

Objectives: The Neurophysiopathology Technicians (NTs) are exposed to psychosocial risks, exposure to psychosocial risks that cause related work stress has been related to numerous physical and mental illnesses. The aim of this study is to evaluate the perception of psychosocial risks in a population of this population.

Materials And Methods: 54 technicians of Neurophysiopathology were enrolled, consisting of 23 males (42,6 %) and 31 females (57,4 %). Read More

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December 2018

Official controls regarding artisanal ice cream shops: public health policies and consumer protection in the Italian and European legislative frameworks.

Ann Ig 2019 Jan-Feb;31(1):76-85

Department of Medical and Surgical Sciences and Translational Medicine, Sapienza University of Rome, Rome, Italy.

Ice cream is a widely enjoyed food that is especially popular during summer. To ensure it is safe and ready-to-eat for consumers, legislation imposes a series of obligations for food business operators, and for competent authorities that have to carry out official controls, including official sampling. This article reviews the general and specific requirements applicable to the premises where ice cream is produced, concerning aspects related to health notification obligations and to implementing and maintaining procedures based on the principles of the Hazard Analysis and Critical Control Point system. Read More

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December 2018

Better Being Single? Omics Improves Kidney Organoids.

Nephron 2018 Dec 14;141(2):1-5. Epub 2018 Dec 14.

Context: Human kidney organoids are complex structures resembling nephron arrays, which can be derived in a variety of ways. Whether all of these differentiation protocols produce qualitatively similar organoid cell types is not yet clear. Subject of Review: A comparative analysis of 2 organoid differentiation protocols is recently reported in Cell Stem Cell [Wu et al. Read More

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December 2018

Transbronchial Cryobiopsies for Diagnosing Interstitial Lung Disease: Real-Life Experience from a Tertiary Referral Center for Interstitial Lung Disease.

Respiration 2018 Dec 14:1-7. Epub 2018 Dec 14.

Center for Interstitial and Rare Lung Diseases, Thoraxklinik, University of Heidelberg, Heidelberg,

Background: Transbronchial cryobiopsy (cTBB) may offer an alternative to surgical lung biopsy (SLB) for histopathological diagnosis of interstitial lung diseases (ILDs). However, real-life experience is limited, although case series are increasingly reported.

Objectives: We aimed to evaluate the value of cTBB performed under real-life conditions in a tertiary care center for ILDs. Read More

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December 2018

Insufficient sleep and fitness to drive in shift workers: a systematic literature review protocol.

Inj Prev 2018 Dec 15. Epub 2018 Dec 15.

Faculty of Health Sciences, Western University, London, Ontario, Canada.

Background: The majority of shift workers experience insufficient sleep as a result of their employment. Insufficient sleep is associated with impaired neurocognitive functioning, affecting key skills required for driving, resulting in shift workers experiencing a disproportionate burden of RTC injuries and fatalities. Yet, to our knowledge, no systematic literature review (SLR) exists to critically appraise and synthesise evidence on the determinants of fitness to drive (assessed on-road) and driving performance (assessed in a driving simulator) in shift workers with insufficient sleep. Read More

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December 2018

Use of supplemental oxygen in emergency patients: a systematic review and recommendations for military clinical practice.

J R Army Med Corps 2018 Dec 15. Epub 2018 Dec 15.

Emergency Department, University Hospitals Plymouth NHS Trust, Plymouth, UK.

Introduction: Supplemental oxygen is a key element of emergency treatment algorithms. However, in the operational environment, oxygen supply poses a challenge. The lack of high-quality evidence alongside emerging technologies provides the opportunity to challenge current guidelines. Read More

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December 2018

Use of Consensus Methodology to Determine Candidate Items for Systemic Lupus Erythematosus Classification Criteria.

J Rheumatol 2018 Dec 15. Epub 2018 Dec 15.

S.R. Johnson MD PhD FRCPC, Division of Rheumatology, Department of Medicine, Toronto Western Hospital, Mount Sinai Hospital; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada. D. Khanna MD MS, Division of Rheumatology, Department of Medicine, University of Michigan, USA. R. Cervera MD PhD FRCP, Hospital Clínic, Barcelona, Spain. N. Costedoat-Chalumeau MD PhD AP-HP, Cochin Hospital, Internal Medicine Department, Centre de référence maladies auto-immunes et systémiques rares d'île de France, Paris, France ; Université Paris Descartes-Sorbonne Paris Cité, Paris, France ; INSERM U 1153, Center for Epidemiology and Statistics Sorbonne Paris Cité (CRESS), Paris, France. D.D. Gladman MD FRCPC, Division of Rheumatology, Department of Medicine, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada. B.H. Hahn MD, University of California Los Angeles, Los Angeles, USA. F. Hiepe MD, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Rheumatology and Clinical Immunology, Charitéplatz 1, 10117 Berlin, Germany. J. Sánchez-Guerrero MD MSc, Division of Rheumatology, Department of Medicine Mount Sinai Hospital/University Health Network, University of Toronto, Toronto, Ontario, Canada; and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico. E. Massarotti MD, Brigham and Women's Hospital, Boston MA; Harvard Medical School, Boston, USA. D.T. Boumpas MD FACP FACR, National and Kapodestrian University of Athens, and Biomedical Research Foundation of the Athens Academy, Athens, Greece. K.H Costenbader MD MPH, Brigham and Women's Hospital, Boston, MA; Harvard Medical School, Boston, USA. D. Daikh MD, University of California, San Francisco, USA. D. Jayne MD FRCP FRCPE FMedSci, Department of Medicine, University of Cambridge, United Kingdom. T. Dörner MD, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Rheumatology and Clinical Immunology, Charitéplatz 1, 10117 Berlin, Germany. D.L. Kamen MD MSCR, Medical University of South Carolina, Charleston, USA. M. Mosca MD PhD, University of Pisa, Italy. R. Ramsey-Goldman MD DrPH, Northwestern University Feinberg School of Medicine, Chicago, USA. J.S. Smolen MD, Medical University of Vienna, Austria. D. Wofsy MD, University of California, San Francisco, USA. M. Aringer MD, University Medical Center and Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany. Address correspondence to Sindhu Johnson MD PhD, Division of Rheumatology, Ground Floor, East Wing, Toronto Western Hospital, 399 Bathurst Street, Toronto, Ontario, Canada, M5T 2S8. Phone 1-416-603-6417 Fax.1-416-603- 4348. Email:

Objective: Given the complexity and heterogeneity of systemic lupus erythematosus (SLE), high performing classification criteria are critical to advancing research and clinical care. A collaborative effort by EULAR and ACR was undertaken to generate candidate criteria, and then to reduce them to a smaller set. The objective of the current study was to select a set of criteria that maximizes the likelihood of accurate classification of SLE, particularly early disease. Read More

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December 2018

A serine in the first transmembrane domain of the human E3 ubiquitin ligase MARCH9 is critical for down-regulation of its protein substrates.

J Biol Chem 2018 Dec 15. Epub 2018 Dec 15.

Structural Biology, The Walter and Eliza Hall Institute of Medical Research, Australia.

The membrane-associated RING-CH (MARCH) family of membrane-bound E3 ubiquitin ligases regulates the levels of cell-surface membrane proteins, many of which are involved in immune responses. Although their role in ubiquitin-dependent endocytosis and degradation of cell-surface proteins is extensively documented, the features of MARCH proteins and their substrates that drive the molecular recognition events leading to ubiquitin transfer remain poorly defined. In this study, we sought to determine the features of human MARCH9 that are required for regulating the surface levels of its substrate proteins. Read More

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December 2018

TAKling GDF-15 and skeletal muscle atrophy in pulmonary hypertension: are we there yet?

Thorax 2018 Dec 15. Epub 2018 Dec 15.

Division of Pulmonary, Allergy and Critical Care, Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

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December 2018
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Therapeutic targeting of angiogenesis molecular pathways in angiogenesis-dependent diseases.

Biomed Pharmacother 2018 Dec 13;110:775-785. Epub 2018 Dec 13.

Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran; Molecular Medicine Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

Angiogenesis is a critical step in the progression of almost all human malignancies and some other life-threatening diseases. Anti-angiogenic therapy is a novel and effective approach for treatment of angiogenesis-dependent diseases such as cancer, diabetic retinopathy, and age-related macular degeneration. In this article, we will review the main strategies developed for anti-angiogenic therapies beside their clinical applications, the major challenges, and the latest advances in the development of anti-angiogenesis-based targeted therapies. Read More

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December 2018
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Innate T cells in the intensive care unit.

Mol Immunol 2018 Dec 13;105:213-223. Epub 2018 Dec 13.

Brigham and Women's Hospital, Pulmonary and Critical Care Medicine, Boston, MA, 02115, United States; Harvard Medical School, Boston, MA, 02115, United States.

Rapid onset of acute inflammation is a hallmark of critical illnesses that bring patients to the intensive care unit (ICU). In critical illness, innate T cells rapidly reach full activation and drive a robust acute inflammatory response. As "cellular adjuvants," innate T cells worsen inflammation and mortality in several common critical illnesses including sepsis, ischemia-reperfusion injury, stroke, and exacerbations of respiratory disease. Read More

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December 2018

Lipid exchange at ER-mitochondria contact sites: a puzzle falling into place with quite a few pieces missing.

Curr Opin Cell Biol 2018 Dec 13;57:71-76. Epub 2018 Dec 13.

Institute of Biochemistry, ETH Zurich, 8093 Zurich, Switzerland. Electronic address:

Over the last years, the importance of inter-organelle communication has become more and more evident, attested by the fast growing number of newly-identified membrane contact sites (MCS). At MCSs two organelles are connected via protein tethers that bring them in close proximity to facilitate metabolite exchange. In this review, we will focus on the MCSs connecting the ER and mitochondria, which have been implicated in phospholipid transport. Read More

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December 2018

Distinct microbially induced concrete corrosion at the tidal region of reinforced concrete sewers.

Water Res 2018 Dec 6;150:392-402. Epub 2018 Dec 6.

Advanced Water Management Centre, The University of Queensland, St. Lucia, QLD, 4072, Australia. Electronic address:

Microbially induced concrete corrosion (MICC) is a major deterioration affecting sewers worldwide. MICC is not uniform on sewer inner walls and often occurs at hot spots such as crown and tidal regions, which are critical to determine sewer service life. Especially, concrete corrosion in tidal regions is complicated due to the fluctuation of wastewater levels and the hydraulic scouring effects. Read More

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December 2018

"It's about bloody time": Perceptions of people who use drugs regarding drug law reform.

Int J Drug Policy 2018 Dec 13;64:40-46. Epub 2018 Dec 13.

Drug Policy Modelling Program, University of New South Wales, 22-32 King Street, Randwick NSW 2031, Australia.

Background: In Australia and elsewhere, the impacts of drug prohibition have sparked a critical dialogue about the state of current drug laws. While a range of 'experts' have offered their opinion and participation in these deliberations, the voices of the affected community have largely been excluded. This study aimed to gather the opinions and preferences of people who use drugs about the current or alternative models of drug laws, in addition to how they think drug laws could be changed Author Conflict of Interest Declaration. Read More

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December 2018

White spot syndrome virus infection activates Caspase 1-mediated cell death in crustacean.

Virology 2018 Dec 13;528:37-47. Epub 2018 Dec 13.

College of Life Sciences and Laboratory for Marine Biology and Biotechnology of Qingdao National Laboratory for Marine Science and Technology, Zhejiang University, Hangzhou 310058, People's Republic of China. Electronic address:

In vertebrates, pyroptosis is an intense inflammatory form of programmed cell death. This death pathway is critical for controlling pathogenic infection. In invertebrates, however, due to the lack of adaptive immune response, it is still elusive whether Caspase 1-dependent cell death pathway exists. Read More

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December 2018

Chemical and odor characterization of gas emissions released during composting of solid wastes and digestates.

J Environ Manage 2018 Dec 13;233:39-53. Epub 2018 Dec 13.

Irstea, UR OPAALE, 17 Avenue de Cucillé, CS 64427, F-35044, Rennes, France. Electronic address:

Hazardous and odorous gas emissions from composting and methanization plants are an issue of public concern. Odor and chemical monitoring are thus critical steps in providing suitable strategies for air pollution control at waste treatment units. In this study, 141 gas samples were extensively analyzed to characterize the odor and chemical emissions released upon the aerobic treatment of 10 raw substrates and five digestates. Read More

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December 2018

A new sequence based encoding for prediction of host-pathogen protein interactions.

Comput Biol Chem 2018 Dec 5;78:170-177. Epub 2018 Dec 5.

Department of Computer and Information Sciences, Sakarya University, Serdivan, Sakarya, 54050, Turkey.

Pathogen-host interactions are very important to figure out the infection process at the molecular level, where pathogen proteins physically bind to human proteins to manipulate critical biological processes in the host cell. Data scarcity and data unavailability are two major problems for computational approaches in the prediction of pathogen-host interactions. Developing a computational method to predict pathogen-host interactions with high accuracy, based on protein sequences alone, is of great importance because it can eliminate these problems. Read More

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December 2018

Doppler-defined pulmonary hypertension in sepsis and septic shock.

J Crit Care 2018 Dec 8;50:201-206. Epub 2018 Dec 8.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, United States; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, Rochester, MN, United States.

Background: The association of pulmonary hypertension (PH) in patients with sepsis is lesser understood.

Methods: This was a retrospective study of adult patients admitted to the intensive care unit during 2007-2014 for sepsis and septic shock, with echocardiography performed <72 h. PH was defined as tricuspid regurgitation peak velocity (TRV) > 3 m/s on Doppler echocardiography. Read More

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December 2018
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μImpact of a nursing-driven sedation protocol with criteria for infusion initiation in the surgical intensive care unit.

J Crit Care 2018 Nov 30;50:195-200. Epub 2018 Nov 30.

Department of Pharmacy, The Ohio State University Wexner Medical Center, 410 W. 10th Avenue, Columbus, OH 43210, USA. Electronic address:

Purpose: Analgesia and sedation protocols (ASPs) reduce duration of mechanical ventilation (MV) in the medical intensive care unit (ICU), but data in the surgical ICU (SICU) are limited. The objective of this study was to determine the impact of a nursing-driven ASP with criteria for infusion initiation in the SICU.

Materials And Methods: A single-center, retrospective study compared ventilator-free days at day 28 from start of MV (VFD28) before and after ASP implementation. Read More

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November 2018

Regional differences in the treatment of refractory vasodilatory shock using Angiotensin II in High Output Shock (ATHOS-3) data.

J Crit Care 2018 Dec 8;50:188-194. Epub 2018 Dec 8.

Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Emory University, Atlanta, GA, United States.

Introduction: Despite international guidelines, regional differences in treatment of vasodilatory shock remain. We characterized these differences using data from Angiotensin II in High Output Shock (ATHOS-3) trial.

Methods: The 321 patients treated in the ATHOS-3 trial were included. Read More

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December 2018

A regression model including fetal orbit measurements to predict parturition in Standardbred mares with normal pregnancy.

Theriogenology 2018 Dec 10;126:153-158. Epub 2018 Dec 10.

Department of Veterinary Medical Sciences, University of Bologna, Via Tolara di Sopra 50, 40064, Ozzano Emilia, Bologna, Italy. Electronic address:

In the mare, foaling is a critical unpredictable event due to a wide range of gestational length and the absence of clear signs of impending parturition. To predict foaling, pH, inversion sodium potassium and increase of calcium concentration in mammary secretions are used. The aim of this study was to find how many days are left until parturition knowing mare's age (A) and parity (P) combined with ultrasonographic measurements of the fetal orbit in Standardbred mares with normal pregnancy. Read More

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December 2018

Assessing the risk of drug crystallization in vivo.

J Pharmacol Toxicol Methods 2018 Dec 13. Epub 2018 Dec 13.

Research & Development, Bristol-Myers Squibb Company, Princeton, NJ, USA; University of Kansas, Lawrence, KS, USA.

Introduction: Low intrinsic solubility leading to poor oral bioavailability is a common challenge in drug discovery that can often be overcome by formulation strategies, however, it remains a potential limitation that can pose challenges for early risk assessment and represent a significant obstacle to drug development. We identified a selective inhibitor (BMS-986126) of the IL-1 receptor-associated kinase 4 (IRAK4) with favorable properties as a lead candidate, but with unusually low intrinsic solubility of <1 μg/mL.

Methods: Conventional histopathology identified the issue of crystal formation in vivo. Read More

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December 2018

EGR-mediated control of STIM expression and function.

Cell Calcium 2018 Dec 6;77:58-67. Epub 2018 Dec 6.

Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA, 19140, USA; Department of Medical Genetics & Molecular Biochemistry, Temple University School of Medicine, Philadelphia, PA, 19140, USA. Electronic address:

Ca is a ubiquitous, dynamic and pluripotent second messenger with highly context-dependent roles in complex cellular processes such as differentiation, proliferation, and cell death. These Ca signals are generated by Ca-permeable channels located on the plasma membrane (PM) and endoplasmic reticulum (ER) and shaped by PM- and ER-localized pumps and transporters. Differences in the expression of these Ca homeostasis proteins contribute to cell and context-dependent differences in the spatiotemporal organization of Ca signals and, ultimately, cell fate. Read More

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December 2018

Melatonin receptor activation provides cerebral protection after traumatic brain injury by mitigating oxidative stress and inflammation via the Nrf2 signaling pathway.

Free Radic Biol Med 2018 Dec 13. Epub 2018 Dec 13.

Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address:

Traumatic brain injury (TBI) is a principal cause of death and disability worldwide. Melatonin, a hormone made by the pineal gland, is known to have anti-inflammatory and antioxidant properties. In this study, using a weight-drop model of TBI, we investigated the protective effects of ramelteon, a melatonin MT1/MT2 receptor agonist, and its underlying mechanisms of action. Read More

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December 2018

PERK is essential for proliferation of intestinal stem cells in mice.

Exp Cell Res 2018 Dec 14. Epub 2018 Dec 14.

Division of Emergency Medicine, Department of General Internal Medicine, Department of Emergency Intensive Care Unit, The First Affiliated Hospital of Sun Yat-sen University, No.58, Zhongshan 2nd Road, Guangzhou, 510080, China. Electronic address:

Protein kinase RNA-like Endoplasmic Reticulum Kinase (PERK) is an endoplasmic reticulum stress sensor that possesses pro-survival capability and contributes to cell homeostasis and survival. Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) has been recognized as a stem cell marker in intestinal epithelial cells. To determine whether PERK modulates the proliferation of intestinal stem cells, we investigated the effects of PERK knock-down on intestinal Lgr5-positive stem cells in mice. Read More

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December 2018

Exposure to tobacco smoke during the early postnatal period modifies receptors and enzymes of the endocannabinoid system in the brainstem and striatum in mice.

Toxicol Lett 2018 Dec 13. Epub 2018 Dec 13.

Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 580, bloco 13B, 05508-000, São Paulo, SP, Brazil. Electronic address:

Environmental tobacco smoke (ETS) exposure during brain development has been associated with several disorders, such as depression, anxiety, sudden infant death syndrome, and the predisposition to addiction. The endocannabinoid system plays an essential role in neuronal development. We investigated the effects of early postnatal ETS exposure on the endocannabinoid system in different brain regions. Read More

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December 2018
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A mechanistic account of bodily resonance and implicit bias.

Cognition 2018 Dec 13;184:1-10. Epub 2018 Dec 13.

UCL Institute of Cognitive Neuroscience, London, UK; UCL Queen Square Institute of Neurology, London, UK. Electronic address:

Implicit social biases play a critical role in shaping our attitudes towards other people. Such biases are thought to arise, in part, from a comparison between features of one's own self-image and those of another agent, a process known as 'bodily resonance'. Recent data have demonstrated that implicit bias can be remarkably plastic, being modulated by brief immersive virtual reality experiences that place participants in a virtual body with features of an out-group member. Read More

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December 2018

Prolonged ad libitum access to low-concentration sucrose changes the neurochemistry of the nucleus accumbens in male Sprague-Dawley rats.

Physiol Behav 2018 Dec 13. Epub 2018 Dec 13.

School of Medical Sciences, Discipline of Anatomy & Histology, University of Sydney, NSW, Australia, 2006.

Overconsumption of sugars contributes to poor health outcomes. Sugars are often added to commercial foods and beverages in low concentrations and these hidden sugars are consumed unnoticed, continuously. These hidden sugars are suggested to increase the motivation for foodstuffs with higher sugar contents, due to their rewarding properties. Read More

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December 2018

Injectable PLGA microspheres with tunable magnesium ions release for promoting bone regeneration.

Acta Biomater 2018 Dec 13. Epub 2018 Dec 13.

State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, PR China. Electronic address:

Magnesium ions (Mg) are bioactive and proven to promote bone tissue regeneration, in which the enhancement efficiency is closely related to Mg concentrations. Currently, there are no well-established bone tissue engineering scaffolds that can precisely control Mg release, although this capability could have a marked impact in bone regeneration. Leveraging the power of biodegradable microspheres to control the release of bioactive factors, we developed lactone-based biodegradable microspheres that served as both injectable scaffolds and Mg release system for bone regeneration. Read More

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December 2018

Structural alteration of glycosaminoglycan side chains and spatial disorganization of collagen networks in the skin of patients with mcEDS-CHST14.

Biochim Biophys Acta Gen Subj 2018 Dec 13. Epub 2018 Dec 13.

Laboratory of Anatomy, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido, Japan. Electronic address:

Musculocontractural Ehlers-Danlos syndrome (mcEDS) due to CHST14/D4ST1 deficiency (mcEDS-CHST14) is a recently delineated type of EDS caused by biallelic loss-of-function mutations in CHST14, which results in the depletion of dermatan sulfate (DS). Clinical characteristics of mcEDS-CHST14 consist of multiple malformations and progressive fragility-related manifestations, including skin hyperextensibility and fragility. Skin fragility is suspected to result from the impaired assembly of collagen fibrils caused by alteration of the glycosaminoglycan (GAG) chain of decorin-proteoglycan (PG) from DS to chondroitin sulfate (CS). Read More

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December 2018
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Menthol-induced facilitation of cerebrocortical excitatory propagation induced by air puff stimulation of the nasal cavity in the rat: An optical imaging study.

Neurosci Lett 2018 Dec 13. Epub 2018 Dec 13.

Department of Pharmacology, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-8310, Japan; Division of Oral and Craniomaxillofacial Research, Dental Research Center, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-8310, Japan; Molecular Dynamics Imaging Unit, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.

Temperature plays a critical role in the sensation of airflow in the nasal mucosa. Neural activities of the ethmoidal nerve, a trigeminal afferent, responding to airflow are suppressed by warm airflow, whereas cold airflow enhances the ethmoidal nerve activities, which is mimicked by application of menthol, a cold-sensitive TRPM8 receptor agonist. However, it has been an open issue how menthol modulates the spatiotemporal profiles of neural activities of somatosensory cortical neurons. Read More

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December 2018

Rational combination immunotherapeutic approaches for effective cancer treatment.

J Control Release 2018 Dec 13. Epub 2018 Dec 13.

College of Pharmacy, Yeungnam University, 280 Deahak-ro, Gyeongsan 38541, Republic of Korea. Electronic address:

Immunotherapy is an important mode of cancer treatment. Over the past decades, immunotherapy has improved the clinical outcome for cancer patients. However, in many cases, mutations in cancer cells, lack of selectivity, insufficiency of tumor-reactive T cells, and host immunosuppression limit the clinical benefit of immunotherapy. Read More

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December 2018

Platelet-Derived Growth Factor-D Enables Liver Myofibroblasts to Promote Tumor Lymphangiogenesis in Cholangiocarcinoma.

J Hepatol 2018 Dec 13. Epub 2018 Dec 13.

Department of Molecular Medicine, University of Padua, Padova, Italy; International Center for Digestive Health (ICDH), University of Milan-Bicocca, Milan, Italy; Section of Digestive Diseases, Department of Internal Medicine, Yale University, New Haven, CT, USA. Electronic address:

Background: /Aims. In cholangiocarcinoma, early metastatic spread via lymphatic vessels often precludes curative therapies. Cholangiocarcinoma invasiveness is fostered by an extensive stromal reaction, enriched in cancer-associated fibroblasts (CAF) and lymphatic endothelial cells (LEC). Read More

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December 2018

The critical role of microRNAs in stress response: therapeutic prospect and limitation.

Pharmacol Res 2018 Dec 13. Epub 2018 Dec 13.

Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410008, China; National Clinical Research Center for Geriatric Disorders (XIANGYA), Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China. Electronic address:

Stress response refers to the systemic nonspecific response upon exposure to strong stimulation or chronic stress, such as severe trauma, shock, infection, burn, major surgery or improper environment, which disturb organisms and damage their physical and psychological health. However, the pathogenesis of stress induced disorder remains complicated and diverse under different stress exposure. Recently, studies have revealed a specific role of microRNAs (miRNAs) in regulating cellular function under different types of stress, suggesting a significant role in the treatment and prevention of stress-related diseases, such as stress ulcer, posttraumatic stress disorder, stress-induced cardiomyopathy and so on. Read More

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December 2018

Mediatory role of BLT2 in the proliferation of KRAS mutant colorectal cancer cells.

Biochim Biophys Acta Mol Cell Res 2018 Dec 13. Epub 2018 Dec 13.

School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea. Electronic address:

Inflammatory lipid mediators play various roles in colorectal cancer progression through complex pathways. However, the mechanism by which lipoxygenase-derived inflammatory lipid mediators contribute to colorectal cancer progression remains elusive. In this study, we found that BLT2, a cell surface GPCR for leukotriene B and 12‑hydroxyeicosatetraenoic acid, is highly upregulated in KRAS mutant LOVO and SW480 colorectal cancer cells and plays critical roles in mediating proliferation through activation of phosphatidylinositol 3‑kinase (PI3K)/protein kinase B (Akt) and subsequent upregulation of cyclin D1. Read More

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December 2018
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Addressing the Nutritional Phenotype through Personalized Nutrition for Chronic Disease Prevention and Management.

Prog Cardiovasc Dis 2018 Dec 13. Epub 2018 Dec 13.

Internal Medicine-Obesity Medicine, Palo Alto Veterans Affairs Health Care System, Palo Alto, CA, USA; Internal Medicine-Primary Care, San Mateo County Health System, San Mateo, CA, USA.

The primary focus of public health recommendations related to the prevention of food-related chronic disease has been on the adoption of healthy dietary patterns; however, implementation has been challenging. There has been increasing recognition that an individual's diet and environment may impact disease susceptibility by affecting the expression of genes involved in critical metabolic pathways. Precision nutrition (PN) has emerged to translate discoveries about diversity in nutrient metabolism between subgroups and the inter-individual variability in the responses to dietary interventions. Read More

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December 2018

Deletion of myeloid IRS2 enhances adipose tissue sympathetic nerve function and limits obesity.

Mol Metab 2018 Nov 28. Epub 2018 Nov 28.

MRC London Institute of Medical Sciences, Du Cane Road, London, W12 0NN, UK; Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, Du Cane Road, London, W12 0NN, UK. Electronic address:

Objective: Sympathetic nervous system and immune cell interactions play key roles in the regulation of metabolism. For example, recent convergent studies have shown that macrophages regulate obesity through brown adipose tissue (BAT) activation and beiging of white adipose tissue (WAT) via effects upon local catecholamine availability. However, these studies have raised issues about the underlying mechanisms involved including questions regarding the production of catecholamines by macrophages, the role of macrophage polarization state and the underlying intracellular signaling pathways in macrophages that might mediate these effects. Read More

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November 2018

TFAM overexpression diminishes skeletal muscle atrophy after hindlimb suspension in mice.

Arch Biochem Biophys 2018 Dec 13. Epub 2018 Dec 13.

Department of Physiology, University of Louisville, KY, USA.

The present study aims to investigate if overexpressing the mitochondrial transcription factor A (TFAM) gene in a transgenic mouse model diminishes soleus and gastrocnemius atrophy occurring during hindlimb suspension (HLS). Additionally, we aim to observe if combining exercise training in TFAM transgenic mice prior to HLS has a synergistic effect in preventing skeletal muscle atrophy. Male C57BL/6J-based transgenic mice (12-14 weeks old) overexpressing TFAM were assigned to a control (T-Control), 7-day HLS (T-HLS), and 2-week exercise training prior to 7-day HLS (T-Ex + HLS) groups. Read More

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December 2018

Uncovering metastability and disassembly hotspots in whole viral particles.

Prog Biophys Mol Biol 2018 Dec 13. Epub 2018 Dec 13.

Department of Biological Sciences, National University of Singapore, 117543, Singapore. Electronic address:

Viruses are metastable macromolecular assemblies that toggle between multiple conformational states through molecular rearrangements that are critical for mediating viral host entry. Viruses respond to different host specific environmental cues to form disassembly intermediates for the eventual release of genomic material required for replication. Although static snapshots of these intermediates have been captured through structural techniques such as X-ray crystallography and cryo-EM, the mechanistic details of these conformational rearrangements underpinning viral metastability have been poorly understood. Read More

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December 2018

Rapid Next-Generation Sequencing Method for Prediction of Prostate Cancer Risks.

J Mol Diagn 2018 Dec 6. Epub 2018 Dec 6.

Department of Pathology, Albert Einstein College of Medicine, Bronx, New York. Electronic address:

Prostate cancer is the most commonly diagnosed male cancer and the second leading cause of cancer deaths among men in the United States, with approximately 220,000 new diagnoses and approximately 27,000 deaths each year. Men with clinical low-risk disease can receive active surveillance to safely preserve quality of life, provided that the risk of an undetected aggressive cancer can be managed. Thus, prediction of a tumor's metastatic potential, ideally using only a biopsy sample, is critical to choosing appropriate treatment. Read More

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December 2018
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