2,574 results match your criteria pathway passive

GlcNAc is a mast-cell chromatin-remodeling oncometabolite that promotes systemic mastocytosis aggressiveness.

Blood 2021 May 11. Epub 2021 May 11.

Centre de Recherche en Cancérologie de Marseille - Inserm U1068, CNRS UMR7258, Aix-Marseille Université, Institut Paoli-Calmettes, Marseille, France.

Systemic mastocytosis (SM) is a KIT-driven hematopoietic neoplasm characterized by the excessive accumulation of neoplastic mast cells (MCs) in various organs and, mainly, the bone marrow (BM). Multiple genetic and epigenetic mechanisms contribute to the onset and severity of SM. However, little is known to date about the metabolic underpinnings underlying SM aggressiveness, which has thus far impeded the development of strategies to leverage metabolic dependencies when existing KIT-targeted treatments fail. Read More

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Early Passive Leg Movement Prevents Against the Development of Heart Failure With Preserved Ejection Fraction in Rats.

Front Cardiovasc Med 2021 21;8:655009. Epub 2021 Apr 21.

Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

Exercising was reported by several studies to bring great benefits to heart failure with preserved ejection fraction (HFpEF), which reduced the hospitalization and the mortality of heart failure. However, the underlying mechanism of exercising on HFpEF remains unclear. In the present study, we designed and constructed a device that can perform early passive leg movement (ePLM) in rats and further observed whether treatment of ePLM exerts protective effects on HFpEF of rats. Read More

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Double Loop Ventricular Tachycardia Activation Patterns with Single Loop Mechanisms: Asymmetric Entrainment Responses During "Pseudo-Figure-of-Eight" Reentry.

Heart Rhythm 2021 May 6. Epub 2021 May 6.

The University of Chicago Medicine, Center for Arrhythmia Care, Pritzker School of Medicine, Chicago, IL. Electronic address:

Background: The classical paradigm of scar-related reentrant VT features a circuit with a double loop figure-of-eight (F8) activation pattern.

Objective: To interrogate VT circuits with F8 activation pattern by entrainment mapping to differentiate active from passive loops.

Methods: Sixty VT circuits with >90% of tachycardia cycle length delineated in high resolution were retrospectively analyzed in 55 patients (nonischemic 49%). Read More

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An intracellular pathway controlled by the N-terminus of the pump subunit inhibits the bacterial KdpFABC ion pump in high K conditions.

J Mol Biol 2021 May 2:167008. Epub 2021 May 2.

PHYLIFE: Physical Life Science, Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, Odense 5230 M, Denmark. Electronic address:

The heterotetrameric bacterial KdpFABC transmembrane protein complex is an ion channel-pump hybrid that consumes ATP to import K against its transmembrane chemical potential gradient in low external K environments. The KdpB ion-pump subunit of KdpFABC is a P-type ATPase, and catalyses ATP hydrolysis. Under high external K conditions, K can diffuse into the cells through passive ion channels. Read More

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Organic Cation Transporter 1 an Intestinal Uptake Transporter: Fact or Fiction?

Front Pharmacol 2021 14;12:648388. Epub 2021 Apr 14.

Institute of Pharmacology and Toxicology, Rostock University Medical Center, Rostock, Germany.

Intestinal transporter proteins are known to affect the pharmacokinetics and in turn the efficacy and safety of many orally administered drugs in a clinically relevant manner. This knowledge is especially well-established for intestinal ATP-binding cassette transporters such as P-gp and BCRP. In contrast to this, information about intestinal uptake carriers is much more limited although many hydrophilic or ionic drugs are not expected to undergo passive diffusion but probably require specific uptake transporters. Read More

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Passive torque influences the Hoffmann reflex pathway during the loading and unloading phases of plantar flexor muscles stretching.

Physiol Rep 2021 Apr;9(8):e14834

Laboratory of Applied Biology & Research Unit in Applied Neurophysiology (LABNeuro), ULB-Neurosciences Institute (UNI), Université Libre de Bruxelles (ULB), Brussels, Belgium.

This study investigated the influence of passive tension on Hoffmann reflex during the loading (muscle stretched by passive joint movement) and unloading phase (joint returned to initial position) of muscle stretching. The maximal H-reflex amplitude (H ) was recorded in soleus in 19 young adults during the loading and unloading phases of a passive 30° dorsiflexion, from 90° ankle angle (reference position). H was evoked at similar angles (Protocol-1) or similar passive torque (PT; Protocol-2) during the loading and unloading phases, or during two loading phases separated by a 5-min stretch hold at 30° ankle dorsiflexion relative to the reference position (Protocol-3). Read More

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Single-Line Bidirectional Optical Add/Drop Multiplexer for Ring Topology Optical Fiber Networks.

Sensors (Basel) 2021 Apr 9;21(8). Epub 2021 Apr 9.

Department of Electrical Engineering, National Chiayi University, Chiayi 60004, Taiwan.

A new type of passive single-line bidirectional optical add/drop multiplexer (SBOADM) is proposed and experimentally demonstrated. When the proposed SBOADM is placed as a node of a ring topology optical fiber network, the special routing function of the SBOADM can always drop down the desired downstream signals whether the signals are injected into the SBOADM in either the clockwise (CW) or counterclockwise (CCW) direction and can upload and send back the upstream signals via the reversed optical pathway of the downstream signals. Once fiber link failure occurs in the optical network, the blocked network connections can be recovered immediately by sending out the downstream signals in both the CW and CCW directions of the fiber ring. Read More

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KDM4B Overexpression Promotes the Growth, Migration, and Invasion of Rheumatoid Arthritis Fibroblast-Like Synoviocytes by Activating STAT3 Pathway.

Biochem Genet 2021 Apr 28. Epub 2021 Apr 28.

Department of Gynecologic Oncosurgery-1, Ji Lin Tumor Hospital, Changchun, 130031, Jilin, China.

In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) present a unique aggressive phenotype and have a passive response to the inflammatory microenvironment, which are critical for the disease's progression. KDM4B, as a histone demethylase, functions as an oncogenic factor in many cancers and is implicated in osteoclastogenesis as well as pro-inflammatory cytokine release in inflammatory diseases. However, the effects of KDM4B on RA FLS have not been reported. Read More

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Bromelain and Olea europaea (L.) leaf extract mediated alleviation of benzo(a)pyrene induced lung cancer through Nrf2 and NFκB pathway.

Environ Sci Pollut Res Int 2021 Apr 23. Epub 2021 Apr 23.

Immunology Microbiology Lab, Department of Human Physiology, Tripura University, Suryamaninagar Tripura, 799022, India.

Lung cancer is the most aggressive as well as deadly form of cancer and most of the lung cancer cases are involved in direct smoking or passive smoking. Oxidative stress and pulmonary inflammation regulated by some transcription factors like Nrf2, NF-κB etc. play important roles in lung cancer. Read More

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Bacteria-induced mineral precipitation: a mechanistic review.

Microbiology (Reading) 2021 Apr;167(4)

Department of Biology and Biochemistry, Milner Centre for Evolution, University of Bath, Claverton Down, Bath, BA2 7AY, UK.

Micro-organisms contribute to Earth's mineral deposits through a process known as bacteria-induced mineral precipitation (BIMP). It is a complex phenomenon that can occur as a result of a variety of physiological activities that influence the supersaturation state and nucleation catalysis of mineral precipitation in the environment. There is a good understanding of BIMP induced by bacterial metabolism through the control of metal redox states and enzyme-mediated reactions such as ureolysis. Read More

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The Use of Bruton's Tyrosine Kinase Inhibitors to Treat Allergic Disorders.

Curr Treat Options Allergy 2021 Apr 16:1-13. Epub 2021 Apr 16.

Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD USA.

Purpose Of Review: Studies show that inhibitors of Bruton's tyrosine kinase (BTKis), currently FDA-approved for the treatment of B cell malignancies, can prevent IgE-mediated reactions through broad inhibition of the FcεRI signaling pathway in human mast cells and basophils. This review will summarize recent data supporting the use of these drugs as novel therapies in various allergic disorders.

Recent Findings: Recent studies have shown that BTKis can prevent IgE-mediated degranulation and cytokine production in primary human mast cells and basophils. Read More

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Neuroprotective effects of dexpanthenol on streptozotocin-induced neuronal damage in rats.

Drug Chem Toxicol 2021 Apr 20:1-9. Epub 2021 Apr 20.

Department of Physiology, Faculty of Medicine, Ege University, Izmir, Turkey.

Aim: Although the most common age-related neurodegenerative disease defined by memory loss is Alzheimer's disease (AD), only symptomatic therapies are present. A complex pathway for the AD pathogenesis that includes an increase in inflammation has recently been suggested. Since in previous animal experiments dexpanthenol has anti-inflammatory and neuroprotective activities, effects and role of dexpanthenol in an intracerebroventricular (ICV)-streptozotocin (STZ) induced sporadic-AD(memory impairment) animal model have been examined. Read More

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Stress-dependent activation of myosin in the heart requires thin filament activation and thick filament mechanosensing.

Proc Natl Acad Sci U S A 2021 Apr;118(16)

Randall Centre for Cell and Molecular Biophysics, School of Basic and Medical Biosciences and British Heart Foundation Centre of Research Excellence, King's College London, SE1 1UL London, United Kingdom

Myosin-based regulation in the heart muscle modulates the number of myosin motors available for interaction with calcium-regulated thin filaments, but the signaling pathways mediating the stronger contraction triggered by stretch between heartbeats or by phosphorylation of the myosin regulatory light chain (RLC) remain unclear. Here, we used RLC probes in demembranated cardiac trabeculae to investigate the molecular structural basis of these regulatory pathways. We show that in relaxed trabeculae at near-physiological temperature and filament lattice spacing, the RLC-lobe orientations are consistent with a subset of myosin motors being folded onto the filament surface in the interacting-heads motif seen in isolated filaments. Read More

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Converting endogenous genes of the malaria mosquito into simple non-autonomous gene drives for population replacement.

Elife 2021 04 13;10. Epub 2021 Apr 13.

Department of Life Sciences, Imperial College London, London, United Kingdom.

Gene drives for mosquito population replacement are promising tools for malaria control. However, there is currently no clear pathway for safely testing such tools in endemic countries. The lack of well-characterized promoters for infection-relevant tissues and regulatory hurdles are further obstacles for their design and use. Read More

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Subretinal Rather Than Intravitreal Adeno-Associated Virus-Mediated Delivery of a Complement Alternative Pathway Inhibitor Is Effective in a Mouse Model of RPE Damage.

Invest Ophthalmol Vis Sci 2021 Apr;62(4):11

Department of Ophthalmology, Medical University of South Carolina, Charleston, South Carolina, United States.

Purpose: The risk for age-related macular degeneration has been tied to an overactive complement system. Despite combined attempts by academia and industry to develop therapeutics that modulate the complement response, particularly in the late geographic atrophy form of advanced AMD, to date, there is no effective treatment. We have previously demonstrated that pathology in the smoke-induced ocular pathology (SIOP) model, a model with similarities to dry AMD, is dependent on activation of the alternative complement pathway and that a novel complement activation site targeted inhibitor of the alternative pathway can be delivered to ocular tissues via an adeno-associated virus (AAV). Read More

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Attention reinforces human corticofugal system to aid speech perception in noise.

Neuroimage 2021 Mar 29;235:118014. Epub 2021 Mar 29.

Institute for Intelligent Systems, University of Memphis, Memphis, TN, USA; School of Communication Sciences and Disorders, University of Memphis, 4055 North Park Loop, Memphis, TN 38152, USA; Department of Anatomy and Neurobiology, University of Tennessee Health Sciences Center, Memphis, TN, USA. Electronic address:

Perceiving speech-in-noise (SIN) demands precise neural coding between brainstem and cortical levels of the hearing system. Attentional processes can then select and prioritize task-relevant cues over competing background noise for successful speech perception. In animal models, brainstem-cortical interplay is achieved via descending corticofugal projections from cortex that shape midbrain responses to behaviorally-relevant sounds. Read More

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Everolimus: A potential therapeutic agent targeting PI3K/Akt pathway in brain insulin system dysfunction and associated neurobehavioral deficits.

Fundam Clin Pharmacol 2021 Mar 30. Epub 2021 Mar 30.

Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Background: It is well accepted that PI3k/Akt signaling pathway is a potential therapeutic window which regulates metabolism and energy homeostasis within the brain, and is an important mediator of normal neuronal physiological functions. Dysregulation of this pathway results in impaired insulin signaling, learning and memory and neuronal survival.

Objectives: Elucidating the role of everolimus in intracerebroventricular (ICV) streptozotocin induced Insulin/IGF-1 dependent PI3K/Akt/mTOR pathway dysregulation and associated neurobehavioral deficits. Read More

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Nucleoside Analogs Radiosensitize G0 Cells by Activating DNA End Resection and Alternative End-Joining.

Radiat Res 2021 Mar 23. Epub 2021 Mar 23.

Institute of Medical Radiation Biology, University of Duisburg-Essen Medical School, Essen, Germany.

Alternative end-joining (alt-EJ) is a DNA end resection-dependent, error-prone pathway utilized by vertebrate cells to repair DNA double-strand breaks (DSBs), but its engagement is linked to chromosomal translocations and genomic instability. Here, we report that when proliferating cells are exposed to ionizing radiation, treatment with nucleoside analogs (NAs) causes strong radiosensitization by increasing engagement of alt-EJ, while at the same time suppressing homologous recombination (HR) in S- and G2-phase cells. This NA-mediated pathway shift may reflect a passive compensatory engagement of alt-EJ following HR suppression that is specific for S- and G2-phase cells, and/or the direct activation of alt-EJ throughout the cell cycle. Read More

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Responsiveness of EbN1 to lignin-derived phenylpropanoids.

Appl Environ Microbiol 2021 Mar 19. Epub 2021 Mar 19.

General and Molecular Microbiology, Institute for Chemistry and Biology of the Marine Environment (ICBM), Carl von Ossietzky University of Oldenburg, Oldenburg, Germany

The betaproteobacterial degradation specialist EbN1 utilizes several plant-derived 3-phenylpropanoids coupled to denitrification. responsiveness of EbN1 was studied by exposing non-adapted cells to distinct pulses (spanning 100 M to 0.1 nM) of 3-phenylpropanoate, cinnamate, 3-(4-hydroxyphenyl)propanoate, or -coumarate. Read More

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Use of Ussing Chambers to Measure Paracellular Permeability to Macromolecules in Mouse Intestine.

Methods Mol Biol 2021 Mar 18. Epub 2021 Mar 18.

Centre de Recherche Saint-Antoine, INSERM UMRS 938, Sorbonne Université, Paris, France.

An increased intestinal permeability has been described in many diseases including inflammatory bowel disease and metabolic disorders, and a better understanding of the contribution of intestinal barrier impairment to pathogenesis is needed. In recent years, attention has been paid to the leak pathway, which is the route of paracellular transport allowing the diffusion of macromolecules through the tight junctions of the intestinal epithelial lining. While the passage of macromolecules by this pathway is very restricted under physiological conditions, its amplification is thought to promote an excessive immune activation in the intestinal mucosa. Read More

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Social networks strongly predict the gut microbiota of wild mice.

ISME J 2021 Mar 17. Epub 2021 Mar 17.

Department of Zoology, University of Oxford, Oxford, UK.

The mammalian gut teems with microbes, yet how hosts acquire these symbionts remains poorly understood. Research in primates suggests that microbes can be picked up via social contact, but the role of social interactions in non-group-living species remains underexplored. Here, we use a passive tracking system to collect high resolution spatiotemporal activity data from wild mice (Apodemus sylvaticus). Read More

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Tooth Loss Induces Memory Impairment and Gliosis in App Knock-In Mouse Models of Alzheimer's Disease.

J Alzheimers Dis 2021 ;80(4):1687-1704

Department of Biochemistry, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

Background: Epidemiological studies have shown that tooth loss is associated with Alzheimer's disease (AD) and dementia. However, the molecular and cellular mechanisms by which tooth loss causes AD remain unclear.

Objective: We investigated the effects of tooth loss on memory impairment and AD pathogenesis in AppNL-G-F mice. Read More

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January 2021

Differential normal skin transcriptomic response in total body irradiated mice exposed to scattered versus scanned proton beams.

Sci Rep 2021 Mar 12;11(1):5876. Epub 2021 Mar 12.

Normandie Univ, UNICAEN, UNIROUEN, ABTE-EA4651, ToxEMAC, Cancer Centre François Baclesse, 14000, Caen, France.

Proton therapy allows to avoid excess radiation dose on normal tissues. However, there are some limitations. Indeed, passive delivery of proton beams results in an increase in the lateral dose upstream of the tumor and active scanning leads to strong differences in dose delivery. Read More

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Acetyl-L-carnitine confers neuroprotection against lipopolysaccharide (LPS) -induced neuroinflammation by targeting TLR4/NFκB, autophagy, inflammation and oxidative stress.

Metab Brain Dis 2021 Mar 12. Epub 2021 Mar 12.

Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Acetyl-L-carnitine has been shown to exert neuroprotection against neurodegenerative diseases. The present study was performed to evaluate neuroprotection effects of acetyl-L-carnitine against lipopolysaccharide (LPS) -induced neuroinflammation and clarify possible mechanisms. A single dose (500 µg/kg) of LPS was intraperitoneally injected to rats to induce model. Read More

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Role of protein tyrosine phosphatase 1B inhibitor in central insulin resistance and associated cognitive deficits.

Brain Res Bull 2021 Jun 5;171:113-125. Epub 2021 Mar 5.

Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India. Electronic address:

Background: Protein tyrosine phosphatase 1B (PTP1B) inhibitors are potential candidates for the treatment of peripheral insulin resistance and diabetes mellitus. Similar to peripheral action within the brain also, PTP1B activation impairs insulin signaling pathways. Activation of PTP1B in brain also accentuates neuroinflammation, oxidative stress and decreases neurotrophic factors in various brain dysfunctions including cognitive decline. Read More

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Research on the Mechanism of Soybean Resistance to Infection Using Machine Learning Methods.

Front Genet 2021 11;12:634635. Epub 2021 Feb 11.

College of Computer Science and Technology, Jilin University, Changchun, China.

Since the emergence of the infection, economic losses of 10-20 billion U.S. dollars have been annually reported. Read More

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February 2021

ORMDL3 Functions as a Negative Regulator of Antigen-Mediated Mast Cell Activation an ATF6-UPR-Autophagy-Dependent Pathway.

Front Immunol 2021 19;12:604974. Epub 2021 Feb 19.

Department of Laboratory Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Antigen (Ag)-mediated mast cell activation plays a critical role in the immunopathology of IgE-dependent allergic diseases. Restraining the signaling cascade that regulates the release of mast cell-derived inflammatory mediators is an attractive therapeutic strategy to treat allergic diseases. Orosomucoid-like-3 (ORMDL3) regulates the endoplasmic reticulum stress (ERS)-induced unfolded protein response (UPR) and autophagy. Read More

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February 2021

Fine particulate matter (PM2.5) promotes IgE-mediated mast cell activation through ROS/Gadd45b/JNK axis.

J Dermatol Sci 2021 Feb 17. Epub 2021 Feb 17.

Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, China; Hunan Engineering Research Center of Skin Health and Disease, Changsha, China. Electronic address:

Background: Mast cells play an important role in allergic responses and persistently exposure to environmental fine particulate matter (PM2.5) exacerbates allergic diseases,but the details remained elucidative.

Objectives: To investigate the effect of PM2. Read More

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February 2021

Alzheimer Disease Clinical Trials Targeting Amyloid: Lessons Learned From Success in Mice and Failure in Humans.

Neurologist 2021 Mar 4;26(2):52-61. Epub 2021 Mar 4.

Fresno Center for Medical Education and Research, Department of Medicine, University of California-San Francisco, Fresno, CA.

Background: The goal of slowing or halting the development of Alzheimer disease (AD) has resulted in the huge allocation of resources by academic institutions and pharmaceutical companies to the development of new treatments. The etiology of AD is elusive, but the aggregation of amyloid-β and tau peptide and oxidative processes are considered critical pathologic mechanisms. The failure of drugs with multiple mechanisms to meet efficacy outcomes has caused several companies to decide not to pursue further AD studies and has left the field essentially where it has been for the past 15 years. Read More

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Lymphatic pathway evaluation in congenital heart disease using 3D whole-heart balanced steady state free precession and T2-weighted cardiovascular magnetic resonance.

J Cardiovasc Magn Reson 2021 03 1;23(1):16. Epub 2021 Mar 1.

Department of Pediatrics, Division of Pediatric Cardiology, University of Texas Southwestern Medical Center, Dallas Children's Medical Center, Dallas, TX, USA.

Background: Due to passive blood flow in palliated single ventricle, central venous pressure increases chronically, ultimately impeding lymphatic drainage. Early visualization and treatment of these malformations is essential to reduce morbidity and mortality. Cardiovascular magnetic resonance (CMR) T2-weighted lymphangiography (T2w) is used for lymphatic assessment, but its low signal-to-noise ratio may result in incomplete visualization of thoracic duct pathway. Read More

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