159,533 results match your criteria clinical pathways


The role of human C5a as a non-genomic target in corticosteroid therapy for management of severe COVID19.

Comput Biol Chem 2021 Apr 5;92:107482. Epub 2021 Apr 5.

Chemical Biology Laboratory, School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Odisha, 752050, India. Electronic address:

Complement system plays a dual role; physiological as well as pathophysiological. While physiological role protects the host, pathophysiological role can substantially harm the host, by triggering several hyper-inflammatory pathways, referred as "hypercytokinaemia". Emerging clinical evidence suggests that exposure to severe acute respiratory syndrome coronavirus-2 (SARS-CoV2), tricks the complement to aberrantly activate the "hypercytokinaemia" loop, which significantly contributes to the severity of the COVID19. Read More

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Tombusviruses orchestrate the host endomembrane system to create elaborate membranous replication organelles.

Curr Opin Virol 2021 Apr 9;48:30-41. Epub 2021 Apr 9.

Department of Plant Pathology, University of Kentucky, Lexington, KY 40546, USA.

Positive-strand RNA viruses depend on intensive manipulation of subcellular organelles and membranes to create unique viral replication organelles (VROs), which represent the sites of robust virus replication. The host endomembrane-based protein-trafficking and vesicle-trafficking pathways are specifically targeted by many (+)RNA viruses to take advantage of their rich resources. We summarize the critical roles of co-opted endoplasmic reticulum subdomains and associated host proteins and COPII vesicles play in tombusvirus replication. Read More

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The potential role of oxytocin in addiction: What is the target process?

Curr Opin Pharmacol 2021 Apr 9;58:8-20. Epub 2021 Apr 9.

Department of Biomedical Sciences, University of Cagliari, Monserrato, Cagliari 09042, Italy. Electronic address:

Oxytocin regulates a variety of centrally-mediated functions, ranging from socio-sexual behavior, maternal care, and affiliation to fear, stress, anxiety. In the past years, both clinical and preclinical studies characterized oxytocin for its modulatory role on reward-related neural substrates mainly involving the interplay with the mesolimbic and mesocortical dopaminergic pathways. This suggests a role of this nonapeptide on the neurobiology of addiction raising the possibility of its therapeutic use. Read More

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Deciphering the synergistic network regulation of active components from SiNiSan against irritable bowel syndrome via a comprehensive strategy: Combined effects of synephrine, paeoniflorin and naringin.

Phytomedicine 2021 Feb 24;86:153527. Epub 2021 Feb 24.

College of Life Sciences, Nanjing Normal University, Nanjing 210023, China. Electronic address:

Background: SiNiSan (SNS) is an ancient Chinese herbal prescription, and the current clinical treatment of irritable bowel syndrome (IBS) is effective. In the previous study of the research team, the multi-functional co-synergism of SNS against IBS was presented. Some potential drug targets and candidate ligands were predicted. Read More

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February 2021

Network Pharmacology Dissection of Multiscale Mechanisms for Jiaoqi Powder in Treating Ulcerative Colitis.

J Ethnopharmacol 2021 Apr 9:114109. Epub 2021 Apr 9.

Department of Gastroenterology,The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, China; Baiyun Hospital of the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510000, China. Electronic address:

Ethnopharmacological Relevance: The incidence of ulcerative colitis (UC) is increasing worldwide, making it a serious public health challenge. Currently, there are no accepted curative treatments for UC. As such, the exploration of new therapeutic strategies for UC treatment is of considerable clinical importance. Read More

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CHROMATIN ACCESSIBILITY IN NEUROPSYCHIATRIC DISORDERS.

Authors:
Gabor Egervari

Neurobiol Learn Mem 2021 Apr 9:107438. Epub 2021 Apr 9.

Epigenetics Institute, Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States. Electronic address:

Epigenetic mechanisms have recently emerged as critical regulators of brain function in health and disease. By controlling the accessibility and the expression of specific genes, these pathways can mediate transient and long-lasting changes in neuronal function in both physiological and pathological contexts. Due to the extreme complexity of the epigenetic regulatory landscape, emerging methods that directly assay chromatin accessibility are of particular interest. Read More

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Intestinal microbiota: A potential target for enhancing the antitumor efficacy and reducing the toxicity of immune checkpoint inhibitors.

Cancer Lett 2021 Apr 9. Epub 2021 Apr 9.

Division of Cancer Biology, Laboratory Animal Center, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, China. Electronic address:

Accumulating evidence suggests that the intestinal microbiota is associated with the antitumor efficacy of immune checkpoint inhibitors (ICIs) and the occurrence of immune-related adverse events (irAEs) following ICI treatment. However, the mechanisms underlying these interactions remain unclear. Recent technological advances have allowed more extensive investigation into the interplay between the intestinal microbiota and the tumor immune microenvironment. Read More

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Myelofibrosis: challenges for preclinical models and emerging therapeutic targets.

Expert Opin Ther Targets 2021 Apr 12. Epub 2021 Apr 12.

Division of Hematology, Mayo Clinic, Rochester, MN, USA.

: Myelofibrosis (MF) is characterized by anemia, splenomegaly, constitutional symptoms and bone marrow fibrosis. MF has no curative treatment to date, except for a small subset of patients that are eligible for allogeneic hematopoietic stem cell transplant. The discovery in recent years of the MF mutational landscape and the role of bone marrow microenvironment in disease pathogenesis has led to further insights into disease biology and consequentially rationally derived therapies. Read More

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Lessons from Cancer Metabolism for Pulmonary Arterial Hypertension and Fibrosis.

Am J Respir Cell Mol Biol 2021 Apr 12. Epub 2021 Apr 12.

Northwestern University, chicago, Illinois, United States;

Metabolism is essential for a living-organism to sustain life. It provides energy to a cell by breaking down compounds (catabolism), and supplies building blocks for the synthesis of macromolecules (anabolism). Signal transduction pathways tightly regulate mammalian cellular metabolism. Read More

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Transcriptomic evaluation of pediatric localized scleroderma skin with histological and clinical correlation.

Arthritis Rheumatol 2021 Apr 12. Epub 2021 Apr 12.

University of Pittsburgh, Pittsburgh, PA, USA.

Objective: Juvenile localized scleroderma (jLS) is an autoimmune disease of the skin in which the pathogenesis is not well understood due to its rarity. Our goal was to determine the skin transcriptome of LS tissue compared with healthy controls to identify molecular targets using RNA sequencing (RNAseq). Differentially expressed genes (DEGs) identified in jLS patients were compared with histopathological features, clinical features and used to cluster jLS patients. Read More

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Integrative metabolic profile of myelodysplastic syndrome based on UHPLC-MS.

Biomed Chromatogr 2021 Apr 12:e5136. Epub 2021 Apr 12.

School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, P. R. China.

Myelodysplastic syndrome (MDS) is neoplastic disease originating from hematopoietic stem cells, and hematopoietic stem cell transplantation (HSCT) is currently the most effective cure despite lenalidomide, azacytidine and decitabine were applied to relieve symptoms of MDS. The purpose of this study is to evaluate the changes of endogenous metabolites by UHPLC-MS (ultra performance liquid chromatography-mass spectrometry) metabolomics and to investigate related metabolic pathways related MDS. An untargeted metabolomics approach based on UHPLC-MS combined multivariate data analysis, including PLS-DA (partial least squares discrimination analysis) and OPLS-DA (orthogonal partial least squares discriminant analysis), was established to investigate potential biomarkers in plasma of MDS patients. Read More

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RNA Sequencing and Pathways Analyses of Middle Ear Epithelia From Patients With Otitis Media.

Laryngoscope 2021 Apr 12. Epub 2021 Apr 12.

Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, U.S.A.

Objectives: Otitis media (OM) is the most common pediatric diagnosis in the United States. However, our understanding of the molecular pathogenesis of OM remains relatively poor. Investigation of molecular pathways involved in OM may improve the understanding of this disease process and elucidate novel therapeutic targets. Read More

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Comparative Metabolic Modeling of Multiple Sulfate-reducing Prokaryotes Reveals Versatile Energy Conservation Mechanisms.

Biotechnol Bioeng 2021 Apr 12. Epub 2021 Apr 12.

Department of Civil and Environmental Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.

Sulfate-reducing prokaryotes (SRPs) are crucial participants in the cycling of sulfur, carbon, and various metals in the natural environment and in engineered systems. Despite recent advances in genetics and molecular biology bringing a huge amount of information about the energy metabolism of SRPs, little effort has been made to link this important information with their biotechnological studies. This study aims to construct multiple metabolic models of SRPs that systematically compile genomic, genetic, biochemical, and molecular information about SRPs to study their energy metabolism. Read More

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Distinctive clinical presentation and pathogenic specificities of anti-AK5 encephalitis.

Brain 2021 Apr 12. Epub 2021 Apr 12.

French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique, Bron, France.

Limbic encephalitis (LE) with antibodies against adenylate kinase 5 (AK5) has been difficult to characterize because of its rarity. In this study, we identified 10 new cases and reviewed 16 previously reported patients, investigating clinical features, IgG subclasses, human leukocyte antigen (HLA), and CSF proteomic profiles. Patients with anti-AK5 LE were mostly men (20/26, 76. Read More

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Acceptability and effectiveness of antimicrobial stewardship implementation strategies on fluoroquinolone prescribing.

Infect Control Hosp Epidemiol 2021 Apr 12:1-8. Epub 2021 Apr 12.

Department of Infectious Diseases, VA Greater Los Angeles Healthcare System, Los Angeles, California.

Objective: To assess the effectiveness and acceptability of antimicrobial stewardship-focused implementation strategies on inpatient fluoroquinolones.

Methods: Stewardship champions at 15 hospitals were surveyed regarding the use and acceptability of strategies to improve fluoroquinolone prescribing. Antibiotic days of therapy (DOT) per 1,000 days present (DP) for sites with and without prospective audit and feedback (PAF) and/or prior approval were compared. Read More

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, one gene associated with multiple neurodevelopmental disorders.

Autophagy 2021 Apr 12:1-16. Epub 2021 Apr 12.

Department of Biomedical Sciences of Cells & Systems, Molecular Cell Biology Section, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

The gene is localized on the X-chromosome and variants in this gene are linked to six different neurodegenerative disorders, i.e., ß-propeller protein associated neurodegeneration, Rett-like syndrome, intellectual disability, and epileptic encephalopathies including developmental and epileptic encephalopathy, early-onset epileptic encephalopathy and West syndrome and potentially also specific malignancies. Read More

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A 3D image segmentation for lung cancer using V.Net architecture based deep convolutional networks.

J Med Eng Technol 2021 Apr 12:1-7. Epub 2021 Apr 12.

Scientific Research Group in Egypt (SRGE), Cairo, Egypt.

Lung segmentation of chest CT scan is utilised to identify lung cancer and this step is also critical in other diagnostic pathways. Therefore, powerful algorithms to accomplish this accurate segmentation task are highly needed in the medical imaging domain, where the tumours are required to be segmented with the lung parenchyma. Also, the lung parenchyma needs to be detached from the tumour regions that are often confused with the lung tissue. Read More

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CXCR4 allows T cell acute lymphoblastic leukemia to escape from JAK1/2 and BCL2 inhibition through CNS infiltration.

Leuk Lymphoma 2021 Apr 11:1-11. Epub 2021 Apr 11.

Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.

Targeting the JAK/STAT and BCL2 pathways in patients with relapsed/refractory T cell acute lymphoblastic leukemia (T-ALL) may provide an alternative approach to achieve clinical remissions. Ruxolitinib and venetoclax show a dose-dependent effect on T-ALL individually, but combination treatment reduces survival and proliferation of T-ALL . Using a xenograft model, the combination treatment fails to improve survival, with death from hind limb paralysis. Read More

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The comparative effects of brief or multidisciplinary intervention on return to work at 1 year in employees on sick leave due to low back pain: A randomized controlled trial.

Clin Rehabil 2021 Apr 11:2692155211005387. Epub 2021 Apr 11.

Section of Clinical Social Medicine and Rehabilitation, Department of Public Health, Aarhus University, Aarhus, Denmark.

Objective: To compare return to work (RTW) rates among patients with low back pain (LBP) and different job relations randomized to brief or multidisciplinary intervention.

Design: A randomized controlled trial with 1-year follow-up.

Setting: Silkeborg Regional Hospital, Denmark. Read More

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Combined effects of a ketogenic diet and exercise training alter mitochondrial and peroxisomal substrate oxidative capacity in skeletal muscle.

Am J Physiol Endocrinol Metab 2021 Apr 12. Epub 2021 Apr 12.

Skeletal Muscle Metabolism, Pennington Biomedical Research Center, United States.

Ketogenic diets (KD) are reported to improve body weight, fat mass, and exercise performance in humans. Unfortunately, most rodent studies have used a low-protein KD, which does not recapitulate diets used by humans. Since skeletal muscle plays a critical role in responding to macronutrient perturbations induced by diet and exercise, the purpose of this study was to test if a normal-protein KD (NPKD) impacts shifts in skeletal muscle substrate oxidative capacity in response to exercise training (ExTr). Read More

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NMR-Based Serum and Urine Metabolomic Profile Reveals Suppression of Mitochondrial Pathways in Experimental Sepsis-Associated Acute Kidney Injury.

Am J Physiol Renal Physiol 2021 Apr 12. Epub 2021 Apr 12.

Chemistry and Biochemistry, Miami University, United States.

Sepsis-associated acute kidney injury (SA-AKI) is a significant problem in the critically ill that causes increased death. Emerging understanding of this disease implicates metabolic dysfunction in its pathophysiology. This study sought to identify specific metabolic pathways amenable to potential therapeutic intervention. Read More

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Mutation of P-element somatic inhibitor induces male sterility in the diamondback moth, Plutella xylostella.

Pest Manag Sci 2021 Apr 11. Epub 2021 Apr 11.

CAS Key Laboratory of Insect Developmental and Evolutionary Biology, CAS Center for Excellence in Molecular Plant Sciences/Institute of Plant Physiology and Ecology, Shanghai, 200032, China.

Background: Genetic manipulation of sex determination pathways in insects provides the basis for a broad range of strategies to benefit agricultural security and human health. The P-element somatic inhibitor (PSI) protein, an exon splicing silencer that promotes male-specific splicing of dsx, plays a critical role in male sexual differentiation and development. The functions of PSI have been characterized in the lepidopteran model species Bombyx mori. Read More

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Genetic causes of preimplantation embryo developmental failure.

Mol Reprod Dev 2021 Apr 12. Epub 2021 Apr 12.

9.Baby, Family and Fertility Center, Bologna, Italy.

Embryo development requires orchestrated events, finely regulated at the molecular and cellular level by mechanisms which are progressively emerging from animal studies. With progress in genetic technologies-such as genome editing and single-cell RNA analysis-we can now assess embryo gene expression with increased precision and gain new insights into complex processes until recently difficult to explore. Multiple genes and regulative pathways have been identified for each developmental stage. Read More

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Examining sources and pathways of phosphorus transfer in a ditch-drained field with concentration -discharge relationships and isotope hydrograph separation.

J Environ Qual 2021 Apr 11. Epub 2021 Apr 11.

Department of Plant and Soil Sciences, University of Delaware, 531 S. College Ave., Newark, DE, 19716.

Understanding the processes that mobilize and transport dissolved phosphorus (P) during storms is critical to managing P in flat landscapes with open ditch drainage and legacy soil P. In this study, we employed routine baseflow monitoring and intensive storm sampling at a ditch-drained site on Maryland's Lower Eastern Shore (July 2017 to September 2018) to assess whether concentration-discharge (C-Q) relationships and chemical and isotopic hydrograph separation could provide insight into the processes that mobilize and transport dissolved P in ditch drainage. Using a segmented regression model, we determined that long-term C-Q relationships for dissolved P differed above and below a discharge threshold of 6. Read More

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Urinary biomarkers indicative of recovery from spinal cord injury: A pilot study.

IBRO Neurosci Rep 2021 Jun 18;10:178-185. Epub 2021 Feb 18.

Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, Lethbridge, Alberta, Canada.

Current assessments of recovery following spinal cord injury (SCI) focus on clinical outcome measures. These assessments bear an inherent risk of bias, emphasizing the need for more reliable prognostic biomarkers to measure SCI severity. This study evaluated fluid biomarkers as an objective tool to aid with prognosticating outcomes following SCI. Read More

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Integrated Screening of Effective Anti-Insomnia Fractions of Zhi-Zi-Hou-Po Decoction via and Network Pharmacology Analysis of the Underlying Pharmacodynamic Material and Mechanism.

ACS Omega 2021 Apr 24;6(13):9176-9187. Epub 2021 Mar 24.

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China.

Insomnia is an anabatic epidemiology, while the mechanism is extremely complicated; it remains one of the major scientific challenges in life sciences. Because of the advantage of having a similar genetic background and circadian rhythm as those of humans, the model organism is hugely popular in sleep-related drug screening studies. Seven-day-old virgin was used to establish the sleep deprivation model by repeated light stimulation at night. Read More

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Morphea: progress to date and the road ahead.

Ann Transl Med 2021 Mar;9(5):437

Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

Morphea is a rare autoimmune condition causing inflammation and sclerosis of the skin and underlying soft tissue. It is characterized by periods of activity (inflammation admixed with fibrosis), ultimately resulting in permanent damage (pigment change and tissue loss). Damage resulting from unchecked activity can lead to devastating, permanent cosmetic and functional sequelae including hair loss; cutaneous, soft tissue and bony atrophy; joint contractures; and growth restriction of the affected body site in children. Read More

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Rosavin suppresses osteoclastogenesis and by blocking the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways.

Ann Transl Med 2021 Mar;9(5):383

Department of Oral and Craniofacial Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Bone homeostasis is mediated by osteoblast-related bone formation and osteoclast-related resorption. The imbalance of bone homeostasis due to excessive osteoclastogenesis or reduced osteogenesis can result in various disorders, such as postmenopausal osteoporosis (PMOP). The receptor activator of nuclear factor-κB ligand (RANKL)-induced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) pathways are essential in osteoclastogenesis. Read More

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Protective effects and molecular mechanisms of polypeptide k on Schwann cells.

Ann Transl Med 2021 Mar;9(5):381

Key Laboratory of Neuroregeneration of Jiangsu, Ministry of Education, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China.

Background: polypeptide k (ABPPk) is an active ingredient used in traditional Chinese medicine separated from polypeptides. So far, the role of ABPPk in peripheral nerve protection has not been comprehensively studied.

Methods: In this study, primary Schwann cells exposed to serum deprivation were treated with ABPPk or nerve growth factor (NGF) . Read More

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