782 results match your criteria p38 controlled

Active p38α causes macrovesicular fatty liver in mice.

Proc Natl Acad Sci U S A 2021 Apr;118(14)

Singapore-HUJ Alliance for Research and Enterprise, Molecular Mechanisms of Inflammatory Diseases Program, National University of Singapore, 138602, Singapore;

One third of the western population suffers from nonalcoholic fatty liver disease (NAFLD), which may ultimately develop into hepatocellular carcinoma (HCC). The molecular event(s) that triggers the disease are not clear. Current understanding, known as the multiple hits model, suggests that NAFLD is a result of diverse events at several tissues (e. Read More

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The second phase of brain trauma can be controlled by nutraceuticals that suppress DAMP-mediated microglial activation.

Expert Rev Neurother 2021 Apr 5:1-12. Epub 2021 Apr 5.

Chaim Sheba Medical Center, The Zabludowicz Research Center for Autoimmune Diseases, Tel Hashomer, Israel.

Introduction: A delayed second wave of brain trauma is mediated in large part by microglia that are activated to a pro-inflammatory M1 phenotype by DAMP proteins released by dying neurons. These microglia can promote apoptosis or necrosis in neighboring neurons by producing a range of pro-inflammatory cytokines and the deadly oxidant peroxynitrite. This second wave could therefore be mitigated with agents that blunt the post-traumatic M1 activation of microglia and that preferentially promote a pro-healing M2 phenotype. Read More

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Peripheral inflammatory biomarkers define biotypes of bipolar depression.

Mol Psychiatry 2021 Mar 3. Epub 2021 Mar 3.

Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.

We identified biologically relevant moderators of response to tumor necrosis factor (TNF)-α inhibitor, infliximab, among 60 individuals with bipolar depression. Data were derived from a 12-week, randomized, placebo-controlled clinical trial secondarily evaluating the efficacy of infliximab on a measure of anhedonia (i.e. Read More

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Andrographolide upregulates protein quality control mechanisms in cell and mouse through upregulation of mTORC1 function.

Biochim Biophys Acta Gen Subj 2021 Jun 25;1865(6):129885. Epub 2021 Feb 25.

Division of Molecular Medicine, Bose Institute, P1/12 CIT Scheme VIIM, Kolkata 700054, India. Electronic address:

Background: Heat shock response (HSR), a component of cellular protein quality control mechanisms, is defective in different neurodegenerative conditions such as Parkinson's disease (PD). Forced upregulation of heat shock factor 1 (HSF1), an HSR master regulator, showed therapeutic promise in PD models. Many of the reported small-molecule HSF1 activators have limited functions. Read More

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Experimental Agents for the Treatment of Atherosclerosis: New Directions.

J Exp Pharmacol 2021 18;13:161-179. Epub 2021 Feb 18.

Internal Medicine Department, Elpis General Hospital, Athens, Greece.

Cardiovascular and related metabolic disorders constitute a worldwide health challenge. Atherosclerosis is a chronic inflammatory condition based on both dyslipidemia and inflammation. Therefore, even when dyslipidemia is controlled, the risk of atherosclerosis remains. Read More

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February 2021

A chinese herbal formula ameliorates COPD by inhibiting the inflammatory response via downregulation of p65, JNK, and p38.

Phytomedicine 2021 Mar 20;83:153475. Epub 2021 Jan 20.

Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou 450046, Henan Province, China; Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou 450046, Henan Province, China.

Background: Bufei Yishen formula (BYF), a traditional Chinese medicine (TCM), is an effective therapeutic strategy for patients with chronic obstructive pulmonary disease (COPD).

Purpose: To evaluate the efficacy of BYF and investigate its therapeutic mechanisms.

Methods: A total of 134 patients completed the study: 68 patients treated by BYF combined with conventional Western medicine in the trial group; and 66 patients treated using conventional Western medicine in the control group. Read More

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The Taming of Nuclear Factor Erythroid-2-Related Factor-2 (Nrf2) Deglycation by Fructosamine-3-Kinase (FN3K)-Inhibitors-A Novel Strategy to Combat Cancers.

Cancers (Basel) 2021 Jan 14;13(2). Epub 2021 Jan 14.

Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR), Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER), Mysuru, Karnataka 570015, India.

Glycated stress is mediated by the advanced glycation end products (AGE) and the binding of AGEs to the receptors for advanced glycation end products (RAGEs) in cancer cells. RAGEs are involved in mediating tumorigenesis of multiple cancers through the modulation of several downstream signaling cascades. Glycated stress modulates various signaling pathways that include p38 mitogen-activated protein kinase (p38 MAPK), nuclear factor kappa-B (NF-κB), tumor necrosis factor (TNF)-α, etc. Read More

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January 2021

Acetylation regulation associated with the induction of protective response to polystyrene nanoparticles in Caenorhabditis elegans.

J Hazard Mater 2021 Jun 6;411:125035. Epub 2021 Jan 6.

Medical School, Southeast University, Nanjing 210009, China. Electronic address:

Caenorhabditis elegans is a useful animal model to assess nanoplastic toxicity. Using polystyrene nanoparticles (PS-NPs) as the example of nanoplastics, we found that exposure to PS-NPs (1-100 μg/L) from L1-larvae for 6.5 days increased expression of cbp-1 encoding an acetyltransferase. Read More

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SCAMP3 is regulated by miR-128-3p and promotes the metastasis of hepatocellular carcinoma cells through EGFR-MAPK p38 signaling pathway.

Am J Transl Res 2020 15;12(12):7870-7884. Epub 2020 Dec 15.

Department of Jiamusi College, Heilongjiang University of Chinese Medicine Jiamusi 154000, Heilongjiang Province, China.

Purpose: To explore the regulatory mechanism of secretory carrier membrane protein 3 (SCAMP3) and miR-128-3p in hepatocellular carcinoma (HCC).

Patients And Methods: Cancer tissues and adjacent tissues of 52 HCC patients treated in our hospital were collected to explore the prognostic factors affecting their 3-year survival. HCC cells were purchased, the gene expression of Huh-7 and MHCC97 were adjusted by transfection, and the levels of SCAMP3, miR-128-3p, EGFR, p-EGFR, MAPK p38, p-MAPK p38, N-cadherin, vimentin, E-cadherin, cell proliferation, migration, invasion, apoptosis and epithelial-mesenchymal transition (EMT) were detected. Read More

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December 2020

Babao Dan improves neurocognitive function by inhibiting inflammation in clinical minimal hepatic encephalopathy.

Biomed Pharmacother 2021 Mar 28;135:111084. Epub 2020 Dec 28.

Shuguang Hospital, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address:

Background And Purpose: Inflammation has been considered a precipitating event that contributes to neurocognitive dysfunction in minimal hepatic encephalopathy (MHE). Inhibition TLR-4 related inflammation can effectively improve neurocognitive dysfunction of MHE. Our previous study showed that Babao Dan (BBD) effectively inhibited inflammation and ameliorated neurocognitive function in rats with acute hepatic encephalopathy (HE) and chronic HE. Read More

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Exploring brain insulin resistance in adults with bipolar depression using extracellular vesicles of neuronal origin.

J Psychiatr Res 2021 01 4;133:82-92. Epub 2020 Dec 4.

Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.

Accumulating evidence suggests that disrupted insulin signaling is involved in bipolar disorder (BD) pathogenesis. Herein, we aimed to directly explore the potential role of neuronal insulin signaling using an innovative technique based on biomarkers derived from plasma extracellular vesicles enriched for neuronal origin (NEVs). We leveraged plasma samples from a randomized, double-blind, placebo-controlled, 12-week clinical trial evaluating infliximab as a treatment of bipolar depression. Read More

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January 2021

Transcriptome analysis in Takifugu rubripes and Dicentrarchus labrax gills during Cryptocaryon irritans infection.

J Fish Dis 2021 Mar 13;44(3):249-262. Epub 2020 Dec 13.

Key Laboratory of Environment Controlled Aquaculture (KLECA), Ministry of Education, Dalian, China.

Takifugu rubripes and Dicentrarchus labrax are important commercial fish in China that are under serious threat from Cryptocaryon irritans. C. irritans is a ciliated obligate parasite that causes marine white spot disease and leads to heavy economic losses. Read More

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Proof of pharmacology of Org 48775-0, a p38 MAP kinase inhibitor, in healthy volunteers.

Br J Clin Pharmacol 2020 Nov 17. Epub 2020 Nov 17.

Centre for Human Drug Research, Leiden, the Netherlands.

Aim: To investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of the highly selective oral p38alpha/beta mitogen-activated protein (MAP) kinase inhibitor Org 48,775-0 in a first-in-human study.

Methods: In the single ascending dosing (SAD) study, an oral dose of Org 48,775-0 (0.3-600 mg) was evaluated in healthy males. Read More

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November 2020

Co-regulation of the transcription controlling ATF2 phosphoswitch by JNK and p38.

Nat Commun 2020 11 13;11(1):5769. Epub 2020 Nov 13.

Biomolecular Interactions Research Group, Institute of Organic Chemistry, Research Center for Natural Sciences, H-1117, Budapest, Hungary.

Transcription factor phosphorylation at specific sites often activates gene expression, but how environmental cues quantitatively control transcription is not well-understood. Activating protein 1 transcription factors are phosphorylated by mitogen-activated protein kinases (MAPK) in their transactivation domains (TAD) at so-called phosphoswitches, which are a hallmark in response to growth factors, cytokines or stress. We show that the ATF2 TAD is controlled by functionally distinct signaling pathways (JNK and p38) through structurally different MAPK binding sites. Read More

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November 2020

Adenosine A receptor as a novel therapeutic target to reduce secondary events and improve neurocognitive functions following traumatic brain injury.

J Neuroinflammation 2020 Nov 12;17(1):339. Epub 2020 Nov 12.

Department of Pharmacology and Physiology, Saint Louis University School of Medicine, 1402 S. Grand Blvd, St. Louis, MO, 63104, USA.

Background: Traumatic brain injury (TBI) is a common pathological condition that presently lacks a specific pharmacological treatment. Adenosine levels rise following TBI, which is thought to be neuroprotective against secondary brain injury. Evidence from stroke and inflammatory disease models suggests that adenosine signaling through the G protein-coupled A adenosine receptor (AAR) can provide antiinflammatory and neuroprotective effects. Read More

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November 2020

evaluation of a pro-healing polydopamine coated stent through an in-stent restenosis rat model.

Biomater Sci 2021 Jan;9(1):212-220

Univ. Lille, INSERM, CHU Lille, U1008 - Controlled Drug Delivery Systems and Biomaterials, F-59000 Lille, France.

Drug-eluting stents have demonstrated efficiency in in-stent restenosis (ISR) but induced a risk of late acute thrombosis by delaying strut re-endothelialization. Polydopamine (PDA), a biocompatible polymer inspired from adhesive proteins of mussels, has been reported to promote endothelial cell (EC) proliferation while limiting SMC proliferation in vitro, thus suggesting the pro-healing potential. This study aimed at evaluating in vivo the impact of the pro-healing PDA-coated stent on ISR and on the quality of the strut re-endothelialization in a rat model. Read More

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January 2021

Inhibition of p38 MAPK regulates epileptic severity by decreasing expression levels of A1R and ENT1.

Mol Med Rep 2020 Dec 19;22(6):5348-5357. Epub 2020 Oct 19.

Department of Neurology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China.

Epilepsy is a chronic nervous system disease. Excessive increase of the excitatory neurotransmitter glutamate in the body results in an imbalance of neurotransmitters and excessive excitation of neurons, leading to epileptic seizures. Long‑term recurrent seizures lead to behavior and cognitive changes, and even increase the risk of death by 2‑ to 3‑fold relative to the general population. Read More

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December 2020

Netrin G1 Promotes Pancreatic Tumorigenesis through Cancer-Associated Fibroblast-Driven Nutritional Support and Immunosuppression.

Cancer Discov 2021 Feb 30;11(2):446-479. Epub 2020 Oct 30.

Cancer Biology Program, Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania.

Pancreatic ductal adenocarcinoma (PDAC) has a poor 5-year survival rate and lacks effective therapeutics. Therefore, it is of paramount importance to identify new targets. Using multiplex data from patient tissue, three-dimensional coculturing assays, and orthotopic murine models, we identified Netrin G1 (NetG1) as a promoter of PDAC tumorigenesis. Read More

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February 2021

Capsaicin-loaded solid lipid nanoparticles: design, biodistribution, in silico modeling and in vitro cytotoxicity evaluation.

Nanotechnology 2021 Feb;32(9):095101

Department of Biotechnology, Kalasalingam Academy of Research and Education, Krishnankoil-626126, India.

Lower doses of capsaicin (8-methyl-N-vanillyl-6-nonenamide) have the potential to serve as an anticancer drug, however, due to its pungency, irritant effect, poor water solubility and high distribution volume often linked to various off-target effects, its therapeutic use is limited. This study aimed to determine the biodistribution and anticancer efficacy of capsaicin loaded solid lipid nanoparticles (SLNs) in human hepatocellular carcinoma in vitro. In this study, SLNs of stearic acid loaded with capsaicin was formulated by the solvent evaporation-emulsification technique and were instantly characterized for their encapsulation efficiency, morphology, loading capacity, stability, particle size, charge and in vitro drug release profile. Read More

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February 2021

Pharmacological management of dementia with Lewy bodies with a focus on zonisamide for treating parkinsonism.

Expert Opin Pharmacother 2021 Feb 6;22(3):325-337. Epub 2020 Oct 6.

Department of Research and Development, Chiesi Farmaceutici, Parma , Italy.

Introduction: Dementia with Lewy bodies (DLB) has no approved symptomatic or disease-modifying treatments in the US and Europe, despite being the second most common cause of neurodegenerative dementia.

Areas Covered: Herein, the authors briefly review the DLB drug development pipeline, providing a summary of the current pharmacological intervention studies. They then focus on the anticonvulsant zonisamide, a benzisoxazole derivative with a sulfonamide group and look at its value for treating parkinsonism in DLB. Read More

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February 2021

COX2 inhibition in the treatment of COVID-19: Review of literature to propose repositioning of celecoxib for randomized controlled studies.

Int J Infect Dis 2020 Dec 30;101:29-32. Epub 2020 Sep 30.

Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty, Department of Plastic, Reconstructive and Aesthetic Surgery, Istanbul, Turkey.

Coronavirus-triggered pulmonary and systemic disease, i.e. systemic inflammatory response to virally triggered lung injury, named COVID-19, and ongoing discussions on refining immunomodulation in COVID-19 without COX2 inhibition prompted us to search the related literature to show a potential target (COX2) and a weapon (celecoxib). Read More

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December 2020

TRIM28 regulates sprouting angiogenesis through VEGFR-DLL4-Notch signaling circuit.

FASEB J 2020 11 12;34(11):14710-14724. Epub 2020 Sep 12.

Central Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Sprouting angiogenesis is a highly coordinately process controlled by vascular endothelial growth factor receptor (VEGFR)-Notch signaling. Here we investigated whether Tripartite motif-containing 28 (TRIM28), which is an epigenetic modifier implicated in gene transcription and cell differentiation, is essential to mediate sprouting angiogenesis. We observed that knockdown of TRIM28 ortholog in zebrafish resulted in developmental vascular defect with disorganized and reduced vasculatures. Read More

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November 2020

Effect of the p38 MAPK inhibitor doramapimod on the systemic inflammatory response to intravenous lipopolysaccharide in horses.

J Vet Intern Med 2020 Sep 23;34(5):2109-2116. Epub 2020 Jul 23.

Department of Veterinary Biosciences, Melbourne Veterinary School, Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Parkville, Australia.

Background: Doramapimod, a p38 MAPK inhibitor, is a potent anti-inflammatory drug that decreases inflammatory cytokine production in equine whole blood in vitro. It may have benefits for treating systemic inflammation in horses.

Objective: To determine whether doramapimod is well tolerated when administered IV to horses, and whether it has anti-inflammatory effects in horses in a low-dose endotoxemia model. Read More

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September 2020

Triiodothyronine for the treatment of critically ill patients with COVID-19 infection: A structured summary of a study protocol for a randomised controlled trial.

Trials 2020 Jun 26;21(1):573. Epub 2020 Jun 26.

Department of Pharmacology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Ave.,11527 Goudi, Athens, Greece.

Objectives: Tissue hypoxia is the main cause of multi-organ dysfunction in sepsis. However, effective pharmacological treatments to combat sepsis-induced tissue hypoxia are not available. Emerging experimental and clinical evidence reveals an evolutionary conserved action of thyroid hormone (TH) to adapt injured tissue to hypoxic conditions via its action on p38 MAPK, Akt signaling pathways. Read More

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Tubular transcriptional co-activator with PDZ-binding motif protects against ischemic acute kidney injury.

Clin Sci (Lond) 2020 07;134(13):1593-1612

Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.

Transcriptional co-activator with PDZ-binding motif (TAZ) is a key downstream effector of the Hippo tumor-suppressor pathway. The functions of TAZ in the kidney, especially in tubular epithelial cells, are not well-known. To elucidate the adaptive expression, protective effects on kidney injury, and signaling pathways of TAZ in response to acute kidney injury (AKI), we used in vitro (hypoxia-treated human renal proximal tubular epithelial cells [RPTECs]) and in vivo (mouse ischemia-reperfusion injury [IRI]) models of ischemic AKI. Read More

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Blockade of p38 kinase impedes the mobilization of protumorigenic myeloid populations to impact breast cancer metastasis.

Int J Cancer 2020 10 28;147(8):2279-2292. Epub 2020 May 28.

Department of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA.

Patients with metastatic breast cancer (MBC) have limited therapeutic options and novel treatments are critically needed. Prior research implicates tumor-induced mobilization of myeloid cell populations in metastatic progression, as well as being an unfavorable outcome in MBC; however, the underlying mechanisms for these relationships remain unknown. Here, we provide evidence for a novel mechanism by which p38 promotes metastasis. Read More

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October 2020

Stanniocalcin 2 contributes to aggressiveness and is a prognostic marker for oral squamous cell carcinoma.

Exp Cell Res 2020 08 20;393(2):112092. Epub 2020 May 20.

Department of Oral Diagnosis, School of Dentistry, University of Campinas, Piracicaba, SP, Brazil. Electronic address:

Stanniocalcin 2 (STC2), a glycoprotein that regulates calcium and phosphate homeostasis during mineral metabolism, appears to display multiple roles in tumorigenesis and cancer progression. This study aimed to access the prognostic value of STC2 in oral squamous cell carcinoma (OSCC) and its implications in oral tumorigenesis. STC2 expression was examined in 2 independent cohorts of OSCC tissues by immunohistochemistry. Read More

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A new model of repeat mTBI in adolescent rats.

Exp Neurol 2020 09 20;331:113360. Epub 2020 May 20.

Department of Neurological Surgery, University of California, Davis School of Medicine, 4800 Y St Suite 3740, Sacramento, CA 95817, United States of America; Center for Neuroscience, University of California, Davis, 1544 Newton Ct, Davis, CA 95818, United States of America. Electronic address:

Sports-related injury is frequently associated with repeated diffuse and mild traumatic brain injury (mTBI). We combined two existing models for inducing TBI in rats, the Impact Acceleration and Controlled Cortical Impact models, to create a new method relevant to the study of cognitive sequelae of repeat mTBI in adolescent athletes. Repeated mTBI, such as those incurred in sports, can result in a wide range of outcomes, with many individuals experiencing no chronic sequela while others develop profound cognitive and behavioral impairments, typically in the absence of lasting motor symptoms or gross tissue loss appreciable antemortem. Read More

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September 2020

The IL-33-induced p38-/JNK1/2-TNFα axis is antagonized by activation of β-adrenergic-receptors in dendritic cells.

Sci Rep 2020 05 18;10(1):8152. Epub 2020 May 18.

Institute of Immunology, Jena University Hospital, 07743, Jena, Germany.

IL-33, an IL-1 cytokine superfamily member, induces the activation of the canonical NF-κB signaling, and of Mitogen Activated Protein Kinases (MAPKs). In dendritic cells (DCs) IL-33 induces the production of IL-6, IL-13 and TNFα. Thereby, the production of IL-6 depends on RelA whereas the production of IL-13 depends on the p38-MK2/3 signaling module. Read More

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The first-in-human study of CNTO 7160, an anti-interleukin-33 receptor monoclonal antibody, in healthy subjects and patients with asthma or atopic dermatitis.

Br J Clin Pharmacol 2020 12 14;86(12):2507-2518. Epub 2020 Jun 14.

Janssen Research & Development, LLC, Spring House, PA, USA.

Aims: To assess safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity of CNTO 7160, an anti-interleukin-33 receptor (IL-33R) monoclonal antibody, in healthy subjects and patients with asthma or atopic dermatitis (AD).

Methods: In Part 1 of this Phase I, randomized, double-blind, placebo-controlled study, healthy subjects (n = 68) received single ascending intravenous (IV) CNTO 7160 dose (0.001 to 10 mg/kg) or placebo. Read More

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December 2020