163 results match your criteria overactivated key

Camptothecin Inhibits Neddylation to Activate the Protective Autophagy Through NF-B/AMPK/mTOR/ULK1 Axis in Human Esophageal Cancer Cells.

Front Oncol 2021 8;11:671180. Epub 2021 Apr 8.

Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

The neddylation pathway is overactivated in esophageal cancer. Our previous studies indicated that inactivation of neddylation by the NAE inhibitor induced apoptosis and autophagy in cancer cells. Camptothecin (CPT), a well-known anticancer agent, could induce apoptosis and autophagy in cancer cells. Read More

View Article and Full-Text PDF

Bioinformatics and experimental findings reveal the therapeutic actions and targets of pachymic acid against cystitis glandularis.

Biofactors 2021 Apr 24. Epub 2021 Apr 24.

The Second Affiliated Hospital of Guilin Medical University, Guilin Medical University, Guilin, Guangxi, People's Republic of China.

Pachymic acid (PA), a bioactive ingredient isolated from Poria cocos Wolf, is reported with potential benefits of anti-inflammatory, anti-oxidative actions. It is reasoned that PA may play the potential benefits against cystitis glandularis (CG), an inflammation of the bladder tissue. In this study, we aimed to apply the network pharmacology and molecular docking analyses to reveal concrete anti-CG targets and mechanisms of PA, and then the bioinformatic findings were verified by using clinical and animal samples. Read More

View Article and Full-Text PDF

Polysaccharide mycophenolate-based nanoparticles for enhanced immunosuppression and treatment of immune-mediated inflammatory diseases.

Theranostics 2021 26;11(8):3694-3709. Epub 2021 Jan 26.

Key Laboratory of Material Chemistry for Energy Conversion and Storage (HUST) of Ministry of Education, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology (HUST), Wuhan 430074, China.

Immune-mediated inflammatory diseases (IMIDs) are characterized by immune dysregulation and severe inflammation caused by the aberrant and overactive host immunological response. Mycophenolic acid (MPA)-based immunosuppressive drugs are potential treatments for IMIDs because of their mild side-effect profile; however, their therapeutic effects are limited by the high albumin binding rate, unsatisfactory pharmacokinetics, and undefined cellular uptake selectivity. Polysaccharide mycophenolate was synthesized by conjugating MPA molecules to dextran (a typical polysaccharide widely used in drug delivery) and encapsulated extra free MPA molecules to fabricate MPA@Dex-MPA nanoparticles (NPs). Read More

View Article and Full-Text PDF
January 2021

Inhibition of innate immune response ameliorates Zika virus-induced neurogenesis deficit in human neural stem cells.

PLoS Negl Trop Dis 2021 Mar 3;15(3):e0009183. Epub 2021 Mar 3.

Department of Neuroscience, Cell Biology and Anatomy, University of Texas Medical Branch, Galveston, Texas, United States of America.

Global Zika virus (ZIKV) outbreaks and their strong link to microcephaly have raised major public health concerns. ZIKV has been reported to affect the innate immune responses in neural stem/progenitor cells (NS/PCs). However, it is unclear how these immune factors affect neurogenesis. Read More

View Article and Full-Text PDF

ABT-263 Reduces Hypertrophic Scars by Targeting Apoptosis of Myofibroblasts.

Front Pharmacol 2020 14;11:615505. Epub 2021 Jan 14.

Department of Burn Surgery, Changhai Hospital, Naval Medical University, Shanghai, China.

Inhibiting proliferation and inducing apoptosis of myofibroblasts is becoming one of the promising and effective ways to treat hypertrophic scar. ABT-263, as an orally bioavailable BCL-2 family inhibitor, has showed great antitumor characteristics by targeting tumor cell apoptosis. The objective of this study was to explore whether ABT-263 could target apoptosis of overactivated myofibroblasts in hypertrophic scar. Read More

View Article and Full-Text PDF
January 2021

Catenin α 1 mutations cause familial exudative vitreoretinopathy by overactivating Norrin/β-catenin signaling.

J Clin Invest 2021 Mar;131(6)

Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.

Familial exudative vitreoretinopathy (FEVR) is a severe retinal vascular disease that causes blindness. FEVR has been linked to mutations in several genes associated with inactivation of the Norrin/β-catenin signaling pathway, but these account for only approximately 50% of cases. We report that mutations in α-catenin (CTNNA1) cause FEVR by overactivating the β-catenin pathway and disrupting cell adherens junctions. Read More

View Article and Full-Text PDF

Trpv4 regulates Nlrp3 inflammasome via SIRT1/PGC-1α pathway in a cuprizone-induced mouse model of demyelination.

Exp Neurol 2021 Mar 31;337:113593. Epub 2020 Dec 31.

Department of Cell Biology and Neurobiology, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou 221004, PR China. Electronic address:

Increasing evidence has demonstrated that the Nod-like receptor pyrin domain containing 3 (Nlrp3) inflammasome overactivated during demyelinating disorders. It has been implicated that transient receptor potential type 4 (Trpv4) is regarded as a polymodal ionotropic receptor that plays an important role in a multitude of pathological conditions, including inflammation. The aim of this study was to investigate whether the Trpv4 channel regulates Nlrp3 inflammasome in the corpus callosum of mice with demyelination. Read More

View Article and Full-Text PDF

RTN1-C mediates cerebral ischemia/reperfusion injury via modulating autophagy.

Acta Biochim Biophys Sin (Shanghai) 2021 Feb;53(2):170-178

Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, China.

It has been widely accepted that autophagic cell death exacerbates the progression of cerebral ischemia/reperfusion (I/R). Our previous study revealed that overexpression of reticulon protein 1-C (RTN1-C) is involved in cerebral I/R injury. However, the underlying mechanisms have not been studied intensively. Read More

View Article and Full-Text PDF
February 2021

Merlin cooperates with neurofibromin and Spred1 to suppress the Ras-Erk pathway.

Hum Mol Genet 2021 Feb;29(23):3793-3806

Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), 07745 Jena, Germany.

The Ras-Erk pathway is frequently overactivated in human tumors. Neurofibromatosis types 1 and 2 (NF1, NF2) are characterized by multiple tumors of Schwann cell origin. The NF1 tumor suppressor neurofibromin is a principal Ras-GAP accelerating Ras inactivation, whereas the NF2 tumor suppressor merlin is a scaffold protein coordinating multiple signaling pathways. Read More

View Article and Full-Text PDF
February 2021

Herbal cake-partitioned moxibustion inhibits colonic autophagy in Crohn's disease signaling involving distinct classes of phosphatidylinositol 3-kinases.

World J Gastroenterol 2020 Oct;26(39):5997-6014

Key Laboratory of Acupuncture-Moxibustion and Immunology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Background: Autophagy is an evolutionarily conserved biological process in eukaryotic cells that involves lysosomal-mediated degradation and recycling of related cellular components. Recent studies have shown that autophagy plays an important role in the pathogenesis of Crohn's disease (CD). Herbal cake-partitioned moxibustion (HM) has been historically practiced to treat CD. Read More

View Article and Full-Text PDF
October 2020

Development of novel benzimidazole-derived neddylation inhibitors for suppressing tumor growth invitro and invivo.

Eur J Med Chem 2021 Jan 24;210:112964. Epub 2020 Oct 24.

State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, East China University of Science and Technology, 130 Mei Long Road, Shanghai, 200237, China; College of Pharmacy and Chemistry, Dali University, 5 Xue Ren Road, Dali, Yunnan, 671000, China; Frontiers Science Center for Materiobiology and Dynamic Chemistry, East China University of Science and Technology, 130 Mei Long Road, Shanghai, 200237, China. Electronic address:

Ubiquitin-like protein neddylation is overactivated in various human cancers and correlates with disease progression, and targeting this pathway represents a valuable therapeutic strategy. Our previous work disclosed an antihypertensive agent, candesartan cilexetic (CDC), serves as a novel neddylation inhibitor for suppressing tumor growth by targeting Nedd8-activating enzyme (NAE). In this study, 42 benzimidazole derivatives were designed and synthesized based on lead compound CDC to improve the neddylation inhibition and anticancer efficacy. Read More

View Article and Full-Text PDF
January 2021

Correction: Overactivated sonic hedgehog signaling aggravates intrauterine adhesion via inhibiting autophagy in endometrial stromal cells.

Cell Death Dis 2020 Oct 30;11(10):935. Epub 2020 Oct 30.

Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper. Read More

View Article and Full-Text PDF
October 2020

Pretreatment with atorvastatin ameliorates cobra venom factor-induced acute lung inflammation in mice.

BMC Pulm Med 2020 Oct 12;20(1):263. Epub 2020 Oct 12.

State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, 550014, China.

Background: The complement system plays a critical role as the pathogenic factor in the models of acute lung injury due to various causes. Cobra venom factor (CVF) is a commonly used complement research tool. The CVF can cause acute inflammation in the lung by producing complement activation components. Read More

View Article and Full-Text PDF
October 2020

Cerebral Fructose Metabolism as a Potential Mechanism Driving Alzheimer's Disease.

Front Aging Neurosci 2020 11;12:560865. Epub 2020 Sep 11.

Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.

The loss of cognitive function in Alzheimer's disease is pathologically linked with neurofibrillary tangles, amyloid deposition, and loss of neuronal communication. Cerebral insulin resistance and mitochondrial dysfunction have emerged as important contributors to pathogenesis supporting our hypothesis that cerebral fructose metabolism is a key initiating pathway for Alzheimer's disease. Fructose is unique among nutrients because it activates a survival pathway to protect animals from starvation by lowering energy in cells in association with adenosine monophosphate degradation to uric acid. Read More

View Article and Full-Text PDF
September 2020

Rapid humoral immune responses are required for recovery from haemorrhagic fever with renal syndrome patients.

Emerg Microbes Infect 2020 Dec;9(1):2303-2314

Key Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases in Universities of Shandong, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, People's Republic of China.

Haemorrhagic fever with renal syndrome (HFRS) following Hantaan virus (HTNV) infection displays variable clinical signs. Humoral responses elicited during HTNV infections are considered important, however, this process remains poorly understood. Herein, we have investigated the phenotype, temporal dynamics, and characteristics of B-cell receptor (BCR) repertoire in an HFRS cohort. Read More

View Article and Full-Text PDF
December 2020

Overactivated sonic hedgehog signaling aggravates intrauterine adhesion via inhibiting autophagy in endometrial stromal cells.

Cell Death Dis 2020 09 15;11(9):755. Epub 2020 Sep 15.

Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China.

Autophagy can be dynamically induced in response to stresses and is an essential, ubiquitous intracellular recycling system that impacts the fate of damaged resident cells, thereby influencing wound healing. Endometrial fibrosis is a form of abnormal wound healing that causes intrauterine adhesion (IUA) and infertility. We previously demonstrated that overactivated sonic hedgehog (SHH) signaling exacerbated endometrial fibrosis, but the role of autophagy in this process is still unknown. Read More

View Article and Full-Text PDF
September 2020

Does hereditary angioedema make COVID-19 worse?

World Allergy Organ J 2020 Sep 10;13(9):100454. Epub 2020 Aug 10.

Department of Allergy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China.

The coronavirus disease 2019 (COVID-19) pandemic has spread rapidly worldwide. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent for COVID-19, enters host cells via angiotensin-converting enzyme 2 (ACE2) and depletes ACE2, which is necessary for bradykinin metabolism. The depletion of ACE2 results in the accumulation of des-Arg (9)-bradykinin and possible bradykinin, both of which bind to bradykinin receptors and induce vasodilation, lung injury, and inflammation. Read More

View Article and Full-Text PDF
September 2020

Melatonin Alleviates Neuroinflammation and Metabolic Disorder in DSS-Induced Depression Rats.

Oxid Med Cell Longev 2020 30;2020:1241894. Epub 2020 Jul 30.

Guangdong Laboratory for Lingnan Modern Agriculture/College of Veterinary Medicine, South China Agricultural University/Guangdong Technology Research for Traditional Chinese Veterinary Medicine and Natural Medicine, Guangzhou 510642, China.

There is a bidirectional relationship between inflammatory bowel disease (IBD) and depression/anxiety. Emerging evidences indicate that the liver may be involved in microbiota-gut-brain axis. This experiment focused on the role of melatonin in regulating the gut microbiota and explores its mechanism on dextran sulphate sodium- (DSS-) induced neuroinflammation and liver injury. Read More

View Article and Full-Text PDF

Role of cannabinoids in alcohol-induced neuroinflammation.

Prog Neuropsychopharmacol Biol Psychiatry 2021 01 3;104:110054. Epub 2020 Aug 3.

Neurobiology of Behaviour Research Group (GReNeC-NeuroBio), Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain; Neuroscience Research Programme, IMIM-Hospital del Mar Research Institute, Barcelona, Spain. Electronic address:

Alcohol is a psychoactive substance highly used worldwide, whose harmful use might cause a broad range of mental and behavioural disorders. Underlying brain impact, the neuroinflammatory response induced by alcohol is recognised as a key contributing factor in the progression of other neuropathological processes, such as neurodegeneration. These sequels are determined by multiple factors, including age of exposure. Read More

View Article and Full-Text PDF
January 2021

Downregulation of LAPTM4B Contributes to the Impairment of the Autophagic Flux via Unopposed Activation of mTORC1 Signaling During Myocardial Ischemia/Reperfusion Injury.

Circ Res 2020 Sep 22;127(7):e148-e165. Epub 2020 Jul 22.

CAS Key Laboratory of Tissue Microenvironment and Tumor, Laboratory of Molecular Cardiology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences (CAS), CAS (S.G., J.T., Q.L., S.L., Y.Z., J.L., W.B., P.S., X.L., H.-T.Y.).

Rationale: Impaired autophagic flux contributes to ischemia/reperfusion (I/R)-induced cardiomyocyte death, but the underlying molecular mechanisms remain largely unexplored.

Objective: To determine the role of LAPTM4B (lysosomal-associated transmembrane protein 4B) in the regulation of autophagic flux and myocardial I/R injury.

Methods And Results: LAPTM4B was expressed in murine hearts but downregulated in hearts with I/R (30 minutes/2 hours) injury and neonatal rat cardiomyocytes with hypoxia/reoxygenation (6 hours/2 hours) injury. Read More

View Article and Full-Text PDF
September 2020

On-Demand Autophagy Cascade Amplification Nanoparticles Precisely Enhanced Oxaliplatin-Induced Cancer Immunotherapy.

Adv Mater 2020 Aug 28;32(32):e2002160. Epub 2020 Jun 28.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu, 610064, P. R. China.

Chemoimmunotherapy-induced antitumor immune response is highly dependent on tumor autophagy. When tumor cells are treated with chemoimmunotherapy, timely overactivated autophagy can not only lead more tumor cells to death, but also participate in the endogenous antigen presentation and immune stimulators secretion of dying cells, thus plays a vital role. However, timely and accurately overactivated tumor autophagy during chemoimmunotherapy is of great difficulty. Read More

View Article and Full-Text PDF

TJ-M2010-5, a novel MyD88 inhibitor, corrects R848-induced lupus-like immune disorders of B cells in vitro.

Int Immunopharmacol 2020 Aug 5;85:106648. Epub 2020 Jun 5.

Academy of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

B cell hyperactivities are involved in the development of systemic lupus erythematosus (SLE). Toll-like receptor 7 (TLR7) in the B cells plays a pivotal role in the pathogenesis of SLE. Previous studies have focused on the intrinsic role of B cells in TLR7/MyD88 signaling and consequently on immune activation, autoantibody production, and systemic inflammation. Read More

View Article and Full-Text PDF

Virtual Screening and Optimization of Novel mTOR Inhibitors for Radiosensitization of Hepatocellular Carcinoma.

Drug Des Devel Ther 2020 8;14:1779-1798. Epub 2020 May 8.

Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan 430072, People's Republic of China.

Background: Radiotherapy has an ameliorative effect on a wide variety of tumors, but hepatocellular carcinoma (HCC) is insensitive to this treatment. Overactivated mammalian target of rapamycin (mTOR) plays an important part in the resistance of HCC to radiotherapy; thus, mTOR inhibitors have potential as novel radiosensitizers to enhance the efficacy of radiotherapy for HCC.

Methods: A lead compound was found based on pharmacophore modeling and molecular docking, and optimized according to the differences between the ATP-binding pockets of mTOR and PI3K. Read More

View Article and Full-Text PDF

GPR39 Overexpression in OSCC Promotes YAP-Sustained Malignant Progression.

J Dent Res 2020 07 23;99(8):949-958. Epub 2020 Apr 23.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

The clinical outcome of oral squamous cell carcinoma (OSCC) has not improved in recent years, mainly due to the limited effective targeted therapy that has been applied. Recently, a transcriptional coactivator, YAP, has been shown to have a key regulatory role in malignant progression in multiple cancers, including OSCC. But pharmacologically targeting YAP or the Hippo pathway, which is the main signaling pathway regulating YAP, has been proven to be challenging. Read More

View Article and Full-Text PDF

Liraglutide Attenuates Non-Alcoholic Fatty Liver Disease in Mice by Regulating the Local Renin-Angiotensin System.

Front Pharmacol 2020 8;11:432. Epub 2020 Apr 8.

Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

The renin-angiotensin system (RAS) is involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and represents a potential therapeutic target for NAFLD. Glucagon-like peptide-1 (GLP-1) signaling has been shown to regulate the RAS within various local tissues. In this study, we aimed to investigate the functional relationship between GLP-1 and the local RAS in the liver during NAFLD. Read More

View Article and Full-Text PDF

Prolyl Isomerase Pin1 in Human Cancer: Function, Mechanism, and Significance.

Front Cell Dev Biol 2020 31;8:168. Epub 2020 Mar 31.

Laboratory of Molecular Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University Collaborative Innovation Center of Biotherapy, Chengdu, China.

Peptidyl-prolyl isomerase NIMA-interacting 1 (Pin1) is an evolutionally conserved and unique enzyme that specifically catalyzes the isomerization of phosphorylated serine/threonine-proline (pSer/Thr-Pro) motif and, subsequently, induces the conformational change of its substrates. Mounting evidence has demonstrated that Pin1 is widely overexpressed and/or overactivated in cancer, exerting a critical influence on tumor initiation and progression via regulation of the biological activity, protein degradation, or nucleus-cytoplasmic distribution of its substrates. Moreover, Pin1 participates in the cancer hallmarks through activating some oncogenes and growth enhancers, or inactivating some tumor suppressors and growth inhibitors, suggesting that Pin1 could be an attractive target for cancer therapy. Read More

View Article and Full-Text PDF

Mitochondrial membrane protein mitofusin 2 as a potential therapeutic target for treating free fatty acid-induced hepatic inflammation in dairy cows during early lactation.

J Dairy Sci 2020 Jun 8;103(6):5561-5574. Epub 2020 Apr 8.

Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun 130062, Jilin, China. Electronic address:

Inflammation is critical in the progression from benign hepatic lipidosis to pathological hepatic steatosis. The objective of this study was to examine the potential role of the outer mitochondrial membrane protein mitofusin 2 (MFN2) in the etiology of hepatic steatosis in dairy cows during early lactation. Using a nested case-control design, we compared blood and liver samples from 10 healthy cows and 10 age-matched cows with moderate fatty liver. Read More

View Article and Full-Text PDF

Transplantation of ACE2 Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia.

Aging Dis 2020 Apr 9;11(2):216-228. Epub 2020 Mar 9.

9The Executive Committee on Anti-aging and Disease Prevention in the framework of Science and Technology, Pharmacology and Medicine Themes under an Interactive Atlas along the Silk Roads, UNESCO, Paris, France.

A coronavirus (HCoV-19) has caused the novel coronavirus disease (COVID-19) outbreak in Wuhan, China. Preventing and reversing the cytokine storm may be the key to save the patients with severe COVID-19 pneumonia. Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. Read More

View Article and Full-Text PDF

Functional loss of inactive rhomboid-like protein 2 mitigates obesity by suppressing pro-inflammatory macrophage activation-triggered adipose inflammation.

Mol Metab 2020 04 22;34:112-123. Epub 2020 Jan 22.

Chongqing Key Laboratory of Medicinal Resources in the Three Gorges Reservoir Region, School of Biological and Chemical Engineering, Chongqing University of Education, Chongqing, 400067, PR China; Research Center of Brain Intellectual Promotion and Development for Children Aged 0-6 Years, Chongqing University of Education, Chongqing, 400067, PR China. Electronic address:

Objective: Chronic inflammation of adipose tissues contributes to obesity-triggered insulin resistance. Unfortunately, the potential molecular mechanisms regarding obesity-associated systemic inflammation and metabolic disorder remain complicated. Here, we report that inactive rhomboid-like protein 2 (iRhom2) was increased in overweight mice with adipose inflammation. Read More

View Article and Full-Text PDF

PL201, a Reported Rhamnoside Against Alzheimer's Disease Pathology, Alleviates Neuroinflammation and Stimulates Nrf2 Signaling.

Front Immunol 2020 27;11:162. Epub 2020 Feb 27.

State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.

Neuroinflammation induced by overactivated glia cells is believed to be a major hallmark of Alzheimer's disease (AD) and a hopeful target against AD. A rhamnoside PL201 was previously reported to promote neurogenesis and ameliorate AD, and in this study, we revealed that PL201 also significantly reduced accumulation of the activated microglia and proinflammatory cytokines in APP/PS1 mice. , PL201 consistently suppressed the microglia induction of proinflammatory cytokines after stimulation with lipopolysaccharides and Aβ42. Read More

View Article and Full-Text PDF