40,988 results match your criteria pathway inhibits

Shape switching of CaCO-templated nanorods into stiffness-adjustable nanocapsules to promote efficient drug delivery.

Acta Biomater 2021 Apr 17. Epub 2021 Apr 17.

Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, P.R. China. Electronic address:

Geometry and mechanical property have emerged as important parameters in designing nanocarriers, in addition to their size, surface charge, and hydrophilicity. However, inconsistent and even contradictory demands regarding the shape and stiffness of nanoparticles have been noted in blood circulation, tumor accumulation, and tumor cell internalization. Herein, CaCO nanorods (NRs) with an aspect ratio of around 2. Read More

View Article and Full-Text PDF

β-elemonic acid inhibits growth and triggers apoptosis in human castration-resistant prostate cancer cells through the suppression of JAK2/STAT3/MCL-1 and NF-ĸB signal pathways.

Chem Biol Interact 2021 Apr 17:109477. Epub 2021 Apr 17.

School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 210009, People's Republic of China. Electronic address:

Castration-resistant prostate cancer (CRPC) has become a significant problem in the current treatment of prostate cancer (PCa) with the characteristics of high metastatic potential, resistance and easy recurrence. The abnormal activation of JAK2/STAT3/MCL-1 and NF-κB has been confirmed as the main reason for the development of CRPC. We previously found that β-elemonic acid (β-EA) as a natural triterpene has potential anti-inflammatory and anti-osteosarcoma effects with lower toxicity. Read More

View Article and Full-Text PDF

Bisphenol-A inhibits mitochondrial biogenesis via impairment of GFER mediated mitochondrial protein import in the rat brain hippocampus.

Neurotoxicology 2021 Apr 17. Epub 2021 Apr 17.

Developmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhavan, 31, Mahatma Gandhi Marg, Lucknow, Uttar Pradesh, 226001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India. Electronic address:

Mitochondrial biogenesis relies on different protein import machinery, as mitochondrial proteins are imported from the cytosol. The mitochondrial intermembrane space assembly (MIA) pathway consists of GFER/ALR and CHCHD4/Mia40, responsible for importing proteins and their oxidative folding inside the mitochondria. The MIA pathway plays an essential role in complex IV (COX IV) biogenesis via importing copper chaperone COX17, associated with the respiratory chain. Read More

View Article and Full-Text PDF

Survivin as a Biological Biomarker for Diagnosis and Therapy.

Expert Opin Biol Ther 2021 Apr 20. Epub 2021 Apr 20.

Department of Oncology, University of Oxford, Oxford, UK.

Introduction: Survivin (SVN) is a member of the inhibitor of apoptosis (IAP) protein family that promotes cellular proliferation and inhibits apoptosis. Overexpression of SVN is associated with autoimmune disease, hyperplasia and tumours and can be used as a biomarker in these diseases. SVN is widely recognized as a tumour-associated antigen (TAA) and has become an important target for cancer diagnosis and treatment. Read More

View Article and Full-Text PDF

Purpurin, a anthraquinone induces ROS-mediated A549 lung cancer cell apoptosis via inhibition of PI3K/AKT and proliferation.

J Pharm Pharmacol 2021 Apr 20. Epub 2021 Apr 20.

Department of Thoracic Oncology, Jilin Cancer Hospital, Jilin, Changchun 130000, China.

Objectives: In this study, we sought to evaluate purpurin, a natural biomedicine and a potential inhibitor in decreasing the growth rate of lung cancer cells by modulating the role of PI3K/AKT signalling-associated proliferation and apoptosis.

Methods: A549 cells were treated with purpurin (30 μM) for 24 and 48 h incubation, respectively, and it has been analysed for cytotoxicity, ROS-mediated apoptotic staining. Moreover, purpurin-mediated lipid peroxidation and GSH were measured by biochemical estimation. Read More

View Article and Full-Text PDF

A Novel Competence Pathway in the Oral Pathogen .

J Dent Res 2021 May;100(5):542-548

Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.

is an etiologic cause of dental caries (tooth decay) in humans. Our knowledge of is scant despite the organism's important role in oral health. It is widely believed that lacks the natural competence pathways that are used by other streptococci to regulate growth, virulence, and quorum sensing. Read More

View Article and Full-Text PDF

Tenascin C Promotes Glioma Cell Malignant Behavior and Inhibits Chemosensitivity to Paclitaxel via Activation of the PI3K/AKT Signaling Pathway.

J Mol Neurosci 2021 Apr 19. Epub 2021 Apr 19.

Department of Neurosurgery, Southern University of Science and Technology Yantian Hospital, Shenzhen 518081, Guangdong, People's Republic of China.

The present study aimed to detect the effect of tenascin C (TNC) on cell function and chemosensitivity to paclitaxel and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling in glioma cells.Human glioma cells U87, LN-229, T98G and U251 and normal human astrocytes were obtained, in which TNC expression was detected. The U87 cells and U251 cells were chosen and infected with lentivirus of control overexpression, TNC overexpression, control knockdown, and TNC knockdown for functional experiments. Read More

View Article and Full-Text PDF

YM155 inhibits retinal pigment epithelium cell survival through EGFR/MAPK signaling pathway.

Int J Ophthalmol 2021 18;14(4):489-496. Epub 2021 Apr 18.

First Affiliated Hospital of Northwest University, Northwest University, Xi'an 710069, Shaanxi Province, China.

Aim: To investigate YM155's effect on retinal pigment epithelium (RPE) cells' viability and the potential regulatory mechanisms.

Methods: Human immortalized RPE cell lines (ARPE-19 cell line) were processed with YM155 and epidermal growth factor (EGF). ARPE-19 cell viability was detected by methyl thiazolyl tetrazolium assay, and apoptosis was tested by flow cytometry assay. Read More

View Article and Full-Text PDF

Activation of GPR30 with G1 inhibits oscillatory shear stress-induced adhesion of THP-1 monocytes to HAECs by increasing KLF2.

Aging (Albany NY) 2021 Apr 19;13. Epub 2021 Apr 19.

Department of Geriatrics, Sichuan Provincial People's Hospital, Affiliated Hospital of University of Electronic Science and Technology of China, Chengdu 610072, Sichuang, China.

Atherosclerosis is a chronic inflammatory disease known to be mediated by numerous factors, among which endothelial dysfunction plays a critical role. Oscillatory shear stress induces endothelial cells to lose their anti-atherosclerotic properties and downregulates the expression of the innate protective transcription factor, Krüppel-like factor 2 (KLF2), which is typically upregulated in vascular endothelial cells in response to harmful stimuli. Oxidative stress and inflammation impair endothelial function and damage their survival. Read More

View Article and Full-Text PDF

Inhibition of lipoprotein diacylglyceryl transferase is insensitive to resistance caused by deletion of Braun's lipoprotein.

J Bacteriol 2021 Apr 19. Epub 2021 Apr 19.

Departments of Infectious Diseases, Structural Biology, Biochemical and Cellular Pharmacology, Translational Immunology, Pathology, Protein Chemistry, and Early Discovery Biochemistry, Genentech, South San Francisco, CA 94080 USA

Lipoprotein diacylglyceryl transferase (Lgt) catalyzes the first step in the biogenesis of Gram-negative bacterial lipoproteins which play crucial roles in bacterial growth and pathogenesis. We demonstrate that Lgt depletion in a clinical uropathogenic strain leads to permeabilization of the outer membrane and increased sensitivity to serum killing and antibiotics. Importantly, we identify G2824 as the first described Lgt inhibitor that potently inhibits Lgt biochemical activity and is bactericidal against wild-type and strains. Read More

View Article and Full-Text PDF

Select antitumor cytotoxic CD8 T clonotypes expand in patients with chronic lymphocytic leukemia treated with ibrutinib.

Clin Cancer Res 2021 Apr 19. Epub 2021 Apr 19.

Hematology Branch, National Heart Lung and Blood Institute

Purpose: In chronic lymphocytic leukemia (CLL), the T-cell receptor (TCR) repertoire is skewed and tumor-derived antigens are hypothesized as drivers of oligoclonal expansion. Ibrutinib, a standard treatment for CLL, inhibits not only Bruton tyrosine kinase of the B-cell receptor signaling pathway, but also interleukin-2-inducible kinase of the TCR signaling pathway. T-cell polarization and activation are affected by ibrutinib, but it is unknown if T cells contribute to clinical response. Read More

View Article and Full-Text PDF

Cyclic mechanical stimulation inhibits rheumatoid arthritis fibroblast-like synoviocytes proliferation via cell cycle arrest.

J Biomech 2021 Apr 8;121:110424. Epub 2021 Apr 8.

Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400030, PR China. Electronic address:

The imbalance between proliferation and apoptosis of fibroblast-like synoviocytes (FLSs) has been the main cause of rheumatoid arthritis (RA) synovial hyperplasia. Our previous study confirmed that the cyclic mechanical stimulation (CMS) inhibited the proliferation of RA FLSs, but the underlying mechanisms are still unclear. This study aimed to investigate these underlying mechanisms. Read More

View Article and Full-Text PDF

Paricalcitol inhibits oxidative stress-induced cell senescence of the bile duct epithelium dependent on modulating Sirt1 pathway in cholestatic mice.

Free Radic Biol Med 2021 Apr 16. Epub 2021 Apr 16.

Department of Cell Biology, School of Medicine, Taizhou University, Taizhou, PR China. Electronic address:

Background: Clinical studies indicate that vitamin D receptor (VDR) expression is reduced in primary biliary cirrhosis patient livers. However, the mechanism by which activated VDR effect cholestatic liver injury remains unclear.

Methods: Mice were injected intraperitoneally with the VDR agonist paricalcitol or a vehicle 3 days prior to bile duct ligation (BDL) and for 5 or 28 days after surgery. Read More

View Article and Full-Text PDF

Astegolimab (anti-ST2) efficacy and safety in adults with severe asthma: a randomized clinical trial.

J Allergy Clin Immunol 2021 Apr 16. Epub 2021 Apr 16.

Department of Respiratory Sciences, University of Leicester, Leicestershire, United Kingdom. Electronic address:

Background: The interleukin (IL)-33/ST2 pathway is linked with asthma susceptibility. Inhaled allergens, pollutants, and respiratory viruses, which trigger asthma exacerbations, induce release of IL-33, an epithelial-derived "alarmin." Astegolimab, a human IgG2 monoclonal antibody, selectively inhibits the IL-33 receptor, ST2. Read More

View Article and Full-Text PDF

Efficient Heterogeneous Palladium Catalysts in Oxidative Cascade Reactions.

Acc Chem Res 2021 Apr 19. Epub 2021 Apr 19.

Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, SE-10691 Stockholm, Sweden.

ConspectusPalladium-catalyzed oxidations involving cascade processes provide a versatile platform for streamlined conversion of simple feedstocks into functional molecules with high atom and step economy. However, the achievement of high palladium efficiency and selectivity in Pd-catalyzed oxidative cascade reactions is still challenging in many cases, as a result of the aggregation of active palladium species to Pd black and the possible side reactions during each bond-forming step. The two current solutions for addressing these issues are either to utilize oxidant-stable ligands or to use electron transfer mediators (ETMs). Read More

View Article and Full-Text PDF

Combination of tea polyphenols and proanthocyanidins prevents menopause-related memory decline in rats via increased hippocampal synaptic plasticity by inhibiting p38 MAPK and TNF-α pathway.

Nutr Neurosci 2021 Apr 19:1-19. Epub 2021 Apr 19.

Department of Nutrition and Food Hygiene, School of Public Health, Shanxi Medical University, Taiyuan, People's Republic of China.

Objective: Many studies have examined the beneficial effects of tea polyphenols (TP) and proanthocyanidins (PC) on the memory impairment in different animal models. However, the combined effects of them on synaptic, memory dysfunction and molecular mechanisms have been poorly studied, especially in the menopause-related memory decline in rats.

Methods: In this rat study, TP and PC were used to investigate their protective effects on memory decline caused by inflammation. Read More

View Article and Full-Text PDF

Nuclear export protein CSE1L interacts with P65 and promotes NSCLC growth via NF-κB/MAPK pathway.

Mol Ther Oncolytics 2021 Jun 10;21:23-36. Epub 2021 Mar 10.

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.

Non-small cell lung cancer (NSCLC) is characterized with high morbidity and mortality, mainly due to frequent recurrence and metastasis. However, the underlying molecular mechanisms of NSCLC tumorigenesis are largely unclear. Through data mining in the ONCOMINE and Gene Expression Omnibus (GEO) databases, the expression of CSE1L (chromosome segregation like 1 protein/CAS), an exportin, was identified to be significantly upregulated in NSCLC and positively associated with poor prognosis of patients. Read More

View Article and Full-Text PDF

IKKe in osteoclast inhibits the progression of methylprednisolone-induced osteonecrosis.

Int J Biol Sci 2021 30;17(5):1353-1360. Epub 2021 Mar 30.

Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.

Previous studies have described that NF-κB signaling mediated by NFκB-inducing kinase (NIK) plays a critical role of the differentiation of osteoclasts. We aim to explore the role of IKKe in methylprednisolone -induced osteonecrosis of the femoral head (ONFH). Methylprednisolone-induced ONFH mice model was successfully established, and subjected to micro computed tomography to detect the femoral head image of the mice. Read More

View Article and Full-Text PDF

PAK5-mediated AIF phosphorylation inhibits its nuclear translocation and promotes breast cancer tumorigenesis.

Int J Biol Sci 2021 27;17(5):1315-1327. Epub 2021 Mar 27.

Department of Cell Biology, Key Laboratory of Cell Biology of National Health Commission of the PRC, Key Laboratory of Medical Cell Biology of Ministry of Education of the PRC, China Medical University, No.77, Puhe Road, Shenyang, 110122, Liaoning, China.

Although p21 activated kinase 5 (PAK5) is related to the progression of multiple cancers, its biological function in breast cancer remains unclear. Apoptosis-inducing factor (AIF) is a vital apoptosis factor in mitochondria, which can be released from mitochondria and enter the nucleus, causing caspase-independent apoptosis. In this study, we reveal that PAK5 inhibits apoptosis by preventing the nuclear translocation of AIF. Read More

View Article and Full-Text PDF

Betulinic acid inhibits pyroptosis in spinal cord injury by augmenting autophagy via the AMPK-mTOR-TFEB signaling pathway.

Int J Biol Sci 2021 11;17(4):1138-1152. Epub 2021 Mar 11.

Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.

Spinal cord injury (SCI) results in a wide range of disabilities. Its complex pathophysiological process limits the effectiveness of many clinical treatments. Betulinic acid (BA) has been shown to be an effective treatment for some neurological diseases, but it has not been studied in SCI. Read More

View Article and Full-Text PDF

Silencing PRSS1 suppresses the growth and proliferation of gastric carcinoma cells via the ERK pathway.

Int J Biol Sci 2021 1;17(4):957-971. Epub 2021 Mar 1.

Cancer Research Institute of Hengyang Medical College, University of South China; Key Laboratory of Cancer Cellular and Molecular Pathology in Hunan Province, Hunan Hengyang 421001, China.

Gastric carcinoma (GC) is one of the most common malignant tumors and seriously threatens human life and health. In the present study, 243 differentially expressed proteins in GC were identified using laser capture microdissection (LCM) combined with isotopically labeled quantitative proteomics technology. The expression of serine protease 1 (PRSS1) protein was analyzed by immunohistochemistry and Western blot. Read More

View Article and Full-Text PDF

Interference of TGF-β1/Smad7 signal pathway affects myocardial fibrosis in hypertension.

Pak J Pharm Sci 2020 Nov;33(6):2625-2631

Department of Cardiology, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi, China.

Hypertension can cause myocardial fibrosis, during which tumor growth factor-beta 1 (TGF-β1) can facilitate myocardial cell proliferation and transition towards myofibroblast (MFB). Smad7 is a negative regulator of TGF-β1/Smads signal pathway. This study used hypertension rat model to investigate the regulatory role of TGF-β1/Smad7 signal pathway in myocardial fibrosis. Read More

View Article and Full-Text PDF
November 2020

MiR-137 promotes cell growth and inhibits extracellular matrix protein expression in HO-induced human trabecular meshwork cells by targeting Src.

Neurosci Lett 2021 Apr 15:135902. Epub 2021 Apr 15.

Department of Ophthalmology, Xi'an NO.1 Hospital, Xi'an, 710002, China. Electronic address:

Glaucoma is a progressive optic neuropathy in more than 25% of cases in patients with permanent blindness. The microRNA is implicated in modulating the cellular function of the trabecular meshwork (TM). The aim of this study is to investigate the role of miR-137 in glaucoma and illustrate the potential molecular mechanisms. Read More

View Article and Full-Text PDF

Nuclear IL-33 plays an important role in the suppression of filaggrin, loricrin, keratin 1, and keratin 10 by IL-4 and IL-13 in human keratinocytes.

J Invest Dermatol 2021 Apr 15. Epub 2021 Apr 15.

Department of Dermatology, Ehime University Graduate School of Medicine, Ehime, Japan.

IL-33 is a chromatin-associated multifunctional cytokine implicated in the pathogenesis of atopic dermatitis (AD), an inflammatory skin disorder characterized by skin barrier dysfunction. The previous reports show that IL-33 is highly detected in the nucleus of epidermal keratinocytes in AD lesions compared to unaffected or normal skin. However, it is unclear whether intracellular IL-33 directly contributes to the pathogenesis of AD. Read More

View Article and Full-Text PDF

LRRc17 controls BMSC senescence via mitophagy and inhibits the therapeutic effect of BMSCs on ovariectomy-induced bone loss.

Redox Biol 2021 Apr 1;43:101963. Epub 2021 Apr 1.

Key Laboratory of Transplant Engineering and Immunology, NHFPC; Regenerative Medicine Research Center; National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, PR China. Electronic address:

Senescence of bone marrow-derived mesenchymal stem cells (BMSCs) has been widely reported to be closely correlated with aging-related diseases, including osteoporosis (OP). Moreover, the beneficial functions of BMSCs decline with age, limiting their therapeutic efficacy in OP. In the present study, using RNA sequencing (RNA-Seq), we found that leucine-rich repeat containing 17 (LRRc17) expression in BMSCs was highly positively correlated with age. Read More

View Article and Full-Text PDF

Neuroprotective and antioxidative effects of pioglitazone in brain tissue adjacent to the ischemic core are mediated by PI3K/Akt and Nrf2/ARE pathways.

J Mol Med (Berl) 2021 Apr 16. Epub 2021 Apr 16.

Institute of Experimental and Clinical Pharmacology, Faculty of Medicine, University Hospital of Schleswig-Holstein, Campus Kiel, Arnold Heller Strasse 3, 24105, Kiel, Germany.

The present study elucidates the neuroprotective mechanisms of the PPARγ (peroxisome proliferator-activated receptor γ) agonist pioglitazone in survival of ischemic neurons following middle cerebral artery occlusion with reperfusion (MCAO). Intracerebroventricular infusion of pioglitazone over 5 days before and 24 or 48 h after MCAO alleviated neurological impairments, inhibited apoptosis 24 h, and activated the PI3K/Akt pathway along with increased phosphorylation of Akt (ser473) and GSK-3β (ser9) in the peri-infarct cortical areas 48 h after MCAO. In primary cortical neurons, pioglitazone suppressed the glutamate-induced release of lactate dehydrogenase by a PPARγ-dependent mechanism. Read More

View Article and Full-Text PDF

Corrigendum to "Myricetin inhibits TNF-α-induced inflammation in A549 cells via the SIRT1/NF-κB pathway" [Pulm. Pharmacol. Therapeut. 65 (2020) 102000].

Pulm Pharmacol Ther 2021 Apr 13:102031. Epub 2021 Apr 13.

Institute of Respiratory Diseases, Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China. Electronic address:

View Article and Full-Text PDF

Piperlongumine inhibits the progression of osteosarcoma by downregulating the SOCS3/JAK2/STAT3 pathway via miR-30d-5p.

Life Sci 2021 Apr 15;277:119501. Epub 2021 Apr 15.

Department of Spine Surgery, People's Hospital of Longhua, Affiliated Hospital of Southern Medical University, Guangdong 518000, Shenzhen, China. Electronic address:

Aims: The present study evaluated the functions of Piperlongumine (PL) in osteosarcoma (OS) cell growth and metastasis both in vitro and in vivo.

Main Methods: MTT assay was conducted to test the cytotoxic effects of PL on the human osteoblasts line HFOB1.19 and the human normal chondrocyte line C28/I2T. Read More

View Article and Full-Text PDF

miR-30c inhibits angiogenesis by targeting delta-like ligand 4 in liver sinusoidal endothelial cell to attenuate liver fibrosis.

FASEB J 2021 May;35(5):e21571

Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Liver fibrosis is a common feature of liver dysfunction during chronic liver diseases and is frequently associated with angiogenesis, a dynamic process that forms new blood vessels from preexisting vasculature. MicroRNAs (miRNAs), which act as posttranscriptional regulators of gene expression, have been shown to regulate liver fibrosis; however, how miRNAs regulate angiogenesis and its mechanism in fibrosis are not well understood. We aimed to elucidate the role and mechanism of miR-30c in attenuating liver fibrosis. Read More

View Article and Full-Text PDF

Macroautophagy in lymphatic endothelial cells inhibits T cell-mediated autoimmunity.

J Exp Med 2021 Jun;218(6)

Department of Pathology and Immunology, School of Medicine, University of Geneva, Geneva, Switzerland.

Lymphatic endothelial cells (LECs) present peripheral tissue antigens to induce T cell tolerance. In addition, LECs are the main source of sphingosine-1-phosphate (S1P), promoting naive T cell survival and effector T cell exit from lymph nodes (LNs). Autophagy is a physiological process essential for cellular homeostasis. Read More

View Article and Full-Text PDF