3,497 results match your criteria mtor ampk


Omarigliptin ameliorated high glucose-induced nucleotide oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation through activating adenosine monophosphate-activated protein kinase α (AMPKα) in renal glomerular endothelial cells.

Bioengineered 2021 Dec;12(1):4805-4815

Department of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.

Diabetic nephropathy (DN) is a complication of diabetes that induces the development of end-stage renal disease (ESRD). The pathogenesis of DN is reported to be closely related to the activation of the NOD-like receptor 3 (NLRP3) inflammasome in renal glomerular endothelial cells. Omarigliptin is a novel dipeptidyl peptidase-4 (DPP-4) inhibitor developed for the management of type II diabetes, it has been recently reported to possess a significant anti-inflammatory property. Read More

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December 2021

Exendin-4 stimulates autophagy in pancreatic β-cells via the RAPGEF/EPAC-Ca-PPP3/calcineurin-TFEB axis.

Autophagy 2021 Aug 2:1-17. Epub 2021 Aug 2.

Biosciences Institute, Newcastle University, Newcastle Upon Tyne, UK.

Macroautophagy/autophagy is critical for the regulation of pancreatic β-cell mass and its deregulation has been implicated in the pathogenesis of type 2 diabetes (T2D). We have previously shown that treatment of pancreatic β-cells with the GLP1R (glucagon like peptide 1 receptor) agonist exendin-4 stimulates autophagic flux in a setting of chronic nutrient excess. The aim of this study was to identify the underlying pathways contributing to enhanced autophagic flux. Read More

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Mechanism of Exosomes Involved in Osteoimmunity Promoting Osseointegration Around Titanium Implants With Small-Scale Topography.

Front Bioeng Biotechnol 2021 15;9:682384. Epub 2021 Jul 15.

Department of Prosthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, China.

Exosomes are nanoscale extracellular vesicles. Several studies have shown that exosomes participate in intercellular communication and play a key role in osseointegration. However, it is unclear whether exosomes and their contents participate in the communication between the immune and skeletal systems in the process of osseointegration. Read More

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Sinensetin Reduces Osteoarthritis Pathology in the Tert-Butyl Hydroperoxide-Treated Chondrocytes and the Destabilization of the Medial Meniscus Model Mice the AMPK/mTOR Signaling Pathway.

Front Pharmacol 2021 16;12:713491. Epub 2021 Jul 16.

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

As a common degenerative disease, osteoarthritis (OA) usually causes disability in the elderly and socioeconomic burden. Previous studies have shown that proper autophagy has a protective effect on OA. Sinensetin (Sin) is a methylated flavonoid derived from citrus fruits. Read More

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Autosomic dominant polycystic kidney disease and metformin: Old knowledge and new insights on retarding progression of chronic kidney disease.

Med Res Rev 2021 Jul 30. Epub 2021 Jul 30.

Department of Health Sciences, Renal Unit, "Magna Graecia" University, Catanzaro, Italy.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common congenital kidney disorder, generally caused by mutations in the PKD1 and PKD2 genes, coding for polycystins 1 and 2. Its pathogenesis is accompanied by alterations of the cAMP, mTOR, MAPK/ERK, and JAK/STAT pathways. ADPKD is clinically characterized by the formation of many growing cysts with kidney enlargement and a progressive damage to the parenchyma, up to its complete loss of function, and the onset of end-stage renal disease (ESRD). Read More

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Oleanolic Acid Induces Autophagy and Apoptosis via the AMPK-mTOR Signaling Pathway in Colon Cancer.

J Oncol 2021 14;2021:8281718. Epub 2021 Jul 14.

Colorectal and Anal Surgery, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, No. 71 Baoshan North Road, Guiyang 550001, China.

Aims: The purpose of this study was to explore the biological functions of the mTOR and AMPK signaling pathways in colon cancer (CC). The potential molecular mechanisms by which oleanolic acid (OA) induces autophagy and apoptosis were also investigated.

Methods: The biological functions of mTOR were analyzed by GeneCards, the Search Tool for the Retrieval of Interacting Genes (STRING), and the Database for Annotation, Visualization and Integrated Discovery (DAVID). Read More

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MyD88-mediated signaling intercedes in neurogenic muscle atrophy through multiple mechanisms.

FASEB J 2021 08;35(8):e21821

Department of Pharmacological and Pharmaceutical Sciences, University of Houston College of Pharmacy, Houston, TX, USA.

Skeletal muscle atrophy is a debilitating complication of many chronic disease states and disuse conditions including denervation. However, molecular and signaling mechanisms of muscle wasting remain less understood. Here, we demonstrate that the levels of several toll-like receptors (TLRs) and their downstream signaling adaptor, myeloid differentiation primary response 88 (MyD88), are induced in skeletal muscle of mice in response to sciatic nerve denervation. Read More

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Regulation on Citrate Influx and Metabolism through Inhibiting SLC13A5 and ACLY: A Novel Mechanism Mediating the Therapeutic Effects of Curcumin on NAFLD.

J Agric Food Chem 2021 Jul 29. Epub 2021 Jul 29.

Center of Drug Metabolism and Pharmacokinetics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.

Upregulated de novo lipogenesis (DNL) plays a pivotal role in the progress of the nonalcoholic fatty liver disease (NAFLD). Cytoplasmic citrate flux, mediated by plasma membrane citrate transporter (SLC13A5), mitochondrial citrate carrier (SLC25A1), and ATP-dependent citrate lyase (ACLY), determines the central carbon source for acetyl-CoA required in DNL. Curcumin, a widely accepted dietary polyphenol, can attenuate lipid accumulation in NAFLD. Read More

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MSC-Derived Extracellular Vesicles in Preclinical Animal Models of Bone Injury: A Systematic Review and Meta-Analysis.

Stem Cell Rev Rep 2021 Jul 27. Epub 2021 Jul 27.

Stem Cells, Canadian Blood Services, Ottawa, ON, Canada.

Background And Objective: Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) are a promising treatment for bone injuries, although studies remain preclinical. A systematic review and meta-analysis can assess the efficacy of MSC-EVs and identify treatment aspects associated with enhanced bone repair.

Methods: English language, preclinical, controlled, in vivo studies identified in our systematic search (up to May 8, 2020) examining the use of MSC-EVs in bone healing were included. Read More

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LOC100996425 acts as a promoter in prostate cancer by mediating hepatocyte nuclear factor 4A and the AMPK/mTOR pathway.

J Cell Mol Med 2021 Jul 26. Epub 2021 Jul 26.

Department of Urology, The Second Hospital of Jilin University, Changchun, China.

The involvement of long non-coding RNAs (lncRNAs), differentially expressed genes and signals in prostate cancer (PCa) continues to be a subject of investigation. This study determined effects of LOC100996425 on human PCa by targeting hepatocyte nuclear factor 4A (HNF4A) via the AMPK/mTOR pathway. PCa and adjacent normal tissues were obtained to characterize expression pattern of LOC100996425, HNF4A and the AMPK/mTOR pathway-related genes. Read More

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Quercetin protects oral mucosal keratinocytes against lipopolysaccharide-induced inflammatory toxicity by suppressing the AKT/AMPK/mTOR pathway.

Immunopharmacol Immunotoxicol 2021 Jul 26:1-8. Epub 2021 Jul 26.

Department of Pharmacy, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China.

Background: Cytokines can induce a chronic inflammatory response in the periodontium, leading to periodontitis. Quercetin, a naturally occuring flavonoid, has been shown to inhibit periodontitis, but how it works is poorly understood. In this study, we assessed the impact of quercetin on lipopolysaccharide (LPS)-induced inflammatory damage in oral mucosal keratinocytes (hOMK107) and explored its underlying mechanism. Read More

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Omics Multi-Layers Networks Provide Novel Mechanistic and Functional Insights Into Fat Storage and Lipid Metabolism in Poultry.

Front Genet 2021 7;12:646297. Epub 2021 Jul 7.

One Health at UCalgary, University of Calgary, Calgary, AB, Canada.

Fatty acid metabolism in poultry has a major impact on production and disease resistance traits. According to the high rate of interactions between lipid metabolism and its regulating properties, a holistic approach is necessary. To study omics multilayers of adipose tissue and identification of genes and miRNAs involved in fat metabolism, storage and endocrine signaling pathways in two groups of broiler chickens with high and low abdominal fat, as well as high-throughput techniques, were used. Read More

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Knockdown of CNN3 Impairs Myoblast Proliferation, Differentiation, and Protein Synthesis via the mTOR Pathway.

Front Physiol 2021 8;12:659272. Epub 2021 Jul 8.

Guangdong Traditional Medical and Sports Injury Rehabilitation Research Institute, Guangdong Second Provincial General Hospital, Guangzhou, China.

Background: Myogenesis is a complex process that requires optimal outside-in substrate-cell signaling. Calponin 3 (CNN3) plays an important role in regulating myogenic differentiation and muscle regeneration; however, the precise function of CNN3 in myogenesis regulation remains poorly understood. Here, we investigated the role of CNN3 in a knockdown model in the mouse muscle cell line C2C12. Read More

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Geniposide Combined With Notoginsenoside R1 Attenuates Inflammation and Apoptosis in Atherosclerosis the AMPK/mTOR/Nrf2 Signaling Pathway.

Front Pharmacol 2021 7;12:687394. Epub 2021 Jul 7.

School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.

Inflammation and apoptosis of vascular endothelial cells play a key role in the occurrence and development of atherosclerosis (AS), and the AMPK/mTOR/Nrf2 signaling pathway plays an important role in alleviating the symptoms of AS. Geniposide combined with notoginsenoside R1 (GN combination) is a patented supplement for the prevention and treatment of AS. It has been proven to improve blood lipid levels and inhibit the formation of AS plaques; however, it is still unclear whether GN combination can inhibit inflammation and apoptosis in AS by regulating the AMPK/mTOR/Nrf2 signaling pathway and its downstream signals. Read More

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Ginsenoside-Rg2 exerts anti-cancer effects through ROS-mediated AMPK activation associated mitochondrial damage and oxidation in MCF-7 cells.

Arch Pharm Res 2021 Jul 24;44(7):702-712. Epub 2021 Jul 24.

College of Pharmacy, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, South Korea.

In this study, we investigated the anti-cancer effects of ginsenoside Rg2 (G-Rg2) and its underlying signaling pathways in breast cancer (BC) cells. G-Rg2 significantly induced cytotoxicity and reactive oxygen species (ROS) production in MCF-7 cells among various types of BC cells including HCC1428, T47D, and BT-549. G-Rg2 significantly inhibited protein and mRNA expression of cell cycle G1-S phase regulators, including p-Rb, cyclin D1, CDK4, and CDK6, whereas it enhanced the protein and mRNA expression of cell cycle arrest and apoptotic molecules including cleaved PARP, p21, p27, p53 and Bak through ROS production. Read More

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Estrogen Receptor-Alpha and p53 Status as Regulators of AMPK and mTOR in Luminal Breast Cancer.

Cancers (Basel) 2021 Jul 19;13(14). Epub 2021 Jul 19.

Center for Genetics & Pharmacology, Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.

Luminal breast cancer (LBC) driven by dysregulated estrogen receptor-alpha (ERα) signaling accounts for 70% of the breast cancer cases diagnosed. Although endocrine therapy (ET) is effective against LBC, about one-third of these patients fail to respond to therapy owing to acquired or inherent resistance mechanisms. Aberrant signaling via ERα, oncogenes, growth factor receptors, and mutations in tumor suppressors such as p53 impinge on downstream regulators such as AMPK and mTOR. Read More

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Deregulation of Exo70 Facilitates Innate and Acquired Cisplatin Resistance in Epithelial Ovarian Cancer by Promoting Cisplatin Efflux.

Cancers (Basel) 2021 Jul 11;13(14). Epub 2021 Jul 11.

Cancer Research Center, School of Medicine, Xiamen University, Xiamen 361102, China.

Whilst researches elucidating a diversity of intracellular mechanisms, platinum-resistant epithelial ovarian cancer (EOC) remains a major challenge in the treatment of ovarian cancer. Here we report that Exo70, a key subunit of the exocyst complex, contributes to both innate and acquired cisplatin resistance of EOC. Upregulation of Exo70 is observed in EOC tissues and is related to platinum resistance and progression-free survival of EOC patients. Read More

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Metformin alleviates oxidative stress-induced senescence of human lens epithelial cells via AMPK activation and autophagic flux restoration.

J Cell Mol Med 2021 Jul 23. Epub 2021 Jul 23.

Department of Ophthalmology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Cataracts are the leading cause of blindness worldwide owing to the increasing proportion of elderly individuals in the population. The purpose of this study was to investigate whether metformin could alleviate the occurrence and development of age-related cataract (ARC) and the underlying mechanism. In the present study, we established a senescence model induced by oxidative stress, which was confirmed by measuring β-galactosidase activity, qRT-PCR and Western blotting. Read More

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PPAR Plays an Important Role in Acute Hepatic Ischemia-Reperfusion Injury via AMPK/mTOR Pathway.

PPAR Res 2021 3;2021:6626295. Epub 2021 Jul 3.

Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.

Background: Hepatic ischemia-reperfusion (IR) injury is one of the severe complications associated with liver surgery and leads to liver dysfunction. PPAR is always linked with various physiologic pathways, and it can alleviate liver damage in IR injury.

Aim: In this study, we explored the potential mechanism of PPAR in the pathogenesis of hepatic IR injury by mice model. Read More

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Bioinformatics Analysis of Neuroblastoma miRNA Based on GEO Data.

Pharmgenomics Pers Med 2021 13;14:849-858. Epub 2021 Jul 13.

Department of Hematology, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.

Objective: To analyze the changes in downstream genes, signaling pathways, and proteins based on the difference of microRNA (miRNA) expression in neuroblastoma (NB).

Methods: GSE128004 second-generation sequencing expression data were downloaded from GEO, and Limma package of R language was used to analyze differential expression, and a volcano map and heat map were drawn; the target genes corresponding to the differential miRNA were found using the miWalk web tool, and GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) were performed. The key genes were identified and verified in the TCGA database. Read More

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IRF-8/miR-451a regulates M-MDSC differentiation via the AMPK/mTOR signal pathway during lupus development.

Cell Death Discov 2021 Jul 16;7(1):179. Epub 2021 Jul 16.

The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, 210093, PR China.

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease. Myeloid-derived suppressor cells (MDSCs) have been found to be involved in the regulation of SLE development. However, little is known about the association between MDSC subsets and the factors that draw MDSCs into abnormal expansion. Read More

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Adenosine Induces Autophagy in Cholangiocarcinoma Cells.

Anticancer Res 2021 Aug;41(8):3769-3778

Laboratory of Pharmacology, Chulabhorn Research Institute, Bangkok, Thailand

Background/aim: Cholangiocarcinoma is a lethal disease with increasing incidence worldwide. New therapeutic compounds are urgently needed for this disease. Here, the inhibitory effect of adenosine on cholangiocarcinoma cells was studied. Read More

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γ-Linolenic Acid Prevents Lipid Metabolism Disorder in Palmitic Acid-Treated Alpha Mouse Liver-12 Cells by Balancing Autophagy and Apoptosis via the LKB1-AMPK-mTOR Pathway.

J Agric Food Chem 2021 Jul 19;69(29):8257-8267. Epub 2021 Jul 19.

Institute of Goats and Sheep Science, Nanjing Agricultural University, No. 1 Weigang, Nanjing, Jiangsu 210095, PR China.

Excessive fat deposition is the main character in nonalcoholic fatty liver disease (NAFLD), while γ-linolenic acid (GLA) is a polyunsaturated fatty acid that can reduce lipid deposition. This study investigated the effect and regulatory mechanism of GLA (100 μM) on lipid metabolism in alpha mouse liver 12 (AML-12) cells treated by 400 μM palmitic acid (PA). GLA reduced lipid content and increased fatty acid β oxidation, as indicated by decreasing triglyceride and cholesterol contents and increasing mRNA and protein expressions of CPT1α and PPARα. Read More

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Metformin as a Treatment Strategy for Sjögren's Syndrome.

Int J Mol Sci 2021 Jul 5;22(13). Epub 2021 Jul 5.

Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.

Sjögren's syndrome (SS), a chronic inflammatory disease involving the salivary and lacrimal glands, presents symptoms of sicca as well as systemic manifestations such as fatigue and musculoskeletal pain. Only a few treatments have been successful in management of SS; thus treatment of the disease is challenging. Metformin is the first-line agent for type 2 diabetes and has anti-inflammatory potential. Read More

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Norcantharidin triggers apoptotic cell death in non-small cell lung cancer via a mitophagy-mediated autophagy pathway.

Ann Transl Med 2021 Jun;9(12):971

Department of Biochemistry, Medical College, Jinan University, Guangzhou, China.

Background: Norcantharidin (NCTD) is known to impact on cell progression in many cancers; however, its activity in non-small cell lung cancer (NSCLC) has not yet been characterized. In the present study, we set out to determine the cytotoxic effects of NCTD on the proliferation and apoptosis on A549 cells and their underlying mechanisms.

Methods: NSCLC cell line A549 cells were cultured. Read More

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Metformin inhibits polyphosphate-induced hyper-permeability and inflammation.

Int Immunopharmacol 2021 Jul 13;99:107937. Epub 2021 Jul 13.

Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Metabolic syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Circulating inflammatory factor inorganic polyphosphate (polyP) released from activated platelets could enhance factor XII and bradykinin resulted in increased capillary leakage and vascular permeability. PolyP induce inflammatory responses through mTOR pathway in endothelial cells, which is being reported in several diseases including atherosclerosis, thrombosis, sepsis, and cancer. Systems and molecular biology approaches were used to explore the regulatory role of the AMPK activator, metformin, on polyP-induced hyper-permeability in different organs in three different models of polyP-induced hyper-permeability including local, systemic short- and systemic long-term approaches in murine models. Read More

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Terpenoids' anti-cancer effects: focus on autophagy.

Apoptosis 2021 Jul 16. Epub 2021 Jul 16.

Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon.

Terpenoids are the largest class of natural products, most of which are derived from plants. Amongst their numerous biological properties, their anti-tumor effects are of interest for they are extremely diverse which include anti-proliferative, apoptotic, anti-angiogenic, and anti-metastatic activities. Recently, several in vitro and in vivo studies have been dedicated to understanding the 'terpenoid induced autophagy' phenomenon in cancer cells. Read More

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HSP60-knockdown suppresses proliferation in colorectal cancer cells via activating the adenine/AMPK/mTOR signaling pathway.

Oncol Lett 2021 Aug 1;22(2):630. Epub 2021 Jul 1.

School of Nursing, Binzhou Medical University, Yantai, Shandong 264003, P.R. China.

Colorectal cancer (CRC) is the fourth most lethal cancer in the world. Heat shock protein 60 (HSP60), a mitochondrial chaperone that maintains mitochondrial proteostasis, is highly expressed in tumors compared with in paracancerous tissues, suggesting that high HSP60 expression benefits tumor growth. To determine the effects of HSP60 expression on tumor progression, stable HSP60-knockdown HCT116 cells were constructed in the present study, revealing that knockdown of HSP60 inhibited cell proliferation. Read More

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High Glucose Induces Apoptosis, Glycogen Accumulation and Suppresses Protein Synthesis in Muscle Cells of Olive Flounder .

Br J Nutr 2021 Jul 14:1-42. Epub 2021 Jul 14.

The Key Laboratory of Aquaculture Nutrition and Feeds (Ministry of Agriculture and Rural Affairs), the Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, Qingdao266003, China.

The effect and the mechanism of high glucose on fish muscle cells are not fully understood. In the present study, muscle cells of olive flounder (Paralichthys olivaceus) were treated with high glucose (33 mM) in vitro. Cells were incubated in three kinds of medium containing 5 mM glucose, 5 mM glucose and 28 mM mannitol (as an isotonic contrast) or 33 mM glucose named the Control group, the Mannitol group and the HG (high glucose) group, respectively. Read More

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Viral model of maternal immune activation alters placental AMPK and mTORC1 signaling in rats.

Placenta 2021 Jul 8;112:36-44. Epub 2021 Jul 8.

Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College St, Toronto, ON, M5S 3M2, Canada. Electronic address:

Introduction: Maternal immune activation (MIA) is associated with neurodevelopmental disorders in offspring. We previously demonstrated that poly(I:C)-mediated MIA alters placental and fetal brain amino acid transporter expression in rats, which could potentially play a role in altered neurodevelopment; however, the mechanism(s) underlying these changes in amino acid transporter expression remain unknown. The objective of the current study was to investigate the mechanism(s) underlying poly(I:C)-mediated changes in the expression of the amino acid transporters in the placenta. Read More

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