39,293 results match your criteria mtor

Autophagy is required for the promoting effect of angiogenic factor with G patch domain and forkhead-associated domain 1 (AGGF1) in retinal angiogenesis.

Microvasc Res 2021 Jul 30:104230. Epub 2021 Jul 30.

Department of Endocrinology, The First Affiliated Hospital of Xi'an Medical University, No.48 West Fenghao Road, Xi'an, 710077, Shaanxi, China.

Objective: To investigate the effect of angiogenic factor with G patch domain and forkhead-associated domain 1 (AGGF1) on retinal angiogenesis in ischemic retinopathy and its association with autophagy.

Methods: RF/6A cells were divided into the control group, hypoxia group and high-glucose group, and the expression of AGGF1 in cells was detected. C57BL/6 J mice were divided into the control group, oxygen-induced retinopathy (OIR) group and diabetic retinopathy (DR) group, and AGGF1 expression in the retina was observed. Read More

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A systems-level study reveals host-targeted repurposable drugs against SARS-CoV-2 infection.

Mol Syst Biol 2021 Aug;17(8):e10239

Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

Understanding the mechanism of SARS-CoV-2 infection and identifying potential therapeutics are global imperatives. Using a quantitative systems pharmacology approach, we identified a set of repurposable and investigational drugs as potential therapeutics against COVID-19. These were deduced from the gene expression signature of SARS-CoV-2-infected A549 cells screened against Connectivity Map and prioritized by network proximity analysis with respect to disease modules in the viral-host interactome. Read More

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The regulatory mechanism of amino acids on milk protein and fat synthesis in mammary epithelial cells: a mini review.

Anim Biotechnol 2021 Aug 2:1-11. Epub 2021 Aug 2.

College of Animal Science, Yangtze University, Jingzhou, China.

Mammary epithelial cell (MEC) is the basic unit of the mammary gland that synthesizes milk components including milk protein and milk fat. MECs can sense to extracellular stimuli including nutrients such as amino acids though different sensors and signaling pathways. Here, we review recent advances in the regulatory mechanism of amino acids on milk protein and fat synthesis in MECs. Read More

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A 3D spheroid-specific role of Wnt/β-catenin and Eph-Ephrin in nasopharyngeal carcinoma cells.

J Cell Sci 2021 Aug 2. Epub 2021 Aug 2.

School of Biomedical Sciences, University of Hong Kong, Sassoon Road, Hong Kong.

One of the greatest unmet needs hindering the successful treatment of nasopharyngeal carcinomas (NPC) is the lack of representative, physiological, and cost-effective models. Although Epstein-Barr virus (EBV) infection is consistently present in NPC, most studies have focused on EBV-negative NPC. For the first time, 3D spheroids model of EBV-positive and -negative NPC cells were established and analyzed as compared to classical 2D culture in various aspects of tumor phenotype and drugs response. Read More

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Wnt5a Regulates Junctional Function of Sertoli cells Through PCP-Mediated Effects on mTORC1 and mTORC2.

Endocrinology 2021 Aug 2. Epub 2021 Aug 2.

Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, P.R China.

The blood-testis barrier (BTB) and apical ectoplasmic specialization (ES), which are synchronized through the crosstalk of Sertoli cells and Sertoli-germ cells, are required for spermatogenesis and sperm release. Here, we show that Wnt5a, a noncanonical Wnt signaling pathway ligand, is predominately expressed in both the BTB and apical ES and has a specific expression pattern during the seminiferous epithelium cycle. We employed siRNA to knockdown Wnt5a expression in testis and Sertoli cells and then identified elongated spermatids that lost their polarity, and were embedded in the seminiferous epithelium. Read More

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Combined endocrine and targeted therapy in luminal breast cancer.

Expert Rev Anticancer Ther 2021 Aug 2. Epub 2021 Aug 2.

AC Camargo Cancer Center, Rua Pires da Mota, 1167, São Paulo, Brazil.

Introduction: For decades, endocrine therapy has been the cornerstone of management for luminal breast cancer. Despite the substantial benefit derived by patients from endocrine therapy, primary and secondary resistance to endocrine therapy are serious clinical issues.

Areas Covered: Today, in the advanced setting, 3 distinct classes of targeted agents - mTOR, CDK 4/6 and PI3K inhibitors are approved for use. Read More

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Arbutin exerts anticancer activity against rat C6 glioma cells by inducing apoptosis and inhibiting the inflammatory markers and P13/Akt/mTOR cascade.

J Biochem Mol Toxicol 2021 Aug 2:e22857. Epub 2021 Aug 2.

Scigen Research and Innovation Pvt. Ltd., Thanjavur, Tamil Nadu, India.

Gliomas are a type of brain cancer that occurs in the supporting glial cells of the brain. It is highly malignant and accounts for 80% of brain tumors with high mortality and morbidity. Phytomedicines are potent alternatives for allopathic drugs which cause side effects. Read More

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Local anesthetic bupivacaine inhibits proliferation and metastasis of hepatocellular carcinoma cells via suppressing PI3K/Akt and MAPK signaling.

J Biochem Mol Toxicol 2021 Aug 2:e22871. Epub 2021 Aug 2.

Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Dalian Medical University, Dalian, China.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Retrospective studies suggest that using local/regional anesthetic (LA/RA) is associated with better outcomes in primary HCC patients. In this study, we evaluated the effects of LA/RA bupivacaine in HCC cells and the underlying molecular mechanisms. Read More

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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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Inhibition of MicroRNA miR-101-3p on prostate cancer progression by regulating Cullin 4B (CUL4B) and PI3K/AKT/mTOR signaling pathways.

Bioengineered 2021 Dec;12(1):4719-4735

Department of Urology, Wuxi Traditional Chinese Medicine Hospital, Wuxi, China.

To probe into the efffects of miR-101-3p via regulating CUL4B within PI3K/AKT/mTOR signaling pathway on progression of prostate cancer (PCA). Western blot and qRT-PCR were adopted to detect CUL4B and miR-101-3p expressions in 75 cases with PCA . The cellular strains of PCA (LNCaP and PC3) were chose as the objects to check the targeting correlation between CUL4B and miR-101-3p through dual-luciferase reporter experiments. Read More

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December 2021

The Effects of Sterol-Related Signaling Pathways on Glioma.

Nutr Cancer 2021 Aug 2:1-11. Epub 2021 Aug 2.

Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Gliomas are considered as one of the important brain tumors in adults due to their impact on life quality and cognitive functions. Current methods that are used for treating glioma are not satisfying enough. Understanding cellular and molecular events underlying its pathogenesis and progression may lead to the discovery of novel therapeutic approaches. Read More

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The Synergistic Effects of Celastrol in combination with Tamoxifen on Apoptosis and Autophagy in MCF-7 Cells.

J Immunol Res 2021 22;2021:5532269. Epub 2021 Jul 22.

Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, China.

Breast cancer is one of the most common cancers among females and is associated with high mortality and morbidity rates. Several studies have demonstrated that combination treatments with natural products and tamoxifen can improve the sensitivity and cytotoxicity of oestrogen-positive breast cancer cells in response to tamoxifen. Celastrol, a triterpene from traditional Chinese medicine, has been proven to exert significant anticancer effects on various cancers. Read More

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Whole-Transcriptome Analysis of LncRNAs Mediated ceRNA Regulation in Granulosa Cells Isolated From Healthy and Atresia Follicles of Chinese Buffalo.

Front Vet Sci 2021 14;8:680182. Epub 2021 Jul 14.

State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Animal Reproduction Institute, Guangxi University, Nanning, China.

Granulosa cells (GCs) are the main supporting cells in follicles and play an important role in the regulation of oocyte maturation and follicular atresia. Accumulating evidence indicates that non-coding RNAs participate in regulation of the physiological function of GCs. However, whole-transcriptome analysis for GCs of buffalo has yet to be reported. 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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Trehalose Augments Neuron Survival and Improves Recovery from Spinal Cord Injury via mTOR-Independent Activation of Autophagy.

Oxid Med Cell Longev 2021 10;2021:8898996. Epub 2021 Jul 10.

Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Spinal cord injury (SCI) is a major cause of irreversible nerve injury and leads to serious tissue loss and neurological dysfunction. Thorough investigation of cellular mechanisms, such as autophagy, is crucial for developing novel and effective therapeutics. We administered trehalose, an mTOR-independent autophagy agonist, in SCI rats suffering from moderate compression injury to elucidate the relationship between autophagy and SCI and evaluate trehalose's therapeutic potential. Read More

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Genomic Profiling of Circulating Tumor DNA from Patients with Extensive-Stage Small Cell Lung Cancer Identifies Potentially Actionable Alterations.

J Cancer 2021 22;12(17):5099-5105. Epub 2021 Jun 22.

Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Comprehensive genomic profiling may help uncover potentially actionable alterations in small cell lung cancer (SCLC) patients who have progressed on standard chemotherapy. However, tissue procurement may be extremely challenging for extensive-stage patients. We aimed to investigate the possibility of genomic profiling and detecting actionable alterations from blood in Chinese SCLC patients. Read More

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Integrative Bioinformatics Study of Tangeretin Potential Targets for Preventing Metastatic Breast Cancer.

Evid Based Complement Alternat Med 2021 13;2021:2234554. Epub 2021 Jul 13.

Laboratory of Macromolecular Engineering, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada Sekip Utara II, Yogyakarta 55281, Indonesia.

Agents that target metastasis are important to improve treatment efficacy in patients with breast cancer. Tangeretin, a citrus flavonoid, exhibits antimetastatic effects on breast cancer cells, but its molecular mechanism remains unclear. Tangeretin targets were retrieved from PubChem, whereas metastatic breast cancer regulatory genes were downloaded from PubMed. Read More

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Mammalian Target of Rapamycin Signaling Pathway Regulates Mitochondrial Quality Control of Brown Adipocytes in Mice.

Front Physiol 2021 14;12:638352. Epub 2021 Jul 14.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, China.

The mammalian target of rapamycin (mTOR) is an important protein kinase that senses changes in extracellular and intracellular energy levels and plays a key role in regulating energy metabolism. Brown adipose tissue, which can be converted to white adipose tissue, contains a large number of mitochondria and regulates energy expenditure through thermogenesis. Because obesity is a process of fat accumulation due to chronic excessive energy intake, we attempted to determine whether the mTOR signaling pathway can affect the mitochondrial quality control of brown adipocytes through sensing energy status, thereby regulating brown/white adipocyte transformation. 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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Expression of specific signaling components related to muscle protein turnover and of branched-chain amino acid catabolic enzymes in muscle and adipose tissue of preterm and term calves.

J Dairy Sci 2021 Jul 29. Epub 2021 Jul 29.

Institute of Animal Science, Physiology Unit, University of Bonn, 53111 Bonn, Germany. Electronic address:

Postnatal metabolism depends on maturation of key metabolic pathways around birth. In this regard, endogenous glucose production is impaired in calves born preterm. Concerning protein metabolism, the rates of protein turnover are greater during the neonatal period than at any other period of postnatal life. Read More

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FBXL16 modulates the proliferation and autophagy in breast cancer cells via activating SRC-3-AKT signaling pathway.

Mei Yang Fei Jing

Reprod Biol 2021 Jul 29;21(3):100538. Epub 2021 Jul 29.

Department of Radiotherapy, The Affiliated Changzhou No 2 People's Hospital of Nanjing Medical University, No. 29 Xinglong Alley, Changzhou, Jiangsu, 213000, China. Electronic address:

Breast cancer (BC) is the major reason of cancer deaths in females. However, the underlying mechanism remains to be elucidated. F-box and leucine-rich repeat protein 16 (FBXL16) is known to be an important protein in regulating cancer growth. Read More

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In-depth investigation of the effective substances of traditional Chinese medicine formula based on the novel concept of co-decoction reaction-using Zuojin decoction as a model sample.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 Jul 24;1179:122869. Epub 2021 Jul 24.

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

Zuojin decoction (ZJD) is a classic pair composed of Coptidis Rhizoma and Evodiae Fructus, which is suitable for treating gastrointestinal diseases and tumours, etc. In recent years, scientists have been widely focused on research into the treatment of liver cancer using ZJD; however, the effective substances have not yet been comprehensively elucidated. The difference between the co-decoction and the single decoction of ZJD is revealed in this paper based on the UPLC-QE-Orbitrap-MS, and the chemical components absorbed into the blood and liver of mice have been analyzed simultaneously. Read More

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2,6-Dimethoxy-1,4-benzoquinone increases skeletal muscle mass and performance by regulating AKT/mTOR signaling and mitochondrial function.

Phytomedicine 2021 Jul 10;91:153658. Epub 2021 Jul 10.

Division of Food Functionality Research, Korea Food Research Institute, Wanju-gun 55365, South Korea; Division of Food Biotechnology, University of Science and Technology, Daejeon 34113, South Korea. Electronic address:

Background: 2,6-Dimethoxy-1,4-benzoquinone (DMBQ), a natural phytochemical present in fermented wheat germ, has been reported to exert anti-cancer, anti-inflammatory, and anti-adipogenic effects. However, the effect of DMBQ on muscle hypertrophy and myoblast differentiation has not been elucidated.

Purpose: We investigated the effect of DMBQ on skeletal muscle mass and muscle function and then determined the possible mechanism of DMBQ. Read More

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Respiratory syncytial virus nonstructural protein 1 breaks immune tolerance in mice by downregulating Tregs through TSLP-OX40/OX40L-mTOR axis.

Mol Immunol 2021 Jul 28;138:20-30. Epub 2021 Jul 28.

Department of Pediatrics, Children's Digital Health and Data Center, Zhongnan Hospital of Wuhan University, Wuhan, China. Electronic address:

Respiratory syncytial virus (RSV) infection in early life is associated strongly with the subsequent development and exacerbation of asthma, however, the mechanism is still ambiguous. In this study, we identified that RSV nonstructural protein (NS) 1 plays a critical role. Plasmid-mediated overexpression of NS1 induced significant airway hyperresponsiveness, eosinophilia, and mucus hyperproduction in mice. Read More

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Rapamycin promotes autophagy cell death of Kaposi's sarcoma cells through P75NTR activation.

Exp Dermatol 2021 Jul 31. Epub 2021 Jul 31.

"Kidney and Transplantation" Research Centre, Dep. Nephrology, Dialysis and Transplantation, Annunziata Hospital, Cosenza, Italy.

The mammalian target of rapamycin inhibitor (mTOR-I) Rapamycin, a drug widely used in kidney transplantation, exerts important anti-cancer effects, particularly in Kaposi's Sarcoma (KS), through several biological interactions. In this in vivo and in vitro study we explored whether the activation of the autophagic pathway through the low-affinity receptor for Nerve Growth Factor, p75 , may have a pivotal role in the anti-cancer effect exerted by Rapamycin in KS. Our immunohistochemistry results revealed a significant hyper-activation of the autophagic pathway in KS lesions. Read More

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Morin Acts as a USP7 Inhibitor to Hold Back the Migration of Rheumatoid Arthritis Fibroblast-Like Synoviocytes in a "Prickle1-mTORC2" Dependent Manner.

Mol Nutr Food Res 2021 Jul 30:e2100367. Epub 2021 Jul 30.

Department of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, China.

Scope: To investigate the effect and detailed mechanisms of morin, an anti-arthritis compound widely distributed in foods of plant origin, on the pathological migration of fibroblast-like synoviocytes (FLS).

Methods And Results: The migration of FLS collected from arthritis rats and MH7A cells was induced by platelet-derived growth factor, and an arthritis model in rats was established by Freund's complete adjuvant. The results showed that morin remarkably restrained FLS migration but slightly affected FLS apoptosis and proliferation. Read More

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Synergistic melanoma cell death mediated by inhibition of both MCL1 and BCL2 in high-risk tumors driven by NF1/PTEN loss.

Oncogene 2021 Jul 30. Epub 2021 Jul 30.

Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Melanomas driven by loss of the NF1 tumor suppressor have a high risk of treatment failure and effective therapies have not been developed. Here we show that loss-of-function mutations of nf1 and pten result in aggressive melanomas in zebrafish, representing the first animal model of NF1-mutant melanomas harboring PTEN loss. MEK or PI3K inhibitors show little activity when given alone due to cross-talk between the pathways, and high toxicity when given together. Read More

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Restoring glutamate receptosome dynamics at synapses rescues autism-like deficits in Shank3-deficient mice.

Mol Psychiatry 2021 Jul 30. Epub 2021 Jul 30.

IGF, University of Montpellier, CNRS, INSERM, Montpellier, France.

Shank3 monogenic mutations lead to autism spectrum disorders (ASD). Shank3 is part of the glutamate receptosome that physically links ionotropic NMDA receptors to metabotropic mGlu5 receptors through interactions with scaffolding proteins PSD95-GKAP-Shank3-Homer. A main physiological function of the glutamate receptosome is to control NMDA synaptic function that is required for plasticity induction. Read More

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The PI3K/mTOR Inhibitor Ompalisib Suppresses Nonhomologous End Joining and Sensitizes Cancer Cells to Radio- and Chemotherapy.

Mol Cancer Res 2021 Jul 30. Epub 2021 Jul 30.

Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University

As the predominant pathway for the repair of DNA double-strand breaks (DSBs), non-homologous end joining (NHEJ) attenuates the efficacy of cancer treatment which relies on the introduction of DSBs, such as radiotherapy and genotoxic drugs. Identifying novel NHEJ inhibitors is of great importance for improving the therapeutic efficiency of radio- or chemotherapy. Here we miniaturized our recently developed NHEJ detecting system into a 96-well plate-based format and interrogated an FDA approved drug library containing 1732 compounds. Read More

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