Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42345 (mTOR)
 26,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Porcine epidemic diarrhea virus (PEDV) is responsible for the acute infectious swine disease porcine epidemic diarrhea (PED). PED causes damage to the intestine, including villus atrophy and shedding, leading to serious economic losses to the pig industry worldwide. We carried out an in vitro study to investigate cell apoptosis and the cell cycle in a PEDV-infected host using transcriptomic shotgun sequencing (RNA-Seq) to study gene responses to PEDV infection. Results revealed that the PEDV infection reduced proliferation activity, blocked the cell cycle at S-phase and induced apoptosis in IPEC-J2 cells. The expression of gene levels related to ribosome proteins and oxidative phosphorylation were significantly up-regulated post-PEDV infection. Although the significantly down-regulated on PI3K/Akt signaling pathway post-PEDV infection, the regulator-related genes of mTOR signaling pathway exerted significantly up-regulated or down-regulated in IPEC-J2 cells. These results indicated that ribosome proteins and oxidative phosphorylation process were widely involved in the pathological changes and regulation of host cells caused by PEDV infection, and PI3K/AKT and mTOR signaling pathways played a vital role in antiviral regulation in IPEC-J2 cells. These data might provide new insights into the specific pathogenesis of PEDV infection and pave the way for the development of effective therapeutic strategies.
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PMID:Porcine epidemic diarrhea virus infection blocks cell cycle and induces apoptosis in pig intestinal epithelial cells. 3265 34

Recently many therapeutic classes have emerged in advanced hormone receptor-positive breast cancer, which is the leading cause of cancer death in women. In absence of visceral crisis, treatment relies on endocrine therapy combined with cyclin dependent kinase 4 and 6 inhibitor. Many mechanisms lead to resistance to endocrine therapy, including the activation of intracellular signaling pathways critical for cell survival. Approximately 70% of breast tumors harbor an alteration in the phosphoinositide 3 kinase (PI3K)/Akt pathway, leading to its hyper activation. This pathway is involved in the regulation of growth, proliferation and cell survival as well as in angiogenesis and is consequently a major target in the oncogenesis. An aberrant PIK3CA mutation is a common phenomenon in breast cancer and found in approximately 40% of patients with advanced hormone receptor-positive breast cancer. For the moment, the only positive trials showing a progression free survival benefit in this population are BOLERO-2 (2012), SOLAR-1 (2019), which tested everolimus, a mammalian target of rapamycin inhibitor, and alpelisib, a PI3K inhibitor, and led to their marketing authorization. However, many other inhibitors of this pathway are promising; nevertheless their development is actually limited by toxicity, mainly cutaneous (rash), digestive (diarrhea) and endocrine (diabetes).
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PMID:Targeting the PI3K/Akt/mTOR pathway in estrogen-receptor positive HER2 negative advanced breast cancer. 3278 89

Glucagonoma is a hormonally active rare pancreatic neuroendocrine tumour causing an excess of glucagon. This is a narrative review based on a multidisciplinary approach of the tumour. Typically associated dermatosis is necrolytic migratory erythema (NME) which is most frequently seen at disease onset. Insulin-dependent diabetes mellitus, depression, diarrhoea, deep vein thrombosis are also identified, as parts of so-called 'D' syndrome. Early diagnosis is life saving due to potential aggressive profile and high risk of liver metastasis. NME as paraneoplastic syndrome may be present for months and even years until adequate recognition and therapy; it is remitted after successful pancreatic surgery. Thus the level of practitioners' awareness is essential. If surgery is not curative, debulking techniques may improve the clinical aspects and even the outcome in association with other procedures such as embolization of hepatic metastasis; ablation of radiofrequency type; medical therapy including chemotherapy, targeted therapy with mTOR inhibitors such as everolimus, PRRT (peptide receptor radiotherapy), and somatostatin analogues (including combinations of medical treatments). Increased awareness of the condition involves multidisciplinary practitioners.
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PMID:Glucagonoma: From skin lesions to the neuroendocrine component (Review). 3290 95

Porcine deltacoronavirus (PDCoV) is an emergent enteropathogenic coronavirus associated with swine diarrhea. Porcine small intestinal epithelial cells (IPEC) are the primary target cells of PDCoV infection in vivo. Here, isobaric tags for relative and absolute quantification (iTRAQ) labeling coupled to liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to quantitatively identify differentially expressed proteins (DEPs) in PDCoV-infected IPEC-J2 cells. A total of 78 DEPs, including 23 upregulated and 55 downregulated proteins, were identified at 24 h postinfection. The data are available via ProteomeXchange with identifier PXD019975. To ensure reliability of the proteomics data, two randomly selected DEPs, the downregulated anaphase-promoting complex subunit 7 (ANAPC7) and upregulated interferon-induced protein with tetratricopeptide repeats 1 (IFIT1), were verified by real-time PCR and Western blot, and the results of which indicate that the proteomics data were reliable and valid. Bioinformatics analyses, including GO, COG, KEGG, and STRING, further demonstrated that a majority of the DEPs are involved in numerous crucial biological processes and signaling pathways, such as immune system, digestive system, signal transduction, RIG-I-like receptor, mTOR, PI3K-AKT, autophagy, and cell cycle signaling pathways. Altogether, this is the first study on proteomes of PDCoV-infected host cells, which shall provide valuable clues for further investigation of PDCoV pathogenesis.
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PMID:Quantitative Proteomic Analysis of Porcine Intestinal Epithelial Cells Infected with Porcine Deltacoronavirus Using iTRAQ-Coupled LC-MS/MS. 3304 33

Recently, a new coronavirus (SARS-CoV-2) was discovered in China. Due to its high level of contagion, it has already reached most countries, quickly becoming a pandemic. Although the most common symptoms are related to breathing problems, SARS-CoV-2 infections also affect the gastrointestinal tract culminating in inflammation and diarrhea. However, the mechanisms related to these enteric manifestations are still not well understood. Evidence shows that the SARS-CoV-2 binds to the angiotensin-converting enzyme receptor 2 (ACE2) in host cells as a viral invasion mechanism and can infect the lungs and the gut. Other viruses have already been linked to intestinal symptoms through binding to ACE2. In turn, this medical hypothesis article conjectures that the ACE2 downregulation caused by the SARS-CoV-2 internalization could lead to decreased activation of the mechanistic target of mTOR with increased autophagy and lead to intestinal dysbiosis, resulting in diarrhea. Besides that, dysbiosis can directly affect the respiratory system through the lungs. Although there are clues to other viruses that modulate the ACE2/gut/lungs axis, including the participation of autophagy and dysbiosis in the development of gastrointestinal symptoms, there is still no evidence of the ACE2/mTOR/autophagy pathway in SARS-CoV-2 infections. Thus, we propose that the new coronavirus causes a change in the intestinal microbiota, which culminates in a diarrheal process through the ACE2/mTOR/autophagy pathway into enterocytes. Our assumption is supported by premises that unregulated intestinal microbiota increases the susceptibility to other diseases and extra-intestinal manifestations, which can even cause remote damage in lungs. These putative connections lead us to suggest and encourage future studies aiming at assessing the aforementioned hypothesis and regulating dysbiosis caused by SARS-CoV-2 infection, in order to confirm the decrease in lung injuries and the improvement in the prognosis of the disease.
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PMID:Premises among SARS-CoV-2, dysbiosis and diarrhea: Walking through the ACE2/mTOR/autophagy route. 3325 49

The present study was conducted to test the hypothesis that dietary supplementation with a nano chitosan-zinc complex (CP-Zn, 100 mg/kg zinc) could alleviate weaning stress in piglets challenged with ETEC K88 by improving growth performance and intestinal antioxidant capacity. The in vivo effects of CP-Zn on growth performance variables (including gastrointestinal digestion and absorption functions and the levels of key proteins related to muscle growth) and the antioxidant capacity of the small intestine were evaluated in 72 weaned piglets. The porcine jejunal epithelial cell line IPEC-J2 was used to further investigate the antioxidant mechanism of CP-Zn in vitro. The results showed that CP-Zn supplementation increased the jejunal villus height and decreased the diarrhoea rate in weaned piglets. CP-Zn supplementation also improved growth performance (ADG and ADFI), increased the activity of carbohydrate digestion-related enzymes (amylase, maltase, sucrase and lactase) and the mRNA expression levels of nutrient transporters (SGLT1, GLUT2, PEPT1 and EAAC1) in the jejunum, and upregulated the expression levels of mTOR pathway-related proteins (IRS1, phospho-mTOR and phospho-p70S6K) in muscle. In addition, CP-Zn supplementation increased glutathione content, enhanced T-SOD and GSH-px activity, and reduced MDA content in the jejunum. Furthermore, CP-Zn decreased the content of MDA and ROS, enhanced the activity of T-SOD and GSH-px, and upregulated the expression levels of Nrf2 pathway-related proteins (Nrf2, NQO1 and HO1) in LPS-stimulated IPEC-J2 cells. Collectively, these findings indicate that CP-Zn supplementation can improve growth performance and the antioxidant capacity of the small intestine in piglets, thus alleviating weaning stress.
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PMID:Nano chitosan-zinc complex improves the growth performance and antioxidant capacity of the small intestine in weaned piglets. 3325 56


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