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https://www.readbyqxmd.com/read/28731147/beclin-1-overexpression-inhibits-chondrocyte-apoptosis-and-downregulates-extracellular-matrix-metabolism-in-osteoarthritis
#1
Bin Song, Hong Song, Weiguo Wang, Hongru Wang, Hanyuan Peng, Jing Cui, Rong Wang, Hua Huang, Wei Wang, Lili Wang
In the present study, the expression of Beclin 1 in osteoarthritis (OA) cartilage tissue was investigated, and also its role in proliferation, apoptosis and expression of matrix metalloproteinases (MMPs) in chondrocytes obtained from patients with OA. Beclin 1 expression in cartilage tissue from OA patients, and in the age- and sex-matched controls, was detected by immunohistochemistry, semi-quantitative polymerase chain reaction and western blotting. Chondrocytes were divided into control and Beclin 1-overexpressed groups...
July 21, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28730648/calcineurin-inhibitor-withdrawal-or-tapering-for-kidney-transplant-recipients
#2
REVIEW
Krishna M Karpe, Girish S Talaulikar, Giles D Walters
BACKGROUND: Calcineurin inhibitors (CNI) can reduce acute transplant rejection and immediate graft loss but are associated with significant adverse effects such as hypertension and nephrotoxicity which may contribute to chronic rejection. CNI toxicity has led to numerous studies investigating CNI withdrawal and tapering strategies. Despite this, uncertainty remains about minimisation or withdrawal of CNI. OBJECTIVES: This review aimed to look at the benefits and harms of CNI tapering or withdrawal in terms of graft function and loss, incidence of acute rejection episodes, treatment-related side effects (hypertension, hyperlipidaemia) and death...
July 21, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28730238/altered-expression-of-mtor-and-autophagy-in-term-normal-human-placentas
#3
Qiu Xia Zhang, Quan Na, Weiwei Song
Mammalian target of rapamycin (mTOR) and autophagy have been implied in trophoblast cells proliferation and invasion. This study investigated whether mTOR and autophagy were involved in placental development and fetal programming. A total of 90 term normal placentas (37-42 gestational weeks) were collected from women who underwent elective cesarean section, with large for gestational age (LGA), fetal growth restriction (FGR), and appropriate for gestational age (AGA) infants (n=30, respectively). Capillary volume density within peripheral villi significantly decreased in the FGR placentas compared with the AGA group (p<0...
2017: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/28724388/o-glcnac-regulation-of-autophagy-and-%C3%AE-synuclein-homeostasis-implications-for-parkinson-s-disease
#4
Willayat Y Wani, Xiaosen Ouyang, Gloria A Benavides, Matthew Redmann, Stacey S Cofield, John J Shacka, John C Chatham, Victor Darley-Usmar, Jianhua Zhang
Post-translational modification on protein Ser/Thr residues by O-linked attachment of ß-N-acetyl-glucosamine (O-GlcNAcylation) is a key mechanism integrating redox signaling, metabolism and stress responses. One of the most common neurodegenerative diseases that exhibit aberrant redox signaling, metabolism and stress response is Parkinson's disease, suggesting a potential role for O-GlcNAcylation in its pathology. To determine whether abnormal O-GlcNAcylation occurs in Parkinson's disease, we analyzed lysates from the postmortem temporal cortex of Parkinson's disease patients and compared them to age matched controls and found increased protein O-GlcNAcylation levels...
July 19, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28721811/moving-to-the-rhythm-with-clock-circadian-genes-autophagy-mtor-and-sirt1-in-degenerative-disease-and-cancer
#5
Kenneth Maiese
BACKGROUND: The mammalian circadian clock and its associated clock genes are increasingly be recognized as critical components for a number of physiological and disease processes that extend beyond hormone release, thermal regulation, and sleep-wake cycles. New evidence suggests that clinical behavior disruptions that involve prolonged shift work and even space travel may negatively impact circadian rhythm and lead to multi-system disease. METHODS: In light of the significant role circadian rhythm can hold over the body's normal physiology as well as disease processes, we examined and discussed the impact circadian rhythm and clock genes hold over lifespan, neurodegenerative disorders, and tumorigenesis...
July 17, 2017: Current Neurovascular Research
https://www.readbyqxmd.com/read/28720684/fsgs-as-an-adaptive-response-to-growth-induced-podocyte-stress
#6
Ryuzoh Nishizono, Masao Kikuchi, Su Q Wang, Mahboob Chowdhury, Viji Nair, John Hartman, Akihiro Fukuda, Larysa Wickman, Jeffrey B Hodgin, Markus Bitzer, Abhijit Naik, Jocelyn Wiggins, Matthias Kretzler, Roger C Wiggins
Glomerular sclerotic lesions develop when the glomerular filtration surface area exceeds the availability of podocyte foot process coverage, but the mechanisms involved are incompletely characterized. We evaluated potential mechanisms using a transgenic (podocin promoter-AA-4E-BP1) rat in which podocyte capacity for hypertrophy in response to growth factor/nutrient signaling is impaired. FSGS lesions resembling human FSGS developed spontaneously by 7 months of age, and could be induced earlier by accelerating kidney hypertrophy by nephrectomy...
July 18, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28707282/a-system-to-identify-inhibitors-of-mtor-signaling-using-high-resolution-growth-analysis-in-saccharomyces-cerevisiae
#7
Mitchell B Lee, Daniel T Carr, Michael G Kiflezghi, Yan Ting Zhao, Deborah B Kim, Socheata Thon, Margarete D Moore, Mary Ann K Li, Matt Kaeberlein
The mechanistic target of rapamycin (mTOR) is a central regulator of growth and proliferation and mTOR inhibition is a promising therapy for a variety of diseases and disorders. Inhibition of mTOR complex I (mTORC1) with rapamycin delays aging and increases healthy longevity in laboratory animals and is used clinically at high doses to prevent organ transplant rejection and to treat some forms of cancer. Clinical use of rapamycin is associated with several unwanted side effects, however, and several strategies are being taken to identify mTORC1 inhibitors with fewer side effects...
July 13, 2017: GeroScience
https://www.readbyqxmd.com/read/28701309/arhgap18-protects-against-thoracic-aortic-aneurysm-formation-by-mitigating-the-synthetic-and-pro-inflammatory-smooth-muscle-cell-phenotype
#8
Renjing Liu, Lisa Lo, Angelina J Lay, Yang Zhao, Ka Ka Ting, Elizabeth N Robertson, Andrew G Sherrah, Sorour R Jarrah, Haibo Li, Zhaoxiong Zhou, Brett D Hambly, David R Richmond, Richmond W Jeremy, Paul G Bannon, Matthew A Vadas, Jennifer Gamble
Rationale: Thoracic aortic aneurysm (TAA) is a potentially lethal condition which can affect individuals of all ages. TAA may be complicated by the sudden onset of life threatening dissection or rupture. The underlying mechanisms leading to TAA formation, particularly in the non-syndromal idiopathic group of patients, are not well understood. Thus, identification of new genes and targets that are involved in TAA pathogenesis are required to help prevent and/or reverse the disease phenotype. Objective: Here we explore the role of ARHGAP18, a novel Rho GAP expressed by smooth muscle cells (SMC), in the pathogenesis of TAA...
July 12, 2017: Circulation Research
https://www.readbyqxmd.com/read/28698309/differential-control-of-ageing-and-lifespan-by-isoforms-and-splice-variants-across-the-mtor-network
#9
REVIEW
Patricia Razquin Navas, Kathrin Thedieck
Ageing can be defined as the gradual deterioration of physiological functions, increasing the incidence of age-related disorders and the probability of death. Therefore, the term ageing not only reflects the lifespan of an organism but also refers to progressive functional impairment and disease. The nutrient-sensing kinase mTOR (mammalian target of rapamycin) is a major determinant of ageing. mTOR promotes cell growth and controls central metabolic pathways including protein biosynthesis, autophagy and glucose and lipid homoeostasis...
July 15, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/28691365/cooperation-between-p21-and-akt-is-required-for-p53-dependent-cellular-senescence
#10
Young Yeon Kim, Hye Jin Jee, Jee-Hyun Um, Young Mi Kim, Sun Sik Bae, Jeanho Yun
Cellular senescence has been implicated in normal aging, tissue homeostasis, and tumor suppression. Although p53 has been shown to be a central mediator of cellular senescence, the signaling pathway by which it induces senescence remains incompletely understood. In this study, we have shown that both Akt and p21 are required to induce cellular senescence in response to p53 expression. In a p53-induced senescence model, we found that Akt activation was essential for inducing a cellular senescence phenotype. Surprisingly, Akt inhibition did not abolish p53-induced cell cycle arrest, but it suppressed the increase in intracellular reactive oxygen species (ROS) levels...
July 9, 2017: Aging Cell
https://www.readbyqxmd.com/read/28685671/experimental-models-for-aging-and-their-potential-for-novel-drug-discovery
#11
Jaume Folch, Oriol Busquets, Miren EttchetoElena Sánchez-López, Mercè Pallàs, Carlos Beas-Zarate, Miguel Marin, Gemma Casadesus, Jordi Olloquequi, Carme Auladell, Antoni Camins
The development of antiaging drugs is an interesting area of scientific research. In order to evaluate the beneficial effects of new potential drugs, it is necessary to gather the specific knowledge on the adequate preclinical models that are available. This review focuses on invertebrate and vertebrate preclinical models used to evaluate the efficacy of antiaging compounds, with the objective to extend lifespan and health span. Dietary restriction (DR), a common experimental process to extend lifespan in all organisms, is also discussed...
July 7, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28683067/early-postnatal-exposure-to-isoflurane-causes-cognitive-deficits-and-disrupts-development-of-newborn-hippocampal-neurons-via-activation-of-the-mtor-pathway
#12
Eunchai Kang, Danye Jiang, Yun Kyoung Ryu, Sanghee Lim, Minhye Kwak, Christy D Gray, Michael Xu, Jun H Choi, Sue Junn, Jieun Kim, Jing Xu, Michele Schaefer, Roger A Johns, Hongjun Song, Guo-Li Ming, C David Mintz
Clinical and preclinical studies indicate that early postnatal exposure to anesthetics can lead to lasting deficits in learning and other cognitive processes. The mechanism underlying this phenomenon has not been clarified and there is no treatment currently available. Recent evidence suggests that anesthetics might cause persistent deficits in cognitive function by disrupting key events in brain development. The hippocampus, a brain region that is critical for learning and memory, contains a large number of neurons that develop in the early postnatal period, which are thus vulnerable to perturbation by anesthetic exposure...
July 2017: PLoS Biology
https://www.readbyqxmd.com/read/28681509/akt2-ablation-prolongs-life-span-and-improves-myocardial-contractile-function-with-adaptive-cardiac-remodeling-role-of-sirt1-mediated-autophagy-regulation
#13
Jun Ren, Lifang Yang, Li Zhu, Xihui Xu, Asli F Ceylan, Wei Guo, Jian Yang, Yingmei Zhang
Aging is accompanied with unfavorable geometric and functional changes in the heart involving dysregulation of Akt and autophagy. This study examined the impact of Akt2 ablation on life span and cardiac aging as well as the mechanisms involved with a focus on autophagy and mitochondrial integrity. Cardiac geometry, contractile, and intracellular Ca(2+) properties were evaluated using echocardiography, IonOptix(®) edge-detection and fura-2 techniques. Levels of Sirt1, mitochondrial integrity, autophagy, and mitophagy markers were evaluated using Western blot...
July 5, 2017: Aging Cell
https://www.readbyqxmd.com/read/28677234/anti-aging-pharmacology-in-cutaneous-wound-healing-effects-of-metformin-resveratrol-and-rapamycin-by-local-application
#14
Pan Zhao, Bing-Dong Sui, Nu Liu, Ya-Jie Lv, Chen-Xi Zheng, Yong-Bo Lu, Wen-Tao Huang, Cui-Hong Zhou, Ji Chen, Dan-Lin Pang, Dong-Dong Fei, Kun Xuan, Cheng-Hu Hu, Yan Jin
Cutaneous wounds are among the most common soft tissue injuries and are particularly hard to heal in aging. Caloric restriction (CR) is well documented to extend longevity; pharmacologically, profound rejuvenative effects of CR mimetics have been uncovered, especially metformin (MET), resveratrol (RSV), and rapamycin (RAPA). However, locally applied impacts and functional differences of these agents on wound healing remain to be established. Here, we discovered that chronic topical administration of MET and RSV, but not RAPA, accelerated wound healing with improved epidermis, hair follicles, and collagen deposition in young rodents, and MET exerted more profound effects...
July 5, 2017: Aging Cell
https://www.readbyqxmd.com/read/28675698/the-mtor-inhibition-in-concurrence-with-erk1-2-activation-is-involved-in-excessive-autophagy-induced-by-glycyrrhizin-in-hepatocellular-carcinoma
#15
Xuan Zhang, Hua Yang, Shuqiang Yue, Guangbin He, Shibin Qu, Zhuochao Zhang, Ben Ma, Rui Ding, Wei Peng, Hongtao Zhang, Zhaoxu Yang, Kefeng Dou, Kaishan Tao, Xiao Li
Autophagy is a life phenomenon in which autophagosomes remove damaged or aging organelles and long-lived circulating proteins to maintain the cell's stability. However, disorders of excessive autophagy are a response of cancer cells to a variety of anticancer treatments which lead to cancer cell death. The Akt/mammalian target of rapamycin (mTOR) and the extracellular signal-regulated kinase 1/2 (ERK1/2) pathways are both involved in nutrient-induced autophagic phenomenon and exhibit vital relevance to oncogenesis in various cancer cell types, including hepatocellular carcinoma (HCC)...
July 3, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28656269/high-glucose-induces-the-aging-of-mesenchymal-stem-cells-via-akt-mtor-signaling
#16
Dayong Zhang, Huifei Lu, Zhongxing Chen, Yayan Wang, Jiuzhou Lin, Shan Xu, Chong Zhang, Baoming Wang, Zhanggen Yuan, Xiao Feng, Xuefan Jiang, Jianping Pan
It has previously been demonstrated that glucose is important in the process of stem cell aging. However, the mechanisms of cell senescence induced by high glucose (HG) remain to be elucidated. The preliminary study indicated that D‑galactose induced mesenchymal stem cell (MSCs) aging. The present study demonstrated, following treatment with 11.0 or 22.0 mM HG for 14 days, that HG significantly promoted MSCs aging and the expression levels of phosphorylated (p-)phosphatidylinositol 3-kinase/protein kinase B (Akt) and p‑mammalian target of rapamycin signaling (mTOR) in the HG groups were increased compared with the control group...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28653281/fingolimod-exerts-only-temporary-antiepileptogenic-effects-but-longer-lasting-positive-effects-on-behavior-in-the-wag-rij-rat-absence-epilepsy-model
#17
Antonio Leo, Rita Citraro, Nicola Amodio, Caterina De Sarro, Maria Eugenia Gallo Cantafio, Andrew Constanti, Giovambattista De Sarro, Emilio Russo
One of the major challenges in the epilepsy field is identifying disease-modifying drugs in order to prevent or delay spontaneous recurrent seizure onset or to cure already established epilepsy. It has been recently reported that fingolimod, currently approved for the treatment of relapsing-remitting multiple sclerosis, has demonstrated antiepileptogenic effects in 2 different preclinical models of acquired epilepsy. However, to date, no data exist regarding the role of fingolimod against genetic epilepsy. Therefore, we have addressed this issue by studying the effects of fingolimod in Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats, a well-established genetic model of absence epilepsy, epileptogenesis, and neuropsychiatric comorbidity...
June 26, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28641136/age-exacerbates-abnormal-protein-expression-in-a-mouse-model-of-down-syndrome
#18
Md Mahiuddin Ahmed, Aaron Block, Suhong Tong, Muriel T Davisson, Katheleen J Gardiner
The Ts65Dn is a popular mouse model of Down syndrome (DS). It displays DS-relevant features of learning/memory deficits and age-related loss of functional markers in basal forebrain cholinergic neurons. Here we describe protein expression abnormalities in brain regions of 12-month-old male Ts65Dn mice. We show that the magnitudes of abnormalities of human chromosome 21 and non-human chromosome 21 orthologous proteins are greater at 12 months than at ∼6 months. Age-related exacerbations involve the number of components affected in the mechanistic target of rapamycin pathway, the levels of components of the mitogen-activated protein kinase pathway, and proteins associated with Alzheimer's disease...
May 10, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28641125/an-altered-redox-environment-assisted-by-over-expression-of-fetal-hemoglobins-protects-from-inflammatory-colitis-and-reduces-inflammatory-cytokine-expression
#19
R M Gorczynski, C Alexander, K Brandenburg, Z Chen, A Heini, D Neumann, J P Mach, E T Rietschel, A Tersikh, A J Ulmer, Kai Yu, U Zahringer, I Khatri
C5BL/6 female mice receiving dextran sodium sulfate in their drinking water develop an acute inflammatory colitis within 7d, with weight loss, histopathologic signs of inflammation, and colonic expression of inflammatory cytokines. In previous studies we have reported that increased inflammatory cytokine expression in aged mice can be attenuated by oral gavage of a crude fetal extract containing glutathione (GSH), MPLA and fetal hemoglobin, or more specifically by injection of a combination of these purified reagents...
June 19, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28639903/targeting-the-mtor-pathway-in-breast-cancer
#20
REVIEW
Jia Liu, Hui-Qing Li, Fu-Xia Zhou, Jie-Wen Yu, Ling Sun, Zhong-Hou Han
Mechanistic target of rapamycin controls cell growth, metabolism, and aging in response to nutrients, cellular energy stage, and growth factors. In cancers including breast cancer, mechanistic target of rapamycin is frequently upregulated. Blocking mechanistic target of rapamycin with rapamycin, first-generation and second-generation mechanistic target of rapamycin inhibitors, called rapalogs, have shown potent reduction of breast cancer tumor growth in preclinical models and clinical trials. In this review, we summarize the fundamental role of the mechanistic target of rapamycin pathway in driving breast tumors...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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