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https://www.readbyqxmd.com/read/28526373/coffee-consumption-in-aged-mice-increases-energy-production-and-decreases-hepatic-mtor-levels
#1
Keita Takahashi, Shuichi Yanai, Kentaro Shimokado, Akihito Ishigami
OBJECTIVE: Coffee, one of the world's most consumed beverages, has many benefits. Some studies have reported the effects of coffee on aging. The aim of this study was to investigate the locomotor activity, energy metabolism, and lipid metabolism of aged (20-mo-old) mice given coffee. METHODS: Aged C57 BL/6 NCr mice were divided into three groups: controls that were not given coffee (n = 9), a group that received 0.1% caffeinated coffee (n = 9), and a group that received 0...
June 2017: Nutrition
https://www.readbyqxmd.com/read/28522687/integrin-linked-kinase-signaling-promotes-cyst-growth-and-fibrosis-in-polycystic-kidney-disease
#2
Archana Raman, Gail A Reif, Yuqiao Dai, Aditi Khanna, Xiaogang Li, Lindsay Astleford, Stephen C Parnell, James P Calvet, Darren P Wallace
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by innumerous fluid-filled cysts and progressive deterioration of renal function. Previously, we showed that periostin, a matricellular protein involved in tissue repair, is markedly overexpressed by cyst epithelial cells. Periostin promotes cell proliferation, cyst growth, interstitial fibrosis, and the decline in renal function in PKD mice. Here, we investigated the regulation of these processes by the integrin-linked kinase (ILK), a scaffold protein that links the extracellular matrix to the actin cytoskeleton and is stimulated by periostin...
May 18, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28514891/synergistic-effect-of-rapamycin-and-metformin-against-age-dependent-oxidative-stress-in-rat-erythrocyte
#3
Abhishek Kumar Singh, Geetika Garg, Sandeep Singh, Syed Ibrahim Rizvi
Erythrocytes are particularly vulnerable towards age-dependent oxidative stress mediated damage. Caloric restriction mimetics (CRMs) may provide a novel strategy for the maintenance of redox balance as well as effective treatment of age associated diseases. Herein, we have investigated the beneficial effect of co-treatment of CRM-candidate drugs, rapamycin (an immunosuppressant drug and inhibitor of mammalian target of rapamycin) and metformin (an anti-diabetic biguanide and activator of adenosine monophosphate kinase) against aging-induced oxidative stress in erythrocytes and plasma of aging rats...
May 17, 2017: Rejuvenation Research
https://www.readbyqxmd.com/read/28511572/mtor-drives-cerebral-blood-flow-and-memory-deficits-in-ldlr-mice-modeling-atherosclerosis-and-vascular-cognitive-impairment
#4
Jordan B Jahrling, Ai-Ling Lin, Nicholas DeRosa, Stacy A Hussong, Candice E Van Skike, Milena Girotti, Martin Javors, Qingwei Zhao, Leigh Ann Maslin, Reto Asmis, Veronica Galvan
We recently showed that mTOR attenuation blocks progression and abrogates established cognitive deficits in Alzheimer's disease (AD) mouse models. These outcomes were associated with the restoration of cerebral blood flow (CBF) and brain vascular density (BVD) resulting from relief of mTOR inhibition of NO release. Recent reports suggested a role of mTOR in atherosclerosis. Because mTOR drives aging and vascular dysfunction is a universal feature of aging, we hypothesized that mTOR may contribute to brain vascular and cognitive dysfunction associated with atherosclerosis...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28500276/while-reinforcing-cell-cycle-arrest-rapamycin-and-torins-suppress-senescence-in-uva-irradiated-fibroblasts
#5
Olga V Leontieva, Mikhail V Blagosklonny
Sunlight predisposes to skin cancer and melanomas. Ultraviolet A (UVA), a long wave component of sunlight, can reach dermal fibroblasts. Here we studied UVA-induced senescence in human fibroblasts in vitro. It is known that senescence occurs, when cell cycle is arrested, but mTOR is still active, thus converting arrest to senescence (geroconversion). We showed that, while arresting cell cycle, UVA did not inhibit mTOR, enabling geroconversion. In UVA-treated cells, mTOR remained fully active. Rapamycin and Torins 1/ 2 prevented UVA-induced senescent phenotype, although they further re-enforced cell cycle arrest...
May 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28499984/systemic-pten-akt1-mtor-pathway-activity-in-patients-with-normal-tension-glaucoma-and-ocular-hypertension-a-case-series
#6
Gerassimos Lascaratos, Kai-Yin Chau, Haogang Zhu, Despoina Gkotsi, Deborah Kamal, Ivan Gout, Philip J Luthert, Anthony H V Schapira, David F Garway-Heath
Glaucoma is the most common optic neuropathy in humans and the leading cause of irreversible blindness worldwide. Its prevalence and incidence increase exponentially with ageing and raised intraocular pressure (IOP), while increasing evidence suggests that systemic mitochondrial abnormalities may also be implicated in its pathogenesis. We have recently shown that patients who have not developed glaucoma despite being exposed for many years to high IOP (ocular hypertension - OHT) have more efficient mitochondria, measured in peripheral blood lymphocytes, when compared to age-similar controls and fast progressing normal tension glaucoma (NTG) patients...
May 9, 2017: Mitochondrion
https://www.readbyqxmd.com/read/28480182/experiences-of-renal-transplants-from-donors-with-renal-cell-carcinoma-after-ex-vivo-partial-nephrectomy
#7
Sung Yoon Lim, Myung Gyu Kim, Kwon Tae Park, Cheol Woong Jung
PURPOSE: Routine evaluation of kidney donors occasionally reveals an incidental renal mass with an otherwise satisfactory kidney function. The use of such a kidney with an enhancing mass for transplantation is a matter of debate owing to a possible risk of transmission of donor malignancies. We report our experience of kidney transplants from donors with renal cell carcinoma, after ex vivo resection of the renal mass. METHODS: Two women aged 44 and 56 years were diagnosed with enhancing renal masses measuring 0...
May 2017: Annals of Surgical Treatment and Research
https://www.readbyqxmd.com/read/28475412/pi3k-akt-mtor-axis-sustains-rotavirus-infection-via-the-4e-bp1-mediated-autophagy-pathway-and-represents-an-antiviral-target
#8
Yuebang Yin, Wen Dang, Xinying Zhou, Lei Xu, Wenshi Wang, Wanlu Cao, Sunrui Chen, Junhong Su, Xuepeng Cai, Shaobo Xiao, Maikel P Peppelenbosch, Qiuwei Pan
Rotavirus infection is a major cause of severe dehydrating diarrhea in infants younger than five years old and in particular cases of immunocompromised patients irrespective to the age of the patients. Although vaccines have been developed, antiviral therapy is an important complement that cannot be substituted. Because of the lack of specific approved treatment, it is urgent to facilitate the cascade of further understanding of the infection biology, identification of druggable targets and the final development of effective antiviral therapies...
May 5, 2017: Virulence
https://www.readbyqxmd.com/read/28474160/-hereditary-tumor-syndromes-in-neuropathology
#9
REVIEW
C Mawrin
Neoplasms in the central (CNS) and peripheral nervous system (PNS) in hereditary tumor syndromes play an important role in the neuropathological diagnostics. The benign and malignant PNS and CNS tumors that occur in the frequent neurofibromatosis type 1 (NF1) and type 2 (NF2) often represent essential factors for the course of the disease in those affected. Furthermore, certain clinical constellations (e.g. bilateral schwannomas of the auditory nerve, schwannomas at a young age and multiple meningiomas) can be important indications for a previously undiagnosed hereditary tumor disease...
May 4, 2017: Der Pathologe
https://www.readbyqxmd.com/read/28468668/proteomic-anaysis-of-aged-microglia-shifts-in-transcription-bioenergetics-and-nutrient-response
#10
Antwoine Flowers, Harris Bell-Temin, Ahmad Jalloh, Stanley M Stevens, Paula C Bickford
BACKGROUND: Age is the primary risk factor for many diseases. As such, age is a critical co-factor for examination in order to understand the progression and potential intervention in disease progression. Studies examining both the phenotype and transcriptome of aged microglia demonstrated a propensity for the development of a pro-inflammatory phenotype. Less well studied is the concomitant blunting of anti-inflammatory aspects of microglial function with age which also impact plasticity and repair in the CNS...
May 3, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28457396/nephrotic-range-proteinuria-in-renal-transplantation-clinical-and-histologic-correlates-in-a-10-year-retrospective-study
#11
R Leal, H Pinto, A Galvão, L Santos, C Romãozinho, F Macário, R Alves, J Pratas, V Sousa, C Marinho, L Prado E Castro, M Campos, A Mota, A Figueiredo
INTRODUCTION: There is a high incidence of nephrotic proteinuria in renal transplant recipients, which is an accurate predictor of graft loss. Despite this, its histologic correlates and prognostic implications are still not well characterized. We assessed the clinical and histological correlates of kidney transplantation patients with nephrotic range proteinuria. METHODS: We have retrospectively analyzed clinical and histological data from 50 kidney transplantation biopsy specimens from 44 renal transplant recipients with nephrotic range proteinuria between 2006 and 2015...
May 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28457365/understanding-bone-damage-after-kidney-transplantation-a%C3%A2-retrospective-monocentric-cross-sectional-analysis
#12
M Gregorini, G Sileno, E F Pattonieri, V Corradetti, M Abelli, E Ticozzelli, L Scudeller, M A Grignano, P Esposito, L Bogliolo, A Giacomoni, T Rampino
BACKGROUND: Kidney transplantation (KT) immunosuppression may induce bone tissue damage with bone mineral density (BMD) loss increasing bone fractures risk. Steroid therapy is considered the major player, but others factors are still under review. PATIENTS AND METHODS: We designed an observational retrospective cohort study to evaluate bone damage after KT. The prevalence of osteopenia, osteoporosis, bone fractures, and the associated risk factors were investigated...
May 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28447781/artemisinin-protectes-retinal-neuronal-cells-against-oxidative-stress-and-restores-rat-retinal-physiological-function-from-light-exposed-damage
#13
Fengxia Yan, Hai-Tao Wang, Yang Gao, Jiang-Ping Xu, Wenhua Zheng
Oxidative stress plays a key role in the pathogenesis of age-related macular degeneration (AMD), a leading cause of severe visual loss and blindness in the aging population which lacks any effective treatments currently. In this study, artemisinin, a well-known anti-malarial drug was found to suppress hydrogen peroxide (H2O2)-induced cell death in retinal neuronal RGC-5 cells. Artemisinin, in the therapeutically relevant dosage, concentration-dependently attenuated the accumulation of intracellular reactive oxygen species (ROS), increased mitochondrial mitochondrial membrane potential and decreased cell apoptosis in RGC-5 cells induced by H2O2...
April 27, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28439198/assessment-of-tumors-in-children-with-tuberous-sclerosis-a-single-centre-s-experience
#14
Suna Emir, Şadan Hacısalihoğlu, Derya Özyörük, Filiz Ekici, Aydan Değerliyurt, Alev Güven, İlker Çetin
AIM: As a result of mutations in TSC1 (9q34) and TSC2 (16p13.3) tumor supressor genes, the mammalian target of the rapamycin (mTor) signaling pathway is overactivated in patients with tuberous sclerosis. Abnormal cell proliferation and differentiation is responsible for the growth several different tumors. The aim of this study was to review tumors in our patients with tuberous sclerosis. MATERIAL AND METHODS: Thirty-six patients with tuberous sclerosis were reviewed retrospectively in terms of age, sex, family history, clinical findings, presence of tumors, and treatments...
March 2017: Türk Pediatri Arşivi
https://www.readbyqxmd.com/read/28416958/keratinization-of-lung-squamous-cell-carcinoma-is-associated-with-poor-clinical-outcome
#15
Hye Jung Park, Yoon-Jin Cha, Seong Han Kim, Arum Kim, Eun Young Kim, Yoon Soo Chang
BACKGROUND: Although the World Health Organization (WHO) classification of lung squamous cell carcinoma (SCC) was revised in 2015, its clinical implications for lung SCC subsets remain unclear. We investigated whether the morphologic characteristics of lung SCC, including keratinization, were associated with clinical parameters and clinical outcome of patients. METHODS: A total of 81 patients who underwent curative surgical resection of diagnosed lung SCC, were enrolled in this study...
April 2017: Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/28413127/evolution-of-circulating-tumor-dna-profile-from-first-line-to-subsequent-therapy-in-metastatic-renal-cell-carcinoma
#16
Sumanta K Pal, Guru Sonpavde, Neeraj Agarwal, Nicholas J Vogelzang, Sandy Srinivas, Naomi B Haas, Sabina Signoretti, Bradley A McGregor, Jeremy Jones, Richard B Lanman, Kimberly C Banks, Toni K Choueiri
BACKGROUND: Treatment of metastatic renal cell carcinoma (mRCC) typically entails mechanistically distinct agents across the first- and second-line setting. Activity of these agents may be predicated on selective pressure that modulates RCC biology. Circulating tumor DNA (ctDNA) is a platform to noninvasively ascertain temporal changes in genomic profile. OBJECTIVE: To assess the ctDNA profile in a large cohort of mRCC patients, and to assess changes across patients receiving first-line and later lines of therapy...
April 13, 2017: European Urology
https://www.readbyqxmd.com/read/28410911/comprehensive-analysis-of-survival-outcomes-in-non-clear-cell-renal-cell-carcinoma-patients-treated-in-clinical-trials
#17
Guillermo de Velasco, Rana R McKay, Xun Lin, Raphel B Moreira, Ronit Simantov, Toni K Choueiri
BACKGROUND: Clinical data from patients with non-clear cell renal cell carcinoma (nccRCC) receiving targeted therapy are limited, and many clinical trials have excluded these patients from study entry. We sought to investigate the outcomes of patients with nccRCC treated in clinical trials in the modern era compared with the outcomes of patients with clear cell RCC (ccRCC). PATIENTS AND METHODS: We conducted a retrospective study of patients with metastatic RCC who had received targeted therapy in Pfizer-sponsored phase II and III clinical trials from 2003 to 2013...
March 21, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28410084/clinical-and-electroencephalographic-characteristics-of-infantile-onset-epilepsies-caused-by-genetic-mutations
#18
Yun Jung Hur, Sookyong Koh, John Millichap, Srishti Nangia, Lawrence J Jennings, Douglas R Nordli
OBJECTIVES: To determine whether certain characteristic electroencephalography (EEG) features are indicative of a genetic cause in early-life epilepsy. STUDY DESIGN: We enrolled a total of 100 patients with infantile-onset (<3 years) epilepsy due to known genetic cause (n = 50) and nongenetic cause (acquired, structural, or unknown, n = 50). The genetic group was classified into synaptopathies, channelopathies, mTOR (mammalian target of rapamycin)-opathies, and chromosomal abnormalities...
May 2017: Journal of Pediatrics
https://www.readbyqxmd.com/read/28400571/moderate-lifelong-overexpression-of-tuberous-sclerosis-complex-1-tsc1-improves-health-and-survival-in-mice
#19
Hong-Mei Zhang, Vivian Diaz, Michael E Walsh, Yiqiang Zhang
The tuberous sclerosis complex 1/2 (TSC1/2) is an endogenous regulator of the mechanistic target of rapamycin (mTOR). While mTOR has been shown to play an important role in health and aging, the role of TSC1/2 in aging has not been fully investigated. In the current study, a constitutive TSC1 transgenic (Tsc1 (tg) ) mouse model was generated and characterized. mTORC1 signaling was reduced in majority of the tissues, except the brain. In contrast, mTORC2 signaling was enhanced in Tsc1 (tg) mice. Tsc1 (tg) mice are more tolerant to exhaustive exercises and less susceptible to isoproterenol-induced cardiac hypertrophy at both young and advanced ages...
April 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28394250/ampk-and-vacuole-associated-atg14p-orchestrate-%C3%AE-lipophagy-for-energy-production-and-long-term-survival-under-glucose-starvation
#20
Arnold Y Seo, Pick-Wei Lau, Daniel Feliciano, Prabuddha Sengupta, Mark A Le Gros, Bertrand Cinquin, Carolyn A Larabell, Jennifer Lippincott-Schwartz
Dietary restriction increases the longevity of many organisms, but the cell signaling and organellar mechanisms underlying this capability are unclear. We demonstrate that to permit long-term survival in response to sudden glucose depletion, yeast cells activate lipid-droplet (LD) consumption through micro-lipophagy (µ-lipophagy), in which fat is metabolized as an alternative energy source. AMP-activated protein kinase (AMPK) activation triggered this pathway, which required Atg14p. More gradual glucose starvation, amino acid deprivation or rapamycin did not trigger µ-lipophagy and failed to provide the needed substitute energy source for long-term survival...
April 10, 2017: ELife
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