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https://www.readbyqxmd.com/read/28105938/the-influence-of-pro-longevity-gene-gclc-overexpression-on-the-age-dependent-changes-in-drosophila-transcriptome-and-biological-functions
#1
Alexey Moskalev, Mikhail Shaposhnikov, Ekaterina Proshkina, Alexey Belyi, Alexander Fedintsev, Svetlana Zhikrivetskaya, Zulfiya Guvatova, Asiya Sadritdinova, Anastasia Snezhkina, George Krasnov, Anna Kudryavtseva
BACKGROUND: Transcriptional changes that contribute to the organism's longevity and prevent the age-dependent decline of biological functions are not well understood. Here, we overexpressed pro-longevity gene encoding glutamate-cysteine ligase catalytic subunit (Gclc) and analyzed age-dependent changes in transcriptome that associated with the longevity, stress resistance, locomotor activity, circadian rhythmicity, and fertility. RESULTS: Here we reproduced the life extension effect of neuronal overexpression of the Gclc gene and investigated its influence on the age-depended dynamics of transcriptome and biological functions such as fecundity, spontaneous locomotor activity and circadian rhythmicity, as well as on the resistance to oxidative, proteotoxic and osmotic stresses...
December 28, 2016: BMC Genomics
https://www.readbyqxmd.com/read/28105749/octopamine-enhances-oxidative-stress-resistance-through-the-fasting-responsive-transcription-factor-daf-16-foxo-in%C3%A2-c-%C3%A2-elegans
#2
Haruka Hoshikawa, Masaharu Uno, Sakiko Honjoh, Eisuke Nishida
Dietary restriction regimens lead to enhanced stress resistance and extended life span in many species through the regulation of fasting and/or diet-responsive mechanisms. The fasting stimulus is perceived by sensory neurons and causes behavioral and metabolic adaptations. Octopamine (OA), one of the Caenorhabditis elegans neurotransmitters, is involved in behavioral adaptations, and its levels are increased under fasting conditions. However, it remains largely unknown how OA contributes to the fasting responses...
January 20, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28102444/patients-with-bicuspid-and-tricuspid-aortic-valve-exhibit-distinct-regional-microrna-signatures-in-mildly-dilated-ascending-aorta
#3
Sebastian Albinsson, Alessandro Della Corte, Azra Alajbegovic, Katarzyna K Krawczyk, Ciro Bancone, Umberto Galderisi, Marilena Cipollaro, Marisa De Feo, Amalia Forte
MicroRNAs are able to modulate gene expression in a range of diseases. We focused on microRNAs as potential contributors to the pathogenesis of ascending aorta (AA) dilatation in patients with stenotic tricuspid (TAV) or bicuspid aortic valve (BAV). Aortic specimens were collected from the 'concavity' and the 'convexity' of mildly dilated AAs and of normal AAs from heart transplant donors. Aortic RNA was analyzed through PCR arrays, profiling the expression of 84 microRNAs involved in cardiovascular disease...
January 19, 2017: Heart and Vessels
https://www.readbyqxmd.com/read/28100702/zanthoxylum-alkylamides-ameliorate-protein-metabolism-disorder-in-stz-induced-diabetic-rats
#4
Tingyuan Ren, Zhu Yu Ping, Xuejuan Xia, Ding Bo Yong, Guo Jing, Kan Jian Quan
This study aimed to evaluate the protein metabolism effect of Zanthoxylum alkylamides and to explore the potential mechanism in streptozotocin (STZ)-induced diabetic rats. Diabetic rats were orally treated with 2, 4 and 8 mg per kg bw of alkylamides daily for 28 days. Alkylamides decreased the relative weight of the liver and food intake, significantly increased the relative skeletal muscle weight and significantly decreased the blood urea nitrogen levels. Insulin, insulin-like growth factor I, total protein (TP) and albumin (ALB), globular proteins and ALB proteins/globulin protein levels in serum significantly increased...
January 18, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28090761/modest-overexpression-of-foxo-maintains-cardiac-proteostasis-and-ameliorates-age-associated-functional-decline
#5
Anna C Blice-Baum, Alexander C Zambon, Gaurav Kaushik, Meera C Viswanathan, Adam J Engler, Rolf Bodmer, Anthony Cammarato
Heart performance declines with age. Impaired protein quality control (PQC), due to reduced ubiquitin-proteasome system (UPS) activity, autophagic function, and/or chaperone-mediated protein refolding, contributes to cardiac deterioration. The transcription factor FOXO participates in regulating genes involved in PQC, senescence, and numerous other processes. Here, a comprehensive approach, involving molecular genetics, novel assays to probe insect cardiac physiology, and bioinformatics, was utilized to investigate the influence of heart-restricted manipulation of dFOXO expression in the rapidly aging Drosophila melanogaster model...
February 2017: Aging Cell
https://www.readbyqxmd.com/read/28087474/foxo1-downregulation-is-associated-with-worse-outcome-in-bladder-cancer-and-adds-significant-prognostic-information-to-p53-overexpression
#6
Josep Lloreta, Alba Font-Tello, Núria Juanpere, Albert Frances, Marta Lorenzo, Lara Nonell, Silvia de Muga, Ivonne Vázquez, Lluís Cecchini, Silvia Hernández-Llodrà
Nuclear FOXOs mediate cell cycle arrest and promote apoptosis. FOXOs and p53 could have similar effects as tumor suppressor genes. In spite of extensive literature, little is known about the role of FOXO1 and its relationship with p53 status in bladder cancer. Expression of FOXO1 and p53 were analyzed by immunohistochemistry in 162 urothelial carcinomas (UC). Decreased FOXO1 expression, p53 overexpression and the combination FOXO1 downregulation/p53 overexpression were strongly associated with high grade (P=...
January 10, 2017: Human Pathology
https://www.readbyqxmd.com/read/28076775/nutritional-programming-of-lifespan-by-foxo-inhibition-on-sugar-rich-diets
#7
Adam J Dobson, Marina Ezcurra, Charlotte E Flanagan, Adam C Summerfield, Matthew D W Piper, David Gems, Nazif Alic
Consumption of unhealthy diets is exacerbating the burden of age-related ill health in aging populations. Such diets can program mammalian physiology to cause long-term, detrimental effects. Here, we show that, in Drosophila melanogaster, an unhealthy, high-sugar diet in early adulthood programs lifespan to curtail later-life survival despite subsequent dietary improvement. Excess dietary sugar promotes insulin-like signaling, inhibits dFOXO-the Drosophila homolog of forkhead box O (FOXO) transcription factors-and represses expression of dFOXO target genes encoding epigenetic regulators...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28076456/propofol-inhibits-lung-cancer-cell-viability-and-induces-cell-apoptosis-by-upregulating-microrna-486-expression
#8
N Yang, Y Liang, P Yang, T Yang, L Jiang
Propofol is a frequently used intravenous anesthetic agent. Recent studies show that propofol exerts a number of non-anesthetic effects. The present study aimed to investigate the effects of propofol on lung cancer cell lines H1299 and H1792 and functional role of microRNA (miR)-486 in these effects. H1299 and/or H1792 cells were treated with or without propofol and transfected or not with miR-486 inhibitor, and then cell viability and apoptosis were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry...
January 5, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28067237/environmental-stresses-induce-transgenerationally-inheritable-survival-advantages-via-germline-to-soma-communication-in-caenorhabditis-elegans
#9
Saya Kishimoto, Masaharu Uno, Emiko Okabe, Masanori Nono, Eisuke Nishida
Hormesis is a biological phenomenon, whereby exposure to low levels of toxic agents or conditions increases organismal viability. It thus represents a beneficial aspect of adaptive responses to harmful environmental stimuli. Here we show that hormesis effects induced in the parental generation can be passed on to the descendants in Caenorhabditis elegans. Animals subjected to various stressors during developmental stages exhibit increased resistance to oxidative stress and proteotoxicity. The increased resistance is transmitted to the subsequent generations grown under unstressed conditions through epigenetic alterations...
January 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28064564/aspartate-inhibits-lps-induced-mafbx-and-murf1-expression-in-skeletal-muscle-in-weaned-pigs-by-regulating-akt-ampk%C3%AE-and-foxo1
#10
Yulan Liu, Xiuying Wang, Weibo Leng, Dingan Pi, Zhixiao Tu, Huiling Zhu, Haifeng Shi, Shuang Li, Yongqing Hou, Chien-An Andy Hu
Infection and inflammation can result in the rapid loss of muscle mass and myofibrillar proteins (muscle atrophy). In addition, aspartate (Asp) is necessary for protein synthesis in mammalian cells. We hypothesized that Asp could attenuate LPS-induced muscle atrophy in a piglet model. Twenty-four weaning piglets were allotted to four treatments, including non-challenged control, LPS challenged control, LPS+0.5% Asp and LPS+1.0% Asp. On d 21, the piglets were injected with i.p. injection of LPS (100 ug/kg BM) or saline...
January 2017: Innate Immunity
https://www.readbyqxmd.com/read/28046124/changes-of-ovarian-microrna-profile-in-long-living-ames-dwarf-mice-during-aging
#11
Augusto Schneider, Scot J Matkovich, Berta Victoria, Lina Spinel, Andrzej Bartke, Pawel Golusinski, Michal M Masternak
The Ames dwarf (df/df) mice have extended longevity and can preserve the ovarian reserve longer than Normal (N) mice. Based on this, the aim of our study was to evaluate the ovarian microRNA (miRNA) profile in young and aged df/df and N mice. Ovarian tissue was collected at 5-6 months and at 21-22 months of age for miRNA sequencing. We detected a total of 404 miRNAs in the ovarian samples, from which the abundance of 22 and 33 miRNAs changed with age in N and df/df mice, respectively. Of these, only three miRNAs were commonly regulated with age between N and df/df mice, indicating a very divergent miRNA profile between genotypes...
2017: PloS One
https://www.readbyqxmd.com/read/28041781/the-fountain-of-youth-by-targeting-senescent-cells
#12
REVIEW
Peter L J de Keizer
The potential to reverse aging has long been a tantalizing thought, but has equally been considered mere utopia. Recently, the spotlights have turned to senescent cells as being a culprit for aging. Can these cells be therapeutically eliminated? When so? And is this even safe? Recent developments in the tool box to study senescence have made it possible to begin addressing these questions. It will be especially relevant to identify how senescence impairs tissue rejuvenation and to prospectively design compounds that can both target senescence and stimulate rejuvenation in a safe manner...
December 20, 2016: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28041565/the-fountain-of-youth-by-targeting-senescent-cells
#13
REVIEW
Peter L J de Keizer
The potential to reverse aging has long been a tantalizing thought, but has equally been considered mere utopia. Recently, the spotlights have turned to senescent cells as being a culprit for aging. Can these cells be therapeutically eliminated? When so? And is this even safe? Recent developments in the tool box to study senescence have made it possible to begin addressing these questions. It will be especially relevant to identify how senescence impairs tissue rejuvenation and to prospectively design compounds that can both target senescence and stimulate rejuvenation in a safe manner...
January 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28026080/transcriptomic-gene-profiling-of-porcine-muscle-tissue-depending-on-histological-properties
#14
Katarzyna Ropka-Molik, Anna Bereta, Kacper Żukowski, Katarzyna Piórkowska, Artur Gurgul, Grzegorz Żak
In pig, the histological profile of muscle tissue, especially the proportion of individual fiber types, is one of the main factors affecting meat quality properties. In the present research, RNA sequencing (RNA-seq) by using next generation sequencing method was applied to estimate the whole gene expression profile of Longissimus lumborum muscle of pigs (Large White breed) differing in the percentage of two fiber types (slow-twitch (type I) fibers and fast-twitch glycolytic (type IIB) fibers). The RNA-seq approach allowed us to identify 355 differentially expressed genes (DEGs) indicated as significant (false discovery rate-adjusted P < 0...
December 27, 2016: Animal Science Journal, Nihon Chikusan Gakkaihō
https://www.readbyqxmd.com/read/27998725/cgmp-signaling-increases-antioxidant-gene-expression-by-activating-forkhead-box-o-3a-in-the-colon-epithelium
#15
Rui Wang, Bianca Islam, Allison Bridges, Sarah Sharman, Muhan Hu, Yali Hou, Payaningal R Somanath, Laine Venable, Nagendra Singh, Sangmi Kim, Subbaramiah Sridhar, Franz Hofmann, Darren D Browning
Signaling through cGMP has therapeutic potential in the colon, where it has been implicated in the suppression of colitis and colon cancer. In this study, we tested the ability of cGMP and type 2 cGMP-dependent protein kinase (PKG2) to activate forkhead box O (FoxO) in colon cancer cells and in the colon epithelium of mice. We show that activation of PKG2 in colon cancer cells inhibited cell proliferation, inhibited AKT, and activated FoxO. Treatment of colon explants with 8Br-cGMP also activated FoxO target gene expression at both RNA and protein levels, and reduced epithelial reduction-oxidation (redox) stress...
December 17, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27980063/brd4-promotes-p63-and-grhl3-expression-downstream-of-foxo-in-mammary-epithelial-cells
#16
Sankari Nagarajan, Upasana Bedi, Anusha Budida, Feda H Hamdan, Vivek Kumar Mishra, Zeynab Najafova, Wanhua Xie, Malik Alawi, Daniela Indenbirken, Stefan Knapp, Cheng-Ming Chiang, Adam Grundhoff, Vijayalakshmi Kari, Christina H Scheel, Florian Wegwitz, Steven A Johnsen
Bromodomain-containing protein 4 (BRD4) is a member of the bromo- and extraterminal (BET) domain-containing family of epigenetic readers which is under intensive investigation as a target for anti-tumor therapy. BRD4 plays a central role in promoting the expression of select subsets of genes including many driven by oncogenic transcription factors and signaling pathways. However, the role of BRD4 and the effects of BET inhibitors in non-transformed cells remain mostly unclear. We demonstrate that BRD4 is required for the maintenance of a basal epithelial phenotype by regulating the expression of epithelial-specific genes including TP63 and Grainy Head-like transcription factor-3 (GRHL3) in non-transformed basal-like mammary epithelial cells...
December 15, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27978807/oxidative-stress-foxo-transcription-factors-in-cardiovascular-aging
#17
Juewon Kim, Si Young Cho, Donghyun Cho, Su Hwan Kim, Dae Bang Seo, Song Seok Shin
BACKGROUND: Aging is a phenomenon in which the functions, adaptability and resistance of an organism decrease over time. With the global population aging at an accelerating pace, delaying the negative aspects of aging is vital for advancing the human life span and quality of life. The aging of multiple organs can lead to many diseases, and the cardiovascular system is no exception. Indeed, one of the primary risk factors for cardiovascular diseases is aging because of altered cardiovascular metabolism resulting in metabolic disorders and inflammation...
December 12, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27966458/gabarapl1-suppresses-metastasis-by-counteracting-pi3k-akt-pathway-in-prostate-cancer
#18
Wei Su, Shibao Li, Xiaofan Chen, Lingyu Yin, Ping Ma, Yingyu Ma, Bing Su
Metastasis remains the primary cause of prostate cancer (CaP)-related death. Using a genome wide shRNA screen, we identified GABARAPL1 as a potential CaP metastasis suppressor. GABARAPL1 mRNA levels inversely correlate with the invasive potential of a panel of human CaP cell lines. Lower mRNA levels correlate with higher Gleason scores in clinical CaP tumor samples. Moreover, Kaplan-Meier curves analysis showed that GABARAPL1 down-regulation in cancer tissues is associated with decreased disease-free survival in CaP patients...
December 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27936162/discovery-of-a-novel-isothiazolonaphthoquinone-based-small-molecule-activator-of-foxo-nuclear-cytoplasmic-shuttling
#19
Bastien Cautain, Francisco Castillo, Loana Musso, Bibiana I Ferreira, Nuria de Pedro, Lorena Rodriguez Quesada, Susana Machado, Francisca Vicente, Sabrina Dallavalle, Wolfgang Link
FOXO factors are tumour suppressor proteins commonly inactivated in human tumours by posttranslational modifications. Furthermore, genetic variation within the FOXO3a gene is consistently associated with human longevity. Therefore, the pharmacological activation of FOXO proteins is considered as an attractive therapeutic approach to treat cancer and age-related diseases. In order to identify agents capable of activating FOXOs, we tested a collection of small chemical compounds using image-based high content screening technology...
2016: PloS One
https://www.readbyqxmd.com/read/27936150/oxidative-stress-induces-mouse-follicular-granulosa-cells-apoptosis-via-jnk-foxo1-pathway
#20
Qiannan Weng, Zequn Liu, Bojiang Li, Kaiqing Liu, Wangjun Wu, Honglin Liu
The c-Jun N-terminal protein kinase (JNK) plays an important role in the regulation of cell apoptosis. Forkhead box O (FoxO) transcription factors are involved in diverse biological processes, including cellular metabolism, cell apoptosis, and cell cycle. However, the JNK/FoxO1 pathway involved in the process of apoptosis induced by oxidative stress remains to be elucidated. Here, we demonstrated that the JNK activity significantly increased in response to oxidative stress in mouse follicular granulosa cells (MGCs)...
2016: PloS One
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