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https://www.readbyqxmd.com/read/27913811/discovery-of-piperlongumine-as-a-potential-novel-lead-for-the-development-of-senolytic-agents
#1
Yingying Wang, Jianhui Chang, Xingui Liu, Xuan Zhang, Suping Zhang, Xin Zhang, Daohong Zhou, Guangrong Zheng
Accumulating evidence indicates that senescent cells play an important role in many age-associated diseases. The pharmacological depletion of senescent cells (SCs) with a "senolytic agent", a small molecule that selectively kills SCs, is a potential novel therapeutic approach for these diseases. Recently, we discovered ABT-263, a potent and highly selective senolytic agent, by screening a library of rationally-selected compounds. With this screening approach, we also identified a second senolytic agent called piperlongumine (PL)...
November 19, 2016: Aging
https://www.readbyqxmd.com/read/27913779/comparison-of-proliferative-and-immunomodulatory-potential-of-adipose-derived-mesenchymal-stem-cells-from-young-and-geriatric-cats
#2
Lara B Zajic, Tracy L Webb, Polly Webb, Jonathan W Coy, Steve W Dow, Jessica M Quimby
OBJECTIVES: The objective of this study was to compare the ability of adipose-derived mesenchymal stem cells (aMSC) generated from young vs geriatric cats to proliferate in culture, suppress lymphocyte proliferation and undergo senescence. METHODS: Adipose tissues from five young (<5 years) and six geriatric (>10 years) cats were harvested and cryopreserved for subsequent aMSC isolation and culture. aMSC proliferation in culture was compared via determination of time until passage two and by 3-(4,5-demethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay...
December 2, 2016: Journal of Feline Medicine and Surgery
https://www.readbyqxmd.com/read/27913300/suppression-of-nadph-oxidase-attenuates-hypoxia-induced-dysfunctions-of-endothelial-progenitor-cells
#3
Bin Liu, Kai-Di Ren, Jing-Jie Peng, Tao Li, Xiu-Ju Luo, Chengming Fan, Jin-Fu Yang, Jun Peng
NADPH oxidases (NOX) - derived reactive oxygen species (ROS) contribute to oxidative injury in hypoxia-induced pulmonary arterial hypertension. This study aims to evaluate the status of NOX in endothelial progenitor cells (EPCs) under hypoxic condition and to determine whether NOX inhibitors could attenuate hypoxia-induced dysfunctions of EPCs. EPCs were isolated from peripheral blood of SD rats and subjected to hypoxia (O2/N2/CO2, 1/94/5) for 24 h. The cells were collected for β-galactosidase or Hoechst staining, or for functional analysis (migration, adhesion and tube formation)...
November 29, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27913155/early-molecular-stratification-of-high-risk-primary-biliary-cholangitis
#4
Claire Hardie, Kile Green, Laura Jopson, Ben Millar, Barbara Innes, Sarah Pagan, Dina Tiniakos, Jessica Dyson, Muzlifah Haniffa, Venetia Bigley, David E Jones, John Brain, Lucy J Walker
High-risk primary biliary cholangitis (PBC), defined by inadequate response at one year to Ursodeoxycholic acid (UDCA), is associated with disease progression and liver transplantation. Stratifying high-risk patients early would facilitate improved approaches to care. Using long-term follow-up data to define risk at presentation, 6 high-risk PBC patients and 8 low-risk patients were identified from biopsy, transplant and biochemical archival records. Formalin-fixed paraffin-embedded (FFPE) liver biopsies taken at presentation were graded (Scheuer and Nakanuma scoring) and gene expression analysed using the NanoString® nCounter PanCancer Immunity 770-gene panel...
November 21, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27912109/characterization-and-fine-mapping-of-a-novel-premature-leaf-senescence-mutant-yellow-leaf-and-dwarf-1-in-rice
#5
Luchang Deng, Peng Qin, Zhi Liu, Geling Wang, Weilan Chen, Jianhua Tong, Langtao Xiao, Bin Tu, Yuantao Sun, Wei Yan, Hang He, Jun Tan, Xuewei Chen, Yuping Wang, Shigui Li, Bingtian Ma
Leaves are the main organs in which photosynthates are produced. Leaf senescence facilitates the translocation of photosynthates and nutrients from source to sink, which is important for plant development and especially for crop yield. However, the molecular mechanism of leaf senescence is unknown. Here, we identified a mutant, yellow leaf and dwarf 1 (yld1), which exhibited decreased plant height and premature leaf senescence. Nitroblue tetrazolium and diamiobenzidine staining analyses revealed that the concentrations of reactive oxygen species were higher in yld1 leaves than in wild type leaves...
November 22, 2016: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/27911443/transient-mitochondrial-dna-double-strand-breaks-in-mice-cause-accelerated-aging-phenotypes-in-a-ros-dependent-but-p53-p21-independent-manner
#6
Milena Pinto, Alicia M Pickrell, Xiao Wang, Sandra R Bacman, Aixin Yu, Aline Hida, Lloye M Dillon, Paul D Morton, Thomas R Malek, Siôn L Williams, Carlos T Moraes
We observed that the transient induction of mtDNA double strand breaks (DSBs) in cultured cells led to activation of cell cycle arrest proteins (p21/p53 pathway) and decreased cell growth, mediated through reactive oxygen species (ROS). To investigate this process in vivo we developed a mouse model where we could transiently induce mtDNA DSBs ubiquitously. This transient mtDNA damage in mice caused an accelerated aging phenotype, preferentially affecting proliferating tissues. One of the earliest phenotypes was accelerated thymus shrinkage by apoptosis and differentiation into adipose tissue, mimicking age-related thymic involution...
December 2, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27911402/utilizing-the-ethylene-releasing-compound-2-chloroethylphosphonic-acid-as-a-tool-to-study-ethylene-response-in-bacteria
#7
Richard V Augimeri, Andrew J Varley, Janice L Strap
Ethylene (C2H4) is a gaseous phytohormone that is involved in numerous aspects of plant development, playing a dominant role in senescence and fruit ripening. Exogenous ethylene applied during early plant development triggers the triple response phenotype; a shorter and thicker hypocotyl with an exaggerated apical hook. Despite the intimate relationship between plants and bacteria, the effect of exogenous ethylene on bacteria has been greatly overlooked. This is partly due to the difficulty of controlling gaseous ethylene within the laboratory without specialized equipment...
November 10, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27908889/microrna-146a-induces-lineage-negative-bone-marrow-cell-apoptosis-and-senescence-by-targeting-polo-like-kinase-2-expression
#8
Shanming Deng, Huilan Wang, Chunling Jia, Shoukang Zhu, Xianming Chu, Qi Ma, Jianqin Wei, Emily Chen, Wei Zhu, Conrad J Macon, Dushyantha T Jayaweera, Derek M Dykxhoorn, Chunming Dong
OBJECTIVE: Lineage-negative bone marrow cells (lin- BMCs) are enriched in endothelial progenitor cells and mediate vascular repair. Aging-associated senescence and apoptosis result in reduced number and functionality of lin- BMCs, impairing their prorepair capacity. The molecular mechanisms underlying lin- BMC senescence and apoptosis are poorly understood. MicroRNAs (miRNAs) regulate many important biological processes. The identification of miRNA-mRNA networks that modulate the health and functionality of lin- BMCs is a critical step in understanding the process of vascular repair...
December 1, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27908660/targeting-of-multiple-senescence-promoting-genes-and-signaling-pathways-by-triptonide-induces-complete-senescence-of-acute-myeloid-leukemia-cells
#9
Yanyan Pan, Mei Meng, Nana Zheng, Zhifei Cao, Ping Yang, Xiaodong Xi, Quansheng Zhou
Leukemia cells aberrantly overexpress senescence-suppression telomerase reverse transcriptase (TERT) and down-regulate key senescence-promoting genes to escape complete senescence, resulting in immortalization and malignant progression. Accordingly, induction of complete senescence is a sensible strategy for anti-leukemia therapy. However, effective senescence-based anti-leukemia drugs with low toxicity are currently lacking. In this study, we found that triptonide (chemical name diterpene triepoxide), a small molecule derived from the herb Tripterygium wilfordii Hook, strongly induced complete senescence in cultured acute myeloid leukemia (AML) cell lines, and potently inhibited growth and colony formation of U937 and HL-60 AML cell line with IC50 values of 7...
November 28, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27907906/senescent-fibroblast-derived-chemerin-promotes-squamous-cell-carcinoma-migration
#10
Vida Farsam, Abhijit Basu, Martina Gatzka, Nicolai Treiber, Lars A Schneider, Medhanie A Mulaw, Tanja Lucas, Stefan Kochanek, Reinhard Dummer, Mitchell P Levesque, Meinhard Wlaschek, Karin Scharffetter-Kochanek
Aging is associated with a rising incidence of cutaneous squamous cell carcinoma (cSCC), an aggressive skin cancer with the potential for local invasion and metastasis. Acquisition of a senescence-associated secretory phenotype (SASP) in dermal fibroblasts has been postulated to promote skin cancer progression in elderly individuals. The underlying molecular mechanisms are largely unexplored. We show that Chemerin, a previously unreported SASP factor released from senescent human dermal fibroblasts, promotes cSCC cell migration, a key feature driving tumor progression...
November 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27907136/immune-activation-and-bacterial-translocation-a-link-between-impaired-immune-recovery-and-frequent-visceral-leishmaniasis-relapses-in-hiv-infected-patients
#11
Maria Luciana Silva-Freitas, Glaucia Fernandes Cota, Talia S Machado-de-Assis, Carmem Giacoia-Gripp, Ana Rabello, Alda M Da-Cruz, Joanna R Santos-Oliveira
The maintenance of chronic immune activation due to leishmaniasis or even due to microbial translocation is associated with immunosenescence and may contribute to frequent relapses. Our aim was to investigate whether patients with HIV-associated visceral leishmaniasis (VL/HIV) who experience a single episode of VL have different immunological behaviors in comparison to those who experience frequent relapses. VL/HIV patients were allocated to non-relapsing (NR, n = 6) and relapsing (R, n = 11) groups and were followed from the active phase of VL up to 12 months post-treatment (mpt)...
2016: PloS One
https://www.readbyqxmd.com/read/27905874/are-sexually-selected-traits-affected-by-a-poor-environment-early-in-life
#12
Regina Vega-Trejo, Michael D Jennions, Megan L Head
BACKGROUND: Challenging conditions experienced early in life, such as a restricted diet, can detrimentally affect key life-history traits. Individuals can reduce these costs by delaying their sexual maturation, albeit at the price of the later onset of breeding, to eventually reach the same adult size as individuals that grow up in a benevolent environment. Delayed maturation can, however, still lead to other detrimental morphological and physiological changes that become apparent later in adulthood (e...
December 1, 2016: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/27905509/the-er-stress-regulator-bip-mediates-cadmium-induced-autophagy-and-neuronal-senescence
#13
Tao Wang, Yan Yuan, Hui Zou, Jinlong Yang, Shiwen Zhao, Yonggang Ma, Yi Wang, Jianchun Bian, Xuezhong Liu, Jianhong Gu, Zongping Liu, Jiaqiao Zhu
Autophagy is protective in cadmium (Cd)-induced oxidative damage. Endoplasmic reticulum (ER) stress has been shown to induce autophagy in a process requiring the unfolded protein response signalling pathways. Cd treatment significantly increased senescence in neuronal cells, which was aggravated by 3-MA or silencing of Atg5 and abolished by rapamycin. Cd increased expression of ER stress regulators Bip, chop, eIf2α, and ATF4, and activated autophagy as evidenced by upregulated LC3. Moreover, the ER stress inhibitor mithramycin inhibited the expression of ER stress protein chaperone Bip and blocked autophagic flux...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27904274/pretreatment-of-ferulic-acid-protects-human-dermal-fibroblasts-against-ultraviolet-a-irradiation
#14
Hyung Jin Hahn, Ki Bbeum Kim, Seunghee Bae, Byung Gon Choi, Sungkwan An, Kyu Joong Ahn, Su Young Kim
BACKGROUND: Approximately 90%~99% of ultraviolet A (UVA) ray reaches the Earth's surface. The deeply penetrating UVA rays induce the formation of reactive oxygen species (ROS), which results in oxidative stress such as photoproducts, senescence, and cell death. Thus, UVA is considered a primary factor that promotes skin aging. OBJECTIVE: Researchers investigated whether pretreatment with ferulic acid protects human dermal fibroblasts (HDFs) against UVA-induced cell damages...
December 2016: Annals of Dermatology
https://www.readbyqxmd.com/read/27904036/differential-regulation-of-lympho-myelopoiesis-by-stromal-cells-in-the-early-and-late-phases-in-balb-c-mice-repeatedly-exposed-to-lipopolysaccharide
#15
Isao Tsuboi, Tomonori Harada, Yoko Hirabayashi, Jun Kanno, Shin Aizawa
Chronic lipopolysaccharide (LPS) exposure to mice reduces the lymphoid compartment and skews the hematopoietic cell compartment toward myeloid-cells, which is considered to be a direct effect of LPS on hematopoietic stem cells. However, the effect of chronic LPS exposure on stromal-cells, which compose the hematopoietic microenvironment, has not been elucidated. Here, we investigated early- and late-phase effects of repeated LPS exposure on stromal-cells. During the early phase, when mice were treated with 5 or 25 µg LPS three times at weekly intervals, the numbers of myeloid-progenitor (colony forming unit-granulocyte macrophage (CFU-GM)) cells and B lymphoid-progenitor (CFU-preB) cells in the bone-marrow (BM) rapidly decreased after each treatment...
2016: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27903989/repression-of-yap-by-nctd-disrupts-nsclc-progression
#16
Jiwei Guo, Yan Wu, Lijuan Yang, Jing Du, Kaikai Gong, Weiwei Chen, Juanjuan Dai, XueLin Li, Sichuan Xi
The efficacy of available lung cancer therapeutic interference is significantly limited by various resistance mechanisms to those drugs. Activation of the oncogene YAP underlying the initiation, progression, and metastasis of lung cancer associates with poor prognosis and confers drug resistance against targeted therapy. In this study, we evaluated the specificity of norcantharidin (NCTD) in repressing YAP to inhibit non-small cell lung carcinoma (NSCLC) progression. Our study revealed that YAP signal pathways were aberrantly activated in lung cancer tissues and cells which rendered more proliferative and invasive phenotypes to human lung cancer cells...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27903806/oschx14-is-involved-in-the-k-homeostasis-in-rice-oryza-sativa-flowers
#17
Yi Chen, Jingkun Ma, Anthony J Miller, Bingbing Luo, Mei Wang, Zhen Zhu, Pieter B F Ouwerkerk
Previously we showed in the osjar1 mutants that the lodicule senescence which controls the closing of rice flowers was delayed. This resulted in florets staying open longer when compared with the wild type. The gene OsJAR1 is silenced in osjar1 mutants and is a key member of the jasmonic acid (JA) signaling pathway. We found that K concentrations in lodicules and flowers of osjar1-2 were significantly elevated compared with the wild type, indicating that K(+) homeostasis may play a role in regulating the closure of rice flowers...
July 2016: Plant & Cell Physiology
https://www.readbyqxmd.com/read/27903783/uncovering-the-mechanisms-of-caenorhabditis-elegans-ageing-from-global-quantification-of-the-underlying-landscape
#18
Lei Zhao, Jin Wang
Recent studies on Caenorhabditis elegans reveal that gene manipulations can extend its lifespan several fold. However, how the genes work together to determine longevity is still an open question. Here we construct a gene regulatory network for worm ageing and quantify its underlying potential and flux landscape. We found ageing and rejuvenation states can emerge as basins of attraction at certain gene expression levels. The system state can switch from one attractor to another driven by the intrinsic or external perturbations through genetics or the environment...
November 2016: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/27903634/distinct-receptor-tyrosine-kinase-subsets-mediate-anti-her2-drug-resistance-in-breast-cancer
#19
Peter B Alexander, Rui Chen, Chang Gong, Lifeng Yuan, Jeff S Jasper, Yi Ding, Geoffrey J Markowitz, Pengyuan Yang, Xin Xu, Donald P McDonnell, Erwei Song, Xiao-Fan Wang
Targeted inhibitors of the human epidermal growth factor receptor 2 (HER2) such as trastuzumab and lapatinib are among the first examples of molecularly targeted cancer therapy and have proven largely effective for the treatment of HER2-positive breast cancers. However, approximately half of those patients either do not respond to these therapies or develop secondary resistance. Although a few signaling pathways have been implicated, a comprehensive understanding of mechanisms underlying HER2 inhibitor drug resistance is still lacking...
November 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27903586/microrna-125a-5p-alleviates-the-deleterious-effects-of-ox-ldl-on-multiple-functions-of-human-brain-microvessel-endothelial-cells
#20
Qunwen Pan, Xiaorong Liao, Hua Liu, Yan Wang, Yanfang Chen, Bin Zhao, Eric Lazartigues, Yi Yang, Xiaotang Ma
MicroRNA-125a-5p(miR-125a-5p)could participate in the pathogenesis of vascular diseases. In this study, we investigated the role of miR-125a-5p in oxidized low density lipoprotein (ox-LDL) induced functional changes in human brain microvessel endothelial cells (HBMEC). The reactive oxygen species (ROS) production, nitric oxide (NO) generation, senescence, apoptosis and functions of HBMEC were analyzed. For mechanism study, the epidermal growth factor receptor (EGFR)/ extracellular regulated protein kinases (ERK)/ p38 mitogen-activated protein kinase (p38 MAPK), and phosphatidylinositol-3-kinase (PI3K), serine/threonine kinase (Akt), endothelial nitric oxide synthase (eNOS), and p-Akt were analyzed...
November 30, 2016: American Journal of Physiology. Cell Physiology
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