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https://www.readbyqxmd.com/read/29352998/two-weeks-of-variable-stress-increases-gamma-h2ax-levels-in-the-mouse-bed-nucleus-of-the-stria-terminalis
#1
Brendan D Hare, Tina M Thornton, Mercedes Rincon, Borivoj Golijanin, S Bradley King, Diane M Jaworski, William A Falls
Recent reports demonstrate that DNA damage is induced, and rapidly repaired, in circuits activated by experience. Moreover, stress hormones are known to slow DNA repair, suggesting that prolonged stress may result in persistent DNA damage. Prolonged stress is known to negatively impact physical and mental health; however, DNA damage as a factor in stress pathology has only begun to be explored. Histone H2A-X phosphorylated at serine 139 (γH2AX) is a marker of DNA double strand breaks (DSB), a type of damage that may lead to cell death if unrepaired...
January 15, 2018: Neuroscience
https://www.readbyqxmd.com/read/29345572/breaking-the-dna-damage-response-via-serine-threonine-kinase-inhibitors-to-improve-cancer-treatment
#2
Wioletta Rozpedek, Dariusz Pytel, Alicja Nowak-Zdunczyk, Dawid Lewko, Radoslaw Wojtczak, John Alan Diehl, Ireneusz Majsterek
Multiple, both endogenous and exogenous, sources may induce DNA damage and DNA replication stress. Cells have developed DNA damage response (DDR) signaling pathways to maintain genomic stability and effectively detect and repair DNA lesions. Serine/threonine kinases such as Ataxia-telangiectasia mutated (ATM) and Ataxia-telangiectasia and Rad3-Related (ATR) are the major regulators of DDR, since after sensing stalled DNA replication forks, DNA double- or single-strand breaks, may directly phosphorylate and activate their downstream targets, that play a key role in DNA repair, cell cycle arrest and apoptotic cell death...
January 16, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29342113/mitochondria-oxidative-stress-and-the-kynurenine-system-with-a-focus-on-ageing-and-neuroprotection
#3
REVIEW
Katalin Sas, Elza Szabó, László Vécsei
In this review, the potential causes of ageing are discussed. We seek to gain insight into the main physiological functions of mitochondria and discuss alterations in their function and the genome, which are supposed to be the central mechanisms in senescence. We conclude by presenting the potential modulating role of the kynurenine pathway in the ageing processes. Mitochondrial dynamics are supposed to have important physiological roles in maintaining cell homeostasis. During ageing, a decrease in mitochondrial dynamics was reported, potentially compromising the function of mitochondria...
January 17, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29336467/nox4-ros-mediate-ethanol%C3%A2-induced-apoptosis-via-mapk-signal-pathway-in-l%C3%A2-02-cells
#4
Cheng-Fang Yang, Yu-Juan Zhong, Zuheng Ma, Li Li, Lin Shi, Li Chen, Chen Li, Dan Wu, Qi Chen, Yong-Wen Li
The aim of the present study was to assess the molecular mechanism of ethanol‑induced oxidative stress‑mediated apoptosis in L‑02 liver cells in order to elucidate novel pathways associated with alcoholic liver disease. L‑02 cells were treated with 400 mM ethanol with or without inhibitors. The cell viability was measured by an MTT assay. Cell apoptosis was assessed by flow cytometry and a single‑stranded DNA (ssDNA) assay. Intracellular reactive oxygen species (ROS) production of L‑02 cells was determined using the 2',7'‑dichlorofluorescein‑diacetate dye...
January 16, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29333049/marine-derived-fungi-extracts-enhance-the-cytotoxic-activity-of-doxorubicin-in-nonsmall-cell-lung-cancer-cells-a459
#5
Bruno Castro-Carvalho, Alice A Ramos, Maria Prata-Sena, Fernanda Malhão, Márcia Moreira, Daniela Gargiulo, Tida Dethoup, Suradet Buttachon, Anake Kijjoa, Eduardo Rocha
Background: Drug resistance is a major concern in the current chemotherapeutic approaches and the combination with natural compounds may enhance the cytotoxic effects of the anticancer drugs. Therefore, this study evaluated the cytotoxicity of crude ethyl extracts of six marine-derived fungi - Neosartorya tsunodae KUFC 9213 (E1), Neosartorya laciniosa KUFC 7896 (E2), Neosartorya fischeri KUFC 6344 (E3), Aspergillus similanensis KUFA 0013 (E4), Neosartorya paulistensis KUFC 7894 (E5), and Talaromyces trachyspermum KUFC 0021 (E6) - when combined with doxorubicin (Dox), in seven human cancer cell lines...
December 2017: Pharmacognosy Research
https://www.readbyqxmd.com/read/29329095/investigation-of-silver-ag-deposition-in-tissues-from-stranded-cetaceans-by-autometallography-amg
#6
Wen-Ta Li, Hui-Wen Chang, Meng-Hsien Chen, Hue-Ying Chiou, Bang-Yeh Liou, Victor Fei Pang, Wei-Cheng Yang, Chian-Ren Jeng
Silver, such as silver nanoparticles (AgNPs), has been widely used in commercial products and may be released into the environment. The interaction between Ag deposition and biological systems is raising serious concerns because of one health consideration. Cetaceans, as the top predators of the oceans, may be exposed to Ag/Ag compounds and suffer negative health impacts from the deposition of these compounds in their bodies. In the present study, we utilized autometallography (AMG) to localize the Ag in the liver and kidney tissues of cetaceans and developed a model called the cetacean histological Ag assay (CHAA) to estimate the Ag concentrations in the liver and kidney tissues of cetaceans...
January 9, 2018: Environmental Pollution
https://www.readbyqxmd.com/read/29319493/cyclosporine-for-the-treatment-of-lupus-nephritis-in-patients-with-systemic-lupus-erythematosus
#7
Tzu-Han Yang, Tsai-Hung Wu, Yuh-Lih Chang, Hsien-Tzung Liao, Chia-Chen Hsu, Chang-Youh Tsai, Yueh-Ching Chou
AIMS: This study aimed to assess retrospectively the efficacy and safety of cyclosporin A (CsA) therapy in patients with lupus nephritis (LN). MATERIALS AND METHODS: From September 2005 to August 2015, eligible patients with LN undergoing CsA treatment were enrolled in the study. Medical charts as well as clinical and laboratory data were retrospectively reviewed. The data were evaluated at 0, 1, 6, 12 month(s) after the start of CsA. Serum creatinine (SCr), estimated glomerular filtration rate (eGFR), urine protein/creatinine ratio (uPCR), complement components C3, C4, and anti-double stranded DNA antibody (anti-dsDNA) titers were recorded...
January 10, 2018: Clinical Nephrology
https://www.readbyqxmd.com/read/29317830/quercetin-suppresses-dna-double-strand-break-repair-and-enhances-the-radiosensitivity-of-human-ovarian-cancer-cells-via-p53-dependent-endoplasmic-reticulum-stress-pathway
#8
Cheng Gong, Zongyuan Yang, Lingyun Zhang, Yuehua Wang, Wei Gong, Yi Liu
Quercetin is proven to have anticancer effects for many cancers. However, the role of tumor suppressor p53 on quercetin's radiosensitization and regulation of endoplasmic reticulum (ER) stress response in this process remains obscure. Here, quercetin exposure resulted in ER stress, prolonged DNA repair, and the expression of p53 protein; phosphorylation on serine 15 and 20 increased in combination with X-irradiation. Quercetin pretreatment could potentiate radiation-induced cell death. The combination of irradiation and quercetin treatment aggravated DNA damages and caused typical apoptotic cell death; as well the expression of Bax and p21 elevated and the expression of Bcl-2 decreased...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29312614/3d-structured-illumination-microscopy-reveals-clustered-dna-double-strand-break-formation-in-widespread-%C3%AE-h2ax-foci-after-high-let-heavy-ion-particle-radiation
#9
Yoshihiko Hagiwara, Atsuko Niimi, Mayu Isono, Motohiro Yamauchi, Takaaki Yasuhara, Siripan Limsirichaikul, Takahiro Oike, Hiro Sato, Kathryn D Held, Takashi Nakano, Atsushi Shibata
DNA double-strand breaks (DSBs) induced by ionising radiation are considered the major cause of genotoxic mutations and cell death. While DSBs are dispersed throughout chromatin after X-rays or γ-irradiation, multiple types of DNA damage including DSBs, single-strand breaks and base damage can be generated within 1-2 helical DNA turns, defined as a complex DNA lesion, after high Linear Energy Transfer (LET) particle irradiation. In addition to the formation of complex DNA lesions, recent evidence suggests that multiple DSBs can be closely generated along the tracks of high LET particle irradiation...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29309644/pidd-mediates-the-association-of-dna-pkcs-and-atr-at-stalled-replication-forks-to-facilitate-the-atr-signaling-pathway
#10
Yu-Fen Lin, Hung-Ying Shih, Zeng-Fu Shang, Ching-Te Kuo, Jiaming Guo, Chunying Du, Hsinyu Lee, Benjamin P C Chen
The DNA-dependent protein kinase (DNA-PK), consisting of the DNA binding Ku70/80 heterodimer and the catalytic subunit DNA-PKcs, has been well characterized in the non-homologous end-joining mechanism for DNA double strand break (DSB) repair and radiation resistance. Besides playing a role in DSB repair, DNA-PKcs is required for the cellular response to replication stress and participates in the ATR-Chk1 signaling pathway. However, the mechanism through which DNA-PKcs is recruited to stalled replication forks is still unclear...
January 4, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29306194/downregulation-of-parp1-transcription-by-cdk4-6-inhibitors-sensitizes-human-lung-cancer-cells-to-anticancer-drug-induced-death-by-impairing-ogg1-dependent-base-excision-repair
#11
Dominika Tempka, Paulina Tokarz, Kinga Chmielewska, Magdalena Kluska, Julita Pietrzak, Żaneta Rygielska, László Virág, Agnieszka Robaszkiewicz
Hallmarks of cancer cells include uncontrolled growth and rapid proliferation; thus, cyclin-dependent kinases are a therapeutic target for cancer treatment. Treating non-small lung cancer cells with sublethal concentrations of the CDK4/6 inhibitors, ribociclib (LEE011) and palbociclib (PD0332991), which are approved by the FDA for anticancer therapies, caused cell cycle arrest in the G1 phase and suppression of poly(ADP-ribose) polymerase 1 (PARP1) transcription by inducing recruitment of the RB1-E2F1-HDAC1-EZH2 repressive complex to the PARP1 promoter...
December 29, 2017: Redox Biology
https://www.readbyqxmd.com/read/29297932/inhibition-of-novel-gcn5-atm-axis-restricts-the-onset-of-acquired-drug-resistance-in-leukemia
#12
Sameer Salunkhe, Saket V Mishra, Jyothi Nair, Samadri Ghosh, Neha Choudhary, Ekjot Kaur, Sanket Shah, Ketaki Patkar, Dev Anand, Navin Khattry, Syed K Hasan, Shilpee Dutt
Leukemia is majorly treated by topoisomerase inhibitors that induce DNA double strand breaks (DSB) resulting in cell death. Consequently, modulation of DSB repair pathway renders leukemic cells resistant to therapy. Since we do not fully understand the regulation of DSB repair acquired by resistant cells, targeting these cells has been a challenge. Here we investigated the regulation of DSB repair pathway in Early Drug Resistant Population (EDRP) and Late Drug Resistant Population (LDRP). We found that doxorubicin induced equal DSBs in parent and EDRP cells however; cell death is induced only in the parent cells...
January 3, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29288494/nuclear-cytochrome-c-a-mitochondrial-visitor-regulating-damaged-chromatin-dynamics
#13
Irene Díaz-Moreno, Alejandro Velázquez-Cruz, Seamus Curran-French, Antonio Díaz-Quintana, Miguel A De la Rosa
Over the past decade, evidence has emerged suggesting a broader role for cytochrome c (Cyt c) in programmed cell death. Recently, we demonstrated the ability of Cyt c to inhibit the nucleosome assembly activity of histone chaperones SET/TAF-Iβ and NRP1 during DNA damage in humans and plants, respectively. Here, we hypothesise a dual concentration-dependent function for nuclear Cyt c in response to DNA damage. We propose that low levels of highly cytotoxic DNA lesions - such as double-strand breaks - induce nuclear translocation of Cyt c, leading to the attenuation of nucleosome assembly and, thereby, increasing the time available for DNA repair...
December 30, 2017: FEBS Letters
https://www.readbyqxmd.com/read/29283424/integrated-microrna-mrna-analysis-reveals-mir-204-inhibits-cell-proliferation-in-gastric-cancer-by-targeting-cks1b-cxcl1-and-gprc5a
#14
Sirjana Shrestha, Chi-Dung Yang, Hsiao-Chin Hong, Chih-Hung Chou, Chun-San Tai, Men-Yee Chiew, Wen-Liang Chen, Shun-Long Weng, Chung-Chu Chen, Yi-An Chang, Meng-Lin Lee, Wei-Yun Huang, Sheng-Da Hsu, Yi-Chang Chen, Hsien-Da Huang
Gastric cancer (GC) is the second most frequent cause of cancer-related deaths worldwide. MicroRNAs are single-stranded RNA molecules of 21-23 nucleotides that regulate target gene expression through specific base-pairing interactions between miRNA and untranslated regions of targeted mRNAs. In this study, we generated a multistep approach for the integrated analysis of miRNA and mRNA expression. First, both miRNA and mRNA expression profiling datasets in gastric cancer from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) identified 79 and 1042 differentially expressed miRNAs and mRNAs, respectively, in gastric cancer...
December 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29281054/radiation-induced-unrepairable-dsbs-their-role-in-the-late-effects-of-radiation-and-possible-applications-to-biodosimetry
#15
Asao Noda
Although the vast majority of DNA damage induced by radiation exposure disappears rapidly, some lesions remain in the cell nucleus in very small quantities for days to months. These lesions may cause a considerable threat to an organism and include certain types of DNA double-strand breaks (DSBs) called 'unrepairable DSBs'. Unrepairable DSBs are thought to cause persistent malfunctioning of cells and tissues or cause late effects of radiation, especially the induction of delayed cell death, mutation, senescence, or carcinogenesis...
December 21, 2017: Journal of Radiation Research
https://www.readbyqxmd.com/read/29273513/zerumbone-protects-human-skin-keratinocytes-against-uva-irradiated-damages-through-nrf2-induction
#16
Hsin-Ling Yang, Chin-Ling Lee, Mallikarjuna Korivi, Jiunn-Wang Liao, Peramaiyan Rajendran, Jia-Jiuan Wu, You-Cheng Hseu
Ultraviolet A (UVA) irradiation is toxic to skin as it penetrates deep into the dermis and damages cellular components through excessive reactive oxygen species (ROS) production, which accelerates photoaging and skin cancer. We evaluated the dermato-protective efficacies of zerumbone (natural sesquiterpene of Zingiber zerumbet) in UVA-irradiated human skin keratinocyte (HaCaT) cells and mouse epidermis. Zerumbone pretreatment (2-10 μM) substantially suppressed UVA (15 J/cm2)-induced HaCaT cell death and lactate dehydrogenase release in a dose-dependent manner...
December 19, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29259246/structure-and-interactions-of-a%C3%A2-host-defense-antimicrobial-peptide-thanatin-in-lipopolysaccharide-micelles-reveal-mechanism-of-bacterial-cell-agglutination
#17
Sheetal Sinha, Liangzhen Zheng, Yuguang Mu, Wun Jern Ng, Surajit Bhattacharjya
Host defense cationic Antimicrobial Peptides (AMPs) can kill microorganisms including bacteria, viruses and fungi using various modes of action. The negatively charged bacterial membranes serve as a key target for many AMPs. Bacterial cell death by membrane permeabilization has been well perceived. A number of cationic AMPs kill bacteria by cell agglutination which is a distinctly different mode of action compared to membrane pore formation. However, mechanism of cell agglutinating AMPs is poorly understood...
December 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29237843/human-parvovirus-b19-utilizes-cellular-dna-replication-machinery-for-viral-dna-replication
#18
Wei Zou, Zekun Wang, Min Xiong, Aaron Yun Chen, Peng Xu, Safder S Ganaie, Yomna Badawi, Steve Kleiboeker, Hiroshi Nishimune, Shui Qing Ye, Jianming Qiu
Human parvovirus B19 (B19V) infection of human erythroid progenitor cells (EPCs) induces a DNA damage response and cell cycle arrest at late S phase, which facilitates viral DNA replication. However, it is not clear exactly which cellular factors are employed by this single-stranded DNA virus. Here, we used microarrays to systematically analyze the dynamic transcriptome of EPCs infected with B19V. We found that DNA metabolism, DNA replication, DNA repair, DNA damage response, cell cycle, and cell cycle arrest pathways were significantly regulated after B19V infection...
December 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29237842/human-norovirus-ns3-has-rna-helicase-and-chaperoning-activities
#19
Teng-Feng Li, Myra Hosmillo, Hella Schwanke, Ting Shu, Zhaowei Wang, Lei Yin, Stephen Curry, Ian G Goodfellow, Xi Zhou
RNA remodeling proteins, including RNA helicases and chaperones, act to remodel RNA structures and/or protein-RNA interactions, and are required for all processes involving RNAs. Although many viruses encode RNA helicases and chaperones, their in vitro activities and their roles in infected cells largely remain elusive. Noroviruses are a diverse group of positive-stranded RNA viruses in the family Caliciviridae, and constitute a significant and potentially fatal threat to human health. Here we report that protein NS3 encoded by human norovirus has both ATP-dependent RNA helicase activity that unwinds RNA helices and ATP-independent RNA chaperoning activity that can remodel structured RNAs and facilitate strand-annealing...
December 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29237839/upon-infection-the-cellular-wd-repeat-containing-protein-5-wdr5-localizes-to-cytoplasmic-inclusion-bodies-and-enhances-measles-virus-replication
#20
Dzwokai Ma, Cyril X George, Jason Nomburg, Christian K Pfaller, Roberto Cattaneo, Charles E Samuel
Replication of negative-strand RNA viruses occurs in association with discrete cytoplasmic foci called inclusion bodies. Whereas inclusion bodies represent a prominent subcellular structure induced by viral infection, our knowledge of the cellular protein components involved in inclusion body formation and function is limited. Using measles virus-infected HeLa cells, we found that the WD repeat-containing protein 5 (WDR5), a subunit of histone H3 lysine 4 methyltransferases, was selectively recruited to virus-induced inclusion bodies...
December 13, 2017: Journal of Virology
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