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https://www.readbyqxmd.com/read/29352723/which-hiv-infected-adults-with-high-cd4-t-cell-counts-benefit-most-from-immediate-initiation-of-antiretroviral-therapy-a-post-hoc-subgroup-analysis-of-the-start-trial
#1
Jean-Michel Molina, Birgit Grund, Fred Gordin, Ian Williams, Mauro Schechter, Marcello Losso, Matthew Law, Ernest Ekong, Noluthando Mwelase, Athanasios Skoutelis, Martin J Wiselka, Linos Vandekerckhove, Thomas Benfield, David Munroe, Jens D Lundgren, James D Neaton
BACKGROUND: Immediate initiation of antiretroviral therapy (ART) in asymptomatic adults with CD4 counts higher than 500 cells per μL, as recommended, might not always be possible in resource-limited settings. We aimed to identify subgroups of individuals who would benefit most from immediate treatment. METHODS: The START trial was a randomised controlled trial in asymptomatic, HIV-positive adults previously untreated with ART. Participants with CD4 counts higher than 500 cells per μL were randomly assigned to receive immediate ART or to defer ART until CD4 counts were lower than 350 cells per μL...
January 15, 2018: Lancet HIV
https://www.readbyqxmd.com/read/29352609/induction-of-mitophagy-in-the-hei-oc1-auditory-cell-line-and-activation-of-the-atg12-lc3-pathway-in-the-organ-of-corti
#2
Cristian Setz, Anne-Sophie Benischke, Anna Catharina Pinho Ferreira Bento, Yves Brand, Soledad Levano, Franziska Paech, Katharina Leitmeyer, Daniel Bodmer
Autophagy is a highly evolutionary conserved quality control defense mechanism within cells, which has also been implicated in cell death processes. In the mammalian inner ear, autophagy has been shown to play a role during early morphogenesis as well as in adult cochlear hair cells exposed to ototoxic insults. Mitophagy, a selective autophagic cell process targeting mitochondria, hasn't been studied in the inner ear so far. On this work, we searched for molecular indicators of mitophagy within House Ear Institute-Organ of Corti-1 (HEI-OC1) cells as well as in the organ of Corti (OC)...
January 11, 2018: Hearing Research
https://www.readbyqxmd.com/read/29352505/p53-independent-noxa-induction-by-cisplatin-is-regulated-by-atf3-atf4-in-head-and-neck-squamous-cell-carcinoma-cells
#3
Kanika Sharma, Thien-Trang Vu, Wade Cook, Mitra Naseri, Kevin Zhan, Wataru Nakajima, Hisashi Harada
The platinum-based DNA damaging agent cisplatin is used as a standard therapy for locally advanced head and neck squamous cell carcinoma (HNSCC). However, the mechanisms underpinning the cytotoxic effects of this compound are not entirely elucidated. Cisplatin produces anticancer effects primarily via activation of the DNA damage response, followed by inducing BCL-2 family-dependent mitochondrial apoptosis. We have previously demonstrated that cisplatin induces the expression of pro-apoptotic BCL-2 family protein, Noxa, that can bind to the pro-survival BCL-2 family protein, MCL-1, to inactivate its function and induce cell death...
January 19, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29352490/oral-lichenoid-reaction-showing-multiple-ulcers-associated-with-anti-programmed-death-cell-receptor-1-treatment-a-report-of-two-cases-and-published-work-review
#4
Koya Obara, Mamiko Masuzawa, Yasuyuki Amoh
Anti-programmed cell death receptor-1 (PD-1) antibodies represent an effective treatment opinion for advanced melanoma and non-small-cell lung cancer, as well as other cancerous entities. Immune checkpoint inhibitors such as anti-PD-1 antibody result in a unique side-effect profile, commonly described as immune-related adverse events (irAE). These irAE affect the skin, gastrointestinal tract, liver, endocrine system and other organ systems. We report two cases of oral lichenoid reaction showing multiple ulcers associated with nivolumab treatment...
January 20, 2018: Journal of Dermatology
https://www.readbyqxmd.com/read/29352431/analysis-and-comparison-of-the-8th-edition-american-joint-committee-on-cancer-ajcc-nodal-staging-system-in-cutaneous-and-oral-squamous-cell-cancer-of-the-head-and-neck
#5
Nikolaus Moeckelmann, Ardalan Ebrahimi, Richard Dirven, Jessica Liu, Tsu-Hui Hubert Low, Ruta Gupta, Bruce Ashford, Sydney Ch'ng, Carsten E Palme, Jonathan R Clark
BACKGROUND: The American Joint Committee on Cancer (AJCC) uses the same nodal staging system for cutaneous and mucosal squamous cell carcinoma of the head and neck in its 8th edition (AJCC 8) despite differences in the etiology, risk factors, and clinical behavior of the two diseases. This study aims to evaluate the performance of the AJCC 8 nodal staging system by direct comparison of cutaneous (cSCC) versus oral squamous cell carcinoma (oSCC) patients. METHODS: Patients with metastatic cSCC (N = 382) and oSCC (N = 325) were identified from a prospective database (years 1987-2016)...
January 19, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29352371/innate-and-adaptive-t-cells-in-influenza-disease
#6
REVIEW
Simone Nüssing, Sneha Sant, Marios Koutsakos, Kanta Subbarao, Thi H O Nguyen, Katherine Kedzierska
Influenza is a major global health problem, causing infections of the respiratory tract, often leading to acute pneumonia, life-threatening complications and even deaths. Over the last seven decades, vaccination strategies have been utilized to protect people from complications of influenza, especially groups at high risk of severe disease. While current vaccination regimens elicit strain-specific antibody responses, they fail to generate cross-protection against seasonal, pandemic and avian viruses. Moreover, vaccines designed to generate influenza-specific T-cell responses are yet to be optimized...
January 20, 2018: Frontiers of Medicine
https://www.readbyqxmd.com/read/29352272/nuclear-p53-mediated-repression-of-autophagy-involves-pink1-transcriptional-down-regulation
#7
Thomas Goiran, Eric Duplan, Lila Rouland, Wejdane El Manaa, Inger Lauritzen, Julie Dunys, Han You, Frédéric Checler, Cristine Alves da Costa
p53 is a transcription factor that is implicated in the control of both apoptotic and autophagic cell death. This tumor suppressor elicits both pro-autophagic and anti-autophagic phenotypes depending of its intracellular localization. The ability of p53 to repress autophagy has been exclusively associated to its cytoplasmic localization. Here, we show that transcriptional activity of p53 also contributes to autophagy down-regulation. Thus, nuclear p53 controls PINK1, a key protein involved in the control of mitophagy, by repressing its promoter activity, protein and mRNA levels, ex-vivo and in vivo...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29352271/sex-disparity-in-cancer-roles-of-micrornas-and-related-functional-players
#8
REVIEW
Alessandra Carè, Maria Bellenghi, Paola Matarrese, Lucia Gabriele, Stefano Salvioli, Walter Malorni
A sexual dimorphism at the cellular level has been suggested to play a role in cancer onset and progression. In particular, very recent studies have unraveled striking differences between cells carrying XX or XY chromosomes in terms of response to stressful stimuli, indicating the presence of genetic and epigenetic differences determining sex-specific metabolic or phenotypic traits. Although this field of investigation is still in its infancy, available data suggest a key role of sexual chromosomes in determining cell life or death...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29352268/cylindromatosis-mediates-neuronal-cell-death-in-vitro-and-in-vivo
#9
Goutham K Ganjam, Nicole Angela Terpolilli, Sebastian Diemert, Ina Eisenbach, Lena Hoffmann, Christina Reuther, Christiane Herden, Joachim Roth, Nikolaus Plesnila, Carsten Culmsee
The tumor-suppressor cylindromatosis (CYLD) is a deubiquitinating enzyme and key regulator of cell proliferation and inflammation. A genome-wide siRNA screen linked CYLD to receptor interacting protein-1 (RIP1) kinase-mediated necroptosis; however, the exact mechanisms of CYLD-mediated cell death remain unknown. Therefore, we investigated the precise role of CYLD in models of neuronal cell death in vitro and evaluated whether CYLD deletion affects brain injury in vivo. In vitro, downregulation of CYLD increased RIP1 ubiquitination, prevented RIP1/RIP3 complex formation, and protected neuronal cells from oxidative death...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29352265/type-i-ifn-operates-pyroptosis-and-necroptosis-during-multidrug-resistant-a-baumannii-infection
#10
Yang Li, Xiaomin Guo, Chunmiao Hu, Yan Du, Chuansheng Guo, Di Wang, Weiheng Zhao, Gonghua Huang, Chunliang Li, Qiumin Lu, Ren Lai, Tao Xu, Xiaopeng Qi
Multidrug-resistant Acinetobacter baumannii, a common pathogen responsible for nosocomial infections, is the main cause for outbreaks of infectious diseases, such as pneumonia, meningitis, and bacteremia, especially among critically ill patients. Epidemic A. baumannii is a growing public health concern as it is resistant to all existing antimicrobial agents, thereby necessitating the development of new therapeutic approaches to mount an effective immune response against this bacterial pathogen. In this study, we identified a critical role for type I interferon (IFN) in epigenetic regulation during A...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29352207/ethanol-sensitizes-hepatocytes-for-tgf-%C3%AE-triggered-apoptosis
#11
Haristi Gaitantzi, Christoph Meyer, Pia Rakoczy, Maria Thomas, Kristin Wahl, Franziska Wandrer, Heike Bantel, Hamed Alborzinia, Stefan Wölfl, Sabrina Ehnert, Andreas Nüssler, Ina Bergheim, Loredana Ciuclan, Matthias Ebert, Katja Breitkopf-Heinlein, Steven Dooley
Alcohol abuse is a global health problem causing a substantial fraction of chronic liver diseases. Abundant TGF-β-a potent pro-fibrogenic cytokine-leads to disease progression. Our aim was to elucidate the crosstalk of TGF-β and alcohol on hepatocytes. Primary murine hepatocytes were challenged with ethanol and TGF-β and cell fate was determined. Fluidigm RNA analyses revealed transcriptional effects that regulate survival and apoptosis. Mechanistic insights were derived from enzyme/pathway inhibition experiments and modulation of oxidative stress levels...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352194/sirt6-overexpression-suppresses-senescence-and-apoptosis-of-nucleus-pulposus-cells-by-inducing-autophagy-in-a-model-of-intervertebral-disc-degeneration
#12
Jian Chen, Jun-Jun Xie, Meng-Yun Jin, Yun-Tao Gu, Cong-Cong Wu, Wei-Jun Guo, Ying-Zhao Yan, Zeng-Jie Zhang, Jian-Le Wang, Xiao-Lei Zhang, Yan Lin, Jia-Li Sun, Guang-Hui Zhu, Xiang-Yang Wang, Yao-Sen Wu
Treatment of intervertebral disc degeneration (IDD) seeks to prevent senescence and death of nucleus pulposus (NP) cells. Previous studies have shown that sirt6 exerts potent anti-senescent and anti-apoptotic effects in models of age-related degenerative disease. However, it is not known whether sirt6 protects against IDD. Here, we explored whether sirt6 influenced IDD. The sirt6 level was reduced in senescent human NP cells. Sirt6 overexpression protected against apoptosis and both replicative and stress-induced premature senescence...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352186/glycolysis-promotes-caspase-3-activation-in-lipid-rafts-in-t-cells
#13
Michael A Secinaro, Karen A Fortner, Oliver Dienz, Angela Logan, Michael P Murphy, Vikas Anathy, Jonathan E Boyson, Ralph C Budd
Resting T cells undergo a rapid metabolic shift to glycolysis upon activation in the presence of interleukin (IL)-2, in contrast to oxidative mitochondrial respiration with IL-15. Paralleling these different metabolic states are striking differences in susceptibility to restimulation-induced cell death (RICD); glycolytic effector T cells are highly sensitive to RICD, whereas non-glycolytic T cells are resistant. It is unclear whether the metabolic state of a T cell is linked to its susceptibility to RICD. Our findings reveal that IL-2-driven glycolysis promotes caspase-3 activity and increases sensitivity to RICD...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352167/srebp1c-mediates-the-effect-of-acetaldehyde-on-cidea-expression-in-alcoholic-fatty-liver-mice
#14
Qi He, Yan Diao, Tingting Zhao, Baoyu Hou, Linel Darrel Ngokana, Huan Liang, Junhui Nie, Peizhu Tan, Hui Huang, Yanze Li, Lin Qi, Yuanyuan Zhao, Ying Liu, Xu Gao, Lingyun Zhou
Cell death inducing DNA fragmentation factor-alpha-like A (Cidea) is a member of cell death-inducing DFF45-like effector (CIDE) protein. The initial function of CIDE is the promotion of cell death and DNA fragmentation in mammalian cells. Cidea was recently reported to play critical roles in the development of hepatic steatosis. The purpose of present study is to determine the effect of chronic alcohol intake on Cidea expression in the livers of mice with alcoholic fatty liver disease. Cidea expression was significantly increased in the liver of alcohol-induced fatty liver mice...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352166/epstein-barr-virus-encoded-latent-membrane-protein-1-suppresses-necroptosis-through-targeting-ripk1-3-ubiquitination
#15
Xiaolan Liu, Yueshuo Li, Songling Peng, Xinfang Yu, Wei Li, Feng Shi, Xiangjian Luo, Min Tang, Zheqiong Tan, A M Bode, Ya Cao
Necroptosis is an alternative programmed cell death pathway that is unleashed in the absence of apoptosis and mediated by signaling complexes containing receptor-interating protein kinase 1 (RIPK1) and RIPK3. This form of cell death has recently been implicated in host defense system to eliminate pathogen-infected cells. However, only a few viral species such as herpes simplex virus (HSV) and cytomegalovirus (CMV) have evolved mechanisms inhibiting necroptosis to overcome host antiviral defense, which is important for successful pathogenesis...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352138/mir-663-sustains-nsclc-by-inhibiting-mitochondrial-outer-membrane-permeabilization-momp-through-puma-bbc3-and-btg2
#16
Micol E Fiori, Lidia Villanova, Chiara Barbini, Maria Laura De Angelis, Ruggero De Maria
Treatment of lung cancer is an unmet need as it accounts for the majority of cancer deaths worldwide. The development of new therapies urges the identification of potential targets. MicroRNAs' expression is often deregulated in cancer and their modulation has been proposed as a successful strategy to interfere with tumor cell growth and spread. We recently reported on an unbiased high-content approach to identify miRNAs regulating cell proliferation and tumorigenesis in non-small cell lung cancer (NSCLC). Here we studied the oncogenic role of miR-663 in NSCLC biology and analyzed the therapeutic potential of miR-663 targeting...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352135/blocking-zika-virus-vertical-transmission
#17
Pinar Mesci, Angela Macia, Spencer M Moore, Sergey A Shiryaev, Antonella Pinto, Chun-Teng Huang, Leon Tejwani, Isabella R Fernandes, Nicole A Suarez, Matthew J Kolar, Sandro Montefusco, Scott C Rosenberg, Roberto H Herai, Fernanda R Cugola, Fabiele B Russo, Nicholas Sheets, Alan Saghatelian, Sujan Shresta, Jeremiah D Momper, Jair L Siqueira-Neto, Kevin D Corbett, Patricia C B Beltrão-Braga, Alexey V Terskikh, Alysson R Muotri
The outbreak of the Zika virus (ZIKV) has been associated with increased incidence of congenital malformations. Although recent efforts have focused on vaccine development, treatments for infected individuals are needed urgently. Sofosbuvir (SOF), an FDA-approved nucleotide analog inhibitor of the Hepatitis C (HCV) RNA-dependent RNA polymerase (RdRp) was recently shown to be protective against ZIKV both in vitro and in vivo. Here, we show that SOF protected human neural progenitor cells (NPC) and 3D neurospheres from ZIKV infection-mediated cell death and importantly restored the antiviral immune response in NPCs...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352134/pseudoalteromonas-haloplanktis-tac125-produces-4-hydroxybenzoic-acid-that-induces-pyroptosis-in-human-a459-lung-adenocarcinoma-cells
#18
Filomena Sannino, Clementina Sansone, Christian Galasso, Sara Kildgaard, Pietro Tedesco, Renato Fani, Gennaro Marino, Donatella de Pascale, Adrianna Ianora, Ermenegilda Parrilli, Thomas Ostenfeld Larsen, Giovanna Romano, Maria Luisa Tutino
In order to exploit the rich reservoir of marine cold-adapted bacteria as a source of bioactive metabolites, ethyl acetate crude extracts of thirteen polar marine bacteria were tested for their antiproliferative activity on A549 lung epithelial cancer cells. The crude extract from Pseudoalteromonas haloplanktis TAC125 was the most active in inhibiting cell proliferation. Extensive bioassay-guided purification and mass spectrometric characterization allowed the identification of 4-hydroxybenzoic acid (4-HBA) as the molecule responsible for this bioactivity...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352110/melatonin-inhibits-apoptotic-cell-death-induced-by-vibrio-vulnificus-vvha-via-melatonin-receptor-2-coupling-with-ncf-1
#19
Sei-Jung Lee, Hyun Jik Lee, Young Hyun Jung, Jun Sung Kim, Sang Ho Choi, Ho Jae Han
Melatonin, an endogenous hormone molecule, has a variety of biological functions, but a functional role of melatonin in the infection of Gram-negative bacterium Vibrio vulnificus has yet to be described. In this study, we investigated the molecular mechanism of melatonin in the apoptosis of human intestinal epithelial (HCT116) cells induced by the hemolysin (VvhA) produced by V. vulnificus. Melatonin (1 μM) significantly inhibited apoptosis induced by the recombinant protein (r) VvhA, which had been inhibited by the knockdown of MT2...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29351916/pathways-impacted-by-genomic-alterations-in-pulmonary-carcinoid-tumors
#20
Michael K Asiedu, Charles F Thomas, Jie Dong, Sandra C Schulte Tomaszek, Prasidda Khadka, Zhifu Sun, Farhad Kosari, Jin Jen, Julian R Molina, George Vasmatzis, Rui Kuang, Marie Christine Aubry, Ping Yang, Dennis A Wigle
PURPOSE: Pulmonary carcinoid tumors account for up to 5% of all lung malignancies in adults, comprise 30% of all carcinoid malignancies, and are defined histologically as typical carcinoid (TC) and atypical carcinoid (AC) tumors. The role of specific genomic alterations in the pathogenesis of pulmonary carcinoid tumors remains poorly understood. We sought to identify genomic alterations and pathways that are deregulated in these tumors to find novel therapeutic targets for pulmonary carcinoid tumors...
January 19, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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