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https://www.readbyqxmd.com/read/28928392/mucosa-associated-lymphoid-tissue-lymphoma-translocation-1-as-a-novel-therapeutic-target-for-rheumatoid-arthritis
#1
Chang Hoon Lee, Su Jeong Bae, Miok Kim
Emerging evidence suggests that mucosa-associated lymphoid tissue lymphoma translocation 1 (MALT1) is a key regulator of inflammatory diseases; however, the pathological role of MALT1 in rheumatoid arthritis (RA) is not well understood. Consequently, this protein has not been therapeutically targeted for the treatment of RA. MALT1 plays a role in the paracaspase pathway, has proteolytic activity and is involved in the regulation of inflammatory responses. In this study, we found that the MALT1-targeting inhibitory small molecule, MALT1 selective inhibitor 2-chloro-N-[4-[5-(3,4-dichlorophenyl)-3-(2-methoxyethoxy)-1H-1,2,4-triazol-1-yl]phenylacetamide (MI-2) strongly suppresses the differentiation of monocytes into osteoclasts in the absence or presence of the inflammatory cytokine tumour necrosis factor α...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28915586/hepatitis-c-virus-core-protein-targets-4e-bp1-expression-and-phosphorylation-and-potentiates-myc-induced-liver-carcinogenesis-in-transgenic-mice
#2
Cosette Abdallah, Charlène Lejamtel, Nassima Benzoubir, Serena Battaglia, Nazha Sidahmed-Adrar, Christophe Desterke, Matthieu Lemasson, Arielle R Rosenberg, Didier Samuel, Christian Bréchot, Delphine Pflieger, François Le Naour, Marie-Françoise Bourgeade
Hepatitis C virus (HCV) is a leading cause of liver diseases including the development of hepatocellular carcinoma (HCC). Particularly, core protein has been involved in HCV-related liver pathologies. However, the impact of HCV core on signaling pathways supporting the genesis of HCC remains largely elusive. To decipher the host cell signaling pathways involved in the oncogenic potential of HCV core, a global quantitative phosphoproteomic approach was carried out. This study shed light on novel differentially phosphorylated proteins, in particular several components involved in translation...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28913364/the-nrf2-keap1-are-pathway-and-oxidative-stress-as-a-therapeutic-target-in-type-ii-diabetes-mellitus
#3
REVIEW
Joshua A David, William J Rifkin, Piul S Rabbani, Daniel J Ceradini
Despite improvements in awareness and treatment of type II diabetes mellitus (TIIDM), this disease remains a major source of morbidity and mortality worldwide, and prevalence continues to rise. Oxidative damage caused by free radicals has long been known to contribute to the pathogenesis and progression of TIIDM and its complications. Only recently, however, has the role of the Nrf2/Keap1/ARE master antioxidant pathway in diabetic dysfunction begun to be elucidated. There is accumulating evidence that this pathway is implicated in diabetic damage to the pancreas, heart, and skin, among other cell types and tissues...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28888322/tor-the-gateway-to-cellular-metabolism-cell-growth-and-disease
#4
John Blenis
Michael N. Hall is this year's recipient of the Lasker Basic Medical Research Award for the identification of the target of rapamycin, TOR. TOR is a master regulator of the cell's growth and metabolic state, and its dysregulation contributes to a variety of diseases, including diabetes, obesity, neurodegenerative disorders, aging, and cancer, making the TOR pathway an attractive therapeutic target.
September 21, 2017: Cell
https://www.readbyqxmd.com/read/28887210/can-half-marathon-affect-overall-health-the-yin-yang-of-sport
#5
Luca Dalle Carbonare, Marcello Manfredi, Giuseppe Caviglia, Eleonora Conte, Elisa Robotti, Emilio Marengo, Samuele Cheri, Francesco Zamboni, Daniele Gabbiani, Michela Deiana, Daniela Cecconi, Federico Schena, Monica Mottes, Maria Teresa Valenti
Physical activity improves overall health and counteracts metabolic pathologies. Adipose tissue and bone are important key targets of exercise; the prevalence of diseases associated with suboptimal physical activity levels has increased in recent times as a result of lifestyle changes. Mesenchymal stem cells (MSCs) differentiation in either osteogenic or adipogenic lineage is regulated by many factors. Particularly, the expression of master genes such as RUNX2 and PPARγ2 is essential for MSC commitment to osteogenic or adipogenic differentiation, respectively...
September 5, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28886986/role-of-connexin-and-pannexin-containing-channels-in-hiv-infection-and-neuroaids
#6
REVIEW
Shaily Malik, Eliseo A Eugenin
Neuron-Glia crosstalk is essential for efficient synaptic communication, cell growth and differentiation, neuronal activity, neurotransmitter recycling, and brain immune response. The master regulators of this neuron-glia communication are connexin containing Gap Junctions (GJs) and Hemichannels (HCs) as well as pannexin HCs. However, the role of these channels under pathological conditions, especially in infectious diseases is still in exploratory stages. Human Immunodeficiency Virus-1 (HIV) is one such infectious agent that takes advantage of the host intercellular communication systems, GJs and HCs, to exacerbate viral pathogenesis in the brain in spite of the antiretroviral therapy effectively controlling viral replication in the periphery...
September 5, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28880992/innate-lymphoid-cells-at-the-interface-between-obesity-and-asthma
#7
REVIEW
Laetitia Everaere, Saliha Ait Yahia, Mélodie Bouté, Camille Audousset, Cécile Chenivesse, Anne Tsicopoulos
Obesity and asthma prevalence has dramatically and concomitantly increased over the last 25 years, and many epidemiological studies have highlighted obesity as an important risk factor for asthma. Although many studies have been performed, the underlying mechanisms remain poorly understood. Innate mechanisms have been involved in both diseases in particular through the recently described innate lymphoid cells (ILCs). ILCs are subdivided in three groups that are defined by their cytokine production and by their master transcription factor expression, in sharp correlation with their T helper counterparts...
September 7, 2017: Immunology
https://www.readbyqxmd.com/read/28879523/regulatory-t-cells-molecular-and-cellular-basis-for-immunoregulation
#8
Yosuke Togashi, Hiroyoshi Nishikawa
CD4(+) regulatory T cells (Tregs) are a highly immune-suppressive subset of CD4(+) T cells, characterized by expression of the master regulatory transcription factor FOXP3. Tregs are proven to play central roles in the maintenance of self-tolerance in healthy individuals. Tregs are involved in maintaining immune homeostasis: they protect hosts from developing autoimmune diseases and allergy, whereas in malignancies, they promote tumor progression by suppressing anti-tumor immunity. Elucidating factors influencing Treg homeostasis and function have important implications for understanding disease pathogenesis and identifying therapeutic opportunities...
September 7, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28877953/anti-inflammatory-roles-of-p38%C3%AE-mapk-in-macrophages-are-context-dependent-and-require-il-10
#9
Abbas Raza, Jessica W Crothers, Mahalia M McGill, Gary M Mawe, Cory Teuscher, Dimitry N Krementsov
The p38 MAPK pathway was originally identified as a master regulator of proinflammatory cytokine production by myeloid cells. Numerous drugs targeting this kinase showed promise in preclinical models of inflammatory disease, but so far, none have shown efficacy in clinical trials. The reasons behind this are unclear, but may, in part, be explained by emerging anti-inflammatory functions of this kinase or overly refined selectivity of second-generation pharmacologic inhibitors. Here, we show that p38α signaling in macrophages plays pro- and anti-inflammatory functions in vivo and in vitro, with the outcome depending on the stimulus, output, kinetics, or mode of kinase inhibition (genetic vs...
September 6, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28871224/nfix-as-a-master-regulator-for-lung-cancer-progression
#10
Nor I A Rahman, Nor A Abdul Murad, Mohammad M Mollah, Rahman Jamal, Roslan Harun
About 40% of lung cancer cases globally are diagnosed at the advanced stage. Lung cancer has a high mortality and overall survival in stage I disease is only 70%. This study was aimed at finding a candidate of transcription regulator that initiates the mechanism for metastasis by integrating computational and functional studies. The genes involved in lung cancer were retrieved using in silico software. 10 kb promoter sequences upstream were scanned for the master regulator. Transient transfection of shRNA NFIXs were conducted against A549 and NCI-H1299 cell lines...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28862076/timing-the-microbes-the-circadian-rhythm-of-the-gut-microbiome
#11
Xue Liang, Garret A FitzGerald
The mammalian circadian clock system, which includes the master clock and peripheral clocks, times different biological processes in reaction to external cues, such as the light-dark cycle. However, the chronobiology of prokaryotic cells is less well understood, except for in cyanobacteria. The recent blooming of gut microbiome research has revealed a critical role for the trillions of microbes residing in the vertebrate gut in determining both health and disease in the host. The question of whether the gut microbiome exhibits circadian oscillation and how it synchronizes with the host circadian clock has attracted considerable interest...
August 1, 2017: Journal of Biological Rhythms
https://www.readbyqxmd.com/read/28860071/circadian-clock-as-possible-protective-mechanism-to-pollution-induced-keratinocytes-damage
#12
Mascia Benedusi, Elena Frigato, Mattia Beltramello, Cristiano Bertolucci, Giuseppe Valacchi
Ozone is among the most toxic environmental stressors to which we are continuously exposed. Due to its critical location, skin is one of the most susceptible tissues to oxidative stress damaging effect of ozone. An increasing collection of data suggests a significant role of circadian system in regulation of cellular response to oxidative stress. However, the molecular mechanism linking circadian clock and antioxidant pathway it is not completely understood. Here we investigated a possible protective role of entrained circadian clock to ozone induced damage in keratinocytes, the main cellular component of human epidermis...
August 28, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28852028/insulin-resistance-is-associated-with-reductions-in-specific-cognitive-domains-and-increases-in-csf-tau-in-cognitively-normal-adults
#13
Simon M Laws, Scott Gaskin, Amy Woodfield, Velandai Srikanth, David Bruce, Paul E Fraser, Tenielle Porter, Philip Newsholme, Nadeeja Wijesekara, Samantha Burnham, Vincent Doré, Qiao-Xin Li, Paul Maruff, Colin L Masters, Stephanie Rainey-Smith, Christopher C Rowe, Olivier Salvado, Victor L Villemagne, Ralph N Martins, Giuseppe Verdile
Growing evidence supports the hypothesis that type 2 diabetes (T2D) increases the risk of developing dementia. Experimental evidence from mouse models demonstrates that the induction of T2D/insulin resistance (IR) can promote the accumulation of Alzheimer's disease (AD) pathological features. However, the association of T2D with pathological and clinical phenotypes in humans is unclear. Here we investigate the relationship of indices of IR (HOMA-IR) and pancreatic β-cell function (HOMA-B) with cognitive performance across several domains (Verbal/Visual Episodic Memory, Executive Function, Language and a measure of Global cognition) and AD biomarkers (CSF Aβ42, T-tau/P-tau, hippocampal volume and neocortical Aβ-amyloid burden)...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28838841/mitochondria-as-pharmacological-targets-in-down-syndrome
#14
REVIEW
Daniela Valenti, Nady Braidy, Domenico De Rasmo, Anna Signorile, Leonardo Rossi, Atanas Georgiev Atanasov, Mariateresa Volpicella, Alexandra Henrion-Caude, Seyed Mohammad Nabavi, Rosa Anna Vacca
Mitochondria play a pivotal role in cellular energy-generating processes and are considered master regulators of cell life and death fate. Mitochondrial function integrates signalling networks in several metabolic pathways controlling neurogenesis and neuroplasticity. Indeed, dysfunctional mitochondria and mitochondrial-dependent activation of intracellular stress cascades are critical initiating events in many human neurodegenerative or neurodevelopmental diseases including Down syndrome (DS). It is well established that trisomy of human chromosome 21 can cause DS...
August 31, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28838620/emerging-roles-for-the-lysosome-in-lipid-metabolism
#15
REVIEW
Ashley M Thelen, Roberto Zoncu
Precise regulation of lipid biosynthesis, transport, and storage is key to the homeostasis of cells and organisms. Cells rely on a sophisticated but poorly understood network of vesicular and nonvesicular transport mechanisms to ensure efficient delivery of lipids to target organelles. The lysosome stands at the crossroads of this network due to its ability to process and sort exogenous and endogenous lipids. The lipid-sorting function of the lysosome is intimately connected to its recently discovered role as a metabolic command-and-control center, which relays multiple nutrient cues to the master growth regulator, mechanistic target of rapamycin complex (mTORC)1 kinase...
August 21, 2017: Trends in Cell Biology
https://www.readbyqxmd.com/read/28836724/sleeper-cells-the-stringent-response-and-persistence-in-the-borreliella-borrelia-burgdorferi-enzootic-cycle
#16
REVIEW
Felipe C Cabello, Henry P Godfrey, Julia V Bugrysheva, Stuart A Newman
Infections with tick-transmitted Borreliella (Borrelia) burgdorferi, the cause of Lyme disease, represent an increasingly large public health problem in North America and Europe. The ability of these spirochetes to maintain themselves for extended periods of time in their tick vectors and vertebrate reservoirs is crucial for continuance of the enzootic cycle as well as for the increasing exposure of humans to them. The stringent response mediated by the alarmone (p)ppGpp has been determined to be a master regulator in B...
August 24, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/28835462/a-novel-pyrin-associated-autoinflammation-with-neutrophilic-dermatosis-mutation-further-defines-14-3-3-binding-of-pyrin-and-distinction-to-familial-mediterranean-fever
#17
Fiona Moghaddas, Rafael Llamas, Dominic De Nardo, Helios Martinez-Banaclocha, Juan J Martinez-Garcia, Pablo Mesa-Del-Castillo, Paul J Baker, Vanessa Gargallo, Anna Mensa-Vilaro, Scott Canna, Ian P Wicks, Pablo Pelegrin, Juan I Arostegui, Seth L Masters
OBJECTIVE: Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis (PAAND) is a recently described monogenic autoinflammatory disease. The causal p.S242R MEFV mutation disrupts a binding motif of the regulatory 14-3-3 proteins within pyrin. Here, we investigate a family with clinical features consistent with PAAND in whom the novel p.E244K MEFV mutation, located in the +2 site of the 14-3-3 binding motif in pyrin, has been found. METHODS: Multiplex cytokine analyses were performed on p...
August 23, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28834744/mediator-med23-links-pigmentation-and-dna-repair-through-the-transcription-factor-mitf
#18
Min Xia, Kun Chen, Xiao Yao, Yichi Xu, Jiaying Yao, Jun Yan, Zhen Shao, Gang Wang
DNA repair is related to many physiological and pathological processes, including pigmentation. Little is known about the role of the transcriptional cofactor Mediator complex in DNA repair and pigmentation. Here, we demonstrate that Mediator MED23 plays an important role in coupling UV-induced DNA repair to pigmentation. The loss of Med23 specifically impairs the pigmentation process in melanocyte-lineage cells and in zebrafish. Med23 deficiency leads to enhanced nucleotide excision repair (NER) and less DNA damage following UV radiation because of the enhanced expression and recruitment of NER factors to chromatin for genomic stability...
August 22, 2017: Cell Reports
https://www.readbyqxmd.com/read/28832635/expression-of-the-angiogenic-mediator-angiopoietin-like-4-in-the-eyes-of-patients-with-proliferative-sickle-retinopathy
#19
Kathleen Jee, Murilo Rodrigues, Fabiana Kashiwabuchi, Brooks P Applewhite, Ian Han, Gerard Lutty, Morton F Goldberg, Gregg L Semenza, Silvia Montaner, Akrit Sodhi
The recent success of therapies directly targeting the angiogenic mediator, vascular endothelial growth factor (VEGF), for the treatment of proliferative diabetic retinopathy has encouraged clinicians to extend the use of anti-VEGF therapies for the treatment of another ischemic retinal vascular disease, proliferative sickle cell retinopathy (PSR), the most common cause of irreversible blindness in patients with sickle cell disease. However, results from case reports evaluating anti-VEGF therapies for PSR have been mixed...
2017: PloS One
https://www.readbyqxmd.com/read/28811274/hypoxia-in-combination-with-muscle-contraction-improves-insulin-action-and-glucose-metabolism-in-human-skeletal-muscle-via-the-hif-1%C3%AE-pathway
#20
Sven W Görgens, Tim Benninghoff, Kristin Eckardt, Christian Springer, Alexandra Chadt, Anita Melior, Jakob Wefers, Andrea Cramer, Jørgen Jensen, Kåre I Birkeland, Christian A Drevon, Hadi Al-Hasani, Jürgen Eckel
Skeletal muscle insulin resistance is the hallmark of type 2 diabetes, and develops long before the onset of the disease. It is well accepted that physical activity improves glycemic control but the knowledge on underlying mechanisms mediating the beneficial effects remains incomplete. Exercise is accompanied by a decrease in intramuscular oxygen levels resulting in induction of HIF-1α. HIF-1α is a master regulator of gene expression and might play an important role in skeletal muscle function and metabolism...
August 15, 2017: Diabetes
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