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https://www.readbyqxmd.com/read/28938518/antimicrobial-peptides-amps-the-quintessential-offense-and-defense-molecules-are-more-than-antimicrobials
#1
REVIEW
Seema Patel, Nadeem Akhtar
Antimicrobial peptides (AMPs) are cationic amphiphilic molecules with α-helix or β-sheet linear motifs and linear or cyclic configurations. For their role in 'defense and offense', they are present in all living organisms. AMPs are named so, as they inhibit a wide array of microbes by membrane pore formation and subsequent perturbation of mitochondrial membrane ionic balance. However, their functional repertoire is expanding with validated roles in cytotoxicity, wound healing, angiogenesis, apoptosis, and chemotaxis [1]...
September 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28936716/induction-of-reactive-oxygen-species-an-emerging-approach-for-cancer-therapy
#2
REVIEW
Zhengzhi Zou, Haocai Chang, Haolong Li, Songmao Wang
Reactive oxygen species (ROS), a group of ions and molecules, include hydroxyl radicals (·OH), alkoxyl radicals, superoxide anion (O2·-), singlet oxygen ((1)O2) and hydrogen peroxide (H2O2). Hydroxyl radicals and alkoxyl radicals are extremely and highly reactive species respectively. Endogenous ROS are mainly formed in mitochondrial respiratory chain. Low levels of ROS play important roles in regulating biological functions in mammalian cells. However, excess production of ROS can induce cell death by oxidative damaging effects to intracellular biomacromolecules...
September 21, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28935446/mitochondrial-adaptation-in-steatotic-mice
#3
Claudia Einer, Simon Hohenester, Ralf Wimmer, Lena Wottke, Renate Artmann, Sabine Schulz, Christian Gosmann, Alisha Simmons, Christin Leitzinger, Carola Eberhagen, Sabine Borchard, Sabine Schmitt, Stefanie M Hauck, Christine von Toerne, Martin Jastroch, Ellen Walheim, Christian Rust, Alexander L Gerbes, Bastian Popper, Doris Mayr, Max Schnurr, Angelika M Vollmar, Gerald Denk, Hans Zischka
Western lifestyle-associated malnutrition causes steatosis that may progress to liver inflammation and mitochondrial dysfunction has been suggested as a key factor in promoting this disease. Here we have molecularly, biochemically and biophysically analyzed mitochondria from steatotic wild type and immune-compromised mice fed a Western diet (WD) - enriched in saturated fatty acids (SFAs). WD-mitochondria demonstrated lipidomic changes, a decreased mitochondrial ATP production capacity and a significant sensitivity to calcium...
September 18, 2017: Mitochondrion
https://www.readbyqxmd.com/read/28931762/emerging-therapies-for-acute-myeloid-leukemia-translating-biology-into-the-clinic
#4
REVIEW
Simon Kavanagh, Tracy Murphy, Arjun Law, Dana Yehudai, Jenny M Ho, Steve Chan, Aaron D Schimmer
Acute myeloid leukemia (AML) is an aggressive hematological malignancy with a poor outcome; overall survival is approximately 35% at two years and some subgroups have a less than 5% two-year survival. Recently, significant improvements have been made in our understanding of AML biology and genetics. These fundamental discoveries are now being translated into new therapies for this disease. This review will discuss recent advances in AML biology and the emerging treatments that are arising from biological studies...
September 21, 2017: JCI Insight
https://www.readbyqxmd.com/read/28930519/divergent-impact-of-gender-in-advancement-of-liver-injuries-diseases-and-carcinogenesis
#5
Subhrajit Biswas, Sampa Ghose
Several investigations have revealed that liver diseases exhibit gender biases, but identifying the root causes of such biases has been challenging. Evidence of gender differences in liver function is present from the early stage of embryonic development. The differences in access to care and treatment as well as diagnostic deliberation may affect gender-specific differences in liver disease progression. Apart from the pathogenesis, xenobiotic metabolism, immune responses, gene expressions, mitochondrial function, lipid composition, and enzyme activities also differ in this sexually dimorphic organ...
January 1, 2018: Frontiers in Bioscience (Scholar Edition)
https://www.readbyqxmd.com/read/28928729/high-throughput-genetic-screen-reveals-that-early-attachment-and-biofilm-formation-are-necessary-for-full-pyoverdine-production-by-pseudomonas-aeruginosa
#6
Donghoon Kang, Natalia V Kirienko
Pseudomonas aeruginosa is a re-emerging, multidrug-resistant, opportunistic pathogen that threatens the lives of immunocompromised patients, patients with cystic fibrosis, and those in critical care units. One of the most important virulence factors in this pathogen is the siderophore pyoverdine. Pyoverdine serves several critical roles during infection. Due to its extremely high affinity for ferric iron, pyoverdine gives the pathogen a significant advantage over the host in their competition for iron. In addition, pyoverdine can regulate the production of multiple bacterial virulence factors and perturb host mitochondrial homeostasis...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28928268/mild-acidosis-delays-neutrophil-apoptosis-via-multiple-signaling-pathways-and-acts-in-concert-with-inflammatory-mediators
#7
Driss El Kebir, Everton de Oliveira Lima Dos Santos, Soukaina Mansouri, Meriem Sekheri, János G Filep
Accumulating evidence indicates development of local extracellular acidosis in inflamed tissues in response to infection and tissue injury. Activation of infiltrating neutrophils contributes to a transient decrease in pH, which, in turn, triggers innate immunity. In this study, we investigated the impact of extracellular acidosis on neutrophil apoptosis, a critical determinant of the outcome of the inflammatory response and analyzed the underlying signaling pathways. Culture of human isolated neutrophils in mildly acidotic conditions (pH 6...
September 19, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28926641/impact-of-monotherapy-on-hiv-1-reservoir-immune-activation-and-co-infection-with-epstein-barr-virus
#8
Maria Raffaella Petrara, Anna Maria Cattelan, Lolita Sasset, Riccardo Freguja, Francesco Carmona, Silvia Sanavia, Marisa Zanchetta, Paola Del Bianco, Anita De Rossi
OBJECTIVES: Although monotherapy (mART) effectiveness in maintaining viral suppression and CD4 cell count has been extensively examined in HIV-1-infected patients, its impact on HIV-1 reservoir, immune activation, microbial translocation and co-infection with Epstein-Barr Virus (EBV) is unclear. METHODS: This retrospective study involved 32 patients who switched to mART; patients were studied at baseline, 48 and 96 weeks after mART initiation. Thirty-two patients who continued combined antiretroviral therapy (cART) over the same period of time were included in the study...
2017: PloS One
https://www.readbyqxmd.com/read/28923365/mitochondrial-dynamics-at-the-interface-of-immune-cell-metabolism-and-function
#9
REVIEW
Angelika S Rambold, Erika L Pearce
Immune cell differentiation and function are crucially dependent on specific metabolic programs dictated by mitochondria, including the generation of ATP from the oxidation of nutrients and supplying precursors for the synthesis of macromolecules and post-translational modifications. The many processes that occur in mitochondria are intimately linked to their morphology that is shaped by opposing fusion and fission events. Exciting evidence is now emerging that demonstrates reciprocal crosstalk between mitochondrial dynamics and metabolism...
September 8, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28923349/katp-channel-block-inhibits-the-toll-like-receptor-2-mediated-stimulation-of-nf-%C3%AE%C2%BAb-by-suppressing-the-activation-of-akt-mtor-jnk-and-p38-mapk
#10
Yoon Jeong Nam, Arum Kim, Min Sung Lee, Dong Suep Sohn, Chung Soo Lee
Changes in the KATP channel activity have been shown to regulate inflammation and immune responses. Using human keratinocytes, we investigated the effect of KATP channel inhibition on inflammatory mediator production in relation to the Toll like receptor-2-mediated-Akt, mTOR and NF-κB pathways, as well as JNK and p38-MAPK, which regulate the transcription genes involved in immune and inflammatory responses. 5-Hydroxydecanoate (a selective KATP channel blocker), glibenclamide (a cell surface and mitochondrial KATP channel inhibitor), the Akt inhibitor, rapamycin, Bay 11-7085 and N-acetylcysteine reduced the lipoteichoic acid- or peptidoglycan-induced production of cytokines and chemokines, and production of reactive oxygen species and increased the levels and activities of Kir 6...
September 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28922472/mirna-506-promotes-primary-biliary-cholangitis-like-features-in-cholangiocytes-and-immune-activation
#11
Oihane Erice, Patricia Munoz-Garrido, Javier Vaquero, Maria J Perugorria, Maite G Fernandez-Barrena, Elena Saez, Alvaro Santos-Laso, Ander Arbelaiz, Raul Jimenez-Agüero, Joaquin Fernandez-Irigoyen, Enrique Santamaria, Verónica Torrano, Arkaitz Carracedo, Meenakshisundaram Ananthanarayanan, Marco Marzioni, Jesus Prieto, Ulrich Beuers, Ronald P Oude Elferink, Nicholas F LaRusso, Luis Bujanda, Jose J G Marin, Jesus M Banales
Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease associated with autoimmune phenomena targeting intrahepatic bile duct cells (cholangiocytes). Although PBC etiopathogenesis still remains obscure, development of anti-mitochondrial auto-antibodies against pyruvate dehydrogenase complex-E2 (PDC-E2) is a common feature. MicroRNA (miR) dysregulation occurs in liver and immune cells of PBC patients, but their functional relevance is largely unknown. We previously reported that miR-506 is overexpressed in PBC cholangiocytes and directly targets both Cl(-) /HCO3(-) anion exchanger 2 (AE2) and type III inositol 1,4,5-trisphosphate receptor (InsP3R3), leading to cholestasis...
September 18, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28920955/mir-25-93-mediates-hypoxia-induced-immunosuppression-by-repressing-cgas
#12
Min-Zu Wu, Wei-Chung Cheng, Su-Feng Chen, Shin Nieh, Carolyn O'Connor, Chia-Lin Liu, Wen-Wei Tsai, Cheng-Jang Wu, Lorena Martin, Yaoh-Shiang Lin, Kou-Juey Wu, Li-Fan Lu, Juan Carlos Izpisua Belmonte
The mechanisms by which hypoxic tumours evade immunological pressure and anti-tumour immunity remain elusive. Here, we report that two hypoxia-responsive microRNAs, miR-25 and miR-93, are important for establishing an immunosuppressive tumour microenvironment by downregulating expression of the DNA sensor cGAS. Mechanistically, miR-25/93 targets NCOA3, an epigenetic factor that maintains basal levels of cGAS expression, leading to repression of cGAS during hypoxia. This allows hypoxic tumour cells to escape immunological responses induced by damage-associated molecular pattern molecules, specifically the release of mitochondrial DNA...
September 18, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28916263/autophagy-dependent-generation-of-free-fatty-acids-is-critical-for-normal-neutrophil-differentiation
#13
Thomas Riffelmacher, Alexander Clarke, Felix C Richter, Amanda Stranks, Sumeet Pandey, Sara Danielli, Philip Hublitz, Zhanru Yu, Errin Johnson, Tobias Schwerd, James McCullagh, Holm Uhlig, Sten Eirik W Jacobsen, Anna Katharina Simon
Neutrophils are critical and short-lived mediators of innate immunity that require constant replenishment. Their differentiation in the bone marrow requires extensive cytoplasmic and nuclear remodeling, but the processes governing these energy-consuming changes are unknown. While previous studies show that autophagy is required for differentiation of other blood cell lineages, its function during granulopoiesis has remained elusive. Here, we have shown that metabolism and autophagy are developmentally programmed and essential for neutrophil differentiation in vivo...
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28915214/non-hemodynamic-effects-of-catecholamines
#14
Clair Hartmann, Peter Radermacher, Martin Wepler, Benedikt Nußbaum
Circulatory shock is defined as an imbalance between tissue oxygen supply and demand, and mostly results from a loss of blood volume, cardiac pump failure, and/or reduction of vasomotor tone. The clinical hallmarks of circulatory shock are arterial hypotension and lactate acidosis. Since the degree and duration of hypotension are major determinants of outcome, vasopressor administration represents a cornerstone therapy to treat these patients. Current guidelines recommend the use of catecholamines as the drug of first choice...
October 2017: Shock
https://www.readbyqxmd.com/read/28904196/vaccinia-virus-encodes-a-novel-inhibitor-of-apoptosis-that-associates-with-the-apoptosome
#15
Melissa R Ryerson, Monique M Richards, Marc Kvansakul, Christine J Hawkins, Joanna L Shisler
Apoptosis is an important anti-viral host defense mechanism. Here we report the identification of a novel apoptosis inhibitor encoded by the vaccinia virus (VACV) M1L gene. M1L is absent in the attenuated MVA strain of VACV, a strain that stimulates apoptosis in several types of immune cells. M1 expression increased the viability of MVA-infected THP-1 and Jurkat cells and reduced several biochemical hallmarks of apoptosis such as PARP-1 and procaspase-3 cleavage. Furthermore, ectopic M1L expression decreased staurosporine-induced (intrinsic) apoptosis in HeLa cells...
September 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28902841/cgas-senses-long-and-hmgb-tfam-bound-u-turn-dna-by-forming-protein-dna-ladders
#16
Liudmila Andreeva, Björn Hiller, Dirk Kostrewa, Charlotte Lässig, Carina C de Oliveira Mann, David Jan Drexler, Andreas Maiser, Moritz Gaidt, Heinrich Leonhardt, Veit Hornung, Karl-Peter Hopfner
Cytosolic DNA arising from intracellular pathogens triggers a powerful innate immune response. It is sensed by cyclic GMP-AMP synthase (cGAS), which elicits the production of type I interferons by generating the second messenger 2'3'-cyclic-GMP-AMP (cGAMP). Endogenous nuclear or mitochondrial DNA can also be sensed by cGAS under certain conditions, resulting in sterile inflammation. The cGAS dimer binds two DNA ligands shorter than 20 base pairs side-by-side, but 20-base-pair DNA fails to activate cGAS in vivo and is a poor activator in vitro...
September 21, 2017: Nature
https://www.readbyqxmd.com/read/28899515/the-water-extract-of-liuwei-dihuang-possesses-multi-protective-properties-on-neurons-and-muscle-tissue-against-deficiency-of-survival-motor-neuron-protein
#17
Yu-Ting Tseng, Yuh-Jyh Jong, Wei-Fang Liang, Fang-Rong Chang, Yi-Ching Lo
BACKGROUND: Deficiency of survival motor neuron (SMN) protein, which is encoded by the SMN1 and SMN2 genes, induces widespread splicing defects mainly in spinal motor neurons, and leads to spinal muscular atrophy (SMA). Currently, there is no effective treatment for SMA. Liuwei dihuang (LWDH), a traditional Chinese herbal formula, possesses multiple therapeutic benefits against various diseases via modulation of the nervous, immune and endocrine systems. Previously, we demonstrated water extract of LWDH (LWDH-WE) protects dopaminergic neurons and improves motor activity in models of Parkinson's disease...
October 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28889481/a-review-of-the-biologic-and-clinical-significance-of-genetic-mutations-in-angioimmunoblastic-t-cell-lymphoma
#18
REVIEW
Kota Fukumoto, Tran B Nguyen, Shigeru Chiba, Mamiko Sakata-Yanagimoto
Angioimmunoblastic T-cell lymphoma (AITL) is an age-related malignant lymphoma, characterized by immune system-dysregulated symptoms. Recent sequencing studies have clarified the recurrent mutations in ras homology family member A (RHOA) and in genes encoding epigenetic regulators, tet methyl cytosine dioxygenase 2 (TET2), DNA methyl transferase 3 alpha (DNMT3A), and isocitrate dehydrogenase 2, mitochondrial (IDH2), as well as those related to the T-cell receptor signaling pathway in AITL. In this review, we will focus on how this genetic information has changed the understanding of the developmental process of AITL and will in future lead to individualized therapies for AITL patients...
September 10, 2017: Cancer Science
https://www.readbyqxmd.com/read/28884828/neutrophil-extracellular-traps-in-acrolein-promoted-hepatic-ischemia-reperfusion-injury-therapeutic-potential-of-nox2-and-p38mapk-inhibitors
#19
Arumugam Suyavaran, Kesthuru Subbiah Girish, K Kemparaju, Chinnasamy Thirunavukkarasu
Neutrophil is a significant contributor to ischemia reperfusion (IR) induced liver tissue damage. However, the underlying mechanisms of IR induced innate immune activation and liver damage is not quite clear. Our study sheds light on the role of chronic oxidative stress end products in worsening the IR inflammatory process by neutrophil recruitment and activation following liver surgery. We employed specific inhibitors for molecular targets - NOX2 (NADPH oxidase 2) and P38 MAPK (Mitogen activated protein kinase) signal to counteract neutrophil activation and neutrophil extracellular trap (NET) release induced liver damage in IR injury...
September 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28881757/antagonistic-effects-of-selenium-on-cadmium-induced-apoptosis-by-restoring-the-mitochondrial-dynamic-equilibrium-and-energy-metabolism-in-chicken-spleens
#20
Zhe Xu, Xi Jin, Tingru Pan, Tianqi Liu, Na Wan, Shu Li
The aim of this study was to investigate the mechanism of cadmium-induced apoptosis in chicken spleens and the antagonistic effects of selenium. We duplicated the selenium-cadmium interaction model and examined the expression of apoptosis-, immune-, mitochondrial dynamics- and energy metabolism-related genes. The results demonstrated that after treatment with cadmium, the frequency of apoptosis was significantly increased, and the morphological characteristics of apoptosis were observed. The expression of pro-apoptotic genes was increased, and that of anti-apoptotic genes was decreased...
August 8, 2017: Oncotarget
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