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https://www.readbyqxmd.com/read/28699644/roles-of-apol1%C3%A2-g1-and-g2-variants-in-sickle-cell-disease-patients-kidney-is-the-main-target
#1
Raphaël Kormann, Anne-Sophie Jannot, Céline Narjoz, Jean-Antoine Ribeil, Sandra Manceau, Marianne Delville, Valentin Joste, Dominique Prié, Jacques Pouchot, Eric Thervet, Marie Courbebaisse, Jean-Benoît Arlet
In African-American patients with sickle cell disease (SCD), APOL1 G1 and G2 variants are associated with increased risk of sickle cell nephropathy (SCN). To determine the role of APOL1 variants in SCD patients living in Europe, we genotyped 152 SCD patients [aged 30·4 (24·3-36·4) years], mainly of Sub-Saharan African ancestry, for APOL1 G1 and G2 and for variants of four genes with kidney tropism (GSTM1, GSTT1, GSTP1, and HMOX1). Homozygous or double-heterozygous APOL G1 and G2 genotypes were strongly associated with end stage renal disease (P = 0·003) and worse Kidney Disease: Improving Global Outcomes stages (P = 0·001)...
July 12, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28682603/comparison-of-the-acute-immunotoxicity-of-non-fractionated-and-fractionated-oil-sands-process-affected-water-using-mammalian-macrophages
#2
Li Fu, Chao Li, Dustin M E Lillico, Nicole A I Phillips, Mohamed Gamal El-Din, Miodrag Belosevic, James L Stafford
OSPW is a complex mixture of inorganic and organic substances and its principal toxic components have yet to be fully characterized. Previously, we showed that the OSPW organic fraction (OF) caused a concentration-dependent immunotoxicity in mammals. In the present study we further explore the immunotoxicological properties of OSPW in mammals using a series of in vitro bioassays. Specifically, using the RAW 264.7 mouse macrophage cell line we show that whole OSPW containing NA concentrations ranging from 12-18 mg/L, significantly inhibited cell proliferation, reduced cell viability, and was directly cytotoxic, whereas the exposure of cells to equivalent doses of the OSPW-OF had no effects...
July 6, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28681934/3-4-dihydroxybenzalacetone-and-caffeic-acid-phenethyl-ester-induce-preconditioning-er-stress-and-autophagy-in-sh-sy5y-cells
#3
Ryoichi Tomiyama, Ken Takakura, Shouhei Takatou, Thuong Manh Le, Takumi Nishiuchi, Yutaka Nakamura, Tetsuya Konishi, Seiichi Matsugo, Osamu Hori
3,4-dihydroxybenzalacetone (DBL) and Caffeic acid phenethyl ester (CAPE) are both catechol-containing phenylpropanoid derivatives with diverse bioactivities. In the present study, we analyzed the ability of these compounds to activate the unfolded protein response (UPR) and the oxidative stress response. When human SH-SY5Y neuroblastoma cells were treated with DBL or CAPE, the expression of endoplasmic reticulum (ER) stress-related genes such as HSPA5, HYOU1, DDIT3, and SEC61b increased to a larger extent in response to CAPE treatment, while that of antioxidant genes such as HMOX1, GCLM, and NQO1 increased to a larger extent in response to DBL treatment...
July 6, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28659758/chronic-oxidative-stress-mitochondrial-dysfunction-nrf2-activation-and-inflammation-in-the-hippocampus-accompany-heightened-systemic-inflammation-and-oxidative-stress-in-an-animal-model-of-gulf-war-illness
#4
Geetha A Shetty, Bharathi Hattiangady, Dinesh Upadhya, Adrian Bates, Sahithi Attaluri, Bing Shuai, Maheedhar Kodali, Ashok K Shetty
Memory and mood dysfunction are the key symptoms of Gulf war illness (GWI), a lingering multi-symptom ailment afflicting >200,000 veterans who served in the Persian Gulf War-1. Research probing the source of the disease has demonstrated that concomitant exposures to anti-nerve gas agent pyridostigmine bromide (PB), pesticides, and war-related stress are among the chief causes of GWI. Indeed, exposures to GWI-related chemicals (GWIR-Cs) and mild stress in animal models cause memory and mood impairments alongside reduced neurogenesis and chronic low-level inflammation in the hippocampus...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28652203/effects-of-mild-ozonisation-on-gene-expression-and-nuclear-domains-organization-in-vitro
#5
C Scassellati, M Costanzo, B Cisterna, A Nodari, M Galiè, A Cattaneo, V Covi, G Tabaracci, C Bonvicini, M Malatesta
In the last two decades, the use of ozone (O3) as a complementary medical approach has progressively been increasing; however, its application is still limited due to the numerous doubts about its possible toxicity, despite the low concentrations used in therapy. For an appropriate and safe clinical application of a potentially toxic agent such as O3, it is crucial to elucidate the cellular response to its administration. Molecular analyses and transmission electron microscopy were here combined to investigate in vitro the effects of O3 administration on transcriptional activity and nuclear domains organization of cultured SH-SY5Y neuronal cells; low O3 concentrations were used as those currently administered in clinical practice...
June 23, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28647573/focal-adhesion-kinase-signaling-regulates-anti-inflammatory-function-of-bone-marrow-mesenchymal-stromal-cells-induced-by-biomechanical-force
#6
Hyun Jung Lee, Miguel F Diaz, Adesuwa Ewere, Scott D Olson, Charles S Cox, Pamela L Wenzel
Mesenchymal stromal cells (MSCs) have tremendous potential for use in regenerative medicine due to their multipotency and immune cell regulatory functions. Biomimetic physical forces have been shown to direct differentiation and maturation of MSCs in tissue engineering applications; however, the effect of force on immunomodulatory activity of MSCs has been largely overlooked. Here we show in human bone marrow-derived MSCs that wall shear stress (WSS) equivalent to the fluid frictional force present in the adult arterial vasculature significantly enhances expression of four genes that mediate MSC immune regulatory function, PTGS2, HMOX1, IL1RN, and TNFAIP6...
June 21, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28603087/cysteine-rich-whey-protein-isolate-immunocal%C3%A2-ameliorates-deficits-in-the-gfap-hmox1-mouse-model-of-schizophrenia
#7
Wei Song, Ayda Tavitian, Marisa Cressatti, Carmela Galindez, Adrienne Liberman, Hyman M Schipper
Schizophrenia is a neuropsychiatric disorder that features neural oxidative stress and glutathione (GSH) deficits. Oxidative stress is augmented in brain tissue of GFAP.HMOX1 transgenic mice which exhibit schizophrenia-relevant characteristics. The whey protein isolate, Immunocal® serves as a GSH precursor upon oral administration. In this study, we treated GFAP.HMOX1 transgenic mice daily with either Immunocal (33mg/ml drinking water) or equivalent concentrations of casein (control) between the ages of 5 and 6...
June 8, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28591612/role-of-ambient-gas-composition-on-cold-physical-plasma-elicited-cell-signaling-in-keratinocytes
#8
Anke Schmidt, Sander Bekeschus, Helena Jablonowski, Annemarie Barton, Klaus-Dieter Weltmann, Kristian Wende
A particularly promising medical application of cold physical plasma is the support of wound healing. This is presumably achieved by modulating inflammation as well as skin cell signaling and migration. Plasma-derived reactive oxygen and nitrogen species (ROS/RNS) are assumed the central biologically active plasma components. We hypothesized that modulating the environmental plasma conditions from pure nitrogen (N2) to pure oxygen (O2) in an atmospheric pressure argon plasma jet (kINPen) will change type and concentration of ROS/RNS and effectively tune the behavior of human skin cells...
June 6, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28575702/gene-expression-profiles-and-bioinformatics-analysis-of-human-umbilical-vein-endothelial-cells-exposed-to-pm2-5
#9
Hejing Hu, Collins Otieno Asweto, Jing Wu, Yanfeng Shi, Lin Feng, Xiaozhe Yang, Shuang Liang, Lige Cao, Junchao Duan, Zhiwei Sun
Cardiovascular system is demonstrated the main target of PM2.5 and the objective of this study was to explore the toxic effect and molecular mechanisms caused by PM2.5 in primary human umbilical vein endothelial cells (HUVECs) using microarray and bioinformatics analysis. The results showed that 591 genes were differentially expressed triggered by PM2.5, of which 174 genes were down-regulated, while 417 genes were up-regulated. Gene ontology analysis revealed that PM2.5 caused significant changes in gene expression patterns, including response to stimuli, immune response, and cellular processes...
May 27, 2017: Chemosphere
https://www.readbyqxmd.com/read/28534119/splenic-ly6c-hi-monocytes-contribute-to-adverse-late-post-ischemic-left-ventricular-remodeling-in-heme-oxygenase-1-deficient-mice
#10
Mateusz Tomczyk, Izabela Kraszewska, Krzysztof Szade, Karolina Bukowska-Strakova, Marco Meloni, Alicja Jozkowicz, Jozef Dulak, Agnieszka Jazwa
Heme oxygenase-1 (Hmox1) is a stress-inducible protein crucial in heme catabolism. The end products of its enzymatic activity possess anti-oxidative, anti-apoptotic and anti-inflammatory properties. Cardioprotective effects of Hmox1 were demonstrated in experimental models of myocardial infarction (MI). Nevertheless, its importance in timely resolution of post-ischemic inflammation remains incompletely understood. The aim of this study was to determine the role of Hmox1 in the monocyte/macrophage-mediated cardiac remodeling in a mouse model of MI...
July 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28511916/pre-treatment-with-amitriptyline-causes-epigenetic-up-regulation-of-neuroprotection-associated-genes-and-has-anti-apoptotic-effects-in-mouse-neuronal-cells
#11
Nguyen Quoc Vuong Tran, An Nghia Nguyen, Kyoko Takabe, Zentaro Yamagata, Kunio Miyake
Antidepressants, such as imipramine and fluoxetine, are known to alter gene expression patterns by inducing changes in the epigenetic status of neuronal cells. There is also some evidence for the anti-apoptotic effect of various groups of antidepressants; however, this effect is complicated and cell-type dependent. Antidepressants of the tricyclic group, in particular amitriptyline, have been suggested to be beneficial in the treatment of neurodegenerative disorders. We examined whether amitriptyline exerts an anti-apoptotic effect via epigenetic mechanisms...
May 13, 2017: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/28506826/an-x-chromosome-linked-mouse-model-ndufa1-s55a-for-systemic-partial-complex-i-deficiency-for-studying-predisposition-to-neurodegeneration-and-other-diseases
#12
Chul Kim, Prasanth Potluri, Ahmed Khalil, Daria Gaut, Meagan McManus, Shannon Compton, Douglas C Wallace, Nagendra Yadava
The respiratory chain Complex I deficiencies are the most common cause of mitochondrial diseases. Complex I biogenesis is controlled by 58 genes and at least 47 of these cause mitochondrial disease in humans. Two of these are X-chromosome linked nuclear (nDNA) genes (NDUFA1 and NDUFB11), and 7 are mitochondrial (mtDNA, MT-ND1-6, -4L) genes, which may be responsible for sex-dependent variation in the presentation of mitochondrial diseases. In this study, we describe an X-chromosome linked mouse model (Ndufa1(S55A)) for systemic partial Complex I deficiency...
May 12, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28503778/a-topical-zinc-ionophore-blocks-tumorigenic-progression-in-uv-exposed-skh-1-high-risk-mouse-skin
#13
Rebecca Justiniano, Jessica Perer, Anh Hua, Mohammad Fazel, Andrea Krajisnik, Christopher M Cabello, Georg T Wondrak
Nonmelanoma skin cancer (NMSC) is the most common malignancy in the United States representing a considerable public health burden. Pharmacological suppression of skin photocarcinogenesis has shown promise in preclinical and clinical studies, but more efficacious photochemopreventive agents are needed. Here, we tested feasibility of harnessing pharmacological disruption of intracellular zinc homeostasis for photochemoprevention in vitro and in vivo. Employing the zinc ionophore and FDA-approved microbicidal agent zinc pyrithione (ZnPT), used worldwide in over-the-counter (OTC) topical consumer products, we first demonstrated feasibility of achieving ZnPT-based intracellular Zn(2+) overload in cultured malignant keratinocytes (HaCaT-ras II-4; SCC-25) employing membrane-permeable fluorescent probes...
May 15, 2017: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/28475120/protective-effect-of-fragaria-ananassa-crude-extract-on-cadmium-induced-lipid-peroxidation-antioxidant-enzymes-suppression-and-apoptosis-in-rat-testes
#14
Mohammed I Y Elmallah, Manal F Elkhadragy, Ebtesam M Al-Olayan, Ahmed E Abdel Moneim
Cadmium is a deleterious environmental pollutant that threats both animals and human health. Oxidative stress and elevated levels of reactive oxygen species (ROS) have recently been reported to be the main cause of cellular damage as a result of cadmium exposure. We investigate, here, the protective effect of strawberry crude extracts on cadmium-induced oxidative damage of testes in rats. Four groups (n = 8) of 32 adult male Wistar rats weighing 160-180 g were used. The control group received 0.9% saline solution all over the experimental period (5 days)...
May 5, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28466968/clinical-and-genetic-predictors-of-renal-dysfunctions-in-sickle-cell-anaemia-in-cameroon
#15
Amy Geard, Gift D Pule, Bernard Chetcha Chemegni, Valentina J Ngo Bitoungui, Andre P Kengne, Emile R Chimusa, Ambroise Wonkam
Micro-albuminuria and glomerular hyperfiltration are primary indicators of renal dysfunctions in Sickle Cell Disease (SCD), with more severe manifestations previously associated with variants in APOL1 and HMOX1 among African Americans. We have investigated 413 SCD patients from Cameroon. Anthropometric variables, haematological indices, crude albuminuria, albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were measured. Patients were genotyped for 3·7 kb alpha-globin gene (HBA1/HBA2) deletion, and for variants in APOL1 (G1/G2; rs60910145, rs73885319, rs71785313) and HMOX1 (rs3074372, rs743811)...
May 3, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28458133/scutellarin-derivatives-as-apoptosis-inducers-design-synthesis-and-biological-evaluation
#16
Tong Han, Jia Li, Jingjing Xue, He Li, Fanxing Xu, Keguang Cheng, Dahong Li, Zhanlin Li, Ming Gao, Huiming Hua
To explore novel antitumor agents with high efficiency and low toxicity, a series of NO-donating scutellarin derivatives (14-17) were synthesized and the antiproliferative activities against MCF-7, HCT-116, PC-3 and HepG2 cancer cell lines were assessed. Among them, compound 14b was the strongest with IC50 values of 2.96 μM, 7.25 μM, 0.09 μM and 0.50 μM, respectively, and displayed low toxicity against normal human liver L-O2 cells with an IC50 of 47.96 μM, showing good selectivity between normal and malignant liver cells...
April 21, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28450126/flavonolignan-2-3-dehydrosilydianin-activates-nrf2-and-upregulates-nad-p-h-quinone-oxidoreductase-1-in-hepa1c1c7-cells
#17
Lenka Roubalová, Albena T Dinkova-Kostova, David Biedermann, Vladimír Křen, Jitka Ulrichová, Jiří Vrba
Silybum marianum (milk thistle) is a medicinal plant used for the treatment of various liver disorders. This study examined whether the main flavonolignans from S. marianum (i.e. silybin, silychristin, silydianin) and their 2,3-dehydro derivatives (i.e. 2,3-dehydrosilybin, 2,3-dehydrosilychristin, 2,3-dehydrosilydianin) activate the Nrf2 pathway, which regulates the expression of genes encoding many cytoprotective enzymes, including NAD(P)H:quinone oxidoreductase 1 (NQO1). After 48h of exposure, 2,3-dehydrosilydianin at concentrations of 25μM and higher significantly elevated the activity of NQO1 in murine hepatoma Hepa1c1c7 cells...
June 2017: Fitoterapia
https://www.readbyqxmd.com/read/28445367/adipose-tissue-drives-response-to-ischemia-reperfusion-injury-in-a-murine-pressure-sore-model
#18
Madeleine J Gust, Seok Jong Hong, Robert C Fang, Steven T Lanier, Donald W Buck, Jennifer M Nuñez, Shengxian Jia, Eugene D Park, Robert D Galiano, Thomas A Mustoe
BACKGROUND: Ischemia-reperfusion injury contributes significantly to the pathogenesis of chronic wounds such as pressure sores and diabetic foot ulcers. The authors' laboratory has previously developed a cyclical murine ischemia-reperfusion injury model. The authors here use this model to determine factors underlying tissue response to ischemia-reperfusion injury. METHODS: C57BL/6 mice were subjected to cycles of ischemia-reperfusion that varied in number (one to four cycles) and duration of ischemia (1 to 2 hours)...
May 2017: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28441900/placental-nfe2l2-is-discordantly-activated-in-monochorionic-twins-with-selective-intrauterine-growth-restriction-and-possibly-regulated-by-hypoxia
#19
Jing Wu, Zhiming He, Yu Gao, Guanglan Zhang, Xuan Huang, Qun Fang
INTRODUCTION: Nuclear factor, erythroid 2 like 2 (NFE2L2) is an important transcription factor that protects cells from oxidative stress (OS). NFE2L2 deficiency in placentas is associated with pregnancy complications. We have demonstrated that elevated OS existed in placental shares of the smaller fetus in selective intrauterine growth restriction (sIUGR); however, the role of NFE2L2 in the development of sIUGR remains unknown. In this study, we examined the levels of NFE2L2 and heme oxygenase 1 (HMOX1), a major antioxidant regulated by NFE2L2, in sIUGR placentas...
April 25, 2017: Free Radical Research
https://www.readbyqxmd.com/read/28438516/global-transcriptomic-profiling-of-cortex-and-striatum-cerebral-injury-after-ischemia-reperfusion-in-a-mouse-model
#20
Zhenying Zhao, Zhiqiang Lu, Xiuying Sun, Tianhong Zhao, Jihong Zhang, Cunxia Zhou, Xiaohui Zheng, Huijuan Zhang, Guiling Shi
OBJECTIVE: This study aims to investigate the molecular mechanism of injury development in the cortex and the striatum after cerebral ischemia/reperfusion (I/R). METHODS: Gene expression data (GSE23160) in the cortex and the striatum of an intraluminal middle cerebral artery occlusion-I/R mouse model (N = 12) and sham controls (N = 4) were downloaded from the Gene Expression Omnibus. Limma package was used to identify the differentially expressed genes (DEGs) between the I/R (2, 8, and 24 hours) and control groups...
April 21, 2017: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
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