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https://www.readbyqxmd.com/read/28934392/nceh-1-modulates-cholesterol-metabolism-and-protects-against-%C3%AE-synuclein-toxicity-in-a-c-elegans-model-of-parkinson-s-disease
#1
Siyuan Zhang, Samantha A Glukhova, Kim A Caldwell, Guy A Caldwell
Parkinson's disease (PD) is an aging-associated neurodegenerative disease affecting millions worldwide. Misfolding, oligomerization and accumulation of the human α-synuclein protein is a key pathological hallmark of PD and is associated with the progressive loss of dopaminergic neurons over the course of aging. Lifespan extension via the suppression of IGF-1/insulin-like signaling (IIS) offers a possibility to retard disease onset through induction of metabolic changes that provide neuroprotection. The nceh-1 gene of Caenorhabditis elegans encodes an ortholog of neutral cholesterol ester hydrolase 1 (NCEH-1), an IIS downstream protein that was identified in a screen as a modulator of α-synuclein accumulation in vivo...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28932752/local-rhbmp-12-on-an-absorbable-collagen-sponge-as-an-adjuvant-therapy-for-rotator-cuff-repair-a-phase-1-randomized-standard-of-care-control-multicenter-study-part-2-a-pilot-study-of-functional-recovery-and-structural-outcomes
#2
Junji Ide, Yu Mochizuki, Arthur van Noort, Hiroshi Ochi, Sudhakar Sridharan, Eiji Itoi, Stefan Greiner
BACKGROUND: The high failure rate of rotator cuff repairs requires the development of methods to enhance healing at the tendon-bone junction of the repair site. PURPOSE: To assess functional recovery and structural outcomes in detail after implanting recombinant human bone morphogenetic protein-12 (rhBMP-12)/absorbable collagen sponge (ACS) as adjuvant treatment during open rotator cuff repair in patients over a 1-year postoperative follow-up. STUDY DESIGN: Randomized controlled trial; Level of evidence, 2...
September 2017: Orthopaedic Journal of Sports Medicine
https://www.readbyqxmd.com/read/28931831/hyperhomocysteinemia-alters-retinal-endothelial-cells-barrier-function-and-angiogenic-potential-via-activation-of-oxidative-stress
#3
Riyaz Mohamed, Isha Sharma, Ahmed S Ibrahim, Heba Saleh, Nehal M Elsherbiny, Sadanand Fulzele, Khaled Elmasry, Sylvia B Smith, Mohamed Al-Shabrawey, Amany Tawfik
Hyperhomocysteinemia (HHcy) is associated with several human visual disorders, such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). Breakdown of the blood-retinal barrier (BRB) is linked to vision loss in DR and AMD. Our previous work revealed that HHcy altered BRB in retinal endothelial cells in vivo. Here we hypothesize that homocysteine (Hcy) alters retinal endothelial cell barrier function and angiogenic potential via activation of oxidative stress. Human retinal endothelial cells (HRECs) treated with and without different concentrations of Hcy showed a reduction of tight junction protein expression, increased FITC dextran leakage, decreased transcellular electrical resistance and increased angiogenic potential...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28931462/paradoxical-development-of-polymyositis-like-autoimmunity-through-augmented-expression-of-autoimmune-regulator-aire
#4
Hitoshi Nishijima, Tatsuya Kajimoto, Yoshiki Matsuoka, Yasuhiro Mouri, Junko Morimoto, Minoru Matsumoto, Hiroshi Kawano, Yasuhiko Nishioka, Hisanori Uehara, Keisuke Izumi, Koichi Tsuneyama, Il-Mi Okazaki, Taku Okazaki, Kazuyoshi Hosomichi, Ayako Shiraki, Makoto Shibutani, Kunitoshi Mitsumori, Mitsuru Matsumoto
Autoimmunity is prevented by the function of the autoimmune regulator [AIRE (Aire in mice)], which promotes the expression of a wide variety of tissue-restricted antigens (TRAs) from medullary thymic epithelial cells (mTECs) and from a subset of peripheral antigen-presenting cells (APCs). We examined the effect of additive expression of human AIRE (huAIRE) in a model of autoimmune diabetes in NOD mice. Unexpectedly, we observed that mice expressing augmented AIRE/Aire developed muscle-specific autoimmunity associated with incomplete maturation of mTECs together with impaired expression of Aire-dependent TRAs...
September 17, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28930754/simvastatin-a-novel-stimulator-of-eryptosis-the-suicidal-erythrocyte-death
#5
Abdulla Al Mamun Bhuyan, Sigrid Nüßle, Hang Cao, Shaqiu Zhang, Florian Lang
BACKGROUND/AIMS: The 3-hydroxy-3-methyl-glutaryl-Coenzyme A (HMG-CoA) reductase inhibitor simvastatin has been shown to trigger apoptosis of several cell types. The substance has thus been proposed as an additional treatment of malignancy. Similar to apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal erythrocyte death. Hallmarks of eryptosis include cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the extracellular face of the erythrocyte cell membrane...
September 20, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28930753/camel-milk-attenuates-rheumatoid-arthritis-via-inhibition-of-mitogen-activated-protein-kinase-pathway
#6
Hany H Arab, Samir A Salama, Tamer M Abdelghany, Hany A Omar, El-Shaimaa A Arafa, Majed M Alrobaian, Ibrahim A Maghrabi
BACKGROUND/AIMS: Camel milk (CM) has shown beneficial anti-inflammatory actions in several experimental and clinical settings. So far, its effect on rheumatoid arthritis (RA) has not been previously explored. Thus, the current work aimed to evaluate the effects of CM in Adjuvant-induced arthritis and air pouch edema models in rats, which mimic human RA. METHODS: CM was administered at 10 ml/kg orally for 3 weeks starting on the day of Freund's adjuvant paw inoculation...
September 20, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28928945/pathogenic-helminths-in-the-past-much-ado-about-nothing
#7
Christian Mulder
Despite a long tradition on the extent to which Romanisation has improved human health, some recent studies suggest that Romanisation in general, and Roman sanitation in particular, may not have made people any healthier, given that in Roman times gastrointestinal parasites were apparently widespread, whilst in the present day such parasites rarely cause diseases. Unfortunately, this novel claim neglects the empirical evidence that worldwide infections in over 1.5 billion people are caused by ubiquitous foodborne nematodes...
2017: F1000Research
https://www.readbyqxmd.com/read/28928674/the-gly-16-allele-of-the-g16r-single-nucleotide-polymorphism-in-the-%C3%AE-2-adrenergic-receptor-gene-augments-the-glycemic-response-to-adrenaline-in-humans
#8
Kim Z Rokamp, Jonatan M Staalsø, Morten Zaar, Peter Rasmussen, Lonnie G Petersen, Rikke V Nielsen, Niels H Secher, Niels V Olsen, Henning B Nielsen
Cerebral non-oxidative carbohydrate consumption may be driven by a β2-adrenergic mechanism. This study tested whether the 46G > A (G16R) single nucleotide polymorphism of the β2-adrenergic receptor gene (ADRB2) influences the metabolic and cerebrovascular responses to administration of adrenaline. Forty healthy Caucasian men were included from a group of genotyped individuals. Cardio- and cerebrovascular variables at baseline and during a 60-min adrenaline infusion (0.06 μg kg(-1) min(-1)) were measured by Model flow, near-infrared spectroscopy and transcranial Doppler sonography...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28928469/activation-of-mir-34a-5p-sirt1-p66shc-pathway-contributes-to-doxorubicin-induced-cardiotoxicity
#9
Jie-Ning Zhu, Yong-Heng Fu, Zhi-Qin Hu, Wen-Yu Li, Chun-Mei Tang, Hong-Wen Fei, Hui Yang, Qiu-Xiong Lin, De-Ming Gou, Shu-Lin Wu, Zhi-Xin Shan
The molecular mechanisms underlying anthracyclines-induced cardiotoxicity have not been well elucidated. MiRNAs were revealed dysregulated in the myocardium and plasma of rats received Dox treatment. MicroRNA-34a-5p (miR-34a-5p) was verified increased in the myocardium and plasma of Dox-treated rats, but was reversed in rats received Dox plus DEX treatments. Human miR-34a-5p was also observed increased in the plasma of patients with diffuse large B-cell lymphoma after 9- and 16-week epirubicin therapy. Up-regulation of miR-34a-5p was observed in Dox-induced rat cardiomyocyte H9c2 cells...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28928458/agonist-immunotherapy-restores-t-cell-function-following-mek-inhibition-improving-efficacy-in-breast-cancer
#10
Sathana Dushyanthen, Zhi Ling Teo, Franco Caramia, Peter Savas, Christopher P Mintoff, Balaji Virassamy, Melissa A Henderson, Stephen J Luen, Mariam Mansour, Michael H Kershaw, Joseph A Trapani, Paul J Neeson, Roberto Salgado, Grant A McArthur, Justin M Balko, Paul A Beavis, Phillip K Darcy, Sherene Loi
The presence of tumor-infiltrating lymphocytes in triple-negative breast cancers is correlated with improved outcomes. Ras/MAPK pathway activation is associated with significantly lower levels of tumor-infiltrating lymphocytes in triple-negative breast cancers and while MEK inhibition can promote recruitment of tumor-infiltrating lymphocytes to the tumor, here we show that MEK inhibition adversely affects early onset T-cell effector function. We show that α-4-1BB and α-OX-40 T-cell agonist antibodies can rescue the adverse effects of MEK inhibition on T cells in both mouse and human T cells, which results in augmented anti-tumor effects in vivo...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28928438/zyxin-stabilizes-rig-i-and-mavs-interactions-and-promotes-type-i-interferon-response
#11
Takahisa Kouwaki, Masaaki Okamoto, Hirotake Tsukamoto, Yoshimi Fukushima, Misako Matsumoto, Tsukasa Seya, Hiroyuki Oshiumi
RIG-I and MDA5 are cytoplasmic viral RNA sensors that belong to the RIG-I-like receptors (RLRs), which induce antiviral innate immune responses, including the production of type I interferon and other pro-inflammatory cytokines. After recognition of viral RNA, the N-terminal caspase activation and recruitment domains (CARDs) of RIG-I and MDA5 bind to a CARD in the MAVS adaptor molecule, resulting in MAVS oligomerization and downstream signaling. To reveal the molecular mechanism of MAVS-dependent signaling, we performed a yeast two-hybrid screening and identified zyxin as a protein that binds to MAVS...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28928421/upregulation-of-cisd2-augments-ros-homeostasis-and-contributes-to-tumorigenesis-and-poor-prognosis-of-lung-adenocarcinoma
#12
Shih-Miao Li, Chung-Hsing Chen, Ya-Wen Chen, Yi-Chen Yen, Wen-Tsen Fang, Fang-Yu Tsai, Junn-Liang Chang, Ying-Ying Shen, Shiu-Feng Huang, Chih-Pin Chuu, I-Shou Chang, Chao A Hsiung, Shih Sheng Jiang
CISD2 is a redox-sensitive gene critical for normal development and mitochondrial integrity. CISD2 was known to have aberrant expression in several types of human cancers. However, its relation with lung cancer is still not clear. In this study we found CISD2 mRNA was significantly upregulated in lung adenocarcinoma (ADC) samples, compared with their adjacent normal counterparts, and was correlated with tumor stage, grade, and prognosis based on analysis of clinical specimens-derived expression data in public domain and our validation assay...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28928268/mild-acidosis-delays-neutrophil-apoptosis-via-multiple-signaling-pathways-and-acts-in-concert-with-inflammatory-mediators
#13
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/28928217/peptides-derived-from-evolutionarily-conserved-domains-in-beclin1-and-beclin2-enhance-the-entry-of-lentiviral-vectors-into-human-cells
#14
Saliha Majdoul, Jérémie Cosette, Ababacar K Seye, Eric Bernard, Sophie Frin, Nathalie Holic, Nathalie Chazal, Laurence Briant, Lucile Espert, Anne Galy, David Fenard
Autophagy-related proteins such as Beclin1 are involved in an array of complex processes including antiviral responses, and may also modulate the efficiency of gene therapy viral vectors. The TatBeclin1 (TB1) peptide has been reported as an autophagy-inducing factor inhibiting the replication of pathogens such as HIV-1. Yet, autophagy-related proteins are also essential for the early steps of HIV-1 infection. Therefore, we examined here the effects of the Beclin1-evolutionarily conserved domain in TB1 on viral transduction and autophagy in single-round HIV infection or with nonreplicative HIV-1-derived lentiviral vectors (LV)...
September 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28927097/inhibition-of-lhx2-by-mir-124-suppresses-cellular-migration-and-invasion-in-non-small-cell-lung-cancer
#15
Qinghui Yang, Liang Wan, Can Xiao, Haibo Hu, Longqiang Wang, Jun Zhao, Zhe Lei, Hong-Tao Zhang
Downregulated microRNA (miR)-124 is common in numerous types of cancer, including non-small cell lung cancer (NSCLC). A previous study by the authors demonstrated that LIM-homeobox domain 2 (LHX2) was upregulated and promoted cell growth in NSCLC. However, whether LHX2 affects the migratory and invasive abilities of NSCLC cells and the association of LHX2 with miR-124 remains unclear. The present study revealed that miR-124 expression was frequently decreased in human NSCLC cells and tissues and negatively correlated with LHX2 expression, which was increased in NSCLC cells and tissues...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28926966/augmented-renal-clearance-in-critical-illness-an-important-consideration-in-drug-dosing
#16
REVIEW
Sherif Hanafy Mahmoud, Chen Shen
Augmented renal clearance (ARC) is a manifestation of enhanced renal function seen in critically ill patients. The use of regular unadjusted doses of renally eliminated drugs in patients with ARC might lead to therapy failure. The purpose of this scoping review was to provide and up-to-date summary of the available evidence pertaining to the phenomenon of ARC. A literature search of databases of available evidence in humans, with no language restriction, was conducted. Databases searched were MEDLINE (1946 to April 2017), EMBASE (1974 to April 2017) and the Cochrane Library (1999 to April 2017)...
September 16, 2017: Pharmaceutics
https://www.readbyqxmd.com/read/28925877/4-aryl-heteroaryl-4h-fused-pyrans-as-anti-proliferative-agents-design-synthesis-and-biological-evaluation
#17
Dinesh Kumar, Gurpreet Singh, Pooja Sharma, Arem Quayum, Girish Mahajan, M J Mintoo, Shashank Kumar Singh, Dilip Manikrao Mondhe, Pms Bedi, Subheet K Jain, Girish Kumar Gupta
The current study is focused on the design and synthesis of 4-aryl/heteroaryl-4H-fused pyrans as anti-proliferative agents. All the synthesized molecules were screened against a panel of human carcinoma cell lines. Significant inhibition was exhibited by the compounds against HCT-116 (Colon) and PC-3 (Prostate) cell lines while A-549 (Lung) cell lines, MiaPaCa-2 (Pancreatic) cell lines and HL-60 (Leukemia Cancer) cell lines were almost resistant to the exposure of the test compounds. Compound FP-(v)n displayed noteworthy cytotoxicity towards HCT-116 malignant cells with IC50 value of 0...
September 18, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28924375/lncrna-afap1-as-functions-as-a-competing-endogenous-rna-to-regulate-rap1b-expression-by-sponging-mir-181a-in-the-hscr
#18
Guanglin Chen, Lei Peng, Zhongxian Zhu, Chunxia Du, Ziyang Shen, Rujin Zang, Yang Su, Yankai Xia, Weibing Tang
Background: Long noncoding RNAs (lncRNAs) have recently emerged as important regulators in a broad spectrum of cellular processes including development and disease. Despite the known engagement of the AFAP1-AS in several human diseases, its biological function in Hirschsprung disease (HSCR) remains elusive. Methods: We used qRT-PCR to detect the relative expression of AFAP1-AS in 64 HSCR bowel tissues and matched normal intestinal tissues. The effects of AFAP1-AS on cell proliferation, migration, cell cycle, apoptosis and cytoskeletal organization were evaluated using CCK-8, transwell assay, flow cytometer analysis and immunofluorescence, in 293T and SH-SY5Y cell lines, respectively...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28923278/can-adjunctive-therapies-augment-the-efficacy-of-endovascular-thrombolysis-a-potential-role-for-activated-protein-c
#19
REVIEW
Arun Paul Amar, Abhay P Sagare, Zhen Zhao, Yaoming Wang, Amy R Nelson, John H Griffin, Berislav V Zlokovic
In the management of acute ischemic stroke, vessel recanalization correlates with functional status, mortality, cost, and other outcome measures. Thrombolysis with intravenous tissue plasminogen activator has many limitations that restrict its applicability, but recent advances in the development of mechanical thrombectomy devices as well as improved systems of stroke care have resulted in greater likelihood of vessel revascularization. Nonetheless, there remains substantial discrepancy between rates of recanalization and rates of favorable outcome...
September 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28922428/diminished-neutrophil-extracellular-trap-net-formation-is-a-novel-innate-immune-deficiency-induced-by-acute-ethanol-exposure-in-polymicrobial-sepsis-which-can-be-rescued-by-cxcl1
#20
Liliang Jin, Sanjay Batra, Samithamby Jeyaseelan
Polymicrobial sepsis is the result of an exaggerated host immune response to bacterial pathogens. Animal models and human studies demonstrate that acute alcohol intoxication is a key risk factor for sepsis-induced mortality. Multiple chemokines, such as CXCL1, CXCL2 and CXCL5 are critical for neutrophil recruitment and proper function of neutrophils. However, it is not quite clear the mechanisms by which acute alcohol suppresses immune responses and whether alcohol-induced immunosuppression can be rescued by chemokines...
September 18, 2017: PLoS Pathogens
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