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https://www.readbyqxmd.com/read/28719024/the-immunoproteasome-an-old-player-with-a-novel-and-emerging-role-in-alloimmunity
#1
S K Eskandari, M A J Seelen, G Lin, J R Azzi
Modern treatment strategies for the maintenance of allograft acceptance frequently target ubiquitously-expressed pathways, leading to significant side-effects and poor long-term allograft outcomes. Constitutive proteasome inhibitors, which have recently been introduced for the treatment of antibody-mediated rejection, target the ubiquitously-expressed proteasome. To limit off-target effects and serious mechanism-based toxicity, however, these inhibitors are administered intermittently and suboptimally. Immunoproteasomes, which are an inducible subset of proteasomes enriched in immune cells, replace constitutive proteasomes after cell exposure to proinflammatory cytokines such as interferon-γ...
July 18, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28719015/bisphenol-a-induced-oxidative-stress-and-apoptosis-in-mice-testes-modulation-by-selenium
#2
S Kaur, M Saluja, M P Bansal
Spermatogenesis, a highly coordinated process, is prone to environmental insults which may lead to impaired spermatogenesis or, at worst, infertility. Bisphenol A (BPA) is a well-known global environmental toxicant and a ubiquitous oestrogenic chemical. This study evaluated the role of selenium (0.5 ppm sodium selenite/kg diet) on spermatogenesis after BPA treatment in different groups of male BALB/c mice: control, selenium, BPA and selenium+BPA. Markers of oxidative stress and apoptosis were evaluated in testis after BPA treatment...
July 18, 2017: Andrologia
https://www.readbyqxmd.com/read/28718834/dna-interacting-characteristics-of-the-archaeal-rudiviral-protein-sirv2_gp1
#3
Eveline Peeters, Maarten Boon, Clare Rollie, Ronnie G Willaert, Marleen Voet, Malcolm F White, David Prangishvili, Rob Lavigne, Tessa E F Quax
Whereas the infection cycles of many bacterial and eukaryotic viruses have been characterized in detail, those of archaeal viruses remain largely unexplored. Recently, studies on a few model archaeal viruses such as SIRV2 (Sulfolobus islandicus rod-shaped virus) have revealed an unusual lysis mechanism that involves the formation of pyramidal egress structures on the host cell surface. To expand understanding of the infection cycle of SIRV2, we aimed to functionally characterize gp1, which is a SIRV2 gene with unknown function...
July 18, 2017: Viruses
https://www.readbyqxmd.com/read/28718812/therapeutic-efficacy-of-the-novel-stimuli-sensitive-nano-ferritins-containing-doxorubicin-in-a-head-and-neck-cancer-model
#4
Verena Damiani, Elisabetta Falvo, Giulio Fracasso, Luca Federici, Martina Pitea, Vincenzo De Laurenzi, Gianluca Sala, Pierpaolo Ceci
Doxorubicin is employed alone or in combination for the treatment of several hematological and solid malignancies; despite its efficacy, there are associated cardiotoxicity limits both in its application in patients with heart disease risk factors and also in its long-term use. HFt-MP-PAS40 is a genetically engineered human ferritin heavy chain (HFt)-based construct able to efficiently entrap and deliver doxorubicin to cancer cells. HF-MP-PAS contains a short motif sequence (defined as MP) responsive to proteolytic cleavage by tumor matrix metalloproteases (MMPs), located between each HFt subunit and a masking polypeptide sequence rich in proline (P), alanine (A), and serine (S) residues (PAS)...
July 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28717878/the-isolation-of-primary-hepatocytes-from-human-tissue-optimising-the-use-of-small-non-encapsulated-liver-resection-surplus
#5
Charlotte J Green, Catriona A Charlton, Lai-Mun Wang, Michael Silva, Karl J Morten, Leanne Hodson
Two-step perfusion is considered the gold standard method for isolating hepatocytes from human liver tissue. As perfusion may require a large tissue specimen, which is encapsulated and has accessible vessels for cannulation, only a limited number of tissue samples may be suitable. Therefore, the aim of this work was to develop an alternative method to isolate hepatocytes from non-encapsulated and small samples of human liver tissue. Healthy tissue from 44 human liver resections were graded for steatosis and tissue weights between 7...
July 17, 2017: Cell and Tissue Banking
https://www.readbyqxmd.com/read/28717379/hepatoprotective-effect-of-citral-on-acetaminophen-induced-liver-toxicity-in-mice
#6
Nancy Sayuri Uchida, Saulo Euclides Silva-Filho, Gabriel Fernando Esteves Cardia, Edivaldo Cremer, Francielli Maria de Souza Silva-Comar, Expedito Leite Silva, Ciomar Aparecida Bersani-Amado, Roberto Kenji Nakamura Cuman
High doses of acetaminophen (APAP) lead to acute liver damage. In this study, we evaluated the effects of citral in a murine model of hepatotoxicity induced by APAP. The liver function markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (γGT) were determined to evaluate the hepatoprotective effects of citral. The livers were used to determine myeloperoxidase (MPO) activity and nitric oxide (NO) production and in histological analysis...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28717105/ephedrine-induced-mitophagy-via-oxidative-stress-in-human-hepatic-stellate-cells
#7
Ah Young Lee, Yoonjeong Jang, Seong-Ho Hong, Seung-Hee Chang, Sungjin Park, Sanghwa Kim, Kyung-Sun Kang, Ji-Eun Kim, Myung-Haing Cho
The herb Ephedra sinica (also known as Chinese ephedra or Ma Huang), used in traditional Chinese medicine, contains alkaloids identical to ephedrine and pseudoephedrine as its principal active constituents. Recent studies have reported that ephedrine has various side effects in the cardiovascular and nervous systems. In addition, herbal Ephedra, a plant containing many pharmacologically active alkaloids, principally ephedrine, has been reported to cause acute hepatitis. Many studies reported clinical cases, however, the cellular mechanism of liver toxicity by ephedrine remains unknown...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28716815/exposure-response-analyses-of-ramucirumab-from-two-randomized-phase-iii-trials-of-second-line-treatment-for-advanced-gastric-or-gastroesophageal-junction-cancer
#8
Josep Tabernero, Atsushi Ohtsu, Kei Muro, Eric Van Cutsem, Sang Cheul Oh, György Bodoky, Yasuhiro Shimada, Shuichi Hironaka, Jaffer A Ajani, Jiri Tomasek, Howard Safran, Kumari Chandrawansa, Yanzhi Hsu, Michael Heathman, Azhar Khan, Lan Ni, Allen S Melemed, Ling Gao, David Ferry, Charles S Fuchs
Ramucirumab is an IgG1 monoclonal antibody specific for the vascular endothelial growth factor receptor-2. Ramucirumab, 8 mg/kg every two weeks, administered as monotherapy (REGARD) or in combination with paclitaxel (RAINBOW), was safe and effective in patients with previously treated advanced gastric or gastroesophageal junction (GEJ) cancer. We evaluated exposure-efficacy and exposure-safety relationships of ramucirumab from two randomized, placebo-controlled phase III trials. Sparse pharmacokinetic samples were collected and a population pharmacokinetic analysis was conducted to predict ramucirumab minimum trough concentration at steady-state (Cmin,ss)...
July 17, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28716727/systematic-review-and-meta-analysis-links-autism-and-toxic-metals-and-highlights-the-impact-of-country-development-status-higher-blood-and-erythrocyte-levels-for-mercury-and-lead-and-higher-hair-antimony-cadmium-lead-and-mercury
#9
REVIEW
Amene Saghazadeh, Nima Rezaei
BACKGROUND: Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder that affects cognitive and higher cognitive functions. Increasing prevalence of ASD and high rates of related comorbidities has caused serious health loss and placed an onerous burden on the supporting families, caregivers, and health care services. Heavy metals are among environmental factors that may contribute to ASD. However, due to inconsistencies across studies, it is still hard to explain the association between ASD and toxic metals...
July 14, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28716507/a-novel-topoisomerase-2a-inhibitor-cryptotanshinone-suppresses-the-growth-of-pc3-cells-without-apparent-cytotoxicity
#10
Eun Ju Kim, Sun Young Kim, Sang-Man Kim, Minyoung Lee
DNA topoisomerase 2, which is ubiquitously expressed in eukaryotic cells, is an essential nuclear enzyme that promotes cell survival by regulating DNA topology and chromatid separation. This enzyme has been validated as a target for anticancer agent screening. It can be poisoned by common chemotherapeutics, such as etoposide and doxorubicin, which leads to the accumulation of cytotoxic enzyme-linked DNA double-stranded breaks. However, recent studies have suggested that the topoisomerase 2a isozyme is predominantly responsible for the carcinogenic side effects associated with etoposide and doxorubicin chemotherapy...
July 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28716455/the-vitamin-b6-paradox-supplementation-with-high-concentrations-of-pyridoxine-leads-to-decreased-vitamin-b6-function
#11
Misha F Vrolijk, Antoon Opperhuizen, Eugène H J M Jansen, Geja J Hageman, Aalt Bast, Guido R M M Haenen
Vitamin B6 is a water-soluble vitamin that functions as a coenzyme in many reactions involved in amino acid, carbohydrates and lipid metabolism. Since 2014, >50 cases of sensory neuronal pain due to vitamin B6 supplementation were reported. Up to now, the mechanism of this toxicity is enigmatic and the contribution of the various B6 vitamers to this toxicity is largely unknown. In the present study, the neurotoxicity of the different forms of vitamin B6 is tested on SHSY5Y and CaCo-2 cells. Cells were exposed to pyridoxine, pyridoxamine, pyridoxal, pyridoxal-5-phosphate or pyridoxamine-5-phosphate for 24h, after which cell viability was measured using the MTT assay...
July 14, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28715870/neuroprotective-effect-of-trans-n-caffeoyltyramine-from-lycium-chinense-against-h2o2-induced-cytotoxicity-in-pc12-cells-by-attenuating-oxidative-stress
#12
Opeyemi J Olatunji, Hongxia Chen, Yifeng Zhou
Natural products play a critical role in the promotion of good health as regards the prevention and management of oxidative stress related and neurodegenerative disorders. Oxidative stress has been implicated in several apoptotic pathways associated with cell damages in neuronal disorders. The aim of this study was to investigate the antioxidant effect of trans-N-caffeoyltyramine (TNC) isolated from Cortex lycii against hydrogen peroxide (H2O2) induced cell damages in PC12 cells as well as its mechanism of action...
July 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28715775/evolution-of-anti-her2-therapies-for-cancer-treatment
#13
REVIEW
Sagun Parakh, Hui K Gan, Adam C Parslow, Ingrid J G Burvenich, Antony W Burgess, Andrew M Scott
The development of HER2-directed monoclonal antibodies and tyrosine kinase inhibitors have provided benefits to cancer patients, as well as produced many insights into the biology of the ErbB receptor family. Current therapies based on ErbB family members have resulted in improved overall survival with associated improvements in quality of life for the cancer patients that respond to treatment. Compared to monotherapy using either two antibodies to block the HER2 receptor blockade or combinatorial approaches with HER2 antibodies and standard therapies has provided additional benefits...
July 6, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28715159/alcohol-antiretroviral-interactive-toxicity-beliefs-as-a-potential-barrier-to-hiv-pre-exposure-prophylaxis-among-men-who-have-sex-with-men
#14
Seth C Kalichman, Lisa Eaton
INTRODUCTION: Pre-exposure prophylaxis (PrEP) offers as much as 90% protection against HIV transmission. However, the effectiveness of PrEP depends on uptake and adherence to even intermittent dosing. Along with intoxication leading to unintentional non-adherence, believing that alcohol mixed with pharmaceuticals is harmful (i.e., interactive toxicity beliefs) may lead to poor uptake and intentional non-adherence. METHODS: HIV-negative sexually active men who have sex with men (N = 272) at a large Gay Pride event in Atlanta, GA, completed anonymous surveys of demographic characteristics, sexual behaviour, alcohol use and PrEP-related alcohol interactive toxicity beliefs...
July 17, 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/28714917/larvicidal-and-nematicidal-activities-of-3-acylbarbituric-acid-analogues-against-asian-tiger-mosquito-aedes-albopictus-and-pine-wood-nematode-bursaphelenchus-xylophilus
#15
Seon-Mi Seo, Hyo-Rim Lee, Ji-Eun Lee, Yong-Chul Jeong, Hyung-Wook Kwon, Joon-Kwan Moon, Mark G Moloney, Il-Kwon Park
Widespread concern for the occurrence of resistant strains, along with the avoidance of the use of highly toxic insecticides and their wide environmental dispersal, highlights the need for the development of new and safer pest control agents. Natural products provide inspiration for new chemical entities with biological activities, and their analogues are good lead compounds for the development of new pest control agents. For this purpose, we evaluated the larvicidal and nematicidal activities of 48 3-acylbarbituric acid analogues against the Asian tiger mosquito, Aedes albopictus and the pine wood nematode, Bursaphelenchus xylophilus, organisms of increasing global concern...
July 17, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28714280/ph-responsive-nanoscale-coordination-polymer-for-efficient-drug-delivery-and-real-time-release-monitoring
#16
Kai Han, Wei-Yun Zhang, Jin Zhang, Zhao-Yu Ma, He-You Han
Both excess dosages of drug and unwanted drug carrier can lead to severe side effects as well as the failure of tumor therapy. Here, an Fe(3+) -gallic acid based drug delivery system is designed for efficient monitoring of drug release in tumor. Fe(3+) and polyphenol gallic acid can form polygonal nanoscale coordination polymer in aqueous solution, which exhibits certain antitumor effect. Importantly, this coordination polymer possesses extremely high doxorubicin (DOX) loading efficacy (up to 48.3%). In vitro studies demonstrate that the fluorescence of DOX can be quenched efficiently when DOX is loaded on the coordination polymer...
July 17, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28714245/drug-loaded-multifunctional-nanoparticles-targeted-to-the-endocardial-layer-of-the-injured-heart-modulate-hypertrophic-signaling
#17
Mónica P A Ferreira, Sanjeev Ranjan, Sini Kinnunen, Alexandra Correia, Virpi Talman, Ermei Mäkilä, Brianda Barrios-Lopez, Marianna Kemell, Vimalkumar Balasubramanian, Jarno Salonen, Jouni Hirvonen, Heikki Ruskoaho, Anu J Airaksinen, Hélder A Santos
Ischemic heart disease is the leading cause of death globally. Severe myocardial ischemia results in a massive loss of myocytes and acute myocardial infarction, the endocardium being the most vulnerable region. At present, current therapeutic lines only ameliorate modestly the quality of life of these patients. Here, an engineered nanocarrier is reported for targeted drug delivery into the endocardial layer of the left ventricle for cardiac repair. Biodegradable porous silicon (PSi) nanoparticles are functionalized with atrial natriuretic peptide (ANP), which is known to be expressed predominantly in the endocardium of the failing heart...
July 17, 2017: Small
https://www.readbyqxmd.com/read/28714224/codelivery-for-paclitaxel-and-bcl-2-conversion-gene-by-phb-pdmaema-amphiphilic-cationic-copolymer-for-effective-drug-resistant-cancer-therapy
#18
Xiaoyuan Wang, Sing Shy Liow, Qiaoqiong Wu, Chuang Li, Cally Owh, Zibiao Li, Xian Jun Loh, Yun-Long Wu
Antiapoptotic Bcl-2 protein's upregulated expression is a key reason for drug resistance leading to failure of chemotherapy. In this report, a series of biocompatible amphiphilic cationic poly[(R)-3-hydroxybutyrate] (PHB)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) copolymer, comprising hydrophobic PHB block and cationic PDMAEMA block, is designed to codeliver hydrophobic chemotherapeutic paclitaxel and Bcl-2 converting gene Nur77/ΔDBD with enhanced stability, due to the micelle formation by hydrophobic PHB segment...
July 17, 2017: Macromolecular Bioscience
https://www.readbyqxmd.com/read/28713335/a-novel-regulatory-cascade-involving-blur-ycgz-and-lon-controls-the-expression-of-escherichia-coli-ompf-porin
#19
Valérie Duval, Kimberly Foster, Jennifer Brewster, Stuart B Levy
In Escherichia coli, OmpF is an important outer membrane protein, which serves as a passive diffusion pore for small compounds including nutrients, antibiotics, and toxic compounds. OmpF expression responds to environmental changes such as temperature, osmolarity, nutrients availability, and toxic compounds via complex regulatory pathways involving transcriptional and post-transcriptional regulation. Our study identified a new regulatory cascade that controls the expression of OmpF porin. This pathway involves BluR, a transcriptional regulator repressing the expression of the ycgZ-ymgABC operon...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28713333/algevir-an-expression-system-for-microalgae-based-on-viral-vectors
#20
Bernardo Bañuelos-Hernández, Elizabeth Monreal-Escalante, Omar González-Ortega, Carlos Angulo, Sergio Rosales-Mendoza
The use of recombinant algae for the production of valuable compounds is opening promising biotechnological applications. However, the development of efficient expression approaches is still needed to expand the exploitation of microalgae in biotechnology. Herein, the concept of using viral expression vectors in microalgae was explored for the first time. An inducible geminiviral vector leading to Rep-mediated replication of the expression cassette allowed the production of antigenic proteins at high levels...
2017: Frontiers in Microbiology
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