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https://www.readbyqxmd.com/read/28550810/rigid-aromatic-linking-moiety-in-cationic-lipids-for-enhanced-gene-transfection-efficiency
#1
Bing Wang, Rui-Mo Zhao, Ji Zhang, Yan-Hong Liu, Zheng Huang, Qing-Ying Yu, Xiao-Qi Yu
Although numerous cationic lipids have been developed as non-viral gene vectors, the structure-activity relationship (SAR) of these materials remains unclear and needs further investigation. In this work, a series of lysine-derived cationic lipids containing linkages with different rigidity were designed and synthesized. SAR studies showed that lipids with rigid aromatic linkage could promote the formation of tight liposomes and enhance DNA condensation, which is essential for the gene delivery process. These lipids could give much higher transfection efficiency than those containing more flexible aliphatic linkage in various cell lines...
May 17, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28550804/dispersant-approval-procedures-in-france-and-italy-a-comparative-ecotoxicity-study
#2
Loredana Manfra, Andrea Tornambè, Julien Guyomarch, Pascale Le Guerrogue, Loïc Kerambrun, Alice Rotini, Federica Savorelli, Fulvio Onorati, Erika Magaletti
A research project has been performed to the request of the RAMOGE Executive Secretariat to identify differences between dispersant approval procedures in France and Italy and propose ways to harmonize them. A collaborative study has been conducted by CEDRE (Centre of Documentation, Research and Experimentation on Accidental Water Pollution) and ISPRA (Italian Institute for Environmental Protection and Research) to: a) compare current approval procedures in Italy and France with identification of differences and commonalities; b) carry out toxicity tests using both procedures on two selected dispersants; c) propose a common approach between Italy and France...
May 24, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28550798/sediment-quality-in-a-metal-contaminated-tropical-bay-assessed-with-a-multiple-lines-of-evidence-approach
#3
Sarah K Rodrigues, Denis M S Abessa, Ana Paula de C Rodrigues, Abílio Soares-Gomes, Carolina B Freitas, Ricardo E Santelli, Aline S Freire, Wilson Machado
A sediment quality assessment was performed near to the main industrial source of metal contamination in Sepetiba Bay, Brazil, which represents one of the worst cases of trace metal contamination reported for coastal areas. Acute and chronic toxicity tests, benthic fauna community analysis and metal bioavailability evaluations were applied to identify risks to the benthic community. Significant amphipod mortality was observed close to the major pollution source and lower copepod fertility was observed for all stations...
May 24, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28550769/mk-8776-a-novel-chk1-inhibitor-exhibits-an-improved-radiosensitizing-effect-compared-to-ucn-01-by-exacerbating-radiation-induced-aberrant-mitosis
#4
Motofumi Suzuki, Tohru Yamamori, Tomoki Bo, Yuri Sakai, Osamu Inanami
Checkpoint kinase 1 (Chk1) is an evolutionarily conserved serine/threonine kinase that plays an important role in G2/M checkpoint signaling. Here, we evaluate the radiosensitizing effects of a novel selective Chk1 inhibitor MK-8776, comparing its efficacy with a first-generation Chk1 inhibitor UCN-01, and attempt to elucidate the mechanism of radiosensitization. In a clonogenic survival assay, MK-8776 demonstrated a more pronounced radiosensitizing effect than UCN-01, with lower cytotoxicity. Importantly, radiosensitization by MK-8776 can be achieved at doses as low as 2...
May 24, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28550754/linear-polysialoside-outperforms-dendritic-analogs-for-inhibition-of-influenza-virus-infection-in%C3%A2-vitro-and-in%C3%A2-vivo
#5
Sumati Bhatia, Daniel Lauster, Markus Bardua, Kai Ludwig, Stefano Angioletti-Uberti, Nicole Popp, Ute Hoffmann, Florian Paulus, Matthias Budt, Marlena Stadtmüller, Thorsten Wolff, Alf Hamann, Christoph Böttcher, Andreas Herrmann, Rainer Haag
Inhibition of influenza A virus infection by multivalent sialic acid inhibitors preventing viral hemagglutinin binding to host cells of the respiratory tract is a promising strategy. However, optimal geometry and optimal ligand presentation on multivalent scaffolds for efficient inhibition both in vitro and in vivo application are still unclear. Here, by comparing linear and dendritic polyglycerol sialosides (LPGSA and dPGSA) we identified architectural requirements and optimal ligand densities for an efficient multivalent inhibitor of influenza virus A/X31/1 (H3N2)...
May 20, 2017: Biomaterials
https://www.readbyqxmd.com/read/28550712/combined-immune-checkpoint-blockade-anti-pd-1-anti-ctla-4-evaluation-and-management-of-adverse-drug-reactions
#6
REVIEW
Jessica C Hassel, Lucie Heinzerling, Jens Aberle, Oliver Bähr, Thomas K Eigentler, Marc-Oliver Grimm, Victor Grünwald, Jan Leipe, Niels Reinmuth, Julia K Tietze, Jörg Trojan, Lisa Zimmer, Ralf Gutzmer
Combined immune checkpoint blockade (ICB) provides unprecedented efficacy gains in numerous cancer indications, with PD-1 inhibitor nivolumab plus CTLA-4 inhibitor ipilimumab in advanced melanoma as first-ever approved therapies for combined ICB. However, gains in efficacy must be balanced against a higher frequency and severity of adverse drug reactions (ADR). Because delays in diagnosis and management might result in symptom worsening and further complications, clinicians shall be well trained to identify ADR promptly and monitor patients adequately...
May 18, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28550601/potential-toxicity-of-trace-elements-and-nanomaterials-to-chinese-cabbage-in-arsenic-and-lead-contaminated-soil-amended-with-biochars
#7
Yasser Mahmoud Awad, Meththika Vithanage, Nabeel Khan Niazi, Muhammad Rizwan, Jörg Rinklebe, Jae E Yang, Yong Sik Ok, Sang Soo Lee
To our knowledge, this is the first report on exploring the interactive effects of various biochars (BCs) and nanomaterials (NMs) on plant growth and bioavailability of trace elements in soil. This study evaluated the bioavailability and toxicity of arsenic (As), lead (Pb), and NMs to cabbage plants. The BCs were produced from rice husk (RB), sewage sludge, and bamboo wood (WB). The BCs at 2.5 and 5% (w w(-1)), NMs for removing As (NMs-As) and heavy metals (NMs-HM) at 3000 mg kg(-1), and multi-walled carbon nanotubes (CNT) at 1000 mg kg(-1) were applied in bioassay and incubation experiments (40 days), along with the unamended soil as the control...
May 26, 2017: Environmental Geochemistry and Health
https://www.readbyqxmd.com/read/28550350/recent-advances-in-the-study-of-immunodeficiency-and-dna-damage-response
#8
REVIEW
Tomohiro Morio
DNA breaks can be induced by exogenous stimuli or by endogenous stress, but are also generated during recombination of V, D, and J genes (V(D)J recombination), immunoglobulin class switch recombination (CSR). Among various DNA breaks generated, DNA double strand break (DSB) is the most deleterious one. DNA damage response (DDR) is initiated when DSBs are detected, leading to DNA break repair by non-homologous end joining (NHEJ). The process is critically important for the generation of diversity for foreign antigens; and failure to exert DNA repair leads to immunodeficiency such as severe combined immunodeficiency and hyper-IgM syndrome...
May 26, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28550339/effect-of-fungal-endophytes-on-biomass-yield-nutritive-value-and-accumulation-of-minerals-in-ornithopus-compressus
#9
Oscar Santamaria, Santiago Lledó, Sara Rodrigo, Maria J Poblaciones
Yellow serradella (Ornithopus compressus), a valuable pasture species in Mediterranean areas, presents a high diversity of endophytic mycoflora. In the present work, the hypothesis of a significant effect of fungal endophytic species on the parameters of forage production, nutritive value and mineral status of herbage was tested. O. compressus plants were inoculated with each of seven endophytes (four in 2012/2013 and three in 2013/2014). After inoculation, two experiments (under greenhouse and field conditions) were established...
May 27, 2017: Microbial Ecology
https://www.readbyqxmd.com/read/28550279/cinnamon-induces-browning-in-subcutaneous-adipocytes
#10
Hiu Yee Kwan, Jiahui Wu, Tao Su, Xiao-Juan Chao, Bin Liu, Xiuqiong Fu, Chi Leung Chan, Rebecca Hiu Ying Lau, Anfernee Kai Wing Tse, Quan Bin Han, Wang Fun Fong, Zhi-Ling Yu
Browning is the process of increasing the number of brite cells, which helps to increase energy expenditure and reduce obesity. Consumption of natural and non-toxic herbal extracts that possess the browning effect is an attractive anti-obesity strategy. In this study, we examined the browning effect of cinnamon extract. We found that cinnamon extract (CE) induced typical brown adipocyte multiocular phenotype in 3T3-L1 adipocytes. The treatment also increased brown adipocytes markers and reduced white adipocytes markers in the 3T3-L1 adipocytes...
May 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28550259/transport-of-non-transferrin-bound-iron-to-the-brain-implications-for-alzheimer-s-disease
#11
Ajai K Tripathi, Shilpita Karmakar, Abhishek Asthana, Ajay Ashok, Vilok Desai, Shounak Baksi, Neena Singh
A direct correlation between brain iron and Alzheimer's disease (AD) raises questions regarding the transport of non-transferrin-bound iron (NTBI), a toxic but less researched pool of circulating iron that is likely to increase due to pathological and/or iatrogenic systemic iron overload. Here, we compared the distribution of radiolabeled-NTBI (59Fe-NTBI) and transferrin-bound iron (59Fe-Tf) in mouse models of iron overload in the absence or presence of inflammation. Following a short pulse, most of the 59Fe-NTBI was taken up by the liver, followed by the kidney, pancreas, and heart...
May 25, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28550248/cd44-splice-variants-as-potential-players-in%C3%A2-alzheimer-s-disease-pathology
#12
Elhanan Pinner, Yaron Gruper, Micha Ben Zimra, Don Kristt, Moshe Laudon, David Naor, Nava Zisapel
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive deficits, deposition of amyloid-β (Aβ) plaques, intracellular neurofibrillary tangles, and neuronal cell death. Neuroinflammation is commonly believed to participate in AD pathogenesis. CD44 is an inflammation-related gene encoding a widely-distributed family of alternatively spliced cell surface glycoproteins that have been implicated in inflammation, metastases, and inflammation-linked neuronal injuries. Here we investigated the expression patterns of CD44S (which does not contain any alternative exon) and CD44 splice variants in postmortem hippocampal samples from AD patients and matched non-AD controls...
May 25, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28550041/central-nervous-system-involvement-in-acute-lymphoblastic-leukemia-is-mediated-by-vascular-endothelial-growth-factor
#13
Vera Münch, Luca Trentin, Julia Herzig, Salih Demir, Felix Seyfried, Johann M Kraus, Hans A Kestler, Rolf Köhler, Thomas F E Barth, Geertruy Te Kronnie, Klaus-Michael Debatin, Lüder H Meyer
In acute lymphoblastic leukemia (ALL), central nervous system (CNS) involvement is a major clinical concern. Despite non-detectable CNS leukemia in many cases, prophylactic CNS-directed conventional intrathecal chemotherapy is required for relapse free survival indicating subclinical CNS manifestation in most patients. However, CNS-directed therapy is associated with long-term sequelae including neurocognitive deficits and secondary neoplasms. Therefore, molecular mechanisms and pathways mediating leukemia cell entry into the CNS need to be understood in order to identify targets for prophylactic and therapeutic interventions and develop alternative CNS-directed treatment strategies...
May 26, 2017: Blood
https://www.readbyqxmd.com/read/28550039/a-phase-1-2-study-of-the-oral-proteasome-inhibitor-ixazomib-in-relapsed-or-refractory-light-chain-al-amyloidosis
#14
Vaishali Sanchorawala, Giovanni Palladini, Vishal Kukreti, Jeffrey A Zonder, Adam D Cohen, David C Seldin, Angela Dispenzieri, Arnaud Jaccard, Stefan O Schönland, Deborah Berg, Huyuan Yang, Neeraj Gupta, Ai-Min Hui, Raymond L Comenzo, Giampaolo Merlini
This phase 1/2 study assessed the safety, tolerability, and preliminary efficacy of the oral proteasome inhibitor (PI) ixazomib in patients with relapsed/refractory AL amyloidosis (RRAL). Ixazomib was administered to adult patients with RRAL after ≥1 prior line of therapy (including bortezomib) on days 1, 8, and 15 of 28-day cycles, for up to 12 cycles. Patients with less than partial response after 3 cycles received oral dexamethasone (40 mg, days 1-4) from cycle 4. A 3+3 dose-escalation phase was followed by 2 expansion cohorts (PI-naïve and PI-exposed patients) at the maximum tolerated dose (MTD)...
May 26, 2017: Blood
https://www.readbyqxmd.com/read/28550029/pulmonary-function-changes-after-radiotherapy-for-lung-or-esophageal-cancer-a-systematic-review-focusing-on-dose-volume-parameters
#15
Anne G H Niezink, Renske A de Jong, Christina T Muijs, Johannes A Langendijk, Joachim Widder
BACKGROUND: Despite technical developments in treatment delivery, radiation-induced lung toxicity (RILT) remains a crucial problem in thoracic radiotherapy. Clinically based RILT scores have their limitations, and more objective measures such as pulmonary functions tests (PFTs) might help to improve treatment strategies. PURPOSE: To summarize the available evidence about the effect of dose to the lung in thoracic radiotherapy on forced expiratory volume in one second (FEV1) and diffusion capacity (DLCO) in patients with lung and esophageal cancer treated with curative intent...
May 26, 2017: Oncologist
https://www.readbyqxmd.com/read/28549954/amlexanox-enhances-premature-termination-codon-read-through-in-col7a1-and-expression-of-full-length-type-vii-collagen-potential-therapy-for-recessive-dystrophic-epidermolysis-bullosa
#16
Velina S Atanasova, Qiujie Jiang, Marco Prisco, Christina Gruber, Josefina Piñón Hofbauer, Mei Chen, Cristina Has, Leena Bruckner-Tuderman, John A McGrath, Jouni Uitto, Andrew P South
Recessive dystrophic epidermolysis bullosa (RDEB) is a rare monogenic blistering disorder caused by lack of functional type VII collagen, leading to skin fragility and subsequent trauma-induced separation of the epidermis from the underlying dermis. 46% of RDEB patients harbor at least one premature termination codon (PTC) mutation in COL7A1 and previous studies have shown that aminoglycosides are able to overcome RDEB PTC mutations by inducing "read-through" and incorporation of an amino acid at the PTC site...
May 23, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28549953/incidence-and-triggers-of-stevens-johnson-syndrome-and-toxic-epidermal-necrolysis-in-a-large-cancer-patient-cohort
#17
Nancy K Gillis, J Kevin Hicks, Gillian C Bell, Ashley J Daly, Peter A Kanetsky, Howard L McLeod
No abstract text is available yet for this article.
May 23, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28549949/recent-advancements-in-liposomes-targeting-strategies-to-cross-blood-brain-barrier-bbb-for-the-treatment-of-alzheimer-s-disease
#18
REVIEW
Mukta Agrawal, Ajazuddin, Dulal K Tripathi, Swarnlata Saraf, Shailendra Saraf, Sophia G Antimisiaris, Spyridon Mourtas, Margareta Hammarlund-Udenaes, Amit Alexander
In this modern era, with the help of various advanced technologies, medical science has overcome most of the health-related issues successfully. Though, some diseases still remain unresolved due to various physiological barriers. One such condition is Alzheimer; a neurodegenerative disorder characterized by progressive memory impairment, behavioral abnormalities, mood swing and disturbed routine activities of the person suffering from. It is well known to all that the brain is entirely covered by a protective layer commonly known as blood brain barrier (BBB) which is responsible to maintain the homeostasis of brain by restricting the entry of toxic substances, drug molecules, various proteins and peptides, small hydrophilic molecules, large lipophilic substances and so many other peripheral components to protect the brain from any harmful stimuli...
May 23, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28549911/insecticidal-activity-of-stemona-collinsiae-root-extract-against-parasarcophaga-ruficornis-diptera-sarcophagidae
#19
Aurapa Sakulpanich, Siriluck Attrapadung, Wandee Gritsanapan
In Thai indigenous knowledge, Stemona plant has traditionally been used as insecticide on plantations. Recently, S. collinsiae extract was showed to be an anti-feedant and growth inhibitor and to exert strong insecticidal activity. Here, the insecticidal activity of S. collinsiae root extract against Parasarcophaga ruficornis is studied. The larvicidal and pupacidal activities of the ethanolic root extract of S. collinsiae were tested using contact toxicity tests, and adulticidal activity was tested using the topical contact toxicity and sugar bait methods The ethanolic extract at concentration ranging of 0...
May 23, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28549899/utility-of-published-dna-reactivity-alerts
#20
Alun Myden, Sebastien Guesne, Alex Cayley, Richard V Williams
The identification of impurities with mutagenic potential is required for any potential pharmaceutical. The ICH M7 guidelines state that two complementary in silico toxicity prediction tools may be used to predict the mutagenic potential of pharmaceutical impurities. An expert review of the resulting in silico predictions is required, and numerous publications have been released to guide the expert review process. One such publication suggests that literature-based structural alerts (LBSAs) may provide a suitable aid in the expert review process...
May 23, 2017: Regulatory Toxicology and Pharmacology: RTP
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