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Xiuxiu Wang, Ru Cheng, Liang Cheng, Zhiyuan Zhong
PLGA, a copolymer of lactide and glycolide, is one of the most used biodegradable polymers that find a wide range of biomedical applications including drug delivery and tissue engineering. However, in spite of remarkable advancement, nanotherapeutics based on PLGA might have drawbacks of inadequate stability, drug leakage, and slow drug release at the tumor site, which reduces its targeting ability and therapeutic efficacy. Here, we report that direct modification of star PLGA ends with lipoic acid, a natural antioxidant present in our human body, affords a smart material (sPLGA-LA) that forms reversibly crosslinked and bioresponsive multifunctional nanoparticles (sPLGA XNPs)...
March 19, 2018: Biomacromolecules
Aisha Nazli, Sara Dizzell, Muhammad Atif Zahoor, Victor H Ferreira, Jessica Kafka, Matthew William Woods, Michel Ouellet, Ali A Ashkar, Michel J Tremblay, Dawn Me Bowdish, Charu Kaushic
More than 40% of HIV infections occur via female reproductive tract (FRT) through heterosexual transmission. Epithelial cells that line the female genital mucosa are the first line of defense against HIV-1 and other sexually transmitted pathogens. These sentient cells recognize and respond to external stimuli by induction of a range of carefully balanced innate immune responses. Previously, we have shown that in response to HIV-1 gp120, the genital epithelial cells (GECs) from upper reproductive tract induce an inflammatory response that may facilitate HIV-1 translocation and infection...
March 19, 2018: Cellular & Molecular Immunology
Lan Huang, Huaxi Xu, Guangyong Peng
Cellular energy metabolism not only promotes tumor cell growth and metastasis but also directs immune cell survival, proliferation and the ability to perform specific and functional immune responses within the tumor microenvironment. A better understanding of the molecular regulation of metabolism in different cell components in the tumor-suppressive microenvironment is critical for the development of effective strategies for human cancer treatments. Toll-like receptors (TLRs) have recently been recognized as critical factors involved in tumor pathogenesis, regulating both tumor cells and tumor-infiltrating innate and adaptive immune cells...
March 19, 2018: Cellular & Molecular Immunology
Tanya B Dorff, Neeraj Agarwal
Bone metastases are the main driver of morbidity and mortality in advanced prostate cancer. Targeting the bone microenvironment, a key player in the pathogenesis of bone metastasis, has become one of the mainstays of therapy in men with advanced prostate cancer. This review will evaluate the data supporting the use of bone-targeted therapy, including (1) bisphosphonates such as zoledronic acid, which directly target osteoclasts, (2) denosumab, a receptor activator of nuclear factor-kappa B (RANK) ligand inhibitor, which targets a key component of bone stromal interaction, and (3) radium-223, an alpha-emitting calcium mimetic, which hones to the metabolically active areas of osteoblastic metastasis and induces double-strand breaks in the DNA...
March 16, 2018: Asian Journal of Andrology
Yi Cao, Shengxing Tan, Yi Tu, Guoyang Zhang, Yi Liu, Daojiang Li, Shan Xu, Zhibiao Le, Jianbo Xiong, Wenyu Zou, Peitao Gong, Zhengrong Li, Zhigang Jie
Accumulating studies have demonstrated microRNAs (miRNAs/miRs) have an important role in multiple processes of human malignant tumor development and progression. Decreased expression of miR-125a-5p has been observed in several types of cancer, including gastric cancer (GC). However, the mechanism and exact function of miR-125a-5p in GC have not been largely elucidated. In the present study, reverse transcription-quantitative polymerase chain reaction indicated that the expression of miR-125a-5p was downregulated in GC tissues and cell lines compared with matched normal tissues (P<0...
April 2018: Oncology Letters
Juan P Gallino, Cecilia Ruibal, Esteban Casaretto, Andrea L Fleitas, Victoria Bonnecarrère, Omar Borsani, Sabina Vidal
Water is usually the main limiting factor for soybean productivity worldwide and yet advances in genetic improvement for drought resistance in this crop are still limited. In the present study, we investigated the physiological and molecular responses to drought in two soybean contrasting genotypes, a slow wilting N7001 and a drought sensitive TJS2049 cultivars. Measurements of stomatal conductance, carbon isotope ratios and accumulated dry matter showed that N7001 responds to drought by employing mechanisms resulting in a more efficient water use than TJS2049...
2018: Frontiers in Plant Science
Jessica Da Gama Duarte, Sagun Parakh, Miles C Andrews, Katherine Woods, Anupama Pasam, Candani Tutuka, Simone Ostrouska, Jonathan M Blackburn, Andreas Behren, Jonathan Cebon
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced melanoma. The first ICI to demonstrate clinical benefit, ipilimumab, targets cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4); however, the long-term overall survival is just 22%. More than 40 years ago intralesional (IL) bacillus Calmette-Guérin (BCG), a living attenuated strain of Mycobacterium bovis , was found to induce tumor regression by stimulating cell-mediated immunity following a localized and self-limiting infection...
2018: Frontiers in Immunology
Antonietta Romano, Paolo Angeli, Sara Piovesan, Franco Noventa, Georgios Anastassopoulos, Liliana Chemello, Luisa Cavalletto, Martina Gambato, Francesco Paolo Russo, Patrizia Burra, Valter Vincenzi, Pier Giorgio Scotton, Sandro Panese, Diego Tempesta, Tosca Bertin, Maurizio Carrara, Antonio Carlotto, Franco Capra, Giada Carolo, Giovanna Scroccaro, Alfredo Alberti
BACKGROUND & AIMS: Direct-acting antiviral agents (DAAs) are safe and effective in patients with hepatitis C. Conflicting data were reported on the risk of Hepatocellular carcinoma (HCC) during/after therapy with DAAs. Aim of this study was to evaluate incidence of newly diagnosed hepatocellular carcinoma and associated risk factors in patients with advanced hepatitis C treated with DAAs. METHODS: The study is based on the NAVIGATORE platform, a prospectively recording database of all patients with hepatitis C receiving DAAs in Veneto region (Italy)...
March 15, 2018: Journal of Hepatology
Lindsay Bonsignore, Nicholas Bloom, Karen Steinhauser, Reginald Nichols, Todd Allen, Martha Twaddle, Janet Bull
CONTEXT: The impact of telehealth and remote patient monitoring have not been well established in palliative care populations in rural communities. OBJECTIVES: The objective of this study was to 1) Describe a telehealth palliative care program using the TapCloud remote patient monitoring application and videoconferencing, 2) Evaluate the feasibility, usability, and acceptability of a telehealth system in palliative care, and 3) Use a quality data assessment collection tool (QDACT) in addition to TapCloud ratings of symptom burden and hospice transitions...
March 15, 2018: Journal of Pain and Symptom Management
Jesse J McClure, Xiaoyang Li, C James Chou
Since the identification and cloning of human histone deacetylases (HDACs) and the rapid approval of vorinostat (Zolinza®) for the treatment of cutaneous T-cell lymphoma, the field of HDAC biology has met many initial successes. However, many challenges remain due to the complexity involved in the lysine posttranslational modifications, epigenetic transcription regulation, and nonepigenetic cellular signaling cascades. In this chapter, we will: review the discovery of the first HDAC inhibitor and present discussion regarding the future of next-generation HDAC inhibitors, give an overview of different classes of HDACs and their differences in lysine deacylation activity, discuss different classes of HDAC inhibitors and their HDAC isozyme preferences, and review HDAC inhibitors' preclinical studies, their clinical trials, their pharmacokinetic challenges, and future direction...
2018: Advances in Cancer Research
Mitchell E Menezes, Praveen Bhoopathi, Anjan K Pradhan, Luni Emdad, Swadesh K Das, Chunqing Guo, Xiang-Yang Wang, Devanand Sarkar, Paul B Fisher
Subtraction hybridization identified genes displaying differential expression as metastatic human melanoma cells terminally differentiated and lost tumorigenic properties by treatment with recombinant fibroblast interferon and mezerein. This approach permitted cloning of multiple genes displaying enhanced expression when melanoma cells terminally differentiated, called melanoma differentiation associated (mda) genes. One mda gene, mda-7, has risen to the top of the list based on its relevance to cancer and now inflammation and other pathological states, which based on presence of a secretory sequence, chromosomal location, and an IL-10 signature motif has been named interleukin-24 (MDA-7/IL-24)...
2018: Advances in Cancer Research
Kunal Bailoor, Leslie H Kamil, Ed Goldman, Laura M Napiewocki, Denise Winiarski, Christian J Vercler, Andrew G Shuman
Advance care planning allows patients to articulate preferences for their medical treatment, lifestyle, and surrogate decision-makers in order to anticipate and mitigate their potential loss of decision-making capacity. Written advance directives are often emphasized in this regard. While these directives contain important information, there are several barriers to consider: veracity and accuracy of surrogate decision-makers in making choices consistent with the substituted judgement standard, state-to-state variability in regulations, literacy issues, lack of access to legal resources, lack of understanding of medical options, and cultural disparities...
March 17, 2018: Journal of Bioethical Inquiry
S S Chung, J S Zheng, S R Burket, B W Brooks
Though antibiotic resistance (ABR) represents a major global health threat, contributions of landfill leachate to the life cycle of antibiotics and ABR development are poorly understood in rapidly urbanizing regions of developing countries. We selected one of the largest active landfills in Asia and two landfills that have been closed for 20 years to examine antibiotic occurrences in leachates and associated hazards during wet and dry season sampling events. We focused on some of the most commonly used human antibiotics in Hong Kong, one of the most populous Asian cities and the fourth most densely populated cities in the world...
March 15, 2018: Environment International
Jianling Wang, Shibing Wang, Jijun Zhou, Qian Qian
Our previous study has showed doublecortin like kinase 1 (DCLK1) serves as an oncogene to regulate basal-like breast cancer cell proliferation, migration and invasion, and is associated with malignant status and poor prognosis. The aim of this study is to identify microRNAs (miRNAs), which target DCLK1 to regulate basal-like breast cancer cell proliferation, migration and invasion. In our results, we observed that miR-424-5p expression was decreased in basal-like breast cancer tissues and cell lines. Furthermore, we found 3'-UTR of DCLK1 had binding site of miR-424-5p based on microRNA target databases, and there was an inverse correlation between miR-424-5p and DCLK1 in basal-like breast cancer tissues...
March 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Carolien J Aantjes, Andrew Gilmoor, Elena V Syurina, Tamaryn L Crankshaw
OBJECTIVE: To conduct a systematic review of the status of post-abortion care (PAC) provision in Eastern and Southern Africa with particular reference to reach, quality and costs of these services. STUDY DESIGN: We searched Pubmed, EMBASE, Science Direct, POPLINE and Web of Science for articles published between 2000 and October 2017 presenting primary or secondary data from one or more countries in the region. RESULTS: Seventy articles representing data from fourteen countries were abstracted and included in the review...
March 14, 2018: Contraception
Maria J Rodriguez, Thomas A Dixon, Eliad Cohen, Wenwen Huang, Fiorenzo G Omenetto, David L Kaplan
Freeform fabrication has emerged as a key direction in printing biologically-relevant materials and structures. With this emerging technology, complex structures with microscale resolution can be created in arbitrary geometries and without the limitations found in traditional bottom-up or top-down additive manufacturing methods. Recent advances in freeform printing have used the physical properties of microparticle-based granular gels as a medium for the submerged extrusion of bioinks. However, most of these techniques require post-processing or crosslinking for the removal of the printed structures [1,2]...
March 14, 2018: Acta Biomaterialia
Adriana Ferreira Lopes Vilela, Cláudia Seidl, Juliana Maria de Lima, Carmen Lúcia Cardoso
Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are key cholinesterase enzymes responsible for the hydrolysis of acetylcholine into choline and acetic acid, an essential process for the restoration of the cholinergic neuron. The loss of cholinergic function in the central nervous system contributes to the cognitive decline associated with advanced age and Alzheimer's disease (AD). Inhibitions assays represent a significant role in the drug discovery process. Herein, we describe an improved label free method to screen and characterize new BChE ligands...
March 14, 2018: Analytical Biochemistry
Kerstin Nowotny, José Pedro Castro, Martín Hugo, Sabine Braune, Daniela Weber, Marc Pignitter, Veronika Somoza, Julia Bornhorst, Tanja Schwerdtle, Tilman Grune
Methylglyoxal (MG), a highly reactive dicarbonyl, interacts with proteins to form advanced glycation end products (AGEs). AGEs include a variety of compounds which were shown to have damaging potential and to accumulate in the course of different conditions such as diabetes mellitus and aging. After confirming collagen as a main target for MG modifications in vivo within the extracellular matrix, we show here that MG-collagen disrupts fibroblast redox homeostasis and induces endoplasmic reticulum (ER) stress and apoptosis...
March 14, 2018: Free Radical Biology & Medicine
Andre Pittig, Michael Treanor, Richard T LeBeau, Michelle G Craske
Anxiety disorders are the most common mental disorders, and are often chronic and disabling. Although exposure-based treatments are effective, a substantial number of individuals fail to fully remit or experience a return of symptoms after treatment. Understanding the critical processes underlying the development and treatment of anxiety disorders will help identify individuals at risk and optimize treatments. Aversive associative learning offers explanatory pathways through which fear and anxiety emerge, spread, persist, and resurge...
March 14, 2018: Neuroscience and Biobehavioral Reviews
Brianne J Lindsay, Michal M Bonar, Ian N Costas-Cancelas, Kristin Hunt, Alexander I Makarkov, Sabrina Chierzi, Connie M Krawczyk, Nathalie Landry, Brian J Ward, Isabelle Rouiller
Plant-made virus-like particle (VLP) vaccines that display wild-type influenza hemagglutinin (HA) are rapidly advancing through clinical trials. Produced by transient transfection of Nicotiana benthamiana, these novel vaccines are unusually immunogenic, eliciting both humoral and cellular responses. Here, we directly visualized VLPs bearing either HA trimers derived from strains A/California/7/2009 or A/Indonesia/5/05 using cryo-electron microscopy and determined the 3D organization of the VLPs using cryo-electron tomography...
March 14, 2018: Vaccine
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