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Yale Journal of Biology and Medicine

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https://www.readbyqxmd.com/read/28356903/biomarkers-translational-medicine-and-drug-development-an-interview-with-chirag-r-parikh-md-phd
#1
Corey Horien
No abstract text is available yet for this article.
March 2017: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28356902/is-open-science-the-future-of-drug-development
#2
REVIEW
Daniel L Shaw
Traditional drug development models are widely perceived as opaque and inefficient, with the cost of research and development continuing to rise even as production of new drugs stays constant. Searching for strategies to improve the drug discovery process, the biomedical research field has begun to embrace open strategies. The resulting changes are starting to reshape the industry. Open science-an umbrella term for diverse strategies that seek external input and public engagement-has become an essential tool with researchers, who are increasingly turning to collaboration, crowdsourcing, data sharing, and open sourcing to tackle some of the most pressing problems in medicine...
March 2017: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28356901/penicillin-s-discovery-and-antibiotic-resistance-lessons-for-the-future
#3
REVIEW
Mariya Lobanovska, Giulia Pilla
Undoubtedly, the discovery of penicillin is one of the greatest milestones in modern medicine. 2016 marks the 75th anniversary of the first systemic administration of penicillin in humans, and is therefore an occasion to reflect upon the extraordinary impact that penicillin has had on the lives of millions of people since. This perspective presents a historical account of the discovery of the wonder drug, describes the biological nature of penicillin, and considers lessons that can be learned from the golden era of antibiotic research, which took place between the 1940s and 1960s...
March 2017: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28356900/medication-safety-in-clinical-trials-role-of-the-pharmacist-in-optimizing-practice-collaboration-and-education-to-reduce-errors
#4
REVIEW
Jamie N Brown, Sara R Britnell, Andrew P Stivers, Jennifer L Cruz
Standardized safety practices for investigational drugs in clinical research protocols are limited and the vast majority of research pharmacists have concerns regarding its safety. Identified areas for medication safety risks include protocol complexity, medication ordering, and the processes for packaging, storage, and dispensing investigational medications. Inclusion of a pharmacist creates multiple mechanisms to promote safety and improve the quality of clinical research. This is accomplished through collaborating in the development of a research protocol, reviewing as a member of an advisory committee, developing mechanisms that contribute to safety, and assuring compliance with local and national regulations and standards...
March 2017: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28356899/drug-development-against-metastatic-cancers
#5
REVIEW
Chen Wang, Sui Huang
While combinational diagnostic and treatment strategies over the past decades have significantly improved the overall survival of cancer patients, metastatic cancer remains a leading cause of death in developed countries. The lack of successful treatment strategies for the disease is in large part due to the complexity of the metastatic transformation, which embodies extensive cellular and extracellular alterations, enabling metastatic cancer cells to reach and colonize other organs. The mode of action for the majority of anti-cancer drugs used in clinics today is primarily tumor growth inhibition...
March 2017: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28356898/novel-pharmacologic-candidates-for-treatment-of-primary-open-angle-glaucoma
#6
REVIEW
Louise J Lu, James C Tsai, Ji Liu
Primary open-angle glaucoma (OAG) affects approximately 45 million people worldwide and more than 2.5 million people aged 40 years or older in the United States. Pharmacologic treatment for glaucoma is directed towards lowering intraocular pressure (IOP) to slow disease progression and delay visual field loss. Current medical treatment options for the lowering of IOP include the following classes of topical medications: beta-adrenergic antagonists, alpha-adrenergic agonists, cholinergic agonists, carbonic anhydrase inhibitors, and prostaglandin analogs...
March 2017: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28356897/novel-molecular-strategies-and-targets-for-opioid-drug-discovery-for-the-treatment-of-chronic-pain
#7
REVIEW
Keith M Olson, Wei Lei, Attila Keresztes, Justin LaVigne, John M Streicher
Opioid drugs like morphine and fentanyl are the gold standard for treating moderate to severe acute and chronic pain. However, opioid drug use can be limited by serious side effects, including constipation, tolerance, respiratory suppression, and addiction. For more than 100 years, we have tried to develop opioids that decrease or eliminate these liabilities, with little success. Recent advances in understanding opioid receptor signal transduction have suggested new possibilities to activate the opioid receptors to cause analgesia, while reducing or eliminating unwanted side effects...
March 2017: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28356896/a-cell-based-assay-to-assess-hemichannel-function
#8
REVIEW
Srinivasan Krishnan, Mariana C Fiori, Luis G Cuello, Guillermo A Altenberg
Activation of connexin hemichannels is involved in the pathophysiology of disorders that include deafness, stroke, and cardiac infarct. This aspect makes hemichannels an attractive therapeutic target. Unfortunately, most available inhibitors are not selective or isoform specific, which hampers their translational application. The absence of a battery of useful inhibitors is due in part to the absence of simple screening assays for the discovery of hemichannel-active drugs. Here, we present an assay that we have recently developed to assess hemichannel function...
March 2017: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28356895/exploiting-long-noncoding-rnas-as-pharmacological-targets-to-modulate-epigenetic-diseases
#9
REVIEW
Bindu Prabhakar, Xiao-Bo Zhong, Theodore P Rasmussen
Long non-coding RNAs (lncRNAs) constitute the largest class of non-coding transcripts in the human genome. Results from next-generation sequencing and bioinformatics advances indicate that the human genome contains more non-coding RNA genes than protein-coding genes. Validated functions of lncRNAs suggest that they are master regulators of gene expression and often exert their influences via epigenetic mechanisms by modulating chromatin structure. Specific lncRNAs can regulate transcription in gene clusters...
March 2017: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28356894/a-novel-epi-drug-therapy-based-on-the-suppression-of-bet-family-epigenetic-readers
#10
REVIEW
Dong-Guk Shin, Dashzeveg Bayarsaihan
Recent progress in epigenetic research has made a profound influence on pharmacoepigenomics, one of the fastest growing disciplines promising to provide new epi-drugs for the treatment of a broad range of diseases. Histone acetylation is among the most essential chromatin modifications underlying the dynamics of transcriptional activation. The acetylated genomic regions recruit the BET (bromodomain and extra-terminal) family of bromodomains (BRDs), thereby serving as a molecular scaffold in establishing RNA polymerase II specificity...
March 2017: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28356893/alzheimer-s-toxic-amyloid-beta-oligomers-unwelcome-visitors-to-the-na-k-atpase-alpha3-docking-station
#11
Thomas DiChiara, Nadia DiNunno, Jeffrey Clark, Riana Lo Bu, Erika N Cline, Madeline G Rollins, Yuesong Gong, David L Brody, Stephen G Sligar, Pauline T Velasco, Kirsten L Viola, William L Klein
Toxic amyloid beta oligomers (AβOs) are known to accumulate in Alzheimer's disease (AD) and in animal models of AD. Their structure is heterogeneous, and they are found in both intracellular and extracellular milieu. When given to CNS cultures or injected ICV into non-human primates and other non-transgenic animals, AβOs have been found to cause impaired synaptic plasticity, loss of memory function, tau hyperphosphorylation and tangle formation, synapse elimination, oxidative and ER stress, inflammatory microglial activation, and selective nerve cell death...
March 2017: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28356892/discovery-of-a-structurally-unique-small-molecule-that-inhibits-protein-synthesis
#12
Durga Thakral, Hyun Seop Tae
Identifying and characterizing natural products and synthetic small molecules that inhibit biochemical processes such as ribosomal translation can lead to novel sources of molecular probes and therapeutics. The search for new antibiotics has been invigorated by the increasing burden of drug-resistant bacteria and has identified many clinically essential prokaryote-specific ribosome inhibitors. However, the current cohort of antibiotics is limited with regards to bacterial resistance mechanisms because of structural similarity within classes...
March 2017: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28356891/variable-effects-of-autophagy-induction-by-trehalose-on-herpesviruses-depending-on-conditions-of-infection
#13
Jeffery L Meier, Charles Grose
Trehalose is a non-reducing sugar formed from two glucose units. Trehalose induces abundant autophagy in cultured cells and also reduces the rate of aggregation of the huntingtin protein in the animal model of Huntington disease, a chronic neurological disease in humans. The mechanism of this effect on autophagy is now known to be caused by starvation secondary to inhibition of a family of glucose transporters known as the solute carrier 2 or the glucose transporter family. Variable effects of trehalose treatment have been observed during infections with two herpesviruses-human cytomegalovirus and varicella-zoster virus...
March 2017: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28356890/evaluation-and-optimization-of-in-silico-designed-sphingosine-1-phosphate-s1p-receptor-subtype-1-modulators-for-the-management-of-multiple-sclerosis
#14
Daphne H Gusman, Claire Shoemake
Multiple Sclerosis (MS) is a chronic autoimmune disorder affecting the Central Nervous System (CNS) through inflammation, demyelination and neurodegeneration. Sphingosine-1-phosphate receptor (S1PR1) modulators have been approved for the management of MS. Phosphorylated fingolimod mimics endogenous sphingosine-1-phosphate (S1P), a bioactive lipid that regulates remyelination and cell injury. Amiselimod was developed as a successor of fingolimod, with more specificity for S1PR1, and showed promising results until phase 2 clinical trials...
March 2017: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28356889/the-effects-of-different-intensities-of-exercise-on-behavioral-and-molecular-pain-related-reactions-in-rats-implications-for-medication-development
#15
Hong-Yu Liu, Kun Yang, Yuan Guo, Marc N Potenza, Yan Zhao
Drug discovery for pain management is an important area of research given current limitations in medications for pain, including the addictive potential of opiates. While exercise may help worsen or lessen pain, the precise molecular mechanisms involved are incompletely understood. Thus, in the present study, we evaluated the effects of exercise intensity on pain via assessment of behavior and c-Fos expression. An animal model of moderate and high-intensity treadmill exercise was established. The specific nociceptive behaviors, such as flinches, favoring, lifting, and licking, were observed within 60 min following intraplantar injection of formalin...
March 2017: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28018148/epigenetics-and-common-ophthalmic-diseases
#16
REVIEW
Wendy Li, Ji Liu, Jennifer A Galvin
The study of ocular diseases and epigenetic dysregulation is an emerging area of research. The knowledge from the epigenetic mechanisms of DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs regarding the pathogenesis of ocular diseases will be helpful for improved treatment modalities for our patients. In particular, we focus upon the how epigenetic regulatory mechanisms impact five common ocular diseases: age related macular degeneration, age-related cataract, pterygium, retinoblastoma, and uveal melanoma...
December 2016: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28018147/receptor-signaling-directs-global-recruitment-of-pre-existing-transcription-factors-to-inducible-elements
#17
REVIEW
Peter N Cockerill
Gene expression programs are largely regulated by the tissue-specific expression of lineage-defining transcription factors or by the inducible expression of transcription factors in response to specific stimuli. Here I will review our own work over the last 20 years to show how specific activation signals also lead to the wide-spread re-distribution of pre-existing constitutive transcription factors to sites undergoing chromatin reorganization. I will summarize studies showing that activation of kinase signaling pathways creates open chromatin regions that recruit pre-existing factors which were previously unable to bind to closed chromatin...
December 2016: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28018146/pancreatic-cancer-a-mis-interpreter-of-the-epigenetic-language
#18
REVIEW
Eriko Iguchi, Stephanie L Safgren, David L Marks, Rachel L Olson, Martin E Fernandez-Zapico
Pancreatic cancer is the third leading cause of cancer mortality in the U.S. with close to 40,000 deaths per year. Pancreatic ductal adenocarcinoma (PDAC) represents approximately 90 percent of all pancreatic cancer cases and is the most lethal form of the disease. Current therapies for PDAC are ineffective and most patients cannot be treated by surgical resection. Most research efforts have primarily focused on how genetic alterations cause, alter progression, contribute to diagnosis, and influence PDAC management...
December 2016: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28018145/epigenetics-of-renal-development-and-disease
#19
REVIEW
Sylvia A Hilliard, Samir S El-Dahr
An understanding of epigenetics is indispensable to our understanding of gene regulation under normal and pathological states. This knowledge will help with designing better therapeutic approaches in regenerative tissue medicine. Epigenetics allows us to parse out the mechanisms by which transcriptional regulators gain access to specific gene loci thereby imprinting epigenetic information affecting chromatin function. This epigenetic memory forms the basis of cell lineage specification in multicellular organisms...
December 2016: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28018144/deciphering-the-epigenetic-code-in-embryonic-and-dental-pulp-stem-cells
#20
REVIEW
Dashzeveg Bayarsaihan
A close cooperation between chromatin states, transcriptional modulation, and epigenetic modifications is required for establishing appropriate regulatory circuits underlying self-renewal and differentiation of adult and embryonic stem cells. A growing body of research has established that the epigenome topology provides a structural framework for engaging genes in the non-random chromosomal interactions to orchestrate complex processes such as cell-matrix interactions, cell adhesion and cell migration during lineage commitment...
December 2016: Yale Journal of Biology and Medicine
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