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Medicinal Research Reviews

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https://www.readbyqxmd.com/read/28094448/human-antimicrobial-peptides-in-bodily-fluids-current-knowledge-and-therapeutic-perspectives-in-the-postantibiotic-era
#1
REVIEW
Paulo Bastos, Fábio Trindade, João da Costa, Rita Ferreira, Rui Vitorino
Antimicrobial peptides (AMPs) are an integral part of the innate immune defense mechanism of many organisms. Due to the alarming increase of resistance to antimicrobial therapeutics, a growing interest in alternative antimicrobial agents has led to the exploitation of AMPs, both synthetic and isolated from natural sources. Thus, many peptide-based drugs have been the focus of increasing attention by many researchers not only in identifying novel AMPs, but in defining mechanisms of antimicrobial peptide activity as well...
January 17, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28094444/the-current-state-of-nad-dependent-histone-deacetylases-sirtuins-as-novel-therapeutic-targets
#2
REVIEW
Matthias Schiedel, Dina Robaa, Tobias Rumpf, Wolfgang Sippl, Manfred Jung
Sirtuins are NAD(+) -dependent protein deacylases that cleave off acetyl, as well as other acyl groups, from the ε-amino group of lysines in histones and other substrate proteins. Seven sirtuin isotypes (Sirt1-7) have been identified in mammalian cells. As sirtuins are involved in the regulation of various physiological processes such as cell survival, cell cycle progression, apoptosis, DNA repair, cell metabolism, and caloric restriction, a dysregulation of their enzymatic activity has been associated with the pathogenesis of neoplastic, metabolic, infectious, and neurodegenerative diseases...
January 17, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28084618/drugs-in-clinical-trials-for-alzheimer-s-disease-the-major-trends
#3
REVIEW
Sergey O Bachurin, Elena V Bovina, Aleksey A Ustyugov
Alzheimer's disease (AD) is characterized by a chronic and progressive neurodegenerative process resulting from the intracellular and extracellular accumulation of fibrillary proteins: beta-amyloid and hyperphosphorylated Tau. Overaccumulation of these aggregates leads to synaptic dysfunction and subsequent neuronal loss. The precise molecular mechanisms of AD are still not fully understood but it is clear that AD is a multifactorial disorder and that advanced age is the main risk factor. Over the last decade, more than 50 drug candidates have successfully passed phase II clinical trials, but none has passed phase III...
January 13, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28052344/understanding-the-molecular-mechanisms-of-the-interplay-between-herbal-medicines-and-gut-microbiota
#4
REVIEW
Jun Xu, Hu-Biao Chen, Song-Lin Li
Herbal medicines (HMs) are much appreciated for their significant contribution to human survival and reproduction by remedial and prophylactic management of diseases. Defining the scientific basis of HMs will substantiate their value and promote their modernization. Ever-increasing evidence suggests that gut microbiota plays a crucial role in HM therapy by complicated interplay with HM components. This interplay includes such activities as: gut microbiota biotransforming HM chemicals into metabolites that harbor different bioavailability and bioactivity/toxicity from their precursors; HM chemicals improving the composition of gut microbiota, consequently ameliorating its dysfunction as well as associated pathological conditions; and gut microbiota mediating the interactions (synergistic and antagonistic) between the multiple chemicals in HMs...
January 4, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28029168/trends-in-regenerative-medicine-repigmentation-in-vitiligo-through-melanocyte-stem-cell-mobilization
#5
REVIEW
Stanca A Birlea, Gertrude-E Costin, Dennis R Roop, David A Norris
Vitiligo is the most frequent human pigmentary disorder, characterized by progressive autoimmune destruction of mature epidermal melanocytes. Of the current treatments offering partial and temporary relief, ultraviolet (UV) light is the most effective, coordinating an intricate network of keratinocyte and melanocyte factors that control numerous cellular and molecular signaling pathways. This UV-activated process is a classic example of regenerative medicine, inducing functional melanocyte stem cell populations in the hair follicle to divide, migrate, and differentiate into mature melanocytes that regenerate the epidermis through a complex process involving melanocytes and other cell lineages in the skin...
December 28, 2016: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28029167/drug-mediated-regulation-of-glycosaminoglycan-biosynthesis
#6
REVIEW
Giancarlo Ghiselli
Glycosaminoglycans (GAGs) are a heterogeneous family of unbranched polysaccharides that exist in either a free state or attached to proteins and are found on the cell surface as well as in the extracellular matrix. GAGs play essential roles in cellular and tissue homeostasis, and their metabolism is altered in response to several pathological conditions. Despite strong experimental evidence supporting the function of GAGs in various diseases, little is known about the regulation of GAG biosynthesis via pharmacological intervention...
December 28, 2016: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28005280/abcg2-bcrp-specific-and-nonspecific-modulators
#7
REVIEW
Diana Peña-Solórzano, Simone Alexandra Stark, Burkhard König, Cesar Augusto Sierra, Cristian Ochoa-Puentes
Multidrug resistance (MDR) in cancer cells is the development of resistance to a variety of structurally and functionally nonrelated anticancer drugs. This phenomenon has become a major obstacle to cancer chemotherapy seriously affecting the clinical outcome. MDR is associated with increased drug efflux from cells mediated by an energy-dependent mechanism involving the ATP-binding cassette (ABC) transporters, mainly P-glycoprotein (ABCB1), the MDR-associated protein-1 (ABCC1), and the breast cancer resistance protein (ABCG2)...
December 22, 2016: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28005273/nonsteroidal-anti-inflammatory-therapy-a-journey-toward-safety
#8
REVIEW
Catarina Pereira-Leite, Cláudia Nunes, Sarah K Jamal, Iolanda M Cuccovia, Salette Reis
The efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) against inflammation, pain, and fever has been supporting their worldwide use in the treatment of painful conditions and chronic inflammatory diseases until today. However, the long-term therapy with NSAIDs was soon associated with high incidences of adverse events in the gastrointestinal tract. Therefore, the search for novel drugs with improved safety has begun with COX-2 selective inhibitors (coxibs) being straightaway developed and commercialized...
December 22, 2016: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28004409/recent-advances-in-anticancer-activities-and-drug-delivery-systems-of-tannins
#9
REVIEW
Yuee Cai, Jinming Zhang, Nelson G Chen, Zhi Shi, Jiange Qiu, Chengwei He, Meiwan Chen
Tannins, polyphenols in medicinal plants, have been divided into two groups of hydrolysable and condensed tannins, including gallotannins, ellagitannins, and (-)-epigallocatechin-3-gallate (EGCG). Potent anticancer activities have been observed in tannins (especially EGCG) with multiple mechanisms, such as apoptosis, cell cycle arrest, and inhibition of invasion and metastases. Furthermore, the combinational effects of tannins and anticancer drugs have been demonstrated in this review, including chemoprotective, chemosensitive, and antagonizing effects accompanying with anticancer effect...
December 22, 2016: Medicinal Research Reviews
https://www.readbyqxmd.com/read/27976413/medicinal-chemistry-pharmacology-and-clinical-implications-of-trpv1-receptor-antagonists
#10
REVIEW
Mojgan Aghazadeh Tabrizi, Pier Giovanni Baraldi, Stefania Baraldi, Stefania Gessi, Stefania Merighi, Pier Andrea Borea
Transient receptor potential vanilloid 1 (TRPV1) is an ion channel expressed on sensory neurons triggering an influx of cations. TRPV1 receptors function as homotetramers responsive to heat, proinflammatory substances, lipoxygenase products, resiniferatoxin, endocannabinoids, protons, and peptide toxins. Its phosphorylation increases sensitivity to both chemical and thermal stimuli, while desensitization involves a calcium-dependent mechanism resulting in receptor dephosphorylation. TRPV1 functions as a sensor of noxious stimuli and may represent a target to avoid pain and injury...
December 15, 2016: Medicinal Research Reviews
https://www.readbyqxmd.com/read/27957758/enzyme-tunnels-and-gates-as-relevant-targets-in-drug-design
#11
REVIEW
Sergio M Marques, Lukas Daniel, Tomas Buryska, Zbynek Prokop, Jan Brezovsky, Jiri Damborsky
Many enzymes contain tunnels and gates that are essential to their function. Gates reversibly switch between open and closed conformations and thereby control the traffic of small molecules-substrates, products, ions, and solvent molecules-into and out of the enzyme's structure via molecular tunnels. Many transient tunnels and gates undoubtedly remain to be identified, and their functional roles and utility as potential drug targets have received comparatively little attention. Here, we describe a set of general concepts relating to the structural properties, function, and classification of these interesting structural features...
December 13, 2016: Medicinal Research Reviews
https://www.readbyqxmd.com/read/27925266/marine-mollusk-derived-agents-with-antiproliferative-activity-as-promising-anticancer-agents-to-overcome-chemotherapy-resistance
#12
REVIEW
Maria Letizia Ciavatta, Florence Lefranc, Marianna Carbone, Ernesto Mollo, Margherita Gavagnin, Tania Betancourt, Ramesh Dasari, Alexander Kornienko, Robert Kiss
The chemical investigation of marine mollusks has led to the isolation of a wide variety of bioactive metabolites, which evolved in marine organisms as favorable adaptations to survive in different environments. Most of them are derived from food sources, but they can be also biosynthesized de novo by the mollusks themselves, or produced by symbionts. Consequently, the isolated compounds cannot be strictly considered as "chemotaxonomic markers" for the different molluscan species. However, the chemical investigation of this phylum has provided many compounds of interest as potential anticancer drugs that assume particular importance in the light of the growing literature on cancer biology and chemotherapy...
December 7, 2016: Medicinal Research Reviews
https://www.readbyqxmd.com/read/27879006/allosteric-modulation-an-alternate-approach-targeting-the-cannabinoid-cb1-receptor
#13
REVIEW
Thuy Nguyen, Jun-Xu Li, Brian F Thomas, Jenny L Wiley, Terry P Kenakin, Yanan Zhang
The cannabinoid CB1 receptor is a G protein coupled receptor and plays an important role in many biological processes and physiological functions. A variety of CB1 receptor agonists and antagonists, including endocannabinoids, phytocannabinoids, and synthetic cannabinoids, have been discovered or developed over the past 20 years. In 2005, it was discovered that the CB1 receptor contains allosteric site(s) that can be recognized by small molecules or allosteric modulators. A number of CB1 receptor allosteric modulators, both positive and negative, have since been reported and importantly, they display pharmacological characteristics that are distinct from those of orthosteric agonists and antagonists...
November 23, 2016: Medicinal Research Reviews
https://www.readbyqxmd.com/read/27870126/discovery-of-therapeutic-approaches-for-polyglutamine-diseases-a-summary-of-recent-efforts
#14
REVIEW
Sofia Esteves, Sara Duarte-Silva, Patrícia Maciel
Polyglutamine (PolyQ) diseases are a group of neurodegenerative disorders caused by the expansion of cytosine-adenine-guanine (CAG) trinucleotide repeats in the coding region of specific genes. This leads to the production of pathogenic proteins containing critically expanded tracts of glutamines. Although polyQ diseases are individually rare, the fact that these nine diseases are irreversibly progressive over 10 to 30 years, severely impairing and ultimately fatal, usually implicating the full-time patient support by a caregiver for long time periods, makes their economic and social impact quite significant...
November 21, 2016: Medicinal Research Reviews
https://www.readbyqxmd.com/read/27862081/arginase-inhibitors-a-rational-approach-over-one-century
#15
REVIEW
Marc Pudlo, Céline Demougeot, Corine Girard-Thernier
Arginase (EC 3.5.3.1) is the bimanganese enzyme that converts L-arginine into ornithine and urea. This enzyme was discovered more than a century ago and early α-amino acids were identified as weak inhibitors. It was only during the 90s, after nitric oxide (NO) was reported as one of the most important biological mediators and when tight interrelation of arginase and NO synthase was found, that the development of arginase inhibitors was accelerated. The regulation of arginase activity by the N-hydroxy-L-arginine (3, NOHA) intermediate of the NO synthesis was the starting point of the N-hydroxy-nor-arginine (21, nor-NOHA) that proved to be the first micromolar inhibitor...
November 15, 2016: Medicinal Research Reviews
https://www.readbyqxmd.com/read/27859448/nanotechnology-in-glycomics-applications-in-diagnostics-therapy-imaging-and-separation-processes
#16
REVIEW
Erika Dosekova, Jaroslav Filip, Tomas Bertok, Peter Both, Peter Kasak, Jan Tkac
This review comprehensively covers the most recent achievements (from 2013) in the successful integration of nanomaterials in the field of glycomics. The first part of the paper addresses the beneficial properties of nanomaterials for the construction of biosensors, bioanalytical devices, and protocols for the detection of various analytes, including viruses and whole cells, together with their key characteristics. The second part of the review focuses on the application of nanomaterials integrated with glycans for various biomedical applications, that is, vaccines against viral and bacterial infections and cancer cells, as therapeutic agents, for in vivo imaging and nuclear magnetic resonance imaging, and for selective drug delivery...
November 15, 2016: Medicinal Research Reviews
https://www.readbyqxmd.com/read/27775833/targeting-deubiquitinating-enzymes-in-glioblastoma-multiforme-expectations-and-challenges
#17
Wei-Lin Jin, Xiao-Yuan Mao, Guan-Zhong Qiu
Glioblastoma (GBM) is regarded as the most common primary intracranial neoplasm. Despite standard treatment with tumor resection and radiochemotherapy, the outcome remains gloomy. It is evident that a combination of oncogenic gain of function and tumor-suppressive loss of function has been attributed to glioma initiation and progression. The ubiquitin-proteasome system is a well-orchestrated system that controls the fate of most proteins by striking a dynamic balance between ubiquitination and deubiquitination of substrates, having a profound influence on the modulation of oncoproteins, tumor suppressors, and cellular signaling pathways...
October 24, 2016: Medicinal Research Reviews
https://www.readbyqxmd.com/read/27775829/approved-and-experimental-small-molecule-oncology-kinase-inhibitor-drugs-a-mid-2016-overview
#18
Peter M Fischer
Kinase inhibitor research is a comparatively recent branch of medicinal chemistry and pharmacology and the first small-molecule kinase inhibitor, imatinib, was approved for clinical use only 15 years ago. Since then, 33 more kinase inhibitor drugs have received regulatory approval for the treatment of a variety of cancers and the volume of reports on the discovery and development of kinase inhibitors has increased to an extent where it is now difficult-even for those working in the field-easily to keep an overview of the compounds that are being developed, as currently there are 231 such compounds, targeting 38 different protein and lipid kinases (not counting isoforms), in clinical use or under clinical investigation...
October 24, 2016: Medicinal Research Reviews
https://www.readbyqxmd.com/read/27604144/the-role-of-interleukin-1-in-inflammatory-and-malignant-human-skin-diseases-and-the-rationale-for-targeting-interleukin-1-alpha
#19
REVIEW
Mayassa J Bou-Dargham, Zahraa I Khamis, Armand B Cognetta, Qing-Xiang Amy Sang
Inflammation plays a major role in the induction and progression of several skin diseases. Overexpression of the major epidermal proinflammatory cytokines interleukin (IL) 1 alpha (IL-1α) and 1 beta (IL-1β) is positively correlated with symptom exacerbation and disease progression in psoriasis, atopic dermatitis, neutrophilic dermatoses, skin phototoxicity, and skin cancer. IL-1β and the interleukin-1 receptor I (IL-1RI) have been used as a therapeutic target for some autoinflammatory skin diseases; yet, their system-wide effects limit their clinical usage...
January 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/27569556/metastatic-melanoma-insights-into-the-evolution-of-the-treatments-and-future-challenges
#20
REVIEW
Antoine Millet, Anthony R Martin, Cyril Ronco, Stéphane Rocchi, Rachid Benhida
Melanoma is the deadliest form of skin cancer. While associated survival prognosis is good when diagnosed early, it dramatically drops when melanoma progresses into its metastatic form. Prior to 2011, the favored therapies include interleukin-2 and chemotherapies, regardless of their low efficiency and their toxicity. Following key biological findings, two new types of therapy have been approved. First, there are the targeted therapies, which rely on small molecule B-Raf and MEK inhibitors and allow the treatment of patients with B-Raf mutated melanoma...
January 2017: Medicinal Research Reviews
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