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Medicinal Research Reviews

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https://www.readbyqxmd.com/read/28422298/bridging-type-2-diabetes-and-alzheimer-s-disease-assembling-the-puzzle-pieces-in-the-quest-for-the-molecules-with-therapeutic-and-preventive-potential
#1
REVIEW
Ana Marta de Matos, Maria Paula de Macedo, Amélia Pilar Rauter
Type 2 diabetes (T2D) and Alzheimer's disease (AD) are two age-related amyloid diseases that affect millions of people worldwide. Broadly supported by epidemiological data, the higher incidence of AD among type 2 diabetic patients led to the recognition of T2D as a tangible risk factor for the development of AD. Indeed, there is now growing evidence on brain structural and functional abnormalities arising from brain insulin resistance and deficiency, ultimately highlighting the need for new approaches capable of preventing the development of AD in type 2 diabetic patients...
April 19, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28328012/free-fatty-acid-receptor-1-ffar1-as-an-emerging-therapeutic-target-for-type-2-diabetes-mellitus-recent-progress-and-prevailing-challenges
#2
REVIEW
Zheng Li, Xue Xu, Wenlong Huang, Hai Qian
The free fatty acid receptor 1 (FFAR1/GPR40) amplifies glucose-dependent insulin secretion; therefore, it has attracted widespread attention as a promising antidiabetic target. Current clinical proof of concept also indicates that FFAR1 agonists achieve the initially therapeutic endpoint for the treatment of type 2 diabetes mellitus (T2DM) without the hypoglycemic risk. Thus, many pharmaceutical companies and academic institutes are competing to develop FFAR1 agonists. However, several candidates have been discontinued in clinical trials, often without reporting the underlying reasons...
March 22, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28295439/genome-engineering-and-modification-toward-synthetic-biology-for-the-production-of-antibiotics
#3
REVIEW
Xuan Zou, Lianrong Wang, Zhiqiang Li, Jie Luo, Yunfu Wang, Zixin Deng, Shiming Du, Shi Chen
Antibiotic production is often governed by large gene clusters composed of genes related to antibiotic scaffold synthesis, tailoring, regulation, and resistance. With the expansion of genome sequencing, a considerable number of antibiotic gene clusters has been isolated and characterized. The emerging genome engineering techniques make it possible towards more efficient engineering of antibiotics. In addition to genomic editing, multiple synthetic biology approaches have been developed for the exploration and improvement of antibiotic natural products...
March 15, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28240384/toward-hydrogen-sulfide-based-therapeutics-critical-drug-delivery-and-developability-issues
#4
REVIEW
Yueqin Zheng, Bingchen Yu, Ladie Kimberly De La Cruz, Manjusha Roy Choudhury, Abiodun Anifowose, Binghe Wang
Hydrogen sulfide (H2 S), together with nitric oxide (NO) and carbon monoxide (CO), belongs to the gasotransmitter family and plays important roles in mammals as a signaling molecule. Many studies have also shown the various therapeutic effects of H2 S, which include protection against myocardial ischemia injury, cytoprotection against oxidative stress, mediation of neurotransmission, inhibition of insulin signaling, regulation of inflammation, inhibition of the hypoxia-inducible pathway, and dilation of blood vessels...
February 27, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28295428/atheroprotective-effects-and-molecular-targets-of-tanshinones-derived-from-herbal-medicine-danshen
#5
REVIEW
Jian Fang, Peter J Little, Suowen Xu
Medicinal plant-derived bioactive compounds modulate multiple therapeutic targets in cardiovascular diseases (CVDs), rendering herb-derived phytochemicals effective against one of the major CVDs-atherosclerosis. Danshen (Salvia milthiorriza Bunge) is a Chinese medicine that has been used in cardio- and cerebro-vascular therapeutic remedies in Asian countries for many years. Emerging evidence from cellular, animal, and clinical studies suggests that major lipophilic tanshinones from Danshen can treat atherosclerotic CVDs...
February 16, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28181261/the-search-for-potent-small-molecule-hdacis-in-cancer-treatment-a-decade-after-vorinostat
#6
REVIEW
Chiara Zagni, Giuseppe Floresta, Giulia Monciino, Antonio Rescifina
Histone deacetylases (HDACs) play a crucial role in the remodeling of chromatin, and are involved in the epigenetic regulation of gene expression. In the last decade, inhibition of HDACs came out as a target for specific epigenetic changes associated with cancer and other diseases. Until now, more than 20 HDAC inhibitors (HDACIs) have entered clinical studies, and some of them (e.g., vorinostat, romidepsin) have been approved for the treatment of cutaneous T-cell lymphoma. This review provides an overview of current knowledge, progress, and molecular mechanisms of HDACIs, covering a period from 2011 until 2015...
February 9, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/27879006/allosteric-modulation-an-alternate-approach-targeting-the-cannabinoid-cb1-receptor
#7
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...
May 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28128443/potential-therapeutic-applications-of-adenosine-a2a-receptor-ligands-and-opportunities-for-a2a-receptor-imaging
#8
REVIEW
Aren van Waarde, Rudi A J O Dierckx, Xiaoyun Zhou, Shivashankar Khanapur, Hideo Tsukada, Kiichi Ishiwata, Gert Luurtsema, Erik F J de Vries, Philip H Elsinga
Adenosine A2A receptors (A2A Rs) are highly expressed in the human striatum, and at lower densities in the cerebral cortex, the hippocampus, and cells of the immune system. Antagonists of these receptors are potentially useful for the treatment of motor fluctuations, epilepsy, postischemic brain damage, or cognitive impairment, and for the control of an immune checkpoint during immunotherapy of cancer. A2A R agonists may suppress transplant rejection and graft-versus-host disease; be used to treat inflammatory disorders such as asthma, inflammatory bowel disease, and rheumatoid arthritis; be locally applied to promote wound healing and be employed in a strategy for transient opening of the blood-brain barrier (BBB) so that therapeutic drugs and monoclonal antibodies can enter the brain...
January 27, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28094448/human-antimicrobial-peptides-in-bodily-fluids-current-knowledge-and-therapeutic-perspectives-in-the-postantibiotic-era
#9
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
#10
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
#11
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
#12
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/27604144/the-role-of-interleukin-1-in-inflammatory-and-malignant-human-skin-diseases-and-the-rationale-for-targeting-interleukin-1-alpha
#13
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
#14
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
https://www.readbyqxmd.com/read/27518199/mechanistic-studies-of-viral-entry-an-overview-of-dendrimer-based-microbicides-as-entry-inhibitors-against-both-hiv-and-hsv-2-overlapped-infections
#15
REVIEW
Daniel Sepúlveda-Crespo, Rafael Ceña-Díez, José Luis Jiménez, Ma Ángeles Muñoz-Fernández
This review provides an overview of the development of different dendrimers, mainly polyanionic, against human immunodeficiency virus (HIV) and genital herpes (HSV-2) as topical microbicides targeting the viral entry process. Vaginal topical microbicides to prevent sexually transmitted infections such as HIV and HSV-2 are urgently needed. To inhibit HIV/HSV-2 entry processes, new preventive targets have been established to maximize the current therapies against wild-type and drug-resistant viruses. The entry of HIV/HSV-2 into target cells is a multistep process that triggers a cascade of molecular interactions between viral envelope proteins and cell surface receptors...
January 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/27502146/applications-of-polymers-as-pharmaceutical-excipients-in-solid-oral-dosage-forms
#16
REVIEW
Nir Debotton, Arik Dahan
Over the last few decades, polymers have been extensively used as pharmaceutical excipients in drug delivery systems. Pharmaceutical polymers evolved from being simply used as gelatin shells comprising capsule to offering great formulation advantages including enabling controlled/slow release and specific targeting of drugs to the site(s) of action (the "magic bullets" concept), hence hold a significant clinical promise. Oral administration of solid dosage forms (e.g., tablets and capsules) is the most common and convenient route of drug administration...
January 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/27480072/therapeutic-strategies-and-pharmacological-tools-influencing-s1p-signaling-and-metabolism
#17
REVIEW
Dominik Vogt, Holger Stark
During the last two decades the study of the sphingolipid anabolic, catabolic, and signaling pathways has attracted enormous interest. Especially the introduction of fingolimod into market as first p.o. therapeutic for the treatment of multiple sclerosis has boosted this effect. Although the complex regulation of sphingosine-1-phosphate (S1P) and other catabolic and anabolic sphingosine-related compounds is not fully understood, the influence on different (patho)physiological states from inflammation to cytotoxicity as well as the availability of versatile pharmacological tools that represent new approaches to study these states are described...
January 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28029168/trends-in-regenerative-medicine-repigmentation-in-vitiligo-through-melanocyte-stem-cell-mobilization
#18
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
#19
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
#20
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
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