3,970 results match your criteria Drug Discoveries & Therapeutics [Journal]


Adhesion G protein-coupled receptors - candidate metabotropic mechanosensors and novel drug targets.

Authors:
Tobias Langenhan

Basic Clin Pharmacol Toxicol 2019 Mar 11. Epub 2019 Mar 11.

Rudolf Schönheimer Institute of Biochemistry, Division of General Biochemistry, Medical Faculty, Leipzig University, Johannisallee 30, 04103, Leipzig, Germany.

While a wide range of G protein-coupled receptors (GPCR) have emerged as prime targets for pharmacological intervention long ago, a distinct group of GPCR has only recently been identified and become a research subject to fundamental and clinical scientists. Adhesion-type GPCR (aGPCR) are exceptional members of the GPCR superfamily in many aspects: structurally they appear as chimeric surface molecules that possess signature domains of heptahelical (7TM) and adhesion proteins, many aGPCR are autoproteolytically processed, and several homologues have lately been shown to operate as mechanosensors. Bound together by the recent discovery of tethered agonism in aGPCR, these molecular and functional features have entered first models on how aGPCR are activated. Read More

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http://dx.doi.org/10.1111/bcpt.13223DOI Listing

TRPV2 suppresses Rac1 and RhoA activation and invasion in rheumatoid arthritis fibroblast-like synoviocytes.

Int Immunopharmacol 2019 Mar 6;70:268-273. Epub 2019 Mar 6.

Division of Rheumatology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. Electronic address:

The TRPV2 cation channel has been recently implicated in the regulation of arthritis severity, joint damage, and in the invasive behavior of the fibroblast-like synoviocyte (FLS). However, its mechanism of action was unknown. In this study we characterize the cell signaling events mediating the TRPV2 suppressive activity in FLS invasiveness. Read More

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http://dx.doi.org/10.1016/j.intimp.2019.02.051DOI Listing
March 2019
1 Read

Enhancement of hippocampal plasticity by physical exercise as a polypill for stress and depression: A review.

CNS Neurol Disord Drug Targets 2019 Mar 7. Epub 2019 Mar 7.

Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Joint International Research Laboratory of CNS Regeneration Ministry of Education, Jinan University, Guangzhou. China.

Generation of newborn neurons that form functional synaptic connections in the dentate gyrus of adult mammals, known as adult hippocampal neurogenesis, has been suggested to play critical roles in regulating mood, as well as certain forms of hippocampus-dependent learning and memory. Environmental stress suppresses structural plasticity including adult neurogenesis and dendritic remodeling in the hippocampus, whereas physical exercise exerts opposite effects. Here, we review recent discoveries on the potential mechanisms concerning how physical exercise mitigates the stress-related depressive disorder, with a focus on the perspective of modulation on hippocampal neurogenesis, dendritic remodeling and synaptic plasticity. Read More

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http://dx.doi.org/10.2174/1871527318666190308102804DOI Listing
March 2019
1 Read
2.628 Impact Factor

A Hierarchical Taxonomy of Psychopathology Can Transform Mental Health Research.

Perspect Psychol Sci 2019 Mar 7:1745691618810696. Epub 2019 Mar 7.

36 Department of Psychology, Stony Brook University.

For more than a century, research on psychopathology has focused on categorical diagnoses. Although this work has produced major discoveries, growing evidence points to the superiority of a dimensional approach to the science of mental illness. Here we outline one such dimensional system-the Hierarchical Taxonomy of Psychopathology (HiTOP)-that is based on empirical patterns of co-occurrence among psychological symptoms. Read More

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http://dx.doi.org/10.1177/1745691618810696DOI Listing

Harnessing the Inflammatory Reflex for the Treatment of Inflammation-Mediated Diseases.

Cold Spring Harb Perspect Med 2019 Mar 4. Epub 2019 Mar 4.

SetPoint Medical, Inc., Valencia, California 91355.

Treating diseases nonpharmacologically, using targeted neurostimulation instead of systemic drugs, is a hallmark of the burgeoning field of bioelectronic medicine. In this review, we provide a brief overview of the discovery and function of the prototypical neuroimmune reflex, the "inflammatory reflex." We discuss various biomarkers developed and used to translate early physiological discoveries into dosing parameters used in experimental settings, from the treatment of animal models of disease through a proof-of-concept clinical study in rheumatoid arthritis (RA). Read More

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http://dx.doi.org/10.1101/cshperspect.a034330DOI Listing

Thermophiles and the applications of their enzymes as new biocatalysts.

Bioresour Technol 2019 May 13;280:478-488. Epub 2019 Feb 13.

Fundación Biociencia, José Domingo Cañas 2280, Ñuñoa, Santiago, Chile; Facultad de Química y Biología, Universidad de Santiago de Chile, Alameda 3363, Estación Central, Santiago, Chile. Electronic address:

Ecological and efficient alternatives to industrial processes have sparked interest for using microorganisms and enzymes as biocatalysts. One of the difficulties is finding candidates capable of resisting the harsh conditions in which industrial processes usually take place. Extremophiles, microorganisms naturally found in "extreme" ecological niches, produce robust enzymes for bioprocesses and product development. Read More

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http://dx.doi.org/10.1016/j.biortech.2019.02.008DOI Listing

IPCT: Integrated Pharmacogenomic Platform of Human Cancer Cell Lines and Tissues.

Genes (Basel) 2019 Feb 22;10(2). Epub 2019 Feb 22.

Gachon Institute of Genome Medicine and Sciences, Incheon 400-011, Korea.

(1) : The exponential increase in multilayered data, including omics, pathways, chemicals, and experimental models, requires innovative strategies to identify new linkages between drug response information and omics features. Despite the availability of databases such as the Cancer Cell Line Encyclopedia (CCLE), the Cancer Therapeutics Response Portal (CTRP), and The Cancer Genome Atlas (TCGA), it is still challenging for biologists to explore the relationship between drug response and underlying genomic features due to the heterogeneity of the data. In light of this, the Integrated Pharmacogenomic Database of Cancer Cell Lines and Tissues (IPCT) has been developed as a user-friendly way to identify new linkages between drug responses and genomic features, as these findings can lead not only to new biological discoveries but also to new clinical trials. Read More

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http://www.mdpi.com/2073-4425/10/2/171
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http://dx.doi.org/10.3390/genes10020171DOI Listing
February 2019
1 Read

Impact of Active Antihyperglycemic Components as herbal therapy for Preventive Health Care Management of Diabetes.

Curr Mol Med 2019 Feb 19. Epub 2019 Feb 19.

Department of Bioscience and Biotechnology, Banasthali Vidyapith, Rajasthan. India.

Diabetes is a metabolic hyperglycemic condition that progressively develops, effect small and large sensory fibers in affected population. It has various complications as hypertension, coronary artery disease, stroke, blindness, kidney disease as well as peripheral neuropathy. Sulfonylureas, thiazolidinediones, metformin, biguanidine, acarbose and insulin are commonly used drugs by diabetic patients, but these all have certain side effects. Read More

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http://dx.doi.org/10.2174/1566524019666190219124301DOI Listing
February 2019
5 Reads

Adenosine and lipids: A forced marriage or a love match?

Adv Drug Deliv Rev 2019 Feb 21. Epub 2019 Feb 21.

Institut Galien Paris-Sud, Université Paris-Sud, CNRS, Université Paris Saclay, Châtenay-Malabry, France. Electronic address:

Adenosine is a fascinating compound, crucial in many biochemical processes: this ubiquitous nucleoside serves as an essential building block of RNA, is also a component of ATP and regulates numerous pathophysiological mechanisms via binding to four extracellular receptors. Due to its hydrophilic nature, it belongs to a different world than lipids, and has no affinity for them. Since the 1970's, however, new discoveries have emerged and prompted the scientific community to associate adenosine with the lipid family, especially via liposomal preparations and bioconjugation. Read More

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http://dx.doi.org/10.1016/j.addr.2019.02.005DOI Listing
February 2019
6 Reads

The Search for Disease-Modifying Therapies in Pulmonary Hypertension.

J Cardiovasc Pharmacol Ther 2019 Feb 17:1074248419829172. Epub 2019 Feb 17.

1 Division of Cardiology, Department of Medicine, Center for Pulmonary Vascular Biology and Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Pulmonary hypertension (PH) and its severe subtype pulmonary arterial hypertension (PAH) encompass a set of multifactorial diseases defined by sustained elevation of pulmonary arterial pressure and pulmonary vascular resistance leading to right ventricular failure and subsequent death. Pulmonary hypertension is characterized by vascular remodeling in association with smooth muscle cell proliferation of the arterioles, medial thickening, and plexiform lesion formation. Despite our recent advances in understanding its pathogenesis and related therapeutic discoveries, PH still remains a progressive disease without a cure. Read More

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http://dx.doi.org/10.1177/1074248419829172DOI Listing
February 2019

Dose-dependence of chemical carcinogenicity: Biological mechanisms for thresholds and implications for risk assessment.

Chem Biol Interact 2019 Mar 11;301:112-127. Epub 2019 Feb 11.

Ramboll US Corporation, Research Triangle Park, NC, USA.

Current regulatory practices for chemical carcinogens were established when scientific understanding of the molecular mechanisms of chemical carcinogenesis was in its infancy. Initial discovery that DNA mutation was the root of cancer led quickly to regulatory processes that assumed such a simple relationship could be described with a linear approach. This linear, no threshold approach has since become the default approach to risk assessment of chemicals with carcinogenic potential. Read More

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http://dx.doi.org/10.1016/j.cbi.2019.01.025DOI Listing

Light-triggered release of photocaged therapeutics - Where are we now?

J Control Release 2019 Mar 8;298:154-176. Epub 2019 Feb 8.

3B's Research Group - Biomaterials, Biodegradable and Biomimetic, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Avepark 4805-017 Barco, Guimarães, Portugal; ICVS/3B's PT Government Associated Laboratory, Braga/Guimarães, Portugal; The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Avepark 4805-017 Barco, Guimarães, Portugal.

The current available therapeutics face several challenges such as the development of ideal drug delivery systems towards the goal of personalized treatments for patients benefit. The application of light as an exogenous activation mechanism has shown promising outcomes, owning to the spatiotemporal confinement of the treatment in the vicinity of the diseased tissue, which offers many intriguing possibilities. Engineering therapeutics with light responsive moieties have been explored to enhance the bioavailability, and drug efficacy either in vitro or in vivo. Read More

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http://dx.doi.org/10.1016/j.jconrel.2019.02.006DOI Listing

New Frontiers in Lp(a)-Targeted Therapies.

Trends Pharmacol Sci 2019 03 4;40(3):212-225. Epub 2019 Feb 4.

Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada; Robarts Research Institute, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada. Electronic address:

Interest in lipoprotein (a) [Lp(a)] has exploded over the past decade with the emergence of genetic and epidemiological studies pinpointing elevated levels of this unique lipoprotein as a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve disease (CAVD). This review summarizes the most recent discoveries regarding therapeutic approaches to lower Lp(a) and presents these findings in the context of an emerging, although far from complete, understanding of the biosynthesis and catabolism of Lp(a). Application of Lp(a)-specific lowering agents to outcome trials will be the key to opening this new frontier in the battle against CVD. Read More

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http://dx.doi.org/10.1016/j.tips.2019.01.004DOI Listing
March 2019
2 Reads

A Longitudinal Study of the Neurologic Safety of Acute Baclofen Use After Spinal Cord Injury.

Neurotherapeutics 2019 Feb 6. Epub 2019 Feb 6.

International Collaboration on Repair Discoveries (ICORD), University of British Columbia, 818 West 10th Avenue, Vancouver, British Columbia, V5Z 1M9, Canada.

The objective of our study was to determine whether treatment with baclofen is neurologically safe with respect to exposure during recovery from spinal cord injury. We performed a secondary longitudinal analysis of a cohort of adult patients with traumatic acute spinal cord injury. Cumulative baclofen dose was computed over the first 4 weeks following injury from concomitant medication information from a completed clinical trial. Read More

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http://dx.doi.org/10.1007/s13311-019-00713-8DOI Listing
February 2019
2 Reads

The effect of physiological stretch and the valvular endothelium on mitral valve proteomes.

Exp Biol Med (Maywood) 2019 Mar 5;244(3):241-251. Epub 2019 Feb 5.

Department of Chemical Engineering, Texas Tech University, Lubbock, TX 79409-3121, USA.

Impact Statement: This work is important to the field of heart valve pathophysiology as it provides new insights into molecular markers of mechanically induced valvular degeneration as well as the protective role of the valvular endothelium. These discoveries reported here advance our current knowledge of the valvular endothelium and how its removal essentially takes valve leaflets into an environmental shock. In addition, it shows that static conditions represent a mild pathological state for valve leaflets, while 10% cyclic stretch provides valvular cell quiescence. Read More

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http://dx.doi.org/10.1177/1535370219829006DOI Listing
March 2019
1 Read

Understanding chondrodysplasia (cho): A comprehensive review of cho as an animal model of birth defects, disorders, and molecular mechanisms.

Birth Defects Res 2019 Mar 4;111(5):237-247. Epub 2019 Feb 4.

Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah.

Background: The mutant chondrodysplasia (cho) is a cartilage-targeting disorder in C57BL mice that results in dwarfing and other malformations stemming from this collagenopathy. Clarke Fraser made the discovery of the mutation accidentally in the early 1960s during the thalidomide tragedy.

Methods: For this review we identified key research on cho as since its discovery. Read More

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http://dx.doi.org/10.1002/bdr2.1473DOI Listing
March 2019
2 Reads

Self-mineralizing Ca-enriched methacrylated gellan gum beads for bone tissue engineering.

Acta Biomater 2019 Jan 29. Epub 2019 Jan 29.

3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal; The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, AvePark, 4805-017 Barco, Guimarães, Portugal. Electronic address:

In this study, methacrylated gellan-gum (GG-MA) heteropolysaccharide is proposed as a hydrogel for drug delivery and bone tissue engineering applications. Calcium-enriched beads obtained from the crosslinking of 1% (w/v) GG-MA solutions with 0.1 MCaCl were investigated, considering their intrinsic capacity to promote self-mineralization by ion binding and deposition. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S17427061193007
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http://dx.doi.org/10.1016/j.actbio.2019.01.053DOI Listing
January 2019
2 Reads

Emergence of membrane sphingolipids as a potential therapeutic target.

Biochimie 2019 Mar 28;158:257-264. Epub 2019 Jan 28.

State Key Laboratory of Biocontrol, Guangdong Key Laboratory of Plant Resources, School of Life Science, Sun Yat-sen University, Guangzhou, 510275, China. Electronic address:

Background: Though sphingolipids are ubiquitously present in eukaryotic cells, but until the last decade, they were merely considered as a structural component of the plasma membrane with limited function. However, over the last decade, numerous functions have been ascribed to sphingolipids after the seminal discoveries on the bioactivities of several sphingolipids.

Scope Of Review: Sphingolipids are now well-recognized signals for fundamental cellular processes. Read More

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http://dx.doi.org/10.1016/j.biochi.2019.01.018DOI Listing

Rodent models of frailty and their application in preclinical research.

Mech Ageing Dev 2019 Jan 28;179:1-10. Epub 2019 Jan 28.

Department of Pharmacology, Dalhousie University, Halifax, NS, Canada; Department of Medicine (Geriatric Medicine), Dalhousie University, Halifax, NS, Canada. Electronic address:

In clinical medicine, the concept of frailty is viewed as a state of high vulnerability to adverse health outcomes in people of the same age. Frailty is an important challenge because the loss of physiological reserve means that even minor stressors can lead to disability and death in those who are frail. Even so, the biology of frailty is not well understood. Read More

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http://dx.doi.org/10.1016/j.mad.2019.01.008DOI Listing
January 2019

Current and future influenza vaccines.

Nat Med 2019 Feb 28;25(2):212-220. Epub 2019 Jan 28.

Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.

Although antiviral drugs and vaccines have reduced the economic and healthcare burdens of influenza, influenza epidemics continue to take a toll. Over the past decade, research on influenza viruses has revealed a potential path to improvement. The clues have come from accumulated discoveries from basic and clinical studies. Read More

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http://www.nature.com/articles/s41591-018-0340-z
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http://dx.doi.org/10.1038/s41591-018-0340-zDOI Listing
February 2019
5 Reads

Post-Genomic Methodologies and Preclinical Animal Models: Chances for the Translation of Cardioprotection to the Clinic.

Int J Mol Sci 2019 Jan 25;20(3). Epub 2019 Jan 25.

Cardiovascular Program- ICCC, Research Institute-Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, 08025 Barcelona, Spain. (L.B.).

Although many cardioprotective strategies have demonstrated benefits in animal models of myocardial infarction, they have failed to demonstrate cardioprotection in the clinical setting highlighting that new therapeutic target and treatment strategies aimed at reducing infarct size are urgently needed. Completion of the Human Genome Project in 2001 fostered the post-genomic research era with the consequent development of high-throughput "omics" platforms including transcriptomics, proteomics, and metabolomics. Implementation of these holistic approaches within the field of cardioprotection has enlarged our understanding of ischemia/reperfusion injury with each approach capturing a different angle of the global picture of the disease. Read More

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http://dx.doi.org/10.3390/ijms20030514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387468PMC
January 2019

Catalysis Concepts in Medicinal Inorganic Chemistry.

Chemistry 2019 Jan 25. Epub 2019 Jan 25.

Donostia International Physics Center, Paseo Manuel de Lardizabal 4, Donostia, 20018, Spain.

Catalysis has strongly emerged in the field of medicinal inorganic chemistry as a suitable tool to deliver new drug candidates and to overcome drawbacks associated to metallodrugs. In this Concept article, we discuss representative examples of how catalysis has been applied in combination with metal complexes to deliver new therapy approaches. In particular, we explain key achievements in the design of catalytic metallodrugs that damage biomolecular targets and in the development of metal catalysis schemes for the activation of exogenous organic prodrugs. Read More

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http://dx.doi.org/10.1002/chem.201806341DOI Listing
January 2019

Agnostic-Histology Approval of new drugs in Oncology: are we already there?

Clin Cancer Res 2019 Jan 22. Epub 2019 Jan 22.

Oncology, Vall de Hebron Institute of Oncology ( VHIO).

Over the last years, several molecular aberrations have been unevenly described across cancers, although the distinct functional relevance in each biological context is not yet fully understood. Novel discoveries have led to the development of drugs tailored according to the molecular profile of patients, thus increasing the likelihood of response among biomarker-selected patients. In this context, there has been a progressive redefinition of a precision medicine framework where evidence-based development and earlier approvals might be now driven by this molecular information. Read More

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http://clincancerres.aacrjournals.org/lookup/doi/10.1158/107
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http://dx.doi.org/10.1158/1078-0432.CCR-18-3694DOI Listing
January 2019
11 Reads

dbHDPLS: A database of human disease-related protein-ligand structures.

Comput Biol Chem 2019 Feb 11;78:353-358. Epub 2019 Jan 11.

School of Electrical and Information Engineering, Anhui University of Technology, 243032 Ma'anshan, Anhui, China. Electronic address:

Protein-ligand complexes perform specific functions, most of which are related to human diseases. The database, called as human disease-related protein-ligand structures (dbHDPLS), collected 8833 structures which were extracted from protein data bank (PDB) and other related databases. The database is annotated with comprehensive information involving ligands and drugs, related human diseases and protein-ligand interaction information, with the information of protein structures. Read More

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http://dx.doi.org/10.1016/j.compbiolchem.2018.12.023DOI Listing
February 2019
1 Read

Krϋppel-like factors (KLFs) in renal physiology and disease.

EBioMedicine 2019 Feb 17;40:743-750. Epub 2019 Jan 17.

Pediatric Research Institute, Department of Pediatrics, Radiation Oncology, Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, USA. Electronic address:

Dysregulated Krϋppel-like factor (KLF) gene expression appears in many disease-associated pathologies. In this review, we discuss physiological functions of KLFs in the kidney with a focus on potential pharmacological modulation/therapeutic applications of these KLF proteins. KLF2 is critical to maintaining endothelial barrier integrity and preventing gap formations and in prevention of glomerular endothelial cell and podocyte damage in diabetic mice. Read More

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http://dx.doi.org/10.1016/j.ebiom.2019.01.021DOI Listing
February 2019
2 Reads

The MAPK Signaling Pathways as a Novel Way in Regulation and Treatment of Parasitic Diseases.

Diseases 2019 Jan 17;7(1). Epub 2019 Jan 17.

Department of Nursing teaching and Research, School of Basic Medicine, Guilin Medical University, Guangxi 541004, China.

Few major advances in fighting parasitic diseases have been made in China since the development of new methods for prevention, control, and elimination. However, the proportion of immunocompromised individuals has increased due to the growth of chronic diseases, population aging, and more frequent cases of patients with AIDS and cancer. All these problems can promote development of parasitic infections, which is commonly associated with manipulation of host signaling pathways and the innate immune system. Read More

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http://www.mdpi.com/2079-9721/7/1/9
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http://dx.doi.org/10.3390/diseases7010009DOI Listing
January 2019
7 Reads

The effect of vitamin D pathway genes and deferasirox pharmacogenetics on liver iron in thalassaemia major patients.

Pharmacogenomics J 2019 Jan 17. Epub 2019 Jan 17.

Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149, Turin, Italy.

Monitoring and treating iron overload is crucial in transfusion-dependent thalassaemia patients. Liver stiffness measurement by transient elastography and T2* magnetic resonance imaging represent non-invasive ways to evaluate the adequacy of the iron chelation treatment. We explored the role of single nucleotide polymorphisms involved in vitamin D metabolism, transport and activity, and in deferasirox metabolism on liver iron burden parameters. Read More

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http://dx.doi.org/10.1038/s41397-019-0071-7DOI Listing
January 2019
3 Reads

State of the science on mild cognitive impairment (MCI).

CNS Spectr 2019 Feb 17;24(1):78-87. Epub 2019 Jan 17.

Departments of Psychology and Psychiatry,University of Toronto,Rotman Research Institute,Baycrest Health Sciences,Toronto,Ontario,Canada.

Mild cognitive impairment (MCI) represents a transitional stage between healthy aging and dementia, and affects 10-15% of the population over the age of 65. The failure of drug trials in Alzheimer's disease (AD) treatment has shifted researchers' focus toward delaying progression from MCI to dementia, which would reduce the prevalence and costs of dementia profoundly. Diagnostic criteria for MCI increasingly emphasize the need for positive biomarkers to detect preclinical AD. Read More

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http://dx.doi.org/10.1017/S1092852918001347DOI Listing
February 2019
9 Reads

Neurodegenerative Charcot-Marie-Tooth disease as a case study to decipher novel functions of aminoacyl-tRNA synthetases.

J Biol Chem 2019 01 14. Epub 2019 Jan 14.

The Scripps Research Institute, United States.

Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes that catalyze the first reaction in protein biosynthesis, namely, the charging of transfer RNAs (tRNAs) with their cognate amino acids. aaRSs have been increasingly implicated in dominantly and recessively inherited human diseases. The most common aaRS-associated monogenic disorder is the incurable neurodegenerative disease Charcot-Marie-Tooth neuropathy (CMT), caused by dominant mono-allelic mutations in aaRSs. Read More

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http://www.jbc.org/lookup/doi/10.1074/jbc.REV118.002955
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http://dx.doi.org/10.1074/jbc.REV118.002955DOI Listing
January 2019
9 Reads

Halcyon days of TOR: Reflections on the multiple independent discovery of the yeast and mammalian TOR proteins.

Authors:
George P Livi

Gene 2019 Apr 9;692:145-155. Epub 2019 Jan 9.

Department of Human Genetics, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA 19426, USA. Electronic address:

The quest to elucidate the molecular mechanism of action of rapamycin in the early 1990s led to the discovery of the novel TOR (target of rapamycin) proteins in yeast and mammalian cells. This was a major breakthrough that resulted in the development of new rapamycin analogs as anti-cancer agents, and launched new research that revealed the pre-eminent biological role of mTOR (mammalian or mechanistic TOR). Beyond mediating rapamycin sensitivity, the TOR proteins are nutrient sensing protein kinases, conserved from yeast to man, with a core function in regulating cell growth, metabolism and overall cell survival. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S03781119183130
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http://dx.doi.org/10.1016/j.gene.2018.12.046DOI Listing
April 2019
7 Reads

Nanotechnology in peripheral nerve repair and reconstruction.

Adv Drug Deliv Rev 2019 Jan 11. Epub 2019 Jan 11.

3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017, Barco, Guimarães, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal; The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, AvePark, 4805-017 Barco, Guimarães, Portugal. Electronic address:

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http://dx.doi.org/10.1016/j.addr.2019.01.006DOI Listing
January 2019
1 Read

Precision Psychiatry and Dual Disorders.

J Dual Diagn 2019 Jan 14:1-10. Epub 2019 Jan 14.

b Research Unit and Dual Disorders Program, Centre Neuchâtelois de Psychiatrie (CNP) , Neuchâtel , Switzerland.

Objective: Addiction co-occurs with distinct pathological personality traits, other psychiatric disorders or symptoms and cognitive impairment, which are known as dual disorders or co-occurring disorders. This symptomatic high concurrency suggests that both conditions are in some ways causally linked. Research is ongoing to identify distinctive neurobehavioral mechanisms and endophenotypes that predispose individuals to compulsive drug use and other mental disorders. Read More

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https://www.tandfonline.com/doi/full/10.1080/15504263.2018.1
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http://dx.doi.org/10.1080/15504263.2018.1512727DOI Listing
January 2019
8 Reads

EU-OPENSCREEN: A Novel Collaborative Approach to Facilitate Chemical Biology.

SLAS Discov 2019 Mar 7;24(3):398-413. Epub 2019 Jan 7.

8 Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Screening Port, Hamburg, Germany.

Compound screening in biological assays and subsequent optimization of hits is indispensable for the development of new molecular research tools and drug candidates. To facilitate such discoveries, the European Research Infrastructure EU-OPENSCREEN was founded recently with the support of its member countries and the European Commission. Its distributed character harnesses complementary knowledge, expertise, and instrumentation in the discipline of chemical biology from 20 European partners, and its open working model ensures that academia and industry can readily access EU-OPENSCREEN's compound collection, equipment, and generated data. Read More

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http://dx.doi.org/10.1177/2472555218816276DOI Listing
March 2019
12 Reads

Water and soil pollution as determinant of water and food quality/contamination and its impact on male fertility.

Reprod Biol Endocrinol 2019 Jan 6;17(1). Epub 2019 Jan 6.

Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy.

Over the past two decades, public health has focused on the identification of environmental chemical factors that are able to adversely affect hormonal function, known as endocrine disruptors (EDs). EDs mimic naturally occurring hormones like estrogens and androgens which can in turn interfere with the endocrine system. As a consequence, EDs affect human reproduction as well as post and pre-natal development. Read More

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https://rbej.biomedcentral.com/articles/10.1186/s12958-018-0
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http://dx.doi.org/10.1186/s12958-018-0449-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321708PMC
January 2019
10 Reads

Mechanistic Pathways of ATP Sensitive Potassium Channels Referring to Cardio-Protective Effects and Cellular Functions.

Drug Res (Stuttg) 2019 Jan 4. Epub 2019 Jan 4.

Department of Pharmacology, R.R.S College of Pharmacy, Amethi, Uttar Pradesh, India.

A study of potassium channels correlates the fundamentals of mechanistic pathways and various physiological functions. The knowledge of these pathways provides the background, how to determine unit cell functions and to affect cardio protection. ATP sensitive potassium channels adjust excitability of membrane and functions as per metabolic status of cell. Read More

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http://dx.doi.org/10.1055/a-0806-7207DOI Listing
January 2019
2 Reads

Harnessing the Chemistry of the Indole Heterocycle to Drive Discoveries in Biology and Medicine.

Chembiochem 2019 Jan 4. Epub 2019 Jan 4.

University of Florida, Medicinal Chemistry, 1345 Center Dr., Medical Sciences Building, P5-33, 32610, Gainesville, UNITED STATES.

Indole-containing compounds demonstrate an array of biological activities relevant to numerous human diseases. The biological activities of diverse indole-based agents are driven by molecular interactions between indole agent and critical therapeutic target. The chemical inventory of medicinally useful or promising indole compounds spans the entire structural spectrum, from simple synthetic indoles to highly complex indole alkaloids. Read More

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http://dx.doi.org/10.1002/cbic.201800768DOI Listing
January 2019
1 Read

Integrative molecular analysis of colorectal cancer and gastric cancer: What have we learnt?

Cancer Treat Rev 2019 Feb 21;73:31-40. Epub 2018 Dec 21.

Gastrointestinal and Lymphoma Unit, The Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5PT, United Kingdom. Electronic address:

Gastrointestinal (GI) malignancies comprise a diverse group of cancers with varying aetiology, clinical course, management and prognosis. Advances over the last decade in molecular diagnostics in colorectal cancer (CRC) have helped to improve our understanding of the underlying complex mechanisms in the development and progression of this highly heterogenous disease. Large scale integrative analysis has identified molecularly distinct subgroups of CRC with differing clinical behaviour. Read More

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http://dx.doi.org/10.1016/j.ctrv.2018.12.004DOI Listing
February 2019
2 Reads

Rasputin a decade on and more promiscuous than ever? A review of G3BPs.

Biochim Biophys Acta Mol Cell Res 2019 Mar 5;1866(3):360-370. Epub 2018 Sep 5.

Griffith Institute for Drug Discovery, 46 Don Young Road, Nathan, QLD 4111, Australia; School of Environment and Sciences, Griffith University, Brisbane, QLD 4111, Australia. Electronic address:

Ras-GTPase-activating protein (SH3 domain)-binding proteins (G3BPs, also known as Rasputin) are a family of RNA binding proteins that regulate gene expression in response to environmental stresses by controlling mRNA stability and translation. G3BPs appear to facilitate this activity through their role in stress granules for which they are considered a core component, however, it should be noted that not all stress granules contain G3BPs and this appears to be contextual depending on the environmental stress and the cell type. Although the role of G3BPs in stress granules appears to be one of its major roles, data also strongly suggests that they interact with mRNAs outside of stress granules to regulate gene expression. Read More

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http://dx.doi.org/10.1016/j.bbamcr.2018.09.001DOI Listing
March 2019
1 Read

Pivotal role of carnosine in the modulation of brain cells activity: Multimodal mechanism of action and therapeutic potential in neurodegenerative disorders.

Prog Neurobiol 2019 Apr 26;175:35-53. Epub 2018 Dec 26.

DPNC, University of Geneva, Geneva, Switzerland; CERN, Geneva, Switzerland. Electronic address:

Carnosine (β-alanyl-l-histidine), a dipeptide, is an endogenous antioxidant widely distributed in excitable tissues like muscles and the brain. Although discovered more than a hundred years ago and having been extensively studied in the periphery, the role of carnosine in the brain remains mysterious. Carnosinemia, a rare metabolic disorder with increased levels of carnosine in urine and low levels or absence of carnosinase in the blood, is associated with severe neurological symptoms in humans. Read More

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http://dx.doi.org/10.1016/j.pneurobio.2018.12.004DOI Listing
April 2019
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Bridging the gap between the laboratory and the clinic for patients with sarcopenia.

Authors:
Miles D Witham

Biogerontology 2019 Apr 27;20(2):241-248. Epub 2018 Dec 27.

AGE Research Group, NIHR Newcastle Biomedical Research Centre, Biomedical Research Building, Campus for Ageing and Vitality, Newcastle, NE4 5PL, UK.

Sarcopenia-the age-related loss of skeletal muscle mass and strength-is a major public health issue. Sarcopenia is associated with an increased risk of falls, disability, dependency, institutionalization, hospital stay and early death. Finding interventions to stabilize, reverse or prevent sarcopenia is therefore a key goal for clinical ageing research. Read More

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http://link.springer.com/10.1007/s10522-018-09793-z
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http://dx.doi.org/10.1007/s10522-018-09793-zDOI Listing
April 2019
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The Crown and the Scepter: Roles of the Protein Corona in Nanomedicine.

Adv Mater 2018 Dec 27:e1805740. Epub 2018 Dec 27.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, China.

Engineering nanomaterials are increasingly considered promising and powerful biomedical tools or devices for imaging, drug delivery, and cancer therapies, but few nanomaterials have been tested in clinical trials. This wide gap between bench discoveries and clinical application is mainly due to the limited understanding of the biological identity of nanomaterials. When they are exposed to the human body, nanoparticles inevitably interact with bodily fluids and thereby adsorb hundreds of biomolecules. Read More

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http://dx.doi.org/10.1002/adma.201805740DOI Listing
December 2018
1 Read

Parkinson Diseases in the 2020s and Beyond: Replacing Clinico-Pathologic Convergence With Systems Biology Divergence.

J Parkinsons Dis 2018 ;8(s1):S59-S64

The Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic, University Health Network, University of Toronto, Toronto, Canada.

Parkinson disease has been considered for practical purposes a heterogeneous clinico-pathological entity. The operational definition requires clinical ascertainment of a levodopa-responsive parkinsonism with no "atypical" features, and pathological criteria based on the finding, usually at postmortem, of aggregates of α-synuclein in Lewy bodies and Lewy neurites. The underlying assumption has been that a molecular-biological disorder, targetable for disease modification as a whole, underlies this clinico-pathologic, convergent model of disease. Read More

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http://dx.doi.org/10.3233/JPD-181465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311362PMC
January 2018
1 Read

DNA Mismatch Repair Deficiency and Immune Checkpoint Inhibitors in Gastrointestinal Cancers.

Gastroenterology 2019 Mar 19;156(4):890-903. Epub 2018 Dec 19.

Center for Gastrointestinal Research, Center for Translational Genomics and Oncology, Baylor Scott & White Research Institute and Charles A Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas. Electronic address:

In the recent few years, significant efforts have been undertaken for the development of different immunotherapeutic approaches against cancer. In this context, immune checkpoint inhibitors (ICIs), a novel class of immunotherapeutic drugs with the potential to unleash the immune system, have emerged as authentic game-changers for managing patients with various cancers, including gastrointestinal malignancies. Although the majority of gastrointestinal cancers are generally considered poorly immunogenic, basic research findings and data from clinical trials have proven that subset(s) of patients with various digestive tract cancers are highly responsive to ICI-based therapy. Read More

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http://dx.doi.org/10.1053/j.gastro.2018.11.071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409193PMC
March 2019
1 Read

Clinical Needs as a Starting Point for Different Strategies in Computational Drug Development.

Authors:
César Portela

Drug Res (Stuttg) 2018 Dec 20. Epub 2018 Dec 20.

Military Laboratory of Chemical and Pharmaceutical Products, Lisboa, Portugal.

Traditionally, the first step in the development of drugs is the definition of the target, by choice of a biological structure involved in a disease or by recognition of a molecule with some degree of a biological activity that presents itself as druggable and endowed with therapeutic potential. The complexity of the pathophysiological mechanisms of disease and of the structures of the molecules involved creates several challenges in this drug discovery process. These difficulties also come from independent operation of the different parts involved in drug development, with little interaction between clinical practitioners, academic institutions and large pharmaceutical companies. Read More

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http://dx.doi.org/10.1055/a-0820-9278DOI Listing
December 2018
2 Reads

Translating GWAS findings into therapies for depression and anxiety disorders: gene-set analyses reveal enrichment of psychiatric drug classes and implications for drug repositioning.

Psychol Med 2018 Dec 20:1-17. Epub 2018 Dec 20.

School of Biomedical Sciences, The Chinese University of Hong Kong,Shatin,Hong Kong.

Background: Depression and anxiety disorders (AD) are the first and sixth leading causes of disability worldwide. Despite their high prevalence and significant disability resulted, there are limited advances in new drug development. Recently, genome-wide association studies (GWAS) have greatly advanced our understanding of the genetic basis underlying psychiatric disorders. Read More

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http://dx.doi.org/10.1017/S0033291718003641DOI Listing
December 2018
1 Read

Human Induced Pluripotent Stem Cells in the Curative Treatment of Diabetes and Potential Impediments Ahead.

Adv Exp Med Biol 2018 Dec 21. Epub 2018 Dec 21.

Clinical Islet Transplant Program, Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada.

The successful landmark discovery of mouse and human inducible pluripotential stem cells (iPSC's) by Takahashi and Yamanaka in 2006 and 2007 has triggered a revolution in the potential generation of self-compatible cells for regenerative medicine, and further opened up a new avenue for "disease in dish" drug screening of self-target cells (Neofytou et al. 2015). The introduction of four 'Yamanaka' transcription factors through viral or other transfection of mature cells can induce pluripotency and acquired plasticity. Read More

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http://link.springer.com/10.1007/5584_2018_305
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http://dx.doi.org/10.1007/5584_2018_305DOI Listing
December 2018
5 Reads

Drosophila Jak/STAT Signaling: Regulation and Relevance in Human Cancer and Metastasis.

Int J Mol Sci 2018 Dec 14;19(12). Epub 2018 Dec 14.

Department of Biological Sciences, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA.

Over the past three-decades, Janus kinase (Jak) and signal transducer and activator of transcription (STAT) signaling has emerged as a paradigm to understand the involvement of signal transduction in development and disease pathology. At the molecular level, cytokines and interleukins steer Jak/STAT signaling to transcriptional regulation of target genes, which are involved in cell differentiation, migration, and proliferation. Jak/STAT signaling is involved in various types of blood cell disorders and cancers in humans, and its activation is associated with carcinomas that are more invasive or likely to become metastatic. Read More

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http://dx.doi.org/10.3390/ijms19124056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320922PMC
December 2018
1 Read

Invasive and Non-invasive Stimulation of the Obese Human Brain.

Authors:
Burkhard Pleger

Front Neurosci 2018 29;12:884. Epub 2018 Nov 29.

Department of Neurology, BG University Clinic Bergmannsheil, Ruhr-University Bochum, Bochum, Germany.

Accumulating evidence suggests that non-invasive and invasive brain stimulation may reduce food craving and calorie consumption rendering these techniques potential treatment options for obesity. Non-invasive transcranial direct current stimulation (tDCS) or repetitive transcranial magnet stimulation (rTMS) are used to modulate activity in superficially located executive control regions, such as the dorsolateral prefrontal cortex (DLPFC). Modulation of the DLPFC's activity may alter executive functioning and food reward processing in interconnected dopamine-rich regions such as the striatum or orbitofrontal cortex. Read More

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http://dx.doi.org/10.3389/fnins.2018.00884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6281888PMC
November 2018
2 Reads

From Discovery to Bedside: Targeting the Ubiquitin System.

Cell Chem Biol 2019 Feb 13;26(2):156-177. Epub 2018 Dec 13.

Department of Discovery Chemistry, Genentech, Inc., South San Francisco, CA 94008, USA.

The ubiquitin/proteasome system is a primary conduit for selective intracellular protein degradation. Since its discovery over 30 years ago, this highly regulated system continues to be an active research area for drug discovery that is exemplified by several approved drugs. Here we review compounds in preclinical testing, clinical trials, and approved drugs, with the aim of highlighting innovative discoveries and breakthrough therapies that target the ubiquitin system. Read More

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http://dx.doi.org/10.1016/j.chembiol.2018.10.022DOI Listing
February 2019
2 Reads

LncRNAs in ovarian cancer.

Clin Chim Acta 2019 Mar 13;490:17-27. Epub 2018 Dec 13.

Department of Obstetrics and Gynecology, Zhangjiagang First People's Hospital, Zhangjiagang 215600, Jiangsu, PR China. Electronic address:

Ovarian cancer is one of the most common gynecologic malignancies and has a poor prognosis. Recently, long noncoding RNAs (lncRNAs) have been identified as key regulators of cancer development. Studies have shown that the dysregulation of lncRNAs is frequently observed in ovarian cancer and greatly contributes to malignant phenotypical changes. Read More

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http://dx.doi.org/10.1016/j.cca.2018.12.013DOI Listing
March 2019
3 Reads