Target discovery using biobanks and human genetics.

Target discovery using biobanks and human genetics. Drug Discov Today. 2019 Sep 25;: Authors: Hicks MA, Hou CYC, Iranmehr A, Marosi K, Kirkness E Abstract Large-scale biobanks can yield unprecedented insights into our health and provide discoveries of new and potentially targetable biomarkers. Several protective loss-of-function alleles have been identified, including variants that protect against cardiovascular disease, obesity, type 2 diabetes, and asthma and allergic diseases. These alleles serve as indicators of efficacy, mimicking the effects of drugs and suggesting that inhibiting these genes could provide therapeutic benefit, as has been observed for PCSK9. We provide a context for these findings through a multifaceted review covering the use of genetics in drug discovery efforts through genome-wide and phenome-wide association studies, linking deep mutation scanning data to molecular function and highlighting some additional tools that might help in the interpretation of newly discovered variants. PMID: 31562982 [PubMed - as supplied by publisher]
Source: Drug Discovery Today - Category: Drugs & Pharmacology Authors: Tags: Drug Discov Today Source Type: research

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Abstract Obesity negatively affects children's health because of its associations with cardiovascular disease risk factors, type 2 diabetes, asthma, fatty liver disease, victimization stemming from social stigma and bullying, and poor mental health (e.g., anxiety and depression) (1). Children who have overweight or obesity in early childhood are approximately four times as likely to have overweight or obesity in young adulthood as their normal weight peers (2). Obesity prevalence is especially high among children from low-income families (3). In 2010, the overall upward trend in obesity prevalence turned downward ...
Source: MMWR Morb Mortal Wkl... - Category: Epidemiology Authors: Tags: MMWR Morb Mortal Wkly Rep Source Type: research
Study identifies new mechanism for airway pathophysiology in obese asthmatic patients Related items fromOnMedica Low fat vs low carb diet success not linked to genetics Type 2 diabetes in 10 times more young people than realised Should we recognise obesity as a disease? WHO dietary fat guidance fails to consider crucial evidence Taxing sugary foods would cut prevalence of obesity
Source: OnMedica Latest News - Category: UK Health Source Type: news
Abstract Cellular damage produced by conditions generating oxidative stress have far-reaching implications in human disease that encompass, but are not restricted to aging, cardiovascular disease, type 2 diabetes, airway inflammation/asthma, cancer, and metabolic syndrome including visceral obesity, insulin resistance, fatty liver disease, and dyslipidemia. Although there are numerous sources and cellular targets of oxidative stress, this review will highlight literature that has investigated downstream consequences of oxidatively-induced DNA damage in both nuclear and mitochondrial genomes. The presence of such d...
Source: DNA Repair - Category: Genetics & Stem Cells Authors: Tags: DNA Repair (Amst) Source Type: research
PPARγ: Potential therapeutic target for ailments beyond diabetes and its natural agonism. Curr Drug Targets. 2019 May 27;: Authors: Shafi S, Gupta P, Khatik GL, Gupta J Abstract The intense research interests have been observed in establishing PPAR gamma as a therapeutic target for diabetes. However, PPARγ is also emerging as an important therapeutic target for varied diseased states other than type2 diabetes like neurodegenerative disorders, cancer, spinal cord injury, asthma, and cardiovascular problems. Furthermore, glistazones, the synthetic thiazolidinediones, also known as insulin se...
Source: Current Drug Targets - Category: Drugs & Pharmacology Authors: Tags: Curr Drug Targets Source Type: research
Alessandro Poggi1*, Roberto Benelli2, Roberta Venè1, Delfina Costa1, Nicoletta Ferrari1, Francesca Tosetti1 and Maria Raffaella Zocchi3 1Molecular Oncology and Angiogenesis Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy 2Immunology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy 3Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy It is well established that natural killer (NK) cells are involved in both innate and adaptive immunity. Indeed, they can recognize molecules induced at the cell surface by stress signals ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
In this study, we investigated the antihypertensive effect and underlying mechanisms of P. asiatica L. seeds extract (PASE) in spontaneously hypertensive rat (SHR). Male SHRs were treated with 2.5 mg/kg of fosinopril (FOS) and 400 mg/kg of PASE orally per day for once or 12 weeks. SHR or Wistar-Kyoto rats (WKY) receiving vehicle (distilled water) was used as control. The results demonstrated systolic, diastolic, and mean blood pressures (SBP, DBP, and MBP) were significantly lowered after single and long-term intragastric administration of PASE. The cardiac and aortic index and collagen accumulation were improved in the PA...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
We examined the effects of the independent and combined effects of Zataria Multiflora supplementation and circuit resistance training (CRT) on selected adipokines among postmenopausal women. Forty-eight postmenopausal women were divided into four groups: Exercise (EG, n = 12), Zataria Multiflora (ZMG, n = 12), exercise and Zataria Multiflora (ZMEG, n = 12), and control (CG, n = 12). Participants in experimental groups either performed CRT (3 sessions per week with intensity at 55% of one-repetition maximum) or supplemented with Zataria Multiflora (500 mg every day after breakfast with 100 ml of water), or their combination...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Parental excess weight and especially pregestational maternal obesity and excessive weight gain during pregnancy have been related to an increased risk of metabolic (obesity, type 2 diabetes, cardiovascular disease, metabolic syndrome) and nonmetabolic (cancer, osteoporosis, asthma, neurologic alterations) diseases in the offspring, probably mediated by epigenetic mechanisms of fetal programming. Maternal underweight is less common in developed societies, but the discrepancy between a poor nutritional environment in utero and a normal or excessive postnatal food supply with rapid growth catch-up appears to be the main cand...
Source: Fertility and Sterility - Category: Reproduction Medicine Authors: Tags: Views and reviews Source Type: research
Conclusions In conclusion, articles in this Research Topic made a very significant contribution to our understanding of the role played by environmental factors, dysbiotic conditions, and infections in triggering diseases. Since this is a rapidly expanding area of research, many other factors contributing to the onset of these diseases are not covered here. We are confident, however, that further studies will expand the list as well as bring a better understanding of mechanisms involved in the onset of autoimmune and autoinflammatory diseases. Author Contributions All authors listed have made a substantial, direct and i...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
In this study, we attempted to find a DNA extraction protocol which could be effectively used to analyze both the bacterial and fungal community. We evaluated the effect of five DNA extraction methods (QIAamp DNA Stool Mini Kit, PureLinkTM Microbiome DNA Purification Kit, ZR Fecal DNA MiniPrepTM Kit, NucleoSpin® DNA Stool Kit, and IHMS protocol Q) on bacterial and fungal gut microbiome recovery using (i) a defined system of germ-free mice feces spiked with bacterial or fungal strains, and (ii) non-spiked human feces. In our experimental setup, we confirmed that the examined methods significantly differed in efficiency ...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
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