Leveraging high-dimensional molecular datasets can help us develop mechanistic insight into associations between genetic variants and complex traits. In this study, we integrated human proteome data derived from brain tissue to evaluate whether targeted proteins putatively mediate the effects of genetic variants on seven neurological phenotypes (Alzheimer disease, amyotrophic lateral sclerosis, depression, insomnia, intelligence, neuroticism, and schizophrenia). Applying the principles of Mendelian randomization (MR) systematically across the genome highlighted 43 effects between genetically predicted proteins derived from the dorsolateral prefrontal cortex and these outcomes. Furthermore, genetic colocalization provided evidence that the same causal variant at 12 of these loci was responsible for variation in both protein and neurological phenotype. This included genes such as DCC, which encodes the netrin-1 receptor and has an important role in the development of the nervous system (p = 4.29 × 10-11 with neuroticism), as well as SARM1, which has been previously implicated in axonal degeneration (p = 1.76 × 10-08 with amyotrophic lateral sclerosis). We additionally conducted a phenome-wide MR study for each of these 12 genes to assess potential pleiotropic effects on 700 complex traits and diseases. Our findings suggest that genes such as SNX32, which was initially associated with increased risk of Alzheimer disease, may potentially influence other complex traits in the opposite direction. In contrast, genes such as CTSH (which was also associated with Alzheimer disease) and SARM1 may make worthwhile therapeutic targets because they did not have genetically predicted effects on any of the other phenotypes after correcting for multiple testing.Obstructive sleep apnea (OSA) is a common clinical condition associated with increased cardiovascular morbidity and mortality. https://www.selleckchem.com/products/nd-630.html Recent evidence from clinical studies and animal models suggest that OSA can promote cardiovascular disease by inducing autonomic, hemodynamic, inflammatory and metabolic dysregulation. However, most of the evidence addressing hard endpoints in humans is derived from observational studies. Several challenges have been noted in the pursuit of a comprehensive knowledge base about the impact of OSA including 1) the precise mechanisms by which OSA causes metabolic and cardiovascular consequences are not clear, which limits our current ability to address potential targets in OSA; 2) several patients with OSA, even with severe forms, present with no or mild daytime symptoms. Beyond the obvious challenges for obtaining good adherence for conventional OSA treatments, there is evidence that symptomatic vs. asymptomatic patients with OSA do not necessarily have the same metabolic and cardiovascular outcomes; and 3) the cardiovascular response to OSA treatment may vary even in those patients with good adherence. In this scenario, there is an obvious need to develop biomarkers in the OSA research area. This review focuses on describing the advances that have occurred so far in exploring potential OSA biomarkers with clear emphasis for the cardiovascular risk. Particular attention will be devoted to discuss molecular biomarkers including the potential role of microRNAs, proteomics and metabolomics. We also discuss the major challenges and perspectives in this growing research field.Background Periodontitis is one of the most prevalent inflammatory diseases in humans. It is associated with the presence of bacteria and is mediated by the host's immune response This study represents a systematic review and meta-analysis trying to answer the following question "What is the effect of antimicrobial photodynamic therapy (aPDT) as an adjunct to scaling and root planing (SRP) compared to systemic antibiotic therapy with amoxicillin plus metronidazole (AMX+MTZ) on the non-surgical treatment of periodontitis?". Methods Clinical studies comparing aPDT with systemic use of AMX+MTZ were searched until January of 2020 using the databases PubMed, MEDLINE, SCOPUS, EMBASE, Cochrane Central, Web of Science and Scielo, as well manual searches in related journals. Periodontal clinical parameters such as probing depth (PD), clinical attachment level (CAL) and bleeding on probing (BOP) were statistically analyzed. Results Five randomized clinical studies (RCTs) were included within the eligibility criteria, and served as a basis for qualitative and quantitative analyzes. All the studies reported an improvement in the clinical parameters with both therapies, although in a direct comparison, our analyzes did not find statistical differences that indicate the superiority of one supporting treatment in relation to the other. Conclusion Although the limited number of RCTs and the great heterogeneity between them, it can conclude that aPDT presents similar clinical results compared to antibiotic therapy with AMX+MTZ as adjuvants in the non-surgical treatment of periodontitis.Background and aims The pathogenesis Metabolic Syndrome (MetS), a common global problem, remains to be elucidated. As part of our exploratory metabolomics research we determined if homoserine levels are an early biomarker of nascent MetS. Methods An exploratory study involving 28 patients with nascent MetS and 20 matched controls. Metabolites were studied from early morning urine samples and assayed by the NIH Western Metabolomics Center using gas chromatography time-of-flight mass spectrometry and were standardized to urine creatinine. All of the patients enrolled in the study had normal renal and hepatic function. Results Patients with MetS had statistically significant increases in overall waist circumference, blood pressure, glucose, HOMA-IR, HbA1C in comparison to the control group. Additionally, increases in IL-1b, IL-6, TLR-4, endotoxin, and leptin were also seen in the MetS group subjects compared to the control group. The concentrations of homoserine were significantly decreased 3-fold in patients with MetS in comparison to the matched controls, p = 0.0027. Furthermore, levels of homoserine were inversely correlated to multiple biomarkers of inflammation and cardio-metabolic risk factors such as HbA1C, blood pressure, TLR-4, leptin, endotoxin, and SAT secreted fetuin A. In addition, homoserine was positively correlated with lysine and NAT. Conclusions In conclusion, low levels of homoserine could potentially contribute to the proinflammatory state in MetS.