Quantitative trait locus (xQTL) approaches identify risk genes and drug targets from human non-coding genomes.

Advances and reduction of costs in various sequencing technologies allow for a closer look at variations present in the non-coding regions of the human genome. Correlating non-coding variants with large-scale multi-omic data holds the promise not only of a better understanding of likely causal connections between non-coding DNA and expression of traits but also identifying potential disease-modifying medicines. Genome-phenome association studies have created large datasets of DNA variants that are associated with multiple traits or diseases, such as Alzheimer's disease; yet, the functional consequences of variants, in particular of non-coding variants, remain largely unknown. Recent advances in functional genomics and computational approaches have led to the identification of potential roles of DNA variants, such as various quantitative trait locus (xQTL) techniques. Multi-omic assays and analytic approaches toward xQTL have identified links between genetic loci and human transcriptomic, epigenomic, proteomic and metabolomic data. In this review, we first discuss the recent development of xQTL from multi-omic findings. We then highlight multimodal analysis of xQTL and genetic data for identification of risk genes and drug targets using Alzheimer's disease as an example. We finally discuss challenges and future research directions (e.g. artificial intelligence) for annotation of non-coding variants in complex diseases.

Thermal desorption treatment of petroleum hydrocarbon-contaminated soils of tundra, taiga, and forest steppe landscapes.

The results of field, analytical, and experimental research at a number of production facilities reflect the properties of oil-contaminated soils in 3 landscapes: the permafrost treeless Arctic ecosystem, boreal forest, and temperate-climate grassland-woodland ecotone. Laboratory studies have revealed the concentrations of petroleum hydrocarbons in soils, ranging from medium levels of 2000-3000 mg/kg to critical figures over 5000 mg/kg, being 2-25 times higher than the permissible content of oil products in soils. The experimentally applied thermal effects for the oil products desorption from the soil allowed finding an optimal regime: the treatment temperature from 25 to 250 °C reduces the concentrations to an acceptable value. The conditions are environmentally sound, given that the complete combustion point of humates is ca. 450 °C. The outcomes suggest the eco-friendly solution for soil remediation, preserving the soil fertility in fragile cold environments and in more resilient temperate climates, where revitalized brownfields are essential for food production.

Systematic characterization of multi-omics landscape between gut microbial metabolites and GPCRome in Alzheimer's disease.

Shifts in the magnitude and nature of gut microbial metabolites have been implicated in Alzheimer's disease (AD), but the host receptors that sense and respond to these metabolites are largely unknown. Here, we develop a systems biology framework that integrates machine learning and multi-omics to identify molecular relationships of gut microbial metabolites with non-olfactory G-protein-coupled receptors (termed the "GPCRome"). We evaluate 1.09 million metabolite-protein pairs connecting 408 human GPCRs and 335 gut microbial metabolites. Using genetics-derived Mendelian randomization and integrative analyses of human brain transcriptomic and proteomic profiles, we identify orphan GPCRs (i.e., GPR84) as potential drug targets in AD and that triacanthine experimentally activates GPR84. We demonstrate that phenethylamine and agmatine significantly reduce tau hyperphosphorylation (p-tau181 and p-tau205) in AD patient induced pluripotent stem cell-derived neurons. This study demonstrates a systems biology framework to uncover the GPCR targets of human gut microbiota in AD and other complex diseases if broadly applied.

The biopuncture in dorsopathy.

The article summarizes the results of our own scientific and practical research on biopuncture (or pharmacopuncture) - local stimulation of acupuncture points with small doses of drugs or other agents. The "object" of the work was dorsopathies at the lumbosacral level, the choice of which was explained by the widest coverage of the population, the protracted course and the severity of the consequences. In the course of the research, the addition and even potentiation of the reflex and drug links of the method under consideration was noted. In particular, favorable changes in the status of patients observed against the background of biopuncture by complex agents were accompanied by a significant improvement in the results of psychological and electrophysiological examination. In a series of studies on biopuncture with Alflutop, a significant superiority of this approach over the compared methods was manifested, in addition to clinical effects, in structurally-modifying changes in the intervertebral discs. Using the same drug, an original scheme of therapeutic action was proposed, combining the techniques of drug blockade and pharmacopuncture. Special attention should be paid to the fact that the effectiveness of biopuncture is enhanced due to the combined use of modern hardware techniques. In a series of separate studies, the efficacy of biopuncture with essential oils in dorsopathies was confirmed, largely explained by the cumulative effects.

Acutely blocking excessive mitochondrial fission prevents chronic neurodegeneration after traumatic brain injury.

Progression of acute traumatic brain injury (TBI) into chronic neurodegeneration is a major health problem with no protective treatments. Here, we report that acutely elevated mitochondrial fission after TBI in mice triggers chronic neurodegeneration persisting 17 months later, equivalent to many human decades. We show that increased mitochondrial fission after mouse TBI is related to increased brain levels of mitochondrial fission 1 protein (Fis1) and that brain Fis1 is also elevated in human TBI. Pharmacologically preventing Fis1 from binding its mitochondrial partner, dynamin-related protein 1 (Drp1), for 2 weeks after TBI normalizes the balance of mitochondrial fission/fusion and prevents chronically impaired mitochondrial bioenergetics, oxidative damage, microglial activation and lipid droplet formation, blood-brain barrier deterioration, neurodegeneration, and cognitive impairment. Delaying treatment until 8 months after TBI offers no protection. Thus, time-sensitive inhibition of acutely elevated mitochondrial fission may represent a strategy to protect human TBI patients from chronic neurodegeneration.

Study of the Clinical Efficiency of an Interdisciplinary Approach to the Treatment of Orofacial Pain and Temporomandibular Joint Disorders in Patients with Complete or Partial Edentulism.

OBJECTIVE: The aim of this study is to improve the safety and efficiency of prosthodontic treatment of patients with dental defects. It is necessary to perform a comprehensive assessment of the dentofacial system disorders, including the analysis of the features of pain manifestations. This study also supports to improve the efficiency of prosthodontic rehabilitation of patients with complete dental reconstruction on the basis of an assessment of the severity of orofacial pain manifestations. MATERIALS AND METHODS: The study was a single-site prospective open nonrandomized study with the examination and treatment of 452 patients (age = 44.3 ± 15.2 years, including 282 men and 170 women) with partial or total edentulism. The patients were divided into two groups: group 1 (control) of 218 patients treated with a standard prosthodontic approach and group 2 (study) of 234 patients treated which the proposed interdisciplinary approach to prosthodontic rehabilitation. RESULTS: The study establishes higher safety and clinical efficiency of the proposed interdisciplinary approach. The patients undergoing full-mouth reconstruction with the use of the interdisciplinary approach demonstrated statistically significant decrease in the rate of pain in muscles of the maxillofacial area on palpation, pain, and spasms in the neck area, statistically significantly less frequent pains in the temporomandibular joint (TMJ) during chewing, pain during opening and closing the mouth. CONCLUSION: The application of the developed comprehensive approach to prosthodontic rehabilitation planning makes it possible to improve essentially the results of treatment at the expense of reduction of pain manifestations in the area of maxillofacial muscles and pain sensations associated with functioning of the TMJ.

Comparative Analysis of the Reproduction Accuracy of Main Methods for Finding the Mandible Position in the Centric Relation Using Digital Research Method. Comparison between Analog-to-Digital and Digital Methods: A Preliminary Report.

Purpose: To compare the aspect of the reproduction accuracy in studied methods of determination of the (CR) of jaws using the digital research methods. The methods used were bilateral manipulation by P.E. Dawson, frontal deprogrammer, leaf gauge, and intraoral device for recording of Gothic arch angle. Methods: To determine the reproduction accuracy of the centric relation of jaws, we examined 5 patients with intact dentition in a prosthetic dentistry clinic (first class in Angle's system). For each method, 20 registrations of the centric jaw relation were carried out by one operator. The breaks between definitions were 30 minutes. A total of 400 CR recording operations were carried out (400 records of CR). In order to study the reproducibility of CR determination methods, 200 recorded mandible positions were analyzed by means of an analog-to-digital method (a macro kit Canon 650D, Canon 60 mm macro IS USM f2.8, Canon macro ring MR-14 EX and the computer program Adobe Photoshop) to assess the first occlusal contact obtained in the CR of jaws, while the other 200 were analyzed by means of a digital method (the computer program Avantis for 3D modeling, Prime as a laboratory 3D scanner (DOF), and Trios as an intraoral scanner (3Shape)) to assess the spatial position of the mandible in the CR. Statistical analysis was carried out using STATISTICA-10. In all statistical analysis procedures, the critical significance level p was assumed to be 0.05. Results: In the study of the data by means of the computer program Avanti 3D, the reproducibility of the mandible position in the CR reached 0.119 ± 0.012 mm for frontal deprogrammer, 0.225 ± 0.028, p ≤ 0.05 for bilateral manipulation by Dawson P.E., 0.207 ± 0.02, p ≤ 0.05 for leaf gauge, and 0.120 ± 0,013, p ≤ 0.05 using an intraoral device for recording the Gothic arch angle. The analog-to-digital method showed an identical tendency for reproduction of the mandible position. Conclusions: The digital analysis we made using the Avantis 3D program showed, with high confidence, that the maximum reproducibility of the CR position was reached by using our own design frontal deprogrammer and the device for recording Gothic arch angle.