Personified treatment and prevention of sexual developmental disorders in pubertal age girls with diffusive liver diseases

Diffuse liver disease can have a pronounced detrimental effect on the developing reproductive system. Hepatoprotection in gynecological practice is not so much in the choice of drugs that protect or restore the liver, as in the appointment of optimal safe therapy for this category of patients, especially in adolescence. The aim: to study the effectiveness of therapeutic and prophylactic drugs for disorders of the reproductive system in adolescent girls with diffuse liver disease. Material and methods. Under observation for the period 2010-2020 were 486 girls aged 12-17 years, of which 120 - with chronic viral hepatitis (CVH), 120 - with non-alcoholic fatty liver disease (NAFLD), 66 - with autoimmune hepatitis (AIH), 180 - conditionally somatically and gynecologically healthy girls with normal sexual development of the control group. All patients underwent general clinical, hepatological examination, determination of features of neuroendocrine status, sexual development. The author proposed a differentiated method of treatment and prevention measures to restore reproductive health in adolescents with chronic diffuse liver disease, which included the appointment of vitamin D, phytocompositions, vitamin-mineral complexes with myo-inositol, if necessary - hormonal hemostasis. Results. Against the background of improved neuroendocrine status in the examined girls there was a decrease in the number of cases of amenorrhea in the group with CVH from 5.00% to 0.00% (p<0.01), in the group of NAFLD - from 27.50% to 3.33% (OR 11.00 [3.757-32.207]), in the AIH group - from 13.64% to 0.00% (p<0.01); opsomenorrhea - from 24.17% to 2.50% (OR 12.43 [3,670-42,092]), from 67.50% to 7.50% (OR 25.62 [11.750-55.843]) and from 27. 27% to 6.06% (OR 5.81 [1.846-18.304]); oligomenorrhea - from 25.83% to 1.67% (OR 20.55 [4.791-88.152]), from 62.50% to 5.83% (OR 26.91 [11.52-62.83]) and from 27.27% to 4.55% (OR 7.88 [2.192-28.286]); juvenile uterine bleeding - from 18.33% to 1.67% (OR 13.25 [3.039-57.728]), from 10.00% to 0.00% (p<0.01) and from 9.09% to 0.00% (p<0.01); dysmenorrhea - from 38.33% to 12.50% (OR 4.20 [2.181-8.087]), from 14.17% to 5.00% (OR 3.14 [1.191-8.257]) and from 31.82 % to 13.64% (OR 2.96 [1.234-7.078]). Conclusions. The applied personalized treatment-and-prophylactic measures taking into account individual disorders of neuroendocrine status and menstrual health in adolescent girls with diffuse liver diseases are effective and allow to recommend this complex as a means of treatment and prevention of reproductive disorders

Spina bifida-predisposing heterozygous mutations in Planar Cell Polarity genes and Zic2 reduce bone mass in young mice

Fractures are a common comorbidity in children with the neural tube defect (NTD) spina bifida. Mutations in the Wnt/planar cell polarity (PCP) pathway contribute to NTDs in humans and mice, but whether this pathway independently determines bone mass is poorly understood. Here, we first confirmed that core Wnt/PCP components are expressed in osteoblasts and osteoclasts in vitro. In vivo, we performed detailed µCT comparisons of bone structure in tibiae from young male mice heterozygous for NTD-associated mutations versus WT littermates. PCP signalling disruption caused by Vangl2 (Vangl2Lp/+) or Celsr1 (Celsr1Crsh/+) mutations significantly reduced trabecular bone mass and distal tibial cortical thickness. NTD-associated mutations in non-PCP transcription factors were also investigated. Pax3 mutation (Pax3Sp2H/+) had minimal effects on bone mass. Zic2 mutation (Zic2Ku/+) significantly altered the position of the tibia/fibula junction and diminished cortical bone in the proximal tibia. Beyond these genes, we bioinformatically documented the known extent of shared genetic networks between NTDs and bone properties. 46 genes involved in neural tube closure are annotated with bone-related ontologies. These findings document shared genetic networks between spina bifida risk and bone structure, including PCP components and Zic2. Genetic variants which predispose to spina bifida may therefore independently diminish bone mass

Cobalt and Zinc in Toenails of Some Kano Inhabitants

Quantitative determination of Co and Zn concentrations in toenails of 42 volunteers with a mean age of 25.01 ± 11.46 years and resident in Kano for at least six months were assayed by atomic absorption (AAS). .Significantly high levels of Co and Zn were present in the toenails of some individuals with a mean Co of 75.72 ± 24.67ìg/g and 108.51 ± 61.40 ìg/g for Co and Zn respectively. With respect to age there was increase relation in zinc concentrations with age with approximate average of 18% in its concentrations with each decade but no such uniform pattern for the cobalt concentrations

Knowledge Discovery Through Large-Scale Literature-Mining of Biological Text-Data

The aim of this study is to develop scalable and efficient literature-mining framework for knowledge discovery in the field of medical and biological sciences. Using this scalable framework, customized disease-disease interaction network can be constructed. Features of the proposed network that differentiate it from existing networks are its 1) flexibility in the level of abstraction, 2) broad coverage, and 3) domain specificity. Empirical results for two neurological diseases have shown the utility of the proposed framework. The second goal of this study is to design and implement a bottom-up information retrieval approach to facilitate literature-mining in the specialized field of medical genetics. Experimental results are being corroborated at the moment

Model-based clustering reveals vitamin D dependent multi-centrality hubs in a network of vitamin-related proteins

<p>Abstract</p> <p>Background</p> <p>Nutritional systems biology offers the potential for comprehensive predictions that account for all metabolic changes with the intricate biological organization and the multitudinous interactions between the cellular proteins. Protein-protein interaction (PPI) networks can be used for an integrative description of molecular processes. Although widely adopted in nutritional systems biology, these networks typically encompass a single category of functional interaction (<it>i.e</it>., metabolic, regulatory or signaling) or nutrient. Incorporating multiple nutrients and functional interaction categories under an integrated framework represents an informative approach for gaining system level insight on nutrient metabolism.</p> <p>Results</p> <p>We constructed a multi-level PPI network starting from the interactions of 200 vitamin-related proteins. Its final size was 1,657 proteins, with 2,700 interactions. To characterize the role of the proteins we computed 6 centrality indices and applied model-based clustering. We detected a subgroup of 22 proteins that were highly central and significantly related to vitamin D. Immune system and cancer-related processes were strongly represented among these proteins. Clustering of the centralities revealed a degree of redundancy among the indices; a repeated analysis using subsets of the centralities performed well in identifying the original set of 22 most central proteins.</p> <p>Conclusions</p> <p>Hierarchical and model-based clustering revealed multi-centrality hubs in a vitamin PPI network and redundancies among the centrality indices. Vitamin D-related proteins were strongly represented among network hubs, highlighting the pervasive effects of this nutrient. Our integrated approach to network construction identified promiscuous transcription factors, cytokines and enzymes - primarily related to immune system and cancer processes - representing potential gatekeepers linking vitamin intake to disease.</p

The impact of vitamin D on cancer: A mini review.

In this review, we summarize the most recent advances in vitamin D cancer research to provide molecular clarity, as well as its translational trajectory across the cancer landscape. Vitamin D is well known for its role in regulating mineral homeostasis; however, vitamin D deficiency has also been linked to the development and progression of a number of cancer types. Recent epigenomic, transcriptomic, and proteomic studies have revealed novel vitamin D-mediated biological mechanisms that regulate cancer cell self-renewal, differentiation, proliferation, transformation, and death. Tumor microenvironmental studies have also revealed dynamic relationships between the immune system and vitamin D\u27s anti-neoplastic properties. These findings help to explain the large number of population-based studies that show clinicopathological correlations between circulating vitamin D levels and risk of cancer development and death. The majority of evidence suggests that low circulating vitamin D levels are associated with an increased risk of cancers, whereas supplementation alone or in combination with other chemo/immunotherapeutic drugs may improve clinical outcomes even further. These promising results still necessitate further research and development into novel approaches that target vitamin D signaling and metabolic systems to improve cancer outcomes

Nitric oxide and plant mineral nutrition: current knowledge

Plants under conditions of essential mineral deficiency trigger signaling mechanisms that involve common components. Among these components, nitric oxide (NO) has been identified as a key participant in responses to changes in nutrient availability. Usually, nutrient imbalances affect the levels of NO in specific plant tissues, via modification of its rate of synthesis or degradation. Changes in the level of NO affect plant morphology and/or trigger responses associated with nutrient homeostasis, mediated by its interaction with reactive oxygen species, phytohormones, and through post-translational modification of proteins. NO-related events constitute an exciting field of research to understand how plants adapt and respond to conditions of nutrient shortage. This review summarizes the current knowledge on NO as a component of the multiple processes related to plant performance under conditions of deficiency in mineral nutrients, focusing on macronutrients such as nitrogen, phosphate, potassium, and magnesium, as well as micronutrients such as iron and zinc.Fil: Buet, Agustina. Universidad Nacional de La Plata. Facultad de Ciencias Agrarias y Forestales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Fisiología Vegetal. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Fisiología Vegetal; ArgentinaFil: Galatro, Andrea Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Fisiología Vegetal. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Fisiología Vegetal; ArgentinaFil: Ramos Artuso, Facundo Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Fisiología Vegetal. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Fisiología Vegetal; ArgentinaFil: Simontacchi, Marcela Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Fisiología Vegetal. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Fisiología Vegetal; Argentin

Slc20a2, Encoding the Phosphate Transporter PiT2, Is an Important Genetic Determinant of Bone Quality and Strength.

Osteoporosis is characterized by low bone mineral density (BMD) and fragility fracture and affects over 200 million people worldwide. Bone quality describes the material properties that contribute to strength independently of BMD, and its quantitative analysis is a major priority in osteoporosis research. Tissue mineralization is a fundamental process requiring calcium and phosphate transporters. Here we identify impaired bone quality and strength in Slc20a2-/- mice lacking the phosphate transporter SLC20A2. Juveniles had abnormal endochondral and intramembranous ossification, decreased mineral accrual, and short stature. Adults exhibited only small reductions in bone mass and mineralization but a profound impairment of bone strength. Bone quality was severely impaired in Slc20a2-/- mice: yield load (-2.3 SD), maximum load (-1.7 SD), and stiffness (-2.7 SD) were all below values predicted from their bone mineral content as determined in a cohort of 320 wild-type controls. These studies identify Slc20a2 as a physiological regulator of tissue mineralization and highlight its critical role in the determination of bone quality and strength. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc

Vitamin D inhibits osteosarcoma by reprogramming nonsense-mediated RNA decay and SNAI2-mediated epithelial-to-mesenchymal transition.

Osteosarcomas are immune-resistant and metastatic as a result of elevated nonsense-mediated RNA decay (NMD), reactive oxygen species (ROS), and epithelial-to-mesenchymal transition (EMT). Although vitamin D has anti- cancer effects, its effectiveness and mechanism of action against osteosarcomas are poorly understood. In this study, we assessed the impact of vitamin D and its receptor (VDR) on NMD-ROS-EMT signaling in in vitro and in vivo osteosarcoma animal models. Initiation of VDR signaling facilitated the enrichment of EMT pathway genes, after which 1,25(OH)2D, the active vitamin D derivative, inhibited the EMT pathway in osteosarcoma subtypes. The ligand- bound VDR directly downregulated the EMT inducer SNAI2, differentiating highly metastatic from low metastatic subtypes and 1,25(OH)2D sensitivity. Moreover, epigenome-wide motif and putative target gene analysis revealed the VDR’s integration with NMD tumorigenic and immunogenic pathways. In an autoregulatory manner, 1,25(OH)2D inhibited NMD machinery genes and upregulated NMD target genes implicated in anti-oncogenic activity, immunorecognition, and cell-to-cell adhesion. Dicer substrate siRNA knockdown of SNAI2 revealed superoxide dismutase 2 (SOD2)-mediated antioxidative responses and 1,25(OH)2D sensitization via non-canonical SOD2 nuclear-to-mitochondrial translocalization leading to overall ROS suppression. In a mouse xenograft metastasis model, the therapeutically relevant vitamin D derivative calcipotriol inhibited osteosarcoma metastasis and tumor growth shown for the first time. Our results uncover novel osteosarcoma-inhibiting mechanisms for vitamin D and calcipotriol that may be translated to human patients