Systems biology and network pharmacology of frailty reveal novel epigenetic targets and mechanisms.

Frailty is an age-associated condition, characterized by an inappropriate response to stress that results in a higher frequency of adverse outcomes (e.g., mortality, institutionalization and disability). Some light has been shed over its genetic background, but this is still a matter of debate. In the present study, we used network biology to analyze the interactome of frailty-related genes at different levels to relate them with pathways, clinical deficits and drugs with potential therapeutic implications. Significant pathways involved in frailty: apoptosis, proteolysis, muscle proliferation, and inflammation; genes as FN1, APP, CREBBP, EGFR playing a role as hubs and bottlenecks in the interactome network and epigenetic factors as HIST1H3 cluster and miR200 family were also involved. When connecting clinical deficits and genes, we identified five clusters that give insights into the biology of frailty: cancer, glucocorticoid receptor, TNF-α, myostatin, angiotensin converter enzyme, ApoE, interleukine-12 and -18. Finally, when performing network pharmacology analysis of the target nodes, some compounds were identified as potentially therapeutic (e.g., epigallocatechin gallate and antirheumatic agents); while some other substances appeared to be toxicants that may be involved in the development of this condition.

Post-Renal Transplantation Bone Health in Children Evaluated by Means of Quantitative Ultrasound and Densitometry.

BACKGROUND: Patients with end-stage renal disease develop bone mineral disease, which is not always resolved after a successful renal transplantation; moreover, some of the immunosuppressants used to prevent graft rejection may affect bone health. The aim of this study was to evaluate bone health in post-renal transplantation children with the use of quantitative ultrasound (QUS) and dual-energy X-ray absorptiometry (DXA). METHODS: A descriptive study was performed in children >3 months after renal transplantation and with stable function of graft. Radial QUS and DXA (lumbar spine and total body less head (TBLH) were performed on the same day. RESULTS: A total of 35 patients were included. Mean age was 13.9 ± 3.9 years. Ten subjects had total bone density score <2 (28.5%), 4 a lumbar spine (L1-L4) Z-score of <2 (11.4%) as well as TBLH <2, and 6 subjects had a radial QUS Z-score of <2 (17.1%), and only 2 of them had concomitant Z-score <2 with the use of DXA. There was a positive non-significant correlation between TBLH and radial QUS Z-scores (Pearson r = 0.317; P = .016) and a positive significant correlation of DXA lumbar spine and radial QUS Z-scores (Pearson r = 0.452; P = .014). CONCLUSIONS: Despite a good correlation between TBLH and QUS Z-scores, there are subjects that can be considered normal by QUS and have osteopenia by TBLH DXA and vice versa; this could be due to the different bone areas evaluated.

Electrochemical treatment of mouse Ehrlich tumor with direct electric current.

Electrochemical treatment of cancer utilizes direct electric current (DEC) to produce direct alterations and chemical changes in tumors. However, the DEC treatment is not established and mechanisms are not well understood. In vivo studies were conducted to evaluate the effectiveness of DEC on animal tumor models. Ehrlich tumors were implanted subcutaneously in sixty male BALB/c mice. When the tumor volumes reached 850 mm(3), four platinum electrodes were inserted into the tumors. DEC of 4 mA was applied for 21 min to the treated group; the total charge was 5 C. The healthy and sick control groups were subjected to the same conditions but without DEC. Hematological and chemical parameters as well as histopathological and peritumoral findings were studied. After the electrochemical therapy it was observed that both tumor volume decrease and necrosis percentage increase were significant in the treated group. Moreover, 24 h after treatment an acute inflammatory response, as well as sodium ion decrease, and potassium ion and spleen weight increase were observed in this group. It was concluded that both electrochemical reactions (fundamentally those in which reactive oxygen species are involved), and immune system stimulation induced by cytotoxic action of the DEC could constitute the most important antitumor mechanisms.

Role of solid-phase microextraction in the identification of highly volatile pheromones of two Rhinoceros beetles Scapanes australis and Strategus aloeus (Coleoptera, Scarabaeidae, Dynastinae).

Solid-phase microextraction (SPME) samplings from live insects or natural secretion allowed one to identify the aggregation pheromones of the pest beetles Scapanes australis and Strategus aloeus by efficient and rapid isolation of their highly volatile (72 < M(r) < 116) components. S. australis male pheromone was identified as a 84:12:4 (w/w) mixture of 2-butanol [67:33 (R)-(-):(S)-(+) ratio], 3-hydroxy-2-butanone and 2,3-butanediol [43:17:40 (R,R)-(-):(S,S)-(+):meso ratio], and S. aloeus pheromone as a 95.5:4.0:0.5 (w/w) mixture of 2-butanone, 3-pentanone and sec.-butyl acetate by GC-MS using conventional and chiral capillary columns. This is the first report of Scarabaeidae pheromones based on such small and common molecules.