Bone healing during electrostimulation.

Aim To investigate the effect of direct epineural electrical stimulation of the nerve on the nature of reparative processes in the bone stump. Methods Three series of experiments were carried out with amputation of the thigh in the middle third and muscle plasty. In the 1st and 2nd experimental series a perineural catheter was brought to the stump of the sciatic nerve, through which mechanical irritation of the nerve was performed for 20 days daily for 20 minutes. In the 2nd series, an electrode was added to the nerve and epineural electrical stimulation was performed daily for 20 days. Animals of the 3rd series served as control. The observation periods were 1, 3, 6 months. Histological research method with filling vessels with ink-gelatin mixture was applied. Results In the 1st series, there was a sharp distortion of the reparative process, which consisted of a violation of microcirculation, changes in shape, resorption of the cortical diaphyseal plate, fractures, deformations. In most experiments of the 2nd series, organotypic stumps were formed with normalization of microcirculation. In the 3rd series, results of the formation of the stump were better than in the 1st, but worse than in the 2nd series. Conclusions Painful nerve irritation after amputation leads to a significant disturbance of microcirculation and reparative regeneration at the end of the bone stump with the development of pathological restructuring of bone tissue. Electrostimulation of the nerve improves microcirculation and reparative regeneration of the bone tissue.

PECULIARITIES OF BONE MINERAL DENSITY IN WOMEN OF DIFFERENT REPRODUCTIVE AGE WITH SYSTEMIC LUPUS ERYTHEMATOSUS.

OBJECTIVE: The aim: To study the peculiarities of bone mineral density in the Ukrainian population of women of different reproductive age with systemic lupus erythematosus and to evaluate its connection with traditional and specific (typical for systemic lupus erythematosus) risk factors. PATIENTS AND METHODS: Materials and methods: A total of 91 women with systemic lupus erythematosus and 29 healthy individuals were examined. Along with the clinical study of the activity and severity of the disease, the serum levels of interleukin-6 were determined by the enzyme immunoassay. The peculiarities of bone mineral density were studied using dual-energy X-ray absorptiometry. The presence of fractures was evaluated by the X-ray method. RESULTS: Results: Patients with systemic lupus erythematosus frequently suffer from reduced bone mineral density. Reduced bone mineral density and the appearance of fragility fractures are associated with patients' age, disease duration, damage index, inflammatory activity, and cumulative dose of glucocorticoids. CONCLUSION: Conclusions: Progressive reduced bone mineral density in patients with systemic lupus erythematosus occurs not only during the aging process of a woman, but is also associatedwith a number of systemic lupus erythematosus - related osteoporosis risk factors.

THE EFFECT OF ATORVASTATINUM IN THE TREATMENT OF PATIENTS WITH RHEUMATOID ARTHRITIS.

OBJECTIVE: The aim: Was to evaluate the effect of 6-month pathogenetic treatment in combination with atorvastatinum on the endothelium function, lipid and adipokine levels, paroxonase activity and activity of inflammatory process in RA patients. PATIENTS AND METHODS: Materials and methods: The study included 55 patients with RA, dividing into two groups depending on the intended therapy. The first group included 33 patients with "traditional" treatment by methotrexate, glucocorticoids, and non-steroid anti-inflammatory drugs. The second group included 22 patients with "traditional" treatment and additionally prescribed of atorvastatinum 20 mg/day. The lipid profile, leptin, adipokine, paroxonase activity. C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) levels, FMDBA and IMT of carotid artery were determined in all participants of the study. Control parameters were recorded before the start, after 1 and 6 months of treatment. RESULTS: Results: The FMDBA has increased by 32% in the second group, compared by only 10.9% in the first group. The dynamics of IMT in the first group was also twice lower than in group with the additional use of atorvastatinum. The leptin levels in the second group significantly decreased by 27% and adiponectin levels increased by 12.8%, than in the first group - by 12.8% and by 7% respectively. The appointment of statins over 6 months resulted in DAS28, TNF-α, ESR and CRP reduction by 15%, 31%, 25% and 21.5% respectively. In the first group the dynamics of indicate rates ranged from 7.8% to 22.5%, and was significantly lower than in the second group. CONCLUSION: Conclusions: As a result of the study, it was found that the appointment of atorvastatinum 20 mg/day during 6 months not only reduces dyslipidemia, but also significantly reduces the inflammatory process and adipokine dysregulation, normalizes serum paraoxonase activity and improves the endothelium function.

Author Correction: A compendium of geochemical information from the Saanich Inlet water column.

In Table 3 of this Data Descriptor the units of Mean_N2O and Mean_CH4 are incorrectly stated as "Nanomolar (µM)". This should instead read "Nanomolar (nM)".

3-Hydroxyphenylboronic Acid-Based Carbon Dot Sensors for Fructose Sensing.

The selective fluorescence sensing of fructose was achieved by fluorescence quenching of the emission of hydrothermal-synthesized carbon quantum dots prepared by 3-hydroxyphenylboronic acid. Quantification of fructose was possible in aqueous solutions with pH of 9 (Limit of Detection LOD and Limit of Quantification LOQ of 2.04 and 6.12 mM), by quenching of the emission at 376 nm and excitation ~380 nm with a linearity range of 0-150 mM. A Stern-Volmer constant (KSV) of 2.11 × 10-2 mM-1 was obtained, while a fluorescent quantum yield of 31% was calculated. The sensitivity of this assay towards fructose was confirmed by comparison with other sugars (such as glucose, sucrose and lactose). Finally, the validity of the proposed assays was further demonstrated by performing recovery assays in different matrixes. Graphical Abstract.

RUNX1 promotes cell growth in human T-cell acute lymphoblastic leukemia by transcriptional regulation of key target genes.

RUNX1 is frequently mutated in T-cell acute lymphoblastic leukemia (T-ALL). The spectrum of RUNX1 mutations has led to the notion that it acts as a tumor suppressor in this context; however, other studies have placed RUNX1, along with transcription factors TAL1 and NOTCH1, as core drivers of an oncogenic transcriptional program. To reconcile these divergent roles, we knocked down RUNX1 in human T-ALL cell lines and deleted Runx1 or Cbfb in primary mouse T-cell leukemias. RUNX1 depletion consistently resulted in reduced cell proliferation and increased apoptosis. RUNX1 upregulated variable sets of target genes in each cell line, but consistently included a core set of oncogenic effectors including insulin-like growth factor 1 receptor (IGF1R) and NRAS. Our results support the conclusion that RUNX1 has a net positive effect on cell growth in the context of established T-ALL.

A compendium of multi-omic sequence information from the Saanich Inlet water column.

Marine oxygen minimum zones (OMZs) are widespread regions of the ocean that are currently expanding due to global warming. While inhospitable to most metazoans, OMZs are hotspots for microbial mediated biogeochemical cycling of carbon, nitrogen and sulphur, contributing disproportionately to marine nitrogen loss and climate active trace gas production. Our current understanding of microbial community responses to OMZ expansion is limited by a lack of time-resolved data sets linking multi-omic sequence information (DNA, RNA, protein) to geochemical parameters and process rates. Here, we present six years of time-resolved multi-omic observations in Saanich Inlet, a seasonally anoxic fjord on the coast of Vancouver Island, British Columbia, Canada that undergoes recurring changes in water column oxygenation status. This compendium provides a unique multi-omic framework for studying microbial community responses to ocean deoxygenation along defined geochemical gradients in OMZ waters.

A compendium of geochemical information from the Saanich Inlet water column.

Extensive and expanding oxygen minimum zones (OMZs) exist at variable depths in coastal and open ocean waters. As oxygen levels decline, nutrients and energy are increasingly diverted away from higher trophic levels into microbial community metabolism, resulting in fixed nitrogen loss and production of climate active trace gases including nitrous oxide and methane. While ocean deoxygenation has been reported on a global scale, our understanding of OMZ biology and geochemistry is limited by a lack of time-resolved data sets. Here, we present a historical dataset of oxygen concentrations spanning fifty years and nine years of monthly geochemical time series observations in Saanich Inlet, a seasonally anoxic fjord on the coast of Vancouver Island, British Columbia, Canada that undergoes recurring changes in water column oxygenation status. This compendium provides a unique geochemical framework for evaluating long-term trends in biogeochemical cycling in OMZ waters.

Composition, Microstructure, and Electrical Properties Control of the Powders Synthesized by Sol-Gel Auto-Combustion Method Using Citric Acid as the Fuel.

Nanocrystalline lithium ferrite Li 0.5 Fe 1.7 Mg 0.8 O 4 powders were synthesized by the sol-gel auto-combustion method from the corresponding metal nitrates using citric acid as fuel.The results from XRD, SEM, and AC electrical conductivity studies are summarized as follows: The results of XRD analysis showed that all the samples were formed in single-phase cubic spinel structure at different annealing temperatures from 300 to 700 °C for 2 h. The lattice parameter was found to decrease on increasing the temperature. The microstructure of lithium ferrite powders was temperature dependent. The particle size was increased with the annealing temperature. AC electrical properties were investigated using the super-linear power law and activation energies were calculated for all compositions. The electron mobility in Li 0.5 Fe 1.7 Mg 0.8 O 4 samples ranged from 0.05 to 0.29 eV, which clearly indicated that the present lithium ferrites have semiconductor-like behavior. The frequency exponent "s" of lithium ferrite lies in the range 0.5 < s < 1, which confirms the electron hopping between Fe 2 + and Fe 3 + ions.

NOTCH1 promotes T cell leukemia-initiating activity by RUNX-mediated regulation of PKC-θ and reactive oxygen species.

Reactive oxygen species (ROS), a byproduct of cellular metabolism, damage intracellular macromolecules and, when present in excess, can promote normal hematopoietic stem cell differentiation and exhaustion. However, mechanisms that regulate the amount of ROS in leukemia-initiating cells (LICs) and the biological role of ROS in these cells are largely unknown. We show here that the ROS(low) subset of CD44(+) cells in T cell acute lymphoblastic leukemia (T-ALL), a malignancy of immature T cell progenitors, is highly enriched in the most aggressive LICs and that ROS accumulation is restrained by downregulation of protein kinase C θ (PKC-θ). Notably, primary mouse T-ALLs lacking PKC-θ show improved LIC activity, whereas enforced PKC-θ expression in both mouse and human primary T-ALLs compromised LIC activity. We also show that PKC-θ is regulated by a new pathway in which NOTCH1 induces runt-related transcription factor 3 (RUNX3), RUNX3 represses RUNX1 and RUNX1 induces PKC-θ. NOTCH1, which is frequently activated by mutation in T-ALL and required for LIC activity in both mouse and human models, thus acts to repress PKC-θ. These results reveal key functional roles for PKC-θ and ROS in T-ALL and suggest that aggressive biological behavior in vivo could be limited by therapeutic strategies that promote PKC-θ expression or activity, or the accumulation of ROS.

IGF signaling contributes to malignant transformation of hematopoietic progenitors by the MLL-AF9 oncoprotein.

Malignant transformation of normal hematopoietic progenitors is a multistep process that likely requires interaction between collaborating oncogenic signals at critical junctures. For instance, the MLL-AF9 fusion oncogene is thought to contribute to myeloid leukemogenesis by driving a hematopoietic stem cell-like "self-renewal" gene expression signature in committed myeloid progenitors. In addition, insulin-like growth factor (IGF) signaling has been implicated in self-renewal/pluripotency in hematopoietic and embryonic stem cell contexts and supports cell growth/survival by activation of downstream pathways, including phosphatidylinositol 3-kinase/Akt and Ras/Raf/extracellular signal-regulated kinase. We hypothesized that IGF signaling could be an important contributor in the process of cellular transformation and/or clonal propagation. Utilizing an MLL-AF9 mouse bone marrow transplantation model of acute myelogenous leukemia, we discovered that committed myeloid progenitor cells with genetically reduced levels of IGF1R were less susceptible to leukemogenic transformation due, at least in part, to a cell-autonomous defect in clonogenic activity. Rather unexpectedly, genetic deletion of IGF1R by inducible Cre recombinase had no effect on growth/survival of established leukemia cells. These findings suggest that IGF1R signaling contributes to transformation of normal myeloid progenitor cells, but is not required for propagation of the leukemic clone once it has become established. We also show that treatment of mouse MLL-AF9 acute myelogenous leukemia cells with BMS-536924, an IGF1R/insulin receptor-selective tyrosine kinase inhibitor, blocked cell growth, suggesting its efficacy in this model may be due to inhibition of insulin receptor and/or related tyrosine kinases, and raising the possibility that similar IGF1R inhibitors in clinical development may be acting through alternate/related pathways.