Radioprotectors and Mitigators of Radiation-Induced Normal Tissue Injury

The article reviews agents in clinical use or in development as radioprotectors and mitigators of radiation-induced normal tissue injury

Synthesis and characterization of hybrid nanostructures

There has been significant interest in the development of multicomponent nanocrystals formed by the assembly of two or more different materials with control over size, shape, composition, and spatial orientation. In particular, the selective growth of metals on the tips of semiconductor nanorods and wires can act to couple the electrical and optical properties of semiconductors with the unique properties of various metals. Here, we outline our progress on the solution-phase synthesis of metal-semiconductor heterojunctions formed by the growth of Au, Pt, or other binary catalytic metal systems on metal (Cd, Pb, Cu)-chalcogenide nanostructures. We show the ability to grow the metal on various shapes (spherical, rods, hexagonal prisms, and wires). Furthermore, manipulating the composition of the metal nanoparticles is also shown, where PtNi and PtCo alloys are our main focus. The magnetic and electrical properties of the developed hybrid nanostructures are shown

New trends in the economic systems management in the context of modern global challenges

New trends in the economic systems management in the context of modern global challenges: collective monograph / scientific edited by M. Bezpartochnyi, in 2 Vol. // VUZF University of Finance, Business and Entrepreneurship. – Sofia: VUZF Publishing House “St. Grigorii Bogoslov”, 2020. – Vol. 1. – 309 p

Amifostine reduces the seminiferous epithelium damage in doxorubicin-treated prepubertal rats without improving the fertility status

<p>Abstract</p> <p>Background</p> <p>Amifostine is an efficient cytoprotector against toxicity caused by some chemotherapeutic drugs. Doxorubicin, a potent anticancer anthracycline, is known to produce spermatogenic damage even in low doses. Although some studies have suggested that amifostine does not confer protection to doxorubicin-induced testicular damage, schedules and age of treatment have different approach depending on the protocol. Thus, we proposed to investigate the potential cytoprotective action of amifostine against the damage provoked by doxorubicin to prepubertal rat testes (30-day-old) by assessing some macro and microscopic morphometric parameters 15, 30 and 60 days after the treatment; for fertility evaluation, quantitative analyses of sperm parameters and reproductive competence in the adult phase were also carried out.</p> <p>Methods</p> <p>Thirty-day-old male rats were distributed into four groups: Doxorubicin (5 mg/kg), Amifostine (400 mg/kg), Amifostine/Doxorubicin (amifostine 15 minutes before doxorubicin) and Sham Control (0.9% saline solution). "Standard One Way Anova" parametric and "Anova on Ranks" non-parametric tests were applied according to the behavior of the obtained data; significant differences were considered when p < 0.05.</p> <p>Results</p> <p>The rats killed 30 and 60 days after doxorubicin treatment showed diminution of seminiferous epithelium height and reduction on the frequency of tubular sections containing at least one type of differentiated spermatogonia; reduction of sperm concentration and motility and an increase of sperm anomalous forms where observed in doxorubicin-treated animals. All these parameters were improved in the Amifostine/Doxorubicin group only when compared to Doxorubicin group. Such reduction, however, still remained below the values obtained from the Sham Control group. Nevertheless, the reproductive competence of doxorubicin-treated rats was not improved by amifostine pre-administration.</p> <p>Conclusions</p> <p>These results suggest that amifostine promotes a significant reduction of the doxorubicin long-term side effects on the seminiferous epithelium of prepubertal rats, which is reflected in the epidydimal fluid parameters in the adult phase. However, fertility status results suggest that such protection may not be effective against sperm DNA content damage. Further investigation of sperm DNA integrity must be carried out using amifostine and doxorubicin-treated experimental models.</p

Cholesterol Influences Voltage-Gated Calcium Channels and BK-Type Potassium Channels in Auditory Hair Cells

The influence of membrane cholesterol content on a variety of ion channel conductances in numerous cell models has been shown, but studies exploring its role in auditory hair cell physiology are scarce. Recent evidence shows that cholesterol depletion affects outer hair cell electromotility and the voltage-gated potassium currents underlying tall hair cell development, but the effects of cholesterol on the major ionic currents governing auditory hair cell excitabilityare unknown. We investigated the effects of a cholesterol-depleting agent (methyl beta cyclodextrin, MβCD) on ion channels necessary for the early stages of sound processing. Large-conductance BK-type potassium channels underlie temporal processing and open in a voltage- and calcium-dependent manner. Voltage-gated calcium channels (VGCCs) are responsible for calcium-dependent exocytosis and synaptic transmission to the auditory nerve. Our results demonstrate that cholesterol depletion reduced peak steady-state calcium-sensitive (BK-type) potassiumcurrent by 50% in chick cochlear hair cells. In contrast, MβCD treatment increased peak inward calcium current (∼30%), ruling out loss of calcium channel expression or function as a cause of reduced calcium-sensitive outward current. Changes in maximal conductance indicated a direct impact of cholesterol on channel number or unitary conductance. Immunoblotting following sucrose-gradient ultracentrifugation revealed BK expression in cholesterol-enriched microdomains. Both direct impacts of cholesterol on channel biophysics, as well as channel localization in the membrane, may contribute to the influence of cholesterol on hair cell physiology. Our results reveal a new role for cholesterol in the regulation of auditory calcium and calcium-activated potassium channels and add to the growing evidence that cholesterol is a key determinant in auditory physiology

Conformal and continuous deposition of bifunctional cobalt phosphide layers on p-silicon nanowire arrays for improved solar hydrogen evolution

Vertically aligned p-silicon nanowire (SiNW) arrays have been extensively investigated in recent years as promising photocathodes for solar-driven hydrogen evolution. However, the fabrication of SiNW photocathodes with both high photoelectrocatalytic activity and long-term operational stability using a simple and affordable approach is a challenging task. Herein, we report conformal and continuous deposition of a di-cobalt phosphide (Co2P) layer on lithography-patterned highly ordered SiNW arrays via a cost-effective drop-casting method followed by a low-temperature phosphorization treatment. The as-deposited Co2P layer consists of crystalline nanoparticles and has an intimate contact with SiNWs, forming a well-defined SiNW@Co2P core/shell nanostructure. The conformal and continuous Co2P layer functions as a highly efficient catalyst capable of substantially improving the photoelectrocatalytic activity for the hydrogen evolution reaction (HER) and effectively passivates the SiNWs to protect them from photo-oxidation, thus prolonging the lifetime of the electrode. As a consequence, the SiNW@Co2P photocathode with an optimized Co2P layer thickness exhibits a high photocurrent density of -21.9 mA.cm(-2) at 0 V versus reversible hydrogen electrode and excellent operational stability up to 20 h for solar-driven hydrogen evolution, outperforming many nanostructured silicon photocathodes reported in the literature. The combination of passivation and catalytic functions in a single continuous layer represents a promising strategy for designing high-performance semiconductor photoelectrodes for use in solar-driven water splitting, which may simplify fabrication procedures and potentially reduce production costsThis work was funded by ERDF funds through the Portuguese Operational Programme for Competitiveness and Internationalization COMPETE 2020, and national funds through FCT – The Portuguese Foundation for Science and Technology, under the project “PTDC/CTM-ENE/2349/2014” (Grant Agreement No. 016660). The work is also partially funded by the Portugal-China Bilateral Collaborative Programme (FCT/21102/28/12/2016/S). L. F. Liu acknowledges the financial support of the FCT Investigator Grant (IF/01595/2014) and Exploratory Grant (IF/01595/2014/CP1247/CT0001). L. Qiao acknowledges the financial support of the Ministry of Science and Technology of China (Grant Agreement No. 2016YFE0132400).info:eu-repo/semantics/publishedVersio

Activation of the steroid and xenobiotic receptor, SXR, induces apoptosis in breast cancer cells

<p>Abstract</p> <p>Background</p> <p>The steroid and xenobiotic receptor, SXR, is an orphan nuclear receptor that regulates metabolism of diverse dietary, endobiotic, and xenobiotic compounds. SXR is expressed at high levels in the liver and intestine, and at lower levels in breast and other tissues where its function was unknown. Since many breast cancer preventive and therapeutic compounds are SXR activators, we hypothesized that some beneficial effects of these compounds are mediated through SXR.</p> <p>Methods</p> <p>To test this hypothesis, we measured proliferation of breast cancer cells in response to SXR activators and evaluated consequent changes in the expression of genes critical for proliferation and cell-cycle control using quantitative RT-PCR and western blotting. Results were confirmed using siRNA-mediated gene knockdown. Statistical analysis was by t-test or ANOVA and a P value ≤ 0.05 was considered to be significant.</p> <p>Results</p> <p>Many structurally and functionally distinct SXR activators inhibited the proliferation of MCF-7 and ZR-75-1 breast cancer cells by inducing cell cycle arrest at the G1/S phase followed by apoptosis. Decreased growth in response to SXR activation was associated with stabilization of p53 and up-regulation of cell cycle regulatory and pro-apoptotic genes such as p21, PUMA and BAX. These gene expression changes were preceded by an increase in inducible nitric oxide synthase and nitric oxide in these cells. Inhibition of iNOS blocked the induction of p53. p53 knockdown inhibited up-regulation of p21 and BAX. We infer that NO is required for p53 induction and that p53 is required for up-regulation of cell cycle regulatory and apoptotic genes in this system. SXR activator-induced increases in iNOS levels were inhibited by siRNA-mediated knockdown of SXR, indicating that SXR activation is necessary for subsequent regulation of iNOS expression.</p> <p>Conclusion</p> <p>We conclude that activation of SXR is anti-proliferative in p53 wild type breast cancer cells and that this effect is mechanistically dependent upon the local production of NO and NO-dependent up-regulation of p53. These findings reveal a novel biological function for SXR and suggest that a subset of SXR activators may function as effective therapeutic and chemo-preventative agents for certain types of breast cancers.</p