Resveratrol-Mediated Reversal of Doxorubicin-Induced Osteoclast Differentiation

Secondary osteoporosis has been associated with cancer patients undertaking Doxorubicin (DOX) chemotherapy. However, the molecular mechanisms behind DOX-induced bone loss have not been elucidated. Molecules that can protect against the adverse effects of DOX are still a challenge in chemotherapeutic treatments. We investigated the effect and mechanism of DOX in osteoclast differentiation and used the Sirt 1 activator resveratrol (RES) to counteract DOX-induced effects. RAW 264.7 cells were differentiated into osteoclasts under cotreatment with DOX and RES, alone or combined. RES treatment inhibited DOX-induced osteoclast differentiation, reduced the expression of osteoclast fusion marker Oc-stamp and osteoclast differentiation markers Rank, Trap, Ctsk and Nfatc1. Conversely, RES induced the upregulation of antioxidant genes Sod 1 and Nrf 2 while DOX significantly reduced the FoxM1 expression, resulting in oxidative stress. Treatment with the antioxidant MitoTEMPO did not influence DOX-induced osteoclast differentiation. DOX-induced osteoclastogenesis was studied using the cathepsin-K zebrafish reporter line (Tg[ctsk:DsRed]). DOX significantly increased ctsk signal, while RES cotreatment resulted in a significant reduction in ctsk positive cells. RES significantly rescued DOX-induced mucositis in this model. Additionally, DOX-exposed zebrafish displayed altered locomotor behavior and locomotory patterns, while RES significantly reversed these effects. Our research shows that RES prevents DOX-induced osteoclast fusion and activation in vitro and in vivo and reduces DOX-induced mucositis, while improving locomotion parameters.     

One-Step Combustion Synthesis of Novel Nanocarbons via Magnesiothermic Reduction of Carbon-Containing Oxidants

The aim of this work was to transform carbon-containing ammonium oxalate, (NH₄)₂C₂O₄, and ammonium acetate, NH₄CH₃CO₂, into 3D graphene-like carbon nanomaterials via magnesiothermic reduction. Both raw and purified products were characterized by XRD, SEM, TGA, and Raman spectra. The conversion of the initial amount of carbon (in salts) into solid carbon (in purified product) varied between 8.5% (for oxalate) and 90.0% (for acetate). The XRD results confirmed the absence of starting salts in the raw products (MgO and C). The purified product was found to contain largely the turbostratic carbon forming a petal-like 3D graphene material. The application potential of synthesized materials was demonstrated on the example of the removal of 4-chlorophenol from its aqueous solution.     

Compact Bidirectional Promoters for Dual-Gene Expression in a Sleeping Beauty Transposon

Promoter choice is an essential consideration for transgene expression in gene therapy. The expression of multiple genes requires ribosomal entry or skip sites, or the use of multiple promoters. Promoter systems comprised of two separate, divergent promoters may significantly increase the size of genetic cassettes intended for use in gene therapy. However, an alternative approach is to use a single, compact, bidirectional promoter. We identified strong and stable bidirectional activity of the RPBSA synthetic promoter comprised of a fragment of the human Rpl13a promoter, together with additional intron/exon structures. The Rpl13a-based promoter drove long-term bidirectional activity of fluorescent proteins. Similar results were obtained for the EF1-α and LMP2/TAP1 promoters. However, in a lentiviral vector, the divergent bidirectional systems failed to produce sufficient titres to translate into an expression system for dual chimeric antigen receptor (CAR) expression. Although bidirectional promoters show excellent applicability to drive short RNA in Sleeping Beauty transposon systems, their possible use in the lentiviral applications requiring longer and more complex RNA, such as dual-CAR cassettes, is limited.     

Ligandability Assessment of Human Glutathione Transferase M1-1 Using Pesticides as Chemical Probes

Glutathione transferases (GSTs; EC 2.5.1.18) form a group of multifunctional enzymes that are involved in phase II of the cellular detoxification mechanism and are associated with increased susceptibility to cancer development and resistance to anticancer drugs. The present study aims to evaluate the ligandability of the human GSTM1-1 isoenzyme (hGSTM1-1) using a broad range of structurally diverse pesticides as probes. The results revealed that hGSTM1-1, compared to other classes of GSTs, displays limited ligandability and ligand-binding promiscuity, as revealed by kinetic inhibition studies. Among all tested pesticides, the carbamate insecticide pirimicarb was identified as the strongest inhibitor towards hGSTM1-1. Kinetic inhibition analysis showed that pirimicarb behaved as a mixed-type inhibitor toward glutathione (GSH) and 1-chloro-2,4-dinitrobenzene (CDNB). To shine a light on the restricted hGSTM1-1 ligand-binding promiscuity, the ligand-free crystal structure of hGSTM1-1 was determined by X-ray crystallography at 1.59 Å-resolution. Comparative analysis of ligand-free structure with the available ligand-bound structures allowed for the study of the enzyme’s plasticity and the induced-fit mechanism operated by hGSTM1-1. The results revealed important structural features of the H-site that contribute to xenobiotic-ligand binding and specificity. It was concluded that hGSTM1-1 interacts preferentially with one-ring aromatic compounds that bind at a discrete site which partially overlaps with the xenobiotic substrate binding site (H-site). The results of the study form a basis for the rational design of new drugs targeting hGSTM1-1.     

Recent Progress on Stability and Passivation of Black Phosphorus

From a fundamental science perspective, black phosphorus (BP) is a canonical example of a material that possesses fascinating surface and electronic properties. It has extraordinary in‐plane anisotropic electrical, optical, and vibrational states, as well as a tunable band gap. However, instability of the surface due to chemical degradation in ambient conditions remains a major impediment to its prospective applications. Early studies were limited by the degradation of black phosphorous surfaces in air. Recently, several robust strategies have been developed to mitigate these issues, and these novel developments can potentially allow researchers to exploit the extraordinary properties of this material and devices made out of it. Here, the fundamental chemistry of BP degradation and the tremendous progress made to address this issue are extensively reviewed. Device performances of encapsulated BP are also compared with nonencapsulated BP. In addition, BP possesses sensitive anisotropic photophysical surface properties such as excitons, surface plasmons/phonons, and topologically protected and Dirac semi‐metallic surface states. Ambient degradation as well as any passivation method used to protect the surface could affect the intrinsic surface properties of BP. These properties and the extent of their modifications by both the degradation and passivation are reviewed.     

Ready to Use Therapeutic Foods (RUTF) improves undernutrition among ART-treated, HIV-positive children in Dar es Salaam, Tanzania

ABSTRACT: BACKGROUND: HIV/AIDS is associated with an increased burden of undernutrition among children even under antiretroviral therapy (ART). To treat undernutrition, WHO endorsed the use of Ready to Use Therapeutic Foods (RUTF) that can reduce case fatality and undernutrition among ART-naive HIV-positive children. However, its effects are not studied among ART-treated, HIV-positive children. Therefore, we examined the association between RUTF use with underweight, wasting, and stunting statuses among ART-treated HIV-positive children in Dar es Salaam, Tanzania. METHODS: This cross-sectional study was conducted from September-October 2010. The target population was 219 ART-treated, HIV-positive children and the same number of their caregivers. We used questionnaires to measure socio-economic factors, food security, RUTF-use, and ART-duration. Our outcome variables were underweight, wasting, and stunting statuses. RESULTS: Of 219 ART-treated, HIV-positive children, 140 (63.9%) had received RUTF intervention prior to the interview. The percentages of underweight and wasting among non-RUTF-receivers were 12.4% and 16.5%; whereas those of RUTF-receivers were 3.0% (P = 0.006) and 2.8% (P = 0.001), respectively. RUTF-receivers were less likely to have underweight (Adjusted Odd Ratio (AOR) =0.19, CI: 0.04, 0.78), and wasting (AOR = 0.24, CI: 0.07, 0.81), compared to non RUTF-receivers. Among RUTF receivers, children treated for at least four months (n = 84) were less likely to have underweight (P = 0.049), wasting (P = 0.049) and stunting (P < 0.001). CONCLUSIONS: Among HIV-positive children under ART, the provision of RUTF for at least four months was associated with low proportions of undernutrition status. RUTF has a potential to improve undernutrition among HIV-positive children under ART in the clinical settings in Dar es Salaam, Tanzania.     

Shape evolution of lead telluride and selenide nanostructures under different hydrothermal synthesis conditions

Face-open nanoboxes of lead telluride and selenide have been synthesized by a simple hydrothermal method. Nano- and microcrystals of various morphologies, including microflowers, semi-microflowers, cubic nanoparticles, etc., have also been observed at different synthesis conditions. Temperature, time, and concentrations of various reactants play a major role in controlling the morphology and shape evolution of the product. This simple synthesis technique for the growth of various nano- and microstructures opens a new route to prepare hierarchical structures of a variety of binary semiconducting materials in a large quantity. A possible growth mechanism of such nano- and microstructures has been proposed.     

Sodium molybdate-hexagonal boron nitride composites enabled by cold sintering for microwave dielectric substrates

To fulfill the demands of more bandwidth in 5G and 6G communication technology, new dielectric substrates that can be co-fired into packages and devices that have low dielectric loss and improved thermal conductivity are desired. The motivation for this study is to design composites with low dielectric loss (tan δ) and high thermal conductivity (κ), while still limiting the electrical conductivity, for microwave applications involving high power and high frequency. This work describes the fabrication of high-density electroceramic composites with a model dielectric material for cold sintering, namely sodium molybdate (Na₂Mo₂O₇), and fillers with higher thermal conductivity such as hexagonal boron nitride. The physical properties of the composites were characterized as a function of filler vol.%, temperature, and frequency. Understanding the variation in measured properties is achieved through analyzing the respective transport mechanisms.