Transcriptomic Profiles of CD47 in Breast Tumors Predict Outcome and Are Associated with Immune Activation

Targeting the innate immune system has attracted attention with the development of anti- CD47 antibodies. Anti-CD47 antibodies block the inhibition of the phagocytic activity of macrophages caused by the up-regulation of CD47 on tumor cells. In this study, public genomic data was used to identify genes highly expressed in breast tumors with elevated CD47 expression and analyzed the association between the presence of tumor immune infiltrates and the expression of the selected genes. We found that 142 genes positively correlated with CD47, of which 83 predicted favorable and 32 detrimental relapse-free survival (RFS). From those associated with favorable RFS, we selected the genes with immunologic biological functions and defined a CD47-immune signature composed of PTPRC, HLA-E, TGFBR2, PTGER4, ETS1, and OPTN. In the basal-like and HER2+ breast cancer subtypes, the expression of the CD47-immune signature predicted favorable outcome, correlated with the presence of tumor immune infiltrates, and with gene expression signatures of T cell activation. Moreover, CD47 up-regulated genes associated with favorable survival correlated with pro-tumoral macrophages. In summary, we described a CD47-immune gene signature composed of 6 genes associated with favorable prognosis, T cell activation, and pro-tumoral macrophages in breast cancer tumors expressing high levels of CD47.     

Cyclic Nigerosyl-Nigerose as Oxygen Nanocarrier to Protect Cellular Models from Hypoxia/Reoxygenation Injury: Implications from an In Vitro Model

Heart failure (HF) prevalence is increasing among the aging population, and the mortality rate remains unacceptably high despite improvements in therapy. Myocardial ischemia (MI) and, consequently, ischemia/reperfusion injury (IRI), are frequently the basis of HF development. Therefore, cardioprotective strategies to limit IRI are mandatory. Nanocarriers have been proposed as alternative therapy for cardiovascular disease. Controlled reoxygenation may be a promising strategy. Novel nanocarriers, such as cyclic nigerosyl-nigerose (CNN), can be innovative tools for oxygen delivery in a controlled manner. In this study we analyzed new CNN-based formulations as oxygen nanocarriers (O₂-CNN), and compared them with nitrogen CNN (N₂-CNN). These different CNN-based formulations were tested using two cellular models, namely, cardiomyoblasts (H9c2), and endothelial (HMEC) cell lines, at different concentrations. The effects on the growth curve during normoxia (21% O₂, 5% CO₂ and 74% N₂) and their protective effects during hypoxia (1% O₂, 5% CO₂ and 94% N₂) and reoxygenation (21% O₂, 5% CO₂ and 74% N₂) were studied. Neither O₂-CNN nor N₂-CNN has any effect on the growth curve during normoxia. However, O₂-CNN applied before hypoxia induces a 15–30% reduction in cell mortality after hypoxia/re-oxygenation when compared to N₂-CNN. O₂-CNN showed a marked efficacy in controlled oxygenation, which suggests an interesting potential for the future medical application of soluble nanocarrier systems for MI treatment.     

Biomarkers in Glycogen Storage Diseases: An Update

Glycogen storage diseases (GSDs) are a group of 19 hereditary diseases caused by a lack of one or more enzymes involved in the synthesis or degradation of glycogen and are characterized by deposits or abnormal types of glycogen in tissues. Their frequency is very low and they are considered rare diseases. Except for X-linked type IX, the different types are inherited in an autosomal recessive pattern. In this study we reviewed the literature from 1977 to 2020 concerning GSDs, biomarkers, and metabolic imbalances in the symptoms of some GSDs. Most of the reported studies were performed with very few patients. Classification of emerging biomarkers between different types of diseases (hepatics GSDs, McArdle and PDs and other possible biomarkers) was done for better understanding. Calprotectin for hepatics GSDs and urinary glucose tetrasaccharide for Pompe disease have been approved for clinical use, and most of the markers mentioned in this review only need clinical validation, as a final step for their routine use. Most of the possible biomarkers are implied in hepatocellular adenomas, cardiomyopathies, in malfunction of skeletal muscle, in growth retardation, neutropenia, osteopenia and bowel inflammation. However, a few markers have lost interest due to a great variability of results, which is the case of biotinidase, actin alpha 2, smooth muscle, aorta and fibroblast growth factor receptor 4. This is the first review published on emerging biomarkers with a potential application to GSDs.     

Peptides to Tackle Leishmaniasis: Current Status and Future Directions

Peptide-based drugs are an attractive class of therapeutic agents, recently recognized by the pharmaceutical industry. These molecules are currently being used in the development of innovative therapies for diverse health conditions, including tropical diseases such as leishmaniasis. Despite its socioeconomic influence on public health, leishmaniasis remains long-neglected and categorized as a poverty-related disease, with limited treatment options. Peptides with antileishmanial effects encountered to date are a structurally heterogeneous group, which can be found in different natural sources—amphibians, reptiles, insects, bacteria, marine organisms, mammals, plants, and others—or inspired by natural toxins or proteins. This review details the biochemical and structural characteristics of over one hundred peptides and their potential use as molecular frameworks for the design of antileishmanial drug leads. Additionally, we detail the main chemical modifications or substitutions of amino acid residues carried out in the peptide sequence, and their implications in the development of antileishmanial candidates for clinical trials. Our bibliographic research highlights that the action of leishmanicidal peptides has been evaluated mainly using in vitro assays, with a special emphasis on the promastigote stage. In light of these findings, and considering the advances in the successful application of peptides in leishmaniasis chemotherapy, possible approaches and future directions are discussed here.     

Improvement of flexural bond strength of zirconia-resin cement by surface patterning using sub-nanosecond UV laser

Zirconia is a dental material that shows excellent biocompatibility and high strength in clinical applications. This study aims to evaluate the effects of ultrafast laser applications. The surface nanostructures were classified into three groups. Group 1 was generated using the burst mode, with three different distances between dots: 52 µm (Group 1a), 104 µm (Group 1b), and 156 µm (Group 1c). Group 2 was processed using the scanning mode configuration, with a set of parallel lines. Group 3 was also processed using this scanning configuration creating a set of square-shaped patterning. Group 4 was the control group. After the surface treatments, a pair of zirconia specimens was bonded end to end with resin cement. Flexural bond strength (FBS) test was applied in a universal test machine. Multiple comparisons were performed using a one-way analysis of variance and the Tukey's HSD test. All the samples that were treated with the laser showed higher FBS values than the untreated surface. Using the burst mode, preformed circular-shaped surface on an angle of 90⁰ at 52 µm distance (Group 1a) showed the highest FBS values among all groups (p < .05). Groups 2 and 3 had significantly higher values than 1b and 1c.     

Design of fluidized bed photoreactors: Optical properties of photocatalytic composites of titania CVD-coated onto quartz sand

Volumetric optical properties (spectral absorption, scattering and extinction coefficients) of differently expanded narrow-path fluidized beds (FB) of a photocatalyst obtained by plasma-CVD deposition of titania onto quartz sand, relevant for photoreactor design purposes, are determined by using an unidirectional and unidimensional (1DD) model for the solution of the radiative transfer equation (RTE). Two simplified approaches are used: a Kubelka-Munk (KM) type of solution, by which the RTE is transformed into a pair of ordinary differential equations, and a discrete ordinate method (DOM) by which the complete RTE is transformed into an algebraic system that can be solved computationally. The second approach was validated by introducing the obtained optical parameters into a more elaborated bi-directional and two-dimensional (2DD) DOM model. Despite its simplicity, the KM method was able to yield fair order-of-magnitude estimates of the spectral optical properties of these FB.     

Nitrogen dynamics during till and no-till pasture restoration sequences in Rondônia,Brazil

The clearing of tropical rain forest in the Amazon basin has created large areas of cattle pasture that are now declining in productivity. Practices adopted by ranchers to restore productivity to degraded pastures have the potential to alter soil N availability and gaseous N losses from soils. We examined how soil inorganic N pools, net N mineralization and net nitrification rates, nitrification potential and NO and N₂O emissions from soils of a degraded pasture responded to the following restoration treatments: (1) soil tillage followed by replanting of grass and fertilization, (2) no-till application of non-selective herbicide, planting of rice, harvest followed by no-till replanting of grass and fertilization, and (3) the same no-till sequence with soybeans instead of rice. Tillage increased soil NH₄⁺ and NO₃^? pools but NH₄⁺ and NO₃^? pools remained relatively constant in the control and no-till treatments. Cumulative rates of net N mineralization and net nitrification during the first 6 months after treatment varied widely but were hightest in the tilled treatment. Emissions of NO and N₂O fluxes increased with tillage and with N fertilization. There were no clear relationships among rates of N fertilizer application, net N mineralization, net nitrification, NO, N₂O and total N oxide emissions. Our results indicate that pasture restoration sequences involving tilling and fertilizing will increase emissions of N oxides, but the magnitude of the increase is likely to differ based on timing of fertilizer application relative to the presence of plants and the magnitude of plant N demand. Emissions of N oxides appear to be decreased by the use of restoration sequences that minimize reductions in pasture grass cover.     

SELECTIVITY STUDIES IN THE PHOTOCHLORINATION OF METHANE II: EFFECT OF THE RADIATION SOURCE OUTPUT POWER AND OUTPUT SPECTRAL DISTRIBUTION

The effect of the output power and output spectral distribution of the radiation energy fed to a photoreactor upon the reaction yield and selectivities is studied both theoretically and experimentally. The study aims at the analysis of these influences in a series reaction such as the photochlorination of methane where methylene chloride and eventually chloroform are the most valuable products. The computational model employed has been verified for a group of selected conditions by means of bench-sale experiments.

It is found that the chlorine conversion shows the expected square root dependence with respect to the Local Volumetric Rate of Energy Absorption (LVREA). This dependence, in a first approximation, can also be assigned to the effect of the radiation source output power upon yield. It is also found that by manipulating the amount of radiation power fed to the reactor it is possible to ascertain the operating conditions favoring the production of predetermined intermediate products (e.g., methylene chloride or chloroform).

It is concluded that the use of customized lamps especially designed for each particular product on the basis of feasible changes in the characteristics of the existing radiation sources will favor a selective and more economical production of some of the stable intermediates, i.e., lamp design is an important feature in any optimal process design.