COVID-19 and Lung Mast Cells: The Kallikrein–Kinin Activation Pathway

Mast cells (MCs) have relevant participation in inflammatory and vascular hyperpermeability events, responsible for the action of the kallikrein–kinin system (KKS), that affect patients inflicted by the severe form of COVID-19. Given a higher number of activated MCs present in COVID-19 patients and their association with vascular hyperpermeability events, we investigated the factors that lead to the activation and degranulation of these cells and their harmful effects on the alveolar septum environment provided by the action of its mediators. Therefore, the pyroptotic processes throughout caspase-1 (CASP-1) and alarmin interleukin-33 (IL-33) secretion were investigated, along with the immunoexpression of angiotensin-converting enzyme 2 (ACE2), bradykinin receptor B1 (B1R) and bradykinin receptor B2 (B2R) on post-mortem lung samples from 24 patients affected by COVID-19. The results were compared to 10 patients affected by H1N1pdm09 and 11 control patients. As a result of the inflammatory processes induced by SARS-CoV-2, the activation by immunoglobulin E (IgE) and degranulation of tryptase, as well as Toluidine Blue metachromatic (TB)-stained MCs of the interstitial and perivascular regions of the same groups were also counted. An increased immunoexpression of the tissue biomarkers CASP-1, IL-33, ACE2, B1R and B2R was observed in the alveolar septum of the COVID-19 patients, associated with a higher density of IgE⁺ MCs, tryptase⁺ MCs and TB-stained MCs, in addition to the presence of intra-alveolar edema. These findings suggest the direct correlation of MCs with vascular hyperpermeability, edema and diffuse alveolar damage (DAD) events that affect patients with a severe form of this disease. The role of KKS activation in events involving the exacerbated increase in vascular permeability and its direct link with the conditions that precede intra-alveolar edema, and the consequent DAD, is evidenced. Therapy with drugs that inhibit the activation/degranulation of MCs can prevent the worsening of the prognosis and provide a better outcome for the patient.     

Cold Atmospheric Plasma Apoptotic and Oxidative Effects on MCF7 and HCC1806 Human Breast Cancer Cells

Breast cancer (BC) is a malignant neoplasia with the highest incidence and mortality rates in women worldwide. Currently, therapies include surgery, radiotherapy, and chemotherapy, including targeted therapies in some cases. However, treatments are often associated with serious adverse effects. Looking for new options in BC treatment, we evaluated the therapeutic potential of cold atmospheric plasma (CAP) in two cell lines (MCF7 and HCC1806) with distinct histological features. Apoptosis seemed to be the most prevalent type of death, as corroborated by several biochemical features, including phosphatidylserine exposure, the disruption of mitochondrial membrane potential, an increase in BAX/BCL2 ratio and procaspase 3 loss. Moreover, the accumulation of cells in the G2/M phase of the cell cycle points to the loss of replication ability and decreased survival. Despite reported toxic concentrations of peroxides in culture media exposed to plasma, intracellular peroxide concentration was overall decreased accompanying a reduction in GSH levels shortly after plasma exposure in both cell lines. In HCC1806, elevated nitric oxide (NO) concentration accompanied by reduced superoxide levels suggests that these cells are capable of converting plasma-derived nitrites into NO that competes with superoxide dismutase (SOD) for superoxide to form peroxinitrite. The concomitant inhibition of the antioxidative activity of cells during CAP treatment, particularly the inhibition of cytochrome c oxidase with sodium azide, synergistically increased plasma toxicity. Thus, this in vitro research enlightens the therapeutic potential of CAP in the treatment of breast cancer, elucidating its possible mechanisms of action.     

Composites based on high-density polyethylene,polylactide and calcium carbonate: effect of calcium carbonate nanoparticles as co-compatibilizers

Polymer Bulletin - Investigating the compatibility mechanism of hybrid composites based on two polymers and one mineral nanofiller is a challenge that needs to be better understood. This study...     

Fatty Acids,CD36, Thrombospondin-1, and CD47 in Glioblastoma: Together and/or Separately?

Glioblastoma (GBM) is one of the most aggressive tumors of the central nervous system, characterized by a wide range of inter- and intratumor heterogeneity. Accumulation of fatty acids (FA) metabolites was associated with a low survival rate in high-grade glioma patients. The diversity of brain lipids, especially polyunsaturated fatty acids (PUFAs), is greater than in all other organs and several classes of proteins, such as FA transport proteins (FATPs), and FA translocases are considered principal candidates for PUFAs transport through BBB and delivery of PUFAs to brain cells. Among these, the CD36 FA translocase promotes long-chain FA uptake as well as oxidated lipoproteins. Moreover, CD36 binds and recognizes thrombospondin-1 (TSP-1), an extracellular matrix protein that was shown to play a multifaceted role in cancer as part of the tumor microenvironment. Effects on tumor cells are mediated by TSP-1 through the interaction with CD36 as well as CD47, a member of the immunoglobulin superfamily. TSP-1/CD47 interactions have an important role in the modulation of glioma cell invasion and angiogenesis in GBM. Separately, FA, the two membrane receptors CD36, CD47, and their joint ligand TSP-1 all play a part in GBM pathogenesis. The last research has put in light their interconnection/interrelationship in order to exert a cumulative effect in the modulation of the GBM molecular network.     

CircRNAs as Potential Blood Biomarkers and Key Elements in Regulatory Networks in Gastric Cancer

Gastric cancer (GC) is the fifth most common type of cancer and the third leading cause of cancer death in the world. It is a disease that encompasses a variety of molecular alterations, including in non-coding RNAs such as circular RNAs (circRNAs). In the present study, we investigated hsa_circ_0000211, hsa_circ_0000284, hsa_circ_0000524, hsa_circ_0001136 and hsa_circ_0004771 expression profiles using RT-qPCR in 71 gastric tissue samples from GC patients (tumor and tumor-adjacent samples) and volunteers without cancer. In order to investigate the suitability of circRNAs as minimally invasive biomarkers, we also evaluated their expression profile through RT-qPCR in peripheral blood samples from patients with and without GC (n = 41). We also investigated the predicted interactions between circRNA-miRNA-mRNA and circRNA-RBP using the KEGG and Reactome databases. Overall, our results showed that hsa_circ_0000211, hsa_circ_0000284 and hsa_circ_0004771 presented equivalent expression profiles when analyzed by different methods (RNA-Seq and RT-qPCR) and different types of samples (tissue and blood). Further, functional enrichment results identified important signaling pathways related to GC. Thus, our data support the consideration of circRNAs as new, minimally invasive biomarkers capable of aiding in the diagnosis of GC and with great potential to be applied in clinical practice.     

Adsorption onto fluidized powdered activated carbon flocs-pACF

This work presents a new adsorption technique where the adsorbent (powdered activated carbon-PAC) is in the form of suspended flocs formed with water-soluble polymer flocculants. Thus, the adsorption of a typical dye, methylene blue (MB), was studied onto polyacrylamide flocs of PAC (PACF) in a fluidized bed reactor. The technique is based on the fact that the adsorption capacity of PAC does not decrease after flocculation because the adsorbed polymer occupies only a few surface sites, in the form of trains, loops, and tails. Moreover, the adsorption was found to proceed through a rapid mass transfer of MB to the adsorbing PAC flocs, in the same extent as onto PAC. Because of the rapid settling characteristics of the aggregates formed, the two phase separations, loaded PAC and solution, become easier. Thus, the technique offers the advantages of conducting simultaneously both adsorption and solid/liquid separation all in one single stage. Results obtained showed that high MB removal values can be attained in a fluidized bed reactor (>90%) and that PACF presents a much higher adsorption capacity (breakthrough points) than granulated activated carbon (GAC) in the same adsorbing bed. It is believed that this technique highly broadens the potential of the use of powdered activated carbon or other similar ultrafine adsorbents.     

Physico-chemical and sensory properties of yogurt from ultrafiltreted soy milk concentrate added with inulin

The total solids required for yogurt preparation were obtained by soy milk microfiltration and ultrafiltration. Inulin was incorporated at the level of 20–70 g/L, and the soy milk containing inulin was fermented using conventional microorganisms. The chemical, physical and sensory properties of the products were evaluated. The membrane concentration of soy proteins leads to yogurts with an increase of 59 g/L of proteins and 15 g/L of vegetable fats, reducing ash and anti-nutrients content. The clot had high stability and protein concentration generated a buffer effect smoothing the acidity and the flavor obtained is more agreeable. In addition, the proteins were concentrated without thermal treatment. As the inulin content increased, creaminess and viscosity increased as well. The products prepared presented nice smell, flavor and color, being the sample with higher global acceptability the yogurt with 50 g/L of inulin (P < 0.05).     

Antioxidant activity, ascorbic acid, phenolic compounds and sugars of wild and commercial Tuberaria lignosa samples: Effects of drying and oral preparation methods

The antioxidant activity and phytochemical composition (ascorbic acid, free sugars and phenolic compounds) of decoctions and infusions of wild and commercial samples of Tuberaria lignosa (Sweet) Samp. Aerial parts were evaluated and compared. Among wild samples, the effects of the drying method (freeze or shade-drying) on those parameters were studied. Infusion of the freeze-dried wild sample gave the highest levels of sugars, while infusion of shade-dried wild sample and decoction of the freeze-dried sample presented higher ascorbic acid and phenolic compounds content (including ellagitannins and flavonoids) than the other samples. The last two samples also revealed higher antioxidant activity, in some cases even higher than Trolox. Decoctions gave lower amounts of disaccharides than infusions, which seemed to be hydrolysed, increasing the content of monosaccharides. Commercial samples showed the lowest content in phenolic compounds, mainly in ellagitannins and flavonoids, and also the lowest antioxidant activity. This work gives scientific evidence to the traditional medicinal uses of wild Tuberaria lignosa, highlighting the interest of its decoctions and infusions as a source of bioactive compounds and functional beverages.