Electrospun curcumin/polycaprolactone/copolymer F-108 fibers as a new therapy for wound healing

The application of fibers associated with drugs is a promising alternative to meet the clinical needs of tissue repair. Curcumin exhibits great cicatricial potential because it has numerous pharmacological properties. This research aimed to produce fibers of polycaprolactone and copolymer F-108 associated with curcumin and to evaluate in vivo their action on the process of wound healing. The fibers were produced by electrospinning technique and characterized by scanning electron microscopy (SEM), X-ray diffractometry (XRD), and fluorescence microscopy. They were applied in cutaneous wounds of rats for the analysis of photoacoustic permeation and histological study. The characterization showed that the electrospinning allowed the preparation of homogeneous material with curcumin. The fibers benefited healing of the wounds and allowed the permeation of curcumin at all stages. The use of PCL/F-108 fibers allowed the elaboration of a new curcumin delivery system, improving its bioavailability and action in the healing of excisional wound. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48415.     

Amine-impregnated natural zeolite as filler in mixed matrix membranes for CO2/CH4 separation

Flat mixed matrix membranes (MMMs) comprising polysulfone and clinoptilolite-type natural zeolite were prepared by casting. Zeolite was modified with three alkylamines: ethanolamine (EA), bis(2-hydroxypropyl)amine (BHPA), and polyethylenimine (PEI) by the impregnation method. Impregnated zeolite samples were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, and N₂ adsorption–desorption. The alkylamine loading extent determined by thermogravimetric analysis was 5.2, 4.8, and 8.5% for EA, BHPA, and PEI, respectively. Analyses of MMMs showed that the incorporation of impregnated zeolite affected the glass-transition temperature (T_g) and mixed-gas transport properties. In this regard, a decreasing trend of the T_g values from 185.5 °C for the polymeric membrane up to 176.6 °C for Clino-EA-based MMM was recorded. In addition, the gas separation performance was evaluated at two different feed pressures. At 50 psi, MMMs showed an enhancement up to 30% on the CO₂ permeability (22.79 Barrer) and 55% on the CO₂/CH₄ selectivity (45.78) in comparison with the polymeric membrane (CO₂ permeability 17.34 Barrer; CO₂/CH₄ selectivity 29.38). These values varied depending on the alkylamine, BHPA being the most selective. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48286.     

Synthesis of Alkyl Fructosides

The anomeric alkylation of D-fructose is efficiently catalyzed by mild acid catalysts. Degradation of fructose is negligible under the conditions applied.     

Gal3 Plays a Deleterious Role in a Mouse Model of Endotoxemia

Lipopolysaccharide (LPS)-induced endotoxemia induces an acute systemic inflammatory response that mimics some important features of sepsis, the disease with the highest mortality rate worldwide. In this work, we have analyzed a murine model of endotoxemia based on a single intraperitoneal injection of 5 mg/kg of LPS. We took advantage of galectin-3 (Gal3) knockout mice and found that the absence of Gal3 decreased the mortality rate oflethal endotoxemia in the first 80 h after the administration of LPS, along with a reduction in the tissular damage in several organs measured by electron microscopy. Using flow cytometry, we demonstrated that, in control conditions, peripheral immune cells, especially monocytes, exhibited high levels of Gal3, which were early depleted in response to LPS injection, thus suggesting Gal3 release under endotoxemia conditions. However, serum levels of Gal3 early decreased in response to LPS challenge (1 h), an indication that Gal3 may be extravasated to peripheral organs. Indeed, analysis of Gal3 in peripheral organs revealed a robust up-regulation of Gal3 36 h after LPS injection. Taken together, these results demonstrate the important role that Gal3 could play in the development of systemic inflammation, a well-established feature of sepsis, thus opening new and promising therapeutic options for these harmful conditions.     

Macrophage-Mediated Melanoma Reduction after HP-NAP Treatment in a Zebrafish Xenograft Model

The Helicobacter pylori Neutrophil Activating Protein (HP-NAP) is endowed with immunomodulatory properties that make it a potential candidate for anticancer therapeutic applications. By activating cytotoxic Th1 responses, HP-NAP inhibits the growth of bladder cancer and enhances the anti-tumor activity of oncolytic viruses in the treatment of metastatic breast cancer and neuroendocrine tumors. The possibility that HP-NAP exerts its anti-tumor effect also by modulating the activity of innate immune cells has not yet been explored. Taking advantage of the zebrafish model, we examined the therapeutic efficacy of HP-NAP against metastatic human melanoma, limiting the observational window to 9 days post-fertilization, well before the maturation of the adaptive immunity. Human melanoma cells were xenotransplanted into zebrafish embryos and tracked in the presence or absence of HP-NAP. The behavior and phenotype of macrophages and the impact of their drug-induced depletion were analyzed exploiting macrophage-expressed transgenes. HP-NAP administration efficiently inhibited tumor growth and metastasis and this was accompanied by strong recruitment of macrophages with a pro-inflammatory profile at the tumor site. The depletion of macrophages almost completely abrogated the ability of HP-NAP to counteract tumor growth. Our findings highlight the pivotal role of activated macrophages in counteracting melanoma growth and support the notion that HP-NAP might become a new biological therapeutic agent for the treatment of metastatic melanomas.     

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.     

Medicated Scaffolds Prepared with Hydroxyapatite/Streptomycin Nanoparticles Encapsulated into Polylactide Microfibers

The preparation, characterization, and controlled release of hydroxyapatite (HAp) nanoparticles loaded with streptomycin (STR) was studied. These nanoparticles are highly appropriate for the treatment of bacterial infections and are also promising for the treatment of cancer cells. The analyses involved scanning electron microscopy, dynamic light scattering (DLS) and Z-potential measurements, as well as infrared spectroscopy and X-ray diffraction. Both amorphous (ACP) and crystalline (cHAp) hydroxyapatite nanoparticles were considered since they differ in their release behavior (faster and slower for amorphous and crystalline particles, respectively). The encapsulated nanoparticles were finally incorporated into biodegradable and biocompatible polylactide (PLA) scaffolds. The STR load was carried out following different pathways during the synthesis/precipitation of the nanoparticles (i.e., nucleation steps) and also by simple adsorption once the nanoparticles were formed. The loaded nanoparticles were biocompatible according to the study of the cytotoxicity of extracts using different cell lines. FTIR microspectroscopy was also employed to evaluate the cytotoxic effect on cancer cell lines of nanoparticles internalized by endocytosis. The results were promising when amorphous nanoparticles were employed. The nanoparticles loaded with STR increased their size and changed their superficial negative charge to positive. The nanoparticles’ crystallinity decreased, with the consequence that their crystal sizes reduced, when STR was incorporated into their structure. STR maintained its antibacterial activity, although it was reduced during the adsorption into the nanoparticles formed. The STR release was faster from the amorphous ACP nanoparticles and slower from the crystalline cHAp nanoparticles. However, in both cases, the STR release was slower when incorporated in calcium and phosphate during the synthesis. The biocompatibility of these nanoparticles was assayed by two approximations. When extracts from the nanoparticles were evaluated in cultures of cell lines, no cytotoxic damage was observed at concentrations of less than 10 mg/mL. This demonstrated their biocompatibility. Another experiment using FTIR microspectroscopy evaluated the cytotoxic effect of nanoparticles internalized by endocytosis in cancer cells. The results demonstrated slight damage to the biomacromolecules when the cells were treated with ACP nanoparticles. Both ACP and cHAp nanoparticles were efficiently encapsulated in PLA electrospun matrices, providing functionality and bioactive properties.     

The Role of the Lymphatic System in the Pathogenesis and Treatment of Inflammatory Bowel Disease

Although the number of therapeutic options for the treatment of inflammatory bowel disease (IBD) has increased in recent years, patients suffer from decreased quality of life due to non-response or loss of response to the currently available treatments. An increased understanding of the disease’s etiology could provide novel insights for treatment strategies in IBD. Lymphatic system components are generally linked to immune responses and presumably related to inflammatory diseases pathophysiology. This review aims to summarize findings on immune-mediated mechanisms in lymphoid tissues linked with IBD pathogenesis and (potential) novel treatments. Enhanced innate and adaptive immune responses were observed in mesenteric lymph nodes (MLNs) and other lymphoid structures, such as Peyer’s patches, in patients with IBD and in animal models. Furthermore, the phenomenon of lymphatic obstruction in the form of granulomas in MLNs and lymphatic vessels correlates with disease activity. There is also evidence that abnormalities in the lymphatic stromal components and lymph node microbiome are common in IBD and could be exploited therapeutically. Finally, novel agents targeting lymphocyte trafficking have been added to the treatment armamentarium in the field of IBD. Overall, gut-associated lymphoid tissue plays a key role in IBD immunopathogenesis, which could offer novel therapeutic targets.     

Physicochemical Properties,Lipid Oxidation,and Fatty Acid Composition of Sausage Prepared with Meat of Young Nellore Bulls Fed a Diet with Lauric Acid

This study evaluates the quality of sausage obtained from the meat of Nellore cattle fed diets containing different levels (0, 5, 10, and 15 g per kg total DM) of lauric acid (C12:0) from palm kernel cake. A linear reduction (p ≤ 0.05) in lipid oxidation, as reflected by linear decreases in the lightness (L*), yellowness (b*), and saturation (C*) color parameters, is observed on days 7, 14, and 21 of maturation of sausage, and these decreases are accompanied by linear increases in the redness (a*) color and the linoleic (C18:2n–6) and linolenic (C18:3n–3) fatty acid contents. The inclusion of lauric acid in the diet induces linear reductions in the shear force and cooking loss and does not significantly affect various indices, including the centesimal composition, water activity, water holding capacity, composition of most fatty acids (FA), hypocholesterolemic‐to‐hypercholesterolemic FA ratio, atherogenicity, thrombogenicity, and desirable fatty acids. The use of dietary lauric acid from palm kernel cake is recommended at doses up to 15 g per kg because its presence reduces lipid oxidation and improves color parameters, softness, and linoleic and linolenic FA without affecting the FA composition of sausage from Nellore bull's meat. Practical applications : Sausages are products manufactured from chopped or ground meats packaged into animal casings. This product appeared in Brazil through the adaptation of traditional recipes brought by German and Italian immigrant families to weather conditions and the national palate. However, due to its production characteristics, sausage can become a product with lipid characteristics that are undesirable for human consumption. The inclusion of lauric acid (C12:0) in the animal diet might change the biohydrogenation process in the rumen, improve the quality of the deposited FA and reduce lipid oxidation in sausage manufactured from meat. The FA composition and physicochemical properties of sausage predict its acceptance by the consumer market. An optimal advantage would be achieved if these products can be used as not only preservatives but also functional ingredients with antioxidant properties and products for the treatment of metabolic syndrome and cardiovascular diseases through atherogenic action.