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Agricultural crop residues are known to be a renewable source of value-added products, and their application as a bio-based production chain type in the circular bioeconomy system is considered efficient in minimizing environmental problems. Value-added products, such as cellulose nanofibers (CNFs) from lignocellulose in agriculture residues, have been widely applied in the production of membranes that have desirable physicochemical characteristics. In this work, orange bagasse residue was used to obtain cellulose nanofiber and then applied to starch membranes as a mechanical reinforcement. The 1-methylimidazolium ionic liquid was used as biomass treatment for cellulose nanofiber isolation, and then two starch membranes were prepared with 5% (v/v) of cellulose nanofiber solution at 70 °C and 90 °C by the casting method. The cellulose nanofibers and membranes were characterized by scanning electron microscopy, fourier transform infrared spectroscopy, thermogravimetric analysis, and X-ray diffraction. Thickness and tensile tests were applied to the membranes. Cellulose nanofibers less than 100 nm in diameter were obtained by the 1-methylimidazolium treatment, and the characterization analyses showed that the CNFs were incorporated into the membranes, which improved their mechanical resistance and thermal degradation capacity. However, membrane 1, which was prepared at 70 °C, showed a particularly significant gain in tensile strength.

Glioblastoma (GBM) is the most aggressive and lethal among the primary brain tumors, with a low survival rate and resistance to radio and chemotherapy. The P2Y(12) is an adenosine diphosphate (ADP) purinergic chemoreceptor, found mainly in platelets. In cancer cells, its activation has been described to induce proliferation and metastasis. Bearing in mind the need to find new treatments for GBM, this study aimed to investigate the role of the P2Y(12)R in the proliferation and migration of GBM cells, as well as to evaluate the expression of this receptor in patients’ data obtained from the TCGA data bank. Here, we used the P2Y(12)R antagonist, ticagrelor, which belongs to the antiplatelet agent’s class. The different GBM cells (cell line and patient-derived cells) were treated with ticagrelor, with the agonist, ADP, or both, and the effects on cell proliferation, colony formation, ADP hydrolysis, cell cycle and death, migration, and cell adhesion were analyzed. The results showed that ticagrelor decreased the viability and the proliferation of GBM cells. P2Y(12)R antagonism also reduced colony formation and migration potentials, with alterations on the expression of metalloproteinases, and induced autophagy in GBM cells. Changes were observed at the cell cycle level, and only the U251 cell line showed a significant reduction in the ADP hydrolysis profile. TCGA data analysis showed a higher expression of P2Y(12)R in gliomas samples when compared to the other tumors. These data demonstrate the importance of the P2Y(12) receptor in gliomas development and reinforce its potential as a pharmacological target for glioma treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11302-022-09888-w.

Chitosan (CS) is considered a suitable biomaterial for enzyme immobilization. CS combination with polyethylene glycol (PEG) can improve the biocompatibility and the properties of the immobilized system. Thus, the present work investigated the effect of the PEG in the horseradish peroxidase (HRP) immobilization into chitosan nanoparticles from the morphological, physicochemical, and biochemical perspectives. CS and CS/PEG nanoparticles were obtained by ionotropic gelation and provided immobilization efficiencies (IE) of 65.8 % and 51.7 % and activity recovery (AR) of 76.4 % and 60.4 %, respectively. The particles were characterized by DLS, ZP, SEM, FTIR, TGA and DSC analysis. Chitosan nanoparticles showed size around 135 nm and increased to 229 nm after PEG addition and HRP immobilization. All particles showed positive surface charges (20−28 mV). Characterizations suggest nanoparticles formation and effective immobilization process. Similar values for optimum temperature and pH for immobilized HRP into both nanoparticles were found (45 °C, 7.0). Vmax value decreased by 5.07 to 3.82 and 4.11 mM/min and KM increased by 17.78 to 18.28 and 19.92 mM for free and immobilized HRP into chitosan and chitosan/PEG nanoparticles, respectively. Another biochemical parameters (Kcat, Ke, and Kα) evaluated showed a slight reduction for the immobilized enzyme in both nanoparticles compared to the free enzyme.

Fructose-1,6-bisphosphate (F1,6BP), an intermediate of the glycolytic pathway, has been found to play a promising anticancer effect; nevertheless, the mechanisms involved remain poorly understood. The present study aimed to evaluate the effect and mechanisms of F1,6BP in a human endometrial cancer cell line (Ishikawa). F1,6BP showed an antiproliferative and non-cytotoxic effect on endometrial cancer cells. These effects are related to the increase in reactive oxygen species (ROS) levels and mitochondrial membrane potential (ΔΨm). These harmful stimuli trigger the upregulation of the expression of pro-apoptotic genes (p53 and Bax), leading to the reduction of cell proliferation through inducing programmed cell death by apoptosis. Furthermore, F1,6BP-treated cells had the formation of autophagosomes induced, as well as a decrease in their proliferative capacity after withdrawing the treatment. Our results demonstrate that F1,6BP acts as an anticancer agent through the generation of mitochondrial instability, loss of cell function, and p53-dependent cell death. Thus, F1,6BP proves to be a potential molecule for use in the treatment against endometrial cancer.

Indole-3-carbinol (I3C) is a plant molecule known to be active against several types of cancer, but some chemical characteristics limit its clinical applications. In order to overcome these limitations, polymeric nanoparticles can be used as carrier systems for targeted delivery of I3C. In this study, chitosan and chitosan/polyethylene glycol nanoparticles (CS NP and CS/PEG NP, respectively) were prepared to encapsulate I3C by ionic gelation method. The polymeric nanoparticles were characterized by Dynamic Scattering Light (DLS), Zeta Potential (ZP), Fourier Transform Infrared (FTIR) spetroscopy, X-Ray Diffraction (XRD), Thermogravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), and Field Emission Gun Scanning Electron Microscopy (FEG-SEM). I3C release testing was performed at an acidic media and the interactions between I3C and chitosan or PEG were evaluated by Density Functional Theory (DFT). Cytotoxicity of nanoparticles in bladder cancer T24 cell line was evaluated by the Methyl-thiazolyl-tetrazolium (MTT) colorimetric assay. The average size of the nanoparticles was observed to be in the range from 133.3 ± 3.7 nm to 180.4 ± 2.7 nm with a relatively homogeneous distribution. Samples had relatively high positive zeta potential values (between +20.3 ± 0.5 mV and + 24.3 ± 0.5 mV). Similar encapsulation efficiencies (about 80%) for both nanoparticles were obtained. Physicochemical and thermal characterizations pointed to the encapsulation of I3c. electron microscopy showed spherical particles with smooth or ragged surface characteristics, depending on the presence of PEG. The mathematical fitting of the release profile demonstrated that I3C-CS NP followed the Higuchi model whereas I3C-CS/PEG NP the Korsmeyer-Peppas model. Chemical differences between the nanoparticles as based on the I3C/CS or I3C/PEG interactions were demonstrate by computational characterization. The assessment of cell viability by the MTT test showed that the presence of both free I3C and I3C-loaded nanoparticles lead to statistically significant reduction in T24 cells viability in the concentrations from 500 to 2000 μM, when comparison to the control group after 24 h of exposure. Thus, CS and CS/PEG nanoparticles present as feasible I3C carrier systems for cancer therapy.

Glioblastoma is the most malignant and lethal subtype of glioma. Despite progress in therapeutic approaches, issues with the tumor immune landscape persist. Multiple immunosuppression pathways coexist in the tumor microenvironment, which can determine tumor progression and therapy outcomes. Research in immune checkpoints, such as the PD-1/PD-L1 axis, has renewed the interest in immune-based cancer therapies due to their ability to prevent immunosuppression against tumors. However, PD-1/PD-L1 blockage is not completely effective, as some patients remain unresponsive to such treatment. The production of adenosine is a major obstacle for the efficacy of immune therapies and is a key source of innate or adaptive resistance. In general, adenosine promotes the pro-tumor immune response, dictates the profile of suppressive immune cells, modulates the release of anti-inflammatory cytokines, and induces the expression of alternative immune checkpoint molecules, such as PD-1, thus maintaining a loop of immunosuppression. In this context, this review aims to depict the complexity of the immunosuppression in glioma microenvironment. We primarily consider the PD-1/PD-L1 axis and adenosine pathway, which may be critical points of resistance and potential targets for tumor treatment strategies.

Ethnopharmacological relevance Plant-derived compounds are a reservoir of natural chemicals and can act as drug precursors or prototypes and pharmacological probes. Methoxyeugenol is a natural compound found in plant extracts, such as nutmeg (Myristica fragrans), and it presents anthelmintic, antimicrobial, anti-inflammatory activities. Recently, interest in the anticancer activity of plant extracts is increasing and the therapeutic activity of methoxyeugenol against cancer has not yet been explored. Aim of the study The present study aimed to evaluate the cancer-suppressive role and the molecular signaling pathways of methoxyeugenol in human endometrial cancer (Ishikawa) cell line. Materials and methods Proliferation, viability, and cell toxicity were assessed by direct counting, MTT assay, and LDH enzyme release assay, respectively. Antiproliferative effect were evaluated by nuclear morphological changes along with the cellular mechanisms of apoptosis and senescence by flow cytometry. The underlying molecular and cellular mechanisms were investigated by RT-qPCR, reactive oxygen species (ROS) levels, mitochondrial dysfunction, and proliferative capacity. Results and conclusions Methoxyeugenol treatment significantly inhibited the proliferation and viability of Ishikawa cells. Probably triggered by the higher ROS levels and mitochondrial dysfunction, the gene expression of p53 and p21 increased and the gene expression of CDK4/6 decreased in response to the methoxyeugenol treatment. The rise in nuclear size and acidic vesicular organelles corroborate with the initial senescence-inducing signals in Ishikawa cells treated with methoxyeugenol. The antiproliferative effect was not related to cytotoxicity and proved to effectively reduce the proliferative capacity of endometrial cancer cells even after treatment withdrawal. These results demonstrated that methoxyeugenol has a promising anticancer effect against endometrial cancer by rising ROS levels, triggering mitochondrial instability, and modulating cell signaling pathways leading to an inhibition of cell proliferation.

Nanostructured surfaces feature promising biological properties on biomaterials attracting large interest at basic research, implant industry development, and bioengineering applications. Thou, nanoscale interactions at a molecular and cellular level are not yet completely understood and its biological and clinical implications need to be further elucidated. As follows, the aim of this comprehensive review was to evaluate nanostructured surfaces at biomedical implants focusing on surface development, nanostructuration, and nanoengineered drug delivery systems that can induce specific cell interactions in all relevant aspects of biological, reparative, anti-bacterial, anti-inflammatory and clinical processes. The methods and the physio-chemical properties involved in nanotopography performance, the main cellular characteristics involved at surface/cell interaction, and a summary of results and outlooks reported in studies applying nanostructured surfaces and nano-drug delivery systems is presented. The future prospects and commercial translation of this developing field, particularly concerning multifunctional nanostructured surfaces and its clinical implications are further discussed. At a cellular level, nanostructured biomedical implant surfaces can enhance osteogenesis by targeting osteoblasts, osteocytes, and mesenchymal cells, stimulate fibroblast/epithelial cells proliferation and adherence, inhibit bacterial cell proliferation and biofilm accumulation, and act as immune-modulating surfaces targeting macrophages and reducing pro-inflammatory cytokine expression. Moreover, several methodological options to create drug-delivery systems on metallic implant surfaces are available, however, the clinical translation is yet incomplete. The efficiency of which nanostructured/nano-delivery surfaces may target specific cell interactions and favor clinical outcomes needs to be further elucidated in pre-clinical and clinical studies, along with engineering solutions for commercial translation and approval of controlling agencies.

Quercetin is a flavonoid found in a great variety of foods such as vegetables and fruits. This compound has been shown to inhibit the proliferation of various types of cancer cells, as well as the growth of tumors in animal models. In the present study, we analyze morphological and mechanical changes produced by quercetin in T24 bladder cancer cells. Decreased cell viability and cell number were observed following quercetin treatment at 40 μM and 60 μM, respectively, as observed by the MTT assay and trypan blue exclusion test, supporting the hypothesis of quercetin anticancer effect. These assays also allowed us to determine the 40, 60, and 80 μM quercetin concentrations for the following analyses, Lactate Dehydrogenase assay (LDH); Nuclear Morphometric Analysis (NMA); and atomic force microscopy (AFM). The LDH assay showed no cytotoxic effect of quercetin on T24 cancer cells. The AFM showed morphological changes following quercetin treatment, namely decreased cell body, cytoplasmic retraction, and membrane condensation. Following quercetin treatment, the NMA evidenced an increased percentage of nuclei characteristic to the apoptotic and senescence processes. Cells also presented biophysical alterations consistent with cell death by apoptosis, as increased roughness and aggregation of membrane proteins, in a dose-dependent manner. Cellular elasticity, obtained through force curves, showed increased stiffness after quercetin treatment. Data presented herein demonstrate, for the first time, in a quantitative and qualitative form, the morphological and mechanical alterations induced by quercetin on bladder cancer cells.

Hybrid nanoparticles composed of different biopolymers for delivery of enzyme/prodrug systems are of interest for cancer therapy. Hyaluronic acid-coated chitosan nanoparticles (CS/HA NP) were prepared to encapsulate individually an enzyme/pro-drug complex based on horseradish peroxidase (HRP) and indole-3-acetic acid (IAA). CS/HA NP showed size around 158 nm and increase to 170 and 200 nm after IAA and HRP encapsulation, respectively. Nanoparticles showed positive zeta potential values (between +20.36 mV and +24.40 mV) and higher encapsulation efficiencies for both nanoparticles (up to 90 %) were obtained. Electron microscopy indicated the formation of spherical particles with smooth surface characteristic. Physicochemical and thermal characterizations suggest the encapsulation of HRP and IAA. Kinetic parameters for encapsulated HRP were similar to those of the free enzyme. IAA-CS/HA NP showed a bimodal release profile of IAA with a high initial release (72 %) followed by a slow-release pattern. The combination of HRP-CS/HA NP and IAA- CS/HA NP reduced by 88 % the cell viability of human bladder carcinoma cell line (T24) in the concentrations 0.5 mM of pro-drug and 1.2 μg/mL of the enzyme after 24 h.

The aim of the present study is to evaluate the antioxidant activity (AA) of different fractions of the supercritical extract of Baccharis uncinella, in addition to investigating and relating AA to the potential antitumor action in bladder cancer (T24) and glioblastoma cells (U87) and also its toxicity against normal cells (Vero) for the fraction with the highest percentage of free radical scavenging (% FRS). The extracts were obtained sequentially by extraction with supercritical CO2 (150 and 200 bar and 60 °C) using ethanol as a co-solvent. The fractionation was carried out by column chromatography with hexane, dichloromethane, ethyl acetate and methanol as eluents. AA was tested by the DPPH free radical scavenging method and cell toxicity tests were performed by the MTT assay. The methanolic fraction had the highest AA, with %FRS of 86.7 %, very close to the antioxidant standard used in the test, quercetin, with 87.9 %. The methanolic fraction was able to reduce cell viability to less than 50 % at a concentration of 158.8 μg/mL to T24, 213.9 μg/mL to U87 and 702.5 μg/mL to Vero cells. According to the results, the methanolic fraction of the supercritical extract of B. uncinella has an antiproliferative effect for the tumor cells tested, with less effects on the normal cells evaluated.

One of the highlighted areas in the development of new materials is the generation of micro- and nanoparticles as drug carriers which allow the progress in formulations with the ability to release active agents in a controlled way. The proanthocyanidins (PAC) extracted from the bark of the Black Wattle have stood out for their biological activities. However, most polyflavonoids have some features which limit their application in the pharmaceutical field, such as light fastness, low bioavailability of active agents, and unpleasant taste. In this context, this study aims to present the synthesis and characterization of PAC-loaded lactic-co-glycolic acid (PLGA) microparticles obtained by the multiple emulsion method. The incorporation of PAC into PLGA was successfully achieved with PAC encapsulation efficiency around 73%. Spherical microparticles were obtained with a size distribution in the range of 0.6 to 2.4 μm. The presence of PAC modified the thermal properties of the PLGA matrix. The results of in vitro assays with Vero and T24 lineage celss showed that PLGA/PAC microparticles did not promote any effect on cell proliferation by MTT assay after 24 h. The novel Acacia mearnsii proanthocyanidin-loaded PLGA microparticles have potential for application in biological systems.

An eco-friendly approach to obtain LTA-type zeolites has been developed using biosilica-based sources derived from industrial wastes, rice husks and diatoms. Both are residues derived from the milling industry with no commercial value. The type of silica was determined in the synthesis of LTA-type zeolites with relative crystallinities of 98 and 48% and cubic crystal sizes of 1.2 and 2.5 μm, respectively. The LTA zeolites and their silver-exchanged derivatives were evaluated for the first time to treat the human bladder cancer cell line T24. The Ag-LTA synthesized with rice husks, diatoms, or commercial silica materials have a vital role of the cytotoxicity of the T24 human bladder cells with reduction of cell viability of 77, 69 and 50%, respectively. The significance of this work lies in the fact that industrial wastes can be transformed into potential zeolitic materials applied in fields not usually explored, such as biomedical, for new anticancer therapies.

Interest in nanostructures such as titanate nanotubes (TNT) has grown notably in recent years due to their biocompatibility and economic viability, making them promising for application in the biomedical field. Quercetin (Qc) has shown great potential as a chemopreventive agent and has been widely studied for the treatment of diseases such as bladder cancer. Motivated by the possibilities of developing a new hybrid nanostructure with potential in biomedical applications, this study aimed to investigate the incorporation of quercetin in sodium (NaTNT) and zinc (ZnTNT) titanate nanotubes, and characterize the nanostructures formed. Qc release testing was also performed and cytotoxicity in Vero and T24 cell lines evaluated by the MTT assay. The effect of TNTs on T24 bladder cancer cell radiosensitivity was also assessed, using cell proliferation and a clonogenic assay. The TNT nanostructures were synthesized and characterized by FESEM, EDS, TEM, FTIR, XRD and TGA. The results showed that the nanostructures have a tubular structure and that the exchange of Na+ ions for Zn2+ and incorporation of quercetin did not alter this morphology. In addition, interaction between Zn and Qc increased the thermal stability of the nanostructures. The release test showed that maximum Qc delivery occurred after 24 h and the presence of Zn controlled its release. Biological assays indicated that the NaTNTQc and ZnTNTQc nanostructures decreased the viability of T24 cells after 48 h at high concentrations. Furthermore, the clonogenic assay showed that NaTNT, NaTNTQc, ZnTNT and ZnTNTQc combined with 5 Gy reduced the formation of polyclonal colonies of T24 cells after 48 h. The results suggest that the nanostructures synthesized in this study interfere in cell proliferation and can therefore be a powerful tool in the treatment of bladder cancer.

Background The skin is the largest organ of the human body and corresponds to the first line of defense against external aggression. The extent and the commitment of organ and tissue will depend on the severity and intensity of trauma. The regeneration and healing are two processes that compose the restoration of tissues. It is a complex process involving a number of cellular and molecular events, as well as biochemical and physiological phenomena. The process of healing by secondary intention occurs in tissue repair in wounds with a higher degree of injury (injuries that may involve the subcutaneous tissue, muscle or bone). A range of biomaterials have been used in an attempt to incorporate substances that facilitate the process of tissue repair, especially the collagen to be biocompatible and not immunogenic. Essential fatty acids (EFAs) has been used in various types of injuries and different stages of the healing process. Therefore, this study aims to develop, characterize and physically evaluate the effect of collagen films containing EFAs on wound healing of second intention. The cicatricial part has already generated paper in Acta Cirurgica Brasileira, vol.28 no.5 Sao Paulo May 2013 (http://dx.doi.org/10.1590/S0102-86502013000500005).

Production and characterization of films from nanocomposite coating of sunflower seeds Andriele Mendonca Barbosa, Klebson Silva Santos, Malone Santos Pinheiro, Isabelle Souza de Melo Silva, Flavia Manuella Ribeiro de Mendonca, Fernando Mendonca Diz , Luzia Nilda Tabosa Andrade , Resende Yane Tainara Menezes , Rafaela Andrade Fonseca , Juliana Cordeiro Cardoso, Maria Lucila Hernandez Macedo , Francine Ferreira Padilha 1

Background Caseous lymphadenitis (CLA) has high relevance. It is a chronic disease that affects sheep and goats. The causative agent is Corynebacterium pseudotuberculosis, facultative intracellular bacteria. The prevalence of caseous lymphadenitis is high in many regions of the world, including South America. Brazil has 78% of seroprevalence in goats [1,2]. Therefore, prophylaxis becomes the best strategy as an effective vaccine able to eradicate disease, but also to formulate a serologic test able to detect visceral cases. One of the first steps for developing of a serological test and an effective vaccine is the choice of a target, which must present appropriate antigenic characteristics. The CP40 protein (corynebacterial protease 40) have been studied in several studies. This protease is considered one of the virulence factors of C. pseudotuberculosis. Encoded by the gene CP40 and characterized as a serine protease, proteins responsible for several functions, such as providing the activation of pro-inflammatory citocines which will help in the activation of the immune response. However the aim of this study was to evaluate the potential immune serine protease recombinant in BALB/c mice.