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The present work consist of the synthesis of photo-cross-linkable materials, based on unsaturated polyesters (UPs), synthesized from biobased monomers from renewable sources such as itaconic acid and 1,4-butanediol. The UPs were characterized to assess the influence of polycondensation reaction temperature and cross-linking time on their final properties. For this purpose, different UV irradiation exposure periods were tested. Homogeneous, uniform, and transparent films were obtained after 1, 3, and 5 min of UV exposure. These cross-linked films were then characterized. All materials presented high gel content, which was dependent on the reaction's temperature. The thermal behaviors of the UPs were shown to be similar. In vitro hydrolytic degradation tests showed that the materials can undergo degradation in phosphate-buffered saline (PBS) at pH 7.4 and 37 °C, ensuring their biodegradability over time. Finally, to assess the applicability of the polyesters as biomaterials, their cytocompatibility was determined by using human dermal fibroblasts.
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BACKGROUND: Chikungunya virus (CHIKV) is an arbovirus from the Togaviridae family which has four genotypes: West African (WA), East/Central/South African (ECSA) and Asian/Caribbean lineage (AL) and Indian Ocean Lineage (IOL). The ECSA genotype was first registered in Brazil in Feira de Santana and spread to all Brazilian regions. This study reports the characterization of CHIKV isolates recovered from sera samples of fifty patients from seventeen cities in Maranhão, a state from Brazilian northeast region and part of the Legal Amazon area. METHODS AND RESULTS: Primers were developed to amplify the partial regions coding structural proteins (E1, E3, E2, 6 K, and Capsid C). The consensus sequences have 2871 bp, covering approximately 24% of the genome. The isolates were highly similar (> 99%) to the ECSA isolate from Feira de Santana (BHI3734/H804698), presenting 30 non-synonymous mutations in E1 (5.95%), 18 in E2 (4.46%), and 1 in E3 (3.03%), taking the BHI3734/H804698 isolate as standard. Although the mutations described have not previously been related to increased infectivity or transmissibility of CHIKV, in silico analysis showed changes in physicochemical characteristics, antigenicity, and B cell epitopes of E1 and E2. CONCLUSIONS: These findings demonstrate the importance of molecular approaches for monitoring the viral adaptations undergone by CHIKV and its geographic distribution.
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Febre de Chikungunya , Vírus Chikungunya , Humanos , Vírus Chikungunya/genética , Febre de Chikungunya/epidemiologia , Brasil , Surtos de Doenças , Filogenia , GenótipoRESUMO
Enteropathogenic Escherichia coli (EPEC) produce a capsule of polysaccharides identical to those composing the O-antigen polysaccharide of its LPS (lipopolysaccharide) molecules. In light of this, the impact of O26 polysaccharides on the immune evasion mechanisms of capsulated O26 EPEC compared to non-capsulated enterohemorrhagic Escherichia coli (EHEC) was investigated. Our findings reveal that there was no significant difference between the levels in EPEC and EHEC of rhamnose (2.8:2.5), a molecule considered to be a PAMP (Pathogen Associated Molecular Patterns). However, the levels of glucose (10:1.69), heptose (3.6:0.89) and N-acetylglucosamine (4.5:2.10), were significantly higher in EPEC than EHEC, respectively. It was also observed that the presence of a capsule in EPEC inhibited the deposition of C3b on the bacterial surface and protected the pathogen against lysis by the complement system. In addition, the presence of a capsule also protected EPEC against phagocytosis by macrophages. However, the immune evasion provided by the capsule was overcome in the presence of anti-O26 polysaccharide antibodies, and additionally, these antibodies were able to inhibit O26 EPEC adhesion to human epithelial cells. Finally, the results indicate that O26 polysaccharides can generate an effective humoral immune response, making them promising antigens for the development of a vaccine against capsulated O26 E. coli.
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Escherichia coli Êntero-Hemorrágica , Escherichia coli Enteropatogênica , Infecções por Escherichia coli , Proteínas de Escherichia coli , Humanos , Evasão da Resposta Imune , Infecções por Escherichia coli/microbiologia , Proteínas de Escherichia coli/farmacologia , Lipopolissacarídeos/farmacologia , Desenvolvimento de VacinasRESUMO
Silica aerogel is a material composed of SiO2 that has exceptional physical properties when utilized for tissue engineering applications. Poly-ε-caprolactone (PCL) is a biodegradable polyester that has been widely used for biomedical applications, namely as sutures, drug carriers, and implantable scaffolds. Herein, a hybrid composite of silica aerogel, prepared with two different silica precursors, tetraethoxysilane (TEOS) or methyltrimethoxysilane (MTMS), and PCL was synthesized to fulfil bone regeneration requirements. The developed porous hybrid biocomposite scaffolds were extensively characterized, regarding their physical, morphological, and mechanical features. The results showed that their properties were relevant, leading to composites with different properties. The water absorption capacity and mass loss were evaluated as well as the influence of the different hybrid scaffolds on osteoblasts' viability and morphology. Both hybrid scaffolds showed a hydrophobic character (with water contact angles higher than 90°), low swelling (maximum of 14%), and low mass loss (1-7%). hOB cells exposed to the different silica aerogel-PCL scaffolds remained highly viable, even for long periods of incubation (7 days). Considering the obtained results, the produced hybrid scaffolds may be good candidates for future application in bone tissue engineering.
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Dióxido de Silício , Engenharia Tecidual , Engenharia Tecidual/métodos , Dióxido de Silício/química , Alicerces Teciduais/química , Poliésteres/química , ÁguaRESUMO
Bioprinting holds great promise towards engineering functional cardiac tissue constructs for regenerative medicine and as drug test models. However, it is highly limited by the choice of inks that require maintaining a balance between the structure and functional properties associated with the cardiac tissue. In this regard, we have developed a novel and mechanically robust biomaterial-ink based on non-mulberry silk fibroin protein. The silk-based ink demonstrated suitable mechanical properties required in terms of elasticity and stiffness (~40 kPa) for developing clinically relevant cardiac tissue constructs. The ink allowed the fabrication of stable anisotropic scaffolds using a dual crosslinking method, which were able to support formation of aligned sarcomeres, high expression of gap junction proteins as connexin-43, and maintain synchronously beating of cardiomyocytes. The printed constructs were found to be non-immunogenic in vitro and in vivo. Furthermore, delving into an innovative method for fabricating a vascularized myocardial tissue-on-a-chip, the silk-based ink was used as supporting hydrogel for encapsulating human induced pluripotent stem cell derived cardiac spheroids (hiPSC-CSs) and creating perfusable vascularized channels via an embedded bioprinting technique. We confirmed the ability of silk-based supporting hydrogel towards maturation and viability of hiPSC-CSs and endothelial cells, and for applications in evaluating drug toxicity.
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Developing biomimetic cartilaginous tissues that support locomotion while maintaining chondrogenic behavior is a major challenge in the tissue engineering field. Specifically, while locomotive forces demand tissues with strong mechanical properties, chondrogenesis requires a soft microenvironment. To address this challenge, 3D cartilage-like tissue is bioprinted using two biomaterials with different mechanical properties: a hard biomaterial to reflect the macromechanical properties of native cartilage, and a soft biomaterial to create a chondrogenic microenvironment. To this end, a hard biomaterial (MPa order compressive modulus) composed of an interpenetrating polymer network (IPN) of polyethylene glycol (PEG) and alginate hydrogel is developed as an extracellular matrix (ECM) with self-healing properties, but low diffusive capacity. Within this bath supplemented with thrombin, fibrinogen containing human mesenchymal stem cell (hMSC) spheroids is bioprinted forming fibrin, as the soft biomaterial (kPa order compressive modulus) to simulate cartilage's pericellular matrix and allow a fast diffusion of nutrients. The bioprinted hMSC spheroids improve viability and chondrogenic-like behavior without adversely affecting the macromechanical properties of the tissue. Therefore, the ability to print locally soft and cell stimulating microenvironments inside of a mechanically robust hydrogel is demonstrated, thereby uncoupling the micro- and macromechanical properties of the 3D printed tissues such as cartilage.
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Leukocyte and platelet-rich plasma (L-PRP) is an autologous product that when activated forms fibrin nanofibers, which are useful in regenerative medicine. As an important part of the preparation of L-PRP, the centrifugation parameters may affect the release of soluble factors that modulate the behavior of the cells in the nanofibers. In this study, we evaluated the influences of four different centrifugation conditions on the concentration of platelets and leukocytes in L-PRP and on the anabolic/catabolic balance of the nanofiber microenvironment. Human adipose-derived mesenchymal stem cells (h-AdMSCs) were seeded in the nanofibers, and their viability and growth were evaluated. L-PRPs prepared at 100× g and 100 + 400× g released higher levels of transforming growth factor (TGF)-ß1 and platelet-derived growth factor (PDGF)-BB due to the increased platelet concentration, while inflammatory cytokines interleukin (IL)-8 and tumor necrosis factor (TNF)-α were more significantly released from L-PRPs prepared via two centrifugation steps (100 + 400× g and 800 + 400× g) due to the increased concentration of leukocytes. Our results showed that with the exception of nanofibers formed from L-PRP prepared at 800 + 400× g, all other microenvironments were favorable for h-AdMSC proliferation. Here, we present a reproducible protocol for the standardization of L-PRP and fibrin nanofibers useful in clinical practices with known platelet/leukocyte ratios and in vitro evaluations that may predict in vivo results.
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Centrifugação , Fibrina , Células-Tronco Mesenquimais/metabolismo , Nanofibras , Plasma Rico em Plaquetas , Plaquetas/metabolismo , Proliferação de Células , Células Cultivadas , Citocinas/metabolismo , Fibrina/química , Humanos , Mediadores da Inflamação/metabolismo , Leucócitos/metabolismo , Nanofibras/química , Nanofibras/ultraestruturaRESUMO
Nanomaterials' application in cancer therapy has been driven by their ability to encapsulate chemotherapeutic drugs as well as to reach the tumor site. Nevertheless, nanomedicines' translation has been limited due to their lack of specificity towards cancer cells. Although the nanomaterials' surface can be coated with targeting ligands, such has been mostly achieved through non-covalent functionalization strategies that are prone to premature detachment. Notwithstanding, cancer cells often establish resistance mechanisms that impair the effect of the loaded drugs. This bottleneck may be addressed by using near-infrared (NIR)-light responsive nanomaterials. The NIR-light triggered hyperthermic effect generated by these nanomaterials can cause irreversible damage to cancer cells or sensitize them to chemotherapeutics' action. Herein, a novel covalently functionalized targeted NIR-absorbing nanomaterial for cancer chemo-photothermal therapy was developed. For such, dopamine-reduced graphene oxide nanomaterials were covalently bonded with hyaluronic acid, and then loaded with doxorubicin (DOX/HA-DOPA-rGO). The produced nanomaterials showed suitable physicochemical properties, high encapsulation efficiency, and photothermal capacity. The in vitro studies revealed that the nanomaterials are cytocompatible and that display an improved uptake by the CD44-overexpressing breast cancer cells. Importantly, the combination of DOX/HA-DOPA-rGO with NIR light reduced breast cancer cells' viability to just 23 %, showcasing their potential chemo-photothermal therapy.
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Neoplasias da Mama , Grafite , Hipertermia Induzida , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Ácido Hialurônico/química , Terapia Fototérmica , Grafite/química , Doxorrubicina/química , Di-Hidroxifenilalanina , FototerapiaRESUMO
Nanomaterials with responsiveness to near-infrared light can mediate the photoablation of cancer cells with an exceptional spatio-temporal resolution. However, the therapeutic outcome of this modality is limited by the nanostructures' poor tumor uptake. To address this bottleneck, it is appealing to develop injectable in situ forming hydrogels due to their capacity to perform a tumor-confined delivery of the nanomaterials with minimal off-target leakage. In particular, injectable in situ forming hydrogels based on Pluronic F127 have been emerging due to their FDA-approval status, biocompatibility, and thermosensitive sol-gel transition. Nevertheless, the application of Pluronic F127 hydrogels has been limited due to their fast dissociation in aqueous media. Such limitation may be addressed by combining the thermoresponsive sol-gel transition of Pluronic F127 with other polymers with crosslinking capabilities. In this work, a novel dual-crosslinked injectable in situ forming hydrogel based on Pluronic F127 (thermosensitive gelation) and Chitosan (ionotropic gelation in the presence of NaHCO3), loaded with Dopamine-reduced graphene oxide (DOPA-rGO; photothermal nanoagent), was developed for application in breast cancer photothermal therapy. The dual-crosslinked hydrogel incorporating DOPA-rGO showed a good injectability (through 21 G needles), in situ gelation capacity and cytocompatibility (viability > 73 %). As importantly, the dual-crosslinking improved the hydrogel's porosity and prevented its premature degradation. After irradiation with near-infrared light, the dual-crosslinked hydrogel incorporating DOPA-rGO produced a photothermal heating (ΔT ≈ 22 °C) that reduced the breast cancer cells' viability to just 32 %. In addition, this formulation also demonstrated a good antibacterial activity by reducing the viability of S. aureus and E. coli to 24 and 33 %, respectively. Overall, the dual-crosslinked hydrogel incorporating DOPA-rGO is a promising macroscale technology for breast cancer photothermal therapy and antimicrobial applications.
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Antibacterianos , Neoplasias da Mama , Quitosana , Grafite , Hidrogéis , Terapia Fototérmica , Poloxâmero , Poloxâmero/química , Hidrogéis/química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/terapia , Neoplasias da Mama/patologia , Humanos , Grafite/química , Quitosana/química , Feminino , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Antibacterianos/química , Terapia Fototérmica/métodos , Linhagem Celular Tumoral , Reagentes de Ligações Cruzadas/química , Escherichia coli/efeitos dos fármacos , Nanoestruturas/química , Staphylococcus aureus/efeitos dos fármacos , Células MCF-7 , Sobrevivência Celular/efeitos dos fármacosRESUMO
Although the area with the seam is approximately 4% of the total area of an industrial filter bag, a more extensive investigation of the influence of this region on surface filtration is necessary since the small seam holes can be a conduit for the passage of fine particles even after a certain time of use of the filter bag. Therefore, this work aimed to assess the influence of aging time on the filtration performance of P84 filter bags (samples without and with seam) used in an industrial bag filter, regarding tensile mechanical properties, air permeability, fractional separation efficiency, and filtration cycles. The particulate matter applied (sinter dust) to evaluate the efficiency and to perform the cycles was collected in the hoppers of an industrial bag filter installed in the primary dedusting system of a sinter plant in the steel industry. The results showed that the filter bag aged for 10 months presented a fractional separation efficiency of almost 100%, even for the samples with a seam, suggesting that the seam holes were sealed by the powder in the industrial installation. As for the tensile mechanical properties, the tests showed that the aging of the filter bag caused a reduction in the tensile strength of the filter medium. With respect to air permeability and filtration cycles, the longer the aging time of the filter bag, the more similar was the filtration performance of the samples without and with seam.
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Recent studies have demonstrated that cannabinoids are potentially effective in the treatment of various neurological conditions, and cannabidiol (CBD), one of the most studied compounds, has been proposed as a non-toxic option. However, the adverse effects of CBD on neurodevelopmental processes have rarely been studied in cell culture systems. To better understand CBD's influence on neurodevelopment, we exposed neural progenitor cells (NPCs) to different concentrations of CBD (1 µM, 5 µM, and 10 µM). We assessed the morphology, migration, differentiation, cell death, and gene expression in 2D and 3D bioprinted models to stimulate physiological conditions more effectively. Our results showed that CBD was more toxic at higher concentrations (5 µM and 10 µM) and affected the viability of NPCs than at lower concentrations (1 µM), in both 2D and 3D models. Moreover, our study revealed that higher concentrations of CBD drastically reduced the size of neurospheres and the number of NPCs within neurospheres, impaired the morphology and mobility of neurons and astrocytes after differentiation, and reduced neurite sprouting. Interestingly, we also found that CBD alters cellular metabolism by influencing the expression of glycolytic and ß-oxidative enzymes in the early and late stages of metabolic pathways. Therefore, our study demonstrated that higher concentrations of CBD promote important changes in cellular functions that are crucial during CNS development.
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Canabidiol , Síndromes Neurotóxicas , Humanos , Canabidiol/toxicidade , Neurônios , Astrócitos , CarbidopaRESUMO
BACKGROUND: Orally transmitted acute Chagas disease (ACD) primarily affects low-visibility and low-income individuals in tropical and subtropical zones. Managing ACD remains challenging even after more than 100 years of its discovery. Its spread to non-endemic areas has made it a global health issue. The aim of this work is to demonstrate the difficulties encountered in handling a real-life situation. METHODOLOGY AND FINDINGS: This report examines an outbreak of 39 cases of ACD due to oral transmission by bacaba juice ingestion that occurred in Pedro do Rosário, Maranhão, Brazil. A clinical and epidemiological investigation, including an entomological search, was conducted. Diagnosis criteria included positive peripheral blood smear (PBS), seroconversion of IgG, and a two-fold increase in IgG titer (laboratory criteria); and clinical findings, epidemiological exposure, and at least one positive IgG test (clinical-epidemiological criteria). In-house conventional polymerase chain reaction (PCR) was performed on 33 samples. All patients were treated with benznidazole. After 4.5 years, IgG levels were reassessed in 26 individuals. The mean age was 33.6 years, with no gender difference. The mean incubation period was 13.8 days, and the mean between symptom onset and treatment was 16.6 days. The most common symptoms were fever and lymphadenopathy (90%). Diagnostic success rates were 66.6% (laboratory criteria), 23% (clinical-epidemiological criteria), and 10.2% (high clinical suspicion despite negative tests). Test positivity rates were 69.7% (PBS), 91.4% (serology), and 100% (PCR). There were no deaths. Serological cure was achieved in 34.6% of cases, and IgG titers decreased in 15.3%. CONCLUSIONS AND SIGNIFICANCE: We encountered several barriers in managing ACD, including population vulnerability, reliance on outdated diagnostic techniques, lack of standardized molecular biology methods, and limited therapeutic options. This report underscores the importance of rapid surveillance and early treatment to prevent fatalities. We recommend the standardization of conventional PCR in diagnostic routines.
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Doença de Chagas , Surtos de Doenças , Trypanosoma cruzi , Humanos , Doença de Chagas/epidemiologia , Doença de Chagas/tratamento farmacológico , Doença de Chagas/diagnóstico , Masculino , Adulto , Feminino , Brasil/epidemiologia , Trypanosoma cruzi/imunologia , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Imunoglobulina G/sangue , Sucos de Frutas e Vegetais , Tripanossomicidas/uso terapêutico , Nitroimidazóis/uso terapêutico , Animais , Criança , Anticorpos Antiprotozoários/sangue , IdosoRESUMO
Nanomaterials with near infrared light absorption can mediate an antitumoral photothermal-photodynamic response that is weakly affected by cancer cells' resistance mechanisms. Such nanosystems are commonly prepared by loading photosensitizers into nanomaterials displaying photothermal capacity, followed by functionalization to achieve biological compatibility. However, the translation of these multifunctional nanomaterials has been limited by the fact that many of the photosensitizers are not responsive to near infrared light. Furthermore, the reliance on poly(ethylene glycol) for functionalizing the nanomaterials is also not ideal due to some immunogenicity reports. Herein, a novel photoeffective near infrared light-responsive nanosystem for cancer photothermal-photodynamic therapy was assembled. For such, dopamine-reduced graphene oxide was, for the first time, functionalized with sulfobetaine methacrylate-brushes, and then loaded with IR780 (IR780/SB/DOPA-rGO). This hybrid system revealed a nanometric size distribution, optimal surface charge and colloidal stability. The interaction of IR780/SB/DOPA-rGO with near infrared light prompted a temperature increase (photothermal effect) and production of singlet oxygen (photodynamic effect). In in vitro studies, the IR780/SB/DOPA-rGO per se did not elicit cytotoxicity (viability > 78 %). In contrast, the combination of IR780/SB/DOPA-rGO with near infrared light decreased breast cancer cells' viability to just 21 %, at a very low nanomaterial dose, highlighting its potential for cancer photothermal-photodynamic therapy.
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Neoplasias , Fotoquimioterapia , Fármacos Fotossensibilizantes , Di-Hidroxifenilalanina , Fototerapia , Linhagem Celular Tumoral , Neoplasias/terapiaRESUMO
Near infrared (NIR) light-responsive nanomaterials hold potential to mediate combinatorial therapies targeting several cancer hallmarks. When irradiated, these nanomaterials produce reactive oxygen species (photodynamic therapy) and/or a temperature increase (photothermal therapy). These events can damage cancer cells and trigger the release of drugs from the nanomaterials' core. However, engineering nanomaterials for cancer chemo-photodynamic/photothermal therapy is a complex process. First, nanomaterials with photothermal capacity are synthesized, being then loaded with photosensitizers plus chemotherapeutics, and, finally functionalized with polymers for achieving suitable biological properties. To overcome this limitation, in this work, a novel straightforward approach to attain NIR light-responsive nanosystems for cancer chemo-photodynamic/photothermal therapy was established. Such was accomplished by synthesizing poly(2-ethyl-2-oxazoline)-IR780 amphiphilic conjugates, which can be assembled into nanoparticles with photodynamic/photothermal capabilities that simultaneously encapsulate Doxorubicin (DOX/PEtOx-IR NPs). The DOX/PEtOx-IR NPs presented a suitable size and surface charge for cancer-related applications. When irradiated with NIR light, the DOX/PEtOx-IR NPs produced singlet oxygen as well as a smaller thermic effect that boosted the release of DOX by 1.7-times. In the in vitro studies, the combination of DOX/PEtOx-IR NPs and NIR light could completely ablate breast cancer cells (viability ≈ 4 %), demonstrating the enhanced outcome arising from the nanomaterials' chemo-photodynamic/photothermal therapy.
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Nanopartículas , Nanoestruturas , Neoplasias , Fotoquimioterapia , Doxorrubicina , Fármacos Fotossensibilizantes , Linhagem Celular TumoralRESUMO
Asymmetric wound dressings have captured researchers' attention due to their ability to reproduce the structural and functional properties of the skin layers. Furthermore, recent studies also report the benefits of using near-infrared (NIR) radiation-activated photothermal therapies in treating infections and chronic wounds. Herein, a chitosan (CS) and reduced graphene oxide (rGO) hydrogel (CS_rGO) was combined with a polycaprolactone (PCL) and cellulose acetate (CA) electrospun membrane (PCL_CA) to create a new NIR-responsive asymmetric wound dressing. The rGO incorporation in the hydrogel increased the NIR absorption capacity and allowed a mild hyperthermy effect, a temperature increase of 12.4 °C when irradiated with a NIR laser. Moreover, the PCL_CA membrane presented a low porosity and hydrophobic nature, whereas the CS_rGO hydrogel showed the ability to provide a moist environment, prevent exudate accumulation and allow gaseous exchanges. Furthermore, the in vitro data demonstrate the capacity of the asymmetric structure to act as a barrier against bacteria penetration as well as mediating a NIR-triggered antibacterial effect. Additionally, human fibroblasts were able to adhere and proliferate in the CS_rGO hydrogel, even under NIR laser irradiation, presenting cellular viabilities superior to 90 %. Altogether, our data support the application of the NIR-responsive asymmetric wound dressings for skin regeneration.
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Quitosana , Hipertermia Induzida , Nanofibras , Humanos , Quitosana/química , Hidrogéis/farmacologia , Hidrogéis/química , Nanofibras/química , Antibacterianos/farmacologiaRESUMO
Covid-19 is transmitted mainly by respiratory droplets and as the upper airway mucosa is the first innate immune barrier, it is crucial to understand the effects of SARS-CoV-2 on this system. In the current study, we aimed to evaluate the nasal mucociliary clearance in patients with SARS-CoV-2 infection and their symptom development. Observational cross-sectional study. The nasal mucociliary clearance (NMC) time was evaluated by the saccharin test and the results were compared between patients with SARS-CoV-2 infection (group 1) and controls (group 2, asymptomatic patients with a negative polymerase chain reaction test). We also compared the NMC time for each specific symptom suffered by participants in group 1 with the NMC time of the control group as well as with the patients in group 1 who were asymptomatic. There was a significant increase in NMC time in group 1 with dyspnea when compared to the control group (p = 0.032) and also when compared to patients who were infected were not dyspneic (p = 0.04). There were no differences in the clearance times when considering other symptoms. COVID-19 patients with dyspnea present with altered nasal mucociliary clearance.
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Nano-sized materials have been widely explored in the biomedicine field, especially due to their ability to encapsulate drugs intended to be delivered to cancer cells. However, systemically administered nanomaterials face several barriers that can hinder their tumor-homing capacity. In this way, researchers are now focusing their efforts in developing technologies that can deliver the nanoparticles directly into the tumor tissue. Particularly, hydrogels assembled using Thiol-Maleimide Michael type additions are emerging for this purpose due to their capacity to incorporate high nanoparticles' doses in a compact 3D structure as well as good chemical selectivity, biocompatibility, and straightforward preparation. Nevertheless, such hydrogels have been mostly prepared using synthetic polymers, which is not ideal due to their poor biodegradability. In this work, a novel natural polymer-based Thiol-Maleimide hydrogel was produced for application in breast cancer chemo-photothermal therapy. To obtain natural polymers compatible with this crosslinking chemistry, Hyaluronic acid was endowed with Thiol groups and deacetylated Chitosan was grafted with Maleimide groups. Parallelly, Doxorubicin loaded Dopamine-reduced graphene oxide (DOX/DOPA-rGO) was prepared for attaining Near Infrared (NIR) light responsive chemo-photothermal nanoagents. By simply mixing Hyaluronic Acid-Thiol, deacetylated Chitosan-Maleimide and DOX/DOPA-rGO, Thiol-Maleimide crosslinked hydrogels incorporating this nanomaterial could be assembled (DOX/DOPA-rGO@TMgel). When breast cancer cells were incubated with DOPA-rGO@TMgel and exposed to NIR light (photothermal therapy), their viability was reduced to about 59 %. On the other hand, DOX/DOPA-rGO@TMgel (chemotherapy) reduced cancer cells' viability to 50 %. In stark contrast, the combined action of DOX/DOPA-rGO@TMgel and NIR light decreased breast cancer cells' viability to just 21 %, highlighting its chemo-photothermal potential.
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Neoplasias da Mama , Quitosana , Grafite , Hipertermia Induzida , Nanoestruturas , Humanos , Feminino , Grafite/química , Terapia Fototérmica , Hidrogéis/química , Compostos de Sulfidrila , Ácido Hialurônico/química , Doxorrubicina , Neoplasias da Mama/tratamento farmacológico , Polímeros/química , Maleimidas , Di-Hidroxifenilalanina , Fototerapia , Linhagem Celular TumoralRESUMO
OBJECTIVE: To analyze risk factors for sickness absence due to mental disorders among judicial workers in Bahia, Brazil. METHODS: Retrospective cohort with follow-up from 2011 to 2016 with 2,660 workers of a judicial sector in Bahia, Brazil. The main outcome measures were survival curves estimated for the independent variables using the Kaplan-Meier product limit estimator and risk factors for the first episode of sickness absence calculated based on the Cox regression model. RESULTS: The survival estimate of the population of this study for the event was 0.90 and from the Cox model the risk factors for the first episode of sickness absence due to mental disorders were: female (HR = 1.81), occupation of magistrate (HR = 1.80), and age over 30 years old (HR = 1.84). In addition, the risk for new cases of sickness absence among women reached 4.0 times the risk for men, in 2015. The estimated relative risks of sickness absence and the observed survival reduction behavior over time add information to the literature on sociodemographic and occupational factors associated with sickness absence due to mental disorders in the public sector. CONCLUSION: These results highlight the need for further research to more precisely identify vulnerable groups at risk of preventable mental health-related sickness absence in the workplace, better identify the workplace organizational factors that contribute to these disorders as well as studies on the effectiveness of workplace interventions to improve mental health among judicial and other public sectors workers.
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Absenteísmo , Transtornos Mentais , Masculino , Humanos , Feminino , Adulto , Estudos de Coortes , Estudos Retrospectivos , Licença Médica , Brasil/epidemiologia , Transtornos Mentais/epidemiologiaRESUMO
Progress in the nanotechnology field has led to the development of a new class of materials capable of producing a temperature increase triggered by near infrared light. These photothermal nanostructures have been extensively explored in the ablation of cancer cells. Nevertheless, the available data in the literature have exposed that systemically administered nanomaterials have a poor tumor-homing capacity, hindering their full therapeutic potential. This paradigm shift has propelled the development of new injectable hydrogels for the local delivery of nanomaterials aimed at cancer photothermal therapy. These hydrogels can be assembled at the tumor site after injection (in situ forming) or can undergo a gel-sol-gel transition during injection (shear-thinning/self-healing). Besides incorporating photothermal nanostructures, these injectable hydrogels can also incorporate or be combined with other agents, paving the way for an improved therapeutic outcome. This review analyses the application of injectable hydrogels for the local delivery of nanomaterials aimed at cancer photothermal therapy as well as their combination with photodynamic-, chemo-, immuno- and radio-therapies.
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Nanoestruturas , Neoplasias , Humanos , Fototerapia , Hidrogéis/química , Terapia Fototérmica , Nanoestruturas/química , Neoplasias/tratamento farmacológicoRESUMO
Sensory and consumer research performs a pivotal role in gluten-free (GF) food research and development due to consumer dissatisfaction about currently available products, despite the continued growth of this market and promising research developments. Nowadays, almost half of the original articles about GF products include sensory analysis. A current overview is needed to help both food scientists and industry indentify current trends and forward-looking approaches. This current review has gathered information concerning sensory and consumer research for GF bakery and pasta products, from studies published in the last decade, and then discusses future challenges in the light of recent advances. Among the promising approaches, projective techniques that collect data using social media can provide quick, spontaneous and direct opinions from GF consumers. They can also be used to evaluate trends and cross-cultural or global insights. Participatory methods have highlighted the importance of label information and may further explore the behavior of GF consumers in more realistic environments, as well as to evaluate the intrinsic GF food factors in GF consumer opinions, emotions, behavior and choices. This review details current issues occurring in sensory analysis of GF products, which still need to be resolved. The combination of affective and analytical methods allows for a better characterization of the samples and such sensory analysis of GF products in the future could guide product development and quality control, overcoming technological, nutritional, and shelf-life issues.