História da construção de saberes em enfermagem traumato-ortopédica / History of knowledge construction in trauma and orthopedic nursing care / Historia de la construcción del conocimiento en enfermería traumatológica ortopédica

Objetivo: analisar o desenvolvimento da enfermagem traumato-ortopédica a partir da primeira turma de residentes de um hospital especializado. Método: o estudo seguiu a metodologia histórica com abordagem qualitativa. As fontes foram documentos escritos e orais. Resultados: trabalhar em uma instituição especializada foi o ponto de partida para a busca por especialização de enfermeiras atuantes no cuidado traumato-ortopédico, que perceberam o saber/poder adquirido no trabalho assistencial, além da intenção de qualificar a assistência e elevar o hospital a instituto. Estratégias empregadas reúnem a busca por parcerias com instituições universitárias e associativas, além da criação de uma associação própria. Considerações finais: a enfermagem traumato-ortopédica ampliou seu espaço científico ao criar um curso de especialização com uma unidade acadêmica. Foi possível delimitar o poder acadêmico e institucional da enfermagem na instituição de saúde pela formação de enfermeiras especialistas constituindo um grupo de reconhecido pelo saber científico.

Objective: to analyze the development of trauma and orthopedic nursing care from the very first class of residents of a specialized hospital. Method: historical methodology study with a qualitative approach. The sources consisted of written and oral documents. Results: working in a specialized institution was the starting point for nurses who were seeking specialization in the field of trauma and orthopedic care as they noticed the power-knowledge acquired through care work, plus they were willing to improve assistance and take the hospital up to an institute level. Strategies used include the search for partnerships with universities and associative-type institutions, in addition to creating their own association. Final considerations: trauma and orthopedic nursing care expanded its scientific space by creating a specialization course together with an academic unit. It was possible to define the academic and institutional power of the nursing staff in the health institution by considering the training process of its nurse specialists, who consisted of a group recognized for their scientific knowledge.

Objetivo: analizar el desarrollo de la enfermería traumatológica ortopédica a partir del primer grupo de residentes de un hospital especializado. Método: estudio con metodología histórica con un enfoque cualitativo. Las fuentes fueron documentos escritos y orales. Resultados: el trabajo en una institución especializada fue el punto de partida para la búsqueda de la especialización de las enfermeras que trabajaban en la atención traumatológica ortopédica, quienes notaron el saber/poder adquirido en el trabajo asistencial, además de la intención de cualificar la atención y elevar el hospital al nivel de instituto. Las estrategias empleadas incluyen la búsqueda de alianzas con instituciones universitarias y asociaciones, y la creación de una asociación propia. Consideraciones finales: la enfermería traumatológica ortopédica amplió su espacio científico mediante la creación de un curso de especialización con una unidad académica. Se logró delimitar el poder académico e institucional de la enfermería en la institución de salud a través de la formación de enfermeros especialistas, que es un grupo reconocido por el conocimiento científico.

CD4+ and CD8+ T-cell multi-epitope chimeric protein associated with an MPLA adjuvant induce protective efficacy and long-term immunological memory for the immunoprophylaxis of American Tegumentary Leishmaniasis.

American Tegumentary Leishmaniasis (ATL) is a disease of high severity and incidence in Brazil, in addition to being a worldwide concern in public health. Leishmania amazonensis is one of the etiological agents of ATL, and the inefficiency of control measures, associated with the high toxicity of the treatment and the lack of effective immunoprophylactic strategies, makes the development of vaccines indispensable and imminent. In this light, the present study proposes to elaborate a chimeric protein (rChiP), based on the fusion of multiple epitopes of CD4+/CD8+ T cells, identified in the immunoproteome of the parasites L. amazonensis and L. braziliensis. The designed chimeric protein was tested in the L. amazonensis murine model of infection using the following formulations: 25 µg of the rChiP in saline (rChiP group) and 25 µg of the rChiP plus 25 µg of MPLA-PHAD® (rChiP+MPLA group). After completing immunization, CD4+ and CD8+ T cells, stimulated with SLa-Antigen or rChiP, showed an increased production of nitric oxide and intracytoplasmic pro-inflammatory cytokines, in addition to the generation of central and effector memory T cells. rChiP and rChiP+MPLA formulations were able to promote an effective protection against L. amazonensis infection determined by a reduction in the development of skin lesions and lower parasitic burden. Reduction in the development of skin lesions and lower parasitic burden in the vaccinated groups were associated with an increase of nitrite, CD4+/CD8+IFN-γ+TNF-α+ and CD4+/CD8+CD44highCD62Lhigh/low T cells, IgGTotal, IgG2a, and lower rates of IgG1 and CD4+/CD8+IL-10+. This data suggests that proposed formulations could be considered potential tools to prevent ATL.

Enhancing Colorectal Cancer Screening with Droplet Digital PCR (ddPCR) Analysis of Fusobacterium nucleatum in Fecal Immunochemical Test (FIT) Samples.

Fecal immunochemical test (FIT) followed by colonoscopy in positive cases is commonly used for population-based colorectal cancer (CRC) screening. However, specificity of FIT for CRC is not ideal, and has poor performance for advanced adenoma detection. Fecal Fusobacterium nucleatum (Fn) detection has been proposed as a potential non-invasive biomarker for CRC and advanced adenoma detection. We aimed to evaluate the diagnostic performance of Fn detection using droplet digital PCR (ddPCR) in FIT samples from individuals enrolled in a CRC screening program with colorectal adenoma or cancer. We evaluated Fn presence in DNA isolated from FIT leftover material of 300 participants in a CRC Screening Program using ddPCR. The Fn DNA amount was classified as Fn-low/negative and Fn-high, and the association with patients clinicopathological features and accuracy measurements was calculated. Fn high levels were more prevalent in FIT-positive (47.2%n=34 of72) than FIT-negative samples (28.9%, n=66 of 228) (p<0.04). Among FIT-positive samples, high Fn levels were significantly more frequent in cancer patients (CA, n=8) when compared to normal (NT, n=16) (p=0.02), non-advanced adenomas (NAA, n=36) (p=0.01), and advanced adenomas (AA, n=12) (p=0.01). Performance analysis of Fn in FIT-positive samples for colorectal cancer detection yielded an AUC of 0.8203 (CI: 0.6464-0.9942), with high sensitivity (100%) and specificity of 50%%. Concluding, we showed the feasibility of detecting Fn in FIT leftovers using the ultrasensitive ddPCR technique. Furthermore, we highlighted the potential use of Fn levels in fecal samples to ameliorate CRC detection.

Cardiovascular risk assessment using SCORE2 in a population with hypertension - the reality at a primary health care unit.

INTRODUCTION AND OBJECTIVES: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in Portugal, thus it is important to identify individuals at risk. Patients with hypertension have an increased risk of adverse cardiovascular (CV) events. The role of LDL cholesterol (LDL-C) in atherosclerotic CVD is well-established. SCORE2, a new CV risk calculation tool, is used to predict the 10-year risk of fatal or non-fatal CVD. The aim of this study was to understand the impact of SCORE2 on CV risk assessment in a population with hypertension from a moderate risk country, compared to the previously used SCORE. METHODS: This observational cross-sectional study analyzed a population census of 3146 patients diagnosed with hypertension without complications (K86). After applying inclusion and exclusion criteria, 654 patients were included. Data from medical records were collected to calculate and compare SCORE and SCORE2 categories and LDL-C targets. RESULTS: Patients were classified into SCORE categories: 188 (28.75%) low, 448 (68.5%) moderate, 17 (2.6%) high and 1 (0.15%) very high risk. Using SCORE2, individuals in the SCORE low risk category were reclassified, requiring new targets: 149 individuals (80%) as low to moderate and 39 (20%) as high risk. These differences became more evident when considering SCORE moderate and high-risk categories, where 358 patients (77%) received a higher CV risk categorization, and therefore a lower LDL-C target. There was a significant increase in individuals failing to meet the target when using SCORE2, compared to SCORE (p<0.001). CONCLUSION: These findings support the importance of CV risk assessment using SCORE2 algorithm in patients with hypertension.

Enteral adequacy of the diet of low-birth-weight preterm newborns: A prospective cohort study.

OBJECTIVE: This study aimed to verify the dietary adequacy of full enteral feeding in preterm newborns (PTNB) and its relationship with birth weight (BW) during the period of hospitalization in the neonatal intensive care unit (NICU). METHODS: This is a prospective cohort study whose population were babies born at less than 37 gestational weeks and weighing less than 2500 g, admitted to a NICU. PTNB were monitored regarding their dietary evolution, considering parenteral and enteral nutrition and adequacy of diet supply in terms of volume, energy, and protein. For statistical analysis, the Statistical Package for the Social Sciences (SPSS) software was used, considering p < 0.05 as significant. RESULTS: A total of 76 PTNB were included. The mean time of using parenteral nutrition was 14 days. The mean time to reach the full enteral feeding for nutrition (FEF-N) was 29 days. However, half of the PTNB reached nutritional recommendations after this means. The time to achieve FEF-N was influenced by BW. Additionally, BW significantly influenced the length of stay in the NICU (p < 0.001). When reaching the recommended full enteral feeding for hydration (FEF-H), 60% of the sample was unable to reach the recommended energy and protein intake. CONCLUSIONS: BW influenced the time needed to reach the FEF-H and FEF-N. The lower the BW, the longer it took to achieve dietary adequacy. Despite achieving the FEF-H, most premature babies did not reach the necessary energy and protein intake at the appropriate time.

A case of larva migrans representing a pitfall in oral diagnosis.

The present work reports a case of a female patient complaining of itching and painful lesions affecting the oral mucosa for 7 months. Buccal and lip mucosa showed swelling and erythema, with serpiginous tracks. The patient was diagnosed with oral larva migrans, and the lesions resolved after ivermectin administration. At 18-month follow-up, no sign of recurrence was observed. Larva migrans can represent a pitfall in oral diagnosis and a stressful condition for the patient. Oral health care providers should be aware of this and keep this disease in mind as a possible differential diagnosis in oral mucosa lesions.

Phenolic composition and encapsulation of Brazilian grape seed extracts: evaluating color stabilizing capacity in grape juices.

The color of grape juice is an important acceptance attribute by consumers, but it suffers losses during storage. The use of commercial antioxidants has limitations because the concept of a "100% natural drink" of Brazilian legislation. This work characterized Brazilian grape seeds, and the cultivar extract with the greatest potential was encapsulated in arabic-gum (encapsulated extract-EE) to evaluate the color stabilizing capacity. The EE used in the grape juice was compared with the commercial antioxidants sulphite and enological tannin during storage (150 days). The BRS Magna and BRS Violeta grape seeds had the highest phenolic content, and the EE showed high catechin (4108 mg/kg), epicatechin (1161 mg/kg) and procyanidin-B2 (905 mg/kg) values. Sulfite was found to be the best color stabilizer. The use of EE (0.5 g/L) in grape juice improved color stability and anthocyanin stability. It was demonstrated that encapsulated grape seed extract has color stabilizing potential and that Brazilian grape seeds are a raw material of high technological value. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-024-05956-8.

Detection of Multiple Human Viruses, including Mpox, Using a Wastewater Surveillance Approach in Brazil.

Sewage surveillance can be used as an effective complementary tool for detecting pathogens in local communities, providing insights into emerging threats and aiding in the monitoring of outbreaks. In this study using qPCR and whole genomic sewage surveillance, we detected the Mpox virus along with other viruses, in municipal and hospital wastewaters in Belo Horizonte, Brazil over a 9-month period (from July 2022 until March 2023). MPXV DNA detection rates varied in our study, with 19.6% (11 out of 56 samples) detected through the hybrid capture method of whole-genome sequencing and 20% (12 out of 60 samples) through qPCR. In hospital wastewaters, the detection rate was higher, at 40% (12 out of 30 samples) compared to 13.3% (4 out of 30 samples) in municipal wastewaters. This variation could be attributed to the relatively low number of MPXV cases reported in the city, which ranged from 106 to 341 cases during the study period, and the dilution effects, given that each of the two wastewater treatment plants (WWTP) investigated serves approximately 1.1 million inhabitants. Additionally, nine other virus families were identified in both hospitals and municipal wastewaters, including Adenoviridade, Astroviridae, Caliciviridae, Picornaviridade, Polyomaviridae, Coronaviridae (which includes SARS-CoV-2), Herspesviridae, Papillomaviridae and Flaviviridae (notably including Dengue). These findings underscore the potential of genomic sewage surveillance as a robust public health tool for monitoring a wide range of viruses circulating in both community and hospitals environments, including MPXV.

Synchrotron nano-FTIR spectroscopy for probing anticancer drugs at subcellular scale.

The cellular response to cisplatin was assessed in human osteosarcoma cells, using synchrotron-based (SR) Fourier Transform InfraRed nanospectroscopy (nano-FTIR) at the MIRIAM beamline B22 of Diamond Light Source (UK). This label-free mapping method delivered simultaneous morphological and biochemical information on a subcellular level (i.e. 100 s nanometer or better). Based on specific spectral biomarkers, the main biochemical constituents affected by the drug were identified at distinct locations within the cell´s inner body. Cisplatin was shown to have a noteworthy effect on proteins, mostly within the cytoplasm. A clear drug impact on cellular lipids was also observed. Within current literature on s-SNOM, this nanospectroscopy work represents a first successful application in life sciences providing full fingerprint nano-FTIR spectra across intact human cancer cells.

Influence of Aldehyde Dehydrogenase Inhibition on Stemness of Endometrial Cancer Stem Cells.

Endometrial cancer is one of the most common gynaecological malignancies. Although often diagnosed at an early stage, there is a subset of patients with recurrent and metastatic disease for whom current treatments are not effective. Cancer stem cells (CSCs) play a pivotal role in triggering tumorigenesis, disease progression, recurrence, and metastasis, as high aldehyde dehydrogenase (ALDH) activity is associated with invasiveness and chemotherapy resistance. Therefore, this study aimed to evaluate the effects of ALDH inhibition in endometrial CSCs. ECC-1 and RL95-2 cells were submitted to a sphere-forming protocol to obtain endometrial CSCs. ALDH inhibition was evaluated through ALDH activity and expression, sphere-forming capacity, self-renewal, projection area, and CD133, CD44, CD24, and P53 expression. A mass spectrometry-based proteomic study was performed to determine the proteomic profile of endometrial cancer cells upon N,N-diethylaminobenzaldehyde (DEAB). DEAB reduced ALDH activity and expression, along with a significant decrease in sphere-forming capacity and projection area, with increased CD133 expression. Additionally, DEAB modulated P53 expression. Endometrial cancer cells display a distinct proteomic profile upon DEAB, sharing 75 up-regulated and 30 down-regulated proteins. In conclusion, DEAB inhibits ALDH activity and expression, influencing endometrial CSC phenotype. Furthermore, ALDH18A1, SdhA, and UBAP2L should be explored as novel molecular targets for endometrial cancer.

Ultraviolet Resistance of Microorganisms Isolated from Uranium-Rich Minerals from Perus, Brazil.

The district of Perus, located in the city of São Paulo, Brazil, is renowned for its weathered granitic-pegmatitic masses, which harbor a significant number of uraniferous minerals that contribute to ionizing radiation levels up to 20 times higher than the background levels. In this study, aseptically collected mineral samples from the area were utilized to isolate 15 microorganisms, which were subjected to pre-screening tests involving UV-C and UV-B radiation. The microorganisms that exhibited the highest resistance to ultraviolet (UV) radiation were selected for the construction of survival curves for UV-C, broad-band UV-B, and solar simulation resistance testing. Subsequently, the four strains that demonstrated superior survival capabilities under UV radiation exposure were chosen for 16S rRNA gene sequencing. Among these, Nocardioides sp. O4R and Nocardioides sp. MA2R demonstrated the most promising outcomes in the UV radiation resistance assessments, showcasing comparable performance to the well-established radioresistant model organism Deinococcus radiodurans. These findings underscore the potential of naturally occurring high-radiation environments as valuable resources for the investigation of UV-resistant microorganisms.

Natural mycobacterium tuberculosis complex infection in a brown howler monkey (Alouatta guariba clamitans) in Brazil.

Neotropical primates rarely exhibit active tuberculosis. A brown howler monkey was found injured in an urban area. Histopathology revealed granulomatous inflammation in the lungs, lymph nodes, and liver. Immunohistochemistry and molecular analysis confirmed the presence of Mycobacterium tuberculosis complex. The findings highlight the importance of TB surveillance in nonhuman primates.

Treatment of Parkinson's disease by deep brain stimulation: a bibliometric analysis.

BACKGROUND: For more than 30 years, deep brain stimulation (DBS) has been a therapeutic tool for Parkinson's disease (PD) treatment. DBS can ameliorate several motor and non-motor symptoms and improve the patients' quality of life. OBJECTIVES: To analyze the global scientific production of original and review articles on Parkinson's disease treatment using deep brain stimulation. DESIGN AND SETTING: Descriptive, bibliometric study with a quantitative approach. METHOD: The research protocol was conducted in March 2023 using the Web of Science database. Six hundred eighty-four articles were included in the analysis. Data were imported into RStudio Desktop Software, linked to R Software. The Bibliometrix R package, its Biblioshiny web interface, and VOSviewer software were used for the analysis. RESULTS: The international production began in 1998. Movement Disorders is the journal with the largest number of published articles and the most cited. Michael Okun and Andres Lozano are the authors who produced the most in this area. The University of Florida is the most active affiliated institution in Brazil. The United States has the largest number of collaborations and is mainly published by local researchers. In contrast, countries such as the United Kingdom and Canada have a high number of multi-country publications. The 15 most cited studies predominantly investigated subthalamic nucleus stimulation. CONCLUSION: DBS for Parkinson's disease is a relatively novel therapeutic approach, with studies that have expanded over the last twenty-five years. Most scientific production was quantitative and restricted to specialized journals. The United States, Europe, and China held the most articles.

The fate of Salmonella enterica and Listeria monocytogenes in the pulp of eight native Brazilian and exotic fruits.

Despite the wide variety of native and exotic fruits in Brazil, there is limited understanding of their ability to support pathogens during storage. This study aimed to evaluate the behavior of Salmonella enterica and Listeria monocytogenes inoculated into the pulp of eight fruits native and exotic to Brazil: Jenipapo (Genipa americana L.), Umbu (Spondias tuberosa Arruda), Maná (Solanum sessiliflorum), Cajá-manga (Spondias dulcis), Physalis (Physalis angulata L.), Feijoa (Acca sellowiana), Cupuaçu (Theobroma grandiflorum) (average pH < 3.3) and in a low acidy fruit: Abiu (Pouteria caimito) (pH 6.11). The pathogens were inoculated into the different fruits and stored at 10, 20, 30 and 37 °C for up to 12 h and 6 days, respectively. Among the fruits evaluated, Abiu was the only one that allowed Salmonella growth, showing higher δ-values at 20 and 30 °C (5.6 log CFU/g for both temperatures). For Physalis and Feijoa, there was a small reduction in the pathogen concentration (<1 log-cycle), mainly at 10 and 20 °C, indicating its ability to remain in the matrices. For the other fruits, notable negative δ-values were obtained, indicating a tendency towards microbial inactivation. The survival potential was significantly affected by temperature in Abiu, Maná, Cupuaçu, and Cajá-manga (p < 0.05). The same phenomena regarding δ-value were observed for L. monocytogenes population, with the greatest survival potential observed at 20 °C in Abiu (3.3 log CFU/g). Regarding the exponential growth rates in Abiu, the highest values were observed at 30 and 37 °C, both for Salmonella (4.6 and 4.9 log (CFU/g)/day, respectively) and for L. monocytogenes (2.8 and 2.7 log (CFU/g)/day, respectively), with no significant difference between both temperatures. Regarding microbial inactivation, L. monocytogenes showed greater resistance than Salmonella in practically all matrices. Jenipapo and Umbu were the pulps that, in general, had the greatest effect on reducing the population of pathogens. Furthermore, the increase in storage temperature seems to favor the increase on inactivation rates. In conclusion, Salmonella and L. monocytogenes can grow only in Abiu pulp, although they can survive in some acidic tropical fruits kept at refrigeration and abusive temperatures.

MYCOLICIBACTERIUM FORTUITUM INFECTION IN EX SITU EMERALD TREE BOA (Corallus batesii).

Emerald tree boas (Corallus batesii) are boids that in situ occurs in forested habitats in the Amazon Basin. The mycobacterial species can infect reptiles but the species Mycolicibacterium fortuitum was identified only in feces samples of ex situ Python regius and was isolated from granulomatous lesions of an ex situ Iguana iguana when was still part of the genus Mycobacterium. This article aims to report a mycobacteria infection case in a female Corallus batesii kept under human care. The animal presented apathy and 2 months of anorexia, being found dead. The necropsy revealed presence of tracheal and pulmonary nodules besides multifocal, bacterial, granulomatous pneumonia. After Fite-Faraco histochemical staining, immunohistochemistry, semi-nested polymerase chain reaction (PCR) and genetic sequencing the Mycolicibacterium fortuitum complex was diagnosed with 99.54% of nucleotide similarity. This mycobacterial species was already pointed out as an important nosocomial pathogen and more studies are necessary to explore their zoonotic potential.

Factors impacting the microbial production of eicosapentaenoic acid.

The increasing applications for eicosapentaenoic acid (EPA) and the potential shortfall in supply due to sustainability and contamination issues related with its conventional sources (i.e., fish oils; seafood) led to an extensive search for alternative and sustainable sources, as well as production processes. The present mini-review covers all the steps involved in the production of EPA from microorganisms, with a deeper focus on microalgae. From production systems to downstream processing, the most important achievements within each area are briefly highlighted. Comparative tables of methodologies are also provided, as well as additional references of recent reviews, so that readers may deepen their knowledge in the different issues addressed. KEY POINTS: • Microorganisms are more sustainable alternative sources of EPA than fish. • Due to the costly separation from DHA, species that produce only EPA are preferable. • EPA production can be optimised using non-genetic and genetic tailoring engineering.

Technology Readiness Level Roadmap for Developing Innovative Herbal Medicinal Products.

Despite the vast global botanical diversity, the pharmaceutical development of herbal medicinal products (HMPs) remains underexploited. Of over 370,000 described plant species, only a few hundred are utilized in HMPs. Most of these have originated from traditional use, and only a minority come from megadiverse countries. Exploiting the pharmacological synergies of the hundreds of compounds found in poorly studied plant species may unlock new therapeutic possibilities, enhance megadiverse countries' scientific and socio-economic development, and help conserve biodiversity. However, extensive constraints in the development process of HMPs pose significant barriers to transforming this unsatisfactory socio-economic landscape. This paper proposes a roadmap to overcome these challenges, based on the technology readiness levels (TRLs) introduced by NASA to assess the maturity of technologies. It aims to assist research entities, manufacturers, and funding agencies from megadiverse countries in the discovery, development, and global market authorization of innovative HMPs that comply with regulatory standards from ANVISA, EMA, and FDA, as well as WHO and ICH guidelines.

Cytogenetic and Molecular Effects of Kaolin's Foliar Application in Grapevine (Vitis vinifera L.) under Summer's Stressful Growing Conditions.

Grapevine varieties from "Douro Superior" (NE Portugal) experience high temperatures, solar radiation, and water deficit during the summer. This summer's stressful growing conditions induce nucleic acids, lipids, and protein oxidation, which cause cellular, physiological, molecular, and biochemical changes. Cell cycle anomalies, mitosis delay, or cell death may occur at the cellular level, leading to reduced plant productivity. However, the foliar application of kaolin (KL) can mitigate the impact of abiotic stress by decreasing leaf temperature and enhancing antioxidant defence. Hence, this study hypothesised that KL-treated grapevine plants growing in NE Portugal would reveal, under summer stressful growing conditions, higher progression and stability of the leaf mitotic cell cycle than the untreated (control) plants. KL was applied after veraison for two years. Leaves, sampled 3 and 5 weeks later, were cytogenetically, molecularly, and biochemically analysed. Globally, integrating these multidisciplinary data confirmed the decreased leaf temperature and enhanced antioxidant defence of the KL-treated plants, accompanied by an improved regularity and completion of the leaf cell cycle relative to the control plants. Nevertheless, the KL efficacy was significantly influenced by the sampling date and/or variety. In sum, the achieved results confirmed the hypothesis initially proposed.

Doxorubicin-induced neurotoxicity differently affects the hippocampal formation subregions in adult mice.

Doxorubicin (DOX) is an anthracycline used to treat a wide range of tumours. Despite its effectiveness, it is associated with a long range of adverse effects, of which cognitive deficits stand out. The present study aimed to assess the neurologic adverse outcome pathways of two clinically relevant cumulative doses of DOX. Adult male CD-1 mice received biweekly intraperitoneal administrations for 3 weeks until reaching cumulative doses of 9 mg/kg (DOX9) or 18 mg/kg (DOX18). Animals were euthanized one week after the last administration, and biomarkers of oxidative stress and brain metabolism were evaluated in the whole brain. Coronal sections of fixed brains were used for specific determinations of the prefrontal cortex (PFC) and hippocampal formation (HF). In the whole brain, DOX18 tended to disrupt the antioxidant defences, affecting glutathione levels and manganese superoxide dismutase expression. Considering the regional analysis, DOX18 increased the volume of all brain areas evaluated, while GFAP-immunoreactive astrocytes decreased in the dentate gyrus (DG) and increased in the CA3 region of HF, both in a dose-dependent manner. Concerning the apoptosis pathway, whereas Bax increased in the DOX9 group, it decreased in the DOX18 group. Only in the latter group did Bcl-2 levels also decrease. While p53 only increased in the CA3 region of the DOX9 group, AIF increased in the PFC and DG of DOX18. Finally, phosphorylation of Tau decreased with the highest DOX dose in DG and CA3, while TNF-α levels increased in CA1 of DOX18. Our results indicate new pathways not yet described that could be responsible for the cognitive impairments observed in treated patients.

Bifunctional naringenin-laden gelatin methacryloyl scaffolds with osteogenic and anti-inflammatory properties.

OBJECTIVE: To fabricate and characterize an innovative gelatin methacryloyl/GelMA electrospun scaffold containing the citrus flavonoid naringenin/NA with osteogenic and anti-inflammatory properties. METHODS: GelMA scaffolds (15 % w/v) containing 0/Control, 5, 10, or 20 % of NA w/w were obtained via electrospinning. The chemical composition, fiber morphology/diameter, swelling/degradation profile, and NA release were investigated. Cytotoxicity, cell proliferation, adhesion and spreading, total protein/TP production, alkaline phosphatase/ALP activity, osteogenic genes expression (OCN, OPN, RUNX2), and mineralized nodules deposition/MND with human alveolar bone-derived mesenchymal stem cells (aBMSCs) seeded on the scaffolds were assessed. Moreover, aBMSCs seeded on the scaffolds and stimulated with tumor necrosis factor-alpha/TNF-α were submitted to collagen, nitric oxide/NO, interleukin/IL-1α, and IL-6 production assessment. Data were analyzed using ANOVA and t-student/post-hoc tests (α = 5 %). RESULTS: NA-laden scaffolds presented increased fiber diameter, lower swelling capacity, and faster degradation profile over 28 days (p < 0.05). NA release was detected over time. Cell adhesion and spreading, and TP production were similar between GelMA and GelMA+NA5 % scaffolds, while cell proliferation, ALP activity, OCN/OPN/RUNX2 gene expression, and MND were higher for GelMA+NA5 % scaffolds (p < 0.05). Cells seeded on control scaffolds and TNF-α-stimulated presented higher levels of NO, IL-1α/IL-6, and lower levels of collagen (p < 0.05). In contrast, cells seeded on GelMA+NA5 % scaffolds showed downregulation of inflammatory markers and higher collagen synthesis (p < 0.05). SIGNIFICANCE: GelMA+NA5 % scaffold was cytocompatible, stimulated aBMSCs proliferation and differentiation, and downregulated inflammatory mediators' synthesis, suggesting its therapeutic effect as a multi-target bifunctional scaffold with osteogenic and anti-inflammatory properties for bone tissue engineering.