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Obesity is increasing in incidence worldwide, especially in women, which can affect the outcome of pregnancy. During this period, viral infections represent a risk to the mother, the placental unit, and the fetus. The Zika virus (ZIKV) outbreak in Brazil has been the cause of congenital Zika syndrome (CZS), with devastating consequences such as microcephaly in newborns. Herein, we analyzed the impact of maternal overweight/obesity on the antiviral factors’ expression in the placental tissue of Zika-infected mothers. We accessed placentas from women with and without obesity from 34 public health units (São Paulo) and from Zika-infected mothers with and without obesity from the Clinical Cohort Study of ZIKV pregnant women (Rio de Janeiro, Brazil). We first verified that obesity, without infection, did not alter the constitutive transcriptional expression of antiviral factors or IFN type I/III expression. Interestingly, obesity, when associated with ZIKV infection, showed a decreased transcriptional expression of RIG-I and IFIH1 (MDA-5 protein precursor gene). At the protein level, we also verified a decreased RIG-I and IRF-3 expression in the decidual placenta from the Zika-infected obese group, regardless of microcephaly. This finding shows, for the first time, that obesity associated with ZIKV infection leads to an impaired type I IFN downstream signaling pathway in the maternal–fetal interface.

There are few studies on the role of innate immune response in dermatophytosis. An investigation was conducted to define the involvement of Toll-Like Receptors (TLRs) 2 and 4 in localized (LD) and disseminated (DD) dermatophytosis due to T. rubrum. Fifteen newly diagnosed patients, eight patients with LD and seven with DD, defined by involvement of at least three body segments were used in this study. Controls comprised twenty skin samples from healthy individuals undergoing plastic surgery. TLR2 and TLR4 were quantified in skin lesions by immunohistochemistry. A reduced expression of TLR4 in the lower and upper epidermis of both LD and DD patients was found compared to controls; TLR2 expression was preserved in the upper and lower epidermis of all three groups. As TLR4 signaling induces the production of inflammatory cytokines and neutrophils recruitment, its reduced expression likely contributed to the lack of resolution of the infection and the consequent chronic nature of the dermatophytosis. As TLR2 expression acts to limit the inflammatory process and preserves the epidermal structure, its preserved expression may also contribute to the persistent infection and limited inflammation that are characteristic of dermatophytic infections. A literatura sobre o papel da resposta imune inata em dermatofitose é escassa. Este estudo se propôs a investigar a participação dos receptores do tipo Toll 2 e 4 (TLRs) 2 e 4 em pacientes com dermatofitose localizada (LD) e disseminada (DD, definida como lesões em pelo menos três segmentos corpóreos distintos), causadas por Trichophyton rubrum. Foram analisados cortes histológicos de 15 pacientes recém-diagnosticados, oito com LD e sete com DD. O grupo controle foi composto por 20 amostras de pele de indivíduos saudáveis submetidos a cirurgia plástica. TLR-2 e TLR-4 foram quantificados em lesões cutâneas por imunohistoquímica. Encontramos uma expressão reduzida de TLR-4 na epiderme superior e inferior nos dois grupos, LD e DD, quando comparados com o grupo controle; a expressão de TLR-2 foi preservada na epiderme superior e inferior de todos os três grupos. Como a sinalização por TLR-4 induz produção de citocinas inflamatórias e recrutamento de neutrófilos, a menor expressão desta molécula provavelmente contribui para a não resolução da infecção e conseqüente natureza persistente da dermatofitose. Como a sinalização via TLR-2 tem sido descrita como fator de regulação do processo inflamatório e de preservação da estrutura epidérmica, a sua expressão inalterada nas lesões dos pacientes com DD e DL pode contribuir também para a persistência da infecção e do reduzido processo inflamatório que são característicos das infecções por dermatófitos.

Glucose modulates plant metabolism, growth, and development. In Arabidopsis (Arabidopsis thaliana), Hexokinasel (HXK1) is a glucose sensor that may trigger abscisic acid (ABA) synthesis and sensitivity to mediate glucose-induced inhibition of seedling development. Here, we show that the intensity of short-term responses to glucose can vary with ABA activity. We report that the transient (2 h/4 h) repression by 2% glucose of AtbZlP63, a gene encoding a basic-leucine zipper (bZIP) transcription factor partially involved in the Snfl-related kinase KINlO-induced responses to energy limitation, is independent of HXK1 and is not mediated by changes in ABA levels. However, high-concentration (6%) glucose-mediated repression appears to be modulated by ABA, since full repression of AtbZlP63 requires a functional ABA biosynthetic pathway. Furthermore, the combination of glucose and ABA was able to trigger a synergistic repression of AtbZlP63 and its homologue AtbZlP3, revealing a shared regulatory feature consisting of the modulation of glucose sensitivity by ABA. The synergistic regulation of AtbZlP63 was not reproduced by an AtbZlP63 promoter-5'-untranslated region::β-glucuronidase fusion, thus suggesting possible posttranscriptional control. A transcriptional inhibition assay with cordycepin provided further evidence for the regulation of mRNA decay in response to glucose plus ABA. Overall, these results indicate that AtbZIP63 is an important node of the glucose-ABA interaction network. The mechanisms by which AtbZIP63 may participate in the finetuning of ABA-mediated abiotic stress responses according to sugar availability (i.e., energy status) are discussed.

The extract from Moringa oleifera seeds is used worldwide, especially in rural areas of developing countries, to treat drinking water. M. oleifera seeds contain the lectins cmol and WSMoL, which are carbohydrate-binding proteins that are able to reduce water turbidity because of their coagulant activity. Studies investigating the ability of natural products to damage normal cells are essential for the safe use of these substances. This study evaluated the cytotoxic and anti-inflammatory properties of the aqueous seed extract, the extract used by population to treat water (named diluted seed extract in this work), and the isolated lectins cmol and WSMoL. The data showed that the aqueous seed extract and cmol were potentially cytotoxic to human peripheral blood mononuclear cells, while WSMoL and diluted seed extract were not cytotoxic. The M. oleifera aqueous seed extract and the lectins cmol and WSMoL were weakly/moderately cytotoxic to the NCI-H292, HT-29 and HEp-2 cancer cell lines and were not hemolytic to murine erythrocytes. Evaluation of acute toxicity in mice revealed that the aqueous seed extract (2.000 mg/kg) did not cause systemic toxicity. The aqueous seed extract, cmol and WSMoL (6.25 µg/mL) and diluted seed extract at 50 µg/mL exhibited anti-inflammatory activity on lipopolyssaccharide-stimulated murine macrophages by regulating the production of nitric oxide, TNF-α and IL-1β. The aqueous seed extract reduced leukocyte migration in a mouse model of carrageenan-induced pleurisy; the myeloperoxidase activity and nitric oxide, TNF-α and IL-1β levels were similarly reduced. Histological analysis of the lungs showed that the extract reduced the number of leukocytes. This study shows that the extract prepared according to folk use and WSMoL may be non-toxic to mammalian cells; however, the aqueous seed extract and cmol may be cytotoxic to immune cells which may explain the immunosuppressive potential of the extract.

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder that involves different pathogenic mechanisms. In this regard, the goal of this study was the design and synthesis of new compounds with multifunctional pharmacological activity by molecular hybridization of structural fragments of curcumin and resveratrol connected by an N-acyl-hydrazone function linked to a 1,4-disubstituted triazole system. Among these hybrid compounds, derivative 3e showed the ability to inhibit acetylcholinesterase activity, the intracellular formation of reactive oxygen species as well as the neurotoxicity elicited by Aβ42 oligomers in neuronal SH-SY5Y cells. In parallel, compound 3e showed a good profile of safety and ADME parameters. Taken together, these results suggest that 3e could be considered a lead compound for the further development of AD therapeutics.

Body mass index (BMI) is a key factor in the progression of breast cancer (BC), with conflicting evidence on its influence on pathological complete response (pCR) following neoadjuvant chemotherapy (NAC). Despite these global findings, studies focusing on real-world Brazilian data remain scarce. This study aimed to evaluate the impact of BMI on pCR rates, recurrence-free survival (RFS), and overall survival (OS) in Brazilian women with BC treated with NAC. A retrospective cohort of 1,751 patients with stage I–III invasive primary BC treated between January 2011 and December 2020 at two public healthcare centers Hospital Pérola Byington (HPB) and Hospital do Servidor Público Estadual (HSPE) in Brazil was analyzed. Data included BMI categories (normal, overweight, and obese) and their associations with pCR, RFS, and OS outcomes. Obesity was prevalent (35.5%) among the cohort, with most patients being postmenopausal (50.9%). Tumors were predominantly stage III invasive ductal carcinoma, with triple-negative and luminal B subtypes being the most common. Radical surgery was performed in 79.8% of cases, achieving a pCR rate of 22.3%, and 30.9% of patients experienced recurrence, predominantly systemic (27.7%). No significant differences in pCR, RFS, or OS were observed across BMI categories. BMI was not associated with pCR, RFS, or OS in this large Brazilian cohort, highlighting the need for further studies to explore BMI dynamics during treatment and its potential influence on therapeutic outcomes. Future investigations in diverse healthcare settings may provide additional insights into optimizing breast cancer management across BMI strata.

The incorporation of drugs into nanostructured silica has proven to be an effective strategy for delaying drug release, protecting against enzymatic degradation, and enhancing therapeutic efficacy. Specifically, crotoxin, a component derived from the venom of Crotalus durissus terrificus, exhibits notable analgesic and immunomodulatory properties. Previous studies have demonstrated that encapsulating crotoxin within SBA-15 nanostructured mesoporous silica not only reduces its toxicity and enhances its analgesic effects but also enables effective oral administration. Given its promising efficacy and the expanding interest in its application across various experimental models and potential therapeutic uses, this study aimed to conduct a detailed analysis of the physicochemical properties of crotoxin when incorporated into SBA-15 silica. Following characterization, the crotoxin–SBA-15 complex was orally administered to mice in an experimental model of ulcerative colitis (UC). The most widely adopted experimental model for studying UC involves the administration of dextran sodium sulfate (DSS) in drinking water to induce colonic inflammation in susceptible animals. In this study, we hypothesized that crotoxin incorporated into ordered mesoporous silica (SBA-15) could modulate DSS-induced UC. Crotoxin was successfully incorporated into SBA-15 and administered orally, as its physicochemical properties supported this route of delivery. Mice received the crotoxin–SBA-15 complex either at the onset of UC induction or on days 1 and 4 after DSS exposure. Seven days after the start of DSS administration, we observed a substantial reduction (approximately 50%) in Disease Activity Index (DAI) scores, accompanied by marked improvements in the histopathological features of the colon. These findings indicate for the first time that crotoxin incorporated into SBA-15 exhibits significant therapeutic potential in the treatment of experimentally induced ulcerative colitis.

Euphorbia hirta L. is traditionally used to treat tumors and has demonstrated anticancer effects. This study evaluated the phytochemical composition, toxicity, and antitumor activity of saline extract (SE) from E. hirta leaves in mice. Phytochemical analysis included thin layer chromatography, high-performance liquid chromatography, and quantification of phenols, flavonoids, and proteins. Acute toxicity (2000 mg/kg) assessed mortality, hematological, biochemical, histological parameters, water/feed intake, and body weight. Genotoxicity was evaluated via comet and micronucleus assays. Antitumor activity was tested in vitro and in vivo on sarcoma 180. SE contained 107.3 mg GAE/g phenolics and 22.9 mg QE/g flavonoids; the presence of gallic and ellagic acids was detected. Protein concentration was 12.16 mg/mL with lectin activity present. No mortality, organ damage, or genotoxic effects occurred in toxicity tests. SE demonstrated in vitro cytotoxicity against sarcoma cells (IC50: 10 µg/mL). In vivo, SE (50–200 mg/kg) reduced tumor weight by 70.2–72.3%. SE modulated IL-2, IL-4, IL-6, IL-17, IFN-γ, and TNF-α in tumor environment. Tumors showed inflammatory infiltrate, necrosis, and fibrosis after treatment. These findings position the extract as a promising candidate for further development as a safe, plant-based antitumor agent.

ABSTRACT Introduction: The use of clear aligners as an alternative to fixed orthodontic appliances has become popular due to the aesthetic demands of adult patients seeking orthodontic treatment. However, orthodontists’ lack of knowledge about the legal consequences of their activities, and the lack of solid scientific evidence raise concerns regarding civil liability in this type of treatment. Marketing campaigns of manufacturing companies often exaggerate promises of results, and ignore the lack of scientific evidence. Patients, as consumers, are protected by the Consumer Protection Code, whereas orthodontists are considered treatment providers. Therefore, they can be held liable for damage caused to patients, whether by subjective or objective fault. Objective: This article aims to identify the civil responsibilities of orthodontists and aligner manufacturing companies, by means of a literature review, providing basic legal guidance to help professionals protect themselves from possible lawsuits related to treatment with orthodontic aligners. Conclusions: The study highlights the importance of knowledge of legal notions in treatments with orthodontic aligners by orthodontists, who should legally safeguard themselves through individual written contracts, avoiding obligation of results. In addition, in cases of legal claims, it is possible that the manufacturing companies are jointly and severally liable for possible damages claimed by the patient. RESUMO Introdução: O uso de alinhadores transparentes como alternativa aos aparelhos ortodônticos fixos tem se tornado popular, devido às demandas estéticas dos pacientes adultos em busca de tratamento ortodôntico. No entanto, a falta de conhecimento dos ortodontistas sobre as consequências jurídicas de suas atividades, e a falta de evidências científicas sólidas levantam preocupações em relação à responsabilidade civil nesse tipo de tratamento. Muitas vezes, as campanhas de marketing das empresas fabricantes exageram nas promessas de resultados e desconsideram a falta de evidências científicas. O paciente, como consumidor, é protegido pelo Código de Defesa do Consumidor, e o ortodontista é considerado um fornecedor de tratamento. Portanto, ele pode ser responsabilizado por danos causados ao paciente, seja por culpa subjetiva ou objetiva. Objetivo: Identificar, por meio de uma revisão bibliográfica, as responsabilidades civis dos ortodontistas e das empresas fabricantes de alinhadores, fornecendo orientações jurídicas básicas para ajudar os profissionais a se protegerem de possíveis demandas judiciais relacionadas ao tratamento com alinhadores ortodônticos. Conclusões: O estudo destaca a importância do conhecimento de noções jurídicas em tratamentos com alinhadores ortodônticos, devendo o profissional resguardar-se juridicamente por meio de contratos individuais por escrito, prevenindo-se de assumir uma obrigação de resultado com o paciente. Além disso, em casos de demandas judiciais, é possível que as empresas fabricantes respondam solidariamente a possíveis danos reclamados pelo paciente.

Background The COVID-19 pandemic has dramatically impacted in patients from Intensive Care Units (ICUs), making them more vulnerable to infection/colonization by clinically relevant pathogens. However, little is known about the  Staphylococcus aureus  isolates that colonized these patients during the pandemic. Methods Consecutive  S. aureus  isolates from surveillance swabs of patients of two ICUs of a hospital in Rio de Janeiro, between September 2020 and September 2021, were evaluated for phenotypic antimicrobial resistance. Methicillin-resistant  S. aureus  (MRSA) isolates were evaluated for resistance and virulence genes, biofilm production, and their genotypic profiles. Medical records were accessed for clinical and demographic data. Results Among 255 patients colonized by  S. aureus , 79 (30.9%) were in the cICU (COVID-19 ICU) and 176 (69.1%) in the ncICU (non-COVID-19 ICU). COVID-19 patients made greater use of antimicrobials during hospitalization ( p <  0.05). Higher rates of resistance for erythromycin and clindamycin, as well as the inducible macrolide-lincosamide-streptogramin B resistance phenotype and multidrug resistance were found in cICU isolates ( p <  0.05). An overall rate of 36.5% of MRSA isolates was detected, with 41.7% in cICU and 34% in ncICU ( p  = 0.22). SCC mec  types II (22.6%) and IV (71%) were the most found, and the latter was more frequent in the ncICU ( p <  0.01). More than 50% of the isolates carried the resistance genes  erm (C),  msr (A),  mrs (B),  mph (C),  aph (3’)-III3a and  smr , and the virulence genes  ica A,  sas G,  ebp S,  scn , egc cluster,  fnbp B and  cna . The cICU presented isolates that primarily carried the  erm (C),  smr , and  cna  genes and that showed strong biofilm production ( p <  0.05). Clonal complex (CC) 5 was prevalent (65.6%) and associated with the hospital clones USA800/ST5-IV and USA100/ST105-II, which were most found in ncICU and cICU, respectively ( p <  0.05). Community MRSA comprised 31.2% of isolates and mainly included the USA300/ST8-IV lineage (18.3%), with all isolates carrying the  pvl  genes. Conclusions The significant impact on antimicrobial resistance rates and the emergence of virulent lineages among  S. aureus  isolates during the COVID-19 pandemic highlights the close relationship between this disease and antimicrobial resistance and the importance of constant microbiological surveillance to reduce the risks associated with future pandemics.