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INTRODUÇÃO: A terapia com células T receptoras de antígeno quimérico (CAR-T) mostrou-se promissora no tratamento de malignidades hematológicas, mas seus potenciais efeitos cardiotóxicos requerem investigação aprofundada. Esse trabalho tem como objetivo realizar uma meta-análise, examinando os efeitos cardiotóxicos da terapia CAR-T em adultos com malignidadeshematológicas. MÉTODOS: Como estratégia de busca, foram utilizadas as bases de dados PubMed, Embase e o Registro Cochrane Central de Ensaios Controlados para estudos que relataram desfechos cardiovasculares, como arritmias, insuficiência cardíaca e redução da fração de ejeção do ventrículo esquerdo (FEVE). RESULTADOS: Foi feita análise de 20 estudos envolvendo 4.789 pacientes, que revelou uma taxa de incidência de eventos cardiovasculares de 19,68%, sendo as arritmias (10,19%), insuficiência cardíaca (5,73%) e redução da FEVE (3,86%) as mais prevalentes. Elevação de troponina foi observada em 23,61% dos pacientes, enquanto a elevação de NT-Pro-BNP foi observada em 9,4%. Análises de subgrupos mostraram riscos maiores em pacientes com condições pré-existentes, como arritmia atrial (OR 3,12; p<0,001), hipertensão (OR 1,85; p=0,002), insuficiência cardíaca anterior (OR 3,38; p=0,003) e doença arterial coronariana (OR 2,80; p=0,003). CONCLUSÃO: A partir dos dados obtidos neste estudo, que analisou 20 artigos e envolveu 4.789 pacientes, conclui-se que há uma incidência significativa de eventos cardiovasculares entre os pacientes tratados com terapia CAR-T, particularmente aqueles com condições cardíacas pré-existentes. As arritmias, a insuficiência cardíaca e a redução da FEVE foram as complicações mais frequentes. Este achado ressalta a importância de um monitoramento cardiovascular rigoroso durante a terapia CAR-T, a fim de maximizar a segurança e eficácia do tratamento, especialmente para aqueles em maior risco devido a condições pré-existentes.
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Troponina , Doença da Artéria Coronariana , Arritmias Cardíacas , Neoplasias Hematológicas , Indicadores de Qualidade em Assistência à Saúde , Insuficiência Cardíaca , HipertensãoRESUMO
This study aims to investigate the essential oil from leaves of Eugenia pohliana (EOEP) in regard to its chemical composition, antimicrobial and drug-enhancing activity, as well as the reduction of fungal virulence capacity. Chemical characterization using GC-MS showed as major components the sesquiterpenes δ-cadinene, Epi-α-Muurolol, and bicyclogermacrene. The results of antibacterial tests indicated that Staphylococcus aureus was more sensitive to EOEP, that also enhanced the efficacy of gentamicin, erythromycin, and norfloxacin. EOEP exhibited antifungal properties against Candida albicans, in addition to potentiating the effectiveness of fluconazole against Candida tropicalis. It showed anti-virulence effects in all fungal strains. These findings underscore E. pohliana as a potential candidate for the prospection of novel therapeutic agents to treat infectious diseases caused by resistant microbes.
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Syagrus coronata, a native palm tree in the Caatinga domain, produces fixed oil (ScFO) used therapeutically and dietary by Northeast Brazilian communities. This study evaluated its anti-inflammatory potential of CFA-induced arthritis and its effect on behavioral parameters. In the acute model, ScFO at 25, 50, and 100 mg/kg showed edematogenic effects similar to indomethacin at 4 mg/kg (p > 0.05). In the arthritis model, 100 mg/kg ScFO treatment was comparable to indomethacin (4 mg/kg) (p > 0.05). TNF-α and IL-1ß levels were significantly reduced in ScFO-treated groups at 25, 50, and 100 mg/kg, and the indomethacin group (4 mg/kg) versus the positive control (p > 0.05). Radiographs showed severe soft-tissue swelling and bone deformities in the control group, while the 100 mg/kg ScFO group had few alterations, similar to the indomethacin group. Histopathological analysis revealed intense lymphocytic infiltration in the control group, mild diffuse lymphocytic infiltration in the indomethacin group, and mild lymphoplasmacytic infiltration with focal polymorphonuclear infiltrates in the 100 mg/kg ScFO group. Behavioral analysis showed improved exploratory stimuli in ScFO and indomethacin-treated mice compared to the positive control (p > 0.05). ScFO demonstrated anti-inflammatory effects in both acute and chronic arthritis models, reducing edema and pro-inflammatory cytokines, and improved exploratory behavior due to its analgesic properties.
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Anti-Inflamatórios , Artrite Experimental , Adjuvante de Freund , Animais , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Camundongos , Anti-Inflamatórios/farmacologia , Masculino , Óleos de Plantas/farmacologia , Arecaceae/química , Edema/tratamento farmacológico , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-1beta/metabolismo , Óleo de Palmeira/farmacologia , Indometacina/farmacologia , Brasil , Relação Dose-Resposta a DrogaRESUMO
Eugenia flavescens is a species cultivated in Brazil for food purposes. Given the potential application of essential oils from plants of the genus Eugenia, this study was carried out to investigate the chemical composition, acute toxicity, antioxidant, antinociceptive, gastroprotective activities, and possible mechanisms of action of the essential oil from the leaves of E. flavescens (EOEf). The EOEf was extracted by hydrodistillation, and the chemical composition was obtained using gas chromatography-mass spectrometry. The antioxidant activity was evaluated, as well as the acute toxicity and the antinociceptive and anti-inflammatory effects in mice. In addition, the gastroprotective effect was investigated using an acute gastric lesion model, considering possible mechanisms of action. The major components found in the EOEf were guaiol (19.97%), germacrene B (12.53%), bicyclogermacrene (11.11%), and E-caryophyllene (7.53%). The EOEf did not cause signs of toxicity in the acute oral toxicity test and showed in vitro antioxidant activity with IC50 ranging from 247.29 to 472.39 µg/mL in the tests ABTS and DPPH. In the nociceptive test, EOEf showed a 72.05% reduction in nociception at a dose of 100 mg/kg. In evaluating the anti-inflammatory effect, the essential oil inhibited paw edema by 95.50% and 97.69% at doses of 50 and 100 mg/kg. The results showed that EOEf has a gastroprotective effect, acting through the sulfhydryl compounds (-SH), nitric oxide (NO), and synthesis PGE2 pathways. The results suggested that EOEf is a promising source of constituents with antioxidant, antinociceptive, anti-inflammatory, and gastroprotective properties with application in the food and pharmaceutical industries.
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Analgésicos , Anti-Inflamatórios , Antioxidantes , Etanol , Eugenia , Inflamação , Óleos Voláteis , Dor , Folhas de Planta , Úlcera Gástrica , Animais , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/induzido quimicamente , Óleos Voláteis/farmacologia , Camundongos , Folhas de Planta/química , Analgésicos/farmacologia , Analgésicos/isolamento & purificação , Antioxidantes/farmacologia , Masculino , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/isolamento & purificação , Dor/tratamento farmacológico , Dor/induzido quimicamente , Eugenia/química , Inflamação/tratamento farmacológico , Brasil , Antiulcerosos/farmacologia , Antiulcerosos/isolamento & purificação , FemininoRESUMO
Chronic low-grade inflammation is a common feature of obesity and plays a crucial role in the progression of its complications. Vitamin D (VitD) plays an important role in modulating the immune response and regulating inflammation. Thus, this systematic review and meta-analysis aimed to evaluate the effects of isolated VitD supplementation on main inflammatory markers in overweight and obese individuals with no comorbidities and with VitD deficiency. We hypothesized that the increase in serum VitD concentrations after supplementation would significantly reduce the concentrations of inflammatory markers. The search was conducted in Medline/PubMed, SCOPUS, EMBASE, and Web of Science. Eleven randomized placebo-controlled studies were included in the final analysis, with a total of 504 participants and daily (1000-7000 international units) or bolus (100,000-200,000 international units) doses of VitD lasting from 2 to 26 weeks. The VitD supplementation did not influence C-reactive protein (mean difference [MD]: 0.01; 95% confidence interval [CI] -0.37, 0.39; P = .97), interleukin-6 (MD: -0.34; 95% CI -1.09, 0.42; P = .38), and tumor necrosis factor concentrations (MD: -0.02; 95% CI -0.23, 0.19; P = .85). In the analysis considering the studies with a significant increase in serum VitD concentrations, VitD supplementation also did not influence C-reactive protein (MD: -0.17; 95% CI -0.88, 0.54; P = .64), interleukin-6 (MD: -0.47; 95% CI -1.31, 0.37; P = .27), and tumor necrosis factor concentrations (MD: 0.01; 95% CI -1.34, 1.37; P = .98). This meta-analysis suggests that VitD supplementation does not significantly alter inflammatory markers in overweight and obese individuals.
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Suplementos Nutricionais , Inflamação , Obesidade , Sobrepeso , Vitamina D , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores/sangue , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Inflamação/sangue , Interleucina-6/sangue , Obesidade/sangue , Obesidade/complicações , Sobrepeso/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto , Fator de Necrose Tumoral alfa/sangue , Vitamina D/sangue , Vitamina D/uso terapêutico , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/tratamento farmacológicoRESUMO
OBJECTIVES: The present study aims to evaluate the impact of early exposure to brain injury and malnutrition on episodic memory and behavior. METHODS: For this, a systematic review was carried out in the Medline/Pubmed, Web of Science, Scopus, and LILACS databases with no year or language restrictions. RESULTS: Initially, 1759 studies were detected. After screening, 53 studies remained to be read in full. The meta-analysis demonstrated that exposure to double insults worsens episodic recognition memory but does not affect spatial memory. Early exposure to low-protein diets has been demonstrated to aggravate locomotor and masticatory sequelae. Furthermore, it reduces the weight of the soleus muscle and the muscle fibers of the masseter and digastric muscles. Early exposure to high-fat diets promotes an increase in oxidative stress and inflammation in the brain, increasing anxiety- and depression-like behavior and reducing locomotion. DISCUSSION: Epigenetic modifications were noted in the hippocampus, hypothalamus, and prefrontal cortex depending on the type of dietetic exposure in early life. These findings demonstrate the impact of the double insult on regions involved in cognitive and behavioral processes. Additional studies are essential to understand the real impact of the double insults in the critical period.
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Pseudobombax marginatum, popularly known as "embiratanha," is widely used by traditional communities as anti-inflammatory and analgesic agent. This study aimed to determine the phytochemical profile as well as cytotoxicity, acute oral toxicity, genotoxicity, and mutagenicity attributed to exposure to aqueous (AqEx) and ethanolic (EtEx) extracts of embiratanha bark. Phytochemical screening was conducted using thin-layer chromatography (TLC). Cell viability was analyzed using MTT assay with human mammary gland adenocarcinoma (MDA-MB-231) and macrophage (J774A.1) cell lines, exposed to concentrations of 12.5, 25, 50, or 100 µg/ml of either extract. For acute oral toxicity, comet assay and micronucleus (MN) tests, a single dose of 2,000 mg/kg of either extract was administered orally to Wistar rats. TLC analysis identified classes of metabolites in the extracts, including cinnamic acid derivatives, flavonoids, hydrolyzable tannins, condensed tannins, coumarins, and terpenes/steroids. In the cytotoxicity assay, the varying concentrations of extracts derived from embiratanha induced no significant alterations in the viability of MDA-MB-231 cells. The lowest concentration of EtEx significantly increased macrophage J774A.1 viability. However, the higher concentrations of AqEx markedly lowered macrophage J774A.1 viability. Animals exhibited no toxicity in the parameters analyzed in acute oral toxicity, comet assay, and MN tests. Further, EtEx promoted a significant reduction in DNA damage index and DNA damage frequency utilizing the comet assay, while the group treated with AqEx exhibited no marked differences. Thus, data demonstrated that AqEx or EtEx of embiratanha may be considered safe at a dose of 2,000 mg/kg orgally under our experimental conditions tested.
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Extratos Vegetais , Ratos Wistar , Extratos Vegetais/toxicidade , Extratos Vegetais/química , Animais , Humanos , Ratos , Linhagem Celular Tumoral , Masculino , Ensaio Cometa , Testes para Micronúcleos , Feminino , Sobrevivência Celular/efeitos dos fármacos , Compostos Fitoquímicos/toxicidade , Compostos Fitoquímicos/análise , Camundongos , Casca de Planta/química , Mutagênicos/toxicidade , Testes de Mutagenicidade , Etanol/químicaRESUMO
CONTEXT: Riboflavin (vitamin B2) is a water-soluble micronutrient considered to be a precursor of the nucleotides flavin adenine dinucleotide and flavin mononucleotide. This vitamin makes up mitochondrial complexes and participates as an enzymatic cofactor in several mechanisms associated with energy metabolism. OBJECTIVE: This systematic review collected and discussed the most relevant results on the role of riboflavin in the energy metabolism of lipids, proteins, and carbohydrates. DATA SOURCES: A systematic search was carried out in the PubMed-Medline, Scopus, Embase, and Web of Science databases using the PICOS (Population, Intervention, Comparison, Outcome, Study design) strategy. DATA EXTRACTION: The screening of studies went through 2 stages following predefined eligibility criteria. The information extracted covered reference details, study design, population characteristics, experimental model, treatment parameters and dosage, route of administration, duration of treatment, and results found. DATA ANALYSIS: The risk of bias was assessed using the SYRCLE Risk of Bias (RoB) tool for in vivo studies and the QUIN tool adapted for in vitro studies, utilizing 10 domains, including selection bias, performance bias, detection bias, attrition bias, reporting bias, and other biases, to evaluate the methodological quality of the included studies. CONCLUSION: This review concludes that riboflavin regulates energy metabolism by activating primary metabolic pathways and is involved in energy balance homeostasis.
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Punica granatum, popularly known as pomegranate, is a fruit tree with wide worldwide distribution, containing numerous phytochemicals of great medicinal value. The aim of the present study was to determine the phytochemical profile and antioxidant potential of a protein fraction (PF) derived from P. granatum sarcotesta which is rich in lectin. In addition, the acute oral toxicity, genotoxicity and antigenotoxicity of this protein fraction (PF) from P. granatum sarcotesta was measured. The phytochemical profile of PF was determined using HPLC. The in vitro antioxidant effect was assessed using the methods of total antioxidant capacity (TAC) and DPPH and ABTS+ radical scavenging. Acute oral toxicity was determined in female Swiss mice administered a single dose of 2000 mg/kg. This PF was examined for genotoxicity and antigenotoxicity at doses of 500, 1000 and 2000 mg/kg, utilizing mouse peripheral blood cells. Phytochemical characterization detected a high content of ellagic acid and antioxidant capacity similar to that of ascorbic acid (positive control). PF was not toxic (LD50 >2000 mg/kg) and did not exert a genotoxic effect in mice. PF protected the DNA of peripheral blood cells against damage induced by cyclophosphamide. In conclusion, this PF fraction exhibited significant antioxidant activity without initiating toxic or genotoxic responses in mice.
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Antioxidantes , Extratos Vegetais , Punica granatum , Animais , Camundongos , Antioxidantes/farmacologia , Feminino , Extratos Vegetais/toxicidade , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Punica granatum/química , Lectinas/toxicidade , Testes de Mutagenicidade , Dano ao DNA/efeitos dos fármacos , Testes de Toxicidade AgudaRESUMO
An alternative approach to assay iron (Fe) in biodiesel by differential pulse adsorptive cathodic stripping voltammetry (DPAdCSV) is presented herein. The sample treatment involved a simple, rapid, but effective extraction of Fe from biodiesel into an aqueous phase after microemulsion (ME) breaking. Then, Fe was determined as the complex Fe(III)-PAN (1-(2-pyridylazo)-2-naphthol) on a glassy carbon electrode (GCE) in the presence of bismuth (Bi(III)). The extraction induced by microemulsion breaking (EIMB) was achieved by adding 0.80 mL of ultrapure water into a water-in-oil ME containing 7.00 mL biodiesel, 2.70 mL n-propanol and 0.30 mL of 0.25 mol L-1 HNO3 solution. No deliberate addition of surfactant was necessary to form and maintain the ME. The EIMB resulted in a 1.30 mL lower aqueous phase extract (APhEx) and an upper oily phase. DP voltammograms were recorded with a portable potentiostat, showing the potentiality of carrying out the determination out of a central laboratory. Another feature was the non-necessity of deaerating the solution to eliminate the dissolved O2. The limits of detection (LOD) and quantification (LOQ) were 1.7 µg L-1 (140 mg kg-1) and 5.5 µg L-1 (455 mg kg-1), respectively. The accuracy of the method was evaluated by recovery assays of spiked samples, by analyzing a standard reference material and by comparisons with high-resolution continuum source graphite furnace atomic absorption spectrometry (HR-CS GF AAS).
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The objective of this study was to compare the indirect methods of obtaining digestibility with the direct method of total fecal collection to estimate the apparent digestibility of nutrients in sheep and goats supplemented with non-protein nitrogen. Five goats and five sheep with no defined racial pattern were used, distributed in two 5 × 5 Latin squares, with split plots, considering the diets as plots and the apparent digestibility determination methodologies as subplots. The diets were composed of buffelgrass hay and the addition, via ruminal infusion, of increasing amounts of nitrogen supplementation in order to gradually raise the CP level of the basal diet in intervals of 2% points, that is, + 2, +4, + 6 and + 8%. Samples of the feeds offered, and the leftovers were collected daily during the five days of collection to determine the nutrient intake, as well as the total collection of feces to determine the apparent digestibility of the nutrients. The amount of fecal dry matter excreted was estimated by the concentration of Indigestible Acid Detergent Fiber (ADFi), Indigestible Neutral Detergent Fiber (NDFi), Indigestible Dry Matter at 244 h (DMi 244 h) and Indigestible Dry Matter at 264 h (DMi 264 h). Among the evaluated markers, DMi 264 h had the lowest accuracy in estimating fecal excretion and nutrient digestibility. For the goat species, the markers ADFi and DMi 244 h proved to be able to adequately predict fecal excretion and digestibility indices, while NDFi stood out for both species. Among the evaluated markers, NDFi is the one that most accurately estimates the nutrient digestibility of the diet for goats and sheep.
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Detergentes , Cabras , Animais , Ovinos , Nutrientes , Suplementos Nutricionais , NitrogênioRESUMO
Modeling human pregnancy is challenging as two subjects, the mother and fetus, must be evaluated in tandem. To understand pregnancy, parturition, and adverse pregnancy outcomes, the two feto-maternal interfaces (FMi) that form during gestation (i.e., the placenta and fetal membrane) need to be investigated to understand their biological roles, and organ dysfunction can lead to adverse outcomes. Adverse pregnancy outcomes such as preterm rupture of the membranes, spontaneous preterm birth, preeclampsia, intra-uterine growth restriction, and gestational diabetes rates are on the rise worldwide, highlighting the need for future studies and a better understanding of molecular and cellular pathways that contribute to disease onset. Current in vivo animal models nor in vitro cell culture systems can answer these questions as they do not model the function or structure of human FMis. Utilizing microfabrication and soft-lithography techniques, microfluidic organ-on-chip (OOC) devices have been adapted by many fields to model the anatomy and biological function of complex organs and organ systems within small in vitro platforms.These techniques have been adapted to recreate the fetal membrane FMi (FMi-OOC) using immortalized cells and collagen derived from patient samples. The FMi-OOC is a four-cell culture chamber, concentric circle system, that contains both fetal (amniochorion) and maternal (decidua) cellular layers and has been validated to model physiological and pathological states of pregnancy (i.e., ascending infection, systemic oxidative stress, and maternal toxicant exposure). This platform is fully compatible with various analytical methods such as microscopy and biochemical analysis. This protocol will outline this device's fabrication, cell loading, and utility to model ascending infection-related adverse pregnancy outcomes.
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Nascimento Prematuro , Recém-Nascido , Gravidez , Feminino , Animais , Humanos , Placenta/metabolismo , Membranas Extraembrionárias/metabolismo , Linhagem Celular , TecnologiaRESUMO
Herein, a simple, green, and relatively inexpensive approach to determine nickel (Ni) in biodiesel samples by square wave adsorptive cathodic stripping voltammetry (SWAdCSV) is presented. A method based on the accumulation of Ni as Ni(II)-dimethylglyoxime (Ni(II)(HDMG)2) on the glassy carbon electrode was carried out in a solution containing the aqueous phase extract (APhEx) obtained from an extraction induced by microemulsion breaking (EIMB), which was achieved by adding a few microliters of ultrapure water to a microemulsion composed of biodiesel, n-propanol and a diluted HNO3 solution. The LOD and LOQ were 0.2 µg L-1 and 0.8 µg L-1, respectively, and the accuracy was evaluated by recovery assays of spiked samples and by analyzing a standard reference material. Results obtained from a comparative method (HR-CS GF AAS) were also used for this evaluation. The method was applied to biodiesel samples produced from different feedstocks. To the best of the authors knowledge, it is the first time that: 1) Ni in biodiesel is determined by a voltammetric method; 2) EIMB is applied to extract Ni from this matrix and 3) this type of sample preparation method is used with adsorptive stripping voltammetry.
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Stingless bees belong to the Meliponini tribe and are widely distributed in the tropics and subtropics, where they perform important ecological services. Among the best distributed groups of stingless bees is the genus Scaptotrigona, which includes 22 species distributed throughout the neotropical region, including the area from Mexico to Argentina. Bees of this genus are responsible for the production of products such as honey, propolis, geopropolis and fermented pollen ("saburá"). This review aimed to provide an overview of the chemical composition and biological activities associated with derived products from stingless bees of the genus Scaptotrigona. The bibliographic review was carried out through searches in the Scopus, Web of Science, ScienceDirect and PubMed databases, including publications from 2003 to January 2023. The study of the chemodiversity of products derived from Scaptotrigona demonstrated the mainly presence of flavonoids, phenolic acids, terpenoids and alkaloids. It was also demonstrated that products derived from bees of the genus Scaptotrigona exhibit a wide range of biological effects, such as antibacterial, antioxidant, anti-inflammatory and antifungal activities, among other bioactivities. This review provides an overview of phytochemical and pharmacological investigations of the genus Scaptotrigona. However, it is essential to clarify the toxicity and food safety of these products.
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Mel , Himenópteros , Própole , Animais , Antibacterianos/farmacologia , Abelhas , México , Própole/farmacologia , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Hidroxibenzoatos/química , Hidroxibenzoatos/isolamento & purificação , Hidroxibenzoatos/farmacologia , Terpenos/química , Terpenos/isolamento & purificação , Terpenos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologiaRESUMO
The raising of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants led to the use of COVID-19 bivalent vaccines, which include antigens of the wild-type (WT) virus, and of the Omicron strain. In this study, we aimed to evaluate the impact of bivalent vaccination on the neutralizing antibody (NAb) response. We enrolled 93 volunteers who had received three or four doses of monovalent vaccines based on the original virus (n = 61), or a booster shot with the bivalent vaccine (n = 32). Serum samples collected from volunteers were subjected to neutralization assays using the WT SARS-CoV-2, and Omicron subvariants. In addition, immunoinformatics to quantify and localize highly conserved NAb epitopes were performed. As main result, we observed that the neutralization titers of samples from individuals vaccinated with the bivalent vaccine were higher for the original virus, in comparison to their capacity of neutralizing the Omicron variant and its subvariants. NAb that recognize epitopes mostly conserved in the WT SARS-CoV-2 were boosted, while those that recognize epitopes mostly present in the Omicron variant, and subvariants were primed. These results indicate that formulation of future vaccines shall consider to target present viruses, and not viruses that no longer circulate.
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Vacinas contra COVID-19 , COVID-19 , Humanos , COVID-19/prevenção & controle , SARS-CoV-2/genética , Vacinação , Imunização Secundária , Anticorpos Neutralizantes , Epitopos/genética , Vacinas CombinadasRESUMO
Wounds encompass physical, chemical, biological, induced damages to the skin or mucous membranes. In wound treatment, combating infections is a critical challenge due to their potential to impede recovery and inflict systemic harm on patients. Previously, the essential oil extracted from Psidium glaziovianum (PgEO) demonstrated antinociceptive and anti-inflammatory attributes, along with negligible oral toxicity. Hence, our study aimed to assess the effects of topically applying a gel formulation containing PgEO to excisional wounds in mice. Additionally, an in vitro antimicrobial assessment was conducted. The formulated gel underwent characterization and toxicological evaluation on erythrocytes, as well as a dermal irritation test. Its antimicrobial activity was tested against both gram-positive and gram-negative bacteria, as well as fungi. Subsequently, an assessment of its efficacy in excisional wound healing was conducted in mice. The findings of this investigation highlight the gel's efficacy against both gram-positive and gram-negative bacteria, as well as fungi. Moreover, this study underscores that the PgEO-gel treatment enhances skin wound healing, potentially due to its capacity to trigger antioxidant enzymes and suppress pro-inflammatory cytokines. Furthermore, the gel exhibited minimal toxicity to erythrocytes and skin irritation. These findings hold promise for prospective preclinical and clinical trials across diverse wound types. In conclusion, this study sheds light on the potential therapeutic applications of the gel formulation containing essential oil from P. glaziovianum in the context of wound healing.
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Óleos Voláteis , Psidium , Humanos , Animais , Camundongos , Antibacterianos , Estudos Prospectivos , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Cicatrização , Óleos Voláteis/farmacologiaRESUMO
OBJECTIVES: This study aims to assess the effect of neonatal treatment with kaempferol on neuromotor development, proliferation of neural precursor cells, the microglia profile, and antioxidant enzyme gene expression in the hippocampus. METHODS: A rat model of cerebral palsy was established using perinatal anoxia and sensorimotor restriction of hindlimbs during infancy. Kaempferol (1â mg/ kg) was intraperitoneally administered during the neonatal period. RESULTS: Neonatal treatment with kaempferol reduces the impact of the cerebral palsy model on reflex ontogeny and on the maturation of physical features. Impairment of locomotor activity development and motor coordination was found to be attenuated by kaempferol treatment during the neonatal period in rats exposed to cerebral palsy. Neonatal treatment of kaempferol in cerebral palsy rats prevents a substantial reduction in the number of neural precursor cells in the dentate gyrus of the hippocampus, an activated microglia profile, and increased proliferation of microglia in the sub-granular zone and in the granular cell layer. Neonatal treatment with kaempferol increases gene expression of superoxide dismutase and catalase in the hippocampus of rats submitted to the cerebral palsy model. DISCUSSION: Kaempferol attenuates the impact of cerebral palsy on neuromotor behavior development, preventing altered hippocampal microglia activation and mitigating impaired cell proliferation in a neurogenic niche in these rats. Neonatal treatment with kaempferol also increases antioxidant defense gene expression in the hippocampus of rats submitted to the cerebral palsy model.
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Paralisia Cerebral , Células-Tronco Neurais , Gravidez , Feminino , Animais , Ratos , Antioxidantes/farmacologia , Microglia , Quempferóis/farmacologia , Quempferóis/metabolismo , Hipocampo , Proliferação de CélulasRESUMO
PROBLEM: Ascending bacterial infection is associated with â¼ 40% of spontaneous preterm birth (PTB), and Ureaplasma spp. is one of the most common bacteria isolated from the amniotic fluid. Developing novel in vitro models that mimic in vivo uterine physiology is essential to study microbial pathogenesis. We utilized the feto-maternal interface organ-on-chip (FMi-OOC) device and determined the propagation of Ureaplasma parvum, and its impact on cell signaling and inflammation. METHOD OF STUDY: FMi-OOC is a microphysiologic device mimicking fetal membrane/decidua interconnected through microchannels. The impact of resident decidual CD45+ leukocytes was also determined by incorporating them into the decidual chamber in different combinations with U. parvum. We tested the propagation of live U. parvum from the decidual to the amniochorion membranes (immunocytochemistry and quantitative PCR), determined its impact on cytotoxicity (LDH assay), cell signaling (JESSTM Western Blot), cellular transition (immunostaining for vimentin and cytokeratin), and inflammation (cytokine bead array). RESULTS: U. parvum transversed the chorion and reached the amnion epithelium after 72 hours but did not induce cell signaling kinases (p38MAPK and JNK) activation, or cellular transition (epithelial-mesenchymal), regardless of the presence of immune cells. The inflammatory response was limited to the choriodecidual interface and did not promote inflammation in the amnion layer. CONCLUSIONS: Our data suggest that U. parvum is poorly immunogenic and does not produce massive inflammatory changes at the feto-maternal interface. We speculate that the presence of U. parvum may still compromise the feto-maternal interface making it susceptible to other pathogenic infection.
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Nascimento Prematuro , Ureaplasma , Recém-Nascido , Feminino , Humanos , Transdução de Sinais , Âmnio , InflamaçãoRESUMO
Disturbed vaginal microbiota have a role in the persistence of high-oncogenic-risk human papillomavirus (hrHPV) and Gardnerella spp. is closely related with this condition. Such bacteria are the major source of cervicovaginal sialidases, important for microbiota alterations. The sialidase-encoding gene nanH3 is account for their sialidase activity. Thus, a subset of 212 women positive for hrHPV at the first visit were included in the analysis of the current study aiming to compare the loads of nanH3 in cervicovaginal fluid (CFV) of women with persistent hrHPV infection and with those cleared the infection after a year. Participants were assigned to two study groups named "persistence" (n = 124, 53.22%) or "clearance" (n = 88, 37.77%), according to the HPV status upon enrollment and follow-up. Absolute quantification of nanH3 gene was performed using quantitative real-time PCR (qPCR). Persistence and clearance group did not show statistical difference in the load of nanH3 gene (p = 0.19). When considering the subset of women with HPV16, differences in number of copies of nanh3 gene was observed between the persistent (7.39E+08 copies/µL) and clearance group (2.85E+07 copies/µL) (p = 0.007). Therefore, baseline loads of nanH3 gene is increased in women that persist with cervical HPV16 infection after 12 months.