Neutralizing antibody response after immunization with a COVID-19 bivalent vaccine: Insights to the future.

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.

Early-life malnutrition role in memory, emotional behavior and motor impairments in early brain lesions with potential for neurodevelopmental disorders: a systematic review with meta-analysis.

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.

Neonatal kaempferol exposure attenuates impact of cerebral palsy model on neuromotor development, cell proliferation, microglia activation, and antioxidant enzyme expression in the hippocampus of rats.

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 (1 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.

Evaluation of cytotoxicity, acute toxicity, genotoxicity and antioxidant and antigenotoxicity activities of the sarcotesta fraction of punica granatum L. rich in lectin (PgTel).

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.

Phytochemical profile and determination of cytotoxicity, acute oral toxicity, genotoxicity, and mutagenicity of aqueous and ethanolic extracts of Pseudobombax marginatum (A. St.-Hil.) A. Robyns.

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.

THE COMBINATORY EFFECTS OF ESSENTIAL OIL FROM Lippia macrophylla ON MULTIDRUG RESISTANT Acinetobacter baumannii CLINICAL ISOLATES.

To assess the antibacterial effectiveness of Lippia macrophylla essential oil (LMEO) against multidrug-resistant Acinetobacter baumannii isolates, both as a standalone treatment and in combination with conventional antibiotics. LMEO demonstrated a significant inhibitory effect on the growth of A. baumannii, with a minimum inhibitory concentration (MIC) below 500µg/mL. Notably, LMEO was capable of reversing the antibiotic resistance of clinical isolates or reducing their MIC values when used in combination with antibiotics, showing synergistic (FICI ≤ 0.5) or additive effects. The combination of LMEO and imipenem was particularly effective, displaying synergistic interactions for most isolates. Ultrastructural analyses supported these findings, revealing that the combination of LMEO + ceftazidime compromised the membrane integrity of the Acb35 isolate, leading to cytoplasmic leakage and increased formation of Outer Membrane Vesicles (OMVs). Taken together our results point for the use of LMEO alone or in combination as an antibacterial agent against A. baumannii. These findings offer promising avenues for utilizing LMEO as a novel antibacterial strategy against drug-resistant infections in healthcare settings, underscoring the potential of essential oils in enhancing antibiotic efficacy.

Eugenia pohliana leaves essential oil inhibits fungal virulence and restores antibiotic efficacy in multidrug-resistant bacterial strains.

This study aims to investigate the essential oil from leaves of E. 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 Eugenia pohliana as a potential candidate for the prospection of novel therapeutic agents to treat infectious diseases caused by resistant microbes.

Chemical Profile and Biological Potential of Scaptotrigona Bee Products (Hymenoptera, Apidae, Meliponini): An Review.

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.

Development of gel containing Psidium glaziovianum essential oil has in vitro antimicrobial activity and improves healing of excisional wounds in mice.

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.

Chemical characterization of the essential oil from the leaves of Eugenia flavescens DC. (Myrtaceae) and its potential in the treatment of pain, inflammation, and ethanol- and ethanol/HCL-induced gastric ulcers in mice.

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.

Fixed oil from the Caatinga palm Syagrus coronata with effect on Complete Freund's Adjuvant (CFA)-induced arthritis.

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.

Cosmetic application of the stem-bark extract of Bertholletia excelsa H.B.K.

OBJECTIVE: The Amazon has a rich biodiversity where many different plant species can be found. This diversity is an important source of bioactive substances, mainly due to the different structural components of their phytometabolites. Research for natural products is a strategy for the development of new agents in therapeutic applications, especially cosmetic applications, that have better pharmacological potential. Within this perspective, the objective of the study was to investigate the cosmetic application (anti-aging potential) of the stem-bark extract of Bertholletia excelsa H.B.K - (SBEBE), popularly known as the Brazil nut tree, here called SBEBE, a noble plant species of the Amazon that is rich in selenium. METHODS: Enzymatic, glycation, proliferation, cell-healing, collagen quantification, toxicity and genotoxicity assays were used. RESULTS: Among the enzymes involved in the extracellular matrix of the skin, SBEBE was able to inhibit only elastase (62.67 ± 3.75) when compared to the standard sivelestat (89.04 ± 0.53), and the extract was also able to inhibit both the oxidative and the non-oxidative pathway. When cell toxicity in fibroblasts (MRC-5) and keratinocytes (HACAT) was evaluated, SBEBE did not present toxicity in 24 h of incubation. After this period, the extract showed average cytotoxicity in 48 and 72 h, but not enough to reach the concentration of 50% of MRC-5 fibroblasts. In the trypan blue assay, the extract promoted fibroblast proliferation in 24, 48 and 72 h of incubation, which was evaluated through exponential cell growth, with emphasis mainly on the lowest concentration with results higher than the standard. When the cell healing capacity was evaluated, in 48 h of exposure to fibroblast, SBEBE was able to induce a cell carpet (cell film) in the cell monolayer scratch assay. CONCLUSIONS: SBEBE stimulated collagen production at all concentrations tested. In the alkaline comet assay, at the lowest concentration, the extract did not induce DNA damage when compared to the reference drug doxorubicin. This study proved that SBEBE extract can be considered an ally in the treatment of skin anti-ageing as a possible biotechnological, phytocosmetic product.

OBJECTIF: L'Amazonie possède une riche biodiversité ou l'on trouve de nombreuses espèces végétales différentes. Cette diversité constitue une source importante de substances bioactives, principalement en raison des différents composants structurels de leurs phytométabolites. La recherche de produits naturels est une stratégie de développement de nouveaux agents à applications thérapeutiques, notamment cosmétiques, présentant un meilleur potentiel pharmacologique. Dans cette perspective, l'objectif de l'étude était d'étudier l'application cosmétique (potentiel anti-âge) de l'extrait d'écorce de tige de Bertholletia excelsa H.B.K - (SBEBE), communément connu sous le nom de noix du Brésil, ici appelé SBEBE, un arbre noble, espèce végétale d'Amazonie riche en sélénium. MÉTHODES: Des tests enzymatiques, de glycation, de prolifération, de guérison cellulaire, de quantification du collagène, de toxicité et de génotoxicité ont été utilisés. RÉSULTATS: Parmi les enzymes impliquées dans la matrice extracellulaire de la peau, le SBEBE était capable d'inhiber uniquement l'élastase (62,67 +- 3,75) par rapport au sivelestat standard (89,04 +- 0,53), et l'extrait était également capable d'inhiber à la fois la voie oxydative et non-oxydative. Lorsque la toxicité cellulaire dans les fibroblastes (MRC-5) et les kératinocytes (HACAT) a été évaluée, SBEBE n'a présenté aucune toxicité en 24 heures d'incubation. Après cette période, l'extrait a montré une cytotoxicité moyenne en 48 et 72 h, mais pas suffisamment pour atteindre la concentration de 50 % de fibroblastes MRC-5. Dans le test au bleu trypan, l'extrait a favorisé la prolifération des fibroblastes en 24, 48 et 72 heures d'incubation, qui a été évaluée par une croissance cellulaire exponentielle, en mettant l'accent principalement sur la concentration la plus faible avec des résultats supérieurs à la norme. Lorsque la capacité de guérison cellulaire a été évaluée, en 48 heures d'exposition aux fibroblastes, SBEBE a pu induire un tapis cellulaire (film cellulaire) dans le test de grattage de la monocouche cellulaire. CONCLUSIONS: SBEBE a stimulé la production de collagène à toutes les concentrations testées. Dans le test alcalin des comètes, à la concentration la plus faible, l'extrait n'a pas induit de dommages à l'ADN par rapport au médicament de référence, la doxorubicine. Cette étude a prouvé que l'extrait de SBEBE peut être considéré comme un allié dans le traitement anti-âge cutané en tant que possible produit biotechnologique et phytocosmétique.

Evaluation of internal markers in digestibility estimation for sheep and goats.

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.

Leukoreduction as a control measure in transfusion transmission of visceral leishmaniasis.

BACKGROUND: Asymptomatic visceral leishmaniasis (VL) infection is a risk for transfusion safety. Leukoreduction has been an alternative for the prevention of some blood-borne diseases, including VL. This study aimed to evaluate the role of leukoreduction of cellular blood components as a control measure for transfusional VL transmission. RESEARCH DESIGN AND METHODS: A total of 161 polytransfused patients with non-leukoreduced blood components (HNL), 95 polytransfused with leukoreduced blood components (LH), and 202 non-transfused (NT) from endemic regions for VL and with a similar epidemiological profile. The detection of antibodies against VL was performed by ELISA and the presence of the parasite was investigated by real-time PCR. Statistical significance was defined as p < .05. RESULTS: When comparing three groups, ELISA results were statistically significant (p = .0065). The residual analysis of ELISA showed statistically significant for the HNL group compared to the general group (p = .002; OR: 5.6; CI: 1.7-25.8), demonstrating that individuals who received non-leukoreduced transfusions are five times more likely to acquire Leishmania infantum infection than the general. DISCUSSION: Higher prevalence in the group with HNL and low prevalence in those who received LH, similar to NT patients, highlight the risk of transfusional VL transmission and reinforce the role of leukoreduction in its prevention.

Evaluation of 28-day repeated doses oral toxicity of essential oil from Psidium glaziovianum Kiaersk leaves on various biological parameters in Swiss mice.

Only a small number of the many medicinally important species in the genus Psidium L. have had their safety assessed. Psidium glaziovianum, a plant native to Brazil, is reported to exert antinociceptive and anti-inflammatory effects; however, there are no apparent reports of long-term safety following administering of repeated doses. The aim of this study was to examine the effects of 28-day oral of treatment at 250, 500 or 1,000 mg/kg Psidium glaziovianum essential oil (PgEO) on behavioral and physiological parameters in male and female Swiss mice. First, PgEO was chemically characterized by gas chromatography mass spectrometry (GC-MS). The following parameters were examined: motor activity, body temperature, blood glucose, urine, hematology, biochemistry, histology, and oxidative stress. Characterization of PgEO revealed 48 components which were dominated by sesquiterpenes 1,8-cineol (24.29%), α-pinene (19.73%) and ß-pinene (17.31%). Data showed that PgEO treatment in mice increased activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) without markedly affecting body weight, hematological or biochemical parameters, as well as water or food consumption. Administration of PgEO in repeated daily dosages over 28 days did not significantly alter exploratory or locomotor activities. Based upon our findings, PgEO administration daily for 28 days, exhibited low toxicity and absence of effects on the nervous system. Data demonstrated that PgEO produced hypoglycemic and antioxidant actions which need to be considered in safety assessment.

Toxicological safety, antioxidant activity and phytochemical characterization of leaf and bark aqueous extracts of Commiphora leptophloeos (Mart.) J.B. Gillett.

This study aimed to characterize the phytochemical profile of bark and leaves aqueous extract Commiphora leptophloeos, and conduct in vivo and in vitro assays to determine the presence of any toxicological consequences due to exposure. The phytochemical analysis was carried out using high-performance liquid chromatography (HPLC). The antioxidant activity was estimated utilizing DPPH free radical scavenging and phosphomolybdenum assays. Cell viability was measured by the MTT method on J774 and human adenocarcinoma cells, which were treated with concentrations of 12,5, 25, 50, 100 or 200 µg/ml of both extracts. Acute oral toxicity, genotoxicity, and mutagenicity assays were determined using a single oral dose of 2000 g/kg in male Swiss albino mice (Mus musculus). Biochemical analysis of the blood and histological analyses of the kidneys, liver, spleen, pylorus, duodenum and jejunum were undertaken. Genotoxicity and mutagenicity were determined utilizing blood samples. Gallic acid, catechin, and epicatechin were identified in the bark and chlorogenic acid in leaves. Data demonstrated a high content of phenolic compounds and flavonoids associated with significant antioxidant potential. No significant signs in damage or symptoms of toxicity were detected. No marked reduction in cell viability was found at lower concentrations tested. On histomorphometry, only the gastrointestinal organs exhibited significant difference. Renal hepatic and blood parameters were within the normal range. No apparent signs of toxicity, genotoxicity, mutagenicity or cytotoxicity were found in vivo and in vitro experiments.

Vitamin D Receptor and Retinoid X Receptor Alpha in Melanocytic Benign Lesions and Melanoma.

ABSTRACT: Vitamin D receptor (VDR) exerts its biological effects when it heterodimerizes to a nuclear receptor of the retinoid family called retinoid X receptor α (RXRα), stimulating or inhibiting DNA transcription. VDR stimulation by vitamin D analogs led to in vitro antiproliferative effects, and experimental RXRα knockout led to loss of proliferation control in melanoma cells. The aim of this study was to determine VDR and RXRα positivity in melanocytic lesions, compared with normal skin species. By immunohistochemistry assays, nuclear VDR, cytoplasmic VDR, and RXRα and RXRα in keratinocytes surrounding melanocytes were evaluated in 77 controls, 92 intradermal nevi, 54 dysplastic nevi, and 83 melanomas in this retrospective cross-sectional study. Nuclear VDR, cytoplasmic VDR, and RXRα were less expressed in exposed areas ( P < 0.001, P = 0.0006, and P < 0.001, respectively) than covered areas. All melanocytic lesions had loss of VDR and RXRα comparing with the control group. In the melanoma group, nuclear VDR tended to inversely correlate with the Breslow index (r = -0.11, P = 0.29) but directly correlated with histological regression ( P = 0.0293). RXRα inversely correlated with mitosis (r = -0.245; P = 0.0263). We can suggest that sun exposure affected VDR and RXRα immunopositivity. Nuclear VDR tendency of inverse correlation with the Breslow index showed that worse melanomas have a greater loss of VDR. RXRα inversely correlated with mitosis, indicating that RXRα can have a role in proliferation control. VDR and RXRα may participate in the development of melanocytic lesions and be a future target of new studies and directed therapies.

Milk and Dairy Consumption and Its Relationship With Abundance of Lactobacillus crispatus in the Vaginal Microbiota: Milk Intake and Vaginal Lactobacillus.

OBJECTIVES: Diet habits, such as low milk and dairy intake, have been associated with bacterial vaginosis. Thus, the authors compared vaginal Lactobacillus crispatus abundances in women with different molecularly defined community state types (CSTs) according to the consumption of milk and/or dairy products. METHODS: A total of 516 women from the 5 geographic regions of Brazil were included. Participants were interviewed with a structured questionnaire for assessment of milk and/or dairy intake. Vaginal samples were used for sequencing of V3-V4 regions of the 16S ribosomal RNA gene for further determination of L. crispatus relative abundance (RA) and clustering into 1 of the 5 CSTs (CSTI-CSTV), as firstly described by Ravel et al. (2011). The nonparametric Mann-Whitney test was used to compare L. crispatus RA within the most representative CSTs ( L. crispatus -dominant CSTI, Lactobacillus iners -dominant CSTIII, and Lactobacillus -depleted CSTIV) in this population, according to the frequency of milk and/or dairy intake. RESULTS: The prevalence of CSTI was 33.3% ( n = 172), CSTIII was 39% ( n = 201), and CSTIV was 27.7% ( n = 143). Among the participants with CSTIII, higher L. crispatus RA was observed for those who reported milk/dairy intake (median = 0.02; interquartile range = 0.01-0.09) than those with no consumption (median = 0.01; interquartile range = 0-0.03) ( p = .03). Such difference was not observed for participants with CSTI and CSTIV. CONCLUSIONS: Women with vaginal microbiota dominated by L. iners who consume milk and/or dairy present increased abundances of L. crispatus . Therefore, they could benefit from L. crispatus protective properties conferring greater temporal microbiota stability and, consequently, increased protection against infections.

Circulating Extracellular Vesicles microRNAs Are Altered in Women Undergoing Preterm Birth.

Preterm labor (PTL) and preterm premature rupture of membranes (PPROM) lead to high perinatal morbidity/mortality rates worldwide. Small extracellular vesicles (sEV) act in cell communication and contain microRNAs that may contribute to the pathogenesis of these complications. We aimed to compare the expression, in sEV from peripheral blood, of miRNAs between term and preterm pregnancies. This cross-sectional study included women who underwent PTL, PPROM, and term pregnancies, examined at the Botucatu Medical School Hospital, SP, Brazil. sEV were isolated from plasma. Western blot used to detect exosomal protein CD63 and nanoparticle tracking analysis were performed. The expression of 800 miRNAs was assessed by the nCounter Humanv3 miRNA Assay (NanoString). The miRNA expression and relative risk were determined. Samples from 31 women-15 preterm and 16 term-were included. miR-612 expression was increased in the preterm groups. miR-612 has been shown to increase apoptosis in tumor cells and to regulate the nuclear factor κB inflammatory pathway, processes involved in PTL/PPROM pathogenesis. miR-1253, miR-1283, miR378e, and miR-579-3p, all associated with cellular senescence, were downregulated in PPROM compared with term pregnancies. We conclude that miRNAs from circulating sEV are differentially expressed between term and preterm pregnancies and modulate genes in pathways that are relevant to PTL/PPROM pathogenesis.

Essential oil from leaves of Myrciaria floribunda (H. West ex Willd.) O. Berg has antinociceptive and anti-inflammatory potential.

Myrciaria floribunda is a plant that is distributed across different Brazilian biomes such as the Amazon, Caatinga, Cerrado, and Atlantic Forest, and it possesses antioxidant, antimicrobial, and anticancer properties. The antinociceptive and anti-inflammatory properties of the essential oil from M. floribunda leaves (MfEO) were examined in this study using mouse models. Gas chromatography-mass spectrometry was employed to describe the oil, and the results revealed that δ-cadinene, bicyclogermacrene, α-cadinol, and epi-α-muurolol predominated in the chemical profile. The oil stimulated a decrease in nociception in the chemical and thermal models used to evaluate acute antinociceptive activity. Findings from the use of pain pathway blockers to study the presumed underlying mechanism indicated opioid pathway activity. The anti-edematogenic effect, decreased cell migration, and generation of pro-inflammatory cytokines provided evidence of the anti-inflammatory potential of the essential oil from M. floribunda. According to this research, the essential oil from M. floribunda can effectively alleviate acute pain and inflammation.