RID: Evaluation of the Possible Inhibiting Effect of the Proinflammatory Signaling Induced by TNF-α through NF-κß and AP-1 in Two Cell Lines of Breast Cancer.

Receptor internalization and degradation (RID), is a transmembrane protein coded within the E3 region expression cassette of adenoviruses. RID downregulates the cell surface expression of epidermal growth factor receptor (EGFR), tumor necrosis factor receptor (TNFR), and apoptosis antigen 1 (FAS), causing a reduction of the effects of their respective ligands. In addition, RID inhibits apoptosis by decreasing the secretion of TNF-related apoptosis-inducing ligand (TRAIL) by normal tissue cells. In this article, we report that RID inhibited chemokine expression in human breast cancer cell line MDA-MB-231 but showed no effect in cell line MCF7. These dissimilar results may be due to the different molecular and functional properties of both cell lines. Therefore, it is necessary to replicate this study in other breast cancer cell models.

Diphtheria outbreak in Maranhão, Brazil: microbiological, clinical and epidemiological aspects.

We describe microbiological, clinical and epidemiological aspects of a diphtheria outbreak that occurred in Maranhão, Brazil. The majority of the 27 confirmed cases occurred in partially (n = 16) or completely (n = 10) immunized children (n = 26). Clinical signs and characteristic symptoms of diphtheria such as cervical lymphadenopathy and pseudomembrane formation were absent in 48% and 7% of the cases, respectively. Complications such as paralysis of lower limbs were observed. Three cases resulted in death, two of them in completely immunized children. Microbiological analysis identified the isolates as Corynebacterium diphtheriae biovar intermedius with a predominant PFGE type. Most of them were toxigenic and some showed a decrease in penicillin G susceptibility. In conclusion, diphtheria remains endemic in Brazil. Health professionals need to be aware of the possibility of atypical cases of C. diphtheriae infection, including pharyngitis without pseudomembrane formation.

A case report and literature overview: Abiotrophia defectiva aortic valve endocarditis in developing countries.

A fatal case of aortic valve endocarditis due to Abiotrophia defectiva was reported in Brazil. An overview of cases of endocarditis and other human infections related to A. defectiva in developing countries was also accomplished.

Cellular senescence in brain aging and neurodegeneration.

Cellular senescence is a state of terminal cell cycle arrest associated with various macromolecular changes and a hypersecretory phenotype. In the brain, senescent cells naturally accumulate during aging and at sites of age-related pathologies. Here, we discuss the recent advances in understanding the accumulation of senescent cells in brain aging and disorders. Here we highlight the phenotypical heterogeneity of different senescent brain cell types, highlighting the potential importance of subtype-specific features for physiology and pathology. We provide a comprehensive overview of various senescent cell types in naturally occurring aging and the most common neurodegenerative disorders. Finally, we critically discuss the potential of adapting senotherapeutics to improve brain health and reduce pathological progression, addressing limitations and future directions for application and development.

Synthesis of novel fatty acid 3,4-dihydropyrimidin-2-(1H)-one and antitumoral activity against breast and gastric cancer cells.

Monastrol is the best-known small compound from the dihydropyrimidinones/thiones (DHPMs) heterocycle family, a cell-permeable molecule recognized as an inhibitor of mitotic kinesin Eg5, that is over-expressed in tumor cells and is a very promising target for the development of new drugs for cancer. The lipophilic properties of the DHPMs have been demonstrated to be of pivotal importance in the design of new molecules. This work describes the synthesis and antitumoral activity of novel C5-substituted fatty-DHPMs against breast and gastric cancer cell lines. The compounds were synthesized via Biginelli multicomponent reaction from oleyl ß-ketoester in good yields (40-72%) using a simple approach catalyzed by nontoxic and free-metal sulfamic acid. Among the compounds tested, the compound 10c, derived from 3-hydroxybenzaldehyde and urea, exhibited 77% cellular viability to normal cells (C2C12) and was selected to be evaluated against tumoral breast (MCF-7) and gastric (AGS) cell lines. The results obtained afforded an IC50 of breast cancer cells of 2.3 µM, qualifying the molecule as the most potent, and making it a promising compound for future experiments in vivo.

Cellular responses induced in vitro by pestheic acid, a fungal metabolite, in a gastric adenocarcinoma cell line (PG100).

There is a constant search for new cancer treatments that are less aggressive and economically affordable. In this context, natural products extracted from plants, fungi, and microorganisms are of great interest. Pestheic acid, or dihidromaldoxin, is a chlorinated diphenylic ether extracted from the phytopathogenic fungus Pestalotiopsis guepinii (Amphisphaeriaceae). We assessed the cytotoxic, cytostatic, and genotoxic effects of pestheic acid in a gastric adenocarcinoma cell line (PG100). A decrease in clonogenic survival was observed. Pestheic acid also induced significant increases in both micronucleus and nucleoplasmic bridge frequency. However, we did not observe changes in cell cycle kinetics or apoptosis induction. Reactive oxygen species induced by diphenylic ethers may explain the genotoxicity and mutagenicity of pestheic acid. The absence of repair checkpoints that we observed is probably due to the fact that the PG100 cell line lacks the TP53 gene, which is common in gastric cancers. Even though pestheic acid has had a clear cytotoxic effect, the minimal inhibitory concentration was high, which shows that pestheic acid is not an active anticancer compound under these conditions.

Antioxidant, anti-inflammatory and anti-obesity effects of onion and its by-products in high-fat fed rodents: a systematic review.

The effects of onion and its by-products on metabolic changes induced by excessive consumption of a high fat diet have been the focus of many studies. The aim of this study was to systematically review the effects of onion and its by-products antioxidant, anti-inflammatory and anti-obesity in rats exposed to a high-fat diet. Five databases were used: Pubmed, EMBASE, Science Direct, Web of science and Scopus until June 2020 updated December 1, 2022. Research of the articles was carried out by two reviewers, searching and selecting studies after an initial reading of the titles and abstracts. In total, 2,448 papers were found and, after assessing against the inclusion and exclusion criteria, 18 papers were selected for this review. The findings of this review show the beneficial effects of onion and its by-products on inflammatory parameters, obesity, cardiovascular disease, thermogenesis and hepatic alterations generally associated with the consumption of a high-fat diet.

Circulating monocytes expressing senescence-associated features are enriched in COVID-19 patients with severe disease.

Accurate biomarkers for predicting COVID-19 severity have remained an unmet need due to an incomplete understanding of virus pathogenesis and heterogeneity among patients. Cellular senescence and its pro-inflammatory phenotype are suggested to be a consequence of SARS-CoV-2 infection and potentially drive infection-dependent pathological sequelae. Senescence-associated markers in infected individuals have been identified primarily in the lower respiratory tract, while little is known about their presence in more easily accessible bio-specimens. Here, we measured the abundance of senescence-associated signatures in whole blood, plasma and peripheral blood mononuclear cells (PBMCs) of COVID-19 patients and patients without an infection. Bulk transcriptomic and targeted proteomic assays revealed that the level of senescence-associated markers, including the senescence-associated secretory phenotype (SASP), is predictive of SARS-CoV-2 infection. Single-cell RNA-sequencing data demonstrated that a senescence signature is particularly enriched in monocytes of COVID-19 patients, partially correlating with disease severity. Our findings suggest that monocytes are prematurely induced to senescence by SARS-CoV-2 infection, might contribute to exacerbating a SASP-like inflammatory response and can serve as markers and predictors for COVID-19 and its sequelae.

Multilocus sequence types of invasive Corynebacterium diphtheriae isolated in the Rio de Janeiro urban area, Brazil.

Invasive infections caused by Corynebacterium diphtheriae in vaccinated and non-vaccinated individuals have been reported increasingly. In this study we used multilocus sequence typing (MLST) to study genetic relationships between six invasive strains of this bacterium isolated solely in the urban area of Rio de Janeiro, Brazil, during a 10-year period. Of note, all the strains rendered negative results in PCR reactions for the tox gene, and four strains presented an atypical sucrose-fermenting ability. Five strains represented new sequence types. MLST results did not support the hypothesis that invasive (sucrose-positive) strains of C. diphtheriae are part of a single clonal complex. Instead, one of the main findings of the study was that such strains can be normally found in clonal complexes with strains related to non-invasive disease. Comparative analyses with C. diphtheriae isolated in different countries provided further information on the geographical circulation of some sequence types.

Mitochondrial lineages reveal intense gene flow between Iberian wild boars and South Iberian pig breeds.

The phylogeography of wild boars (WB) and domestic pigs (Sus scrofa) has contributed important insights into where and when domestication occurred. The geographic distribution of two core haplotypes (E1a and E1c) of the main European phylogenetic clade suggests that Central Europe was an early domestication centre, although the complexity of the pattern does not exclude the possibility that multiple domestication events occurred in different regions. To investigate the relationships among WB and domestic pig breeds in Iberia, a fragment of the mitochondrial DNA control region from a large sample (n=409) of WB and local pig breeds was co-analysed with published sequences from other European populations. The Iberian sample revealed a high frequency of a sub-cluster (E1c) of the European haplogroup E1 in 77% of total Iberian samples, 96% of WB, 90% of Alentejano (Portugal) and 87% of Iberian breed pigs (Spain; Black Hairy, Black Hairless and Red varieties). Low genetic distance (F'(ST) = 0.105) was observed between Alentejano (Portugal) and Iberian breed pigs (Spain). Alentejano and Iberian breed pigs showed low genetic distances to both Iberian and Central European WB (average F'(ST) =0.345 and 0.215, respectively). This pattern suggests that early pig husbandry in the Iberian Peninsula did not solely rely on imported Central European stock, but also included the recruitment of local WB.

Phenolic compounds and antifungal activity of ethyl acetate extract and methanolic extract from Capsicum chinense Jacq. ripe fruit.

Food loss due to contamination caused by fungi has much impact on agriculture and leads to significant economic losses. Synthetic and natural fungicides have been used for avoiding losses of several food products due to fungal contamination. As a result, species of the genus Capsicum have been used for preserving food because of their chemical compounds with antifungal activity. Therefore, this study aimed at identifying some phenolic compounds found in both ethyl acetate extract (EAE) and methanolic extract (ME) from habanero pepper (C. chinense) ripe fruit by liquid chromatography tandem mass spectrometry with electrospray ionization (LC-ESI-MS/MS) and at evaluating their antifungal activities against fungi Sclerotinia sclerotiorum, Rhizopus stolonifer and Colletotrichum gloeosporioides. Extracts resulted from a sequential process of maceration. Antifungal activity was evaluated by the disk diffusion method (DDM) at the following doses of both diluted extracts: 25 µL, 50 µL, 100 µL and 200 µL. The chemical analysis showed that there were protocatechuic acid, gentisic acid, vanillic acid, kaempferol-3-O-robinobiosideo and naringenin in both extracts. EAE showed high inhibition of mycelial growth at both doses 100µL and 200µL against the three fungi while methanolic exhibited weak activity even at the highest dose under investigation. However, further in-depth studies are needed to reinforce their uses and practical applications to the agricultural field.

Similarity of rpoB gene sequences of sucrose-fermenting and non-fermenting Corynebacterium diphtheriae strains.

During the last decades, the majority of Brazilian Corynebacterium diphtheriae isolates were shown to be capable to metabolize sucrose, sometimes leading to erroneous identification as a non-diphtheric Corynebacterium species. The sequencing of the polymorphic region of the RNA polymerase beta subunit-encoding gene (rpoB) is an important taxonomic tool for identification of corynebacteria. The present study aimed to investigate the rpoB gene polymorphic features of sucrose-fermenting and non sucrose-fermenting strains. The results showed that sucrose-fermenting strains presented rpoB gene polymorphic regions with more than 98% similarity with the sequences deposited in the gene bank corresponding to non sucrose-fermenting strains. Data indicate that sucrose-fermenting isolates may act as a variant of C. diphtheriae biotype mitis. In addition we alert that sucrose-fermenting strains should not be discarded as contaminants mainly in countries where the possibility of isolation of this variant is higher.

Transoperative glycemia in pets: validating old ones, and presenting lip mucosa as new sampling site.

The aim of our study was to investigate the viability and validity of blood sampling from the upper lip mucosa in healthy dogs and cats for monitoring transoperative glycemia and compare the results with those obtained from samples taken from previously described blood sampling sites for determination of glycemia using a glucose meter. Blood glucose (BG) levels were determined in samples taken from the upper lip mucosa of 24 dogs and 31 cats undergoing neutering or spaying surgeries. These values were compared to those of samples obtained from other sites previously described for capillary blood glucose monitoring (marginal ear vein, carpal pad in dogs, metacarpal pad in cats) using a glucose meter. Additionally, BG from peripheral venous blood was determined using a glucose meter, and the gold standard enzymatic colorimetric assay. The clinical reliability of BG values taken from lip mucosa and from all the other BG values measured by the glucose meter was evaluated using the error grid analysis modified by Parkes et al (2000). The upper lip mucosa was an easily accessible site for the obtainment of appropriate blood samples, and glucose levels read in these samples correlated positively with glycemic values read in blood samples from all other sites in dogs and cats. All BG made using glucose meters taken from all sites were within the clinically acceptable range when compared with enzymatic colorimetric assay (gold standard), and were analytically accurate according to the error grid (zones A and B). All blood sampling sites described in this work can be used to assess transoperative glycemia. The upper lip mucosa is a viable blood sampling site for precise monitoring of transoperative glycemia in healthy dogs and cats and shows promise for alternative blood glucose monitoring.

Crude glycerin in the supplementation of crossbred heifers in tropical pastures.

Crude glycerin (CG) is a biodiesel byproduct that has been tested as an alternative feed additive for use in beef production. After being absorbed, it is used in the liver to produce glucose, an important precursor of intramuscular fat in ruminants. This study aimed to evaluate the effect of CG (439 g/kg glycerol) on the performance and meat quality of crossbred heifers finished in Urochloa brizantha cv. Marandu. Thirty-six heifers with an initial BW of 301.5 ±â€¯23.02 kg were used. They were supplemented for 154 days with the following levels of CG: mineral mixture (without CG), 33.3, 66.6 and 99.9 g/kg CG in the DM of the supplement. Supplement or pasture DM intakes, slaughter BW and carcass traits were not influenced (P > 0.05) by increasing levels of CG. The total fat content of the meat, the vaccenic (18:1 n-7t) and conjugated linoleic acid (18:2 c9-t11) increased with the addition of CG in the diet (P < 0.05). Crude glycerin can be included up to 99.9 g/kg of the total diet without changing the performance of crossbred heifers finished in the tropical pasture.

Chemical composition, in vitro larvicidal and antileishmanial activities of the essential oil from Citrus reticulata Blanco fruit peel.

Numerous studies have investigated the chemical composition and biological activities of essential oils from different Citrus species fruit peel, leaves and flowers. This paper aims to investigate the chemical composition, larvicidal and antileishmanial activities of essential oil from Citrus reticulata fruit peel (CR-EO). CR-EO was obtained by hydrodistillation in a Clevenger-type apparatus and its chemical composition was analyzed by GC-MS and GC-FID. Limonene (85.7%), É£-terpinene (6.7%) and myrcene (2.1%) were identified as its major components. CR-EO showed high activity against promastigote forms of Leishmania amazonensis (IC50 = 8.23 µg/mL). CR-EO also exhibited high larvicidal activity against third instar Aedes aegypti larvae at a lethal concentration (LC50 = 58.35 µg/mL) and 100% mortality at 150 µg/mL. This study suggests, for the first time, the potential use of CR-EO against this important mosquito-borne viral disease caused by the genus Aedes.

Murinometric measurements and retroperitoneal adipose tissue in young rats exposed to the high-fat diet: Is there correlation?

AIM: This study aimed to verify the correlation between murine measurements and retroperitoneal adipose tissue in rats exposed to the high-fat diet. Material and methods: Wistar male adult rats, descendants of mothers who consumed a high-fat diet during pregnancy and lactation and fed the same diet after weaning were used. At 60 days of life, body weight, longitudinal axis and waist circumference (WC) were measured. The Body Mass Index (BMI) and the Lee Index were calculated for a posterior analysis of the correlation with the amount of retroperitoneal adipose tissue dissected on the same day. For analysis of the data, the Pearson correlation test was used, considering statistical significance for p <0.05. Results: Body weight had a weak correlation (r= 0.31; p= 0.38) with retroperitoneal adipose tissue. While the longitudinal correlated moderately and negative (r= -0.40; p= 0.25). Abdominal circumference (r= 0.62; p= 0.05), body mass index (r= 0.61; p= 0.03) and Lee (r= 0.69; p= 0.03) correlated moderately and positively with adipose tissue. Conclusion: Among the measured murine measurements, weight and longitudinal axis were not good indicators to represent accumulation of retroperitoneal adipose tissue in rats. However, Lee's index seems to be the best murine marker to diagnose the accumulation of retroperitoneal fat. BMI, CA and Lee index were murine parameters with higher correlation.

Perinatal exposure to a high-fat diet alters proopiomelanocortin, neuropeptide Y and dopaminergic receptors gene expression and the food preference in offspring adult rats.

Exposure to the hight-fat diet may alter the control of food intake promoting hyperphagia and obesity. The objective of this study was to investigate the effects of this diet on dopamine receptors (drd1 and drd2), proopiomelanocortin (pomc), neuropeptideY (npy) genes expression, and preference food in adult rats. Wistar female rats were fed a hight-fat or control diet during pregnancy and lactation. The offspring were allocated into groups: Lactation - Control (C) and High-fat (H). Post-weaning - Control Control (CC), offspring of mothers C, fed a control diet after weaning; Control Hight-fat (CH), offspring of mothers C, fed a hight-fat diet after weaning; Hight-fat Control (HC), offspring of mothers H, fed with control diet after weaning; and Hight-fat Hight-fat (HH), offspring of mothers H, fed a H diet after weaning. The groups CH and HH presented greater expression of drd1 in comparison to the CC. The drd2 of CH and HC presented higher gene expression than did CC. HH presented higher pomc expression in comparison to the other groups. HC also presented greater expression in comparison to CH. The npy of HH presented greater expression in relation to CH and HC. HH and HC have had a higher preference for a high-fat diet at 102º life's day. The high-fat diet altered the gene expression of the drd1, drd2, pomc and npy, and influencing the food preference for high-fat diet.

Toward better estimates of the real-time individual amino acid requirements of growing-finishing pigs showing deviations from their typical feeding patterns.

Pigs exposed to stressors might change their daily typical feeding intake pattern. The objective of this study was to develop a method for the early identification of deviations from an individual pig's typical feeding patterns. In addition, a general approach was proposed to model feed intake and real-time individual nutrient requirements for pigs with atypical feeding patterns. First, a dynamic linear model (DLM) was proposed to model the typical daily feed intake (DFI) and daily gain (DG) patterns of pigs. Individual DFI and DG dynamics are described by a univariate DLM in conjunction with Kalman filtering. A standardized tabular cumulative sum (CUMSUM) control chart was applied to the forecast errors generated by DLM to activate an alarm when a pig showed deviations from its typical feeding patterns. The relative feed intake (RFI) during a challenge period was calculated. For that, the forecasted individual pig DFI is expressed as its highest DFI relative to the intake during pre-challenge period. Finally, the DLM and RFI approaches were integrated into the actual precision-feeding model (original model) to estimate real-time individual nutrient requirements for pigs with atypical feeding patterns. This general approach was evaluated with data from two studies (130 pigs, at 35.25 ± 3.9 kg of initial BW) that investigated during 84 days the effect of precision-feeding systems for growing-finishing pigs. The proposed general approach to estimating real-time individual nutrient requirements (updated model) was evaluated by comparing its estimates with those generated by the original model. For 11 individuals out of 130, the DLM did not fit the observed data well in a specific period, resulting in an increase in the sum of standardized forecast errors and in the number of time steps that the model needed to adapt to the new patterns. This poor fit can be identified by the increase in the CUMSUM with a consequent alarm generated. The results of this study show that the updated model made it possible to reduce intra-individual variation for the estimated lysine requirements in comparison with the original model, especially for individuals with atypical feeding patterns. In conclusion, the DLM in conjunction with CUMSUM could be used as a tool for the online monitoring of DFI for growing-finishing pigs. Moreover, the proposed general approach allows the estimation of real-time amino acid requirements and accounts for the reduced feed intake and growth potential of pigs with atypical feeding patterns.

Phenolic compounds and antifungal activity of ethyl acetate extract and methanolic extract from Capsicum chinense Jacq. ripe fruit / Compostos fenólicos e atividade antifúngica dos extratos acetato de etila e metanólico dos frutos maduros de Capsicum chinense Jacq

Food loss due to contamination caused by fungi has much impact on agriculture and leads to significant economic losses. Synthetic and natural fungicides have been used for avoiding losses of several food products due to fungal contamination. As a result, species of the genus Capsicum have been used for preserving food because of their chemical compounds with antifungal activity. Therefore, this study aimed at identifying some phenolic compounds found in both ethyl acetate extract (EAE) and methanolic extract (ME) from habanero pepper (C. chinense) ripe fruit by liquid chromatography tandem mass spectrometry with electrospray ionization (LC-ESI-MS/MS) and at evaluating their antifungal activities against fungi Sclerotinia sclerotiorum, Rhizopus stolonifer and Colletotrichum gloeosporioides. Extracts resulted from a sequential process of maceration. Antifungal activity was evaluated by the disk diffusion method (DDM) at the following doses of both diluted extracts: 25 µL, 50 µL, 100 µL and 200 µL. The chemical analysis showed that there were protocatechuic acid, gentisic acid, vanillic acid, kaempferol-3-O-robinobiosideo and naringenin in both extracts. EAE showed high inhibition of mycelial growth at both doses 100µL and 200µL against the three fungi while methanolic exhibited weak activity even at the highest dose under investigation. However, further in-depth studies are needed to reinforce their uses and practical applications to the agricultural field.

As perdas de alimentos por contaminação causada por fungos são de grande impacto negativo para a agricultura, gerando altos prejuízos econômicos. Para evitar as perdas de diversos produtos alimentícios pela contaminação fúngica são utilizados fungicidas sintéticos e naturais. As espécies do gênero Capsicum são usadas há muitos anos para auxiliar na conservação de alimentos por possuírem substâncias químicas com ação antifúngica entre outras. Neste contexto, o objetivo deste estudo foi identificar alguns compostos fenólicos por cromatografia líquida de alta eficiência acoplada à espectrometria de massas sequencial (LC-ESI-MS/MS) presentes nos extratos acetato de etila (EAE) e metanólico (ME) dos frutos maduros da pimenta biquinho (C. chinense) e avaliar atividade antifúngica de EAE e ME contra os fungos Sclerotinia sclerotiorum, Rhizopus stolonifer e Colletotrichum gloeosporioides. Os extratos foram obtidos de forma sequencial, utilizando o procedimento de maceração. A atividade antifúngica foi avaliada seguindo a metodologia de difusão em disco, nas doses de 25 µL, 50 µL, 100 µL e 200 µL de cada extrato diluído. A análise química evidenciou a presença de ácido protocatequico, ácido gentisico, ácido vanílico, kaempferol-3-O-robinobiosídeo e naringenina em ambos os extratos. EAE revelou maior poder de inibição do crescimento micelial nas doses de 100µL e 200µL contra os três fungos testados, enquanto ME exibiu fraca atividade inclusive na maior dose investigada. Entretanto, estudos mais aprofundados ainda são necessários para consolidar seu uso e aplicação prática na área agronômica.