Isoflurane increases the activity of the vascular matrix metalloproteinase-2 in non-pregnant rats and increases the nitric oxide metabolites in pregnancy.

Surgeries that require general anesthesia occur in 1.5-2% of gestations. Isoflurane is frequently used because of its lower possibility of affecting fetal growth. Therefore, we examined the isoflurane anesthesia-induced effects on maternal hemodynamic and vascular changes. We hypothesized that isoflurane would enhance endothelium-dependent vasodilation as a consequence of increased nitric oxide and decreased metalloproteinases (MMPs). Female rats (n=28) were randomized into 4 groups (7 rats/group): conscious (non-anesthetized) non-pregnant group, non-pregnant anesthetized group, conscious pregnant group, and pregnant anesthetized group. Anesthesia was performed on the 20th pregnancy day, and hemodynamic parameters were monitored. Nitric oxide metabolites, gelatinolytic activity of MMP-2 and MMP-9, and the vascular function were assessed. Isoflurane caused no significant hemodynamic changes in pregnant compared with non-pregnant anesthetized group. Impaired acetylcholine-induced relaxations were observed only in conscious non-pregnant group (by approximately 62%) versus 81% for other groups. Phenylephrine-induced contractions were greater in endothelium-removed aorta segments of both pregnant groups (with or without isoflurane) compared with non-pregnant groups. Higher nitric oxide metabolites were observed in anesthetized pregnant in comparison with the other groups. Reductions in the 75 kDa activity and concomitant increases in 64 kDa MMP-2 isoforms were observed in aortas of pregnant anesthetized (or not) groups compared with conscious non-pregnant group. Isoflurane anesthesia shows stable effects on hemodynamic parameters and normal MMP-2 activation in pregnancy. Furthermore, there were increases in nitric oxide bioavailability, suggesting that isoflurane provides protective actions to the endothelium in pregnancy.

An Intricate Network Involving the Argonaute ALG-1 Modulates Organismal Resistance to Oxidative Stress.

Cellular response to redox imbalance is crucial for organismal health. microRNAs are implicated in stress responses. ALG-1, the C. elegans ortholog of human AGO2, plays an essential role in microRNA processing and function. Here we investigated the mechanisms governing ALG-1 expression in C. elegans and the players controlling lifespan and stress resistance downstream of ALG-1. We show that upregulation of ALG-1 is a shared feature in conditions linked to increased longevity (e.g., germline-deficient glp-1 mutants). ALG-1 knockdown reduces lifespan and oxidative stress resistance, while overexpression enhances survival against pro-oxidant agents but not heat or reductive stress. R02D3.7 represses alg-1 expression, impacting oxidative stress resistance at least in part via ALG-1. microRNAs upregulated in glp-1 mutants (miR-87-3p, miR-230-3p, and miR-235-3p) can target genes in the protein disulfide isomerase pathway and protect against oxidative stress. This study unveils a tightly regulated network involving transcription factors and microRNAs which controls organisms' ability to withstand oxidative stress.

Applications of high-intensity ultrasound on shrimp: Potential, constraints, and prospects in the extraction and retrieval of bioactive compounds, safety, and quality.

The global shrimp market holds substantial prominence within the food industry, registering a significant USD 24.7 billion in worldwide exportation in 2020. However, the production of a safe and high-quality product requires consideration of various factors, including the potential for allergenic reactions, occurrences of foodborne outbreaks, and risks of spoilage. Additionally, the exploration of the recovery of bioactive compounds (e.g., astaxanthin [AX], polyunsaturated fatty acids, and polysaccharides) from shrimp waste demands focused attention. Within this framework, this review seeks to comprehend and assess the utilization of high-intensity ultrasound (HIUS), both as a standalone method and combined with other technologies, within the shrimp industry. The objective is to evaluate its applications, limitations, and prospects, with a specific emphasis on delineating the impact of sonication parameters (e.g., power, time, and temperature) on various applications. This includes an examination of undesirable effects and identifying areas of interest for current and prospective research. HIUS has demonstrated promise in enhancing the extraction of bioactive compounds, such as AX, lipids, and chitin, while concurrently addressing concerns such as allergen reduction (e.g., tropomyosin), inactivation of pathogens (e.g., Vibrio parahaemolyticus), and quality improvement, manifesting in reduced melanosis scores and improved peelability. Nonetheless, potential impediments, particularly related to oxidation processes, especially those associated with lipids, pose a hindrance to its widespread implementation, potentially impacting texture properties. Consequently, further optimization studies remain imperative. Moreover, novel applications of sonication in shrimp processing, including brining, thawing, and drying, represent a promising avenue for expanding the utilization of HIUS in the shrimp industry.

Oil-in-water emulsion loaded with optimized antioxidant blend improved the shelf-life of trout (Oncorhynchus mykiss) fillets: a study with simplex-centroid design.

This study aimed to obtain optimized mixture with three essential oils (EOs) for maximum antioxidant activity through the augmented simplex-centroid mixture design and evaluate the effect of this optimized blend on total aerobic psychrotrophic count (TAPC), lipid and protein oxidation, instrumental color parameters and texture profile in rainbow trout fillets at refrigerated storage for nine days. Considering the DPPH and FRAP assays, the ideal EO blend was 66% lemongrass and 34% oregano. During refrigerated storage, this blend at 2000 ppm was equally effective as BHT (100 ppm) (p > 0.05), mitigating the discoloration (a* and b*), lipid, and protein oxidation in 38.83%, 12.95%, 76.13%, and 35.13%, respectively, besides shows greater effectiveness for preserving texture changes (p < 0.05) and extending the shelf life in 13 h. The lemongrass + oregano EO blend reveals a promising natural alternative to enhance the quality of rainbow trout fillets under refrigerated storage. Furthermore, the multiresponse optimization showed to be a strong ally in enabling the use of these EOs by food industries.

Tissue-specific overexpression of systemic RNA interference components limits lifespan in C. elegans.

Intertissue RNA transport recently emerged as a novel signaling mechanism. In mammals, mounting evidence suggests that small RNA transfer between cells is widespread and used in various physiological contexts. In the nematode C. elegans, a similar mechanism is conferred by the systemic RNAi pathway. Members of the Systemic RNA Interference Defective (SID) family act at different steps of cellular RNA uptake and export. The limiting step in systemic RNA interference (RNAi) is the import of extracellular RNAs via the conserved double-stranded (dsRNA)-gated dsRNA channel SID-1. To better understand the role of RNAs as intertissue signaling molecules, we modified the function of SID-1 in specific tissues of C. elegans. We observed that sid-1 loss-of-function mutants are as healthy as wild-type worms. Conversely, overexpression of sid-1 in C. elegans intestine, muscle, or neurons rendered worms short-lived. The effects of intestinal sid-1 overexpression were attenuated by silencing the components of systemic RNAi sid-1, sid-2 and sid-5, implicating systemic RNA signaling in the lifespan reduction. Accordingly, tissue-specific overexpression of sid-2 and sid-5 also reduced worm lifespan. Additionally, an RNAi screen for components of several non-coding RNA pathways revealed that silencing the miRNA biogenesis proteins PASH-1 and DCR-1 rendered the lifespan of worms with intestinal sid-1 overexpression similar to controls. Collectively, our data support the notion that systemic RNA signaling must be tightly regulated, and unbalancing that process provokes a reduction in lifespan. We termed this phenomenon Intercellular/Extracellular Systemic RNA imbalance (InExS).

An ERK5-PFKFB3 axis regulates glycolysis and represents a therapeutic vulnerability in pediatric diffuse midline glioma.

Metabolic reprogramming in pediatric diffuse midline glioma is driven by gene expression changes induced by the hallmark histone mutation H3K27M, which results in aberrantly permissive activation of oncogenic signaling pathways. Previous studies of diffuse midline glioma with altered H3K27 (DMG-H3K27a) have shown that the RAS pathway, specifically through its downstream kinase, extracellular-signal-related kinase 5 (ERK5), is critical for tumor growth. Further downstream effectors of ERK5 and their role in DMG-H3K27a metabolic reprogramming have not been explored. We establish that ERK5 is a critical regulator of cell proliferation and glycolysis in DMG-H3K27a. We demonstrate that ERK5 mediates glycolysis through activation of transcription factor MEF2A, which subsequently modulates expression of glycolytic enzyme PFKFB3. We show that in vitro and mouse models of DMG-H3K27a are sensitive to the loss of PFKFB3. Multi-targeted drug therapy against the ERK5-PFKFB3 axis, such as with small-molecule inhibitors, may represent a promising therapeutic approach in patients with pediatric diffuse midline glioma.

TIM-3 blockade in diffuse intrinsic pontine glioma models promotes tumor regression and antitumor immune memory.

Diffuse intrinsic pontine glioma (DIPG) is an aggressive brain stem tumor and the leading cause of pediatric cancer-related death. To date, these tumors remain incurable, underscoring the need for efficacious therapies. In this study, we demonstrate that the immune checkpoint TIM-3 (HAVCR2) is highly expressed in both tumor cells and microenvironmental cells, mainly microglia and macrophages, in DIPG. We show that inhibition of TIM-3 in syngeneic models of DIPG prolongs survival and produces long-term survivors free of disease that harbor immune memory. This antitumor effect is driven by the direct effect of TIM-3 inhibition in tumor cells, the coordinated action of several immune cell populations, and the secretion of chemokines/cytokines that create a proinflammatory tumor microenvironment favoring a potent antitumor immune response. This work uncovers TIM-3 as a bona fide target in DIPG and supports its clinical translation.

Sevoflurane and isoflurane anesthesia induce redox imbalance, but only sevoflurane impairs vascular contraction.

Volatile anesthetics may cause vascular dysfunction; however, underlying effects are unclear. The aim of the present study was to investigate whether sevoflurane and isoflurane affect vascular function, nitric oxide (NO) bioavailability, and biomarkers of oxidative stress and inflammation. Wistar rats were divided into three experimental groups: Not anesthetized (control group) or submitted to anesthesia with isoflurane (Iso group) or sevoflurane (Sevo group). Hemodynamic parameters were monitored during anesthesia, and blood gas values and biochemical determinants were analyzed. Isometric contractions were recorded in aortic rings. Vasoconstriction induced by potassium chloride (KCl) and phenylephrine (Phe) were measured. No differences in hemodynamic parameters and blood gasses variables were observed. Impaired KCl and Phe-induced contractions were observed in endothelium-intact aorta of Sevo compared to Iso and Control groups. Redox imbalance was found in Sevo and Iso groups. Reduced NO bioavailability and increased activity of matrix metalloproteinase 2 (MMP-2) were observed in Sevo, but not in the Iso group. While reduced IL-10 and IL-1ß were observed in Sevo, increases in IL-1ß in the Iso group were found. Sevoflurane, but not isoflurane, anesthesia impairs vasocontraction, and reduced NO and cytokines and increased MMP-2 activity may be involved in vascular dysfunction after sevoflurane anesthesia.

Experimental Yellow Fever in Squirrel Monkey: Characterization of Liver In Situ Immune Response.

Non-human primates contribute to the spread of yellow fever virus (YFV) and the establishment of transmission cycles in endemic areas, such as Brazil. This study aims to investigate virological, histopathological and immunohistochemical findings in livers of squirrel monkeys (Saimiri spp.) infected with the YFV. Viremia occurred 1-30 days post infection (dpi) and the virus showed a predilection for the middle zone (Z2). The livers were jaundiced with subcapsular and hemorrhagic multifocal petechiae. Apoptosis, lytic and coagulative necrosis, steatosis and cellular edema were also observed. The immune response was characterized by the expression of S100, CD11b, CD57, CD4 and CD20; endothelial markers; stress and cell death; pro and anti-inflammatory cytokines, as well as Treg (IL-35) and IL-17 throughout the experimental period. Lesions during the severe phase of the disease were associated with excessive production of apoptotic pro-inflammatory cytokines, such as IFN-γ and TNF-α, released by inflammatory response cells (CD4+ and CD8+ T lymphocytes) and associated with high expression of molecules of adhesion in the inflammatory foci observed in Z2. Immunostaining of the local endothelium in vascular cells and the bile duct was intense, suggesting a fundamental role in liver damage and in the pathogenesis of the disease.

Lab-made 3D printed electrochemical sensors coupled with chemometrics for Brazilian coffee authentication.

Analytical assurance of coffees' geographical indication (GI) authenticity is essential for producers and consumers. In this way, chemometric methods, electrochemical techniques, and 3D printed sensors become attractive to assure the coffee's quality. These sensors are low-cost, fast, and simple, with the possibility of miniaturization and portability. Therefore, 3D printed electrodes with chemometrics were used to classify-three Brazilian coffees from regions with GI. Further, Au/Gpt-PLA electrodes with partial least squares regression were used to detect the blending of GI coffee with traditional coffee. Soft independent modelling of class analogies coupled with cyclic voltammetry had the best performance, with 91-95% accuracy, specificity of 94-100%, and 80-83% sensitivity. Furthermore, the calibration models detected and quantified traditional coffee in all three coffees from regions with GI. The detection limits ranged from 1.4 to 10% (w/w), and quantification 4.6-32%, depending on the specific coffee.

Large-scale genomic analysis reveals the pESI-like megaplasmid presence in Salmonella Agona, Muenchen, Schwarzengrund, and Senftenberg.

Salmonella spp. remains one of the main pathogens causing diarrhea in humans worldwide. Lately, Salmonella Infantis has become endemic in several European, American, and Asian countries, presenting a multi-drug resistance profile and increased virulence. Various studies have attributed the high endemicity of Salmonella Infantis to pESI (plasmid to Emergent Salmonella Infantis). The ease of Salmonella to acquire pESI is of concern to health authorities and the food production chain. We searched for the presence of pESI in Salmonella genomes from the NCBI to understand the distribution of pESI worldwide and predict the main serovars and sequence types associated with the plasmid. We identified the pESI backbone, virulence, and resistance genes among Salmonella spp. isolated from 45 countries on five continents. We found the pESI-like structure in four different serovars: S. Muenchen, S. Schwarzengrund, S. Agona and S. Senftenberg. The pESI markers were also identified in 24 different sequence types. Most of the analyzed genomes were isolated from poultry, especially broiler and chicken. These results confirm the high dissemination of pESI-like megaplasmid among Salmonella Infantis worldwide and its ability to infect different serovars, as well as placing poultry production as the most favorable environment for pESI dissemination. Therefore, further studies are needed to prevent the spread of pESI to humans and the food chain.

Health from Brazilian Amazon food wastes: Bioactive compounds, antioxidants, antimicrobials, and potentials against cancer and oral diseases.

Brazilian Amazon contains over 30,000 plant species and foods rich in bioactive compounds such as terpenes, phenolic acids, alkaloids, and flavonoids, of potential health benefits (antioxidant, antimicrobial, antiparasitic, anticancer, gastroprotection, prebiotic effects, among others). The existence of residues from non-edible parts of plants (leaves, roots, stems, branches, barks) or fruit wastes (peel, bagasse, seeds) in the agri-food industry and its supply chain is an important challenge in food loss and waste management. In this critical review several Amazon species, focusing on extracts/essential oils from nonedible parts or wastes, were analyzed in terms of phytochemicals, biological activity, and underlying mechanisms. We hope this review emphasizes the importance of Amazon's sustainability initiatives on population health due to the potential shown against cancer, infectious diseases, and prevention of oral diseases. It is urgent to think about the conversion of amazon food wastes and co-products into high-added-value raw materials to develop novel drugs, food packaging systems, or nutraceutical foods.

Multivariate Nature of Fish Freshness Evaluation by Consumers.

The aim of the present study was to evaluate the sensory acceptability limit of refrigerated fish through a multivariate approach, involving classic physicochemical and bacteriological indicators and considering different consumer profiles. The results of the survival analysis demonstrated that, in general, consumers still considered the fish to be suitable for purchase (4.128 days of storage), despite being microbiologically unsuitable for consumption. However, the subsequent division of consumers into clusters indicated that women and individuals with high income and education levels tend to reject fish with few days of storage (3.650 days), mainly due to discoloration, despite still being microbiologically suitable for consumption. Thus, these segments present a safer behavior regarding the purchase of fresh fish. The influence of different frequencies of fish consumption and age of consumers on the assessment of fish freshness was not clarified. The responsibility for ensuring safe and healthy products at the point of sale must lie with the producers and distributors. However, improving consumers' ability to make good choices when buying fresh fish would bring social and economic benefits related to public health and to the seafood industry, because it would enable them to make relevant claims and demand their rights.

Pequi (Caryocar brasiliense) Waste Extract as a Synergistic Agent in the Microbial and Physicochemical Preservation of Low-Sodium Raw Goat Cheese.

The growth of spoilage and pathogenic bacteria during storage represents significant losses in marketing raw milk cheeses. Thus, reducing NaCl in these products is challenging, as sodium has a critical antimicrobial role. Despite advances in non-thermal technologies, the short shelf life still limits the availability of raw goat cheese. Thus, combined preservation methods can be promising because their synergies can extend shelf life more effectively. In this context, Principal Component Analysis (PCA) was applied to variables to investigate the effect of pequi waste extract (PWE), a native Brazilian fruit, combined with UV-C radiation (CEU) and vacuum packaging (CEV) on the preservation of low-sodium raw goat cheese. CEV samples had lower loadings for Staphylococcus subsp. and Enterobacteriaceae than other treatments in PC2, having a count's reduction up to 3-fold (P < 0.05) compared to vacuum alone. In contrast, CEU showed an increase of up to 1.2-fold on staphylococcal count compared to UV-C alone. Still, the addition of PWE to UV-C-treated cheeses resulted in 8.5% protein loss. Furthermore, PWE, especially in CEV, delayed post-acidification during storage. It made CEV up to 4.5 and 1.6-fold more stable for color and texture, respectively than vacuum alone. These data strongly suggest that PWE may be a novel and promising synergistic agent in the microbial and physicochemical preservation of low-sodium raw milk cheese when combined with the vacuum.

A single screen-printed electrode in tandem with chemometric tools for the forensic differentiation of Brazilian beers.

In the present study a single screen-printed carbon electrode (SPCE) and chemometric techniques were utilized for forensic differentiation of Brazilian American lager beers. To differentiate Brazilian beers at the manufacturer and brand level, the classification techniques: soft independent modeling of class analogy (SIMCA), partial least squares regression discriminant analysis (PLS-DA), and support vector machines discriminant analysis (SVM-DA) were tested. PLS-DA model presented an inconclusive assignment ratio of 20%. On the other hand, SIMCA models had a 0 inconclusive rate but an sensitivity close to 85%. While the non-linear technique (SVM-DA) showed an accuracy of 98%, with 95% sensitivity and 98% specificity. The SPCE-SVM-DA technique was then used to distinguish at brand level two highly frauded beers. The SPCE coupled with SVM-DA performed with an accuracy of 97% for the classification of both brands. Therefore, the proposed electrochemicalsensor configuration has been deemed an appropriate tool for discrimination of American lager beers according to their producer and brands.

Rheological, Physical and Sensory Evaluation of Low-Fat Cupuassu Goat Milk Yogurts Supplemented with Fat Replacer.

The use of skim milk is a strategy to increase goat milk yogurt acceptability. However, it can negatively affect yogurt rheology because fat plays a vital role in dairy structural integrity. Thus, this study aimed to investigate the effects of fat replacers on the rheological, physical, and sensory parameters of low-fat cupuassu goat milk yogurts during refrigerated storage (28 days). Five goat milk yogurts formulations were carried out: whole yogurt (WY), skim yogurt (SY), skim yogurt with inulin (SIY), skim yogurt with maltodextrin (SMY), and skim yogurt with whey protein (SWY). Treatments were subjected to bacterial counts, chemical composition, pH, water holding capacity, instrumental color and texture, rheological and sensory analyses. All samples showed reducing pH values, water holding capacity, and L* and b* value during storage. Regarding texture, the firmness and consistency decreased during storage. On the other hand, the viscosity index significantly increased during refrigerated storage time. Moreover, all treatments exhibited viscoelastic behaviour. In addition, SIY and SMY showed the highest apparent viscosity. Furthermore, SIY, SMY, and SWY formulations exhibited positive sensory scores for appearance, color, aroma, texture, and viscosity. However, the overall acceptability and purchase intention did not differ statistically between WY and the fat-replacement treatments (SIY, SMY, and SWY). These results indicate that fat substitutes improved the quality of skimmed formulations. Thus, inulin and maltodextrin have the potential as functional fat replaces to produce low-fat goat milk yogurts.

What Do Consumers Think About Foods Processed by Ultraviolet Radiation and Ultrasound?

This study aimed to investigate Brazilian consumers' perception concerning foods processed by ultraviolet (UV) radiation and ultrasound (US) and define consumer segments considering their socioeconomic characteristics and eating habits towards industrialized products through free word association tasks answered by 1004 participants via an online platform. UV- and US-treated foods were more frequently related to unfamiliar words/terms (21.51 and 36.95%) and negative associations (36.25 and 26.70%) than positive ones (29.89 and 24.20%), respectively. Unfamiliarity and health risk concerns were more reported for US-treated foods by women aged 18-25 and ≥46 with low income, and low and frequent industrialized products consumption, as well as for UV-treated foods by consumers ≤35 years old with low and medium income, and low and frequent industrialized products consumption. This indicates that more clear and trustworthy information is needed before introducing these products in the Brazilian market, mainly for potential target consumer groups identified in this study.

Reproductive plasticity and oogenesis in the queen honey bee (Apis mellifera).

In the honey bee (Apis mellifera), queen and worker castes originate from identical genetic templates but develop into different phenotypes. Queens lay up to 2000 eggs daily whereas workers are sterile in the queen's presence. Periodically queens stop laying: during swarming, when resources are scarce in winter, and when they are confined to a cage by beekeepers. We used confocal microscopy and gene expression assays to investigate the control of oogenesis in the ovaries of honey bee queens that were caged inside and outside the colony. We find evidence that queens use a different combination of 'checkpoints' to regulate oogenesis compared to honey bee workers and other insect species. However, both queen and worker castes likely use the same programmed cell death pathways to terminate oocyte development at their caste-specific checkpoints. Our results also suggest that a key factor driving the termination of oogenesis in queens is nutritional stress. Thus, queens may regulate oogenesis via the same regulatory pathways that were utilised by ancestral solitary species but likely have adjusted physiological checkpoints to suit their highly-derived life history.

Bioactive Compounds from Kefir and Their Potential Benefits on Health: A Systematic Review and Meta-Analysis.

Despite evidence of health benefits from kefir administration, a systematic review with meta-analysis on bioactive compounds associated with these benefits is still absent in the literature. Kefir is fermented milk resulting from the metabolism of a complex microbiota in symbiosis. Recent researches have investigated the bioactive compounds responsible for the preventive and therapeutic effects attributed to kefir. However, differences in functional potential between industrial and artisanal kefir are still controversial. Firstly, we identified differences in the microbial composition among both types of kefir. Available evidence concerning the action of different bioactive compounds from kefir on health, both from in vitro and in vivo studies, was subsequently summarized to draw a primary conclusion of the dose and the intervention time for effect, the producer microorganisms, the precursor in the milk, and the action mechanism. Meta-analysis was performed to investigate the statistically significant differences (P < 0.05) between intervention and control and between both types of kefir for each health effect studied. In summary, the bioactive compounds more commonly reported were exopolysaccharides, including kefiran, bioactive peptides, and organic acids, especially lactic acid. Kefir bioactive compounds presented antimicrobial, anticancer, and immune-modulatory activities corroborated by the meta-analysis. However, clinical evidence is urgently needed to strengthen the practical applicability of these bioactive compounds. The mechanisms of their action were diverse, indicating that they can act by different signaling pathways. Still, industrial and artisanal kefir may differ regarding functional potential-OR of 8.56 (95% CI: 2.27-32.21, P ≤ .001)-according to the observed health effect, which can be associated with differences in the microbial composition between both types of kefir.