Effect of senolytic drugs in young female mice chemically induced to estropause.

AIMS: This study aimed to assess metabolic responses and senescent cell burden in young female mice induced to estropause and treated with senolytic drugs. MAIN METHODS: Estropause was induced by 4-vinylcyclohexene diepoxide (VCD) injection in two-month-old mice. The senolytics dasatinib and quercetin (D + Q) or fisetin were given by oral gavage once a month from five to 11 months of age. KEY FINDINGS: VCD-induced estropause led to increased body mass and reduced albumin concentrations compared to untreated cyclic mice, without affecting insulin sensitivity, lipid profile, liver enzymes, or total proteins. Estropause decreased catalase activity in adipose tissue but had no significant effect on other redox parameters in adipose and hepatic tissues. Fisetin treatment reduced ROS levels in the hepatic tissue of estropause mice. Estropause did not influence senescence-associated beta-galactosidase activity in adipose and hepatic tissues but increased senescent cell markers and fibrosis in ovaries. Senolytic treatment did not decrease ovarian cellular senescence induced by estropause. SIGNIFICANCE: Overall, the findings suggest that estropause leads to minor metabolic changes in young females, and the senolytics D + Q and fisetin had no protective effects despite increased ovarian senescence.

MASLD does not affect fertility and senolytics fail to prevent MASLD progression in male mice.

Senescent cells have been linked to the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the effectiveness of senolytic drugs in reducing liver damage in mice with MASLD is not clear. Additionally, MASLD has been reported to adversely affect male reproductive function. Therefore, this study aimed to evaluate the protective effect of senolytic drugs on liver damage and fertility in male mice with MASLD. Three-month-old male mice were fed a standard diet (SD) or a choline-deficient western diet (WD) until 9 months of age. At 6 months of age mice were randomized within dietary treatment groups into senolytic (dasatinib + quercetin [D + Q]; fisetin [FIS]) or vehicle control treatment groups. We found that mice fed choline-deficient WD had liver damage characteristic of MASLD, with increased liver size, triglycerides accumulation, fibrosis, along increased liver cellular senescence and liver and systemic inflammation. Senolytics were not able to reduce liver damage, senescence and systemic inflammation, suggesting limited efficacy in controlling WD-induced liver damage. Sperm quality and fertility remained unchanged in mice developing MASLD or receiving senolytics. Our data suggest that liver damage and senescence in mice developing MASLD is not reversible by the use of senolytics. Additionally, neither MASLD nor senolytics affected fertility in male mice.

New curcumin-loaded nanocapsules as a therapeutic alternative in an amnesia model.

This study aimed to investigate the action of two different formulations of curcumin (Cur)-loaded nanocapsules (Nc) (Eudragit [EUD] and poly (ɛ-caprolactone) [PCL]) in an amnesia mice model. We also investigated the formulations' effects on scopolamine-induced (SCO) depressive- and anxiety-like comorbidities, the cholinergic system, oxidative parameters, and inflammatory markers. Male Swiss mice were randomly divided into five groups (n = 8): group I (control), group II (Cur PCL Nc 10 mg/kg), group III (Cur EUD Nc 10 mg/kg), group IV (free Cur 10 mg/kg), and group V (SCO). Treatments with Nc or Cur (free) were performed daily or on alternate days. After 30 min of treatment, the animals received the SCO and were subjected to behavioral tests 30 min later (Barnes maze, open-field, object recognition, elevated plus maze, tail suspension tests, and step-down inhibitory avoidance tasks). The animals were then euthanized and tissue was removed for biochemical assays. Our results demonstrated that Cur treatment (Nc or free) protected against SCO-induced amnesia and depressive-like behavior. The ex vivo assays revealed lower acetylcholinesterase (AChE) and catalase (CAT) activity, reduced thiobarbituric species (TBARS), reactive species (RS), and non-protein thiols (NSPH) levels, and reduced interleukin-6 (IL-6) and tumor necrosis factor (TNF) expression. The treatments did not change hepatic markers in the plasma of mice. After treatments on alternate days, Cur Nc had a more significant effect than the free Cur protocol, implying that Cur may have prolonged action in Nc. This finding supports the concept that it is possible to achieve beneficial effects in nanoformulations, and treatment on alternate days differs from the free Cur protocol regarding anti-amnesic effects in mice.

ß-Cyclodextrins alter the energy metabolism-related enzyme activities in rats.

Although widely used in medicine, separation technology, and other fields, the effects of cyclodextrins on the activities of phosphoryl transfer enzymes have not been previously evaluated. In vivo studies evaluated the function of cyclodextrins as active compounds. Despite the use of cyclodextrins as active compounds, the effects of cyclodextrins on hepatic and renal tissues remain to be fully elucidated. The primary objective of this study was to evaluate the effects of ß- cyclodextrins, methyl-ß-cyclodextrin (M-ß- cyclodextrins), and (2-hydroxypropyl)-ß-cyclodextrin (HP-ß-cyclodextrins) on enzyme activities regulating the maintenance of energy homeostasis in the kidney and liver tissues in relation to toxicity. Serum levels of liver and kidney markers were measured, and oxidative stress parameters were assessed. After 60-day treatments, we observed that the administration of ß-cyclodextrins and M-ß-cyclodextrins inhibited the hepatic activity of pyruvate kinase, an irreversible enzyme within the glycolytic pathway. Additionally, administration of HP-ß-cyclodextrins inhibited creatine kinase activity and increased the total sulfhydryl content in kidneys. Here, we demonstrated for the first time that ß-cyclodextrins, M-ß-cyclodextrins, and HP-ß-cyclodextrins cause bioenergetic dysfunction in renal and hepatic tissues. These findings suggest that understanding the balance between cyclodextrins' efficacy and adverse effects is essential for better accepting their use in medicine.

MicroRNA qPCR normalization in Nile tilapia (Oreochromis niloticus): Effects of acute cold stress on potential reference targets.

The Nile tilapia (Oreochromis niloticus) is one of the most important cultured fish worldwide, but tilapia culture is largely affected by low temperatures. Recent studies suggest that microRNAs (miRNAs) regulate cold tolerance traits in fish. In general, qPCR-based methods are the simplest and most accurate forms of miRNA quantification. However, qPCR data heavily depends on appropriate normalization. Therefore, the aim of the present study is to determine whether the expression of previously tested, stably expressed miRNAs are affected by acute cold stress in Nile tilapia. For this purpose, one small nuclear RNA (U6) and six candidate reference miRNAs (miR-23a, miR-25-3, Let-7a, miR-103, miR-99-5, and miR-455) were evaluated in four tissues (blood, brain, liver, and gills) under two experimental conditions (acute cold stress and control) in O. niloticus. The stability of the expression of each candidate reference miRNA was analyzed by four independent methods (the delta Ct method, geNorm, NormFinder, and BestKeeper). Further, consensual comprehensive ranking of stability was built with RefFinder. Overall, miR-103 was the most stable reference miRNA in this study, and miR-103 and Let-7a were the best combination of reference targets. Equally important, Let-7a, miR-23a, and miR-25-3 remained consistently stable across different tissues and experimental groups. Considering all variables, U6, miR-99-5, and miR-455 were the least stable candidates under acute cold stress. Most important, suitable reference miRNAs were validated in O. niloticus, facilitating further accurate miRNA quantification in this species.

Carrageenan from Gigartina skottsbergii: A Novel Molecular Probe to Detect SARS-CoV-2.

The COVID-19 pandemic has caused an unprecedented health and economic crisis, highlighting the importance of developing new molecular tools to monitor and detect SARS-CoV-2. Hence, this study proposed to employ the carrageenan extracted from Gigartina skottsbergii algae as a probe for SARS-CoV-2 virus binding capacity and potential use in molecular methods. G. skottsbergii specimens were collected in the Chilean subantarctic ecoregion, and the carrageenan was extracted -using a modified version of Webber's method-, characterized, and quantified. After 24 h of incubation with an inactivated viral suspension, the carrageenan's capacity to bind SARS-CoV-2 was tested. The probe-bound viral RNA was quantified using the reverse transcription and reverse transcription loop-mediated isothermal amplification (RT-LAMP) methods. Our findings showed that carrageenan extraction from seaweed has a similar spectrum to commercial carrageenan, achieving an excellent proportion of binding to SARS-CoV-2, with a yield of 8.3%. Viral RNA was also detected in the RT-LAMP assay. This study shows, for the first time, the binding capacity of carrageenan extracted from G. skottsbergii, which proved to be a low-cost and highly efficient method of binding to SARS-CoV-2 viral particles.

Reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay as a rapid molecular diagnostic tool for COVID-19 in healthcare workers.

In December 2019, the Chinese Center for Disease Control (CDC of China) reported an outbreak of pneumonia in the city of Wuhan (Hubei province, China) that haunted the world, resulting in a global pandemic. This outbreak was caused by a betacoronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several of these cases have been observed in healthcare professionals working in hospitals and providing care on the pandemic's frontline. In the present study, nasopharyngeal swab samples of healthcare workers were used to assess the performance of the reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay and subsequently compared with the real-time reverse-transcription quantitative PCR (RT-qPCR) method. Thus, in this study, we validated a method for detecting SARS-CoV-2 based on RT-LAMP that can be used to diagnose these workers. The methodology used was based on analyzing the sensitivity, specificity, evaluation of the detection limit, and cross-reaction with other respiratory viruses. The agreement was estimated using a dispersion diagram designed using the Bland-Altman method. A total of 100 clinical specimens of nasopharyngeal swabs were collected from symptomatic and asymptomatic healthcare workers in Pelotas, Brazil, during the SARS-CoV-2 outbreak. RT-LAMP assay, it was possible to detect SARS-CoV-2 in 96.7% of the healthcare professionals tested using the E gene and N gene primers approximately and 100% for the gene of human ß-actin. The observed agreement was considered excellent for the primer set of the E and N genes (k = 0.957 and k = 0.896), respectively. The sensitivity of the RT-LAMP assay was positive for the primer set of the E gene, detected to approximately 2 copies per reaction. For the primer set of the N gene, the assay was possible to verify an LoD of approximately 253 copies per reaction. After executing the RT-LAMP assay, no positive reactions were observed for any of the virus respiratory tested. Therefore, we conclude that RT-LAMP is effective for rapid molecular diagnosis during the COVID-19 outbreak period in healthcare professionals.

SARS-CoV-2 removal with a polyurethane foam composite.

The pandemic of COVID-19 (SARS-CoV-2 disease) has been causing unprecedented health and economic impacts, alerting the world to the importance of basic sanitation and existing social inequalities. The risk of the spread and appearance of new diseases highlights the need for the removal of these pathogens through efficient techniques and materials. This study aimed to develop a polyurethane (PU) biofoam filled with dregs waste (leftover from the pulp and paper industry) for removal SARS-CoV-2 from the water. The biofoam was prepared by the free expansion method with the incorporation of 5wt% of dregs as a filler. For the removal assays, the all materials and its isolated phases were incubated for 24 h with an inactivated SARS-CoV-2 viral suspension. Then, the RNA was extracted and the viral load was quantified using the quantitative reverse transcription (RT-qPCR) technique. The biofoam (polyurethane/dregs) reached a great removal percentage of 91.55%, whereas the isolated dregs waste was 99.03%, commercial activated carbon was 99.64%, commercial activated carbon/polyurethane was 99.30%, and neat PU foam reached was 99.96% for this same property and without statistical difference. Those new materials endowed with low cost and high removal efficiency of SARS-CoV-2 as alternatives to conventional adsorbents.

Higher frequency of specific periodontopathogens in hypertensive patients. A pilot study.

Periodontitis and arterial hypertension are two of the pathologies with the highest global prevalence; evidence reported so far has been favorable to an association between them. This cross-sectional study aimed to evaluate and compare the microbiological counts of hypertensive and normotensive patients with periodontitis. Sociodemographic, behavioral, systemic health data and periodontal clinical parameters were assessed. Counts of A. actinomycetemcomitans, P. intermedia, P. gingivalis and F. nucleatum were performed by real-time polymerase chain reaction using subgingival biofilm samples. Thirty-eight patients were included in this preliminary analysis, divided into two groups: Normotensive Group (NG) (n = 14) and Hypertensive Group (HG) (n = 24). Patients diagnosed with periodontitis composed both groups. Data analysis was performed with significance level of 5%. There was no significant difference between groups for clinical periodontitis diagnosis. In addition, hypertensive individuals had higher P. intermedia, P. gingivalis, and F. nucleatum counts when compared to normotensive individuals. The parameters probing pocket depth, bleeding on probing, and A. actinomycetemcomitans count did not presented statistical differences between groups. With these preliminary results, it can be concluded that the presence of arterial hypertension may be associated with a greater quantity of periodontopathogenic bacterial of some species in individuals with periodontitis.

Higher frequency of specific periodontopathogens in hypertensive patients. A pilot study

Abstract Periodontitis and arterial hypertension are two of the pathologies with the highest global prevalence; evidence reported so far has been favorable to an association between them. This cross-sectional study aimed to evaluate and compare the microbiological counts of hypertensive and normotensive patients with periodontitis. Sociodemographic, behavioral, systemic health data and periodontal clinical parameters were assessed. Counts of A. actinomycetemcomitans, P. intermedia, P. gingivalis and F. nucleatum were performed by real-time polymerase chain reaction using subgingival biofilm samples. Thirty-eight patients were included in this preliminary analysis, divided into two groups: Normotensive Group (NG) (n = 14) and Hypertensive Group (HG) (n = 24). Patients diagnosed with periodontitis composed both groups. Data analysis was performed with significance level of 5%. There was no significant difference between groups for clinical periodontitis diagnosis. In addition, hypertensive individuals had higher P. intermedia, P. gingivalis, and F. nucleatum counts when compared to normotensive individuals. The parameters probing pocket depth, bleeding on probing, and A. actinomycetemcomitans count did not presented statistical differences between groups. With these preliminary results, it can be concluded that the presence of arterial hypertension may be associated with a greater quantity of periodontopathogenic bacterial of some species in individuals with periodontitis.

Resumo A periodontite e a hipertensão arterial são duas das patologias com maior prevalência global, as evidências relatadas até o momento têm sido favoráveis ​​a uma associação entre elas. Este estudo transversal teve como objetivo avaliar e comparar contagem microbiológicas de pacientes hipertensos e normotensos com periodontite. Dados sociodemográficos, comportamentais, de saúde sistêmica e parâmetros clínicos periodontais foram avaliados. Contagens de A. actinomycetemcomitans, P. intermedia, P. gingivalis e F. nucleatum foram realizadas por reação em cadeia da polimerase em tempo real utilizando amostras de biofilme subgengival. Trinta e oito pacientes foram incluídos nesta análise preliminar, divididos em dois grupos: Grupo Normotenso (GN) (n = 14) e Grupo Hipertenso (GH) (n = 24). Pacientes diagnosticados com periodontite compuseram os dois grupos. A análise dos dados foi realizada com nível de significância de 5%. Não houve diferença significativa entre os grupos para o diagnóstico clínico de periodontite. Além disso, os hipertensos apresentaram maior contagem de P. intermedia, P. gingivalis e F. nucleatum quando comparados aos normotensos. Os parâmetros profundidade de sondagem, sangramento à sondagem e contagem de A. actinomycetemcomitans não apresentaram diferenças estatísticas entre os grupos. Com esses resultados preliminares, pode-se concluir que a presença de hipertensão arterial pode estar associada a uma maior quantidade de bactérias periodontopatogênicas de algumas espécies em indivíduos com periodontite.

Chronic cold exposure modulates genes related to feeding and immune system in Nile tilapia (Oreochromis niloticus).

Nile tilapia is the fourth most produced species in the global aquiculture panorama. This species requires water temperatures higher than 16 °C to grow and survive, and so, little is known about the effects of low temperatures on genes related to food intake and inflammatory responses. This study brought insights about the modulation of genes in different tissues of Nile tilapia chronically exposed to low temperatures. Thus, sixty animals were divided in two experimental groups: a control group in which the animals remained at the optimum temperature of 24 °C; and an exposed to cold group, in which a decrease in the water temperature was applied until reaching 15 °C. These conditions were maintained for 28 days. Blood samples were collected for flow cytometry analysis, while brain, spleen, liver, and kidney tissues were collected for total RNA extraction, followed by quantitative PCR (RT-qPCR). For genes related to feeding process pathway, it was observed an upregulation in pyy and a downregulation of npy and cart gene expression. Also, pro-inflammatory cytokine genes were modulated in the spleen, kidney and liver with a higher expression of il-1b and tnfα and a reduction in the il-8 and nf-κß gene expressions in the group exposed to 15 °C. The fish exposed to cold presented higher serum cortisol levels than the ones from control group. The blood cell analysis showed a lower level of membrane fluidity and a higher DNA fragmentation and cell disruption in the group exposed to cold. These findings suggest an important effect of a stressful situation in the tilapia organism due to cold exposure. This study brings insights on tilapia wellbeing under low temperature stress. It can be a first step to understanding the appropriate way to cope with cold impacts on aquaculture.

Brief dispersion of a putative B.1.1.28-derived SARS-CoV-2 lineage harboring additional N234P and E471Q spike protein mutations in individuals crossing the Argentina-Brazil border.

BACKGROUND: SARS-CoV-2, the virus that causes COVID-19, is constantly mutating, leading to new variants that culminate in a temporal lineages fluctuation. B.1.1.28 lineage has been evolving in Brazil since February 2020 and originated P.1 (VOC), P.2 (VOI) and other P.Xs proposed as new variants. METHODS AND RESULTS: In this study, through the Illumina platform, we performed the whole-genome sequencing of 26 positive samples of SARS-CoV-2. Employing variant calling analysis on FASTQ reads and phylogenetic inference, we report a brief dispersion of a potentially new B.1.1.28-derived variant detected between 2021 May and June in individuals crossing the border between Brazil and Argentina, and local spread to inpatients from hospitals at the Rio Grande do Sul state capital (Porto Alegre). Besides, the Rio Grande do Sul State SARS-CoV-2 genomic epidemiological data was analyzed and showed an important B.1.1.28 peak in RS at the same period (May-June), even in the presence of a major Gamma wave. CONCLUSIONS: The emergence of a putative B.1.1.28-derived lineage was identified in travelers crossing Brazil-Argentina border representing an important peak of B.1.1.28 in RS State with a decreased in Gamma variant frequency in the same period of time.

New low-cost biofilters for SARS-CoV-2 using Hymenachne grumosa as a precursor.

The ongoing global spread of COVID-19 (SARS-CoV-2 2019 disease) is causing an unprecedented repercussion on human health and the economy. Despite the primary mode of transmission being through air droplets and contact, the transmission via wastewater is a critical concern. There is a lack of techniques able to provide complete disinfection, along with the uncertainty related to the behavior of SARS-CoV-2 in the natural environment and risks of contamination. This fact makes urgent the research towards new alternatives for virus removal from water and wastewater. Thus, this research aimed to characterize new lost-cost adsorbents for SARS-CoV-2 using Hymenachne grumosa as a precursor and verify its potential for removing SARS-CoV-2 from the solution. The aquatic macrophyte H. grumosa had in natura and activated carbon produced with H. grumosa and zinc chloride (ZnCl2,1:1) impregnation and carbonization (700 °C, 1 h) were incubated for 24 h with inactivated SARS-CoV-2 viral suspension, and then the ribonucleic acid (RNA) was extracted and viral load quantified through reverse transcription-quantitative polymerase chain reaction (RT-qPCR) technique. The results demonstrated the great adsorption potential, achieving removal of 98.44% by H. grumosa "in natura", and 99.61% by H. grumosa with carbon activation, being similar to commercial activated carbon (99.67%). Thus, this study highlights the possibility of low-cost biofilters to be used for SARS-CoV-2 removal, as an excellent alternative for wastewater treatment or watercourses decontamination.

Detection of SARS-CoV-2 virus using an alternative molecular method and evaluation of biochemical, hematological, inflammatory, and oxidative stress in healthcare professionals.

In early December 2019, an outbreak of coronavirus disease 2019 caused by a new strain of coronavirus (SARS-CoV-2), occurred in the city of Wuhan, Hubei Province, China. On January 30, 2020, the World Health Organization (WHO) declared the outbreak a public health emergency of international concern. Since then, frontline healthcare professionals have been experiencing extremely stressful situations and damage to their physical and mental health. These adverse conditions cause stress and biochemical, hematological, and inflammatory changes, as well as oxidative damage, and could be potentially detrimental to the health of the individual. The study population consisted of frontline health professionals working in BHU in a city in southern Brazil. Among the 45 participants, two were infected with the SARS-CoV-2 virus and were diagnosed using immunochromatographic tests such as salivary RT-LAMP and qRT-PCR. We also evaluated biochemical, hematological, inflammatory, and oxidative stress markers in the participants. The infected professionals (CoV-2-Prof) showed a significant increase in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol, lactic dehydrogenase, lymphocytes, and monocytes. In this group, the levels of uric acid, triglycerides, leukocytes, neutrophils, hemoglobin, hematocrit, and platelets decreased. In the group of uninfected professionals (NoCoV-2-Prof), significant increase in HDL levels and the percentages of eosinophils and monocytes, was observed. Further, in this group, uric acid, LDH, triglyceride, and cholesterol levels, and the hematocrit count and mean corpuscular volume were significantly reduced. Both groups showed significant inflammatory activity with changes in the levels of C-reactive protein and mucoprotein. The NoCoV-2-Prof group showed significantly elevated plasma cortisol levels. To our kowledge, this study is the first to report the use of the RT-LAMP method with the saliva samples of health professionals, to evalute of SARS-CoV-2.

Bioactivity and composition of lipophilic metabolites extracted from Antarctic macroalgae.

Macroalgae comprise a vast group of aquatic organisms known for their richness in phytochemicals. In this sense, the lipophilic profile of five Antarctic seaweed species was characterized by chromatographic and spectroscopic analysis and their antioxidant and antimicrobial potential was evaluated. Results showed there were 31 lipophilic substances, mainly fatty acids (48.73 ± 0.77 to 331.91 ± 10.79 mg.Kg-1), sterols (14.74 ± 0.74 to 321.25 ± 30.13 mg.Kg-1), and alcohols (13.07 ± 0.04 to 91.87 ± 30.07 mg.Kg-1). Moreover, Desmarestia confervoides had strong antioxidant activity, inhibiting 86.03 ± 1.47% of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical at 1 mg.mL-1. Antimicrobial evaluation showed that extracts from Ulva intestinalis, Curdiea racovitzae, and Adenocystis utricularis inhibited the growth of Escherichia coli (ATCC 25922), Staphylococcus aureus (ATCC 25923), and Salmonella typhimurium (ATCC 14028) from concentrations of 1.5 to 6 mg.mL-1. Therefore, the evaluated brown, red, and green macroalgae contained several phytochemicals with promising biological activities that could be applied in the pharmaceutical, biotechnological, and food industries.

Bioprospection of novel synthetic monocurcuminoids: Antioxidant, antimicrobial, and in vitro cytotoxic activities.

The irrational use of medications has increased the incidence of microbial infections, which are a major threat to public health. Moreover, conventional therapeutic strategies are starting to become ineffective to treat these infections. Hence, there is a need to develop and characterize novel antimicrobial compounds. Phytochemicals are emerging as a safe and accessible alternative to conventional therapeutics for treating infectious diseases. Curcumin is extracted from the dried rhizome of the spice turmeric (Curcuma longa (Zingiberaceae)). However, the bioavailability of curcumin is low owing to its lipophilic property and thus has a low therapeutic efficacy in the host. A previous study synthesized structural variants of curcumin, which are called monocurcuminoids (CNs). CNs are synthesized based on the chemical structure of curcumin with only one methyl bridge. The biological activities of four previously synthesized CNs (CN59, CN63, CN67, and CN77), curcumin, and turmeric powder were examined in this study. Gas chromatography-tandem mass spectrometry analysis of curcumin and turmeric powder revealed similar peaks, which indicated the presence of curcumin in turmeric powder. The antioxidant activity of the test compounds was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) assays. The ABTS radical scavenging activities of the test compounds were similar to those of vitamin C. The minimum inhibitory concentration (MIC) values of the test compounds against seven microbial strains were in the range of 4.06-150 µg/mL. The MIC value was equal to minimum bactericidal concentration value for CN63 (150 µg/mL) and CN67 (120 µg/mL) against Staphylococcus aureus. The treatment combination of CN77 (8.75 or 4.37 µg/mL) and turmeric powder (9.37 or 4.68 µg/mL) exerted synergistic growth-inhibiting effects on Aeromonas hydrophila, Candida albicans, and Pseudomonas aeruginosa. Photodynamic therapy using 2X MIC of CN59 decreased the growth of Enterococcus faecalis by 4.18-fold compared to the control group and completely inhibited the growth of Escherichia coli. The results of the hemolytic assay revealed that the test compounds were not cytotoxic with half-maximal inhibitory concentration values ranging from 49.65-130.9 µM. The anticoagulant activity of most compounds was comparable to that of warfarin but higher than that of heparin. This indicated that these compounds target the intrinsic coagulation pathway. These results demonstrated that these CNs are a safe and promising alternative for curcumin.

Toxicological response of silver catfish (Rhamdia quelen) after acute exposure to a commercial insecticide containing thiamethoxam.

This study assessed the hematological, enzymatic and osmoregulatory responses of silver catfish (Rhamdia quelen) exposed to sublethal concentrations (1.125 and 3.750 µg/L) of a commercial thiamethoxam-containing insecticide used on rice crops. Groups of 6 fish per tank (in triplicate, n = 3, total 54 fish) were exposed for up to 96 h to different concentrations of the compound. After this period, fish were placed in clean water for 48 h. Two fish from each tank (6 per treatment) that had been exposed to the insecticide for 24 h were anesthetized with eugenol and blood was collected to evaluate hematological and biochemical parameters. Blood, liver and muscle were collected for determination of metabolic parameters, plasma cortisol, Cl-, Na+ and K+ levels and H+-ATPase and Na+/K+-ATPase activity in the gill. H+-ATPase activity was higher in fish exposed to 1.125 µg/L insecticide at 24 h compared to control (0.0 µg/L). Differences in cortisol levels were evidenced throughout the experimental period. These results indicated that exposure to the insecticide changed the hematological, biochemical and metabolic profile of the animals, suggesting concern about environmental safety. Therefore, we discourage the use of this pesticide in areas that come into contact with water bodies inhabited by fish.

Lipid-core nanocapsules containing simvastatin improve the cognitive impairment induced by obesity and hypercholesterolemia in adult rats.

The development of cognitive impairment may be related to high levels of plasma cholesterol and obesity. Simvastatin (SV) and lovastatin (LV) are drugs that can potentially be used for the treatment of cognitive deficit. This study aimed to develop and characterize lipid-core nanocapsules (LNC) containing SV (SV-LNC) or LV (LV-LNC), evaluating the effects of SV-LNC in an animal model of cognitive deficit. The formulations SV-LNC and LV-LNC presented a particle average size around 200 nm, a low-polydispersity index, and negative zeta potential. Analysis of differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray diffraction, and scanning electron microscopy showed that there is no reaction among LNC components: LV was crystallized in the suspensions, and SV was molecularly dispersed. The encapsulation efficiency of the SV was high (98.9 ± 1.4%), while that of the LV was low (21.5 ± 1.5%).Based on these results, SV-LNC was used in the preclinical studies. Animals fed with a hyperlipidic diet (HD) developed obesity, hypercholesterolemia, and cognitive impairment, which was corroborated by the brain lesions indicated by histological analysis of some of the animals that received the high-fat diet. We observed that free simvastatin (CS3) was able to reduce the enzymatic activity of pyruvate kinase, an important enzyme for brain energy homeostasis, without affecting the memory of the animals that received a standard diet. However, it failed to improve the cognitive damage caused by a diet high in cholesterol and saturated fats. On the other hand, when simvastatin is "camouflaged" in the lipid-core nanocapsules (HNS3), this cognitive impairment improves. Thus, SV-LNC is a promising alternative therapy for the treatment of cognitive impairment.

Low frataxin mRNA expression is associated with inflammation and oxidative stress in patients with type 2 diabetes.

BACKGROUND: The mitochondrial protein frataxin is involved in iron metabolism, as well as regulation of oxidative stress. To elucidate the association of frataxin with the pathophysiology of diabetes, we evaluated the mRNA levels of frataxin in leukocytes of patients with type 2 diabetes (T2D). In addition, we investigated the relation between frataxin mRNA levels, inflammatory cytokines, and oxidative stress biomarkers. METHODS: A study including 150 subjects (115 patients with T2D and 35 healthy subjects) was performed to evaluate the frataxin mRNA levels in leukocytes. We assessed the relation between frataxin and interleukin (IL)-6, IL-1, tumour necrosis factor-alpha (TNF-α), total oxidation status (TOS), total antioxidant capacity (TAC), and serum iron. RESULTS: The frataxin mRNA levels in the T2D group were significantly lower than those in healthy subjects. It was also demonstrated that T2D patients with frataxin mRNA levels in the lowest quartile had significantly elevated levels of serum iron, TOS, and inflammatory cytokines, such as TNF-α, IL-1, and IL-6, while TAC levels were significantly lower in this quartile when compared with the upper quartile. CONCLUSIONS: Our findings showed that T2D patients with low frataxin mRNA levels showed a high degree of inflammation and oxidative stress. It is speculated that frataxin deficiency in T2D patients can contribute to the imbalance in mitochondrial iron homeostasis leading to the acceleration of oxidative stress and inflammation.