Antimalarial analysis of pharmaceutical formulations and biological samples by capillary electrophoresis: the state of the art and applications.

Malaria is a serious public health problem, being an endemic disease in 84 countries, mainly in Africa. This review explores the application of capillary electrophoresis (CE) techniques for analyzing antimalarial drugs, highlighting methods from 2000 to 2023 for the analysis of pharmaceutical formulations and human biological samples. The versatility, selectivity, high efficiency, cost-effectiveness, and high analytical frequency of CE techniques have become attractive choices for pharmaceutical analysis, focusing on quality control and impurity analysis applications. The evolution of achiral and chiral electromigration methods has been described based on the features of each mode of separation: capillary zone electrophoresis (CZE), micellar electrokinetic chromatography, microemulsion electrokinetic chromatography, and capillary electrochromatography. As expected, CZE is reported in most articles owing to its compatibility with drug properties and separation mode. However, it is necessary to perform other separation modes for a few drugs that are present in neutral form. After exhaustive research using different databases and statistical analyses, 27 articles using CE techniques for antimalarial drug analysis were found and are mentioned in this review.

A new standardization for the use of chicken embryo: selection of target from the phage display library and infection.

The filamentous bacteriophage M13KO7 (M13) is the most used in phage display (PD) technology and, like other phages, has been applied in several areas of medicine, agriculture, and in the food industry. One of the advantages is that they can modulate the immune response in the presence of pathogenic microorganisms, such as bacteria and viruses. This study evaluated the use of phage M13 in the chicken embryos model. We inoculated 13-day-old chicken embryos with Salmonella Pullorum (SP) and then evaluated survival for the presence of phage M13 or E. coli ER2738 (ECR) infected with M13. We found that the ECR bacterium inhibits SP multiplication in 0.32 (M13-infected ECR) or 0.44 log UFC/mL (M13-uninfected ECR) and that the ECR-free phage M13 from the PD library can be used in chicken embryo models. This work provides the use of the chicken embryo as a model to study systemic infection and can be employed as an analysis tool for various peptides that M13 can express from PD selection. KEY POINTS: • SP-infected chicken embryo can be a helpful model of systemic infection for different tests. • Phage M13 does not lead to embryonic mortality or cause serious injury to embryos. • Phage M13 from the PD library can be used in chicken embryo model tests.

Analysing chemical composition and antimicrobial activity of geopropolis from Melipona scutellaris: HPLC-DAD and in vitro/in silico investigations.

This study evaluated the chemical profile, antimicrobial activity, and the presence of potentially toxic elements in geopropolis extracts produced by Melipona scutellaris in the Recôncavo region of Bahia, Brazil. It was found that the major chemical compounds belong to the class of phenolic compounds, with emphasis on the presence of gallic acid. In this study, no potentially toxic elements were found in the analysed geopropolis. Regarding the antimicrobial potential, gram-positive bacteria were susceptible to the action of geopropolis extract at concentrations of 0.25 to 2.5 mg.mL-1, highlighting its microbiological activity against Streptococcus mitis (ATCC 00456) and Candida albicans (CCMB 251). Thus, this geopropolis extract can be used as a bacteriostatic rather than a bactericide. Our results suggest the potential for the economic and therapeutic use of M. scutellaris geopropolis, adding value to one of the meliponiculture products.

A combined experimental-molecular modeling study of crown ether europium complexes: Effects of the coordinated anion on structural and luminescence properties.

It is reported the synthesis, characterization by elemental analysis, thermogravimetry; electronic absorption, infrared, excitation, and emission spectroscopies of the [Eu(12C4)(phen)2(X)n]X2 complexes, where 12C4 = 12-crown-4, phen = 1,10-phenanthroline, and X  = F-, Cl-, Br-, SCN-, ClO4-, and NO3-. It is verified that the polarizability of the anion X- exerts remarkable effects on the emission process. As a general trend, lower wavenumbers for the 7F0→5L6, 7F0→5D2 and 7F0→5D1 transitions are associated with the anions with higher volumes and, consequently, higher polarizability. The molecular modeling results performed with quantum methods (RHF and DFT) suggest some relationships between the calculated structures, electronic, and luminescence properties with the presence of the LMCT (ligand-to-metal charge transfer) states, which explains the differences in the emission spectra of these complexes due to the coordinated anion.

Long-term mortality of critically ill patients with cancer and delirium who survived to discharge: a retrospective cohort study.

PURPOSE: Delirium is common in critically ill patients and has been associated with lower short-term survival; however, its association with long-term survival has been scarcely evaluated and few studies have shown divergent results. METHODS: We conducted a retrospective cohort study of adult patients with cancer admitted to the intensive care unit (ICU) and discharged from hospital from January 2015 to December 2018. We considered delirium present if the Confusion Assessment Method for Intensive Care Unit (CAM-ICU) result was positive. We assessed the association between delirium during ICU stay and long-term mortality (up to three years after discharge). We also assessed the association between delirium type (hypoactive, hyperactive, and mixed) with long-term mortality. RESULTS: We included 3,079 patients. Of these, 430 (14%) were considered delirious at some point during their ICU stay. Delirium was associated with one-year mortality after hospital discharge (hazard ratio [HR], 1.58; 95% confidence interval [CI], 1.36 to 1.83) after adjustment for potential confounders, but not with one to three year-mortality (HR, 0.92; 95% CI, 0.61 to 1.39). Hypoactive and mixed delirium were associated with one-year mortality (HR, 1.77; 95% CI, 1.46 to 2.14 and HR, 1.56; 95% CI, 1.21 to 2.00, respectively), but none of the delirium motor types was associated with one to three-year mortality. CONCLUSIONS: We observed that delirium during ICU stay was associated with increased one-year mortality, but was not with mortality after one year. This association was observed in hypoactive and mixed delirium types but not with hyperactive delirium.

RéSUMé: OBJECTIF: Le delirium est fréquent chez la patientèle gravement malade et a été associé à une survie réduite à court terme; son association avec la survie à long terme n'a cependant que très peu été évaluée et les rares études ont affiché des résultats divergents. MéTHODE: Nous avons mené une étude de cohorte rétrospective de patient·es adultes atteint·es de cancer admis·es à l'unité de soins intensifs (USI) et ayant reçu leur congé de l'hôpital entre janvier 2015 et décembre 2018. Nous avons considéré qu'un delirium était présent si le résultat de la Méthode d'évaluation de la confusion pour l'unité de soins intensifs (CAM-USI) était positif. Nous avons évalué l'association entre le delirium pendant le séjour aux soins intensifs et la mortalité à long terme (jusqu'à trois ans après le congé). Nous avons également évalué l'association entre le type de delirium (hypoactif, hyperactif et mixte) et la mortalité à long terme. RéSULTATS: Nous avons inclus 3079 patient·es. De ce nombre, 430 (14 %) personnes ont été considérées comme en delirium à un moment donné pendant leur séjour à l'USI. Le delirium était associé à la mortalité à un an après le congé de l'hôpital (rapport de risque [RR], 1,58; intervalle de confiance [IC] à 95%, 1,36 à 1,83) et après ajustement des données pour tenir compte des facteurs de confusion potentiels, mais pas à la mortalité d'un à trois ans après le congé (RR, 0,92; IC 95%, 0,61 à 1,39). Les deliriums hypoactif et mixte étaient associés à la mortalité à un an (RR, 1,77; IC 95 %, 1,46 à 2,14 et RR, 1,56; IC 95 %, 1,21 à 2,00, respectivement), mais aucun des types moteurs de delirium n'était associé à la mortalité d'un à trois ans. CONCLUSION: Nous avons observé qu'un delirium pendant le séjour à l'USI était associé à une augmentation de la mortalité à un an, mais pas à la mortalité après un an. Cette association a été observée dans les types de delirium hypoactif et mixte, mais pas avec le type hyperactif.

Factorial design applied to LC-ESI-QTOF mass spectrometer parameters for untargeted metabolomics.

Investigations of untargeted metabolomics are based on high-quality data acquisition usually from multiplatform systems that include high-resolution mass spectrometry equipment. The comprehensive set of results is used as data entry for bioinformatics and machine learning sciences to access reliable metabolic and biochemical information for clinical, forensic, environmental, and endless applications. In this context, design of experiments is a powerful tool for optimizing data acquisition procedures, using a multivariate approach, which enables the maximization of a high-quality amount of information with reduced number of tests. In this study, we applied a 33 Box-Behnken factorial design with central point triplicate for optimizing the ionization of an HPLC-ESI-QTOF method used for screening urine samples. Nozzle voltage (V), fragmentor voltage (V) and nebulizer pressure (psig) were the factors selected for variation. The response surface methodology was applied in the molecular features extracted at each level, resulting in a statistical model that helps evaluating the synergic interaction between these factors. Together with the qualitative analysis of the resulting total ion chromatograms, we came across a reproducible (6.14% RSD) and highly efficient method for untargeted metabolomics of human urine samples. The proposed method can be useful for applications in several urine-based metabolomics-driven studies, as the factorial design can be applied in the development of any analytical protocol considering different LC-MS setups.

Investigating interactive methods in remote chestfeeding support for lactation consulting professionals in Brazil.

Objective: Lactation consultants (LCs) positively impact chestfeeding rates by providing in-person support to struggling parents. In Brazil, LCs are a scarce resource and in high demand, risking chestfeeding rates across many communities nationwide. The transition to remote consultations during the COVID-19 pandemic made LCs face several challenges to solve chestfeeding problems due to limited technical resources for management, communication, and diagnosis. This study investigates the main technological issues LCs have in remote consultations and what technology features are helpful for chestfeeding problem-solving in remote settings. Methods: This paper implements qualitative investigation through a contextual study ( n = 10 ) and a participatory session ( n = 5 ) to determine stakeholders' preferences for technology features in solving chestfeeding problems. Findings: The contextual study with LCs in Brazil characterized (1) the current appropriation of technologies that help during consultations, (2) technology limitations that affect LCs' decision-making, (3) challenges and benefits of remote consultations, and (4) cases that are easy and difficult to solve remotely. The participatory session brings LCs' perceptions on (1) components for an effective remote evaluation, (2) preferred elements by professionals when providing remote feedback to parents, and (3) feelings about using technology resources for remote consultations. Conclusion: Findings suggest that LCs adapted their methodologies for remote consultations, and the perceived benefits of this modality show interest in continuing to provide remote care as long as more integrative and nurturing applications are offered to their clients. We learned that fully remote lactation care might not be the main objective for overall populations in Brazil, but as a hybrid mode of care that benefits parents by having both modalities of consultations available to them. Finally, remote support helps reduce financial, geographic, and cultural barriers in lactation care. However, future research must identify how generalized solutions for remote lactation care can be, especially for different cultures and regions.

Synthesis, solid state characterization, theoretical and experimental spectroscopic studies of the new lanthanide complexes.

Three new complexes Na[Ln(pic)4]ּ⋅2.5H2O (Ln = Tb, Eu or Gd; pic = picolinate) were synthesized and characterized by infrared spectroscopy, powder X-ray diffraction and thermogravimetric analyses. The molecular structures of the complexes have been determined by single-crystal X-ray diffraction. The three isostructural lanthanide complexes crystalize in the hexagonal system with space group P6122 to Eu complex and Gd complex and space group P6522 to Tb complex. In each of the complexes, the picolinate ligands are bonded to Ln3+ and Na+ ions by different coordination modes promoting polymeric structures. The photoluminescent properties of complexes were studied and combined with theoretical studies using the density functional theory (DFT: B3LYP, PBE1PBE) and the semiempirical method AM1/Sparkle from the single crystal X-ray diffraction structures to assign a suitable model for describing the system. The B3LYP DFT functional was considered the most adequate for providing structural properties of the compounds and for describing luminescence properties. The excited triplet states (T1) and excited singlet states (S1) of the ligand were determined theoretically using Time-dependent DFT calculations (TD-DFT: B3LYP, CAM-B3LYP and LC-wPBE) and INDO/S-CIS, with the best agreement with experimental values obtained from the LC-wPBE DFT functional. The photoluminescent spectra of the complexes and their lifetime measurements were determined indicating that the Eu complex and Tb complex display different intramolecular energy transfer mechanisms with higher efficiency to ligand-to-terbium energy transfer. In addition, the experimental and theorical Judd-Ofelt intensity parameters and quantum yields of the complexes were also determined and discussed besides to a proposed 9-state diagram to describe the luminescence properties of the Eu complex. The low value of emission quantum efficiency of 5D0 emitting level of Eu(III) ion was explained by the presence of the ligand-to-metal charge transfer state (LMCT) evidenced experimentally and theoretically. A good agreement was obtained between the proposed kinetic model and experimental results showing the consistency of the set of rate equations assumed and the intramolecular pathways proposed.

Roles of viable but non-culturable state in the survival of Campylobacter jejuni.

Despite being considered fragile and fastidious, Campylobacter jejuni is the most prevalent cause of foodborne bacterial gastroenteritis, and chicken meat is considered the main vehicle of transmission to humans. This agent can survive adverse conditions in the form of biofilms, but extreme stress (nutritional, oxidative and thermal) promotes the acquisition of a state called viable but not culturable (VBNC). The emergence of this pathogen worldwide and the recent international requirements in its control instigated us to qualitatively and quantitatively estimate the time required for the acquisition of the VBNC form in 27 strains of C. jejuni, characterize morphological aspects, determine its adaptive and invasive potential and perform comparative metabolomic evaluation. Extreme stress promoted the complete acquisition of the VBNC form in a mean time of 26 days. Starting from an average initial count of 7.8 log CFU/mL, the first four days determined the greatest average reduction of the culturable form of 3.2 log CFU/mL. The scanning and transmission image analyses showed a transition from the typical viable form (VT) to the VBNC form, with initial acquisition of the straight rod shape, followed by loss of the flagella and subdivision into two to 11 imperfect cocci arranged in a chain and rich in cellular content, until their individual release. RT-PCR identified the presence of ciaB and p19 transcripts in the 27 cultivable C. jejuni strains, a character maintained in the VBNC form only for p19 and in 59.3% (16/27) of the VBNC strains for the ciaB gene. The average inoculation of 1.8 log CFU/mL of C. jejuni VBNC into primary chicken embryo hepatocyte cells promoted the occurrence of apoptosis processes significantly after 24 hours of contact by one of the strains tested. In C. jejuni VBNC, we detected higher expression of metabolites linked to protective and adaptation mechanisms and of volatile organic precursor compounds indicative of metabolism interruption. The oscillations in the time of acquisition of the VBNC form together with the presence of transcripts for ciaB and p19, the identification of cell lysis and metabolites that ensure the maintenance of the pathogen alert to the fact that C. jejuni VBNC remains virulent and adapted to stress, which makes evident the potential danger of this latent form, which is not detectable by official methodologies.

Temperature Dependence of Hydrogen Bond Networks of Liquid Water: Thermodynamic Properties and Structural Heterogeneity from Topological Descriptors.

Topological analyses of hydrogen bond networks were performed based on the complex network and island statistics of liquid water at different temperatures. The influence of temperature on the liquid water structures and the topological properties of the hydrogen bond networks was investigated by Metropolis Monte Carlo simulations with the TIP4P/2005 potential model. The bilinear behavior of the second peak in the radial distribution function with the temperature was properly reproduced by these simulations. The average connectivity also displayed a bilinear behavior consistent with being a local descriptor. The semiglobal average path length (or geodesic distance) descriptor showed an unprecedented trimodal distribution, whose areas were dependent on the temperature. Considering equilibrium between these three sets of networks, standard enthalpy and entropy of equilibrium were determined for the first time, providing new insights into the structural heterogeneities of liquid water with interesting perspectives for modeling these quantitative properties of hydrogen bond networks.

Determination of creatinine in urine and blood serum human samples by CZE-UV using on-column internal standard injection.

Creatinine is a well-stablished biomarker for kidney malfunctions and for normalization parameter of urinary quantitative information. Recently, metabolic studies have been discovering other functionalities for creatinine tests in human urine and blood serum. In this work we present an enhanced capillary electrophoresis (CE) based protocol for determination of creatinine. CE is a high-throughput separation technique that have been getting attention through the last decades and might be considered to be adopted as an analytical instrumentation for clinical purposes. In the proposed method, we performed a short injection program with on-column addition of internal standard. Additionally, the method allows a simultaneous screening of non-proteinogenic amino acids that could be considered for metabolomics purposes. We design a pilot study that successfully estimated the creatinine value in 100 urine samples with (2.85 ± 1.78) mg dL-1 LOD; (8.24 ± 5.93) mg dL-1 LOQ and 82.4% accuracy. Considering that serum creatinine is also included in the clinical laboratory routines for estimated Glomerular Filtration Rate dosage, the method was complementary applied to 10 blood serum samples, which resulted in a model with (0.4 ± 0.2) mg dL-1 LOD; (2.0 ± 0.6) mg dL-1 LOQ and 83.8% of accuracy. All results were in agreement with reference values. The proposed method promotes a great analytical frequency and reproducibility with enhanced specificity compared with the ongoing protocol by Jaffe's reaction, thereby proving to be useful as an alternative for creatinine exams that might help complete a diagnosis of a series of health-related issues.

Antiplasmodial activity of coumarins isolated from Polygala boliviensis: in vitro and in silico studies.

Polygala boliviensis is found in the Brazilian semiarid region. This specie is little chemically and biologically studied. Polygala spp. have different metabolites, especially coumarins. Studies indicate that coumarins have antimalarial potential, denoting the importance of researching new active compounds from plants, since the resistance of Plasmodium strains to conventional therapy has increased. The present study aimed to evaluate the antiplasmodial activity of auraptene and poligalen against a chloroquine-resistant strain of Plasmodium falciparum. Coumarins were isolated from P. boliviensis by open column chromatography and identified by Nuclear Magnetic Resonance Spectroscopy. A cytotoxicity assay was carried out using MTT test, and the in vitro antiplasmodial activity was evaluated using the W2 strain. The antiplasmodial activity results found were IC50=0.171 ± 0.016 for auraptene and 0.164 ± 0.012 for poligalen; the selectivity indexes were 78.71 and 609.76, respectively. Inverse virtual screening in the BRAMMT database by OCTOPUS 1.2 was applied to coumarins to find potential P. falciparum targets and showed higher affinity energy of auraptene for purine nucleoside phosphorylase (PfPNP) and of poligalen for dihydroorotate dehydrogenase (PfDHODH). Molecular Dynamics studies (MD and MM-GBSA) approach were applied to calculate binding energies against selected P. falciparum targets and showed that all coumarins were stable at the binding site during simulations. Furthermore, energies were favorable for complexation. This is the first report of auraptene in P. boliviensis species and of in vitro antiplasmodial activity of auraptene and poligalen. In silico studies indicated that the mechanism of action of coumarins is the inhibition of PfPNP and PfDHODH.Communicated by Ramaswamy H. Sarma.

Sound stimulus effects on dusky damselfish behavior and cognition.

Anthropogenic noises are widespread and affect marine wildlife. Despite the growing knowledge on noise pollution in the marine environment, its effects on fish cognition are scarce. Here, we investigated the effects of sound exposure on anxiety-like behavior and memory retention on dusky damselfish Stegastes fuscus. The animals were trained in a conditioned place aversion task, and exposed to two daily sessions of music at intensities of 60-70 dBA or 90-100 dBA, while the control group was kept at 42-46 dBA (no music) for five days. After that, fish were tested in the novel tank paradigm and tested for the memory of the aversive task. In the novel tank, animals exposed to sound spent more time still and decreased the distance from the bottom of the tank. Animals also spent more time on the aversive side of the conditioning tank. These results suggest that anthropogenic noise applied through high-intensity music can increase anxiety and decrease memory retention in S. fuscus, suggesting the deleterious potential of noise for reef species.

In Utero Exposure to Zika Virus Results in sex-Specific Memory Deficits and Neurological Alterations in Adult Mice.

SUMMARY STATEMENT: In utero exposure to ZIKV leads to decreased number of neurons in adult mice. Female mice exposed to ZIKV in utero exhibit lower levels of BDNF, a decrease in synaptic markers, memory deficits, and risk-taking behavior during adulthood.

mGluR5 ablation leads to age-related synaptic plasticity impairments and does not improve Huntington's disease phenotype.

Glutamate receptors, including mGluR5, are involved in learning and memory impairments triggered by aging and neurological diseases. However, each condition involves distinct molecular mechanisms. It is still unclear whether the mGluR5 cell signaling pathways involved in normal brain aging differ from those altered due to neurodegenerative disorders. Here, we employed wild type (WT), mGluR5-/-, BACHD, which is a mouse model of Huntington's Disease (HD), and mGluR5-/-/BACHD mice, at the ages of 2, 6 and 12 months, to distinguish the mGluR5-dependent cell signaling pathways involved in aging and neurodegenerative diseases. We demonstrated that the memory impairment exhibited by mGluR5-/- mice is accompanied by massive neuronal loss and decreased dendritic spine density in the hippocampus, similarly to BACHD and BACHD/mGluR5-/- mice. Moreover, mGluR5 ablation worsens some of the HD-related alterations. We also show that mGluR5-/- and BACHD/mGluR5-/- mice have decreased levels of PSD95, BDNF, and Arc/Arg3.1, whereas BACHD mice are mostly spared. PSD95 expression was affected exclusively by mGluR5 ablation in the aging context, making it a potential target to treat age-related alterations. Taken together, we reaffirm the relevance of mGluR5 for memory and distinguish the mGluR5 cell signaling pathways involved in normal brain aging from those implicated in HD.

Detection of SARS-CoV-2 in different human biofluids using the loop-mediated isothermal amplification assay: A prospective diagnostic study in Fortaleza, Brazil.

We adopted the reverse-transcriptase-loop-mediated isothermal amplification (RT-LAMP) to detect severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) in patient samples. Two primer sets for genes N and Orf1ab were designed to detect SARS-CoV-2, and one primer set was designed to detect the human gene Actin. We collected prospective 138 nasopharyngeal swabs, 70 oropharyngeal swabs, 69 salivae, and 68 mouth saline wash samples from patients suspected to have severe acute respiratory syndrome (SARS) caused by SARS-CoV-2 to test the RT-LAMP in comparison with the gold standard technique reverse-transcription quantitative polymerase chain reaction  (RT-qPCR). The accuracy of diagnosis using both primers, N5 and Orf9, was evaluated. Sensitivity and specificity for diagnosis were 96% (95% confidence interval [CI]: 87-99) and 85% (95% CI: 76-91) in 138 samples, respectively. Accurate diagnosis results were obtained only in nasopharyngeal swabs processed via extraction kit. Accurate and rapid diagnosis could aid coronavirus disease 2019 (COVID-19) pandemic management by identifying, isolating, and treating patients rapidly.

Interleukin-6 Signaling in Triple Negative Breast Cancer Cells Elicits the Annexin A1/Formyl Peptide Receptor 1 Axis and Affects the Tumor Microenvironment.

Annexin A1 (AnxA1) is a pleiotropic protein that exerts essential roles in breast cancer (BC) growth and aggressiveness. In our previous work, we described the autocrine signaling of AnxA1 through formyl peptide receptor 1 (FPR1) in the triple-negative (TN) BC cell line, MDA-MB-231. Here, we aimed to describe the interaction between the AnxA1/FPR1 and the Interleukin-6 (IL-6) signaling pathways and their role in the tumor microenvironment (TME). First, we demonstrated that AnxA1 and IL-6 expression levels are correlated in BC tissue samples. In three TNBC cell lines, overexpression of both AnxA1 and IL-6 was also identified. Next, we inhibited FPR1, the IL-6 receptor and STAT3 in both MDA-MB-231 and MDA-MB-157 cells. The FPR1 inhibition led to increased levels of IL-6 and secreted AnxA1 in both cell lines. On the other side, inhibition of the IL-6 receptor or STAT3 led to the impairment of AnxA1 secretion, suggesting the essential role of the IL-6 signaling cascade in the activation of the AnxA1/FPR1 autocrine axis. Finally, we described the interaction between IL-6 and the AnxA1/FPR1 pathways and their role on the TME by analyzing the effect of supernatants derived from MDA-MB-231 and MDA-MB-157 cells under the inhibition of FPR1 or IL-6 signaling on fibroblast cell motility.

Metabotropic glutamate receptor 5 knockout rescues obesity phenotype in a mouse model of Huntington's disease.

Obesity represents a global health problem and is characterized by metabolic dysfunctions and a low-grade chronic inflammatory state, which can increase the risk of comorbidities, such as atherosclerosis, diabetes and insulin resistance. Here we tested the hypothesis that the genetic deletion of metabotropic glutamate receptor 5 (mGluR5) may rescue metabolic and inflammatory features present in BACHD mice, a mouse model of Huntington's disease (HD) with an obese phenotype. For that, we crossed BACHD and mGluR5 knockout mice (mGluR5-/-) in order to obtain the following groups: Wild type (WT), mGluR5-/-, BACHD and BACHD/mGluR5-/- (double mutant mice). Our results showed that the double mutant mice present decreased body weight as compared to BACHD mice in all tested ages and reduced visceral adiposity as compared to BACHD at 6 months of age. Additionally, 12-month-old double mutant mice present increased adipose tissue levels of adiponectin, decreased leptin levels, and increased IL-10/TNF ratio as compared to BACHD mice. Taken together, our preliminary data propose that the absence of mGluR5 reduce weight gain and visceral adiposity in BACHD mice, along with a decrease in the inflammatory state in the visceral adipose tissue (VAT), which may indicate that mGluR5 may play a role in adiposity modulation.

Mass spectrometry applied to diagnosis, prognosis, and therapeutic targets identification for the novel coronavirus SARS-CoV-2: A review.

Mass spectrometry (MS) has found numerous applications in medicine and has been widely used in the detection and characterization of biomolecules associated with viral infections such as COVID-19. COVID-19 is a multisystem disease and, therefore, the need arises to carry out a careful and conclusive assessment of the pathophysiological parameters involved in the infection, to develop an effective therapeutic approach, assess the prognosis of the disease, and especially the early diagnosis of the infected population. Thus, the urgent need for highly accurate methods of diagnosis and prognosis of this infection presents new challenges for the development of laboratory medicine, whose methods require sensitivity, speed, and accuracy of the techniques for analyzing the biological markers involved in the infection. In this context, MS stands out as a robust analytical tool, with high sensitivity and selectivity, accuracy, low turnaround time, and versatility for the analysis of biological samples. However, it has not yet been adopted as a frontline clinical laboratory technique. Therefore, this review explores the potential and trends of current MS methods and their contribution to the development of new strategies to COVID-19 diagnosis and prognosis and how this tool can assist in the discovery of new therapeutic targets, in addition, to comment what could be the future of MS in medicine.

Brazilian Theraphosidae: a toxicological point of view.

The Theraphosidae family includes the largest number of species of the Mygalomorphae infraorder, with hundreds of species currently catalogued. However, there is a huge lack on physiologic and even ecologic information available, especially in Brazil, which is the most biodiverse country in the world. Over the years, spiders have been presented as a source of multiple biologically active compounds with basic roles, such as primary defense against pathogenic microorganisms or modulation of metabolic pathways and as specialized hunters. Spider venoms also evolved in order to enable the capture of prey by interaction with a diversity of molecular targets of interest, raising their pharmaceutical potential for the development of new drugs. Among the activities found in compounds isolated from venoms and hemocytes of Brazilian Theraphosidae there are antimicrobial, antifungal, antiparasitic and antitumoral, as well as properties related to proteinase action and neuromuscular blockage modulated by ionic voltage-gated channel interaction. These characteristics are present in different species from multiple genera, which is strong evidence of the important role in spider survival. The present review aims to compile the main results of studies from the last decades on Brazilian Theraphosidae with special focus on results obtained with the crude venom or compounds isolated from both venom and hemocytes, and their physiological and chemical characterization.