Investigation of the activity of 4-aminoquinolines as cysteine protease inhibitors with application in the treatment of Chagas disease.

Background: Chagas disease (CD) is a neglected tropical disease caused by Trypanosoma cruzi. The current drugs used to treat these diseases have limited efficacy and produce severe side effects. 4-aminoquinoline derivatives were shown to be a promising class of inhibitors of cysteine proteases cruzain and TbrCATL.

IL-1β enhances susceptibility to atrial fibrillation in mice by acting through resident macrophages and promoting caspase-1 expression.

Atrial fibrillation (AF) is more prevalent in patients with elevated interleukin (IL)-1β levels. Here we show that daily administration of IL-1β for 15 days sensitizes mice to AF, leading to fibrosis, accumulation of β-pleated sheet proteins in the left atrium, and systemic inflammation, resembling the pathophysiological changes observed in patients with AF. IL-1β administration creates a positive feedback loop, dependent on the IL-1 receptor (IL-1R) activity in cardiac resident macrophages.

Characterization of resistance to Bacillus thuringiensis toxin Cry1Ac in Crocidosema sp. (Lepidoptera: Tortricidae) from Brazil.

Background: Crocidosema aporema (Walsingham 1914) has historically been the main bud borer species in soybean in Brazil; however, a recent study reported that this species is not C. aporema but an undescribed species. In recent seasons, injury by Crocidosema sp.

Association Between Single-Nucleotide Polymorphisms in (), , and Genes with Severe Symptoms in Children Presenting COVID-19.

The global number of COVID-19 deaths has reached 7 million, with 4% of these deaths occurring in children and adolescents. In Brazil, around 1500 children up to 11 years old died from the disease. The most common symptoms in children are respiratory, potentially progressing to severe illnesses, such as severe acute respiratory syndrome (SARS) and MIS-C.

Comparative study of ergosterol and 7-dehydrocholesterol and their endoperoxides: Generation, identification, and impact in phospholipid membranes and melanoma cells.

Melanoma is an aggressive cancer that has attracted attention in recent years due to its high mortality rate of 80%. Damage caused by oxidative stress generated by radical (type I reaction) and singlet oxygen, O (type II reaction) oxidative reactions may induce cancer. Thus, studies that aim to unveil the mechanism that drives these oxidative damage processes become relevant.

Discovery of a Potent Triazole-Based Reversible Targeted Covalent Inhibitor of Cruzipain.

Cruzipain (CZP) is an essential cysteine protease of , the etiological agent of Chagas disease, and a promising druggable target. To date, no CZP inhibitors have reached clinical use, with research efforts mostly hampered by insufficient potency, limited target selectivity or lack of bioactivity translation from the isolated enzyme to the parasite in cellular environments. In this study, we report the design of , a 1,2,3-triazole-based targeted covalent inhibitor with nanomolar potency (IC = 28 nM) and null inhibition of human cathepsin L.

Invasive infections by group A Streptococcus infections in Brazil: a pediatric case series.

Objective: Group A Streptococcus (GAS) are Gram-positive cocci that colonize the nasopharynx and/or skin and in rare cases may cause severe invasive infections. Although these infections decreased during the COVID-19 pandemic, some countries have observed an increased number of invasive GAS (iGAS) diseases in recent years. The objective of this study was to describe a series of iGAS diseases in a referral hospital for the treatment of pediatric infectious disease in Minas Gerais State, Brazil, between September 2022 and August 2023.

Construction and Validation of CRISPR/Cas Vectors for Editing the Gene in Banana ( spp.).

Bananas and plantains are important staple food crops affected by biotic and abiotic stresses. The gene editing technique via Clustered Regularly Interspaced Short Palindromic Repeats associated with the Cas protein (CRISPR/Cas) has been used as an important tool for development of cultivars with high tolerance to stresses. This study sought to develop a protocol for the construction of vectors for gene knockout.

Aging promotes an increase in mitochondrial fragmentation in astrocytes.

Introduction: Brain aging involves a complex interplay of cellular and molecular changes, including metabolic alterations and the accumulation of senescent cells. These changes frequently manifest as dysregulation in glucose metabolism and mitochondrial function, leading to reduced energy production, increased oxidative stress, and mitochondrial dysfunction-key contributors to age-related neurodegenerative diseases.

Methods: We conducted experiments on two models: young (3-4 months) and aged (over 18 months) mice, as well as cultures of senescent and control mouse astrocytes.

Demographic profile of surgical approaches to obstructive sleep apnea in the United States from 2004 to 2020: a descriptive study.

Objectives: This study aims to evaluate the quantity, types, and trends of surgical procedures used to treat obstructive sleep apnea (OSA) within a diverse national population, utilizing a comprehensive proprietary healthcare database.

Methods: This descriptive observational study analyzed longitudinal data from the Optum Clinformatics® Data Mart databases, covering the period from January 2004 to December 2020. The study included patients aged 18 to 89 years, both male and female, with a confirmed diagnosis of OSA.

Susceptibility of Brazilian populations of Rachiplusia nu (Lepidoptera: Noctuidae) to insecticides and determination of diagnostic concentrations for a proactive resistance management program.

Background: The sunflower looper, Rachiplusia nu (Guenée), evolved resistance to the insecticidal protein Cry1Ac expressed in soybean and emerged as an important soybean pest in Brazil, requiring the application of insecticides for their control. Here, we characterized the susceptibility of Brazilian populations of R. nu to several insecticides and developed diagnostic concentrations for a proactive insect resistance management (IRM) program.

Anti-Inflammatory and Antioxidant Activities of Eugenol: An Update.

Medicinal plants are a rich source of bioactive compounds that possess pharmacological properties for preventing and treating inflammation-related diseases. Essential oils is a chemical class that contains many bioactive compounds, such as eugenol, which is capable of inhibiting or modulating the inflammatory response. This natural product emerges as a compound that promotes various biological activities, including antioxidant activity, which makes it useful in the food industry.

PRDX6 contributes to selenocysteine metabolism and ferroptosis resistance.

Selenocysteine (Sec) metabolism is crucial for cellular function and ferroptosis prevention and begins with the uptake of the Sec carrier, selenoprotein P (SELENOP). Following uptake, Sec released from SELENOP is metabolized via selenocysteine lyase (SCLY), producing selenide, a substrate for selenophosphate synthetase 2 (SEPHS2), which provides the essential selenium donor, selenophosphate (HSePO), for the biosynthesis of the Sec-tRNA. Here, we discovered an alternative pathway in Sec metabolism mediated by peroxiredoxin 6 (PRDX6), independent of SCLY.

Structure-Aided Computational Design of Triazole-Based Targeted Covalent Inhibitors of Cruzipain.

Cruzipain (CZP), the major cysteine protease present in , the ethiological agent of Chagas disease, has attracted particular attention as a therapeutic target for the development of targeted covalent inhibitors (TCI). The vast chemical space associated with the enormous molecular diversity feasible to explore by means of modern synthetic approaches allows the design of CZP inhibitors capable of exhibiting not only an efficient enzyme inhibition but also an adequate translation to anti- activity. In this work, a computer-aided design strategy was developed to combinatorially construct and screen large libraries of 1,4-disubstituted 1,2,3-triazole analogues, further identifying a selected set of candidates for advancement towards synthetic and biological activity evaluation stages.

Can electroencephalography (EEG) identify the different dimensions of pain in fibromyalgia? A pilot study.

Background: Electroencephalography (EEG) is a promising tool for identifying the physiological biomarkers of fibromyalgia (FM). Evidence suggests differences in power band and density between individuals with FM and healthy controls. EEG changes appear to be associated with pain intensity; however, their relationship with the quality of pain has not been examined.

Accumulation of damaged mitochondria in aging astrocytes due to mitophagy dysfunction: Implications for susceptibility to mitochondrial stress.

Aging disrupts brain function, leading to cognitive decline and neurodegenerative diseases. Senescent astrocytes, a hallmark of aging, contribute to this process through unknown mechanisms. This study investigates how senescence impacts astrocytic mitochondrial dynamics, which are critical for brain health.

Beliefs regarding the use of imaging among patients with low back pain: A cross-sectional study in the context of a middle-income country.

Introduction: Patients with low back pain may play an active role in the prescription of excessive spine imaging.

Objective: To determine the proportion of patients with low back pain who have beliefs not aligned with current evidence regarding the use of imaging and to identify factors associated with these beliefs.

Design: Secondary analysis of baseline data of a previously published randomized clinical trial.

Histone deacetylase inhibition mitigates cognitive deficits and astrocyte dysfunction induced by amyloid-β (Aβ) oligomers.

Background And Purpose: Inhibitors of histone deacetylases (iHDACs) are promising drugs for neurodegenerative diseases. We have evaluated the therapeutic potential of the new iHDAC LASSBio-1911 in Aβ oligomer (AβO) toxicity models and astrocytes, key players in neuroinflammation and Alzheimer's disease (AD).

Experimental Approach: Astrocyte phenotype and synapse density were evaluated by flow cytometry, Western blotting, immunofluorescence and qPCR, in vitro and in mice.

Plasmalogen oxidation induces the generation of excited molecules and electrophilic lipid species.

Plasmalogens are glycerophospholipids with a vinyl ether linkage at the sn-1 position of the glycerol backbone. Despite being suggested as antioxidants due to the high reactivity of their vinyl ether groups with reactive oxygen species, our study reveals the generation of subsequent reactive oxygen and electrophilic lipid species from oxidized plasmalogen intermediates. By conducting a comprehensive analysis of the oxidation products by liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS), we demonstrate that singlet molecular oxygen [O (Δ)] reacts with the vinyl ether bond, producing hydroperoxyacetal as a major primary product (97%) together with minor quantities of dioxetane (3%).

Highly Soluble Dacarbazine Multicomponent Crystals Less Prone to Photodegradation.

Dacarbazine (DTIC) is a widely prescribed oncolytic agent to treat advanced malignant melanomas. Nevertheless, the drug is known for exhibiting low and pH-dependent solubility, in addition to being photosensitive. These features imply the formation of the inactive photodegradation product 2-azahypoxanthine (2-AZA) during pharmaceutical manufacturing and even drug administration.

Outcomes of SARS-CoV-2 and Seasonal Viruses Among 2 Million Adults Hospitalized for Severe Acute Respiratory Infection During the COVID-19 Pandemic in Brazil.

Background: The outbreak of the COVID-19 pandemic has had a profound impact on the circulation of seasonal respiratory viruses. This study aimed to compare the outcomes of SARS-CoV-2 and seasonal viruses in adults hospitalized with severe acute respiratory infection during the COVID-19 pandemic.

Methods: This population-based cohort study included patients aged >18 years hospitalized for severe acute respiratory infection in Brazil between February 2020 and February 2023.

Characterizing the differential susceptibility and resistance to insecticides in populations of Chrysodeixis includens and Rachiplusia nu (Lepidoptera: Noctuidae) in Brazil.

Background: Chrysodeixis includens (Walker) and Rachiplusia nu (Guenée) are major Plusiinae pests of soybean in the Southern Cone region of South America. In recent decades, C. includens was the main defoliator of soybean in Brazil, but from 2021 onwards, R.