Cisplatin (cis-diamminedichloroplatinum (II), DDP) is an antineoplastic agent widely used in the treatment of solid tumors because of its extensive cytotoxic activity. However, the main limiting side ...effect of DDP use is nephrotoxicity, a rapid deterioration in kidney function due to toxic chemicals. Several studies have shown that epigenetic processes are involved in DDP-induced nephrotoxicity. Noncoding RNAs (ncRNAs), a class of epigenetic processes, are molecules that regulate gene expression under physiological and pathological conditions. MicroRNAs (miRNAs) are the most characterized class of ncRNAs and are engaged in many cellular processes. In this review, we describe how different miRNAs regulate some pathways leading to cell death by apoptosis, specifically the intrinsic apoptosis pathway. Accordingly, many classes of natural products have been tested for their ability to prevent DDP-induced apoptosis. The study of epigenetic regulation for underlying cell death is still being studied, which will allow new strategies for the diagnosis and therapy of this unwanted disease, which is presented as a side effect of antineoplastic treatment.
Chagas cardiomyopathy (CC), caused by the protozoan
, is an important cause of cardiovascular morbidity and mortality in developing countries. It is estimated that 6 to 7 million people worldwide are ...infected, and it is predicted that it will be responsible for 200,000 deaths by 2025. The World Health Organization (WHO) considers Chagas disease (CD) as a Neglected Tropical Disease (NTD), which must be acknowledged and detected in time, as it remains a clinical and diagnostic challenge in both endemic and non-endemic regions and at different levels of care. The literature on CC was analyzed by searching different databases (Medline, Cochrane Central, EMBASE, PubMed, Google Scholar, EBSCO) from 1968 until October 2022. Multicenter and bioinformatics trials, systematic and bibliographic reviews, international guidelines, and clinical cases were included. The reference lists of the included papers were checked. No linguistic restrictions or study designs were applied. This review is intended to address the current incidence and prevalence of CD and to identify the main pathogenic mechanisms, clinical presentation, and diagnosis of CC.
This study evaluated the antifungal efficacy of gentian violet (GV) in an experimental vulvovaginal candidiasis (VVC) model.
susceptibility and cytotoxicity assays were performed to validate the ...antifungal potential and safety of GV. The antifungal efficacy was then evaluated
through comparative analysis of the fungal burden following treatment with GV or nystatin, as well as assessment of the vaginal tissue by histology and electron microscopy.
GV demonstrated a safe antifungal profile against
, with a significant decrease in fungal burden and an improvement in the inflammatory process evaluated histologically.
The results of this study motivate further assessment of GV as a promising alternative for VVC therapy.
Display omitted
•Coffee husk was used as precursor of hydrochar.•The experimental parameters were successfully optimized from RSM.•Temperature and time were the significant effects.•The optimized ...hydrochar (HCop) exhibited well-developed surface area.•HCop showed monolayer adsorption capacity of 34.85mgg−1 for MB.
The coffee husk was used as precursor of hydrochar and chemometrics tools were applied to optimize the experimental conditions in order to obtain hydrochar with well-development surface area. The central composite rotatable design was employed and the optimization of parameters (temperature, time and water:precursor ratio) was performed from Response Surface Methodology (RSM). The analysis of variance showed that significant effects were: temperature and time. The optimal condition was found to be: temperature of 210°C, time of 243min, and water:precursor ratio of (3.4:1), resulting in a hydrochar (HCop) with BET surface area value (SBET) of 31.3m2g−1. The HCop was properly characterized and applied in adsorption studies of methylene blue (MB) dye. The adsorption studies showed that the Elovich kinetic model and Langmuir isotherm model were that better described the experimental data. The monolayer adsorption maximum capacity of HCop was estimated to be 34.85mgg−1. Additionally, the thermodynamic study showed that adsorption occurs via spontaneous and endothermic process.
Objectives
Invasive aspergillosis (IA) is a major cause of mortality in immunocompromised patients and it is difficult to diagnose because of the lack of reliable highly sensitive diagnostics. We ...aimed to identify circulating immunological markers that could be useful for an early diagnosis of IA.
Methods
We collected longitudinally serum samples from 33 cases with probable/proven IA and two matched control cohorts without IA (one with microbiological and clinical evidence of bacterial or viral non-fungal pneumonia and one without evidence of infection, all matched for neutropenia, primary underlying disease, and receipt of corticosteroids/other immunosuppressants) at a tertiary university hospital. In addition, samples from an independent cohort (n = 20 cases of proven/probable IA and 20 matched controls without infection) were obtained. A panel of 92 circulating proteins involved in inflammation was measured by proximity extension assay. A random forest model was used to predict the development of IA using biomarkers measured before diagnosis.
Results
While no significant differences were observed between IA cases and infected controls, concentrations of 30 inflammatory biomarkers were different between cases and non-infected controls, of which nine were independently replicated: PD-L1, MMP-10, Interleukin(IL)-10, IL-15RA, IL-18, IL-18R1, CDCP1, CCL19 and IL-17C. From the differential abundance analysis of serum samples collected more than 10 days before diagnosis and at diagnosis, increased IL-17C concentrations in IA patients were replicated in the independent cohort.
Conclusions
An increased circulating concentration of IL-17C was detected both in the discovery and independent cohort, both at the time of diagnosis and in samples 10 days before the diagnosis of IA, suggesting it should be evaluated further as potential (early) biomarker of infection.
Display omitted
•12 flavonols from Vaccinium macrocarpon were identified by LC-MS and HPLC.•Nanopacomposites were synthesized from flavonols, keratine and silver nitrate.•Nanopacomposites were ...characterized using spectroscopic techniques.•Flavonols entrapped in nanocomposites shown inhibition on formation of ROS.•Nanopacomposites protect β-cell physiology against oxidant stress.
Flavonols (FLA) fromVaccinium macrocarpon (V. macrocarpon) were identified using high-performance liquid chromatography coupled with mass spectrometry detection. Nanoparticles were prepared using highly crosslinked keratin (KER) from human hair andsilver and entrapped with flavonols KER + FLA + AgNPs.Nanocomposites were characterized using UV–Vis spectroscopy, transmission electron microscopy (TEM), X-ray diffraction,zeta potential, and dynamic light scattering, andrelease profiles.The interactions between the capping agent and the silver core have been investigated using FTIR spectroscopy·H2O2 is a source of Reactive Oxygen Species (ROS) and acts as an activator of oxidative stress affecting NS-1 cells, and the protective effect of the nanocomposites were evaluated against H2O2-induced pancreatic β-cell damage.LC-MS/MS and HPLC analyses revealed the presence of 12 flavonols inV. macrocarponplant extract.The cell apoptosis and proliferation, were evaluated by Hoechst 33342 staining, flow cytometry and Cell Counting Kit-8 respectively. Preincubation of the NS-1 cells with 250 µg/mL of H2O2induced oxidative stress conditions that showpancreatic β-cell dysfunction, includingROS, cell death, mitochondrial function, antioxidant enzymes, and lipid peroxidation. Nevertheless, pretreatment with FLA and KER + FLA + AgNPs prevented mitochondria disruption, maintained cellular ATP levels, inhibited LDH release, intracellular ROS production, decreased lipid peroxidation, increased expression of antioxidant enzymes (CAT, SOD, and GPx) and GSH levels. These results indicate that nanocomposites couldprotect rat INS-1 pancreaticβ-cell from H2O2-induced oxidative damage, apoptosis and proliferation by reducing the production of intracellular reactive oxygen species.
Toxoplasmosis is a zoonotic disease caused by the ubiquitous coccidia Toxoplasma gondii. Rodents play an important role in maintaining its life cycle, as they are one of the main diet sources for ...felids (wild and domestic), the unique definitive hosts. However, reports of toxoplasmosis in porcupines (Order Rodentia) are uncommon, with gaps concerning its pathophysiology. South America is the continent with the greatest genetic diversity of rodents and T. gondii. A free‐ranging hairy dwarf porcupine was admitted to a wildlife rescue centre with a history of trauma. During rehabilitation, the animal presented neurological symptoms (sporadic episodes of hind limbs paresis) and died 5 months later. The main findings during necropsy were brain congestion and severe incisor overgrowth associated with maxillary perforation. The histopathological exam showed moderate encephalitis, with variable‐sized round cysts, positive for PAS stain and immunohistochemistry for T. gondii. Additionally, two cysts were observed in the medulla of the adrenal gland. Molecular techniques were performed to characterize the parasite load by qPCR (Cq = 30) and the genotype by PCR‐RFLP with 11 markers, which revealed a potential new genotype. This case adds to the body of knowledge in comparative pathology of Neotropical Rodentia and reports a new potential genotype circulating in South America.
Maternal exposure to coconut oil metabolically programs adult offspring for overweight, hyperphagia and hyperleptinemia. We studied the neuroendocrine mechanisms by which coconut oil supplementation ...during breastfeeding as well as continued exposure of this oil throughout life affect the feeding behavior of the progeny. At birth, pups were divided into two groups: Soybean oil (SO) and Coconut oil (CO). Dams received these oils by gavage (0.5 g/kg body mass/day) during lactation. Half of the CO group continued to receive CO in chow throughout life (CO + C). Adult CO and CO + C groups had overweight; the CO group had hyperphagia, higher visceral adiposity, and hyperleptinemia, while the CO + C group had hypophagia only. The CO group showed higher DAGLα (endocannabinoid synthesis) but no alteration of FAAH (endocannabinoid degradation) or CB1R. Leptin signaling and GLP1R were unchanged in the CO group, which did not explain its phenotype. Hyperphagia in these animals can be due to higher DAGLα, increasing the production of 2-AG, an orexigenic mediator. The CO + C group had higher preference for fat and lower hypothalamic GLP1R content. Continuous exposure to coconut oil prevented an increase in DAGLα. The CO + C group, although hypophagic, showed greater voracity when exposed to a hyperlipidemic diet, maybe due to lower GLP1R, since GLP1 inhibits short-term food intake.
Maternal treatment with coconut oil during lactation led to long-term overweight, higher adiposity, hyperphagia, hyperleptinemia and endocannabinoid system dysfunction. But continuous exposure to coconut oil in chow throughout life prevented most of these dysfunctions. A greater voracity was observed in CO + C group when exposed to HFD, possibly due lower expression of GLP-1 receptor in the ARC, since this peptide inhibits short-term food intake. CO = coconut oil gavage on lactation; CO + C = coconut oil gavage on lactation + coconut oil supplemented in the chow throughout life; ECS = endocannabinoid system; HFD = high-fat diet. Display omitted
•Maternal intake of coconut oil during lactation, increases offspring's endocannabinoids.•Coconut oil leads to hyperphagia in adult progeny without change dopaminergic system.•Lifelong exposure to coconut oil prevents some side effects compared to exposure to coconut oil only during lactation.
ABSTRACT Objective: To identify barriers to adherence to home oral maintenance chemotherapy in children with leukemia treated at a specialized cancer center. Methods: We used the Brief Medication ...Questionnaire (BMQ) as a tool for screening barriers to adherence. The level of adherence was calculated considering at least one positive response in each BMQ domain, defined as Regimen Screen, Belief Screen, and Recall Screen. A positive screening for belief barriers (PSB) indicates that the caregiver reports not understanding the medication's mechanism of action and adverse effects. Results: Three important barriers to adherence were identified: beliefs, number of children of the caregiver, and age of the caregiver. The primary caregivers included 32 mothers (80%), four fathers (10%), three grandmothers (7.5%), and one unrelated caregiver (2.5 %). Most caregivers with a PSB were mothers. A PSB indicates that the caregiver reports not understanding the medication's mechanism of action and adverse effects. Caregivers with two or more children (median, three) had more barriers to adherence. Caregivers with potential non-adherence tended to be older than those with potential adherence, although without statistical significance (p=0.079, Mann-Whitney U test). Conclusions: The main barriers to adherence to home oral maintenance chemotherapy in children with leukemia identified through interviews with their caregivers, most often mothers, were lack of understanding of the treatment regimen, a greater number of children, and older age.
RESUMO Objetivo: Identificar barreiras de adesão ao tratamento de manutenção da quimioterapia via oral domiciliar, em uma amostra de crianças diagnosticadas com leucemia atendidas em um serviço especializado em oncologia. Métodos: O Brief Medication Questionnaire (BMQ) foi utilizado como instrumento de coleta para a identificação de barreiras de adesão. O nível de adesão foi calculado considerando-se pelo menos uma resposta positiva no domínio do BMQ, definido como regime, crença e recordação. Uma crença positiva mostra que o cuidador reporta não entender o mecanismo de ação e os efeitos adversos. Resultados: Três importantes barreiras de adesão foram identificadas, incluindo crença, o número de filhos do casal e a idade dos cuidadores. A mãe como principal responsável pelo tratamento da criança apresentou frequência maior entre as pessoas com rastreamento positivo para barreiras de crenças (BPC). Crença positiva significa que o cuidador relata não entender o mecanismo de ação dos medicamentos e os efeitos adversos. Quanto ao número de filhos, o estudo mostrou que quanto mais filhos (dois filhos ou mais, mediana=três) maior a barreira de adesão. Houve tendência de responsáveis com potencial não adesão serem mais velhos que os responsáveis com potencial adesão, embora sem significância estatística ao nível de significância de 5% (p=0,079, teste U de Mann-Whitney). Conclusões: As principais barreiras de adesão dos cuidadores de crianças com leucemia ao tratamento medicamentoso de manutenção foram dificuldades relatadas pelos cuidadores, na maioria das vezes as mães, que não entenderam como o medicamento funcionava, o número de filhos — quanto mais filhos menor a adesão — e a idade dos cuidadores. Cuidadores mais velhos aderiram menos ao tratamento prescrito.
The availability of purified antibodies is a prerequisite for many applications and the appropriate choice(s) for antibody-purification is crucial. Numerous methods have been developed for the ...purification of antibodies from different sources with affinity chromatography-based methods being the most extensively utilized. These methods are based on high specificity, easy reversibility and biological interactions between two molecules (e.g., between receptor and ligand or antibody and antigen). However, no simple techniques have yet been described to characterize and purify subclasses of immunoglobulins (Ig) from some animals of biotechnology importance such as equines, which are frequently used to produce biotherapeutic antibodies. The sera of these animals present a large number of Ig classes that have a greater complexity than other animals. The implementation of an effective protocol to purify the desired antibody class/subclasses requires meticulous planning to achieve yields at a high purity. The IgG3 subclass of equine-Ig has recently been used as antigen in a new diagnostic test for allergic responses to horse sera-based therapies. Here, we defined a simple method using Jacalin lectin immobilized on Sepharose beads to prepare highly pure equine IgG3 antibodies with a determination of the affinity constants for Jacalin lectin and horse IgG3.
•Jacalin-Sepharose was used to purify IgG3 from equine sera.•The eqIgG3 is the major allergenic compound of therapeutic sera.•The interaction jacalin-hIgG3 is strong with an affinity of 0.43 nM.
PDF
