Lisdexamfetamine dimesylate-exposition in male rats during the peripubertal period impairs inflammatory mechanisms, antioxidant activity, and apoptosis process in kidneys of male pubertal rats.

Lisdexamfetamine dimesylate (LDX) is a prodrug of dextroamphetamine, which has been widely recommended for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD). There are still no data in the literature relating the possible toxic effects of LDX in the kidney. Therefore, the present study aims to evaluate the effects of LDX exposure on morphological, oxidative stress, cell death and inflammation parameters in the kidneys of male pubertal Wistar rats, since the kidneys are organs related to the excretion of most drugs. For this, twenty male Wistar rats were distributed randomly into two experimental groups: LDX group-received 11,3 mg/kg/day of LDX; and Control group-received tap water. Animals were treated by gavage from postnatal day (PND) 25 to 65. At PND 66, plasma was collected to the biochemical dosage, and the kidneys were collected for determinations of the inflammatory profile, oxidative status, cell death, and for histochemical, and morphometric analyses. Our results show that there was an increase in the number of cells marked for cell death, and a reduction of proximal and distal convoluted tubules mean diameter in the group that received LDX. In addition, our results also showed an increase in MPO and NAG activity, indicating an inflammatory response. The oxidative status showed that the antioxidant system is working undisrupted and avoiding oxidative stress. Therefore, LDX-exposition in male rats during the peripubertal period causes renal changes in pubertal age involving inflammatory mechanisms, antioxidant activity and apoptosis process.

Doxorubicin causes cachexia, sarcopenia, and frailty characteristics in mice.

While chemotherapy treatment can be lifesaving, it also has adverse effects that negatively impact the quality of life. To investigate the effects of doxorubicin chemotherapy on body weight loss, strength and muscle mass loss, and physical function impairments, all key markers of cachexia, sarcopenia, and frailty. Seventeen C57/BL/6 mice were allocated into groups. 1) Control (n = 7): mice were exposed to intraperitoneal (i.p.) injections of saline solution. 2) Dox (n = 10): mice were exposed to doxorubicin chemotherapy cycles (total dose of 18 mg/kg divided over 15 days). The body weight loss and decreased food intake were monitored to assess cachexia. To assess sarcopenia, we measured muscle strength loss using a traction method and evaluated muscle atrophy through histology of the gastrocnemius muscle. To evaluate physical function impairments and assess frailty, we employed the open field test to measure exploratory capacity. Doxorubicin administration led to the development of cachexia, as evidenced by a significant body weight loss (13%) and a substantial decrease in food intake (34%) over a 15-day period. Furthermore, 90% of the mice treated with doxorubicin exhibited sarcopenia, characterized by a 20% reduction in traction strength (p<0,05), a 10% decrease in muscle mass, and a 33% reduction in locomotor activity. Importantly, all mice subjected to doxorubicin treatment were considered frail based on the evaluation of their overall condition and functional impairments. The proposed model holds significant characteristics of human chemotherapy treatment and can be useful to understand the intricate relationship between chemotherapy, cachexia, sarcopenia, and frailty.

Trilobolide-6-O-isobutyrate from Sphagneticola trilobata acts by inducing oxidative stress, metabolic changes and apoptosis-like processes by caspase 3/7 activation of human lung cancer cell lines.

BACKGROUND: Lung cancer, a chronic and heterogeneous disease, is the leading cause of cancer-related death on a global scale. Presently, despite a variety of available treatments, their effectiveness is limited, often resulting in considerable toxicity and adverse effects. Additionally, the development of chemoresistance in cancer cells poses a challenge. Trilobolide-6-O-isobutyrate (TBB), a natural sesquiterpene lactone extracted from Sphagneticola trilobata, has exhibited antitumor effects. Its pharmacological properties in NSCLC lung cancer, however, have not been explored. PURPOSE: This study evaluated the impact of TBB on the A549 and NCI-H460 tumor cell lines in vitro, examining its antiproliferative properties and initial mechanisms of cell death. METHODS: TBB, obtained at 98 % purity from S. trilobata leaves, was characterized using chromatographic techniques. Subsequently, its impact on inhibiting tumor cell proliferation in vitro, TBB-induced cytotoxicity in LLC-MK2, THP-1, AMJ2-C11 cells, as well as its effects on sheep erythrocytes, and the underlying mechanisms of cell death, were assessed. RESULTS: In silico predictions have shown promising drug-likeness potential for TBB, indicating high oral bioavailability and intestinal absorption. Treatment of A549 and NCI-H460 human tumor cells with TBB demonstrated a direct impact, inducing significant morphological and structural alterations. TBB also reduced migratory capacity without causing toxicity at lower concentrations to LLC-MK2, THP-1 and AMJ2-C11 cell lines. This antiproliferative effect correlated with elevated oxidative stress, characterized by increased levels of ROS, superoxide anion radicals and NO, accompanied by a decrease in antioxidant markers: SOD and GSH. TBB-stress-induced led to changes in cell metabolism, fostering the accumulation of lipid droplets and autophagic vacuoles. Stress also resulted in compromised mitochondrial integrity, a crucial aspect of cellular function. Additionally, TBB prompted apoptosis-like cell death through activation of caspase 3/7 stressors. CONCLUSION: These findings underscore the potential of TBB as a promising candidate for future studies and suggest its viability as an additional component in the development of novel anticancer drugs prototypes.

Implementation and impact of integrated health and social care services: an umbrella review.

Governments in many European countries have been working towards integrating health and social care services to eliminate the fragmentation that leads to poor care coordination for patients. We conducted a systematic review to identify and synthesize knowledge about the integration of health and social care services in Europe. We identified 490 records, in 14 systematic reviews that reported on 1148 primary studies and assessed outcomes of integration of health care and social care. We categorized records according to three purposes: health outcomes, service quality and integration procedures outcomes. Health outcomes include improved clinical outcomes, enhanced quality of life, and positive effects on quality of care. Service quality improvements encompass better access to services, reduced waiting times, and increased patient satisfaction. Integration procedure outcomes involve cost reduction, enhanced collaboration, and improved staff perceptions; however, some findings rely on limited evidence. This umbrella review provides a quality-appraised overview of existing systematic reviews.

Polyvinylpyrrolidone Nanofibers Incorporating Mesoporous Bioactive Glass for Bone Tissue Engineering.

Composite biomaterials that combine osteoconductive and osteoinductive properties are a promising approach for bone tissue engineering (BTE) since they stimulate osteogenesis while mimicking extracellular matrix (ECM) morphology. In this context, the aim of the present research was to produce polyvinylpyrrolidone (PVP) nanofibers containing mesoporous bioactive glass (MBG) 80S15 nanoparticles. These composite materials were produced by the electrospinning technique. Design of experiments (DOE) was used to estimate the optimal electrospinning parameters to reduce average fiber diameter. The polymeric matrices were thermally crosslinked under different conditions, and the fibers' morphology was studied using scanning electron microscopy (SEM). Evaluation of the mechanical properties of nanofibrous mats revealed a dependence on thermal crosslinking parameters and on the presence of MBG 80S15 particles inside the polymeric fibers. Degradation tests indicated that the presence of MBG led to a faster degradation of nanofibrous mats and to a higher swelling capacity. The assessment of in vitro bioactivity in simulated body fluid (SBF) was performed using MBG pellets and PVP/MBG (1:1) composites to assess if the bioactive properties of MBG 80S15 were kept when it was incorporated into PVP nanofibers. FTIR and XRD analysis along with SEM-EDS results indicated that a hydroxy-carbonate apatite (HCA) layer formed on the surface of MBG pellets and nanofibrous webs after soaking in SBF over different time periods. In general, the materials revealed no cytotoxic effects on the Saos-2 cell line. The overall results for the materials produced show the potential of the composites to be used in BTE.

Biogenic silver nanoparticle exhibits schistosomicidal activity in vitro and reduces the parasitic burden in experimental schistosomiasis mansoni.

Schistosomiasis is a neglected tropical parasitic disease that affects millions of people, being the second most prevalent parasitic disease worldwide. The current treatment has limited effectiveness, drug-resistant strains, and is not effective in different stages of the disease. This study investigated the antischistosomal activity of biogenic silver nanoparticles (Bio-AgNp) against Schistosoma mansoni. Bio-AgNp presented direct schistosomicidal activity on newly transformed schistosomula causing plasma membrane permeabilization. In S. mansoni adult worms, reduced the viability and affected the motility, increasing oxidative stress parameters, and inducing plasma membrane permeabilization, loss of mitochondrial membrane potential, lipid bodies accumulation, and autophagic vacuoles formation. During the experimental schistosomiasis mansoni model, Bio AgNp restored body weight, reduced hepatosplenomegaly, and decrease the number of eggs and worms in feces and liver tissue. The treatment also ameliorates liver damage and reduces macrophage and neutrophil infiltrates. A reduction in count and size was evaluated in the granulomas, as well as a change to an exudative-proliferative phase, with a local increase of IFN-γ. Together our results showed that Bio-AgNp is a promising therapeutic candidate for studies of new therapeutic strategies against schistosomiasis.

Treatment of Pain in Ferrets.

Ferrets often require pain management as part of comprehensive veterinary care. Recognition and objective quantification of pain, such as the ferret grimace scale, are the first steps of an analgesic plan. As in other species, a multimodal approach to pain management is preferred, which includes combining analgesic drugs of multiple classes and/or techniques to affect different areas of the pain pathway. This article reviews the current published literature on analgesic medications in domestic ferrets, including specific drugs, doses, dosing intervals, and routes of administration.

Polycomb group (PcG) proteins prevent the assembly of abnormal synaptonemal complex structures during meiosis.

The synaptonemal complex (SC) is a proteinaceous scaffold that is assembled between paired homologous chromosomes during the onset of meiosis. Timely expression of SC coding genes is essential for SC assembly and successful meiosis. However, SC components have an intrinsic tendency to self-organize into abnormal repetitive structures, which are not assembled between the paired homologs and whose formation is potentially deleterious for meiosis and gametogenesis. This creates an interesting conundrum, where SC genes need to be robustly expressed during meiosis, but their expression must be carefully regulated to prevent the formation of anomalous SC structures. In this manuscript, we show that the Polycomb group protein Sfmbt, the Drosophila ortholog of human MBTD1 and L3MBTL2, is required to avoid excessive expression of SC genes during prophase I. Although SC assembly is normal after Sfmbt depletion, SC disassembly is abnormal with the formation of multiple synaptonemal complexes (polycomplexes) within the oocyte. Overexpression of the SC gene corona and depletion of other Polycomb group proteins are similarly associated with polycomplex formation during SC disassembly. These polycomplexes are highly dynamic and have a well-defined periodic structure. Further confirming the importance of Sfmbt, germ line depletion of this protein is associated with significant metaphase I defects and a reduction in female fertility. Since transcription of SC genes mostly occurs during early prophase I, our results suggest a role of Sfmbt and other Polycomb group proteins in downregulating the expression of these and other early prophase I genes during later stages of meiosis.

Human Identification by Comparative Analysis of Frontal Sinuses: Study on Computed Tomography

ABSTRACT: Generally, primary methods of identification as the fingerprint analysis, dental analysis or DNA examination are indicated for the establishment of the identity of a corpse. In situations with poor body conservation, such as in advanced stage of putrefaction or skeletonization, imaging exams like medical and dental computed tomography can assist in the process of identification. The frontal sinuses present anatomical characteristics that allow the establishment of the identity of an in dividual. In this case report we used the technique of three-dimensional construction of the frontal sinuses through the generation of solid figures representative of the sinus morphology. After the comparative analysis of the antemortem and postmortem tomography of the alleged victim, we could establish similarities in both the variations in size, shape, symmetry and contour of borders, and the presence and number of septa, allowing us to infer that the two images described belong to the same individual, thus establishing the identity of the corpse found.

RESUMEN: Generalmente, los métodos primarios de identificación como el análisis dactiloscópico, el análisis dental o el examen de ADN están indicados para el establecimiento de la identidad de un cadáver. En situaciones de mala conservación del cuerpo, como en etapa avanzada de putrefacción o esqueletización, los exámenes de imagen como la tomografía computarizada médica y dental pueden ayudar en el proceso de identificación. Los senos frontales presentan características anatómicas que permiten establecer la identidad de un individuo. En este reporte de caso utilizamos la técnica de construcción tridimensional de los senos frontales a través de la generación de figuras sólidas representativas de la morfología sinusal. Tras el análisis comparativo de la tomografía antemortem y postmortem de la presunta víctima, pudimos establecer similitudes tanto en las variaciones de tamaño, forma, simetría y contorno de márgenes, como en la presencia y número de septos, lo que nos permite inferir que las dos imágenes descritas pertenecen al mismo individuo, estableciéndose así la identidad del cadáver encontrado.

Voice rehabilitation with voice prosthesis: Long term results, complications and risk factors.

OBJECTIVES: Despite the advances in surgical and non-surgical organ preservation treatments, total laryngectomy (TL) remains the most effective treatment in advanced larynx cancer and as salvage procedure in chemoradiation failure. One of the most devastating sequel after TL is loss of voice. Voice prosthesis (VP) is currently the preferred choice for voice rehabilitation. The purpose of this study is to identify VP complications, its lifespan and factors that influence the longevity of the VP. METHODS: We performed a retrospective study at a Tertiary University Hospital. Medical records of patients that underwent total laryngectomy, between January 1st of 2008 and 31st of December of 2017 were analyzed. RESULTS: Of the 84 patients that underwent laryngectomy, 60 had VP. The average age at the time of surgery 60.2 years old and there was a male preponderance (57:3). The mean lifespan of the prosthesis was 7.53 months. Leakage through the prosthesis was the most common reason for replacement of the prosthesis, followed by leakage around the prosthesis. Follow up time and manual suture were associated with prosthesis replacement. There was no significant relationship between the staging, tumor location or adjuvant radiotherapy and number of prosthesis replacement or its lifespan. CONCLUSIONS: Rehabilitation after TL is of major importance to improve quality of life after surgery. Tracheoesophageal puncture with voice prosthesis is a safe procedure for vocal rehabilitation and was performed in the majority of patients in our study. Follow-up time and type of suture were the main determinants of the lifespan of the prosthesis.

Voice rehabilitation with voice prosthesis: Long term results, complications and risk factors

Objectives: Despite the advances in surgical and non-surgical organ preservation treatments, total laryngectomy (TL) remains the most effective treatment in advanced larynx cancer and as salvage procedure in chemoradiation failure.One of the most devastating sequel after TL is loss of voice. Voice prosthesis (VP) is currently the preferred choice for voice rehabilitation. The purpose of this study is to identify VP complications, its lifespan and factors that influence the longevity of the VP.MethodsWe performed a retrospective study at a Tertiary University Hospital. Medical records of patients that underwent total laryngectomy, between January 1st of 2008 and 31st of December of 2017 were analyzed.ResultsOf the 84 patients that underwent laryngectomy, 60 had VP. The average age at the time of surgery 60.2 years old and there was a male preponderance (57:3).The mean lifespan of the prosthesis was 7.53 months. Leakage through the prosthesis was the most common reason for replacement of the prosthesis, followed by leakage around the prosthesis.Follow up time and manual suture were associated with prosthesis replacement. There was no significant relationship between the staging, tumor location or adjuvant radiotherapy and number of prosthesis replacement or its lifespan.ConclusionsRehabilitation after TL is of major importance to improve quality of life after surgery. Tracheoesophageal puncture with voice prosthesis is a safe procedure for vocal rehabilitation and was performed in the majority of patients in our study.Follow-up time and type of suture were the main determinants of the lifespan of the prosthesis. (AU)

Objetivos: A pesar de los avances en los tratamientos quirúrgicos y no quirúrgicos para la preservación de órganos, la laringectomía total (LT) sigue siendo el tratamiento más efectivo en el cáncer avanzado de laringe, y como procedimiento de rescate en caso de fallo de la radioquimioterapia.Una de las secuelas más devastadoras tras la LT es la pérdida de la voz. Las prótesis de voz (PV) son actualmente la elección preferida para la rehabilitación de la voz. El objetivo de este estudio es identificar las complicaciones de las PV, su vida útil y los factores que influyen en la longevidad de dichas prótesis.MétodosRealizamos un estudio retrospectivo en un hospital universitario terciario, en el que se analizaron los registros médicos de los pacientes sometidos a laringectomía total entre el 1 de enero de 2008 y el 31 de diciembre de 2017.ResultadosDe los 84 pacientes sometidos a laringectomía, 60 tenían PV. La edad media en el momento de la cirugía fue de 60,2 años, y hubo una preponderancia de varones (57:3).La vida útil media de las prótesis fue de 7,53 meses. La fuga a través de la prótesis fue el motivo más común de su sustitución, seguida de la fuga alrededor del dispositivo.El tiempo de seguimiento y la sutura manual estuvieron asociados a la sustitución de la prótesis. No existió una relación significativa entre la estadificación, la localización del tumor o la radioterapia adyuvante y el número de sustituciones de prótesis o su vida útil.ConclusionesLa rehabilitación tras la LT es de gran importancia para mejorar la calidad de vida tras la cirugía. La punción traqueoesofágica con prótesis de voz es un procedimiento seguro para la rehabilitación de la voz, habiéndose realizado en la mayoría de los pacientes de nuestro estudio.El tiempo de seguimiento y el tipo de sutura fueron los principales determinantes de la vida útil de las prótesis. (AU)

Solidagenone in vivo leishmanicidal activity acting in tissue repair response, and immunomodulatory capacity in Leishmania amazonensis.

Leishmaniasis is a group of chronic parasitic diseases in humans caused by species of the Leishmania genus. Current treatments have high toxicity, cost, duration, limited effectiveness, significantly complex administration, and drug-resistant strains. These factors highlight the importance of research into new therapies that use drugs without toxic effects. Solidagenone (SOL), the main labdane diterpene isolated from the plant Solidago chilensis, has anti-inflammatory, gastroprotective, antioxidant, tissue repair-inducing effects, suggesting a role in novel drug development. This study investigates in vivo mechanism action of SOL treatment in L. amazonensis-infected BALB/c mice. SOL was isolated from the roots of S. chilensis, and L. amazonensis-infected mice were treated daily with SOL (10, 50, 100 mg/kg) by gavage for 30 days. Gastric (NAG, MPO), hepatic (AST, ALT), systemic (body weight, NO) toxicity, leishmanicidal activity (lesion size, parasite burden), cell profile (macrophage, neutrophil infiltration), antioxidant (ABTS, NBT, NO), oxidant parameters (FRAP, ABTS), Th1, Th2, Th17 cytokines (CBA), collagen deposition (picrosirius), arginase, iNOS, NF-kB, and NRF2 (immunofluorescence) were evaluated. In vivo results showed SOL-treatment did not induce gastric, hepatic, or systemic toxicity in L. amazonensis-infected mice. SOL was able to reduce the lesion size and parasite load at the site of infection, increasing macrophage infiltration and neutrophil migration, exerting a balance in antioxidant (increased ABTS, NBT reduction, and NO), oxidative (increased FRAP and ABTS), and anti-inflammatory responses (reduced TNF-α, IFN-γ and increased IL-6, IL-17 production), and inducing arginase, iNOS, NF-kB, NRF2 and collagen deposition (type III), favoring wound healing and accelerating tissue repair at the site injury.

Hydroethanolic Extract of Grape Peel from Vitis labrusca Winemaking Waste: Antinociceptive and Anti-Inflammatory Activities.

Research background: Extracts from grape pomace, including the wine, show many biological effects such as antioxidant and anti-inflammatory activities. Unfortunately, winemakers discard the bagasse, so the waste is not exploited, although it contains bioactive compounds with antioxidant and anti-inflammatory properties. The work aims to analyze the hydroethanolic extract of peels from Vitis labrusca agro-industrial waste and to evaluate its antinociceptive and anti-inflammatory properties. This study is relevant for reusing a residue and adding value to the grape economic chain. Experimental approach: A representative sample of pomace was obtained and the peels were used to produce the extract. The phenolic compounds were determined by mass spectrometry in multiple reaction monitoring mode and Folin-Ciocalteu colorimetric method, using gallic acid as standard. The biological analyses were carried out using mice orally treated with crude extract at doses of 30, 100 and 300 mg/kg. We evaluated mechanical hyperalgesia by the von Frey method, thermal heat hyperalgesia using a hot plate at 55 °C, paw edema using a pachymeter, and neutrophil recruitment by measurement of myeloperoxidase activity. The nephrotoxicity and hepatotoxicity were evaluated by biochemical analyses using blood samples that were collected after the Vitis labrusca administration. Results and conclusions: In all wet winemaking residues peel mass fraction was 75%, and in dry residues 59%. We identified nine anthocyanins (3-O-glucosides: peonidin, delphinidin, petunidin and malvidin; 3-p-coumaroyl-glucosides: cyanidin, peonidin, petunidin and malvidin, and malvidin-3,5-diglucoside), five flavonoids (apigenin-7-glucoside, luteolin-7-glucoside, quercetin-3-galactoside, isorhamnetin-3-glucoside and myricetin-3-rutinoside), and mass fraction of phenolic compounds, expressed as gallic acid equivalents, was 26.62 mg/g. In vivo assays showed that Vitis labrusca extract at mass fractions 100 and 300 mg/kg reduced carrageenan-induced mechanical and thermal hyperalgesia, 50% of the paw edema, and neutrophil recruitment. In addition, there were no indications of nephrotoxicity and hepatotoxicity. Our extract obtained from winemaking residue has analgesic and anti-inflammatory properties, related at least in part to the presence of phenolic compounds, and it is not toxic to renal and hepatic tissues. Novelty and scientific contribution: This bio-product can be used as an alternative to synthetic anti-inflammatory agents with the same pharmacological potential and fewer side effects. We demonstrated that Vitis labrusca winemaking waste can be used for the production of antinociceptive and anti-inflammatory products (nutraceutical, pharmaceutical and cosmetics) without toxicity, contributing to the environmental economy.

Effect of running exercise on titanium dioxide (TiO2)-induced chronic arthritis and sarcopenia in mice. A titanium prosthesis loosening injury model study.

AIMS: This study aimed to investigate if titanium dioxide (TiO2) joint administration is a useful pre-clinical model to study sarcopenia-related chronic arthritis, and if exercise is a useful therapeutic approach against the pathogenesis of TiO2-induced arthritis and sarcopenia in mice. MAIN METHODS: Two experiments were conducted. Firstly, 36 female Swiss mice were randomly divided into a control group (n = 12) and two groups who received intra-articular TiO2 injections of 0.3-mg (n = 12) and 3-mg (n = 12), respectively. Mice were euthanized 4 and 8 weeks after TiO2 injections. Based on data of the first experiment, mice were exposed to four groups: control (C, n = 10), exercised (Ex, n = 10), injected with 3-mg of TiO2 (TiO2, n = 10), and injected with 3-mg of TiO2 and exercised (TiO2 + Ex, n = 10) for a total of 8-weeks. KEY FINDINGS: Eight-week of 3 mg of TiO2 joint administration promoted characteristics of chronic inflammation such as elevated histopathological score, inflammation, edema and pain. Hallmarks of sarcopenia were also observed such as muscle atrophy and loss of strength. Furthermore, voluntary exercise running reduced TiO2-induced chronic inflammation and pain, attenuating chronic arthritis-related muscle atrophy, strength loss and impairment of locomotion capacity. In addition, exercise was also able to prevent TiO2-induced collagen degradation, an important marker of functional and structural integrity loss of cartilage and chronic arthritis disease progression. SIGNIFICANCE: TiO2 joint administration mimed titanium prosthesis release-induced joint chronic arthritis and sarcopenia-related chronic arthritis, disturbances that were attenuated by voluntary exercise.

Clown Nose: A Rare Hypopharyngeal Cancer Metastasis.

Cutaneous metastases from squamous cell carcinomas of the head and neck region are uncommon, and their location at the nasal tip is exceptionally rare. A patient, previously treated with surgery and chemoradiation for a hypopharyngeal squamous cell carcinoma, developed several red nodular skin lesions at the nasal tip. Biopsy revealed cutaneous metastasis from the primary tumor. This manifestation was previously described as a "clown nose," given their appearance and location. Skin lesions should raise suspicion of malignancy, despite their location at uncommon places, particularly in patients with previous diagnosed cancer. Clinicians must be aware that metastases from head and neck cancer can present as a "clown nose."

Grandiflorenic acid isolated from Sphagneticola trilobata against Trypanosoma cruzi: Toxicity, mechanisms of action and immunomodulation.

Grandiflorenic acid (GFA) is one of the main kaurane diterpenes found in different parts of Sphagneticola trilobata. It has several biological activities, especially antiprotozoal action. In turn, Chagas disease is a complex systemic disease caused by the protozoan Trypanosoma cruzi, and the drugs available to treat it involve significant side effects and impose an urgent need to search for therapeutic alternatives. In this context, our goal was to determine the effect of GFA on trypomastigote and intracellular amastigote forms. Our results showed that GFA treatment led to significantly less viability of trypomastigote forms, with morphological and ultrastructural changes in the parasites treated with IC50 of GFA (24.60 nM), and larger levels of reactive oxygen species (ROS), mitochondrial depolarization, lipid droplets accumulation, presence of autophagic vacuoles, phosphatidylserine exposure, and plasma membrane damage. In addition, the GFA treatment was able to reduce the percentage of infected cells and the number of amastigotes per macrophage (J774A.1) without showing cytotoxicity in mammalian cell lines (J774A.1, LLCMK2, THP-1, AMJ2-C11), in addition to increasing TNF-α and reducing IL-6 levels in infected macrophages. In conclusion, the GFA treatment exerted influence on trypomastigote forms through an apoptosis-like mechanism and by eliminating intracellular parasites via TNF-α/ROS pathway, without generating cellular cytotoxicity.

Spray-drying of casein/pectin bioconjugate microcapsules containing grape (Vitis labrusca) by-product extract.

Novel microcapsules containing grape peel by-product extract were obtained. In this pursuit, complex coacervation of casein/pectin bioconjugate and spray-drying were combined. We have investigated the role of the dispersion feed rate (FR), drying air inlet temperature (IT) and drying air flow rate (AR) in the drying yield, microencapsulation efficiency, total polyphenols and anthocyanins contents, antioxidant activity, and morphology of the products. Also, the first-order degradation kinetics of the phytochemicals for both the extract and dried microcapsules was assessed and compared. The loss on the phytochemicals during spray-drying was attenuated in up to 88%, and the IT was the main factor affecting the particle properties. The polyphenols on the extract interacted with the polymers, influencing the assemble of the bioconjugate and the particle's features. Such microencapsulation strategy enhanced the thermal stability of the phytochemicals and rendered biocompatible and biodegradable products of which the nutraceutical and cosmeceutical application may have potential.