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1.
An Acad Bras Cienc ; 96(2): e20230043, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38808874

RESUMEN

Sesbania virgata (Cav.) Pers. seeds are protein sources with health and environmental benefits. In this research, proteins with lectin activity were identified in a protein fraction from S. virgata seeds (PFLA), as well its antioxidant and antimicrobial potentials, in addition to cytotoxic effects. To obtain PFLA, seed flour was homogenized in Glycine-NaOH (100 mM; pH 9.0; NaCl 150 mM) and precipitated in ammonium sulfate. PFLA concentrates bioactive lectins (32 HU/mL, 480 HU/gFa, 18.862 HU/mgP) and essential amino acids (13.36 g/100g protein). PFLA exerts antioxidant activity, acting as a promising metal chelating agent (~77% of activity). Analyzes of cell culture assay results suggest that antioxidant activity of PFLA may be associated with the recruitment of essential molecules to prevent the metabolic impairment of cells exposed to oxidative stress. PFLA (256 - 512 µg/mL) also exhibits antifungal activity, inhibiting the growth of Aspergillus flavus, Candida albicans, Candida tropicalis and Penicillium citrinum. Cytotoxic analysis indicates a tendency of low interference in the proliferation of 3T3 and HepG2 cells in the range of PFLA concentrations with biological activity. These findings support the notion that PFLA is a promising adjuvant to be applied in current policies on the management of metal ion chelation and fungal infections.


Asunto(s)
Antifúngicos , Antioxidantes , Semillas , Sesbania , Semillas/química , Antioxidantes/farmacología , Antifúngicos/farmacología , Antifúngicos/aislamiento & purificación , Antifúngicos/química , Sesbania/química , Humanos , Proteínas de Plantas/farmacología , Pruebas de Sensibilidad Microbiana , Animales , Ratones , Extractos Vegetales/farmacología , Extractos Vegetales/química , Células Hep G2
2.
Int J Mol Sci ; 25(5)2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38474103

RESUMEN

Maize ranks as the second most widely produced crop globally, yielding approximately 1.2 billion tons, with corn cob being its primary byproduct, constituting 18 kg per 100 kg of corn. Agricultural corn production generates bioactive polysaccharide-rich byproducts, including xylan (Xyl). In this study, we used the redox method to modify corn cob xylan with gallic acid, aiming to enhance its antioxidant and protective capacity against oxidative stress. The conjugation process resulted in a new molecule termed conjugated xylan-gallic acid (Xyl-GA), exhibiting notable improvements in various antioxidant parameters, including total antioxidant capacity (1.4-fold increase), reducing power (1.2-fold increase), hydroxyl radical scavenging (1.6-fold increase), and cupric chelation (27.5-fold increase) when compared with unmodified Xyl. At a concentration of 1 mg/mL, Xyl-GA demonstrated no cytotoxicity, significantly increased fibroblast cell viability (approximately 80%), and effectively mitigated intracellular ROS levels (reduced by 100%) following oxidative damage induced by H2O2. Furthermore, Xyl-GA exhibited non-toxicity toward zebrafish embryos, offered protection against H2O2-induced stress, and reduced the rate of cells undergoing apoptosis resulting from H2O2 exposure. In conclusion, our findings suggest that Xyl-GA possesses potential therapeutic value in addressing oxidative stress-related disturbances. Further investigations are warranted to elucidate the molecular structure of this novel compound and establish correlations with its pharmacological activities.


Asunto(s)
Antioxidantes , Ácido Gálico , Animales , Antioxidantes/farmacología , Ácido Gálico/farmacología , Xilanos/farmacología , Zea mays/metabolismo , Peróxido de Hidrógeno/farmacología , Pez Cebra/metabolismo , Estrés Oxidativo
3.
Int J Mol Sci ; 25(6)2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38542525

RESUMEN

Among the many lysosomal storage disorders (LSDs) that would benefit from the establishment of novel cell models, either patient-derived or genetically engineered, is mucopolysaccharidosis type II (MPS II). Here, we present our results on the establishment and characterization of two MPS II patient-derived stem cell line(s) from deciduous baby teeth. To the best of our knowledge, this is the first time a stem cell population has been isolated from LSD patient samples obtained from the dental pulp. Taking into account our results on the molecular and biochemical characterization of those cells and the fact that they exhibit visible and measurable disease phenotypes, we consider these cells may qualify as a valuable disease model, which may be useful for both pathophysiological assessments and in vitro screenings. Ultimately, we believe that patient-derived dental pulp stem cells (DPSCs), particularly those isolated from human exfoliated deciduous teeth (SHEDs), may represent a feasible alternative to induced pluripotent stem cells (iPSCs) in many labs with standard cell culture conditions and limited (human and economic) resources.


Asunto(s)
Enfermedades por Almacenamiento Lisosomal , Mucopolisacaridosis II , Humanos , Células Madre , Línea Celular , Diente Primario , Lisosomas , Pulpa Dental , Diferenciación Celular/fisiología , Proliferación Celular
4.
Adm Policy Ment Health ; 51(2): 147-161, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37971543

RESUMEN

OBJECTIVE: To characterize the profile of patients who were readmitted for mental and behavioral disorders, in the Brazilian Unified Health System, from 2001 to 2014, and the factors associated with early and frequent readmission. METHOD: A retrospective, non-concurrent cohort study of patients admitted with a primary diagnosis of mental or behavioral disorders, from 2001 to 2014. This study selected demographic variables and clinical variables, as well as variables related to the characteristics of the hospitals. Poisson Regression methods with a robust variance estimator were used to estimate the incidence rate ratio (IRR) for each of the outcomes. RESULTS: Early readmission occurred for 6.8% of the patients and frequent readmission for 8.3%. Characteristics such as being male, younger, with a diagnosis of a bipolar disorder, and admitted to a specialized hospital show a higher IRR for early readmission. The occurrence of early readmission was the most heavily associated characteristic with an increased rate of early readmission, and the magnitude of this increase depends on the patient's age. CONCLUSION: Early and frequent readmissions are linked to patients' demographics, clinical information and health system's organization. Early readmission should be a priority in treatment planning to prevent frequent readmissions due to its strong association.


Asunto(s)
Readmisión del Paciente , Humanos , Masculino , Femenino , Estudios de Cohortes , Estudios Retrospectivos , Brasil , Factores de Riesgo
5.
Mar Drugs ; 21(7)2023 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-37504919

RESUMEN

A blend refers to the combination of two or more components to achieve properties that are superior to those found in the individual products used for their production. Gracilaria birdiae agaran (SPGb) and chromium picolinate (ChrPic) are both antioxidant agents. However, there is no documentation of blends that incorporate agarans and ChrPic. Hence, the objective of this study was to generate blends containing SPGb and ChrPic that exhibit enhanced antioxidant activity compared to SPGb or ChrPic alone. ChrPic was commercially acquired, while SPGb was extracted from the seaweed. Five blends (B1; B2; B3; B4; B5) were produced, and tests indicated B5 as the best antioxidant blend. B5 was not cytotoxic or genotoxic. H2O2 (0.6 mM) induced toxicity in fibroblasts (3T3), and this effect was abolished by B5 (0.05 mg·mL-1); neither ChrPic nor SPGb showed this effect. The cells also showed no signs of toxicity when exposed to H2O2 after being incubated with B5 and ChrPic for 24 h. In another experiment, cells were incubated with H2O2 and later exposed to SPGb, ChrPic, or B5. Again, SPGb was not effective, while cells exposed to ChrPic and B5 reduced MTT by 100%. The data demonstrated that B5 has activity superior to SPGb and ChrPic and points to B5 as a product to be used in future in vivo tests to confirm its antioxidant action. It may also be indicated as a possible nutraceutical agent.


Asunto(s)
Gracilaria , Rhodophyta , Algas Marinas , Antioxidantes/farmacología , Peróxido de Hidrógeno/farmacología , Verduras
6.
Mar Drugs ; 21(11)2023 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-37999381

RESUMEN

Fucans from marine algae have been the object of many studies that demonstrated a broad spectrum of biological activities, including anti-inflammatory effects. The aim of this study was to verify the protective effects of a fucan extracted from the brown algae Spatoglossum schröederi in animals submitted to a generalized inflammation model induced by zymosan (ZIGI). BALB/c mice were first submitted to zymosan-induced peritonitis to evaluate the treatment dose capable of inhibiting the induced cellular migration in a simple model of inflammation. Mice were treated by the intravenous route with three doses (20, 10, and 5 mg/kg) of our fucan and, 1 h later, were inoculated with an intraperitoneal dose of zymosan (40 mg/kg). Peritoneal exudate was collected 24 h later for the evaluation of leukocyte migration. Doses of the fucan of Spatoglossum schröederi at 20 and 10 mg/kg reduced peritoneal cellular migration and were selected to perform ZIGI experiments. In the ZIGI model, treatment was administered 1 h before and 6 h after the zymosan inoculation (500 mg/kg). Treatments and challenges were administered via intravenous and intraperitoneal routes, respectively. Systemic toxicity was assessed 6 h after inoculation, based on three clinical signs (bristly hair, prostration, and diarrhea). The peritoneal exudate was collected to assess cellular migration and IL-6 levels, while blood samples were collected to determine IL-6, ALT, and AST levels. Liver tissue was collected for histopathological analysis. In another experimental series, weight loss was evaluated for 15 days after zymosan inoculation and fucan treatment. The fucan treatment did not present any effect on ZIGI systemic toxicity; however, a fucan dose of 20 mg/kg was capable of reducing the weight loss in treated mice. The treatment with both doses also reduced the cellular migration and reduced IL-6 levels in peritoneal exudate and serum in doses of 20 and 10 mg/kg, respectively. They also presented a protective effect in the liver, with a reduction in hepatic transaminase levels in both doses of treatment and attenuated histological damage in the liver at a dose of 10 mg/kg. Fucan from S. schröederi presented a promising pharmacological activity upon the murine model of ZIGI, with potential anti-inflammatory and hepatic protective effects, and should be the target of profound and elucidative studies.


Asunto(s)
Peritonitis , Phaeophyceae , Ratones , Animales , Zimosan/toxicidad , Interleucina-6 , Modelos Animales de Enfermedad , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Peritonitis/inducido químicamente , Peritonitis/tratamiento farmacológico , Antiinflamatorios/efectos adversos , Ascitis , Pérdida de Peso
7.
An Acad Bras Cienc ; 95(3): e20220865, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37878908

RESUMEN

In recent years, cold atmospheric plasma (CAP) is used for surface disinfection. However, little is known about its ability to improve biocompatibility of metallic surfaces when compared to thermal plasma methods. In this context, the study aimed to evaluate the response of human endothelial cells (Ea.hy926) on titanium surfaces treated by non-thermal plasma method and thermal plasma method under nitriding atmosphere. The wettability was characterized by the sessile drop method, the topography and roughness were evaluated by atomic force microscopy (AFM), and the microstructure by grazing angle X-ray diffraction (GIXRD). Endothelial cells were cultured and evaluated for morphology by scanning electron microscopy and viability by an MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. CAP treatment reduced the contact angle of the Ti surface (13.43° ± 1.48; p<0.05), increasing hydrophilicity. Rz roughness was higher on the nitrided surface (220.44±20.30; p< 0.001) compared to the CAP treated surfaces (83.29 ± 11.61; p< 0.001) and polished (75.98 ±34.21a); p<0.001). The different applied plasma treatments created different titanium surfaces improving the biocompatibility of endothelial cells, however CAP results demonstrate its potential for biomedical applications, considering the low cost and ease of use of the technique, allowing surface treatments before clinical procedures.


Asunto(s)
Gases em Plasma , Humanos , Propiedades de Superficie , Gases em Plasma/farmacología , Gases em Plasma/química , Células Endoteliales , Titanio/farmacología , Humectabilidad , Microscopía Electrónica de Rastreo
8.
Int J Mol Sci ; 24(21)2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37958868

RESUMEN

Oxidative stress has been associated with different diseases, and different medicinal plants have been used to treat or prevent this condition. The leaf ethanolic extract (EE) and aqueous extract (AE) from Coccoloba alnifolia have previously been characterized to have antioxidant potential in vitro and in vivo. In this study, we worked with EE and AE and two partition phases, AF (ethyl acetate) and BF (butanol), from AE extract. These extracts and partition phases did not display cytotoxicity. The EE and AE reduced NO production and ROS in all three concentrations tested. Furthermore, it was observed that EE and AE at 500 µg/mL concentration were able to reduce phagocytic activity by 30 and 50%, respectively. A scratch assay using a fibroblast cell line (NHI/3T3) showed that extracts and fractions induced cell migration with 60% wound recovery within 24 h, especially for BF. It was also observed that AF and BF had antioxidant potential in all the assays evaluated. In addition, copper chelation was observed. This activity was previously not detected in AE. The HPLC-DAD analysis showed the presence of phenolic compounds such as p-cumaric acid and vitexin for extracts, while the GNPS annotated the presence of isoorientin, vitexin, kanakugiol, and tryptamine in the BF partition phase. The data presented here demonstrated that the EE, AE, AF, and BF of C. alnifolia have potential immunomodulatory effects, antioxidant effects, as well as in vitro wound healing characteristics, which are important for dynamic inflammation process control.


Asunto(s)
Antioxidantes , Cicatrización de Heridas , Antioxidantes/farmacología , Estrés Oxidativo , Fenoles/farmacología , Línea Celular , Extractos Vegetales/farmacología , Extractos Vegetales/análisis , Etanol/farmacología , Hojas de la Planta
9.
Molecules ; 28(7)2023 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-37049845

RESUMEN

Oreochromis niloticus (tilapia) is one of the most cultivated fish species worldwide. Tilapia farming generates organic waste from fish removal processes in nurseries. Visceral waste can damage natural ecosystems. Therefore, the use of this material as a source of biomolecules helps reduce environmental impacts and improve pharmacological studies. Tilapia viscera were subjected to proteolysis and complexation with an ion-exchange resin. The obtained glycosaminoglycans were purified using ion exchange chromatography (DEAE-Sephacel). The electrophoretic profile and analysis of 1H/13C nuclear magnetic resonance (NMR) spectra allowed for the characterization of the compound as chondroitin sulfate and its sulfation position. This chondroitin was named CST. We tested the ability of CST to reduce leukocyte influx in acute peritonitis models induced by sodium thioglycolate and found a significant reduction in leukocyte migration to the peritoneal cavity, similar to the polymorphonuclear population of the three tested doses of CST. This study shows, for the first time, the potential of CST obtained from O. niloticus waste as an anti-inflammatory drug, thereby contributing to the expansion of the study of molecules with pharmacological functions.


Asunto(s)
Cíclidos , Peritonitis , Tilapia , Animales , Sulfatos de Condroitina , Ecosistema , Peritonitis/inducido químicamente , Peritonitis/tratamiento farmacológico
10.
Arch Biochem Biophys ; 730: 109419, 2022 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-36183841

RESUMEN

Exercise training provides several cardiovascular benefits in both physiological and pathological conditions; however, its use as a therapeutic tool for pulmonary arterial hypertension (PAH) has been poorly explored. This study aimed to extend the comprehension of the cardioprotective effects of exercise training in the set of PAH focusing on the metabolic changes promoted by exercise in the right ventricle (RV). The monocrotaline animal model of PAH was used and male Wistar rats were submitted to two weeks of treadmill exercise training (5 days/week, 60 min/day, 25 m/min) following disease establishment. Trained rats showed an improved diastolic function (lower end-diastolic pressure and tau) despite the presence of cardiac overload (increased peak systolic pressure, end-diastolic pressure and arterial elastance). This enhanced hemodynamic response was paralleled by an increased uptake of glucose to cardiomyocytes through glucose transporter type 4 (GLUT4) followed by increased lactate dehydrogenase (LDH) activity. Exercise did not reverse the decrease of fatty acid oxidation related to PAH but increased the content of the transcription factors peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and peroxisome proliferator-activated receptor gamma (PPAR-γ). Two weeks of exercise did not modulate the changes in amino acid metabolism secondary to PAH. Our work suggests that continuous aerobic exercise of moderate intensity, despite its short-term duration and application in a late stage of the disease, supports the RV response to PAH by promoting a shift in the cardiac metabolic phenotype.


Asunto(s)
Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Masculino , Ratas , Animales , Monocrotalina/efectos adversos , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Hipertensión Pulmonar/terapia , Hipertensión Pulmonar/patología , PPAR gamma/metabolismo , Transportador de Glucosa de Tipo 4 , Ratas Wistar , Modelos Animales de Enfermedad , Glucosa , Lactato Deshidrogenasas/metabolismo , Aminoácidos , Ácidos Grasos
11.
Anal Bioanal Chem ; 414(24): 7085-7101, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35840669

RESUMEN

Dried blood spots (DBS) are being considered as an alternative sampling method of blood collection that can be used in combination with lipidomic and other omic analysis. DBS are successfully used in the clinical context to collect samples for newborn screening for the measurement of specific fatty acid derivatives, such as acylcarnitines, and lipids from whole blood for diagnostic purposes. However, DBS are scarcely used for lipidomic analysis and investigations. Lipidomic studies using DBS are starting to emerge as a powerful method for sampling and storage in clinical lipidomic analysis, but the major research work is being done in the pre- and analytical steps and procedures, and few in clinical applications. This review presents a description of the impact factors and variables that can affect DBS lipidomic analysis, such as the type of DBS card, haematocrit, homogeneity of the blood drop, matrix/chromatographic effects, and the chemical and physical properties of the analyte. Additionally, a brief overview of lipidomic studies using DBS to unveil their application in clinical scenarios is also presented, considering the studies of method development and validation and, to a less extent, for clinical diagnosis using clinical lipidomics. DBS combined with lipidomic approaches proved to be as effective as whole blood samples, achieving high levels of sensitivity and specificity during MS and MS/MS analysis, which could be a useful tool for biomarker identification. Lipidomic profiling using MS/MS platforms enables significant insights into physiological changes, which could be useful in precision medicine.


Asunto(s)
Lipidómica , Espectrometría de Masas en Tándem , Biomarcadores , Pruebas con Sangre Seca/métodos , Ácidos Grasos , Humanos , Recién Nacido , Lípidos , Espectrometría de Masas en Tándem/métodos
12.
Mar Drugs ; 20(8)2022 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-35892938

RESUMEN

Sulfated polysaccharides (SPS) from seaweeds have great biochemical and biotechnological potential. This study aimed to investigate the effect of SPS isolated from the seaweed Caulerpa sertularioides on adipogenic differentiation as a possible alternative treatment for obesity. The SPS-rich extract from the seaweed C. sertularioides was fractioned into three SPS-rich fractions (F0.5; F0.9; and F1.8) chemically characterized. Among these four samples, only F0.9 showed a significant inhibitory effect on adipogenesis of 3T3-L1 preadipocytes. Ten SPS-rich fractions were isolated from F0.9 through ion-exchange chromatography. However, only the fraction (CS0.2) containing a sulfated glucan was able to inhibit adipogenesis. CS0.2 reduces lipid accumulation and inhibits the expression of key adipogenic (PPARγ, C/EBPß, and C/EBPα) and lipogenic markers (SREBP-1c, Fabp4, and CD36). The data points to the potential of sulfated glucan from C. sertularioides for the development of functional approaches in obesity management.


Asunto(s)
Caulerpa , Algas Marinas , Células 3T3-L1 , Adipocitos , Adipogénesis , Animales , Caulerpa/metabolismo , Glucanos/farmacología , Ratones , PPAR gamma/metabolismo , Polisacáridos/metabolismo , Polisacáridos/farmacología , Algas Marinas/química , Sulfatos/farmacología
13.
Mar Drugs ; 20(8)2022 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-36005493

RESUMEN

Antioxidant compounds decrease the amount of intracellular reactive oxygen species (ROS) and, consequently, reduce the deleterious effects of ROS in osteoblasts. Here, we modified a 21 kDa fucoidan (FucA) with gallic acid (GA) using the redox method, to potentiate its antioxidant/protective capacity on pre-osteoblast-like cells (MC3T3) against oxidative stress. The 20 kDa FucA-GA contains 37 ± 3.0 mg GA per gram of FucA. FucA-GA was the most efficient antioxidant agent in terms of total antioxidant capacity (2.5 times), reducing power (five times), copper chelation (three times), and superoxide radical scavenging (2 times). Exposure of MC3T3 cells to H2O2 increased ROS levels and activated caspase-3 along with caspase-9. In addition, the cell viability decreased approximately 80%. FucA-GA also provided the most effective protection against oxidative damage caused by H2O2. Treatment with FucA-GA (1.0 mg/mL) increased cell viability (~80%) and decreased intracellular ROS (100%) and caspase activation (~80%). In addition, Fuc-GA (0.1 mg/mL) abolished H2O2-induced oxidative stress in zebra fish embryos. Overall, FucA-GA protected MC3T3 cells from oxidative stress and could represent a possible adjuvant for the treatment of bone fragility by counteracting oxidative phenomena.


Asunto(s)
Antioxidantes , Ácido Gálico , Animales , Antioxidantes/farmacología , Ácido Gálico/farmacología , Peróxido de Hidrógeno/farmacología , Oxidación-Reducción , Estrés Oxidativo , Polisacáridos , Especies Reactivas de Oxígeno
14.
Int J Mol Sci ; 23(7)2022 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-35409278

RESUMEN

Mothers' antenatal strategies to improve the intrauterine environment can positively decrease pregnancy-derived intercurrences. By challenging the mother-fetus unit, gestational exercise (GE) favorably modulates deleterious stimuli, such as high-fat, high-sucrose (HFHS) diet-induced adverse consequences for offspring. We aimed to analyze whether GE alters maternal HFHS-consumption effects on male offspring's maximal workload performance (MWP) and in some skeletal muscle (the soleus-SOL and the tibialis anterior-TA) biomarkers associated with mitochondrial biogenesis and oxidative fitness. Infant male Sprague-Dawley rats were divided into experimental groups according to mothers' dietary and/or exercise conditions: offspring of sedentary control diet-fed or HFHS-fed mothers (C-S or HFHS-S, respectively) and of exercised HFHS-fed mothers (HFHS-E). Although maternal HFHS did not significantly alter MWP, offspring from GE dams exhibited increased MWP. Lower SOL AMPk levels in HFHS-S were reverted by GE. SOL PGC-1α, OXPHOS C-I and C-IV subunits remained unaltered by maternal diet, although increased in HFHS-E offspring. Additionally, GE prevented maternal diet-related SOL miR-378a overexpression, while upregulated miR-34a expression. Decreased TA C-IV subunit expression in HFHS-S was reverted in HFHS-E, concomitantly with the downregulation of miR-338. In conclusion, GE in HFHS-fed dams increases the offspring's MWP, which seems to be associated with the intrauterine modulation of SM mitochondrial density and functional markers.


Asunto(s)
MicroARNs , Condicionamiento Físico Animal , Animales , Dieta Alta en Grasa/efectos adversos , Femenino , Humanos , Masculino , MicroARNs/genética , Condicionamiento Físico Animal/fisiología , Embarazo , Ratas , Ratas Sprague-Dawley , Sacarosa , Carga de Trabajo
15.
Int J Mol Sci ; 23(22)2022 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-36430419

RESUMEN

Fatty acid oxidation disorders (FAODs) are inborn errors of metabolism (IEMs) caused by defects in the fatty acid (FA) mitochondrial ß-oxidation. The most common FAODs are characterized by the accumulation of medium-chain FAs and long-chain (3-hydroxy) FAs (and their carnitine derivatives), respectively. These deregulations are associated with lipotoxicity which affects several organs and potentially leads to life-threatening complications and comorbidities. Changes in the lipidome have been associated with several diseases, including some IEMs. In FAODs, the alteration of acylcarnitines (CARs) and FA profiles have been reported in patients and animal models, but changes in polar and neutral lipid profile are still scarcely studied. In this review, we present the main findings on FA and CAR profile changes associated with FAOD pathogenesis, their correlation with oxidative damage, and the consequent disturbance of mitochondrial homeostasis. Moreover, alterations in polar and neutral lipid classes and lipid species identified so far and their possible role in FAODs are discussed. We highlight the need of mass-spectrometry-based lipidomic studies to understand (epi)lipidome remodelling in FAODs, thus allowing to elucidate the pathophysiology and the identification of possible biomarkers for disease prognosis and an evaluation of therapeutic efficacy.


Asunto(s)
Errores Innatos del Metabolismo Lipídico , Enfermedades Mitocondriales , Enfermedades Musculares , Animales , Lipidómica , Enfermedades Musculares/tratamiento farmacológico , Ácidos Grasos/metabolismo , Lípidos/uso terapéutico
16.
Int J Mol Sci ; 23(15)2022 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-35955687

RESUMEN

Leishmanolysin, also known as major promastigote protease (PSP) or gp63, is the most abundant surface glycoprotein of Leishmania spp., and has been extensively studied and recognized as the main parasite virulence factor. Characterized as a metalloprotease, gp63 can be powerfully inactivated in the presence of a metal chelator. In this study, we first used the structural parameters of a 7-hydroxycoumarin derivative, L1 compound, to evaluate the theoretical-computational experiments against gp63, comparing it with an available metal chelator already described. The methodology followed was (i) analysis of the three-dimensional structure of gp63 as well as its active site, and searching the literature and molecular databases for possible inhibitors; (ii) molecular docking simulations and investigation of the interactions in the generated protein-ligand complexes; and (iii) the individual energy of the gp63 amino acids that interacted most with the ligands of interest was quantified by ab initio calculations using Molecular Fraction with Conjugated Caps (MFCC). MFCC still allowed the final quantum balance calculations of the protein interaction to be obtained with each inhibitor candidate binder. L1 obtained the best energy quantum balance result with -2 eV, followed by DETC (-1.4 eV), doxycycline (-1.3 eV), and 4-terpineol (-0.6 eV), and showed evidence of covalent binding in the enzyme active site. In vitro experiments confirmed L1 as highly effective against L. amazonensis parasites. The compound also exhibited a low cytotoxicity profile against mammalian RAW and 3T3 cells lines, presenting a selective index of 149.19 and 380.64 µM, respectively. L1 induced promastigote forms' death by necrosis and the ultrastructural analysis revealed disruption in membrane integrity. Furthermore, leakage of the contents and destruction of the parasite were confirmed by Spectroscopy Dispersion analysis. These results together suggested L1 has a potential effect against L. amazonensis, the etiologic agent of diffuse leishmaniasis, and the only one that currently does not have a satisfactory treatment.


Asunto(s)
Leishmania , Animales , Quelantes , Leishmania/metabolismo , Mamíferos/metabolismo , Metaloendopeptidasas/metabolismo , Metaloproteasas , Ratones , Simulación del Acoplamiento Molecular , Fagocitosis
17.
Mar Drugs ; 19(2)2021 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-33673266

RESUMEN

The global rise of infectious disease outbreaks and the progression of microbial resistance reinforce the importance of researching new biomolecules. Obtained from the hydrolysis of chitosan, chitooligosaccharides (COSs) have demonstrated several biological properties, including antimicrobial, and greater advantage over chitosan due to their higher solubility and lower viscosity. Despite the evidence of the biotechnological potential of COSs, their effects on trypanosomatids are still scarce. The objectives of this study were the enzymatic production, characterization, and in vitro evaluation of the cytotoxic, antibacterial, antifungal, and antiparasitic effects of COSs. NMR and mass spectrometry analyses indicated the presence of a mixture with 81% deacetylated COS and acetylated hexamers. COSs demonstrated no evidence of cytotoxicity upon 2 mg/mL. In addition, COSs showed interesting activity against bacteria and yeasts and a time-dependent parasitic inhibition. Scanning electron microscopy images indicated a parasite aggregation ability of COSs. Thus, the broad biological effect of COSs makes them a promising molecule for the biomedical industry.


Asunto(s)
Antiinfecciosos/farmacología , Antiparasitarios/farmacología , Quitina/análogos & derivados , Antiinfecciosos/química , Antineoplásicos/química , Antineoplásicos/farmacología , Antiparasitarios/química , Quitina/química , Quitina/farmacocinética , Quitosano , Microscopía Electrónica de Rastreo , Oligosacáridos , Factores de Tiempo
18.
Int J Mol Sci ; 22(19)2021 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-34638973

RESUMEN

The search for promising biomolecules such as chitooligosaccharides (COS) has increased due to the need for healing products that act efficiently, avoiding complications resulting from exacerbated inflammation. Therefore, this study aimed to produce COS in two stages of hydrolysis using chitosanases derived from Bacillus toyonensis. Additionally, this study aimed to structurally characterize the COS via mass spectrometry, to analyze their biocompatibility in acute toxicity models in vivo, to evaluate their healing action in a cell migration model in vitro, to analyze the anti-inflammatory activity in in vivo models of xylol-induced ear edema and zymosan-induced air pouch, and to assess the wound repair action in vivo. The structural characterization process pointed out the presence of hexamers. The in vitro and in vivo biocompatibility of COS was reaffirmed. The COS stimulated the fibroblast migration. In the in vivo inflammatory assays, COS showed an antiedematogenic response and significant reductions in leukocyte migration, cytokine release, and protein exudate. The COS healing effect in vivo was confirmed by the significant wound reduction after seven days of the experiment. These results indicated that the presence of hexamers influences the COS biological properties, which have potential uses in the pharmaceutical field due to their healing and anti-inflammatory action.


Asunto(s)
Antiinflamatorios/administración & dosificación , Materiales Biocompatibles/administración & dosificación , Quitosano/administración & dosificación , Enfermedades del Oído/tratamiento farmacológico , Edema/tratamiento farmacológico , Oligosacáridos/administración & dosificación , Cicatrización de Heridas/efectos de los fármacos , Células 3T3 , Animales , Antiinflamatorios/química , Bacillus/enzimología , Materiales Biocompatibles/química , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Quitosano/química , Citocinas/metabolismo , Modelos Animales de Enfermedad , Enfermedades del Oído/inducido químicamente , Edema/inducido químicamente , Femenino , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Glicósido Hidrolasas/química , Hidrólisis , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Leucocitos/efectos de los fármacos , Leucocitos/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Oligosacáridos/química
19.
Int J Mol Sci ; 22(21)2021 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-34768954

RESUMEN

Reactive oxygen species (ROS) are aerobic products generated during cellular respiration, but in the case of oxidative stress, they become key factors in the development of inflammatory processes and chronic diseases such as diabetes and rheumatoid arthritis. In this work, Euterpe oleracea oil (EOO), as well as the complexes produced by slurry (S) and kneading (K), were analyzed for antioxidant capacity in vitro, while only the ß-cyclodextrin complex obtained by kneading (EOO-ßCD-K), which showed better complexation, was selected for anti-inflammatory assays in vivo. In the scavenging activity of OH·, the hydroxypropyl-ß-cyclodextrin complex obtained by kneading (EOO-HPßCD-K) exhibited an activity 437% higher than the pure oil. In the paw edema assay, EOO-ßCD-K reduced edema by 200% and myeloperoxidase (MPO) activity by 112%. In an air pouch model, this treatment showed a reduction in leukocyte, MPO, and Interleukin-1ß (IL-1ß) levels; meanwhile those of glutathione and IL-10 were increased, demonstrating its ability to potentiate the anti-inflammatory effect of EOO.


Asunto(s)
Euterpe/química , Aceites de Plantas/química , Aceites de Plantas/farmacología , 2-Hidroxipropil-beta-Ciclodextrina/administración & dosificación , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antioxidantes/administración & dosificación , Antioxidantes/química , Antioxidantes/farmacología , Edema/tratamiento farmacológico , Femenino , Técnicas In Vitro , Masculino , Ratones , Fitoquímicos/administración & dosificación , Fitoquímicos/química , Fitoquímicos/farmacología , Aceites de Plantas/administración & dosificación , Plantas Medicinales/química , beta-Ciclodextrinas/administración & dosificación
20.
Molecules ; 27(1)2021 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-35011403

RESUMEN

Animal chitosan (Chit-A) is gaining more acceptance in daily activities. It is used in a range of products from food supplements for weight loss to even raw materials for producing nanoparticles and hydrogel drug carriers; however, it has low antioxidant activity. Fungal oligochitosan (OChit-F) was identified as a potential substitute for Chit-A. Cunninghamella elegans is a fungus found in the Brazilian savanna (Caatinga) that produces OligoChit-F, which is a relatively poorly studied compound. In this study, 4 kDa OChit-F with a 76% deacetylation degree was extracted from C. elegans. OChit-F showed antioxidant activity similar to that of Chit-A in only one in vitro test (copper chelation) but exhibited higher activity than that of Chit-A in three other tests (reducing power, hydroxyl radical scavenging, and iron chelation). These results indicate that OChit-F is a better antioxidant than Chit-A. In addition, Chit-A significantly increased the formation of calcium oxalate crystals in vitro, particularly those of the monohydrate (COM) type; however, OChit-F had no effect on this process in vitro. In summary, OChit-F had higher antioxidant activity than Chit-A and did not induce the formation of CaOx crystals. Thus, OChit-F can be used as a Chit-A substitute in applications affected by oxidative stress.


Asunto(s)
Antioxidantes/química , Antioxidantes/farmacología , Quitosano/química , Quitosano/farmacología , Cunninghamella/metabolismo , Oligosacáridos/biosíntesis , Oligosacáridos/farmacología , Animales , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Oxalato de Calcio/química , Estrés Oxidativo/efectos de los fármacos , Tamaño de la Partícula , Espectroscopía Infrarroja por Transformada de Fourier
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