Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 158
Filtrar
Más filtros

Intervalo de año de publicación
1.
Life Sci ; 351: 122800, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38880169

RESUMEN

BACKGROUND: Aging increases the prevalence of prostate cancer. The circadian clock coordinates metabolism, cell cycle, and tumor suppressor p53. Although physical exercise has several effects on preventing prostate diseases, its effect on regulating genes and proteins of the circadian rhythm of the prostate needs to be better evaluated. The present study verified expression of REV-ERBα (Nr1d1), Bmal1, apoptosis, tumor suppressors, energetic metabolism markers, and androgen receptors in the prostatic microenvironment in 18-month-old mice submitted to combined physical training. METHODS: C57BL/6 J mice were divided into 2 groups: 6 months-old (n = 10) and 18 months-old, (n = 20). The 18-month-old animals were divided into 2 subgroups: sedentary (n = 10, 18 m Sed) and submitted to combined physical training (n = 10, 18 m TR). Combined physical training protocol was performed by running on the treadmill (40-60 % of incremental load test) and climbing strength training (40-50 % of maximum repetition test), consisting of 5×/week (3 days aerobic and 2 days strength) for 3 weeks. The prostate was prepared for Western blot and RT-qPCR analysis, and the plasm was prepared for the biochemistry analysis. RESULTS: Combined physical exercise during aging led to increased levels of Bmal1 and decreased levels of REV-ERBα in the prostate. These results were accompanied by a reduction in the AMPK/SIRT1/PGC-1α proteins and an increase in the PI3K/AKT and p53/PTEN/caspase 3 pathways, promoting apoptotic potential. CONCLUSION: These findings suggest that strength and aerobic physical exercise may be preventive in the development of preneoplastic molecular alterations and age-related features by re-synchronizes Bmal1 and REV-ERBα in prostatic tissues.


Asunto(s)
Factores de Transcripción ARNTL , Envejecimiento , Apoptosis , Ratones Endogámicos C57BL , Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares , Condicionamiento Físico Animal , Próstata , Masculino , Animales , Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares/metabolismo , Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares/genética , Factores de Transcripción ARNTL/metabolismo , Factores de Transcripción ARNTL/genética , Ratones , Condicionamiento Físico Animal/fisiología , Envejecimiento/metabolismo , Próstata/metabolismo , Próstata/patología , Regulación hacia Arriba , Ritmo Circadiano/fisiología
2.
SLAS Technol ; : 100158, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38908548

RESUMEN

This work aimed to synthesize and characterize a biocompatible hydrogel of alginate and chitosan enriched with iron sulfide nanoparticles. Three concentrations of iron sulfide nanoparticles (FeS2NCs) 0.03905, 0.0781, and 0.2343 mg/ml were used. Gel swelling was determined using phosphate-buffered saline solution at 1, 2, 4, 6, 24, 48, and 72 h. The microstructure, the morphology, and the elastic strength were determined by optical microscopy, scanning electron microscopy, and rheological studies, respectively. The functional groups were identified through Fourier transform infrared spectroscopy. Biocompatibility was determined in a murine model; after seven days of subdermal inoculation, histological sections stained with H&E were analyzed, and then histopathological features were evaluated. All the compounds obtained showed a loss modulus lower than the storage modulus. The 0.2343 mg/ml FeS2NCs hydrogel showed higher swelling than the control. In the in vivo evaluation, no adverse effects were found. The presence of FeS2NCs was well tolerated in the subcutaneous tissue of mice, according to histopathological analysis. The hydrogels synthesized with added FeS2NCs demonstrate a swelling ratio of 150%, rheologically exhibiting gel-like behavior rather than viscous liquids. Furthermore, they did not present any adverse effects on the subcutaneous tissue.

3.
Sci Rep ; 14(1): 9626, 2024 04 26.
Artículo en Inglés | MEDLINE | ID: mdl-38671015

RESUMEN

The variability in response to conventional prostate cancer (PC) therapies, coupled with the emergent issue of drug resistance, underscores the critical need for innovative treatment strategies. Aerobic physical exercise reduced incidence of several cancers, but the mechanism underlying these effects associated the nanoemulsion not fully understood. The application of a lipid nanoemulsion (LDE) delivery system for docetaxel (DTX), showing marked enhancement in therapeutic efficacy when combined with aerobic physical exercise. This novel intervention potentiates the antitumor activity of LDE-delivered DTX by augmenting nanoparticle internalization and inducing cell cycle arrest. Our findings reveal that this synergistic treatment not only significantly reduces prostate weight and mitigates adenocarcinoma proliferation but also attenuates anti-apoptotic BCL-2 protein expression. Concurrently, it elevates pro-apoptotic proteins and diminishes inflammatory markers. Metabolic profiling of the combined therapy group disclosed additional benefits, such as reduced lipid and plasma glucose levels. Collectively, our data illuminate the profound impact of integrating LDE-mediated DTX delivery with structured physical exercise, which together spearhead a dual-front assault on PC. This multimodal approach heralds a new paradigm in PC management, accentuating the promise of combined pharmacological and non-pharmacological interventions to elevate tumor suppressor protein activity and refine patient outcomes.


Asunto(s)
Docetaxel , Neoplasias de la Próstata , Masculino , Docetaxel/farmacología , Docetaxel/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/terapia , Neoplasias de la Próstata/metabolismo , Humanos , Animales , Emulsiones , Línea Celular Tumoral , Apoptosis/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Ratones , Lípidos/sangre , Progresión de la Enfermedad , Ejercicio Físico , Nanopartículas/química , Proliferación Celular/efectos de los fármacos , Condicionamiento Físico Animal
4.
RSC Adv ; 14(7): 4436-4447, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38312721

RESUMEN

In this study, we developed an ink using hexanethiol and Cu(In,Ga)Se2 microcrystals (CIGSe MCs) to make thin films via doctor blade coating. Besides, crack-free thin films were obtained by optimizing CIGSe MC powder concentration and annealing temperature. Subsequently, single-step selenization was performed with and without sodium chloride (NaCl) surface treatment by carefully tuning the temperature. A crack-free surface with densely packed grains was obtained at 500 °C after NaCl treatment. Moreover, the structural parameters of the thin film (annealed at 350 °C) were significantly modified via selenization with NaCl at 500 °C. For instance, the FWHM of the prominent (112) plane reduced from 1.44° to 0.47°, the dislocation density minimized from 13.10 to 1.40 × 1015 lines per m2, and the microstrain decreased from 4.14 to 1.35 × 10-3. Remarkably, these thin films exhibited a high mobility of 26.7 cm2 V-1 s-1 and a low resistivity of 0.03 Ω cm. As a proof of concept, solar cells were engineered with a device structure of SLG/Mo/CIGSe/CdS/i-ZnO/Al-ZnO/Ag, wherein a power conversion efficiency (PCE) of 5.74% was achieved with exceptional reproducibility. Consequently, the outcomes of this investigation revealed the impact of selenization temperature and NaCl treatment on the physical properties and PCE of hexanethiol-based crack-free CIGSe MC ink-coated absorbers, providing new insights into the groundwork of cost-effective solar cells.

5.
Artículo en Inglés | MEDLINE | ID: mdl-38324875

RESUMEN

Bartonella spp. are bacteria responsible for neglected diseases worldwide. Bartonella henselae is the species most associated with human infections. It is associated with a large spectrum of clinical manifestations and is potentially fatal. The identification of Bartonella spp. is considered a challenge in clinical routine. These bacteria are fastidious, and the time required to isolate them varies from one to six weeks. MALDI-TOF mass spectrometry has emerged as an application for research on Bartonella spp. , and has still been little explored. We investigated whether three different B. henselae strains with different growth times-14 and 28 days-could be correctly identified by MALDI-TOF mass spectra fingerprint comparison and matching. We found that the spectra from strains with different growth times do not match each other, leading to misidentification. We suggest creating database entries with multiple spectra from strains with different growth times to increase the chances of accurate identification of Bartonella spp. by MALD-TOF MS.


Asunto(s)
Bartonella henselae , Bartonella , Humanos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos
6.
Am J Med Genet A ; 194(6): e63536, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38243380

RESUMEN

Adrenal hypoplasia congenita, attributed to NR0B1 pathogenic variants, accounts for more than 50% of the incidence of primary adrenal insufficiency in children. Although more than 250 different deleterious variations have been described, no genotype-phenotype correlation has been defined to date. We report a case of an adopted boy who reported the onset of an adrenal crisis at 2 weeks of age, requiring replacement therapy with mineralocorticoids and glucocorticoids for 4 months. For 3 years, he did well without treatment. At almost 4 years of age, the disorder was restarted. A long follow-up showed the evolution of hypogonadotropic hypogonadism. Molecular studies on NR0B1 revealed a novel and deleterious deletion-insertion-inversion-deletion complex rearrangement sorted in the 5'-3' direction, which is described as follows: (1) deletion of the intergenic region (between TASL and NR0B1 genes) and 5' region, (2) insertion of a sequence containing 37 bp at the junction of the intergenic region of the TASL gene and a part of exon 1 of the NR0B1 gene, (3) inversion of a part of exon 1, (4) deletion of the final portion of exon 1 and exon 2 and beginning of the 3'UTR region, (5) maintenance of part of the intergenic sequence (between genes MAGEB1 and NR0B1, telomeric sense), (6) large posterior deletion, in the same sense. The path to molecular diagnosis was challenging and involved several molecular biology techniques. Evaluating the breakpoints in our patient, we assumed that it was a nonrecurrent rearrangement that had not yet been described. It may involve a repair mechanism known as nonhomologous end-joining (NHEJ), which joins two ends of DNA in an imprecise manner, generating an "information scar," represented herein by the 37 bp insertion. In addition, the local Xp21 chromosome architecture with sequences capable of modifying the DNA structure could impact the formation of complex rearrangements.


Asunto(s)
Insuficiencia Suprarrenal , Receptor Nuclear Huérfano DAX-1 , Preescolar , Humanos , Masculino , Insuficiencia Suprarrenal/genética , Insuficiencia Suprarrenal/patología , Insuficiencia Suprarrenal/diagnóstico , Insuficiencia Suprarrenal/congénito , Receptor Nuclear Huérfano DAX-1/genética , Estudios de Seguimiento , Estudios de Asociación Genética/métodos , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/patología , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Insuficiencia Corticosuprarrenal Familiar/genética , Mutación/genética , Fenotipo , Recién Nacido , Adolescente
7.
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1535309

RESUMEN

ABSTRACT Bartonella spp. are bacteria responsible for neglected diseases worldwide. Bartonella henselae is the species most associated with human infections. It is associated with a large spectrum of clinical manifestations and is potentially fatal. The identification of Bartonella spp. is considered a challenge in clinical routine. These bacteria are fastidious, and the time required to isolate them varies from one to six weeks. MALDI-TOF mass spectrometry has emerged as an application for research on Bartonella spp. , and has still been little explored. We investigated whether three different B. henselae strains with different growth times—14 and 28 days—could be correctly identified by MALDI-TOF mass spectra fingerprint comparison and matching. We found that the spectra from strains with different growth times do not match each other, leading to misidentification. We suggest creating database entries with multiple spectra from strains with different growth times to increase the chances of accurate identification of Bartonella spp. by MALD-TOF MS.

8.
Environ Sci Pollut Res Int ; 30(47): 104015-104028, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37697193

RESUMEN

Endocrine disruptors (ED) are compounds dispersed in the environment that modify hormone biosynthesis, affecting hormone-dependent organs such as the prostate. Studies have only focused on evaluating the effects of ED alone or in small groups and short intervals and have not adequately portrayed human exposure. Therefore, we characterized the prostate histoarchitecture of rats exposed to an ED mixture (ED Mix) mimicking human exposure. Pregnant females of the Sprague-Dawley strain were randomly distributed into two experimental groups: Control group (vehicle: corn oil, by gavage) and ED Mix group: received 32.11 mg/kg/day of the ED mixture diluted in corn oil (2 ml/kg), by gavage, from gestational day 7 (DG7) to post-natal day 21 (DPN21). After weaning at DPN22, the male pups continued to receive the complete DE mixture until they were 220 days old when they were euthanized. The ED Mix decreased the epithelial compartment, increased the fractal dimension, and decreased glandular dilation. In addition, low-grade prostatic intraepithelial neoplasia was observed in addition to regions of epithelial atrophy in the group exposed to the ED Mix. Exposure to the mixture decreased both types I and III collagen area in the stroma. We concluded that the ED Mix was able to cause alterations in the prostatic histoarchitecture and induce the appearance of preneoplastic lesions.


Asunto(s)
Disruptores Endocrinos , Humanos , Embarazo , Femenino , Ratas , Animales , Masculino , Ratas Sprague-Dawley , Disruptores Endocrinos/toxicidad , Próstata , Aceite de Maíz/farmacología , Hormonas
9.
Arch Oral Biol ; 155: 105805, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37741048

RESUMEN

OBJECTIVE: To investigate the effects of the anticonvulsant valproic acid (VPA) on salivary glands in male rat using biochemical, functional, histomorphometric, and redox state parameters. MATERIALS AND METHODS: Twenty-four male Wistar rats were randomly distributed into three groups (n = 8 per group): Control (0.9% saline solution), VPA100 (100 mg/kg), and VPA400 (400 mg/kg). After 21 consecutive days of treatment with by intragastric gavage. Pilocarpine-induced saliva was collected to determine salivary flow rate, pH, buffering capacity, and biochemical composition. Analyses of histomorphometric parameters and redox balance markers were performed on the parotid and submandibular glands. RESULTS: Salivary flow rate, pH, buffering capacity, total protein, potassium, sodium, and chloride were similar between groups. However, phosphate and calcium were reduced in VPA400, while amylase was increased in both VPA100 and VPA400. We did not detect significant differences in the areas of acini, ducts, and connective tissue in the salivary glands between the groups. There were no significant changes in the redox status of the submandibular glands. In turn, in the parotid glands we detected reduced total oxidizing capacity and lipid peroxidation, measured as thiobarbituric acid reactive substances (TBARs) and higher uric acid concentration in both the VPA100 and VPA400 groups, and increased superoxide dismutase (SOD) in the VPA400 group. CONCLUSION: Chronic treatment with VPA modified the salivary biochemical composition and caused disruption in the redox state of the parotid gland in rats.


Asunto(s)
Anticonvulsivantes , Ácido Valproico , Ratas , Masculino , Animales , Anticonvulsivantes/farmacología , Ácido Valproico/farmacología , Ácido Valproico/análisis , Ácido Valproico/metabolismo , Ratas Wistar , Glándulas Salivales/metabolismo , Saliva/química , Glándula Parótida/metabolismo , Glándula Submandibular/metabolismo , Oxidación-Reducción
10.
Life Sci ; 332: 122097, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37741323

RESUMEN

Exercise is recognized for its potential role in reducing the risk of certain cancers. However, the molecular mechanisms behind this risk reduction are not fully understood. Here, we hypothesized that aerobic physical exercise induces cancer attenuating effects through the modulation of oxidative stress and inflammation. To test this hypothesis, twenty male Sprague Dawley rats with chemically induced prostate tumors were divided into two groups: Prostate cancer (PC) in the absence and presence of exercise (PC + Ex). Rats in the PC + Ex group performed exercises on a treadmill for 8 weeks, 5 sessions per week, at an intensity of 60 % of maximum capacity. Weight and feed efficiency, Ki-67, apoptosis, prostatic inflammation, and markers of oxidative stress were analyzed. We found that aerobic physical exercise significantly decreased prostate cell proliferation (p < 0.05) across modulation, tumor size, and prostate weight. The PC + Ex group also significantly reduced anti-apoptosis protein expression (p < 0.05) and increased pro-apoptotic protein expression. Furthermore, physical exercise increased enzymatic antioxidant defenses in the prostate, plasma, and whole blood. Moreover, PC + Ex reduced lipid peroxidation and protein carbonyl levels (p < 0.05). In the prostate, there was an increase in anti-inflammatory cytokines (IL-10), and a reduction in pro-inflammatory cytokines (IL-6, TNF-α, and NF-κB) after 8 weeks of physical exercise. In conclusion, we found that aerobic physical exercise is a functional, beneficial, and applicable approach to control PC progression, because it modifies the systemic environment, including the regulation of glucose and circulating lipids. This modification of the cancer cells environment has anti-inflammatory and antioxidant effects that attenuate tumor growth.

11.
Toxicology ; 496: 153615, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37572749

RESUMEN

Levetiracetam (LEV) is an anticonvulsant for epilepsy. The toxic effects of this medication in tissues have been associated with redox state imbalance, which can lead to salivary gland dysfunction. Therefore, the current work investigated the effects of LEV on the biochemical, functional, and redox parameters of the parotid and submandibular glands in rats. For this, male Wistar rats (Rattus norvegicus albinus) were randomly divided into 3 groups (n = 10/group): Control (0.9% saline solution), LEV100 (100 mg/kg), and LEV300 (300 mg/kg). After 21 consecutive days of intragastric gavage treatments, pilocarpine stimulated saliva secretion was collected for salivary biochemical analysis. The extracted salivary glands were utilized for histomorphometry and redox state analyses. Our results showed that LEV300 increased plasma hepatotoxicity markers and reduced salivary amylase activity and the acinar surface area of the parotid gland. Total oxidant capacity and oxidative damage to lipids and proteins were higher in the parotid gland, while total antioxidant capacity and uric acid levels were reduced in the submandibular gland of the LEV100 group compared to Control. On the other hand, total oxidant capacity, oxidative damage to lipids and proteins, total antioxidant capacity, and uric acid levels were lower in both salivary glands of the LEV300 group compared to Control. Superoxide dismutase and glutathione peroxidase activities were lower in the salivary glands of treated animals compared to Control. In conclusion our data suggest that treatment with LEV represents a potentially toxic agent, that contributes to drug-induced salivary gland dysfunction.


Asunto(s)
Antioxidantes , Ácido Úrico , Ratas , Masculino , Animales , Ratas Wistar , Antioxidantes/farmacología , Levetiracetam/toxicidad , Levetiracetam/metabolismo , Ácido Úrico/metabolismo , Ácido Úrico/farmacología , Glándulas Salivales/metabolismo , Oxidación-Reducción , Proteínas/metabolismo , Oxidantes/metabolismo , Lípidos
12.
Crit Rev Oncol Hematol ; 189: 104067, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37454703

RESUMEN

Colorectal cancer (CRC) is the third most common malignant tumor and one of the deadliest cancers. At molecular level, CRC is a heterogeneous disease that could be divided in four Consensus Molecular Subtypes. Given the differences in the disease due to its anatomical location (proximal and distal colon), another classification should be considered. Here, we review the current knowledge on CRC dichotomic´s behaviour based on two different entities; right and left-sided tumors, their impact on clinical trial data, microbiota spatial composition and the interaction with the nervous system. We discuss recent advances in understanding how the spatial tumor heterogeneity influences the tumor growth, progression, and responses to current therapies.


Asunto(s)
Neoplasias del Colon , Neoplasias Colorrectales , Humanos , Neoplasias Colorrectales/terapia , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias del Colon/patología
13.
Appl Microbiol Biotechnol ; 107(16): 5161-5178, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37389589

RESUMEN

Kefir is a fermented beverage made of a symbiotic microbial community that stands out for health benefits. Although its microbial profile is still little explored, its effects on modulation of gut microbiota and production of short-chain fatty acids (SCFAs) seems to act by improving brain health. This work aimed to analyze the microbiota profile of milk kefir and its effect on metabolism, oxidative stress, and in the microbiota-gut-brain axis in a murine model. The experimental design was carried out using C57BL-6 mice (n = 20) subdivided into groups that received 0.1 mL water or 0.1 mL (10% w/v) kefir. The kefir proceeded to maturation for 48 h, and then it was orally administered, via gavage, to the animals for 4 weeks. Physicochemical, microbiological, antioxidant analyzes, and microbial profiling of milk kefir beverage were performed as well as growth parameters, food intake, serum markers, oxidative stress, antioxidant enzymes, SCFAs, and metabarcoding were analyzed in the mice. Milk kefir had 76.64 ± 0.42% of free radical scavenging and the microbiota composed primarily by the genus Comamonas. Moreover, kefir increased catalase and superoxide dismutase (colon), and SCFAs in feces (butyrate), and in the brain (butyrate and propionate). Kefir reduced triglycerides, uric acid, and affected the microbiome of animals increasing fecal butyrate-producing bacteria (Lachnospiraceae and Lachnoclostridium). Our results on the brain and fecal SCFAs and the antioxidant effect found were associated with the change in the gut microbiota caused by kefir, which indicates that kefir positively influences the gut-microbiota-brain axis and contributes to the preservation of gut and brain health. KEY POINTS: • Milk kefir modulates fecal microbiota and SCFA production in brain and colon. • Kefir treatment increases the abundance of SCFA-producing bacteria. • Milk kefir increases antioxidant enzymes and influences the metabolism of mice.


Asunto(s)
Kéfir , Microbiota , Ratones , Animales , Kéfir/microbiología , Leche/metabolismo , Antioxidantes , Ratones Endogámicos C57BL , Heces/microbiología , Ácidos Grasos Volátiles/metabolismo , Butiratos , Encéfalo/metabolismo
14.
Int J Mol Sci ; 24(12)2023 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-37373426

RESUMEN

One of the largest health problems worldwide is the development of chronic noncommunicable diseases due to the consumption of hypercaloric diets. Among the most common alterations are cardiovascular diseases, and a high correlation between overnutrition and neurodegenerative diseases has also been found. The urgency in the study of specific damage to tissues such as the brain and intestine led us to use Drosophila melanogaster to study the metabolic effects caused by the consumption of fructose and palmitic acid in specific tissues. Thus, third instar larvae (96 ± 4 h) of the wild Canton-S strain of D. melanogaster were used to perform transcriptomic profiling in brain and midgut tissues to test for the potential metabolic effects of a diet supplemented with fructose and palmitic acid. Our data infer that this diet can alter the biosynthesis of proteins at the mRNA level that participate in the synthesis of amino acids, as well as fundamental enzymes for the dopaminergic and GABAergic systems in the midgut and brain. These also demonstrated alterations in the tissues of flies that may help explain the development of various reported human diseases associated with the consumption of fructose and palmitic acid in humans. These studies will not only help to better understand the mechanisms by which the consumption of these alimentary products is related to the development of neuronal diseases but may also contribute to the prevention of these conditions.


Asunto(s)
Drosophila melanogaster , Enfermedades Neurodegenerativas , Animales , Humanos , Drosophila melanogaster/metabolismo , Fructosa/metabolismo , Ácido Palmítico/farmacología , Larva/metabolismo , Enfermedades Neurodegenerativas/genética , Expresión Génica
15.
Toxins (Basel) ; 15(6)2023 05 25.
Artículo en Inglés | MEDLINE | ID: mdl-37368659

RESUMEN

Zearalenone (ZEN) is a non-steroidal mycoestrogen produced by the Fusarium genus. ZEN and its metabolites compete with 17-beta estradiol for cytosolic estrogen receptors, causing reproductive alterations in vertebrates. ZEN has also been associated with toxic and genotoxic effects, as well as an increased risk for endometrial adenocarcinomas or hyperplasia, breast cancer, and oxidative damage, although the underlying mechanisms remain unclear. Previous studies have monitored cellular processes through levels of transcripts associated with Phase I Xenobiotic Metabolism (Cyp6g1 and Cyp6a2), oxidative stress (hsp60 and hsp70), apoptosis (hid, grim, and reaper), and DNA damage genes (Dmp53). In this study, we evaluated the survival and genotoxicity of ZEN, as well as its effects on emergence rate and fecundity in Drosophila melanogaster. Additionally, we determined levels of reactive oxygen species (ROS) using the D. melanogaster flare and Oregon R(R)-flare strains, which differ in levels of Cyp450 gene expression. Our results showed that ZEN toxicity did not increase mortality by more than 30%. We tested three ZEN concentrations (100, 200, and 400 µM) and found that none of the concentrations were genotoxic but were cytotoxic. Taking into account that it has previously been demonstrated that ZEN administration increased hsp60 expression levels and apoptosis gene transcripts in both strains, the data agree with an increase in ROS and development and fecundity alterations. Since Drosophila lacks homologous genes for mammalian estrogen receptors alpha and beta, the effects of this mycotoxin can be explained by a mechanism different from estrogenic activity.


Asunto(s)
Zearalenona , Animales , Zearalenona/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Estrés Oxidativo , Daño del ADN , Fertilidad , Mamíferos/metabolismo
16.
J Nutr Biochem ; 119: 109372, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37169229

RESUMEN

High-fat diet consumption causes hypothalamic inflammation, dysregulating the leptin pathway, which, in turn, compromises the modulation of hypothalamic neuronal activities and predisposes obesity development. Intermittent fasting (IF) and exercise training (ET) have been demonstrated as efficient interventions to modulate hypothalamic inflammation and neuronal activity. However, no studies have evaluated whether combining these interventions could induce better results in reestablishing hypothalamic homeostasis disrupted by high-fat diet intake. The 8-week-old male C57BL/6 mice were randomly assigned into 2 groups: sedentary mice fed a standard diet (CT), and sedentary mice fed a high-fat diet (HF). After 8 weeks of an HF diet, part of the HF group (now 16 weeks old) was randomly subjected to different interventions for 6 weeks: HF-IF = HF diet mice submitted to IF; HF-T = HF diet mice submitted to ET; HF-IFT = HF diet mice submitted to IF and ET. All interventions decreased the body weight gain induced by high-fat diet intake, associated with reduced calorie consumption in week 14. Only the HF-IFT group presented improved serum insulin, leptin, resistin, and Tnf-alpha levels concomitantly with decreased hypothalamic inflammation. The HF-IFT group also demonstrated increased Pomc mRNA expression associated with enhanced pSTAT3 expression in the hypothalamic arcuate and ventromedial hypothalamic nuclei. Our data indicate that the beneficial effects of the combination of IF and ET on energy homeostasis are associated with increased leptin sensitivity in the hypothalamic arcuate nucleus and ventromedial hypothalamic nucleus, which is likely due to an improvement in hypothalamic inflammatory pathways in these nuclei.


Asunto(s)
Dieta Alta en Grasa , Leptina , Masculino , Ratones , Animales , Dieta Alta en Grasa/efectos adversos , Ayuno Intermitente , Grasas de la Dieta/farmacología , Ratones Endogámicos C57BL , Hipotálamo/metabolismo , Inflamación/metabolismo
17.
Oncoimmunology ; 12(1): 2205336, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37114242

RESUMEN

Immune checkpoint blockade (ICB) with antibodies has shown durable clinical responses in a wide range of cancer types, but the overall response rate is still limited. Other effective therapeutic modalities to increase the ICB response rates are urgently needed. New bispecific antibody (bsAb) formats combining the ICB effect and a direct action on cancer cells could improve the efficacy of current immunotherapies. Here, we report the development of a PD-L1/EGFR symmetric bsAb by fusing a dual-targeting tandem trimmer body with the human IgG1 hinge and Fc regions. The bsAb was characterized in vitro and the antitumor efficacy was evaluated in humanized mice bearing xenografts of aggressive triple-negative breast cancer and lung cancer. The IgG-like hexavalent bsAb, designated IgTT-1E, was able to simultaneously bind both EGFR and PD-L1 antigens, inhibit EGF-mediated proliferation, effectively block PD-1/PD-L1 interaction, and induce strong antigen-specific antibody-dependent cellular cytotoxicity activity in vitro. Potent therapeutic efficacies of IgTT-1E in two different humanized mouse models were observed, where tumor growth control was associated with a significantly increased proportion of CD8+ T cells. These results support the development of IgTT-1E for the treatment of EGFR+ cancers.


Asunto(s)
Anticuerpos Biespecíficos , Neoplasias , Humanos , Ratones , Animales , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Antígeno B7-H1 , Linfocitos T CD8-positivos , Anticuerpos Biespecíficos/farmacología , Anticuerpos Biespecíficos/uso terapéutico , Receptores ErbB
18.
Oxid Med Cell Longev ; 2023: 9979397, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36865350

RESUMEN

Arterial hypertension promotes urological complications by modifying the functional capacity of the urinary bladder. On the other hand, physical exercise has been suggested as a nonpharmacological tool to improve blood pressure regulation. High-intensity interval training (HIIT) can effectively increase peak oxygen consumption, body composition, physical fitness, and health-related characteristics of adults; however, its action on the urinary bladder is little discussed. In the present study, we verified the effect of HIIT on the modulation of the redox state, morphology, and inflammatory and apoptotic processes of the urinary bladder of hypertensive rats. Spontaneously hypertensive rats (SHR) were divided into two groups: SHR sedentary and SHR submitted to HIIT. Arterial hypertension promoted an increase in the plasma redox state, modified the volume of the urinary bladder, and increased collagen deposition in detrusor muscle. It was also possible to identify, in the sedentary SHR group, an increase in inflammatory markers such as IL-6 and TNF-α in the urinary bladder, as well as a reduction in BAX expression. However, in the HIIT group, reduced blood pressure levels were observed, together with an improvement in morphology, such as a decrease in collagen deposition. HIIT also regulated the proinflammatory response, promoting increases in IL-10 and BAX expressions and in the number of plasma antioxidant enzymes. The present work highlights the intracellular pathways involved with the oxidative and inflammatory capacity of the urinary bladder and the potential effect of HIIT on the regulation of the urothelium and detrusor muscle of hypertensive rats.


Asunto(s)
Entrenamiento de Intervalos de Alta Intensidad , Hipertensión , Condicionamiento Físico Animal , Vejiga Urinaria , Animales , Ratas , Proteína X Asociada a bcl-2 , Hipertensión/complicaciones , Hipertensión/terapia , Ratas Endogámicas SHR
19.
Micromachines (Basel) ; 14(3)2023 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-36984996

RESUMEN

Bismuth telluride thin films were grown by pulsed laser deposition by implementing a novel method that combines both Te and Bi plasmas resulting from the laser ablation of individual Bi and Te targets. Furthermore, the mean kinetic ion energy and density of the plasmas, as estimated by TOF curves obtained from Langmuir probe measurements, were used as control parameters for the deposition process. The obtained thin films exhibit a metallic mirror-like appearance and present good adhesion to the substrate. Morphology of the thin films was observed by SEM, yielding smooth surfaces where particulates were also observed (splashing). Chemical composition analysis obtained by EDS showed that apparently the films have a Te-rich composition (ratio of Te/Bi of 3); however, Te excess arises from the splashing as revealed by the structural characterization (XRD and Raman spectroscopy). The XRD pattern indicated that depositions have the rhombohedral (D3d5 (R3¯m)) structure of Bi2Te3. Likewise, Raman spectra exhibited the presence of signals that correspond to Eg2, A1u2 and A1g2(LO) vibrational modes of the same rhombohedral phase of Bi2Te3. Additionally, oxidation states, analyzed by XPS, resulted in signals associated to Bi3+ and Te2- that correspond to the Bi2Te3 compound. Finally, surface topology and thickness profiles were obtained from AFM measurements, confirming a combination of a smooth surface with particulates on top of it and a film thickness of 400 nm.

20.
Polymers (Basel) ; 15(6)2023 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-36987186

RESUMEN

Sargassum spp. affects the Caribbean shores; thus, its remotion or valorization is a priority. This work aimed to synthesize a low-cost magnetically retrievable Hg+2 adsorbent functionalized with ethylenediaminetetraacetic acid (EDTA) based on Sargassum. The Sargassum was solubilized to synthesize by co-precipitation a magnetic composite. A central composite design was assessed to maximize the adsorption of Hg+2. The solids yield magnetically attracted mass, and the saturation magnetizations of the functionalized composite were 60.1 ± 17.2%, 75.9 ± 6.6%, and 1.4 emu g-1. The functionalized magnetic composite yielded 29.8 ± 0.75 mg Hg+2 g-1 of chemisorption after 12 h, pH 5, and 25 °C achieving 75% Hg+2 adsorption after four reuse cycles. Crosslinking and functionalization with Fe3O4 and EDTA created differences in surface roughness as well as the thermal events of the composites. The Fe3O4@Sargassum@EDTA composite was a magnetically recovered biosorbent of Hg2+.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA