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BACKGROUND: Ultraviolet radiation (UV) is the main environmental factor that causes histological degenerative changes of the skin giving rise to a chronic process called photodamage. Non-melanoma skin cancer induced by UVB radiation is a result of a cascade of molecular events caused by DNA damage in epidermis cells, including persistent inflammation, oxidative stress, and suppression of T cell-mediated immunity. Retinoids such as tretinoin have been widely used in skin to treat photoaging and photodamage, though its secondary adverse effects have been recognized. Pirfenidone (PFD) has emerged as an antifibrogenic, anti-inflammatory and antioxidant agent, and in this work its efficacy was evaluated in a model of UVB-induced photodamage. METHODS: Epidermal, dermal, and inflammatory changes were measured by histomorphometric parameters. In addition, gene, and protein expression of key molecules in these processes were evaluated. RESULTS: Our results revealed an anti-photodamage effect of topical PFD with absence of inflammatory skin lesions determined by dermoscopy. In addition, PFD reduced elastosis, improved organization, arrangement, and deposition of dermal collagens, downregulated several pro-inflammatory markers such as NF-kB, IL-1, IL-6 and TNFα, and decreased keratinocyte damage. CONCLUSION: Topical pirfenidone represents a promising agent for the treatment of cell photodamage in humans. Clinical trials need to be carried out to explore this premise.
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Envejecimiento de la Piel , Rayos Ultravioleta , Animales , Ratones , Humanos , Rayos Ultravioleta/efectos adversos , Ratones Pelados , Piel , EpidermisRESUMEN
PURPOSE: Obesity is associated with systemic insulin resistance and cardiac hypertrophy with fibrosis. Peroxisome proliferator-activated receptors (PPARs) regulate carbohydrate and lipid metabolism, improving insulin sensitivity, triglyceride levels, inflammation, and oxidative stress. We previously demonstrated that prolonged-release pirfenidone (PR-PFD) is an agonistic ligand for Pparα with anti-inflammatory and anti-fibrotic effects, and might be a promising drug for cardiac diseases-treatment. Here, we investigated the effects of PR-PFD in ventricular tissue of mice with nonalcoholic steatohepatitis (NASH) and obesity induced by high-fat/high-carbohydrate (HFHC) diet. METHODS: Five male C57BL/6 J mice were fed with normal diet (ND) and ten with HFHC diet for 16 weeks; at 8 weeks of feeding, five mice with HFHC diet were administered PR-PFD (350 mg/kg/day) mixed with HFHC diet. RESULT: Systemic insulin resistance, heart weight/body weight ratio, myocardial steatosis with inflammatory foci, hypertrophy, and fibrosis were prevented by PR-PFD. In addition, HFHC mice showed significantly increased desmin, Tgfß1, Timp1, collagen I (Col I), collagen III (Col III), TNF-α, and Nrf2 mRNA levels, including α-SMA, NF-kB, Nrf2, troponin I, Acox1, Cpt1A, and Lxrα protein levels compared with the ND ventricular tissues. Mechanistically, HFHC mice with PR-PFD treatment significantly decreased these genes overexpressed by HFHC diet. Furthermore, PR-PFD overexpressed the Pgc1a mRNA levels and Pparα, Pparγ, Acox1, and Cpt1A protein levels. CONCLUSIONS: The results suggest that PR-PFD could be a promising drug for the prevention and treatment of cardiac steatosis and fibrosis induced by obesity.
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Fibrosis/prevención & control , Cardiopatías/prevención & control , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Obesidad/fisiopatología , PPAR alfa/agonistas , Piridonas/farmacología , Animales , Peso Corporal/efectos de los fármacos , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Fibrosis/fisiopatología , Cardiopatías/fisiopatología , Resistencia a la Insulina/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Tamaño de los Órganos/efectos de los fármacos , Distribución AleatoriaRESUMEN
Carbohydrates and lipids are two components of the diet that provide the necessary energy to carry out various physiological processes to help maintain homeostasis in the body. However, when the metabolism of both biomolecules is altered, development of various liver diseases takes place; such as metabolic-associated fatty liver diseases (MAFLD), hepatitis B and C virus infections, alcoholic liver disease (ALD), and in more severe cases, hepatocelular carcinoma (HCC). On the other hand, PPARs are a family of ligand-dependent transcription factors with an important role in the regulation of metabolic processes to hepatic level as well as in other organs. After interaction with specific ligands, PPARs are translocated to the nucleus, undergoing structural changes to regulate gene transcription involved in lipid metabolism, adipogenesis, inflammation and metabolic homeostasis. This review aims to provide updated data about PPARs' critical role in liver metabolic regulation, and their involvement triggering the genesis of several liver diseases. Information is provided about their molecular characteristics, cell signal pathways, and the main pharmacological therapies that modulate their function, currently engaged in the clinic scenario, or in pharmacological development.
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Hepatopatías/tratamiento farmacológico , Hepatopatías/patología , Receptores Activados del Proliferador del Peroxisoma/metabolismo , Preparaciones Farmacéuticas/administración & dosificación , Animales , Humanos , Hepatopatías/metabolismo , Terapia Molecular DirigidaRESUMEN
Targeted therapies for regulating processes such as inflammation, apoptosis, and fibrogenesis might modulate human HCC development. Pirfenidone (PFD) has shown anti-fibrotic and anti-inflammatory functions in both clinical and experimental studies. The aim of this study was to evaluate PPARγ expression and localization in samples of primary human tumors and assess PFD-effect in early phases of hepatocarcinogenic process. Human HCC tissue samples were obtained by surgical resection. Experimental hepatocarcinogenesis was induced in male Fischer-344 rats. TGF-ß1 and α-SMA expression was evaluated as fibrosis markers. NF-kB cascade, TNFα, IL-6, and COX-2 expression and localization were evaluated as inflammation indicators. Caspase-3, p53, and PARP-1 were used as apoptosis markers, PCNA for proliferation. Finally, PPARα and PPARγ expression were evaluated to understand the effect of PFD on the activation of such pathways. PPARγ expression was predominantly localized in cytoplasm in human HCC tissue. PFD was effective to prevent histopathological damage and TGF-ß1 and α-SMA overexpression in the experimental model. Anti-inflammatory effects of PFD correlate with diminished IKK and decrease in both IkB-phosphorylation/NF-kB p65 expression and p65-translocation into the nucleus. Pro-apoptotic PFD-induced effects are related with p53 expression, Caspase-3 p17 activation, and PARP-1-cleavage. In conclusion, PFD acts as a tumor suppressor by preventing fibrosis, reducing inflammation, and promoting apoptosis in MRHM.
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Carcinoma Hepatocelular/metabolismo , PPAR gamma/metabolismo , Piridonas/farmacología , Animales , Antiinflamatorios/farmacología , Carcinogénesis , Carcinoma Hepatocelular/prevención & control , Fibrosis , Inflamación/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/prevención & control , Masculino , FN-kappa B/metabolismo , Subunidad p50 de NF-kappa B/metabolismo , Fosforilación/efectos de los fármacos , Piridonas/metabolismo , Ratas , Ratas Endogámicas F344 , Transducción de Señal/efectos de los fármacos , Factor de Transcripción ReIA/metabolismo , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
BACKGROUND AND OBJECTIVES: Gene therapy using urokinase-type plasminogen activator (uPA) has been shown to induce extracellular matrix degradation, hepatocyte proliferation and liver tissue function restoration in liver cirrhosis models. Physiologically, uPA activates plasminogen conversion to plasmin, which leads, depending on the organ, to thrombolysis or extracellular matrix degradation. The purpose of this study was to compare the regenerative effect of gene therapy with adenoviruses encoding wild-type uPA (huPA), as well as its truncated isoform (ΔhuPA), in healthy and cirrhotic animals. In addition, possible adverse effects on coagulation were assessed. METHODS: 6 x 1011 vp/kg of Ad-huPA or Ad-ΔhuPA were administered via the iliac vein to healthy male Wistar rats or to male Wistar rats with cirrhosis induced by chronic poisoning with carbon tetrachloride (CCl4). The animals were sacrificed at day 2, 4 or 6 post-treatment. Liver fibrosis, proliferating cell nuclear antigen expression, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) serum levels and coagulation markers were evaluated. RESULTS: On day 6 post-treatment, a fibrosis reversal of 48.7-41.5% was achieved. AST and ALT levels did not change in cirrhotic animals treated with ΔhuPA, but showed an elevation in healthy animals. Cell proliferation increased in healthy and cirrhotic animals with both transgene isoforms. No coagulation adverse effects were observed in the ΔhuPA group, and by day 6, they had disappeared in the huPA group. CONCLUSIONS: Gene therapy with Ad-huPA and Ad-ΔhuPA favors cell proliferation in cirrhotic animals, without important side effects.
ANTECEDENTES Y OBJETIVOS: La terapia génica empleando el activador de plasminógeno tipo urocinasa (huPA) ha demostrado que induce la degradación de matriz extracelular, la proliferación de hepatocitos y el restablecimiento de la funcionalidad tisular en modelos de cirrosis hepática. Fisiológicamente, el uPA activa la conversión del plasminógeno en plasmina, lo que conlleva, dependiendo del órgano, una trombólisis o a degradación de la matriz extracelular. El objetivo de este estudio fue comparar el efecto regenerador de la terapia génica con adenovirus codificando la forma silvestre (huPA), así como su isoforma truncada (DhuPA) en animales sanos y cirróticos. Además, se valoraron los posibles efectos adversos sobre la coagulación. MÉTODOS: Se administró 6x1011 pv/kg del Ad-huPA o Ad-ΔhuPA a ratas Wistar macho sanas o con cirrosis por intoxicación crónica con tetracloruro de carbono (CCl4) vía vena ilíaca. El sacrificio fue al día 2, 4 o 6 postratamiento. Se evaluó la fibrosis hepática, la expresión de antígeno nuclear de proliferación celular y niveles séricos de alanina aminotransferasa (ALT) y aspartato aminotransferasa (AST), y marcadores de coagulación. RESULTADOS: Al día 6 postratamiento se alcanzó una reversión de fibrosis del 48.7-41.5%. Los niveles de AST y ALT no cambiaron en animales cirróticos tratados con DhuPA, pero aumentaron en animales sanos comparados con el control sano no tratado. La proliferación aumenta en animales sanos y cirróticos con ambas isoformas del transgén. No se observaron efectos adversos en la coagulación en el grupo DhuPA y para el día 6 habían desaparecido en el grupo huPA. CONCLUSIONES: La terapia génica con Ad-uPA y Ad-ΔhuPA favorece la proliferación celular en animales cirróticos, sin efectos secundarios importantes.
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Hígado , Activador de Plasminógeno de Tipo Uroquinasa , Animales , Tetracloruro de Carbono , Terapia Genética , Masculino , Ratas , Ratas Wistar , Activador de Plasminógeno de Tipo Uroquinasa/genéticaRESUMEN
OBJECTIVE: The study aimed to assess the effect of a symbiotic gel on presence and severity of gastrointestinal symptoms (GIS) in hemodialysis patients. DESIGN: A double-blinded, placebo-controlled, randomized, clinical trial was designed. The study was conducted at 2 public hospitals in Guadalajara, Mexico. SUBJECTS AND INTERVENTION: Twenty-two patients were randomized to the intervention group (nutritional counseling + symbiotic gel) and 20 patients were randomized to the control group (nutritional counseling + placebo), during 2 months of follow-up. MAIN OUTCOME MEASURE: Presence and monthly episodes of GIS were assessed by direct interview and severity by using the self-administered GIS questionnaire. Additionally, biochemical parameters, inflammatory markers, and nutritional status (dietary intake, subjective global assessment, anthropometry, and body composition) were evaluated. RESULTS: After a 2-month treatment, intervention group had a significant reduction in prevalence and monthly episodes of vomit, heartburn, and stomachache, as well as a significant decrease in GIS severity compared with control group. Moreover, intervention group had a greater yet not significant decrease in the prevalence of malnutrition and a trend to reduce their C-reactive protein and tumor necrosis factor α levels compared with control group. No symbiotic-related adverse side effects were shown in these patients. Clinical studies with longer follow-up and sample size are needed to confirm these results. CONCLUSIONS: We concluded that administration of a symbiotic gel is a safe and simple way to improve common GIS in dialysis patients.
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Enfermedades Gastrointestinales/prevención & control , Inflamación/prevención & control , Inulina/administración & dosificación , Prebióticos/administración & dosificación , Probióticos/administración & dosificación , Diálisis Renal/efectos adversos , Adulto , Bifidobacterium , Método Doble Ciego , Femenino , Enfermedades Gastrointestinales/epidemiología , Humanos , Inflamación/epidemiología , Lactobacillus acidophilus , Masculino , Desnutrición/epidemiología , Desnutrición/prevención & control , México/epidemiología , Persona de Mediana Edad , Terapia Nutricional , Placebos , SimbiosisRESUMEN
BACKGROUND: The aim of this study was to assess whether two-years treatment with Pirfenidone influences necroinflammation, fibrosis and steatosis, serum levels of TGF-ß1, IL-6, TNF-α and CB1 and CB2 gene expression, in patients with chronic hepatitis C (CHC). METHODS: Twenty-eight patients out of 34 with CHC virus infection were enrolled in the study and received Pirfenidone (1200 mg/day) for 24 months. Six patients dropped out after 12 months of PFD. Liver biopsies and serum samples were obtained at the beginning and end of treatment. Modified HAI was calculated. CB1 and CB2 gene expression was correlated with fibrosis progression alongside with necroinflammation and steatosis. TGF-ß1, IL-6, TNF-α and liver transaminases were measured in serum at two-months intervals. HCV genotype and viral load were also assessed. Quality of life was evaluated by SF36 questionnaires and the prognosis of disease was assessed with Child-Pugh score. The Wilcoxon test matched-pair signed ranks were used to analyze the outcomes. RESULTS: Intention to treat analyses were performed for biochemistry and clinical parameters. At the end of treatment, necroinflammation grading was reduced in an average of 3.2 points in 82% of patients (p < 0.05) and Ishak's fibrosis stage decreased 2-points average in 67% of patients (p < 0.05). Steatosis decreased in 61% of patients. IL-6 and TGF-ß1 serum levels decreased significantly in 93% and 67% of patients (p < 0.05), respectively, while TNF-α diminished in 47% of patients. ALT and AST tended to normalize in 81% of patients; CB2 mRNA levels increased in 86% and CB1 expression diminished in 29% of patients. Both, quality of life and Child-Pugh score improvements were reported in all patients. CONCLUSIONS: Pirfenidone for two years benefits CHC patients and improves inflammation, fibrosis and steatosis in higher number of patients as previously shown for 12-months treatment with PFD. Additionally, PFD improved TGFß1 and IL-6 levels and diminished liver expression of anti-fibrogenic receptor CB2. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02161952. Protocol Registration Date: 06/11/2014.
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Antiinflamatorios no Esteroideos/uso terapéutico , Citocinas/inmunología , Hepatitis C Crónica/tratamiento farmacológico , Hígado/patología , Piridonas/uso terapéutico , ARN Mensajero/genética , Anciano , Estudios de Cohortes , Hígado Graso/patología , Femenino , Expresión Génica , Hepatitis C Crónica/genética , Hepatitis C Crónica/inmunología , Humanos , Interleucina-6/inmunología , Cirrosis Hepática/patología , Masculino , Persona de Mediana Edad , Receptor Cannabinoide CB1/genética , Receptor Cannabinoide CB2/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Crecimiento Transformador beta1/inmunología , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
INTRODUCTION: Orthodontic tooth movement implies application of forces that generate an inflammatory process. The myeloperoxidase (MPO) enzyme is found inside neutrophil granules. MPO activity indirectly reflects the level of inflammation. The aim of this study was to measure MPO activity in gingival crevicular fluid (GCF) and whole saliva in orthodontic patients with different levels of dental crowding at the alignment phase of orthodontic treatment with the same archwires. METHODS: Twenty patients were classified according to the irregularity index into 2 groups: severe and minimum crowding (10 in each group). MPO activity was evaluated in GCF and saliva at 0 and 2 hours, and 7 and 14 days after the orthodontic appliances were activated. MPO activity was measured using the modified Bradley-Bozeman technique. RESULTS: In both groups, the maximum activity was at 2 hours (P <0.05) after activation. MPO activity remained elevated until day 7, and values similar to baseline were found at day 14 in the GCF and saliva samples. Enzymatic activity did not show statistical differences between the groups. CONCLUSIONS: The amount of dental crowding does not seem to influence MPO activity, which showed similar patterns in GCF and saliva, but the values in GCF reflected the inflammatory changes more accurately than did the values in saliva. The quantification of MPO activity is a useful biologic marker as an indirect measurement of inflammation generated with tooth movement independent of the amount of crowding.
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Líquido del Surco Gingival/enzimología , Maloclusión/terapia , Peroxidasa/análisis , Saliva/enzimología , Técnicas de Movimiento Dental/métodos , Biomarcadores/análisis , Aleaciones Dentales/química , Elastómeros/química , Femenino , Estudios de Seguimiento , Humanos , Masculino , Maloclusión/clasificación , Níquel/química , Soportes Ortodóncicos , Alambres para Ortodoncia , Proteínas y Péptidos Salivales/análisis , Titanio/química , Técnicas de Movimiento Dental/instrumentación , Adulto JovenRESUMEN
Obesity has increasingly become a worldwide epidemic, as demonstrated by epidemiological and clinical studies. Obesity may lead to the development of a broad spectrum of cardiovascular diseases (CVDs), such as coronary heart disease, hypertension, heart failure, cerebrovascular disease, atrial fibrillation, ventricular arrhythmias, and sudden cardiac death. In addition to hypertension, there are other cardiometabolic risk factors (CRFs) such as visceral adiposity, dyslipidemia, insulin resistance, diabetes, elevated levels of fibrinogen and C-reactive protein, and others, all of which increase the risk of CVD events. The mechanisms involved between obesity and CVD mainly include insulin resistance, oxidative stress, inflammation, and adipokine dysregulation, which cause maladaptive structural and functional alterations of the heart, particularly left-ventricular remodeling and diastolic dysfunction. Natural products of plants provide a diversity of nutrients and different bioactive compounds, including phenolics, flavonoids, terpenoids, carotenoids, anthocyanins, vitamins, minerals, fibers, and others, which possess a wide range of biological activities including antihypertensive, antilipidemic, antidiabetic, and other activities, thus conferring cardiometabolic benefits. In this review, we discuss the main therapeutic interventions using extracts from herbs and plants in preclinical and clinical trials with protective properties targeting CRFs. Molecular mechanisms and therapeutic targets of herb and plant extracts for the prevention and treatment of CRFs are also reviewed.
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Hepatocellular carcinoma (HCC) development is associated with altered modifications in DNA methylation, changing transcriptional regulation. Emerging evidence indicates that DNA methyltransferase 1 (DNMT1) plays a key role in the carcinogenesis process. This study aimed to investigate how pirfenidone (PFD) modifies this pathway and the effect generated by the association between c-Myc expression and DNMT1 activation. Rats F344 were used for HCC development using 50 mg/kg of diethylnitrosamine (DEN) and 25 mg/kg of 2-Acetylaminofluorene (2-AAF). The HCC/PFD group received simultaneous doses of 300 mg/kg of PFD. All treatments lasted 12 weeks. On the other hand, HepG2 cells were used to evaluate the effects of PFD in restoring DNA methylation in the presence of the inhibitor 5-Aza. Histopathological, biochemical, immunohistochemical, and western blot analysis were carried out and our findings showed that PFD treatment reduced the amount and size of tumors along with decreased Glipican-3, ß-catenin, and c-Myc expression in nuclear fractions. Also, this treatment improved lipid metabolism by modulating PPARγ and SREBP1 signaling. Interestingly, PFD augmented DNMT1 and DNMT3a protein expression, which restores global methylation, both in our in vivo and in vitro models. In conclusion, our results suggest that PFD could slow down HCC development by controlling DNA methylation.
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Carcinoma Hepatocelular , ADN (Citosina-5-)-Metiltransferasa 1 , Metilación de ADN , Antígeno Nuclear de Célula en Proliferación , Piridonas , Animales , ADN (Citosina-5-)-Metiltransferasa 1/metabolismo , ADN (Citosina-5-)-Metiltransferasa 1/genética , Metilación de ADN/efectos de los fármacos , Metilación de ADN/genética , Piridonas/farmacología , Ratas , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Humanos , Células Hep G2 , Antígeno Nuclear de Célula en Proliferación/metabolismo , Masculino , Ratas Endogámicas F344 , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Dietilnitrosamina , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Neoplasias Hepáticas Experimentales/patología , Neoplasias Hepáticas Experimentales/metabolismo , Neoplasias Hepáticas Experimentales/genéticaRESUMEN
Microbial community control is crucial for maintaining homeostasis of the gut-liver axis in metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we show that supplementation with a mixture of Mexican foodstuffs (MexMix)-Opuntia ficus indica (nopal), Theobroma cacao (cocoa) and Acheta domesticus (crickets)-enriches several beneficial taxa in MASLD mice and overweight/obese humans. Thus, MexMix induces an important prebiotic effect. In mice, a restoration of intestinal health was observed due to the increased short-chain fatty acids (SCFAs) and intestinal crypt depth, Ocln and Cldn1 expression, and decreased Il6 and Tnfa expression. MexMix significantly reduced steatosis in the mice's liver and modified the expression of 1668 genes. By PCR, we corroborated a Tnfa and Pparg decrease, and a Cat and Sod increase. In addition, MexMix increased the hepatic NRF2 nuclear translocation and miRNA-34a, miRNA-103, and miRNA-33 decline. In overweight/obese humans, MexMix improved the body image satisfaction and reduced the fat intake. These findings indicate that this new food formulation has potential as a therapeutic approach to treat conditions associated with excessive consumption of fats and sugars.
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Nanotechnology has emerged as a promising technology in the field of hepatocellular carcinoma (HCC), specifically in the implementation of diagnosis and treatment strategies. Nanotechnology-based approaches, such as nanoparticle-based contrast agents and nanoscale imaging techniques, have shown great potential for enhancing the sensitivity and specificity of HCC detection. These approaches provide high-resolution imaging and allow for the detection of molecular markers and alterations in cellular morphology associated with HCC. In terms of treatment, nanotechnology has revolutionized HCC therapy by enabling targeted drug delivery, enhancing therapeutic efficacy, and minimizing off-target effects. Nanoparticle-based drug carriers can be functionalized with ligands specific to HCC cells, allowing for selective accumulation of therapeutic agents at the tumor site. Furthermore, nanotechnology can facilitate combination therapy by co-encapsulating multiple drugs within a single nanoparticle, allowing for synergistic effects and overcoming drug resistance. This review aims to provide an overview of recent advances in nanotechnology-based approaches for the diagnosis and treatment of HCC. Further research is needed to optimize the design and functionality of nanoparticles, improve their biocompatibility and stability, and evaluate their long-term safety and efficacy. Nonetheless, the integration of nanotechnology in HCC management holds great promise and may lead to improved patient outcomes in the future.
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Diet containing Mexican ancestral foods such as cocoa, nopal, avocado, and common bean have been individually reported to have beneficial effects on obesity and comorbidities. Methods: A systematic review and meta-analysis on the effect of Mexican ancestral foods on the anthropometric, lipid, and glycemic control variables in obese patients was performed following PRISMA guidelines. Data were analyzed using a random-effects model. Results: We selected 4664 articles from an initial search, of which only fifteen studies satisfied the inclusion criteria. Data for 1670 participants were analyzed: 843 in the intervention group and 827 in the control group. A significant reduction in body mass index (mean difference: -0.80 (-1.31 to -0.30)) (95% confidence interval), p = 0.002, heterogeneity I2 = 92% was showed after the ingestion of cocoa, nopal, avocado, or common bean. The mean difference for body weight was -0.57 (-1.93 to 0.79), waist of circumference: -0.16 (-2.54 to -2.21), total cholesterol: -5.04 (-11.5 to 1.08), triglycerides: -10.11 (-27.87 to 7.64), fasting glucose: -0.81 (-5.81 to 4.19), and insulin: -0.15 (-0.80 to 0.50). Mexican ancestral food supplementation seems to improve anthropometric, lipid, and glycemic control variables in obesity; however, more randomized controlled trials are needed to have further decisive evidence about dosage and method of supplementation and to increase the sample size.
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The development of several vaccines against the SARS-CoV2 virus and their application in millions of people have shown efficacy and safety in the transfer of genes to muscle turning this tissue into a protein-producing factory. Established advanced liver fibrosis, is characterized by replacement of hepatic parenchyma by tissue scar, mostly collagen type I, with increased profibrogenic and proinflammatory molecules gene expression. Matrix metalloproteinase 8 (MMP-8) is an interstitial collagen-degrading proenzyme acting preferentially on collagen type I when activated. This study was carried out to elucidate the effect of an intramuscularly delivered adenoviral vector containing proMMP-8 gene cDNA (AdhMMP8) in male Wistar rats with experimental advanced liver fibrosis induced by thioacetamide. Therapeutic effects were monitored after 1, 2, or 3 weeks of a single dose (3 × 1011 vp/kg) of AdhMMP8. Circulating and liver concentration of MMP-8 protein remained constant; hepatic fibrosis decreased up to 48%; proinflammatory and profibrogenic genes expression diminished: TNF-α 2.28-fold, IL-1 1.95-fold, Col 1A1 4-fold, TGF-ß1 3-fold and CTGF 2-fold; and antifibrogenic genes expression raised, MMP-9 2.8-fold and MMP-1 10-fold. Our data proposes that the administration of AdhMMP8 in muscle is safe and effective in achieving liver fibrosis regression at a comparable extent as when the adenoviral vector is delivered systemically to reach the liver, using a minimally invasive procedure.
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COVID-19 , Metaloproteinasa 8 de la Matriz , Masculino , Ratas , Animales , Ratas Wistar , Colágeno Tipo I , ARN Viral , SARS-CoV-2 , Músculos , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/terapiaRESUMEN
BACKGROUND AND AIM: Development of hepatic cirrhosis involves oxidative stress, inflammation, hepatic stellate cells (HSC)s activation and fibrosis. On the other hand, quercetin, a natural flavonoid is a potent antioxidant and activator of superoxide dismutase and catalase. The aim was to determinate the effect of quercetin on HSCs and development of hepatic fibrosis. METHODS: Wistar male rats were chronically intoxicated with CCl(4) for 8 weeks and concomitantly treated with 100 mg/kg per day of quercetin. Oxidative state, inflammation and fibrosis were evaluated. Effect of quercetin on apoptosis of HSC was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling reaction. RESULTS: Sixty percent of reduction in fibrosis index was observed with quercetin treatment compared with control animals. Considerable reduction on hepatic enzymes was detected in the quercetin group. Expression of pro-fibrotic genes (transforming growth factor-ß [TGF-ß], Collagen 1α [Col-1α] and connective tissue growth factor [CTGF]) were decreased by quercetin. Quercetin increased gene expression and functional activity of antioxidant enzymes superoxide dismutase and catalase. Inflammatory index was highly reduced as determined by H-E staining and pro-inflammatory cytokines expression and nuclear factor-κB activation were also inhibited. A significant reduction of 65% on activated HSC number was detected when rats were treated with quercetin. Quercetin also induced activation of matrix metalloproteinases MMP2 and MMP9 contributing to decreased index of fibrosis. CONCLUSIONS: Treatment with quercetin reduces oxidation and inflammation and also prevents liver fibrosis, through induction of HSC apoptosis and activation of MMPs.
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Células Estrelladas Hepáticas/patología , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/metabolismo , Quercetina/uso terapéutico , Animales , Modelos Animales de Enfermedad , Matriz Extracelular/metabolismo , Inflamación/prevención & control , Cirrosis Hepática/patología , Masculino , Metaloproteasas/metabolismo , Estrés Oxidativo/efectos de los fármacos , Quercetina/farmacología , Ratas , Ratas Wistar , Inhibidores Tisulares de Metaloproteinasas/metabolismoRESUMEN
The raising prevalence of obesity is associated with an increased risk for cardiovascular diseases (CVDs), particularly coronary artery disease (CAD), and heart failure, including atrial fibrillation, ventricular arrhythmias and sudden death. Obesity contributes directly to incident cardiovascular risk factors, including hyperglycemia or diabetes, dyslipidemia, and hypertension, which are involved in atherosclerosis, including structural and functional cardiac alterations, which lead to cardiac dysfunction. CVDs are the main cause of morbidity and mortality worldwide. In obesity, visceral and epicardial adipose tissue generate inflammatory cytokines and reactive oxygen species (ROS), which induce oxidative stress and contribute to the pathogenesis of CVDs. Nuclear factor erythroid 2-related factor 2 (NRF2; encoded by Nfe2l2 gene) protects against oxidative stress and electrophilic stress. NRF2 participates in the regulation of cell inflammatory responses and lipid metabolism, including the expression of over 1000 genes in the cell under normal and stressed environments. NRF2 is downregulated in diabetes, hypertension, and inflammation. Nfe2l2 knockout mice develop structural and functional cardiac alterations, and NRF2 deficiency in macrophages increases atherosclerosis. Given the endothelial and cardiac protective effects of NRF2 in experimental models, its activation using pharmacological or natural products is a promising therapeutic approach for obesity and CVDs. This review provides a comprehensive summary of the current knowledge on the role of NRF2 in obesity-associated cardiovascular risk factors.
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Introduction: An obesogenic diet, a diet high in saturated fats and sugars, is a risk factor for the development of multiple obesity-related diseases. In this study, our aim was to evaluate the effect of supplementation with a mixture of Mexican functional foods (MexMix), Opuntia ficus indica (nopal), Theobroma cacao, and Acheta domesticus (edible crickets), compared with a high-fat and fructose/sucrose diet on an obesogenic mice model. Methods: For this study, 18 male C57BL/6J mice were used, which were divided into three groups: (1) control group: normal diet (ND), (2) HF/FS group: high-fat diet along with 4.2% fructose/sucrose and water (ad libitum access), and (3) therapeutic group (MexMix): HF/FS diet up to week 8, followed by HF/FS diet supplemented with 10% nopal, 10% cocoa, and 10% cricket for 8 weeks. Results: MexMix mice showed significantly reduced body weight, liver weight, visceral fat, and epididymal fat compared with HF/FS mice. Levels of triglycerides, cholesterol, LDL cholesterol, insulin, glucose, GIP, leptin, PAI-1, and resistin were also significantly reduced. For identifying the gut microbiota in the model, 16S rRNA gene sequencing analysis was performed, and the results showed that MexMix supplementation increased the abundance of Lachnospira, Eubacterium coprostanoligenes, and Blautia, bacteria involved in multiple beneficial metabolic effects. It is noteworthy that the mice supplemented with MexMix showed improvements in cognitive parameters, as evaluated by the novel object recognition test. Conclusion: Hence, supplementation with MexMix food might represent a potential strategy for the treatment of obesity and other diseases associated with excessive intake of fats and sugars.
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BACKGROUND AND AIMS: Metabolic Associated Fatty Liver Disease (MAFLD) encompasses a spectrum of diseases from simple steatosis to nonalcoholic steatohepatitis (NASH). Here, we investigated the hepatoprotective role of Moringa oleifera aqueous extract on hepatic miRNAs, genes and protein expression, as well as histological and biochemical parameters in an experimental model of NASH. METHODS: Male C57BL/6J mice were fed with a high fat diet (HFD, 60% lipids, 42 gr/L sugar in water) for 16 weeks. Moringa extract was administered via gavage during the final 8 weeks. Insulin Tolerance Test (ITT) and HOMA-IR were calculated. Serum levels of insulin, resistin, leptin and PAI-1 and hepatic expression of miR-21a-5p, miR-103-3p, miR-122-5p, miR-34a-5p and SIRT1, AMPKα and SREBP1c protein were evaluated. Alpha-SMA immunohistochemistry and hematoxylin-eosin, Masson's trichrome and sirius red staining were made. Hepatic transcriptome was analyzed using microarrays. RESULTS: Animals treated with Moringa extract improved ITT and decreased SREBP1c hepatic protein, while SIRT1 increased. Hepatic expression of miR-21a-5p, miR-103-3p and miR-122-5p, miR34a-5p was downregulated. Hepatic histologic analysis showed in Moringa group (HF + MO) a significant decrease in inflammatory nodules, macro steatosis, fibrosis, collagen and αSMA reactivity. Analysis of hepatic transcriptome showed down expression of mRNAs implicated in DNA response to damage, endoplasmic reticulum stress, lipid biosynthesis and insulin resistance. Moringa reduced insulin resistance, de novo lipogenesis, hepatic inflammation and ER stress. CONCLUSIONS: Moringa prevented progression of liver damage in a model of NASH and improved biochemical, histological and hepatic expression of genes and miRNAs implicated in MAFLD/NASH development.
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Resistencia a la Insulina , MicroARNs , Moringa oleifera , Enfermedad del Hígado Graso no Alcohólico , Extractos Vegetales , Animales , Masculino , Ratones , Dieta Alta en Grasa/efectos adversos , Epigénesis Genética , Insulina/metabolismo , Leptina , Lípidos , Hígado/metabolismo , Ratones Endogámicos C57BL , MicroARNs/metabolismo , Moringa oleifera/química , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/etiología , Inhibidor 1 de Activador Plasminogénico/metabolismo , Resistina/metabolismo , Sirtuina 1/genética , Sirtuina 1/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Extractos Vegetales/farmacologíaRESUMEN
The muscle fiber ultrastructure in Idiopathic Inflammatory Myopathies (IIM) has been scarcely explored, especially in Inclusion Body Myositis. The aim of this study was to implement the Scanning Electron Microscopy (SEM) in a small cohort of IIM patients, together with the characterization of immunological profile for a better understanding of the pathophysiology. For immunological profile characterization, we identified the presence of autoantibodies (Ro-52, OJ, EJ, PL7, PL12, SRP, Jo-1, PMScl75, PMScl100, Ku, SAE1, NXP2, MDA5, TIF1γ, Mi-2α, Mi-2ß) and quantified cytokines (IL-1ß, IFN-α2, IFN-γ, TNF-α, IL-6, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-33) and chemokines (CCL2, CXCL8). The histological analysis was made by hematoxylin-eosin staining while the muscle fiber ultrastructure was characterized by SEM. We observed changes in the morphology and structure of the muscle fiber according to muscle strength and muscle enzymes. We were able to find and describe muscle fiber ultrastructure with marked irregularities, porosities, disruption in the linearity and integrity of the fascicle, more evident in patients with increased serum levels of muscle enzymes and diminished muscle strength. Despite the scarce reports about the use of SEM as a tool in all clinical phenotypes of IIM, our work provides an excellent opportunity to discuss and reframe the clinical usefulness of SEM in the diagnostic approach of IIM.
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Interleucina-17 , Miositis , Humanos , Interleucina-33 , Interleucina-10 , Interleucina-18 , Factor de Necrosis Tumoral alfa , Eosina Amarillenta-(YS) , Hematoxilina , Interleucina-6 , Autoanticuerpos , Fuerza Muscular , Interleucina-23RESUMEN
Positive attitudes towards breastfeeding in health professionals/students have been associated with increasing their confidence to provide support and accompaniment to mothers. In Mexico, there is no valid/reliable tool to assess attitudes towards breastfeeding in this population. The Australian Breastfeeding Attitudes (and Knowledge) Questionnaire (ABAQ) measures attitudes in the Australian population. We aimed to adapt and validate the ABAQ in Mexican health students. We included 264 health students (nursing, nutrition, and medicine) from the University of Guadalajara. Bilingual translators carried out the Spanish adaptation with a reverse translation into English. Experts evaluated the content validity. Reliability was evaluated through an internal consistency analysis (Cronbach's alpha) and construct validity through convergent-divergent validation, item-total correlation, exploratory factor analysis (by principal components), and confirmatory factor analysis. According to the exploratory factor analysis, only one component was identified. Seven items were removed (low correlation between items ≤0.2 and low factor load ≤0.3). The Cronbach's alpha was 0.78. According to the confirmatory factor analysis, the one-factor solution of the ABAQ-13Mx showed a good model fit (X2 = 98.41, G = 62, p = 0.02, CFI = 0.940, and RMSEA = 0.048). The ABAQ-13Mx is a reliable and valid instrument for evaluating attitudes towards breastfeeding in Mexican health degree students.