Deflamin Attenuated Lung Tissue Damage in an Ozone-Induced COPD Murine Model by Regulating MMP-9 Catalytic Activity.

Chronic obstructive pulmonary disease (COPD) is comprised of histopathological alterations such as pulmonary emphysema and peribronchial fibrosis. Matrix metalloproteinase 9 (MMP-9) is one of the key enzymes involved in both types of tissue remodeling during the development of lung damage. In recent studies, it was demonstrated that deflamin, a protein component extracted from Lupinus albus, markedly inhibits the catalytic activity of MMP-9 in experimental models of colon adenocarcinoma and ulcerative colitis. Therefore, in the present study, we investigated for the first time the biological effect of deflamin in a murine COPD model induced by chronic exposure to ozone. Ozone exposure was carried out in C57BL/6 mice twice a week for six weeks for 3 h each time, and the treated group was orally administered deflamin (20 mg/kg body weight) after each ozone exposure. The histological results showed that deflamin attenuated pulmonary emphysema and peribronchial fibrosis, as evidenced by H&E and Masson's trichrome staining. Furthermore, deflamin administration significantly decreased MMP-9 activity, as assessed by fluorogenic substrate assay and gelatin zymography. Interestingly, bioinformatic analysis reveals a plausible interaction between deflamin and MMP-9. Collectively, our findings demonstrate the therapeutic potential of deflamin in a COPD murine model, and suggest that the attenuation of the development of lung tissue damage occurs by deflamin-regulated MMP-9 catalytic activity.

[Metabolic profile and concentration of ghrelin and obestatin in children and adolescents with obesity]. / Perfil metabólico, concentración de grelina y obestatina en niños y adolescentes con obesidad.

Background: It has been pointed out that ghrelin and obestatin could have an impact on the genesis of obesity, since they estimulate and inhibit apetite and, therefore, food consumption. Objective: To compare the metabolic profile, lipid profile and the concentrations of ghrelin and obestatin in children with normal weight or obesity. Material and methods: Cross-sectional design with 97 normal weight or obese children, 6 to 18 years of age, who did not present systemic diseases. The serum concentrations of glucose, insulin, total cholesterol, triglycerides, high (HDL), low (LDL) and very low density (VLDL) lipoproteins, aspartate aminotransferase (AST), alanine aminotransferase (ALT), ghrelin and obestatin were determined. Descriptive statistics were performed. Student's t test was used to compare groups, and correlation coefficients of ghrelin and obestatin values with biochemical and anthropometric variables. A p value of ≤ 0.05 was significant. Results: 55 children with normal weight and 42 with obesity were included; mean age was 10.7 years. Triglycerides, LDL, VLDL, ALT and insulin were higher, and HDL lower in obese children (p < 0.05). Ghrelin values were higher in normal weight children (p < 0.05), and there was no difference in obestatin values. Conclusions: The lower concentration of ghrelin in obese children may indicate a negative feedback to regulate energy consumption. Children and adolescents with obesity show metabolic and lipid profile alterations that place them at risk of early development of cardiovascular risk factors.

Introducción: se ha señalado que la grelina y la obestatina podrían incidir en la génesis de la obesidad al estimular o inhibir el apetito y, por ende, el consumo de alimentos. Objetivo: comparar el perfil metabólico, el perfil de lípidos y las concentraciones de grelina y obestatina en niños con normopeso u obesidad. Material y métodos: diseño transversal con 97 niños de 6 a 18 años con normopeso u obesidad que no presentaran enfermedades sistémicas. Se determinaron las concentraciones séricas de glucosa, insulina, colesterol total, triglicéridos, lipoproteínas de colesterol de alta (HDL), baja (LDL) y muy baja densidad (VLDL), aspartato aminotransferasa (AST), alanina aminotransferasa (ALT), grelina y obestatina. Se usó estadística descriptiva. Se utilizó la prueba t de Student para comparar grupos, y coeficientes de correlación de los valores de grelina y obestatina con las variables bioquímicas y antropométricas. Un valor de p ≤ 0.05 fue significativo. Resultados: se incluyeron 55 niños con normopeso y 42 con obesidad; la edad promedio fue de 10.7 años. Los triglicéridos, LDL, VLDL, ALT y la insulina fueron superiores, y el HDL inferior en niños con obesidad (p < 0.05). Los valores de la grelina fueron superiores en niños con normopeso (p < 0.05) y no hubo diferencia en los de la obestatina. Conclusiones: la menor concentración de grelina en niños con obesidad puede indicar una retroalimentación negativa para regular el consumo de energía. Los niños y adolescentes con obesidad muestran alteraciones metabólicas y del perfil de lípidos que los ponen en riesgo de desarrollar tempranamente factores de riesgo cardiovascular.

Nanoparticles Formulation Improves the Antifibrogenic Effect of Quercetin on an Adenine-Induced Model of Chronic Kidney Disease.

Renal fibrosis is the final stage of chronic kidney injury characterized by glomerulosclerosis and tubulointerstitial fibrosis with parenchymal destruction. Quercetin belongs to the most studied flavonoids with antioxidant, anti-inflammatory, antifibrogenic, and antitumor activity. It modifies the TGF-ß/Smad signaling pathway, decreasing profibrogenic expression molecules and inducing the expression of antioxidant, anti-inflammatory, and antifibrogenic molecules. However, quercetin exhibits poor water solubility and low absorption and bioavailability. This limitation was solved by developing a nanoparticles formulation that improves the solubility and bioavailability of several bioactive compounds. Therefore, we aimed to investigate the in vivo antifibrogenic effect of a quercetin nanoparticles formulation. Male C57BL/6 mice were induced into chronic renal failure with 50 mg/kg of adenine for four weeks. The animals were randomly grouped and treated with 25, 50, or 100 mg/kg of quercetin, either macroparticles or nanoparticles formulation. We performed biochemical, histological, and molecular analyses to evaluate and compare the effect of macroparticles versus nanoparticles formulation on kidney damage. Here, we demonstrated that smaller doses of nanoparticles exhibited the same beneficial effect as larger doses of macroparticles on preventing kidney damage. This finding translates into less quercetin consumption reaching the desired therapeutic effect.

Cladodes from Nopalea cochenillifera (L.) Salm-Dyck (Cactaceae) attenuate postprandial glycaemia without markedly influencing α-glucosidase activity.

Although the cladodes of Nopalea cochenillifera are used in Mexican traditional medicine to treat diabetes and various other diseases, its antihyperglycaemic properties, phenolic content, and antioxidant activity are not well documented. Thus, we determined the activity of a single dose of fresh, blended cladodes on postprandial glycaemia in rats after a starch load. We prepared a methanolic extract of N. cochenillifera cladodes and measured its phenolic content, antioxidant capacity, and α-glucosidase inhibitory activity. The antihyperglycaemic effect of blended cladodes was similar to that of acarbose when considering the changes in glucose levels from baseline. Furthermore, the methanolic extract contained a considerable amount of phenolic compounds and exhibited antioxidant activity in the DPPH assay, but did not markedly inhibit α-glucosidase and had a low antioxidant effect in the ABTS test.

Inhibitory mechanisms of two Uncaria tomentosa extracts affecting the Wnt-signaling pathway.

Uncaria tomentosa ("uña de gato"; "cat's claw"), a woody vine native to the Amazon rainforest, is commonly used in South American traditional medicine to treat a broad spectrum of diseases. Although recent studies have reported anti-inflammatory and anti-proliferative properties of different alkaloids extracted from this plant, the underlying molecular mechanisms of these effects have not been elucidated yet. Our study investigates the inhibitory mechanisms of Uncaria tomentosa extracts on the Wnt-signaling pathway, a central regulator of development and tissue homoeostasis. A modified cell-based luciferase assay for screening inhibitors of the Wnt-pathway was used for analysis. Three cancer cell lines displaying different levels of aberrant Wnt-signaling activity were transfected with Wnt-signaling responsive Tcf-reporter plasmids and treated with increasing concentrations of two Uncaria tomentosa bark extracts. Wnt-signaling activity was assessed by luciferase activity and by expression of Wnt-responsive target genes. We show that both, an aqueous and an alkaloid-enriched extract specifically inhibit Wnt-signaling activity in HeLa, HCT116 and SW480 cancer cells resulting in reduced expression of the Wnt-target gene: c-Myc. The alkaloid-enriched extract (B/S(rt)) was found to be more effective than the aqueous extract (B/W(37)). The strongest effect was observed in SW480 cells, displaying the highest endogenous Wnt-signaling activity. Downregulation of Wnt-signaling by a dominant negative-TCF-4 variant in non-cancer cells rendered the cells insensitive towards treatment with B/S(rt). B/Srt was less toxic in non-cancer cells than in cancer cells. Our data suggest that the broad spectrum of pharmacological action of Uncaria tomentosa involves inhibition of the Wnt-signaling pathway, downstream of beta-Catenin activity.

[Lung cancer histological types and diagnostic methods in a tertiary care facility]. / Tipos histológicos y métodos diagnósticos en cáncer pulmonar en un centro hospitalario de tercer nivel.

OBJECTIVE: To describe the histological frequencies, diagnostic methods, gender and age of lung cancer patients in a third level care hospital in western Mexico. METHODS: A retrospective and descriptive study (2002 to 2005) was undertaken. From all reviewed cases, 242 patients had a diagnosis compatible with lung cancer. We analyzed the histological type, gender, age group, and diagnostic method. RESULTS: The histological type frequencies of lung cancer were as follows: 63.6% adenocarcinoma, 19.0% squamous cell carcinoma, 15.2% small cell carcinoma, and 2.2% large-cell carcinoma. Among these patients, a male-female ratio of 2:1 with a mean age of 63 years was found. Regarding the diagnostic methods followed, the most common included: transthoracic needle aspiration, bronchial biopsy, and bronchial washing. CONCLUSIONS: Adenocarcinoma was the most frequent histological type in the sample studied, an association between female gender and risk of developing adenocarcinoma was detected.

Tipos histológicos y métodos diagnósticos en cáncer pulmonar en un centro hospitalario de tercer nivel / Lung cancer histological types and diagnostic methods in a tertiary care facility

Objetivo: Describir las frecuencias de tipos histológicos, métodos diagnósticos, sexo y edad de pacientes con cáncer pulmonar, en el Centro Médico Nacional de Occidente del Instituto Mexicano del Seguro Social, Guadalajara, Jalisco. Métodos: Estudio descriptivo y retrospectivo de los casos revisados entre 2002 y 2005; 242 pacientes presentaron diagnóstico de cáncer pulmonar. Se analizó el tipo histológico, sexo, edad y métodos diagnósticos. Resultados: Los tipos histológicos de cáncer pulmonar presentaron las siguientes frecuencias: adenocarcinoma 63.6%, carcinoma de células escamosas 19.0%, carcinoma de células pequeñas 15.2% y carcinoma de células grandes 2.2%. Se encontró una relación varón:mujer de 2:1, con una edad promedio de 63 años. Los métodos diagnósticos más utilizados fueron biopsia por aspiración con aguja fina, biopsia bronquial y lavado bronquial. Conclusiones: En la población analizada, el adenocarcinoma fue el tipo histológico más frecuente. Además, se encontró asociación entre el sexo femenino y el riesgo de presentar adenocarcinoma.

OBJECTIVE: To describe the histological frequencies, diagnostic methods, gender and age of lung cancer patients in a third level care hospital in western Mexico. METHODS: A retrospective and descriptive study (2002 to 2005) was undertaken. From all reviewed cases, 242 patients had a diagnosis compatible with lung cancer. We analyzed the histological type, gender, age group, and diagnostic method. RESULTS: The histological type frequencies of lung cancer were as follows: 63.6% adenocarcinoma, 19.0% squamous cell carcinoma, 15.2% small cell carcinoma, and 2.2% large-cell carcinoma. Among these patients, a male-female ratio of 2:1 with a mean age of 63 years was found. Regarding the diagnostic methods followed, the most common included: transthoracic needle aspiration, bronchial biopsy, and bronchial washing. CONCLUSIONS: Adenocarcinoma was the most frequent histological type in the sample studied, an association between female gender and risk of developing adenocarcinoma was detected.