Mitochondrial Aging and Metabolism: The Importance of a Good Relationship in the Central Nervous System

The mitochondrial theory of aging suggests that mitochondria have a decrease in production capacity of adenosine triphosphate (ATP). The question may seem trivial, but it becomes more complex when considering that dysfunctional mitochondria can be eliminated by lysosomal digestion and that cell with dysfunctional mitochondria can undergo the process of apoptosis. In organs with regenerative capacity, like the liver, cell proliferation can almost completely hide mitochondrial dysfunction. However, evidence indicates selective damage in mitochondria during aging, and so the mitochondrial aging theory is gaining recognition and respect. There is solid evidence that accumulated DNA damage in mitochondria is a cause directly related to metabolic disorders such as diabetes and degenerative disorders such as Alzheimer’s disease. The central nervous system is particularly susceptible to oxidative damage due to several factors, among which are its high oxygen consumption, its dependence on aerobic carbohydrate metabolism, and its complex composition of membrane lipids. Free radicals are generated at many cell sites, and the mitochondrial respiratory chain is one of the main sources. While many studies have been conducted in experimental animal models, the results are relevant because at least some of their interventions suggest a directing aim at reducing the effects of aging

Spare PRELI Gene Loci: Failsafe Chromosome Insurance?

LEA (late embryogenesis abundant) proteins encode conserved N-terminal mitochondrial signal domains and C-terminal (A/TAEKAK) motif repeats, long-presumed to confer cell resistance to stress and death cues. This prompted the hypothesis that LEA proteins are central to mitochondria mechanisms that connect bioenergetics with cell responses to stress and death signaling. In support of this hypothesis, recent studies have demonstrated that mammalian LEA protein PRELI can act as a biochemical hub, which upholds mitochondria energy metabolism, while concomitantly promoting B cell resistance to stress and induced death. Hence, it is important to define in vivo the physiological relevance of PRELI expression.Given the ubiquitous PRELI expression during mouse development, embryo lethality could be anticipated. Thus, conditional gene targeting was engineered by insertion of flanking loxP (flox)/Cre recognition sites on PRELI chromosome 13 (Chr 13) locus to abort its expression in a tissue-specific manner. After obtaining mouse lines with homozygous PRELI floxed alleles (PRELI(f/f)), the animals were crossed with CD19-driven Cre-recombinase transgenic mice to investigate whether PRELI inactivation could affect B-lymphocyte physiology and survival. Mice with homozygous B cell-specific PRELI deletion (CD19-Cre/Chr13 PRELI(-/-)) bred normally and did not show any signs of morbidity. Histopathology and flow cytometry analyses revealed that cell lineage identity, morphology, and viability were indistinguishable between wild type CD19-Cre/Chr13 PRELI(+/+) and CD19-Cre/Chr13 PRELI(-/-) deficient mice. Furthermore, B cell PRELI gene expression seemed unaffected by Chr13 PRELI gene targeting. However, identification of additional PRELI loci in mouse Chr1 and Chr5 provided an explanation for the paradox between LEA-dependent cytoprotection and the seemingly futile consequences of Chr 13 PRELI gene inactivation. Importantly, PRELI expression from spare gene loci appeared ample to surmount Chr 13 PRELI gene deficiency.These findings suggest that PRELI is a vital LEA B cell protein with failsafe genetics

EFECTO DE LA PECTINA EXTRAÍDA DE GUAYABA SOBRE EL PERFIL LIPÍDICO EN ADULTOS CON DIFERENTE CONDICIÓN CARDIOVASCULAR

Antecedentes. Objetivo. Se buscaron nuevas aplicaciones de la guayaba (Psidium guajava L.), fruta rica en nutrientes funcionales como pectina y compuestos antioxidantes, enriqueciendo alimentos de alto consumo (pan y arepa), con la pectina extraída de esta fruta.Material y métodos. Se realizó un estudio clínico en 31 adultos entre 20-70 años, clasificados en dos categorías de riesgo cardiovascular (latente y alto), quienes consumieron durante 15 días los productos pan o arepa enriquecidos con 5 ó 10 % de pectina extraída de guayaba. Se evaluaron los niveles séricos de colesterol total (CT), lipoproteínas de baja densidad (cLDL) y de alta densidad (cHDL), y triglicéridos (TG), antes y después de dicho consumo.Resultados. Se encontró una disminución en los niveles de colesterol total dependiente de la dosis de pectina adicionada al alimento, tanto en el grupo de riesgo latente como en el de alto riesgo. La mayor disminución (36 mg/dl) se observó en el grupo latente que consumió el alimento con 10% de pectina, igualmente en este grupo se encontró la mayor disminución en el cLDL (24 mg/dl). Respecto a los niveles de cHDL y TG no se observó relación con el contenido de pectina adicionada a los alimentos. En cuanto al tipo de alimento suministrado (pan o arepa) se observó una mayor disminución en los niveles de CT y cLDL en los individuos que consumieron arepa. Conclusiones. El consumo de los alimentos pan y arepa enriquecidos con 5 y 10% de pectina extraída de guayaba, durante 15 días, produjo una disminución en los niveles séricos de CT y de cLDL dependiente de la dosis tanto en el grupo de riesgo cardiovascular latente como en el grupo de alto riesgo. El efecto hipolipemiante fue mayor en los pacientes que consumieron arepa enriquecida con 10% de pectina extraída de guayaba

Efecto de la pectina extraída de guayaba sobre el perfil lipídico en adultos con diferente condición cardiovascular

Antecedentes.Objetivo.Se buscaron nuevas aplicaciones de la guayaba (Psidium guajava L.), fruta rica en nutrientes funcionales como pectina y compuestos antioxidantes, enriqueciendo alimentos de alto consumo (pan y arepa), con la pectina extraída de esta fruta.Material y métodos. Se realizó un estudio clínico en 31 adultos entre 20-70 años, clasificados en dos categorías de riesgo cardiovascular (latente y alto), quienes consumieron durante 15 días los productos pan o arepa enriquecidos con 5 ó 10 % de pectina extraída de guayaba. Se evaluaron los niveles séricos de colesterol total (CT), lipoproteínas de baja densidad (cLDL) y de alta densidad (cHDL), y triglicéridos (TG), antes y después de dicho consumo.Resultados.Se encontró una disminución en los niveles de colesterol total dependiente de la dosis de pectina adicionada al alimento, tanto en el grupo de riesgo latente como en el de alto riesgo. La mayor disminución (36 mg/dl) se observó en el grupo latente que consumió el alimento con 10% de pectina, igualmente en este grupo se encontró la mayor disminución en el cLDL (24 mg/dl). Respecto a los niveles de cHDL y TG no se observó relación con el contenido de pectina adicionada a los alimentos. En cuanto al tipo de alimento suministrado (pan o arepa) se observó una mayor disminución en los niveles de CT y cLDL en los individuos que consumieron arepa.Conclusiones.El consumo de los alimentos pan y arepa enriquecidos con 5 y 10% de pectina extraída de guayaba, durante 15 días, produjo una disminución en los niveles séricos de CT y de cLDL dependiente de la dosis tanto en el grupo de riesgo cardiovascular latente como en el grupo de alto riesgo. El efecto hipolipemiante fue mayor en los pacientes que consumieron arepa enriquecida con 10% de pectina extraída de guayaba

Cigarette Smoking Alters the Expression of Circulating microRNAs and Its Potential Diagnostic Value in Female Lung Cancer Patients

Cigarette smoking is a known risk factor for the development of lung cancer. We investigated whether circulating microRNA expression levels and their potential diagnostic value are affected by cigarette smoking in adenocarcinoma (AD) patients and healthy (H) participants. In total, 71 female AD patients and 91 H individuals were recruited, including 42 AD never-smokers (AD/CS−), 29 AD smokers (AD/CS+), 54 H never-smokers (H/CS−), and 37 H smokers (H/CS+). PCR array (754 microRNAs) and qPCR were performed on sera from the discovery and validation cohorts, respectively. The expression levels of miR-532-5p, miR-25-3p, and miR-133a-3p were significantly higher in adenocarcinoma patients than in healthy participants, independent of their smoking status. Multivariate analysis showed that levels of miR-133a-3p were independently associated with smoking. ROC analysis showed that only miR-532-5p discriminated AD patients from H controls (AUC: 0.745). However, when making comparisons according to cigarette smoking status, miR-532-5p discriminated AD/CS− patients from H/CS− controls with a higher AUC (AUC:0.762); miR-25-3p discriminated AD/CS+ patients from H/CS+ controls (AUC: 0.779), and miR-133a discriminated AD/CS+ patients from H/CS+ controls with the highest AUC of 0.935. Cancer and lung-cancer-enriched pathways were significantly associated with the three miRNAs; in addition, nicotinate/nicotinamide metabolism, inflammation, and pulmonary hypertension were associated with miR-133a-3p. Our findings highlight how cigarette smoking affects the reliable identification of circulating miRNAs as diagnostic biomarkers in lung cancer and suggest a smoking-dependent pathogenic role of miR-133a-3p in smokers

Overexpression of <i>MEOX2</i> and <i>TWIST1</i> Is Associated with H3K27me3 Levels and Determines Lung Cancer Chemoresistance and Prognosis

<div><p>Lung cancer is the leading cause of death from malignant diseases worldwide, with the non-small cell (NSCLC) subtype accounting for the majority of cases. NSCLC is characterized by frequent genomic imbalances and copy number variations (CNVs), but the epigenetic aberrations that are associated with clinical prognosis and therapeutic failure remain not completely identify. In the present study, a total of 55 lung cancer patients were included and we conducted genomic and genetic expression analyses, immunohistochemical protein detection, DNA methylation and chromatin immunoprecipitation assays to obtain genetic and epigenetic profiles associated to prognosis and chemoresponse of NSCLC patients. Finally, siRNA transfection-mediated genetic silencing and cisplatinum cellular cytotoxicity assays in NSCLC cell lines A-427 and INER-37 were assessed to describe chemoresistance mechanisms involved. Our results identified high frequencies of CNVs (66–51% of cases) in the 7p22.3–p21.1 and 7p15.3–p15.2 cytogenetic regions. However, overexpression of genes, such as <i>MEOX2</i>, <i>HDAC9</i>, <i>TWIST1</i> and <i>AhR</i>, at 7p21.2–p21.1 locus occurred despite the absence of CNVs and little changes in DNA methylation. In contrast, the promoter sequences of <i>MEOX2</i> and <i>TWIST1</i> displayed significantly lower/decrease in the repressive histone mark H3K27me3 and increased in the active histone mark H3K4me3 levels. Finally these results correlate with poor survival in NSCLC patients and cellular chemoresistance to oncologic drugs in NSCLC cell lines in a <i>MEOX2</i> and <i>TWIST1</i> overexpression dependent-manner. In conclusion, we report for the first time that <i>MEOX2</i> participates in chemoresistance irrespective of high CNV, but it is significantly dependent upon H3K27me3 enrichment probably associated with aggressiveness and chemotherapy failure in NSCLC patients, however additional clinical studies must be performed to confirm our findings as new probable clinical markers in NSCLC patients.</p></div

Outcomes clinical data of NSCLC patients.

<p>(AD) Adenocarcinoma Patients; (N.D.) Not Detected; and (N.A.) Not Applied.</p><p>Outcomes clinical data of NSCLC patients.</p