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Chronic Non-Communicable Diseases (NCDs) have been considered a global health problem, characterized as diseases of multiple factors, which are developed throughout life, and regardless of genetics as a risk factor of important relevance, the increase in mortality attributed to the disease to environmental factors and the lifestyle one leads. Although the reactive species (ROS/RNS) are necessary for several physiological processes, their overproduction is directly related to the pathogenesis and aggravation of NCDs. In contrast, dietary polyphenols have been widely associated with minimizing oxidative stress and inflammation. In addition to their antioxidant power, polyphenols have also drawn attention for being able to modulate both gene expression and modify epigenetic alterations, suggesting an essential involvement in the prevention and/or development of some pathologies. Therefore, this review briefly explained the mechanisms in the development of some NCDs, followed by a summary of some evidence related to the interaction of polyphenols in oxidative stress, as well as the modulation of epigenetic mechanisms involved in the management of NCDs.
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OBJECTIVE: Pycnodysostosis is commonly associated with growth hormone (GH) deficiency and responds well to GH therapy with achievement of normal or near-normal height and restoration of body proportions. CASE REPORT: A 22-month-old extremely short (-4.05 height standard deviation score) disproportionate boy with skeletal dysplasia presented to clinic. Skeletal survey, genetic panel, magnetic resonance imaging, and an insulin-like growth factor generation tests were performed. RESULTS: Skeletal survey showed increased bone density with classic features of pycnodysostosis, subsequently confirmed to be due to a deleterious homozygous frameshift mutation in CTSK. Uniquely among skeletal dysplasias, GH deficiency is a common association, secondary to pituitary hypoplasia. Magnetic resonance imaging confirmed pituitary hypoplasia and he subsequently underwent an insulin-like growth factor generation test that demonstrated biochemical responsiveness to GH therapy. This was thought to be safer than a classic GH stimulation test, in view of his very small size. Subsequently, his height has markedly improved on GH therapy. His height is now -2.25 SD, with an annualized growth velocity of 9.65 cm/y over a period of 18 months . CONCLUSION: It is important to consider GH therapy in children with pycnodysostosis, with the greatest benefit seen in children started at a young age.
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With the complexities that surround myocardial ischemia/reperfusion (MI/R) injury, therapies adjunctive to reperfusion that elicit beneficial pleiotropic effects and do not overlap with standard of care are necessary. This study found that the mitochondrial-derived peptide S14G-humanin (HNG) (2 mg/kg), an analogue of humanin, reduced infarct size in a large animal model of MI/R. However, when ischemic time was increased, the infarct-sparing effects were abolished with the same dose of HNG. Thus, although the 60-min MI/R study showed that HNG cardioprotection translates beyond small animal models, further studies are needed to optimize HNG therapy for longer, more patient-relevant periods of cardiac ischemia.
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microRNAs (miRNAs or miRs) are small non-coding RNAs that are involved in post-transcriptional regulation of their target genes in a sequence-specific manner. Emerging evidence demonstrates that miRNAs are critical regulators of lipid synthesis, fatty acid oxidation and lipoprotein formation and secretion. Dysregulation of miRNAs disrupts gene regulatory network, leading to metabolic syndrome and its related diseases. In this review, we introduced epigenetic and transcriptional regulation of miRNAs expression. We emphasized on several representative miRNAs that are functionally involved into lipid metabolism, including miR-33/33(â), miR122, miR27a/b, miR378/378(â), miR-34a and miR-21. Understanding the function of miRNAs in lipid homeostasis may provide potential therapeutic strategies for fatty liver disease.
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BACKGROUND/OBJECTIVE: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The highest prevalence of hepatitis is an important risk factor contributing to development of HCCs. However, an increasing number of cases are associated metabolic disease and steatohepatitis. Inflammation associated with many liver disease, seems to be a necessary pre-requisite for successful tumor initiation. Mechanisms that link high fat diet and inflammation initial stage of HCC are not completely understood. The present work was designed to investigate the effect of fat, through modulation of the insulin-like growth factors I and II (IGF-I and IGF-II), on the promotion of hepatocellular carcinoma, and the role of cyclooxygenase 2 (COX-2). METHODS: two main groups of rats were used: control and HCC groups. The HCC group was further sub-divide in to two subgroups, HCC fed with standard diet and HCC fed with high fat diet. The effects of celecoxib were also investigated in HCC fed with high fat diet. RESULTS: We found that high fat diet was associated with significant increases in COX2 and interleukin 6 (IL6) with significant promotion of HCC progression. The significant increase in IGF could contribute partially to the observed effects of high fat diet. In addition, celecoxib was found to significantly reduce HCC progression. CONCLUSIONS: We conclude that COX2 could play central role in high prevalence of HCC observed with high fat diet. Several triggering factors such as IGF and IL6, together with the direct modulation of fat metabolism could open several novel preventive strategies of celecoxib treatment, and could be useful biomarkers for assessment of its pharmacological effects.
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Portal vein thrombosis is an important cause of portal hypertension. PVT occurs in association with cirrhosis or as a result of malignant invasion by hepatocellular carcinoma or even in the absence of associated liver disease. With the current research into its genesis, majority now have an underlying prothrombotic state detectable. Endothelial activation and stagnant portal blood flow also contribute to formation of the thrombus. Acute non-cirrhotic PVT, chronic PVT (EHPVO), and portal vein thrombosis in cirrhosis are the three main variants of portal vein thrombosis with varying etiological factors and variability in presentation and management. Procoagulant state should be actively investigated. Anticoagulation is the mainstay of therapy for acute non-cirrhotic PVT, with supporting evidence for its use in cirrhotic population as well. Chronic PVT (EHPVO) on the other hand requires the management of portal hypertension as such and with role for anticoagulation in the setting of underlying prothrombotic state, however data is awaited in those with no underlying prothrombotic states. TIPS and liver transplant may be feasible even in the setting of PVT however proper selection of candidates and type of surgery is warranted. Thrombolysis and thrombectomy have some role. TARE is a new modality for management of HCC with portal vein invasion.
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Resistance to radiation therapy constitutes a significant challenge in the treatment of head and neck squamous cell cancer (HNSCC). Alteration in DNA methylation is thought to play a role in this resistance. Here, we analyzed DNA methylation changes in a matched model of radiation resistance for HNSCC using the Illumina HumanMethylation450 BeadChip. Our results show that compared to radiation-sensitive cells (SCC-61), radiation-resistant cells (rSCC-61) had a significant increase in DNA methylation. After combining these results with microarray gene expression data, we identified 84 differentially methylated and expressed genes between these 2 cell lines. Ingenuity Pathway Analysis revealed ILK signaling, glucocorticoid receptor signaling, fatty acid α-oxidation, and cell cycle regulation as top canonical pathways associated with radiation resistance. Validation studies focused on CCND2, a protein involved in cell cycle regulation, which was identified as hypermethylated in the promoter region and downregulated in rSCC-61 relative to SCC-61 cells. Treatment of rSCC-61 and SCC-61 with the DNA hypomethylating agent 5-aza-2'deoxycitidine increased CCND2 levels only in rSCC-61 cells, while treatment with the control reagent cytosine arabinoside did not influence the expression of this gene. Further analysis of HNSCC data from The Cancer Genome Atlas found increased methylation in radiation-resistant tumors, consistent with the cell culture data. Our findings point to global DNA methylation status as a biomarker of radiation resistance in HNSCC, and suggest a need for targeted manipulation of DNA methylation to increase radiation response in HNSCC.
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Ciclina D2/genética , Metilación de ADN/genética , Neoplasias de Cabeza y Cuello/genética , Tolerancia a Radiación/genética , Azacitidina/administración & dosificación , Azacitidina/análogos & derivados , Línea Celular Tumoral , Islas de CpG , Ciclina D2/biosíntesis , Metilación de ADN/efectos de la radiación , Decitabina , Regulación Neoplásica de la Expresión Génica/efectos de la radiación , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Factor 4 Similar a Kruppel , Regiones Promotoras GenéticasRESUMEN
The methylation status of the IGFBP-3 gene is strongly associated with cisplatin sensitivity in patients with non-small cell lung cancer (NSCLC). In this study, we found in vitro evidence that linked the presence of an unmethylated promoter with poor response to radiation. Our data also indicate that radiation might sensitize chemotherapy-resistant cells by reactivating IGFBP-3-expression through promoter demethylation, inactivating the PI3K/AKT pathway. We also explored the IGFBP-3 methylation effect on overall survival (OS) in a population of 40 NSCLC patients who received adjuvant therapy after R0 surgery. Our results indicate that patients harboring an unmethylated promoter could benefit more from a chemotherapy schedule alone than from a multimodality therapy involving radiotherapy and platinum-based treatments, increasing their OS by 2.5 y (p = .03). Our findings discard this epi-marker as a prognostic factor in a patient population without adjuvant therapy, indicating that radiotherapy does not improve survival for patients harboring an unmethylated IGFBP-3 promoter.