Non-alcoholic fatty liver disease is marked by hepatic fat accumulation not due to alcohol abuse. Several studies have demonstrated that NAFLD is associated with insulin resistance leading to a resistance in the antilipolytic effect of insulin in the adipose tissue with an increase of free fatty acids (FFAs). The increase of FFAs induces mitochondrial dysfunction and development of lipotoxicity. Moreover, in subjects with NAFLD, ectopic fat also accumulates as cardiac and pancreatic fat. In this review we analyzed the mechanisms that relate NAFLD with metabolic syndrome and dyslipidemia and its association with the development and progression of cardiovascular disease.
Ductal pancreatic carcinoma (DPC) is a deadly disease with an incidence of 9 cases in 100,000 people per year and a mortality rate close to 100%. Allelic losses in the long arm of chromosome 9 are commonly encountered in many human malignancies but no data are yet available about DPC. We screened 40 lasermicrodissected DPC samples and 6 pre-invasive lesions for 9 microsatellite mapping markers of region 9q21.3 through 9q34.2. A small overlapping region of deletion, spanning 8 million base pairs, was identified between D9S127 and D9S105. Two genes, RSG3 and KLF4, mapped to 9q31.1 through 9q32, were further investigated. A highly significant association was found between KLF4 gene expression levels and genomic status. Similarly, absence of immunohistochemical expression of KLF4 protein was found in 86.8% cases of DPC (33/ 38). Overexpression of KLF4 in a human pancreatic carcinoma cell line induced a significant decrease in the proliferation associated with up-regulation of p21 and the down-regulation of cyclin D1. In conclusion, we identified a novel oncosuppressor region located at the 9q 31.1-3 locus that is lost in DPC at high frequency. Loss of KLF4 expression is closely related to the genomic loss, and its restoration inhibits cancer cell proliferation, suggesting a key suppressor role in pancreatic tumorigenesis. Pancreatic cancer is the fifth leading cause of cancerrelated death in both men and women in the Western world, being responsible for 5% of all cancer-related deaths.1 The lack of reliable early diagnostic methods and effective therapeutic regimens makes the mortality rates in persons with pancreatic carcinoma virtually the same as the incidence rates. A radical surgical approach is possible in only 10% of cases, and adjuvant therapies are virtually ineffective.2 A better understanding of the molecular mechanisms leading to pancreatic tumorigenesis may provide new markers for early diagnosis and potential targets for therapeutic intervention.Ductal pancreatic carcinoma (DPC) is by far the most common pancreatic tumor type, accounting for about 90% of all pancreatic malignancies. At present, a molecular model of DPC development has been proposed; it involves key genes, such K-ras, HER2neu, p16, p53, and DPC4 (smad4). Activating mutations in the K-ras oncogene and the overexpression of Her-2/neu gene are considered "early" genetic events because they occur in pre-invasive lesions (pancreatic intra-epithelial neoplasias, or PanINs) 3,4 and are followed by homozygous deletions in the p16 tumor suppressor gene locus. 5,6 Later in the tumor's progression, inactivations of p53 and DPC4 tumor suppressor genes are thought to be key events that lead to fully transformed phenotypes (carcinoma in situ, or PanIN-3). 7-11Wide genomic instability characterizes DPC, as has been documented by the large collection of cytogenetic abnormalities reported in the literature. [12][13][14][15][16][17] Among these, 9p (p16 locus), 17p (p53 locus), and 18q (DPC4 locus) have been reported to have been deleted in more than 60%...
Obesity is a major risk factor for cardiovascular disease and its complications. However, not all fat depots share the same characteristics. Recent studies have found that ectopic rather than subcutaneous fat accumulation is associated with increased cardiometabolic risk. However, ectopic fat accumulation can be seen initially as a protective mechanism against lipotoxicity. Subsequently the adipose tissue becomes dysfunctional, thus inducing systemic metabolic alterations (through release of cytokines) or specific organ dysfunctions. The purpose of this review is to summarise the current available data on the impact of excess adiposity vs ectopic fat in the development of cardio-metabolic diseases.
BackgroundGlioblastoma (GB) is the most severe form of brain cancer, with a 12-15 month median survival. Surgical resection, temozolomide (TMZ) treatment, and radiotherapy remain the primary therapeutic options for GB, and no new therapies have been introduced in recent years. This therapeutic standstill is primarily due to preclinical approaches that do not fully respect the complexity of GB cell biology and fail to test efficiently anti-cancer treatments. Therefore, better treatment screening approaches are needed. In this study, we have developed a novel functional precision medicine approach to test the response to anticancer treatments in organoids derived from the resected tumors of glioblastoma patients.MethodsGB organoids were grown for a short period of time to prevent any genetic and morphological evolution and divergence from the tumor of origin. We chose metabolic imaging by NAD(P)H fluorescence lifetime imaging microscopy (FLIM) to predict early and non-invasively ex-vivo anti-cancer treatment responses of GB organoids. TMZ was used as the benchmark drug to validate the approach. Whole-transcriptome and whole-exome analyses were performed to characterize tumor cases stratification.ResultsOur functional precision medicine approach was completed within one week after surgery and two groups of TMZ Responder and Non-Responder tumors were identified. FLIM-based metabolic tumor stratification was well reflected at the molecular level, confirming the validity of our approach, highlighting also new target genes associated with TMZ treatment and identifying a new 17-gene molecular signature associated with survival. The number of MGMT gene promoter methylated tumors was higher in the responsive group, as expected, however, some non-methylated tumor cases turned out to be nevertheless responsive to TMZ, suggesting that our procedure could be synergistic with the classical MGMT methylation biomarker.ConclusionsFor the first time, FLIM-based metabolic imaging was used on live glioblastoma organoids. Unlike other approaches, ex-vivo patient-tailored drug response is performed at an early stage of tumor culturing with no animal involvement and with minimal tampering with the original tumor cytoarchitecture. This functional precision medicine approach can be exploited in a range of clinical and laboratory settings to improve the clinical management of GB patients and implemented on other cancers as well.
Atypical eating habits are more common in children with autism spectrum disorders (ASD) than typically developing (TD) peers. Feeding problems may lead to the double burden of specific nutrient deficiencies and excessive weight gain, with a consequent increase in obesity prevalence. The dietary intake of Italian preschoolers with ASD compared to their TD peers and the impact of their dietary choices on their weight status and relationship to food selectivity (FS) were investigated. Dietary patterns and their associations with body mass index (BMI) were evaluated in 65 children with ASD and 82 peers with TD aged 1.3–6.4 years. Eating habits were assessed with a modified version of a parent-rated semi-quantitative Food Frequency Questionnaire. Moreover, the prevalence of FS and possible links with dietary patterns and BMI were investigated in the ASD group. Children with ASD consumed significantly higher amounts of simple sugars, processed and ultra-processed carbohydrates, both low- and high-fat animal proteins, and lower amounts of vegetables and fruits compared to peers with TD. The obesity rate was 1.5% in children with TD and more than fourfold (6.2%) in children with ASD, although the difference between groups was not statistically significant. FS was significantly more frequent in children with ASD than in peers with TD. Children with ASD and FS showed significantly lower annual intakes of vegetable proteins and fiber (considered essential nutrients for a healthy diet) than children with ASD without FS. Our results showed that children with ASD showed different dietary habits than those with TD, with the higher consumption of energy-dense foods and lower amounts of food-sourced fibers, which could place them at increased risk to develop overweight, obesity, and micronutrient deficiencies later in life.
The recent development of millimeter-wave (mmW) technologies, such as the fifth-generation (5G) network, comes with concerns related to user exposure. A quite large number of dosimetry studies above 6 GHz have been conducted, with the main purpose being to establish the correlation between different dosimetric parameters and the skin surface temperature elevation. However, the dosimetric studies from 28 GHz user equipment using different voxel models have not been comprehensively discussed yet. In this study, we used the finite-difference time-domain (FDTD) method for the estimation of the absorption of radiofrequency (RF) energy from a microstrip patch antenna array (28 GHz) in different human models. Specifically, we analyzed different exposure conditions simulating three real common scenarios (a phone call scenario, message writing scenario, and browsing scenario) regarding the use of smartphones/tablets by four different individuals (adult male and female, child male and female). From the results of Absorbed Power Density (Sab), it is possible to conclude that all the considered exposure scenarios comply with the safety limits, both for adult and children models. However, the high values of the local Specific Absorption Rate (SAR) in the superficial tissues and the slight differences in its distribution between adults and children suggest the need for further and more detailed analysis.
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