131,614 research outputs found
High-Level Petri Nets as Type Theories in the Join Calculus
No full textWe study the expressiveness of the join calculus by comparison with (generalised, coloured) Petri nets and using tools from type theory. More precisely, we consider four classes of nets of increasing expressiveness, , introduce a hierarchy of type systems of decreasing strictness, , , and we prove that a join process is typeable according to if and only if it is (strictly equivalent to) a net of class . In the details, and contain, resp., usual place/transition and coloured Petri nets, while and propose two natural notions of high-level net accounting for dynamic reconfiguration and process creation and called reconfigurable and dynamic Petri nets, respectively
Regulation of the Cell Cycle, Cell Cycle Checkpoints and Cancer
No full textDNA damage response (DDR) pathways are triggered to ensure proper repair of DNA lesions and preserve genome integrity. Key intracellular transducers of the DNA damage are ataxia-telangiectasia mutated kinase (ATM) and ataxia-telangiectasia and Rad3-related kinase (ATR). These nuclear proteins, through dynamic interaction with chromatin-bound sensory components and phosphorylation at T/SQ residues of a multitude of substrates, including the checkpoint kinases Chk1 and Chk2, activate a network of pathways important for DNA repair, multiple cell cycle–phase arrest, transcription, and apoptosis. Interestingly, the DDR machinery is a key mediator of telomere-dependent and telomere-independent forms of cellular senescence, and provides a barrier to aberrant DNA replication induced by oncogenic stimuli. These findings and the constitutive activation of the DDR in human precancerous lesions, underscore the role of the DDR as a tumour suppressor constraining transformation by driving incipient tumour cells into apoptosis or senescence. Since genetic abnormalities of the DDR hypersensitize to genotoxic anticancer agents, this pathway represents a relevant target to increase tumour cell kill and possibly overcome drug resistance. The promising results with a number of chemical inhibitors of ATM, Chk1 and Chk2 are paving the way for new chemoradiation strategies that exploit the DDR machinery
CHK2 kinase in the DNA damage response and beyond
No full textThe serine/threonine kinase CHK2 is a key component of the DNA damage response. In human cells, following genotoxic stress, CHK2 is activated and phosphorylates more than 20 proteins to induce the appropriate cellular response, which, depending on the extent of damage, the cell type, and other factors, could be cell cycle checkpoint activation, induction of apoptosis or senescence, DNA repair, or tolerance of the damage. Recently, CHK2 has also been found to have cellular functions independent of the presence of nuclear DNA lesions. In particular, CHK2 participates in several molecular processes involved in DNA structure modification and cell cycle progression. In this review, we discuss the activity of CHK2 in response to DNA damage and in the maintenance of the biological functions in unstressed cells. These activities are also considered in relation to a possible role of CHK2 in tumorigenesis and, as a consequence, as a target of cancer therapy
Glycaemic variability (measured by 48h continuous glucose monitoring) in subjects with metabolic syndrome, with or without diabetes, is independently associated with IL-6 blood concentrations.
No full textGlycaemic variability and inflammation in subjects with metabolic syndrome.
No full textSubjects who develop diabetes have an increased cardiovascular risk even before the appearance of diabetes. The aim of this study was to investigate the glycaemic var- iability measured by continuous glucose monitoring (CGM CV%) in nondiabetic subjects with metabolic syndrome (MS) and to explore if glycaemic variability was associated with circulating levels of interleukin-6 (IL-6), a proinflam- matory cytokine, or with an anti-inflammatory factor like adiponectin. Three groups of obese subjects with (MS?: 6m, 8f; BMI 33.1 ± 1.4 mean ± SEM) or without metabolic syndrome (MS-: 2m, 4f; BMI 29.2 ± 2.2) and with MS associated with type 2 diabetes (MS/T2D: 3m, 5f; BMI 32.9 ± 1.4) were investigated. The glycaemic variability was measured in all subjects in terms of CV% of the gly- caemic values obtained every 3 min during the course of a 48 h CGM performed using a subcutaneous glucose sensor. The average CGM CV% increased from MS- group (21.1%) to the MS? group (23.9%) and to the MS?/T2D group (27.4%) but it was not correlated to the CGM mean glycaemia (r = 0.20; P = ns). In some instances, CGM CV% was found higher in MS? subjects than in some MS? T2D ones. Stepwise multiple correlation analysis showed that IL-6 predicted CGM CV% (R2 = 0.35, b = 0.13; P \ 0.05) independently from BMI, waist circumference, adiponectin and insulin concentrations. In conclusion, the CGM CV% may contribute to better describe the individual
metabolic state and to understand the pathogenesis of endothelial dysfunction in non diabetic subjects with MS
Glycaemic variability (measured by 48h continous glucose monitoring) in subjects with metabolic syndrome, with ot withoout diabetes,is indipendently associated with IL-6 bood concentrations
No full textPostprandial hyperglycaemia induces endothelial dysfunction thus contributing to the appearance of atherosclerotic lesions and to the high cardiovascular risk of diabetic subjects.
Subjects who develop diabetes have an increased cardiovascular risk even before the appearance of diabetes.
Insulin resistant subjects with metabolic syndrome (MS) are at both high cardiovascular and diabetes risk and it cannot be excluded that higher postprandial glycaemic excursions might induce endothelial dysfunction in this condition. Furthermore, adipose tissue is known to release factors (adipokines) that are able to influence both insulin sensitivity and endothelial function.
The glycaemic variability is an interesting measurement concerning the frequency of hyperglycaemic and hypoglycaemic excursions and it might contribute to describe the glycaemic control independently of fasting plasma glucose and glycated haemoglobin.
Recently, continuous glucose monitoring systems have been developed that are able to measure interstitial glucose levels every 3 min for up to 2 days thus allowing a more accurate detection of both daily glucose load and variability
Emerging Increase in the prevalence and severity of nonalcoholic fatty liver disease: epidemiological study from general Mediterranean population
No full textBackground and Aims: The worldwide spread of obesity and
diabetes is leading to a drastic increase in nonalcoholic fatty liver
disease (NAFLD) and its complications.We aimed to assess prevalence
of NAFLD and of its severity among a general Mediterranean
population.
Methods:We considered 886 consecutive individuals included in the
ABCD study (ISRCTN15840340). Hepatic ultrasound (US) was used to
diagnose steatosis and FibroScan (M and XL probe) to measure
liver stiffness and controlled attenuation parameter (CAP). Liver
stiffness >6.9 KPa was considered suggestive of significant liver
fibrosis (Petta S et al., Hepatology 2015), and CAP ≥ 310 dB was
considered suggestive of moderate-severe steatosis (de Ledinghen V
et al., JHEP 2014).
Results: Steatosis by USwas diagnosed in 396 individuals (44.6%) and
was significantly associated with male gender, type 2 diabetes, low
HDL (<40 mg/mL in males and <50 mg/mL in females), and visceral
obesity. When splitting the analysis according to gender, steatosis
was independently linked to visceral obesity (OR 2.63, 95% CI 1.62–
4.27, p < 0.001) and low HDL (OR 2.06, 95% CI 1.10–3.85, p = 0.02) in
males, and to visceral obesity (OR 2.75, 95% CI 1.80–4.19, p < 0.001)
and type 2 diabetes (OR 2.19, 95% CI 1.00–4.87, p = 0.05) in females.
The rate of US steatosis, stiffness >6.9 kPa and CAP ≥310 progressively
increased from males without obesity and low HDL (35.1% steatosis;
among theme 18.6% CAP ≥310, and 13.5% stiffness >6.9), to those with
one risk factor (from 57.7% to 62.1% steatosis; among them 42.8% CAP
≥310, and from 21.4% to 23.2% stiffness >6.9), and further to those
with both risk factors (74.2% steatosis; among them 35% CAP ≥310,
and 30% stiffness >6.9). Similarly, in females the rate of US steatosis,
stiffness >6.9 kPa and CAP ≥310 progressively increased from patients
without obesity and diabetes (23.7% steatosis; among them 6.1% CAP
≥310, and 6.1% stiffness >6.9), to those with only one risk factor (from
33.3% to 50.8% steatosis; among them CAP ≥310 from 30.5% to 54.5%,
and stiffness >6.9 from 11.1% to 27.2%), and further to those with both
risk factors (74.2% steatosis; among them 47.1% CAP ≥ 310, and 26.4%
stiffness >6.9).
Conclusions: NAFLD is present in more than 40% of general
population and its prevalence, as well as the prevalence of live
Glycaemic variability (measured by 48h contiinous glucose monitoring) in subjects with metabolic syndrome, with ot without diabetes, is indipendently associated wiith IL-6 blood concentrations
No full textEndothelial function in obese patients treated with bariatric surgery
No full textPurpose: Bariatric surgery (BS) is becoming an increasingly frequent treatment option especially in people with morbid obesity, demonstrating that it is able to reduce total mortality and cardiovascular (CV) risk. Despite endothelial dysfunction is an essential requisite contributing to atherosclerosis and predicting CV events, only some studies have investigated the effects of BS on endothelial function with controversial results. In this study, the effects of weight loss on endothelial function were investigated in obese patients after BS and compared with patients after medical nutrition treatment (MNT). Patients and Methods: Seventeen obese patients who underwent BS procedures (9 adjustable gastric bands, 3 gastric by-passes and 5 biliopancreatic diversions) were included in the study and compared with 18 obese individuals who underwent MNT. Endothelial function was investigated by flow-mediated dilation (FMD) of the brachial artery. Also, carotid intima-media thickness (c-IMT) was measured as a marker of subclinical atherosclerosis. Results: At the end of follow-up, the mean weight loss was 18.8% in the BS group and 7.0% in the MNT group. After treatment, FMD significantly decreased in the BS group (mean ± SD before: 9.0 ± 4.7; after: 6.1 ± 2.9%; P= 0.04); however, no significant change was observed in the MNT group (before: 9.4 ± 5.8; after: 8.3 ± 5.3; P= 0.41). The modification of endothelial function was negatively correlated with c-IMT change in the BS group (r= −0.63; P <0.007). Conclusion: A significant endothelial dysfunction occurred following BS but not after MNT. Furthermore, the decline of endothelial function observed in the BS group might have contributed to atherosclerosis
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