Aim: Irisin is a hormone secreted by skeletal muscle able to improve metabolic homeostasis. Serum irisin levels are reduced in type 2 diabetes (T2D), while exogenous irisin administration improves ...glycemic control in diabetic mice. We have previously demonstrated that irisin promotes beta-cell survival and function both in vitro and in vivo in healthy wild type mice. We have also demonstrated that irisin restores the defective glucose-stimulated insulin secretion (GSIS) and reduces apoptosis in human pancreatic islets from patients with T2D. Nevertheless, the beta-cellular effects of in vivo irisin administration to T2D mice are still unknown. Methods: C57Bl/6 mice (n = 8) were fed a high-fat diet (HFD, 60% of energy deriving from fat) for 10 weeks and then intraperitoneally injected with streptozotocin (STZ, 100 mg/kg) to induce diabetes. Four standard diet (SD)-fed mice were used as control. HFD/STZ mice were treated with 0.5 μg/g irisin (n = 4) or vehicle (n = 4), for 14 days. Fasting glycemia, insulinemia, body weight, glucose tolerance, and pancreatic islet function were assessed. Pancreatic islet architecture was also evaluated through immunofluorescence analyses. Results: Compared to SD mice, HFD/STZ mice showed higher fasting glycemia and body weight, glucose intolerance, and reduced GSIS; in addition, HFD/STZ mice showed reduced islet volume (-78%), beta-cell area (-35%), and insulin content (-60%), and increased alpha-cell area (+54%). Irisin administration significantly restored glycemia (-31%), body weight (-13%), glucose tolerance (-27%), GSIS (+23%), islet volume (+61%), beta-cell area (+34%) and alpha-cell area (-49%), and insulin content (+36%). Of note, irisin induced a 9-fold increase in beta-cell proliferation rate. Conclusions: These results show that irisin improves glycemic homeostasis and restores the functional beta-cell mass when administered in vivo to diabetic mice, probably by promoting beta-cell proliferation.
: Several cases of non‐traumatic pulmonary haematoma have been reported in the literature. However, very few of them are related to anticoagulation therapy. The authors report two cases of pulmonary ...haematoma caused by oral anticoagulant therapy without any underlying pathological lesion. The evolution was fatal in the first case, whereas a slow spontaneous resolution of the haematoma was noted in the second. Non‐traumatic pulmonary haematoma can be a complication of oral anticoagulation and should be considered in the differential diagnosis of pulmonary densities in this setting.
The importance of the immune system as a potent anti-tumor defense has been consolidated in recent times, and novel immune-related therapies are today demonstrating a strong clinical benefit in the ...setting of several solid neoplasms. Tumor-infiltrating lymphocytes reflect the attempt of the host to eradicate malignancies, and during the last decades, they have been shown to possess an interesting prognostic utility for breast cancer, especially in case of HER2 positive and triple-negative molecular subtypes. In parallel, the clinical evaluation of tumor-infiltrating lymphocytes has been shown to effectively predict treatment outcomes in both neoadjuvant and adjuvant settings. Currently, tumor-infiltrating lymphocytes are promising further predictive utility in view of novel immune-related therapeutic strategies which are coming into the clinical setting launching a solid rationale for the future next-generation treatment options. In this scenario, tumor-infiltrating lymphocytes might represent an important resource for the selection of the most appropriate therapeutic strategy, as well as further evaluations of the molecular mechanisms underlying tumor-infiltrating lymphocytes and the immunoediting process would eventually provide new insights to augment therapeutic success. Considering these perspectives, we review the potential utility of tumor-infiltrating lymphocytes in the definition of breast cancer prognosis and in the prediction of treatment outcomes, along with the new promising molecular-based therapeutic discoveries.
Administration of iodinated contrast medium (CM) during invasive cardiovascular procedures may be associated with impairment of kidney function.
Urinary dickkopf-3 (DKK3), a stress-induced renal ...tubular epithelium–derived glycoprotein, has been identified as a biomarker predicting both acute kidney injury (AKI) and persistent kidney dysfunction.
Urinary DKK3/creatinine ratio (uDKK3/uCr), urine and serum neutrophil gelatinase-associated lipocalin (uNGAL, sNGAL) and serum cystatin C (sCyC) were assessed in 458 patients with chronic kidney disease scheduled for invasive cardiovascular procedures requiring CM administration with universal adoption of nephroprotective interventions. Contrast-associated AKI (CA-AKI) was defined as serum creatinine increase ≥0.3 mg/dl at 48 h after CM administration. Persistent kidney dysfunction was defined as persistent estimated glomerular filtration rate reduction ≥25% at 1 month compared with baseline.
CA-AKI occurred in 64 or the 458 patients (14%), and baseline uDKK3/uCr ≥491 pg/mg was the best threshold for its prediction. Net reclassification improvement (NRI) was significantly increased by adding baseline uDKK3/uCr to the Mehran, Gurm, and National Cardiovascular Data Registry (NCDR) scores (all p < 0.05), and the same applied to integrated discrimination improvement (IDI) when adding uDKK3/uCr to the Gurm and NCDR scores (p < 0.001). Persistent kidney dysfunction occurred in 57 of the 458 patients (12%) and baseline uDKK3/uCr ≥322 pg/mg appeared as the best threshold for its prediction. Adding baseline uDKK3/uCr to the Mehran, Gurm, and NCDR scores significantly increased IDI and NRI (all p < 0.001).
Baseline uDKK3/uCr seems to be a reliable marker for improving the identification of patients with chronic kidney disease undergoing invasive coronary and peripheral procedures at risk for AKI and persistent kidney dysfunction.
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Aim of the study was to evaluate the gelatinolytic activity in the saliva and gingival crevicular fluid from a sample group of subjects with Marfan syndrome.
Two groups were analyzed in this ...case-control study. A group of 28 subjects with Marfan syndrome (MG) was recruited from the Centre for Rare Disease, Marfan Clinic of Tor Vergata University Hospital. The second sample, 23 subjects, with the same characteristics and without any syndrome, was the control group (CG). Saliva and gingival crevicular fluid were collected and transferred to a sterile test tube and stored frozen at - 20 °C until analysis at the Medical Chemistry Laboratory. Gelatin substrate zymography was used for the evaluation and characterization of saliva and crevicular fluid proteinases. Correlation test and Student's t-test have been used to analyze data.
In all samples different gelatin-degrading activities were observed. Two bands, which are related to the molecular weights of pro-MMP-9 and active MMP-9, respectively, were detectable in 100% of Marfan and control samples. MMP-2 activity was higher in Marfan group. Additional bands (55/48 kDa), corresponding to the activated forms of collagenase (MMP-13), were observed in saliva samples of both groups.
The association of an enhanced activity by MMP-13 with an increased amount of active MMP-9 might be an important biomarker for the diagnosis of Marfan syndrome.
Industrial facilities release a large amount of heat as a by-product of their processes. To improve environmental performance and increase process profitability, a portion of the waste heat can be ...recovered and employed for power generation by recovery systems. Supercritical carbon dioxide (sCO2) plants are emerging as potential alternatives to the well-established technologies for waste heat recovery (WHR) power generation in heavy industry. This paper offers a preliminary techno-economic analysis of a waste heat-to-power system based on a sCO2 closed-loop for a heavy-industrial process.
By conducting a parametric investigation on the WHR sCO2 system’s key design parameters, a number of preferable configurations from a thermodynamic perspective were initially identified; they were subsequently analyzed from the economic point of view in terms of net present value (NPV) and pay-back period (PBP). The privileged WHR system configuration achieved an overall efficiency of 30.4% and a power output of 21.6 kWe, providing an NPV of almost US k$ 376 with a PBP of approximately 4.5 years.
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