Serum Cytokine and miRNA Levels Are Differently Expressed in Right- and Left-Sided Colon Cancer.

The tumor location in colorectal cancer (right- or left-sided colon cancer) is a key factor in determining disease progression. Right- and left-sided colon tumors are different in their clinical and molecular characteristics. Dysregulation of serum levels of proinflammatory cytokines, such as Transforming Growth Factor ß (TGF-ß) and Tumor Necrosis Factor-α (TNF-α), and Peroxisome Proliferator Activated Receptor-γ (PPAR-γ), known to be a growth-limiting and differentiation-promoting factor, as well as changes in miRNAs expression, are the major signaling pathways involved in the pathogenesis of this neoplasia. In the serum from 60 colorectal cancer (CRC) patients, we compared the differences in the expression of the levels of TGF-ß, TNF-α, and PPAR-γ and in the expression of the main human miRNAs between right and left CRC. A significant over-expression in the TGF-ß and TNF-α levels was observed in the serum from right-sided colon cancer patients. For the PPAR-γ, the patients with CRC located on the right-side showed lower levels than those detected in the serum from left-sided CRC subjects. Furthermore, significant differences also existed in the expression of specific circulating miRNAs between right- and left-sided CRC. In particular, the right upregulated miRNAs were all involved in the cell growth and proliferation related pathways. These findings confirm that the analysis of circulating levels of TGF-ß, TNF-α, and PPAR-γ, as well as the study of the specific miRNAs in the serum, are able to identify specific characteristics of CRC patients, useful for choosing a personalized treatment protocol.

Remnant cholesterol as a risk factor for cardiovascular, cancer or other causes mortality: A competing risks analysis.

BACKGROUND AND AIMS: Cardiovascular diseases (CVDis) are leading causes of morbidity and mortality. Even after the introduction of pharmacological therapy to lower Cholesterol, there is still a residual risk that may be ascribed to remnant cholesterol (RC). We aimed, by analyzing two prospective cohort studies, to estimate the effect of RC on risk and hazard of cardiovascular deaths (CVDs), while accounting for competing risks such as cancer (CDs) and other-causes deaths (OCDs). METHODS AND RESULTS: Cohorts were enrolled in 1992 and 2005. Personal data history was recorded. A fasting venous blood sample was obtained, and RC was calculated at baseline. Cause of Death was coded by using ICD-10th version. Follow-up ended on December 31, 2017. Flexible parametric competing-risks models were applied, with age at death as time-axis. In total, 5729 subjects were enrolled. There were 861 (15.1%) deaths: 234 CVDs (27.2%), 245 CDs (28.5%), 271 OCDs (31.5%) and 111 unknown causes of death (12.8%). RC exposure was a strong risk factor only for CVDs (Risk 2.54, 95% Confidence Interval 1.21; 5.34; Trend 1.26 (1.00; 1.58) for ≥1.29 mmol/L). CONCLUSIONS: RC is a strong independent risk factor for cardiovascular mortality. Competing risk analysis is demonstrably a useful tool to disentangle associations among different competing events with a common risk factor.

Irisin Serum Levels in Metabolic Syndrome Patients Treated with Three Different Diets: A Post-Hoc Analysis from a Randomized Controlled Clinical Trial.

BACKGROUND: Irisin, a hormone-like myokine, regulates energy homeostasis and mediates the benefits of physical activity on health. METHODS: To estimate the effect of different diets on irisin concentrations in subjects with the Metabolic Syndrome (MetS). METHODS: Subjects with MetS were derived from a population survey; 163 subjects were enrolled and randomized to a: Low Glycaemic Index (LGID), Mediterranean (MD) or Low Glycaemic Index Mediterranean (LGIMD) Diet, and the groups were compared, also with 80 controls without MetS. Sociodemographic, medical and nutritional data were collected and fasting blood samples drawn. Subjects underwent LUS and bioimpedentiometry. Generalized Estimating Equations were performed. RESULTS: At baseline, lower irisin concentrations were observed in MetS subjects. Mean irisin levels increased in all diet groups but only the LGID group reached statistical significance, as well as showing an interaction between LGID and time at the sixth month examination (4.57, 95% CI −1.27, 7.87). There was a positive effect of Vegetable Proteins (0.03, 95% CI −0.01,0.06) and Saturated Fatty Acids (0.04, 95% CI 0.01, 0.07) on irisin concentrations. In the LGIMD, a positive effect on Fat-Free Mass (0.38, 95% CI 0.19, 0.57) and a negative effect on the Body Mass Index (−0.75, 95% CI −1.30, −0.19) were observed. CONCLUSIONS: There seems to be a link between diet and muscle physiology. We showed that patients following a LGID had higher levels of irisin, a promising biomarker of muscle activity.

Energy system contribution in a maximal incremental test: correlations with pacing and overall performance in a 10-km running trial

This study aimed to verify the association between the contribution of energy systems during an incremental exercise test (IET), pacing, and performance during a 10-km running time trial. Thirteen male recreational runners completed an incremental exercise test on a treadmill to determine the respiratory compensation point (RCP), maximal oxygen uptake (V˙O2max), peak treadmill speed (PTS), and energy systems contribution; and a 10-km running time trial (T10-km) to determine endurance performance. The fractions of the aerobic (WAER) and glycolytic (WGLYCOL) contributions were calculated for each stage based on the oxygen uptake and the oxygen energy equivalents derived by blood lactate accumulation, respectively. Total metabolic demand (WTOTAL) was the sum of these two energy systems. Endurance performance during the T10-km was moderately correlated with RCP, V˙O2maxand PTS (P<@0.05), and moderate-to-highly correlated with WAER, WGLYCOL, and WTOTAL (P<0.05). In addition, WAER, WGLYCOL, and WTOTAL were also significantly correlated with running speed in the middle (P<0.01) and final (P<0.01) sections of the T10-km. These findings suggest that the assessment of energy contribution during IET is potentially useful as an alternative variable in the evaluation of endurance runners, especially because of its relationship with specific parts of a long-distance race.

Energy system contribution in a maximal incremental test: correlations with pacing and overall performance in a 10-km running trial.

This study aimed to verify the association between the contribution of energy systems during an incremental exercise test (IET), pacing, and performance during a 10-km running time trial. Thirteen male recreational runners completed an incremental exercise test on a treadmill to determine the respiratory compensation point (RCP), maximal oxygen uptake (V˙O2max), peak treadmill speed (PTS), and energy systems contribution; and a 10-km running time trial (T10-km) to determine endurance performance. The fractions of the aerobic (WAER) and glycolytic (WGLYCOL) contributions were calculated for each stage based on the oxygen uptake and the oxygen energy equivalents derived by blood lactate accumulation, respectively. Total metabolic demand (WTOTAL) was the sum of these two energy systems. Endurance performance during the T10-km was moderately correlated with RCP, V˙O2max and PTS (P<@0.05), and moderate-to-highly correlated with WAER, WGLYCOL, and WTOTAL (P<0.05). In addition, WAER, WGLYCOL, and WTOTAL were also significantly correlated with running speed in the middle (P<0.01) and final (P<0.01) sections of the T10-km. These findings suggest that the assessment of energy contribution during IET is potentially useful as an alternative variable in the evaluation of endurance runners, especially because of its relationship with specific parts of a long-distance race.

Functionalized mesoporous silica nanoparticles: a possible strategy to target cancer cells reducing peripheral nervous system uptake.

Mesoporous silica materials (MSM) have been proposed as promising tools for cell specific drug delivery or fluorescent cell tracking. In cancer therapy there is an urgent need to develop a cancer cell specific drug carrier able to limit the non-specific uptake of the drug by normal cells thereby reducing serious side effects. Chemotherapy induced peripheral neurotoxicity (CIPN) is one of the most clinically relevant side effects linked to the use of several antineoplastic drugs. In this study we showed that the uptake of MSM (synthesized using a PEG surfactant-based interfacial synthesis procedure), functionalised with folic acid (MSM-FOL) after 1, 6 and 24 hours is very limited in neuronal-like cellular systems such as differentiated SH-SY5Y human neuroblastoma cells and rat embryonic dorsal root ganglia sensory neurons. By contrast, the nanoparticles are highly internalized in A549 and IGROV-1 cancer cells. The 6 hour-treatment of A549 and IGROV-1 cells with nanoparticles loaded with the antineoplastic drug cisplatin (CP) induced significant cytotoxicity with respect to CP alone. These results were observed treating IGROV-1 cells with 25 and 50 µg/ml nanoparticles doses (corresponding respectively to CP 6.25 and 12.5 µM) and treating A549 with 50 µg/ml.Our results demonstrated a selective uptake of functionalized MSM suggesting them as promising tools for targeted antineoplastic therapy. Further studies will be necessary in order to confirm if this approach may be useful in reducing neurotocity of anticancer drugs.

Strength-training with whole-body vibration in long-distance runners: a randomized trial.

A parallel group randomized trial was designed to analyze the impact of 6 weeks of strength training programs performed with or without whole-body vibration on muscular and endurance performance parameters in long-distance runners. 22 endurance runners were allocated into strength with whole-body vibration (n=8), without (n=8), and control (n=6) groups. Before and after the experimental period the subjects performed the following tests: a) maximum dynamic strength test, b) maximal incremental treadmill test, and c) time to exhaustion at velocity corresponding to maximal oxygen uptake. The fractions of the aerobic and anaerobic contribution in time to exhaustion test were also calculated. Both strength trained groups showed a similar increase in maximum dynamic strength (~18%). The aerobic contribution was enhanced for strength training group without whole-body vibration (~25%) after experimental period. No statistical differences were observed in any other variable. These results suggest that 6 weeks of strength training performed with or without whole-body vibration improve similarly the maximum dynamic strength in long-distance runners. In addition, both training modes studied had no deleterious effects on the traditional parameters of endurance performance, traditional strength training program results in increased aerobic contribution during high-intensity aerobic exercise.

[Quality in dialysis]. / La qualità in dialisi.

BACKGROUND: Several clinical and laboratory dialysis parameters have been suggested by national and international guidelines. Our study aimed to evaluate a series of quality indicators in the dialytic treatment of a group of patients in our two dialytic centers. PATIENTS AND METHODS: In a population of 159 patients on renal replacement therapy (RDT) we performed a 1-yr prospective observational study, with common parameters to indicate cardiovascular pathologies (PAS, LVMI), calcium-phosphorous metabolism (Ca, PO 4 , Ca x PO 4 ), dialytic adequacy (Kt/V, URR%), nutritional status (nPCR, Alb, K), and anemia (hemoglobin (Hb)). For each parameter we evaluated the mean average with the standard deviation and the score percentages below and above the acceptable range (AR). RESULTS: The results demonstrated a substantial stability, with a gradual improvement, in dialytic adequacy, in anemic status and in PAS. The LVMI, calculated at the beginning and at the end of the period, did not demonstrate any significant changes. No significant changes were observed in the calcium-phosphorous metabolism parameters. Serum albumin and nPCR demonstrated the presence of malnutrition in 15-20% of patients. CONCLUSIONS: There was a more than adequate correlation between the target guidelines and that concerning the dialytic adequacy and the corrected anemic status. The improvement in parameters related to cardiovascular pathology, the risk of ectopic calcifications and malnutrition status, represented an achievable target.