Association between Resistin Levels and All-Cause and Cardiovascular Mortality: A New Study and a Systematic Review and Meta-Analysis.

CONTEXT: Studies concerning the association between circulating resistin and mortality risk have reported, so far, conflicting results. OBJECTIVE: To investigate the association between resistin and both all-cause and cardiovascular (CV) mortality risk by 1) analyzing data from the Gargano Heart Study (GHS) prospective design (n=359 patients; 81 and 58 all-cause and CV deaths, respectively); 2) performing meta-analyses of all published studies addressing the above mentioned associations. DATA SOURCE AND STUDY SELECTION: MEDLINE and Web of Science search of studies reporting hazard ratios (HR) of circulating resistin for all-cause or CV mortality. DATA EXTRACTION: Performed independently by two investigators, using a standardized data extraction sheet. DATA SYNTHESIS: In GHS, adjusted HRs per one standard deviation (SD) increment in resistin concentration were 1.28 (95% CI: 1.07-1.54) and 1.32 (95% CI: 1.06-1.64) for all-cause and CV mortality, respectively. The meta-analyses included 7 studies (n=4016; 961 events) for all-cause mortality and 6 studies (n=4,187: 412 events) for CV mortality. Pooled HRs per one SD increment in resistin levels were 1.21 (95% CI: 1.03-1.42, Q-test p for heterogeneity<0.001) and 1.05 (95% CI: 1.01-1.10, Q-test p for heterogeneity=0.199) for all-cause and CV mortality, respectively. At meta-regression analyses, study mean age explained 9.9% of all-cause mortality studies heterogeneity. After adjusting for age, HR for all-cause mortality was 1.24 (95% CI: 1.06-1.45). CONCLUSIONS: Our results provide evidence for an association between circulating resistin and mortality risk among high-risk patients as are those with diabetes and coronary artery disease

Long-Term Effect of Physical Exercise on the Risk for Hospitalization and Death in Dialysis Patients. A Post-Trial Long-Term Observational Study

Background and objectives In the EXerCise Introduction to Enhance Performance in Dialysis (EXCITE) trial, a simple, personalized 6-month walking exercise program at home during the day off of dialysis improved the functional status and the risk for hospitalization in patients with kidney failure. In this post-trial observational study, we tested whether the same intervention was associated with a lower long-term risk of death or hospitalization (combined end point) during a follow-up extended up to 36 months. Design, setting, participants, &amp; measurements In total, 227 patients (exercise, n5104; control, n5123) completed the 6-month trial and entered the post-trial observational study. Data were analyzed by unadjusted and adjusted Cox regression analyses and Bayesian analysis. Results In the long-term observation (up to 36 months), 134 events were recorded (eight deaths not preceded by hospitalization and 126 hospitalizations, which were followed by death in 38 cases). The long-term risk for hospitalization or death was 29% lower (hazard ratio, 0.71; 95% confidence interval, 0.50 to 1.00), and in an analysis stratified by adherence to the walking exercise program during the 6-month trial, the subgroup with high adherence (.60% of prescribed sessions) had a 45% lower risk as compared with the control group (hazard ratio, 0.55; 95% confidence interval, 0.35 to 0.87). A Bayesian analysis showed that the posterior probability of a hazard ratio of 0.71 (95% confidence interval, 0.50 to 1.00) for the risk of the composite outcome observed in the post-trial observational study was 93% under the conservative prior and 97% under the optimistic prior. Sensitivity analyses restricted to the risk of hospitalization only or censoring patients at the time of transplantation fully confirmed these findings. Conclusions A simple, personalized, home-based, low-intensity exercise program was associated with a lower risk of hospitalization

FISH testing of HER2 IHC 1+ early breast cancer with unfavorable prognostic factors

FISH testing of HER2 IHC 1+ early breast cancer with unfavorable prognostic factors Background HER2-positive tumors are associated with a poor prognosis and a shortened disease-free and overall survival as well as with other unfavorable prognostic tumor characteristics (high histological grade, high proliferative index, negative or low estrogen receptor expression, etc.). HER2-positive tumors are also responsive to treatment with trastuzumab in reducing the risk of recurrence and improving survival. The aim of this study is to assess the incidence of HER2 gene amplification in selected tumors with adverse prognostic features which scored 1+ by immunohistochemistry (IHC). Methods 75 women with infiltrating ductal carcinoma (IDC) and infiltrating lobular carcinoma (ILC) scoring 1+ by IHC were included. Forty-eight invasive breast carcinoma samples were selected according to unfavorable prognostic tumor characteristics and tested by FISH. HER2 amplification was evaluated using Vysis HER2/Cep17 probe (Path Vysion HER2 DNA Probe Kit®, Abbott Molecular, IL); ratio–based amplification was considered present when the HER2/Cep17 ratio was 2 or more and copy number-based amplification was considered present when the mean HER2 copy number was more than 6, in agreement with the ASCO/CAP/SIAPEC guidelines. Results In 2013, 331 patients with invasive breast tumors were tested by IHC; 75 cases (23%) were scored 1+ of which 62 cases (19%) of IDC and 13 cases (4%) of ILC. Forty-eight invasive breast carcinoma samples (64%) were selected according to one or more unfavorable prognostic tumor characteristics; 22 out of 48 tumors (46%) showed high histological grade (G3); 27 cases (56%) had high proliferative index (Ki-67≥30%); 32 tumor samples (67%) were node-positive; and 29 cases (60%) showed vascular invasion. FISH was performed on 31 of the 1+ patients with adverse tumor characteristics and 7 IDC out of 48 (14.6%) showed HER2 amplification. Conclusions Our preliminary retrospective data suggest that 7 patients out of 48 (14.6%) scoring 1+ by IHC show HER2 amplification, in agreement with the most recently published literature data. In order to not deny the benefit deriving from trastuzumab administration, in breast cancer patients showing IHC 1+, it is advisable to test HER2 gene amplification by FISH. Bibliografia Goldhirsch A, Gelber RD, Piccart-Gebhart MJ, de Azambuja E, Procter M, Suter TM, Jackisch C, Cameron D, Weber HA, Heinzmann D, Dal Lago L, McFadden E, Dowsett M, Untch M, Gianni L, Bell R, Köhne CH, Vindevoghel A, Andersson M, Brunt AM, Otero-Reyes D, Song S, Smith I, Leyland-Jones B, Baselga J; Herceptin Adjuvant (HERA) Trial Study Team. 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial. Lancet. 2013 Sep 21;382(9897):1021-8. Iorfida M, Dellapasqua S, Bagnardi V, Cardillo A, Rotmensz N, Mastropasqua MG, Bottiglieri L, Goldhirsch A, Viale G, Colleoni M. HER2-negative (1+) breast cancer with unfavorable prognostic features: to FISH or not to FISH? Ann Oncol. 2012 May;23(5):1371-2. Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005 Oct 20;353(16):1673-84

Phytochemical and biological characterization of dry outer scales extract from Tropea red onion (Allium cepa L. var. Tropea)–A promising inhibitor of pancreatic lipase

Background: Allium cepa L. var. Tropea is typically cultivated in Calabria (Italy) and it is certified as “Cipolla Rossa di Tropea Calabria-PGI” (Tropea red onion). The use of clinically available anti-obesity drugs such as Orlistat is being gradually dismissed due to their side-effects and this has encouraged the search for alternative inhibitors of intestinal lipases such as phytochemicals showing less side-effects. In this study we aimed to evaluate for the first time the anti-obesity potential of the hydroalcoholic extract from the dry outer scales of Tropea red onion by the assesment of its capacity to inhibit pancreatic lipase. Its possible mechanism of action was also studied with planar lipid membranes (PLMs) surrogate of intestinal membranes. Methods: Specialized metabolites in the extract were determined by GC–MS, HPLC-DAD, HPLC-UV-DAD and HPLC-HRMS analyses. Inhibition of pancreatic lipase was studied in vitro against crude lipase Type II from porcine pancreas. PLMs used in the electrophysiology measurements were made up of DOPS:DOPE:POPC. Results: The extract contained quercetin-4′-O-glucoside, quercetin and quercetin-3,4′-O-diglucoside as the most abundant phenolics. Among apolar constituents, γ-sitosterol, linoleic and stearic acids were dominant. The lipase inhibitory effect of the extract had an IC50 value equal to 0.77±0.03 mg/mL (positive control, IC50 = 0.018 mg/mL). The electrophysiological study demonstrated that the extract is able to incorporate into PLMs and to form transient channel-like events Conclusions: Taken altogether, the results allow us to suggest that the hydroalcoholic extract from the dry outer scales of Tropea red onion could prevent lipid ester hydrolysis and it has a protective effect against phospholipase as found for interfacially active compounds

Olive tree in circular economy as a source of secondary metabolites active for human and animal health beyond oxidative stress and inflammation

none10noExtra-virgin olive oil (EVOO) contains many bioactive compounds with multiple biological activities that make it one of the most important functional foods. Both the constituents of the lipid fraction and that of the unsaponifiable fraction show a clear action in reducing oxidative stress by acting on various body components, at concentrations established by the European Food Safety Authority’s claims. In addition to the main product obtained by the mechanical pressing of the fruit, i.e., the EVOO, the residual by-products of the process also contain significant amounts of antioxidant molecules, thus potentially making the Olea europea L. an excellent example of the circular economy. In fact, the olive mill wastewaters, the leaves, the pomace, and the pits discharged from the EVOO production process are partially recycled in the nutraceutical and cosmeceutical fields also because of their antioxidant effect. This work presents an overview of the biological activities of these by-products, as shown by in vitro and in vivo assays, and also from clinical trials, as well as their main formulations currently available on the market.openMallamaci R.; Budriesi R.; Clodoveo M.L.; Biotti G.; Micucci M.; Ragusa A.; Curci F.; Muraglia M.; Corbo F.; Franchini C.Mallamaci, R.; Budriesi, R.; Clodoveo, M. L.; Biotti, G.; Micucci, M.; Ragusa, A.; Curci, F.; Muraglia, M.; Corbo, F.; Franchini, C

CaCO3 as an environmentally friendly renewable material for drug delivery systems: Uptake of HSA-CaCO3 nanocrystals conjugates in cancer cell lines

Chemical and biochemical functionalization of nanoparticles (NPs) can lead to an active cellular uptake enhancing their efficacy thanks to the targeted localization in tumors. In the present study calcium carbonate nano-crystals (CCNs), stabilized by an alcohol dehydration method, were successfully modified by grafting human serum albumin (HSA) on the surface to obtain a pure protein corona. Two types of CCNs were used: naked CaCO3 and the (3-aminopropyl)triethoxysilane (APTES) modified CaCO3-NH2. The HSA conjugation with naked CCN and amino-functionalized CCN (CCN-NH2) was established through the investigation of modification in size, zeta potential, and morphology by Transmission Electron Microscopy (TEM). The amount of HSA coating on the CCNs surface was assessed by spectrophotometry. Thermogravimetric analysis (TGA) and Differential scanning calorimetry (DSC) confirmed the grafting of APTES to the surface and successive adsorption of HSA. Furthermore, to evaluate the effect of protein complexation of CCNs on cellular behavior, bioavailability, and biological responses, three human model cancer cell lines, breast cancer (MCF7), cervical cancer (HeLa), and colon carcinoma (Caco-2) were selected to characterize the internalization kinetics, localization, and bio-interaction of the protein-enclosed CCNs. To monitor internalization of the various conjugates, chemical modification with fluorescein-isothiocyanate (FITC) was performed, and their stability over time was measured. Confocal microscopy was used to probe the uptake and confirm localization in the perinuclear region of the cancer cells. Flow cytometry assays confirmed that the bio-functionalization influence cellular uptake and the CCNs behavior depends on both cell line and surface features

Plasma cytokines, glomerular filtration rate and adipose tissue cytokines gene expression in chronic kidney disease (CKD) patients

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Coexistence of an imbalance of cytokines, chemokines and growth factors serum levels and symptoms of fatigue and pain in long-term breast cancer survivors.

Background: Fatigue, pain and depression are common problems among long-term cancer survivors (BCS) which in some patients may persist for many years after healing and the completion of treatment. Several studies have reported that increased serum levels of chemokines and growth factors are particularly significantly correlated with the coexistence of these disorders in cancer survivors. The aim of this study was to assess whether the altered imbalance of pro-inflammatory cytokines, growth factors and chemokine serum levels are associated to presence of fatigue and pain in long-term breast cancer survivors . Methods: Ninety-three BCS were enrolled in this study and blood samples taken from each. Serum levels of 25 analytes including cytokines, growth factors and chemokines were tested by enzyme immunoassay using the flexible Bio-Plex System. Participants also completed a questionnaire measuring demographic, clinical and behavioral variables. Results: Non-parametric discriminant analysis showed that fatigued BCS had significantly higher serum levels of FGF and lower IL-4 and IL-8 compared to the non-fatigued group, while BCS with pain had an increase in eotaxin serum levels and lower IL-4 and Il-7 compared to the group without pain. Univariate analysis showed a statistically significant difference in both mental and physical qol, with levels lower in the subgroup who presented pain than in those without: p = 0.0003 and p < 0.0001 respectively. A lower value of Rantes (p = 0.0131) in breast cancer survivors with pain compared to the group without pain, and a higher median value of TNF-α (p = 0.054) in the pain group than in those without pain was observed. The level of depression was higher than the score of 50 on the Zung scale in fatigued survivors compared to non-fatigued survivors (p = 0.0006). Conclusions: Our results suggest that an altered balance of chemokines, cytokines and growth factors serum levels may be associated to presence of symptoms such as fatigue and pain in breast cancer survivors at an average of 5 years after diagnosis