The development of more sensitive diagnostic tools allowing an early-stageand highly efficient medical imaging of tumors remains a challenge. Magneticnanoparticles seem to be the contrast agents with ...the highest potential, if properlyconstructed. Therefore, in this study, hybrid magnetic nanoarchitectures weredeveloped using a new amphiphilic inulin-based graft copolymer （INU-LA-PEG-FA） as coating material for 10-nm spinel iron oxide （magnetite, Fe304）superparamagnetic nanoparticles （SPION）. Folic acid （FA） covalently linked tothe coating copolymer in order to be exposed onto the nanoparticle surface waschosen as the targeting agent because folate receptors are upregulated in manycancer types. Physicochemical characterization and in vitro biocompatibilitystudy was then performed on the prepared magnetic nanoparticles. The improvedtargeting and imaging properties of the prepared FA-SPIONs were furtherevaluated in nude mice using 7-Tesla magnetic resonance imaging （MRI）.FA-SPIONs exhibited the ability to act as efficient contrast agents in conventionalMRI, providing a potential nanoplatform not only for tumor diagnosis but alsofor cancer treatment, through the delivery of anticancer drug or locoregional magnetic hvverthermia.
Combination therapies of fluorouracil (FU) with irinotecan (CPT-11) and docetaxel plus cisplatin have been proven to be active in metastatic gastric cancer. In this paper, we present the results of a ...phase III trial in which these two combinations given sequentially were compared to mitomycin C (MMC) monochemotherapy in an adjuvant setting.
169 patients with radically resected gastric cancer were randomized to receive CPT-11 (180 mg/m2 day 1), leucovorin (100 mg/m2 days 1-2), FU (400-600 mg/m2 days 1-2, q 14; for four cycles; FOLFIRI regimen), followed by docetaxel (85 mg/m2 day 1), cisplatin (75 mg/m2 day 1, q 21; for three cycles; arm A), or MMC (8 mg/m2 days 1-2 as 2-hour infusion, q 42; for four cycles; arm B). All patients had histologically confirmed gastric carcinoma with nodal positivity or pT3/4. A total of 166 patients (85 in arm A and 81 in arm B) were treated. Adjuvant treatment was completed in 76% of the patients in arm A and in 70% of the patients in arm B. The main grade 3/4 side effects recorded were neutropenia in 35%, with only 1 febrile patient, and diarrhea in 11% in arm A, and thrombocytopenia in 10% and neutropenia in 7% in arm B. The FOLFIRI regimen and docetaxel/cisplatin given in sequence was well tolerated and feasible in adjuvant setting. This sequence treatment currently represents the experimental arm of an ongoing multicenter trial.
Multiple factors contribute to transplant-related complications after high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation, including conditioning regimens, number ...of infused stem cells and clinical characteristics of patient at transplant. We compared the transplant-related complications of 141 patients affected with hematological malignancies with those of 109 patients with solid tumors. The total number of peripheral blood stem cell transplantations performed was 339. High-dose chemotherapy mainly consisted of melphalan-, busulphan- or thiotepa-based regimens. Despite the equal number of infused CD34+ cells, patients with a hematological malignancy showed a slower absolute neutrophil count (days to neutrophils > 0.5 x 10(9)/L, 10.6 +/- 3.6 for hematological malignancies versus 9.1 +/- 1.2 for solid tumors, P < 0.0001) and platelet recovery (days to platelets > 20 x 10(9)/L, 16.4 +/- 9.8 for hematological malignancies versus 12.3 +/- 4.1 for solid tumors, P < 0.0001) than patients with a solid tumor. A significantly higher requirement of red blood cell (3.3 +/- 4.1 versus 2.0 +/- 1.9, P < 0.0029) and platelet units (7.5 +/- 10.4 versus 4.2 +/- 3.4, P < 0.0001) was observed for hematological malignancies than for solid tumors. Five graft failures were documented exclusively in patients with a hematological malignancy. Moreover, such patients displayed a longer duration of mucositis (P < 0.0028) and hospital stay (P < 0.0001), but no difference was observed in terms of febrile episodes. Transplant-related mortality was similar between the two groups. In conclusion, patients with a hematological malignancy overall have more complications than those with a solid tumor.
Hematological and extra-hematological toxicity of mitoxantrone-containing regimens with autologous stem cell rescue was evaluated in 32 metastatic breast cancer patients. The schedule was the final ...part of two high-dose chemotherapy programs, including an induction phase with three courses of conventional chemotherapy with epirubicin (120 mg/m2) and cyclophosphamide (600 mg/m2) plus three courses of docetaxel (100 mg/m2) and a first high-dose chemotherapy consisting of cyclophosphamide (6000 mg/m2), thiotepa (500 mg/m2) and carboplatin (800 mg/m2) or melphalan (160 mg/m2) plus thiotepa (600 mg/m2). The final second autograft phase included mitoxantrone (60 mg/m2) associated with melphalan (160 mg/m2) and autologous stem cell rescue infusion. The median duration of severe neutropenia and thrombocytopenia was 9 (range, 7-13) and 11.5 (range, 9-29) days. The median number of units of erythrocytes and platelets transfused was 1 (0-11) and 4 (1-9), respectively. Fever for a median of 2 (0-8) days developed in 71.8% of the patients. Mucositis was observed in 81.2% (WHO grade 3-4 in 25%). No acute or late cardiac toxicity was observed. One patient died because of a transplant-unrelated cause. The response according to the program phase showed an increased rate of complete response, from 12.5% at the end of conventional chemotherapy to 21.9% after the first high-dose chemotherapy course, to increase to 43.9% after the treatment with mitoxantrone-melphalan. We conclude that a conditioning regimen with high dose mitoxantrone-melphalan fits well within the high-dose chemotherapy program.
Cereals and legumes are key components of a healthy and balanced diet. Accordingly, many national nutritional guidelines emphasize their health promoting properties by placing them at the base of ...nutritional food pyramids. This concept is further validated by the observed correlation between a lower risk and occurrence of chronic diseases and the adherence to dietary patterns, like the Mediterranean diet, in which cereal grains, legumes and derived products represent a staple food. In the search for a dietary approach to control/prevent chronic degenerative diseases, protein derived bioactive peptides may represent one such source of health-enhancing components. These peptides may already be present in foods as natural components or may derive from hydrolysis by chemical or enzymatic treatments (digestion, hydrolysis or fermentation). Many reports are present in the literature regarding the bioactivity of peptides in vitro and a wide range of activities has been described, including antimicrobial properties, blood pressure-lowering (ACE inhibitory) effects, cholesterol-lowering ability, antithrombotic and antioxidant activities, enhancement of mineral absorption/bioavailability, cyto- or immunomodulatory effects, and opioid-like activities. However it is difficult to translate these observed effects to human. In fact, the active peptide may be degraded during digestion, or may not be absorbed or reach the target tissues at a concentration necessary to exert its function. This review will focus on bioactive peptides identified in cereals and legumes, from an agronomical and biochemical point of view, including considerations about requirements for the design of appropriate clinical trials necessary for the assessment of their nutraceutical effect in vivo.
COVID-19 is characterized by severe acute lung injury, which is associated with neutrophil infiltration and the release of neutrophil extracellular traps (NETs). COVID-19 treatment options are ...scarce. Previous work has shown an increase in NETs release in the lung and plasma of COVID-19 patients suggesting that drugs that prevent NETs formation or release could be potential therapeutic approaches for COVID-19 treatment.
Here, we report the efficacy of NET-degrading DNase I treatment in a murine model of COVID-19. SARS-CoV-2-infected K18-hACE2 mice were performed for clinical sickness scores and lung pathology. Moreover, the levels of NETs were assessed and lung injuries were by histopathology and TUNEL assay. Finally, the injury in the heart and kidney was assessed by histopathology and biochemical-specific markers.
DNase I decreased detectable levels of NETs, improved clinical disease, and reduced lung, heart, and kidney injuries in SARS-CoV-2-infected K18-hACE2 mice. Furthermore, our findings indicate a potentially deleterious role for NETs lung tissue in vivo and lung epithelial (A549) cells in vitro, which might explain part of the pathophysiology of severe COVID-19. This deleterious effect was diminished by the treatment with DNase I.
Together, our results support the role of NETs in COVID-19 immunopathology and highlight NETs disruption pharmacological approaches as a potential strategy to ameliorate COVID-19 clinical outcomes.
Purpose
The potential mechanisms of endocrine therapy for thrombosis remain currently unclear, and more studies are warranted for further investigation and elucidation. However, high plasma ...concentration of lipoprotein(a) (Lp(a)) is a recognized prothrombotic factor. The aim of our study was to systematically evaluate the effect of different anti-oestrogen therapy on plasma Lp(a) level in postmenopausal women.
Methods
A systematic literature search was conducted in multiple electronic databases to identify the randomized, double-blind, placebo-controlled clinical studies on this topic. Effect size for changes in Lp(a) was expressed as mean difference (MD) and 95% confidence intervals (CI).
Results
Data were pooled from 10 clinical trials comprising 24 treatment arms, which included 2049 women (1128 women in the active-treated arms and 921 women in the control arms). Meta-analysis of data suggested that anti-oestrogen therapy in women significantly reduced Lp(a) MD = −5.92% (95%CI: −9.05%,−2.8%).
Conclusions
This observation is of both clinical and pathophysiological relevance, also in view that the identification of molecular determinants and cellular pathways implicated in Lp(a) synthesis and metabolism is still of concern as a critical issue in lipidology and CV prevention.
Fish waste utilization to obtain protein hydrolysates has been demonstrated to be a useful strategy to face both environmental and economic impacts while obtaining high-value products with remarkable ...biological and nutritional properties. In the present study, protein hydrolysates obtained from anchovy
(APH) by-products were assessed for their potential biological activities in both in vitro and in vivo models. The treatment with APH exerted a significant protection against LPS-induced inflammation in RAW 264.7 cells, decreasing the protein expression of pro-inflammatory mediators (i.e., COX-2) and inhibiting the nuclear translocation of NF-κB through IκB-α. Moreover, APH modulated the expression of iNOS, MnSOD and HO-1, thus decreasing the severity of oxidative stress. The supplementation of APH in the diet of ApoE knockout mice down-regulated the proinflammatory cytokines (i.e.,
, IL-1α, IL-1β, IL-6) in both aorta and heart tissues, and modulated the expression of oxidative stress-related genes (Cu/ZnSod, MnSod, Cat, Gpx and Ho), indicating that APH can exert a beneficial role, having anti-inflammatory and antioxidant activities. The nutritional properties of APH, together with their biological activities herein reported, highlight the possibility of obtaining bioactive molecules from fish waste and encourage their use as potential nutraceuticals in food and pharmaceutical industries in the next future.
Cocoa has a rich history in human use. Skin is prone to the development of several diseases, and the mechanisms in the pathogenesis of aged skin are still poorly understood. However, a growing body ...of evidence from clinical and bench research has begun to provide scientific validation for the use of cocoa-derived phytochemicals as an effective approach for skin protection. Although the specific molecular and cellular mechanisms of the beneficial actions of cocoa phytochemicals remain to be elucidated, this review will provide an overview of the current literature emphasizing potential cytoprotective pathways modulated by cocoa and its polyphenolic components. Moreover, we will summarize in vivo studies showing that bioactive compounds of cocoa may have a positive impact on skin health.
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