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1.
Glioblastoma and Internal Carotid Artery Calcium Score: A Possible Novel Prognostic Partnership?
Pasqualetti, F, Gabelloni, M, Faggioni, L, Aquaro, GD, De Vietro, F, Mendola, V, Spina, N, Frey, J, Montemurro, N, Cantarella, M, et al
Journal of clinical medicine. 2024;(5)
Abstract
Purpose: Clinical evidence suggests an association between comorbidities and outcome in patients with glioblastoma (GBM). We hypothesised that the internal carotid artery (ICA) calcium score could represent a promising prognostic biomarker in a competing risk analysis in patients diagnosed with GBM. Methods: We validated the use of the ICA calcium score as a surrogate marker of the coronary calcium score in 32 patients with lung cancer. Subsequently, we assessed the impact of the ICA calcium score on overall survival in GBM patients treated with radio-chemotherapy. Results: We analysed 50 GBM patients. At the univariate analysis, methyl-guanine-methyltransferase gene (MGMT) promoter methylation (p = 0.048), gross total tumour resection (p = 0.017), and calcium score (p = 0.011) were significant prognostic predictors in patients with GBM. These three variables also maintained statistical significance in the multivariate analysis. Conclusions: the ICA calcium score could be a promising prognostic biomarker in GBM patients.
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Enhanced molecular release from elderly bone samples using collagenase I: insights into fatty acid metabolism alterations.
Malvandi, AM, Halilaj, E, Faraldi, M, Mangiavini, L, Cristoni, S, Leoni, V, Lombardi, G
Journal of translational medicine. 2024;(1):143
Abstract
BACKGROUND Bone is a metabolically active tissue containing different cell types acting as endocrine targets and effectors. Further, bone is a dynamic depot for calcium, phosphorous and other essential minerals. The tissue matrix is subjected to a constant turnover in response to mechanical/endocrine stimuli. Bone turnover demands high energy levels, making fatty acids a crucial source for the bone cells. However, the current understanding of bone cell metabolism is poor. This is partly due to bone matrix complexity and difficulty in small molecules extraction from bone samples. This study aimed to evaluate the effect of metabolite sequestering from a protein-dominated matrix to increase the quality and amount of metabolomics data in discovering small molecule patterns in pathological conditions. METHODS Human bone samples were collected from 65 to 85 years old (the elderly age span) patients who underwent hip replacement surgery. Separated cortical and trabecular bone powders were treated with decalcifying, enzymatic (collagenase I and proteinase K) and solvent-based metabolite extraction protocols. The extracted mixtures were analyzed with the high-resolution mass spectrometry (HRMS). Data analysis was performed with XCMS and MetaboAnalystR packages. RESULTS Fast enzymatic treatment of bone samples before solvent addition led to a significantly higher yield of metabolite extraction. Collagenase I and proteinase K rapid digestion showed more effectiveness in cortical and trabecular bone samples, with a significantly higher rate (2.2 folds) for collagenase I. Further analysis showed significant enrichment in pathways like de novo fatty acid biosynthesis, glycosphingolipid metabolism and fatty acid oxidation-peroxisome. CONCLUSION This work presents a novel approach for bone sample preparation for HRMS metabolomics. The disruption of bone matrix conformation at the molecular level helps the molecular release into the extracting solvent and, therefore, can lead to higher quality results and trustable biomarker discovery. Our results showed β-oxidation alteration in the aged bone sample. Future work covering more patients is worthy to identify the effective therapeutics to achieve healthy aging.
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Low circulating levels of miR-17 and miR-126-3p are associated with increased mortality risk in geriatric hospitalized patients affected by cardiovascular multimorbidity.
Marchegiani, F, Recchioni, R, Di Rosa, M, Piacenza, F, Marcheselli, F, Bonfigli, AR, Galeazzi, R, Matacchione, G, Cardelli, M, Procopio, AD, et al
GeroScience. 2024;(2):2531-2544
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Abstract
MultiMorbidity (MM), defined as the co-occurrence of two or more chronic conditions, is associated with poorer health outcomes, such as recurrent hospital readmission and mortality. As a group of conditions, cardiovascular disease (CVD) exemplifies several challenges of MM, and the identification of prognostic minimally invasive biomarkers to stratify mortality risk in patients affected by cardiovascular MM is a huge challenge. Circulating miRNAs associated to inflammaging and endothelial dysfunction, such as miR-17, miR-21-5p, and miR-126-3p, are expected to have prognostic relevance. We analyzed a composite profile of circulating biomarkers, including miR-17, miR-21-5p, and miR-126-3p, and routine laboratory biomarkers in a sample of 246 hospitalized geriatric patients selected for cardiovascular MM from the Report-AGE INRCA database and BioGER INRCA biobank, to evaluate the association with all-cause mortality during 31 days and 12 and 24 months follow-up. Circulating levels of miR-17, miR-126-3p, and some blood parameters, including neutrophil to lymphocyte ratio (NLR) and eGFR, were significantly associated with mortality in these patients. Overall, our results suggest that in a cohort of geriatric hospitalized patients affected by cardiovascular MM, lower circulating miR-17 and miR-126-3p levels could contribute to identify patients at higher risk of short- and medium-term mortality.
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Update on vitamin D role in severe infections and sepsis.
Cutuli, SL, Ferrando, ES, Cammarota, F, Franchini, E, Caroli, A, Lombardi, G, Tanzarella, ES, Grieco, DL, Antonelli, M, De Pascale, G
Journal of anesthesia, analgesia and critical care. 2024;(1):4
Abstract
Severe infections frequently require admission to the intensive care unit and cause life-threatening complications in critically ill patients. In this setting, severe infections are acknowledged as prerequisites for the development of sepsis, whose pathophysiology implies a dysregulated host response to pathogens, leading to disability and mortality worldwide.Vitamin D is a secosteroid hormone that plays a pivotal role to maintain immune system homeostasis, which is of paramount importance to resolve infection and modulate the burden of sepsis. Specifically, vitamin D deficiency has been widely reported in critically ill patients and represents a risk factor for the development of severe infections, sepsis and worse clinical outcomes. Several studies have demonstrated the feasibility, safety and effectiveness of vitamin D supplementation strategies to improve vitamin D body content, but conflictual results support its benefit in general populations of critically ill patients. In contrast, small randomised clinical trials reported that vitamin D supplementation may improve host-defence to pathogen invasion via the production of cathelicidin and specific cytokines. Nonetheless, no large scale investigations have been designed to specifically assess the impact of vitamin D supplementation on the outcome of critically ill septic patients admitted to the intensive care unit.
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Effects of AIDiet intervention to improve diet quality, immuno-metabolic health in normal and overweight PCOS girls: a pilot study.
Mizgier, M, Więckowska, B, Formanowicz, D, Lombardi, G, Brożek, A, Nowicki, M, Durkalec-Michalski, K, Kędzia, W, Jarząbek-Bielecka, G
Scientific reports. 2024;(1):3525
Abstract
This study was conducted in two groups of girls with PCOS (polycystic ovary syndrome) categorized as slim (group N) and overweight-to-obese (group Ov/Ob). The study's primary outcome was to assess the impact of a 12-week anti-inflammatory diet (AIDiet) intervention, without energy deficit, on daily diet quality improvement, evaluated according to the KIDMED index. The secondary outcome was improving inflammatory, redox, hormonal, and metabolic statuses. In the study, which was completed by 13 girls from the Ov/Ob group and 19 girls from the N group, a significant improvement in the mean KIDMED score was obtained. Moreover, the intervention significantly improves concentration of total antioxidant capacity (TAC), fasting insulin, and the homeostatic model assessment for insulin resistance (HOMA-IR) index, in the Ov/Ob group, while both groups experienced a reduction in the concentration of interleukin (IL)-1 and IL-6, tumour necrosis factor (TNF-α), and androstenedione. The AIDiet intervention effectively improved the quality of the subjects' diets, which was associated with the improvement of hormonal and immuno-metabolic markers. However, these changes in normal-weight patients were observed regardless of body weight reduction. ClinicalTrials.gov Identifier NCT04738409.
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Present and Future of Immunotherapy in Patients With Glioblastoma: Limitations and Opportunities.
Maccari, M, Baek, C, Caccese, M, Mandruzzato, S, Fiorentino, A, Internò, V, Bosio, A, Cerretti, G, Padovan, M, Idbaih, A, et al
The oncologist. 2024;(4):289-302
Abstract
Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor. Standard therapies, including surgical resection, chemoradiation, and tumor treating fields, have not resulted in major improvements in the survival outcomes of patients with GBM. The lack of effective strategies has led to an increasing interest in immunotherapic approaches, considering the success in other solid tumors. However, GBM is a highly immunosuppressive tumor, as documented by the presence of several mechanisms of immune escape, which may represent a reason why immunotherapy clinical trials failed in this kind of tumor. In this review, we examine the current landscape of immunotherapy strategies in GBM, focusing on the challenge of immunoresistance and potential mechanisms to overcome it. We discussed completed and ongoing clinical trials involving immune checkpoint inhibitors, oncolytic viruses, vaccines, and CAR T-cell therapies, to provide insights into the efficacy and outcomes of different immunotherapeutic interventions. We also explore the impact of radiotherapy on the immune system within the GBM microenvironment highlighting the complex interactions between radiation treatment and the immune response.
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Downhill running increases markers of muscle damage and impairs the maximal voluntary force production as well as the late phase of the rate of voluntary force development.
Coratella, G, Varesco, G, Rozand, V, Cuinet, B, Sansoni, V, Lombardi, G, Vernillo, G, Mourot, L
European journal of applied physiology. 2024
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Abstract
PURPOSE To examined the time-course of the early and late phase of the rate of voluntary force development (RVFD) and muscle damage markers after downhill running. METHODS Ten recreational runners performed a 30-min downhill run at 10 km h-1 and -20% (-11.3°) on a motorized treadmill. At baseline and each day up to 4 days RVFD, knee extensors maximum voluntary isometric force (MVIC), serum creatine kinase (CK) concentration, quadriceps swelling, and soreness were assessed. The early (0-50 ms) and late (100-200 ms) phase of the RVFD, as well as the force developed at 50 and 200 ms, were also determined. RESULTS MVIC showed moderate decrements (p < 0.05) and recovered after 4 days (p > 0.05). Force at 50 ms and the early phase were not impaired (p > 0.05). Conversely, force at 200 ms and the late phase showed moderate decrements (p < 0.05) and recovered after 3 and 4 days, respectively (p > 0.05). CK concentration, quadriceps swelling, and soreness increased (p < 0.05) were overall fully resolved after 4 days (p > 0.05). CONCLUSION Downhill running affected the knee extensors RVFD late but not early phase. The RVFD late phase may be used as an additional marker of muscle damage in trail running.
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Metabolism of vitamin D is not affected by sport activity.
Książek, A, Zagrodna, A, Lombardi, G, Słowińska-Lisowska, M
Clinica chimica acta; international journal of clinical chemistry. 2023;:117507
Abstract
BACKGROUND Higher levels of physical activity are related to higher 25-(OH)D levels. Total 25-(OH)D (25-(OH)DT) are routinely used in clinical practice to assess vitamin D, however novel biomarkers are currently being investigated as free 25-(OH)D (25-(OH)DF) or vitamin D metabolite ratios (VMRs). The primary aim of our study was to assess 25-(OH)DF, vitamin D metabolites and VMRs in inactive men and athletes. A secondary aim was to check whether regular physical activity influence on vitamin D metabolome. A tertiary aim was to determine the relationship between 25-(OH)DT, 25-(OH)DF, vitamin D binding protein (VDBP), vitamin D metabolites and VMRs in this cohort. METHODS A total of 69 participants (27 inactive men, 18 indoor and 24 outdoor athletes) participated in the study. Vitamin D metabolites (25-(OH)DT, 24,25-(OH)2D3, 3-epi-25-(OH)D3, and 1,25-(OH)2D) were assessed using LC-MS/MS. The 25-(OH)DF concentration was calculated based on serum albumin and VDBP levels. RESULTS There were no differences in vitamin D metabolites and VMRs between inactive men and between the two groups of athletes. We showed a strong relationship between 25-(OH)DT, 25-(OH)DF and 24,25-(OH)D3, 3-epi-25(OH)D3, 24,25-(OH)2D3:25-(OH)D3 VMR in each group. Analysis showed that 25-(OH)DT, 25-(OH)DF inversely associated with 25-(OH)D3:24,25-(OH)2D3, 25-(OH)D3:3-epi-25-(OH)D3, 1,25-(OH)2D:24,25-(OH)2D3 ratios in inactive men and athletes (indoor and outdoor). CONCLUSIONS On the basis of our results, we concluded that regular long-term physical activity has no effect on the concentration of vitamin D metabolites at rest. Furthermore, free vitamin D does not correlate more strongly with vitamin D metabolites and VMRs compared to total.
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Effects of running a marathon on sclerostin and parathyroid hormone concentration in males aged over 50.
Zagrodna, A, Książek, A, Słowińska-Lisowska, M, Chmura, J, Ponikowski, P, Lombardi, G
Journal of sports sciences. 2023;(8):796-802
Abstract
The aim of our study was to verify whether running a marathon (32nd Wroclaw Marathon) was associated with changes in sclerostin and intact PTH (iPTH) concentration in middle-aged males. We enrolled 33 males who completed the marathon race. Blood samples were taken 60 minutes before (V1), immediately after (V2), and 7 days after the run (V3). The mean serum sclerostin concentration was 42.4 ± 10.8 pmol/L at V1, increased to 62.9 ± 12.6 pmol/L at V2 (t= -11.206; p < 0.001) and returned to baseline in V3 (t = 8.344; p < 0.001, V3 vs. V2). A similar trend was recorded for iPTH (t= -7.440; p < 0.001, for V2 vs. V1; t = 6.229; p < 0.001, for V3 vs. V2), at V3, iPTH levels remained significantly higher than V1 (t= -2.759; p = 0.010). The results of our study suggest that, in middle-aged males, running a marathon affects skeletal metabolism by activating two counteracting mechanisms, although temporarily overlapping: first, by a sudden inhibition of bone formation, through induction sclerostin expression and, secondly, by a long-lasting induction of PTH, which also guarantees the maintenance of adequate circulating levels of calcium. The net effect would be the maintenance of adequately high levels of circulating calcium to be used for neuromuscular activity and muscle contraction.
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Seasonal changes in free 25-(OH)D and vitamin D metabolite ratios and their relationship with psychophysical stress markers in male professional football players.
Książek, A, Zagrodna, A, Lombardi, G, Słowińska-Lisowska, M
Frontiers in physiology. 2023;:1258678
Abstract
Introduction: Novel markers of vitamin D status are currently being investigated, including free 25-(OH)D (25-(OH)DF) and the vitamin D metabolite ratio (24,25-(OH)2D3:25-(OH)D3; VMR). The VMR may provide additional functional information on vitamin D metabolism in athletes. Therefore, the main objective of the current study was to evaluate 25-(OH)DF, bioavailable 25-(OH)D (25-(OH)DB), VMR, and psychophysical stress markers during different training periods over a half-season. The second aim was to assess the association between vitamin D binding protein (VDBP), total and free 25-(OH)D, VMRs, and psychophysical stress markers in professional football players. Moreover, we examined the relationship between 25-(OH)D3 and vitamin D metabolites (24,25-(OH)2D3, 3-epi-25-(OH)D3) to determine if training loads in different training periods influenced the vitamin D metabolome. Methods: Twenty professional football players were tested at six different time points across half a year (V1-June; V2-July; V3-August; V4-October; V5-December; V6-January). Results: Analyses indicated a significant seasonal rhythm for VDBP, and total 25-(OH)D (25-(OH)DT), 25-(OH)DB, 24,25-(OH)2D3, 3-epi-25-(OH)D3, 25-(OH)D3:24,25-(OH)2D3, and 24,25-(OH)2D3:25-(OH)D3 VMRs throughout the training period. No correlation was detected between 25-(OH)DT, 25-(OH)DB, 25-(OH)DF, vitamin D metabolites, VMRs, VDBP, and ferritin, liver enzymes (aspartate transaminase [AST] and alanine transaminase [ALT]), creatine kinase (CK), cortisol, testosterone, and testosterone-to-cortisol ratio (T/C) in each period (V1-V6). However, there was a strong statistically significant correlation between 25-(OH)D3 and 24,25-(OH)D3 in each training period. Conclusion: In conclusion, a seasonal rhythm was present for VDBP, 25-(OH)DT, 25-(OH)DB, vitamin D metabolites (24,25-(OH)2D3, 3-epi-25-(OH)D3), and VMRs (25-(OH)D3:24,25-(OH)2D3, 25-(OH)D3:3-epi-25-(OH)D3). However, no rhythm was detected for 25-(OH)DF and markers of psychophysical stress (ferritin, liver enzymes, CK, testosterone, cortisol, and T/C ratio). Moreover, the relationships between free and total 25-(OH)D with psychophysical stress markers did not demonstrate the superiority of free over total measurements. Furthermore, training loads in different training periods did not affect resting vitamin D metabolite concentrations in football players.