Effect of resveratrol on matrix metalloproteinase-2 (MMP-2) and secreted protein acidic and rich in cysteine (SPARC) on human cultured glioblastoma cells

INTRODUCTION: Glioblastoma is a highly malignant brain tumor with a high-invasive phenotype, so the prognosis is unfavorable, even in response to multidisciplinary treatment strategies. Obviously, therefore, a better therapeutic strategy is needed. Resveratrol has been reported to be one of the most potent chemopreventive agents inhibiting the cellular processes associated with tumor development, including initiation, promotion, and progression. MATERIALS AND METHODS: In this study we used RT-PCR, western blot and SDS-zymography to investigate the effect of resveratrol on the expression of genes and proteins involved in the extracellular matrix remodeling associated with tumor invasion in human cultured glioblastoma cells treated for 24, 48 and 72 h. We analyzed the expression of matrix metalloproteinase-2 (MMP-2), the main mediator of glioblastoma invasiveness, and the Secreted Protein Acidic and Rich in Cysteine (SPARC), involved in the regulation of cell-matrix interactions. RESULTS: Our results show a dose-related decrease of MMP-2 mRNA and protein levels 72 h after resveratrol treatment, and lower SPARC gene and protein expression 72 h after resveratrol treatment. This indicates that resveratrol may influence the two major factors in the ECM remodeling occurring with tumor invasion, suggesting it may have uses as a therapeutic agent for brain tumors

Early cytotoxic effects of ochratoxin A in rat liver: a morphological, biochemical and molecular study

We characterized the overall early effect of chronic ochratoxin A (OTA) treatment on rat liver, analyzing different aspects related to: (i) fibrosis, by measuring collagen content and turnover, and alpha-smooth muscle actin (alphaSMA); (ii) oxidative stress and stress response, by analyzing protein carbonylation, superoxide dismutase (SOD) and heat shock protein (HSP70) gene expression; (iii) the possible tumor promoter effect, evaluating cadherin and connexin (CX) mRNA levels. Light microscopy analysis showed no histological differences in OTA-treated and control (CT) rats. Collagen content, determined by computer analysis of Sirius red-stained liver sections, was similar in both groups. In liver homogenates COL-I, COL-III, TIMP-1 and TGF-beta1 mRNA levels and alphaSMA were unaffected by OTA. Matrix metalloproteinase (MMP)-1, MMP-2 and MMP-9 protein levels were also similar in the two groups. Protein carbonylation, a marker of severe oxidative stress, was not evident in the homogenates of OTA-treated livers; superoxide dismutase (SOD) mRNA tended to be lower and HSP70 was strongly down-regulated. OTA reduced E-cadherin and DSC-2 transcription, and down-regulated liver CX26, CX32 and CX43. In conclusion, these in vivo results show that OTA-induced liver injury involves a reduction in the ability to counterbalance oxidative stress, maybe leading to altered gap junction intercellular communication and loss of cell adhesion and polarity. This suggests that mild oxidative damage might be a key factor, in combination with other cytotoxic effects, in triggering the promotion of liver tumors after exposure to OTA

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Una pianta inedita della chiesa altomedievale di Santa Maria in Trastevere

Il ritrovamento della pianta della chiesa realizzata nel XIX secolo, in occasione di lavori di restauro dell'edificio, permette di ricostruire alcune vicende sulla sua storia e avanzare alcune proposte circa l'aspetto assunto dalla chiesa in età altomedievale