University of Bari Aldo Moro
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A renal biopsy-anchored multi-marker signature involving AOPEP SNP-driven splicing, miR-27b-3p and glycated albumin for stratifying renal damage in type 2 diabetes.
Get PDFAims: Stratifying renal damage in type 2 diabetes is challenging due to overlapping features between diabetic nephropathy (DN) and non-diabetic renal disease (NDRD). While miR-27b-3p modulates kidney fibrosis in DN through the lysine63 ubiquitination pathway, its upstream regulation and diagnostic relevance remain unclear.
Methods: In a biopsy-verified cohort of 231 chronic kidney disease (CKD) patients with and without type 2 diabetes, we investigated whether AOPEP promoter SNPs drive alternative splicing affecting intronic miR-27b-3p expression. We also assessed the diagnostic utility of combining these biomarkers with clinical parameters, such as glycated albumin (GA), to distinguish DN from NDRD.
Results: The rs10761364 minor allele was associated with reduced urinary miR-27b-3p and AOPEP splicing that excluded exons hosting the miR-23b/27b/24 cluster. This pattern, observed in vivo and under hyperglycemia in vitro, led to elevated AOPEP protein isoforms. A model combining rs10761364, GA, and urinary miR-27b-3p showed high diagnostic accuracy (AUC up to 0.93) in discriminating DN from NDRD. miR-27b-3p inversely correlated with GA, and GA-based models outperformed those using HbA1c.
Conclusion: We identify a genotype- and glucose-dependent mechanism regulating miR-27b-3p via AOPEP splicing and propose a biopsy-anchored, non-invasive biomarker panel (rs10761364, GA, miR-27b-3p) to differentiate DN from NDRD, supporting personalized nephrology care
Le Corti e le leggi elettorali. L'uso del principio democratico come parametro di costituzionalità negli Stati Uniti e in Italia
No full textCourts and electoral laws. The use of the democratic principle as a constitutional parameter in the United States and in Italy - The paper explores the intersection of electoral laws, courts, and the democratic principle, emphasizing the role of courts in upholding electoral legitimacy. In the U.S., recent conflicts highlight divergences between federal and state perspectives, with State Courts entrusted with the primary role of ensuring the democratic principle. The analysis extends to Italy, where the Constitutional Court's recent decisions (2014, 2017) underscore a delicate balance between majority representation and political equality. The paper concludes by highlighting the evolving challenges and uncertainties in safeguarding democratic principles within electoral frameworks
Adverse Prognostic Impact of Transitional and Pleomorphic Patterns in Pleural Nonepithelioid Mesothelioma: Insights From Comprehensive Analysis and Reticulin Stain
Get PDFContext.—: Mesothelioma subtyping into epithelioid and nonepithelioid categories plays a crucial role in prognosis and treatment selection, with emerging recognition of the impact of various histologic patterns. Objective.—: To investigate the prognostic implications of transitional and pleomorphic patterns in sarcomatoid mesothelioma. Design.—: A total of 132 mesothelioma cases (87 biphasic, 45 sarcomatoid) were analyzed. Histologic slides were assessed, treatment data collected, and cases categorized into predominant epithelioid or sarcomatoid patterns. The sarcomatoid mesotheliomas were classified into usual, pleomorphic, and transitional patterns, with reticulin staining for the latter. Statistical analysis included Cox regression and Kaplan-Meier methods. Results.—: Younger age (P = .02) and receiving therapy (P < .001) correlated with improved survival for both histotypes. Advanced stage was associated with shorter survival in sarcomatoid cases (P = .02). Predominant epithelioid pattern in biphasic cases led to longer survival (P < .001). Transitional and pleomorphic patterns were indicative of worse prognosis, with significantly lower survival in cases with both patterns than in cases with the usual sarcomatoid pattern (P = .046). Multivariate analysis identified independent survival factors, including predominant epithelioid component in biphasic mesothelioma (P = .001) and chemotherapy (P < .001). Conclusions.—: Histologic subtyping in mesothelioma plays a pivotal role in prognosis. Transitional and pleomorphic patterns, even in low percentages, indicate poorer outcomes. This study highlights the need for standardized diagnostic support and suggests the potential utility of histochemical staining in identifying more aggressive morphologic aspects. Recognizing the significance of these patterns can guide treatment decisions and patient care strategies
Multivariate approach for the optimization of sucrose ethanolysis: Paving the way to the exploitation of sucrose-rich by-products
No full textThe depletion of fossil resources is making the synthesis of renewable compounds urgent. Ethyl levulinate (EL) represents a strategic compound within the biorefinery process, being a valuable intermediate, solvent and biofuel additive of renewable origin. The one-pot ethanolysis is the preferred route for its synthesis, but the proper optimization of the reaction conditions to maximize the EL yield and minimize the critical by-products formation, diethyl ether (DEE) and humins, is still a challenge. In this regard, the present work aims at the optimization of sucrose ethanolysis through the multivariate approach, adopting H2SO4 as catalyst and following the high gravity approach (10.5 wt% sucrose loading), which allows the obtaining of concentrated EL streams, increasing productivity and making downstream operations easier and cheaper. The optimization allowed a compromise between the highest EL yield and the lowest DEE production, thus simplifying EL purification and consuming less solvent that can be recycled in the following run. Under these conditions, the humins formation was also kept low and, for the first time, not only the solid humins were characterized, proving to be suitable as solid fuel turning into a co-product of the process, but also the chemical structure of the soluble ones was investigated. For the first time, a preliminary study regarding the ethanolysis of thick juice was also performed, thus opening the way to the employment of low-cost sucrose-rich feedstocks as substrate for the synthesis of EL. Thus, this work contributes to making the synthesis of a strategic renewable compound as EL more sustainable
Fermi detection of gamma-ray emission from the hot coronae of radio-quiet active galactic nuclei
No full textRelativistic jets around supermassive black holes are well-known powerful gamma-ray emitters. In the absence of the jets in radio-quiet active galactic nuclei, how the supermassive black holes work in gamma-ray bands is still unknown despite great observational efforts in the past three decades. Here, considering the previous efforts, we carefully select an active galactic nucleus sample composed of 37 nearby Seyfert galaxies with ultrahard X-rays for gamma-ray detection by excluding all potential contamination in this band. Adopting a stacking technique, we report the significant gamma-ray detection (test statistic 30.6, or 5.2 sigma) from the sample using 15-year Fermi-LAT observations. We find the average gamma-ray luminosity of the sample to be (1.5 +/- 1.0) x 10(40) erg s(-1) at energies of 1-300 GeV. Limited by the well-known pair production from the interaction of gamma-rays with low-energy photons, gamma-rays of more than several giga-electronvolts are found to originate from an extended corona (similar to 2.7 x 10(6) gravitational radii), whereas the canonical much more compact X-ray corona (similar to 10 gravitational radii) is responsible for gamma-rays of one to several giga-electronvolts. The finding of the compact region lends strong support to the long-time theoretical expectations, but the extended corona is an unexpected finding. One promising scenario is that the electron-positron pairs produced in the compact X-ray corona would expand as a fireball, similar to that in gamma-ray bursts, forming the structure of extended corona
Real-life preliminary evidence for basophils as predictors of Tezepelumab response in severe asthma
No full textBackground: Severe asthma is a complex disease with persistent symptoms despite high-dose inhaled therapy. Tezepelumab, a monoclonal antibody targeting thymic stromal lymphopoietin (TSLP), has shown efficacy across asthma phenotypes. However, identifying early responders remains a challenge. Basophils, key players in type 2 inflammation, may serve as predictive biomarkers. Objective: We evaluated the presence of super-responder status after six months of Tezepelumab therapy and explored the predictive role of blood basophil levels. Methods: A real-life, prospective study was conducted on 16 severe asthma patients. Super-responders were defined per Upham et al.’s criteria, adapted for a six-month assessment. Clinical, functional, and inflammatory parameters, including blood basophil counts, were analyzed. Results: After six months, 62.5% of patients achieved super-responder status, with complete exacerbation elimination, reduced oral corticosteroid use, and improved asthma control. A significant logarithmic association (p = 0.019) was found between baseline basophil levels and super-responder status, indicating that higher basophil counts were associated with an increased likelihood of super-response. This finding was supported by a trend toward significance in ROC curve analysis (AUC = 0.800, p = 0.050), suggesting potential predictive value. Conclusion: Tezepelumab demonstrates early efficacy in severe asthma, and baseline blood basophil levels may represent a promising biomarker for response prediction
Upgrading a horizontal surface flow constructed wetland with forest waste and aeration
No full textConstructed wetlands (CWs) are regarded as sustainable wastewater treatment systems for small to medium-sized communities. However, ponds and horizontal surface flow CWs (SF-CWs) can be an ideal environment for mosquitoes to thrive. In the current context of climate change, this may pose serious health problems for the population, which may predispose authorities against their use. A possible solution for existing SF-CWs is to convert them into sub-surface flow by filling them with conventional media, i.e. gravel and/or sand. However, the mining of these materials poses an enormous environmental threat. Thus, alternative, sustainable filling materials for CWs should be tested. Another constraint of CWs is their large footprint, which in many cases (lack of expensive land) limits their applicability. This work studies the effects of filling a full-scale SF-CW with a forest residue (palm tree branches) and aeration. The results indicate that in terms of percentage removal, filling increased that of E. coli and Total Coliforms, while the combination of filling and aeration resulted in a significant improvement in BOD5, turbidity, and ammonium. However, the analysis of surface loads removed indicated significant increases in E. coli and TC with the filling alone, and of BOD5, turbidity, E. coli, Total Coliformis, and ammonium for the filling + aeration combination. Studies at full-scale level on the use of forest residues as CW substrate and aeration are scarce, thus this work can serve as a guide for more sustainable designs
Plasma Deposition of Coatings for Delivery of Bacterial Spores Active Against Fusarium graminearum
No full textAtmospheric Pressure Plasma Deposition processes have been investigated for the preparation of bio-composite coatings embedding bacterial spores of Bacillus velezensis N3.2, a strain known in agriculture for its antimicrobial activity against phytopathogenic microorganisms. More specifically, an organic film was plasma-deposited onto casted spores with the aim of checking their viability and antifungal activity in the film-embedded state. Interestingly, results indicate that the spores retain their viability after the deposition, with the thickness of the coating influencing to some extent the formation of bacteria colonies. It was found that the plasma film superimposition does not limit the potential antifungal activity of the spores and the bio-composite coatings are effective in inhibiting the growth of the toxigenic fungal plant pathogen, Fusarium graminearum
Prognostic Utility of Arterial Spin Labeling in Traumatic Brain Injury: From Pathophysiology to Precision Imaging
No full textBackground: Traumatic brain injury (TBI) remains a significant contributor to global mortality and long-term neurological disability. Accurate prognostic biomarkers are crucial for enhancing prognostic accuracy and guiding personalized clinical management. Objective: This review assesses the prognostic value of arterial spin labeling (ASL), a non-invasive MRI technique, in adult and pediatric TBI, with a focus on quantitative cerebral blood flow (CBF) and arterial transit time (ATT) measures. A comprehensive literature search was conducted across PubMed, Embase, Scopus, and IEEE databases, including observational studies and clinical trials that applied ASL techniques (pCASL, PASL, VSASL, multi-PLD) in TBI patients with functional or cognitive outcomes, with outcome assessments conducted at least 3 months post-injury. Results: ASL-derived CBF and ATT parameters demonstrate potential as prognostic indicators across both acute and chronic stages of TBI. Hypoperfusion patterns correlate with worse neurocognitive outcomes, while region-specific perfusion alterations are associated with affective symptoms. Multi-delay and velocity-selective ASL sequences enhance diagnostic sensitivity in TBI with heterogeneous perfusion dynamics. Compared to conventional perfusion imaging, ASL provides absolute quantification without contrast agents, making it suitable for repeated monitoring in vulnerable populations. ASL emerges as a promising prognostic biomarker for clinical use in TBI. Conclusion: Integrating ASL into multiparametric models may improve risk stratification and guide individualized therapeutic strategies
Antiproliferative Evaluation of Dextran Polymer-Based Pomegranate Ethanolic Extract
No full textThe pomegranate peel represents an important source of secondary metabolites such as
hydrolysable ellagitannins, which are recognized for their antioxidant, anticancer and neuroprotective
properties. In this work, the freeze-dried pomegranate peel was extracted by a
combined mild maceration at room temperature and ultrasonication at 45 ◦C using ethanol
and acetone as green solvents. The ethanol extract, with an extraction yield of 29%, and
IC50 (mg/mL) 0.1067 and 0.0414 for DPPH and ABTS, respectively, was incorporated into
a polymer based on dextran, using a grafting reaction, to improve its bioavailability and
preserve the chemical integrity. In addition, the potential antitumor activity against breast
cancer was evaluated based on the existing literature. In vitro studies have demonstrated
the safety and biocompatibility of both free pomegranate peel extract (SSE2-L) and its
dextran conjugate (SSPD), with no adverse effects on fibroblasts, erythrocytes, or immune
cells. Both formulations inhibited the proliferation of breast cancer cell lines (MCF-7, MDAMB-
231) in a concentration- and time-dependent manner, with SSPD consistently showing
superior efficacy. This enhanced activity was corroborated by reduced clonogenic growth,
G1 cell-cycle arrest, and improved stability and bioactive retention conferred by polymer
conjugation. Overall, these findings highlight dextran-conjugated pomegranate polyphenols
as promising candidates for next-generation nutraceuticals and phytopharmaceuticals
in cancer chemoprevention and adjunctive therapy, with potential applications extending
to other biomedical fields and functional foods