Gliotic Response and Reprogramming Potential of Human Müller Cell Line MIO-M1 Exposed to High Glucose and Glucose Fluctuations

Retinal neurodegeneration (RN), an early marker of diabetic retinopathy (DR), is closely associated with Müller glia cells (MGs) in diabetic subjects. MGs play a pivotal role in maintaining retinal homeostasis, integrity, and metabolic support and respond to diabetic stress. In lower vertebrates, MGs have a strong regenerative response and can completely repair the retina after injuries. However, this ability diminishes as organisms become more complex. The aim of this study was to investigate the gliotic response and reprogramming potential of the human Müller cell line MIO-M1 cultured in normoglycemic (5 mM glucose, NG) and hyperglycemic (25 mM glucose, HG) conditions and then exposed to sustained high-glucose and glucose fluctuation (GF) treatments to mimic the human diabetic conditions. The results showed that NG MIO-M1 cells exhibited a dynamic activation to sustained high-glucose and GF treatments by increasing GFAP and Vimentin expression together, indicative of gliotic response. Increased expression of SHH and SOX2 were also observed, foreshadowing reprogramming potential. Conversely, HG MIO-M1 cells showed increased levels of the indexes reported above and adaptation/desensitization to sustained high-glucose and GF treatments. These findings indicate that MIO-M1 cells exhibit a differential response under various glucose treatments, which is dependent on the metabolic environment. The in vitro model used in this study, based on a well-established cell line, enables the exploration of how these responses occur in a controlled, reproducible system and the identification of strategies to promote neurogenesis over neurodegeneration. These findings contribute to the understanding of MGs responses under diabetic conditions, which may have implications for future therapeutic approaches to diabetes-associated retinal neurodegeneration

Ejaculate Oxidative Stress Is Related with Sperm DNA Fragmentation and Round Cells

Oxidative stress (OS) plays an essential role in male infertility aetiology by affecting sperm quality, function, and also the integrity of sperm DNA. The assessment of oxidative stress in semen may be an important tool to improve the evaluation of sperm reproductive capacity. The purpose of this study was the evaluation of any possible relation between the unbalance of oxidative stress caused by superoxide anion in the ejaculate with the presence of sperm DNA fragmentation and high concentration of round cells. 56 semen samples from males from couples suffering from infertility were evaluated according to World Health Organisation (WHO) 2010 guidelines. Oxidative stress levels from N1 (low) to N4 (high) were assessed in ejaculates using oxiSperm; DFI (sperm DNA fragmentation index) as assessed by the SCSA (Sperm Chromatin Structure Assay) was used for evaluation of sperm chromatin integrity. Our data show that high oxidative stress (N3-N4 levels) correlated positively with a DFI≥30% (P=0.0379) and round cells ≥1.500.000/mL (P=0.0084). In conclusion, OS increases sperm DNA damage. Thus evaluation of semen OS extent of sperm DNA damage in infertile man could be useful to develop new therapeutic strategies and improve success of assisted reproduction techniques (ART)

Prevalence and risk factors of glomerular hyperfiltration in adults with type 2 diabetes: A population-based study

Aims: Glomerular hyperfiltration characterises the earliest stage of diabetic nephropathy and predicts adverse kidney and cardiovascular outcomes. We aimed to assess the prevalence and risk factors of glomerular hyperfiltration in a population-based contemporary cohort of individuals with type 2 diabetes (T2D). Materials and methods: The prevalence of unequivocal glomerular hyperfiltration (defined by an estimated glomerular filtration rate >120 mL/min/1.73 m(2) ) and its associated risk factors were identified in a cohort of 202,068 adult patients with T2D receiving specialist care in 2021-2022, whose center-aggregated data were automatically extracted from electronic medical records of 75 diabetes clinics in Italy. Results: Glomerular hyperfiltration was identified in 1262 (0.6%) participants. The prevalence of glomerular hyperfiltration varied widely across centers (0%-3.4%) and correlated with mean center age, HbA(1c) , body mass index (BMI), and low-density lipoprotein cholesterol. Patients in centers with high glomerular hyperfiltration prevalence (>0.8%) were more often men and had lower age and BMI, but more frequent albuminuria and worse glucose, lipid, and blood pressure control, compared with low-normal prevalence centers. Conclusions: Unequivocal glomerular hyperfiltration can be identified in up to 3.4% of patients receiving up-to-date specialist diabetes care. Glomerular hyperfiltration prevalence varies across centers and substantially increases with suboptimal control of metabolic risk factors, which would require improved management to mitigate the negative health consequences of this pathological condition

Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42%  60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management

Fiber optic-based sensing revetment technology for monitoring hydraulic protection embankments

In the last decades, many lowlands belonging to the Po Plain in Northern Italy have been flooded several times, as a consequence of the collapse of minor-river levees, as in the case of the tremendous flood events that hit the Emilia-Romagna Region in May 2023, where over 20 levees failed inundating a very huge area. The preservation of the levee integrity represents, therefore, one of the major issues for the Emilia-Romagna Civil Protection Agency, which financed our research on an innovative levee monitoring technology based on an anti-erosion revetment equipped with Fiber Optic Sensors. A test site of this solution has been implemented on a levee stretch by the town of Modena in Spring 2023. The system got over positively the flood events of May 2023 by detecting the evolution of the flood wave. Data interpretation is still ongoing. The paper presents and discusses some results of the experimental investigation carried out so far

New methods for cooling and storing oocytes and embryos in a clean environment of-196 degrees C

It is well documented that oocyte vitrification using open systems provides better results than closed systems. However, its use is limited owing to risks of contamination posed by direct exposure to liquid nitrogen and cross-contamination when stored in liquid nitrogen tanks. A device that produces clean liquid air (CLAir) having similar a temperature as liquid nitrogen and a sterile storage canister device (Esther) that keeps samples sealed in their own compartment while in regular liquid nitrogen tanks were developed. The following experiments were performed: temperature measurements, bioburden tests, vitrification and storage experiments with mice embryos and human oocytes. Results showed similar cooling rates for liquid nitrogen and liquid air. Bioburden tests of CLAir and Esther showed no contamination, while massive contamination was found in "commercial" liquid nitrogen and storage canisters. Mice blastocysts had a survival rate of over 90%, with 80% hatching rate after vitirification in CLAir and 1 week storage in Esther, similar to the fresh (control) results. Human oocytes vitrified in CLAir and in liquid nitrogen for three consecutive vitrification/warming cycles showed 100% survival, seen as re-expansion in both groups. These new systems represent a breakthrough for safe vitrification using open systems and a safe storage process generally. (C) 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved

Experimental contamination assessment of a novel closed ultravitrification device

To evaluate the safety of a new ultravitrification closed device