Nucleic Acids in Human Glioma Treatment: Innovative Approaches and Recent Results

Gliomas are the most common primary central nervous system tumors with a dismal prognosis. Despite recent advances in surgery, radiotherapy, and chemotherapy, current treatment regimens have a modest survival benefit. A crucial challenge is to deliver drugs effectively to invasive glioma cells residing in a sanctuary within the central nervous system. New therapies are essential, and oligonucleotide-based approaches, including antisense, microRNAs, small interfering RNAs, and nucleic acid aptamers, may provide a viable strategy. Thanks to their unique characteristics (low size, good affinity for the target, no immunogenicity, chemical structures that can be easily modified to improve their in vivo applications), these molecules may represent a valid alternative to antibodies particularly to overcome challenges presented by the blood-brain barrier. Here we will discuss recent results on the use of oligonucleotides that will hopefully provide new effective treatment for gliomas

Human cardiomyocyte calcium handling and transverse tubules in mid-stage of post-myocardial-infarction heart failure

Aims: Cellular processes in the heart rely mainly on studies from experimental animal models or explanted hearts from patients with terminal end-stage heart failure (HF). To address this limitation, we provide data on excitation contraction coupling, cardiomyocyte contraction and relaxation, and Ca2+ handling in post-myocardial-infarction (MI) patients at mid-stage of HF. Methods and results: Nine MI patients and eight control patients without MI (non-MI) were included. Biopsies were taken from the left ventricular myocardium and processed for further measurements with epifluorescence and confocal microscopy. Cardiomyocyte function was progressively impaired in MI cardiomyocytes compared with non-MI cardiomyocytes when increasing electrical stimulation towards frequencies that simulate heart rates during physical activity (2 Hz); at 3 Hz, we observed almost total breakdown of function in MI. Concurrently, we observed impaired Ca2+ handling with more spontaneous Ca2+ release events, increased diastolic Ca2+, lower Ca2+ amplitude, and prolonged time to diastolic Ca2+ removal in MI (P < 0.01). Significantly reduced transverse-tubule density (−35%, P < 0.01) and sarcoplasmic reticulum Ca2+ adenosine triphosphatase 2a (SERCA2a) function (−26%, P < 0.01) in MI cardiomyocytes may explain the findings. Reduced protein phosphorylation of phospholamban (PLB) serine-16 and threonine-17 in MI provides further mechanisms to the reduced function. Conclusions: Depressed cardiomyocyte contraction and relaxation were associated with impaired intracellular Ca2+ handling due to impaired SERCA2a activity caused by a combination of alteration in the PLB/SERCA2a ratio and chronic dephosphorylation of PLB as well as loss of transverse tubules, which disrupts normal intracellular Ca2+ homeostasis and handling. This is the first study that presents these mechanisms from viable and intact cardiomyocytes isolated from the left ventricle of human hearts at mid-stage of post-MI HF

Exercise training reverses myocardial dysfunction induced by CaMKIIδC overexpression by restoring Ca2+-homeostasis

Several conditions of heart disease, including heart failure and diabetic cardiomyopathy, are associated with upregulation of cytosolic Ca2+/calmodulin-dependent protein kinase II (CaMKIIδC) activity. In the heart, CaMKIIδC isoform targets several proteins involved in intracellular Ca2+ homeostasis. We hypothesized that high-intensity endurance training activates mechanisms that enable a rescue of dysfunctional cardiomyocyte Ca2+ handling and thereby ameliorate cardiac dysfunction despite continuous and chronic elevated levels of CaMKIIδC. CaMKIIδC transgenic (TG) and wild-type (WT) mice performed aerobic interval exercise training over 6 wk. Cardiac function was measured by echocardiography in vivo, and cardiomyocyte shortening and intracellular Ca2+ handling were measured in vitro. TG mice had reduced global cardiac function, cardiomyocyte shortening (47% reduced compared with WT, P < 0.01), and impaired Ca2+ homeostasis. Despite no change in the chronic elevated levels of CaMKIIδC, exercise improved global cardiac function, restored cardiomyocyte shortening, and reestablished Ca2+ homeostasis to values not different from WT. The key features to explain restored Ca2+ homeostasis after exercise training were increased L-type Ca2+ current density and flux by 79 and 85%, respectively (P < 0.01), increased sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a) function by 50% (P < 0.01), and reduced diastolic SR Ca2+ leak by 73% (P < 0.01), compared with sedentary TG mice. In conclusion, exercise training improves global cardiac function as well as cardiomyocyte function in the presence of a maintained high CaMKII activity. The main mechanisms of exercise-induced improvements in TG CaMKIIδC mice are mediated via increased L-type Ca2+ channel currents and improved SR Ca2+ handling by restoration of SERCA2a function in addition to reduced diastolic SR Ca2+ leak

A solar photothermocatalytic approach for the CO2 conversion: Investigation of different synergisms on CoO-CuO/brookite TiO2-CeO2 catalysts

The photoactive features of the least common polymorph of TiO2, i.e. brookite, were combined with the thermocatalytic redox ones of cerium oxide, focusing on the effects of the addition of small amounts of Co-Cu oxides for the solar CO2 conversion. By considering the characterization data, a surface segregation of the hosted metal oxides on the TiO2-CeO2 composite was evidenced, and their presence increased the amount of oxygen vacancies and improved the charge carriers separation. The bimetallic oxides-based sample was the most performing one in the photocatalytic carbon dioxide reduction at room temperature. The formation of carbon monoxide and methane was 5 and 0.5 μmol g−1h−1, respectively, i.e. about 10 times higher than that found with bare brookite. A further enhancement was obtained with the same CoO-CuO/TiO2-CeO2 catalyst applying the photothermal approach. The CO2-TPD and the FTIR measurements highlighted the high interaction between CO2 and the surface sites

Platelet-Rich Plasma (PRP) and Adipose-Derived Stem Cell (ADSC) Therapy in the Treatment of Genital Lichen Sclerosus: A Comprehensive Review

Lichen sclerosus (LS) is a chronic inflammatory dermatosis mostly localized in the genital area, characterized by vulvar alterations that can severely impact a patient's quality of life. Current treatment modalities often provide incomplete relief, and there is a need for innovative approaches to manage this condition effectively. Platelet-rich plasma (PRP) and adipose-derived stem cells (ADSCs) have emerged as potential regenerative therapies for LS, offering promising results in clinical practice. This comprehensive review explores the utilization of PRP and ADSC therapy in the treatment of genital LS, highlighting their mechanisms of action, safety profiles, and clinical outcomes. PRP is a blood product enriched in growth factors and cytokines, which promotes tissue regeneration, angiogenesis, and immune modulation. ADSC regenerative potential relies not only in their plasticity but also in the secretion of trophic factors, and modulation of the local immune response. Numerous studies have reported the safety of PRP and ADSC therapy for genital LS. Adverse events are minimal and typically involve mild, self-limiting symptoms, such as transient pain and swelling at the injection site. Long-term safety data are encouraging, with no significant concerns identified in the literature. PRP and ADSC therapy have demonstrated significant improvements in LS-related symptoms, including itching, burning, dyspareunia, and sexual function. Additionally, these therapies enable many patients to discontinue the routine use of topical corticosteroids. Several studies have explored the efficacy of combining PRP and ADSC therapy for LS. In combination, PRP and ADSCs seem to offer a synergistic approach to address the complex pathophysiology of LS, particularly in the early stages. The use of PRP and ADSC therapy for genital lichen sclerosus represents a promising and safe treatment modality. These regenerative approaches have shown significant improvements in LS-related symptoms, tissue trophism, and histological features. Combination therapy, which harnesses the synergistic effects of PRP and ADSCs, is emerging as a preferred option, especially in early-stage LS cases. Further research, including randomized controlled trials and long-term follow-up, is warranted to elucidate the full potential and mechanisms of PRP and ADSC therapy in the management of genital LS. These regenerative approaches hold great promise in enhancing the quality of life of individuals suffering from this challenging condition

Heart rate, pr, and qt intervals in normal children: A 24‐hour holter monitoring study

A dynamic electrocardiographic Holter monitoring study was performed in 32 healthy children (20 males and 12 females, age range 6-11 years old), without heart disease, according to clinical and noninvasive instrumental examination. We evaluated atrioventricular conduction time (PR), heart rate (HR), and QT interval patterns defining the range of normality of these electrocardiographic parameters. The PR interval ranged from 154 +/- 10 ms (mean +/- SD) for HR less than or equal to 60 to 102 +/- 12 ms for HR greater than or equal to 120 (range 85-180). The absolute mean HR was 87 +/- 10 beats/min (range 72-104), the minimum observed HR being 61 +/- 10 (range 51-79), the maximum 160 +/- 20 beats/min (range 129-186). Daytime mean HR gave a mean value of 93 +/- 10 (range 71-148), while during night hours it was 74 +/- 11 (range 54-98). The minimum QT interval averaged 261 +/- 10 ms for HR greater than 120 and the maximum 389 +/- 9 ms for HR less than or equal to 60; the corresponding mean value of QTc (i.e., QT corrected for HR) ranged from 388 +/- 8 for HR less than or equal to 60 beats/min to 403 +/- 14 ms for HR greater than 120 beats/min. The results of the present study provide data of normal children which can be readily compared against those of subjects in whom cardiac abnormalities are suspect or patient.(ABSTRACT TRUNCATED AT 250 WORDS

Buschke-Lowenstein tumor: Use of dermal matrix for reconstruction of genital area

none8noBuschke-Lowenstein tumor (BLT) is a rare giant condyloma acuminatum of the anogenital region, first described by Buschke and Lowenstein as a potential malignant condyloma acuminatum. A 64-year-old Moroccan man was referred to our dermatology department with a 10-year-history of a growing mass in the genital region. A diagnosis of giant condyloma acuminatum was made based on clinical and histopathological features. We opted for a two-stage surgical procedure. The first stage consisted in tumor removal with clinically safe margins and positioning of an Integra® Matrix Wound Dressing. After 3 weeks the silicone top layer was removed and a thin split-thickness skin graft was applied.At the 1 year follow-up, the patient still presented an adequate reconstruction of the area and an acceptable cosmesis, without any complication or signs of recurrences.noneCondorelli A.G.; Ferrari B.; Francomano M.; Rocco B.; Sighinolfi M.C.; Giacomelli L.; Pignatti M.; Magnoni C.Condorelli A.G.; Ferrari B.; Francomano M.; Rocco B.; Sighinolfi M.C.; Giacomelli L.; Pignatti M.; Magnoni C

The new generation of SPAD—Single-Photon Avalanche Diodes arrays

In the last years the single-photon detection with silicon devices has become an important goal. Here we present the performance of a new generation of single-photon avalanche diodes manufactured by ST-Microelectronics. The 5 × 5 array configuration has been also realized and the performances, in terms of crosstalk and common readout mode, have been investigated

Integration of epigenetic regulatory mechanisms in heart failure

The number of “omics” approaches is continuously growing. Among others, epigenetics has appeared as an attractive area of investigation by the cardiovascular research community, notably considering its association with disease development. Complex diseases such as cardiovascular diseases have to be tackled using methods integrating different omics levels, so called “multi-omics” approaches. These approaches combine and co-analyze different levels of disease regulation. In this review, we present and discuss the role of epigenetic mechanisms in regulating gene expression and provide an integrated view of how these mechanisms are interlinked and regulate the development of cardiac disease, with a particular attention to heart failure. We focus on DNA, histone, and RNA modifications, and discuss the current methods and tools used for data integration and analysis. Enhancing the knowledge of these regulatory mechanisms may lead to novel therapeutic approaches and biomarkers for precision healthcare and improved clinical outcomes