Detrimental Effect of Cannabidiol on the Early Onset of Diabetic Nephropathy in Male Mice

Anti-inflammatory and antidiabetogenic properties have been ascribed to cannabidiol (CBD). CBD-based medicinal drugs have been approved for over a lustrum, and a boom in the commercialization of CBD products started in parallel. Herein, we explored the efficacy of CBD in streptozotocin (STZ)-induced diabetic mice to prevent diabetic nephropathy at onset. Eight-to-ten-week-old C57BL6J male mice were treated daily intraperitoneally with 10 mg/kg of CBD or vehicle for 14 days. After 8 days of treatment, mice were challenged with STZ or vehicle (healthy-control). At the end of the study, non-fasting blood glucose (FBG) level was 276 ± 42 mg/dL in vehicle-STZ-treated compared to 147 ± 9 mg/dL (p ≤ 0.01) in healthy-control mice. FBG was 114 ± 8 mg/dL in vehicle-STZ-treated compared to 89 ± 4 mg/dL in healthy-control mice (p ≤ 0.05). CBD treatment did not prevent STZ-induced hyperglycemia, and non-FBG and FBG levels were 341 ± 40 and 133 ± 26 mg/dL, respectively. Additionally, treatment with CBD did not avert STZ-induced glucose intolerance or pancreatic beta cell mass loss compared to vehicle-STZ-treated mice. Anatomopathological examination showed that kidneys from vehicle-STZ-treated mice had a 35% increase of glomerular size compared to healthy-control mice (p ≤ 0.001) and presented lesions with a 43% increase in fibrosis and T cell infiltration (p ≤ 0.001). Although treatment with CBD prevented glomerular hypertrophy and reduced T cell infiltration, it significantly worsened overall renal damage (p ≤ 0.05 compared to vehicle-STZ mice), leading to a more severe renal dysfunction than STZ alone. In conclusion, we showed that CBD could be detrimental for patients with type 1 diabetes, particularly those undergoing complications such as diabetic nephropathy

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

(+)-trans-Cannabidiol-2-hydroxy pentyl is a dual CB1R antagonist/CB2R agonist that prevents diabetic nephropathy in mice

Natural cannabidiol ((-)-CBD) and its derivatives have increased interest for medicinal applications due to their broad biological activity spectrum, including targeting of the cannabinoid receptors type 1 (CB1R) and type 2 (CB2R). Herein, we synthesized the (+)-enantiomer of CBD and its derivative (+)-CBD hydroxypentylester ((+)-CBD-HPE) that showed enhanced CB1R and CB2R binding and functional activities compared to their respective (-) enantiomers. (+)-CBD-HPE Ki values for CB1R and CB2R were 3.1 ± 1.1 and 0.8 ± 0.1 nM respectively acting as CB1R antagonist and CB2R agonist. We further tested the capacity of (+)-CBD-HPE to prevent hyperglycemia and its complications in a mouse model. (+)-CBD-HPE significantly reduced streptozo tocin (STZ)-induced hyperglycemia and glucose intolerance by preserving pancreatic beta cell mass. (+)-CBD HPE significantly reduced activation of NF-κB by phosphorylation by 15% compared to STZ-vehicle mice, and CD3+ T cell infiltration into the islets was avoided. Consequently, (+)-CBD-HPE prevented STZ-induced apoptosis in islets. STZ induced inflammation and kidney damage, visualized by a significant increase in plasma proinflammatory cytokines, creatinine, and BUN. Treatment with (+)-CBD-HPE significantly reduced 2.5- fold plasma IFN-γ and increased 3-fold IL-5 levels compared to STZ-treated mice, without altering IL-18. (+)-CBD-HPE also significantly reduced creatinine and BUN levels to those comparable to healthy controls. At the macroscopy level, (+)-CBD-HPE prevented STZ-induced lesions in the kidney and voided renal fibrosis and CD3+ T cell infiltration. Thus, (+)-enantiomers of CBD, particularly (+)-CBD-HPE, have a promising potential due to their pharmacological profile and synthesis, potentially to be used for metabolic and immune-related disorders.Depto. de Bioquímica y Biología MolecularFac. de MedicinaTRUEpu

Use of salivary biomarkers for diagnosis of periodontal disease activity: a literature review

Periodontal disease is an infectious disease characterized by the connective tissue destruction and consequent alveolar bone loss in response to plaque accumulation on the tooth surface. The clinical diagnosis of periodontal disease is based both on clinical examination involving the evaluation of probing depth and radiographic examination of alveolar bone loss but these examinations are not enough to determine the activity of the disease process. For that reason, it has been proposed to seek predictive disease markers in an attempt to assess the disease activity and so, evaluate the efficacy of the periodontal disease treatment. The aim of this review is to present recent advances in the development of proteomic, genomics and microbial biomarkers and potential clinical applications. It was concluded that periodontal treatment based on assessing the levels of salivary biomarkers emerges as a promising method in near future and will become an integral part of the evaluation of periodontal health

Osteoblast differentiation is enhanced by a nano-to-micro hybrid titanium surface created by Yb:YAG laser irradiation

The aim of this study was to analyze the capacity of a new modified laser surface to stimulate calvarial osteoblasts isolated from neonatal mouse bones to differentiate and form mineralized nodules. Titanium discs were subjectezd or not to laser irradiation according to specific parameters and characterized. Osteoblasts isolated from neonatal mouse calvaria were cultured over the discs, and the capacity of these cells to proliferate (MTT assay), form mineralized nodules (Alizarin red assay), and enhance alkaline phosphatase activity (ALPase activity) was analyzed. Real-time PCR was used for quantification of gene expression. Laser-irradiated titanium discs (L) presented a rough nano-to-micrometric oxidized surface contrasting with the smooth pattern on polished discs (P). The Ra on the micrometric level increased from 0.32 ± 0.01 μm on P surfaces to 10.57 ± 0.39 μm on L surfaces. When compared with P, L promoted changes in osteoblast morphology, increased mineralized nodule formation in osteoblasts cultured on the surfaces for 14 days, and enhanced ALPase activity at days 7 and 14. Transcription factors triggering osteoblast differentiation (Runx2 and Sp7) and genes encoding the bone extracellular matrix proteins collagen type-1 (Col1a1), osteopontin (Spp1), and osteocalcin (Bglap) were upregulated in cells on L surfaces compared with those on P surfaces at days 1-14. Laser treatment of titanium surfaces created a rough surface that stimulated osteoblast differentiation. Laser treatment of titanium generates a reproducible and efficient surface triggering osteoblast differentiation that can be of importance for osteointegration.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

The impact of the use of games on student academic performance: gamification as a way to improve the teaching of political, legal and social issues

El juego es una herramienta básica para el aprendizaje, aunque poco utilizada en el Espacio de Educación Superior. El uso de los juegos en las aulas puede contribuir no sólo a mejorar la percepción de la docencia por parte de nuestro alumnado (lo cual a su vez podría transmitirse en una mejor percepción de los estudios de la Universidad Complutense), sino que también pueden conducir a un mayor conocimiento de los procesos dinámicos en los que vivimos hoy día facilitando que los participantes comprendan mejor su naturaleza dinámica. Cuando se simula una situación, los participantes se dan cuenta de cómo funciona el sistema político en movimiento y se preparan para enfrentarlo en la vida real. Además, las simulaciones también son divertidas, hacen que los estudiantes se involucren más en el estudio y profundicen su conocimiento al fomentar su interés. En este Proyecto de Innovación Docente profesores de distintas facultades y universidades analizamos el uso del juego en las aulas y su impacto en el rendimiento de nuestro alumnado.Universidad Complutense de MadridDepto. de Ciencia Política y de la AdministraciónFac. de Ciencias Políticas y SociologíaFALSEsubmitte