• Prater Ibrahim posted an update 6 months, 3 weeks ago

    Undoubtedly, the presence of aggregated alpha-synuclein can disrupt glial function in general and can contribute to neurodegeneration through numerous pathways. Herein, we summarize the current knowledge on the role of alpha-synuclein in both neurons and glia, highlighting the contribution of the neuron-glia connectome in the disease initiation and progression, which may represent potential therapeutic target for a-synucleinopathies.The cytokine interleukin-7 (IL-7) and its receptor are critical for lymphoid cell development. The loss of IL-7 signaling causes severe combined immunodeficiency, whereas gain-of-function alterations in the pathway contribute to malignant transformation of lymphocytes. Binding of IL-7 to the IL-7 receptor results in the activation of the JAK-STAT, PI3K-AKT and Ras-MAPK pathways, each contributing to survival, cell cycle progression, proliferation and differentiation. Here, we discuss the role of deregulated IL-7 signaling in lymphoid malignancies of B- and T-cell origin. Especially in T-cell leukemia, more specifically in T-cell acute lymphoblastic leukemia and T-cell prolymphocytic leukemia, a high frequency of mutations in components of the IL-7 signaling pathway are found, including alterations in IL7R, IL2RG, JAK1, JAK3, STAT5B, PTPN2, PTPRC and DNM2 genes.At the end of the mammalian intra-uterine foetal development, a rapid switch from glycolytic to oxidative metabolism must proceed. Using microarray techniques, qPCR, enzyme activities and coenzyme Q content measurements, we describe perinatal mitochondrial metabolism acceleration in rat liver and skeletal muscle during the perinatal period and correlate the results with those in humans. Out of 1546 mitochondrial genes, we found significant changes in expression in 1119 and 827 genes in rat liver and skeletal muscle, respectively. The most remarkable expression shift occurred in the rat liver at least two days before birth. Coenzyme Q-based evaluation in both the rat model and human tissues showed the same trend the total CoQ content is low prenatally, significantly increasing after birth in both the liver and skeletal muscle. learn more We propose that an important regulator of rat coenzyme Q biosynthesis might be COQ8A, an atypical kinase involved in the biosynthesis of coenzyme Q. Our microarray data, a total of 16,557 RefSeq (Entrez) genes, have been deposited in NCBI’s Gene Expression Omnibus and are freely available to the broad scientific community. Our microarray data could serve as a suitable background for finding key factors regulating mitochondrial metabolism and the preparation of the foetus for the transition to extra-uterine conditions.Thanks to the advanced technologies for energy generation such as solar cells and thermo- or piezo-generators the amount of electricity transformed from light, heat or mechanical pressure sources can be significantly enhanced. However, there is still a demand for effective storage devices to conserve electrical energy which addresses the wide range of large stationary applications from electric vehicles to small portable devices. Among the large variety of energy-storage systems available today, electrochemical energy sources and, in particular, supercapacitors (SC), are rather promising in terms of cost, scaling, power management, life cycle and safety. Therefore, this review surveys recent achievements in the development of SC based on composites of such carbon-derived materials as graphene (G) and reduced graphene oxide (rGO) with carbon nanotubes (CNT). Various factors influencing the specific capacitance are discussed, while specific energy and power as well as cycling stability of SC with G/rGO-CNT composite electrode materials are overviewed.The B.1.1.7 variant of the SARS-CoV-2 virus shows enhanced infectiousness over the wild type virus, leading to increasing patient numbers in affected areas. Amino acid exchanges within the SARS-CoV-2 spike protein variant of B.1.1.7 affect inter-monomeric contact sites within the trimer (A570D and D614G) as well as the ACE2-receptor interface region (N501Y), which comprises the receptor-binding domain (RBD) of the spike protein. However, the molecular consequences of mutations within B.1.1.7 on spike protein dynamics and stability or ACE2 binding are largely unknown. Here, molecular dynamics simulations comparing SARS-CoV-2 wild type with the B.1.1.7 variant revealed inter-trimeric contact rearrangements, altering the structural flexibility within the spike protein trimer. Furthermore, we found increased flexibility in direct spatial proximity of the fusion peptide due to salt bridge rearrangements induced by the D614G mutation in B.1.1.7. This study also implies a reduced binding affinity for B.1.1.7 with ACE2, as the N501Y mutation restructures the RBD-ACE2 interface, significantly decreasing the linear interaction energy between the RBD and ACE2. Our results demonstrate how mutations found within B.1.1.7 enlarge the flexibility around the fusion peptide and change the RBD-ACE2 interface. We anticipate our findings to be starting points for in depth biochemical and cell biological analyses of B.1.1.7.The Special Issue in Cancers, “The Biological and Clinical Aspects of Merkel Cell Carcinoma”, walks the avid reader through the interesting and sometimes even mysterious facets of Merkel cell carcinoma (MCC), starting at its carcinogenesis to also cover innovative treatment options .Vulvovaginal candidiasis (VVC) is a vulvar/vaginal infection that affects approximately 75% of women worldwide. The current treatment consists of antimicrobials with hepatotoxic properties and high drug interaction probabilities. Therefore, this study aimed to develop a new treatment to VVC based on micelles containing curcumin (CUR) dispersed in a ureasil-polyether (U-PEO) hybrid. The physical-chemical characterization was carried out in order to observe size, shape, crystallinity degree and particle dispersion in the formulation and was performed by dynamic light scattering (DLS), scanning electron microscopy (SEM), X-ray diffraction (XRD) and through in vitro release study. The results of DLS and SEM exhibited micelles with 35 nm, and encapsulation efficiency (EE) results demonstrated 100% of EE to CUR dispersed in the U-PEO, which was confirmed by the DRX. The release results showed that CUR loaded in U-PEO is 70% released after 10 days, which demonstrates the potential application of this material in different pharmaceutical forms (ovules and rings), and the possibility of multidose based on a single application, suggesting a higher rate of adherence.

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