10/13/2024


Bioluminescence resonance energy transfer (BRET) is the non-radiative transfer of energy from a bioluminescent protein donor to a fluorophore acceptor. It shares all the formalism of Förster resonance energy transfer (FRET) but differs in one key aspect that the excited donor here is produced by biochemical means and not by an external illumination. Often the choice of BRET source is the bioluminescent protein Renilla luciferase, which catalyzes the oxidation of a substrate, typically coelenterazine, producing an oxidized product in its electronic excited state that, in turn, couples with a proximal fluorophore resulting in a fluorescence emission from the acceptor. The acceptors pertinent to this discussion are semiconductor quantum dots (QDs), which offer some unrivalled photophysical properties. Amongst other advantages, the QD's large Stokes shift is particularly advantageous as it allows easy and accurate deconstruction of acceptor signal, which is difficult to attain using organic dyes or fluorescent proteins. QD-BRET systems are gaining popularity in non-invasive bioimaging and as probes for biosensing as they don't require external optical illumination, which dramatically improves the signal-to-noise ratio by avoiding background auto-fluorescence. Despite the additional advantages such systems offer, there are challenges lying ahead that need to be addressed before they are utilized for translational types of research.Gene therapy with viral vectors has significantly advanced in the past few decades, with adenovirus being one of the most commonly employed vectors for cancer gene therapy. Adenovirus vectors can be divided into 2 groups (1) replication-deficient viruses; and (2) replication-competent, oncolytic (OVs) viruses. Replication-deficient adenoviruses have been explored as vaccine carriers and gene therapy vectors. Oncolytic adenoviruses are designed to selectively target, replicate, and directly destroy cancer cells. Additionally, virus-mediated cell lysis releases tumor antigens and induces local inflammation (e.g., immunogenic cell death), which contributes significantly to the reversal of local immune suppression and development of antitumor immune responses ("cold" tumor into "hot" tumor). There is a growing body of evidence suggesting that the host immune response may provide a critical boost for the efficacy of oncolytic virotherapy. Additionally, genetic engineering of oncolytic viruses allows local expression of immune therapeutics, thereby reducing related toxicities. Therefore, the combination of oncolytic virus and immunotherapy is an attractive therapeutic strategy for cancer treatment. In this review, we focus on adenovirus-based vectors and discuss recent progress in combination therapy of adenoviruses with immunotherapy in preclinical and clinical studies.The alteration of redox homeostasis constitutes an important etiological feature of common human malignancies. We investigated DNA damage, selenium (Se) levels and the expression of cytoprotective genes involved in (1) the KEAP1/NRF2/ARE pathway, (2) selenoprotein synthesis, and (3) DNA methylation and histone deacetylation as putative key players in redox status dysregulation in the blood of urinary bladder cancer (UBC) patients. The study involved 122 patients and 115 control individuals. The majority of patients presented Ta and T1 stages. UBC recurrence occurred within 0.13 to 29.02 months. DNA damage and oxidative DNA damage were significantly higher in the patients compared to the controls, while plasma Se levels were significantly reduced in the cases compared to the controls. https://www.selleckchem.com/products/sgc707.html Of the 25 investigated genes, elevated expression in the peripheral blood leukocytes in patients was observed for NRF2, GCLC, MMP9 and SEP15, while down-regulation was found for KEAP1, GSR, HMOX1, NQO1, OGG1, SEPW1, DNMT1, DNMT3A and SIRT1. After Bonferroni correction, an association was found with KEAP1, OGG1, SEPW1 and DNMT1. Early recurrence was associated with the down-regulation of PRDX1 and SRXN1 at the time of diagnosis. Peripheral redox status is significantly dysregulated in the blood of UBC patients. DNA strand breaks and PRDX1 and SRXN1 expression may provide significant predictors of UBC recurrence.Background Magnetic resonance relaxometry (MRR) offers highly reproducible pixel-wise parametric maps of T1 and T2 relaxation times, reflecting specific tissue properties, while diffusion-tensor imaging (DTI) is a promising technique for the characterization of microstructural changes, depending on the directionality of molecular motion. Both MMR and DTI may be used for non-invasive assessment of parenchymal changes caused by kidney injury or graft dysfunction. Methods We examined 46 patients with kidney transplantation and 16 healthy controls, using T1/T2 relaxometry and DTI at 3 T. Twenty-two early transplants and 24 late transplants were included. Seven of the patients had prior renal biopsy (all of them dysfunctional allografts; 6/7 with tubular atrophy and 7/7 with interstitial fibrosis). Results Compared to healthy controls, T1 and T2 relaxation times in the renal parenchyma were increased after transplantation, with the highest T1/T2 values in early transplants (T1 1700 ± 53 ms/T2 83 ± 6 ms compared to T1 1514 ± 29 ms/T2 78 ± 4 ms in controls). Medullary and cortical ADC/FA values were decreased in early transplants and highest in controls, with medullary FA values showing the most pronounced difference. Cortical renal T1, mean medullary FA and corticomedullary differentiation (CMD) values correlated best with renal function as measured by eGFR (cortical T1 r = -0.63, p less then 0.001; medullary FA r = 0.67, p less then 0.001; FA CMD r = 0.62, p less then 0.001). Mean medullary FA proved to be a significant predictor for tubular atrophy (p less then 0.001), while cortical T1 appeared as a significant predictor of interstitial fibrosis (p = 0.003). Conclusion Cortical T1, medullary FA, and FA CMD might serve as new imaging biomarkers of renal function and histopathologic microstructure.A key element in phage therapy is the establishment of large phage collections, termed herein "banks", where many well-characterized phages, ready to be used in the clinic, are stored. These phage banks serve for both research and clinical purposes. Phage banks are also a key element in clinical phage microbiology, the prior treatment matching of phages and antibiotics to specific bacterial targets. A worldwide network of phage banks can promote a phage-based solution for any isolated bacteria. Herein, we describe the Israeli Phage Bank (IPB) established in the Hebrew University, Jerusalem, which currently has over 300 phages matching 16 bacteria, mainly pathogens. The phage bank is constantly isolating new phages and developing methods for phage isolation and characterization. The information on the phages and bacteria stored in the bank is available online.