Molecular complexity of diffuse large B-cell lymphoma: a molecular perspective and therapeutic implications.

Diffuse large B-cell lymphoma (DLBCL) stands as a formidable challenge in the landscape of non-Hodgkin's lymphomas. This review illuminates the remarkable strides made in comprehending DLBCL's molecular intricacies and devising targeted treatments. DLBCL, the most prevalent non-Hodgkin's lymphoma, has seen transformative progress in its characterization. Genetic investigations, led by high-throughput sequencing, have unveiled recurrent mutations in genes such as MYC, BCL2, and BCL6, casting light on the underlying genetic chaos propelling DLBCL's aggressiveness. A pivotal facet of this understanding centers on cell signaling pathways. Dysregulation of B-cell receptor (BCR) signaling, NF-κB, PI3K/Akt/mTOR, JAK/STAT, Wnt/ß-Catenin, and Toll-like receptor pathways plays a critical role in DLBCL pathogenesis, offering potential therapeutic targets. DLBCL's complex tumor microenvironment (TME) cannot be overlooked. The dynamic interplay among tumor cells, immune cells, stromal components, and the extracellular matrix profoundly influences DLBCL's course and response to therapies. Epigenetic modifications, including DNA methylation and histone changes, add another layer of intricacy. Aberrant epigenetic regulation plays a significant role in lymphomagenesis, offering prospects for epigenetic-based therapies. Promisingly, these molecular insights have spurred the development of personalized treatments. Targeted therapies and immunotherapies, guided by genomic profiling and molecular classification, are emerging as game-changers in DLBCL management. In conclusion, this review underscores the remarkable strides in understanding DLBCL's molecular underpinnings, spanning genetics, cell signaling, the tumor microenvironment, and epigenetics. These advances pave the way for more effective, personalized treatments, renewing hope for DLBCL patients.

Nicaraven-loaded electrospun wound dressings promote diabetic wound healing via proangiogenic and immunomodulatory functions: a preclinical investigation.

The current study developed a biopolymer-based wound dressing by electrospinning of Nicaraven-loaded collagen solution. Firstly, collagen was dissolved in acetic acid, and then Nicaraven was added to the polymeric solution at three different concentrations of 2 w/w%, 4 w/w%, and 6 w/w%. The resulting solution was then electrospun. Various experiments were performed to characterize the produced wound dressings. In vitro studies showed that Nicaraven-loaded scaffolds were not toxic against L929 fibroblast cells and protected them against oxidative stress. Wound healing potential of different formulations of Nicaraven-loaded collagen wound dressings was studied in a rat model of the excisional diabetic wound. The study showed that the collagen/4% Nicaraven and collagen/6% Nicaraven wound dressings exhibited a significantly higher percentage of wound closure, the thickness of the epithelium, and collagen deposition compared with collagen/2% Nicaraven, collagen-only, and sterile gauze groups. Gene expression study showed that the developed wound dressings reduced the tissue expression levels of glutathione peroxidase, NFKß, and matrix metalloproteinase 9 (MMP9) genes. In addition, in the wounds treated with collagen/4% Nicaraven and collagen/6% Nicaraven scaffolds, wound healing was associated with a higher tissue expression level of b-FGF, VEGF, and collagen type I genes. Overall, wound healing activity of collagen/4% Nicaraven and collagen/6% Nicaraven wound dressings was not significantly different. This study implies that collagen wound dressings incorporated with 4% and 6% Nicaraven can be considered a potential candidate to treat diabetic wounds in the clinic.

Frequent loss of BTG1 activity and impaired interactions with the Caf1 subunit of the Ccr4-Not deadenylase in non-Hodgkin lymphoma.

Mutations in the highly similar genes B-cell translocation gene 1 (BTG1) and BTG2 are identified in approximately 10-15% of non-Hodgkin lymphoma cases, which may suggest a direct involvement of BTG1 and BTG2 in malignant transformation. However, it is unclear whether or how disease-associated mutations impair the function of these genes. Therefore, we selected 16 BTG1 variants based on in silico analysis. We then evaluated (i) the ability of these variants to interact with the known protein-binding partners CNOT7 and CNOT8, which encode the Caf1 catalytic subunit of the Ccr4-Not deadenylase complex; (ii) the activity of the variant proteins in cell cycle progression; (iii) translational repression; and (iv) mRNA degradation. Based on these analyses, we conclude that mutations in BTG1 may contribute to malignant transformation and tumor cell proliferation by interfering with its anti-proliferative activity and ability to interact with CNOT7 and CNOT8.