The balance between cell proliferation and programmed cell death plays a crucial role in malignant development. Bcl-2 family proteins, including proapoptosis protein Bak and antiapoptosis protein Bcl-2, regulate the apoptotic process. Mutation of the p53 gene, which results in P53 protein accumulation, was observed in many types of human cancer. The aim of our study was to evaluate immunohistochemical Bcl-2, Bak, and P53 protein expression and the relation between these proteins in conjunctival and eyelid benign and malignant tumors. We examined a series of 42 papillomas (CEP), 12 squamous cell cancers (SCC), and 19 cases of basal cell cancer (BCC). The age in the CEP group ranged from 18-94 years, and in the SCC and BCC groups from 42-87 years. Staining patterns were correlated with sex, age, and tumor localization. P53 protein-positive immunostaining was observed in 71% of cases, Bcl-2 in 83.9%, and Bak in 74.2 cases in the SCC and BCC groups. In the CEP group, P53 overexpression was observed in 90.5% of cases, Bcl-2 in 71.4%, and Bak in 76.2%. No statistically significant correlation was found between examined protein expression and sex, age, and tumor localization. An inverse correlation was observed between P53 and Bak protein expression in the CEP group. No statistically significance correlation was noted between Bcl-2 and P53 and Bcl-2 and Bak protein expression in both examined groups. The obtained data suggests that P53 and Bcl-2 protein expression coupled with decreasing Bak expression are associated with apoptosis and proliferation as well as malignant progression in conjunctival and eyelid tumors.
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http://dx.doi.org/10.1196/annals.1299.135 | DOI Listing |
Brief Bioinform
November 2024
Biotherapeutics Molecule Discovery, Boehringer Ingelheim Pharmaceutical Inc., 900 Ridgebury Road, Ridgefield, CT 06877, United States.
Antibody generation requires the use of one or more time-consuming methods, namely animal immunization, and in vitro display technologies. However, the recent availability of large amounts of antibody sequence and structural data in the public domain along with the advent of generative deep learning algorithms raises the possibility of computationally generating novel antibody sequences with desirable developability attributes. Here, we describe a deep learning model for computationally generating libraries of highly human antibody variable regions whose intrinsic physicochemical properties resemble those of the variable regions of the marketed antibody-based biotherapeutics (medicine-likeness).
View Article and Find Full Text PDFCirc Genom Precis Med
January 2025
Centre for Heart Lung Innovation, University of British Columbia, Vancouver. (K.H., M.A., L.R., Y.L., A.S., H.H., L.R.B., Z.W.L.).
Background: Protein-truncating mutations in the titin gene are associated with increased risk of atrial fibrillation. However, little is known about the underlying pathophysiology.
Methods: We identified a heterozygous titin truncating variant (TTNtv) in a patient with unexplained early onset atrial fibrillation and normal ventricular function.
Front Immunol
January 2025
Immunology Research Center, National Health Research Institute, Zhunan, Taiwan.
CASK, a MAGUK family scaffold protein, regulates gene expression as a transcription co-activator in neurons. However, the mechanism of CASK nucleus translocation and the regulatory function of CASK in myeloid cells remains unclear. Here, we investigated its role in H5N1-infected macrophages.
View Article and Find Full Text PDFFront Immunol
January 2025
Department of Nephrology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
Rationale: Acute kidney injury (AKI) is a clinical syndrome associated with a multitude of conditions. Although renal replacement therapy (RRT) remains the cornerstone of treatment for advanced AKI, its implementation can potentially pose risks and may not be readily accessible across all healthcare settings and regions. Elevated lactate levels are implicated in sepsis-induced AKI; however, it remains unclear whether increased lactate directly induces AKI or elucidates the underlying mechanisms.
View Article and Find Full Text PDFFront Immunol
January 2025
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
The innate immune system promptly detects and responds to invading pathogens, with a key role played by the recognition of bacterial-derived DNA through pattern recognition receptors. The Z-DNA binding protein 1 (ZBP1) functions as a DNA sensor inducing type I interferon (IFN) production, innate immune responses and also inflammatory cell death. ZBP1 interacts with cytosolic DNA via its DNA-binding domains, crucial for its activation.
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