Lyn kinase, a member of the Src family of kinases, is a critical regulator of immune cell signaling, regulating key processes including activation, proliferation, survival, and apoptosis. Dysregulated Lyn kinase activity causes haematological malignancies, autoimmune disorders, solid tumors, neurodegenerative, cardiovascular, and metabolic disorders. Here, we aimed to provide a comprehensive account of Lyn kinase biology, highlighting its structural features, regulatory roles in immune and cellular signaling, and pathological implications across diseases, including cancers, neurodegenerative disorders, autoimmune diseases, and metabolic disorders. We further examined emerging therapeutic strategies, including small-molecule inhibitors, monoclonal antibodies, and natural compounds, and highlighted the therapeutic potential of Lyn kinase as a promising drug target. Overexpression of Lyn contributes to tumor growth, metastasis, and resistance to treatment in leukaemia, prostate, breast, lung, and pancreatic cancers. Beyond oncology, emerging evidence links Lyn kinase to neuroinflammation, synaptic dysfunction, and metabolic regulation, further underscoring its broad disease relevance. Lyn kinase is considered a viable therapeutic target, with ongoing research focusing on small-molecule inhibitors, monoclonal antibodies, and natural compounds like flavonoids and polyphenols that have exhibited promising preclinical and clinical outcomes.We summarized current insights into Lyn kinase biology, highlighting its pathological significance and discussing therapeutic opportunities arising from the modulation of this enzyme.

Mesenchymal stem cells (MSCs) are adult stem cells with the capacity to differentiate into several cell types, including hepatocyte-like cells, neural-like cells, islet-like clusters and so on. However, the differentiation into ovarian-related cells such as ovarian granulosa cells (OGCs) has not been well studied. Here, we established an efficient culture system to differentiate human umbilical cord mesenchymal stem cells (HUCMSCs) into pre-granulosa cells, which can further mature into granulosa-like cells. HUCMSCs were cocultured with hormones (E2, FSH) and cytokines (TGF-β), a simple differentiation method was used to induce morphological changes and positive expression of forkhead transcription factor (FOXL2). In the process of further mature, the cells differentiated into mature granulosa-like cells, expressed mature granulosa cell markers (FSHR, AMHR2, CYP19A1) and likely possesses some granulosa cell hormone secretion capacity. In conclusion, we successfully established an efficient protocol to generate pre-granulosa cells from HUCMSCs that can further differentiate into mature granulosa-like cells, opening a new avenue for the further study of therapies for female reproductive health.

Specificity protein 7 (Sp7) is essential for osteoblast differentiation and bone formation. In humans, Sp7 gene mutations are associated with skeletal abnormalities, including osteogenesis imperfecta. Ubiquitylation regulates the cellular levels of Sp7 protein. However, the role of the largest class of E3 ubiquitin ligases in the turnover of Sp7 protein remains unknown. Here, we report for the first time that both catalytic subunits of multi-subunit RING-box E3 ligase, Rbx1 and Rbx2, are expressed in the skeletal tissues and during osteoblast differentiation. In situ immunofluorescence and biochemical fractionation revealed that in osteoblasts, Rbx1 and Rbx2 E3 ligase reside in both the cell cytoplasm and nucleus. The coimmunoprecipitation experiment in primary osteoblasts showed that endogenous Rbx1 and Rbx2 E3 ligase form a molecular complex with the Sp7 protein. Both Rbx1 and Rbx2 enzymes target Sp7 protein for ubiquitination. Sp7 protein is degraded by Rbx1 and Rbx2 enzymes in a dose-dependent manner in both osseous and non-osseous cells. Chemical inhibition established the requirement of Rbx1 and Rbx2-mediated ubiquitination and degradation of Sp7 protein by the proteasomal pathway. In-silico analysis identified three evolutionarily conserved lysines, K-55, K-227, and K-229, in the Sp7 protein as potential targets for ubiquitination. A panel of Sp7 deletion and point mutants was generated that established the critical requirement of lysine-55 for Rbx1 and Rbx2-mediated ubiquitination and degradation. Deleting the Rbx2 gene in osteoprogenitors led to a significant accumulation of Sp7 protein, enhanced expression of osteoblast marker genes, and accelerated matrix mineralization.

U. K. Misra and S. V. Pizzo, "Epac1-Induced Cellular Proliferation in Prostate Cancer Cells Is Mediated by B-Raf/ERK and mTOR Signaling Cascades," Journal of Cellular Biochemistry 108, no. 4 (2009): 998-1011, https://doi.org/10.1002/jcb.22333. The above article, published online on 1 September 2009 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Christian Behl; and Wiley Periodicals LLC. The retraction has been agreed due to concerns raised by third parties. Specifically, duplication of image elements has been detected between Figures 2A and 4B, between Figure 3B and 3D, and between Figures 3B and 4C. In all instances, these image elements have been used to represent different experimental conditions. An institutional review confirmed the validity of the concerns. Accordingly, the article is retracted as the editors have lost trust in the accuracy and integrity of the whole body of data and consider the conclusions of the article invalid. The authors have been informed of the decision of retraction.

U. K. Misra, F. Wang, and S. V. Pizzo, "Transcription Factor TFII-I Causes Transcriptional Upregulation of GRP78 Synthesis in Prostate Cancer Cells," Journal of Cellular Biochemistry 106, no. 3 (2009): 381-389, https://doi.org/10.1002/jcb.22016. The above article, published online on 18 December 2008 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Christian Behl; and Wiley Periodicals LLC. The retraction has been agreed due to concerns raised by third parties. Specifically, duplication of image elements has been detected between Figures 1A and 3, and within Figure 3. In all instances, these image elements have been used to represent different experimental conditions. An institutional review confirmed the validity of the concerns. Accordingly, the article is retracted as the editors have lost trust in the accuracy and integrity of the whole body of data and consider the conclusions of the article invalid. The authors have been informed of the decision of retraction.