BTK (Bruton Tyrosine Kinase)

The ISOIM/siBTK@Exosome was biocompatible and biosafe in vivo without damage on the major organs in H&E staining. The prepared ISOIM/siBTK@Exosome may provide novel targeted therapeutic strategy to be applied in the clinical management of patients with DLBCL.

By integrating transcriptomic data with functional assays, our findings suggest that high salt-induced neutrophil activation involves mitochondrial ROS production, which subsequently activates p38 MAPK and engages FOS-, Bruton's tyrosine kinase (BTK)-, and cyclooxygenase 2 (COX2)-dependent pathways. Remarkably, the plasticity of the neutrophil transcriptome in response to high salt was further evidenced by the upregulation of genes typically associated with other cell types, including semenogelin 1 (SEMG1), intercellular adhesion molecule-4 (ICAM4), tripartite motif69 (TRIM69), amphiregulin (AREG), oncostatin (OSM), and transducer of ERBB2-1 (TOB1), suggesting a broader role for neutrophils in different biological processes beyond their participation in innate immunity.

However, no review has comprehensively addressed the cardiovascular toxicity of TFKs inhibitors. This review provides a comprehensive and systematic analysis of the cardiovascular toxicity profiles of TFK inhibitors (TFKis), focusing on underlying molecular mechanisms, comparing toxicity across different agents and generations, and discussing clinical implications.

TKI-induced renal injury characteristically presents with edema, hypertension and significant proteinuria, with renal-limited TMA as the predominant histopathological finding. Timely recognition and prompt discontinuation of the offending TKI, coupled with appropriate supportive nephroprotective management, generally yield favorable long-term renal outcomes with preservation of kidney function.

Additionally, the potential of drug delivery systems to address the aforementioned limitations of TPD formulations is discussed, as they may substantially enhance TPD therapeutic efficacy.​ This review provides a comprehensive overview of current TPD types, their research progress in different diseases, and strategies for effective application of TPD. It is expected to offer valuable guidance for the development of TPD formulations and promote their clinical translation.

Altered expression of key surface markers (CD25 and CD38) upon silencing of either PTPN13 or β-catenin further supports this interpretation. In conclusion, our study identifies the PTPN13-β-catenin axis as a critical regulator of lymphoid cell homeostasis and highlights its disruption as a potential driver of haematological abnormalities in patients carrying PTPN13 mutations.

He had tried superpotent topical corticosteroids and oral prednisolone, as well as emollients, none of which had improved his symptoms...Tralokinumab was trialled for 12 weeks, as this has a single therapeutic target (interleukin-13), but unfortunately there was no improvement. Following discussion with the immunologists, he was commenced on upadacitinib as this was felt to have a more targeted immunosuppressive effect above agents such as methotrexate and dupilumab. We await his next follow-up appointment to assess response. This case highlights the complexity of treating an immunocompromised individual with immunosuppressive agents, when the cause of their immunosuppression is unknown.

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PCA and FEL results further revealed the dynamic variations caused by these mutations. These findings underline the significant impact of mutations T474M and C481S on the binding free energy, highlighting the importance of these residues in ibrutinib-BTK interactions.

P3, N=735, Recruiting, Merck Sharp & Dohme LLC | Trial completion date: Mar 2035 --> Jul 2035 | Trial primary completion date: Mar 2035 --> Jun 2032

We present a case of invasive cutaneous mucormycosis in an elderly man with chronic lymphocytic leukemia (CLL), who was receiving a Bruton tyrosine kinase (BTK)-targeted protein degrader trial drug (BGB-16673), obinutuzumab, a newer anti-CD20 monoclonal therapy, and idelalisib, a phosphoinositide 3-kinase inhibitor. Clinical cure was achieved with limb amputation, given the extent of disease. This case underscores the necessity of a low index of suspicion for mucormycosis on presentation, critical appraisal of the patient's risk factors, and a multimodal approach to diagnosis.