MicroRNA miR-274-5p Suppresses Found-in-Neurons Associated with Melanotic Mass Formation and Developmental Growth in Drosophila.

The hematopoietic system plays a crucial role in immune defense response and normal development, and it is regulated by various factors from other tissues. The dysregulation of hematopoiesis is associated with melanotic mass formation; however, the molecular mechanisms underlying this process are poorly understood. Here, we observed that the overexpression of miR-274 in the fat body resulted in the formation of melanotic masses. Moreover, abnormal activation of the JNK and JAK/STAT signaling pathways was linked to these consequences. In addition to this defect, miR-274 overexpression in the larval fat body decreased the total tissue size, leading to a reduction in body weight. miR-274-5p was found to directly suppress the expression of found-in-neurons (fne), which encodes an RNA-binding protein. Similar to the effects of miR-274 overexpression, fne depletion led to melanotic mass formation and growth reduction. Collectively, miR-274 plays a regulatory role in the fne-JNK signaling axis in melanotic mass formation and growth control.

MicroRNA miR-263b-5p Regulates Developmental Growth and Cell Association by Suppressing Laminin A in Drosophila.

Basement membranes (BMs) play important roles under various physiological conditions in animals, including ecdysozoans. During development, BMs undergo alterations through diverse intrinsic and extrinsic regulatory mechanisms; however, the full complement of pathways controlling these changes remain unclear. Here, we found that fat body-overexpression of Drosophila miR-263b, which is highly expressed during the larval-to-pupal transition, resulted in a decrease in the overall size of the larval fat body, and ultimately, in a severe growth defect accompanied by a reduction in cell proliferation and cell size. Interestingly, we further observed that a large proportion of the larval fat body cells were prematurely disassociated from each other. Moreover, we present evidence that miR-263b-5p suppresses the main component of BMs, Laminin A (LanA). Through experiments using RNA interference (RNAi) of LanA, we found that its depletion phenocopied the effects in miR-263b-overexpressing flies. Overall, our findings suggest a potential role for miR-263b in developmental growth and cell association by suppressing LanA expression in the Drosophila fat body.

Carfilzomib's Real-World Safety Outcomes in Korea: Target Trial Emulation Study Using Electronic Health Records.

Carfilzomib is a promising anticancer drug for relapsed/refractory multiple myeloma (RRMM). However, real-world evidence has only investigated the cardiovascular safety of carfilzomib, and there is a high demand for thorough safety evaluations. We aimed to comprehensively evaluate the risk of adverse events associated with carfilzomib in Korean patients with RRMM. We followed up with 138 matched patients with RRMM (69 KRd (carfilzomib, lenalidomide, and dexamethasone) and 69 Rd (lenalidomide and dexamethasone) users). A total of 12 adverse events were evaluated. More than 75% of adverse events occurred during the early cycle (1-6 cycles), and the incidence rate showed a tendency to decrease in the later cycle (7-12 and 13-18 cycles). Severities of most adverse events were evaluated as grade 1-2. The KRd regimen were related with significantly increased risks of dyspnea (adjusted HR (aHR) 2.27, 95% confidence interval (CI) 1.24-4.16), muscle spasm (aHR 5.12, 95% CI 1.05-24.9) and thrombocytopenia (aHR 1.84, 95% CI 1.10-3.06). Although the severities were low, carfilzomib has many side effects in treating RRMM; hence, findings on the patterns of its adverse events could lead to both effective and safe use of KRd therapy in real-world settings.