Molecular Biology Reports最新文献

Tyrosine kinase inhibitors (TKIs) have proven effective in treating chronic myeloid leukemia (CML), but some patients do not benefit from these drugs because TKI-resistant CML cells persist. Galectin-1 (Gal-1) and Galectin-3 (Gal-3) have emerged as critical modulators of CML cell drug resistance. High intracellular Gal-1 levels promote multidrug resistance in vitro by inducing MDR1 expression through p38 MAPK and NF-κB activation, enhancing drug efflux and diminishing anticancer drug efficacy. The effects of Gal-1 have so far been investigated only in in vitro systems; data from in vivo mouse and human studies are not available. Activation of GSK-3β induces Gal-3, which stabilizes anti-apoptotic proteins belonging to the Bcl-2 family and confers resistance to apoptosis-inducing agents in vitro. However, this pathway has not yet been evaluated in CML mouse models or in patients, particularly in the context of TKI resistance mechanisms. Gal-3 is induced by the bone marrow microenvironment (BMME) and promotes AKT and ERK activation to support CML cell proliferation, multidrug resistance (MDR), chemotaxis, and BM lodgment. However, it has not yet been elucidated how Gal-3 is induced by BM stromal cells in CML cells. Furthermore, Gal-3 suppresses the formation of the SERPINA1-albumin complex in vitro, abolishing its growth-inhibitory effects and enhancing paracrine proliferation of CML cells. Although preclinical evidence shows that elevated intracellular Gal-3 protein levels promote drug resistance in CML, these findings have not yet been confirmed at the clinical level. This review underscores that both galectins are critical regulators of CML pathophysiology and highlight their potential as therapeutic targets to overcome TKI resistance.

Background: Marine fish eggs exhibit transversal morphological characteristics that complicate their identification. It is estimated that 75% of pelagic eggs possess oil globule(s). Identifying these eggs provides valuable information about spawning biomass and potential spawning areas for commercially important and threatened species. Molecular markers, such as the FISH (COI gene), enable a precise identification and exploration of the genetic variability within fish populations. San Vicente Bay, located in south-central Chile is partially protected from the effects of the Humboldt current, making it a notable spawning and nursery ground for various fish species. This study aims to identify and characterize, oil-globule-containing eggs present in the bay during October, a period that aligns with the spawning season of many species.

Methods and results: This study seek to standardize the DNA extraction method and PCR process, addressing the challenges posed by the low quantities of tissue in these eggs. We employed 2 methods, by a DNA extraction kit and Chelex resin. Out of 94 eggs, 24 samples yielded positive PCR results, corresponding to a 25% of success. All these eggs were successfully identified using genetic databases, revealing a total of 9 genera and 8 species. The observed genetic distances at the species level were low, supporting the hypothesis that the eggs originated from the same female or gene mutation rate.

Conclusion: The methods employed successfully identified fish eggs and documented species whose early life stages have not been previously reported in the bay.

Background: Juvenile cataract is characterized by the blurredness in eye lens which develops typically before the age of 18 years. Objective of the study was to delineate the underlying causative genetic defect for autosomal recessive juvenile cataract (ARJC) in an affected consanguineous multiplex, multigenerational Pakistani consanguineous family.

Methods and results: Whole-exome sequencing (WES) in an affected family member revealed a homozygous, intragenic 15.40 kb mega-deletion NG_012423.2; g.17485448_17500744del (chr20: 17,485,448-17,500,744-GRCh37/hg19) including three consecutive exons 3, 4, and 5, encompassing two domains of beaded filament structural protein 1 (BFSP1). Sanger sequencing and PCR were performed for all participants of the family which revealed the absence of the exons (3, 4, 5) in affected individuals and their presence in unaffected parents and siblings confirming the segregation of the mutation as autosomal recessive in the family under study. The large deletion potentially forced the junction of exon 2 with exon 6 at mRNA level and resulting in the shift of open reading frame. The mutation was not observed in 200 unrelated in-house controls.

Conclusion: Up to our knowledge, this is the first study reporting the largest mega-deletion encompassing 15.40 kb removal (consisting of 99 amino acids) and reveals the significant role of BFSP1 for physiologic lens function and optical properties. Our findings extend the genotypic spectrum of BFSP1-related cataract.