Molecular Biology Reports最新文献

Background: Diabetic retinopathy (DRP) is a leading cause of vision loss associated with chronic hyperglycemia-induced oxidative stress (OS), inflammation, and mitochondrial dysfunction in retinal pigment epithelium (RPE) cells. Zingerone (ZGN), a phenolic compound derived from Zingiber officinale, exhibits potent antioxidant and anti-inflammatory properties; however, its molecular targets in diabetic retinal damage remain unclear.

Methods: This study investigated the protective effects of ZGN against high glucose (HG)-induced cytotoxicity in human ARPE-19 cells, focusing on the ROS/PARP-1/TRPM2 signaling pathway. The cells were exposed to HG (30 mM) and treated with ZGN (0-80 µM) for 24 h.

Results: HG incubation significantly increased MDA, PARP-1, ROS, intracellular calcium ion ([Ca²⁺]_i), and pro-inflammatory cytokines (IL-1β and TNF-α) in ARPE-19 cells, while decreasing GSH levels and cell viability. ZGN significantly restored OS, reduced cytokine release, [Ca²⁺]_i, and preserved mitochondrial membrane potential. Western blot and fluorescence analyses showed that ZGN reduced TRPM2 protein expression and suppressed [Ca²⁺]_i overload. Moreover, pharmacological inhibition of TRPM2 with 2-APB and of PARP-1 with DPQ enhanced the cytoprotective effects of ZGN, confirming that the ROS/PARP-1/TRPM2 axis mediates HG-induced oxidative damage.

Conclusions: These findings suggest that ZGN protects ARPE-19 cells by integrating OS with [Ca²⁺]_i homeostasis, providing a mechanistic rationale for its potential therapeutic use in preventing OS-related retinal damage in DRP.

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.