Molecular Biology Reports最新文献

Background: Various factors, cause recurrent spontaneous abortion (RSA); however, nearly half of the cases remain unexplained. Most abortions occur during the first trimester, highlighting the importance of early molecular and immunological investigations. Growing evidence links unexplained RSA to maternal immune dysregulation. Complement component C3a and Tumor Necrosis Factor-alpha (TNF-α) are key inflammatory mediators that may serve as biomarkers for RSA.

Methods and results: Seventy-five women in their first trimester of pregnancy were enrolled (33 with normal pregnancies and 42 with RSA). Serum protein concentrations were quantified via Enzyme Linked Immunosorbent Assay (ELISA), and mRNA transcripts in whole blood were analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Serum C3a (p = 0.004) and TNF-α (p = 0.016) were significantly elevated in RSA group. TNF-α mRNA expression was also significantly increased, reflected by lower delta quantification cycle values (p = 0.0003; post hoc power = 98%), while C3 mRNA showed no significant difference. Receiver Operating Characteristic (ROC) curve analyses indicated moderate diagnostic accuracy for serum C3a, TNF-α, and higher accuracy for TNF-α expression with Area Under the Curve (AUC) of 0.776. Correlation analysis indicated a significant association between maternal age and TNF-α transcription. A strong correlation was observed between C3a and TNF-α proteins (p < 0.0001).

Conclusions: C3a and TNF-α, particularly TNF-α mRNA, may serve as potential biomarkers for RSA. These findings support immune dysregulation as a pathogenic factor and suggest that combined protein and gene expression analyses may improve early risk identification.

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.