Int J Med Sci
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Observational Study
UHRF2 promotes Hepatocellular Carcinoma Progression by Upregulating ErbB3/Ras/Raf Signaling Pathway.
Emerging evidence revealed that UHRF2 was implicated in a variety of human diseases, especially in cancer. However, the biological function, clinical significance and underly mechanisms of UHRF2 in hepatocellular carcinoma (HCC) is largely unknown. We analyzed the expression of UHRF2 in 371 HCC tissues and 50 para-cancerous tissues of TCGA database. ⋯ Pearson correlation analysis indicated that the expression of UHRF2 was positively correlated with ErbB3 and its downstream targets SOS1, Ras and Raf-1. Furthermore, we found that overexpression of UHRF2 could upregulate the expression of ErbB3, SOS1, Ras and Raf-1. Our findings suggested that UHRF2 might accelerate HCC progression by upregulating ErbB3/Ras/Raf signaling pathway and it might serve as a diagnostic marker and therapeutic target for HCC patients.
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Deubiquitylating enzyme ubiquitin-specific protease 1 (USP1) has been reported to be aberrantly overexpressed in cancers, and it plays a critical role in regulating various cellular processes, such as cell proliferation, apoptosis, and cell differentiation. However, the role of USP1 in B-cell acute lymphoblastic leukemia (B-ALL) remains largely undefined. USP1 expression in 30 newly diagnosed B-ALL patients was detected by real-time PCR and western blot. ⋯ Similarly, pharmacological inhibition of USP1 by SJB3-019A significantly repressed cell proliferation and triggered B-ALL cell apoptosis. Finally, we found that inhibition of USP1 downregulated the expression of ID1 and p-AKT, and upregulated ID1 expression could reverse the suppressive effects of USP1 inhibitor in B-ALL cells. Taken together, these results demonstrate that USP1 promote B-ALL progression at least partially via the ID1/AKT signaling pathway, and USP1 inhibitors might be promising therapeutic application for B-ALL.
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Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) and agonistic antibodies against TRAIL death receptors (DR) can induce apoptosis preferentially in tumor cells while causing virtually no damage to normal cells. However, their therapeutic potential is limited by occurring resistance in tumor cells, including non-small cell lung cancer (NSCLC). Thus, elucidation of the molecular targets and signaling pathways responsible for TRAIL resistance is imperative for devising effective therapeutic strategies for TRAIL resistant cancers. ⋯ The sensitization did not regulate the death receptors DR4 and DR5. Moreover, BRD4 inhibition can block TRAIL-induced IKK activation by suppressing the transcriptional activity of NF-κB. These findings indicate that targeting combination therapy with TRAIL and BRD4 inhibitors can be a promising strategy to overcome TRAIL resistance in NSCLC.
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Background: Neonatal respiratory disorders, such as transient tachypnea of the newborn and respiratory distress syndrome, occur frequently after an elective cesarean delivery. Although conventional pulse oximetry is recommended for neonatal resuscitation, it often requires several minutes after birth to obtain a reliable signal. In a previous study, we used novel tissue oximetry equipment to detect fetal and neonatal early tissue oxygen saturation (StO2) before and immediately after vaginal delivery. ⋯ At 3 minutes after birth, the median neonatal StO2 (interquartile range) of the RD and NR groups was 41.0% (39.0%-46.0%) and 47.0% (44.3%-53.5%), respectively (P = 0.004). Finally, at 5 minutes after birth, the median neonatal StO2 (interquartile range) of the RD and NR groups was 45.0% (44.0%-52.0%) and 54.0% (49.3%-57.0%), respectively (P = 0.007). Conclusions: The StO2 values in the RD group were lower than those in the NR group at 3 and 5 minutes after birth, suggesting that neonates with low StO2 levels soon after birth may be predisposed to clinically diagnosed neonatal respiratory disorders.
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Clinical Trial
Inhibition of melanogenesis by Aster yomena callus pellet extract in melanoma cells and patients with skin pigmentation.
Plant tissue culture holds immense potential for the production of secondary metabolites with various physiological functions. We recently established a plant tissue culture system capable of producing secondary metabolites from Aster yomena. This study aimed to uncover the mechanisms underlying the potential therapeutic effects of Aster yomena callus pellet extract (AYC-P-E) on photoaging-induced skin pigmentation. ⋯ This anti-melanogenic effect was mediated by mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) phosphorylation. Treatment of subjects with skin pigmentation with AYC-P-E-containing cream formulations resulted in 3.33%, 7.06%, and 8.68% improvement in the melanin levels at 2, 4, and 8 weeks, respectively. Our findings suggest that AYC-P-E inhibits excessive melanogenesis by activating MEK/ERK and AKT signaling, potentiating its cosmetic applications in hyperpigmentation treatment.