The natural compound Zerumbone (hereinafter referred to as ZER), a monocyclic sesquiterpenoid, has been reported to possess many pharmacological properties, including antioxidant and anti-inflammatory properties. This study aimed to investigate the underlying mechanism of ZER against acute liver injury (ALI) in CCl₄-induced mice models. ICR mice were pretreated intraperitoneally with ZER for five days, then received a CCl₄ injection two hours after the last ZER administration and were sacrificed 24 h later. Examination of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and the histopathological analysis confirmed the hepatoprotective effect of ZER. Biochemical assays revealed that ZER pretreatment recovered the activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), restored the glutathione (GSH) reservoir, and reduced the production of malondialdehyde (MDA), all in a dose-dependent manner. Furthermore, administration of ZER in vivo reduced the release amounts of pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) and inhibited the increased protein levels of Toll-like receptor 4 (TLR4), nuclear factor-kappaB (NF-κB) p-p65, and cyclooxygenase (COX-2). Further studies in lipopolysaccharide (LPS)-induced Raw264.7 inflammatory cellular models verified that ZER could inhibit inflammation via inactivating the TLR4/NF-κB/COX-2 pathway. Thus, our study indicated that ZER exhibited a hepatoprotective effect against ALI through its antioxidant and anti-inflammatory activities and the possible mechanism might be mediated by the TLR4/NF-κB/COX-2 pathway. Collectively, our studies indicate ZER could be a potential candidate for chemical liver injury treatment.

Zerumbone has been reported to maintain the anti-cancer effects in many malignant cells. However, the effect and mechanism of Zerumbone on esophageal squamous cell carcinomas (ESCC) is rarely investigated. Here we report the inhibitory effect of Zerumbone (hereinafter referred to as ZER) on ESCC migration and the underlying molecular mechanism. ZER could inhibit the migration of human esophageal squamous cancer KYSE-30 cells and KYSE-150 cells. ZER induced Rac1 protein down-regulation in a dose- and time-dependent manner. The reduction of Rac1 protein was crucial for ZER-induced inhibition of cell migration, as Rac1 knockdown could enhance ZER-induced inhibition of cell migration. We further demonstrated that the decrease of Rac1 after ZER treatment is via proteasome-dependent degradation pathway, and ZER treatment drastically enhanced ubiquitination of Rac1, which finally caused Rac1 degradation. Collectively, our results indicated that ZER inhibits cell migration by suppressing Rac1 expression. This suppresion is achieved through promoting Rac1 ubiquitination and degradation. Thus, the study raises the possibility of ZER as a potential drug for ESCC due to its ability to inhibit cell migration.

Background: Assisted reproductive technology still presents a significant challenge when it comes to repeated implantation failure (RIF). To address this issue, personalized embryo transfer (pET) has been suggested as a potential solution. pET involves guiding the embryo transfer process based on an analysis of endometrial receptivity, known as endometrial receptivity analysis (ERA). However, the clinical value of this approach remains uncertain. Methods: We conducted a comprehensive analysis of 14 studies pertaining to pET guided by ERA in patients with RIF. The outcomes evaluated in these studies encompassed the clinical pregnancy rate (CPR), implantation rate, and live birth rate (LBR). In addition, we performed subgroup analysis by considering different definitions of RIF and utilizing various ERA techniques, such as traditional and optimized gene-enhanced approaches. Results: In general, the utilization of ERA-guided pET did not have a substantial impact on CPR (relative risk [RR], 1.25 [95% CI, 0.85–1.84]), implantation rate (RR, 1.59 [95% CI, 0.89–2.82]), or LBR (RR, 1.55 [95% CI, 0.96–2.50]) compared with standard transfer. However, the implementation of optimized gene-enhanced ERA methods demonstrated significant enhancements in CPR (RR, 2.04 [95% CI, 1.53–2.72]) and LBR (RR, 2.61 [95% CI, 1.58–4.31]). Conclusion: While ERA-guided pET shows limited efficacy in improving pregnancy outcomes in patients with RIF, there lies potential in optimizing gene-enhanced ERA techniques to augment both clinical pregnancy rates and LBRs.