Kisspeptin-10

This study investigated the effects of Kisspeptin-10 (Kp-10) on HIV-1 Tat-induced blood-brain barrier (BBB) permeability and oxidative stress using both in vivo and in vitro models. In vivo, one hour after intraperitoneal administration of 50 nmol/kg (DSS)*6-Kp-10, mice were intravenously injected with HIV-1 Tat (100 μg/kg). Markers of oxidative stress, inflammatory cytokines, and BBB integrity were then evaluated. In vitro, bEnd.3 cells were treated with HIV-1 Tat and Kp-10, and endothelial permeability, Claudin-5 expression, and RhoA/ROCK signaling were assessed. HIV-1 Tat increased oxidative stress in the cortical tissue of mice, as evidenced by elevated malondialdehyde (MDA) and reduced levels of catalase (CAT) activity, glutathione peroxidase (GSH-Px) activity, and total antioxidant capacity (T-AOC). These effects were attenuated by Kp-10 administration. Additionally, Kp-10 suppressed the expression of pro-inflammatory cytokines, including interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-alpha (TNF-α), in response to HIV-1 Tat. Notably, Kp-10 mitigated HIV-1 Tat-induced BBB dysfunction by upregulating Claudin-5 expression in the cortical tissue of mice. In vitro, bEnd.3 cells were treated with HIV-1 Tat in the presence of Kp-10 at various concentrations. Our results demonstrated that Kp-10 prevented HIV-1 Tat-induced increases in trans-endothelial permeability and reductions in transepithelial electrical resistance (TEER) by upregulating Claudin-5 expression. Furthermore, Kp-10 inhibited the activation of the RhoA/Rho-associated protein kinase (RhoA/ROCK) signaling pathway in bEnd.3 cells. Overexpression of the RhoA-GTP Q63L mutant abolished the protective effects of Kp-10, suggesting that these effects are mediated through the RhoA/ROCK axis. These findings suggest that Kp-10 might be a potential therapeutic agent for HIV-associated neurocognitive disorders (HAND).

Esophageal cancer (EC) treatment remains challenging due to the disease's aggressive nature, frequent late‐stage diagnosis, and the need for effective multimodal therapies with minimal side effects. Kisspeptin‐10, a naturally occurring neuropeptide and known GPR54 agonist, has been shown to significantly influence tumor growth and progression. However, its specific role in EC remains poorly understood. To address this knowledge gap, we designed this study to investigate the role of Kisspeptin‐10 (KP‐10) and its receptor GPR54 in EC. We first assessed KP‐10 expression in esophageal carcinoma tissues and cell lines using immunohistochemistry, real‐time PCR, and western blot analysis. Through lentivirus transduction, we manipulated KP‐10 expression and evaluated its effects on cell viability, apoptosis, migration, stemness, epithelial‐mesenchymal transition (EMT), and the SIX1/Wnt/β‐catenin signaling pathway. These evaluations were performed using CCK‐8 assay, TUNEL assay, Transwell assay, mammosphere formation assay, and western blot analysis. Our results demonstrated significantly reduced expression of both KP‐10 and GPR54 in EC samples and cell lines compared to healthy tissues. Following KP‐10 overexpression in KYSE150 EC cells, we observed inhibited cell growth, promoted apoptosis, decreased cell migration, reduced cancer stem cell properties, and suppressed EMT. Furthermore, KP‐10 overexpression inhibited the Wnt/β‐catenin signaling pathway, an effect that was reversed by SIX1 overexpression, suggesting that KP‐10's impact on this pathway is mediated through SIX1. These findings indicate that KP‐10 plays a crucial role in suppressing EC progression and represents a promising therapeutic target for clinical treatment. However, more comprehensive studies are needed to fully elucidate the underlying mechanisms and explore the clinical potential of KP‐10 in EC therapy.