Zhongzhu Healthcare (China)

Acute lung injury (ALI) is a major contributor to the high morbidity and mortality associated with intestinal ischemia-reperfusion (II/R). Despite its severity, current clinical management of ALI remains limited to supportive care without addressing the cause of the disease, underscoring the urgent need to investigate the underlying mechanism and develop targeted therapies. In this study, we employed both in vitro and in vivo models to explore ALI in the setting of II/R. Our findings demonstrated that II/R-induced systemic inflammation activates nucleotide-binding oligomerization (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome in lung endothelium, leading to the release of pro-inflammatory cytokine interleukin-1β (IL-1β) and pyroptotic cell death. This cascade ultimately damages lung vasculature and exacerbates ALI. Importantly, we revealed that sevoflurane, a commonly used anesthetic, can inhibit NLRP3 inflammation under II/R condition and provide protection against ALI. Mechanistically, sevoflurane downregulates NLRP3 expression via deactivating inhibitor of nuclear factor kappa-B kinase (IKK)/nuclear factor kappa-B kinase (NF-κB) signaling pathway, and simultaneously inhibits NLRP3 activation through protein kinase A (PKA)-mediated mechanism. These findings offered novel insights into the pathogenesis of II/R-induced ALI and highlighted the therapeutic potential of sevoflurane. Given sevoflurane's established clinical use, our results could have immediate implications for patient care in II/R situations.

Acyclovir (ACV) is an effective and selective antiviral drug, and the study of its toxicology and the use of appropriate detection techniques to control its toxicity at safe levels are extremely important for medicine efforts and human health. This review discusses the mechanism driving ACV’s ability to inhibit viral coding, starting from its development and pharmacology. A comprehensive summary of the existing preparation methods and synthetic materials, such as 5-aminoimidazole-4-carboxamide, guanine and its derivatives, and other purine derivatives, is presented to elucidate the preparation of ACV in detail. In addition, it presents valuable analytical procedures for the toxicological studies of ACV, which are essential for human use and dosing. Analytical methods, including spectrophotometry, high performance liquid chromatography (HPLC), liquid chromatography/tandem mass spectrometry (LC-MS/MS), electrochemical sensors, molecularly imprinted polymers (MIPs), and flow injection–chemiluminescence (FI-CL) are also highlighted. A brief description of the characteristics of each of these methods is also presented. Finally, insight is provided for the development of ACV to drive further innovation of ACV in pharmaceutical applications. This review provides a comprehensive summary of the past life and future challenges of ACV.