Background and Aims Globally, NAFLD is one of the most common liver disorders, with an estimated prevalence rate of more than 30% in men and 15% in women and an even higher prevalence in people with type 2 diabetes mellitus. Optimal pharmacologic therapeutic approaches for NAFLD are an urgent necessity. Approach and Results In this study, we showed that compared with healthy controls, hepatic ACSL4 levels in patients with NAFLD were found to be elevated. Suppression of ACSL4 expression promoted mitochondrial respiration, thereby enhancing the capacity of hepatocytes to mediate β‐oxidation of fatty acids and to minimize lipid accumulation by up‐regulating peroxisome proliferator‐activated receptor coactivator‐1 alpha. Moreover, we found that abemaciclib is a potent and selective ACSL4 inhibitor, and low dose of abemaciclib significantly ameliorated most of the NAFLD symptoms in multiple NAFLD mice models. Conclusions Therefore, inhibition of ACSL4 is a potential alternative therapeutic approach for NAFLD.
Gestational diabetes mellitus (GDM) is a common disease in pregnant women with a prevalence from 1.4% to 14% based on the population studied. The number of patients with GDM is increasing annually, and yet, the treatment for GDM remains limited. In this study, we aimed to explore the potential of dendrobine against GDM. For this purpose, a genetic mouse model of GDM was established. GDM mice were orally administered with 20 mg/kg dendrobine daily from the beginning of pregnancy to delivery. It was found that dendrobine significantly ameliorated the symptoms of GDM, as evidenced by reduced maternal body‐weight and blood glucose levels, as well as increased insulin levels and insulin sensitivity in GDM mice. Dendrobine also remarkably attenuated the impairments to offspring, such as decreased birth‐weight and birth size. Moreover, dendrobine reduced the secretion of inflammatory cytokines by T helper 17 (Th17) cells, including interleukin‐1β, interleukin‐6, tumour necrosis factor‐α and interleukin‐17. Furthermore, we found that dendrobine also reduced the population of Th17 cells in GDM mice. In conclusion, dendrobine could effectively alleviate GDM in mice and might serve as a potential therapeutic drug candidate for GDM patients.
Stroke is a common disease in clinical practice, which seriously endangers people’s physical and mental health. The neurovascular unit (NVU) plays a key role in the occurrence and development of ischemic stroke. Different from other classical types of cell death such as apoptosis, necrosis, autophagy, and pyroptosis, ferroptosis is an iron-dependent lipid peroxidation-driven new form of cell death. Interestingly, the function of NVU and stroke development can be regulated by activating or inhibiting ferroptosis. This review systematically describes the NVU in ischemic stroke, provides a comprehensive overview of the regulatory mechanisms and key regulators of ferroptosis, and uncovers the role of ferroptosis in the NVU and the progression of ischemic stroke. We further discuss the latest progress in the intervention of ferroptosis as a therapeutic target for ischemic stroke and summarize the research progress and regulatory mechanism of ferroptosis inhibitors on stroke. In conclusion, ferroptosis, as a new form of cell death, plays a key role in ischemic stroke and is expected to become a new therapeutic target for this disease.
<b><i>Background:</i></b> Various kidney diseases such as acute kidney injury, chronic kidney disease, polycystic kidney disease, renal cancer, and kidney stones, are an important part of the global burden, bringing a huge economic burden to people around the world. Ferroptosis is a type of nonapoptotic iron-dependent cell death caused by the excess of iron-dependent lipid peroxides and accompanied by abnormal iron metabolism and oxidative stress. Over the past few decades, several studies have shown that ferroptosis is associated with many types of kidney diseases. Studying the mechanism of ferroptosis and related agonists and inhibitors may provide new ideas and directions for the treatment of various kidney diseases. <b><i>Summary:</i></b> In this review, we discuss the differences between ferroptosis and other types of cell death such as apoptosis, necroptosis, pyroptosis, cuprotosis, pathophysiological features of the kidney, and ferroptosis-induced kidney injury. We also provide an overview of the molecular mechanisms involved in ferroptosis and events that lead to ferroptosis. Furthermore, we summarize the possible clinical applications of this mechanism among various kidney diseases. <b><i>Key Message:</i></b> The current research suggests that future therapeutic efforts to treat kidney ailments would benefit from a focus on ferroptosis.
Objective: To study the differential lncRNA / mRNA expression profiles of placental tissues in patients with gestational hypertension, analyze their possible mechanisms of action, and explore their target genes and small molecule drug-related lncRNAs. Methods: Three patients with gestational hypertension who were treated in our hospital from May 2018 to May 2019 were selected as the research subjects and three healthy pregnant women who underwent a prenatal examination in the same hospital were selected as the control group. The placental tissues were taken from the patients. RNA-sequencing was performed to construct lncRNA/mRNA differential expression profiles; screening differentially expressed lncRNAs were used to predict target genes, and GO and KEGG enrichment analysis predicted the biological functions of target genes and the enriched signal pathways, respectively. Protein-protein interaction network, lncRNA-miRNA-mRNA network, and differentially expressed gene-small molecule drug association networks were constructed. Results: RNA-seq analysis revealed 19 differentially expressed lncRNA (4 up-regulated; 15 down-regulated) (P<0.05). Moreover, 423 differentially expressed genes (DEGs) (84 up-regulated; 339 down-regulated)(P<0.05). GO and KEGG enrichment analysis found that gestational hypertension is mainly related to endothelial cell damage, inflammatory response, abnormal immune regulation, and abnormal trophoblast invasion. The PPI network and lncRNA-miRNA-mRNA network were constructed. Differentially expressed gene-drug small molecule prediction results found 19 pairs of differentially gene-small drug relationship pairs, mainly including antibody, inhibitor et al. Conclusion: Differently expressed lncRNAs in the placenta of patients with gestational hypertension can participate in the regulation of multiple biological functional level-related signal pathways through targeted regulation of their target genes, and play an important role in the occurrence and development of gestational hypertension. The predicted small molecule drug can be used as a reference for clinical treatment.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.