Potential use of the cholesterol transfer inhibitor U18666A as an antiviral drug for research on various viral infections.

Cholesterol plays critical functions in arranging the biophysical attributes of proteins and lipids in the plasma membrane. For various viruses, an association with cholesterol for virus entrance and/or morphogenesis has been demonstrated. Therefore, the lipid metabolic pathways and the combination of membranes could be targeted to selectively suppress the virus replication steps as a basis for antiviral treatment. U18666A is a cationic amphiphilic drug (CAD) that affects intracellular transport and cholesterol production. A robust tool for investigating lysosomal cholesterol transfer and Ebola virus infection is an androstenolone derived termed U18666A that suppresses three enzymes in the cholesterol biosynthesis mechanism. In addition, U18666A inhibited low-density lipoprotein (LDL)-induced downregulation of LDL receptor and triggered lysosomal aggregation of cholesterol. According to reports, U18666A inhibits the reproduction of baculoviruses, filoviruses, hepatitis, coronaviruses, pseudorabies, HIV, influenza, and flaviviruses, as well as chikungunya and flaviviruses. U18666A-treated viral infections may act as a novel in vitro model system to elucidate the cholesterol mechanism of several viral infections. In this article, we discuss the mechanism and function of U18666A as a potent tool for studying cholesterol mechanisms in various viral infections.

Lipid accumulation product (LAP) index for the diagnosis of nonalcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis.

BACKGROUND: Lipid accumulation product (LAP) is an index calculated by waist circumference (WC) and triglyceride (TG), which reflects lipid toxicity. This study aims to investigate the association between the LAP index and nonalcoholic fatty liver disease (NAFLD) in a systematic review and meta-analysis. METHODS AND RESULTS: PubMed, Scopus, and Web of Science online databases were searched for eligible studies that investigated the association of the LAP index and NAFLD. Sixteen observational studies with 96,101 participants, including four cohort studies, one case‒control study and 11 cross-sectional studies with baseline data, were entered into this analysis. Fourteen studies reported a significant association between the LAP index and NAFLD, and two reported that this relation was not significant; two different meta-analyses (1- mean difference (MD) and 2- bivariate diagnostic test accuracy [DTA]) were conducted using Stata version 14. The LAP index was compared in subjects with and without NAFLD, and the difference was significant with 34.90 units (CI 95: 30.59-39.31, P < 0.001) of the LAP index. The DTA meta-analysis was conducted and showed that the LAP index pooled sensitivity and specificity for screening of NAFLD were 94% (CI95: 72%-99%, I2 = 99%, P < 0.001) and 85% (CI95: 62%-96%, I2 = 99%, P < 0.001), respectively. CONCLUSION: The LAP Index is an inexpensive, sensitive, and specific method to evaluate NAFLD and may be valuable for NAFLD screening.

The accuracy of triglyceride-glucose (TyG) index for the screening of metabolic syndrome in adults: A systematic review and meta-analysis.

AIMS: To investigate the relationship between the triglyceride-glucose (TyG) index, a novel surrogate index of insulin resistance (IR), and metabolic syndrome (MetS) in a systematic review and meta-analysis. DATA SYNTHESIS: Studies that report the TyG index in adult subjects with and without MetS were included. Thirteen observational articles were included in this study, with a total of 49,325 participants. Two different categories of meta-analyses were performed. First, the means of the TyG index were compared in participants with and without MetS. The pooled mean difference (MD) of the TyG index between groups was 0.83 units (CI 95: 0.74-0.92, I2 = 98, P-value < 0.001), and the subgroup analyses showed MD significantly differed based on the MetS diagnostic criteria. The pooled MD were 0.80 units (CI 95: 0.70-0.91, I2 = %88, P-value < 0.001) and 0.82 units (CI 95: 0.79-0.86, I2 = %0, P-value > 0.767) for studies reported data for males and females individual, respectively. Second bivariate diagnostic test accuracy (DTA) meta-analysis was performed and determined that the TyG index's pooled sensitivity and specificity for screening of MetS were 80% (CI95: 75%-84%, I2 = 87%, P-value < 0.001) and 81% (CI95: 77%-84%, I2 = 90.45%, P-value < 0.001), respectively. Summary receiver-operating characteristics (sROC) curves were also plotted with the area under the sROC curve of 0.87 (CI 95: 0.84-0.90). CONCLUSIONS: The TyG index is a sensitive and specific index for MetS and may be valuable for MetS screening. PROSPERO: CRD42022316209.

PI3K/Akt/mTOR signaling pathway in cancer stem cells.

Cancer stem cells (CSCs) as a small subpopulation in tumor bulk are believed to initiate tumor formation and are responsible for the resistance to cancer therapy. The proliferation and differentiation of CSCs result in heterogeneity in a tumor which increases the chance of tumor survival and invasion. Many signaling pathways are abnormally activated or repressed in CSCs. Understanding these pathways and the metabolisms in CSCs may help targeted therapy in drug-resistant tumors. The PI3K/Akt/mTOR pathway is one of the major signaling pathways in CSCs involved in the maintenance of stemness, proliferation, differentiation, epithelial to mesenchymal transition (EMT), migration, and autophagy. Thus, suppressing the PI3K/Akt/mTOR pathway with inhibitors might be a promising strategy for targeted cancer therapy. Although the pathway is well-recognized and reviewed in tumor bulks, the functions in CSCs have not been well focused. Here, we reviewed the PI3K/Akt/mTOR signaling pathway and its functions in CSCs and addressed the potential therapeutic applications in drug-resistant tumors.