Understanding metabolic alterations after SARS-CoV-2 infection: insights from the patients' oral microenvironmental metabolites.

BACKGROUND: Coronavirus disease 2019 is a type of acute infectious pneumonia and frequently confused with influenza since the initial symptoms. When the virus colonized the patient's mouth, it will cause changes of the oral microenvironment. However, few studies on the alterations of metabolism of the oral microenvironment affected by SARS-CoV-2 infection have been reported. In this study, we explored metabolic alterations of oral microenvironment after SARS-CoV-2 infection. METHODS: Untargeted metabolomics (UPLC-MS) was used to investigate the metabolic changes between oral secretion samples of 25 COVID-19 and 30 control participants. To obtain the specific metabolic changes of COVID-19, we selected 25 influenza patients to exclude the metabolic changes caused by the stress response of the immune system to the virus. Multivariate analysis (PCA and PLS-DA plots) and univariate analysis (students' t-test) were used to compare the differences between COVID-19 patients and the controls. Online hiplot tool was used to perform heatmap analysis. Metabolic pathway analysis was conducted by using the MetaboAnalyst 5.0 web application. RESULTS: PLS-DA plots showed significant separation of COVID-19 patients and the controls. A total of 45 differential metabolites between COVID-19 and control group were identified. Among them, 35 metabolites were defined as SARS-CoV-2 specific differential metabolites. Especially, the levels of cis-5,8,11,14,17-eicosapentaenoic acid and hexanoic acid changed dramatically based on the FC values. Pathway enrichment found the most significant pathways were tyrosine-related metabolism. Further, we found 10 differential metabolites caused by the virus indicating the body's metabolism changes after viral stimulation. Moreover, adenine and adenosine were defined as influenza virus-specific differential metabolites. CONCLUSIONS: This study revealed that 35 metabolites and tyrosine-related metabolism pathways were significantly changed after SARS-CoV-2 infection. The metabolic alterations of oral microenvironment in COVID-19 provided new insights into its molecular mechanisms for research and prognostic treatment.

Multi-dimensional glycan microarrays with glyco-macroligands.

Glycan microarray has become a powerful high-throughput tool for examining binding interactions of carbohydrates with the carbohydrate binding biomolecules like proteins, enzymes, antibodies etc. It has shown great potential for biomedical research and applications, such as antibody detection and profiling, vaccine development, biomarker discovery, and drug screening. Most glycan microarrays were made with monovalent glycans immobilized directly onto the array surface via either covalent or non-covalent bond, which afford a multivalent glycans in two dimensional (2D) displaying. A variety of glyco-macroligands have been developed to mimic multivalent carbohydrate-protein interactions for studying carbohydrate-protein interactions and biomedical research and applications. Recently, a number of glyco-macroligands have been explored for glycan microarray fabrication, in particular to mimick the three dimensional (3D) multivalent display of cell surface carbohydrates. This review highlights these recent developments of glyco-macroligand-based microarrays, predominantly, novel glycan microarrays with glyco-macroligands like glycodendrimers, glycopolymers, glycoliposomes, neoglycoproteins, and glyconanoparticles with the effort in controlling the density and orientation of glycans on the array surface, which facilitate both their binding specificity and affinity and thus the high performance of glycan microarrays.

Hepatocyte-targeted delivery using oleanolic acid-loaded liposomes for enhanced hepatocellular carcinoma therapy.

Drug-loaded liposomes have been shown to be effective in the treatment of hepatocellular carcinoma (HCC). However, the systemic non-specific distribution of drug-loaded liposomes in tumor patients is a critical therapeutic challenge. To address this issue, we developed galactosylated chitosan-modified liposomes (GC@Lipo) that could selectively bind to the asialoglycoprotein receptor (ASGPR), which is highly expressed on the membrane surface of HCC cells. Our study demonstrated that the GC@Lipo significantly enhanced the anti-tumor efficacy of oleanolic acid (OA) by enabling targeted drug delivery to hepatocytes. Remarkably, treatment with OA-loaded GC@Lipo inhibited the migration and proliferation of mouse Hepa1-6 cells by upregulating E-cadherin expression and downregulating N-cadherin, vimentin, and AXL expressions, compared to a free OA solution and OA-loaded liposomes. Furthermore, using an axillary tumor xenograft mouse model, we observed that OA-loaded GC@Lipo led to a significant reduction in tumor progression, accompanied by concentrated enrichment in hepatocytes. These findings strongly support the clinical translation of ASGPR-targeted liposomes for the treatment of HCC.

Quercetin loaded liposomes modified with galactosylated chitosan prevent LPS/D-GalN induced acute liver injury.

Quercetin (Que) has been proved to have various biological activities, including anti-oxidation, anti-inflammation and anti-virus, showing great potential in liver protection. However, its water insolubility leads to low bioavailability. Therefore, the development of a suitable drug delivery fashion is imminent. In recent years, liposomes have been widely used in the fields of drug delivery and gene transfer thanks to the cell membrane like structure, easy surface-modification and high encapsulation efficiency. Herein, we fabricated Que loaded anionic liposomes. Galactosylated chitosan (GC) was simply attached to the surfaces of liposomes through electrostatic adsorption to achieve targeted delivery by binding to asialoglycoprotein receptor (ASGPR). The results showed that Que loaded liposomes modified with GC (GC-Que-Lipo) could enrich the liver in mice through tail vein injection. Liposomes could achieve sustained drug release and GC-Que-Lipo promoted M2 polarization of macrophages. More importantly, it could maintain low content of AST, ALT, ALP and high level of GSH while reducing lipid oxidation, thereby protecting the liver from damage in acute liver injury model. In general, we expect to be able to acquire targeted and efficient delivery of quercetin through a facile approach, thus fulfill the prevention and treatment of liver diseases.