The development of drugs with rapid distribution in the kidney and long-term retention in the renal tubule is a breakthrough for enhanced treatment of acute kidney injury (AKI). Here, l-serine–modified chitosan (SC) was synthesized as a potential AKI kidney–targeting agent due to the native cationic property of chitosan and specific interaction between kidney injury molecule–1 (Kim-1) and serine. Results indicated that SC was rapidly accumulated and long-term retained in ischemia-reperfusion–induced AKI kidneys, especially in renal tubules, which was possibly due to the specific interactions between SC and Kim-1. SC-TK-SS31 was then prepared by conjugating SS31, a mitochondria-targeted antioxidant, to SC via reactive oxygen species (ROS)–sensitive thioketal linker. Because of the effective renal distribution combined with ROS-responsive drug release behavior, the administration of SC-TK-SS31 led to an enhanced therapeutic effect of SS31 by protecting mitochondria from damage and reducing the oxidative stress, inflammation, and cell apoptosis.
Fourier transform infrared (FTIR) investigations were performed to study the mechanism of catalytic SiO 2 atomic layer deposition (ALD) using pyridine as the catalyst. Pyridine adsorption on hydroxylated SiO 2 surface was examined by monitoring both the changes to the O-H stretching vibrations and the appearance of pyridine molecular vibrations. The strong hydrogen bonding of pyridine to the isolated hydroxyl groups with a desorption energy of 9 ( 2 kcal/mol is believed to make oxygen a stronger nucleophile for nucleophillic attack on the SiCl 4 reactant. The SiCl 4 reaction with the hydroxylated SiO 2 surface was then investigated by monitoring the disappearance of O-H stretching vibrations and appearance of Si-Cl stretching vibrations. These FTIR results revealed that the SiCl 4 reaction completely removed the isolated hydroxyl species and left a small fraction of hydrogen-bonded hydroxyl species. The H 2 O reaction was studied by observing the disappearance of the Si-Cl stretching vibration and the appearance of the O-H stretching vibration. To understand the role of pyridine during the H 2 O reaction, the Si-Cl stretching vibration of the SiCl x surface species was monitored during pyridine adsorption. The weak interaction between pyridine and the SiCl x surface species suggested that the pyridine catalyzes the H 2 O reaction by hydrogen bonding to the incoming H 2 O reactant. The FTIR spectra also revealed that a pyridinium salt was left behind on the SiO 2 surface at lower temperatures after both the SiCl 4 and H 2 O reactions. The pyridinium salt can desorb from the SiO 2 surface and no pyridinium salt was observed for surface temperatures >340 K after either the SiCl 4 or H 2 O reactions.
Background
Rheumatoid arthritis (RA) is the most common chronic autoimmune connective tissue disease. However, early RA is difficult to diagnose due to the lack of effective biomarkers. This study aimed to identify new biomarkers and mechanisms for RA disease progression at the transcriptome level through a combination of microarray and bioinformatics analyses.
Methods
Microarray datasets for synovial tissue in RA or osteoarthritis (OA) were downloaded from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were identified by R software. Tissue/organ-specific genes were recognized by BioGPS. Enrichment analyses were performed and protein–protein interaction (PPI) networks were constructed to understand the functions and enriched pathways of DEGs and to identify hub genes. Cytoscape was used to construct the co-expressed network and competitive endogenous RNA (ceRNA) networks. Biomarkers with high diagnostic value for the early diagnosis of RA were validated by GEO datasets. The ggpubr package was used to perform statistical analyses with Student’s t-test.
Results
A total of 275 DEGs were identified between 16 RA samples and 10 OA samples from the datasets GSE77298 and GSE82107. Among these DEGs, 71 tissue/organ-specific expressed genes were recognized. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that DEGs are mostly enriched in immune response, immune-related biological process, immune system, and cytokine signal pathways. Fifteen hub genes and gene cluster modules were identified by Cytoscape. Eight haematologic/immune system-specific expressed hub genes were verified by GEO datasets. GZMA, PRC1, and TTK may be potential biomarkers for diagnosis of early RA. NEAT1-miR-212-3p/miR-132-3p/miR-129-5p-TTK, XIST-miR-25-3p/miR-129-5p-GZMA, and TTK_hsa_circ_0077158- miR-212-3p/miR-132-3p/miR-129-5p-TTK might be potential RNA regulatory pathways to regulate the disease progression of early RA.
Conclusions
This work identified three haematologic/immune system-specific expressed genes, namely, GZMA, PRC1, and TTK, as potential biomarkers for the early diagnosis and treatment of RA and provided insight into the mechanisms of disease development in RA at the transcriptome level. In addition, we proposed that NEAT1-miR-212-3p/miR-132-3p/miR-129-5p-TTK, XIST-miR-25-3p/miR-129-5p-GZMA, and TTK_hsa_circ_0077158-miR-212-3p/miR-132-3p/miR-129-5p-TTK are potential RNA regulatory pathways that control disease progression in early RA.
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