A hypoxia-activated NO donor for the treatment of myocardial hypoxia injury.

As present NO donor drugs cannot localize to release NO at the hypoxic site, along with the short half-life and bidirectional regulation of NO, they are unable to overcome low bioavailability and side effects in the treatment of myocardial hypoxia injury. In this study, we designed and prepared a novel hypoxia-activated NO donor (Hano) by hybridization of a known NO donor compound (Nno) with a hypoxia-activated group. Hano and isosorbide dinitrate were compared in terms of NO release and anti-myocardial hypoxia injury. Furthermore, the effects of Hano and Nno on releasing NO, dilating blood vessels, and preventing myocardial hypoxia injury were studied and compared in smooth muscle cells, cardiomyocytes and mice. The results showed that the NO release by Hano increased either in smooth muscle cells or in myocardial cells under hypoxia conditions. Significantly, Hano was found capable of dilating blood vessels and attenuating hypoxia injury both in vitro and in vivo, and has great potential as a hypoxia-activated NO donor drug to treat hypoxic heart diseases.

A comprehensive review of the circulation of microplastics in aquatic ecosystem using scientometric method.

Nowadays, the extensive application of microplastics (MPs) has led to the gradual accumulation of toxicity in aquatic environment and caused potential harm to aquatic organisms and human life, which has become a hot issue of worldwide concern. Although MPs show inert or sublethal toxicity in many cases, its long-term existence can still cause harmful ecological effects. However, to our knowledge, there is a lack of comprehensive literature on the current research hotspots, circulation process, and future development trend of MPs in aquatic ecosystem. This study aims to comprehend the current research hotspots and future development trend in the field of the MPs in aquatic ecosystem using scientometric method. And the circulation process of MPs in aquatic ecosystem is also investigated. The results indicate the most of the current publications on MPs in aquatic ecosystems focus on the formation and harmful properties of MPs. The current research hotspots mainly include the causes of the formation of MPs, the extent of contamination, deposition phenomena, and the toxicity and harm caused to aquatic organisms and humans after ingestion. And the future trends in the researches related to MPs mainly include the study of microplastic cycling processes in aquatic and terrestrial ecosystems, as well as the effective collection of microplastics and their conversion into valuable carbon sources. This review has filled in the knowledge gap in the field of MPs research in aquatic ecosystem to some extent and plays a guiding role in the future researches.

An Original Aspirin-Containing Carbonic Anhydrase 9 Inhibitor Overcomes Hypoxia-Induced Drug Resistance to Enhance the Efficacy of Myocardial Protection.

PURPOSE: Hypoxic microenvironment plays a vital role in myocardial ischemia injury, generally leading to the resistance of chemotherapeutic drugs. This induces an intriguing study on mechanism exploration and prodrug design to overcome the hypoxia-induced drug resistance. METHODS: In this study, we hypothesized that the overexpression of carbonic anhydrase 9 (CAIX) in myocardial cells is closely related to the drug resistance. Herein, bioinformatics analysis, gene knockdown, and overexpression assay certificated the correlation between CAIX overexpression and hypoxia. An original aspirin-containing CAIX inhibitor AcAs has been developed. RESULTS: Based on the downregulation of CAIX level, both in vitro and in vivo, AcAs can overcome the acquired resistance and more effectively attenuate myocardial ischemia and hypoxia injury than that of aspirin. CAIX inhibitor is believed to recover the extracellular pH value so as to ensure the stable effect of aspirin. CONCLUSION: Results indicate great potential of CAIX inhibitor for further application in myocardial hypoxia injury therapy.

RNF135 Promoter Methylation Is Associated With Immune Infiltration and Prognosis in Hepatocellular Carcinoma.

RING finger protein 135 has an important role in the occurrence of many cancers; however its regulation and function of RNF135 in hepatocellular carcinoma remains unknown. The promoter methylation status and mRNA expression of RNF135 was evaluated by methylation-specific PCR, semi-quantitative RT-PCR, and real-time quantitative PCR in HCC tissues and cell lines, and further analyzed from The Cancer Genome Atlas database. Wound healing assay, transwell migration, cell viability, and colony formation assay were performed to investigate the function of RNF135. GSEA analysis, TIMER database, and ESTIMATE algorithm were used to decipher the associated pathway and immune infiltration. The survival analysis was applied to assess the prognostic value of RNF135. RNF135 expression was downregulated in HCC tissues and 5 of 8 HCC cell lines, and was negatively correlated with its promoter hypermethylation. Demethylating regent decitabine restored RNF135 expression on the cellular level. Knockdown of RNF135 expression enhanced the migration of HCC cells, while RNF135 overexpression and decitabine treatment repressed cell migration. Bioinformatics analysis and immunohistochemistry revealed a positive relationship between RNF135 expression and six immune cell infiltrates (B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells). Survival analysis disclosed that RNF135 hypermethylation is independently associated with poor clinical outcomes in HCC. Decreased RNF135 expression driven by promoter hypermethylation frequently occurred in HCC and associated with prognosis of HCC. RNF135 functions as a tumor suppressor and is involved in tumor immune microenvironment in HCC.

Cellular localization of the FMRP in rat retina.

The fragile X mental retardation protein (FMRP) is a regulator of local translation through its mRNA targets in the neurons. Previous studies have demonstrated that FMRP may function in distinct ways during the development of different visual subcircuits. However, the localization of the FMRP in different types of retinal cells is unclear. In this work, the FMRP expression in rat retina was detected by Western blot and immunofluorescence double labeling. Results showed that the FMRP expression could be detected in rat retina and that the FMRP had a strong immunoreaction (IR) in the ganglion cell (GC) layer, inner nucleus layer (INL), and outer plexiform layer (OPL) of rat retina. In the outer retina, the bipolar cells (BCs) labeled by homeobox protein ChX10 (ChX10) and the horizontal cells (HCs) labeled by calbindin (CB) were FMRP-positive. In the inner retina, GABAergic amacrine cells (ACs) labeled by glutamate decarbonylase colocalized with the FMRP. The dopaminergic ACs (tyrosine hydroxylase marker) and cholinergic ACs (choline acetyltransferase (ChAT) marker) were co-labeled with the FMRP. In most GCs (labeled by Brn3a) and melanopsin-positive intrinsically photosensitive retinal GCs (ipRGCs) were also FMRP-positive. The FMRP expression was observed in the cellular retinal binding protein-positive Müller cells. These results suggest that the FMRP could be involved in the visual pathway transmission.