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Although the association of elevated homocysteine level with cardiac hypertrophy has been reported, the molecular mechanisms by which homocysteine induces cardiac hypertrophy remain inadequately understood. In this study we aim to uncover the roles of cyclic nucleotide phosphodiesterase 1 (PDE1) and endoplasmic reticulum (ER) stress and their relationship to advance the mechanistic understanding of homocysteine-induced cardiac cell hypertrophy. H9c2 cells and primary neonatal rat cardiomyocytes are exposed to homocysteine with or without ER stress inhibitor TUDCA or PDE1-specific inhibitor Lu AF58027, or transfected with siRNAs targeting PDE1 isoforms prior to homocysteine-exposure. Cell surface area is measured and ultrastructure is examined by transmission electron microscopy. Hypertrophic markers, PDE1 isoforms, and ER stress molecules are detected by q-PCR and western blot analysis. Intracellular cGMP and cAMP are measured by ELISA. The results show that homocysteine causes the enlargement of H9c2 cells, increases the expressions of hypertrophic markers β-MHC and ANP, upregulates PDE1A and PDE1C, promotes the expressions of ER stress molecules, and causes ER dilatation and degranulation. TUDCA and Lu AF58027 downregulate β-MHC and ANP, and alleviate cell enlargement. TUDCA decreases PDE1A and PDE1C levels. Silencing of PDE1C inhibits homocysteine-induced hypertrophy, whereas PDE1A knockdown has minor effect. Both cAMP and cGMP are decreased after homocysteine-exposure, while only cAMP is restored by Lu AF58027 and TUDCA. TUDCA and Lu AF58027 also inhibit cell enlargement, downregulate ANP, β-MHC and PDE1C, and enhance cAMP level in homocysteine-exposed primary cardiomyocytes. ER stress mediates homocysteine-induced hypertrophy of cardiac cells via upregulating PDE1C expression. Cyclic nucleotide, especially cAMP, is the downstream mediator of the ER stress-PDE1C signaling axis in homocysteine-induced cell hypertrophy.

Aiming at the problem that few studies have been conducted on the combination of multiple media in enhanced oil recovery (EOR), the physical simulation experiment of surfactants + CO2 (SPC) was carried out to analyze the influence of surfactant on the CO2 displacement effect of interlayer shale oil reservoir. The results show that when the displacement flow volume (DFV) reaches 20 PV, the oil displacement efficiency (ODE) of SPC displacement is 0.42~3.00% higher than that of CO2 displacement. The ODE of small pore displacement can be increased by 1.51~3.61%. And the relative displacement content (RDC) ratio of free oil of tight shale oil reservoir can be increased by 7.10~20.54%. When the DFV is 5 PV, the ODE can be improved more significantly. It shows that the efficiency of small pore displacement can be increased by 1.74~2.33%. It also indicates that the ODE can be increased by 7.03% of the ultralow permeability shale oil reservoir. And the RDC ratio of free oil of tight shale oil reservoir can be increased by 10.34~21.50%. Surfactant can improve the wettability of the reservoir and make the rock sample wet. This research can help to understand the influence of surfactant on CO2 displacement effect and reveal the mechanism of SPC displacement improving the ODE of interlayer shale oil reservoir, providing theoretical basis for the effective development of interlayer shale oil reservoir. [ABSTRACT FROM AUTHOR]

Aims: Papillary thyroid cancer (PTC) is a serious threat to human health worldwide, while metastasis in the early phase limits therapeutic success and leads to poor survival outcomes. The CXC chemokine receptor type 4 (CXCR4) plays an important role in many cellular movements such as transcriptional modulation, cell skeleton rearrangement, and cell migration, and the change in CXCR4 levels are crucial in various diseases including cancer. In this study, we explored the role of CXCR4 in the migration and invasion of PTC and investigated the potential mechanisms underlying its effects., Subjects and Methods: We analyzed the expression levels of CXCR4 in PTC tissues and cell lines. Would healing migration, Transwell invasion assay in vitro, and tail-vein lung metastasis assay In vivo were performed to evaluated the migration and invasion abilities of PTC cells with stable CXCR4 knockdown or overexpression. Signal transducers and activators of transcription (STAT3) signaling pathway-related protein expressions were examined by Western blotting assays., Results: The results showed that CXCR4 was highly expressed in PTC cell lines and PTC tissues. CXCR4 knockdown in PTC cells dampened the migration, invasion, and epithelial-mesenchymal transition (EMT), whereas CXCR4 overexpression enhanced these properties. In vivo, we also found that CXCR4 promoted the metastasis of PTC. Mechanistic studies showed that CXCR4 played these vital roles through the STAT3 signaling pathway. Furthermore, PTC patients with high CXCR4 or p-STAT3 expression correlated with aggressive clinical characteristics such as extrathyroidal extension (ETE), and lymph node metastasis (LNM)., Conclusions: We provided evidence that CXCR4 might activate the STAT3 signaling pathway and further promote PTC development. Thus, CXCR4 might be a novel therapeutic target for PTC., (Copyright © 2024 Copyright: © 2024 Journal of Cancer Research and Therapeutics.)

Accumulating studies highlight the role of long noncoding RNAs (lncRNAs)/microRNAs (miRNAs)/messenger RNAs (mRNAs) as important regulatory networks in various human cancers, including thyroid cancer (TC). This study aimed to investigate a novel regulatory network dependent on lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in relation to TC development. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot were initially employed to detect the expression of MALAT1, insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2), and myelocytomatosis (MYC) in TC cells. Interactions among MALAT1, miR-204, and IGF2BP2 were then identified in vitro . The biological processes of proliferation, migration, invasion, and apoptosis were evaluated in vitro via gain- and loss-of-function experiments, followed by in vivo validation using xenograft mice. Our data indicated that MALAT1 and IGF2BP2 were highly expressed, while miR-204 was poorly expressed in TC. IGF2BP2 was verified as a target of miR-204. MALAT1 was found to upregulate IGF2BP2 and enhance MYC expression via m6A modification recognition by competitively binding to miR-204, conferring a stimulatory effect on proliferation, migration, and invasion of TC cells, which was accompanied by weakened tumor growth and cell apoptosis. Altogether, the central findings of our study suggest that MALAT1 contributes to TC progression through the upregulation of IGF2BP2 by binding to miR-204., (© 2020 The Authors.)