Background: MicroRNAs (miRNAs) play important roles in the occurrence and development of cancers. In this project, we aimed to explore the role and molecular mechanism of mir-30a-5p in cholangiocarcinoma (CCA). Materials and Methods:The expression profile and clinical significance of miR-30a-5p in CCA patients were investigated in 31 ICC and 52 ECC patients respectively. The role and mechanism of miR-30a-5p in CCA cells were investigated by up-regulating and inhibiting miR-30a-5p expression in vitro functional study. Results: The expression of miR-30a-5p was increased in both CCA tissues and cells. The inhibition of miR-30a-5p decreased cell proliferation and induced cell apoptosis while overexpression of miR-30a-5p achieved the opposite effect. Furthermore, SOCS3 was down-regulated in ICC and ECC tissues and negatively regulated by miR-30a-5p. Dual-luciferase reporter assay revealed that co-transfection of miR-30a-5p significantly inhibited the activity of firefly luciferase reporter carrying the wild-type 3′UTR of SOCS3. The inhibition of SOCS3 could largely rescue the inhibitory effect of miR-30a-5p inhibition on CCA cells proliferation. In clinical, up-regulated miR-30a-5p expression was correlated with large tumor size in both ICC and ECC cohorts. Conclusions: miR-30a-5p promoted CCA cells proliferation through targeting SOCS3. These findings suggested that miR-30a-5p could be a potential therapeutic target.
Objectives. Our previous study showed that aldose reductase (AR) played key roles in fatty liver ischemia-reperfusion (IR) injury by regulating inflammatory response and energy metabolism. Here, we aim to investigate the role and mechanism of AR in the regeneration of normal and fatty livers after liver surgery. Methods. The association of AR expression with liver regeneration was studied in the rat small-for-size liver transplantation model and the mice major hepatectomy and hepatic IR injury model with or without fatty change. The direct role and mechanism of AR in liver regeneration was explored in the AR knockout mouse model. Results. Delayed regeneration was detected in fatty liver after liver surgery in both rat and mouse models. Furthermore, the expression of AR was increased in liver after liver surgery, especially in fatty liver. In a functional study, the knockout of AR promoted liver regeneration at day 2 after major hepatectomy and IR injury. Compared to wild-type groups, the expressions of cyclins were increased in normal and fatty livers of AR knockout mice. AR inhibition increased the expressions of PPAR-α and PPAR-γ in both normal liver and fatty liver groups after major hepatectomy and IR injury. In addition, the knockout of AR promoted the expressions of SDHB, AMPK, SIRT1, and PGC1-α in liver, which regulated mitochondrial biogenesis and energy metabolism. Conclusions. The knockout of AR promoted the regeneration of normal and fatty livers through regulating energy metabolism. AR may be a new potential therapeutic target to accelerate liver regeneration after surgery.
PurposeThe purpose of this article is to understand the current research status and future development trends in the field of numerical simulation on rock mass grouting.Design/methodology/approachThis article first searched the literature database (EI, Web of Science, CNKI, etc.) for keywords related to the numerical simulation of rock mass grouting to obtain the initial literature database. Then, from the initial database, several documents with strong relevance to the numerical simulation theme of rock mass grouting and high citation rate were selected; some documents from the references were selected as supplements, forming the sample database of this review study (a total of 90 articles). Finally, through sorting out the relationship among the literature, this literature review was carried out.FindingsThe numerical simulation of rock mass grouting is mainly based on the porous media model and the fractured media model. It has experienced the development process from Newtonian fluid to non-Newtonian fluid, from time-invariant viscosity to time-varying viscosity, and from generalized theoretical model to engineering application model. Based on this, this article summarizes four scientific problems that need to be solved in the future in this research field: the law of grout distribution at the cross fissures, the grout diffusion mechanism under multi-field coupling, more accurate grouting theoretical model and simulation technology with strong engineering applicability.Originality/valueThis research systematically analyzes the current research status and shortcomings of numerical simulation on rock mass grouting, summarizes four key issues in the future development of this research field and provides new ideas for the future research on numerical simulation on rock mass grouting.
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