Recent studies have exhibited significant roles of lncRNAs in various tumors' development, including colon cancer. Our study focused on the biological roles of lncRNA MALAT1 in colon cancer. In our ...study, it was demonstrated that MALAT1 was upregulated in human colon cancer cell lines including Lovo, HCT116, SW480, and HT29 cells compared to the normal human intestinal epithelial HIEC cells. Moreover, we observed that miR‐129‐5p was downregulated in colon cancer cells with a significant increase of HMGB1 expression. Inhibition of MALAT1 can inhibit the proliferation of colon cancer SW480 and HCT116 cells and next, bioinformatics analysis was used to predict the target microRNA of MALAT1. miR‐129‐5p was identified and confirmed as a direct regulator of MALAT1 and it was shown that miR‐129‐5p mimics were able to restrain the progression of colon cancer cells. In addition, high motility group box protein 1 (HMGB1), was predicted as a mRNA target of miR‐129‐5p. Furthermore, we found that MALAT1 exerted its biological functions through regulating HMGB1 by sponging miR‐129‐5p in vitro. Silencing MALAT1 greatly inhibited HMGB1 expression which can be reversed by miR‐129‐5p inhibitors. It was indicated in our investigation that MALAT1 may serve as a competing endogenous lncRNA (ceRNA) to mediate HMGB1 by sponging miR‐129‐5p in colon cancer. Taken together, our results indicated that MALAT1/miR‐129‐5p/HMGB1 axis could be provided as an important prognostic biomarker in colon cancer development.
We found that MALAT1 can be identified as an oncogene in colon cancer development, and for the first time, we reported a novel mechanism for MALAT1 in colon cancer. Our results revealed that MALAT1/miR‐129‐5p/HMGB1 axis was involved in colon cancer and can act as a therapeutic indicator.
The current study investigates the association between corporate social responsibility (CSR) and financial performance (FP), and discusses the driving motives of banks to engage in CSR. Three ...motives, namely, strategic choices, altruism, and greenwashing, suggest that the relationship between CSR and FP is positive, non-negative, and non-existent, respectively. We obtained our sample, which covered 2003–2009, from the Ethical Investment Research Service (EIRIS) databank and Bankscope database. The data consists of 162 banks in 22 countries. We then classified the banks into four types based on their degree of engagement in CSR. This study proposes the use of an extended version of the Heckman two-step regression, in which the first step adopts a multinomial logit model, and the second step estimates the performance equation with the inverse Mills ratio generated by the first step. The empirical results show that CSR positively associates with FP in terms of return on assets, return on equity, net interest income, and non-interest income. In contrast, CSR negatively associates with non-performing loans. Hence, strategic choice is the primary motive of banks to engage in CSR.
Pancreatic cancer (PC) is a serious malignancy with high mortality and poor prognosis due to nonspecific incipient symptoms and early metastasis. Also, increasing evidence indicates that a panel of ...genes is newly identified in the pathogenesis of PC. As is a regulatory subunit, elevated cyclin B1 (CCNB1) expression has been detected in different cancers including PC. This study is designed to investigate the effects of CCNB1 silencing on cell cycle, senescence, and apoptosis through the p53 signaling pathway in PC. PC tissues and normal pancreatic tissues were collected. Cells were transfected and assigned into different groups. The expressions of CCNB1, p53, MDM2, Bax, caspase‐9, caspase‐3, and p21 in tissues and cells were detected by reverse transcription quantitative polymerase chain reaction and western blot analysis. β‐Galactosidase staining, MTT assay, and flow cytometry were conducted to test cell senescence, proliferation, cell cycle, and apoptosis. PC tissues showed higher expressions of CCNB1 and MDM2 and lower expressions of Bax, caspase‐9, caspase‐3, and p21. Cells transfected with shCCNB1 had lower expressions of CCNB1 and MDM2, whereas higher expressions of Bax, caspase‐9, caspase‐3, p53, and p21. The shCCNB1 group had decreased proliferation and S‐phase cell proportion and increased apoptosis, senescence, and G0/G1‐phase cell proportion. The PFT‐α group showed higher expressions of MDM2 and lower expressions of Bax, caspase‐9, caspase‐3, p53, and p21. The PFT‐α group had increased proliferation and S‐phase cell proportion and declined apoptosis, senescence, and G0/G1‐phase cell proportion. CCNB1 silencing inhibits cell proliferation and promotes cell senescence via activation of the p53 signaling pathway in PC.
CCNB1 silencing inhibits cell proliferation and promotes cell senescence via activation of the p53 signaling pathway in pancreatic cancer.
Although many advances have been made in the pathogenesis of epilepsy recently, the pathological mechanisms of epilepsy are still largely unknown. Exploring the pathological mechanisms and developing ...novel therapeutic strategies for epilepsy are urgently needed. A SD rat model of epilepsy was established with lithium chloride-pilocarpine. Astrocytes were isolated, cultured from 8 to 12 week rats and identified by flow cytometry and immunofluorescence. Immunohistochemical staining was used for MEF2C and NF-κB in paraffin-embedded sections. RT-qPCR and western blot were used to analyze gene expression. ELISA was used to analyze the concentration of IL-6, TNF-α and Cox-2. Cells were transfected with pcDNA-MEFC2, sh-MEFC2, pcDNA-UCA1, sh-UCA1, miR-203 mimic or miR-203 inhibitor. Cell viability was assessed by MTT assay. Dual luciferase assay was used to determine the direct interaction of lncRNA UCA1/miR-203 and miR-203/MEF2C. MEF2C was down-regulated and inhibited NF-κB expression and the secretion of IL-6 and TNF-α in epilepsy. LncRNA UCA1 was also down-regulated in epilepsy. LncRNA UCA1 over-expression increased the expression of MEF2C and its knock-down decreased MEF2C expression. Luciferase activity showed lncRNA UCA1 directly targeted miR-203 and miR-203 directly targeted MEF2C. MiR-203 suppressed the expression of MEF2C, and promoted NF-κB, phosphorylated IκB/IKK and inflammatory effectors, which was reversed by MEF2C knock-down. Moreover, lncRNA UCA1 could increase the expression of MEF2C to inhibit NF-κB, phosphorylated IκB/IKK and inflammatory effectors, which was also reversed by miR-203 mimic transfection. LncRNA UCA1 inhibited the inflammation via regulating miR-203 mediated regulation of MEF2C/NF-κB signaling in epilepsy. Our investigation elucidated novel pathological mechanisms and provided potential therapeutic targets for epilepsy.
Kcnq1 overlapping transcript 1 (kcnq1ot1), an imprinted antisense lncRNA in the kcnq1 locus, acts as a potential contributor to cardiovascular disease, but its role in atherosclerosis remains ...unknown. The aim of this study was to explore the effects of kcnq1ot1 on atherogenesis and the underlying mechanism. Our results showed that kcnq1ot1 expression was significantly increased in mouse aorta with atherosclerosis and lipid-loaded macrophages. Lentivirus-mediated kcnq1ot1 overexpression markedly increased atherosclerotic plaque area and decreased plasma HDL-C levels and RCT efficiency in apoE
mice fed a Western diet. Upregulation of kcnq1ot1 also reduced the expression of miR-452-3p and ABCA1 but increased HDAC3 levels in mouse aorta and THP-1 macrophages. Accordingly, kcnq1ot1 overexpression inhibited cholesterol efflux and promoted lipid accumulation in THP-1 macrophages. In contrast, kcnq1ot1 knockdown protected against atherosclerosis in apoE
mice and suppressed lipid accumulation in THP-1 macrophages. Mechanistically, kcnq1ot1 enhanced HDAC3 expression by competitively binding to miR-452-3p, thereby inhibiting ABCA1 expression and subsequent cholesterol efflux. Taken together, these findings suggest that kcnq1ot1 promotes macrophage lipid accumulation and accelerates the development of atherosclerosis through the miR-452-3p/HDAC3/ABCA1 pathway.
Diosgenin is a spiroketal steroidal natural product extracted from plants and used as the single most important precursor for the world steroid hormone industry. The sporadic occurrences of diosgenin ...in distantly related plants imply possible independent biosynthetic origins. The characteristic 5,6-spiroketal moiety in diosgenin is reminiscent of the spiroketal moiety present in anthelmintic avermectins isolated from actinomycete bacteria. How plants gained the ability to biosynthesize spiroketal natural products is unknown. Here, we report the diosgenin-biosynthetic pathways in himalayan paris (Paris polyphylla), a monocot medicinal plant with hemostatic and antibacterial properties, and fenugreek (Trigonella foenum-graecum), an eudicot culinary herb plant commonly used as a galactagogue. Both plants have independently recruited pairs of cytochromes P450 that catalyze oxidative 5,6-spiroketalization of cholesterol to produce diosgenin, with evolutionary progenitors traced to conserved phytohormone metabolism. This study paves the way for engineering the production of diosgenin and derived analogs in heterologous hosts.
SnS2 has been widely studied as an anode material for sodium‐ion batteries (SIBs) based on the high theoretical capacity and layered structure. Unfortunately, rapid capacity decay associated with ...volume variation during cycling limits practical application. Herein, SnS2/Co3S4 hollow nanocubes anchored on S‐doped graphene are synthesized for the first time via coprecipitation and hydrothermal methods. When applied as the anode for SIBs, the sample delivers a distinguished charge specific capacity of 1141.8 mAh g−1 and there is no significant capacity decay (0.1 A g−1 for 50 cycles). When the rate is increased to 0.5 A g−1, it presents 845.7 mAh g−1 after cycling 100 times. Furthermore, the composite also exhibits an ultrafast sodium storage capability where 392.9 mAh g−1 can be obtained at 10 A g−1 and the charging time is less than 3 min. The outstanding electrochemical properties can be ascribed to the enhancement of conductivity for the addition of S‐doped graphene and the existence of p–n junctions in the SnS2/Co3S4 heterostructure. Moreover, the presence of mesopores between nanosheets can alleviate volume expansion during cycling as well as being beneficial for the migration of Na+.
Nanocube‐shaped SnS2/Co3S4‐rGO composites are synthesized for the first time via coprecipitation of Sn4+, Co2+, and OH− followed by alkaline etching and hydrothermal methods. The SnS2/Co3S4‐rGO electrode exhibits a high reversible capacity (1141.8 mAh g−1 at 0.1 A g−1 after 50 cycles) and excellent rate performance (392.9 mAh g−1 at 10 A g−1) when used as an anode for sodium‐ion batteries.
Chemical warfare agents (CWAs) are toxic chemicals that have been intentionally developed for targeted and deadly use on humans. Although intended for military targets, the use of CWAs more often ...than not results in mass civilian casualties. To prevent further atrocities from occurring during conflicts, a global ban was implemented through the chemical weapons convention, with the aim of eliminating the development, stockpiling, and use of CWAs. Unfortunately, because of their relatively low cost, ease of manufacture and effectiveness on mass populations, CWAs still exist in today's world. CWAs have been used in several recent terrorist-related incidents and conflicts (
, Syria). Therefore, they continue to remain serious threats to public health and safety and to global peace and stability. Analytical methods that can accurately detect CWAs are essential to global security measures and for forensic analysis. Small molecule fluorescent probes have emerged as attractive chemical tools for CWA detection, due to their simplicity, ease of use, excellent selectivity and high sensitivity, as well as their ability to be translated into handheld devices. This includes the ability to non-invasively image CWA distribution within living systems (
and
) to permit in-depth evaluation of their biological interactions and allow potential identification of therapeutic countermeasures. In this review, we provide an overview of the various reported fluorescent probes that have been designed for the detection of CWAs. The mechanism for CWA detection, change in optical output and application for each fluorescent probe are described in detail. The limitations and challenges of currently developed fluorescent probes are discussed providing insight into the future development of this research area. We hope the information provided in this review will give readers a clear understanding of how to design a fluorescent probe for the detection of a specific CWA. We anticipate that this will advance our security systems and provide new tools for environmental and toxicology monitoring.
Most proteins exert their functions by interacting with other proteins, making the identification of protein-protein interactions (PPI) crucial for understanding biological activities, pathological ...mechanisms, and clinical therapies. Developing effective and reliable computational methods for predicting PPI can significantly reduce the time-consuming and labor-intensive associated traditional biological experiments. However, accurately identifying the specific categories of protein-protein interactions and improving the prediction accuracy of the computational methods remain dual challenges. To tackle these challenges, we proposed a novel graph neural network method called GNNGL-PPI for multi-category prediction of PPI based on global graphs and local subgraphs. GNNGL-PPI consisted of two main components: using Graph Isomorphism Network (GIN) to extract global graph features from PPI network graph, and employing GIN As Kernel (GIN-AK) to extract local subgraph features from the subgraphs of protein vertices. Additionally, considering the imbalanced distribution of samples in each category within the benchmark datasets, we introduced an Asymmetric Loss (ASL) function to further enhance the predictive performance of the method. Through evaluations on six benchmark test sets formed by three different dataset partitioning algorithms (Random, BFS, DFS), GNNGL-PPI outperformed the state-of-the-art multi-category prediction methods of PPI, as measured by the comprehensive performance evaluation metric F1-measure. Furthermore, interpretability analysis confirmed the effectiveness of GNNGL-PPI as a reliable multi-category prediction method for predicting protein-protein interactions.
The insecticide exposure has been linked to Parkinson's disease (PD). In the present study, we used a most widely used cell line in study of PD, the SH-SY5Y cells, to investigate mechanisms of ...chlorpyrifos (CPF) induced cell toxicity and the possible roles of cell pyroptosis and oxidative stress in SH-SY5Y cells, as well as role of miR-181/SIRT1/PGC-1α/Nrf2 signaling pathway in this process.
SH-SY5Y cells were treated with different concentrations of CPF. Cell viability was measured using CCK-8 assay. Cell pyroptosis was determined by immunofluorescence of caspase-1 and TUNEL assay. The miR-181 (has-miR-181-5p) level was determined by qRT-PCR. Expression of SIRT1, PGC-1α, Nrf2, and pyroptosis related proteins NLRP3, caspase-1, IL-1β, and IL-18 was determined by both qRT-PCR and Western blotting.
Cell viability was found to be decreased with the increased CPF concentrations. The pyroptosis related proteins, ROS levels, as well as level of caspase-1 and the TUNEL positive cells were all significantly up-regulated by CPF. Meanwhile, expression of miR-181 and pyroptosis proteins was also enhanced, while the SIRT1/PGC-1α/Nrf2 signaling was inhibited by CPF. Knockdown of Nrf2 significantly up-regulated the expression of pyroptosis related proteins, ROS level, caspase-1, and the TUNEL positive cells, while over-expression of Nrf2 resulted in opposite results. The expression of PGC-1α and Nrf2 was significantly down-regulated when SIRT1 was inhibited, while over-expressed SIRT1 led to increased PGC-1α and Nrf2 levels. Besides, miR-181 promoted the CPF induced activation of pyroptosis and oxidative stress, as well as down-regulated SIRT1/PGC-1α/Nrf2 signaling, while inhibition of miR-181 led to opposite results.
Chlorpyrifos could inhibit cell proliferation, activate cell pyroptosis and increase susceptibility on oxidative stress-induced toxicity by elevating miR-181 through down-regulation of the SIRT1/PGC-1α/Nrf2 pathway in human neuroblastoma SH-SY5Y cells. This study might give deeper insights for mechanisms of CPF induced toxicity and might give some novel research targets for PD treatment.
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