Polyoxometalate-Modified g-C3N4 Composites with High Work Function for Triboelectric Nanogenerators.

Designing friction materials with high electron storage capacity, high work function, low cost, and high stability is an important method to improve the output performance of a triboelectric nanogenerator (TENG). Here, we report two kinds of friction materials based on Keggin-type polyoxometalates (POMs)-modified graphite carbon nitride (g-C3N4), namely, g-C3N4@PMo12 and g-C3N4@PW12, and form TENG with commercial indium tin oxide/poly(ethylene terephthalate) (ITO/PET) electrodes. The performance test shows that the g-C3N4@PMo12 TENG device exhibits a high output voltage of about 78 V, a current of about 657 nA, and a transfer charge of about 15 nC, which is more than 3 times higher than that of unmodified TENG. This performance improvement is attributed to the fact that POM loaded on the surface of g-C3N4 can be used as a shallow electron trap to increase the electron storage capacity through electron interaction and to increase the charge density on the surface of the material by increasing the work function of the composite. This work not only broadens the choices of TENG friction materials but also offers a practical means of enhancing TENG's output performance.

Abietic acid inhibits acetaminophen-induced liver injury by alleviating inflammation and ferroptosis through regulating Nrf2/HO-1 axis.

Abietic acid has been known to exhibit anti-inflammatory activity. This study was designed to investigate the protective effects of abietic acid on acetaminophen (APAP)-induced liver injury. The data demonstrated that abietic acid significantly ameliorated APAP-induced liver pathological changes, TNF-α and IL-1ß production. APAP could increase malondialdehyde (MDA) and Fe2+ levels, and decrease ATP and glutathione (GSH) levels, as well as glutathione peroxidase 4 (GPX4) and xCT expression. However, these changes induced by APAP were prevented by abietic acid, indicating abietic acid could inhibit APAP-induced ferroptosis. Furthermore, abietic acid inhibited APAP-induced NF-κB activation and increased the expression of Nrf2 and HO-1. Additionally, the inhibitory effects of abietic acid on APAP-induced liver injury were prevented in Nrf2-/- mice. In vitro, the inhibition of abietic acid on APAP-induced inflammation and ferroptosis were reversed when Nrf2 was knockdown. In summary, abietic acidexhibited a therapeutic effectagainst liver injury by attenuating inflammation and ferroptosis.

Expression of Carboxypeptidase X M14 Family Member 2 Accelerates the Progression of Hepatocellular Carcinoma via Regulation of the gp130/JAK2/Stat1 Pathway.

BACKGROUND: Carboxypeptidase X, M14 family member 2 (CPXM2) has been reported to be involved with several human malignancies. However, the impact of CPXM2 on human hepatocellular carcinoma (HCC) tumorigenesis has not been studied. MATERIALS AND METHODS: Using immunohistochemistry, the detailed CPXM2 expression patterns were examined in HCC cell lines and tissues. Additionally, a hepatic stellate cell line overexpressing CPXM2 and an HCC CPXM2-knockdown cell line were established by lipofection of an expression plasmid or short hairpin RNA, respectively. The transfection efficiencies were confirmed by reverse transcription-quantitative PCR, Western blotting and immunofluorescence. Moreover, Western blotting was conducted to determine the phosphorylation levels of the tyrosine kinase 2 (JAK2)/signal transducer and activator of transcription 3 (Stat1) pathway. Furthermore, gp130-specific hairpin RNA was used to knockdown gp130 expression in hepatic stellate cells overexpressing CPXM2. The malignant phenotype of cultured HCC cells was assessed by a Cell Counting Kit-8 (CCK8) assay, plate cloning assay, Matrigel invasion assay and wound-healing assay in vitro. RESULTS: It was demonstrated that CPXM2 was upregulated in HCC, and its upregulation predicted a poor prognosis. Besides, the upregulation of CPXM2 markedly enhanced the metastatic potential of HCC via the gp130/JAK2/Stat1 signaling pathway in vitro. CONCLUSION: In summary, this evidence suggests a positive role for CPXM2 in HCC progression via modulation of the gp130/JAK2/Stat1 signaling pathway in HCC.

Associations of ACE I/D polymorphism with the levels of ACE, kallikrein, angiotensin II and interleukin-6 in STEMI patients.

This study aimed to compare the plasma levels of angiotensin-I converting enzyme (ACE), Angiotensin II (AngII), kallikrein (KLK1) and interleukin-6 (IL-6) in ST segment elevation myocardial infarction (STEMI) patients with different ACE Insertion/deletion (I/D) polymorphisms in a Chinese population. The ACE genotypes were determined in the 199 STEMI patients and 216 control subjects. STEMI patients were divided into three groups based on the ACE genotypes. Single polymerase chain reaction (PCR) was performed to characterize ACE I/D polymorphisms. Plasma levels of ACE, AngII, KLK1 and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). We found that the DD or ID genotype was significantly independently associated with high ACE (OR = 4.697; 95% CI = 1.927-11.339), KLK1 (3.339; 1.383-8.063) and IL-6 levels (OR = 2.10; 1.025-4.327) in STEMI patients. However, there was no statistical significance between the ACE I/D polymorphism and AngII plasma levels whether in univariate or multivariate logistic regression. Additionally, we detected a significantly positive correlation between plasma KLK1 levels and IL-6 levels in STEMI patients (r = 0.584, P < 0.001). The study showed high levels of ACE, KLK1 and IL-6 were detected when the D allele was present, but AngII plasma levels was not influenced by the ACE I/D polymorphism.

Claudin-9 enhances the metastatic potential of hepatocytes via Tyk2/Stat3 signaling.

BACKGROUND/AIMS: We have previously identified a tight junction protein claudin-9 (CLDN9) as an upregulated gene in hepatocellular carcinoma (HCC) through an immunohistochemistry analysis. Here, we explore its function and clinical relevance in human HCC. MATERIALS AND METHODS: Stable transfection of the hepatocyte line HL7702 with CLDN9 was confirmed by the real-time polymerase chain reaction (PCR), western blotting, and immunofluorescence. The impact of CLDN9 on the cell invasion and migration was assessed in vitro by a transwell assay and wound-healing experiment. Western blotting was used to determine the activation state of the Tyk2 (tyrosine kinase 2)/Stat3 (signal transducer and activator of transcription 3) pathway. Moreover, we used a Tyk2-RNAi assay to silence the expression of Tyk2 in CLDN9 expressing hepatocytes; subsequently, the impact of the Tyk2/Stat3 signaling pathway on the cell invasion and migration in vitro was assessed by a transwell assay and a wound-healing experiment. Furthermore, an immunohistochemistry method was utilized to explore the expression levels of CLDN9 and p-Stat3 in the HCC tissues and histologically non-neoplastic hepatic tissues. RESULTS: We confirmed that the expression of CLDN9 significantly enhanced the metastatic ability of hepatocytes in vitro, and the activation of the Stat3 pathway by Tyk2 was an important mechanism by which CLDN9 promoted hepatocyte aggressiveness in HCC. CONCLUSION: As an HCC proto-oncogene, CLDN9 affected the Stat3 signaling pathway via Tyk2 and ultimately enhanced the metastatic ability of hepatocytes.

A prognostic prediction system for hepatocellular carcinoma based on gene co-expression network.

In the present study, gene expression data of hepatocellular carcinoma (HCC) were analyzed by using a multi-step Bioinformatics approach to establish a novel prognostic prediction system. Gene expression profiles were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The overlapping differentially expressed genes (DEGs) between these two datasets were identified using the limma package in R. Prognostic genes were further identified by Cox regression using the survival package. The significantly co-expressed gene pairs were selected using the R function cor to construct the co-expression network. Functional and module analyses were also performed. Next, a prognostic prediction system was established by Bayes discriminant analysis using the discriminant.bayes function in the e1071 package, which was further validated in another independent GEO dataset. A total of 177 overlapping DEGs were identified from TCGA and the GEO dataset (GSE36376). Furthermore, 161 prognostic genes were selected and the top six were stanniocalcin 2, carbonic anhydrase 12, cell division cycle (CDC) 20, deoxyribonuclease 1 like 3, glucosylceramidase ß3 and metallothionein 1G. A gene co-expression network involving 41 upregulated and 52 downregulated genes was constructed. SPC24, endothelial cell specific molecule 1, CDC20, CDCA3, cyclin (CCN) E1 and chromatin licensing and DNA replication factor 1 were significantly associated with cell division, mitotic cell cycle and positive regulation of cell proliferation. CCNB1, CCNE1, CCNB2 and stratifin were clearly associated with the p53 signaling pathway. A prognostic prediction system containing 55 signature genes was established and then validated in the GEO dataset GSE20140. In conclusion, the present study identified a number of prognostic genes and established a prediction system to assess the prognosis of HCC patients.

(3R)­5,6,7­trihydroxy­3­isopropyl­3­methylisochroman­1­one attenuates cardiac dysfunction via the apelin/APJ signaling pathway.

Myocardial infarction (MI) is associated with a high risk of mortality and is a major global health concern. The present study aimed to investigate the protective effects of (3R)­5,6,7­trihydroxy­3­isopropyl­3­methylisochroman­1­one (TIM) against MI induced by isoproterenol (ISO) in a rat model and the underlying mechanisms. Wistar rats were assigned to 4 groups (n=10): The control group received saline treatment; the ISO group received an intraperitoneal injection of ISO (100 mg/kg); and the TIM (low) and TIM (high) groups received an intraperitoneal injection of ISO, plus a 1 and 2 mg/kg dose of TIM orally, respectively. TIM rats were treated with TIM daily for 12 days and received ISO injections on the final 2 days to induce MI. Cardiac function, apoptosis index and protein expression were subsequently determined. The levels of oxidative stress markers were determined by ELISAs, whereas DNA damage was detected using a Cell Death Detection ELISA kit. Gene and protein expression were determined via reverse transcription­quantitative polymerase chain reaction and western blot analyses, respectively. Following treatment with ISO, the maximum left ventricular contraction/relaxation velocity and left ventricular systolic pressure were significantly decreased, whereas the left ventricular end­diastolic pressure was increased; however, treatment with TIM significantly ameliorated ISO­induced cardiac dysfunction. Additionally, TIM treatment significantly decreased oxidative stress and inhibited the apoptosis of cardiomyocytes, as determined by a decrease in caspase activities, increased expression of B­cell lymphoma 2 (Bcl­2) and reduced expression of cleaved caspase­3, cleaved caspase­9 and Bcl­2­associated X. Furthermore, treatment with TIM upregulated the levels of apelin in the plasma and myocardium of ISO­treated rats. The results indicated that TIM protected cardiomyocytes against ISO­induced MI, potentially via the apelin/apelin receptor signaling pathway. The results of the present study suggested that TIM may be a potential novel therapy for the treatment of MI.

Silencing MicroRNA-134 Alleviates Hippocampal Damage and Occurrence of Spontaneous Seizures After Intraventricular Kainic Acid-Induced Status Epilepticus in Rats.

Epilepsy is a disorder of abnormal brain activity typified by spontaneous and recurrent seizures. MicroRNAs (miRNAs) are short non-coding RNAs, critical for the post-transcriptional regulation of gene expression. MiRNA dysregulation has previously been implicated in the induction of epilepsy. In this study, we examined the effect of silencing miR-134 against status epilepticus (SE). Our results showed that level of miR-134 was significantly up-regulated in rat brain after Kainic acid (KA)-induced SE. TUNEL staining showed that silencing miR-134 alleviated seizure-induced neuronal apoptosis in the CA3 subfield of the hippocampus. Western blot showed that a miR-134 antagonist suppressed lesion-induced endoplasmic reticulum (ER) stress and apoptosis related expression of CHOP, Bim and Cytochrome C, while facilitated the expression of CREB at 24 h post KA-induced lesion in the hippocampus. Consistently, silencing miR-134 significantly diminished loss of CA3 pyramidal neurons using Nissl staining as well as reducing aberrant mossy fiber sprouting (MFS) in a rat epileptic model. In addition, the results of EEG and behavior analyses showed seizures were alleviated by miR-134 antagonist in our experimental models. These results suggest that silencing miR-134 modulates the epileptic phenotype by upregulating its target gene, CREB. This in turn attenuates oxidative and ER stress, inhibits apoptosis, and decreases MFS long term. This indicates that silencing miR-134 might be a promising intervention for the treatment of epilepsy.

RETRACTED: Alkannin inhibits proliferation, migration and invasion of hepatocellular carcinoma cells via regulation of miR-92a.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. Given the comments of Dr Elisabeth Bik regarding this article "… the Western blot bands in all 400+ papers are all very regularly spaced and have a smooth appearance in the shape of a dumbbell or tadpole, without any of the usual smudges or stains. All bands are placed on similar looking backgrounds, suggesting they were copy/pasted from other sources, or computer generated", the journal requested the authors to provide the raw data. However, the authors were not able to fulfil this request and therefore the Editor-in-Chief decided to retract the article.

Circulating microRNAs for the diagnosis of hepatocellular carcinoma.

AIM: There are no existing biomarkers that demonstrate very reliable performance in the diagnosis of hepatocellular carcinoma (HCC), especially in the early stage. Studies have shown that numerous aberrantly expressed circulating microRNAs (miRNAs) can be used as a diagnostic tool for HCC; however, these studies have produced inconsistent results. METHODS: We performed a meta-analysis to summarize the diagnostic accuracy of circulating miRNAs, alpha-fetoprotein (AFP), and AFP combined with miRNAs in differentiating HCC patients from non-HCC controls, healthy controls and chronic liver disease controls. We also evaluated the diagnostic accuracy of circulating miRNAs for early-stage HCC. Furthermore, we systematically reviewed the diagnostic effectiveness of single miRNAs and individual miRNA panels. RESULTS: Circulating miRNAs showed good diagnostic performance. Compared with single miRNAs, the diagnostic accuracy of miRNA panels was clearly better. The combination of AFP and miRNAs improved the diagnostic accuracy compared with the use of miRNAs or AFP alone. For early-stage HCC patients, circulating miRNAs exhibited relatively satisfactory diagnostic accuracy. CONCLUSIONS: Circulating miRNAs can be used as an early diagnostic marker of HCC. The combination of miRNAs and AFP has great potential as a novel strategy for the diagnosis of HCC.

PDCD2 sensitizes HepG2 cells to sorafenib by suppressing epithelial­mesenchymal transition.

Epithelial-mesenchymal transition (EMT) has an established role in the acquisition of therapeutic resistance. Programmed cell death domain 2 (PDCD2) is involved in the progression of multiple types of cancer. However, its mechanism underlying chemoresistance in liver cancer has not been elucidated. In the present study, it was demonstrated that the sorafenib­resistant HepG2 cell line exhibited EMT and multidrug resistance (MDR) phenotypes, and reduced expression of PDCD2, by reverse transcription­quantitative polymerase chain reaction (RT­qPCR), western blot analysis and Cell Counting Kit­8. Annexin V/fluorescein isothiocyanate and cell migration assays further demonstrated that PDCD2 effectively promoted sorafenib­induced cell apoptosis and reduced cell metastasis. Mechanistically, PDCD2 inhibited the expression of Vimentin and increased the expression of E­cadherin in a Snail­dependent manner by RT­qPCR and western blot analysis. In conclusion, the present study elucidated for the first time, to the best of our knowledge, that PDCD2 sensitizes sorafenib­resistant HepG2 cells to sorafenib by the downregulation of EMT. PDCD2 may serve as a potential therapeutic target in the treatment of sorafenib­resistant liver cancer.

Knockdown of lncRNA UCA1 inhibits proliferation and invasion of papillary thyroid carcinoma through regulating miR-204/IGFBP5 axis.

BACKGROUND: Long noncoding RNA (LncRNA) UCA1 has been reported to function as an oncogene in multiple cancers. However, the biological roles and underlying mechanism of UCA1 in papillary thyroid carcinoma (PTC) remain unclear. This study aimed to investigate the underlying function of UCA1 on thyroid cancer progression. MATERIALS AND METHODS: A series of experiments involving Cell Counting Kit-8, wound-healing, and transwell invasion assays were conducted to determine the cellular capabilities of proliferation, migration, and invasion, respectively. Binding sites between UCA1 and miR-204 were identified using a luciferase reporter system, whereas mRNA and protein expression of target genes were determined by real-time quantitative reverse transcription-PCR (qRT-PCR) and Western blot, respectively. RESULTS: The results revealed that UCA1 was upregulated in PTC tissue and cell lines. UCA1 knockdown significantly suppressed the cell proliferation, migration, and invasion of TPC-1 cells. Bioinformatics analysis and luciferase reporter assay verified the complementary binding within UCA1 and miR-204 at the 3'-UTR. Moreover, miR-204 inhibition reversed the UCA1 knockdown-mediated inhibitory effect on cell proliferation, migration, and invasion. We also found that UCA1 could regulate expression of IGFBP5, a direct target of miR-204 in PTC. CONCLUSION: Our study demonstrated that UCA1 exerts activity of oncogenes in PTC through regulating miR-204/IGFBP5 axis.

Up-regulation of miR-10b-3p promotes the progression of hepatocellular carcinoma cells via targeting CMTM5.

In this study, we investigated how miR-10b-3p regulated the proliferation, migration, invasion in hepatocellular carcinoma (HCC) at both in vitro and in vivo levels. CMTM5 was among the differentially expressed genes (data from TCGA). The expression of miR-10b-3p and CMTM5 was detected by qRT-PCR and Western blot (WB). TargetScan was used to acquire the binding sites. Dual-luciferase reporter gene assay was used to verify the direct target relationship between miR-10b-3p and CMTM5. WB analysis proved that miR-10b-3p suppressed CMTM5 expression. Furthermore, proliferation, invasion and migration of HCC cells were measured by MTT assay, colony formation assay, transwell assay and wound-healing assay, respectively. Kaplan-Meier plotter valued the overall survival of CMTM5. Finally, xenograft assay was also conducted to verify the effects of miR-10b-3p/CMTM5 axis in vivo. Up-regulation of miR-10b-3p and down-regulation of CMTM5 were detected in HCC tissues and cell lines. CMTM5 was verified as a target gene of miR-10b-3p. The overexpression of CMTM5 contributed to the suppression of the proliferative, migratory and invasive abilities of HCC cells. Moreover, the up-regulation of miR-10b-3p and down-regulation of CMTM5 were observed to be associated with worse overall survival. Lastly, we have confirmed the carcinogenesis-related roles of miR-10b-3p and CMTM5 in vivo. We concluded that the up-regulation of miR-10b-3p promoted the progression of HCC cells via targeting CMTM5.

Inhibition of MALAT1 sensitizes liver cancer cells to 5-flurouracil by regulating apoptosis through IKKα/NF-κB pathway.

Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) is involved in tumor cell growth process. However, its role and molecular mechanism in liver cancer is still not fully understood. In this study, we found that MALAT1 was significantly expressed in liver cancer cell lines. And knockdown of MALAT1 suppressed proliferation, migration and invasion of HepG2 cells, accompanied with decrease of Rho-associated coiled-coil-forming protein kinase 1 (ROCK1), α-smooth muscle actin (α-SMA), N-cadherin, Vimentin and TWIST. Significantly, MALAT1 deletion sensitized HepG2 cells to 5-FU-induced cell cycle arrest in G1 phase, as evidenced by the significant reduction in Cyclin D1 and CDK4 and increase in p53, p21 and p27 protein levels. In addition, MALAT1 knockdown triggered 5-FU induced apoptosis in HepG2 cells by inducing intrinsic apoptosis-related signals, including Cyto-c, Apaf-1, cleaved Caspase-9/-7/-3 and poly (ADP-ribose) polymerase (PARP). Furthermore, phosphorylated nuclear factor-κB (p-NF-κB) was also down-regulated by MALAT1 silence. Importantly, suppression of IKKα/NF-κB significantly elevated apoptosis and reduced liver cancer cell viability in MALAT1-knockdown cells with 5-FU incubation. The nude mice transplantation model also confirmed the promoted sensitivity of MALAT1-silenced HepG2 cells to 5-FU by blocking tumor cell proliferation and inducing apoptosis. Therefore, our data supplied a potential mechanism by which knockdown of MALAT1 might play an important role in augmenting sensitivity of HepG2 cells to 5-FU in therapeutic approaches, demonstrating suppressing of MALAT1 may serve as a combination with chemotherapeutic agents in liver cancer treatment.

Effects of miR-340 on hepatocellular carcinoma by targeting the DcR3 gene.

In hepatocellular carcinoma (HCC), miR-340 plays a vital role in the regulation of tumor occurrence and deterioration, while DcR3 gene is involved in cancer cell proliferation and apoptosis. This study analyzed miR-340 in the serum of patients with HCC and healthy controls. Then, miR-340, DcR3, TGF-ß1 and Smad2 expression were measured in HCC tissues and adjacent parts. Relationship between miR-340 and DcR3 was verified. Effects of miR-340 on human HepG2 cell proliferation and apoptosis were explored. miR-340, DcR3, TGF-ß1, Smad2 mRNA and protein expression were also determined after miR-340 transfection. Compared with the control, miR-340 was significantly lower in the serum of the HCC patients (p < 0.01). miR-340 was lower in HCC tissues than in adjacent; however, DcR3, TGF-ß1 and Smad2 were higher (p < 0.01). Furthermore, luciferase activity was significantly lower in the cells co-transfected with miR-340 mimics and DcR3-3'UTR-WT (p < 0.01), indicating that DcR3 was a target gene of miR-340. Moreover, decreased expression in DcR3, TGF-ß1 and Smad2 was detected after miR-340 overexpression (p < 0.01), thus promoting apoptosis and blocking the proliferation of human HepG2 cells (p < 0.05). Furthermore, overexpression of DcR3 could activate the TGF-ß1/Smad2 signal transduction pathway and increase the phosphorylation of Smad2. In conclusion, miR-340 plays a suppressive role in HCC development by targeting DcR3 and silencing the TGF-ß1/Smad2 signaling pathway.

Meta-analysis of the association between the Trp64Arg polymorphism of the beta-3 adrenergic receptor and susceptibility to gestational diabetes mellitus.

The study aimed to explore the associations between Trp64Arg polymorphism of Beta-3 Adrenergic receptor (ADRB3) and susceptibility to gestational diabetes mellitus (GDM). Relevant studies till December 2013 were identified through searching electronic databases. A meta-analysis was conducted on associations between Trp64Arg polymorphism in ADRB3 and susceptibility to GDM. We found no association between Trp64Arg polymorphism in ADRB3 and susceptibility to GDM in overall population (Arg vs. Trp: OR = 1.20, 95%CI = 0.99-1.47, p = .16; Trp/Arg + Arg/Arg vs. Trp/Trp: OR = 1.22, 95%CI = 0.99-1.50, p = .11). In subgroup analysis on European Caucasian population, Trp64Arg in ADRB3 was associated with susceptibility to GDM. Trp64Arg polymorphism in ADRB3 had certain association with susceptibility to GDM in the European Caucasian population. Impact statement What is already known on this subject: Gestational diabetes mellitus (GDM) is recognised as carbohydrate intolerance of varied severity that begins or is first recognised during pregnancy. A missense mutation in the codon 64 of the Beta-3 adrenergic receptor (ADRB3), Trp64Arg, leads to the substitution of tryptophan by arginine in the first intracellular loop of the ADRB3 receptor. Trp64Arg Polymorphism has also been reportedly associated with increased body weight, type 2 diabetes mellitus, insulin resistance and obesity. However, other investigators have found that the Trp64Arg polymorphism of ADRB3 has no effect on insulin resistance, obesity or type 2 diabetes mellitus. What the results of the study add: Our present meta-analysis demonstrated that Trp64Arg polymorphism in ADRB3 was associated with susceptibility to GDM in the European Caucasian population. Trp64Arg polymorphism in ADRB3 may be able to predict the occurrence of GDM and used for the diagnosis of it in clinic. What the implications are of these findings for clinical practice and future research: The findings in this study may provide a basis for the further study on Trp64Arg polymorphism in future research.

Application of ionic-liquid-magnetized stirring bar liquid-phase microextraction coupled with HPLC for the determination of naphthoquinones in Zicao.

In this study, a green, rapid, and simple method, ionic-liquid-magnetized stirring bar liquid-phase microextraction was developed for the determination of naphthoquinones, including shikonin and ß,ß'-dimethylacrylshikonin, in Zicao. This method permits active magnetic stirring, extraction, and pre-enrichment in a single device simultaneously, so the extract is conveniently collected. The analytes were extracted from the sample to ionic liquid-magnetized stirring bar, then the analyte-adsorbed magnetized stirring bar can be readily isolated from the sample solution by a magnet. The key experimental parameters were investigated and optimized, including the type and volume of ionic liquid, extraction time, salt concentration, stirring speed, and pH. The recoveries were in the range of 89.47-102.38%, and good reproducibilities were obtained with relative standard deviation below 5.36%. Compared with the conventional extraction methods, the proposed method is quicker and more effective.

Biomarker identification in clear cell renal cell carcinoma based on miRNA-seq and digital gene expression-seq data.

This study aimed to explore the underlying microRNA (miRNA) targets in clear cell renal cell carcinoma (ccRCC). The expression profile with accession number GSE24952 was downloaded from the Gene Expression Omnibus database. Based on the dataset, the differentially expressed genes (DEGs) and miRNAs in ccRCC tissues and matched normal adjacent tissues were analyzed. The target genes of the differentially expressed miRNAs were then predicted. Expression levels of several key miRNAs and genes were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). A total of 168 up- and 288 downregulated DEGs, and 26 up- and 54 downregulated differentially expressed miRNAs were identified. The target genes of miRNA-429 (TGFB1, CCND1, EGFR, and LAMC1) and miRNA-206 (CCND1 and EGFR) were upregulated. Based on the tumor suppressor (TS) gene and tumor-associated gene (TAG) databases, miRNA-142-5p was selected from the upregulated miRNAs. miRNA-429, miRNA-422a, miRNA-206, miRNA-132-3p, and miRNA-184 were selected from the downregulated miRNAs. Moreover, the miRNA regulation network revealed that CCND1 was the common target gene of miRNA-429, miRNA-206, and miRNA-184, and ATP1B1 was the common target gene of miRNA-140-3p and miRNA-142-5p. qRT-PCR revealed that the expression levels of miR-140-3p and CCND1 significantly increased, while that of ATP1B1 significantly decreased in 786-O cells compared with those in human renal tubular epithelial cells, which was in accordance with the predicted results of bioinformatic analysis. In conclusion, miRNA-429, miRNA-206, and miRNA-184 and their target gene CCND1, as well as miRNA-140-3p and miRNA-142-5p and their target gene ATP1B1, might play key roles in ccRCC progression and could be useful biomarkers during ccRCC development.

MiR-874 inhibits metastasis and epithelial-mesenchymal transition in hepatocellular carcinoma by targeting SOX12.

MicroRNA-874 (miR-874), a novel cancer-associated microRNA (miRNA), has been reported to play a suppressive role in multiple malignancies. However, its function in cell migration and invasion in hepatocellular carcinoma (HCC) and the mechanisms responsible remain unclear. Here, we found miR-874 to be significantly downregulated in HCC tissues and cell lines. Moreover, this decreased expression strongly correlated with clinical stage and lymph node metastasis. Accordingly, ectopic expression of miR-874 in HCC cells markedly inhibited their migration, invasion, and epithelial-mesenchymal transition (EMT). Concerning the underlying mechanism, SRY (sex-determining region Y) -box 12 (SOX12) was identified as a direct target of miR-874, and its expression was found to be inversely correlated with that of this miRNA in HCC cells. Importantly, SOX12 knockdown had an inhibitory effect on HCC cells similar to that caused by miR-874 overexpression, whereas SOX12 overexpression in these cells negated the suppressive effects of miR-874 on migration, invasion, and EMT. Overall, these findings demonstrate that miR-874 inhibits metastasis and EMT in HCC by targeting SOX12, suggesting that this miRNA may constitute a promising therapeutic target for this disease.