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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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Insufficient dietary vitamin intake can lead to severe health conditions in humans. Improving the vitamin E (VE) content of food crops such as rice through breeding is an economical and effective means to alleviate this problem. In this study, Homogentisate phytyltransferase (HPT) and γ-tocopherol methyltransferase (γ-TMT), two genes derived from sunflower (Helianthus annuus L., a high VE species), were introduced into an elite rice (Oryza sativa L.) cultivar "Ningjing 7" for biofortification. We verified the successful expression of the two genes in multiple transformation events. High-performance liquid chromatography revealed that transgenic plants expressing either HaHPT alone or HaHPT and HaTMT accumulate more VE compared with the wild type. We also revealed that the level of α-tocopherol, the form of VE with the highest biological activity, had increased to 2.33 times in transgenic HaTMT plants compared with the wild type. Transcriptome analysis revealed that the expression levels of some chlorophyll synthesis pathway genes related to VE precursor synthesis significantly increased during grain filling in transgenic rice grains. No difference in agronomic traits was observed between the transgenic plants and their wild type except for a slightly reduced plant height associated with the transgenic plants. These data demonstrate that the heterologous expression of HaHPT gene is effective in increasing the total VE content, while HaTMT plays an important role in the relative abundance of α-tocopherol in rice grains. This study demonstrates a promising strategy for breeding rice with elevated VE content via metabolic engineering. [ABSTRACT FROM AUTHOR]

Bladder cancer (BC) is one of the ten most common cancers worldwide with late detection and early age of diagnosis. There is abundant evidence that early detection and timely intervention can lead to a better prognosis of BC. Substantial evidence has indicated that microRNAs (miRNAs) are specific to different tumour types and are remarkably stable, indicating that serum miRNAs may serve as potential cancer diagnostic markers. This study aimed to identify suitable serum miRNAs to create a panel that can be used to diagnose primary BC. In this study, 18 miRNAs that were differentially expressed in BC were obtained from the PubMed or Gene Expression Omnibus database. Then, 18 BC-related-miRNAs were verified in screening and validation sets created using 56 (28 primary BC vs. 28 NCs) and 168 (84 primary BC vs. 84 NCs) serum samples, respectively. Quantitative reverse transcription-PCR (qRT-PCR) was performed to verify the identity of the differential miRNAs. A multi-miRNA panel with superior diagnostic performance was constructed. TCGA and KEGG databases were used to conduct the survival analysis and bioinformatics analysis, respectively. Six serum miRNAs (miR-221-5p, miR-181a-5p, miR-98-5p, miR-15a-5p, miR-222-3p, and miR-197-3p) were significantly aberrantly expressed in the BC patients, while four miRNAs from among them (miR-221-5p, miR-181a-5p, miR-15a-5p, miR-222-3p) were assembled into a panel that showed high diagnostic value (AUC = 0.875, 95% CI: 0.815 − 0.921; sensitivity: 82.14%; and specificity: 85.71%) based on the logistic regression analysis. The survival analysis showed that miR-181a-5p was closely associated with BC prognosis (Log-rank p-value < 0.05). The combination of the four miRNAs (miR-221-5p, miR-181a-5p, miR-15a-5p and miR-222-3p) may be a novel non-invasive serological biomarker for BC screening. Early detection and timely intervention can lead to a better prognosis of bladder cancer. This study aimed to identify suitable serum miRNAs to create a panel that can be used to diagnose primary bladder cancer. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis and lipid metabolism are strongly associated, although the precise targets and regulatory mechanisms are unknown. Methods: Osteoarthritis gene expression profiles were acquired from the GEO database, while lipid metabolism-related genes (LMRGs) were sourced from the MigSB database. An intersection was conducted between these datasets to extract gene expression for subsequent differential analysis. Following this, functional analyses were performed on the differentially expressed genes (DEGs). Subsequently, machine learning was applied to identify hub genes associated with lipid metabolism in osteoarthritis. Immune-infiltration analysis was performed using CIBERSORT, and external datasets were employed to validate the expression of these hub genes. Results: Nine DEGs associated with lipid metabolism in osteoarthritis were identified. UGCG and ESYT1, which are hub genes involved in lipid metabolism in osteoarthritis, were identified through the utilization of three machine learning algorithms. Analysis of the validation dataset revealed downregulation of UGCG in the experimental group compared to the normal group and upregulation of ESYT1 in the experimental group compared to the normal group. Conclusions: UGCG and ESYT1 were considered as hub LMRGs in the development of osteoarthritis, which were regarded as candidate diagnostic markers. The effects are worth expected in the early diagnosis and treatment of osteoarthritis. [ABSTRACT FROM AUTHOR]

Objective: Although the use of osimertinib can significantly improve the survival time of lung adenocarcinoma (LUAD) patients with epithelial growth factor receptor mutation, eventually drug resistance will limit the survival benefit of most patients. This study aimed to develop a novel prognostic predictive signature based on genes associated with osimertinib resistance. Methods: The differentially expressed genes (DEGs) associated with osimertinib resistance in LUAD were screened from Gene Expression Omnibus datasets and The Cancer Genome Atlas datasets. Multivariate cox regression was used to establish a prognostic signature, and then a nomogram was developed to predict the survival probability of LUAD patients. We used ROC curve and DCA curve to evaluate its clinical prediction accuracy and net benefit. In addition, the differentially expressed genes significantly associated with prognosis were selected for immune infiltration analysis and drug sensitivity analysis, and their roles in the progression of lung adenocarcinoma were verified by in vitro experiments. Results: Our evaluation results indicated that the new nomogram had higher clinical prediction accuracy and net benefit value than the TN nomogram. Further analysis showed that patients with low STRIP2 expression had a higher level of immune response, and may be more likely to benefit from immune checkpoint inhibitors and conventional antitumor drugs. This may help to select more precise and appropriate therapy for LUAD patients with osimertinib resistance. Furthermore, in vitro experiments showed that STRIP2 promoted the LUAD cells proliferation, migration and invasion. This further demonstrates the importance of this gene signature for prognostic prediction. Conclusion: We developed a reliable prognostic model based on DEGs associated with osimertinib resistance and screened for biomarker that can predict the immune response in LUAD patients, which may help in the selection of treatment regimens after osimertinib resistance. [ABSTRACT FROM AUTHOR]

Plastid-encoded RNA polymerase (PEP) regulates the expression of chloroplast genes involved in photosynthesis and chloroplast development in rice. The PEP-associated protein (PAP) PAP7/pTAC14 is essential for the formation of the PEP complex. However, the function of PAP7 in chloroplast development in rice remains unclear. In this study, we identified a mutant, w81, which displays a yellow-green leaf symptom before the four-leaf stage. The seedlings of the w81 mutant display reduced chlorophyll content, abnormal chloroplast structure, and elevated reactive oxygen species (ROS) level. After the four-leaf stage, plant leaves of the w81 mutant gradually turn green with increased chlorophyll content. Map-based cloning reveals that the PAP7 in the w81 mutant harbors a T to A single-base substitution. This mutation blocks the normal splicing of the fifth intron and generates 74 bp longer transcripts in the mutant. The OsPAP7 protein mainly localizes to the chloroplast and directly interacts with OsPAP5. Our results highlight that OsPAP7 regulates the expression of PEP-dependent chloroplast genes and plays a key role in chloroplast development in rice. [ABSTRACT FROM AUTHOR]

LncRNA HOTAIR exhibited different effects in human cancers. However, the role of HOTAIR was not reported in osteosarcoma. This study aimed to explore the function of HOTAIR in osteosarcoma. Firstly, we examined HOTAIR expression in breast cancer tissues by the RT-qPCR assay and examined HOTAIR protein expression via immunocytochemistry, to chemical assay, and Western blot. Then, for further exploring the function of HOTAIR, we also examined it by CCK-8 and transwell assays. Downregulation of HOTAIR was detected in osteosarcoma, which predicted poor prognosis of patients with osteosarcoma. Moreover, cell migration, invasion, and proliferation were suppressed by HOTAIR overexpression in osteosarcoma. Furthermore, LPR5 was a direct target of HOTAIR, which was upregulated in osteosarcoma. Especially, the upregulation of LPR5 could impair the suppressive effect of HOTAIR in breast cancer. HOTAIR was found to negatively regulate the EMT and Wnt/β-cadherin pathways in osteosarcoma. HOTAIR repressed the progression of osteosarcoma via regulating LPR5 and suppressing the Wnt/β-cadherin pathway. Our findings will provide a positive reference for studying the function of HOTAIR in osteosarcoma. [ABSTRACT FROM AUTHOR]

Fibroblasts in keloids undergo cell identity transition with altered transcriptional characteristics. However, the core transcription factors driving this cellular reprogramming remain largely unknown. Here, we report the results of transcriptional profiling from 48 keloid and 24 control dermal tissues. We identified 1187 upregulated differentially expressed genes (foldchange > 2, false discovery rate < 0.05) in keloids, which were mainly enriched in extracellular matrix organization and bone/cartilage development, with significantly increased expression of bone/cartilage‐associated collagens (COL5A1, COL10A1, and COL11A1) and glycoproteins (ACAN, COMP, and SPARC). Deconvolution analysis also revealed significantly increased composition of osteoblasts in keloid dermis. A total of 92 upregulated transcription factors were screened out from differentially expressed genes and mainly enriched in transcription process and skeleton development. Additional sequencing of six keloid individuals with multiple regions and intersection further narrow the list with 10 transcription factors. Finally, AEBP1, CREB3L1, RUNX2, and ZNF469 have been identified as candidate core regulators in promoting the gaining of bone/cartilage‐like characteristics in keloids. RNA‐sequencing of full‐skin keloids consolidated the existence of these four transcription factors. Immunohistochemistry was employed to verify the expression of AEBP1, CREB3L1, RUNX2, and ZNF469 in keloid fibroblasts. In conclusion, we bioinformatically discovered the increased expression of bone/cartilage‐associated genes and candidate core transcription factors in keloids. Our findings promise to provide molecular clues to develop novel therapeutic modalities against skin fibrosis. [ABSTRACT FROM AUTHOR]

Objective. This study aims to explore the role and mechanism of AXL receptor tyrosine kinase (AXL) in relieving inflammatory pain caused by rheumatoid arthritis (RA). Methods. RA mouse model was constructed by collagen antibody induction. RT-qPCR and Western blot were used to detect the level of AXL in RA fibroblast-like synovial cells (RA-FLS) and joint synovium. The levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nitric oxide (NO) were detected by ELISA. The inflammatory infiltration in joints was determined via HE staining. The mechanical abnormal pain and hyperalgesia were detected by the Von Frey microfilament test. The protein levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (3COX-2), toll-like receptor 4 (TLR4), p65, and phosphor (p)-p65 were detected by Western blotting. Results. The expression of AXL in RA-FLS and RA mice was downregulated, while the expression of iNOS and COX-2 was upregulated. The levels of inflammatory cytokines IL-6, TNF-α, and NO were increased in RA-FLS and RA mice. RA mice presented inflammatory cell infiltration, bone and cartilage destruction, and joint space stenosis. AXL overexpression alleviated inflammatory cell infiltration, inflammatory cytokine secretion, and pathological injury in RA mice. Additionally, AXL overexpression inhibited the expression of TLR4 and p-p65. Conclusion. AXL inhibits inflammatory pain in RA mice by suppressing TLR4/NF-κB pathway. [ABSTRACT FROM AUTHOR]

It has been recently shown that loureirin A (LA), a major active component of resina draconis, might be effective in the prevention and treatment of liver fibrosis. We examined whether LA could inhibit the formation of keloids. To investigate the pharmacological effects of loureirin A on keloid formation and the underlying mechanisms. CellTiter-Blue viability assays were used to examine the proliferation of keloid fibroblasts (KFs) that were treated with LA. Fibroblast migration was evaluated using a cell migration assay. Immunofluorescence staining was used to measure the expression of α-SMA in KFs. RT-qPCR was used to evaluate the mRNA expression of Col-I, Col-III, α-SMA, Bax, and Caspase-3, while Western blotting was used to evaluate the protein expression of Col-I, Col-III, α-SMA, Bax, Caspase-3, p-Smad2, and p-Smad3. LA inhibited the proliferation of KFs and suppressed the migration and TGF-β1-induced myofibroblast differentiation of KFs. In addition, LA downregulated the mRNA and protein levels of Col-I, Col-III, and α-SMA while promoting the mRNA and protein levels of Bax and Caspase-3. Moreover, LA downregulated the protein levels of p-Smad2 and p-Smad3 in cultured TGF-β1-treated KFs ex vivo. These results show that LA has an antikeloid effect on KFs by suppressing the TGF-β1/Smad signalling pathway. Our findings suggest that LA may be a potential candidate drug for the prevention and treatment of keloids. [ABSTRACT FROM AUTHOR]

Tillering is one of the most important agronomic traits for sugarcane which is a vegetatively propagated economic crop. Mining these genes related to tillering trait and utilizing them form an ideal architecture are important to effectively increase cane yield of sugarcane varieties. In this study, qRT-PCR technology was used to explore the expression characteristics of a homologue of HTD2 related to rice tillering, which was named ScHTD2 previously obtained from sugarcane. The polymorphism of ScHTD2 gene in sugarcane germplasm resource population was analyzed, and the correlation between variation sites and tillering trait were also detected. The results showed that relative expression of this gene was tissue specific and highest in leaves. During the germination and development of axillary, the relative expression was the highest in the dormant buds. With the germination of sugar buds, the relative expression level first was significantly down-regulated, and the germination and development of sugar buds were negatively regulated. Treatments of phytokinin, auxin and strigolactone can significantly induce its expression in germinating axillary buds and tiller buds of seedling. By combining with the phenotypic changes after hormone treatment, the high expression of this gene induced auxin and strigolactone could inhibit the continued development of germinating axillary buds and delay the occurrence of tillers, but this inhibitory effect did not occur in the high expression of this gene induced by phytokines. Gene polymorphism analysis on 520 cloned sequences of HTD2 genomic DNA from 26 sugarcane germplasm resources showed that the genome sequence structure of this gene contained two exons and one intron, and the variation was the most abundant in the intron region, followed by the exon 1 region. Much higher nucleotide diversity in intron region was detected in main sugarcane variety population, while the origin species parent population had the higher nucleotide diversity in exon 1 and 2 regions. In terms of haplotype diversity in the coding region, the origin species parent population possessed the most abundant haplotype diversity, followed by the main variety population. In the genetic selectivity test, the original species parent population was subjected to positive selection, with high selection pressure and rapid gene evolution, while the backbone parents population and the main variety populations are subject to negative selection toward purification. Two haplotypes of code region located at radiating center of haplotype evolution map, indicating that they belonged to primitive types. The dose effect of mutation type from 23 SNP sites and 5 InDel sites in the code region was significantly related to the tillering rate of sugarcane germplasm resources, so more attention should be paid to the dose effect of mutation types in sugarcane molecular assisted-breeding plan in future. The present study lays a foundation for further analyzing the biological meaning of tillering related to key genes and the development of functional markers in sugarcane. [ABSTRACT FROM AUTHOR]

Motivation Advanced deep learning techniques have been widely applied in disease diagnosis and prognosis with clinical omics, especially gene expression data. In the regulation of biological processes and disease progression, genes often work interactively rather than individually. Therefore, investigating gene association information and co-functional gene modules can facilitate disease state prediction. Results To explore the gene modules and inter-gene relational information contained in the omics data, we propose a novel multi-level attention graph neural network (MLA-GNN) for disease diagnosis and prognosis. Specifically, we format omics data into co-expression graphs via weighted correlation network analysis, and then construct multi-level graph features, finally fuse them through a well-designed multi-level graph feature fully fusion module to conduct predictions. For model interpretation, a novel full-gradient graph saliency mechanism is developed to identify the disease-relevant genes. MLA-GNN achieves state-of-the-art performance on transcriptomic data from TCGA-LGG/TCGA-GBM and proteomic data from coronavirus disease 2019 (COVID-19)/non-COVID-19 patient sera. More importantly, the relevant genes selected by our model are interpretable and are consistent with the clinical understanding. Availabilityand implementation The codes are available at https://github.com/TencentAILabHealthcare/MLA-GNN. [ABSTRACT FROM AUTHOR]

Background. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer that has a high level of morbidity and mortality. Long noncoding RNA (lncRNA) is a novel regulatory factor of tumour proliferation, apoptosis, and metastasis. Our previous studies indicated that lncRNA FOXP4-AS1 is a functional oncogene in HCC; thus, this study is aimed at further evaluating the clinical and biological function of FOXP4-AS1 in HCC. Material and Methods. First, we detected the expression of FOXP4-AS1 in HCC tissues and paracarcinoma normal tissues by qRT-PCR. Second, the prognostic effects of FOXP4-AS1 in patients with HCC were analysed in a training group and a verification group. Subsequently, to investigate the biological effects of FOXP4-AS1 on HCC cells, downexpression tests were further conducted. Results. The expression of FOXP4-AS1 was higher in HCC tissues than adjacent nontumourous tissues, whereas the low expression of FOXP4-AS1 was correlated with optimistic treatment outcomes, which suggested that FOXP4-AS1 may be an independent prognostic biomarker for HCC. Moreover, the downregulation of FOXP4-AS1 significantly reduced the cell proliferation and clonal abilities and inhibited the invasion, migration, and angiogenesis of hepatoma cells (P < 0.05). Conclusion. These results revealed the clinical significance and biological function of FOXP4-AS1 in HCC development, which may provide a new direction for finding therapeutic targets and potential prognostic biomarkers of HCC. [ABSTRACT FROM AUTHOR]

Background. Hepatocellular carcinoma (HCC) is one of the most highly aggressive cancer worldwide with an extremely poor prognosis. Evidence has revealed that microRNA-587 (miR-587) is abnormally expressed in a series of cancers. However, its expressions and functions in HCC have not been clearly acknowledged. Methods. We detected the expression level of miR-587 both in the Gene Expression Omnibus (GEO) database and 86 paired clinical HCC tissues together with paired adjacent normal tissues by quantitative real-time PCR (qRT-PCR). Afterwards, the transfected HCC cell line SMMC-7721 cells were collected for the cell proliferation assay, cell-cycle arrest, cell migration, and invasion assays to explore the roles of miR-587 in regulating cellular function. In addition, bioinformatics analysis, combined with qRT-PCR and dual-luciferase reporter assays, were performed to confirm whether ribosomal protein SA (RPSA) mRNA was the direct target gene of miR-587. Moreover, the Cancer Genome Atlas (TCGA) and GEO databases as well as 86 paired clinical HCC tissues were used to verify the negative regulation between miR-587 and RPSA. Results. In the present study, both the GEO database (GSE36915 and GSE74618) analysis and qRT-PCR analysis of 86 paired clinical tissues showed that miR-587 was significantly downregulated in HCC tissues. The overexpression of miR-587 inhibited proliferation, cell cycle, migration, and invasion in SMMC-7721 cells. In addition, miR-587 directly interacted with the 3 ′ -untranslated region (UTR) of RPSA. Moreover, miR-587 overexpression directly suppressed RPSA expression, and the two genes were inversely expressed in HCC based on the analyses in TCGA and GEO (GSE36376) databases and qPCR analysis of 86 paired clinical tissues. Conclusion. Our results demonstrate that miR-587 is downexpressed in HCC and regulates the cellular function by targeting RPSA. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BRCA) is the leading cause of cancer‐related death in women worldwide. Pre‐ and postoperative radiotherapy play a pivotal role in BRCA treatment but its efficacy remains limited and plagued by the emergence of radiation resistance, which aggravates patient prognosis. The long noncoding RNA (lncRNA)‐implicated mechanisms underlying radiation resistance are rarely reported. The aim of this study was to determine whether lncRNA HOX transcript antisense RNA (HOTAIR) modulated the radiosensitivity of breast cancer through HSPA1A. Methods: A Gammacell 40 Exactor was used for irradiation treatment. Bioinformatic tools and luciferase reporter assay were adopted to explore gene expression profile and demonstrate the interactions between lncRNA, miRNA and target mRNA 3′‐untranslated region (3′‐UTR). The expression levels of certain genes were determined by real‐time PCR and western‐blot analyses. in vitro and in vivo functional assays were conducted by cell viability and tumorigenicity assays. Results: The levels of oncogenic lncRNA HOTAIR were positively correlated with the malignancy of BRCA but reversely correlated with the radiosensitivity of breast cancer cells. Moreover, the expression levels of HOTAIR were positively associated with those of heat shock protein family A (Hsp70) member 1A (HSPA1A) in clinical BRCA tissues and HOTAIR upregulated HSPA1A at the mRNA and protein levels in irradiated BRCA cells. Mechanistically, miR‐449b‐5p restrained HSPA1A expression through targeting the 3′‐UTR of HSPA1A mRNA, whereas HOTAIR acted as a competing sponge to sequester miR‐449b‐5p and thereby relieved the miR‐449b‐5p‐mediated HSPA1A repression. Functionally, HOTAIR conferred decreased radiosensitivity on BRCA cells, while miR‐449b‐5p overexpression or HSPA1A knockdown abrogated the HOTAIR‐enhanced BRCA growth under the irradiation exposure both in vitro and in vivo. Conclusions: LncRNA HOTAIR facilitates the expression of HSPA1A by sequestering miR‐449b‐5p post‐transcriptionally and thereby endows BRCA with radiation resistance. Key points: Therapeutically, HOTAIR and HSPA1A may be employed as potential targets for BRCA radiotherapy. Our findings shed new light into the mechanism by which lncRNAs modulate the radiosensitivity of tumors. [ABSTRACT FROM AUTHOR]

Internode elongation determines plant height, which in turn affects the cane yield in sugarcane. This study aimed to explore the mechanisms of sugarcane internode elongation regulation by plant growth regulators, gibberellic acid (GA3) and its inhibitor 1, 1-dimethylpiperidinium chloride (DPC, also called mepiquat chloride). We sprayed GA3 or DPC on the leaves at the early shoot elongation stage with water as the control. The contents of endogenous hormones and the expression of GA20 ox1, GID1, and GAI in sugarcane leaves were measured at days 3, 6, 12, and 24 after treatment. It was found that the height of sugarcane plants treated with GA3 showed a significant increase compared to the control, whereas an opposite trend was observed in the DPC-treated plants. Compared to the control, the content of gibberellins (GAs) in leaves was increased significantly, while the indole acetic acid (IAA) content showed an initial increase, then a decline, and eventually remained stable in the GA3-treated plants. The contents of cytokinins (CTK), abscisic acid (ABA), and ethylene (ETH) in leaves exhibited a significant downward trend in the GA3-treated plants compared to the control. In the DCP-treated plants, however, the levels of ABA and ETH in leaves were significantly increased, IAA and GAs significantly decreased, and CTK showed a trend of an initial decline followed by an increase. After GA3 treatment, the gene expression levels of GA20 ox1 and GID1 in sugarcane increased first then decreased, whereas the gene expression level of GAI first decreased and then stabilized. After DPC treatment, the expression of GA20 ox1 in sugarcane showed an initial decrease followed by an increase, while the expression of GID1 decreased gradually and then stabilized, and the expression of GAI showed a trend of an initial increase followed by stabilization. The results of the present study indicate that exogenous GA3 treatment stimulated the internode elongation in sugarcane mainly by increasing the endogenous levels of GAs, decreasing the levels of ABA and ETH, and regulating the expression of GA20 ox1, GID1 and GAI genes; the DPC treatment mainly increased the contents of ABA and ETH and reduced the contents of GAs and IAA, thereby inhibiting the expression of GID1, promoting the expression of GAI, and ultimately inhibiting the internode elongation in sugarcane. [ABSTRACT FROM AUTHOR]

MicroRNA (miR)-199b-5p has been reported to have a critical role in various types of malignancy. However, the exact function miR-199b-5p in renal cancer remains to be fully elucidated. The present study aimed to detect the expression levels of miR-199b-5p in renal cell carcinoma (RCC) tissues and RCC cell lines, and investigated the effect of miR-199b-5p in vitro with Cell Counting Kit-8, MTT, scratch wound, Transwell and flow cytometric assays. The results demonstrated that the expression levels of miR-199b-5p were significantly downregulated in RCC tissues and cell lines compared with those in paired adjacent normal renal tissues and a reference cell line, respectively. Downregulation of miR-199b-5p by transfection with a synthetic inhibitor promoted cellular proliferation and migration, while reducing the apoptotic rate, indicating that miR-199b-5p may serve as a tumor suppressor in RCC. Further study is required to identify target genes of miR-199b-5p to elucidate the mechanisms underlying the role of miR-199b-5p in the occurrence and development of RCC. [ABSTRACT FROM AUTHOR]

Introduction: Rs2292832 is a single nucleotide polymorphism located in the precursor of mir-149 and was reported to be associated with varieties of malignancies. So far, the effect of miR-149 rs2292832 polymorphism on lung cancer risk was unclear. In addition, cooking oil fume exposure was demonstrated to be an important environmental risk factor in Chinese female. The aim of the present study was to evaluate the associations of rs2292832 polymorphism, cooking oil fume exposure and multiplicative interaction of cooking oil fume exposure and rs2292832 polymorphism with lung cancer risk in Chinese non-smoking female population. Methods: The present study was a hospital-based case-control study conducted in Chinese non-smoking females. 555 lung cancer patients and 395 cancer-free controls were interviewed to collect demographic data and exposure status of environmental risk factors, and then donate 10 ml venous blood which was used to be genotyped by Taqman allelic discrimination method. The statistical analyses were performed on SPSS 13.0 software. Results: The association between miR-149 rs2292832 polymorphism and risk of lung cancer(TC vs. TT: OR = 1.006, 95%CI = 0.767–1.321, P = 0.963; CC vs. TT: OR = 0.41, 95%CI = 0.532–1.329, P = 0.458; Dominant model: OR = 0.965, 95%CI = 0.745–1.251, P = 0.788; Recessive model: OR = 0.816, 95%CI = 0.528–1.259, P = 0.357, adjusted for age), non-small cell lung cancer(TC vs. TT: OR = 1.006, 95%CI = 0.767–1.321, P = 0.963; CC vs. TT: OR = 0.841, 95%CI = 0.532–1.329, P = 0.458, adjusted for age), lung adenocarcinoma(TC vs. TT: OR = 0.944, 95%CI = 0.700–1.273, P = 0.707; CC vs. TT: OR = 0.801, 95%CI = 0.485–1.323, P = 0.386, adjusted for age) and squamous cell carcinoma(TC vs. TT: OR = 1.025, 95%CI = 0.641–1.638, P = 0.919; CC vs. TT: OR = 0.792, 95%CI = 0.346–1.813, P = 0.581, adjusted for age) were all not statistically significant. Result of Logistic regression showed that the multiplicative interaction of cooking oil fume exposure and rs2292832 polymorphism was not statistically significant (P = 0.063 for lung cancer and P = 0.064 for lung adenocarcinoma). Conclusion: MicroRNA-149 rs2292832 polymorphism may not be associated with lung cancer risk in Chinese non-smoking female. [ABSTRACT FROM AUTHOR]

Objective: There is no effective and reliable biomarker to distinguish benign thyroid nodules from papillary thyroid carcinomas (PTC). This study aimed at examining the levels of plasma miRNAs in patients with PTC or benign nodules to explore the potential miRNA biomarkers for PTC. Patients and Methods: Genome-wide plasma miRNA expression profiles were determined by the miRNA Microarray and the significantly higher levels of miRNAs were validated in plasma and tissues by quantitative RT-PCR. The levels of two miRNAs were further tested in seven patients before and after tumor excision and the potential values for the diagnosis of PTC were evaluated by receiver operating characteristic curve (ROC). Results: In comparison with that in the patients with benign nodules, eight significantly higher and three lower levels of plasma miRNAs were detected in the PTC patients. Further validation indicated that the levels of plasma miR-25-3p, miR-451a, miR-140-3p and let-7i were significantly higher in the PTC cases than in those with benign nodules or the healthy controls. Significantly higher levels of miR-25-3p and miR-451a were detected in the thyroid tissues from the PTC patients. The levels of plasma miR-25-3p and miR-451a in seven patients significantly decreased after tumor excision. ROC analyses revealed that the levels of plasma miR-25-3p at cut-off 1.41 and miR-451a at 1.38 had sensitivity of 92.8% and 88.9%, and specificity of 68.8% and 66.7% for distinguishing PTC from benign nodules, respectively. Conclusion: Our findings suggest that the levels of plasma miR-25-3p and miR-451a may be valuable for the diagnosis of PTC. [ABSTRACT FROM AUTHOR]

Purpose: PIK3CA gene encoding a catalytic subunit of the phosphatidylinositol-3-kinase (PI3K) is mutated and/or amplified in various neoplasia, including lung cancer. Here we investigated PIK3CA gene alterations, the expression of core components of PI3K pathway, and evaluated their clinical importance in non-small cell lung cancer (NSCLC). Materials and methods: Oncogenic mutations/rearrangements in PIK3CA, EGFR, KRAS, HER2, BRAF, AKT1 and ALK genes were detected in tumors from 1117 patients with NSCLC. PIK3CA gene copy number was examined by fluorescent in situ hybridization and the expression of PI3K p110 subunit alpha (PI3K p110α), p-Akt, mTOR, PTEN was determined by immunohistochemistry in PIK3CA mutant cases and 108 patients without PIK3CA mutation. Results: PIK3CA mutation was found in 3.9% of squamous cell carcinoma and 2.7% of adenocarcinoma. Among 34 PIK3CA mutant cases, 17 tumors harbored concurrent EGFR mutations and 4 had KRAS mutations. PIK3CA mutation was significantly associated with high expression of PI3K p110α (p<0.0001), p-Akt (p = 0.024) and mTOR (p = 0.001), but not correlated with PIK3CA amplification (p = 0.463). Patients with single PIK3CA mutation had shorter overall survival than those with PIK3CA-EGFR/KRAS co-mutation or wildtype PIK3CA (p = 0.004). A significantly worse survival was also found in patients with PIK3CA mutations than those without PIK3CA mutations in the EGFR/KRAS wildtype subgroup (p = 0.043) Conclusions: PIK3CA mutations frequently coexist with EGFR/KRAS mutations. The poor prognosis of patients with single PIK3CA mutation in NSCLC and the prognostic value of PIK3CA mutation in EGFR/KRAS wildtype subgroup suggest the distinct mutation status of PIK3CA gene should be determined for individual therapeutic strategies in NSCLC. [ABSTRACT FROM AUTHOR]

Abstract: Reactive oxygen species (ROS) play an important role in the pathogenesis of diabetic nephropathy. Nuclear factor erythroid 2-related factor 2 (Nrf2) can up-regulate the expression of antioxidant genes and protect cells from oxidative damage. The current study is aimed at examining the effect of modulation of Nrf2 expression on high glucose-induced oxidative stress and Nrf2-targeting antioxidant expression in mouse mesangial cells. In this study, mouse mesangial cells were transiently transfected with Nrf2-plasmid or the Nrf2-specific siRNA. The high glucose-induced intracellular ROS, malondialdehyde, cell proliferation, and TGF-β1 secretion were measured. The levels of Nrf2, heme oxygenase-1 (HO-1), γ-glutamylcysteine synthethase (γ-GCS) expression, and nuclear expression of Nrf2 in mouse mesangial cells were determined. We found that high glucose induced ROS and malondialdehyde generation in mouse mesangial cells. Induction of Nrf2 over-expression reduced the high glucose-induced ROS and malondialdehyde production, inhibited cell proliferation and TGF-β1 secretion, accompanied by up-regulating the expressions of HO-1 and γ-GCS in mouse mesangial cells. However, knockdown of Nrf2 expression displayed reverse effects in mouse mesangial cells. All these results indicated that Nrf2 and its downstream antioxidants, HO-1 and γ-GCS, are negative regulators of high glucose-induced ROS-related mouse mesangial cell dysfunction. [Copyright &y& Elsevier]

To test the hypothesis that combinatorial interference of toll-like receptor 2 (TLR2) and TLR4 is superior to isolated interference of TLR2 or TLR4 in stabilizing atherosclerotic plaques, lentiviruses carrying small interfering RNA of TLR2 or TLR4 were constructed and proved efficacious for knocking down mRNA and protein expression of TLR2 or TLR4 significantly in vitro. One hundred and fifty apolipoprotein E mice fed a high-fat diet were divided into the control, mock, TLR2i, TLR4i and TLR2 + 4i subgroups and a constrictive collar was placed around carotid artery of these mice to induce plaque formation. TLR2i and TLR4i viral suspension was transfected into carotid plaques, respectively, in TLR2i and TLR4i subgroups, or in combination in TLR2 + 4i subgroup. Four weeks after lentivirus transfection, mRNA and protein expression of TLR2 or TLR4 was attenuated markedly in carotid plaques, leading to reduced local inflammatory cytokine expression and plaque content of lipid and macrophages, increased plaque content of collagen and lowered plaque vulnerability index. Factorial ANOVA analysis revealed that there was a synergistic effect between TLR4i and TLR2i in stabilizing plaques. In conclusion, combinatorial interference of TLR2 and TLR4 reduces local inflammation and stabilizes plaques more effectively than interference of TLR2 or TLR4 alone. [ABSTRACT FROM AUTHOR]

AbstractBecause both Toll-like receptor-1 (TLR1) and TLR2 are expressed in atherosclerotic plaques, we hypothesized that TLR1 and TLR2 may play different roles in the formation of vulnerable plaques and that combinatorial knockdown of TLR1 and TLR2 genes may enhance the effects of isolated knockdown of the TLR1 or TLR2 gene on plaque stabilization. Lentiviruses carrying small interfering RNAs of TLR1 or TLR2 were constructed, which knocked down mRNA and protein expression of TLR1 or TLR2 significantly in vitro. One hundred and forty apolipoprotein E-deficient (apoE−/−) mice were randomly allocated to control, mock, TLR1 interference (TLR1i), TLR2 interference (TLR2i), and TLR1+2 interference (TLR1+2i) subgroups and a constrictive collar was placed around the carotid artery of these mice to induce plaque formation. TLR1i and TLR2i viral suspension was transfected into the carotid plaques separately in the TLR1i and TLR2i subgroups or together in the TLR1+2i subgroup. Four weeks after lentivirus transfection, expression of both TLR1 and TLR2 in the carotid plaques was remarkably attenuated. Plaques of the TLR1i subgroup showed lower macrophage content and interleukin (IL)-6 expression and a thicker fibrous cap compared with the control or mock subgroups. Plaques of the TLR2i subgroup showed a higher content of collagen and lower content of lipid and macrophages, a thicker fibrous cap, lower vulnerability index, and lower mRNA expression of IL-6 and monocyte chemoattractant protein-1 than the TLR1i subgroup. In the TLR1+2i subgroup, the macrophage and smooth muscle cell content, and the vulnerability index, were ameliorated as compared with those in the TLR2i subgroup. Lentivirus-mediated RNA interference can be used to efficiently knock down TLR1 and TLR2 genes in carotid plaques of apoE−/−mice. Although isolated knockdown of TLR1 or TLR2 is effective in attenuating plaque vulnerability, combinatorial interference with TLR1 and TLR2 exhibits enhanced improvement of plaque stability, and thus provides a useful approach to the stabilization of vulnerable plaques. [ABSTRACT FROM AUTHOR]

Objective: To study adrenomedullin (ADM) expression and its relation to ciliary beat frequency (CBF) in the nasal mucociliated epithelium in tubal ectopic pregnancy (tEP). Design: Experimental study. Setting: University teaching hospital. Patient(s): Women with tEP and normal intrauterine pregnancy matched for age and gestational age were recruited. Healthy nonpregnant women were also recruited as nonpregnant controls. Intervention(s): Nasal epithelial brushing. Main Outcome Measure(s): Adrenomedullin expression in nasal epithelium (measured by real-time reverse transcription–polymerase chain reaction, plasma ADM concentration (measured by ELISA), and CBF (measured by photometric method). Result(s): We have demonstrated a similar decrease in ADM expression and CBF in the nasal mucociliated epithelium, as well as in plasma ADM concentration, in women with tEP compared with normal pregnant women. Adrenomedullin up-regulates nasal CBF via the ADM receptor, as in the oviduct. There is significant correlation between nasal and oviductal CBF. Conclusion(s): Nasal epithelium ADM and CBF, as well as plasma ADM, are possible predictors of women at risk of tEP. [ABSTRACT FROM AUTHOR]

Essential metals play important roles in the carcinogenic process. However, seldom longitudinal investigations have evaluated their roles in lung cancer development. We aimed to investigate the associations between multiple essential metals and lung cancer incidence and to explore the potential mechanisms. A nested case-control study of 440 incident lung cancer cases and 1:3 frequency matched 1320 healthy controls from the Dongfeng-Tongji Cohort was conducted. The baseline plasma concentrations of 11 essential metals (cobalt, copper, iron, manganese, molybdenum, rubidium, selenium, strontium, stannum, vanadium, and zinc) were measured, and their associations with lung cancer incidence were estimated. Effect of positive metal (zinc) on 4-year telomere attrition was then evaluated among an occupational cohort of 724 workers. We also assessed the transcriptional regulation effects of plasma zinc on mRNA expression profiles, and the expressions of zinc-related genes were further compared in pair-wised lung tumor and normal tissues. Elevated plasma level of zinc was associated with lower incident risk of lung cancer [OR (95% CI) = 0.89 (0.79, 0.99)] and decreased 4-year telomere attrition [β (95% CI) = −0.73 (−1.27, −0.19)]. These effects were pronounced among males. In particularly, zinc could regulate the expressions of 8 cancer-related genes, including SOD1 , APE , TP53BP1 , WDR33 , LAPTM4B , TRIT1 , HUWE1 , and ZNF813 , which were over-expressed in lung tumor tissues. We propose that high plasma zinc could prevent incident lung cancer, probably by slowing down telomere attrition and regulating the expressions of cancer-related genes. These results provided a new insight into lung cancer prevention. • Increased plasma zinc level was associated with a lower risk of lung cancer. • High plasma zinc level was associated with decreased telomere length attrition. • Plasma zinc level was associated with the expressions of 13 cancer-related genes. • 8 of the 13 cancer-related genes were up-regulated in lung tumor tissues. [ABSTRACT FROM AUTHOR]

Glioblastoma downregulated RNA (GLIDR) is a newly discovered long non-coding RNA (lncRNA) that its increased expression indicates a poor prognosis of prostate cancer (PCa). However, the effect of GLIDR on PCa cells is not clear. Our study investigated the role and molecular mechanism of GLIDR in PCa cells. The results showed that GLIDR expression levels were higher in PCa samples and cells than in control. GLIDR could regulate the invasive potential, epithelial-to-mesenchymal transition (EMT) and proliferation in PC-3 and LnCaP cells. Besides, GLIDR could weaken the inhibitory effects of miR-128–3p on invasion, EMT and proliferation in PCa cells. Western blotting proved that miR-128–3p affected the expression of EMT markers, such as E-cadherin, Snail and N-cadherin, and GLIDR could reversed the effects of miR-128–3p on the expression levels of EMT markers in PCa cells. In addition, knockdown of miR-128–3p stimulated the invasion, EMT, and proliferation in PCa cells, whereas these effects were reversed when GLIDR expression was knocked down. GLIDR knockdown inhibited the invasion, EMT, and proliferation in PCa cells, and GLIDR was shown to sponge miR-128–3p. Together, these results highlight GLIDR as a potential therapeutic target for the PCa treatment. [ABSTRACT FROM AUTHOR]

Abstract: To determine whether Th17/Treg balance was abnormal in adult patients with minimal change nephrotic syndrome (MCNS), we studied 25 patients with new-onset MCNS and 20 normal persons. The results showed that MCNS patients exhibited a significant increase in Th17 number, Th17-related cytokines (IL-17 and IL-23), and transcription factor (RORγt) levels, as well as an obvious decrease in Treg number, Treg-related cytokines (TGF-β1 and IL-10), and transcription factor (Foxp3) levels. The Th17/Treg ratios increased along with increased proteinuria and decreased albumin levels in patients with MCNS. IL-17 protein expression was also detected in the renal biopsy tissue of MCNS patients, particularly in patients with acute renal failure. Further, Th17/Treg balance returned to normal after effective corticosteroids therapy in 16 MCNS patients. These results indicated that Th17/Treg imbalance existed in MCNS patients, suggesting a potential role of Th17/Treg imbalance in the pathogenesis of MCNS. [Copyright &y& Elsevier]