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The genus Sophora (Fabaceae) includes medicinal plants that have been used in East Asian countries since antiquity. Sophora flavescens is a perennial herb indigenous to China, India, Japan, Korea, and Russia. Its dried roots have antioxidant, anti-inflammatory, antibacterial, apoptosis-modulating, and antitumor efficacy. The congeneric S. koreensis is endemic to Korea and its genome is less than half the size of that of S. flavescens. Nevertheless, this discrepancy can be used to assemble and validate the S. flavescens genome. A comparative genomic study of the two genomes can disclose the recent evolutionary divergence of the polymorphic phenotypic profiles of these species. Here, we used the PacBio sequencing platform to sequence and assemble the S. koreensis and S. flavescens genomes. We inferred that it was mainly small-scale duplication that occurred in S. flavescens. A KEGG analysis revealed pathways that might regulate the pharmacologically important secondary metabolites in S. flavescens and S. koreensis. The genome assemblies of Sophora spp. could be used in comparative genomics and data mining for various plant natural products. [ABSTRACT FROM AUTHOR]

Background: First metatarsophalangeal joint arthrodesis is commonly performed for symptomatic end-stage hallux rigidus. It has been postulated to produce good results in the literature. Various fixation techniques offer differences in union rates, complications and functional outcomes, stirring debates about which produces the best outcomes for patients. Therefore, this review aims to synthesise and compare the outcomes of modern fixation techniques used for first metatarsophalangeal joint (FMPJ) arthrodesis. Methods: The electronic database searched were PubMed, CINAHL, Cochrane Library, and Google Scholar. The critical appraisal skills programme tool for cohort study was used. The interventions consisted of screw(s), plate(s), and staple(s). Studies comprising outdated fixation techniques such as suture, metallic wire, external fixation, Rush rods or Steinmann pins were excluded. Participants were adults over 18 years, undergoing FMPJ arthrodesis in the UK. Studies with the population consisting primarily of revision cases, patients with rheumatoid arthritis or diabetes were excluded. Results: Seven UK studies included 277 feet and a 95.7% overall union rate at a mean union time of 83.5 days. Staples had the highest union rate of 98.2% at mean union time of 84 days, followed by plates (95.2%, 92 days), and finally screws (94.9%, 71 days). The overall complication incidence is 5.8%. All of the fixation techniques produced good functional outcomes postoperatively. Conclusions: Whilst staple techniques showed the highest union rate, plating techniques are preferable over screws or staples for better results across several outcome measures, including reduced complication incidence, stability, early ambulation, and good functional outcome. The Manchester-Oxford Foot Questionnaire and EuroQol-5Dimensional are recommended as measurement tools to assess functional outcomes following FMPJ arthrodesis. [ABSTRACT FROM AUTHOR]

Background: First metatarsophalangeal joint arthrodesis is commonly performed for symptomatic end-stage hallux rigidus. It has been postulated to produce good results in the literature. Various fixation techniques offer differences in union rates, complications and functional outcomes, stirring debates about which produces the best outcomes for patients. Therefore, this review aims to synthesise and compare the outcomes of modern fixation techniques used for first metatarsophalangeal joint (FMPJ) arthrodesis. Methods: The electronic database searched were PubMed, CINAHL, Cochrane Library, and Google Scholar. The critical appraisal skills programme tool for cohort study was used. The interventions consisted of screw(s), plate(s), and staple(s). Studies comprising outdated fixation techniques such as suture, metallic wire, external fixation, Rush rods or Steinmann pins were excluded. Participants were adults over 18 years, undergoing FMPJ arthrodesis in the UK. Studies with the population consisting primarily of revision cases, patients with rheumatoid arthritis or diabetes were excluded. Results: Seven UK studies included 277 feet and a 95.7% overall union rate at a mean union time of 83.5 days. Staples had the highest union rate of 98.2% at mean union time of 84 days, followed by plates (95.2%, 92 days), and finally screws (94.9%, 71 days). The overall complication incidence is 5.8%. All of the fixation techniques produced good functional outcomes postoperatively. Conclusions: Whilst staple techniques showed the highest union rate, plating techniques are preferable over screws or staples for better results across several outcome measures, including reduced complication incidence, stability, early ambulation, and good functional outcome. The Manchester-Oxford Foot Questionnaire and EuroQol-5Dimensional are recommended as measurement tools to assess functional outcomes following FMPJ arthrodesis. [ABSTRACT FROM AUTHOR]

Background: Femoral head osteonecrosis (FHON) is a worldwide challenging clinical topic. Steroid use is one of the main etiologies of FHON. There are several genetic variants associated with FHON. Therefore, the purpose of this umbrella review was to provide a comprehensive summary of a meta-analysis and systematic review of genetic variations associated with nonsteroidal and steroid-induced FHON. Methods: The eligible studies were selected from the PubMed and MEDLINE databases for the collection of diverse systematic meta-analyses and reviews. The genetic main effect score was assigned using the Human Genome Epidemiology Network's Venice criteria to assess the cumulative evidence on the effects of a single nucleotide polymorphism (SNP) on FHON. Results: Eight articles reported the meta-analysis of candidate SNP-based studies covering eight genes and 13 genetic variants. In the nonsteroid-induced FHON genetic variants including rs2012390 and rs11225394 in MMP8, rs1800629 and rs361525 in tumor necrosis factor (TNF)-α, VNTR in intron 4, rs1799983 and rs2070744 in endothelial nitric oxide synthase (eNOS), rs2010963 in vascular endothelial growth factor (VEGF), and rs6025 in factor V showed significance in each reference. The steroid-induced FHON genetic variants including rs693 and rs1042031 in apolipoprotein (Apo)B, rs1045642 in ABCB1, and rs1799889 in PAI-1 showed significance in each reference. Conclusion: Based on the systematic review conducted in this study, we organized the genomes associated with FHON and looked at each contribution. Our results could give an integrative approach for understanding the mechanism of FHON etiology. It is expected that these results could contribute to the strategy of prediagnosis, evaluating the individual risk of nonsteroid-induced and steroid-induced FHON. Level of Evidence: Level I. [ABSTRACT FROM AUTHOR]

Background: Ewing's sarcoma is an aggressive bone and soft tissue tumor with a high incidence in children and adolescents. Due to its high malignancy and poor prognosis, identification of novel biomarkers for intervention therapies is necessary to improve outcome. The EWS/FLI1 fusion gene is a characteristic of Ewing's sarcoma in most cases. Sex determining region Y-box 2 (SOX2) is a primary target of EWS/FLI1. It has been identified as an oncogene and linked to apoptotic resistance in several types of cancer. However, its role and regulatory mechanisms in Ewing's sarcoma are largely unknown. Methods: We systematically investigated the role of SOX2 in Ewing's sarcoma cell lines, human tissue samples and xenograft models. The expression of SOX2 was detected in Ewing's sarcoma samples by WB and IHC. siRNAs were used to knockdown EWS/FLI1 and SOX2 in A673 and RD-ES cell lines with the efficiencies tested by qRT-PCR and WB. The effect of SOX2 on cell cycle and apoptosis was determined by Flow cytometric and TUNEL assays. Akt overexpression was performed with plasmid. The protein expression of the corresponding factors was examined by WB analysis. Inhibition of SOX2 in vivo was performed by siRNA against SOX2 in xenograft models, and the protein expression of the regulators testified in vitro was examined in xenograft tumors by IHC and WB. Results: The results confirmed that SOX2 was highly expressed in Ewing's sarcoma and was the target of EWS/FLI1. SOX2 advanced Ewing's sarcoma cell survival and proliferation by regulating p21, p27 and cyclin-E to facilitate G1/S phase transition and mediating caspase-3, PARP via both extrinsic (Fas and caspase-8) and intrinsic (caspase-9, Bad, Bcl-2 and XIAP) apoptotic pathways to restrain cell apoptotsis. Additionally, SOX2 regulated the cell-cycle progression and apoptosis via activation of the PI3K/Akt signaling pathway. The mechanisms were proved both in vitro and in vivo. Conclusions: The results demonstrate that SOX2 played a central role in promoting Ewing's sarcoma cell proliferation in vitro and in vivo with the underlying mechanisms expounded. These findings suggest that SOX2 may serve as a potential biomarker for targeted intervention in Ewing's sarcoma. [ABSTRACT FROM AUTHOR]

Background: Plants have adapted to survive under adverse conditions or exploit favorable conditions in response to their environment as sessile creatures. In a way of plant adaptation, plant hormones have been evolved to efficiently use limited resources. Plant hormones including auxin, jasmonic acid, salicylic acid, and ethylene have been studied to reveal their role in plant adaptation against their environment by phenotypic observation with experimental design such as mutation on hormone receptors and treatment / non-treatment of plant hormones along with other environmental conditions. With the development of Next Generation Sequencing (NGS) technology, it became possible to score the total gene expression of the sampled plants and estimate the degree of effect of plant hormones in gene expression. This allowed us to infer the signaling pathway through plant hormones, which greatly stimulated the study of functional genomics using mutants. Due to the continued development of NGS technology and analytical techniques, many plant hormone-related studies have produced and accumulated NGS-based data, especially RNAseq data have been stored in the sequence read archive represented by NCBI, EBI, and DDBJ. Description: Here, hormone treatment RNAseq data of Arabidopsis (Col0), wild-type genotype, were collected with mock, SA, and MeJA treatments. The genes affected by hormones were identified through a machine learning approach. The degree of expression of the affected gene was quantified, visualized in boxplot using d3 (data-driven-document), and the database was built by Django. Conclusion: Using this database, we created a web application (http://pgl.gnu.ac.kr/hormoneDB/) that lists hormone-related or hormone-affected genes and visualizes the boxplot of the gene expression of selected genes. This web application eventually aids the functional genomics researchers who want to gather the cases of the gene responses by the hormones. [ABSTRACT FROM AUTHOR]

Background: Abnormal expression of numerous long non-coding RNAs (lncRNAs) has been reported in esophageal squamous cell carcinoma (ESCC) recently, but the great majority of their roles and mechanisms remain largely unclear. We aim to identify the critical ESCC-associated lncRNAs and elucidate the functions and mechanisms in detail. Methods: Microarrays were used to analyze the differentially expressed lncRNAs in ESCC tissues. qRT-PCR was used to verify the result of microarrays. The effects of the most up-regulated lncRNA, cancer susceptibility candidate 9(CASC9), on cell growth, proliferation and cell cycle were investigated by in vivo and in vitro assays. Microarrays and recovery tests were used to discover the regulatory targets of CASC9. RNA FISH and subcellular fractionation assays were used to detect the subcellular location of CASC9. Finally, the mechanism of CASC9 regulating PDCD4 was explored by RIP, RNA-protein pull down and ChIP assays. Results: ESCC tissue microarrays showed that CASC9 was the most up-regulated lncRNA. qRT-PCR analysis indicated that CASC9 expression was positively associated with tumor size and TNM stage and predicted poor overall survival of ESCC patients. Knockdown of CASC9 inhibited ESCC cell growth in vitro and tumorigenesis in nude mice. Furthermore interfering CASC9 decreased cell proliferation and blocked cell cycle G1/S transition. CASC9-associated microarrays indicated that PDCD4 might be the target of CASC9. Consistent with this, PDCD4 expression was negatively associated with CASC9 expression in ESCC tissues and predicted good prognosis. Manipulating CASC9 expression in ESCC cells altered both PDCD4 mRNA and protein levels and cell cycle arrest caused by CASC9 knockdown could be rescued by suppressing PDCD4 expression. CASC9 located both in the nucleus and cytoplasm. Mechanistically, enhancer of zeste homolog2 (EZH2) could bind to both CASC9 and PDCD4 promoter region. Interfering CASC9 reduced the enrichment of EZH2 and H3K27me3 in the PDCD4 promoter region. Conclusions: Our study firstly demonstrates that lncRNA CASC9 functions as an oncogene by negatively regulating PDCD4 expression through recruiting EZH2 and subsequently altering H3K27me3 level. Our study implicates lncRNA CASC9 as a valuable biomarker for ESCC diagnosis and prognosis. [ABSTRACT FROM AUTHOR]

Background: Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) has been demonstrated to be an important player in various human malignancies; it is thought to promote tumor growth by cell cycle regulating. However, the roles of MALAT1 in esophageal squamous cell carcinoma(ESCC), and the mechanisms involved in cell cycle regulation remain poorly understood. Moreover, the factors contributing to its up-regulation in tumor tissues are still largely unclear. Methods: Expression of MALAT1 was determined from cell lines and clinical samples by qRT-PCR. The effects of MALAT1 knockdown on cell proliferation, cell cycle, apoptosis, migration, and invasion were evaluated by in vitro and in vivo assays. The potential protein expression changes were investigated by Western-blotting. The methylation status of the CpG island in the MALAT1 promoter was explored by bisulfite sequencing, while the copy numbers in tumor tissues and blood samples were detected by a well-established AccuCopy™ method. Results: MALAT1 was over-expressed in 46.3% of ESCC tissues, mostly in the high-stage tumor samples. Enhanced MALAT1 expression levels were positively correlated with clinical stages, primary tumor size, and lymph node metastasis. Inhibition of MALAT1 suppressed tumor proliferation in vitro and in vivo, as well as the migratory and invasive capacity. MALAT1 depletion also induced G2/M phase arrest and increased the percentage of apoptotic cells. Western-blotting results implicated that the ATM-CHK2 pathway which is associated with G2/M arrest was phosphorylated by MALAT1 knockdown. No effects of CpG island methylation status on MALAT1 expression were found, whereas amplification of MALAT1 was found in 22.2% of tumor tissues, which correlated significantly with its over-expression. However, neither association between tissue copy number amplification and germline copy number variation, nor correlation between germline copy number variation and ESCC risk were identified in the case-control study. Conclusions: Our data suggest that MALAT1 serves as an oncogene in ESCC, and it regulates ESCC growth by modifying the ATM-CHK2 pathway. Moreover, amplification of MALAT1 in tumor tissues may play an important role for its up-regulation, and it seems that the gene amplification in tumor tissues emerges during ESCC progression, but is not derived from germline origins. [ABSTRACT FROM AUTHOR]

Background Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) has been demonstrated to be an important player in various human malignancies; it is thought to promote tumor growth by cell cycle regulating. However, the roles of MALAT1 in esophageal squamous cell carcinoma(ESCC), and the mechanisms involved in cell cycle regulation remain poorly understood. Moreover, the factors contributing to its up-regulation in tumor tissues are still largely unclear. Methods Expression of MALAT1 was determined from cell lines and clinical samples by qRT-PCR. The effects of MALAT1 knockdown on cell proliferation, cell cycle, apoptosis, migration, and invasion were evaluated by in vitro and in vivo assays. The potential protein expression changes were investigated by Western-blotting. The methylation status of the CpG island in the MALAT1 promoter was explored by bisulfite sequencing, while the copy numbers in tumor tissues and blood samples were detected by a well-established AccuCopy1M method. Results MALAT1 was over-expressed in 46.3% of ESCC tissues, mostly in the high-stage tumor samples. Enhanced MALAT1 expression levels were positively correlated with clinical stages, primary tumor size, and lymph node metastasis. Inhibition of MALAT1 suppressed tumor proliferation in vitro and in vivo, as well as the migratory and invasive capacity. MALAT1 depletion also induced G2/M phase arrest and increased the percentage of apoptotic cells. Western-blotting results implicated that the ATM-CHK2 pathway which is associated with G2/M arrest was phosphorylated by MALAT1 knockdown. No effects of CpG island methylation status on MALAT1 expression were found, whereas amplification of MALAT1 was found in 22.2% of tumor tissues, which correlated significantly with its overexpression. However, neither association between tissue copy number amplification and germline copy number variation, nor correlation between germline copy number variation and ESCC risk were identified in the case-control study. Conclusions Our data suggest that MALAT1 serves as an oncogene in ESCC, and it regulates ESCC growth by modifying the ATM-CHK2 pathway. Moreover, amplification of MALAT1 in tumor tissues may play an important role for its up-regulation, and it seems that the gene amplification in tumor tissues emerges during ESCC progression, but is not derived from germline origins. [ABSTRACT FROM AUTHOR]

Background/Aim: Fas/FasL system is a major regulator of apoptosis. The mechanisms by which Fas mediates cisplatin resistance remain unclear. The aim of this study is to explore the effect of Fas over-expression on cisplatin resistance of small cell lung cancer cells and its possible mechanisms. Materials and methods: Fas was over-expressed in H446/CDDP cells by infection with the adenoviruses containing Fas. Sensitivity of Fas-overexpressed H446/CDDP cells to cisplatin was evaluated using MTT assay. Expressions of Fas, GST-π and ERCC1 were detected by RT-PCR and Western blot analysis. Apoptosis rate was examined by FACS. Results: Over-expression of Fas in H446/CDDP cells significantly decreased the expressions of GST-π and ERCC1 at mRNA and protein levels, and increased the cell apoptosis. Furthermore, up-regulation of Fas significantly decreased the tolerance of H446/CDDP cells to cisplatin. Conclusion: Over-expression of Fas reverses drug resistance of H446/CDDP cells, possibly due to the increased cell sensitivity to apoptosis and the decreased expressions of GST-π and ERCC1. [ABSTRACT FROM AUTHOR]

Background: The development of next generation sequencer (NGS) and the analytical methods allowed the researchers to profile their samples more precisely and easier than before. Especially for agriculture, the certification of the genomic background of their plant materials would be important for the reliability of seed market and stable yield as well as for quarantine procedure. However, the analysis of NGS data is still difficult for non-computational researchers or breeders to verify their samples because majority of current softwares for NGS analysis require users to access unfamiliar Linux environment. Main body: Here, we developed a web-application, "Soybean-VCF2Genomes", http://pgl.gnu.ac.kr/soy%5fvcf2genome/ to map single sample variant call format (VCF) file against known soybean germplasm collection for identification of the closest soybean accession. Based on principal component analysis (PCA), we simplified genotype matrix for lowering computational burden while maintaining accurate clustering. With our web-application, users can simply upload single sample VCF file created by more than 10x resequencing strategy to find the closest samples along with linkage dendrogram of the reference genotype matrix. Conclusion: The information of the closest soybean cultivar will allow breeders to estimate relative germplasmic position of their query sample to determine soybean breeding strategies. Moreover, our VCF2Genomes scheme can be extended to other plant species where the whole genome sequences of core collection are publicly available. [ABSTRACT FROM AUTHOR]