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Background: Long non-coding RNA (lncRNA) plays a vital role in tumor proliferation, migration, and treatment. Since it is challenging to standardize the gene expression levels detected by different platforms, the signatures composed of many immune-related single lncRNAs are still inaccurate. Utilizing a gene pair formed of two immune-related lncRNAs and strategically assigning values can effectively meet the demand for a higher-accuracy dual biomarker combination. Methods: Co-expression and differential expression analyses were performed on immune genes and lncRNAs data from The Cancer Genome Atlas and the ImmPort database to obtain differentially expressed immune-related lncRNAs for pairwise pairing. The prognostic-related differentially expressed immune-related lncRNAs (PR-DE-irlncRNAs) pairs were then identified by univariate Cox regression and used for lasso regression to construct a prognostic model. Various methods were used to validate the predictive prognostic performance of the model. Additionally, we explored the potential guiding value of the model in immunotherapy and chemotherapy and constructed a nomogram suitable for efficient prognosis prediction. Mechanistic exploration of anti-tumor immunity and mutational perspectives are also included. We also analyzed the correlation between the model and immune checkpoint inhibitors (ICIs)-related, N6-methyadenosine (m6A)-related, and multidrug resistance genes. Results: We used a total of 20 pairs of PR-DE-irlncRNAs to create a prognosis model. Quantitative real-time polymerase chain reaction experiments further verified the abnormal expression of 11 lncRNAs in HNSCC cells. Various methods have confirmed the excellent performance of the model in predicting patient prognosis. We reasoned that lncRNAs/TP53 mutation might play a positive/negative anti-tumor role through the immune system by multi-perspective analyses. Finally, it was found that the prognostic model was closely related to immunotherapy and chemotherapy as well as the expression of ICIs/m6A/multidrug resistance-related genes. Conclusion: The prognostic model performs excellently in predicting the prognosis of patients and provides the potential value of practical guidance for treatment. [ABSTRACT FROM AUTHOR]

Background. An increasing number of studies have indicated that the abnormal expression of certain long noncoding RNAs (lncRNAs) is linked to the overall survival (OS) of patients with myeloma. Methods. Gene expression data of myeloma patients were downloaded from the Gene Expression Omnibus (GEO) database (GSE4581 and GSE57317). Cox regression analysis, Kaplan-Meier, and receiver operating characteristic (ROC) analysis were performed to construct and validate the prediction model. Single sample gene set enrichment (ssGSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to predict the function of a specified lncRNA. Results. In this study, a seven-lncRNA signature was identified and used to construct a risk score system for myeloma prognosis. This system was used to stratify patients with different survival rates in the training set into high-risk and low-risk groups. Test set, the entire test set, the external validation set, and the myeloma subtype achieved the authentication of the results. In addition, functional enrichment analysis indicated that 7 prognostic lncRNAs may be involved in the tumorigenesis of myeloma through cancer-related pathways and biological processes. The results of the immune score showed that IF_I was negatively correlated with the risk score. Compared with the published gene signature, the 7-lncRNA model has a higher C-index (above 0.8). Conclusion. In summary, our data provide evidence that seven lncRNAs could be used as independent biomarkers to predict the prognosis of myeloma, which also indicated that these 7 lncRNAs may be involved in the progression of myeloma. [ABSTRACT FROM AUTHOR]

All known riboswitches use their aptamer to senese one metabolite signal and their expression platform to regulate gene expression. Here, we characterize a SAM-I riboswitch (SAM-IXcc) from the Xanthomonas campestris that regulates methionine synthesis via the met operon. In vitro and in vivo experiments show that SAM-IXcc controls the met operon primarily at the translational level in response to cellular S-adenosylmethionine (SAM) levels. Biochemical and genetic data demonstrate that SAM-IXcc expression platform not only can repress gene expression in response to SAM binding to SAM-IXcc aptamer but also can sense and bind uncharged initiator Met tRNA, resulting in the sequestering of the anti-Shine-Dalgarno (SD) sequence and freeing the SD for translation initiation. These findings identify a SAM-I riboswitch with a dual functioning expression platform that regulates methionine synthesis through a previously unrecognized mechanism and discover a natural tRNA-sensing RNA element. This SAM-I riboswitch appears to be highly conserved in Xanthomonas species. Riboswitches consist of an aptamer domain and expression platform, which senses a signal and regulates gene expression, respectively. Here the authors show that the expression platform of a SAM-I riboswitch from the Gram-negative bacteria can sense and bind uncharged an initiator Met tRNA to control the met operon. [ABSTRACT FROM AUTHOR]

Aim:The receptor for advanced glycation end-products (RAGE) plays an important role in development of atherosclerosis, and C-reactive protein (CRP) has been found to stimulate its expression in endothelial cells. In this study we investigated how CRP regulated the expression of RAGE in human coronary artery endothelial cells (HCAECs).Methods:HCAECs were treated in vitro with CRP (50 μg/mL) in combination with a variety of inhibitors. ROS generation was determined by immunocytochemistry and flow cytometry. The RAGE expression and phosphorylation of relevant signaling proteins were measured using Western blot analyses.Results:CRP stimulated the expression of RAGE in the cells, accompanied by markedly increased ROS generation, phosphorylation of ERK1/2 and NF-κB p65, as well as translocation of NF-κB p65 to the nuclei. CRP also stimulated phosphorylation of JNK and p38 MAPK. Pretreatment of the cells with the ROS scavenger N-acetyl-L-cysteine, ERK inhibitor PD98059 or NF-κB inhibitor PDTC blocked CRP-stimulated RAGE expression, but pretreatment with the NADPH oxidase inhibitor DPI, JNK inhibitor SP600125 or p38 MAPK inhibitor SB203580 did not significantly alter CRP-stimulated RAGE expression.Conclusion:CRP stimulates RAGE expression in HCAECs in vitro via ROS generation and activation of the ERK/NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

In this study, bioinformatics methods were performed to screen the candidate prognosis-related genes of clear cell renal cell carcinoma (ccRCC) by analyzing the tumor microenvironment (TME). Gene expression and clinical data of ccRCC patients were accessed from TCGA, and R package ESTIMATE was applied to calculate immune, stromal, and ESTIMATE scores of the patients. Survival analysis was conducted per median of these three scores. Based on the scoring results, differentially expressed genes (DEGs) were screened. Regression algorithms were utilized to screen prognostic genes and establish a risk model. Finally, pathway activity differences were analyzed through GSEA. Patients with the unfavorable prognosis had high immune scores. 619 DEGs (499 up-regulated and 120 down-regulated) were screened based on the differences in gene expression of the patients with high and low immune scores. These genes mainly participated in immune-related signaling pathways. A prognostic risk model for ccRCC patients was constructed and 7 immune-related signature genes (RORB, TNFSF14, UCN2, USP2, TOX3, KLRC2, SLAMF9) were obtained through regression analysis. The constructed prognostic risk model could be used for determining prognoses of patients with ccRCC. We unraveled the association between TME and prognosis of ccRCC patients and established a prognostic risk model based on the differentially expressed genes. These results contributed to understanding of TME that affected patients' prognosis and progression of ccRCC and conduced to finding potential biomarkers of ccRCC. [Display omitted] • High immune scores of ccRCC were dramatically related to dismal prognosis of patients. • Signature genes related to immunity were screened out to establish a prognostic risk model. • The relationship between prognostic signature genes and immune cell infiltration was explored. [ABSTRACT FROM AUTHOR]

Cardiac hypertrophy is characterized by thickening myocardium and decreasing in heart chamber volume in response to mechanical or pathological stress, but the underlying molecular mechanisms remain to be defined. This study investigated altered miRNA expression and autophagic activity in pathogenesis of cardiac hypertrophy. A rat model of myocardial hypertrophy was used and confirmed by heart morphology, induction of cardiomyocyte autophagy, altered expression of autophagy-related ATG9A, LC3 II/I and p62 proteins, and decrease in miR-34a expression. The in vitro data showed that in hypertrophic cardiomyocytes induced by Ang II, miR-34a expression was downregulated, whereas ATG9A expression was up-regulated. Moreover, miR-34a was able to bind to ATG9A 3′-UTR, but not to the mutated 3′-UTR and inhibited ATG9A protein expression and autophagic activity. The latter was evaluated by autophagy-related LC3 II/I and p62 levels, TEM, and flow cytometry in rat cardiomyocytes. In addition, ATG9A expression induced either by treatment of rat cardiomyocytes with Ang II or ATG9A cDNA transfection upregulated autophagic activity and cardiomyocyte hypertrophy in both morphology and expression of hypertrophy-related genes (i.e., ANP and β-MHC), whereas knockdown of ATG9A expression downregulated autophagic activity and cardiomyocyte hypertrophy. However, miR-34a antagonized Ang II-stimulated myocardial hypertrophy, whereas inhibition of miR-34a expression aggravated Ang II-stimulated myocardial hypertrophy (such as cardiomyocyte hypertrophy-related ANP and β-MHC expression and cardiomyocyte morphology). This study indicates that miR-34a plays a role in regulation of Ang II-induced cardiomyocyte hypertrophy by inhibition of ATG9A expression and autophagic activity. [ABSTRACT FROM AUTHOR]

This study was designed to investigate the effect of curcumin on the expression of thrombospondin-4 (THBS-4) in mouse macrophages treated with oxidized low-density lipoprotein (oxLDL). The mouse macrophage cell line ANA-1 was treated with oxLDL. Cell viability was measured by MTT assay. ANA-1 cells were divided into five groups: control group, model group, 5 μM curcumin group, 15 μM curcumin group and 25 μM curcumin group. The gene and protein expression levels of THBS-4 in each group were determined by real-time quantitative polymerase chain reaction (PCR) and western blotting, respectively. MTT assay showed that curcumin concentrations up to 25 μM and oxLDL concentrations up to 20 μg/ml had no significant cytotoxic effects on macrophages at 24 h. Real-time quantitative PCR revealed that THBS-4 mRNA expression was markedly reduced by stimulation with oxLDL, but subsequently significantly increased by treatment with curcumin. Western blotting confirmed that curcumin (5, 15, and 25 μM) significantly prevented the decrease in THBS-4 expression induced by oxLDL (20 μg/ml) in macrophages. Curcumin prevents the decrease in THBS-4 expression induced by oxLDL, which may represent one of the anti-atherosclerotic mechanisms of curcumin. [ABSTRACT FROM AUTHOR]

Abstract: Mingliutianju (Citrus reticuiata Blanco cv.Mingliutianju, MP) is a novel late ripening cultivar selected from Chuntianju (Citrus reticuiata Blanco cv.Chuntianju, CP) through spontaneous bud mutation. Large-scale analysis of gene expression differences between of peels of MP and CP is studied during the course of 12 weeks and 23 weeks after flowering (WAF) using Affymetrix GeneChip® citrus genome array to provide new insights into the mechanisms behind this bud mutation. Altogether, 395 differentially expressed genes are identified including 132 up-regulated and 263 down-regulated genes. Singular enrichment analysis (SEA) and parametric analysis of gene set enrichment (PAGE) are performed and 7 statistically significant differentially expressed genes are selected finally for further study. Results from semiquantitative RT-PCR performed on these 7 genes show that one gene''s expression situation is totally correlated with that observed with the microarray. These seven genes include three UDP-glucosyltransferase genes, two disease resistance-responsive protein-related genes, one chitinase gene and one protein kinase family protein gene, all of which are involved in 18 different biological processes according to the hierarchical tree of annotated gene ontology (GO) terms. The candidate biological process and its relation to bud mutation are discussed. [Copyright &y& Elsevier]

Abstract: Background: It is believed that preemptive IV lornoxicam treatment can reduce the consumption of other analgesics, improve analgesic efficacy, and ameliorate immune function during patient-controlled IV analgesia. However, the effects of preemptive IV lornoxicam treatment on the analgesic efficacy of patient-controlled epidural analgesia (PCEA) with morphine and on chemokine expression remain unknown. Objective: The aim of this prospective, randomized, controlled study was to observe the effects of preemptive IV lornoxicam treatment on the analgesic efficacy of PCEA with morphine and on the expression of monocyte chemotactic protein-1 (MCP-1) and stromal cell-derived factor-1α (SDF-1α) in women undergoing hysterectomy. Methods: Patients undergoing elective hysterectomy with combined spinal and epidural anesthesia were randomized to 1 of 3 groups to receive IV lornoxicam 8 mg before anesthesia (group 1), lornoxicam 16-mg injection before anesthesia (group 2), or isotonic saline (control) before anesthesia. PCEA was used to treat postoperative pain, and a visual analog scale (VAS) and the Bruggemann Comfort Scale (BCS) were used to evaluate analgesic efficacy. Morphine consumption was recorded. To measure plasma concentrations of MCP-1 and SDF-1α via enzyme-linked immunosorbent assay, venous blood samples were obtained from patients at 4 separate times: before anesthesia (baseline); 0 (immediately after anesthesia administration); and 24 and 48 hours after surgery. Results: Forty-five patients (mean [SD] age, 41 [5] years; mean [SD] weight, 54 [6] kg) undergoing elective hysterectomy were included in the study. There were no significant differences in VAS scores, BCS scores, or morphine consumption between the 3 groups. Compared with baseline values, MCP-1 and SDF-1α concentrations were increased significantly immediately after surgery in all 3 groups (all, P < 0.01) and returned to near-baseline values at 24 hours postsurgery in groups 1 and 2, and by 48 hours postsurgery in the control group. MCP-1 and SDF-1α concentrations in groups 1 and 2 were significantly lower than those in the control group immediately (all, P < 0.01) and 24 hours postsurgery (all, P < 0.05). Conclusion: Preemptive IV lornoxicam treatment was associated with attenuation of the plasma concentrations of MCP-1 and SDF-1α immediately after and 24 hours after hysterectomy and was associated with more rapid resolution to near-baseline concentrations of both cytokines in these patients compared with controls; however, it was not associated with significantly reducing epidural morphine consumption. [Copyright &y& Elsevier]

• Gibberellin, indole-3-acetic acid, and salicylic acid treatments as well as adverse stresses including drought, salt, and mechanical injury altered CsNPR1 gene expression in citrus. • Over-expression of CsNPR1 in citrus caused enhanced resistance against HLB. • CsNPR1 protein plays a role in stress and disease defense in citrus through interaction with CsHSPRO2 or CsHIR2 protein. Huanglongbing (HLB) disease, also known as citrus greening, is a severe threat for citrus fruit cultivation industry. Till date, neither any effective radical method to control HLB nor HLB resistant cultivar is developed. The aim of this study was to provide clues for unraveling the molecular regulatory mechanism of citrus in response to HLB, and to provide reference gene for breeding of HLB resistant cultivar. One-year-old plants of Shatian pomelo (Citrus grandis (L.) Osbeck) were treated with different hormones and adverse stresses. We found the disease resistance gene, CsNPR1, expression was modulated by gibberellin, indole-3-acetic acid, and salicylic acid, whereas significant expression changes also occurred under adverse stresses including drought, salt, and mechanical injury. Additionally, we enhanced the expression of CsNPR1 in citrus and evaluated plant resistance against HLB. Finally, to investigate CsNPR1 interacting proteins, a high-quality citrus cDNA library was constructed. The interacting proteins were screened and verified by yeast two-hybrid (Y2H) and Bimolecular Fluorescence Complementation (BiFC) assay. Two CsNPR1-interacting proteins (CsHSPRO2 and CsHIR2) were screened and verified. The results showed that the transgenic plants overexpressing CsNPR1 exhibited enhance tolerance against HLB. Thus, CsNPR1 plays a role in stress and disease defense in citrus through interaction with CsHSPRO2 or CsHIR2 proteins. [ABSTRACT FROM AUTHOR]

• Developed a highly efficient Agrobacterium-mediated transient expression system in apple fruit. • The system will be a rapid and high throughput technique for gene function analysis. • The texture of apple fruits significantly affect its infiltration efficiency. Studies of gene function in apple fruits (Malus domestica) have been hindered by the long juvenile period of apple fruit trees. Transient gene expression is a relatively simple method for gene functional analyses, and has been broadly applied to several plant species; however, few studies have reported a method for systematic transient expression in apple fruits. Here, we developed a highly efficient and robust Agrobacterium -mediated transient expression system for apple fruit, which allows rapid analysis of diverse gene functions. Using a β-glucuronidase gene (GUS) as a reporter for Agrobacterium -mediated transformation, we found that the most suitable infiltration pressure for gene function assays in 'Red Fuji', 'Granny Smith' and 'Royal Gala' fruits was −90 kPa, but −70 kPa in 'Golden Delicious'. The infiltration efficiency of 'Golden Delicious' was higher than that of the other apple cultivars. Transient silencing of MdMYB10 , an anthocyanin biosynthesis regulator, altered anthocyanin content in 'Red Fuji', demonstrating that vacuum infiltration with Agrobacterium can be used for gene functional analysis. Also a significant positive correlation was found between microcrack density and infiltration efficiency. We conclude that this method represents a general tool for efficient and targeted transient regulation of gene expression in apple fruits. [ABSTRACT FROM AUTHOR]