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Increasing evidence has demonstrated the association between long noncoding RNAs (lncRNAs) and multiple autoimmune diseases. To explore four lncRNAs (GAS5, lnc-DC, linc0597 and linc0949) expression levels and gene polymorphisms in systemic lupus erythematosus (SLE), a two stage design was applied. In the first stage, 85 SLE patients and 71 healthy controls were enrolled to investigate the lncRNAs expression levels. Then, 1260 SLE patients and 1231 healthy controls were included to detect the single nucleotide polymorphisms (SNPs) in the differentially expressed lncRNAs identified in the first stage. Linc0597, lnc-DC and GAS5 expression levels were significantly lower in SLE patients than healthy controls (P < 0.001, P < 0.001, P = 0.003 respectively). Association of five SNPs (rs10515177, rs2070107, rs2632516, rs2877877, rs2067079) with SLE risk were analyzed. No significant association was observed between these gene polymorphisms and susceptibility to SLE (all P > 0.010), and we did not find significant association between any genotypes at five SNPs and their respective lncRNAs expression in SLE (all P > 0.010). In summary, the expression levels of linc0597, lnc-DC and GAS5 are decreased in SLE patients, but their gene polymorphisms are not associated with SLE risk, and do not influence their expression levels.

Receptor interacting protein 2 (RIP2) plays a role in sensing intracellular pathogens, but its function in T cells is unclear. We show that RIP2 deficiency in CD4+ T cells resulted in chronic and severe interleukin-17A-mediated inflammation during Chlamydia pneumoniae lung infection, increased T helper 17 (Th17) cell formation in lungs of infected mice, accelerated atherosclerosis, and more severe experimental autoimmune encephalomyelitis. While RIP2 deficiency resulted in reduced conventional Th17 cell differentiation, it led to significantly enhanced differentiation of pathogenic (p)Th17 cells, which was dependent on RORα transcription factor and interleukin-1 but independent of nucleotide oligomerization domain (NOD) 1 and 2. Overexpression of RIP2 resulted in suppression of pTh17 cell differentiation, an effect mediated by its CARD domain, and phenocopied by a cell-permeable RIP2 CARD peptide. Our data suggest that RIP2 has a T cell-intrinsic role in determining the balance between homeostatic and pathogenic Th17 cell responses.

This document is a correction notice for an article titled "The ANGPTL4-HIF-1α loop: a critical regulator of renal interstitial fibrosis" published in the Journal of Translational Medicine. The correction states that Figure 2 in the original article was published incorrectly and provides the correct version of the graph. The article has been updated to reflect this correction. The publisher, Springer Nature, remains neutral regarding jurisdictional claims and institutional affiliations. The authors of the article are Yan Li, Shuang Chen, Qian Yang, Xiao Liu, Weiming Zhou, Ting Kang, Weihua Wu, and Santao Ou. [Extracted from the article]

Enoblituzumab, an immunotherapeutic agent targeting CD276, shows both safety and efficacy in activating T cells and oligodendrocyte-like cells against various cancers. Preclinical studies and mouse models suggest that therapies targeting CD276 may outperform PD1/PD-L1 blockade. However, data from mouse models indicate a significant non-responsive population to anti-CD276 treatment, with the mechanisms of resistance still unclear. In this study, we evaluate the activity of anti-CD276 antibodies in a chemically-induced murine model of head and neck squamous cell carcinoma. Using models of induced and orthotopic carcinogenesis, we identify ITGB6 as a key gene mediating differential responses to anti-CD276 treatment. Through single-cell RNA sequencing and gene-knockout mouse models, we find that ITGB6 regulates the expression of the tumor-associated chemokine CX3CL1, which recruits and activates PF4+ macrophages that express high levels of CX3CR1. Inhibition of the CX3CL1-CX3CR1 axis suppresses the infiltration and secretion of CXCL16 by PF4+ macrophages, thereby reinvigorating cytotoxic CXCR6+ CD8+ T cells and enhancing sensitivity to anti-CD276 treatment. Further investigations demonstrate that inhibiting ITGB6 restores sensitivity to PD1 antibodies in mice resistant to anti-PD1 treatment. In summary, our research reveals a resistance mechanism associated with immune checkpoint inhibitor therapy and identifies potential targets to overcome resistance in cancer treatment. Response rate to anti-CD276 based immunotherapy remains suboptimal in patients with cancer. Here, in a chemically-induced murine model of head and neck squamous cell carcinoma, the authors show that expression of ITGB6 in tumor cells promotes resistance to anti-CD276 therapy, associated with accumulation of PF4+ macrophages and T cell dysfunction. [ABSTRACT FROM AUTHOR]

Interplay between innate and adaptive immune cells is important for the antitumor immune response. However, the tumor microenvironment may turn immune suppressive, and tumor associated macrophages are playing a role in this transition. Here, we show that CD276, expressed on tumor-associated macrophages (TAM), play a role in diminishing the immune response against tumors. Using a model of tumors induced by N-butyl-N-(4-hydroxybutyl) nitrosamine in BLCA male mice we show that genetic ablation of CD276 in TAMs blocks efferocytosis and enhances the expression of the major histocompatibility complex class II (MHCII) of TAMs. This in turn increases CD4 + and cytotoxic CD8 + T cell infiltration of the tumor. Combined single cell RNA sequencing and functional experiments reveal that CD276 activates the lysosomal signaling pathway and the transcription factor JUN to regulate the expression of AXL and MerTK, resulting in enhanced efferocytosis in TAMs. Proving the principle, we show that simultaneous blockade of CD276 and PD-1 restrain tumor growth better than any of the components as a single intervention. Taken together, our study supports a role for CD276 in efferocytosis by TAMs, which is potentially targetable for combination immune therapy. Tumor associated macrophages (TAM) are playing an active role in tumor immune evasion in multiple cancer type. Here authors show that CD276 expression by TAMs may underpin this immune-suppressive role via promoting efferocytosis and suppressing MHC class II expression, which result in decreased CD4+ and CD8 + T cell infiltration. [ABSTRACT FROM AUTHOR]

Coxsackievirus B (CVB) 3C protease (3Cpro) plays a specific cleavage role on AU-rich binding factor (AUF1, also called hnRNP D), which consequently disputes the regulation of AUF1 on downstream molecules. In our study, the iTRAQ approach was first used to quantify the differentially expressed cellular proteins in AUF1-overexpressing HeLa cells, which provides straightforward insight into the role of AUF1 during viral infection. A total of 1,290 differentially expressed proteins (DEPs), including 882 upregulated and 408 downregulated proteins, were identified. The DEPs are involved in a variety of cellular processes via GO terms, protein–protein interactions, and a series of further bioinformatics analyses. Among the DEPs, some demonstrated important roles in cellular metabolism. In particular, DDX5 was further verified to be negatively regulated by AUF1 and increased in CVB-infected cells, which in turn promoted CVB replication. These findings provide potential novel ideas for exploring new antiviral therapy targets. [ABSTRACT FROM AUTHOR]

Background: Intervertebral disc degeneration (IDD) has become a serious public health problem, the mechanism of which is complex and still unclear. We aimed to construct a ceRNA network related to IDD to explore its pathogenesis. Methods: We downloaded the GSE67566, GSE63492, GSE116726 and GSE124272 datasets from GEO database, and obtained the differentially expressed RNAs. Then, we constructed a ceRNA network and the KEGG and GO enrichment analysis were performed. Finally, we performed immune cell infiltration analysis on the GSE124272 dataset and analysed the correlation between immune cell abundance and hub genes expression levels. Results: The ceRNA network included three down-regulated circRNAs: hsa_circ_0074817, hsa_circ_0002702, hsa_circ_0003600, three up-regulated miRNAs: hsa-miR-4741, hsa-miR-3158-5p, hsa-miR-508-5p, and 57 down-regulated mRNAs, including six hub genes: IGF1, CHEK1, CCNB1, OIP5, BIRC5, AR. GO and KEGG analysis revealed that the network is involved in various biological functions. Immune infiltration analysis showed that IDD was closely related to immune cell infiltration, and hub genes could further affect the development of IDD by affecting immune cell infiltration. Conclusion: This study identified the hsa_circ_0074817-hsa-miR-508-5p-IGF1/CHEK1/CCNB1, the hsa_circ_0003600-hsa-miR-4741-BIRC5/OIP5/AR and the hsa_circ_0002702-hsa-miR-3158-5p-IGF1/AR as important regulatory axis of IDD, which will help us gain further insight into the pathogenesis of IDD and determine potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Background. Inflammatory reactions and pyroptosis play an important role in the pathology of intervertebral disc degeneration (IDD). The aim of the present study was to investigate pyroptosis in the nucleus pulposus cells (NPCs) of inflammatory induced IDD by bioinformatic methods and to search for possible diagnostic biomarkers. Methods. Gene expression profiles related to IDD were downloaded from the GEO database to identify differentially expressed genes (DEGs) between inflammation-induced IDD and non-inflammatory intervention samples. Pyroptosis genes were then searched for, and their expression in IDD was analyzed. Weighted gene co-expression network analysis (WGCNA) was then used to search for modules of IDD genes associated with pyroptosis and intersected with DEGs to discover candidate genes that would be diagnostically valuable. A LASSO model was developed to screen for genes that met the requirements, and ROC curves were created to clarify the diagnostic value of the genetic markers. Ultimately, the screened genes were further validated, and their diagnostic value assessed by selecting gene sets from the GEO database. RT-PCR was used to assess the mRNA expression of diagnostic markers in the nucleus pulposus (NP). Pan-cancer analysis was applied to demonstrate the expression and prognostic value of the screened genes in various tumors. Results. A total of 733 DEGs were identified in GSE41883 and GSE27494, which were mainly enriched in transmembrane receptor protein serine/threonine, kinase signaling pathway, response to lipopolysaccharide, and other biological processes, and they were mainly related to TGF beta signaling pathway, toll-like receptor signaling pathway, and TNF signaling pathway. A total of 81 genes related to pyroptosis were identified in the literature, and eight genes related to IDD were identified in the Veen diagram, namely, IL1A, IL1B, NOD2, GBP1, IL6, AK1, EEF2K, and PYCARD. Eleven candidate genes were obtained after locating the intersection of pyroptosis-related module genes and DEGs according to WGCNA analysis. A total of six valid genes were obtained after constructing a machine learning model, and five key genes were finally identified after correlation analysis. GSE23132 and GSE56081 validated the candidate genes, and the final IDD-related diagnostic markers were obtained as SMIM1 and SEZ6L2. RT-PCR results indicated that the mRNA expression of both was significantly elevated in IDD. The pan-cancer analysis demonstrated that SMIM1 and SEZ6L2 have important roles in the expression and prognosis of various tumors. Conclusion. In conclusion, this research identifies SMIM1 and SEZ6L2 as important biomarkers of IDD associated with pyroptosis, which will help to unravel the development and pathogenesis of IDD and determine potential therapeutic targets. [ABSTRACT FROM AUTHOR]

The transcription factor FgHtf1 is important for conidiogenesis in Fusarium graminearum and it positively regulates the expression of the sporulation-related gene FgCON7. However, the regulatory mechanism underlying its functions is still unclear. The present study intends to uncover the functional mechanism of FgHtf1 in relation to FgCon7 in F. graminearum. We demonstrated that FgCON7 serves as a target gene for FgHtf1. Interestingly, FgCon7 also binds the promoter region of FgHTF1 to negatively regulate its expression, thus forming a negative-feedback loop. We demonstrated that FgHtf1 and FgCon7 have functional redundancy in fungal development. FgCon7 localizes in the nucleus and has transcriptional activation activity. Deletion of FgCON7 significantly reduces conidia production. 4444 genes were regulated by FgCon7 in ChIP-Seq, and RNA-Seq revealed 4430 differentially expressed genes in FgCON7 deletion mutant, with CCAAT serving as a consensus binding motif of FgCon7 to the target genes. FgCon7 directly binds the promoter regions of FgMSN2 , FgABAA , FgVEA and FgSMT3 genes and regulates their expression. These genes were found to be important for conidiogenesis. To our knowledge, this is the first study that unveiled the mutual regulatory functions of FgCON7 and FgHTF1 to form a negative-feedback loop, and how the loop mediates sporulation in F. graminearum. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant cancers with poor prognosis and high incidence. The clinical data analysis of liver hepatocellular carcinoma samples downloaded from The Cancer Genome Atlas reveals that the THO Complex 1 (THOC1) is remarkable upregulated in HCC and associated with poor prognosis. However, the underlying mechanism remains to be elucidated. We hypothesize that THOC1 can promote the proliferation of HCC. The present study aims to identify THOC1 as the target for HCC treatment and broaden our sights into therapeutic strategy for this disease. Methods: Quantitative RT-PCR, Western blot, immunofluorescence and immunohistochemistry were used to measure gene and protein expression. Colony formation and cell cycle analysis were performed to evaluate the proliferation. The gene set enrichment analysis were performed to identify the function which THOC1 was involved in. The effects of THOC1 on the malignant phenotypes of hepatocellular cells were examined in vitro and in vivo. Results: The gene set enrichment analysis reveals that THOC1 can promote the proliferation and G2/M cell cycle transition of HCC. Similarly, experimental results demonstrate that THOC1 promotes HCC cell proliferation and cell cycle progression. The knockdown of THOC1 leads to R-loop formation and DNA damage and confers sensitivity to cisplatin. In addition, in vivo data demonstrate that THOC1 can enhance tumorigenesis by increasing tumor cell proliferation. Furthermore, virtual screening predicts that THOC1 as a direct target of luteolin. Luteolin can induce DNA damage and suppress the proliferation of HCC by targeting THOC1. Furthermore, the inhibition of THOC1 activity by luteolin enhances the chemosensitivity of HCC tumor cells to cisplatin. Conclusions: THOC1 was identified as a predictive biomarker vital for HCC-targeted treatments and improvement of clinical prognosis. Luteolin combined with cisplatin can effectively suppress HCC tumor growth, indicating a potential and effective therapeutic strategy that uses luteolin in combination with conventional cytotoxic agents for HCC treatment. [ABSTRACT FROM AUTHOR]

Many cellular processes are driven by spatially and temporally regulated microRNAs (miRNAs)-dependent signaling events. Substantial evidence collected over the years indicates that miRNAs are pivotal regulators that contribute to the initiation and development of EV71-related disorders. Importantly, so far, no clinical trial has been undertaken to address the effect of miRNAs on EV71-related diseases. In this study, we show that EV71 infection results in up-regulation of hsa-miR-494-3p levels, and that EV71-induced hsa-miR-494-3p impacts PI3K/Akt signaling pathway by targeting PTEN. However, very little is known about the relationship between hsa-miR-494-3p and EV71 infection. The overall goal of the study is to get a better insight into whether or not hsa-miR-494-3p is involved in the EV71 infection. We found that the EV71 infection induces cellular apoptosis, and that this process can be counteracted by the over-expression of hsa-miR-494-3p mimics. We also present evidence that cell lines deficient in hsa-miR-494-3p are more sensitive to EV71-induced cell death than the corresponding control cells. Collectively, these findings confirm and extend the pervious observation suggesting that disturbances in miRNAs expression can influence EV71 propagation. In addition, they lend strong support to the ideas that hsa-miR-494-3p-mediated signaling pathway plays an important role in the EV71 replication, and that this may have profound implications on our views on EV71-related diseases. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance For many years, Guangzhou University of Chinese Medicine has been successfully using the empirical Wenyang Huoxue Jiedu formula (WHJF) to treat coronary heart disease. Modern theories of acute coronary syndrome mainly focus on rupture of thin-cap fibroatheromas (TCFAs), which is closely related to the release of vascular endothelial growth factor and its receptor (VEGF/VEGFR). Aim of study We investigated the effects of WHJF on the formation of TCFA plaques and the potential mechanism (VEGF/VEGFR signaling pathway). Materials and methods For the in vivo experiments, WHJF was administered to ApoE -/- mice, as a model of TCFA plaque formation. Aortic sections of the mice were obtained, and the vulnerability index and new vessel density of plaques were calculated by the Movat staining assay and immunohistochemistry kit, respectively. Protein and mRNA expression levels of VEGF/VEGFR in aortas were assayed by capillary electrophoresis immunoassay and quantitative real-time polymerase chain reaction analyses. In vitro , WHJF serum was produced in rats on the fourth day 2 h after the first administration of different concentrations of WHJF. Proliferation, migration, and lumen formation ability of human umbilical vein endothelial cells (HUVECs) treated with sera from these rats were assayed by the CKK-8 kit, Transwell plates, and Matrigel assay, respectively. Protein and mRNA expression levels of signaling molecules in the VEGF/VEGFR pathways were also examined. Results In vivo , the vulnerability index and new vessel density of plaques in the WHJF group were lower than those values in the blank control group ( P  < 0.05). No differences were found between the groups in the expression levels of VEGF/VEGFR ( P  > 0.05). In vitro , the proliferation, migration, and tube formation of HUVECs in the high-dose WHJF group were reduced compared to the control group ( P  < 0.05). This finding was in agreement with the downregulation of VEGFR-2 and pERK ( P  < 0.05). The mRNA expression of signaling molecules showed no difference between the groups ( P  > 0.05). Conclusions WHJF inhibits TCFA formation by influencing the VEGF/VEGFR signaling pathway. [ABSTRACT FROM AUTHOR]

Circular ssDNA can sequester inhibitory microRNAs to restore tumor suppressor gene function, thereby inhibiting tumor progression. Protecting tumor suppressors: Strategies to target inactive tumor suppressor genes in cancer lag behind advances in targeting oncogenes. In new work, Meng et al. developed a therapeutic strategy to simultaneously up-regulate three different tumor suppressor genes that are sometimes co-silenced in different cancers by a microRNA called miR-9. They created a circular single-stranded DNA (CSSD) containing sequences to bind miR-9, thus sequestering it away from its target tumor suppressor genes. Loading the CSSDs onto nanoparticles improved delivery into human tumor cells. The CSSD increased expression of the three tumor suppressor proteins and displayed an antitumor effect in both cell line–based ex vivo models and dozens of patient-derived xenografts in mice. The co-silencing of multiple tumor suppressor genes can lead to escalated malignancy in cancer cells. Given the limited efficacy of anticancer therapies targeting single tumor suppressor genes, we developed small circular single-stranded DNA (CSSD) that can up-regulate the expression of co-silenced tumor suppressor genes by sequestering microRNAs (miRNAs) that negatively regulate these genes. We found that cancer patients with low tumor expression of the tumor suppressor genes KLF17, CDH1, and LASS2 had shortened survival times. The up-regulation of these genes upon transfection of artificial CSSD-9 inhibited tumor proliferation and metastasis and promoted apoptosis in vitro as well as in ex vivo and patient-derived xenograft models. In addition, CSSD is more stable and effective than current miRNA inhibitors, and transfecting CSSDs via nanoparticles substantially improved delivery efficiency. The use of a single CSSD can promote the inhibition of multiple tumor suppressor genes. This study provides evidence for the possibility of using CSSDs as therapeutic miRNA inhibitors to target the co-silencing of multiple tumor suppressor genes. [ABSTRACT FROM AUTHOR]

Background It has been reported that carnosic acid (CA) exhibits a range of biological activities including hepatoprotective, antioxidant and anti-inflammatory. However, the effect of carnosic acid in neuropathic pain remained elusive. Methods A neuropathic pain model of chronic constriction injury (CCI) was established in adult male Sprague–Dawley rats. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were recorded, and western blot was performed to detect sirtuin1 and p66shc content. Results Intrathecal administration of carnosic acid attenuated mechanical allodynia and thermal hyperalgesia in rats following chronic constriction injury. Interestingly, carnosic acid analgesic effect was positively associated with spinal sirtuin1 activation; however, p66shc was inhibited by carnosic acid in the spinal cord. In additional, sirtuin1 inhibitor EX-527 reversed the anti-nociceptive effect of carnosic acid. Conclusions Carnosic acid is effective in the treatment of the established CCI-induced pain. It may be possible that spinal sirtuin1 activition by carnosic acid attenuates neuropathic pain through a mechanism involving the down-regulation of p66shc expression. [ABSTRACT FROM AUTHOR]

Leptin has been well-established as a canonical anorexic peptide hormone in mammals, though much of its function in fish remains obscure. In this study, the cDNAs of two leptin isoforms ( leptin -A and leptin -B) were cloned from the liver of a small cyprinid fish, Tanichthys albonubes . The two T. albonubes leptins, sharing low primary amino acid sequence homology with their mammalian counterparts, and between themselves, are highly conserved in three-dimensional protein structures and gene structures. Liver is a major source of leptin mRNA in T. albonubes with leptin -A being the dominant form. The expression of hepatic leptin -A but not leptin -B mRNA in female fish is significantly higher than in male fish. Transcriptional hepatic levels of leptin -A and leptin -B in both male and female fish were demonstrated to increase after long-term fasting (10–25 days) but decline upon re-feeding (3 days). Strikingly, estrogen (E 2 ) administration induced only leptin -A but not leptin -B hepatic mRNA expression in both male and female fish. Our study here provides the first evidence for differential regulation of two leptins in fish, and sheds new light on the possible origin of leptin in lower vertebrates. [ABSTRACT FROM AUTHOR]

The article looks at chronic lymphocytic leukemia (CLL), focusing on associations between the disease progression and expression of the glycoprotein CD160. It discusses the authors' study of 57 CLL patients, citing their finding that CD160 expression was correlated with CLL cell counts and certain other disease parameters and thus may be relevant as a marker in diagnosis and determination of prognosis.

Background: The interaction of tumor necrosis factor-α (TNF-α) with its receptors: TNFRSF1A and TNFRSF1B is critical for the promotion of tumor growth, invasion and metastasis. To better understand the roles of single nucleotide polymorphisms (SNPs) in the TNF-α, TNFRSF1A and TNFRSF1B genes in the development of breast cancer, we explored the associations between SNPs in these three genes and breast cancer susceptibility in northeast Chinese Han women. Methodology/Principal Findings: This case-control study was conducted among 1016 breast cancer patients and 806 age-matched healthy controls. Seven SNPs in the TNF-α (rs1800629, rs361525), TNFRSF1A (rs767455, rs4149577 and rs1800693) and TNFRSF1B (rs1061622 and rs1061624) genes were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. In TNFRSF1B, the rs1061622 GT genotype and the G allele conferred a reduced susceptibility to breast cancer (P = 0.000662, OR = 0.706, 95% CI: 0.578–0.863; P = 0.002, OR = 0.769, 95% CI; 0.654–0.905, respectively). Moreover, the AG genotype, the AA genotype and the A allele in rs1061624 conferred an increased risk of breast cancer (P = 0.007, OR = 1.470, 95% CI:1.112–1.943; P = 0.00109, OR = 1.405 95% CI:1.145–1.724; P = 0.001, OR = 1.248 95% CI:1.092–1.426, respectively). These two SNPs also had associations with breast cancer risk under the dominant model. In haplotype analysis, the CTA (rs767455 C-rs4149577 T-rs1800693 A) haplotype in TNFRSF1A and the TA (rs1061622 T-rs1061624 A) haplotype in TNFRSF1B had higher frequencies in breast cancer patients (P = 0.00324; P = 0.000370, respectively), but the frequency of GG (rs1061622 G-rs1061624 G) haplotype in TNFRSF1B was lower in breast cancer patients (P = 0.000251). The associations of the three haplotypes remained significant after correcting for multiple testing. In addition, significant associations were also observed between TNFRSF1A polymorphisms and lymph node metastasis, P53, estrogen receptor (ER) and progesterone receptor (PR) statuses. Conclusions: Our results suggest that rs1061622 and rs1061624 in TNFRSF1B may affect breast cancer risk, and SNPs in TNFRSF1A are associated with the clinical features of breast cancer. [ABSTRACT FROM AUTHOR]

Coronary artery disease (CAD), which is mainly caused by atherosclerotic processes in coronary arteries, became a significant health issue. MicroRNAs (miRNAs), and long noncoding RNAs (lncRNAs), have been shown to be stable in plasma and could thereby be adopted as biomarkers for CAD diagnosis and treatment. MiRNAs can regulate CAD development through different pathways and mechanisms, including modulation of vascular smooth muscle cell (VSMC) activity, inflammatory responses, myocardial injury, angiogenesis, and leukocyte adhesion. Similarly, previous studies have indicated that the causal effects of lncRNAs in CAD pathogenesis and their utility in CAD diagnosis and treatment, has been found to lead to cell cycle transition, proliferation dysregulation, and migration in favour of CAD development. Differential expression of miRNAs and lncRNAs in CAD patients has been identified and served as diagnostic, prognostic and therapeutic biomarkers for the assessment of CAD patients. Thus, in the current review, we summarize the functions of miRNAs and lncRNAs, which aimed to identify novel targets for the CAD diagnosis, prognosis, and treatment. • MicroRNAs are involved in different CAD related processes. • miRNAs as diagnostic, prognostic and therapeutic biomarkers in CAD. • LncRNAs are involved in different CAD related processes. • LncRNAs as diagnostic, prognostic and therapeutic biomarkers in CAD. [ABSTRACT FROM AUTHOR]

Nanomaterials have been widely applied and developed due to its unique physicochemical characteristics, such as their small size. The environmental and biological effects caused by nanomaterials have raised concerns. In particular, some nanometal oxides have obvious biological toxicity and pose a major safety problem. The prediction model established by combining the expression levels of key genes with quantitative structure–activity relationship (QSAR) studies can predict the biotoxicity of nanomaterials by relying on both structural information and gene regulation information. This model can fill the gap of missing mechanisms in QSAR studies. In this study, we exposed A549 cells and BEAS-2B cells to 21 nanometal oxides for 24 h. Cell viability was assessed by measuring absorbance values using the CCK8 assay, and the expression levels of the Dlk1-Dio3 gene cluster were measured. By using the theoretical basis of the nano-QSAR model and the improved principles of the SMILES-based descriptors to combine specific gene expression and structural factors, new models were constructed using Monte Carlo partial least squares (MC-PLS) for the biotoxicity of the nanometal oxides on two different lung cells. The overall quality of the nano-QSAR models constructed by combining specific gene expression and structural parameters for A549 and BEAS-2B cells was better than that of the models constructed based on structural parameters only. The coefficient of determination (R2) of the A549 cell model increased from 0.9044 to 0.9969, and the Root Mean Square Error (RMSE) decreased from 0.1922 to 0.0348. The R2 of the BEAS-2B cell model increased from 0.9355 to 0.9705, and the RMSE decreased from 0.1206 to 0.0874. The model validation proved the proposed models have a good prediction, generalization ability and model stability. This study offers a new research perspective for the toxicity assessment of nanometal oxides, contributing to a more systematic safety evaluation of nanomaterials. [Display omitted] • Exploring the impact of nano metal oxides on the gene expression levels of different lung cells through experiments. • Model combining gene expression and structure shows strong predictability, generalization, and stability. • Providing a new research perspective for the safety assessment of nanomaterials. [ABSTRACT FROM AUTHOR]

The ABA responsive protein (ABR) is an important transcription factor in plants, which plays a unique role in the regulation of plant growth and stress response. Previously, ZjABR1/ERF10 was screened by our work from transcriptome database of Zoysia japonica under salt stress, but the detailed regulatory mechanism of this gene involved in is not well elucidated. In this paper, the ZjABR1 was isolated from Zoysia japonica and its function was identified in Oryza sativa. Analysis of gene expression showed that ZjABR1 might play a regulatory role in Abscisic Acid (ABA), ethylene and salt stress response. Compared with wild-type plants, ZjABR1 overexpression transgenic Oryza sativa showed lower seed setting rate, dwarfing and salt resistance. Furthermore, protein interaction experiments indicated that ZjABR1 interacted with a protein functioned in the regulation of GA signaling pathway, which is ZjCIGR1. Therefore, these results establish that ZjABR1 can be a potential multifunctional genetic gene in the cell signal transduction regulation of GA-ABA cross-talking, which affects the development and stress resistance of plants. • Compared with wild-type plants, exogenous ABA, ethylene and salt stress can significantly affect the expression of ZjABR1. • ZjABR1 transgenic Oryza sativa showed seed setting rate decreased, sprouting earlier and dwarfing. • ZjABR1 transgenic plants showed enhanced tolerances to salt stress. • ZjABR1 interacting with ZjCIGR1 may be involved in the cell signal transduction regulation of GA-ABA cross-talking. [ABSTRACT FROM AUTHOR]

Abstract: Plexin-B1, the receptor for Sema4D, has been reported to trigger multiple and sometimes opposing cellular responses in various types of tumor cells. It has been implicated in the regulation of tumor-cell survival, proliferation, angiogenesis, invasion and metastasis. However, the plexin-B1 gene expression and its regulatory mechanism in cervical cancer remain unclear. The present study shows that plexin-B1 is over-expressed in cervical tumor tissues compared to normal cervical tissues by immunohistochemistry, Western blotting and quantitative RT-PCR. The expression of plexin-B1 is significantly associated with cervical tumor metastasis and invasion according to the analysis of the clinicopathologic data. Plexin-B1 also promotes proliferation, migration and invasion in human cervical cancer HeLa cells. We also found that the plexin-B1 levels are inversely correlated with miR-214 amounts in both cervical cancer tissues and HeLa cells. And miR-214 expression level is also associated with metastasis and invasion of cervical tumor. Furthermore, we demonstrate that plexin-B1 is inhibited by miR-214 through a miR-214 binding site within the 3′UTR of plexin-B1 in HeLa cells. Ectopic expression of miR-214 could inhibit the proliferation capacity, migration and invasion ability of HeLa cells. Our findings suggest that plexin-B1, a target of miR-214, may function as an oncogene in human cervical cancer HeLa cells. [Copyright &y& Elsevier]