Paraspeckle protein NONO attenuates vascular calcification by inhibiting bone morphogenetic protein 2 transcription.

Vascular calcification is a pathological process commonly associated with atherosclerosis, chronic kidney disease, and diabetes. Paraspeckle protein NONO is a multifunctional RNA/DNA binding protein involved in many nuclear biological processes but its role in vascular calcification remains unclear. Here, we observed that NONO expression was decreased in calcified arteries of mice and patients with CKD. We generated smooth muscle-specific NONO-knockout mice and established three different mouse models of vascular calcification by means of 5/6 nephrectomy, adenine diet to induce chronic kidney failure, or vitamin D injection. The knockout mice were more susceptible to the development of vascular calcification relative to control mice, as verified by an increased calcification severity and calcium deposition. Likewise, aortic rings from knockout mice showed more significant vascular calcification than those from control mice ex vivo. In vitro, NONO deficiency aggravated high phosphate-induced vascular smooth muscle cell osteogenic differentiation and apoptosis, whereas NONO overexpression had a protective effect. Mechanistically, we demonstrated that the regulation of vascular calcification by NONO was mediated by bone morphogenetic protein 2 (BMP2). NONO directly bound to the BMP2 promoter using its C-terminal region, exerting an inhibitory effect on the transcription of BMP2. Thus, our study reveals that NONO is a novel negative regulator of vascular calcification, which inhibits osteogenic differentiation of vascular smooth muscle cell and vascular calcification via negatively regulating BMP2 transcription. Hence, NONO may provide a promising target for the prevention and treatment of vascular calcification.

Natural killer cell-based signature: Prognostic analysis in head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSC) is a challenging cancer with significant clinical implications. Natural killer (NK) cells have emerged as important players in tumor immunosurveillance, yet their role and potential as prognostic biomarkers in HNSC remain unclear. METHODS: Quantitative analysis using multiple algorithms identified FCRL1, KIR3DL2 and ZNF541 as molecules significantly associated with local NK cell infiltration and patient survival. A prognostic model based on these molecules demonstrated robust predictive performance. RESULTS: Analysis of high- and low-risk patient groups revealed distinct differences in the tumor microenvironment, indicating an inhibitory immune microenvironment in high-risk patients. Notably, low-risk patients exhibited potential sensitivity to immunotherapy and showed favorable responses to specific drugs such as axitinib, methotrexate, rapamycin and vorinostat. NK cells, important effectors of the innate immune response, were found to play a crucial role in HNSC immunity. The present study provides valuable insights into the correlation between FCRL1, KIR3DL2, ZNF541 and NK cell infiltration, paving the way for future investigations into their roles in HNSC. Activation of NOTCH signaling, MYC targets, DNA repair, E2F targets, epithelial-mesenchymal transition, G2M checkpoint and mitotic spindle pathways in high-risk patients suggests their involvement in disease progression and poor prognosis. CONCLUSIONS: The present study reveals the significance of NK cells in HNSC and their potential as prognostic biomarkers. The CFKZ score offers a promising approach for predicting patient outcomes and guiding personalized treatment decisions in HNSC. These findings contribute to our understanding of HNSC immunobiology and hold implications for precision medicine in HNSC management.

Knowledge-Fusion-Based Iterative Graph Structure Learning Framework for Implicit Sentiment Identification.

Implicit sentiment identification is a significant classical task in text analysis. Graph neural networks (GNNs) have recently been successful in implicit sentiment identification, but the current approaches still suffer from two problems. On the one hand, there is a lack of structural information carried by the single-view graph structure of implicit sentiment texts to accurately capture obscure sentiment expressions. On the other hand, the predefined fixed graph structure may contain some noisy edges that cannot represent semantic information using an accurate topology, which can seriously impair the performance of implicit sentiment analysis. To address these problems, we introduce a knowledge-fusion-based iterative graph structure learning framework (KIG). Specifically, for the first problem, KIG constructs graph structures based on three views, namely, co-occurrence statistics, cosine similarity, and syntactic dependency trees through prior knowledge, which provides rich multi-source information for implicit sentiment analysis and facilitates the capture of implicit obscure sentiment expressions. To address the second problem, KIG innovatively iterates the three original graph structures and searches for their implicit graph structures to better fit the data themselves to optimize the downstream implicit sentiment analysis task. We compared our method with the mainstream implicit sentiment identification methods on two publicly available datasets, and ours outperformed both benchmark models. The accuracy, recall, and F1 values of KIG on the Pun of the Day dataset reached 89.2%, 93.7%, and 91.1%, respectively. Extensive experimental results demonstrate the superiority of our proposed method for the implicit sentiment identification task.

Impaired proliferation of growth plate chondrocytes in a model of osteogenesis imperfecta.

Short stature is the second conspicuous characteristic of osteogenesis imperfecta (OI), but the etiological mechanism is unclear. The proliferation of growth plate chondrocytes (GPCs) plays an essential role in longitudinal bone growth, and chondrocyte division deficiency can cause shortened limbs. However, few studies have reported the abnormal changes of growth plate and GPCs in OI. In this study, the cell proliferative performance of GPCs in heterozygous Col1a2oim/+ mice were studied and the underlying mechanism was explored by RNA-Sequencing. The results indicated that chondrocytes of Col1a2oim/+ background displayed impaired cell division when compared with cells of wild-type littermates. A group of differentially expressed genes involving chondrocyte proliferation related pathways including cell cycle, TGF-ß signaling pathway and Hedgehog signaling pathway were identified. These dysregulated genes and pathways in GPCs of Col1a2oim/+ mice are likely to play an important role in their shortened long bones. Further investigations to reveal the effect of these genes on bone elongation not only facilitate the understanding of OI short stature, but also contribute to developing new treatments.

RALY may cause an aggressive biological behavior and a dismal prognosis in non-small-cell lung cancer.

RALY is a member of the heterogeneous nuclear ribonucleoprotein (hnRNP), an RNA-binding protein that plays a role in mRNA splicing and metabolism, may be involved in tumorigenesis and development. Some studies have shown that RALY plays a role in promoting cancer in a variety of tumors. However, the biological function and molecular mechanism of RALY in non-small cell lung cancer (NSCLC) remain unknown. TCGA databases were used to gather RALY expression data in NSCLC, the results indicate that RALY is highly expressed in cancer tissue of NSCLC patients. Then we demonstrated that RALY gene expression was notably upregulated in NSCLC tissue and cell lines (A549 and SK-MES-1), and was associated with lymph node metastasis (P = 0.007) and poorer overall survival in NSCLC patients. Subsequently, RALY in A549 and SK-MES-1 cells was knocked down by lentivirus to analyze the consequences of RALY on the biological behavior of NSCLC cell lines. Our results indicated that RALY knockdown impaired NSCLC cells proliferation, migration, and invasion, as well as arrested cells in G1 phase, and the reintroduction of RALY recused its biological phenotype. Furthermore, RALY knockdown down-regulated the expression levels of c-Myc, Cyclin D1, CDK4, MMP9, Rho A ,Rho C, N-cadherin and ß-catenin, and up-regulated the expression levels of P27, Rho B and E-cadherin. Therefore, targeting RALY could be a promising molecular target for NSCLC treatment.

Human Schlafen 5 regulates reversible epithelial and mesenchymal transitions in breast cancer by suppression of ZEB1 transcription.

BACKGROUND: Human Schlafen 5 (SLFN5) has been reported to inhibit or promote cell invasion in tumours depending on their origin. However, its role in breast cancer (BRCA) is undetermined. METHODS: Differential expression analyses using The Cancer Genome Atlas (TCGA) data, clinical samples and cell lines were performed. Lentiviral knockdown and overexpression experiments were performed to detect changes in cell morphology, molecular markers and invasion. Chromatin immunoprecipitation-sequencing (ChIP-Seq) and luciferase reporter assays were performed to detect the SLFN5-binding motif. RESULTS: TCGA, clinical samples and cell lines showed that SLFN5 expression was negatively correlated with BRCA metastasis. SLFN5 knockdown induced epithelial-mesenchymal transition (EMT) and enhanced invasion in BRCA cell lines. However, overexpression triggered mesenchymal-epithelial transition (MET). SLFN5 inhibited the expression of ZEB1 but not ZEB2, SNAI1, SNAI2, TWIST1 or TWIST2. Knockdown and overexpression of ZEB1 indicated that it was a mediator of the SLFN5-governed phenotype and invasion changes. Moreover, SLFN5 inhibited ZEB1 transcription by directly binding to the SLFN5-binding motif on the ZEB1 promoter, but a SLFN5 C-terminal deletion mutant did not. CONCLUSION: SLFN5 regulates reversible epithelial and mesenchymal transitions, and inhibits BRCA metastasis by suppression of ZEB1 transcription, suggesting that SLFN5 could be a potential target for BRCA therapy.

Improved TDM scheme and data extracting algorithm for polymerization evaluation.

To quickly evaluate holographic photopolymers with different formulations, the most effective method is to record a volume holographic grating in the samples and detect the grating's diffraction in real time. Since the volume grating is highly sensitive to incident angle, existing schemes need to precisely control many space-related parameters. This study proposes an improved scheme, in which two different sized spots are used to reduce the requirements for the overlap of the two spots and the installation precision of the samples. Transmittances, diffractive efficiencies and diffractive asymmetries are obtained at a high sampling rate, through a specifically designed algorithm with the data from uncalibrated high-speed photodiodes. The experimental results show that the proposed scheme performance well in evaluating holographic photopolymer.

The combination of CTCs and CEA can help guide the management of patients with SPNs suspected of being lung cancer.

OBJECTIVE: Solitary pulmonary nodules (SPNs) is a common radiographic finding and require further evaluation because of the possibility of lung cancer. This study aimed to determine the sensitivity and specificity of circulating tumour cells (CTCs) as a marker for the diagnosis of SPNs and the integration of CTCs, carcinoembryonic antigen (CEA) and imaging findings to improve the sensitivity and specificity of diagnosis in patients with SPNs suspected of being lung cancer. METHOD: For the serum biomarker assay, the concentration of CEA was measured by an automated electrochemiluminescence analyzer. CTCs were collected from 6 ml of blood by the SE i-FISH method, which detects the gene copy number in eight chromosomes and the tumour-associated antigen CK18. RESULTS: With a threshold of 6 CTC units, the method showed a sensitivity of 67.1% and a specificity of 56.5% in the diagnosis of NSCLC, especially in the upper lobe, in which the diagnostic strength was the highest (P < 0.01). CTCs, CEA and nodule type had the highest diagnostic efficacy (area under the curve, 0.827; 95% confidence interval, 0.752-0.901) in patients with SPNs being suspected lung cancer. Combining CTCs (cut-off value 12 units) with CEA (1.78 ng/ml), the method showed a sensitivity of 77.8% and a specificity of 90% in the diagnosis of NSCLC, especially in the upper lobe, subsolid nodules and nodules ≥8 mm. CONCLUSIONS: Our results demonstrated that CTCs are feasible diagnostic biomarkers in patients with SPNs, especially in the upper lobe. Furthermore, CTCs combined with CEA showed higher diagnostic efficacy in the upper lobe, subsolid nodules and nodules ≥8 mm.

Trans fatty acid intake among Chinese population: a longitudinal study from 1991 to 2011.

OBJECTIVE: This study was aimed to roughly describe individual Trans Fatty Acids (TFAs) intake and the percentage of energy intake(E%), and identify major food sources in the Chinese population, taking gender, age, and regional distribution into the consideration, as well as examining temporal changes over the course of 20 years. METHOD: This multi-center study, covering nine provinces among populations aged ≥ 3 in China, was conducted to collect food consumption information from 1991 to 2011. A classical assessment method was used to estimate the level of dietary TFA intake. RESULTS: Over the 20-year period, the intake of TFAs in Chinese populations had increased, but remained at a relatively lower level (from 0.25 g/d(0.11% for E%) to 0.53 g/d(0.24% for E%)) compared with that of other countries and the World Health Organization (WHO) recommended level. Collectively, males and participants aged 19-60 generally consumed more TFA-containing foods. People in eastern regions consumed more TFAs and had a higher E% than those in western area. Industrial sources of TFAs, especially vegetable oil, ranked as the principal food sources of TFAs in the Chinese population. Natural sources of TFAs have gradually increased in proportion among children and adolescents. CONCLUSIONS: TFA intake and the E% are commonly under the recommended level in the general population in China. Presently, restriction of vegetable oil could be a crucial method to reduce TFA intake. It would be critical to facilitate and promote public health that food recommendations might be based on the dietary preferences for population separated by different ages and regions.

Pretreatment with interleukin 35-engineered mesenchymal stem cells protected against lipopolysaccharide-induced acute lung injury via pulmonary inflammation suppression.

Acute lung injury (ALI)-triggered pulmonary injury has been associated with high mortality, despite advances in drug treatment and supportive therapy. Remarkable progress has been made in attenuating the inflammatory injury associated with ALI using mesenchymal stem cells (MSCs)-based cell and gene therapy. However, to date, the benefits of interleukin-35 (IL-35)-modified MSCs in ALI intervention have not been investigated. In the present study, adult male C57BL/6 mice randomly received intravenous infusion of adipose-derived mesenchymal stem cells (ADSCs) constitutively expressing IL-35 (IL-35-GFP-ADSCs) or GFP (GFP-ADSCs) via retrovirus-mediated transduction (8 × 105 cells per mice) or isotonic saline 7 days before ALI modeling to investigate the effect and related mechanism. ALI was performed by lipopolysaccharide (LPS) inhalation for 24 h. Normal mice served as the sham group. The results indicated that compared with GFP-ADSCs, IL-35-modified ADSCs significantly increased cellular and pulmonary IL-10 and IL-35 production. Pretreatment with IL-35-ADSCs markedly reduced body weight loss, pulmonary wet/dry weight ratio and pathological injury. The PO2 was rescued to normal levels in mice that received IL-35-ADSCs. IL-35-ADSCs infusion apparently inhibited IL-6 release, protein leakage and MPO activity but greatly elevated IL-35 level in the bronchoalveolar lavage fluid (BALF). Splenic regulatory T cells in IL-35-ADSCs-pretreated mice got effective increase. Moreover, IL-35-ADSCs pretreatment remarkably inhibited neutrophil and macrophage infiltration and greatly decreased IL-6, tumor necrosis factor α (TNF-α) and Toll-like receptor 4 (TLR4) expression. In conclusion, pretreatment with IL-35-engineered ADSCs provided effective protection against LPS-induced ALI through suppression of pulmonary inflammation and, thus, might be a promising strategy to improve outcomes after ALI. The enhanced paracrine and immunosuppressive capacity of IL-35-ADSCs might contribute to their beneficial effects. However, further studies are needed to illuminate the detailed mechanism.

Rhodium(III)-Catalyzed Atroposelective Synthesis of Biaryls by C-H Activation and Intermolecular Coupling with Sterically Hindered Alkynes.

Reported herein is the atroposelective synthesis of biaryl NH isoquinolones by RhIII -catalyzed C-H activation of benzamides and intermolecular [4+2] annulation for a broad scope of 2-substituted 1-alkynylnaphthalenes, as well as sterically hindered, symmetric diarylacetylenes. The axial chirality is constructed based on dynamic kinetic transformation of the alkyne in redox-neutral annulation with benzamides, with alkyne insertion being stereodetermining. The reaction accommodates both benzamides and heteroaryl carboxamides and proceeds in excellent regioselectivity (if applicable) and enantioselectivities (average 91.8 % ee). An enantiomerically and diastereomerically pure rhodacyclic complex was prepared and offers insight into enantiomeric control of the coupling system, wherein the steric interactions between the amide directing group and the alkyne substrate dictate both the regio- and enantioselectivity.

Temporal contrast reduction techniques for high dynamic-range temporal contrast measurement.

A single-shot characterization of the temporal contrast of a petawatt laser pulse with a high dynamic-range, is important not only for improving conditions of the petawatt laser facility itself, but also for various high-intensity laser physics experiments, which is still a difficult problem. In this study, a new idea for improving the dynamic-range of a single-shot temporal contrast measurement using novel temporal contrast reduction techniques is proposed. The proof-of-principle experiments applying single stage of pulse stretching, anti-saturated absorption, or optical Kerr effect successfully reduce the temporal contrast by approximately one order of magnitude. Combining with the SRSI-ETE method, its dynamic-range characterization capability is improved by approximately one order of magnitude to approximately 109. It is expected that a higher dynamic-range temporal contrast can be characterized by using cascaded temporal contrast reduction processes. The proposed techniques can also be used in the delay-scanning temporal contrast measurement to improve its dynamic range.

The release of tryptase from mast cells promote tumor cell metastasis via exosomes.

BACKGROUND: Cancer cells release exosomes and can be taken up by mast cells (MCs), but the potential functional effects of MCs on tumor metastasis remain unknown. METHOD: Exosomes were isolated from the lung adenocarcinoma cell line A549, and the uptake of PKH26-labeled exosomes by bone marrow MCs was examined via flow cytometry and fluorescence microscopy. Cytokines and tryptase in MC supernatant were analyzed using an ELISA kit, and the presence of tryptase was evaluated by Western blotting. Cell proliferation and migration were determined through CCK-8 and transwell assays. Proteins in the tryptase-JAK-STAT signaling pathway were detected by Western blotting. RESULTS: In this study, we show that exosomes from A549 cells can be taken up by MCs. Moreover, A549 exosomes contain stem cell factor (SCF) to MCs and subsequently induce the activation of MCs through SCF-KIT signal transduction, which leads to MC degranulation and the release of tryptase. Tryptase accelerates the proliferation and migration of human umbilical vein endothelial cells (HUVECs) through the JAK-STAT signaling pathway. CONCLUSIONS: Our results reveal a mechanism for metastasis in which exosomes can transfer SCF to and activate MCs, which can affect the release of tryptase and the angiogenesis of HUVECs.

Peptidyl-prolyl isomerase Pin1 deficiency attenuates angiotensin II-induced abdominal aortic aneurysm formation in ApoE-/- mice.

Peptidyl-prolyl isomerase Pin1 has been reported to be associated with endothelial dysfunction. However, the role of smooth muscle Pin1 in the vascular system remains unclear. Here, we examined the potential function of Pin1 in smooth muscle cells (SMCs) and its contribution to abdominal aortic aneurysm (AAA) pathogenesis. The level of Pin1 expression was found to be elevated in human AAA tissues and mainly localized to SMCs. We constructed smooth muscle-specific Pin1 knockout mice to explore the role of this protein in AAA formation and to elucidate the underlying mechanisms. AAA formation and elastin degradation were hindered by Pin1 depletion in the angiotensin II-induced mouse model. Pin1 depletion reversed the angiotensin II-induced pro-inflammatory and synthetic SMC phenotype switching via the nuclear factor (NF)-κB p65/Klf4 axis. Moreover, Pin1 depletion inhibited the angiotensin II-induced matrix metalloprotease activities. Mechanically, Pin1 deficiency destabilized NF-κB p65 by promoting its polyubiquitylation. Further, we found STAT1/3 bound to the Pin1 promoter, revealing that activation of STAT1/3 was responsible for the increased expression of Pin1 under angiotensin II stimulation. Thus, these results suggest that Pin1 regulates pro-inflammatory and synthetic SMC phenotype switching and could be a novel therapeutic target to limit AAA pathogenesis.

Irisin inhibits high glucose-induced endothelial-to-mesenchymal transition and exerts a dose-dependent bidirectional effect on diabetic cardiomyopathy.

Emerging evidence indicates that irisin provides beneficial effects in diabetes. However, whether irisin influences the development of diabetic cardiomyopathy (DCM) remains unclear. Therefore, we investigated the potential role and mechanism of action of irisin in diabetes-induced myocardial dysfunction in mice. Type 1 diabetes was induced in mice by injecting streptozotocin, and the diabetic mice were administered recombinant r-irisin (low or high dose: 0.5 or 1.5 µg/g body weight/day, I.P.) or PBS for 16 weeks. Irisin treatment did not alter blood glucose levels in the diabetic mice. However, the results of echocardiographical and histopathological assays indicated that low-dose irisin treatment alleviated cardiac fibrosis and left ventricular function in the diabetic mice, whereas high-dose irisin failed to mitigate the ventricular function impairment and increased collagen deposition. The potential mechanism underlying the effect of low-dose irisin involved irisin-mediated inhibition of high glucose-induced endothelial-to-mesenchymal transition (EndMT); conversely, high-dose irisin treatment enhanced high glucose-induced MMP expression by stimulating MAPK (p38 and ERK) signalling and cardiac fibroblast proliferation and migration. Low-dose irisin alleviated DCM development by inhibiting high glucose-induced EndMT. By contrast, high-dose irisin disrupted normal MMP expression and induced cardiac fibroblast proliferation and migration, which results in excess collagen deposition. Thus, irisin can inhibit high glucose-induced EndMT and exert a dose-dependent bidirectional effect on DCM.

The BET/BRD inhibitor JQ1 attenuates diabetes-induced cognitive impairment in rats by targeting Nox4-Nrf2 redox imbalance.

Diabetes-induced oxidative damage is believed to play an important role in the development of cognitive dysfunction. In this study, the involvement of the Nox4-Nrf2 redox imbalance was investigated. STZ-induced diabetic rats exhibited obvious oxidative stress and apoptosis in the hippocampus assessed by augmentation of lipid peroxidation, positive TUNEL staining, elevated ratio of Bax/Bcl-2 and increased caspase 3 activity. Furthermore, hyperglycemia markedly increased Nox4 activity and reduced the activation of Nrf2 by suppressing its up-stream regulatory Akt as well as down-stream target HO-1. Significant improvement of cognitive performance was observed after treatment with the BET/BRD inhibitor JQ1, accompanied by decreased oxidative stress, neuroinflammation and apoptosis in the hippocampus. JQ1 treatment also improved changes in the neuronal cell morphology as well as increased the expression of p-AKT, Nrf2 and HO-1. Our results provide evidence indicating that JQ1 treatment could modulate Nox4-Nrf2 redox imbalance in the hippocampus and may be a promising agent for diabetes-associated cognitive dysfunction.

Association between H19 SNP rs217727 and lung cancer risk in a Chinese population: a case control study.

BACKGROUND: H19 was the first long non-coding RNA (lncRNA) to be confirmed. Recently, studies have suggested that H19 may participate in lung cancer (LC) development and progression. This study assessed whether single nucleotide polymorphisms (SNPs) in H19 are associated with the risk of LC in a Chinese population. METHODS: A case-control study was performed, and H19 SNP rs217727 was analyzed in 555 lung cancer patients from two hospitals and 618 healthy controls to test the association between this SNP and the susceptibility to LC. RESULTS: The A/A homozygous genotype of rs217727 was significantly associated with an increased LC risk (odds ratio (OR) = 1.661, 95% confidence interval (CI) = 1.155 to 2.388, P = 0.006). Significant associations remained after stratification by smoking status (P < 0.001). Furthermore, the A/A genotype had a higher risk of LC than those of G/G in the squamous cell carcinoma (OR = 2.022, P = 0.004) and adenocarcinoma (OR = 1.606, P = 0.045) subgroups. CONCLUSIONS: The rs217727 SNP in lncRNA H19 was significantly associated with susceptibility to LC, particularly in squamous cell carcinoma and adenocarcinoma, and identified the homozygous A/A genotype as a risk factor for LC.

The Role of Psychological Stress on Heart Autophagy in Mice With Heart Failure.

OBJECTIVE: Psychological stress in chronic heart failure (CHF) is associated with systemic neurohormonal and immune system responses and increased mortality. Autophagy refers to the biological process of degradation and recycling of dysfunctional cellular components. We investigated the role of psychological stress on autophagy function in CHF mice. METHODS: C57BL/6 mice underwent transverse aortic constriction, with or without combined acoustic and restraint stress, and cardiac function was assessed by echocardiography analysis. Serum corticosterone and angiotensin II (Ang II) were determined using enzyme-linked immunosorbent assay (ELISA). Autophagy and oxidative stress were measured with immunohistochemistry and quantitative polymerase chain reaction, and chloroquine and rapamycin were used to detect autophagy flux. In vivo, cardiomyocytes were cultured with or without Ang II or N-acetylcysteine, and autophagy and oxidative stress were also detected. RESULTS: A 1-week stress exposure significantly increased serum levels of corticosterone and Ang II (p = .000), increased levels of oxidative stress, induced overt heart failure, and increased mortality (p = .002). Furthermore, stress exposure unregulated messenger RNA expression of Bcl-2-interacting coiled-coil protein 1 (10.891 [3.029] versus 4.754 [1.713], p = .001), cysteine-rich domain containing beclin-1 interacting (6.403 [1.813] versus 3.653 [0.441], p = .006), and autophagy 7 (111.696 [4.049] versus 6.189 [1.931], p = .017), increased expression of autophagosomal, and decreased clearance of autophagosomes. In vitro, Ang II significantly increased autophagy flux in cultured cardiomyocytes, which could be partly inhibited by N-acetylcysteine. CONCLUSIONS: Psychological stress may contribute to the development of CHF by enhancing heart oxidative stress and impairing autophagy flux.

Interleukin-17-induced expression of monocyte chemoattractant protein-1 in cardiac myocytes requires nuclear factor κB through the phosphorylation of p65.

IL-17 plays a key role in a variety of autoimmune diseases. MCP-1 is involved in the infiltration of mononuclear cells of myocardium in VMC. However, the relationship between IL-17 and MCP-1 in myocardial injury remains unclear. In this study, expression of MCP-1 mRNA and protein in cardiac myocytes was detected with qRT-PCR and ELISA, respectively. It was found that IL-17A induced MCP-1 expression in a dose- and time-dependent manner in cardiac myocytes, which could be blocked by IL-17A and IL-17RA neutralizing antibodies. NF-κB p65 and p-p65 protein expression in cardiac myocytes was studied with western blotting. Rates of p-p65 in whole lysates and in nuclear lysates all increased in the first 15 min. Meanwhile, the amount of NF-κB p65 in whole lysates did not change, but the amount of NF-κB p65 in nuclear lysates increased in the first 15 min. Then the optimal sequence and concentration of NF-κB p65 siRNAs was selected. After transfection of 10 nM siRNA-2 of NF-κB p65 into cardiac myocytes before stimulation by IL-17A, expression of MCP-1 mRNA and protein obviously decreased. In conclusion, expression of MCP-1 induced by IL-17 requires NF-κB through the phosphorylation of p65 in cardiac myocytes, which is meaningful to study the onset of chronic viral myocarditis and will provide a new target for the treatment of viral myocarditis.

Association of Topoisomerase II (TOP2A) and Dual-Specificity Phosphatase 6 (DUSP6) Single Nucleotide Polymorphisms with Radiation Treatment Response and Prognosis of Lung Cancer in Han Chinese.

BACKGROUND Mutations of DNA topoisomerase II (TOP2A) are associated with chemotherapy resistance, whereas dual-specificity phosphatase 6 (DUSP6) negatively regulates members of the mitogen-activated protein (MAP) kinase superfamily to control cell proliferation. This study assessed TOP2A and DUSP6 single nucleotide polymorphisms (SNPs) in non-small cell lung cancer (NSCLC) patients for association with chemoradiotherapy responses and prognosis. MATERIAL AND METHODS A total of 140 Chinese patients with histologically confirmed NSCLC were enrolled and subjected to genotyping of TOP2A rs471692 and DUSP6 rs2279574 using Taqman PCR. An independent sample t test was used to analyze differences in tumor regression after radiotherapy versus SNP risk factors. Kaplan-Meier curves analyzed overall survival, followed by the log-rank test and Cox proportional hazard models. RESULTS There were no significant associations of TOP2A rs471692 and DUSP6 rs2279574 polymorphisms or clinicopathological variables with response to chemoradiotherapy (p>0.05). Comparing overall survival of 87 patients with stage I-III NSCLC treated with radiotherapy or chemoradiotherapy to clinicopathological variables, the data showed that tumor regression, weight loss, clinical stage, and cigarette smoking were independent prognostic predictors (p=0.009, 0.043, 0.004, and 0.025, respectively). Tumor regression rate >0.34 was associated with patent survival versus tumor regression rate ≤0.34 (p=0.007). CONCLUSIONS TOP2A rs471692 and DUSP6 rs2279574 SNPs were not associated with chemoradiotherapy response, whereas tumor regression, weight loss, clinical stage, and cigarette smoking were independent prognostic predictors for these Chinese patients with NSCLC.