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Purpose: Cardiovascular diseases are responsible for numerous deaths globally. Long noncoding RNA SNHG1 has presented its protective role in cardiomyocytes previously. Herein, we examined the underlying molecular mechanisms of SNHG1 in cardiac muscle cells from hypoxia and re-oxygenation (H/R) in vitro.Methods: RT-qPCR measured expression of SNHG1, miR-21-5p and miR-30a-5p in rat cardiac muscle cell line HL-1 before and after H/R treatment and cell transfection, which was applied to regulate expression of SNHG1, miR-21-5p and miR-30a-5p for further use. The flow cytometry method was used to compare changes in cellular apoptosis, and cell viability was measured by CCK-8 method.Bioinformatics predicted the bindings ofSNHG1 and miR-21-5p / miR-30a-5p while the luciferase reporter assays further verified this.Results: The outcomes revealedthat SNHG1 was downregulated and meanwhile miR-21-5p / miR-30a5p was elevated that enhanced apoptosis and reduced cell viability in HL-1 cells. However, overexpressed SNHG1 inhibited cell apoptosis and increased cell viability brought by H/R. In addition, SNHG1 targeted at miR-21-5p/ miR-30a-5p, which contributed to the inter-regulation in between. Furthermore, interactive experiments revealed that upregulation of miR-21-5p/ miR-30a-5p added to the cell apoptosis which was induced by H/R and partially counteracted by the upregulation of SNHG1.Conclusion: In this study we have demonstrated the protective role of SNHG1 in the moderation of H/R-induced HL-1 apoptosis and viability through suppression of miR-21-5p/miR-30a-5p. This offers new perspective into the molecular interpretation of cardiovascular diseases such as ischemic reperfusion injury. Keywords: SNHG1; apoptosis; Hypoxia/Re-oxygenation injury;miR-21-5p; miR-30a-5p; Cardiovascular diseases

Objective: Ischemic cardiomyopathy (ICM) is a major cardiovascular state associated with prominently increased morbidity and mortality. Our purpose was to detect reliable gene signatures for ICM through integrated feature selection strategies.Methods: Transcriptome profiles of ICM were curated from the GEO project. Classification models, including least absolute shrinkage and selection operator (LASSO), support vector machine (SVM), and random forest, were adopted for identifying candidate ICM-specific genes for ICM. Immune cell infiltrates were estimated using the CIBERSORT method. Expressions of candidate genes were verified in ICM and healthy myocardial tissues via Western blotting. JC-1 staining, flow cytometry, and TUNEL staining were presented in hypoxia/reoxygenation (H/R)-stimulated H9C2 cells with TRMT5 deficiency.Results: Following the integration of three feature selection methods, we identified seven candidate ICM-specific genes including ASPN, TRMT5, LUM, FCN3, CNN1, PCNT, and HOPX. ROC curves confirmed the excellent diagnostic efficacy of this combination of previous candidate genes in ICM. Most of them presented prominent interactions with immune cell infiltrates. Their deregulations were confirmed in ICM than healthy myocardial tissues. TRMT5 expressions were remarkedly upregulated in H/R-stimulated H9C2 cells. TRMT5 deficiency enhanced mitochondrial membrane potential and reduced apoptosis in H/R-exposed H9C2 cells.Conclusion: Collectively, our findings identified reliable gene signatures through combination strategies of diverse feature selection methods, which facilitated the early detection of ICM and revealed the underlying mechanisms.

Background LCZ696, an angiotensin receptor–neprilysin inhibitor (ARNi), is reported to play a cardioprotective role after acute myocardial infarction (AMI). Angiotensin-converting enzyme inhibitors(ACEIs) have similar roles. However, it is unclear whether the combination of the two drugs has a better protective effect. The purpose of this study was to investigate the effect of this combination therapy after AMI. Methods Male C57BL/6 J mice subjected to ligation of left anterior descending artery were treated for 4 weeks with LCZ696, ACEI(benazepril), or both(combination therapy) after induction of MI. Cardiac function, hemodynamics, and inflammatory factors were evaluated at 1 st day, 14th day, and 28th day. Heart weight and myocardial fibrosis were measured at the end of the experiment. Results Blood pressure was lower in all treatment groups than in the control group. The combination therapy group had the strongest antihypertensive effect. Compared with LCZ696 or benazepril, treatment with combination therapy increased ejection fraction, fractional shortening, and cardiac output and decreased N-terminal pro-B-type natriuretic peptide(NT-proBNP). The ratios of heart weight to body weight in all treatment groups were less than that in the control group. Compared with the control and LCZ696 group, the fibrotic area in the combination therapy group was suppressed and had a lower level of TGF-β1 in the left ventricle. The plasma concentration of bradykinin and renin in the combination therapy group were highest among groups at 14th and 28th day. Conclusions LCZ696 in combination with benazepril showed better positive effects in modulating heart failure and myocardial fibrosis after acute AMI in mice and affect some inflammatory markers.

AimsTo explore clinical features and outcome of 2019 novel coronavirus(2019-nCoV)-infected patients with high BNP levelsMethods and resultsData were collected from patients’ medical records, and we defined high BNP according to the plasma BNP was above > 100 pg/mL. In total,34 patients with corona virus disease 2019(COVID-19)were included in the analysis. Ten patients had high plasma BNP level. The median age for these patients was 60.5 years(interquartile range, 40-80y), and 6/10 (60%) were men. Underlying comorbidities in some patients were coronary heart disease (n=2, 20%), hypertesion (n=3,30%), heart failure (n=1,10%)and diabetes (n=2, 20%). Six (60%) patients had a history of Wuhan exposure. The most common symptoms at illness onset in patients were fever (n=7, 70%), cough (n=3, 30%), headache or fatigue(n=4,40%). These patients had higher aspartate aminotransferase(AST), troponin I, C reactive protein and lower hemoglobin, and platelet count,compared with patients with normal BNP, respectively. Compared with patients with normal BNP, patients with high BNP were more likely to develop severe pneumonia, and receive tracheal cannula, invasive mechanical ventilation, continuous renal replacement therapy, extracorporeal membrane oxygenation, and be admitted to the intensive care unit. One patient with high BNP died during the study.ConclusionHigh BNP is a common condition among patients infected with 2019-nCoV. Patients with high BNP showed poor clinical outcomes

AimsTo explore the epidemiological and clinical features of 2019 novel coronavirus(2019-nCoV)-infected patients with cardiac injury.Methods and resultsData were collected from patients’ medical records, and we defined cardiac injury according to cardiac biomarker troponin I level > 0.03 μg/L. Among the 291 patients, 15 (5.2%) showed evidence of cardiac injury. Of 15 hospitalized patients with cardiac injury, the median age was 65 years, and 11/15 (73.3%) were men. Underlying cardiovascular diseases in some patients were hypertension (n=7, 46.7%), coronary heart disease (n=3, 20%) and diabetes (n=3, 20%). The most common symptoms at illness onset in patients with cardiac injury were fever (n=11, 73.3%), cough (n=7, 46.7%), headache or fatigue (n=5, 33.3%) and dyspnea (n=4, 26.7%). These patients had higher systolic pressures, white blood cell count, neutrophil count, troponin I, brain natriuretic peptide, D-dimer and lower lymphocyte count, and platelet count, compared with patients without cardiac injury, respectively. Bilateral infiltrates on chest X-ray and elevated C-reactive protein occurred in all patients with cardiac injury. Compared with patients without cardiac injury, patients with cardiac injury were more likely to develop acute respiratory distress syndrome, and receive mechanical ventilation, continuous renal replacement therapy, extracorporeal membrane oxygenation and vasopressor therapy and be admitted to the intensive care unit.ConclusionCardiac injury is a common condition among patients infected with 2019-nCoV. Compared with patients without cardiac injury, the clinical outcomes of patients with cardiac injury are relatively worse.

[Objective] Analyze the occurrence of novel coronavirus pneumonia(NCP) in China mainland, explore the epidemiological rules, and evaluate the effect of prevention and control. [Methods] From December 1, 2019 to February 14, 2020, Analysis of 66,492 confirmed cases of NCP in China mainland. [Results] From December 1, 2019 to February 14, 2020, a total of 66,492 cases of NCP were confirmed in China mainland, a total of 54,406 cases were confirmed in Hubei Province, a total of 37,914 cases were confirmed in Wuhan city. On February 5, 2020, the number of suspected cases of NCP in China mainland reached a maximum of 5,328. Since then, the suspected cases have shown a significant downward trend. On February 4, 2020, the number of confirmed cases has gradually decreased in China mainland since then. On February 12, 2020, the number of confirmed cases of NCP in China mainland increased explosively to 15,152, and then began to decline. From February 3, 2020, except for Hubei Province, In China mainland, the number of newly confirmed cases of NCP has continued to decline; From December 1, 2019 to February 14, 2020, a total of 1,523 cases of NCP deaths in China mainland, a cumulative cure of 8096 cases, and mortality and cure rate were 2.29% (1523/66492) and 12.18% (8096/66492) respectively; Starting from January 27, 2020, The spread index of NCP gradually declined, and the extinction index of NCP rose little by little from January 29, 2020. [Conclusion] Starting from February 5, 2020, the number of suspected cases of the NCP is gradually decrease in China mainland. From February 3, 2020, the number of newly confirmed cases of NCP is continuous decline in China mainland except Hubei Province, This shows that the control of the transmission of NCP has achieved. Judged from the number of confirmed cases of NCP, controlling the outbreak in China mainland is to control the epidemic in Hubei province, and the key to controlling the outbreak in Hubei province is to control the epidemic in Wuhan city; Judging from the gradual increase in the number and cure rate of the NCP, and the gradual decline in the number of deaths and mortality, the trend of outbreak control and treatment is getting better; A decrease of the NCP spread index indicates a slowdown in the spread of the virus, but the cumulative confirmed cases is still increase, so the epidemic will continue for some time. However, the turning point of the epidemic in mainland China has not yet occurred. On February 12, 2020, the turning point of the epidemic in China mainland except Hubei province, has turned up.

// Zulong Xie 1,2,* , Nana Dong 1,3,* , Rong Sun 1,3 , Xinxin Liu 1,3 , Xia Gu 4 , Yong Sun 1,3 , Hongwei Du 1,3 , Jiannan Dai 1,3 , Youbin Liu 1,3 , Jingbo Hou 1,3 , Jinwei Tian 1,3 and Bo Yu 1,3 1 Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China 2 Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China 3 The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China 4 Department of Cardiology, Heilongjiang Provincial Hospital, Harbin, China * These authors have contributed equally to this work Correspondence to: Jinwei Tian, email: // Bo Yu, email: // Keywords : atherosclerosis; plaque characteristics; coronary artery remodeling; optical coherence tomography; intravascular ultrasound Received : August 08, 2016 Accepted : December 07, 2016 Published : December 15, 2016 Abstract Atherosclerosis often leads to myocardial infarction and stroke. We examined the influence of baseline plaque characteristics on subsequent vascular remodeling in response to changes in plaque size. Using optical coherence tomography (OCT) and intravascular ultrasound (IVUS), we examined 213 plaques from 138 patients with acute coronary syndrome at baseline and repeated IVUS at the 12-month follow-up. The change in external elastic membrane (EEM) area for each 1 mm2 change in plaque area (i.e., the slope of the regression line) was calculated as a measure of vascular remodeling capacity. In plaques with static positive remodeling, the slope was smaller than in plaques without static positive remodeling. In addition, the slope of the regression line for lesions with a large plaque burden was much smaller than that for lesions with a small plaque burden. Multivariate linear regression analysis showed that diabetes, calcification and static positive remodeling were inversely and independently associated with the level of change in EEM area/change in plaque area. Lesions with a large plaque burden, calcifications or static positive remodeling had less remodeling capacity, and calcification and static positive remodeling were independent predictors of reduced subsequent remodeling. Therefore, calcifications and static positive remodeling could be used as morphological biomarkers to predict decreased subsequent arterial remodeling.

Background The poor viability of transplanted mesenchymal stem cells (MSCs) hampers their therapeutic efficacy for ischemic heart disease. Micro RNA s are involved in regulation of MSC survival and function. The present study was designed to investigate the molecular effects of mi R ‐15a/15b on MSC survival, focusing on the role of vascular endothelial growth factor receptor 2. Methods and Results We first harvested donor luc(Luciferase)‐ MSC s (5×10 5 ) isolated from the luciferase transgenic mice with FVB background. Luc‐ MSC s were transfected with miR‐15a/15b mimics or inhibitors and cultured under oxygen glucose deprivation condition for 12 hours to mimics the harsh microenvironment in infarcted heart; they were subjected to MTT (3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide?Thiazolyl Blue Tetrazolium Bromide) assay, bioluminescence imaging, quantitative reverse transcription–polymerase chain reaction, transferase‐mediated deoxyuridine triphosphate–digoxigenin nick‐end labeling assay, and flow cytometry. Furthermore, the levels of vascular endothelial growth factor receptor 2, protein kinase B, p(Phosphorylate)‐protein kinase B, Bcl‐2, Bax, and caspase‐3 proteins were available by Western blotting assay. In vivo, acute myocardial infarction was induced in 24 mice by coronary ligation, with subsequent receipt of Luc‐ MSC s, Luc‐ MSC s+miR‐15a/15b inhibitors, or PBS treatment. The therapeutic procedure and treatment effects were tracked and assessed using bioluminescence imaging and echocardiographic measurement. Next, ex vivo imaging and immunohistochemistry were conducted to verify the distribution of MSC s. We demonstrated that miR‐15a/15b targeted vascular endothelial growth factor receptor 2 to modulate MSC survival, possibly via phosphatidylinositol 3‐kinase/protein kinase B signaling pathway, which was proved by bioluminescence imaging, immunohistochemistry analysis, and echocardiographic measurement. Conclusions Luc‐ MSC s could be followed dynamically in vitro and in vivo by bioluminescence imaging, and the role of mi R ‐15a/b could be inferred from the loss of signals from luc‐ MSC s. This finding may have practical clinical implications in mi R ‐15a/15b–modified MSC transplantation in treating myocardial infarction.

Mitochondria are dynamic organelles that are able to change their morphology and cellular distribution by either fission or fusion. However, the molecular mechanisms controlling mitochondrial dynamics in vascular endothelial cells (ECs) remain largely unknown. In this study, we observed that knockdown of microtubule-associated tumor suppressor 1 (MTUS1) in ECs inhibited tube formation and migration, accompanied with decreased promigratory signalings. We showed that MTUS1 was localized in the outer membrane of mitochondria in ECs. Knockdown of MTUS1 disturbed the elongated mitochondrial network and induced the formation of perinuclear clusters of mitochondria. Importantly, mitochondrial motility and fusion were suppressed, whereas generation of reactive oxygen species was increased in MTUS1 knockdown ECs. Mechanistically, we showed that the N-terminal coiled-coil domain of MTUS1 interacted with the mitochondrial membrane proteins, mitofusin-1 and mitofusin-2, to maintain mitochondrial morphology in ECs. This study illustrated a novel role of MTUS1 in mitochondrial morphology and EC angiogenic responses.-Wang, Y., Huang, Y., Liu, Y., Li, J., Hao, Y., Yin, P., Liu, Z., Chen, J., Wang, Y., Wang, N., Zhang, P. Microtubule associated tumor suppressor 1 interacts with mitofusins to regulate mitochondrial morphology in endothelial cells.

Aims Compared with intravascular ultrasound (IVUS), optical coherence tomography (OCT) has relative merits and demerits for detecting plaque characteristics. It remains unknown whether the IVUS and OCT evaluations of plaque progression/regression are consistent. We sought to analyse the correlations between IVUS and OCT evaluations of plaques at single time points, and compare temporal changes in the IVUS and OCT data. Methods and results Eighty-eight lipid-rich plaques from 65 patients with coronary artery disease were analysed with IVUS and OCT at baseline and 12-month follow-up. Fibrous cap thickness on OCT was negatively correlated with total atheroma volume on IVUS ( r = −0.28, P = 0.009), but not with percent atheroma volume ( P = 0.84). Changes on OCT were not significantly correlated with changes on IVUS. Plaques that showed progression, regression, or no change on IVUS showed no differences in terms of changes in the OCT parameters fibrous cap thickness ( P = 0.199), maximum lipid core arc ( P = 0.755), mean lipid core arc ( P = 0.936), and lipid index ( P = 0.91). The incidence of thin-cap fibroatheroma (TCFA) was similar among the above three plaque groups at baseline ( P = 0.79) and follow-up ( P = 0.609). Conclusion Although fibrous cap thickness on OCT was negatively correlated with plaque size on IVUS at single time points, changes in OCT parameters were not correlated with changes in IVUS measures over time. Lesion progression/regression on IVUS was not associated with changes in OCT parameters (fibrous cap thickness, lipid core arc, lipid index, and TCFA).

Background/Aims: Urothelial carcinoma-associated 1 (UCA1) is a recently identified long non coding RNA (lncRNA). However, few studies have explored its role in cardiomyocytes after focal cardiac ischemia reperfusion injury (CIR). Methods: Rat CIR models were established using ligation of the Lower Anterior Descending artery (LAD). Cell apoptosis and reactive oxygen species (ROS) production in cardiac tissues were explored using immunohistochemistry and DHE staining. lncRNA expression patterns were detected using microarray and validated by qPCR. Cell viability and apoptosis were examined using MTT assay and flow cytometry. Results: CIR significantly induced cell apoptosis and ROS production in the rat model. The results of microarray demonstrated the reduced expression of UCA1, which was validated by qPCR. Follow-up experiments showed that UCA1 was involved in H2O2-induced cell apoptosis. We further showed that UCA1 negatively correlated with the expression of p27. Moreover, overexpression of p27 could induce primary cardiomyocyte apoptosis. Conclusions: Reduction of UCA1 levels plays a pro-apoptotic role in primary cardiomyocytes partially through stimulation of p27 protein expression. These results are in agreement with the observed levels of UCA1, p27 and apoptosis after cardiac I/R injury, suggesting that UCA1 might have an important role during I/R injury.

Long noncoding RNAs (lncRNAs) play important regulatory roles in cellular physiology. The contributions of lncRNAs to ischemic heart disease remain largely unknown. The aim of this study was to investigate the profile of myocardial lncRNAs and their potential roles at early stage of reperfusion. lncRNAs and mRNAs were profiled by microarray and the expression of some highly-dysregulated lncRNAs was further validated using polymerase chain reaction. Our results revealed that 64 lncRNAs were up-regulated and 87 down-regulated, while 50 mRNAs were up-regulated and 60 down-regulated in infarct region at all reperfusion sampled. Gene ontology analysis indicated that dysregulated transcripts were associated with immune response, spermine catabolic process, taxis, chemotaxis, polyamine catabolic process, spermine metabolic process, chemokine activity and chemokine receptor binding. Target gene-related pathway analysis showed significant changes in cytokine-cytokine receptor interaction, the chemokine signaling pathway and nucleotide oligomerization domain (NOD)-like receptor signaling pathway which have a close relationship with myocardial ischemia/reperfusion injury (MI/RI). Besides, a gene co-expression network was constructed to identify correlated targets of 10 highly-dysregulated lncRNAs. These lncRNAs may play their roles by this network in post-ischemic heart. Such results provide a foundation for understanding the roles and mechanisms of myocardial lncRNAs at early stage of reperfusion.

MRE11 plays an important role in DNA damage response for maintenance of genome stability and is becoming a prognostic marker. Its role, however, remains controversial in colorectal cancer (CRC) as it we don’t know if this difference is caused by the different locations of primary cancer. To figure out the prognostic heterogeneity of MRE11 in CRC, 207 primary CRC samples from Swedish, as well as 596 primary CRC samples from TCGA data were included in present study. The associations of MRE11 expression against tumor-infiltrating inflammatory cells (TIICs) and microsatellite status with overall survival in right-sided CRC (RSCRC) and left-sided CRC (LSCRC) were assessed. The weighed gene co-expression network analysis and ClueGO were adopted to further analyze the different signaling of MRE11-related in RSCRC and LSCRC. The results showd that either high MRE11 expression alone (HR = 0.37, 95% CI = 0.18-0.76, P = 0.007) or the combination of high MRE11 expression with high TIICs was related to a favorable prognosis (HR = 0.150, 95% CI = 0.043-0.524, P = 0.003) in LSCRC. High MRE11 expression associated with a favorable prognosis in LSCRC with microsatellite stability (HR = 0.23, 95% CI = 0.09-0.55, P = 0.001). The relationships furnished above were adjusted for TNM stage, differentiation and/or TIICs, and no such evidence was present in RSCRC. Further analysis of the biological functions and the pathway involving MRE11 was associated with cell cycle process and DNA repair in both RSCRC (cor = 0.55, P = 0.55e-46) and LSCRC (cor = 0.62, P = 3e-64), whereas, activation of the immune response, necrotic cell death specifically correlated with LSCRC (cor = 0.5, P = 8e-38). In Conclusions, High MRE11 expression is associated with a favorable prognosis and the enhanced prognostic potency of combining high MRE11 with high TIICs in LSCRC. The prognostic heterogeneity of MRE11 in CRC may be due to the differential cell signals activated by MRE11 in RSCRC and LSCRC. The prognostic heterogeneity of MRE11 provides a novel rationale for stratifying patients accordingly, in order to obtain a better personalized prognostic evaluation for CRC patients. Citation Format: Chuanwen Fan, Maria Kopsida, Youbin Liu, Hong Zhang, Jingfang Gao, Gunnar Arbman, Siyuwei Cao, Yuan Li, Zongguang Zhou, Xiaofeng Sun. The clinical significance of MRE11 expression based on location of primary tumor in colorectal cancer patients: an integrative analysis of multi-center data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4940.

Angiogenesis and inflammation are regarded as important factors in the pathogenesis of chronic inflammation, cancer, and wound healing. Recent studies have supported prior evidence that common signaling pathways are involved in angiogenesis and inflammatory responses; however, key factors controlling both processes remain unclear. Although tripartite motif-containing (TRIM)-28 is known to have an immunosuppressive role in immune cells, its expression level and role in endothelial cells (ECs) are still unclear. In this study, we investigated the role of TRIM28 in inflammatory responses and angiogenic activity of ECs for the first time. We showed that TRIM28 is the most abundant TRIM family member and is localized in nuclei of ECs. Small interfering RNA-mediated knockdown of TRIM28 strikingly suppressed expression of TNF receptor (TNFR)-1 and -2, decreased TNF-α-induced phosphorylation of IKKα/β and IκBα and degradation of IκBα and nuclear translocation of p65, and suppressed basal level and TNF-α-induced expression of chemokines and adhesion molecules, including VCAM-1, IL-6, ICAM-1, E-selectin, and monocyte chemoattractant protein (MCP)-1. Unexpectedly, IL-8 was potentiated by TRIM28 knockdown in ECs in an NF-κB-inducing kinase-dependent manner. Meanwhile, knockdown of TRIM28 inhibited expression of VEGF receptor 2 and suppressed VEGF-induced proliferation and tube formation by ECs. Finally, knockdown of TRIM28 suppressed recruitment of ECs in vivo in a murine synthetic basement membrane model. In summary, we found that TRIM28 acts as a central factor in controlling endothelial inflammatory responses and angiogenic activities by retaining expression of TNFR-1 and -2 and VEGF receptor 2 in ECs.-Wang, Y., Li, J., Huang Y., Dai, X., Liu, Y., Liu, Z., Wang, Y., Wang, N., Zhang, P. Tripartite motif-containing 28 bridges endothelial inflammation and angiogenic activity by retaining expression of TNFR1 and -2 and VEGFR2 in endothelial cells.

Background Endothelial cell activation is thought to be a key event in atherosclerosis. p38 mitogen-activated protein kinase (p38 MAPK) plays an important role in regulating pro-inflammatory cytokine production in endothelial cells (ECs), however, how p38 MAPK is controlled in EC activation remain unclear. In this study, we investigated the effect of mitochondrial tumor suppressor 1 (MTUS1) on p38 MAPK activation, cytokine induction and the underlying molecular mechanisms in ECs. Methods and results Using qPCR and ELISA methods, we found that knockdown of MTUS1 led to a marked increase in the mRNA and protein expression of E-selectin (SELE) and monocyte chemotactic protein-1 in ECs, which is accompanied with increased phosphorylation of p38 MAPK (Thr180/Tyr182), MKK3/6 (Ser 189) and IκBα (Ser 32). Using luciferase reporter assay, we found that MTUS1 silencing also activated NF-κB transcriptional activity. The inhibition of p38 MAPK and NF-κB pathway was shown to abrogate MTUS1 silencing-induced cytokine expression in ECs. Furthermore, MTUS1 silencing induced p38 MAPK-dependent ubiquitination of cAMP-response element binding protein (CREB) which potentiated CREB-binding protein-mediated NF-κB p65 acetylation and binding to the promoter of the SELE gene. Conversely, adenovirus-mediated overexpression of MTUS1 inhibited p38 MAPK activation in ECs in vitro and in vivo. Importantly, decreased expression of MTUS1 and CREB, accompanied with induced activation of p38 MAPK were observed in aortas of apoE −/− mice after high-fat diet challenge. Conclusions Our findings showed that MTUS1 regulates the p38 MAPK-mediated cytokine production in ECs. MTUS1 gene probably plays a protective role against pro-inflammatory response of ECs.

Background The polyphenol resveratrol (Rev) has been reported to exhibit cardioprotective effects, such as inhibition of TAC (transverse aortic constriction) or isoprenaline (ISO)‐induced hypertrophy. Micro RNA ‐155 (miR‐155) was found to be decreased in hypertrophic myocardium, which could be further reduced by pretreatment of Rev. The study was designed to investigate the molecular effects of miR‐155 on cardiac hypertrophy, focusing on the role of breast cancer type 1 susceptibility protein ( BRCA 1). Methods and Results We demonstrated that Rev alleviated severity of hypertrophic myocardium in a mice model of cardiac hypertrophy by TAC treatment. Down‐regulation of miR‐155 was observed in pressure overload– or ISO ‐induced hypertrophic cardiomyoctyes. Interestingly, administration of Rev substantially attenuated miR‐155 level in cardiomyocytes. In agreement with its miR‐155 reducing effect, Rev relieved cardiac hypertrophy and restored cardiac function by activation of BRCA 1 in cardiomyoctyes. Our results further revealed that forkhead box O3a (FoxO3a) was a miR‐155 target in the heart. And miR‐155 directly repressed FoxO3a, whose expression was mitigated in miR‐155 agomir and mimic treatment in vivo and in vitro. Conclusions We conclude that BRCA 1 inactivation can increase expression of miR‐155, contributing to cardiac hypertrophy. And Rev produces their beneficial effects partially by down‐regulating miR‐155 expression, which might be a novel strategy for treatment of cardiac hypertrophy.

Scientific Reports 5: Article number: 13827; 10.1038/srep13827 published online: September082015; updated: October162015. In this Article, Figure 4 is incorrect. The correct Figure 4 appears below as Figure 1. Figure 1

Recent studies reported miR-497 exhibited inhibitory effects in various cancers. However, whether miR-497 is involved in inhibiting angiogenesis, which is critical for tumor growth and metastasis, is still unknown. The purpose of this study was to investigate the potential role of miR-497 in tumor angiogenesis. In this work, cell proliferation and apoptosis analyses were conducted to explore the potential function of miR-497 in HUVECs by using MTT and TUNEL assays. Western blotting (WB) was employed to validate the downstream targets of miR-497. Furthermore, in order to disclose the role of miR-497 on angiogenesis, VEGFR2-luc transgenic mice were treated with miR-497 mimic and applied to monitor tumor angiogenesis and growth by in vivo bioluminescent imaging (BLI). The results demonstrated that overexpression of miR-497 showed inhibitory effects on VEGFR2 activation and downstream Raf/MEK/ERK signal pathways in vitro and in vivo. Moreover, overexpression of miR-497 effectively induced HUVECs apoptosis by targeting VEGFR2 and downstream PI3K/AKT signaling pathway. Furthermore, miR-497 exhibited anti-angiogenesis and anti-tumor effects in the VEGFR2-luc breast tumor model proven by BLI, WB and immunohistochemistry analysis. In summary, miR-497 inhibits tumor angiogenesis and growth via targeting VEGFR2, indicating miR-497 can be explored as a potential drug candidate for cancer therapy.

OBJECTIVE: The aim of the present study was to explore the potential for hematoporphyrin monomethyl ether-Sonodynamic Therapy (HMME-SDT) treatment of hypertrophic scars within rabbit ears. METHODS: 60 white rabbits were randomly divided into five groups: (1) untreated controls, (2) lesioned, (3) lesioned + HMME, (4) lesioned + US (Ultrasound), and (5) lesioned +HMME-SDT. After induction of a lesion upon the ears of the rabbits, hypertrophic scars were assessed at 14, 28, 42 and 56 days post-lesion +/- treatment. Assessments consisted of visual inspection in the change of the skin, scar formation pathological morphology by hematoxylin and eosin (HE) staining technique with optical microscopy, calculation of a hypertrophic index, fibroblastic density measures, and observation of collagen changes in the scar tissue by Van Gieson's (VG)Stain along with calculation of collagen area density. RESULTS: With continued HMME-SDT treatment there was a gradual improvement in all parameters over the duration of the experiment. The lesion-induced scars of rabbits receiving HMME-SDT treatment were soft, the size was reduced, hyperplasia was flat and the color pale. The fibroblasts and collagens were reduced and the collagens were light red, sparse and orderly. The hypertrophic index was reduced, since the fibroblastic density was lowered and collagen area density was decreased. CONCLUSION: HMME is an effective sonosensitizer and the combination of HMME-SDT treatment can exert significant benefits in reducing the formation of hypertrophic scars.

The antioxidant activities of fermented soybean meal (FSM) extract were evaluated by various methods in vitro and in vivo. The antioxidant tests in vitro, included the total phenolic and flavonoid content, reducing activity, 1,1-diphenyl-2-picryl-hy-drazyl (DPPH·) and superoxide anion radical scavenging activity, inhibition of lipid peroxidation in rat liver homogenate and erythrocyte haemolysis in rat blood. For in vivo test, mice were subcutaneously injected with D-galactose (D-gal) for 6 weeks and intragastric administration of fermented soy milk (FSM)extract simultaneously (500, 250 and 125 mg/kg body weight per day, respectively), and then the superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-px), total antioxidant capacity (T-AOC) and MDA were determined. In antioxidant assays in vitro, FSM extract was found to have Fe3+ reducing activity, moderate 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity, superoxide anion radical scavenging activity, lipid peroxidation and erythrocyte haemolysis inhibition effect, of which IC50 values were found to be 3.168, 0.321, 7.404, 0.737 and 4.599 mg/ml, respectively. For the antioxidant assays in vivo, administration of FSM extract significantly enhanced the activities of antioxidant enzymes and total antioxidant capacity and decreased the levels of malondialdehyde in both serums and livers of aging mice. Key words: Antioxidant activities, fermented soybean meal (FSM) extract, Bacillus natto.