VENOARTERIAL EXTRACORPOREAL MEMBRANE OXYGENATION REDUCES MYOCARDIAL AND MITOCHONDRIAL DAMAGE IN ACUTE MYOCARDIAL INFARCTION.

ABSTRACT: Background: Myocardial infarction (MI) is a common cardiovascular disease with a high fatality rate once accompanied by cardiogenic shock. The efficacy of extracorporeal membrane oxygenation (ECMO) in treating MI is controversial. Methods: MI was induced by ligating the left anterior descending artery (LAD) in adult male rats. Groups were defined as follows: MI group, reperfusion for 90 min after 30 min of LAD occlusion; MI + ECMO group, reperfusion and ECMO were performed for 90 min immediately after 30 min of LAD occlusion; prolonged MI + ECMO group, ECMO was used immediately after 30 min of occlusion with persistent occlusion of the LAD for an additional 30 min, followed by 90 min of reperfusion. The myocardial infarct size and mitochondrial morphology and function data were collected and compared of each group. Results: The ECMO groups had a smaller myocardial infarct size and larger percentage ejection fraction. Compared with the prolonged MI + ECMO group, the immediate reperfusion group had a lower percentage of infarct size (63.28% vs. 17.97% vs. 31.22%, MI vs. MI + ECMO vs. prolonged MI + ECMO). Mitochondria isolated from the ischemic zone showed an intact mitochondrial structure, including fewer voids and broken cristae, and preserved activity of mitochondrial complex II and complex IV in ECMO groups. Conclusions: ECMO support in MI can reduce myocardial injury despite delayed coronary reperfusion.

CD44 connects autophagy decline and ageing in the vascular endothelium.

The decline of endothelial autophagy is closely related to vascular senescence and disease, although the molecular mechanisms connecting these outcomes in vascular endothelial cells (VECs) remain unclear. Here, we identify a crucial role for CD44, a multifunctional adhesion molecule, in controlling autophagy and ageing in VECs. The CD44 intercellular domain (CD44ICD) negatively regulates autophagy by reducing PIK3R4 and PIK3C3 levels and disrupting STAT3-dependent PtdIns3K complexes. CD44 and its homologue clec-31 are increased in ageing vascular endothelium and Caenorhabditis elegans, respectively, suggesting that an age-dependent increase in CD44 induces autophagy decline and ageing phenotypes. Accordingly, CD44 knockdown ameliorates age-associated phenotypes in VECs. The endothelium-specific CD44ICD knock-in mouse is shorter-lived, with VECs exhibiting obvious premature ageing characteristics associated with decreased basal autophagy. Autophagy activation suppresses the premature ageing of human and mouse VECs overexpressing CD44ICD, function conserved in the CD44 homologue clec-31 in C. elegans. Our work describes a mechanism coordinated by CD44 function bridging autophagy decline and ageing.

Transcoronary sinus repair of a severely dilated and tortuous right coronary artery fistulized to coronary sinus complicated with tricuspid valve insufficiency.

BACKGROUND: Right coronary artery (RCA) fistulized to the coronary sinus is rare condition in adult cardiac anomalies, and the management and operative indication are controversial. CASE PRESENTATION: We describe the case of a 45-year female patient who presented with exertional dyspnea, accompanied by intermitted lower limbs and facial edema. She was diagnosed with severe tricuspid regurgitation second to a severely dilated RCA fistulized to the coronary sinus. After multidisciplinary discussion, she underwent surgery through routine medium sternotomy, the right atrium was opened under cardiopulmonary bypass. The coronary arteriovenous fistula from the distal portion of RC to a severely enlarged coronary sinus was found. Trans-coronary sinus closure of the fistula was performed with continuous stitching and a tricuspid ring annuloplasty was done. The patient recovered uneventful post operation. CONCLUSION: According to current literatures, surgical treatment was adopted for this case, instead of endovascular intervention. The optimal approach for these cases should consider the heart's anatomical characteristics. But we need to be aware of the occurrence of myocardial infarction and tricuspid regurgitation in the early and late stage after operation.

Self-Powered Respiratory Monitoring Strategy Based on Adaptive Dual-Network Thermogalvanic Hydrogels.

As a low-grade sustainable heat source, the breath waste heat exhaled by human bodies is always ignored, although producing a greater temperature than ambient. Converting this heat into electric energy for use as power sources or detecting signals is extremely important in cutting-edge wearable medicine. This heat-to-electricity conversion is possible with thermogalvanic hydrogels. However, challenges remain in their antifreezing and antidrying properties, significantly restricting the durability of thermogalvanic gels in practical applications. Herein, a dual-network poly(vinyl alcohol)/gelatin (PVA/GEL) gel thermogalvanic device with Fe(CN)63-/4- as a redox pair is developed, with an outstanding low-temperature durability and antidrying capacity. These features result from the use of a binary H2O/GL (glycerin) solvent to limit hydrogen bonding between water molecules. The prepared thermogalvanic gel patch is capable of easily converting physiological data into understandable electrical impulses using the temperature difference between the ambient environment and the heat produced by human breathing, realizing a simple self-powered respiratory monitoring strategy for the first time. Even below zero temperature, the gel patch-based mask can operate normally, implying it fits into low-temperature environments. This study sheds fresh light on the development of active wearable medical electronics that are powered by demic low-level heat.

The Association Between Psoriasis and Risk of Cardiovascular Disease: A Mendelian Randomization Analysis.

Background: A large number of observational studies showed that patients with psoriasis have a higher risk of cardiovascular disease (CVD), but most studies did not fully adjust for confounding factors, so it is not clear whether the risk of CVD is directly attributed to psoriasis. We used Mendelian randomization (MR) to evaluate the potential causal relationship between psoriasis and CVD. Methods: We used genetic instruments from the genome-wide association study (GWAS) of European descent for psoriasis to investigate its relationship with CVD. Inverse variance-weighted (IVW) MR analyses were used for the primary analysis. In addition, a variety of other methods were used to replicate the analysis. Results: The fixed-effects IVW method indicated that genetic susceptibility to psoriasis was associated with a higher risk of heart failure (HF) [odds ratio (OR) = 1.04; 95% CI, 1.01-1.06, P = 2.72E-03], atrial fibrillation (AF) (OR = 1.04; 95% CI, 1.02-1.07, P = 3.27E-04), myocardial infarction (MI) (OR = 1.07; 95% CI, 1.01-1.12, P = 0.01), valvular heart disease (VHD) (OR = 1.001; 95% CI, 1.000-1.002, P = 1.85E-03), and large artery stroke (LAS) (OR = 1.11; 95% CI, 1.05-1.18, P = 5.37E-04) but not with the other two subtypes of ischemic stroke (IS) [cardioembolic stroke (CES) (OR = 1.03; 95% CI, 0.98-1.07, P = 0.27) and small vessel stroke (SVS) (OR = 1.00; 95% CI, 0.95-1.07), P = 0.88)]. Sensitivity analysis found weak evidence of horizontal diversity and heterogeneity to ensure the stability of the results. Conclusion: Our study provided evidence for a potential causal link between psoriasis and CVD. These findings partly suggest that early monitoring of cardiovascular risk in patients with psoriasis is intentional.

Associations Between Vitamin D Levels and Risk of Heart Failure: A Bidirectional Mendelian Randomization Study.

Background: Although studies suggest that concentrations of serum 25-hydroxyvitamin D (25(OH)D) are lower in individuals with Heart Failure (HF), the beneficial effects of vitamin D supplementation are controversial. Therefore, in this study, we aimed to determine whether there is a causal relationship between serum Vitamin D (VD) levels and HF. Methods: We obtained genetic instruments from the largest available genome-wide association study (GWAS) of European descent for 25(OH)D (443, 734 individuals) to investigate the association with HF (47,309 cases, 930,014 controls), and vice versa. Two-sample bidirectional Mendelian Randomization (MR) analysis was performed to infer the causality. In addition to the primary analysis using inverse variance-weighted (IVW) MR, we applied five additional methods to control for pleiotropy [MR-Egger, weighted median, Maximum-likelihood, MR-robust adjusted profile score (MR-RAPS) and MR-pleiotropy residual sum and outlier (MR-PRESSO)] and compared their respective MR estimates. We also performed a sensitivity analysis to ensure that our results were robust. Results: Mendelian randomized analysis showed that increased serum 25(OH)D was associated with a lower risk of HF in the IVW method (odds ratio [OR] = 0. 81;95%CI, 0.70-0.94, P = 0.006). In the reverse MR analyses, the genetic predisposition to HF was negatively correlated with serum 25(OH)D level (OR = 0. 89;95%CI, (0.82-0.97), P = 0.009). Conclusion: Our study revealed the possible causal role of 25(OH)D on decreasing the risk for HF. Meanwhile, reverse MR analysis suggested that HF may be associated with lower vitamin D levels, it could be the potential implications for dietary recommendations.

Systemic Lupus Erythematosus and Cardiovascular Disease: A Mendelian Randomization Study.

Background: Previous studies have shown that patients with systemic lupus erythematosus (SLE) tend to have a higher risk of cardiovascular disease (CVD), but the potential causal relationship between genetic susceptibility to SLE and CVD risk is not clear. This study systematically investigated the potential association between genetically determined SLE and the risk of CVD. Methods: The genetic tools were obtained from genome-wide association studies of SLE and CVD, with no overlap between their participating populations. Mendelian randomization (MR) analysis was performed using inverse variance weighting as the primary method. Simultaneously, a series of repeated analyses, sensitivity analyses, and instrumental variable strength evaluations were performed to verify the reliability of our results. Results: MR analysis showed that genetic susceptibility to SLE was associated with a higher risk of heart failure (OR=1.025, 95% CI [1.009-1.041], P=0.002), ischemic stroke (OR=1.020, 95% CI [1.005-1.034], P=0.009), and venous thromboembolism (OR=1.001, 95% CI [1.000-1.002], P=0.014). However, genetic susceptibility to SLE was negatively correlated with the risk of type 2 diabetes (OR=0.968, 95% CI [0.947-0.990], P=0.004). Sensitivity analysis found no evidence of horizontal pleiotropy or heterogeneity. Conclusion: Our MR study explored the causal role of SLE in the etiology of CVD, which would help improve our understanding of the basic disease mechanisms of SLE and provide comprehensive CVD assessment and treatment for SLE patients.

The dynamic changes in autophagy activity and its role in lung injury after deep hypothermic circulatory arrest.

Deep hypothermic circulatory arrest (DHCA) can cause acute lung injury (ALI), and its pathogenesis mimics ischaemia/reperfusion (I/R) injury. Autophagy is also involved in lung I/R injury. The present study aimed to elucidate whether DHCA induces natural autophagy activation and its role in DHCA-mediated lung injury. Here, rats were randomly assigned to the Sham or DHCA group. The sham group (n = 5) only received anaesthesia and air intubation. DHCA group rats underwent cardiopulmonary bypass (CPB) followed by the DHCA procedure. The rats were then sacrificed at 3, 6 and 24 h after the DHCA procedure (n = 5) to measure lung injury and autophagy activity. Chloroquine (CQ) was delivered to evaluate autophagic flux. DHCA caused lung injury, which was prominent 3-6 h after DHCA, as confirmed by histological examination and inflammatory cytokine quantification. Lung injury subsided at 24 h. Autophagy was suppressed 3 h but was exaggerated at 6 h. At both time points, autophagic flux appeared uninterrupted. To further assess the role of autophagy in DHCA-mediated lung injury, the autophagy inducer rapamycin and its inhibitor 3-methyladenine (3-MA) were applied, and lung injury was reassessed. When rapamycin was administered at an early time point, lung injury worsened, whereas administration of 3-MA at a late time point ameliorated lung injury, indicating that autophagy contributed to lung injury after DHCA. Our study presents a time course of lung injury following DHCA. Autophagy showed adaptive yet protective suppression 3 h after DHCA, as induction of autophagy caused worsening of lung tissue. In contrast, autophagy was exaggerated 6 h after DHCA, and autophagy inhibition attenuated DHCA-mediated lung injury.

Wearable Electronics Based on the Gel Thermogalvanic Electrolyte for Self-Powered Human Health Monitoring.

There is always a temperature difference of more than 10 degrees between the human body, as a sustainable heat source, and the ambient temperature. Converting body heat into electricity that in turn is used to drive personal medical electronics is of significance in smart wearable medicine. To avoid the frangibility and complex preparation of traditional thermoelectric materials, we fabricated a gel electrolyte-based thermogalvanic generator with Fe3+/Fe2+ as a redox pair, which presents not only moderate thermoelectric performance but also excellent flexibility. With a micropore-widespread polyvinylidene fluoride diaphragm implanted in the gel, a thermal barrier was created between the two halves, effectively improving the Seebeck coefficient by reducing its thermal conductivity. Considering the superior temperature response of the gel, a self-powered body temperature monitoring system was established by conformally affixing it to the forehead. Meanwhile, the gel patch with a high specific heat capacity can effectively cool down fever patients. This work may offer a new train of thought for exploiting self-powered wearable medical electronics by scavenging low-grade body heat.

Small extracellular vesicles containing miR-486-5p promote angiogenesis after myocardial infarction in mice and nonhuman primates.

Stem cell-derived small extracellular vesicles (sEVs) promote angiogenesis after myocardial infarction (MI). However, the components of sEVs that contribute to these effects and the safety and efficiency of engineered sEV treatment for MI remain unresolved. Here, we observed improved cardiac function, enhanced vascular density, and smaller infarct size in mice treated with the sEVs from hypoxia-preconditioned (HP) mesenchymal stem cells (MSCs) (HP-sEVs) than in mice treated with normoxia-preconditioned (N) MSCs (N-sEVs). MicroRNA profiling revealed a higher abundance of miR-486-5p in HP-sEVs than in N-sEVs, and miR-486-5p inactivation abolished the benefit of HP-sEV treatment, whereas miR-486-5p up-regulation enhanced the benefit of N-sEV treatment. Matrix metalloproteinase 19 (MMP19) abundance was lower in HP-sEV-treated than N-sEV-treated mouse hearts but was enriched in cardiac fibroblasts (CFs), and Mmp19 was identified as one of the target genes of miR-486-5p. Conditioned medium from CFs that overexpressed miR-486-5p or silenced MMP19 increased the angiogenic activity of endothelial cells; however, medium from CFs that simultaneously overexpressed Mmp19 and miR-486-5p abolished this effect. Mmp19 silencing in CFs reduced the cleavage of extracellular vascular endothelial growth factor (VEGF). Furthermore, miR-486-5p-overexpressing N-sEV treatment promoted angiogenesis and cardiac recovery without increasing arrhythmia complications in a nonhuman primate (NHP) MI model. Collectively, this study highlights the key role of sEV miR-486-5p in promoting cardiac angiogenesis via fibroblastic MMP19-VEGFA cleavage signaling. Delivery of miR-486-5p-engineered sEVs safely enhanced angiogenesis and cardiac function in an NHP MI model and may promote cardiac repair.

CCAT1 promotes triple-negative breast cancer progression by suppressing miR-218/ZFX signaling.

Long non-coding RNAs (lncRNAs) regulate cancer development and progression. Here, we investigated the role of the lncRNA CCAT1 in triple-negative breast cancer (TNBC). CCAT1 expression was higher in TNBC cells than normal breast epithelial cells. Additionally, CCAT1 expression was higher in TNBC patient tumor tissue than adjacent normal breast tissue. Silencing CCAT1 inhibited TNBC cell proliferation, migration, and invasion in vitro, and tumor growth and progression in vivo. Bioinformatics analysis revealed that microRNA-218 (miR-218) is a potential target of CCAT1. Silencing CCAT1 resulted in an increase in miR-218 expression and inhibited TNBC cell proliferation, migration, and invasion. Silencing miR-218 reversed the effects of CCAT1 knockdown on cell proliferation, migration, and invasion, suggesting that CCAT1 promotes TNBC progression by downregulating miR-218 expression. We identified the zinc finger protein ZFX as a putative downstream target of miR-218 through bioinformatics analysis. ZFX expression was higher in TNBC than normal breast cell lines and higher in TNBC tumor tissue than adjacent normal breast tissue. Overexpression of ZFX reversed the tumor-suppressive effects of miR-218 on TNBC cell proliferation, migration, and invasion. Our data indicate that CCAT1 promotes TNBC progression by targeting the miR-218/ZFX axis.

In situ laser fenestration for revascularization of aortic arch during treatment for iatrogenic type A aortic dissection.

BACKGROUND: Iatrogenic aortic dissection is a rare and fatal complication. Its treatment was challenging and controversial especially in patients with previous cardiac procedure. This study aimed to present the case of a patient with aortic dissection after previous open cardiac surgery who was successfully treated by in situ laser fenestration for revascularization of aortic arch. CASE PRESENTATION: A 65-year-old man suffered severe aortic and mitral valve regurgitation was treated by open cardiac aortic valve replacement (biological valve, Edwards) and mitral valve repair. During the sixth-month follow-up, computed tomography angiography (CTA) scan revealed an aortic dissection that extended from the ascending aorta to both femoral arteries. After stabilized by medical treatment, the patient was treated by endovascular stent-graft implantation and in situ laser (holmium laser, energy: 0 5 J, frequency: 5 Hz.) fenestration for revascularization of aortic arch in our one-stop hybrid operating room. The patient recovered without any clinical complication and was discharged 5 days after the procedure. CONCLUSIONS: Our work suggested that in situ laser fenestration for revascularization of aortic arch is a feasible, effective, and safe treatment in patients with iatrogenic aortic dissection.

Histopathologic features of alcoholic cardiomyopathy compared with idiopathic dilated cardiomyopathy.

BACKGROUND: The histologic difference between alcoholic cardiomyopathy (ACM) and idiopathic dilated cardiomyopathy (IDCM) is unclear. The present study aimed to identify the quantitative pathologic features of ACM compared with IDCM. METHODS: Specimens from 6 regions (anterior left ventricle [LV], lateral LV, inferior LV, interventricular septum [IVS], anterior right ventricle [RV], and inferior RV) were sampled from each explanted heart. Specimens from 4 healthy donor hearts were obtained as normal control. Tissues were sectioned and Masson trichrome stained. Histomorphometry was performed to evaluate the amount of myocyte, fibrosis, fatty tissue, and interstitium by Image-Pro Plus 6.0 (Media Cybernetics). RESULTS: A total of 408 specimens were obtained from 34 ACMs and 34 IDCMs; 8 specimens were obtained from 4 healthy donor hearts. Compared to healthy donor hearts, we observed an increase in fibrosis which replaces myocytes in myocardium of end-stage cardiomyopathy. The overall myocyte ratio in myocardium was 69.5 ±â€Š8.7% in ACM vs 71.9 ±â€Š7.4% in IDCM (P < .05). The percentage of interstitium was 10.8 ±â€Š4.8% in ACM vs 9.2 ±â€Š6.2% in IDCM (P < .05). A significant difference of fibrosis, fatty tissue was not discovered. Moreover, the myocyte area was 65.37 ±â€Š11.8% in ACM LV vs 70.03 ±â€Š9.0% in IDCM LV (P < .001). CONCLUSION: We described histologic characteristics in ACM and IDCM. There might be a quantitative difference of myocyte, interstitium in myocardium between ACM and IDCM, especially in LV. No difference was found in the percentage of fibrosis between the 2 groups.

Cardiac-targeting magnetic lipoplex delivery of SH-IGF1R plasmid attenuate norepinephrine-induced cardiac hypertrophy in murine heart.

Recent studies have demonstrated a number of molecular mechanisms contributing to the initiation of cardiac hypertrophy response to pressure overload. IGF1R (insulin-like growth factor-1 receptor), an important oncogene, is overexpressed in hypertrophic heart and mediates the hypertrophic pathology process. In this study, we applied with liposomal magnetofection that potentiated gene transfection by applying an external magnetic field to enhance its transfection efficiency. Liposomal magnetofection provided high efficiency in transgene expression in vivo. In vivo, IGF1R-specific-shRNA (small-hairpin RNA) by magnetofection inhibited IGF1R protein expression by 72.2 ± 6.8, 80.7 ± 9.6 and 84.5 ± 5.6%, at 24, 48 and 72 h, respectively, after pGFPshIGF1R injection, indicating that liposomal magnetofection is a promising method that allows the targeting of gene therapy for heart failure. Furthermore, we found that the treated animals (liposomal magnetofection with shIGF1R) showed reduced septal and posterior wall thickness, reduced HW:BWs (heart weight-to-body weights) compared with controls. Moreover, we also found that liposomal magnetofection-based shIGF1R transfection decreased the expression level of p-ERK (phosphorylated extracellular-signal-regulated kinase)1/2, p-AKT1 (phosphorylated protein kinase B1) compared with untreated hearts. These results suggested that liposomal magnetofection-mediated IGF1R-specific-shRNA may be a promising method, and suppression the IGF1R expression inhibited norepinephrine-induced cardiac hypertrophic process via inhibiting PI3K (phosphoinositide 3-kinase)/AKT pathway.

Comparing coronary artery bypass grafting with drug-eluting stenting in patients with diabetes mellitus and multivessel coronary artery disease: a meta-analysis.

OBJECTIVES: Although drug-eluting stents (DESs) reduce the rate of target vessel revascularization compared with bare-metal stents, the results of DESs for patients with diabetes and multivessel coronary artery disease (CAD) in the DES era are inconsistent. This meta-analysis was undertaken to assess the efficacy and safety of coronary artery bypass grafting (CABG) compared with drug-eluting stent implantation in patients with diabetes mellitus and multivessel coronary artery disease. METHODS: We conducted a search of Medline, EMBASE from January 2003 to July 2013 by two reviewers independently, using the terms 'coronary artery bypass graft surgery', 'drug-eluting stent', 'sirolimus-eluting stent', 'paclitaxel-eluting stent', 'diabetes mellitus' and 'multivessel disease', according to established criteria. Studies comparing CABG with DES in patients with diabetes and multivessel CAD with a minimum follow-up of 1 year were included. RESULTS: Thirteen studies including 6653 patients with diabetes (3237 who underwent CABG and 3416 who underwent DES implantation) met the selection criteria. The mean follow-up period was 2.9 years (range 1-5). Compared with DES, CABG was associated with a lower risk for major adverse cardiac events (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.46-0.58), driven mainly by a lower risk for repeat revascularization (OR 0.29, 95% CI 0.23-0.35). There was no significant difference with regard to death (OR 0.89, 95% CI 0.75-1.05). Patients in the CABG group had a higher risk for stroke events (OR 2.09, 95% CI 1.45-3.02). CONCLUSIONS: Percutaneous coronary intervention with DES in patients with diabetes and multivessel CAD is safe, but has a high risk of long-term repeat revascularization. CABG should remain the standard procedure for diabetic patients with multivessel CAD.

Polymer-based delivering of shRNA to rabbit aortic smooth muscle cells suppressed the expression of IGF-1R in vitro and in vivo.

Restenosis is one of clinical limitations for vein graft in coronary bypass graft. It has been proved that signal pathway IGF-1 and its receptor (IGF-1R) activated by hemodynamic mechanical stretch are responsible for the vascular smooth muscle cells proliferation in vein graft neointima formation. Unfortunately, there is no routinely successful method to resolve this problem. Gene delivering to vein graft possesses great therapeutic potential to prevent neointima formation. Polymer is one kind of nanoparticles, which can activate the process of endocytosis of cells. In this study, we evaluated the transfection efficiency and therapeutic potential of polymer-based transfection of plasmids expressing GFP and shRNAs targeting IGF-1R (pGFPshIGF-1Rs) to smooth muscle cells and rabbit external jugular vein graft. Results showed that polymer-based transfection provided high efficiency of transgene expression in smooth muscle cells in vitro. In vitro, IGF-1R-specific shRNA transfected by polymer inhibited IGF-1R protein expression by 52 ± 3.6%, when compared with mock transfected cells. In vivo delivering efficiency of pGFPshIGF-1R plasmid into the rabbit external jugular vein graft was significantly high in the polymer-based transfection group, when compared with negative control group. In vivo, polymer-based transfection IGF-1R-specific shRNA efficiently inhibited the expression of IGF-1R protein by 77 ± 3.6%, 65.6 ± 4.9%, and 76.7 ± 4.3% at 24, 48, and 72 h, respectively, when compared with negative control group. Our findings indicated that polymer-based transfection may be a promising technique that allows the targeting of gene therapy for vein graft restenosis.

MicroRNA-150 aggravates H2O2-induced cardiac myocyte injury by down-regulating c-myb gene.

MicroRNAs (miRNAs) are one class of non-coding RNAs that play an important role in post-transcriptional regulation via the degradation or translational inhibition of their target genes. MicroRNA-150 (miR-150) plays a vital role in regulating the development of B and T lymphocytes. Although the dysregulation of miR-150 was confirmed in human myocardial infarction, little is known regarding the biological functions of miR-150 in response to reactive oxygen species (ROS)-mediated gene regulation in cardiac myocytes. Using quantitative real-time reverse transcription-polymerase chain reaction, we demonstrated that the level of miR-150 was up-regulated in cardiac myocytes after treatment with hydrogen peroxide (H2O2). To identify the potential roles of miR-150 in H2O2-mediated gene regulation, we modulated expression of miR-150 using miR-150 inhibitor and miR-150 mimics. Results showed that silencing expression of miR-150 decreased H2O2-induced cardiac cell death and apoptosis. In lymphocytes, c-myb was a direct target of miR-150. In cardiac myocytes, we found that c-myb was also involved in miR-150-mediated H2O2-induced cardiac cell death. These results suggested that miR-150 participates in H2O2-mediated gene regulation and functional modulation in cardiac myocytes. MiR-150 may play an essential role in heart diseases related to ROS, such as cardiac hypertrophy, heart failure, myocardial infarction, and myocardial ischemia/reperfusion injury.

Comparison 30-day clinical complications between transfemoral versus transapical aortic valve replacement for aortic stenosis: a meta-analysis review.

BACKGROUND: Since 2002, transapical aortic valve replacement has been developed as a clinical pathway for transcatheter aortic valve implantation (TAVI). However the appropriate role of TA in the AS population versus TF remains unclear. We performed a meta-analysis to assess if TF has any benefit in reduction of 30-day clinical complications in AS. METHODS: We conducted a comprehensive search on pub-med and web of knowledge from 2002 through September 2012 using following terms: aortic stenosis, aortic valve replacement, transcatheter aortic valve implantation, TAVI, trans-artery, transfemoral, trans-apical. Studies in the original research or review articles were also considered. Included studies must meet the preconditioned criterias. Two investigators independently browsed the studies by title and abstract, finally making decision according to full-text. Disagreements were discussed in group. RESULTS: A total of 20 studies met inclusion criteria's and were included in the analysis (including 4267 patients in TF group, 2242 in TA group). No random clinical trial, one was a retrospective study, others were prospective trials. Our meta-analysis found that TF had the low incidence of 30-day mortality compared with TA procedure (7.5% versus 11.3%). The incidence of stroke at ≤ 30 days was relatively low (3.8% in TF versus 4.0% in TA). Although the incidence of post-operative heart block was high (8.5% versus 7.5%), but no differences were indicated [1.06,95% CI(0.85,1.33)]. CONCLUSIONS: The result of our meta-analysis suggested that TF may have a low risk for 30-day mortality against TA procedure. No difference was found in the incidence of post-operative stroke and heart block.

Tissue distribution and cancer growth inhibition of magnetic lipoplex-delivered type 1 insulin-like growth factor receptor shRNA in nude mice.

The targeted delivery of therapeutic genes into specific tissues, as well as the determination of the biological fate and potential toxicity of nanoparticles, remains a highly relevant challenge for gene-based therapies. Type 1 insulin-like growth factor receptor (IGF-1R), an important oncogene, is frequently over-expressed in lung cancer and mediates cancer cell proliferation as well as tumor growth. In our previous studies, we have successfully applied gene delivery mediated by commercially available nanoparticles (CombiMAG) under a magnetic field, which suppresses IGF-1R expression in a non-small cell lung cancer cell line (A549) in vitro. In the present study, we aimed to investigate the biological distribution and target tumor suppression of magnetofection, as well as its potential toxicity via CombiMAG-carrying plasmids expressing green fluorescent protein (GFP) and short hairpin RNAs (shRNAs) targeting IGF-1R (pGFPshIGF-1Rs) in tumor-bearing mice. The peak expression in various organs appeared 48 h after transfection. Transgene expression via magnetofection was 3-fold improvement than via lipofection. On the 30th day after injection, the tumor size and weight of the CombiMAG-treated group (789.32 ± 39.43 mm(3), 105.5 ± 6.1 mg) were significantly decreased compared with those of the lipofection group (893.83 ± 31.23 mm(3), 164.5 ± 9.1 mg; P< 0.05), and the suppression rate was ∼36%. After a 30-day observation, the injection of CombiMAG did not cause any apparent toxicity. Therefore, IGF-1R shRNA nanoparticles can be valuable and safe delivery agents for RNA interference therapy to tumors in vivo.