NIR-IIb fluorescence antiangiogenesis copper nano-reaper for enhanced synergistic cancer therapy.

The formation of blood vessel system under a relatively higher Cu2+ ion level is an indispensable precondition for tumor proliferation and migration, which was assisted in forming the tumor immune microenvironment. Herein, a copper ions nano-reaper (LMDFP) is rationally designed not only for chelating copper ions in tumors, but also for combination with photothermal therapy (PTT) to improve antitumor efficiency. Under 808 nm laser irradiation, the fabricated nano-reaper converts light energy into thermal energy to kill tumor cells and promotes the release of D-penicillamine (DPA) in LMDFP. Photothermal properties of LMDFP can cause tumor ablation in situ, which further induces immunogenic cell death (ICD) to promote systematic antitumor immunity. The released DPA exerts an anti-angiogenesis effect on the tumor through chelating copper ions, and inhibits the expression of programmed death ligand 1 (PD-L1), which synergizes with PTT to enhance antitumor immunity and inhibit tumor metastasis. Meanwhile, the nanoplatform can emit near-infrared-IIb (NIR-IIb) fluorescence under 980 nm excitation, which can be used to track the nano-reaper and determine the optimal time point for PTT. Thus, the fabricated nano-reaper shows powerful potential in inhibiting tumor growth and metastasis, and holds great promise for the application of copper nanochelator in precise tumor treatment.

Effect of Intensive Glycemic Control on Myocardial Infarction Outcome in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Background: The effect of intensive glucose-lowering treatment on the risk of cardiovascular events in type 2 diabetes remains uncertain, especially the effect on the occurrence of myocardial infarction in patients with type 2 diabetes is still unclear. The purpose of this study was to conduct a systematic review and meta-analysis of relevant RCTs. Methods: We performed a systematic review of randomized clinical trials (RCTS) and observational studies relevant to this study question. We searched the PubMed and Cochrane databases until June 2022. Results: We included data on 14 RCTs and 144,334 patients, all of whom had type 2 diabetes. When all studies were considered, intensive glucose-lowering treatment significantly reduced the incidence of MI compared with conventional therapy and the total OR value is 0.90 (CI 0.84, 0.97; P = 0.004) when considering all the studies. When the target value of intensive glucose-lowering treatment was considered as HbA1c decrease of more than 0.5%, there was no significant protective effect on MI, the total OR value is 0.88 (CI 0.81, 0.96; P = 0.003). When considering all available RCTS, the intensive glucose-lowering treatment group had a protective effect for MACE compared to the conventional treatment group, and the total OR value is 0.92 (CI 0.88, 0.96; P < 0.00001). In the available RCTs, for the patients with a history of prior CAD, the total OR value is 0.94 (CI 0.89, 0.99; P = 0.002). And there was no difference in the incidence of hypoglycemic events between the intensive and conservative treatment groups. Conclusion: Our data support the positive protective effect of glucose-lowering therapy on MI in patients with T2DM, but there is no significant effect of intensive glucose-lowering. In addition, we found no greater protective effect of enhanced glucose control in the HbA1c reduction of more than 0.5%, and no difference in the incidence of adverse events compared with the HbA1c reduction of less than 0.5%.

Prevalence and Pattern of Congenital Heart Diseases in School Children in Dongguan, China.

BACKGROUND: To determine the prevalence and pattern of congenital heart disease (CHD) among elementary school children in Dongguan, China. METHODS: Between November 2011 and November 2012, 540,574 school children from 449 elementary schools were screened for CHD by trained doctors in Dongguan. The school children who were suspected to have CHD were referred to a pediatric cardiologist and/or an echocardiographer for a complete evaluation. RESULTS: The total prevalence of CHD was 2.14 per 1,000 school children (1,157/540,574). The most common form of CHD was isolated ventricular septal defect (37.77%; 437/1,157), followed by isolated atrial septal defect (20.22%; 234/1,157) and patent ductus arteriosus (9.94%; 115/1,157). With respect to sex, CHD was equally distributed between males and females. CONCLUSION: Our data show that the prevalence of CHD in Dongguan is not as high as expected and that isolated ventricular septal defect is the predominant pathology. Echocardiography plays a crucial role in the diagnosis of CHD.

pH-Responsive Selenium Nanoplatform for Highly Efficient Cancer Starvation Therapy by Atorvastatin Delivery.

Recently, starvation-inducing nutrient deprivation has been regarded as a promising strategy for tumor suppression. As a first-line lipid-lowering drug, atorvastatin (ATV) significantly reduces caloric intake, suggesting its potential in starvation therapy for suppressing tumors. Accordingly, we developed a novel starvation therapy agent (HA-Se-ATV) in this study to suppress tumor growth by using hyaluronic acid (HA)-conjugated chitosan polymer-coated nano-selenium (Se) for loading ATV. HA-Se-ATV targets cancer cells, following which it effectively accumulates in the tumor tissue. The HA-Se-ATV nanoplatform was then activated by inducing a weakly acidic tumor microenvironment and subsequently releasing ATV. ATV and Se synergistically downregulate the levels of cellular adenosine triphosphate while inhibiting the expression of thioredoxin reductase 1. Consequently, the starvation-stress reaction of cancer cells is significantly elevated, leading to cancer cell death. Furthermore, the in vivo results indicate that HA-Se-ATV effectively suppresses tumor growth with a low level of toxicity, demonstrating its great potential for clinical translation.

NIR-II Fluorescence Imaging-Guided Oxygen Self-Sufficient Nano-Platform for Precise Enhanced Photodynamic Therapy.

Tumor hypoxia and systemic toxicity seriously affect the efficacy of photodynamic therapy (PDT) and are considered as the "Achilles' heel" of PDT. Herein, to combat such limitations, an intelligent orthogonal emissions LDNP@SiO2 -CaO2 and folic acid-polyethylene glycol-Ce6 nanodrug is rationally designed and fabricated not only for relieving the hypoxic tumor microenvironment (TME) to enhance PDT efficacy, but also for determining the optimal triggering time through second near-infrared (NIR-II) fluorescence imaging. The designed nanodrug continuously releases a large amount of O2 , H2 O2 , and Ca2+ ions when exposed to the acidic TME. Meanwhile, under downshifting NIR-II bioimaging guidance, chlorine e6 (Ce6) consumes oxygen to produce 1 O2 upon excitation of upconversion photon. Moreover, cytotoxic reactive oxygen species (ROS) and calcium overload can induce mitochondria injury and thus enhance the oxidative stress in tumor cells. As a result, the NIR-II bioimaging guided TME-responsive oxygen self-sufficient PDT nanosystem presents enhanced anti-tumor efficacy without obvious systemic toxicity. Thus, the fabricated nanodrug offers great potential for designing an accurate cancer theranostic system.

Multi-omics insights into potential mechanism of SGLT2 inhibitors cardiovascular benefit in diabetic cardiomyopathy.

Background: Metabolic and energy disorders are considered central to the etiology of diabetic cardiomyopathy (DCM). Sodium-glucose cotransporter-2 inhibitors (SGLT2i) can effectively reduce the risk of cardiovascular death and heart failure in patients with DCM. However, the underlying mechanism has not been elucidated. Methods: We established a DCM rat model followed by treatment with empagliflozin (EMPA) for 12 weeks. Echocardiography, blood tests, histopathology, and transmission electron microscopy (TEM) were used to evaluate the phenotypic characteristics of the rats. The proteomics and metabolomics of the myocardium in the rat model were performed to identify the potential targets and signaling pathways associated with the cardiovascular benefit of SGLT2i. Results: The diabetic rat showed pronounced DCM characterized by mitochondrial pleomorphic, impaired lipid metabolism, myocardial fibrosis, and associated diastolic and systolic functional impairments in the heart. To some extent, these changes were ameliorated after treatment with EMPA. A total of 43 proteins and 34 metabolites were identified as targets in the myocardium of diabetic rats treated with EMPA. The KEGG analysis showed that arachidonic acid is associated with the maximum number of related pathways and may be a potential target of EMPA treatment. Fatty acid (FA) metabolism was enhanced in diabetic hearts, and the perturbation of biosynthesis of unsaturated FAs and arachidonic acid metabolism was a potential enabler for the cardiovascular benefit of EMPA. Conclusion: SGLT2i ameliorated lipid accumulation and mitochondrial damage in the myocardium of diabetic rats. The metabolomic and proteomic data revealed the potential targets and signaling pathways associated with the cardiovascular benefit of SGLT2i, which provides a valuable resource for the mechanism of SGLT2i.

A Multifunctional Vanadium-Iron-Oxide Nanoparticle Eradicates Hepatocellular Carcinoma via Targeting Tumor and Endothelial Cells.

Nanoparticles are widely used in biological research and cancer therapy. In hepatocellular carcinoma, several nanoplatforms have been synthesized and studied to improve the drug efficacy; however, these nanoplatforms are still insufficient to eradicate tumors. Herein, we have synthesized a novel vanadium (V)-iron-oxide (ION) nanoparticle (VIO) that combines chemodynamic, photothermal, and diagnostic capacities to enhance the tumor suppression effect in one agent with multiple functions. In the in vitro models, hepatocellular carcinoma cells are significantly inhibited by VIO-based nanoagents. The mechanistic study validates that VIO increases reactive oxygen species (ROS), which led to apoptosis and ferroptosis resulting in cell death. To our surprise, VIO targets not only tumor cells but also endothelial cells. In addition to inducing cell death, VIO also blocks tube formation and cell migration in human umbilical vein endothelial cell (HUVEC) and C166 models, indicating an antiangiogenic potential. In mouse tumor models, VIO retards tumor growth and induces apoptosis in tumor tissues. Furthermore, a significant blood vessel regression is seen in VIO-treated groups accompanied with larger necrotic areas. More interestingly, the activation of photothermal therapy completely eradicates tumor tissues. Taken together, this VIO nanoplatform could be a powerful anticancer candidate for nanodrug development.

RNA Sequencing of Cardiac in a Rat Model Uncovers Potential Target LncRNA of Diabetic Cardiomyopathy.

Background: Diabetic cardiomyopathy (DCM) is one of the major causes of heart failure in diabetic patients; however, its pathogenesis remains unclear. Long non-coding RNAs (lncRNAs) are involved in the development of various cardiovascular diseases, but little is known in DCM. Objective: The present study was conducted to investigate the altered expression signature of lncRNAs and mRNAs by RNA-sequencing and uncovers the potential targets of DCM. Methods: A DCM rat model was established, and the genome-wide expression profile of cardiac lncRNAs and mRNAs was investigated in the rat model with and without DCM by RNA-sequencing. Bioinformatics analysis included the co-expression, competitive endogenous RNA (ceRNA) network, and functional enrichment analysis of deregulated lncRNAs and mRNAs. Results: A total of 355 lncRNA transcripts and 828 mRNA transcripts were aberrantly expressed. The ceRNA network showed that lncRNA XR_351927.3, ENSRNOT00000089581, XR_597359.2, XR_591602.2, and XR_001842089.1 are associated with the greatest number of differentially expressed mRNAs and AURKB, MELK, and CDK1 may be the potential regulatory targets of these lncRNAs. Functional analysis showed that these five lncRNAs are closely associated with fibration, cell proliferation, and energy metabolism of cardiac myocytes, indicating that these core lncRNAs have high significance in DCM. Conclusions: The present study profiled the DCM-specific lncRNAs and mRNAs, constructed the lncRNA-related ceRNA regulatory network, and identified the potential prognostic biomarkers, which provided new insights into the pathogenesis of DCM.

Curcumin attenuates inflammation of Macrophage-derived foam cells treated with Poly-L-lactic acid degradation via PPARγ signaling pathway.

Poly-L-lactic acid (PLLA) is considered to be a promising candidate material for biodegradable vascular scaffolds (BVS) in percutaneous coronary intervention (PCI). But, PLLA-BVS also faces the challenge of thrombosis (ST) and in-stent restenosis (ISR) caused by in-stent neo-atherosclerosis (ISNA) associated with inflammatory reactions in macrophage-derived foam cells. Our previous studies have confirmed that curcumin alleviates PLLA-induced injury and inflammation in vascular endothelial cells, but it remains unclear whether curcumin can alleviate the effect of inflammatory reactions in macrophage-derived foam cells while treated with degraded product of PLLA. In this study, PLLA-BVS was implanted in the porcine coronary artery to examine increased macrophages and inflammatory cytokines such as NF-κb and TNF-α by histology and immunohistochemistry. In vitro, macrophage-derived foam cells were induced by Ox-LDL and observed by Oil Red Staining. Foam cells were treated with pre-degraded PLLA powder, curcumin and PPARγ inhibitor GW9662, and the expression of IL-6, IL-10, TNF-α, NF-κb, PLA2 and PPARγ were investigated by ELISA or RT-qPCR. This study demonstrated that the macrophages and inflammatory factors increased after PLLA-BVS implantation in vivo, and foam cells derived from macrophages promoted inflammation by products of PLLA degradation in vitro. This present study was found that the inflammation of foam cells at the microenvironment of PLLA degraded products were significantly increased, and curcumin can attenuate the inflammation caused by the PLLA degradation via PPARγ signal pathway. In addition, curcumin should be further studied experimentally in vivo experiments on animal models as a potential therapeutic to reduce ISNA of PLLA-BVS. Graphical abstract.

A nanoselenium-coating biomimetic cytomembrane nanoplatform for mitochondrial targeted chemotherapy- and chemodynamic therapy through manganese and doxorubicin codelivery.

The cell membrane is widely considered as a promising delivery nanocarrier due to its excellent properties. In this study, self-assembled Pseudomonas geniculate cell membranes were prepared with high yield as drug nanocarriers, and named BMMPs. BMMPs showed excellent biosafety, and could be more efficiently internalized by cancer cells than traditional red cell membrane nanocarriers, indicating that BMMPs could deliver more drug into cancer cells. Subsequently, the BMMPs were coated with nanoselenium (Se), and subsequently loaded with Mn2+ ions and doxorubicin (DOX) to fabricate a functional nanoplatform (BMMP-Mn2+/Se/DOX). Notably, in this nanoplatform, Se nanoparticles activated superoxide dismutase-1 (SOD-1) expression and subsequently up-regulated downstream H2O2 levels. Next, the released Mn2+ ions catalyzed H2O2 to highly toxic hydroxyl radicals (·OH), inducing mitochondrial damage. In addition, the BMMP-Mn2+/Se nanoplatform inhibited glutathione peroxidase 4 (GPX4) expression and further accelerated intracellular reactive oxygen species (ROS) generation. Notably, the BMMP-Mn2+/Se/DOX nanoplatform exhibited increased effectiveness in inducing cancer cell death through mitochondrial and nuclear targeting dual-mode therapeutic pathways and showed negligible toxicity to normal organs. Therefore, this nanoplatform may represent a promising drug delivery system for achieving a safe, effective, and accurate cancer therapeutic plan.

Manganese-deposited iron oxide promotes tumor-responsive ferroptosis that synergizes the apoptosis of cisplatin.

Background: Ferroptosis is a form of iron-dependent programmed cell death that differs from apoptosis with regards to both mechanism and cell morphology. Therefore, ferroptotic-based cancer therapy has shown significant potential to overcome the weaknesses of conventional therapeutics mediated by apoptosis pathways. Effective ferroptosis can be induced by the intracellular Fenton reaction that is dependent on the adequate supply of iron ions and H2O2 in cells. However, these are often insufficient due to intrinsic cellular regulation. Methods: In this study, we designed a cisplatin prodrug-loaded manganese-deposited iron oxide nanoplatform (Pt-FMO) to trigger intracellular cascade reactions that lead to generation of reactive oxygen species (ROS) to enhance ferroptotic effect. The Pt-FMO causes the tumor microenvironment responsive to release manganese, iron ions and Pt-drugs. As manganese is an element that is able to catalyze the Fenton reaction more effectively than iron, coupled with the Pt-drugs that can promote generation of H2O2 in cells, the Pt-FMO is expected to significantly strengthen catalysis of the Fenton reaction, which favors the ferroptotic effect. Moreover, the Pt-drugs will eventually function as cisplatin. Thus, Pt-FMO is an ideal candidate for tumor ferroptotic combined with apoptotic treatment. Results:In vivo results demonstrated that, at a dosage of only 8.89% Pt content, Pt-FMO is able to achieve a similar treatment effect as cisplatin. Hence, Pt-FMO exhibited significantly lower systemic toxicity compared to cisplatin. Additionally, Pt-FMO exhibits effective T2 -weighted MRI enhancement for tumor imaging. Conclusion: The Pt-FMO nanoplatform is designed to introduce mutual beneficial cascade reactions for promoting ferroptosis and apoptosis in combination with tumor MRI. The Pt-FMO system, which causes ferroptosis combined with apoptosis, can efficiently induce tumor cell death.

Highly sensitiveT1-T2dual-mode MRI probe based on ultra-small gadolinium oxide-decorated iron oxide nanocrystals.

Single-mode magnetic resonance imaging (MRI) contrast agents (CAs) in clinical settings are easily disturbed by calcification, bleeding, and adipose signals, which result in inaccurate diagnoses. In this study, we developed a highly efficientT1-T2dual-mode MRI CA using an ultra-small gadolinium oxide-decorated magnetic iron oxide nanocrystal (GMIO). The gadolinium element could effectively alter the magnetic properties of the GMIO from soft-ferromagnetism to superparamagnetism. In addition, when the Gd/Fe ratio was 15% (designated as GMIO-2), the GMIO-2 possessed the best superparamagnetism and highest magnetism. Subsequently,T1andT2values of GMIO-2 were measured through a series of turbo spin-echo images and then multi-spin echo sequence, respectively. Based on this,T1andT2relaxivities of GMIO-2 were calculated and were the highest (r1: 1.306 m M-1s-1andr2: 234.5 m M-1s-1) when compared to other groups. The cytotoxicity of GMIO-2 was negligible under a wide range of dosages, thus exhibiting excellent cell biocompatibility. Moreover, GMIO-2 could quickly diffuse into cells, leading to its effective accumulation. The systemic delivery of GMIO-2 resulted in an excellentT1-T2dual-mode MRI contrast effect in kidneys, which is expected to improve the diagnosis of kidney lesions. Therefore, this work provides a promising candidate for the development of aT1-T2dual-mode MRI CA.

Long-Term Arterial Remodeling After Bioresorbable Scaffold Implantation 4-Year Follow-up of Quantitative Coronary Angiography, Histology and Optical Coherence Tomography.

PURPOSE: Our previous studies have confirmed the safety and efficacy of the novel fully bioresorbable PLLA scaffold (PowerScaffold®) at 12 months implantation. In the present study, the scaffold absorption and coronary vessel remodeling at 4 years were evaluated. METHODS: After PowerScaffold® were implanted into 13 coronary arteries of 6 miniature pigs, quantitative coronary angiography (QCA) was performed at 15 days and 4 years follow-up to measure the mean lumen diameter (MLD), late lumen loss (LLL), and % stenosis of the coronary arteries. Optical coherence tomography (OCT) was performed to obtain the strut footprints at 4 years before euthanization for histological analysis. In addition, 2 PowerScaffold® were implanted into 2 miniature pigs for 2 years as supplementary data. All stented arteries were dissected and stained with HE, Masson, EVG, and Alcian blue to observe struts, cells, fibrinoid, elastin, and proteoglycans, respectively. RESULTS: There were no significant differences in MLD, LLL and % stenosis in stented coronary arteries between 15 days and 4 years by QCA. At 4 years, most strut sites were indiscernible and replaced by extracellular matrix and connective tissue by histology. Both strut/vessel wall interaction and strut coverage were shown 100% by OCT. CONCLUSION: At 4 years, the scaffold struts were completely embedded into vessel wall and mostly replaced by regenerated tissue. There was no sign of in-stent stenosis in all stented arteries.

Oxygen Vacancy Defect-Induced Activity Enhancement of Gd Doping Magnetic Nanocluster for Oxygen Supplying Cancer Theranostics.

This work finds that Fe3O4 nanoclusters can rearrange by Gd doping and then self-assemble to a hollow magnetic nanocluster (HMNC), providing larger magnetic moments to obtain an excellent MRI capability and increasing the number of oxygen vacancies in HMNC. The hollow structure makes platinum(IV) prodrugs effectively load into HMNC. Second, plenty of oxygen vacancy defects can capture oxygen molecules, enhance the catalytic activity of HMNC, and then promote intracellular ROS generation. On the basis of this, a targeting iRGD-labeled HMNC nanosystem (iHMNCPt-O2) is developed through loading oxygen molecules and platinum(IV) prodrugs for chemo- and chemodynamic therapy of cancer. This nanosystem shows an excellent response ability to weak acid and GSH, which can cause a series of cascade reactions in a cell. These cascade reactions are dramatically enhanced at the intracellular ROS level, cause mitochondria and DNA damage, and then induce cancer cell death. Besides, systemic delivery of iHMNCPt-O2 significantly enhanced the MRI contrast signal of tumors and improved the quality of MR images, accurately diagnosing tumors. Therefore, this work provides a novel method for accelerating the Fenton-like reaction and enhancing the MRI capability and fabricates a promising "all-in-one" system to overwhelm the problems of cancer theranostic.

Effect of Cr on the Mineral Structure and Composition of Cement Clinker and Its Solidification Behavior.

In order to reveal the solidification behavior of Cr in the cement clinker mineral phase, 29Si magic-angle spinning nuclear magnetic resonance, X-ray diffraction, and scanning electron microscopy with energy-dispersive X-ray spectroscopy techniques were used to analyze the morphology and composition of the cement clinker mineral phase doped with Cr. The results showed that the addition of Cr did not change the chemical environment of 29Si in the clinker mineral phase, and it was still an isolated silicon-oxygen tetrahedron. Cr affected the orientation of the silicon-oxygen tetrahedron and the coordination number of calcium, leading to the formation of defects in the crystal structure of the clinker mineral phase, by replacing Ca2+ into the mineral phase lattice to form a new mineral phase Ca3Cr2(SiO4)3. Cr acted as a stabilizer for the formation of ß-C2S in the clinker calcination. As the amount of Cr increased, the relative content of C3S decreased and the relative content of C2S increased. Further, Cr easily dissolved in C2S, while it was not found in C3S. This study is conducive to further research on the mechanism of heavy metal solidification in cement clinker. Furthermore, it is important to evaluate the environmental risk of heavy metals in the process of sludge disposal through cement kiln and promote the utilization of sludge resources and the sustainable development of the cement industry.

Promoting desert biocrust formation using aquatic cyanobacteria with the aid of MOF-based nanocomposite.

Desertification and eutrophication are two global environmental problems human beings face. Inoculating cyanobacteria to form biocrusts is considered an effective technology to inhibit desertification. The main limitation of biocrust formation is the lack of propagules and nutrients in deserts. A possible low cost source of propagules and nutrients is eutrophic water containing aquatic cyanobacteria (AC), nitrogen and phosphorus. In this study, we fabricated a network-structured nanocomposite (designated as MC) using a metal-organic framework (MOF) and carboxymethyl cellulose (CMC). MC, with a large specific surface area and numerous surface groups, had a high retention capacity for water and nutrients and good biosafety. The combination of AC-containing water (ACW) and MC could provide a suitable microenvironment in the soil, promote the growth of desert cyanobacteria (DC), formation of biocrusts and inhibition of desertification. This study provides a novel approach to simultaneously relieve desertification and eutrophication.

Long-term clinical safety and efficacy of drug-coated balloon in the treatment of in-stent restenosis: A meta-analysis and systematic review.

OBJECTIVES: The aim of this study was to evaluate the long-term clinical safety and efficacy of drug-coated balloon (DCB) in the treatment of in-stent restenosis (ISR). BACKGROUND: There is a long-term safety issue in peripheral arterial disease patients treated with paclitaxel-coated balloon, this has also raised concerns on DCB in coronary intervention. METHODS: Nine randomized controlled trials (RCTs) and nine observational studies (OSs) were included with a total of 3,782 patients (1,827 in the DCB group, 1,955 in the drug-eluting stent [DES] group) being analyzed. The primary outcome measure-major adverse cardiovascular events (MACEs), target lesion revascularization (TLR), target vessel revascularization (TVR), myocardial infarction (MI), cardiac death (CD), stent thrombosis (ST), all-cause death (AD), and coronary angiography outcomes included late lumen loss (LLL), minimum luminal diameter (MLD), diameter stenosis (DS) were analyzed. RESULTS: DCB treatment significantly reduced the LLL (MD: -0.13; [CI -0.23 to -0.03], p = .01). No difference was found for MLD (MD: -0.1; [CI -0.24 to 0.04], p = .17) and DS% (RR = 0.98 [CI 0.80-1.20], p = .86). There was no significant difference in TLR, TVR, MI, CD, ST, AD, and the overall incidence of MACEs between the two groups up to 3 years follow-up. Subgroup analysis for different type of ISR and DES showed no significant difference in the incidence of endpoints, and there is no difference when considering RCTs or OSs only. CONCLUSIONS: The safety and efficacy of the DCB and DES in the treatment of ISR is comparable at up to 3 years follow-up.

Effect of miR-134 against myocardial hypoxia/reoxygenation injury by directly targeting NOS3 and regulating PI3K/Akt pathway.

PURPOSE: To reveal the function of miR-134 in myocardial ischemia. METHODS: Real-time PCR and western blotting were performed to measure the expression of miR-134, nitric oxide synthase 3 (NOS3) and apoptotic-associated proteins. Lactic dehydrogenase (LDH) assay, cell counting kit-8 (CCK-8), Hoechst 33342/PI double staining and flow cytometry assay were implemented in H9c2 cells, respectively. MiR-134 mimic/inhibitor was used to regulate miR-134 expression. Bioinformatic analysis and luciferase reporter assay were utilized to identify the interrelation between miR-134 and NOS3. Rescue experiments exhibited the role of NOS3. The involvement of PI3K/AKT was assessed by western blot analysis. RESULTS: MiR-134 was high regulated in the myocardial ischemia model, and miR-134 mimic/inhibitor transfection accelerated/impaired the speed of cell apoptosis and attenuated/exerted the cell proliferative prosperity induced by H/R regulating active status of PI3K/AKT signaling. LDH activity was also changed due to the different treatments. Moreover, miR-134 could target NOS3 directly and simultaneously attenuated the expression of NOS3. Co-transfection miR-134 inhibitor and pcDNA3.1-NOS3 highlighted the inhibitory effects of miR-134 on myocardial H/R injury. CONCLUSION: This present work puts insights into the crucial effects of the miR-134/NOS3 axis in myocardial H/R injury, delivering a potential therapeutic technology in future.

Inflammation and dysfunction in human aortic endothelial cells associated with poly-l-lactic acid degradation in vitro are alleviated by curcumin.

Poly-l-lactic acid (PLLA) is widely used in clinic, for example, as biodegradable coronary artery stents. However, inflammatory responses in endothelial cells associated with PLLA degradation are relatively undefined. We previously reported inflammation in human aortic endothelial cells (HAEC) in vitro and in vivo. Here, we further assessed inflammatory injury, including cell migration, cell function, and inflammatory cytokines expressed in HAEC treated with PLLA and curcumin by CCK-8, wound healing assay, ELISA, and Western blot. Significant inhibition of cell migration, remarkable dysfunction, and inflammatory responses were found in HAEC treated with PLLA degradation extract, and these effects were alleviated by Cur treatment. These findings indicated that cautious evaluation of biodegradable polymers should be performed, and Cur represents a promising anti-inflammatory agent for alleviating endothelial dysfunction and inflammation caused by PLLA degradation. In addition, Cur should be further studied experimentally in in vivo experiments on animal models as a potential therapeutic to reduce thrombosis of biodegradable polymer stents.

A pH-responsive platform combining chemodynamic therapy with limotherapy for simultaneous bioimaging and synergistic cancer therapy.

Chemodynamic therapy (CDT) was widely exploited for cancer therapy and expected to replace traditional anticancer drug therapies. Generally, CDT needs to combine with extra therapeutic methods for obtaining the optimal therapeutic efficacy of cancer. Herein, a multifunctional theranostic platform combing CDT with limotherapy was developed via nanoselenium (nano-Se)-coated manganese carbonate-deposited iron oxide nanoparticle (MCDION-Se). MCDION-Se could release abundant of Mn2+ ions that catalyzed H2O2 into hydroxyl radicals (·OH) via a Fenton-like reaction, effectively inducing the apoptosis of cancer cells. Besides, nano-Se coated onto MCDION-Se also dramatically activated superoxide dismutase (SOD) and promoted the generation of superoxide anion radicals (SOARs) in tumor tissue. Subsequently, a high content of H2O2 was produced via SOD catalysis of SOARs, further enhancing CDT efficiency. Meanwhile, the nano-Se and Mn2+ ions inhibited the generation of adenosine triphosphate (ATP), thus starving cancer cells. In addition, in vitro and in vivo experiments showed that MCDION-Se could effectively enhance the contrast of tumor tissue and improve the quality of magnetic resonance imaging (MRI). Overall, this work provided a nanoplatform that combined CDT with limotherapy for cancer therapy and simultaneously utilized MRI for monitoring the treatment of tumors.