Retraction of "0D/2D Coordination Complexes: Magnetic Studies, Protection, and Mechanism against Ischemic Myocardial Damage by Reducing the Activation of the PI3K/Akt Signaling Pathway".

[This retracts the article DOI: 10.1021/acsomega.0c05601.].

Research Progress of Chinese Medicine in the Treatment of Myocardial Ischemia-Reperfusion Injury.

Vascular recanalization is the essential procedure in which severe coronary artery stenosis is diagnosed. However, the blood flow recovery associated with this procedure may cause myocardial ischemia-reperfusion injury (MIRI), which aggravates heart failure. Unfortunately, the mechanism of MIRI has historically been poorly understood. As we now know, calcium overloading, oxidative stress, mitochondrial dysfunction, inflammatory responses, and ferroptosis take part in the process of MIRI. Modern medicine has shown through clinical studies its own limited effects in the case of MIRI, whereas Chinese traditional medicine demonstrates a strong vitality. Multiple-target effects, such as anti-inflammatory, anti-oxidant, and cardio-protection effects, are central to this vitality. In our clinic center, Yixin formula is commonly used in patients with MIRI. This formula contains Astragalus, Ligusticum Wallichii, Salvia, Rhodiola Rosea, Radix Angelicae Sinensis, Cyperus Rotundus, and Cassia Twig. Its effects include warming yang energy, activating blood circulation, and eliminating blood stasis. In our previous laboratory studies, we have proved that it can reduce MIRI and oxidative stress injury in rats suffering from ischemia myocardiopathy. It can also inhibit apoptosis and protect myocardium. In this paper, we review the research of Yixin formula and other related herbal medicines in MIRI therapy.

SPINK5 is a Tumor-Suppressor Gene Involved in the Progression of Nonsmall Cell Lung Carcinoma through Negatively Regulating PSIP1.

This study aimed to elucidate how SPINK5 affects the malignant phenotypes of NSCLC and the molecular mechanism. NSCLC and adjacent normal tissues were collected to detect the differential level of SPINK5. The influence of SPINK5 on pathological indicators of NSCLC was analyzed. Cellular functions of NSCLC cells overexpressing SPINK5 were assessed by CCK-8, EdU, and transwell assay. By confirming the downstream target of SPINK5, its molecular mechanism on regulating NSCLC was finally explored through rescue experiments. SPINK5 was lowly expressed in NSCLC tissues, and it predicted tumor staging and lymphatic metastasis. In vitro overexpression of SPINK5 declined proliferative and migratory rates in NSCLC cells. PSIP1 was verified as the target gene binding SPINK5, and they displayed a negative correlation in NSCLC tissues. Overexpression of PSIP1 was able to reverse the inhibited proliferative and migratory potentials in NSCLC cells overexpressing SPINK5. SPINK5 level has a close relation to tumor staging and lymphatic metastasis in NSCLC. It serves as a tumor-suppressor gene that inhibits proliferation and migration of NSCLC through negatively regulating PSIP1.

Long Non-Coding RNA MEG8 Suppresses Hypoxia-Induced Excessive Proliferation, Migration and Inflammation of Vascular Smooth Muscle Cells by Regulation of the miR-195-5p/RECK Axis.

It has been recognized that rebalancing the abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) helps relieve vascular injury. Presently, we aim to investigate whether long non-coding RNA (lncRNA) maternally expressed 8 (MEG8) plays a role in affecting the excessive proliferation and migration of VSMCs following hypoxia stimulation. A percutaneous transluminal angioplasty balloon dilatation catheter was adopted to establish vascular intimal injury, the levels of MEG8 and miR-195-5p in the carotid artery were tested by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Hypoxia was used to stimulate VSMCs, then the cell counting kit-8 (CCK-8) assay, Transnwell assay, and wound healing assay were conducted to evaluate the proliferation, and migration of VSMCs. The protein levels of RECK (reversion inducing cysteine rich protein with kazal motifs), MMP (matrix metalloproteinase) 3/9/13, COX2 (cytochrome c oxidase subunit II), macrophage inflammatory protein (MIP)-1beta, VCAM-1 (vascular cell adhesion molecule 1), ICAM-1 (intercellular adhesion molecule 1), and HIF-1α (hypoxia inducible factor 1 subunit alpha) were determined by western blot or cellular immunofluorescence. As the data showed, MEG8 was down-regulated in the carotid artery after balloon injury in rats and hypoxia-treated VSMCs, and miR-195-5p was overexpressed. Forced MEG8 overexpression or inhibiting miR-195-5p attenuated hypoxia-promoted cell proliferation and migration of VSMCs. In addition, miR-195-5p up-regulation reversed MEG8-mediated effects. Hypoxia hindered the RECK expression while boosted MMP3/9/13 levels, and the effect was markedly reversed with MEG8 up-regulation or miR-195-5p down-regulation. Mechanistically, MEG8 functioned as a competitive endogenous (ceRNA) by sponging miR-195-5p which targeted RECK. Moreover, the HIF-1α inhibitor PX478 prevented hypoxia-induced proliferation, and migration of VSMCs, upregulated MEG8, and restrained miR-195-5p expression. Overall, lncRNA MEG8 participated in hypoxia-induced excessive proliferation, inflammation and migration of VSMCs through the miR-195-5p/RECK axis.

0D/2D Coordination Complexes: Magnetic Studies, Protection, and Mechanism against Ischemic Myocardial Damage by Reducing the Activation of the PI3K/Akt Signaling Pathway.

The synthesis of two new coordination compounds was carried out by applying 4-(3-carboxyphenyl)picolinic acid (H2cppa) as building units under the hydrothermal reaction conditions, whose chemical formulae are [Cu(Hcppa)2(H2O)2]·2H2O (1) and [Cu(µ3-cppa)(H2O)2] (2). The analysis of structures suggested that 1 featured a discrete molecular structure, which was extended into the three-dimensional supramolecular network with the topology of pcu topology, whereas complex 2 showed a two-dimensional layered network with the fes topology. The magnetic performances of the two synthesized compounds reveal antiferromagnetic coupling between consecutive metal ions. Their application values on ischemic myocardial damage were assessed, and the detailed mechanism of the synthetic complexes was also investigated. The Elabscience Annexin V detection kit was used in this research to determine the percentage of apoptotic cardiomyocytes after different complex treatments. In addition, the relative expression of PI3K/Akt in the myocardium after the application of the compound was determined using the real-time reverse transcription polymerase chain reaction assay.

Luhong Formula Has a Cardioprotective Effect on Left Ventricular Remodeling in Pressure-Overloaded Rats.

BACKGROUND: Luhong formula (LHF)-a traditional Chinese medicine containing Cervus nippon Temminck, Carthamus tinctorius L., Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao, Codonopsis pilosula (Franch.) Nannf., Cinnamomum cassia Presl, and Lepidium apetalum Willd-is used in the treatment of heart failure, but little is known about its mechanism of action. We have investigated the effects of LHF on antifibrosis. METHODS: Forty-eight SD male rats were randomly assigned into six groups (n = 8), model group, sham-operation group, perindopril group (0.036 mg/ml), LHF high doses (LHF-H, 1.44 g/mL), LHF middle doses (LHF-M, 0.72 g/mL), and LHF low doses (LHF-L, 0.36 g/mL). Except the sham-operation group, the other groups were received an abdominal aorta constriction to establish a model of myocardial hypertrophy. The HW and LVW were measured to calculate the LVW/BW and HW/BW. ELISA was used to detect the serum concentration of BNP. The expressions of eNOS, TGF-ß1, caspase-3, VEGF, and VEGFR2 in heart tissues were assessed by western blot analysis. mRNA expressions of eNOS, Col1a1, Col3a1, TGF-ß1, VEGF, and VEGFR2 in heart tissues were measured by RT-PCR. The specimens were stained with hematoxylin-eosin (HE) and picrosirius red staining for observing the morphological characteristics and collagen fibers I and III of the myocardium under a light microscope. RESULTS: LHF significantly lowered the rat's HW/BW and LVM/BW, and the level of BNP in the LHF-treated group compared with the model group. Histopathological and pathomorphological changes of collagen fibers I and III showed that LHF inhibited myocardial fibrosis in heart failure rats. Treatment with LHF upregulated eNOS expression in heart tissue and downregulated Col1a1, Col3a1, TGF-ß1, caspase-3, VEGF, and VEGFR2 expression. CONCLUSION: LHF can improve left ventricular remodeling in a pressure-overloaded heart failure rat model; this cardiac protective ability may be due to cardiac fibrosis and attenuated apoptosis. Upregulated eNOS expression and downregulated Col1a1, Col3a1, TGF-ß1, caspase-3, VEGF, and VEGFR2 expression may play a role in the observed LHF cardioprotective effect.

Anti-inflammatory effect of up-regulated microRNA-221-3p on coronary heart disease via suppressing NLRP3/ASC/pro-caspase-1 inflammasome pathway activation.

OBJECTIVE: As some evidence has demonstrated the role of microRNA-221 (miR-221) on coronary heart disease (CHD), the aim of the present study was to investigate the effect of miR-221-3p on CHD via regulating NLRP3/ASC/pro-caspase-1 inflammasome pathway. METHODS: Sixty CHD patients and 60 healthy controls were collected to detect the expression of miR-221-3p, NLRP3, ASC, pro-caspase-1 in peripheral blood and the contents of related factors in serum. The rats model of CHD was injected with miR-221-3p agomir or miR-221-3p antagomir to explore its functions in miR-221-3p, NLRP3, ASC and pro-caspase-1 expression, electrocardiogram data, cardiomyocytes apoptosis, myocardial injury, inflammatory reaction and oxidative stress of CHD rats. RESULTS: MiR-221-3p declined and NLRP3, ASC and pro-caspase-1 raised in CHD. Up-regulated miR-221-3p reduced the change value of J-point and T-wave, decreased NLRP3, ASC and pro-caspase-1 expression, suppressed apoptosis in cardiomyocytes, as well as suppressed myocardial injury, inflammatory reaction and oxidative stress in CHD rats. CONCLUSION: This study highlights that up-regulated miR-221-3p suppresses the overactivation of NLRP3/ASC/pro-caspase-1 inflammasome pathway and has an anti-inflammatory effect in CHD. Thus, miR-221-3p may serve as a potential target for the treatment of CHD.

Upregulation of long noncoding RNA RP4 exacerbates hypoxia injury in cardiomyocytes through regulating miR-939/Bnip3/Wnt/ß-catenin pathway.

This research planned to dig the impacts and potential principles of long noncoding RNA RP4 onH9c2 cell injury induced by hypoxia. The H9c2 cardiac muscle cells were cultured under 3% O2 concentration to induce hypoxia injury, followed by detection of RP4 expression. RP4 was then overexpressed and silenced to investigate its effects on cell injury induced by hypoxia. The potential correlation between RP4 and miR-939, between miR-939 and Bnip3, and between RP4/miR-939/Bnip3 axis and Wnt/ß-catenin pathway activation were explored. Biological processes (suppressed cell viability, migration and invasion, but enhanced cell apoptosis) were changed by hypoxia. Upregulation of RP4 enhanced hypoxia-produced damage in H9c2 cells. Additionally, miR-939 expression was opposite regulated by RP4, and miR-939 mimic abrogated the influences of pc-RP4 on enhanced hypoxia damage in H9c2 cells. Moreover, Bnip3 was targeted by miR-939 and their correlation is negative. Furthermore, upregulation of RP4 exacerbated hypoxia-produced injury in H9c2 cells by sensitizing Wnt/ß-catenin signals in H9c2 cells, which was regulated by miR-939/Bnip3 axis. Our findings reveal that RP4 is highly expressed in the hypoxia-resulted H9c2 cells. Enhanced expression of RP4 may exacerbate hypoxia injury in cardiomyocytes through regulating miR-939/Bnip3 axis-mediated briskness of Wnt/ß-catenin signals. Our study will offer a fresh theoretical basis for the treatment of ischemic myocardial injury.

What can we do to optimize stem and progenitor cell therapy for heart failure?

Stem cells are a promising solution for the treatment of heart failure due to their ability to repopulate injured myocardium and restore cardiac function. However, many hindrances (such as low survival/viability and integration of transplanted cells, poor homing and cardiac differentiation efficiency, and inadequate cell retention and engraftment) compromise the full regenerative potential provided by stem cells. Therefore, it is necessary to optimize stem cell/progenitor therapy to improve clinical efficacy. By analogy, in order for crops to grow, good seeds are needed. They also need sufficient fertilizer, herbicides, and pesticides to be "optimized." In this review, we provide a comprehensive overview of "seeds" (comparison of stem cell types, different combinations of stem cells, age, size, and dose of stem cells) and "fertilizers" (optimizing stem/progenitor cells and genetic strategies, preconditioning with drugs, and physical changes) for heart failure.

Efficacy and Safety of L-Carnitine Treatment for Chronic Heart Failure: A Meta-Analysis of Randomized Controlled Trials.

Background. Whether additional benefit can be achieved with the use of L-carnitine (L-C) in patients with chronic heart failure (CHF) remains controversial. We therefore performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the effects of L-C treatment in CHF patients. Methods. Pubmed, Ovid Embase, Web of Science, and Cochrane Library databases, Chinese National Knowledge Infrastructure (CNKI) database, Wanfang database, Chinese Biomedical (CBM) database, and Chinese Science and Technology Periodicals database (VIP) until September 30, 2016, were identified. Studies that met the inclusion criteria were systematically evaluated by two reviewers independently. Results. 17 RCTs with 1625 CHF patients were included in this analysis. L-C treatment in CHF was associated with considerable improvement in overall efficacy (OR = 3.47, P < 0.01), left ventricular ejection fraction (LVEF) (WMD: 4.14%, P = 0.01), strike volume (SV) (WMD: 8.21 ml, P = 0.01), cardiac output (CO) (WMD: 0.88 L/min, P < 0.01), and E/A (WMD: 0.23, P < 0.01). Moreover, treatment with L-C also resulted in significant decrease in serum levels of BNP (WMD: -124.60 pg/ml, P = 0.01), serum levels of NT-proBNP (WMD: -510.36 pg/ml, P < 0.01), LVESD (WMD: -4.06 mm, P < 0.01), LVEDD (WMD: -4.79 mm, P < 0.01), and LVESV (WMD: -20.16 ml, 95% CI: -35.65 to -4.67, P < 0.01). However, there were no significant differences in all-cause mortality, 6-minute walk, and adverse events between L-C and control groups. Conclusions. L-C treatment is effective for CHF patients in improving clinical symptoms and cardiac functions, decreasing serum levels of BNP and NT-proBNP. And it has a good tolerance.