Pd-catalyzed CO-free double carbonylation for the synthesis of 1,4-ketoesters with Mo(CO)6 as the carbonyl source.

An unprecedented Pd-catalyzed CO-free double carbonylation using Mo(CO)6 as a safe carbonyl source for the efficient synthesis of 1,4-ketoesters in an atom- and step-economic manner has been developed. The current method features operational safety, a wide substrate range, good functional group compatibility and easy scale-up. The application of carbonylation using a safe carbonyl source for the synthesis of biologically and synthetically useful carbonyl-containing molecules is underway in our lab.

Roles of MDA-LDL/OX-LDL/LOX-1 and TNF-α/TLR4/NF-κB Signaling Pathways in Myocardial Damage by Implantations of Cardiac Pacemakers in Elderly Patients.

INTRODUCTION: Permanent pacemakers are an established treatment for sick sinus syndrome and high-grade atrioventricular block. Permanent cardiac pacemaker implantations may damage the myocardium. OBJECTIVE: This study evaluated markers of myocardial injury, oxidative stress and inflammation in elderly patients with permanent pacemaker implantations. METHODS: Various markers were measured at 1, 2, 3 and 4 months after permanent pacemaker implantations in elderly patients. RESULTS: The levels of high-sensitivity troponin T (hsTnT), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), malondialdehyde-modified low-density lipoprotein (MDA-LDL), oxidized low-density lipoprotein (OX-LDL), tumour necrosis factor-α (TNF-α), toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) were increased in 2-month group compared with control and 1- month groups (P<0.001), and were further increased at 4-month group compared with 2- and 3- month groups after pacemaker implantations (P<0.001). Patients with dual-chamber pacemakers had higher levels of hsTnT, LOX-1, MDA-LDL, OX-LDL, TNF-α, TLR4 and NF-κB than patients with single chamber pacemakers (P<0.001). Patients who underwent the pacemakers with the active fixation leads had raised levels of hsTnT, LOX-1, MDA-LDL, OX-LDL, TNF-α, TLR4 and NF-κB compared patients with pacemakers using the passive fixation leads (P<0.001). Myocardial blood flows in 3-month and 4-month groups were lower than 1-month and 2-month groups (P<0.001). CONCLUSION: Levels of hsTnT, LOX-1, MDA-LDL, OX-LDL, TNF-α, TLR4 and NF-κB were elevated in elderly patients with permanent pacemaker implantations and the activations of oxidative stress and pro-inflammatory signalling pathways may be associated with myocardial damages and ischemia after pacemaker implantations in elderly patients.

Palladium-Catalyzed Dual C-H Carbonylation of Diarylamines Leading to Diversified Acridones under CO-Free Conditions.

A Pd-catalyzed dual C-H carbonylation of commercially available diarylamines using Co2(CO)8 as a safe CO source has been developed. This methodology provides a facile approach for the synthesis of diversified acridones in moderate to good yields. The protocol features good functional group compatibility, operational safety, easy scale-up, and versatile transformations.

Manipulation of co-pelletization for Chlorela vulgaris harvest by treatment of Aspergillus niger spore.

The co-pelletization of microalgae with filamentous fungi was a promising approach for microalgae harvest. However, the real conditions of microalgae growth limited the arbitrary optimization of co-pellets formation with filamentous fungi. Therefore, it is urgent to develop an approach to manipulate the co-pelletization through treatment of A. niger spores. In this study, Aspergillus niger and Chlorella vulgaris were used as the model species of filamentous fungi and microalgae to investigate co-pellets formation using A. niger spores after by different pH solutions treatment, swelling, snailase treatment. The importance of spore treatments on C. vulgaris harvest in sequence was claimed based on response surface methodology analysis. The pH solutions treatment, swelling, snailase treatment of A. niger spore contributed 21.0%, 10.5%, 40.7% of harvest ratio of C. vulgaris respectively, which guided the application of spore treatment into co-pelletization. Treatment of spore was showed as an efficient approach to manipulate co-pelletization for microalgae harvest in diverse microalgae condition. This results promoted the application of co-pelletization technology in microalgae harvest of various conditions.

Cardiac Radiofrequency Ablation Exacerbates Myocardial Injury through Pro-Inflammatory Response and Pro-Oxidative Stress in Elderly Patients with Persistent Atrial Fibrillation.

BACKGROUND: There is a need to assess myocardial damage after radiofrequency ablation of the pulmonary veins (PV) for persistent atrial fibrillation (PAF) in elderly patients. OBJECTIVE: To evaluate oxidative stress, inflammatory response and myocardial damage in elderly patients with PAF after radiofrequency ablation of the PV. METHODS: High-sensitivity troponin T (hsTnT), malondialdehyde-modified low-density lipoprotein (MDA-LDL), acrolein (ACR), lipid hydroperoxide (LHP), toll-like receptor 4 (TLR4), soluble growth stimulation expressed gene 2 (sST2), angiotensin II (Ang II) and myocardial blood flow (MBF) were determined before ablation and at 1, 3 and 5 months after radiofrequency ablation. RESULTS: The levels of hsTnT, MDA-LDL, ACR, LHP, TLR4, sST2 and Ang II were increased 3 months after ablations compared with before ablation and 1 month after ablation, respectively (P<0.001); they were further increased at 5 months after ablation compared with the 1- and 3-month groups, respectively (P<0.001). MBF was decreased in the 3 months group after ablations compared with before ablation and 1-month after ablation, respectively (P<0.001), and was further decreased in 5-months after ablations compared with 1-month and 3-month groups, respectively (P<0.001). Patients with epicardial monopolar radiofrequency ablation had higher levels of hsTnT, MDA-LDL, ACR, LHP, TLR4, sST2, Ang II and lower MBF than patients with endocardial monopolar and bipolar radiofrequency ablations, respectively (P<0.001). CONCLUSION: Monopolar radiofrequency ablation method could result in more myocardial injury than bipolar radiofrequency ablation. Oxidative stress and inflammatory response may be involved in cardiac radiofrequency ablation-induced myocardial injury, resulting in myocardial ischemia in elderly patients with PAF.

Potential Biomarkers and Therapeutic Targets: Inflammation and Oxidative Stress in Left Carotid Artery Stenosis with Coronary Artery Disease.

INTRODUCTION: Patients with left carotid artery atherosclerotic stenosis have an increased ischemic stroke risk. Left carotid stenosis, the most common cause of the transient ischemic attack, is related to a higher risk of acute stroke. Left carotid artery stenosis is also associated with cerebral artery infarction. The significant coronary stenosis promotes ST-segment elevation myocardial infarctions. The severe coronary stenosis plays an important role in development and progression of myocardial infarction. However, the dynamic changes of circulating oxidative stress and inflammatory markers in the carotid stenosis combined with coronary artery stenosis are not clear, and it also remains unknown whether mark of oxidative stress and inflammation are potential therapeutic targets for carotid stenosis combined with coronary artery stenosis. AIM: This study aims to explore the effects of oxidative stress combined with an inflammatory response on left carotid artery stenosis with coronary artery disease in patients. METHODS: We, therefore, tested the hypothesis that levels of markers of oxidative stress and inflammation are associated with coexistent severe carotid and coronary artery stenosis in patients. We measured the circulating levels of malondialdehyde (MDA), oxidized low-density lipoprotein (OX-LDL), homocysteine (Hcy), F2- isoprostanes (F2-IsoPs), tumor necrosis factor-alpha (TNF-α), high-sensitivity C-reactive protein (hs-CRP), prostaglandin E2 (PG-E2) and interferon-gamma (IFN-γ) in patients with combined carotid and coronary artery severe stenosis. We also assessed the relationships among oxidative stress, inflammation, and severe stenosis of the carotid with a coronary artery in patients. RESULTS: Levels of MDA, OX-LDL, Hcy, F2-IsoPs, TNF-α, hs-CRP, PG-E2, and IFN-γ were remarkably increased (P < 0.001) in patients with combined carotid and coronary artery severe stenosis. High levels of oxidative stress and inflammation may be related to severe stenosis of the carotid with coronary arteries in patients. CONCLUSION: Our observations indicated that measurements of oxidative stress and inflammatory markers may be valuable for the assessment of the degree of carotid with coronary artery stenosis. The biomarkers of oxidative stress and inflammatory response may become therapeutic targets for carotid artery stenosis with coronary artery stenosis in patients.

An inducible Komagataella phaffii system for protein expression using sorbitol dehydrogenase promoter.

OBJECTIVES: The aim of the present work was to develop a methanol-independent Komagataella phaffii (K. phaffii) strain using a non-methanol promoter. RESULTS: In this study, the food grade enzyme xylanase from Aspergillus niger ATCC 1015 was used as the reporter protein, a recombinant K. phaffii containing a cascade gene circus was designed and constructed using sorbitol as inducer. Sorbitol induced PSDH leading to MIT1 expression firstly, and heterologous protein xylanase expression finally. This system showed 1.7 fold of xylanase activity at the condition of single copy number of extra MIT1, and 2.1 fold of xylanase activity at condition of multi-copy extra MIT1 gene. CONCLUSIONS: This sorbitol-induced expression system of K. phaffii avoided toxic and explosive methanol. It was a novel cascade gene expression and a food safety system.

Oxidative Stress and Inflammation Markers Associated with Multiple Peripheral Artery Occlusions in Elderly Patients.

Background: Pro-oxidative stress and pro-inflammatory responses can influence each other in the development of atherosclerosis. This study evaluated the relationship between oxidative stress, inflammation, and multiple peripheral artery occlusions in elderly patients (age mean 71.2 ± 8.1 years). Methods: A total of 723 participants were enrolled: 67 healthy subjects, 214 patients with common iliac artery occlusions, 224 patients with popliteal artery occlusions, and 218 patients with femoral artery occlusions. We measured oxidative stress biomarkers (malondialdehyde [MDA], F2-isoprostane [F2-isoP], total oxidant status [TOS], and ischemia-modified albumin [IMA]) and the expressions of molecules in mimecan (MIME)/nuclear factor kappa B (NF-κB)/P53/Toll-like receptor 4 (TLR4) signaling pathway in older patients with multiple peripheral artery occlusions. Results: The levels of MDA, F2-isoP, TOS, IMA, MIME, NF-κB, P53, and TLR4 were increased in the single-site peripheral artery occlusive group when compared with healthy controls (P < .001) and were further increased in the multiple-site peripheral artery occlusive group compared with the single-site peripheral artery occlusive group (P < .001). Conclusion: Oxidative stress may promote inflammatory signaling pathways and lead to multiple peripheral artery occlusions in elderly patients.

An ultrasensitive lateral flow immunoassay platform for foodborne biotoxins and pathogenic bacteria based on carbon-dots embedded mesoporous silicon nanoparticles fluorescent reporter probes.

Lateral flow immunoassays (LFIAs) are routine methods for rapid foodborne pollutants screening, with detection limits that are closely associated with the label probes used. The exploitation of high performance and robust probe is highly desirable, and remains a great challenge. Herein, we reported an emerging fluorescent nanobeads i.e. carbon-dots (CD) covalently incorporated mesoporous silicon nanoparticles (CD-MSNs) for LFIAs. CD-MSNs revealed brighter fluorescence, larger particle size and more modification sites in comparison with those of single CD. After bio-functionalisation, CD-MSNs probes were introduced to construct LFIA test strips, and designed for ultrasensitive detection of aflatoxin B1 (AFB1) and Staphylococcus aureus (S. aureus), two representative foodborne pollutants, based on the competitive and sandwich models, respectively. Very competitive quantitative detection limits i.e. 0.05 ng/mL and 102 cfu/mL were correspondingly obtained. Additionally, the test strips were successfully applied to rapidly and accurately screen AFB1 and S. aureus in food samples, highlighting their practicality.

The Potential Prognostic, Diagnostic and Therapeutic Targets for Recurrent Arrhythmias in Patients with Coronary Restenosis and Reocclusions After Coronary Stenting.

BACKGROUND: The interplay of oxidative stress, proinflammatory microparticles, and proinflammatory cytokines in recurrent arrhythmias is unknown in elderly patients with coronary restenosis and reocclusions after coronary stenting. OBJECTIVE: This research sought to investigate the potential diagnostic and therapeutic targets for recurrent arrhythmias in patients with coronary restenosis and reocclusions after coronary stenting. METHODS: We examined whether oxidative stress, proinflammatory microparticles, and proinflammatory cytokines could have effects that lead to recurrent arrhythmias in elderly patients with coronary restenosis and reocclusions. We measured the levels of malondialdehyde (MDA), CD31 + endothelial microparticle (CD31 EMP), CD62E + endothelial microparticle (CD62E + EMP), high-sensitivity C-reactive protein (hs-CRP), interleukin- 1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α), as well as oxidized low-density lipoprotein (OX-LDL), and assessed the effects of relationship between oxidative stress, proinflammatory microparticles, and proinflammatory cytokines on recurrent atrial and ventricular arrhythmias in elderly patients with coronary restenosis and reocclusions after coronary stenting. RESULTS: The levels of CD31 + EMP, CD62E + EMP, MDA, hs-CRP, IL-1ß, IL-6, IL-8, TNF-α and OX-LDL were found to be increased significantly in coronary restenosis + recurrent atrial arrhythmia group compared to without coronary restenosis and coronary restenosis + without recurrent atrial arrhythmia groups, respectively (P < 0.001). Patients in the coronary reocclusion + recurrent ventricular arrhythmia group also exhibited significantly increased levels of CD31 + EMP, CD62E + EMP, MDA, hs-CRP, IL-1ß, IL-6, IL-8, TNF-α and OXLDL compared to without coronary reocclusion and coronary reocclusion + without recurrent ventricular arrhythmia groups, respectively (P < 0.001). CONCLUSION: Proinflammatory microparticles, proinflammatory cytokines, and oxidative stress might act as potential targets for recurrent arrhythmias in patients with coronary restenosis and reocclusions after coronary stenting.

Enhancing xylanase expression by Komagataella phaffii by formate as carbon source and inducer.

Komagataella phaffii (syn. Pichia pastoris), a methylotrophic yeast, has many advantages as a protein expression system, but has the disadvantage of hazardous methanol as an inducer and carbon source. To enable substitution of formate for methanol, a formate assimilation pathway was constructed by the co-expression of acetyl-CoA synthase, acetaldehyde dehydrogenase, and transcription factor Mit1, resulting in a 103.5 ± 12.5% increase in xylanase production. Recombinant K. phaffii was able to use formate as a carbon source, indicating successful substitution of formate for methanol. Xylanase production, using the safe and sustainable formate as an inducer and carbon source, is a major advance in the field of industrial enzyme production. KEY POINTS: • Change to formate assimilation by recombinant K. phaffii instead of methanol • K. phaffii expressed xylanase by formate induction instead of methanol induction • Increased xylanase expression by transcription factor co-expression.

Imbalance of Pro- and Anti-inflammatory Cytokines Induced Different Types of Recurrent Atrial Arrhythmias after Drug Eluting Coronary Stent Implantation.

BACKGROUND: Atrial arrhythmias are associated with an increased risk of stroke and death in the elderly. The risk and predictive factors of recurrent atrial arrhythmias in elderly patients after coronary stenting are not well known. OBJECTIVE: This research sought to investigate the roles of pro- and anti-inflammatory cytokine imbalances in different types of recurrent atrial arrhythmias in elderly patients defined as individuals aged 65 years or older after sirolimus eluting stent (Cordis, Warren, New Jersey) implantation. METHODS: We measured interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), interleukin-17 (IL-17), interleukin-13 (IL-13) and interleukin- 37 (IL-37) in elderly patients with recurrent atrial arrhythmias and assessed the impact of pro- and antiinflammatory cytokine imbalances on recurrent atrial arrhythmias in elderly patients after coronary stenting. RESULTS: Levels of IL-1 ß, IL-6, IL-8, and TNF-α were remarkably increased (p<0.001), and IL-10, IL- 17, IL-13, and IL-37 were remarkably lowered (p<0.001) in elderly patients with recurrent atrial arrhythmias after coronary stent implantation. Imbalance of pro- and anti-inflammatory cytokines induced recurrent atrial arrhythmias after coronary stenting. Pro- and anti-inflammatory cytokine imbalances may be used to identify elderly patients who have an increased risk of developing recurrent atrial arrhythmias after coronary stenting. CONCLUSION: The imbalance of pro- and anti-inflammatory cytokines was associated with recurrent atrial arrhythmias in elderly patients after coronary stenting. Pro- and anti-inflammatory cytokines may be clinically useful biomarkers for predicting recurrent atrial arrhythmias in elderly patients after coronary stent implantation.

An Emerging Fluorescent Carbon Nanobead Label Probe for Lateral Flow Assays and Highly Sensitive Screening of Foodborne Toxins and Pathogenic Bacteria.

By virtue of the fascinating merits of low cost, rapid screening, and on-site detection, fluorescence lateral flow assays (FLFAs) have attracted considerable attention. Their detection limits are closely associated with the label probes used. The development of high-performance and robust phosphors remains a great challenge. Herein, we presented a new label probe, i.e., fluorescent carbon nanobeads (FCNBs), for FLFAs. Monodispersive, water-soluble, and highly emissive FCNBs were facilely prepared via a hydrothermal carbonization manner. Their abundant amino groups were beneficial for versatile surface functionalization. After being modified by biomolecules, the fabricated FCNB reporter probes were adopted for the construction of lateral flow test strips toward representative foodborne toxins, i.e., aflatoxin B1 (AFB1), and pathogenic bacteria, i.e., Staphylococcus aureus (S. aureus), respectively. The detection limits (0.01 ng/mL for AFB1 and 102 cfu/mL for S. aureus) were about 1 or 2 orders of magnitude lower than most reported methods. Furthermore, the proposed test strips were successfully applied for the quantitative, accurate, and rapid screening of AFB1 and S. aureus in food samples. This work provided a promising label probe for FLFAs and would open the opportunity to exploit a sensing platform by modifying different ligands onto the FCNBs.

Enhancing xylanase expression of Komagataella phaffii induced by formate through Mit1 co-expression.

Komagataella phaffii (K. phaffii) is a famous microbial cell of heterologous protein and value-added chemicals production because of its strict and strong promoter (alcohol oxidase 1 promoter, PAOX1). Formate is an attractive substitute of traditional inducer methanol because methanol is toxic and explosive. To obtain high level of Aspergillus niger ATCC1015 xylanase as a model of heterologous protein by K. phaffii at formate induction, insertion of three-copy cis-acting element W3A into PAOX1 additionally, and co-expression of transcription factor Mit1 under another PAOX1 were carried out separately and simultaneously. The yield of xylanase increased by 41% at formate induction when Mit1 was co-expressed. Furtherly, the yield of xylanase increased by 42% using sorbitol as supplemental carbon source with the result of 408.3 × 103 U‧L-1 xylanase. Therefore, a non-methanol needed and inducible heterologous protein expression system of Komagataella phaffii was developed successfully.

Construction of Mussel-Inspired Dopamine-Zn2+ Coating on Titanium Oxide Nanotubes to Improve Hemocompatibility, Cytocompatibility, and Antibacterial Activity.

Zinc ions (Zn2+) are a highly potent bioactive factor with a broad spectrum of physiological functions. In situ continuous and controllable release of Zn2+ from the biomaterials can effectively improve the biocompatibility and antibacterial activity. In the present study, inspired by the adhesion and protein cross-linking in the mussel byssus, with the aim of improving the biocompatibility of titanium, a cost-effective one-step metal-catecholamine assembly strategy was developed to prepare a biomimetic dopamine-Zn2+ (DA-Zn2+) coating by immersing the titanium oxide nanotube (TNT) arrays on the titanium surface prepared by anodic oxidation into an aqueous solution containing dopamine (DA) and zinc ions (Zn2+). The DA-Zn2+ coatings with the different zinc contents exhibited excellent hydrophilicity. Due to the continuous release of zinc ions from the DA-Zn2+ coating, the coated titanium oxide nanotubes displayed excellent hemocompatibility characterized by platelet adhesion and activation and hemolysis assay. Moreover, the DA-Zn2+-coated samples exhibited an excellent ability to enhance endothelial cell (EC) adhesion and proliferation. In addition, the DA-Zn2+ coating can also enhance the antibacterial activity of the nanotubes. Therefore, long-term in situ Zn2+-releasing coating of the present study could serve as the bio-surfaces for long-term prevention of thrombosis, improvement of cytocompatibility to endothelial cells, and antibacterial activity. Due to the easy operation and strong binding ability of the polydopamine on various complicated shapes, the method of the present study can be further applied to other blood contact biomaterials or implantable medical devices to improve the biocompatibility.

Synthesis of Star 6-Arm Polyethylene Glycol-Heparin Copolymer to Construct Anticorrosive and Biocompatible Coating on Magnesium Alloy Surface.

Magnesium alloy has become a research hotspot of the degradable vascular stent materials due to its biodegradability and excellent mechanical properties. However, its rapid degradation rate after implantation and the limited biocompatibility restrict its application in clinic. Constructing a multifunctional bioactive polymer coating on the magnesium alloys represents one of the popular and effective approaches to simultaneously improve the corrosion resistance and biocompatibility. In the present study, the copolymer of 6-arm polyethylene glycol and heparin (PEG-Hep) was successfully synthesized and then immobilized on the surface of chitosan (Chi)-modified magnesium alloy surface through electrostatic interaction to improve the corrosion resistance and biocompatibility. The results of attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy showed that a dense and compact coating was created on the magnesium alloy surface. The coating displayed excellent hydrophilicity. At the same time, the as-prepared coating can significantly not only improve the corrosion potential, reduce the corrosion current and the pH changes of the immersion solution, but also keep a relatively intact surface morphology after immersing in simulated body fluid solution for 14 days, demonstrating that the coating can significantly improve the corrosion resistance of the magnesium alloy. Moreover, the magnesium alloy with PEG-Hep coating exhibited excellent hemocompatibility according to the results of the hemolysis rate and platelet adhesion and activation. In addition, the modified magnesium alloy had a good ability to promote the endothelial cell adhesion and proliferation. Therefore, the PEG-Hep multifunctional coating can be applied in the surface modification of the biodegradable magnesium alloy stent to simultaneously improve the corrosion resistance and biocompatibility.

Development of wheat bran hydrolysate as Komagataella phaffii medium for heterologous protein production.

Developing a Komagataella phaffii (K. phaffii, named as Pichia pastoris formerly) medium using wheat bran hydrolysate (WBH) is a potential approach for wheat bran utilization and heterologous protein by K. phaffii because K. phaffii is used as protein producer by researchers and engineers widely. In this research, the detoxification process of WBH was optimized to obtain the final procedure as pH adjusting to 10 by calcium hydroxide addition, then, 2.0 g/L active carbon absorption followed by 1 h shaking and 3,600 × g centrifugation for 10 min, finally, 3.75 mmol/L sodium thiosulfate addition for 10 min shaking followed by 3,600 × g centrifugation for 10 min. Recombinant K. phaffii-xynB harboring xylanase B gene from Aspergillus niger ATCC 1015 under alcohol oxidase 1 promoter (PAOX1) was cultivated in detoxified WBH expressing 1059.8 U/mL xylanase B which was 90.9% of that in complex medium from Pichia protocols. These researches built a solid base for detoxified WBH as a low-cost medium of K. phaffii to express heterologous protein, also provided a bright outlet for wheat bran utilization.

miR­125a­5p and miR­7 inhibits the proliferation, migration and invasion of vascular smooth muscle cell by targeting EGFR.

The ectopic proliferation, migration and invasion of vascular smooth muscle cells (VSMCs) contributes to the progression of various human vascular diseases. Accumulating evidence has demonstrated that microRNAs (miRs) exert vital functions in the proliferation and invasion of VSMCs. The current study aimed to elucidate the functions of miR­125a­5p and miR­7 in VSMCs and investigate the associated molecular mechanisms. The results of EdU and reverse transcription­quantitative PCR assays revealed that platelet­derived growth factor (PDGF)­BB enhanced the proliferation of VSMCs and significantly reduced the expression of miR­125a­5p and miR­7. miR­125a­5p or miR­7 overexpression significantly ameliorated PDGF­BB­induced proliferation, migration and invasion of VSMCs. Furthermore, the results demonstrated that epidermal growth factor receptor (EGFR) may be a target mRNA of miR­125a­5p and miR­7 in VSMCs. The results of western blot analysis indicated that co­transfection of miR­125a­5p mimics or miR­7 mimics distinctly decreased the protein expression of EGFR in EGFR­overexpressed VSMCs. Moreover, rescue experiments indicated that EGFR overexpression alleviated the suppressive impact of the miR­125a­5p and miR­7 s on the growth, migration and invasion of VSMCs. In conclusion, the current study identified that miR­125a­5p and miR­7 repressed the growth, migration and invasion of PDGF­BB­stimulated VSMCs by, at least partially, targeting EGFR. The current study verified that miR­125a­5p and miR­7 may be used as feasible therapeutic targets for cardiovascular diseases.

Serum miR-222 is independently associated with atrial fibrillation in patients with degenerative valvular heart disease.

BACKGROUND: Inflammation is involved in the progression of degenerative valvular heart disease (DVHD). microRNA-222 (miR-222) contributes to inflammation-mediated vascular remodeling, but its involvement in DVHD in relation to atrial fibrillation (AF) is unknown. This study aimed to investigate the changes in miR-222, interleukin (IL)-6, high-sensitivity C-reactive protein (hs-CRP), and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with DVHD complicated with AF. METHODS: This was a case control study of patients with DVHD who were hospitalized at the Geriatrics Department of the Affiliated Huai'an Hospital of Xuzhou Medical University between 01/2017 and 08/2018. The participants were grouped according to the presence of AF, and serum miR-222, IL-6, hs-CRP, and NT-proBNP levels were compared. RESULTS: There were fifty-two participants (28 males) in the DVHD with AF group, aged 60-80 years (73.0 ± 5.9 years). Sixty participants (31 males) were included in the DVHD without AF group, aged 60-80 years (71.9 ± 6.92 years). There were no significant differences in age, sex, body mass index, fasting blood glucose, triglycerides, cholesterol, and blood pressure between the two groups. The serum levels of miRNA-222, IL-6, hs-CRP, and NT-proBNP in DVHD patients were significantly higher in those with AF compared with the non-AF group (all P < 0.05). Correlation analyses revealed that IL-6, hs-CRP, and NT-proBNP levels were positively correlated with miR-222 levels in all patients (IL-6: r = 0.507, P < 0.01; hs-CRP: r = 0.390, P < 0.01; NT-proBNP: r = 0.509, P < 0.01). CONCLUSIONS: Serum miR-222 was independently associated with AF in patients with DVHD.

Pro-inflammatory Mediators and Oxidative Stress: Therapeutic Markers for Recurrent Angina Pectoris after Coronary Artery Stenting in Elderly Patients.

BACKGROUND: Pro-inflammatory mediators and oxidative stress are related to the severity of angina pectoris in patients with coronary heart disease. OBJECTIVE: We evaluated the effects of pro-inflammatory mediators and oxidative stress on recurrent angina pectoris after coronary artery stenting in elderly patients. METHODS: We determined the expression levels of malondialdehyde (MDA), acrolein (ACR), tumour necrosis factor-α (TNF-α), toll-like receptor 4 (TLR4), superoxide dismutase 3 (SOD3), paraoxonase-1 (PON-1), stromal cell-derived factor-1α (SDF-1α) and endothelial progenitor cells (EPCs) in elderly patients with recurrent angina pectoris after coronary artery stenting. RESULTS: Levels of MDA, ACR, TNF-α and TLR4 were significantly increased (p<0.001), and levels of SOD3, PON-1, SDF-1α and EPCs were significantly decreased (p<0.001) in the elderly patients with recurrent angina pectoris after coronary artery stenting. MDA, ACR, TNF-α and TLR4 as markers of oxidative stress and pro-inflammatory mediators may have suppressed SOD3, PON-1, SDF-1α and EPCs as markers of anti-oxidative stress/anti-inflammatory responses. Oxidative stress and proinflammatory mediators were important factors involved in recurrent angina pectoris of elderly patients after coronary artery stenting. CONCLUSION: Oxidative stress and pro-inflammatory mediators could be considered as potential noninvasive prognostic, predictive, and therapeutic biomarkers for stable recurrent angina and recurrent unstable angina in elderly patients after coronary artery stenting.