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This study aims to determine the efficacy of Zinc finger protein ZBTB20 in treatment of post‐infarction cardiac remodelling. For this purpose, left anterior descending (LAD) ligation was operated on mice to induce myocardial infarction (MI) with sham control group as contrast and adeno‐associated virus (AAV9) system was used to deliver ZBTB20 to mouse heart by myocardial injection with vehicle‐injected control group as contrast two weeks before MI surgery. Then four weeks after MI, vehicle‐treated mice with left ventricular (LV) remodelling underwent deterioration of cardiac function, with symptoms of hypertrophy, interstitial fibrosis, inflammation and apoptosis. The vehicle‐injected mice also showed increase of infarct size and decrease of survival rate. Meanwhile, the ZBTB20‐overexpressed mice displayed improvement after MI. Moreover, the anti‐apoptosis effect of ZBTB20 was further confirmed in H9c2 cells subjected to hypoxia in vitro. Further study suggested that ZBTB20 exerts cardioprotection by inhibiting tumour necrosis factor α/apoptosis signal‐regulating kinase 1 (ASK1)/c‐Jun N‐terminal kinase 1/2 (JNK1/2) signalling, which was confirmed by shRNA‐JNK adenoviruses transfection or a JNK activator in vitro as well as ASK1 overexpression in vivo. In summary, our data suggest that ZBTB20 could alleviate cardiac remodelling post‐MI. Thus, administration of ZBTB20 can be considered as a promising treatment strategy for heart failure post‐MI. Significance Statement: ZBTB20 could alleviate cardiac remodelling post‐MI via inhibition of ASK1/JNK1/2 signalling.

Implant failures still happen because of bacterial infections and inferior osteogenic properties. Graphene oxide (GO) could induce osteogenic differentiation as well as exhibit superior antibacterial activity which may provide an answer for this issue. In this work, GO films loaded with minocycline hydrochloride (MH) were fabricated on titanium implant surfaces, and the antibacterial activity and osteogenic properties were studied in the presence of S. aureus and rat bone mesenchymal stem cells (rBMSCs) in in vitro and in vivo environments, respectively. The results indicated that the MH loaded GO films on titanium surfaces (MH&GO@Ti) exhibited enhanced osteogenic activity in vitro with improved alkaline phosphatase (ALP) activity and enhanced osteogenic related gene expressions including ALP, collagen-I, osteocalcin, and osteopontin. The in vitro results of the co-culture of rBMSCs and S. aureus indicated that the rBMSCs grew well on the MH&GO@Ti sample with a higher coverage of cells and the bacteria were almost unobservable on the surface. In the in vivo experiments, the MH&GO@Ti exhibited excellent antibacterial and osteogenic activities in the presence of bacteria. No inflammatory cells for example neutrophils were found and superior bone–implant integration was obtained. This study offers a new proposal for the clinical application of drug-loaded graphene coating.

The aim of this study was to identify the influencing factors of peri-implantitis for implant prosthesis and to establish a predictive model of occurrence in managing patients with chronic periodontitis. 430 patients (a total of 686 implants) with 5 years follow-up were included in the study. The demographic and clinical characteristics independent variables were including patient related factors (age, gender, duration of symptoms, smoking, diabetes, severity of periodontitis, bone mineral density, oral hygiene) and implants related factors (position, implant diameter, implant length, additional operations, probing depth, gingival index, plaque index, load-bearing time). Univariate analysis identified the influencing factors, the statistically significant factors were further analyzed by multivariate logistic regression, and the predictive model was established. After 5 years of follow-up, peri-implantitis occurred in 95 of 686 implants (13.8%). Multiple linear regression indicated that smoking (p = 0.011), diabetes (p 0.05) Logistic regression drew the equation: occurrence of peri-implantitis = [1 + e (16.172+5.395*smoking+4.807*diabetes +8.109*severe periodontitis+5.569*lager implant diameter+11.138*poor oral hygiene)]−1. The sensitivity of predictive factors was 91.77%, 88.43%, 82.64%, 85.21% and 92.02%, respectively. The specificity 45.65%, 49.17%, 66.23%, 42.39% and 65.41%, respectively. The AUC was 0.721, 0.620, 0.453, 0.651 and 0.826, respectively. Hosmer-Lemeshow test showed a good fitting of the predictive model with an overall accuracy of 87.2%. Smoking, diabetes, severe periodontitis, lager implant diameter and poor oral hygiene are important risk factors of peri-implantitis. We also established a novel and accurate predictive model for the occurrence of peri-implantitis in managing patients with chronic periodontitis. The use of these parameters, in the form of a predictive model, has the potential to improve decision-making in the application of the treatment plan.

Excellent antibacterial property of graphene oxide makes it an important antibacterial material. However, in some cases, a synergistic combination of materials with different antibacterial mechanisms is desired. In this work, we developed a simple two-step protocol to prepare ornidazole (ONZ), a nitroimidazole antiprotozoal drug, loaded graphene-based paper for combined antibacterial materials. Graphene oxide (GO) and reduced graphene oxide (rGO) were used as carriers in antibacterial materials. After mixed with ONZ directly in aqueous media and filtrated under vacuum, the freestanding GO/ONZ and rGO/ONZ were peeled off from the filtrate membrane. The ONZ loading contents in the paper was determined by UV/vis spectroscopy and the surface properties were investigated by measuring their contact angle, which will have an important impact on the antibacterial effects of the papers. Keywords: Ornidazole, Graphene oxide, Antibacterial material

Titanium and its alloys have been widely used in orthopedic and dental implants because of their excellent properties. However, implant failures still occur due to implant-associated bacterial infections. Therefore, proper surface modification of titanium and its alloys is necessary. In this work, commercial pure titanium plates were modified with graphene oxide (GO) which was used to load minocycline hydrochloride. Gram-positive Staphylococcus aureus (S. aureus) and Streptococcus mutans (S. mutans) and Gram-negative Escherichia coli (E. coli) were used to investigate the antibacterial activity of the samples. Human gingival fibroblast (HGF) cells were applied to assess the cytocompatibility of the various samples. To investigate cell adhesion and cell surface coverage in the presence of bacteria, the coculture of HGF cells and S. aureus was performed. The results indicated that the GO-modified titanium surface could inhibit the growth of the bacteria which had direct contact with GO, while it could not affect the bacteria without direct contact of GO. Minocycline hydrochloride on the GO-modified titanium surface (M@GO-Ti) showed a slow release behavior and exhibited excellent antibacterial activity with the synergistic effect of contact-killing and release-killing by GO and minocycline hydrochloride, respectively. In the coculture process with the presence of S. aureus, HGF cells on M@GO-Ti demonstrated the best cell viability and cell surface coverage among all the samples.

Background Dental implant failures still occur because of peri-implant diseases such as peri-implantitis. The objective of this study was to treat peri-implantitis in beagle dogs by fabricating minocycline hydrochloride (MH)-loaded graphene oxide (GO) films on implant abutment surfaces. Methods Beagle dogs with silk ligature were used to establish the peri-implantitis model. Modified sulcus bleeding index, peri-implant probing pocket depth, radiographic evaluation, micro-CT tomography analysis, and histological evaluation were determined to evaluate the therapeutic effect of MH-loaded GO films on abutment surfaces for peri-implantitis. Results Radiographic and micro-CT analysis showed that lots of marginal bone loss could be found on Ti and MH/Ti groups, especially for Ti group. Little bone less could be seen on GO/Ti group while bone less on MH/GO/Ti group was negligible. Results of the histological analysis presented that lots of neutrophils could be found on Ti and MH/Ti groups. However, almost none of the neutrophils could be observed on GO/Ti and MH/GO/Ti while lots of osteocytes could be found. Conclusion MH-loaded GO films on implant abutment surfaces could prevent the further development of peri-implantitis and exhibit good therapeutic effect for peri-implantitis in beagle dogs.

Background Apical periodontitis (AP) is essentially an inflammatory disease of microbial etiology primarily caused by infection of the pulp and root canal system. Variation of the bacterial communities caused by AP, as well as their changes responding to dental therapy, are of utmost importance to understand the pathogensis of the apical periodontitis and establishing effective antimicrobial therapeutic strategies. This study aims to uncover the composition and diversity of microbiota associated to the root apex to identify the relevant bacteria highly involved in AP, with the consideration of root apex samples from the infected teeth (with/without root canal treatment), healthy teeth as well as the healthy oral. Methods Four groups of specimens are considered, the apical part of root from diseased teeth with and without root canal treatment, and wisdom teeth extracted to avoid being impacted (tooth healthy control), as well as an additional healthy oral control from biofilm of the buccal mucosa. DNA was extracted from these specimens and the microbiome was examined through focusing on the V3-V4 hypervariable region of the 16S rRNA gene using sequencing on Illumina MiSeq platform. Composition and diversity of the bacterial community were tested for individual samples, and between-group comparisons were done through differential analysis to identify the significant changes. Results We observed reduced community richness and diversity in microbiota samples from diseased teeth compared to healthy controls. Through differential analysis between AP teeth and healthy teeth, we identified 49 OTUs significantly down-regulated as well as 40 up-regulated OTUs for AP. Conclusion This study provides a global view of the microbial community of the AP associated cohorts, and revealed that AP involved not only bacteria accumulated with a high abundance, but also those significantly reduced ones due to microbial infection. Electronic supplementary material The online version of this article (10.1186/s12864-019-5474-y) contains supplementary material, which is available to authorized users.

The aim of this study was to investigate the effect of incorporation of the nano silica modified with (3-aminopropyl)triethoxysilane (APTES@SiO2) on the degree of conversion, bond strength and biocompatibility of an experimental dental adhesive. An amphiphilic bonding system was used as the experimental dentin bonding sys- tem. The APTES@SiO2 with diameter of 70 nm was prepared and added into the experimental dentin bonding sys- tem as nanofiller, and the effect of the modification on the stability of the nano APTES@SiO2 dispersed in the ex- perimental adhesive was studied. In addition, the morphology, degree of conversion, bond strength to dental re- storative resin and biocompatibility of the experimental adhesives containing nanofiller were tested. After modifica- tion, the dispersion stability of the nano particles in the adhesive was improved. With increasing the content of the nano APTES@SiO2, the rate of light conversion increased significantly. However, the ultimate degree of conver- sion, bond strength to resin and bulk compressive strength was not significantly affected. Compared with the adhe- sive without nanofiller, the adhesive with 2 wt% APTES@SiO2 showed better bond strength to dentin and lower polymerization shrinkage. In addition, the experimental adhesive showed slight cytotoxicity with the incorporation of APTES@SiO2, but it was attenuated at low concentration.

Background: The objective of this meta-analysis was to summarize and identify the available evidence from studies to estimate the clinical value of traditional Chinese medicine (TCM) in the treatment of recurrent aphthous stomatitis (RAS) and provides clinicians with evidence on which to base their clinical decision making. Methods: This review will include all studies comparing clinical efficacy of TCM in the treatment of RAS. The search strategy will be performed in 9 databases. We will not establish any limitations to language and publication status, published from inception to the August 2020. Two reviewers will screen, select studies, extract data, and assess quality independently. Outcome is clinical efficacy, pain relief, duration of wound healing, effect on wound healing, rate of recurrence, adverse events, and safety. The methodological quality including the risk of bias of the included studies will be evaluated. We will carry out statistical analysis using RevMan 5.3 software. Results: This study will summarize current evidence to assess the efficacy and safety of TCM in the treatment of RAS. Conclusion: The findings of this study will provide helpful evidence for the clinician, and will promote further studies, as well as studying the value of TCM. Registration number: INPLASY202080126 (DOI number: 10.37766/inplasy2020.8.0126).

NLRP3, a member of the nucleotide-binding oligomerization domain (NOD)-like receptor family, is involved in cardiac inflammation. However, the functional role of NLRP3 in cardiac remodeling is not clear. To investigate the roles of NLRP3 in pressure overload-induced cardiac remodeling, NLRP3 knockout and wild-type mice were subjected to aortic banding to induce cardiac remodeling. The data showed that NLRP3 expression was downregulated in the remodeling process. NLRP3 deficiency accelerated cardiac hypertrophy, fibrosis, and inflammation responses with deteriorating cardiac dysfunction in the pressure overload-induced cardiac remodeling mouse model. Neonatal rat cardiomyocytes were isolated and stimulated with phenylephrine (PE). We identified NLRP3 as a negative regulator of cardiomyocyte remodeling in PE-stimulated cardiomyocyte remodeling using adenovirus-NLRP3 and NLRP3 siRNA. Mechanistically, we found that the expression of Toll-like receptor (TLR) 4 was upregulated in NLRP3-deficient mouse hearts and PE-stimulated cardiomyocytes. NLRP3 knockout mice subjected to a TLR4 inhibitor revealed a relieved cardiac remodeling response with improved cardiac dysfunction. Our data suggested that NLRP3 could be a therapeutic target for cardiac remodeling and heart failure. KEY MESSAGES: NLRP3 expression was downregulated in the remodeling process. NLRP3 deficiency accelerated pressure overload-induced cardiac remodeling. NLRP3 acted as a negative regulator of cardiomyocyte remodeling via downregulating TLR4.

Nuclear localization leucine-rich-repeat protein 1 (NLRP1) is a member of Nod-like receptors (NLRs) family. Recent studies have reported that NLRP1 is involved in various diseases, especially in cardiovascular diseases. However, the effect of NLRP1 on cardiac fibrosis remains unclear. In this study, NLRP1 overexpression and NLRP1 silencing constructs were transfected into neonatal rat cardiac fibroblasts induced by TGF-β1 for 48 h to investigate the effect of NLRP1 in cardiac fibrosis and its molecular mechanisms. Cardiac fibroblasts were transfected with NLRP1 and then cultured in the presence and absence of TGF-β1and Smad3 inhibitor (SIS3). Our data indicated that NLRP1 not only promoted fibroblast activation and myofibroblast differentiation, but also upregulated the mRNA and protein levels of α-SMA in the TGF-β1-treated neonatal rat cardiac fibroblasts. Overexpressing NLRP1 in TGF-β1-induced cardiac fibroblasts upregulated the mRNA and protein levels of Collagen I, Collagen III, and connective tissue growth factor. Moreover, NLRP1 upregulated the protein levels of Smad2, Smad3, and Smad4 in nuclei of fibroblasts, and attenuated levels of phosphorylated Smad2 and Smad3 in the cytoplasm of fibroblasts induced by TGF-β1. In addition, the increase in fibrotic genes and Smad proteins was significantly reduced in the presence of SIS3. Our findings illustrated that NLRP1 promoted myofibroblast differentiation and excessive ECM production in TGF-β1-induced neonatal cardiac fibroblasts through directly targeting TGF-β1/Smad signaling pathways.

Orientin is a flavonoid extracted from Chinese traditional herb, Polygonum orientale L. Previous study has reported that orientin protected myocardial from ischemia reperfusion injury. However, whether orientin could protect against cardiac remodeling after myocardial injury remains unclear. The aim of our study is to investigate the effects of orientin in the progression of cardiac remodeling after myocardial infarction (MI). Mice cardiac remodeling model was established by left coronary artery ligation surgery. Experimental groups were as follows: vehicle-sham, orientin-sham, vehicle-MI, and orientin-MI. Animals were treated with vehicle or orientin (40 mg/kg) for 25 days starting 3 days after surgery. After 4 weeks of MI, mice with orientin treatment had decreased mortality and improved cardiac function. Significantly, at 4 weeks post-MI, orientin treatment decreased fibrosis, inflammatory response, and cardiomyocyte apoptosis. Furthermore, orientin treatment attenuated the hypoxia-induced neonatal rat cardiomyocyte apoptosis and increased cell viability. Additionally, orientin supplementation mitigated oxidative stress in remodeling heart tissue and cardiomyocytes exposed to hypoxia as measured by 2′,7′-dichlorodihydrofluorescein diacetate fluorescent probe. Mechanistically, orientin promotes cardioprotection by activating the eNOS/NO signaling cascades, which was confirmed by eNOS inhibitor (L-NAME) in vitro and in vivo. Inhibition of oxidative stress by orientin via eNOS/NO signaling cascades in the heart may represent a potential therapy for cardiac remodeling.

Background/Aims: Nuclear localization leucine-rich-repeat protein 1 (NLRP1) is a cytoplasmic protein, involved in autoimmune diseases, mammalian reproduction, neuronal cell death, and stroke. However, the role of NLRP1 in cardiac hypertrophy remains unclear. We used in vivo and in vitro models to investigate the effects of NLRP1 on cardiac hypertrophy. Methods: We used NLRP1-deficient mice and cultured neonatal rat cardiomyocytes with gain and loss of NLRP1 function. Cardiac hypertrophy was estimated by echocardiographic and hemodynamic measurements, and by pathological and molecular analysis. Results: Eight weeks after aortic banding (AB), NLRP1 deficiency significantly inhibited aortic banding–induced cardiac hypertrophy, inflammation, and fibrosis. Activation of MAPK, NF-κB, and TGF-β/Smad pathways was reduced in NLRP1-knockout (KO) mice compared with that in wild-type (WT) mice. Consistent with these results, in vitro studies, performed using cultured neonatal mouse cardiomyocytes, confirmed that NLRP1 deficiency protects against cardiomyocyte hypertrophy induced by isoproterenol (PE); this protective activity was associated with the arrest of MAPK and NF-κB signaling. Conclusions: Our data illustrates that NLRP1 plays a crucial role in the development of cardiac hypertrophy via positive regulation of the MAPK, NF-κB, and TGF-β/Smad signaling pathways.

Summary Background New therapeutic targets are required for ischaemic heart disease; our study was designed to assess the theoretical foundation and experimental basis underlying the use of a new anticytokine agent, interleukin-1 receptor antagonist (IL-1ra), in this setting. Aim To investigate the cardioprotective properties of IL-1ra in terms of inhibition of apoptosis and improvement in systolic and diastolic functions of ischaemia/reperfusion (I/R)-injured cardiomyocytes, via a reduction in the inositol 1,4,5-trisphosphate (IP3) receptor-mediated Ca2+ overload induced by myocardial I/R injury. Methods For in vivo animal experiments, 30 adult male Sprague Dawley rats were anaesthetized and randomized into sham, I/R, and IL-1ra + I/R groups (n = 10 in each). All rats except the sham group were subjected to 30 minutes of myocardial ischaemia, followed by 2 hours of reperfusion. At a cellular level, healthy male Sprague Dawley rats under pentobarbital sodium anaesthesia underwent heart removal and isolation of individual ventricular cardiomyocytes using enzymatic hydrolysis, which were randomized into five groups: dimethyl sulphoxide; I/R; IL-1ra + I/R; 2-aminoethoxydiphenyl borate (2-APB) + I/R; and 2-APB + IL-1ra + I/R. Results In the IL-1ra + I/R group, exacerbation of myocardial infarct size and I/R-induced injury was inhibited. At the cellular level, in the I/R group, peak shortening (% cell length) and maximal velocities of shortening and relengthening were significantly decreased and intracellular Ca2+ transient amplitude (measured as fura-fluorescence intensity change) was diminished by electric stimulation, with the decay time constant of Ca2+ transients increased versus the dimethyl sulphoxide group. Compared with the I/R group, statistically ameliorated variables were achieved in the IL-1ra + I/R, 2-APB + I/R and 2-APB + IL-1ra + I/R groups, with the 2-APB + IL-1ra + I/R group presenting more significant improvement, while there was no statistical difference between the IL-1ra + I/R and 2-APB + I/R groups. Conclusions The downregulation of IP3 receptors by IL-1ra attenuates Ca2+ overload and the systolic and diastolic dysfunctions of hypoxia/reoxygenation-injured cardiomyocytes, which contributes to inhibition of apoptosis in I/R-injured cardiomyocytes and reduction of myocardial infarct size in vivo.

Contrast-induced nephropathy (CIN) is at present the third leading cause of hospital-acquired acute kidney injury (AKI). Traditionally, it is diagnosed by measuring an increase of the serum creatinine (SCr) concentration. However, SCr is an insensitive marker for detecting CIN. This study was designed to investigate whether human urinary interleukin-18 (IL-18) is early predictive marker for CIN following coronary interventional procedures. The general clinical data of 180 patients who underwent coronary interventional procedures at the Department of Cardiology, Affiliated Hospital of Xuzhou Medical College from March 1, 2012 to September 31, 2012 were collected. A nonionic, low osmolality contrast agent was used in the laboratory at this time. SCr values and estimated glomerular filtration rate (eGFR) were measured prior to and within 24 and 48 h after the administration of contrast agents. Urine samples were collected prior to and 2, 6, 12, 24 and 48 h after the coronary interventional procedure, and urinary IL-18 levels were measured using an ELISA kit. CIN was defined as an increase of ≥0.5 mg/dl or ≥25% in SCr concentration over baseline 24–48 h after the procedure. CIN occurred in 16 of 180 (8.9%) patients. The levels of urinary IL-18 measured 2 h after the procedure were increased in the CIN group, but the increase was not significant (P>0.05). There were significant differences (P

The association between the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and the severity of coronary artery disease (CAD) diagnosed by coronary angiography and other approaches has been investigated. The clinical application of NT-proBNP is restricted by the drawbacks of these techniques now available in screening out patients who need intensive or conservative treatment. Fractional flow reserve (FFR) is superior to coronary angiography and other functional indicators. Accordingly, we designed to investigate the association between NT-proBNP and myocardial ischemia from the perspective of anatomy and physiology in patients with unstable angina and preserved left ventricular function. Plasma samples were collected from 110 patients and NT-proBNP levels were measured by radioimmunoassay. The severity of coronary artery stenosis in patients was measured by coronary angiography and FFR. Stenosis ≥50% in the left main artery or stenosis of 70%, and fractional flow reserve (FFR) ≤0.80 in one or more coronary branches with diameter ≥2mm were defined as "positive", which require revascularization. NT-proBNP levels increased progressively between patients with negative and positive angiographic results (p

Purpose. To determine the coronary hemodynamic characteristics of acute hibernating myocardium (AHM), evaluate the changes in coronary hemodynamics during dobutamine infusion, and investigate the mechanisms by which dobutamine stress echocardiography (DSE) detects AHM. Methods. The porcine model of acute hibernating myocardium was created in 10 animals, all of which underwent DSE with doses of 0–40 μg/kg/min. Myocardial segments abnormality was used as a DSE criterion for evaluating AHM. An intracoronary Doppler guidewire was used to measure the coronary hemodynamics; electrocardiography and systemic hemodynamics were recorded simultaneously. The ischemic regions of myocardium were reperfused, and all variables were recorded. Finally, the animals were euthanized and pathologic changes in the heart tissue were documented. Results. There was no myocardium necrosis. There were 55 myocardial segments with abnormal DSE responses after stenosis, among which 41 segments were judged as AHM because of a biphasic response. Average peak velocity (APV) and coronary flow velocity reserve were improved during DSE. Coronary and systemic hemodynamics were increased during dobutamine infusion. There were significant differences for APV at all evaluated doses and for heart rate blood pressure product at higher doses. The difference between APV resting values and the values for peak dosage (ΔAPV) correlated with the amount of AHM during DSE. Coronary volume blood flow and coronary flow velocity reserve decreased after stenosis. Conclusions. ΔAPV may reflect the number of hibernating segments. The relative imbalance between blood supply and oxygen consumption in regional myocardium may be one of the mechanisms by which DSE detects AHM. © 2011 Wiley Periodicals, Inc. J Clin Ultrasound, 2011

Objective To investigate in chronic hibernating myocardium in rabbits and the influence and significance of captopril, betaloc, valsartan in angiotensin II subtype 1 receptor(AT 1 R), angiotensin II subtype 2 receptor(AT 2 R), extracellular signal regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase(JNK). Methods The model of chronic hibernating myocardium(CHM) was established. The changes of AT 1 R, AT 2 R, ERK1/2, JNK in different groups were assessed by western blotting and immunohistochemistry. Results The amount of AT 1 R decreased while AT 2 R increased in the CON group compared with in sham group, and both AT 1 R and AT 2 R decreased in drug groups compared with the CON group. The content of ERK had no change in each group, while that of “expression” p-ERK increased in CON group compared with in sham group, and was lower in drug intervention groups than in CON and sham groups. The contents of JNK and p-JNK decreased in CON and drug intervention groups compared with in sham group. The protein levels of JNK, p-JNK in drug intervention groups were lower than in the CON group. Three drugs can inhibit interstitial fibrosis and reduce apoptotic cells. The expression levels in the groups(with different doses) had statistical difference as well as between groups of captopril and other drugs; however the results between betaloc and valsartan had no significant difference. Conclusion AT 1 R, AT 2 R may be the upper stream receptor of ERK and JNK and may participate in generation and evolution of CHM. Captopril, valsartan and betaloc may preserve CHM by inhibiting AT 1 R, AT 2 R and JNK activity.

Recent studies have demonstrated that ginsenoside Rb1 protects the myocardium from ischemia–reperfusion (I/R) injury. However, the precise mechanisms for this protection have not been determined. This study aimed to determine whether the attenuation of I/R-induced myocardial injury by ginsenoside Rb1 (GS Rb1) is due to inhibition of p38α mitogen-activated protein kinase (MAPK). Sprague–Dawley rats were distributed among 6 treatment groups: sham group; I/R group; p38 MAPK inhibitor SB203580 group (SB + I/R); GS Rb1 group (GS + I/R); p38 MAPK agonist anisomycin group (Ani + I/R); and the GS Rb1 + Ani group (GS + Ani + I/R). All of the anaesthetized rats, except those in the sham group, underwent an open-chest procedure that involved 30 min of myocardial ischemia followed by 2 h of reperfusion. Myocardial infarction size (MIS), caspase-3 activity, and levels of the cytokine tumor necrosis factor alpha (TNF-α) in the myocardium were monitored. The expressions of p38α MAPK, caspase-3, and TNF-α in the myocardium were assayed. GS Rb1 reduced MIS and attenuated caspase-3 activity and the levels of TNF-α in the myocardium. Protein expression of total p38α MAPK was not significantly altered. In the Ani + I/R and I/R groups, the levels of phospho-p38α MAPK were significantly increased compared with the sham group, and these increased levels were reduced with GS Rb1. Hemodynamic parameters were not significantly different between the GS + I/R and SB + I/R groups. GS Rb1 exerts an anti-apoptotic effect that protects against I/R injury by inhibiting p38α MAPK phosphorylation, suggesting that GS Rb1-mediated protection requires the inhibition of p38α MAPK.

Contrast-induced nephropathy (CIN) is an important complication in the use of iodinated contrast media. The present study aimed to assess the safety and efficacy of prostaglandin E1 (PGE1) in prevention of CIN in patients with high-risk factors undergoing percutaneous coronary intervention (PCI). The study group consisted of 163 patients who had undergone a coronary intervention procedure between January 1, 2012 and October 31, 2012. Study participants were randomly assigned to either the PGE1 group (82 patients) or the control group (81 patients). Patients in the PGE1 group received PGE1 intravenous infusion of 20 ng/kg/min for 6 h before and after the administration of contrast media. The control group received 0.9 % sodium chloride solution for routine hydration only. A nonionic, low-osmolality contrast agent was used in our laboratory at this time. Serum creatinine (Scr) values and estimated glomerular filtration rate were measured before and within 48 h of the administration of contrast agents. CIN was defined as an increase of ≥0.5 mg/dL or ≥ a 25 % increase in Scr concentrations over baseline within 48 h of angiography. The amount of contrast agent administered was similar for the PGE1 and control groups (156 ± 63 vs. 161 ± 68 mL, P > 0.05). The incidence of CIN was lower in the PGE1 group than in the control group (3.7 vs. 11.1 %, P

Objectives Luteolin is a naturally occurring flavonoid found in many vegetables, fruits and medicinal plants. The migration and proliferation of vascular smooth muscle cells (VSMCs) are the critical pathological processes in various cardiovascular diseases, such as atherosclerosis. In this study, we investigated the effect of luteolin and its latent mechanism on the proliferation and migration of VSMCs stimulated by hydrogen peroxide (H2O2). Methods VSMC proliferation and cell viability was assayed using the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) method or by cell counting, and H2O2-elicited migration of VSMCs was measured using a transwell migration assay. The phosphorylation levels of Src, 3-phosphoinositide-dependent kinase 1 (PDK1) and Akt (protein kinase B) were analysed by immunoblotting. Key findings This study demonstrated that luteolin showed a particularly inhibitory effect on H2O2-elicited VSMC proliferation and migration. In previous research, we originally explored the function of luteolin in blocking H2O2-triggered Src and Akt signalling pathways. The activation of Src, PDK1, Akt (308), Akt (473) in the luteolin-treated group was significantly lower than that seen in the H2O2 group. Conclusions These findings strongly suggested that luteolin suppresses H2O2-directed migration and proliferation in VSMCs partially due to down-regulation of the Akt and Src signalling pathways, which are important participants in the processes of migration and proliferation of VSMCs.