The antimicrobial activity of cethromycin against Staphylococcus aureus and compared with erythromycin and telithromycin.

BACKGROUND: This study aims to explore the antibacterial activity of cethromycin against Staphylococcus aureus (S. aureus), and its relationship with multilocus sequence typing (MLST), erythromycin ribosomal methylase (erm) genes and macrolide-lincosamide-streptogramin B (MLSB) phenotypes of S. aureus. RESULTS: The minimum inhibitory concentrations (MICs) of cethromycin against 245 S. aureus clinical isolates ranged from 0.03125 to ≥ 8 mg/L, with the resistance of 38.8% in 121 methicillin-resistant S. aureus (MRSA). This study also found that cethromycin had strong antibacterial activity against S. aureus, with the MIC ≤ 0.5 mg/L in 55.4% of MRSA and 60.5% of methicillin-sensitive S. aureus (MSSA), respectively. The main MLSTs of 121 MRSA were ST239 and ST59, and the resistance of ST239 isolates to cethromycin was higher than that in ST59 isolates (P = 0.034). The top five MLSTs of 124 MSSA were ST7, ST59, ST398, ST88 and ST120, but there was no difference in the resistance of MSSA to cethromycin between these STs. The resistance of ermA isolates to cethromycin was higher than that of ermB or ermC isolates in MRSA (P = 0.016 and 0.041, respectively), but the resistance of ermB or ermC isolates to cethromycin was higher than that of ermA isolates in MSSA (P = 0.019 and 0.026, respectively). The resistance of constitutive MLSB (cMLSB) phenotype isolates to cethromycin was higher than that of inducible MLSB (iMLSB) phenotype isolates in MRSA (P < 0.001) or MSSA (P = 0.036). The ermA, ermB and ermC genes was mainly found in ST239, ST59 and ST1 isolates in MRSA, respectively. Among the MSSA, the ermC gene was more detected in ST7, ST88 and ST120 isolates, but more ermB genes were detected in ST59 and ST398 isolates. The cMLSB phenotype was more common in ST239 and ST59 isolates of MRSA, and was more frequently detected in ST59, ST398, and ST120 isolates of MSSA. CONCLUSION: Cethromycin had strong antibacterial activity against S. aureus. The resistance of MRSA to cethromycin may had some clonal aggregation in ST239. The resistance of S. aureus carrying various erm genes or MLSB phenotypes to cethromycin was different.

miR-6718-5p and miR-4329 can be used as potential biomarkers for acute myocardial infarction.

BACKGROUND: The prevention and prognosis of the onset or recurrence of acute myocardial infarction (AMI) is a difficult problem in contemporary research. METHODS: In this study, peripheral blood samples were collected from seven patients with AMI and nine healthy adults, and exosome microRNAs (miRNAs) were extracted. The miRNA differential expression profiles of serum exosomes in patients with AMI were obtained by using the next-generation sequencing technology combined with bioinformatics analysis. Reverse-transcriptase polymerase chain reaction (RT-PCR) was used to verify the primary screening of differential exosome miRNAs to reveal the possible mechanism of their action on AMI. RESULTS: Compared with healthy individuals, 544 miRNAs were upregulated and 518 miRNAs were downregulated in AMI patients preoperatively. Among these miRNAs, we selected miR-6718 and miR-4329 for qPCR verification. The expression of miR6718 and miR-4329 in patients with myocardial infarction was significantly lower than that in normal controls.

Tanshinone­IIA inhibits myocardial infarct via decreasing of the mitochondrial apoptotic signaling pathway in myocardiocytes.

Myocardial ischemia triggers an inflammatory reaction and oxidative stress that increases apoptosis of myocardiocytes. It has been evidenced that tanshinone­IIA (Tan­IIA) protects against heart failure post­myocardial infarction via inhibition of the apoptotic pathway. The purpose of the present study was to investigate the therapeutic effect of Tan­IIA in a rat model of myocardial ischemia, and explore the possible mechanism of Tan­IIA in myocardiocytes. The rat model of myocardial ischemia was established by left anterior descending coronary artery and rats received treatment with either Tan­IIA (10 mg/kg) or PBS for 20 days continuously. The cardiac function in the experimental rat model was detected using the Sequoia 512 echocardiography system on day 21. The cell viability of myocardiocytes was assessed by CCK­8 assay. Apoptosis of myocardiocytes and myocardial tissue was evaluated by TUNEL assay. The infarct size of the myocardial ischemia rat was determined through 2,3,5­triphenyltetrazolium chloride (TTC) and Evan blue double staining assay. The expression levels of apoptotic factors were assessed by immunohistochemistry, western blotting and immunofluorescence. The results demonstrated that Tan­IIA reduced myocardial infarct size and improved the myocardial function in myocardial ischemia rats. Compared with PBS, Tan­IIA treatment decreased myocardial tissue apoptosis and the expression levels of caspase­3, Cyto c and Apaf­1 in myocardial tissue. Tan­IIA increased the viability of impaired myocardiocytes, inhibited apoptosis of impaired myocardiocytes and increased Bcl­2 and Bak expression in myocardiocytes. In addition, Tan­IIA increased Bim and CHOP, decreased TBARS, ROS and H2O2 production, decreased ATF4 and IRE1α expression, and reduced intracellular calcium and oxidative stress in myocardiocytes. Furthermore, caspase­3 overexpression blocked Tan­IIA­decreased apoptosis of myocardiocytes. In conclusion, the data in the present study indicated that Tan­IIA improved myocardial infarct and apoptosis via the endoplasmic reticulum stress­dependent pathway and mitochondrial apoptotic signaling pathway.

Prevalence, risk factors and clinical correlates of depression in quarantined population during the COVID-19 outbreak.

BACKGROUND: The COVID-19 outbreak has brought tremendous psychological pressure to the general population, which may lead to depression. Therefore, this study aim to evaluate the prevalence and clinical correlates of depressive symptoms in the general population quarantined during the COVID-19 outbreak in Shenzhen. METHODS: 2237 quarantined general individuals participated in this cross-sectional study from February 14 to March 4, 2020, during their 14 days quarantine. They completed the Zung's Self-Rating Depression Scale (SDS) for depression, Zung's self-rating anxiety scale (SAS) for anxiety, the Pittsburgh Sleep Quality Index (PSQI) for sleep quality, and the Impact of Events Scale-Revised (IES-R) for post-traumatic stress symptoms (PTSS). RESULTS: The prevalence of depressive symptom was 6.21% in quarantined individuals. The depressed group were younger, less married and educated, and had higher SAS, PSQI, IES-R total scores (all p<0.05), as well as more avoidance, intrusion and hyperarousal symptoms than the non-depressed group. Correlation analysis showed significant correlations between SDS score and the following parameters: age, marriage, education, SAS, PSQI, IES-R total and its three subscale scores (Bonferroni corrected all p<0.05). Further multiple regression indicated that age, marriage, education, SAS, PSQI, IES-R total score, Avoidance and Hyperarousal factor were independent predictors of depressive symptom. LIMITATIONS: This study adopted a cross-sectional design and used self-report questionnaires. CONCLUSIONS: Our results suggest an elevated prevalence of depressive symptom in quarantined general individuals in Shenzhen. Some demographic and clinical variables were associated with depressive symptoms.

Increased Legumain/Smad3 expression in atherosclerotic plaque of rat thoracic aorta.

OBJECTIVES: The purpose of this study was to investigate the role of legumain in the formation and stability of atherosclerotic plaque, as well as to explore the association between legumain with Smad3 pathway in a rat atherosclerosis model. METHODS: Rat with thoracic aorta atherosclerosis was established and received treatment with statin (n = 15 each) or controls (n = 10). Serum level of legumain was determined by enzyme-linked immunosorbent assay. Legumain and Smad3 aortic expression levels were assessed by immunohistochemistry and fluorescence microscopy. Protein and mRNA levels were analyzed using Western blot analysis and reverse transcriptase coupled polymerase chain reaction, respectively. RESULTS: The atherosclerotic group showed higher serum legumain level than control and statin group. Expression of legumain and Smad3 in macrophages and foam cells was increased in atherosclerotic group compared to control and statin group. The protein and mRNA levels of legumain and Smad3 were significantly attenuated by statin treatment (p < 0.05). For all groups, legumain expression was correlated linearly with Smad3 at mRNA (coefficient: 0.94) and protein (coefficient: 097) level. CONCLUSIONS: Legumain and Smad3 expression is highly expressed in mainly atherosclerotic plaque macrophages and linearly related, which is attenuated by statin therapy, suggesting legumain a potential Smad3 pathway-related marker of atherosclerosis.

Endothelial stem cells attenuate cardiac apoptosis via downregulating cardiac microRNA-146a in a rat model of coronary heart disease.

Coronary artery disease (CAD) is one of the main causes of hospitalization worldwide and has high morbidity. It has previously been demonstrated that stem cells serve an important role in improving myocardial function. MicroRNA (miRNA)-146a downregulation has been reported to inhibit vascular smooth muscle cell apoptosis in a rat model of coronary heart disease. The aim of the present study was to investigate the mechanisms underlying the effects of endothelial stem cell (ESC)-derived paracrine factors and cardiac miRNAs in CAD. Acute myocardial infarction was induced in 20 rats. Autologous ESCs (n=10; experimental group) or PBS (n=10; control group) were injected in the border zone. Reverse transcription-quantitative polymerase chain reaction, ELISA and immunohistochemistry assays were performed to analyze the therapeutic effects of ESCs in rats with coronary heart disease rats. Serum interleukin (IL)-1, IL-17 and tumor necrosis factor-α were reduced in the experimental group compared with control rats, as was the number of circulating proatherogenic cells. The results demonstrated that ESC transplantation markedly downregulated miRNA-146a expression and decreased apoptosis in the myocardium compared with the control group. Rats in the experimental group also had higher levels of vascular endothelial growth factor compared with the control group. In addition, it was demonstrated that miRNA-146 knockdown reduced cardiac apoptosis and increased VEGF expression. Furthermore, the infarct area in the border zone or rats with CAD was reduced in the experimental group compared with the control group. In conclusion, these results suggest that ESC transplantation may improve cardiac function via downregulating miR-146a, which may be have potential as a treatment for CAD.

Nucleolin protects against doxorubicin-induced cardiotoxicity via upregulating microRNA-21.

Nucleolin is a multifunctional protein and participates in many important biological processes. Our previous study found that nucleolin protects the heart against myocardial ischemia-reperfusion injury. In this study, we aimed to investigate the role of nucleolin in doxorubicin (DOX)-induced cardiotoxicity. The expression pattern of nucleolin in hearts subjected to DOX injury was investigated, and we found that administration of DOX induced nucleolin expression significantly in vivo and in vitro. Gene transfection and RNA interference approaches were used in cardiomyocytes to investigate the function of nucleolin. Nucleolin overexpression protects cardiomyocytes against DOX-induced injury. Nucleolin-ablated cardiomyocytes become susceptible to the injury induced by DOX. The hearts of cardiac-myocyte-specific nucleolin transgenic mice are more resistant to DOX injury. Furthermore, nucleolin upregulates microRNA(miRNA)-21 expression in vivo and in vitro, and the miRNA-21 inhibitor negates the protective effect of nucleolin against injury induced by DOX. These results have demonstrated that nucleolin is involved in the regulation of DOX-induced cardiac injury and dysfunction via the regulation of miRNA-21 expression, and may be a novel therapeutic target for DOX-induced cardiotoxicity.

[Clinical value of dual-source CT in evaluating coronary artery disease].

OBJECTIVE: To analyze the clinical value of dual-source CT (DSCT) in the diagnosis of coronary artery disease. METHODS: Fifty-five patients with suspected coronary heart disease underwent both DSCT coronary angiography (DSCTCA) and selective coronary angiography (CAG) examination, and the diagnostic sensitivity, specificity and accuracy of the DSCTCA was evaluated. RESULTS: The sensitivity, specificity, positive and negative predictive value, and accuracy of DSCT in the diagnosis of coronary heart disease were 97.7%, 72.6%, 93.5%, 88.9% and 92.7% by the number of patients, respectively; by calculating the coronary arteries, the sensitivity, specificity, positive and negative predictive value, accuracy were 94.9%, 95.8%, 92.5%, 97.1%, 95.5%, respectively. According to the lesion segment, these values were 88.2%, 96.9%, 90.5%, 96.1%, 94.7%, respectively. DSCTCA showed no significant difference from CAG for a diagnostic purpose, nor did their vessel sensitivity, specificity, positive and negative predictive value, and accuracy in different coronaries differ significantly. CONCLUSION: DSCT has a diagnostic accuracy of coronary heart disease close to that CAG and can on some occasion serve as an alternative to CAG in the screening of coronary artery disease.

[Change of endothelial progenitor cells from peripheral blood in patients with coronary heart diseases before and after percutaneous coronary intervention].

OBJECTIVE: To investigate the culture of endothelial progenitor cells (EPCs) from peripheral blood in patients with coronary heart diseases (CHD) before and after percutaneous coronary intervention (PCI), and to observe the cells shape and determine the cell number and proliferation activity. METHODS: Ninety-five patients were divided into a CHD group(n=65) and a control group (n=30). The mononuclear cells were isolated from peripheral blood of patients with CHD before, right after and 4 days after PCI by Ficoll-density centrifugation. The isolated cells were cultured in RPMI1640 medium supplemented with VEGF165 and bFGF.EPCs were characterized as adherent cells of double positive for DiL-acLDL uptake and FITC-UEA-I binding by direct fluorescent staining under a fluorescence microscope. The EPCs specific surface mark CD34 and KDR were assessed by fluorescence activated cell sorter analysis. The cell shapes were analysed and the number of colony-forming units(CFU) was counted by phase-contrast microscope. RESULTS: The number of EPCs reduced in patients with CHD before the PCI, but the cell number was significantly increased in patients with CHD after the PCI, and the number reduced in patients with CHD 4 days after the PCI. How-ever, the number of CFUs did not change in patients before and after the PCI. CONCLUSION: PCI can increase endothelial progenitor cells in patients after the PCI; but 4 days after the PCI, this increase will not exist.

[Differentiation of 2 endothelial progenitor cells in vitro and inhibitory effect of asymmetric dimethylarginine on its proliferation].

OBJECTIVE: To investigate the Methods for culturing two types of endothelial progenitor cells (EPC) from human umbilical cord blood and study their differentiation traits and the depressant effect of asymmetric dimethylarginine (ADMA) on its proliferation. METHODS: Mononuclear cells were isolated from fresh cord blood by 6% hydroxyethyl starch(HES) and density gradient centrifugation.Isolated cells were cultured in the medium supplemented with vascular endothelial growth factors (VEGF) and basic fibroblast growth factors (bFGF). The growth characteristics and biological features of the cells were observed at different time points and identified by morphology,immunofluorescence staining,reverse transcription polymerase chain reaction (RT-PCR), and flow cytometry.Attached cells were incubated with different concentrations of ADMA (1,5, and 10 micromol/L) for 24,48, and 72 hours. Methylthiazoletetrazolium (MTT) assay and quantified colony forming units (CFUs) were used to assess the proliferation of endothelial progenitor cells. RESULTS: The attached cells were divided into 2 types:early EPC and late EPC. Early EPC changed from small sized round cells to spindle shaped cells and late EPC formed a typical cobblestone-like cells. Fluorescence microscopy showed that EPC were positive for both Dil-acLDL uptake and FITC-UEA-I binding.RT-PCR and FACS showed the difference of endothelial cell-specific,gene expression and changed AC133,CD34, and KDR among different times.Incubation of EPC with ADMA dose and time-dependently decreased the number and the proliferation of EPC. CONCLUSION: There are 2 types of EPC from a source of human umbilical cord blood and ADMA may depress the EPC proliferation, providing a basis for further research.

[Effect of melatonin on the proliferation, apoptosis, and expression of bcl-2 in oxidized low-density lipoprotein-induced endothelial progenitor cells].

OBJECTIVE: To explore the effect of melatonin(Mel) on the proliferation, apoptosis and expression of bcl-2 in oxidized low-density lipoprotein(ox-LDL)-induced endothelial progenitor cells (EPC) from human umbilical cord blood in vitro. METHODS: Total mononuclear cells were isolated from human umbilical cord blood in vitro by Ficoll density gradient centrifugation, and the cells were plated on fibronectin-coated culture dishes. After 7 days, the attached cells were divided into 7 groups: a control group (normal cells), 3 ox-LDL groups[the attached cells were incubated with different concentrations of ox-LDL(5,10,and 20mg/L) for 24 hours], and 3 Mel groups[the attached cells were incubated with different concentrations of Mel (0.5,1.0, and 2.0 mmol/L) respectively for 24 hours before incubation with 10 mg/L ox-LDL]. EPC was identified by examining the expression of CD34, vascular endothelial growth factor receptor-2(VEGFR-2) and CD133 under a laser scanning confocal microscope. We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to detect the effect of Mel and ox-LDL on the multiplication ability of EPC. Flow cytometry was used to detect the apoptosis. The expressions of Bcl-2 mRNA and protein were detected respectively by RT-PCR and immunohistochemistry technology. RESULTS: After being exposed to the ox-LDL, the proliferation of EPC in the 3 ox-LDL groups was lower, and the apoptosis rate was higher than that in the control group in a dose-dependent manner (P<0.01); Mel was added at different concentrations before the ox-LDL incubation, and the cells in the 3 Mel groups showed higher proliferation and lower apoptosis rate than those of the 3 ox-LDL groups (P<0.01). Expression of Bcl-2 mRNA and protein of EPC in the 3 Mel groups was higher than that in the 3 ox-LDL groups (P<0.01). CONCLUSION: Ox-LDL can inhibit the proliferation of EPC and promote the apoptosis of the cells by down-regulating the bcl-2 expression. Mel can inhibit these effects of ox-LDL.

[Short- and long-term therapeutic effects of combination therapy with perindopril and irbesartan in a rat model of dilated cardiomyopathy].

OBJECTIVE: To evaluate the short-term, and long-term therapeutic effects of combination therapy with perindopril and irbesartan in a rat model of dilated cardiomyopathy (DCM). METHODS: Sprague-Dawley rats were administered adriamycin intraperitoneally to develop DCM. Grouping of rats: Group A contained normal rats, and Group B contained DCM rats. Both Group A and B were not given drug treatment. Group C and D contained DCM rats, however, Group C was administered perindopril 2mg/(kg x d) while Group D was administered perindopril 1mg/(kg x d) and irbesartan 25mg/(kg x d). Brain natriuretic peptide (BNP) was determined by enzyme linked immunosorbent assay; plasma potassium and creatinine were measured; the pathological lesions of cardiac muscle tissues were evaluated after HE staining; and the survival time of each rat during the intervention was recorded. RESULTS: After the three-week intervention, the plasma concentrations of BNP in Group D were lower than those in Group C (P<0.05). In each group, plasma concentrations of potassium and creatinine showed no significant differences between pre-intervention and post-intervention (P>0.05); pathological lesions of cardiac muscle tissues in both Group C and D were attenuated compared with those in Group B (P<0.01), but pathological lesions of cardiac muscle tissues showed no significant differences between Group C and Group D (P>0.05). Log-rank test showed that the life span of Group C was shorter than that of Group D (P<0.05); Cox regression analysis showed that both combination therapy and monotherapy with perindopril could prolong the survival time, but the effect of combination therapy was more obvious. CONCLUSION: Combination therapy with perindopril and irbesartan in a rat model of DCM can more effectively improve the cardiac function and long-term prognosis than those monotherapy with perindopril. Both these two treatment plans can attenuate the pathological lesions of cardiac muscle tissues, without elevating the concentrations of plasma potassium and creatinine.

[Relevant factors of microalbuminuria in aged patients with essential hypertension].

OBJECTIVE: To investigate the relationship between microalbuminuria and endothelial-dependent relaxing function and atherosclerosis of common carotid artery (CCA) in aged patients with essential hypertension (EH). METHODS: Sixty-four aged EH patients were recruited. According to the albumin excretion rate (AER) in the urine measured by immunoturbidimetry, patients were divided into 2 groups: normoalbuminuria group (NAU group) and microalbuminuria group (MAU group). Thirty aged persons without EH were served as the control group. The endothelium-dependent relaxing function of blood vessels, intima-media thickness (IMT) and the plaque of CCA were measured by color Doppler ultrasound. RESULTS: The flow-mediated dilation in the MAU group [(4.98+/-1.35)%] and that in the NAU group [(6.31+/-1.14)%] were significantly lower than that in the control group [(9.09+/-1.83)%, P<0.05, respectively], especially lower in the MAU group. The IMT of CCA in the MAU group [(0.97+/-0.19)mm] and that in the NAU group [(0.86+/-0.10)mm] were significantly thicker than that in the control group [(0.78+/-0.13)mm] (P<0.05, respectively), especially thicker in the MAU group. The analysis of multiple stepwise regression showed that the microalbuminuria was successively related to EDF, the IMT of CCA, the plaque index of CCA, systolic blood pressure, etc. CONCLUSION: EDF is impaired, and there is the atherosclerosis of CCA in aged patients with EH. Microalbuminuria correlates with the decrease of endothelium-dependent relaxing function and the IMT of CCA in aged patients with EH.