Research progress on activation transcription factor 3: A promising cardioprotective molecule.

Activation transcription factor 3 (ATF3), a member of the ATF/cyclic adenosine monophosphate response element binding family, can be induced by a variety of stresses. Numerous studies have indicated that ATF3 plays multiple roles in the development and progression of cardiovascular diseases, including atherosclerosis, hypertrophy, fibrosis, myocardial ischemia-reperfusion, cardiomyopathy, and other cardiac dysfunctions. In past decades, ATF3 has been demonstrated to be detrimental to some cardiac diseases. Current studies have indicated that ATF3 can function as a cardioprotective molecule in antioxidative stress, lipid metabolic metabolism, energy metabolic regulation, and cell death modulation. To unveil the potential therapeutic role of ATF3 in cardiovascular diseases, we organized this review to explore the protective effects and mechanisms of ATF3 on cardiac dysfunction, which might provide rational evidence for the prevention and cure of cardiovascular diseases.

Migration behavior and leaching ability of radioactive uranium during incineration of uranium-containing strippable coating wastes.

It is currently thought that the incineration approach is an effective method to minimize the volume of radioactive wastes. In this paper, we used an incinerator to burn uranium-containing strippable coating waste. The migration behavior of radioactive uranium during the incineration process were investigated based on hierarchical sampling and mass spectrometry. Results shows that the radioactive uranium is more easily to adhere to the particles with smaller size. The leaching abilities of radioactive uranium in the bottom ash and the fly ash were analyzed. The leaching rate of the uranium from the fly ash and bottom ash were 1% and 6%, respectively, indicating that most of the radioactive uranium was fixed in the ash and the same storage/disposal methods can be used for both the fly ash and bottom ash. According to x-ray spectrometry and SEM-EDS, mineral compositions of the original uranium ore and the bottom ash were mostly the same. Calcium plays an important role in uranium fixation during incineration. The potential mechanism of the uranium special transformation during uranium-containing strippable coating waste combustion was revealed. Our research results can provide technical support for nuclear emergency waste treatment and disposal.

Qualitative Analyses of the Reasons Why Patients Do Not Attend Scheduled Inpatient Appointments in a Hospital in Guangzhou, China.

PURPOSE: Exploration of the reasons why people miss scheduled inpatient appointments from the perspectives of patients. METHODS: Semi-structured interviews via telephone were conducted with patients who missed their inpatient appointments. Data were analyzed based on Colaizzi's seven-step method. RESULTS: Twenty-five patients and five dependents were enrolled. Three themes were identified: practical barriers, lack of knowledge about the disease, and negative emotional responses. Personal social obligations, state of illness, financial issues and long waiting times were the main practical barriers preventing patients from attending their inpatient appointment. Patients' perceptions of feasible self-solving symptoms, readily believing people around them, and a blindly optimistic attitude towards disease contributed to their insufficient knowledge about the disease. Negative emotional responses (eg, sense of fear and lack of trust in physicians) had a detrimental effect on inpatient attendance. CONCLUSION: Three main factors contributed to non-attendance of inpatient appointments: practical barriers, lack of knowledge about disease, and negative emotional response. Our study provides new, valuable evidence on non-attendance of inpatient appointments in China. Our findings could offer meaningful insights into developing effective strategies to reduce non-attendance of inpatient appointments in other countries.

A Putative Efflux Transporter of the ABC Family, YbhFSR, in Escherichia coli Functions in Tetracycline Efflux and Na+(Li+)/H+ Transport.

ATP-binding cassette transporters are ubiquitous in almost all organisms. The Escherichia coli genome is predicted to encode 69 ABC transporters. Eleven of the ABC transporters are presumed to be exporters, of which seven are possible drug export transporters. There has been minimal research on the function of YbhFSR, which is one of the putative drug resistance exporters. In this study, the ybhF gene of this transporter was characterized. Overexpression and knockout strains of ybhF were constructed. The ATPase activity of YbhF was studied using the malachite green assay, and the efflux abilities of knockout strains were demonstrated by using ethidium bromide (EB) as a substrate. The substrates of YbhFSR efflux, examined with the minimum inhibitory concentration (MIC), were determined to be tetracycline, oxytetracycline, chlortetracycline, doxycycline, EB, and Hoechst33342. Furthermore, tetracycline and EB efflux and accumulation experiments confirmed that the substrates of YbhFSR were tetracyclines and EB. The MIC assay and the fluorescence test results showed that tetracyclines are likely to be the major antibiotic substrate of YbhFSR. The existence of the signature NatA motif suggested that YbhFSR may also function as a Na+/H+ transporter. Overexpression of YbhF in E. coli KNabc lacking crucial Na+/H+ transporters conferred tolerance to NaCl, LiCl, and an alkaline pH. Together, the results showed that YbhFSR exhibited dual functions as a drug efflux pump and a Na+ (Li+)/H+ antiporter.

Persistence and outcomes of non-vitamin K antagonist oral anticoagulants versus warfarin in patients with non-valvular atrial fibrillation.

AIMS AND OBJECTIVES: To compare persistence and outcomes of non-vitamin K antagonist oral anticoagulants (NOACs) versus warfarin in Chinese patients with non-valvular atrial fibrillation (AF). BACKGROUND: Given the unpredictable warfarin response and the costliness of NOACs, more research is needed to clarify which drug enjoys better persistence and outcomes, helping to provide personalised care for patients. DESIGN: A prospective cohort study. METHODS: Chinese patients taking NOACs or warfarin from March 2016-April 2018 were followed up by telephone or outpatient visit at 3, 6 months and half a year thereafter. Anticoagulant persistence and outcomes including stroke and bleeding were collected. We used Cox regression to analyse data. This study was reported according to the STROBE guideline. RESULTS: A total of 344 patients were enrolled; 146 patients received NOACs including dabigatran and rivaroxaban, and 198 patients received warfarin. Persistence with anticoagulants was low and dropped sharply at the third month. Patients on NOACs had worse persistence at 3, 6 and 12 months than those on warfarin. There was no difference in the incidence of ischaemic stroke and bleeding between groups, although ischaemic stroke and major bleeding occurred less frequently in the NOACs group. Paroxysmal AF, no heart failure and no stroke were predictors of NOACs non-persistence. Prior catheter ablation and no diabetes were associated with poor persistence of warfarin. The main reason for anticoagulant cessation was patient preference. CONCLUSIONS: Chinese patients taking NOACs had lower persistence, similar rate of ischaemic stroke and bleeding compared with those on warfarin. Further inventions are needed to improve persistence in Chinese patients on NOACs. RELEVANCE TO CLINICAL PRACTICE: Anticoagulation should highlight both persistence and outcomes emphasising personalised care of different drugs. Further interventions to improve persistence should be developed based on causes and risk factors and carried out in the third month of therapy.

Comparison of complications between peripheral arm ports and central chest ports: A meta-analysis.

AIM: The aim of this study was to compare peripheral arm ports versus central chest ports in complication rates. BACKGROUND: Late complications of arm ports versus chest ports, including catheter-related infection, venous thrombosis and catheter obstruction, remain controversial. DESIGN: A meta-analysis conducted following the Cochrane handbook. DATA SOURCES: Studies published between 1950-August 2017 were searched through Pubmed, Embase, Web of science and Cochrane library. REVIEW METHODS: Two authors independently searched the eligible studies and extracted the data. Studies reporting complications of arm ports compared with chest ports, published in full texts and abstracts, were included. The quality of the studies was assessed with the Newcastle-Ottawa Scale. We did subgroup analyses according to cancer type, age, follow-up and anticoagulant. Relative ratios were calculated with different models. RESULTS: A total of 15 articles covering 3,524 tumour patients met the eligibility criteria. There was no difference in catheter-related infection and catheter obstruction between arm ports and chest ports. After reducing the high heterogeneity, no difference was observed in thrombosis overall; however, arm ports had a lower thrombosis rate than chest ports in patients with head and neck cancer, while a higher thrombosis rate was observed in patients <60 years old or follow up ≥1 year. Further studies are needed in venous thrombosis. CONCLUSIONS: Arm ports are a safe option beside chest ports for adult patients with malignancy, especially in patients with head-neck cancer or breast cancer. Patients should be well informed of the advantages and disadvantages of different vascular access devices and provided a choice.

Identification of a conserved linear B-cell epitope in the Staphylococcus aureus GapC protein.

The GapC protein of Staphylococcus aureus (S. aureus) is a surface protein that is highly conserved among Staphylococcus strains, and it can induce protective humoral immune responses. However, B-cell epitopes in S. aureus GapC have not been reported. In this study, we generated a monoclonal antibody (mAb2A9) targeting S. aureus GapC. Through a passive immunity test, mAb2A9 was shown to partially protect mice against S. aureus infection. We screened the motif 236PVATGSLTE243 that is recognized by mAb2A9 using a phage-display system. The motif sequence exactly matched amino acids 236-243 of the S. aureus GapC protein. Then, we identified the key amino acids in the motif using site-directed mutagenesis. Site-directed mutagenesis revealed that residues P236, G240, L242, and T243 formed the core of the 236PVATGSLT243 motif. In addition, this epitope was proven to be located on the surface of S. aureus, and it induced a protective humoral immune response against S. aureus infection in immunized mice. Overall, our results characterized a conserved B-cell epitope, which will be an attractive target for designing effective epitope-based vaccines against S. aureus infection.

Protective humoral and CD4+ T cellular immune responses of Staphylococcus aureus vaccine MntC in a murine peritonitis model.

Staphylococcus aureus can cause different types of diseases from mild skin infections to life-threatening sepsis worldwide. Owing to the emergence and transmission of multidrug-resistant strains, developing an impactful immunotherapy especially vaccine control approach against S. aureus infections is increasingly encouraged and supported. S. aureus manganese transport protein C (MntC), which is a highly-conserved cell surface protein, can elicit protective immunity against S. aureus and Staphylococcus epidermidis. In this study, we evaluated the humoral immune response and CD4+ T cell-mediated immune responses in a mouse peritonitis model. The results showed that MntC-specific antibodies conferred an essential protection for mice to reduce invasion of S. aureus, which was corroborated via the opsonophagocytic killing assay and passive immunization experiment in mice, and moreover MntC-induced Th17 played a remarkable part in preventing S. aureus infection since the MntC-induced protective immunity decreased after neutralization of IL-17 by antibody in vivo and the Th17 adoptive transferred-mice could partly resist S. aureus challenge. In conclusion, we considered that the MntC-specific antibodies and MntC-specific Th17 cells play cooperative roles in the prevention of S. aureus infection.

Identification of a protective B-cell epitope of the Staphylococcus aureus GapC protein by screening a phage-displayed random peptide library.

The impact of epidemic Staphylococcus aureus (S. aureus) on public health is increasing. Because of the abuse of antibiotics, the antibiotic resistance of S. aureus is increasing. Thus, there is an urgent need to develop new immunotherapies and immunoprophylaxes. Previous studies showed that the GapC protein of S. aureus, which is a surface protein with high glyceraldehyde 3-phosphate dehydrogenase activity, transferrin binding activity, and other biological activities, is highly conserved. GapC induces an effective humoral immune response in vivo. However, the B-cell epitopes of S. aureus GapC have not been well identified. Here we used the bioinformatics tools to analyze the sequence of GapC, and we generated protective anti-GapC monoclonal antibodies (mAbs). A protective mAb (1F4) showed strong specificity to GapC and the ability to induce macrophages to phagocytose S. aureus. We screened the motif 272GYTEDEIVSSD282, which was recognized by mAb 1F4, using a phage display system. Then, we used site-directed mutagenesis to identify key amino acids in the motif. Residues G272 D276 E277 I278 and V279 formed the core of the 272GYTEDEIVSSD282 motif. In addition, we showed that this epitope peptide induced a protective humoral immune response against S. aureus infection in immunized mice. Our results will be useful for the further study of epitope-based vaccines against S. aureus infection.

Predictors of smoking relapse after percutaneous coronary intervention in Chinese patients.

AIMS AND OBJECTIVES: To evaluate the prevalence and predictors of smoking relapse after percutaneous coronary intervention in Chinese patients. BACKGROUND: Smoking is considered a vital risk factor for coronary heart disease. Although smoking cessation could decrease the risks of adverse cardiac outcomes, many patients resume smoking following a short period of abstinence. However, little is known about smoking resumption in patients who have undergone percutaneous coronary intervention. DESIGN AND METHODS: A longitudinal study was conducted among Chinese patients who underwent percutaneous coronary intervention. Predictive variables were assessed at baseline through medical records and interviews with questionnaires including the Fagerström Test for Nicotine Dependence, Center for Epidemiologic Studies-Depression scale and Smoking Self-Efficacy Questionnaire. Smoking relapses were recorded at three, six, nine and 12 months by the self-reporting through telephone or at routine visits to the cardiology outpatient clinics. RESULTS: A total of 221 patients who quit smoking immediately after percutaneous coronary intervention completed the whole study. Overall, 51.1%(n = 113) of the patients relapsed within 12 months after percutaneous coronary intervention. The prevalence showed a particular rise (49.6%, n = 56) in the first 3 months and a more gradual increase in the following months. The patients who were employed and had higher nicotine dependence, worse depressive symptoms and lower level of smoking self-efficacy were more vulnerable to relapse to cigarettes. CONCLUSION: The prevalence of smoking relapse is high in the patients who stop smoking in the hospital due to percutaneous coronary intervention. The predictors of smoking relapse are employment, nicotine dependence, depression and smoking self-efficacy in the post- percutaneous coronary intervention patients. RELEVANCE TO CLINICAL PRACTICE: This study may prompt the healthcare providers to focus on the issue of smoking relapse and provide some instructions for identification of the patients with a high-risk of relapse after percutaneous coronary intervention.

Identification and characterization of CD4+ T cell epitopes on manganese transport protein C of Staphylococcus aureus.

Manganese transport protein C (MntC) of Staphylococcus aureus represents an excellent vaccine-candidate antigen. The important role of CD4+ T cells in effective immunity against S. aureus infection was shown; however, CD4+ T cell-specific epitopes on S. aureus MntC have not been well identified. Here, we used bioinformatics prediction algorithms to evaluate and identify nine candidate epitopes within MntC. Our results showed that peptide M8 emulsified in Freund's adjuvant induced a much higher cell-proliferation rate as compared with controls. Additionally, CD4+ T cells stimulated with peptide M8 secreted significantly higher levels of interferon-γ and interleukin-17A. These results suggested that peptide M8 represented an H-2d (I-E)-restricted Th17-specific epitope.

Autophagy in cardiac metabolic control: Novel mechanisms for cardiovascular disorders.

As an extensively studied quality control system, autophagy is responsible for clearance of dysfunctional organelles and damaged marcomolecules in cells. In addition to its biological recycling function, autophagy plays a significant role in the pathogenesis of metabolic syndromes such as obesity and diabetes. In particular, metabolic disorders contribute to cardiovascular disease development. As energy required to maintain cardiac cells functional is immense, disturbances in the balance between anabolic and catabolic metabolism possibly contribute to cardiovascular disorders. Therefore, an urgent need to expand our knowledge on the role of autophagy on the metabolic regulation of hearts emerges. In this review, the potential relationship between autophagic activity and cardiac metabolism is explored and we also discuss how dysregulated autophagy leads to severe cardiac disorders from the perspective of metabolic control.

Sulforaphane prevents rat cardiomyocytes from hypoxia/reoxygenation injury in vitro via activating SIRT1 and subsequently inhibiting ER stress.

AIM: Sulforaphane (SFN), a natural dietary isothiocyanate, is found to exert beneficial effects for cardiovascular diseases. This study aimed to investigate the mechanisms underlying the protective effects of SFN in a model of myocardial hypoxia/reoxygenation (H/R) injury in vitro. METHODS: Cultured neonatal rat cardiomyocytes pretreated with SFN were subjected to 3-h hypoxia followed by 3-h reoxygenation. Cell viability and apoptosis were detected. Caspase-3 activity and mitochondrial membrane potential (ΔΨm) was measured. The expression of ER stress-related apoptotic proteins were analyzed with Western blot analyses. Silent information regulator 1 (SIRT1) activity was determined with SIRT1 deacetylase fluorometric assay kit. RESULTS: SFN (0.1-5 µmol/L) dose-dependently improved the viability of cardiomyocytes, diminished apoptotic cells and suppressed caspase-3 activity. Meanwhile, SFN significantly alleviated the damage of ΔΨm and decreased the expression of ER stress-related apoptosis proteins (GRP78, CHOP and caspase-12), elevating the expression of SIRT1 and Bcl-2/Bax ratio in the cardiomyocytes. Co-treatment of the cardiomyocytes with the SIRT1-specific inhibitor Ex-527 (1 µmol/L) blocked the SFN-induced cardioprotective effects. CONCLUSION: SFN prevents cardiomyocytes from H/R injury in vitro most likely via activating SIRT1 pathway and subsequently inhibiting the ER stress-dependent apoptosis.

Blood lipid profiles and factors associated with dyslipidemia assessed by a point-of-care testing device in an outpatient setting: A large-scale cross-sectional study in Southern China.

OBJECTIVE: To promote the concept of POCT and to investigate dyslipidemia in Guangzhou, China, we performed a study examining blood lipids assessed by POCT and reported factors associated with dyslipidemia. DESIGN AND METHODS: This multicenter, cross-sectional study enrolled outpatients from 9 Guangzhou hospitals from May through September 2013. After informed consent was obtained, the following information was collected: age; gender; the presence of diabetes mellitus, obesity, and hypertension as well as current use of cigarettes or alcohol. Patients were asked to fast for 8h before the blood examination performed on a POCT device, the CardioChek PA. RESULTS: Of 4012 patients enrolled (1544 males, 2468 females; mean age 60.35±9.41 years), 1993 (49.7%) patients had dyslipidemia, but only 101 (5.1%) took statins. The multivariate tests of associations between demographic variables, comorbidities, and the risk of having dyslipidemia found that the significant predictors of dyslipidemia were male gender, age ≥60 years, being a current smoker or alcohol drinker, and hypertension. CONCLUSION: Most dyslipidemia patients in Guangzhou remain untreated. POCT in China is feasible, and its widespread use might improve dyslipidemia awareness, treatment and control.

Comparison of the degree of autophagy in neonatal rat cardiomyocytes and H9c2 cells exposed to hypoxia/reoxygenation.

BACKGROUND: Hypoxia/reoxygenation (H/R) is an important in vitro model for exploring the molecular mechanisms and functions of autophagy during myocardial ischemia/reperfusion (I/R). Neonatal rat cardiomyocytes (NRCM) and H9c2 cells are widely used to study H/R. METHODS: The degree of autophagy in NRCM and H9c2 cells exposed to H/R was assessed by detecting the markers of autophagy, Beclin-1 and LC3II. Autophagosomes were confirmed in both NRCM and H9c2 cells exposed to H/R using MDC staining and TEM. RESULTS: The expression levels of Beclin-1 and LC3II were significantly increased in NRCM under H/R conditions (p < 0.05 vs. control). In contrast, the expression levels of Beclin-1 and LC3II were significantly reduced in H9c2 cells exposed to H/R (p < 0.05 vs. control). The fluorescence intensity and the number of MDC-labeled particles were greater in NRCM exposed to H/R, compared to H9c2 cells (p < 0.05 vs. control). The number of autophagosomes exposed to H/R by TEM was greater in NRCM, compared to H9c2 cells, which was similar to the levels of autophagy markers observed in NRCM and H9c2 cells (p < 0.05 vs. control). CONCLUSIONS: NRCM may be more suitable to study autophagy during H/R than H9c2 cells.

Alpha-lipoic acid protects cardiomyocytes against hypoxia/reoxygenation injury by inhibiting autophagy.

Hypoxia/reoxygenation (H/R) is an important in vitro model for exploring the molecular mechanisms and functions of autophagy during myocardial ischemia/reperfusion (I/R). Alpha-lipoic acid (LA) plays an important role in the etiology of cardiovascular disease. Autophagy is widely implicated in myocardial I/R injury. We assessed the degree of autophagy by pretreatment with LA exposed to H/R in H9c2 cell based on the expression levels of Beclin-1, LC3II/LC3I, and green fluorescent protein-labeled LC3 fusion proteins. Autophagic vacuoles were confirmed in H9c2 cells exposed to H/R using transmission electron microscopy. Our findings indicated that pretreatment with LA inhibited the degree of autophagy in parallel to the enhanced cell survival and decreased total cell death in H9c2 cells exposed to H/R. We conclude that LA protects cardiomyocytes against H/R injury by inhibiting autophagy.

[Carvacrol pretreatment attenuates myocardial oxidative stress and apoptosis following myocardial ischemia-reperfusion in mice].

OBJECTIVE: To investigate the effect of carvacrol pretreatment on myocardial ischemia-reperfusion (I/R) injury and its underlying mechanisms. METHODS: Wild-type male C57 BL/6 mice were randomized into 5 groups (n=13), namely the sham-operated group, vehicle (DMSO in saline)+ I/R group, carvacrol (20 mg/kg) + I/R group, carvacrol (40 mg/kg) + I/R group, and carvacrol (60 mg/kg) + I/R group. The mouse models of myocardial I/R injury were established by a 45-min occlusion of the left anterior descending coronary artery (LAD) followed by reperfusion for 2 h. Carvacrol or vehicle was administered intravenously 15 min before LAD occlusion. After reperfusion, the mice were examined for myocardial oxidative stress level and apoptosis rate. RESULTS: Compared with the vehicle group, the 3 carvacrol-pretreated groups showed significantly reduced myocardial infarct size, oxidative stress level and cardiac myocyte apoptosis rate (P<0.01). CONCLUSION: Carvacrol can protect against myocardial I/R injury by inhibiting myocardial oxidative stress and apoptosis in mice.

[Collation and research on the different texts in Qian jin yao fang (Precious essential formulary, PEF)].

There is considerable difference in the texts between PEF and the archaic editions Sun zhen ren qian jin fang (The Immortal Sun's Precious Formulary, ISPF) and the Song - revised edition Bei ji qian jin yao fang (Precious Essential Formulary for Emergency, PEFE). It is hoped that the real features of PEF can be worked out through collated studies on these two editions so as to offer a basis for systematic research on PEF. At the same time, it has been proved that during the revision and collation of PEF by the Song scholars, it is certain that dramatic revisions had been made on its medical materials, especially an abundant amount of medical materials were added. As a result, the current circulated edition of PEFE does have obvious differences with Sun's original work, while ISPF, in contrast, preserves the original features of Sun Simiao. Hence, ISPF is of important academic significance in the in - depth study of PEF.