Preliminary Mechanism of Glial Maturation Factor ß on Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension.

Recent evidence suggests that glia maturation factor ß (GMFß) is important in the pathogenesis of pulmonary arterial hpertension (PAH), but the underlying mechanism is unknown. To clarify whether GMFß can be involved in pulmonary vascular remodeling and to explore the role of the IL-6-STAT3 pathway in this process, the expression of GMFß in PAH rats is examined and the expression of downstream molecules including periostin (POSTN) and interleukin-6 (IL-6) is measured using real-time quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. The location and expression of POSTN is also tested in PAH rats using immunofluorescence. It is proved that GMFß is upregulated in the lungs of PAH rats. Knockout GMFß alleviated the MCT-PAH by reducing right ventricular systolic pressure (RVSP), mean pulmonary arterial pressure (mPAP), and pulmonary vascular remodeling. Moreover, the inflammation of the pulmonary vasculature is ameliorated in PAH rats with GMFß absent. In addition, the IL-6-STAT3 signaling pathway is activated in PAH; knockout GMFß reduced POSTN and IL-6 production by inhibiting the IL-6-STAT3 signaling pathway. Taken together, these findings suggest that knockout GMFß ameliorates PAH in rats by inhibiting the IL-6-STAT3 signaling pathway.

The relationship between glycemic risk and longitudinal changes in total physiological atherosclerotic burden in patients with coronary artery disease.

Background: The effects of glycemic status on coronary physiology have not been well evaluated. This study aimed to investigate changes in coronary physiology by using angiographic quantitative flow ratio (QFR), and their relationships with diabetes mellitus (DM) and glycemic control status. Methods: This retrospective cohort study included 530 patients who underwent serial coronary angiography (CAG) measurements between January 2016 and December 2021 at Tongji Hospital of Tongji University. Based on baseline and follow-up angiograms, 3-vessel QFR (3V-QFR) measurements were performed. Functional progression of coronary artery disease (CAD) was defined as a change in 3V-QFR (Δ3V-QFR = 3V-QFRfollow-up - 3V-QFRbaseline) ≤-0.05. Univariable and multivariable logistic regression analyses were applied to identify the independent predictors of coronary functional progression. Subgroup analysis according to diabetic status was performed. Results: During a median interval of 12.1 (10.6, 14.3) months between the two QFR measurements, functional progression was observed in 169 (31.9%) patients. Follow-up glycosylated hemoglobin (HbA1c) was predictive of coronary functional progression with an area under the curve (AUC) of 0.599 [95% confidence interval (CI): 0.546-0.651; P<0.001] in the entire population. Additionally, the Δ3V-QFR values were significantly lower in diabetic patients with HbA1c ≥7.0% compared to those with well-controlled HbA1c or non-diabetic patients [-0.03 (-0.09, 0) vs. -0.02 (-0.05, 0.01) vs. -0.02 (-0.05, 0.02); P=0.002]. In a fully adjusted multivariable logistics analysis, higher follow-up HbA1c levels were independently associated with progression in 3V-QFR [odds ratio (OR), 1.263; 95% CI: 1.078-1.479; P=0.004]. Furthermore, this association was particularly strong in diabetic patients (OR, 1.353; 95% CI: 1.082-1.693; P=0.008) compared to patients without DM. Conclusions: Among patients with established CAD, on-treatment HbA1c levels were independently associated with progression in physiological atherosclerotic burden, especially in patients with DM.

Promotive effects of marine-derived dimethyl sulfoxide on the photodegradation of phenanthrene in the atmosphere.

Dimethyl sulfoxide (DMSO), a versatile medium, is a particular component in the marine atmosphere that possibly causes polycyclic aromatic hydrocarbons (PAHs) to degrade differently than they do in the continental atmosphere. In this study, phenanthrene (Phe) was used as a model PAH in batch photochemical experiments to investigate the chemical actions of DMSO and the underlying mechanisms. The photodegradation of Phe in aqueous solutions with DMSO volume fractions from 0 % to 100 % was initiated by ultraviolet (UV) radiation and promoted by singlet oxygen, which was consistent with pseudo-first-order kinetics. Phe photodegraded faster in a mixture of DMSO and water than in water or DMSO alone, and the rate constant showed a unimodal distribution over the DMSO fraction range, peaking at 33 % DMSO (0.0333 ± 0.0009 min-1) and 40 % DMSO (0.0199 ± 0.0005 min-1) under 254 nm and 302 nm UV radiation, respectively. This interesting phenomenon was attributed to the competition of DMSO for UV radiation and singlet oxygen and changes in dissolved oxygen and free water contents caused by the interaction between DMSO and water molecules. In addition, 9,10-phenanthrenequinone (9,10-PhQ) with high cytotoxicity was the main photodegradation product of Phe under various conditions. The photodegradation rate of Phe in the mixtures of DMSO and water was comparable to its reaction rate with OH radicals, suggesting that 9,10-PhQ can be rapidly generated in the marine atmosphere, driven by a mechanism different from that in the continental or urban atmosphere. Under the presented experimental conditions, UV intensity and DMSO fraction were the primary factors that affected the photodegradation rate of Phe and 9,10-PhQ and altered their integrated toxicity. The findings of this study support the conclusion that the marine atmosphere is an essential field in the atmospheric transport of PAHs, in which DMSO is an important component that affects their photodegradation.

Preparation and Study of Antifouling and Fouling-Release Surface Materials from Copolymers with Anchoring Functional Groups.

Marine biofouling is a worldwide problem in marine systems. Nowadays, innovative non-toxic antifouling and fouling-release materials are highly desirable. In this study, a strategy for preparing antifouling and fouling-release materials via one-step dip coating is reported. Copolymers were synthesized via the polymerization of a monomer with catechol sticky functional groups and four monomers with antifouling- or fouling-release functional groups, respectively. The copolymers could assemble onto different material surfaces, such as metals and plastics, using biomimetic catechol groups via multivalent complex bonding. The catechol groups were helpful for adhesion onto the surfaces, while the other functional groups endowed the coatings with antifouling or fouling-release properties. The effects of modifying the substrates using these copolymer coatings were verified via X-ray photoelectron spectroscopy; images of Chlorella cell and Ulva zoospore settlement were taken using a microscope and scanning electron microscope. The copolymer-coated surfaces, especially the surface modified by DOPA-PSPMA, displayed the best antifouling activity, and surface modification via DOPA-PTMETH was shown to be the most effective for producing the fouling-release property in the settlement assay.

Integrin ß Expression as a New Diagnostic Marker for Arteriovenous Thrombosis: A Single-Center Prospective Study.

Integrin ß plays an important role in the pathogenesis of thrombosis and inflammation, and it may be a shared pathogenic mechanism between arterial and venous thromboses. With the goal of identifying new treatment targets for thrombotic diseases and specific diagnostic markers for venous thromboembolism (VTE), this prospective clinical study was performed to clarify the relationship between integrin and thrombosis. The levels of integrin ß1-3, interleukin-6 (IL-6), and C-reactive protein were significantly higher in patients with acute myocardial infarction (AMI; n = 44) and acute VTE (n = 43) compared to healthy controls (n = 33). The IL-6 and integrin ß1-3 levels were also significantly higher in the AMI group compared to the VTE and control groups. Logistic regression analysis identified IL-6 and integrin ß1-3 levels as independent risk factors for thrombotic disease. Based on the receiver-operating characteristic curve, Youden index, sensitivity, and specificity, the diagnostic accuracy value for VTE was greater than 0.8 when integrins ß1, ß2, and ß3 were combined. Overall, these results suggest that integrin ß levels can contribute to improving the diagnosis and treatment of arteriovenous thrombosis.

Prognostic Implications of Changes in Total Physiological Atherosclerotic Burden in Patients With Coronary Artery Disease-A Serial QFR Study.

The association between coronary physiological progression and clinical outcomes has not been investigated. A total of 421 patients who underwent serial coronary angiography at least 6 months apart were included. Total physiological atherosclerotic burden was characterized by sum of quantitative flow ratio in 3 epicardial vessels (3V-QFR). The relationships of the 3V-QFR and its longitudinal change (△3V-QFR) with major adverse cardiovascular events (MACE) were explored. 3V-QFR values derived from follow-up angiograms were slightly lower compared with baseline (2.85 [2.77, 2.90] vs 2.86 [2.80, 2.90], P < .001). The median △3V-QFR value was -0.01 (-0.05, 0.02). The multivariable models demonstrated that follow-up 3V-QFR and △3V-QFR were independently associated with MACE (both P < .05). Patients with both low follow-up 3V-QFR (≤2.78) and low △3V-QFR (≤-0.05) presented 3 times higher risk of MACE than those without (hazard ratio: 2.953, 95% confidence interval 1.428-6.104, P = .003). Furthermore, adding patient-level 3V-QFR and △3V-QFR to clinical model significantly improved the predictability for MACE. In conclusion, total physiological atherosclerotic burden and its progression can provide incremental prognostic value over clinical characteristics, supporting the use of coronary physiology in the evaluation of disease progression and for the identification of vulnerable patients.

Single pararectus approach combined with three-dimensional guidance for the treatment of acetabular fracture.

Background: Surgery for acetabular fractures involving both columns is difficult and traumatic, making it necessary to explore a minimally invasive and accurate surgical method. Methods: This retrospective case-control study analyzed the clinical data of 34 patients and divided them into two groups: a control group (9 males and 8 females) and a research group (11 males and 6 females) with acetabular fractures involving the anterior and posterior columns. All patients were placed in the supine position via the pararectus approach. A three-dimensional (3D) guide was placed at the position where the posterior column screw was inserted in the second window, and a posterior column screw was placed percutaneously on the medial side of the iliac spine in the research group. The operation time, intraoperative blood loss, and fracture union time of the two groups were recorded. Pelvic radiographs and computed tomography (CT) scans were routinely performed before and after surgery to evaluate reduction and fixation. Residual gap and step displacement were measured using a standardized CT-based method after the surgery. Hip mobility was assessed according to the modified Merle, d'Aubigné, and Postel criteria. Results: All patients were followed up for 6-30 (16.941±6.571) months. The operation times of the two groups were 126 [interquartile range (IQR), 95-133] min (control group) and 110 (IQR, 85-124) min (research group), the intraoperative blood losses were 430 (IQR, 290-550) mL (control group) and 380 (IQR, 260-500) mL (research group). All patients achieved bone healing, with a union time of 15 (IQR, 12-17) weeks (control group) and 13 (IQR, 11.5-15) weeks (research group). According to the standardized CT-based method, the reduction after surgery was acceptable in 13 (control group) and 14 (research group) of these patients (defined as a gap <5 mm or a step-off <1 mm), and the anatomical reduction rates were 76.47% and 82.35%, respectively. Conclusions: The use of a single pararectus approach combined with 3D guide-assisted percutaneous anterograde posterior column screws can shorten the operation time and place effective posterior column screws precisely with minimal invasiveness. At the same time, the acetabular reduction and functional recovery are satisfactory, and there are fewer postoperative complications, which makes this procedure an ideal surgical option.

Assessing causality between different risk factors and pulmonary embolism: A Mendelian randomization study.

Objectives: Mendelian randomization (MR) was used to estimate the causal relationship between body mass index (BMI), ever smoked, heart failure, alcohol intake frequency, inflammatory bowel disease (IBD), and pulmonary embolism (PE). This study aimed to investigate whether there is a causal relationship between BMI, the presence of smoking, heart failure, frequency of alcohol intake, IBD, and PE. Methods: Pooled data on PE from a published GWAS meta-analysis involving approximately 461,164 participants of European ancestry were selected. A publicly available pooled dataset of BMI (461,460), ever smokers (461,066), heart failure (977,323), IBD (75,000), and frequency of alcohol intake (462,346) was used from another independent GWAS. MR was performed using established analysis methods, including Wald ratios, inverse variance weighted (IVW), weighted median (WM), and MR-Egger. Also, the final expansion was validated with multivariate MR. Results: In the IVW model, genetically elevated BMI was causally associated with PE [OR = 1.002, 95% CI (1.001, 1004), P = 0.039]. Cochran's Q test was used to detect heterogeneity in the MR-Egger analysis (P = 0.576). Therefore, the effect of gene-level heterogeneity was not considered. In the MR analysis of other risk factors, we observed genes for ever smoking [IVW OR = 1.004, 95% CI (0.997, 1.012)], heart failure [IVW OR = 0.999, 95% CI (0.996, 1.001)], IBD [IVW OR = 1.000, 95% CI (0.999, 1.001)], and frequency of alcohol intake [IVW OR = 1.002, 95% CI (1.000, 1.004)] were not causally associated with PE. Analysis using multivariate MR expansion showed no causal effect of BMI on PE considering the effect of height as well as weight (P = 0.926). Conclusion: In European populations, a causal relationship exists between BMI and PE: increased BMI leads to PE. In contrast, ever smoking, heart failure, frequency of alcohol intake, and IBD are not directly associated with PE. There was no causal effect of BMI with PE in multivariate Mendelian randomized analysis.

Study on the correlation and clinical significance of T-lymphocyte Subsets, IL-6 and PCT in the severity of patients with sepsis.

Objective: To evaluate the correlation and clinical significance of T lymphocyte subsets, IL-6 and PCT in the severity of patients with sepsis. Methods: One-hundred and twenty patients with sepsis admitted to Baoding No.1 Central Hospital from March 05, 2021 to March 05, 2022 were selected and divided into three groups according to the severity of the disease: the sepsis group, the severe sepsis group and the septic shock group, with 40 cases in each group. The venous blood of all patients was drawn with a sterile vacuum blood collection tube after admission to detect the levels of T lymphocyte subsets CD3+, CD4+, CD8+, CD4+/CD8+, and the venous blood was collected to detect the levels of interleukin-6 (IL-6) and procalcitonin (PCT). The three groups of patients were compared to analyze whether there were differences, and whether there was a correlation between the level of each indicator and the prognosis of patients after treatment. Results: The levels of CD3+, CD4+ and CD4+/CD8+ in the three groups decreased with the aggravation of the disease, with a significant difference (p=0.00). The levels of IL-6 and PCT increased with the aggravation of the disease among the three groups, with statistically significant differences (IL-6, p=0.00; PCT, p=0.01). The better the patients recovered after treatment, the higher the levels of CD4+ and CD4+/CD8+, and the two were positively correlated; While the lower the levels of IL-6 and PCT, the two were negatively correlated. Conclusion: Peripheral blood T lymphocyte subsets and serum IL-6, PCT are abnormally expressed in patients with sepsis, and have a close bearing on the severity of the disease, which has a certain predictive value for patients after recovery. In view of this, the above indicators are of high clinical significance.

The effect of post-abortion care (PAC) on anxiety in women with spontaneous abortion based on MicroRNA-21 expression, cortisol level, and Fordyce happiness pattern.

Abortion is one of the most common complications in pregnancy, and the cause of its occurrence in many cases remains unknown. The high prevalence and consequences of anxiety in women with spontaneous abortion could highlight the importance and role of post-abortion care (PAC). Detection and identification of biomarkers related to abortion and anxiety can effectively diagnose and prevent complications. Among the known biomarkers, microRNAs and the cortisol level have high potential. Therefore, the present study evaluated the effect of post-abortion care (PAC) on anxiety in women with spontaneous abortion based on MicroRNA-21 expression, cortisol level, and Fordyce happiness pattern. In this randomized clinical trial, 72 women with spontaneous abortion were studied and randomly divided into two groups of intervention (n = 36) and control (n = 36). Data were collected through a demographic questionnaire and HADS. To assess PAC, the intervention group was consulted in 8 sessions of 60 minutes in the first 72 hours after abortion. Meetings were held twice a week for four weeks. Both groups were followed up immediately after and one month after the intervention. To evaluate biological factors, 4ml of blood sample was obtained from the subjects. Blood cortisol levels were measured by the Cortisol Competitive Human ELISA Kit (Thermo-Fisher, USA), and microRNA-21 evaluation was performed by Real-time PCR technique. Data were analyzed using SPSS16 software. Results showed that before the intervention, there was no significant difference in the mean score of anxiety between the control and intervention groups (P> 0.05); But at the time immediately and one month after the intervention, there was a significant difference in the mean score of anxiety (p <0.001). The results of biological factors evaluation showed that in the intervention group, serum cortisol levels and microRNA-21 expression decreased significantly (p <0.05). In general, PAC based on the happiness pattern can control the anxiety of women with spontaneous abortion. Therefore, it is recommended as an effective and non-invasive intervention in preventing women's psychological problems after spontaneous abortion.

MYB2 Is Important for Tapetal PCD and Pollen Development by Directly Activating Protease Expression in Arabidopsis.

Tapetal programmed cell death (PCD) is a complex biological process that plays an important role in pollen formation and reproduction. Here, we identified the MYB2 transcription factor expressed in the tapetum from stage 5 to stage 11 that was essential for tapetal PCD and pollen development in Arabidopsis thaliana. Downregulation of MYB2 retarded tapetal degeneration, produced defective pollen, and decreased pollen vitality. EMSA and transcriptional activation analysis revealed that MYB2 acted as an upstream activator and directly regulated expression of the proteases CEP1 and ßVPE. The expression of these proteases was lower in the buds of the myb2 mutant. Overexpression of either/both CEP1 or/and ßVPE proteases partially recover pollen vitality in the myb2 background. Taken together, our results revealed that MYB2 regulates tapetal PCD and pollen development by directly activating expression of the proteases CEP1 and ßVPE. Thus, a transcription factor/proteases regulatory and activated cascade was established for tapetal PCD during another development in Arabidopsis thaliana. Highlight: MYB2 is involved in tapetal PCD and pollen development by directly regulating expression of the protease CEP1 and ßVPE and establishes a transcription factor/proteases regulatory and activated cascade.

miR-129-5p restores cardiac function in rats with chronic heart failure by targeting the E3 ubiquitin ligase Smurf1 and promoting PTEN expression.

Chronic heart failure (CHF) is a prevalent health concern with complex pathogenesis. This current study set out to estimate the function of the miR-129-5p/Smurf1/PTEN axis on cardiac function injury in CHF. The model of CHF in rats was established. The cardiac function indexes, myocardial tissue damage, and oxidative stress-related factors in CHF rats were evaluated after the interference of Smurf1/miR-129-5p/PTEN. The targeting relationships between miR-129-5p and Smurf1 and between PTEN and Smurf1 were verified. It was found that that after modeling, cardiac functions were impaired, heart/left ventricular/lung weight and the myocardial structure was destroyed, and the degree of fibrosis of myocardial tissue was increased. After Smurf1 knockdown, the cardiac function, myocardial structure, and oxidative stress were improved, and the fibrosis in myocardial tissue was decreased. Smurf1 was a target of miR-129-5p. miR-129-5p could annul the protective effect of Smurf1 silencing on CHF rats. Smurf1 inhibited PTEN expression by promoting PTEN ubiquitination, while miR-129-5p enhanced PTEN expression by inhibiting Smurf1. Meanwhile, overexpression of PTEN annulled the cardiac dysfunction in CHF rats induced by Smurf1. In conclusion, miR-129-5p targeted Smurf1 and repressed the ubiquitination of PTEN, and promoted PTEN expression, thus improving the cardiac function of CHF rats.

Relationship between hyperglycaemia at admission and prognosis in patients with acute myocardial infarction: a retrospective cohort study.

BACKGROUND: The optimal threshold of hyperglycaemia at admission for identifying high-risk individuals in patients with acute myocardial infarction (AMI) and its impact on clinical prognosis are still unclear. METHODS: We retrospectively reviewed 2027 patients with AMI admitted from June 2001 to December 2012 in the 'Medical Information Mart for Intensive Care III' database. The significant cut-off values of admission blood glucose (Glucose_0) for predicting hospital mortality in patients with AMI with and without diabetes were obtained from the receiver operating characteristic (ROC) curve, then patients were assigned to hyperglycaemia and non-hyperglycaemia groups based on corresponding cut-off values. The primary endpoints were the hospital and 1-year mortality. RESULTS: Among 2027 patients, death occurred in 311 patients (15.3%). According to the ROC curve, the significant cut-off values of Glucose_0 to predict hospital mortality were 224.5 and 139.5 mg/dL in patients with diabetes and without diabetes, respectively. The crude hospital and 1-year mortality of the hyperglycaemia subgroup were higher than the corresponding non-hyperglycaemia group (p< 0.01). After adjustment, regardless of the state of diabetes, hyperglycaemia at admission was related to significantly increased hospital mortality in patients with AMI. For patients with AMI without diabetes, hyperglycaemia at admission was positively correlated with the increase of 1-year mortality (HR, 1.47; 95% CI 1.18 to 1.82; p=0.001). Nevertheless, this trend disappeared in those with diabetes (HR, 1.35; 95% CI 0.93 to 1.95; p=0.113). CONCLUSION: Hyperglycaemia at admission was an independent predictor for mortality during hospitalisation and at 1-year in patients with AMI, especially in patients without diabetes.

Mangrove restoration promotes the anti-scouribility of the sediments by modifying inherent microbial community and extracellular polymeric substance.

Coastal erosion will aggravate the loss of shorelines and threaten the safety of coastal engineering facilities. Mangrove is often considered as an efficient coastal guard; however the mechanisms involved in anti-scouribility ascribed to mangrove are still poorly understood. Thus, two artificial mangrove forests (including exotic Sonneratia apetala and native Kandelia obovata) and an unvegetated mudflat control were selected to explore the potential function of microbial extracellular polymeric substance (EPS) on the anti-scouribility of the sediments. A cohesive strength meter was used for the analysis of anti-scouribility, while a sequential extraction and 16S high-throughput sequencing were employed to evaluate the changes in EPS and microbial community driven by mangrove restoration. Principal component, redundancy, and two-matrix correlation heatmap analyses were performed for the analyses of the correlations among shear stress, EPS, microbes, and soil properties. The results showed an obvious enhancement of anti-scouribility after mangrove restoration. Compared to those of unvegetated mudflat, shear stress increased from 1.94 N/m2 to 3.26 and 4.93 N/m2 in the sediments of S. apetala and K. obovata stands, respectively. Mangrove restoration also promoted EPS content in the sediments, irrespective of EPS components and sub-fractions. Both extracellular protein and polysaccharide were found to be positively correlated with anti-scouribility. Coinciding with increased anti-scouribility and EPS, increased bacterial abundances were also detected in the sediments after mangrove restoration (especially K. obovata), whereas Proteobacteria and Bacteroides may be important and influential for EPS secretion and anti-scouribility promotion. Nevertheless, increased total organic carbon, total nitrogen and total phosphorus induced by mangrove restoration may also partially contribute to improvement of anti-scouribility. In conclusion, this is the first study to provide evidence for a link between mangrove restoration and increased EPS which improve resistance to scouring. The present study provides a novel perspective on the revealing of the function of mangrove on erosion mitigation.

Angiographic quantitative flow ratio in acute coronary syndrome: beyond a tool to define ischemia-causing stenosis-a literature review.

Background and Objective: Numerous studies have demonstrated the safety and effectiveness of physiology-guided coronary revascularization in chronic coronary syndrome, resulting in a high level of guideline recommendation for these patients. However, the application of coronary physiology in acute coronary syndrome (ACS), especially in the acute phase of myocardial infarction, remains challenging. Over the last decade, the number of novel physiological indices derived from the computation of angiography have been developed as alternatives to pressure wire-based fractional flow reserve. Among these angiography-based indices, the quantitative flow ratio (QFR) is undoubtedly the one with the largest amount of data cumulated so far. In this article, we aim to review the related studies that describe efforts to investigate the diagnostic role of QFR and discuss perspectives for its current and future applications in the setting of the ACS. Methods: A literature search was performed on the electronic databases, including PubMed, Google Scholar and Web of Science covering publications in English up to May 2022. Key Content and Findings: An emerging body of evidence has validated the diagnostic accuracy of angiography-derived QFR for the assessment of functional severity of coronary stenosis in both acute and chronic coronary syndromes. In parallel, multiple technologies, i.e., QFR-based pullback pressure gradient index, angiography-derived index of microcirculatory resistance and intravascular imaging-based morphofunctional evaluation methods, have been proposed, allowing operators to easily obtained physiological data of micro and macro-circulation, together with atherosclerotic lesion characteristics in catheterization laboratories. More recently, promising results supporting the clinical value of QFR in guiding revascularization and predicting outcomes for ACS patients have been published. Conclusions: Angiography-based QFR bears the potential of a wider adoption of coronary physiology assessment in the ACS setting due to its quicker and less-invasive nature. However, the current evidence mainly derived from retrospective studies or post-hoc analyses of prospective trials. Future studies are needed to further explore the benefits of QFR-guided revascularization on outcomes in ACS.

MiR-155 acts as an inhibitory factor in atherosclerosis-associated arterial pathogenesis by down-regulating NoxA1 related signaling pathway in ApoE-/- mouse.

BACKGROUND: To investigate the protective efficacy of miR-155 on down regulating NADPH oxidase isoform subunit A1 (NoxA1) gene expression, resulting in inhibition of VSMC migration and over proliferation and thus ameliorating the progression of arterial atherosclerosis in AS mouse model. Therefore, to further explore the regulatory effect of miR-155 on neointima formation in AS and locate potential anti-atherosclerosis target. METHODS: The mouse vascular aorta smooth muscle cell (MOVAS) was cultured and transfected with recombinant Pad2YFG adenovirus fluorescent vector with miR-155 fragment into 4 groups. Western blotting and RT-PCR were performed to identify the expression of NoxA1 under different circumstances. Fluorescence microscope was applied to observe the transfection rate of miR-155 into adenovirus. Twelve-week fatty food induced atherosclerotic ApoE-/- mouse model was established as host to accept miR-155 transfected adenovirus transplantation to observe its effect on VSMC in AS progression. Carotid and thoracic artery were extracted at 1 month after dosing. Distribution of miR-155 was quantified via expression levels of protein and RNA to detect NoxA1, Nox1, p47phox and NADPH expression. Immunohistochemistry, fluorescence imaging and other methods were performed in arteries section to compare the thickness of neointima and assess the severity of AS in each group. RESULTS: Luciferase reporter gene assay showed significant expression of miR-155 in mimic group indicating that miR-155 had target binding effect with NoxA1 gene. Western blotting and RT-PCR results both showed significantly decreased NoxA1 expression in miR-155 mimic group while increased with its inhibitor. The miR-155 distribution was observed varied at 1 month after in control, miR-155 mimic and inhibitor groups. The NoxA1, NADPH, Nox1 and pp47phox protein expression in VSMC was decreased in mimic group vs control and inhibitor groups (P<0.05); no significant difference of NADPH expression was observed in all groups. The NoxA1, Nox1 and p47phox gene expression in VSMC were both found reduced compared with those of control group at week 4 (P<0.05). Immunohistochemistry staining of artery frozen sections figured out that the thickness of neointima of carotid artery in miR-155 mimic group was significantly lower vs control and inhibitor groups (P<0.01) at week 4. CONCLUSIONS: miR-155 played an important role in NoxA1-related signaling pathway. miR-155 transfection into VSMC may have anti-inflammatory regulatory effect on NoxA1 expression in vivo and resulting in amelioration of atherosclerotic lesion in AS mouse model. In summary, miR-155 specifically plays in a negative feedback loop and demonstrates a protective role during atherosclerosis-associated VSMC proliferation and neointima formation through the miR-155-NoxA1-p47phox complex signaling pathway.

The metaplastic effects of cordycepin in hippocampal CA1 area of rats.

Metaplasticity is referred to adjustment in the requirements for induction of synaptic plasticity based on the prior history of activity. Synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD), has been considered to be the neural processes underlying learning and memory. Previous observations that cordycepin (an adenosine derivative) improved learning and memory seemed to be contradictory to the findings that cordycepin inhibited LTP. Therefore, we speculated that the conflicting reports of cordycepin might be related to metaplasticity. In the current study, population spike (PS) in hippocampal CA1 area of rats was recorded by using electrophysiological method in vivo. The results showed that cordycepin reduced PS amplitude in hippocampal CA1 with a concentration-dependent relationship, and high frequency stimulation (HFS) failed to induce LTP when cordycepin was intrahippocampally administrated but improved LTP magnitude when cordycepin was pre-treated. Cordycepin increased LTD induced by activating N-Methyl-D-aspartate (NMDA) receptors and subsequently facilitated LTP induced by HFS. Furthermore, we found that 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), an adenosine A1 receptors antagonist, could block the roles of cordycepin on LTD and LTP. Collectively, cordycepin was able to modulate metaplasticity in hippocampal CA1 area of rats through adenosine A1 receptors. These findings would be helpful to reconcile the conflicting reports in the literatures and provided new insights into the mechanisms underlying cognitive function promotions with cordycepin treatment.

Establishment of exercise intensity for patients with chronic heart failure equivalent to anaerobic threshold based on 6-minute walking test.

BACKGROUND: The study aimed to investigate the relationship between the aerobic exercise intensity determined by 6-minute walking distance (6MWD) and its counterpart based on anaerobic threshold (AT) in chronic heart failure (CHF) individuals for exploring suitable means for CHF exercise rehabilitation. METHODS: We retrospectively analyzed data in patient with CHF, who performed cardiopulmonary exercise test (CPET) and 6-minute walking test (6MWT) uniformly. Anthropometric characteristics, left ventricular ejection fraction (LVEF), and multiple parameters of 6MWT and AT were collected. RESULTS: The results of the analysis revealed that the 6MWD was correlated with the AT positively [CHF group: r=0.433, heart failure with reduced ejection fraction (HFrEF) group: r=0.395, heart failure with intermediate ejection fraction (HFmEF) group: r=0.477, heart failure with preserved ejection fraction (HFpEF) group: r=0.445; all P<0.05]. The regression analysis showed that the linear equation model developed can predict exercise intensity based on AT (EIAT) by exercise intensity based on 6MWD (EI6MWD), the aerobic exercise intensity based on AT and 6MWD respectively, of CHF patients. CONCLUSIONS: There is a correlation between EI6MWD and EIAT. 74.6-87.4% of EI6MWD in patients with CHF is equivalent to EIAT. It is feasible to establish the aerobic exercise intensity of patients with CHF equivalent to AT based on 6MWD.

Recent history of metal contamination in the Fangcheng Bay (Beibu Gulf, South China) utilizing spatially-distributed sediment cores: Responding to local urbanization and industrialization.

In this study, the recent history of heavy metal pollution in the Fangcheng Bay (South China) was reconstructed utilizing three 210Pb-dated sediment cores. The metal concentration profiles display three trends since the 1970s and clearly reflect local urbanization and industrialization. The metals in the Fangcheng Bay started to accumulate in the 1970s but remained relatively low until the 1990s which corresponds to the slow urbanization and industrialization. The metal accumulation in the eastern Fangcheng Bay peaked in the early 2000s following the steep increases in accordance with the rapid industrialization of the eastern Fangcheng Bay where the core HSL was collected. Conversely, the heavy metal profiles in the western Fangcheng Bay present slight step increases in the early 2000s followed by a dramatic metal enrichment in the late 2000s; the expansion of these two cores, which begins in the early 2000s, concurs well with the rapid local urbanization and industrialization.

mRNA expression disturbance of complement system related genes in acute arterial thrombotic and paroxysmal atrial fibrillation patients.

BACKGROUND: This study aimed to compare the characteristics of mRNA expression of genes in complement system between acute arterial thrombotic patients and paroxysmal atrial fibrillation (PAF) patients. METHODS: Twenty acute myocardial infarction (AMI) patients and 20 PAF patients were assigned into the experiment groups, and 20 stable angina pectoris (SAP) patients were enrolled in the control group. RESULTS: When compared with the control group, mRNA expression of C1QA, C1QB, C1QC, C1R, CFP, C5, CR1, ITGAM, ITGAX, ITGB2, C5AR1, CD46, CD55 and CD59 genes was significantly upregulated, and CR2 gene significantly downregulated in the AMI group (P<0.05); while mRNA expression of CFD, MBL2, MASP2, C5, C6, C8B, C9, C5AR1, CR2, CFI, CFHR1, CD46, CD55, VTN and CD59 genes was significantly downregulated in PAF patients (P<0.05). Results of the comparison between the AMI and PAF group showed that mRNA expression of C1QA, C1QB, C1QC, C1R, CFB, CFD, CFP, MBL2, MASP2, C5, C6, C8B, C9, CR1, ITGAM, ITGAX, ITGB2, C5AR1, CFI, CFHR1, CD46, CD55, CLU, VTN and CD59 genes was significantly upregulated in the AMI group (P<0.05). CONCLUSIONS: Taken SAP patients as controls, the complement system is in a high-intensive disturbance with simultaneous activation and inhibition in AMI patients, indicating that the cascade response of complement system is disturbed, and then the membrane attack complex (MAC) cannot form finally. The mRNA expression of related genes in the complement system is under a status of downregulation in PAF patients, indicating that the functions of cascade response in the complement system decreased significantly in PAF patients, leading to significantly decreased MAC functions.