Contrast-enhanced transcranial Doppler for the detection of right-to-left shunt: A new provocation method with a syringe-modified Valsalva maneuver.

BACKGROUND: Contrast-enhanced transcranial Doppler (cTCD) study has been established as one of the most common investigations for detecting right-to-left shunt (RLS). Although the conventional Valsalva maneuver (c-VM) has been used to increase the sensitivity of cTCD for RLS, efforts are still needed to improve the detection rate further. We proposed a new provocation method with a syringe-modified Valsalva maneuver (sm-VM) during cTCD and compared the efficacy of this strategy with cTCD measured at resting and with the provocation of c-VM. METHODS: Consecutive patients with suspicion of RLS who underwent cTCD in our institution between September 27, 2021, and April 1, 2022, were included in this study. Examination of cTCD was performed separately at the resting state and provoked with c-VM and sm-VM. The overall proportion of patients with RLS and their distribution with different RLS grades were compared. RESULTS: A total of 389 patients (mean age: 49.37 years, male: 52.2%) were included in this study. The positive rate for RLS was significantly higher for cTCD detected with sm-VM than those detected at resting state and with c-VM (46.8% vs. 21.6% and 34.2%, all p < .05). Besides, cTCD detected with sm-VM was also associated with a higher proportion of patients with grade III RLS than those detected at resting state and with c-VM (11.3% vs. 1.8% and 0%, all p < .05). CONCLUSIONS: Compared to cTCD detected at resting state and with c-VM, cTCD with sm-VM could further increase the positive detection rate of RLS.

M1 Bone Marrow-Derived Macrophage-Derived Extracellular Vesicles Inhibit Angiogenesis and Myocardial Regeneration Following Myocardial Infarction via the MALAT1/MicroRNA-25-3p/CDC42 Axis.

Myocardial infarction (MI) is a severe cardiovascular disease. Some M1 macrophage-derived extracellular vesicles (EVs) are involved in the inhibition of angiogenesis and acceleration dysfunction during MI. However, the potential mechanism of M1 phenotype bone marrow-derived macrophages- (BMMs-) EVs (M1-BMMs-EVs) in MI is largely unknown. This study sought to investigate whether M1-BMMs-EVs increased CDC42 expression and activated the MEK/ERK pathway by carrying lncRNA MALAT1 and competitively binding to miR-25-3p, thus inhibiting angiogenesis and myocardial regeneration after MI. After EV treatment, the cardiac function, infarct size, fibrosis, angiogenesis, and myocardial regeneration of MI mice and the viability, proliferation and angiogenesis of oxygen-glucose deprivation- (OGD-) treated myocardial microvascular endothelial cells (MMECs) were assessed. MALAT1 expression in MI mice, cells, and EVs was detected. MALAT1 downstream microRNAs (miRs), genes, and pathways were predicted and verified. MALAT1 and miR-25-3p were intervened to evaluate EV effects on OGD-treated cells. In MI mice, EV treatment aggravated MI and inhibited angiogenesis and myocardial regeneration. In OGD-treated cells, EV treatment suppressed cell viability, proliferation, and angiogenesis. MALAT1 was highly expressed in MI mice, OGD-treated MMECs, M1-BMMs, and EVs. Silencing MALAT1 weakened the inhibition of EV treatment on OGD-treated cells. MALAT1 sponged miR-25-3p to upregulate CDC42. miR-25-3p overexpression promoted OGD-treated cell viability, proliferation, and angiogenesis. The MEK/ERK pathway was activated after EV treatment. Collectively, M1-BMMs-EVs inhibited angiogenesis and myocardial regeneration following MI via the MALAT1/miR-25-3p/CDC42 axis and the MEK/ERK pathway activation.

SARS-CoV-2 viremia may predict rapid deterioration of COVID-19 patients

ABSTRACT COVID-19 has raised worldwide concern as spiraling into a pandemic. Reports about comprehensive investigation of COVID-19 viremia are extremely scanty. Herein, we present four COVID-19 patients with positive SARS-CoV-2 nucleic acid test in blood, accounting for 12.12% of 33 detected cases. Rapid deterioration of these cases with septic shock, accompanying with lung CT images enlarged rapidly, decrease of blood oxygen, heart rate drop (with asynchrony of hypoxemia) accompanied with SARS-CoV-2 viremia. It indicates that massive replication and releasing into blood of SARS-CoV-2 and secondary inflammation storm may lead to injury of multiple organs and poor prognosis. So, positive COVID-19 nucleic acid test in blood may be a good forecasting marker of rapid deterioration of COVID-19 pneumonia. In addition, clearance of viremia may indicate tendency for recovery.

SARS-CoV-2 viremia may predict rapid deterioration of COVID-19 patients.

COVID-19 has raised worldwide concern as spiraling into a pandemic. Reports about comprehensive investigation of COVID-19 viremia are extremely scanty. Herein, we present four COVID-19 patients with positive SARS-CoV-2 nucleic acid test in blood, accounting for 12.12% of 33 detected cases. Rapid deterioration of these cases with septic shock, accompanying with lung CT images enlarged rapidly, decrease of blood oxygen, heart rate drop (with asynchrony of hypoxemia) accompanied with SARS-CoV-2 viremia. It indicates that massive replication and releasing into blood of SARS-CoV-2 and secondary inflammation storm may lead to injury of multiple organs and poor prognosis. So, positive COVID-19 nucleic acid test in blood may be a good forecasting marker of rapid deterioration of COVID-19 pneumonia. In addition, clearance of viremia may indicate tendency for recovery.

Cardioprotective activity of placental growth factor combined with oral supplementation of l-arginine in a rat model of acute myocardial infarction.

OBJECTIVE: Exogenous administration of placental growth factor (PlGF) stimulates angiogenesis and improves ventricular remodeling after acute myocardial infarction (AMI), and supplementation with l-arginine ameliorates endothelial function. The objective of the present study was to compare the cardioprotective effects of combination therapy of PlGF and l-arginine with those of direct administration of PlGF alone in a rat model of AMI. MATERIALS AND METHODS: Fifty male Sprague Dawley rats were randomly divided into five groups: sham group, normal saline group, l-arginine group, PlGF group, and combination group (PlGF + l-arginine). An AMI rat model was established by ligation of the left anterior descending of coronary arteries. After 4 weeks of postligation treatment, cardiac function, scar area, angiogenesis and arteriogenesis, myocardial endothelial nitric oxide synthase (eNOS) and collagen I protein content, and plasma concentration of brain natriuretic peptide (BNP) were studied. Echocardiography, Masson's staining, immunohistochemical analyses, Western blot, and enzyme-linked immunosorbent assay were performed. RESULTS: Left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), and capillary and arteriole densities were higher in the PlGF group than in the normal saline group (P<0.01). Scar area, collagen I protein content, and plasma concentration of BNP were decreased in the PlGF group (P<0.01). Myocardial eNOS protein level was elevated in the l-arginine group and PlGF + l-arginine group (P<0.01). Compared with the PlGF group, LVEF, LVFS, myocardial eNOS, and capillary and arteriole densities were higher in the combination group (P<0.01). Scar area, content of collagen I protein, and plasma concentration of BNP were reduced in the combination group (P<0.01). CONCLUSION: Exogenous administration of PlGF stimulates angiogenesis and improves cardiac function. l-arginine increases the expression of the eNOS protein. PlGF and l-arginine have a more pronounced, synergistic protective effect on myocardial protection compared with that of exogenous PlGF therapy alone.

miR-22 contributes to the pathogenesis of patients with coronary artery disease by targeting MCP-1: An observational study.

The aim of this study is to determine miR-22 expression levels in peripheral blood mononuclear cells (PBMCs) of patients with coronary artery disease (CAD) and to investigate whether MCP-1 expression is regulated by miR-22. miR-22 expression in PBMCs from 60 CAD patients including stable angina pectoris (SAP) (n = 29), unstable angina pectoris (UAP) or non-ST elevation myocardial infarction (NSTEMI) (n = 17), or ST-elevation MI (STEMI) (n = 14) and 20 non-CAD subjects by real-time polymerase chain reaction (qRT-PCR). The luciferase activity assays were employed to determine whether miR-22 binds to 3'UTR of MCP-1. miR-22 mimics and inhibitors were transfected into healthy PBMCs. MCP-1 mRNA and protein levels were determined by qRT-PCR and enzyme-linked immuno sorbent assay, respectively. The qRT-PCR results showed that miR-22 levels in PBMCs were decreased in CAD patients, and MCP-1 was augmented in CAD patients and was inversely correlated with miR-22 levels. The luciferase activity assays indicated that MCP-1 was a target of miR-22. Overexpression of miR-22 could significantly repress MCP-1 expression at both mRNA and protein levels in PBMCs, whereas inhibition of miR-22 showed the opposite effects. This study revealed that miR-22 is downregulated in PBMCs from patients with CAD and that miR-22 may participate in inflammatory response by targeting MCP-1, therefore contributing CAD.

Plasma miR-10a: A Potential Biomarker for Coronary Artery Disease.

Aims. MicroRNAs (miRNAs) are involved in the pathogenesis of coronary artery disease (CAD). The objective of this study is to determine plasma levels of miR-10a in CAD and analyze its association with the severity of CAD. Materials and Methods. Plasma miR-10a levels in 60 CAD patients including stable angina pectoris (SAP) (n = 29), unstable angina pectoris (UAP) or non-ST elevation myocardial infarction (MI) (NSTEMI) (n = 17), or ST elevation MI (STEMI) (n = 14) and 20 non-CAD subjects were assessed by real-time polymerase chain reaction (qRT-PCR), and associations of miR-10a levels with risk factors of CAD and its severity were analyzed. Results. The qRT-PCR results showed that plasma miR-10a levels were decreased in CAD patients, and CAD with high SYNTAX scores or STEMI was significantly associated with lower miR-10a levels. Conclusions. Lower plasma miR-10a levels were negatively associated with the presence as well as severity of CAD, and plasma miR-10a can act as a potential biomarker for estimating the presence and severity of CAD.

Strain improvement of Trichoderma viride for increased cellulase production by irradiation of electron and (12)C(6+)-ion beams.

OBJECTIVES: To improve cellulase production and activity, Trichoderma viride GSICC 62010 was subjected to mutation involving irradiation with an electron beam and subsequently with a (12)C(6+)-ion beam. RESULTS: Mutant CIT 626 was the most promising cellulase producer after preliminary and secondary screening. Soluble protein production and cellulase activities were increased mutifold. The optimum temperature, pH and culture time for the maximum cellulase production of the selected mutant were 35 °C, pH 5 and 6 days. The highest cellulase production was obtained using wheat bran. The prepared cellulases from T. viride CIT 626 had twice the hydrolytic performance with sawdust (83 %) than that from the parent strain (42.5 %). Furthermore, molecular studies demonstrated that there were some key mutation sites suggesting that some amino acid changes in the protein caused by base mutations had led to the enhanced cellulase production and activity. CONCLUSIONS: Mutagenesis with electron and (12)C(6+)-ion beams could be developed as an effective tool for improvement of cellulase producing strains.

Molecularly imprinted polymer for specific extraction of hypericin from Hypericum perforatum L. herbal extract.

The molecularly imprinted polymers (MIPs) were prepared by an oxidation-reduction polymerization system using a non-covalent molecularly imprinting strategy with hypericin as the template, acrylamide as the functional monomer and pentaerythritol triacrylate as the cross-linker in the porogen of acetone. The UV spectrum revealed that a cooperative hydrogen-bonding complex between hypericin and acrylamide might be formed at the ratio of 1:6 in the prepolymerized system. Two classes of the binding sites were produced in the resulting hypericin-imprinted polymer with the dissociation constants of 16.61µgL(-1) and 69.35µgL(-1), and the affinity binding sites of 456.53µgg(-1) and 603.06µgg(-1), respectively. The synthesized MIPs were characterized by scanning electron microscope, thermogravimetric and differential thermal analysis. High-performance liquid chromatography was used to investigate the adsorption and recognition properties of the MIPs. Selective binding of the template molecule was demonstrated in comparison to the analog pseudohypericin. After the Hypericum perforatum L. plant being air dried and finely ground, an extract was prepared by shaking the powder in a methanol-water solution (80:20, v/v), vacuum filtration though a Büchner funnel, liquid-liquid extraction with ethyl ether and ethyl acetate, and evaporating on a rotary evaporator until dry. With the sorbents of the optimized MIPs, a molecularly imprinted solid-phase extraction (MISPE) procedure was developed for enrichment and separation of hypericin from the Hypericum extract in the presence of interfering substances. The selective extraction of hypericin from herbal medicine was achieved with the recovery of 82.30%. The results showed that MISPE can be a useful tool for specific isolation and effective clean-up of target compounds from natural products.