SIRT3-dependent mitochondrial redox homeostasis mitigates CHK1 inhibition combined with gemcitabine treatment induced cardiotoxicity in hiPSC-CMs and mice.

Administration of CHK1-targeted anticancer therapies is associated with an increased cumulative risk of cardiac complications, which is further amplified when combined with gemcitabine. However, the underlying mechanisms remain elusive. In this study, we generated hiPSC-CMs and murine models to elucidate the mechanisms underlying CHK1 inhibition combined with gemcitabine-induced cardiotoxicity and identify potential targets for cardioprotection. Mice were intraperitoneally injected with 25 mg/kg CHK1 inhibitor AZD7762 and 20 mg/kg gemcitabine for 3 weeks. hiPSC-CMs and NMCMs were incubated with 0.5 uM AZD7762 and 0.1 uM gemcitabine for 24 h. Both pharmacological inhibition or genetic deletion of CHK1 and administration of gemcitabine induced mtROS overproduction and pyroptosis in cardiomyocytes by disrupting mitochondrial respiration, ultimately causing heart atrophy and cardiac dysfunction in mice. These toxic effects were further exacerbated with combination administration. Using mitochondria-targeting sequence-directed vectors to overexpress CHK1 in cardiomyocyte (CM) mitochondria, we identified the localization of CHK1 in CM mitochondria and its crucial role in maintaining mitochondrial redox homeostasis for the first time. Mitochondrial CHK1 function loss mediated the cardiotoxicity induced by AZD7762 and CHK1-knockout. Mechanistically, mitochondrial CHK1 directly phosphorylates SIRT3 and promotes its expression within mitochondria. On the contrary, both AZD7762 or CHK1-knockout and gemcitabine decreased mitochondrial SIRT3 abundance, thus resulting in respiration dysfunction. Further hiPSC-CMs and mice experiments demonstrated that SIRT3 overexpression maintained mitochondrial function while alleviating CM pyroptosis, and thereby improving mice cardiac function. In summary, our results suggest that targeting SIRT3 could represent a novel therapeutic approach for clinical prevention and treatment of cardiotoxicity induced by CHK1 inhibition and gemcitabine.

Effects of Compound Danshen Dripping Pills on Ventricular Remodeling and Cardiac Function after Acute Anterior Wall ST-Segment Elevation Myocardial Infarction (CODE-AAMI): Protocol for a Randomized Placebo-Controlled Trial.

BACKGROUND: Ventricular remodeling after acute anterior wall ST-segment elevation myocardial infarction (AAMI) is an important factor in occurrence of heart failure which additionally results in poor prognosis. Therefore, the treatment of ventricular remodeling needs to be further optimized. Compound Danshen Dripping Pills (CDDP), a traditional Chinese medicine, exerts a protective effect on microcirculatory disturbance caused by ischemia-reperfusion injury and attenuates ventricular remodeling after myocardial infarction. OBJECTIVE: This study is designed to evaluate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function after AAMI on a larger scale. METHODS: This study is a multi-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The total of 268 patients with AAMI after primary percutaneous coronary intervention (pPCI) will be randomly assigned 1:1 to the CDDP group (n=134) and control group (n=134) with a follow-up of 48 weeks. Both groups will be treated with standard therapy of ST-segment elevation myocardial infarction (STEMI), with the CDDP group administrating 20 tablets of CDDP before pPCI and 10 tablets 3 times daily after pPCI, and the control group treated with a placebo simultaneously. The primary endpoint is 48-week echocardiographic outcomes including left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVI), and left ventricular end-systolic volume index (LVESVI). The secondary endpoint includes the change in N terminal pro-B-type natriuretic peptide (NT-proBNP) level, arrhythmias, and cardiovascular events (death, cardiac arrest, or cardiopulmonary resuscitation, rehospitalization due to heart failure or angina pectoris, deterioration of cardiac function, and stroke). Investigators and patients are both blinded to the allocated treatment. DISCUSSION: This prospective study will investigate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function in patients undergoing pPCI for a first AAMI. Patients in the CDDP group will be compared with those in the control group. If certified to be effective, CDDP treatment in AAMI will probably be advised on a larger scale. (Trial registration No. NCT05000411).

Association between urinary cadmium level and subclinical myocardial injury in the general population without cardiovascular disease aged ≥ 50 years.

Cadmium (Cd) is a toxic heavy metal linked to an increased risk of cardiovascular disease (CVD). But the relationship between urinary Cd (U-Cd) and electrocardiographic subclinical myocardial injury (SC-MI) in older people is unclear. This study evaluated the connection between U-Cd and SC-MI in people who did not have CVD. The study involved 4269 participants from the National Health and Nutrition Examination Survey III(NHANES III) aged ≥ 50 years and had no history of CVD. The relationship between U-Cd and cardiac infarction/injury score (CIIS) was assessed by multivariable linear regression. Whether U-Cd and SC-MI were correlated was determined by multivariate logistic regression, restricted cubic spline, and subgroup analysis. There was a significant association between U-Cd and CIIS (ß, 1.04, 95% confidence interval (CI): 0.39-1.69; P = 0.003) in the highest quartile and fully adjusted model. After adjusting for relevant confounders, multivariable logistic regression showed that participants in the highest quartile of U-Cd had a greater chance of having SC-MI than those in the first ( OR (95% CI), 1.37(1.13,1.66), P for trend = 0.003), and this relationship was especially strong among hypertensive participants. And a positive linear correlation between U-Cd and the prevalence of SC-MI was shown by restricted cubic spline analysis. U-Cd may be a novel risk element for SC-MI because it is independently and linearly linked to CIIS and SC-MI.

Ultrasonic optic disc height combined with the optic nerve sheath diameter as a promising non-invasive marker of elevated intracranial pressure.

Background/aim: Patients with elevated intracranial pressure (ICP) tend to have optic disc edema and a thicker optic nerve sheath diameter (ONSD). However, the cut-off value of the optic disc height (ODH) for evaluating elevated ICP is not clear. This study was conducted to evaluate ultrasonic ODH and to investigate the reliability of ODH and ONSD for elevated ICP. Methods: Patients suspected of having increased ICP and who underwent a lumbar puncture were recruited. ODH and ONSD were measured before lumbar puncture. Patients were divided according to elevated and normal ICP. We analyzed the correlations between ODH, ONSD, and ICP. ODH and ONSD cut-off points for the identification of elevated ICP were determined and compared. Results: There were a total of 107 patients recruited for this study, 55 patients with elevated ICP and 52 with normal ICP. Both ODH and ONSD in the elevated ICP group were higher than in the normal group [ODH: median 0.81 (range 0.60-1.06) mm vs. 0.40 [0-0.60] mm, p < 0.001; ONSD: 5.01 ± 0.37 mm vs. 4.20 ± 0.38 mm, p < 0.001]. ICP was positively correlated with ODH (r = 0.613; p < 0.001) and ONSD (r = 0.792; p < 0.001). The cut-off values of ODH and ONSD for evaluating elevated ICP were 0.63 mm and 4.68 mm, respectively, with 73% and 84% sensitivity and 83% and 94% specificity, respectively. ODH combined with ONSD showed the highest value under the receiver operating characteristic curve of 0.965 with a sensitivity of 93% and a specificity of 92%. Conclusion: Ultrasonic ODH combined with ONSD may help monitor elevated ICP non-invasively.

Combination of D-dimer level and neutrophil to lymphocyte ratio predicts long-term clinical outcomes in acute coronary syndrome after percutaneous coronary intervention.

BACKGROUND: High D-dimer (DD) is associated with short-term adverse outcomes in patients with acute coronary syndrome (ACS). In ACS patients who underwent percutaneous coronary intervention (PCI), however, the value of DD (or combined with neutrophil to lymphocyte ratio [NLR]) to predict long-term major adverse cardiovascular events (MACEs) has not been fully evaluated. METHODS: Patients diagnosed with ACS and receiving PCI were included. The primary outcome was MACEs. Cox proportional hazards regression and logistic regression were used to illustrate the relationship between clinical risk factors, biomarkers and MACEs. Survival models were developed based on significant factors and evaluated by the Concordance-index (C-index). RESULTS: The final study cohort was comprised of 650 patients (median age, 64 years; 474 males), including 98 (15%) with MACEs during a median follow-up period of 40 months. According to the cut-off value of DD and NLR, the patients were separated into four groups: high DD or nonhigh DD with high or nonhigh NLR. After adjusting for confounding variables, DD (adjusted hazard ratio [aHR]: 2.39, 95% confidence interval [CI]: 1.52-3.76) and NLR (aHR: 2.71, 95% CI: 1.78-4.11) were independently associated with long-term MACEs. Moreover, patients with both high DD and NLR had a significantly higher risk in MACEs when considering patients with nonhigh DD and NLR as reference (aHR: 6.19, 95% CI: 3.30-11.61). The area under curve increased and reached 0.70 in differentiating long-term MACEs when DD and NLR were combined, and survival models incorporating the two exhibited a stronger predictive power (C-index: 0.75). CONCLUSIONS: D-dimer (or combined with NLR) can be used to predict long-term MACEs in ACS patients undergoing PCI.

SGLT2 Inhibitors: New Hope for the Treatment of Acute Myocardial Infarction?

Among all of the new antidiabetic drugs, an increasing number of studies have evaluated the relationship between the sodium-glucose cotransporter 2 inhibitors (SGLT2i) and acute myocardial infarction (AMI). Since SGLT2i like empagliflozin, canagliflozin, and recently, dapagliflozin have shown impressive positive effects in patients with chronic heart failure with reduced ejection fraction (HFrEF), it has increased research interest to explore the cardiac molecular mechanisms underlying the clinical benefits and attracted more attention to the effects of SGLT2i on a series of cardiovascular events. Experimental and clinical data on SGLT2i treatment after AMI is limited. This is a review of the clinical and preclinical effects of SGLT2i, focusing on available data on the effects of SGLT2i in AMI patients with a brief overview of ongoing trials.

LncRNA FAF attenuates hypoxia/ischaemia-induced pyroptosis via the miR-185-5p/PAK2 axis in cardiomyocytes.

Pyroptosis is associated with various cardiovascular diseases. Increasing evidence suggests that long noncoding RNAs (lncRNAs) have been implicated in gene regulation, but how lncRNAs participate in the regulation of pyroptosis in the heart remains largely unknown. In this study, we aimed to explore the antipyroptotic effects of lncRNA FGF9-associated factor (FAF) in acute myocardial infarction (AMI). The expression patterns of lncRNA FAF, miR-185-5p and P21 activated kinase 2 (PAK2) were detected in hypoxia/ischaemia-induced cardiomyocytes. Hoechst 33342/PI staining, lactate dehydrogenase (LDH) release assay, immunofluorescence and Western blotting were conducted to assay cell pyroptosis. The interaction between lncRNA FAF, miR-185-5p and PAK2 was verified by bioinformatics analysis, small RNA sequencing luciferase reporter assay and qRT-PCR. The expression of LncRNA FAF was downregulated in hypoxic cardiomyocytes and myocardial tissues. Overexpression of lncRNA FAF could attenuate cardiomyocyte pyroptosis, improve cell viability and reduce infarct size during the procession of AMI. Moreover, lncRNA FAF was confirmed as a sponge of miR-185-5p and promoted PAK2 expression in cardiomyocytes. Collectively, our findings reveal a novel lncRNA FAF/miR-185-5p/PAK2 axis as a crucial regulator in cardiomyocyte pyroptosis, which might be a potential therapeutic target of AMI.

MNK2-eIF4E axis promotes cardiac repair in the infarcted mouse heart by activating cyclin D1.

Adult mammals have limited potential for cardiac regeneration after injury. In contrast, neonatal mouse heart, up to 7 days post birth, can completely regenerate after injury. Therefore, identifying the key factors promoting the proliferation of endogenous cardiomyocytes (CMs) is a critical step in the development of cardiac regeneration therapies. In our previous study, we predicted that mitogen-activated protein kinase (MAPK) interacting serine/threonine-protein kinase 2 (MNK2) has the potential of promoting regeneration by using phosphoproteomics and iGPS algorithm. Here, we aimed to clarify the role of MNK2 in cardiac regeneration and explore the underlying mechanism. In vitro, MNK2 overexpression promoted, and MNK2 knockdown suppressed cardiomyocyte proliferation. In vivo, inhibition of MNK2 in CMs impaired myocardial regeneration in neonatal mice. In adult myocardial infarcted mice, MNK2 overexpression in CMs in the infarct border zone activated cardiomyocyte proliferation and improved cardiac repair. In CMs, MNK2 binded to eIF4E and regulated its phosphorylation level. Knockdown of eukaryotic translation initiation factor (eIF4E) impaired the proliferation-promoting effect of MNK2 in CMs. MNK2-eIF4E axis stimulated CMs proliferation by activating cyclin D1. Our study demonstrated that MNK2 kinase played a critical role in cardiac regeneration. Over-expression of MNK2 promoted cardiomyocyte proliferation in vitro and in vivo, at least partly, by activating the eIF4E-cyclin D1 axis. This investigation identified a novel target for heart regenerative therapy.

Association Between Androgenic Alopecia and Coronary Artery Disease: A Cross-Sectional Study of Han Chinese Male Population.

PURPOSE: This research aimed to investigate the correlation between androgenic alopecia (AGA) and coronary artery disease (CAD) and analyze its value in predicting the severity of coronary atherosclerosis in the Han Chinese male population. PATIENTS AND METHODS: A total of 402 Han Chinese male patients aged 28-75 years were enrolled and performed coronary angiography (CAG) after admission. According to the BASP classification, the participants were divided into mild, moderate and severe AGA. CAD was determined via CAG and defined as stenosis of ≥50% in at least one major coronary artery, and the Gensini score was calculated to evaluate the severity of coronary atherosclerosis. RESULTS: In this study, CAD status (P = 0.002), dyslipidemia status (P = 0.002), age (P = 0.003) and coronary atherosclerosis severity (P < 0.001) were different in patients with different levels of AGA. Multivariate logistic regression analysis revealed that severe AGA was independently correlated to CAD risk (OR, 2.111; 95% CI 1.152 to 3.870, P = 0.016), while the relative CAD risk of early-onset AGA was 2.292 (OR, 2.292; 95% CI 1.132 to 4.640, P = 0.021). AGA status (OR, 2.247; 95% CI 1.396 to 3.617, P = 0.001), severe AGA (OR, 2.360; 95% CI 1.506 to 3.699, P < 0.001) and early-onset AGA (OR, 3.474; 95% CI 2.069 to 5.832, P < 0.001) were all independently associated with the severity of coronary atherosclerosis. The area under the receiver operating characteristic (ROC) curve plotted using severe AGA was 0.601, which is predictive of severe coronary atherosclerosis. Moreover, the presence of severe AGA increases the risk of developing CAD associated with obesity (SI = 1.663, SIM = 1.222, AP = 0.289), diabetes (SI = 2.239, SIM = 1.149, AP = 0.503) and dyslipidemia (SI = 1.062, SIM = 0.646, AP = 0.045). CONCLUSION: This study suggested that AGA is independently associated with CAD in a Han Chinese male population. AGA may be a simple and feasible method for screening CAD and indicative of the severity of coronary atherosclerosis.

Stepped Channels Integrated Lithium-Sulfur Separator via Photoinduced Multidimensional Fabrication of Metal-Organic Frameworks.

Multidimensional fabrication of metal-organic frameworks (MOFs) into multilevel channel integrated devices are in high demanded for Li-S separators. Such separators have advantages in pore-engineering that might fulfill requirements such as intercepting the diffusing polysulfides and improving the Li+ /electrolyte transfer in Li-S batteries. However, most reported works focus on the roles of MOFs as ionic sieves for polysulfides while offering limited investigation on the tuning of Li+ transfer across the separators. A photoinduced heat-assisted processing strategy is proposed to fabricate MOFs into multidimensional devices (e.g., hollow/Janus fibers, double-or triple-layer membranes). For the first time, a triple-layer separator with stepped-channels has been designed and demonstrated as a powerful separator with outstanding specific capacity (1365.0 mAh g-1 ) and cycling performance (0.03 % fading per cycle from 100th to 700th cycle), which is superior to single/double-layer and commercial separators. The findings may expedite the development of MOF-based membranes and extend the scope of MOFs in energy-storage technologies.

Effects of dietary Enteromorpha powder on reproduction-related hormones and genes during the late laying period of Zi geese.

OBJECTIVE: The aim of this study was to investigate the effects of Enteromorpha powder supplementation on reproduction-related hormones and genes in the late laying period of Zi geese. METHODS: A total of 312 (1-year-old) Zi geese with similar laying rate were randomly divided into 2 groups with 6 replicates each, each with 21 female geese and 5 male geese. The control group was fed with a basal diet and the test group was fed with a diet containing 3% Enteromorpha powder. The trial period lasted for 7 weeks. RESULTS: Our results showed that the laying rate was improved in the test group at each week of trial (p<0.01), and the levels of estradiol in serum and prolactin in ovary were increased compared with the control group (p<0.05). CONCLUSION: Based on above results, Enteromorpha powder supplementation at 3% could promote reproductive performance during the late laying period of Zi geese.

Hyperplasia suppressor gene polymorphisms and essential hypertension: a case-control association study in a central Han Chinese population.

BACKGROUND: HSG (hyperplasia suppressor gene, also named Mitofusion-2, Mfn-2) gene polymorphisms have been studied as a candidate gene in essential hypertension, but no clear consensus has been reached in the Chinese population. To systematically explore their possible association, a case-control study was conducted in a central Chinese population. METHODS AND RESULTS: We recruited 402 EH patients and 267 normotensive (NT) control subjects. A total of 6 tag SNPs of HSG gene were genotyped successfully by TaqMan assay. The results showed that genotype distribution and the allelic frequency of rs873457, rs2236384, rs4846085, and rs1474868 in the EH and NT groups were significantly different (P < 0.05), although those of rs2295281 and rs17037564 were not. rs2336384, rs873457, rs4846085 and rs1474868 were also closely associated with EH under the dominant genetic model (P < 0.05). Gender-based subgroup analyses showed that significant associations between rs873457, rs2336384, rs4846085, and rs1474868 and EH could be found in males, but not in females. Haplotype analysis indicated that the C-G-T-T-T-G haplotype was positively correlated with EH. CONCLUSION: Our study suggested that HSG gene polymorphisms were significantly associated with EH in a central Han Chinese population, especially in male subjects.

Concurrent aquaporin-4-positive NMOSD and neurosyphilis: A case report.

Neuromyelitis optica spectrum disorder (NMOSD) is a common neuroinflammatory demyelinating disease associated with aquaporin-4 (AQP4) antibody in the central nervous system. Neurosyphilis is a neurological disease caused by Treponema pallidum infection. NMOSD commonly occurs concurrently with autoimmune diseases. However, they have rarely been associated with infectious diseases. In this report we describe a rare case of concurrent AQP4-positive NMOSD and neurosyphilis. A 60-year-old man was admitted to our hospital with a complaint of progressive weakness in his legs for one month. T2-weighted magnetic resonance images of the spinal cord showed longitudinal extensive lesions at C7-T7. The rapid plasma reagin test and T. pallidum particle agglutination assay performed using patient serum and cerebrospinal fluid (CSF) were positive. Additionally, the AQP4-immunoglobulin (Ig) G was detected in the serum and CSF. The patient's symptom gradually improved after penicillin and methylprednisolone treatment. This case report highlights the possibility of the presence of an infectious disease in patients with NMOSD.

A novel long noncoding RNA FAF inhibits apoptosis via upregulating FGF9 through PI3K/AKT signaling pathway in ischemia-hypoxia cardiomyocytes.

Long noncoding RNAs (lncRNAs) have been increasingly considered to play an important role in the pathological process of various cardiovascular diseases, which often bind to the proximal promoters of the protein-coding gene to regulate the protein expression. However, the functions and mechanisms of lncRNAs in cardiomyocytes have not been fully elucidated. High-throughput RNA sequencing was performed to identify the differently expressed lncRNAs and messenger RNAs (mRNAs) between acute myocardial infarction (AMI) rats and healthy controls. One novel lncRNA FGF9-associated factor (termed FAF) and mRNAs in AMI rats were verified by bioinformatics, real-time polymerase chain reaction or western blot. Moreover, RNA fluorescence in situ hybridization was performed to determine the location of lncRNA. Subsequently, a series of in vitro assays were used to observe the functions of lncRNA FAF in cardiomyocytes. The expression of lncRNA FAF and FGF9 were remarkably decreased in ischemia-hypoxia cardiomyocytes and heart tissues of AMI rats. Overexpression of FAF could significantly inhibit cardiomyocytes apoptosis induced by ischemia and hypoxia. Conversely, knockdown of lncRNA FAF could promote apoptosis in ischemia-hypoxia cardiomyocytes. Moreover, overexpression of lncRNA FAF could also increase the expression of FGF9. Knockdown of the FGF9 expression could promote apoptosis in cardiomyocytes with the insult of ischemia and hypoxia, which was consistent with the effect of lncRNA FAF overexpression on cardiomyocyte apoptosis. Mechanistically, FGF9 inhibited cardiomyocytes apoptosis through activating signaling tyrosine kinase FGFR2 via phosphoinositide 3-kinase/protein kinase B signaling pathway. Thus, lncRNA FAF plays a protective role in ischemia-hypoxia cardiomyocytes and may serve as a treatment target for AMI.

Right-to-left shunt and subclinical ischemic brain lesions in Chinese migraineurs: a multicentre MRI study.

BACKGROUND: Migraine is considered as a risk factor for subclinical brain ischemic lesions, and right-to-left shunt (RLS) is more common among migraineurs. This cross-sectional study assessed the association of RLS with the increased prevalence of subclinical ischemic brain lesions in migraineurs. METHODS: We enrolled 334 migraineurs from a multicentre study from June 2015 to August 2016. Participants were all evaluated using contrast-enhanced transcranial Doppler, magnetic resonance imaging (MRI), and completed a questionnaire covering demographics, the main risk factors of vascular disease, and migraine status. RLS was classified into four grades (Grade 0 = Negative; Grade I = 1 ≤ microbubbles (MBs) ≤ 10; Grade II = MBs > 10 and no curtain; Grade III = curtain). Silent brain ischemic infarctions (SBI) and white matter hyperintensities (WMHs) were evaluated on MRI. RESULTS: We found no significant differences between migraineurs with RLS and migraineurs without RLS in subclinical ischemic brain lesions.SBI and WMHs did not increase with the size of the RLS(p for trend for SBI = 0.066, p for trend for WMHs = 0.543). Furthermore, curtain RLS in migraineurs was a risk factor for the presence of SBI (p = 0.032, OR = 3.47; 95%CI: 1.12-10.76). There was no association between RLS and the presence of WMHs. CONCLUSION: Overall, RLS is not associated with increased SBI or WMHs in migraineurs. However, when RLS is present as a curtain pattern, it is likely to be a risk factor for SBIs in migraineurs. TRIAL REGISTRATION: No. NCT02425696 ; registered on April 21, 2015.

Prevalence and extent of right-to-left shunt on contrast-enhanced transcranial Doppler in Chinese patients with migraine in a multicentre case-control study.

Background The association between RLS and migraine is still debated. The aim of this study is to investigate the prevalence and grade of RLS in Chinese patients with migraine and to evaluate the relationship between RLS and migraine. Methods A multi-center case-control study of contrast-enhanced transcranial Doppler was conducted in 931 consecutive patients with migraine (240 of 931 had migraine with aura and 691 of 931 were in the migraine without aura group) and 282 were healthy adults. Clinical trial no. NCT02425696. Results The prevalence of RLS was 63.8% and 39.9% in the migraine with aura group (MA+) and migraine without aura group (MA-), respectively, significantly higher than that of the healthy group (29.4%, p < 0.001; p < 0.001). The positive rate of large RLS in the MA+ group and MA- group was 32.1% and 16.5%, respectively, significantly higher than healthy group (6.4%, p < 0.001; p < 0.001). There was no difference among groups in terms of positive rate of permanent RLS ( p = 0.704). Conclusion This multi-centre case-control study suggested that there is an association between RLS and migraine with and without aura, especially when the shunt is large.

Ankle-brachial index and brachial-ankle pulse wave velocity are risk factors for ischemic stroke in patients with Type 2 diabetes.

The incidence of ischemic stroke in patients with diabetes is increasing. While brachial-ankle pulse wave velocity (BaPWV) and ankle-brachial index (ABI) are known to be associated with ischemic cardiovascular and cerebrovascular diseases, whether these measures predict the risk of ischemic cerebrovascular disease in diabetic patients remains unclear. 117 patients with type 2 diabetes were enrolled in this study. According to the results of head magnetic resonance imaging, the patients were divided into a diabetes-only group (n = 55) and a diabetes and ischemic stroke group (n = 62). We then performed ABI and BaPWV examinations for all patients. Compared with the diabetes-only group, we found decreased ABI and increased BaPWV in the diabetes and ischemic stroke group. Multivariate logistic regression analyses revealed that BaPWV and ABI were risk factors for ischemic stroke in patients with type 2 diabetes. Our findings indicate that decreased ABI and increased BaPWV are objective indicators of increased risk of ischemic stroke in patients with type 2 diabetes.

Epigallocatechin-3-Gallate Inhibits Matrix Metalloproteinase-9 and Monocyte Chemotactic Protein-1 Expression Through the 67-κDa Laminin Receptor and the TLR4/MAPK/NF-κB Signalling Pathway in Lipopolysaccharide-Induced Macrophages.

BACKGROUND/AIMS: Epigallocatechin-3-gallate (EGCG), a major catechin found in green tea, has been shown to prevent cardiovascular diseases. Previously, Matrix metalloproteinase-9 (MMP-9), monocyte chemotactic protein-1 (MCP-1) and toll-like receptor 4 (TLR4) were confirmed to play an important role in atherosclerosis and plaque instability. Both TLR4 and its negative regulator, Toll-interacting protein (Tollip), could be mediated by EGCG. The present study aimed to examine the effect of physiological concentration of EGCG (1 µM) on the expression of MMP-9 and MCP-1 in lipopolysaccharide (LPS)-induced macrophages and the potential mechanisms underlying its actions. METHODS: The RAW264.7 cell line was used. Western blot was used to determine MCP-1, TLR4, Tollip, Mitogen-activated protein kinase (MAPK) and Nuclear factor-κB (NF-κB) protein expression. MMP-9 activity was assayed by gelatine zymography. The mRNA expression of MMP-9 and MCP-1 was measured by realtime polymerase chain reaction (RT-PCR). RESULTS: EGCG (1 µM) significantly suppressed the expression of MMP-9 and MCP-1 and inhibited MAPK and NF-κB in LPS-induced macrophages but was blocked by Tollip silencing. The expression of LPS-induced MMP-9 and MCP-1 and the phosphorylation of the ERK1/2, P38 and NF-κB pathway proteins decreased after TLR4 siRNA treatment. Furthermore, EGCG mediated TLR4 and Tollip expression through binding to 67-kDa laminin receptor (67LR). CONCLUSION: The results of our study suggested that EGCG (1 µM) suppresses the TLR4/MAPK/NF-κB signalling pathway, decreases the expression of the plaque instability-mediating cytokines MMP-9 and MCP-1, and might prove to be effective in stabilizing atherosclerotic plaque.

Right-to-left shunt detection using contrast-enhanced transcranial Doppler: A comparison of provocation maneuvers between coughing and a modified Valsalva maneuver.

Contrast-enhanced transcranial Doppler (c-TCD) has been used to detect right-to-left shunts (RLS) because it is highly sensitive and cost-effective. The use of provocation maneuvers, such as physiologic maneuvers (e.g., coughing) and the Valsalva maneuver (VM) to transiently increase right atrial pressure and induce RLS increases the sensitivity of RLS detection. In this study, we sought to determine whether coughing is as effective as the VM in aiding the detection of RLS. We evaluated 162 subjects for RLS, using c-TCD under three different conditions: (i) resting state, (ii) coughing, and (iii) modified VM (m-VM), which involved blowing into a tube connected to a sphygmomanometer at 40 mmHg for 10 s. The positive rate of RLS detection with the m-VM was significantly higher than that with coughing. In addition, a difference between the two maneuvers was observed in terms of the degree of RLS seen. The m-VM should be widely used to detect RLS, because it is reliable, standardized, and cost-effective.

Complete genome sequence of a distinct calla lily chlorotic spot virus isolated in mainland China.

The first complete genome sequence of calla lily chlorotic spot virus (CCSV) from Lijiang in northwestern Yunnan Province was obtained using RT-PCR with designed primers. The genome of CCSV isolate LJ-1-Yunnan is tripartite. The small (S) RNA is 3182 nucleotides (nt) in length and encodes a nonstructural protein (NSs, 1383 nt) and a nuclear nucleocapsid (N, 834 nt), separated by an 836-nt intergenic region (IGR). The medium (M) RNA is 4749 nt in length and encodes a nonstructural movement protein (NSm, 930 nt) and a glycoprotein (GnGc, 3,372 nt), also separated by a 349-nt IGR. The large (L) RNA is 8912 nt in length and encodes a predicted RNA-dependent RNA polymerase (RdRp, 8652 nt). The nucleotide sequences of the three viral RNA segments are 92-94 % identical to the published CCSV genome sequence, and the amino acid sequences of the encoded proteins are 96-98 % identical. However, the IGRs of the S and M RNAs are less similar, with 86 and 72 % identity, respectively. Genome sequence comparisons and phylogenetic analysis indicate that the Lijiang CCSV isolate is a unique tospovirus isolate that differs from CCSV isolates in other geographic regions.