Sirtuin 1 alleviates alcoholic liver disease by inhibiting HMGB1 acetylation and translocation.

Background: Alcoholic liver disease (ALD) encompasses a spectrum of liver disorders resulting from prolonged alcohol consumption and is influenced by factors such as oxidative stress, inflammation, and apoptosis. High Mobility Group Box 1 (HMGB1) plays a pivotal role in ALD due to its involvement in inflammation and immune responses. Another key factor, Sirtuin 1 (SIRT1), an NAD+-dependent deacetylase, is known for its roles in cellular stress responses and metabolic regulation. Despite individual studies on HMGB1 and SIRT1 in ALD, their specific molecular interactions and combined effects on disease advancement remain incompletely understood. Methods: Alcohol-induced liver injury (ALI) models were established using HepG2 cells and male C57BL/6 mice. HMGB1 and SIRT1 expressions were assessed at the mRNA and protein levels usingreverse transcription-quantitative polymerase chain reaction, western blot, and immunofluorescence staining. The physical interaction between HMGB1 and SIRT1 was investigated using co-immunoprecipitation and immunofluorescence co-expression analyses. Cellular viability was evaluated using the CCK-8 assay. Results: In patients with clinical ALI, HMGB1 mRNA levels were elevated, while SIRT1 expression was reduced, indicating a negative correlation between the two. ALI models were successfully established in cells and mice, as evidenced by increased markers of cellular and liver damage. HMGB1 acetylation and translocation were observed in both ALI cells and mouse models. Treatment with the SIRT1 agonist, SRT1720, reversed the upregulation of HMGB1 acetylation, nuclear translocation, and release in the ethyl alcohol (EtOH) group. Furthermore, SIRT1 significantly attenuated ALI. Importantly, in vivo binding was confirmed between SIRT1 and HMGB1. Conclusions: SIRT1 alleviates HMGB1 acetylation and translocation, thereby ameliorating ALI.

[Overexpression of miRNA-130a-3p alleviates LPS-induced cardiomyocyte injury by regulating autophagy and apoptosis].

Objective: To investigate the effects of miRNA-130a-3p on autophagy and apoptosis induced by LPS in myocardial cells and its molecular mechanisms. Methods: H9C2 cells were divided into five groups: normal control group, LPS model group, miRNA negative control group miRNA-130a-3p mimics group(overexpression of miRNA-130a-3p) and miRNA-130a-3p mimics + LY294002 group(overexpression of miRNA-130a-3p + PI3K inhibitor). The LPS model group was induced by LPS at a final concentration of 10 µg/ml for 24 h. In the miRNA negative control group and miRNA-130a-3p mimics group, negative contro miRNA or miRNA-130a-3p mimics were transfected into H9C2 cells by lipo3000. After 24 h of culture, LPS was added into the medium for 24 hours. In the miRNA -130A-3P mimics + LY294002 group, miRNA -130A-3P mimics was transfected into H9C2 cells by using lipo3000, and LY294002 at a final concentration of 10 µmol/L was added to the culture medium for 24 h, followed by LPS at a concentration of 10 µg/ml for 24 h. The expression of miRNA-130a-3p mRNA in cells was detected by RT-qPCR. The CCK-8 assay was used to detect the cell viability. The contents of TNF-α, IL-6 and IL-1ß were detected by ELISA assay. The contents of SOD and LDH in cell culture medium were detected by colorimetry. Western blot was used to detect the protein expressions of p-PI3K, p-AKT, Bax, Bcl-2, cleaved-caspase-3, LC3 and p62. Results: The results showed that the levels of miRNA-130a-3p mRNA, p-PI3K protein and p-AKT protein in LPS model cells were significantly lower than those in normal control group(P<0.01), and the expressions of p-PI3K, p-AKT protein in miRNA-130a-3p mimics group were increased significantly compared with LPS group(P<0.01,P<0.05). Compared with normal control group, the cell viability was decreased significantly and the contents of TNF-α, IL-6, IL-1ß and LDH were increased significantly(P<0.01), the contents of SOD was decreased significantly in LPS group(P<0.01). The protein expression levels of Bax, cleaved-caspase-3 and p62 were increased significantly, while the expression level of Bcl-2 and LC3II/I ratio were decreased significantly in LPS group(P<0.01). miRNA-130a-3p mimics could increase the cell viability, decrease the contents of TNF-α, IL-6, IL-1ß and LDH(P<0.01,P<0.05), increase the contents of SOD(P<0.05), decrease the expressions of Bax, cleaved caspase-3, p62(P<0.01), promote the expression of Bcl-2(P<0.01) and increase the ratio of LC3II/I(P<0.05). Compared with miRNA-130a-3p mimics group, LY294002 reversed the effects of miRNA-130a-3p mimics on cells. Conclusion: Overexpression miRNA-130a-3p could partly promote autophagy and inhibit cell apoptosis by activating PI3K/AKT signaling pathway to alleviate LPS-induced myocardial injury.

Subclavian artery stenting via bilateral radial artery access: Four case reports.

BACKGROUND: Subclavian artery stenosis refers to the stenosis in the lumen caused by the presence of plaque or thrombus in the subclavian artery. It is a common problem in endovascular interventions. In fact, conventional subclavian artery stenting via the femoral artery approach is effective and safe. Nevertheless, because femoral artery puncture is not easy to stop bleeding, it requires longer femoral artery compression or more expensive hemostatic materials, such as staplers. Patients need to be catheterized and bedridden for a longer time, which may lead to many complications, such as pseudoaneurysm. CASE SUMMARY: Herein, we reported a new interventional therapy of subclavian artery. From March 1, 2020 to August 31, 2021, we operated on four patients with subclavian artery stenting via bilateral radial artery access. CONCLUSION: After reviewing four cases of successful placement of clavicular artery stents via bilateral radial arteries, we concluded that bilateral radial artery approach is feasible. Clavicular artery stenting is safe, effective, and timesaving. It is an excellent alternative to the traditional femoral artery procedure, with few complications and high comfort degree.

Tirofiban combined with heparin's effect and safety in the treatment of mild to moderate acute ischemic stroke.

Tirofiban can be used to treat patients with acute ischemic stroke (AIS), this study was to evaluate the efficacy and safety of tirofiban combined with heparin in the treatment of mild to moderate AIS. A total of 98 patients with mild to moderate AIS randomly were divided into 2 groups within 48 h: the treatment group treated with tirofiban and, and the control group treated with aspirin + clopidogrel. The treatment group was given the same scheme as the control group after the treatment of tirofiban combined with heparin for 48 h. It was found that, compared with the control group, a significant decreased National Institute of Health stroke scale (NIHSS) was found in 48 h and 14 d, especially to the Barthel index (BI) in the treatment group (P < 0.05). Furthermore, Modified Rankin Scale (MRS, ≤2) in the treatment group was significantly upregulated in 90 d (P < 0.05). However, there were no significant differences in the adverse drug reactions between the two groups. It was indicated that nerve function and long-term prognosis in patients undergoing heparin for mild to moderate AIS were obviously improved than the control group.

Predictive value of transcranial doppler ultrasound for cerebral small vessel disease in elderly patients.

OBJECTIVE: To investigate the predictive value of transcranial Doppler (TCD) ultrasound for cerebral small vessel disease in elderly patients. METHODS: Transcranial Doppler ultrasound and magnetic resonance imaging (MRI) were performed on 184 elderly patients with cerebral small vessel disease. The relationship of clinical characteristics and TCD ultrasound parameters with severe white matter lesions (WMLs) in MRI were investigated by univariate analysis and multivariate analysis. RESULTS: The univariate analysis showed that age, left middle cerebral artery (MCA) mean flow velocity, right MCA mean flow velocity and mean MCA pulsatility index were significantly correlated with severe WMLs (p < 0.05). The multivariate logistic regression analysis showed that only age (odds ratio: 1.21; 95%CI: 1.10-1.36; p < 0.01) and MCA pulsatility index (dominance ratio: 1.13; 95%CI: 1.06-1.80; p = 0.02) were significantly correlated with severe WMLs. The analysis of TCD ultrasound parameters showed that when the cut-off for MCA pulsatility index was 1.04, it could identify severe WMLs. The area under the curve was 0.70 (95%CI: 0.60-0.80). The sensitivity and specificity were 63.0% and 72.0%, respectively. The positive and negative predictive values were 35.4% and 86.6%, respectively. CONCLUSION: The MCA pulsatility index in TCD ultrasound is significantly correlated with severe WMLs; and TCD ultrasound can guide selective MRI for the detection of WMLs.

Predictive value of transcranial doppler ultrasound for cerebral small vessel disease in elderly patients / Valor preditivo do ultrassom doppler transcraniano para doença de pequenos vasos em pacientes idosos

ABSTRACT Objective: To investigate the predictive value of transcranial Doppler (TCD) ultrasound for cerebral small vessel disease in elderly patients. Methods: Transcranial Doppler ultrasound and magnetic resonance imaging (MRI) were performed on 184 elderly patients with cerebral small vessel disease. The relationship of clinical characteristics and TCD ultrasound parameters with severe white matter lesions (WMLs) in MRI were investigated by univariate analysis and multivariate analysis. Results: The univariate analysis showed that age, left middle cerebral artery (MCA) mean flow velocity, right MCA mean flow velocity and mean MCA pulsatility index were significantly correlated with severe WMLs (p < 0.05). The multivariate logistic regression analysis showed that only age (odds ratio: 1.21; 95%CI: 1.10-1.36; p < 0.01) and MCA pulsatility index (dominance ratio: 1.13; 95%CI: 1.06-1.80; p = 0.02) were significantly correlated with severe WMLs. The analysis of TCD ultrasound parameters showed that when the cut-off for MCA pulsatility index was 1.04, it could identify severe WMLs. The area under the curve was 0.70 (95%CI: 0.60-0.80). The sensitivity and specificity were 63.0% and 72.0%, respectively. The positive and negative predictive values were 35.4% and 86.6%, respectively. Conclusion: The MCA pulsatility index in TCD ultrasound is significantly correlated with severe WMLs; and TCD ultrasound can guide selective MRI for the detection of WMLs.

RESUMO Objetivo: Investigar o valor preditivo do ultrassom de Doppler transcraniano (TCD) para doença de pequenos vasos (SVD) em pacientes idosos. Métodos: ultrassonografia de TCD e ressonância magnética (RM) foram realizadas em 184 idosos portadores de SVD cerebral. As relações das características clínicas e os parâmetros ultrassonográficos do TCD com lesão grave de substância branca (WML) no desempenho da RM foram investigados por análise univariada e análise multivariada. Resultados: A análise univariada mostrou que, a idade, a velocidade média de fluxo (MFV) da artéria média cerebral (MCA) esquerda, a MFV da MCA direita e o índice de pulsatilidade (PI) médio estiveram significativamente relacionados à WML grave (P <0,05). A análise de regressão logística multivariada mostrou que apenas a idade (razão de chances: 1,21; IC95%: 1,10-1,36; P <0,01) e o PI da MCA (razão de dominância: 1,13; IC 95%: 1,06-1,80; P = 0,02) estiveram significativamente relacionados a WML grave. A análise dos parâmetros ultrassonográficos do TCD mostrou que, quando o ponto de corte do IP do MCA foi 1,04, ele pôde identificar à WML grave. A área sob a curva foi de 0,70 (IC 95%: 0,60-0,80). A sensibilidade e especificidade foram de 63,0% e 72,0%, respectivamente. Os valores preditivos positivos e negativos foram de 35,4% e 86,6%, respectivamente. Conclusão: O PI da MCA na ultrassonografia do TCD está significativamente relacionado à WML grave. A ultrassonografia TCD pode orientar a ressonância magnética seletiva para detecção da WML.

Knockdown of miR-429 Attenuates Aß-Induced Neuronal Damage by Targeting SOX2 and BCL2 in Mouse Cortical Neurons.

Accumulation of amyloid-ß peptide (Aß) and massive neuronal death due to apoptosis were the essential steps in the pathogenesis of Alzheimer's disease (AD). MiR-429 was reported to play an important role in the pathogenesis of AD. However, the detailed function and underlying molecular mechanism of miR-429 in the pathogenesis of AD remain elusive. Cortical neurons were stimulated with 20 µM of Aß25-35 for 24 h to construct AD model in vitro. qRT-PCR assay was used to detect the expression of miR-429, and qRT-PCR or western blot analysis were performed to assess the levels of Sex-determining region Y-box 2 (SOX2) and B cell lymphoma-2 protein (BCL2) at mRNA or proteins levels in the AD mouse model and Aß-induced treated cortical neurons. Luciferase reporter assay and western blot analysis were used to confirm the potential targets of miR-429. CCK-8 assay, flow cytometry analysis, and caspase3 activity assay were used to measure cell viability, cell apoptosis capacity and caspase3 activity, respectively. MiR-429 was upregulated and SOX2 and BCL2 were downregulated in the AD mouse model and Aß-induced mouse cortical neurons. MiR-429 knockdown attenuated Aß-induced cytotoxicity in mouse cortical neurons. SOX2 and BCL2 were direct targets of miR-429. Moreover, anti-miR-429-mediated neuroprotective effect was abated by the restoration of SOX2 or BCL2 expression. Knockdown of miR-429 might attenuate Aß-induced cytotoxicity by targeting SOX2 and BCL2 in mouse cortical neurons, providing a novel prospect in AD therapy.

[Effect of different blood pressure control targets within 48 h after hypertensive cerebral hemorrhage on hematoma enlargement and prognosis].

OBJECTIVE: To study the effect of different blood pressure control targets on hematoma enlargement and prognosis in patients within 48 h after hypertensive cerebral hemorrhage (HCH). METHODS: Between January, 2013 and July, 2016, 102 patients with HCH were randomized into group A (51 cases) and group B (51 cases) with different systolic blood pressure (SBP) control targets within 48 h. The patients in group A were given early active antihypertensive treatment with SBP control target of 130-140 mm Hg; those in group B received standard antihypertensive treatment with SBP control target of 170-180 mm Hg. The changes in the volume of hematomas and the patients' prognosis were compared between the two groups. RESULTS: After 48 h of treatment, SBP, hematoma volume and the National Institutes of Health Stroke Scale (NIHSS) score were significantly lower and Glasgou Coma Scale (GCS) score was significantly higher in group A than in group B (P<0.01 or 0.05). After 30 days of treatment, the patients in group A showed significantly better indicators of treatment efficacy than those in group B (Z=2.331, P=0.020). The mortality rate was lower in group A than in group B, but the difference was not statistically significant (Χ2=2.772, P=0.096). CONCLUSION: Early active antihypertensive treatment is safe and feasible in patients with HCH and can reduce the enlargement of the hematomas, alleviate deterioration of neurological function, and improve the prognosis of the patients.

Basilar artery bending length, vascular risk factors, and pontine infarction.

BACKGROUND: Patients exhibiting basilar artery (BA) curvature (not dolichoectasia) are at an increased risk of posterior circulation ischemic stroke. In this study, pontine infarction patients were analyzed to assess the effect of BA bending length (BL) together with other vascular factors on pontine stroke risk. METHODS: Acute pontine infarction patients were divided into BA bending and non-BA bending groups by magnetic resonance angiography (MRA). Patients with BA bending who reported symptoms of dizziness or vertigo but who had not suffered brain infarction constituted the control group. The diameter of the vertebral artery (VA) and BL were measured using MRA. Based on the bilateral VA diameter data in vertebral artery-dominant (VAD) patients, the study participants were divided into three classes for VA diameter: class one, 0.30-0.80 mm (20 cases); class two, 0.81-1.37 mm (20 cases); and class three, 1.38-3.24 mm (20 cases). The measured BL in VAD cases allowed division of patients into three levels for BL: level one, 1.02-2.68 mm (21 cases); level two, 2.69-3.76 mm (20 cases); and level three, 3.77-7.25 mm (19 cases). Vascular risk factors were compared among the three groups. Correlations of BL and VA diameter differences were studied, and multivariate analysis was applied to search for predictors of ischemic stroke in BA bending patients. RESULTS: Among BA bending, non-BA bending, and control groups, VA dominance (VAD) proved to be a significant differentiator. For all three groups, a patient age of ≥ 65 years, the occurrence of hypertension, smoking, high homocysteine levels, high cholesterol, and a history of type 2 diabetes, were all statistically significant factors (P<0.05). After adjusting for other relevant factors, multivariate analysis shows that BL of level 3 was an independent risk factor for pontine infarction (OR=2.74; 95% CI, 1.27 to 4.48). Both BL and diameter differences between the VAs were positively correlated with risk with statistical significance (r=0.769, P<0.001). CONCLUSIONS: Both BL and diameter differences between the VAs are positively correlated with the risk of pontine infarction. When BA bending was coupled with other vascular risk factors, the probability of pontine infarction increased. BA bending with a BL greater than 3.77 mm was an independent predictor of pontine infarction.

Evaluation of vertebrobasilar artery changes in patients with benign paroxysmal positional vertigo.

The aim of this study was to investigate vertebrobasilar artery (VBA) lesions in elderly patients with benign paroxysmal positional vertigo (BPPV) by magnetic resonance angiography. VBA lesions in patients older than 65 years of age with BPPV were prospectively investigated by magnetic resonance angiography. Vascular risk factors, blood vessel changes, and vertigo severity were recorded. Age-matched individuals without BPPV were included in the control group. Of 126 patients screened for this study, 104 were included. Relevant comorbidities included diabetes (12 patients), hypertension (23 patients), and dyslipidemia (20 patients). Findings included left or right vertebral artery (VA) stenosis or occlusion (22 patients, 21.2%), VA tortuosity (25 patients, 24.0%), VA dominance (20 patients, 19.2%), basilar artery (BA) stenosis or occlusion (nine patients, 8.6%), and BA tortuosity (12 patients, 11.5%). These abnormal vessels differed between BPPV patients and the control group (all P<0.05). The severity of Vertigo did not differ between the abnormal VA and abnormal BA groups (P>0.05), but did differ between the normal group and the abnormal VA or BA group (P<0.05). Vertigo severity correlated with VA stenosis or occlusion, VA dominance, and unilateral or bilateral VA tortuosity. VBA tortuosity and VA dominance were common in BPPV patients and may contribute toward BPPV.

Aldosterone synthase gene (CYP11B2) -344C/T polymorphism contributes to the risk of recurrent cerebral ischemia.

BACKGROUND: Accumulating evidence suggests that CYP11B2 rs1799998 (-344C/T) polymorphism is independently associated with an increased risk of stroke. Our aim was to determine whether -344C/T also predisposes to recurrent cerebral ischemia following in patients with symptomatic intracranial atherosclerosis disease (ICAD). METHODS: Genotypes of the CYP11B2 -344C/T polymorphism were determined by polymerase chain reaction-restriction fragment length polymorphism. A total of 208 ICAD patients were enrolled and underwent a long-term clinical follow-up to detect the recurrent cerebral ischemia. RESULTS: During a median follow-up time of 35 months, 40 recurrent strokes (19.2%) were documented. Kaplan-Meier and multivariable Cox regression analyses adjusted for age, gender, and other cardiovascular risk factors identified that the presence of the TT genotype within the CYP11B2 -344C/T polymorphism was associated with an increased risk of 1.98-fold for recurrent cerebral ischemia (the hazard ratio 1.98, 95% confidence interval 1.16-3.41; p=0.01). CONCLUSIONS: Our findings suggest that the -344C/T polymorphism of the CYP11B2 gene confers an increased risk of recurrent cerebral ischemia.