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Ligustilide, a natural phthalide mainly derived from chuanxiong rhizomes and Angelica Sinensis roots, possesses anti‐inflammatory activity, particularly in the context of the nervous system. However, its application is limited because of its unstable chemical properties. To overcome this limitation, ligusticum cycloprolactam (LIGc) was synthesized through structural modification of ligustilide. In this study, we combined network pharmacological methods with experimental verification to investigate the anti‐neuroinflammatory effects and mechanisms of ligustilide and LIGc. Based on our network pharmacology analysis, we identified four key targets of ligustilide involved in exerting an anti‐inflammatory effect, with the nuclear factor (NF)‐κB signal pathway suggested as the main signalling pathway. To verify these results, we examined the expression of inflammatory cytokines and inflammation‐related proteins, analysed the phosphorylation level of NF‐κB, inhibitor of κBα (IκBα) and inhibitor of κB kinase α and β (IKKα+β), and evaluated the effect of BV2 cell‐conditioned medium on HT22 cells in vitro. Our results, demonstrate for the first time that LIGc can downregulate the activation of the NF‐κB signal pathway in BV2 cells induced by lipopolysaccharide, suppress the production of inflammatory cytokines and reduce nerve injury in HT22 cells mediated by BV2 cells. These findings suggest that LIGc inhibits the neuroinflammatory response mediated by BV2 cells, providing strong scientific support for the development of anti‐inflammatory drugs based on natural ligustilide or its derivatives. However, there are some limitations to our current study. In the future, further experiments using in vivo models may provide additional evidence to support our findings. [ABSTRACT FROM AUTHOR]

Up to date, series of studies on ischemic stroke had resulted in inconsistent conclusion. In this study, we aimed to evaluate which specific genes were associated with increased predisposition to stroke in a Chinese population. To identify the specific genes and polymorphisms associated with predisposition to ischemic stroke, we performed high throughput sequenom based next-generation sequencing from 743 patient with history of ischemic stroke. Variants SNPs in nNOS, renalase, MTHFR, CELSR1 and XYLB genes were found significantly associated with IS, thus suggesting involvement of these loci to IS in Chinese patients. Because of different locations on chromosomes, haplotype analyses were not feasible. Our results demonstrate the top level genes that are related to normal vascular physiology, viz. genes of nitric oxide synthesis, endothelial health and smooth muscle biology. Further validation studies are awaited. © 2015 IUBMB Life, 67(3):170-174, 2015 [ABSTRACT FROM AUTHOR]

Background and Aims Methods Results Conclusion Sleep‐disordered breathing (SDB) and nocturnal hypoxemia were known to be present in patients with chronic thromboembolic pulmonary hypertension (CTEPH), but the difference between SDB and nocturnal hypoxemia in patients who have chronic thromboembolic pulmonary disease (CTEPD) with or without pulmonary hypertension (PH) at rest remains unknown.Patients who had CTEPH (n = 80) or CTEPD without PH (n = 40) and who had undergone sleep studies from July 2020 to October 2022 at Shanghai Pulmonary Hospital were enrolled. Nocturnal mean SpO2 (Mean SpO2) <90% was defined as nocturnal hypoxemia, and the percentage of time with a saturation below 90% (T90%) exceeding 10% was used to evaluate the severity of nocturnal hypoxemia. Logistic and linear regression analyses were performed to investigate the difference and potential predictor of SDB or nocturnal hypoxemia between CTEPH and CTEPD without PH.SDB was similarly prevalent in CTEPH and CTEPD without PH (P = 0.104), both characterised by obstructive sleep apnoea (OSA). Twenty‐two patients with CTEPH were diagnosed with nocturnal hypoxemia, whereas only three were diagnosed with CTEPD without PH (P = 0.021). T90% was positively associated with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance in patients with CTEPH and CTEPD without PH (P < 0.001); T90% was also negatively related to cardiac output in these patients. Single‐breath carbon monoxide diffusing capacity, sex and mPAP were all correlated with nocturnal hypoxemia in CTEPH and CTEPD without PH (all P < 0.05).Nocturnal hypoxemia was worse in CTEPD with PH; T90%, but not SDB, was independently correlated with the hemodynamics in CTEPD with or without PH. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effectiveness and safety of an oral sequential triple combination therapy with selexipag after dual combination therapy with endothelin receptor antagonist (ERA) and phosphodiesterase‐5 inhibitor (PDE5I)/riociguat in pulmonary arterial hypertension (PAH) patients. A total of 192 PAH patients from 10 centers had received oral sequential selexipag therapy after being on dual‐combination therapy with ERA and PDE5i/riociguat for a minimum of 3 months. Clinical data were collected at baseline and after 6 months of treatment. The study analyzed the event‐free survival at 6 months and all‐cause death over 2 years. At baseline, the distribution of patients among the risk groups was as follows: 22 in the low‐risk group, 35 in the intermediate‐low‐risk group, 91 in the intermediate‐high‐risk group, and 44 in the high‐risk group. After 6 months of treatment, the oral sequential triple combination therapy resulted in reduced NT‐proBNP levels (media from 1604 to 678 pg/mL), a decline in the percentage of WHO‐FC III/IV (from 79.2% to 60.4%), an increased in the 6MWD (from 325 ± 147 to 378 ± 143 m) and a rise in the percentage of patients with three low‐risk criteria (from 5.7% to 13.5%). Among the low‐risk group, there was an improvement in the right heart remodeling, marked by a decrease in right atrium area and eccentricity index. The intermediate‐low‐risk group exhibited significant enhancements in WHO‐FC and tricuspid annular plane systolic excursion. For those in the intermediate‐high and high‐risk groups, there were marked improvements in activity tolerance, as reflected by WHO‐FC and 6MWD. The event‐free survival rate at 6 months stood at 88%. Over the long‐term follow‐up, the survival rates at 1 and 2 years were 86.5% and 86.0%, respectively. In conclusion, the oral sequential triple combination therapy enhanced both exercise capacity and cardiac remodeling across PAH patients of different risk stratifications. [ABSTRACT FROM AUTHOR]

The specialized pro‐resolving lipid mediator maresin 1 (MaR1) is involved in the resolution phase of tissue inflammation. It was hypothesized that exogenous administration of MaR1 would attenuate abdominal aortic aneurysm (AAA) growth in a cytokine‐dependent manner via LGR6 receptor signaling and macrophage‐dependent efferocytosis of smooth muscle cells (SMCs). AAAs were induced in C57BL/6 wild‐type (WT) mice and smooth muscle cell specific TGF‐β2 receptor knockout (SMC‐TGFβr2−/−) mice using a topical elastase AAA model. MaR1 treatment significantly attenuated AAA growth as well as increased aortic SMC α‐actin and TGF‐β2 expressions in WT mice, but not SMC‐TGFβr2−/− mice, compared to vehicle‐treated mice. In vivo inhibition of LGR6 receptors obliterated MaR1‐dependent protection in AAA formation and SMC α‐actin expression. Furthermore, MaR1 upregulated macrophage‐dependent efferocytosis of apoptotic SMCs in murine aortic tissue during AAA formation. In vitro studies demonstrate that MaR1‐LGR6 interaction upregulates TGF‐β2 expression and decreases MMP2 activity during crosstalk of macrophage‐apoptotic SMCs. In summary, these results demonstrate that MaR1 activates LGR6 receptors to upregulate macrophage‐dependent efferocytosis, increases TGF‐β expression, preserves aortic wall remodeling and attenuate AAA formation. Therefore, this study demonstrates the potential of MaR1‐LGR6‐mediated mitigation of vascular remodeling through increased efferocytosis of apoptotic SMCs via TGF‐β2 to attenuate AAA formation. [ABSTRACT FROM AUTHOR]

Abdominal aortic aneurysm (AAA) formation is characterized by inflammation, leukocyte infiltration, and vascular remodeling. Resolvin D1 (RvD1) is derived from ω‐3 polyunsaturated fatty acids and is involved in the resolution phase of chronic inflammatory diseases. The aim of this study was to decipher the protective role of RvD1 via formyl peptide receptor 2 (FPR2) receptor signaling in attenuating abdominal aortic aneurysms (AAA). The elastase‐treatment model of AAA in C57BL/6 (WT) mice and human AAA tissue was used to confirm our hypotheses. Elastase‐treated FPR2−/− mice had a significant increase in aortic diameter, proinflammatory cytokine production, immune cell infiltration (macrophages and neutrophils), elastic fiber disruption, and decrease in smooth muscle cell α‐actin expression compared to elastase‐treated WT mice. RvD1 treatment attenuated AAA formation, aortic inflammation, and vascular remodeling in WT mice, but not in FPR2−/− mice. Importantly, human AAA tissue demonstrated significantly decreased FPR2 mRNA expression compared to non‐aneurysm human aortas. Mechanistically, RvD1/FPR2 signaling mitigated p47phox phosphorylation and prevented hallmarks of ferroptosis, such as lipid peroxidation and Nrf2 translocation, thereby attenuating HMGB1 secretion. Collectively, this study demonstrates RvD1‐mediated immunomodulation of FPR2 signaling on macrophages to mitigate ferroptosis and HMGB1 release, leading to resolution of aortic inflammation and remodeling during AAA pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Takayasu arteritis (TAK) is a rare large vessel vasculitis, and epidemiological data on TAK are lacking in China. Thus, we designed this study to estimate the TAK prevalence and incidence in residential Shanghai, China. Methods: Data on diagnosed TAK cases aged over 16 years were retrieved from 22 tertiary hospitals in Shanghai through hospital electronic medical record systems between January 1, 2015 and December 31, 2017 to estimate the prevalence and incidence. A systematic literature review based on searches in PubMed, Ovid‐Medline, Excerpta Medica Database (EMBASE), Web of Science, and China National Knowledge Infrastructure (CNKI) was performed to summarize TAK distribution across the world. Results: In total 102 TAK patients, with 64% female, were identified. The point prevalence (2015‐2017) was 7.01 (95% CI 5.65‐8.37) cases per million, and the mean annual incidence was 2.33 (1.97‐3.21) cases per million. The average age of TAK patients was 44 ± 16 years, with the highest prevalence (11.59 [9.23‐19.50] cases per million) and incidence (3.55 [0.72 3.74] cases per million) in the 16 to 34 years population. Seventeen reports were included in the system review, showing that the epidemiology of TAK varied greatly across the world. The incidence and prevalence were both relatively higher in Asian countries, with the prevalence ranging 3.3‐40 cases per million and annual incidence ranging 0.34‐2.4 cases per million. Conclusions: The prevalence and incidence of TAK in Shanghai was at moderate to high levels among the previous reports. The disease burden varied globally among racial populations. [ABSTRACT FROM AUTHOR]

Abstract: Stimulation of mice dorsal root ganglion neurons (DRGNs) activity by human pancreatic cancer (PanCa) cell line Mia PaCa-2 and its potential molecule mechanism has been investaged. DRGNs were cultured alone or along with the MIA PaCa-2. The effects of MIA PaCa-2 to DRGNs were determined by neurofilament (NF) immunocytochemical and Nissl staining. ELISA was used to detect the concentration of insulin-like growth factor-1 (IGF-1) in the culture supernatant. Cyton size, neurite outgrowth and neuronal activity in the experimental group were greater than in the control groups. However, the concentration of IGF-1 in the supernatants was not significantly different from those in the blank and non-cultured medium groups. In the presence of MIA PaCa-2 cell line, cyton size, neurite outgrowth and neuronal activity were enhanced, which may provide more routes for the invasion of cancer cells along nerves. [Copyright &y& Elsevier]

Background: Acute vasoreactivity testing (AVT) which reflects the compliance of the pulmonary vascular bed has been proven to be of prognostic value. The purpose of the present study is to explore the sex differences of hemodynamics during the AVT and their impact on event‐free survival in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Methods: Eighty‐six patients underwent a right heart catheterization and AVT at Shanghai Pulmonary Hospital from February 2009 to February 2018. Univariate and multiple stepwise regression analysis were performed to determine the predictors of independent event‐free survival, and receiver operating characteristic curve was plotted to determine the cut‐off value of independent parameters in CTEPH. Results: There were no significant differences in both demographics and hemodynamics between male and female patients with CTEPH. Except ΔPVR/PVR showed a significantly higher difference in female than male patients (P = 0.034). Male patients had higher mRAP of pre‐ and post‐AVT than female patients in the event‐free subgroup, while, female patients showed higher PVR of pre‐AVT than male patients in the event subgroup (P < 0.05). The mRAP and SvO2 were independent predictors of event‐free survival in female patients both before and after the AVT, whereas ΔSvO2 was an independent predictor of event‐free survival in male patients. Conclusion: Hemodynamics during the AVT varied between male and female patients with CTEPH. Both sexes displayed unique hemodynamic responses that were independently able to predict event‐free survival. Therefore, better estimates of prognosis in CTEPH can be made when sex differences are also taken into consideration. [ABSTRACT FROM AUTHOR]

Abdominal aortic aneurysm (AAA) formation is characterized by inflammation, leukocyte infiltration, and vascular remodeling. This study investigates the role of TRPV4 channels, which are transmembrane calcium channels that can regulate vascular tone, in modulating AAA formation. The elastase‐treatment model of AAA in C57BL6 (WT) mice and Angiotensin II treatment model in ApoE−/− mice were used to confirm our hypotheses. The administration of a specific TRPV4 antagonist, GSK2193874, in elastase‐treated WT mice and in AngII‐treated ApoE−/− mice caused a significant attenuation of aortic diameter, decrease in pro‐inflammatory cytokines (IL‐1β, IL‐6, IL‐17, MCP‐1, MIP‐1α, MIP‐2, RANTES, and TNF‐α), inflammatory cell infiltration (CD3 + T cells, macrophages, and neutrophils), elastic fiber disruption, and an increase in smooth muscle cell α‐actin expression compared to untreated mice. Similarly, elastase‐treated TRPV4−/− mice had a significant decrease in AAA formation, aortic inflammation, and vascular remodeling compared to elastase‐treated WT mice on Day 14. In vitro studies demonstrated that the inhibition of TRPV4 channels mitigates aortic smooth muscle cell‐dependent inflammatory cytokine production as well as decreases neutrophil transmigration through aortic endothelial cells. Therefore, our results suggest that TRPV4 antagonism can attenuate aortic inflammation and remodeling via decreased smooth muscle cell activation and neutrophil transendothelial migration during AAA formation. [ABSTRACT FROM AUTHOR]

Background: Acute myocardial infarction (AMI) occurred in the heart, which underwent long‐term ischemia, and was mainly caused by hypoxia. Recently, studies have uncovered the participation of long noncoding RNAs (lncRNAs) in the pathogenesis of heart disease. Here, we planned to probe the role and molecular basis of ANRIL in hypoxia‐induced H9c2 cell injury. Methods: Trypan blue exclusion assay and Transwell and flow cytometry assays were conducted to assess hypoxia‐induced injury by determining the viability, migration, invasion, and apoptosis of H9c2 cells in different conditions, respectively. Gene expressions were evaluated by quantitative real‐time polymerase chain reaction or western blot analysis as needed. RNA immunoprecipitation and luciferase reporter assays were applied to confirm the associations among genes. Results: ANRIL expression was dramatically enhanced in hypoxia‐injured H9c2 cells, and silencing ANRIL aggravated hypoxia‐induced H9c2 cell injury. ANRIL positively regulated sirtuin 1 (SIRT1) expression via competitively binding with miR‐7‐5p. Moreover, inhibition of miR‐7‐5p counteracted ANRIL depletion‐exacerbated injury in hypoxic H9c2 cells, meanwhile, forced SIRT1 expression attenuated the injury‐promoting effect of miR‐7‐5p upregulation on hypoxic H9c2 cells. Conclusion: Our findings disclosed that ANRIL plays a protective part in hypoxia‐induced H9c2 cell injury via modulating the miR‐7‐5p/SIRT1 axis, suggesting the great potential of ANRIL as a protective target for AMI. [ABSTRACT FROM AUTHOR]

Objective: This study intended to explore the relation between heart rate recovery at 1 minutes (HRR1) during the recovery phase of cardiopulmonary exercise test (CPET) and exercise capacity in female systemic lupus erythematosus associated pulmonary arterial hypertension (SLE‐PAH) patients. Methods: Twenty‐one female SLE‐PAH patients underwent right heart catheterization (RHC), pulmonary function test (PFT) and CPET. Forty‐two healthy subjects matched with SLE‐PAH patients in age, sex and BMI were recruited as a control group. The correlations between HRR1 with clinical and CPET parameters were performed. Results: Peak HR, ΔHR, HRR1, Peak HR‐warm HR1min, Peak HR‐warm HR2min and CR were significantly lower in SLE‐PAH than in controls (P < .01). Increased incidence of CRI was seen in SLE‐PAH. Except for the Peak PETO2, which was higher in controls, all other CPET parameters were lower in SLE‐PAH. SLE‐PAH patients with HRR1 ≥ 16 had longer 6MWD, lower NT‐proBNP, better percent of predicted gas transfer index or diffusing capacity for carbon monoxide (DLco% pred) as well as better CO and CI. Peak HR, ΔHR, HRR1, Peak HR‐warm HR1min, Peak HR‐warm HR2min, CR, Peak Load, Peak VO2, Peak PETCO2, OUEP and OUES were lower and duration of exercise was shorter in patients with HRR1 < 16. HRR1 had positive correlation with 6MWD, DLco% pred, CO, CI and some key CPET parameters. Conclusions: HRR1 is an easily obtained auxiliary parameter in SLE‐PAH patients to reflect an altered autonomic tone. SLE‐PAH patients with HRR1 < 16 have more severe hemodynamics, worse clinical findings and marked oxygen uptake inefficiency than those with HRR1 ≥ 16. [ABSTRACT FROM AUTHOR]

The aim of the current study was to investigate the effects and the underlying mechanisms of troxerutin on myocardial cell apoptosis during ischemia‐reperfusion (I/R) injury. Hypoxia/reoxygenation (H/R) model in neonatal rat cardiomyocytes, and I/R model in rats, were established following troxerutin preconditioning. The quantitative real‐time polymerase chain reaction analysis was performed to examine the messenger RNA miR‐146a‐5p expression in cardiomyocytes and myocardial tissues. Hemodynamic parameters and serum creatine kinase, lactate dehydrogenase, tumor necrosis factor‐α, and interleukin‐10 were evaluated. Infarct size was examined by 2,3,5‐triphenyltetrazolium chloride staining. Besides, myocardial apoptosis was detected by terminal deoxynucleotidyl transferase (dUTP) nick end labeling (TUNEL) assay. Western blot analysis was performed to determine the protein levels of caspase‐3, Bax, and Bcl‐2. The results showed that, troxerutin decreased rat cardiomyocyte apoptosis during H/R injury. Furthermore, the antiapoptotic effect of troxerutin against I/R injury was mediated by miR‐146a‐5p downregulation. In vivo experiments suggested that troxerutin alleviated myocardial I/R injury in rats via inhibition of miR‐146a‐5p. In conclusion, troxerutin exerted cardioprotective effects during I/R injury by downregulating miR‐146a‐5p. In this study, we examined for the first time, the underlying mechanism through which troxerutin exert neuroprotective effect via regulating specific microRNAs. We concluded that, troxerutin alleviated myocardial ischemia‐reperfusion injury by downregulating miR‐146a‐5p. [ABSTRACT FROM AUTHOR]

Background: Pulmonary hypertension patients with mean pulmonary artery pressure (mPAP) ≥ 25 mm Hg had impaired cardiopulmonary exercise testing (CPET). Borderline mean pulmonary pressures (boPAP; 21‐24 mm Hg) represent early pulmonary vasculopathy. The CPET characteristics of boPAP are a matter of discussion. We aimed to determine the CPET profile of such borderline hemodynamics. Methods: A matched case‐control study was conducted on consecutive boPAP patients at the Shanghai Pulmonary Hospital between Jan 2012 and Jan 2017. Hemodynamics, echocardiography, the pulmonary function test (PFT) and CPET parameters were compared between boPAP patients and normal mPAP patients which were matched 1:1 by sex and age. Conditional logistic regression analysis was performed to determine the efficacy of CPET in detecting boPAP. Results: A total of 48 patients underwent RHC and CPET (24 Normal, 24 boPAP). There were no differences in the demographics, echocardiography and PFT. BoPAP patients had significantly decreased VO2 at the anaerobic threshold and peak VO2/kg (858.4 ± 246.5 mL/min vs 727.9 ± 228.0 mL/min, P = 0.037; 21.1 ± 6.4 mL/min/kg vs. 15.5 ± 5.6 mL/min/kg, P = 0.001, respectively). Significant differences were not observed in ventilation efficiency. A trend of impaired oxygen pulse and submaximal exercise tolerance were observed in boPAP patients. Conditional logistical regression analysis revealed the risk of boPAP increased by 2.493 (95% confident interval: 1.388 to 4.476, P = 0.002) with every 5 mL/min/kg decrease in peak VO2/kg. Conclusions: Patients with boPAP have a greater prevalence of exercise intolerance, a trend of impaired oxygen pulse and submaximal exercise tolerance. [ABSTRACT FROM AUTHOR]

Abstract: Background: Despite using vasoactive and pulmonary hypertension (PH) specific therapies, the in‐hospital mortality of severe PH with right heart failure (RHF) is high. We conducted a prospective analysis evaluating the efficacy and safety of levosimendan in PH patients with severe acute RHF. Methods: Forty‐five PH patients hospitalized between January 2016 and November 2016 were recruited into a single arm, prospective, open‐label study. Levosimendan was administered at the rate of .05–0.1 μg/kg/min, up to a total dose of 12.5 mg. The primary endpoints were changes of World Health Organization Function Class (WHO‐FC) and Borg dyspnoea scores. Secondary endpoints included changes in 6‐min walk distance (6‐MWD), biochemical markers and right heart structure and function together with adverse events on day 7 and incidence of major cardiovascular events (death or readmission due to RHF) on day 30. Results: Forty‐five PH patients were enrolled. On the 7th day after levosimendan infusion, seven out of 13 PH patients with WHO‐FC IV improved by one class (P = .008). Borg dyspnoea scores, 6‐MWD and NT‐proBNP improved significantly (P < .001). Compared with baseline, the right atrial transverse dimension, end‐systolic eccentricity index and tricuspid annular plane systolic excursion improved significantly (58.8 ± 13.1 mm vs 53.7 ± 12.4 mm; 1.50 ± 0.27 vs 1.38 ± 0.23; 15.0 (13.0, 16.0) mm vs 15.8 (14.0, 17.4) mm, P < .005, respectively). One patient occurred sudden death after discharge during follow‐up. Conclusions: Intravenous levosimendan can effectively improve severe RHF of PH patients in hospital and well tolerated. [ABSTRACT FROM AUTHOR]

Abstract: Background: Pulmonary hypertension (PH) is an important complication of interstitial lung disease (ILD). The aim of the present study was to investigate characteristics and prognosis of ILD associated PH in a predominantly Chinese patient cohort. Methods: Consecutive patients with ILD associated PH, confirmed by right heart catheterization at shanghai pulmonary hospital were included in the study. Characteristics at baseline and during follow‐up, as well as survival, were analyzed. Results: This observational study was conducted in 26 patients with a mean age of 60.0 ± 12.2 y old. The 6‐min walking distance was 335.0 ± 190.9 m. The mean pulmonary arterial pressure (PAP) was 42.9 ± 10.9 mmHg, cardiac output was 4.4 ± 1.0 L/min, and pulmonary vascular resistance (PVR) was 8.6 ± 4.1 Wood Units. The mean PAP was ≥35 mmHg in 69.2% of cases. There were no difference in lung function parameters between ILD with PH and ILD without PH. The overall survival rate was 92% at 1 y, 82% at 3 y, and 62% at 5 y. PVR was the only variable significantly associated with death. Conclusions: Severe hemodynamic impairment along with PH can occur in patients with ILD. These patients have more severely impaired exercise capacity and cardiac function than ILD patients without PH. PVR was the only prognostic factor identified in this group of patients. [ABSTRACT FROM AUTHOR]

The article presents a case study of 47-year-old woman with bilateral vision loss and floaters. Her visual acuity (VA) was determined using counting fingers optical density (OD) and hand motion and other anterior segments were normal in examination. A 20-G therapeutic pars plana vitrectomy was performed. Genomic DNA was extracted from peripheral vein whole blood treated with ethylenediaminetetraacetic acid (EDTA).