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1.
J Pharm Biomed Anal ; 226: 115253, 2023 Mar 20.
Article in English | MEDLINE | ID: mdl-36657349

ABSTRACT

Rhizoma Drynariae (RD) was used clinically to treat osteoporosis in China due to stimulating bone formation and inhibiting bone resorption, however, the bioactive constituents with the dual effect on bone are still unknown exactly. Disease-causing mutations in calcium sensing receptor (CaSR) can alter parathyroid hormone secretion and affect Ca2+ release from bone and Ca2+ reabsorption from kidney, which gives an indication that CaSR is a potential target for developing therapeutics to manage osteoporosis. Herein, a chromatographic approach was established, by immobilizing the mutant CaSR onto the surface of silica gels as stationary phase in a one-step procedure and then adding the different amino acids into mobile phase as competitors, for exploring the binding features of the known agonists and further screening ligands from RD. The mutant CaSR-coated column was prepared rapidly without the complicated purification and separation of the receptor, which had the large capacity of 13.1 mg CaSR /g silica gels and kept a good stability and specificity for at least 35 days. The CaSR mutation can weaken the binding affinities for three agonists, and the largest decreases occurred on the mutational site Thr151Met for neomycin, on the two sites of Asn118Lys and Glu191Lys for gentamicin-C, and on the site Phe612Ser for kanamycin, which gained new insights into their structure-function relationship. The potential bioactive compounds from RD were screened using the mutant CaSR-coated column and were recognized as coumaric acid 4-O-ß-D-glucopyranoside, caffeic acid, and naringin using UPLC-MS. Among them, naringin targeting CaSR gives a possible explanation that RD could manage osteoporosis. These results indicated that, such a rapid and simple method, utilizing disease-associated mutation in CaSR to alter the binding affinity for agonists, can be applied in capturing the potential bioactive compounds efficiently from complex matrices like herb medicines.


Subject(s)
Osteoporosis , Polypodiaceae , Humans , Receptors, Calcium-Sensing/genetics , Receptors, Calcium-Sensing/metabolism , Polypodiaceae/metabolism , Chromatography, Liquid , Tandem Mass Spectrometry , Mutation , Calcium
2.
Sci Rep ; 12(1): 21900, 2022 Dec 19.
Article in English | MEDLINE | ID: mdl-36535978

ABSTRACT

Photons with high generation rate is one of the essential resources for quantum communication, quantum computing and quantum metrology. Due to the naturally memory-built-in feature, the memory-based photon source is a promising route towards large-scale quantum information processing. However, such photon sources are mostly implemented in extremely low-temperature ensembles or isolated systems, limiting its physical scalability. Here we realize a single-photon source based on a far off-resonance Duan-Lukin-Cirac-Zoller quantum memory at broadband and room-temperature regime. By harnessing high-speed feedback control and repeat-until-success write process, the photon generation rate obtains considerable enhancement up to tenfold. Such a memory-enhanced single-photon source, based on the broadband room-temperature quantum memory, suggests a promising way for establishing large-scale quantum memory-enabled network at ambient condition.

3.
J Pharm Biomed Anal ; 209: 114516, 2022 Feb 05.
Article in English | MEDLINE | ID: mdl-34894463

ABSTRACT

Consistently, the multiple heart-kidney interactions make pharmaceutical research for cardiorenal syndrome difficult and complex. Guanxinning Injection (GXN) has been reported to provide unique advantage for treating cardiac and renal diseases compared to typical monotherapies. However, the protection mechanism of GXN is largely unknown. This study explored the acting mechanism of GXN on heart failure with renal dysfunction from a metabolic perspective. Transverse aortic constriction (TAC) surgery was performed on C57/BL/6 mice to induce heart failure with renal dysfunction. Using telmisartan as a positive control, GXN treatment was applied during the 12th to 16th week after TAC. Cardiac function and structure were examined using M-mode echocardiography, and renal function was evaluated via representative biochemical parameters and hematoxylin-eosin staining. Moreover, untargeted metabolomic analyses of urine were conducted to screen for differential substances associated with the cardiorenal protection effect of GXN. As a result, GXN provided good cardioprotective effects on left ventricular ejection fraction elevation, fractional shortening, internal diastolic, and mass maintenance. GXN also reduced TAC-induced elevation of blood urea nitrogen, and serum Cystatin C and relieved kidney pathological damage. Metabolomic analyses identified 21 differential metabolites in the TAC model group. Ten metabolites involving the metabolic pathways of carnitine synthesis, valine, leucine and isoleucine degradation, and glutamate metabolism, taurine and hypotaurine metabolism, tryptophan metabolism, arginine and proline metabolism, and purine metabolism were restored by GXN. The main cardiorenal protection mechanism of GXN was found to be related to energy metabolism and oxidative stress. Taken together, this study provides the first evidence of the metabolic protection mechanism of GXN on heart failure with renal dysfunction for the first time and provides a research basis for the application of GXN in CRS-2 pharmaceuticals.


Subject(s)
Heart Failure , Kidney Diseases , Animals , Metabolomics , Mice , Stroke Volume , Ventricular Function, Left
4.
Asian Journal of Andrology ; (6): 154-160, 2022.
Article in English | WPRIM (Western Pacific) | ID: wpr-928527

ABSTRACT

Corticosteroid switching can reverse abiraterone resistance in some patients with metastatic castration-resistant prostate cancer (mCRPC). Here, we investigated the potential biomarkers for predicting the efficacy of corticosteroid switching during treatment with abiraterone acetate (AA). We retrospectively analyzed 101 mCRPC patients receiving corticosteroid switching from West China Hospital and Sun Yat-Sen University Cancer Center between January 2016 and December 2018. All cases received AA plus prednisone as first-line therapy during mCRPC. Primary end points were biochemical progression-free survival (bPFS) and overall survival (OS). The risk groups were defined based on multivariate analysis. A total of 42 (41.6%) and 25 (24.8%) patients achieved 30% and 50% decline in prostate-specific antigen (PSA), respectively, after corticosteroid switching. The median bPFS and median OS on AA plus dexamethasone were 4.9 (95% confidence interval [CI]: 3.7-6.0) months and 18.8 (95% CI: 16.2-30.2) months, respectively. Aldo-keto reductase family 1 member C3 (AKR1C3) expression (hazard ratio [HR]: 2.15, 95% Cl: 1.22-3.80, P = 0.008) and baseline serum alkaline phosphatase (ALP; HR: 4.95, 95% Cl: 2.40-10.19, P < 0.001) were independent predictors of efficacy before corticosteroid switching in the multivariate analysis of bPFS. Only baseline serum ALP >160 IU l-1 (HR: 3.41, 95% Cl: 1.57-7.38, P = 0.002) together with PSA level at switch ≥50 ng ml-1 (HR: 2.59, 95% Cl: 1.22-5.47, P = 0.013) independently predicted poorer OS. Based on the predictive factors in multivariate analysis, we developed two risk stratification tools to select candidates for corticosteroid switching. Detection of serum ALP level, PSA level, and tissue AKR1C3 expression in mCRPC patients could help make clinical decisions for corticosteroid switching.


Subject(s)
Humans , Male , Abiraterone Acetate/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Androstenes , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Dexamethasone/therapeutic use , Disease-Free Survival , Prednisone/therapeutic use , Prostate-Specific Antigen , Prostatic Neoplasms, Castration-Resistant/pathology , Retrospective Studies , Treatment Outcome
5.
Preprint in English | bioRxiv | ID: ppbiorxiv-990317

ABSTRACT

The newly emerged pandemic coronavirus, SARS-CoV-2, has posed a significant public health threat worldwide. However, the mode of virus transmission and tissue tropism is not well established yet. Recent findings of substantial liver damage in patients and ACE2+ cholangiocytes in healthy liver tissues prompted us to hypothesize that human liver ductal organoids could serve as a model to determine the susceptibility and mechanisms underlining the liver damage upon SARS-CoV-2 infection. By single-cell RNA sequencing, we found that long-term liver ductal organoid culture preserved the human specific ACE2+ population of cholangiocytes. Moreover, human liver ductal organoids were permissive to SARS-CoV-2 infection and support robust replication. Notably, virus infection impaired the barrier and bile acid transporting functions of cholangiocytes through dysregulation of genes involved in tight junction formation and bile acid transportation, which could explain the bile acid accumulation and consequent liver damage in patients. These results indicate that control of liver damage caused directly by viral infection should be valued in treating COVID-19 patients. Our findings also provide an application of human organoids in investigating the tropism and pathogenesis of SARS-CoV-2, which would facilitate novel drug discovery.

6.
Sci Adv ; 6(6): eaax1425, 2020 Feb.
Article in English | MEDLINE | ID: mdl-32083174

ABSTRACT

Quantum memory capable of storage and retrieval of flying photons on demand is crucial for developing quantum information technologies. However, the devices needed for long-distance links are different from those envisioned for local processing. We present the first hybrid quantum memory-enabled network by demonstrating the interconnection and simultaneous operation of two types of quantum memory: an atomic ensemble-based memory and an all-optical Loop memory. Interfacing the quantum memories at room temperature, we observe a well-preserved quantum correlation and a violation of Cauchy-Schwarz inequality. Furthermore, we demonstrate the creation and storage of a fully-operable heralded photon chain state that can achieve memory-built-in combining, swapping, splitting, tuning, and chopping single photons in a chain temporally. Such a quantum network allows atomic excitations to be generated, stored, and converted to broadband photons, which are then transferred to the next node, stored, and faithfully retrieved, all at high speed and in a programmable fashion.

7.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-805420

ABSTRACT

Oncoplastic breast surgery (OBS) using omentum has been developed in the past 20 years. This study reviewed related clinical researches at home and abroad. It summarized the surgical indications, criteria of cosmetic evaluation for omentum mammary tumor, the methods of harvesting omentum and the selection of tissue flaps. Meanwhile, postoperative complications, tumor safety, advantages and disadvantages of different methods were evaluated.

8.
Sci Rep ; 6: 22267, 2016 Feb 29.
Article in English | MEDLINE | ID: mdl-26923338

ABSTRACT

The enhanced photocatalytic performance of doped graphene (GR)/semiconductor nanocomposites have recently been widely observed, but an understanding of the underlying mechanisms behind it is still out of reach. As a model system to study the dopant effects, we investigate the electronic structures and optical properties of doped GR/Ag3PO4 nanocomposites using the first-principles calculations, demonstrating that the band gap, near-gap electronic structure and interface charge transfer of the doped GR/Ag3PO4(100) composite can be tuned by the dopants. Interestingly, the doping atom and C atoms bonded to dopant become active sites for photocatalysis because they are positively or negatively charged due to the charge redistribution caused by interaction. The dopants can enhance the visible light absorption and photoinduced electron transfer. We propose that the N atom may be one of the most appropriate dopants for the GR/Ag3PO4 photocatalyst. This work can rationalize the available experimental results about N-doped GR-semiconductor composites, and enriches our understanding on the dopant effects in the doped GR-based composites for developing high-performance photocatalysts.

9.
Yao Xue Xue Bao ; 50(9): 1096-100, 2015 Sep.
Article in Chinese | MEDLINE | ID: mdl-26757544

ABSTRACT

Gray relational analysis is employed to analyze the effects of nano-drug features on phagocytosis of macrophages, including zeta potential, shape factor and scale size of drug particle, the correlation among such factors and macrophage cell is calculated. The results showed that the internalization processe is affected significantly by the zeta potential of the drug in the process of phagocytosis of macrophages, followed by the impact particle shape, and the effect of particle scale behaves relatively small.


Subject(s)
Drug Carriers/chemistry , Macrophages/cytology , Nanoparticles/chemistry , Phagocytosis , Humans , Particle Size
10.
Acta Pharmaceutica Sinica ; (12): 1096-1100, 2015.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-257022

ABSTRACT

Gray relational analysis is employed to analyze the effects of nano-drug features on phagocytosis of macrophages, including zeta potential, shape factor and scale size of drug particle, the correlation among such factors and macrophage cell is calculated. The results showed that the internalization processe is affected significantly by the zeta potential of the drug in the process of phagocytosis of macrophages, followed by the impact particle shape, and the effect of particle scale behaves relatively small.


Subject(s)
Humans , Drug Carriers , Chemistry , Macrophages , Cell Biology , Nanoparticles , Chemistry , Particle Size , Phagocytosis
11.
Acta Crystallogr Sect E Struct Rep Online ; 68(Pt 3): o650, 2012 Mar 01.
Article in English | MEDLINE | ID: mdl-22412553

ABSTRACT

In the title compound, C(10)H(12)O(5), the dihedral angle between the benzene ring is almost coplanar with the attached C(O)-O-C group [dihedral angle = 0.32 (15)°]. In the crystal, two intermolecular O-H⋯O hydrogen bonds make R(4) (4)(26) ring mofits.

12.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-671625

ABSTRACT

The author analyzes the basic information in recent years,including overall students scale,students' age,application trends,etc.Some suggestions are made,regarding to recruiting plan,applicant qualification,recruiting mode,etc,in order to further improve the recruiting and graduate management.

13.
National Journal of Andrology ; (12): 185-188, 2011.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-266192

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the different effects of Shengmai injection on testicular injury after testis torsion/detorsion in rats of different ages.</p><p><b>METHODS</b>Sixteen healthy male SD rats aged 3, 6 and 12 weeks were equally randomized into an experimental group (testicular torsion/detorsion plus Shengmai injection) and a control group (testicular torsion/detorsion plus saline). The rat models of testicular torsion were killed 24 h after surgery for the measurement of total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in the testis.</p><p><b>RESULTS</b>Compared with the controls, the 3- and 6-week-old rats of the experimental group showed no significant changes in T-AOC, SOD activity and MDA content (P > 0.05), while the 12-week-old experimental rats exhibited a remarkable increase in SOD and T-AOC and an obvious decrease in MDA content (P < 0.05).</p><p><b>CONCLUSION</b>Shengmai injection has a protective effect against acute ischemia-reperfusion testicular injury after torsion/detorsion in rats, but the effect varies with the age, more obvious in older ones.</p>


Subject(s)
Animals , Male , Rats , Drug Combinations , Drugs, Chinese Herbal , Therapeutic Uses , Malondialdehyde , Metabolism , Phytotherapy , Rats, Sprague-Dawley , Reperfusion Injury , Spermatic Cord Torsion , Drug Therapy , Metabolism , Superoxide Dismutase , Metabolism , Testis , Wounds and Injuries , Metabolism
14.
Chinese Medical Journal ; (24): 1796-1801, 2011.
Article in English | WPRIM (Western Pacific) | ID: wpr-353926

ABSTRACT

<p><b>BACKGROUND</b>Hemodynamic evaluation is crucial for the management of patients with pulmonary hypertention. Clinicians often prefer a rapid and non-invasive method. This study aimed to examine the feasibility of transthoracic echocardiography for the measurements of hemodynamic parameters in patients with pulmonary hypertension.</p><p><b>METHODS</b>A prospective single-center study was conducted among 42 patients with pulmonary hypertension caused by different diseases. Transthoracic echocardiography and right-heart catheterization were performed within 24 hours. Pulmonary artery systolic, diastolic and mean pressure (PASP, PADP and PAMP), cardiac output (CO), and pulmonary capillary wedge pressure (PCWP) were measured by both methods. A linear correlation and a Bland-Altman analysis were performed to compare the two groups of hemodynamic parameters.</p><p><b>RESULTS</b>A good correlation was found between invasive and non-invasive measurements for PASP (r = 0.96), PADP (r = 0.85), PAMP (r = 0.88), CO (r = 0.82), and PCWP (r = 0.81). Further agreement analysis done by the Bland-Altman method showed that bias and a 95% confidence interval for PASP, PADP, and CO were clinically acceptable while great discrepancies existed for PAMP and PCWP.</p><p><b>CONCLUSIONS</b>The non-invasive measurements by PASP, PADP, and CO in patients with pulmonary hypertension correlate well with the invasive determinations. Transthoracic echocardiography (TTE) was inappropriate for estimating PCWP and PAMP.</p>


Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Cardiac Catheterization , Cardiac Output , Echocardiography , Hemodynamics , Hypertension, Pulmonary , Prospective Studies , Pulmonary Wedge Pressure
15.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-301501

ABSTRACT

<p><b>OBJECTIVE</b>To examine the effect of puerarin on high glucose-induced decrease in contraction of isolated rat aortic rings, and to elucidate its underlying mechanism.</p><p><b>METHODS</b>The thoracic aortic rings with or without endothelium of male Sprague-Dawley rats were mounted on a bath system. Isometric contractions of aortic rings were measured. The activity of heme oxygenase-1 (HO-1) was also measured.</p><p><b>RESULTS</b>(1) After incubation with 44 mmol/L of glucose (high glucose) for 4 h, the vascular contraction responses to phenylephrine (PE) decreased in an endothelium-dependent manner, when compared with the control group (containing 11 mmol/L of glucose). (2) After coincubation with puerarin ( 10(-10) - 10(-8) mol/L) and high glucose, the decrease in contraction responses to PE of arteries was partly inhibited in a dose-dependent manner. (3) After incubation with puerarin for 4 h, the HO-1 activity of thoracic aorta increased; ZnPP, an inhibitor of HO-1, abrogated the protection effect of puerarin.</p><p><b>CONCLUSION</b>Puerarin could prevent the high glucose-induced decrease in contraction responses to PE in intact aortic rings. The mechanism might be involved in the activation of HO-1.</p>


Subject(s)
Animals , Male , Rats , Aorta, Thoracic , Physiology , Glucose , Pharmacology , Heme Oxygenase (Decyclizing) , Metabolism , In Vitro Techniques , Isoflavones , Pharmacology , Rats, Sprague-Dawley , Vasoconstriction , Vasodilator Agents , Pharmacology
16.
Chinese Journal of Cardiology ; (12): 812-815, 2008.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-355889

ABSTRACT

<p><b>OBJECTIVE</b>To summarize the clinical and pathological characteristics of constrictive pericarditis in China.</p><p><b>METHOD</b>Data from 150 patients with constrictive pericarditis who admitted to our hospital from 2000 to 2007 were retrospectively analyzed.</p><p><b>RESULTS</b>Constriction pericarditis was detected by echocardiography in 149 out of 150 patients. Pericardial effusion was evidenced in 59.3% patients (89/150). The diagnostic accuracy rate for identifying constrictive pericarditis by echocardiography (98.7%, 107/109) was comparable to that of surgical diagnosis (100%, 109/109). Tuberculosis was the main cause of constrictive pericarditis in this cohort (78.7%, 118/150) including 25 (16.7%) cases with pathological or etiological evidences of tubercular pericarditis, 8 (5.3%) cases with pathologically active tuberculous focus elsewhere in the body, 66 (44.0%) cases with typical clinical tuberculosis manifestation and responded to anti-tubercular therapy and 19 (12.7%) cases with a diagnosis of suspicious tuberculosis. Pericardiectomy was performed in 108 cases and pericardial biopsy and surgical drainage was performed in 1 patient. In hospital death rate was 8.7% (13/150, 4 tubercular patients and 9 non-tubercular).</p><p><b>CONCLUSION</b>Tuberculosis is the leading cause of constrictive pericarditis in this cohort and the best diagnosis tool is echocardiography other than pathological and etiological findings in pericardium.</p>


Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Humans , Male , Middle Aged , Young Adult , Echocardiography , Mycobacterium tuberculosis , Pericarditis, Constrictive , Diagnosis , Microbiology , Pathology , Pericarditis, Tuberculous , Diagnosis , Pathology , Retrospective Studies
17.
Chinese Journal of Biotechnology ; (12): 730-735, 2004.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-249945

ABSTRACT

The expression of the vgb gene in vivo could improve the fermentation density and then contribute the extracellular secretion of the product of bxn gene. Constructed the recombination plasmid pPIC9K-vgbbxn and transformed into Pichia pastoris GS115. The results of PCR and SDS-PAGE indicate that the vgb gene and bxn gene had integrated into the genome of Pichia pastoris GS115 and expressed in efficient level. Also, the protein activity of their products had been verified respectively. Shake flask fermentation experiments showed that the presence of VHb in yeast Pichia pastoris efficiently enhanced cell growth and secretive expression of bxn gene under hypoxic habitats.


Subject(s)
Aminohydrolases , Genetics , Metabolism , Bacterial Proteins , Genetics , Physiology , Electrophoresis, Polyacrylamide Gel , Pichia , Genetics , Plasmids , Polymerase Chain Reaction , Recombinant Proteins , Truncated Hemoglobins , Genetics , Physiology
18.
Article in English | WPRIM (Western Pacific) | ID: wpr-253996

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the value of 16-slice spiral CT in the demonstration of coronary artery and in the diagnose of coronary artery stenosis.</p><p><b>METHODS</b>Plain and enhanced CT scans were performed with a 16-slice CT scanner (Sensation 16, Siemens, Germany) in 230 patients with suspected coronary heart disease (CHD). Parameters of the plain scan were: 120 kV, 133 mA, slice collimation 16 mm x 1.5 mm, rotation time 0.42 seconds, increment 1.5 mm, and slice width 3 mm. Parameters of the enhanced scan were: 120 kV, 500 mA, slice collimation 16 mm x 0.75 mm, rotation time 0.42 seconds, increment 0.5 mm, and slice width 1 mm. Enhanced CT scan was performed with a rapid intravenous injection of 100 mL iothalamate meglumine (Ultravist) (370 mgI/mL) or Omnipaque (350 mgI/mL) and 30 mL 0.9% NaCl chaser bolus at a flow rate of 3.5 mL/s. Calcium scoring with plain scan images and two and three dimensional reconstruction with enhanced scan images were made in all cases, among which 30 cases underwent conventional coronary angiography. Demonstration of coronary arteries and their stenosis were evaluated and the factors that might influence the image quality were analyzed.</p><p><b>RESULTS</b>Coronary calcium scores were calculated and coronary artery was demonstrated in our study. In the evaluation of image quality with volume rendering technique (VRT) images, 78.3% of the images were of the first class, 12.2% the second class, and 9.6% the third class. Multi-planar reconstruction (MPR) and maximal intensity projection (MIP) were better than VRT in the demonstration of small branches. The image quality was related to the heart rate, with or without arrhythmia, and breath-hold ability of patients. Comparative study of the stenosis of coronary arteries in 30 cases showed that the sensitivity and specificity of 16-slice coronary CT angiography (CTA) to diagnose significant stenosis were 95.8% and 94.8% respectively.</p><p><b>CONCLUSION</b>As a non-invasive and quick method, 16-slice coronary CTA is sensitive and specific to diagnose the stenosis of coronary arteries and can be used as a screening method in the diagnosis of CHD.</p>


Subject(s)
Female , Humans , Male , Middle Aged , Coronary Angiography , Coronary Disease , Diagnostic Imaging , Coronary Stenosis , Diagnostic Imaging , Heart Rate , Imaging, Three-Dimensional , Tomography, Spiral Computed , Methods
19.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-531844

ABSTRACT

AIM:To investigate the effect of puerarin on acute high glucose-induced attenuation of ACh relaxation in isolated rat aortic rings, and to elucidate its underlying mechanism. METHODS: The thoracic aortic rings with endothelium of male Sprague-Dawley rats were mounted on a bath system. Isometric relaxation of aortic rings was measured. RESULTS: ① After incubation with high concentration of glucose (44 mmol/L), the vascular relaxation responses to ACh decreased. ② After coincubation with puerarin (10-10-10-8 mol/L) and high glucose, the high glucose-induced attenuation of ACh relaxation responses of artery was partly inhibited in a dose-dependent manner. ③ After incubation with puerarin for 2 h, the HO-1 activity of thoracic aorta increased. ZnPPIX (an inhibitor of heme oxygenase-1) abrogated the protective effect of puerarin. CONCLUSION: Puerarin prevents the acute high glucose-induced attenuation of endothelium-dependent relaxation in aortic rings. The mechanism might be involved in the activation of heme oxygenase-1.

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