Nafion-Immobilized Functionalized MWCNT-based Electrochemical Immunosensor for Aflatoxin B1 Detection.

The ubiquitous aflatoxin B1 (AFB1) contamination in foods and other complex matrices has brought great challenges for onsite monitoring. In this study, an ultrasensitive Nafion-immobilized functionalized multiwalled carbon nanotube (MWCNT)-based electrochemical (EC) immunosensor was developed for trace AFB1 detection. The introduced Nafion film could steadily stabilize functionalized MWCNTs with uniform distribution and tiling on the surface of a Au electrode. Functionalized MWCNTs with a large specific surface area, numerous active sites to couple with abundant anti-AFB1 monoclonal antibodies (mAbs), and high conductivity served as the signal amplifier for remarkably enhancing the sensing performance of the immunosensor. In the presence of AFB1, it was specifically captured by mAbs to reduce the amplified current signals, which were recorded by differential pulse voltammetry for the accurate quantitation of AFB1. Because of the synergistic effects of Nafion on the stabilization of functionalized MWCNTs as signal enhancers, the developed EC immunosensor exhibited an extremely high selectivity, excellent sensitivity with a limit of detection as low as 0.021 ng/mL, and a wide dynamic range of 0.05-100 ng/mL, besides fascinating merits of easy construction, low cost, good stability in 7 days, and good reusability. The anti-interference ability of the immunosensor was verified against three other mycotoxins, and the practicability and accuracy were confirmed by measuring AFB1 in fortified malt, lotus seed, and hirudo samples with a satisfactory recovery of 92.08-104.62%. This novel immunosensing platform could be extended to detect more mycotoxins in complex matrices to ensure food safety.

Successful true cavity pathfinding with balloon assisted CTO with bifurcation lesions: Two case reports.

BACKGROUND: Coronary artery disease is a prevalent global cardiovascular ailment, with percutaneous coronary intervention (PCI) standing out as a crucial method for relieving symptoms and enhancing the quality of life in patients with coronary heart disease. However, the presence of concurrent chronic total occlusion (CTO) and bifurcation lesions within coronary arteries elevates the complexity and treatment risks, especially when the entry point of the CTO is ambiguous. OBJECTIVE: This study aims to present an innovative approach for treating CTO complicated with bifurcation lesions, focusing on true cavity pathfinding assisted by a balloon. METHODS: Two cases of CTO patients with concomitant bifurcation lesions are described. One case involves CTO of the left anterior descending artery) combined with anterior non-angle trigeminal lesions, while the other entails CTO of the posterior left artery combined with posterior angle trigeminal lesions. True lumen identification using a balloon and subsequent opening of the CTO blood vessel were performed in both cases. RESULTS: In both cases, the true lumen was successfully located with the assistance of a balloon, leading to the successful opening of the CTO blood vessel. This approach not only simplified the procedure but also reduced procedural difficulty and associated risks of complications compared to traditional guide wire operations. CONCLUSION: The application of true cavity pathfinding assisted by a balloon offers a novel and effective strategy for managing CTO complicated with bifurcation lesions. The method simplifies the procedure, decreases procedural difficulty, and lowers the risk of complications associated with guide wire operations. However, further studies and long-term follow-up data are warranted to validate the reliability and long-term efficacy of this innovative approach.

UiOL@AIEgens-assisted lateral flow immunosensor for the ultrasensitive dual-modal point-of-care detection of aflatoxin B1.

Aflatoxin B1 (AFB1) contamination in food has attracted worldwide attention. The sensitive detection of AFB1 is vital for ensuring food quality and safety. This study developed an ultrasensitive signal-enhanced lateral flow immunosensor (LFIS) based on the functionalized zirconium metal-organic framework (MOF) of a UiO linker enriched with abundant aggregation-induced emission luminogen (UiOL@AIEgens) probes for the rapid dual-modal point-of-care (POC) determination of AFB1. Using UiO MOFs with numerous active sites as the carrier facilitated abundant AIEgens enrichment on the surface. After coupling with enough anti-AFB1 monoclonal antibodies (mAbs), the green-emissive UiOL@AIEgens-mAbs probes with high specificity and remarkably-enhanced fluorescence responses were obtained to competitively capture target AFB1 in the standard or sample solution and AFB1 antigen immobilized on the test (T) line of the POC LFIS. Under optimum conditions, the LFIS was capable of visual qualitative and smartphone-assisted dual-modal determination of target AFB1 within 7 min. Detection occurred in a range of 0.01-5 ng/mL at an ultra-low detection limit of 0.003 ng/mL, which was 300- and 600-fold lower than traditional immunoassays and the maximum limit set by the European Union, respectively. Moreover, the feasibility and robustness of the LFIS platform were assessed by detecting AFB1 in maize and lotus seed samples with average recoveries of 94.3-109.0%. The developed UiOL@AIEgens-based POC LFIS can be used for ultrasensitive, reliable, on-site detection in food. This study provides a new method for the real-time monitoring of AFB1 and other harmful contaminants in food and more complex matrices.

Preparation of betaine injection and its therapeutic effect in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterised by elevated pulmonary pressure, right ventricular failure (RVF) and ultimately death. Aggressive treatment of RVF is considered an important therapeutic strategy to treat PAH. Previous studies have indicated that betaine may be may a promising therapeutic approach for PAH-induced RVF. Therefore, in this study, betaine solution for injection was prepared and characterised using various techniques. The therapeutic efficacy of three different methods of administration (intragastric, nebulised inhalation and intravenous injection) were comprehensively evaluated in terms of pharmacokinetics, tissue distribution and pharmacodynamics. The pharmacokinetic results demonstrated that betaine injection administered via nebulised inhalation significantly prolonged betaine's half-life and increased its internal circulation time compared to the intragastric and intravenous routes. Biodistribution experiments verified that the betaine formulation accumulated in the lung tissue when administered via inhalation. The results of the pharmacodynamic analysis further confirmed that right ventricular systolic pressure, mean pulmonary artery pressure and right ventricular hypertrophy index increased in the model group and that inhaled betaine suppressed these pathological changes to a level comparable to those observed in the control group. Taken together, these results indicate that betaine administered by inhalation is a promising strategy for the treatment of PAH-induced RVF.

3D nanocake-like Au-MXene/Au pallet structure-based label-free electrochemical aptasensor for paraquat determination.

3D nanocake-like Au-MXene and Au pallet (Au-MXene/AuP) nanocomposite-modified screen-printed carbon electrodes (SPCEs) were utilized to construct an ultrasensitive label-free electrochemical aptasensor through a self-assembly procedure for trace paraquat (PQ) residue detection. Benefiting from the excellent electrochemical (EC) performances (e.g., high conductivity and large surface area) of Au-MXene nanocomposites and AuP substrate, the developed Apt/Au-MXene/AuP/SPCE-based EC aptasensor displayed excellent specificity and anti-interference ability, good repeatability, and stability. A linear relationship between the log value of the change in current intensity [lg (ΔI)] and the log value of the concentration of PQ [lg (CPQ)] was obtained in the range 0.05-1000 ng/mL. The limit of detection was 0.028 ng/mL, and the sensitivity was 255.5 µA/(µM·cm2). Practical applications in malt and mint samples confirmed the accuracy of the EC aptasensor in complex matrices for PQ detection, providing a universal analytical tool for other trace pesticides in different food samples by simply replacing the corresponding aptamers.

A Single-Center Study Using IVUS to Guide Rotational Atherectomy for Chronic Renal Disease's Calcified Coronary Artery.

Objective: To assess the effectiveness and safety of an IVUS-guided rotational atherectomy (RA) percutaneous coronary intervention (PCI) in chronic renal patients with complex coronary calcification who are at risk for contrast-related acute kidney injury (AKI). Methods: From October 2018 to October 2021, 48 patients with chronic renal disease who were receiving PCI with RA at the General Hospital of NingXia Medical University were informed for data collection for this research. They were randomly assigned to the IVUS-guided RA group and the Standard RA group, which did not use IVUS. According to a clinical expert consensus document on rotational atherectomy in China, both PCI procedures were performed. The intravascular ultrasound (IVUS) results from the study group were used to describe the morphology of the lesion and to guide the selection of burrs, balloons, and stents. IVUS and angiography were used to evaluate the outcome in the end. IVUS-guided RA PCI and Standard RA PCI groups' effects and results were contrasted. Results: There were no appreciable differences in the clinical baseline characteristics between the IVUS-guided RA PCI group and the Standard RA PCI group. The average estimated glomerular filtration rate (eGFR) of two groups was (81.42 ± 20.22 vs 82.34 ± 22.19) mL/min/1.73 m2. Most of them (45.8% vs 54.2%) was in stage 60-90 mL/min/1.73m2. When compared to the standard RA PCI group, RA in IVUS-Guided group was more performed electively (87.5% vs 58.3%; p = 0.02). The IVUS-guided RA PCI group was associated with shorter fluoroscopy time (20.6 ± 8.4 vs 36 ± 22; p<0.01) and less contrast amount (32 ±16 vs 184 ±116mL; p<0.01) than Standard-RA group. Five patients in the Standard RA PCI group developed contrast-induced nephropathy, which was 5 times than the IVUS-guided RA PCI group (20.8% VS 4.1%; p=0.19). Conclusion: In chronic renal patients with complex coronary calcification, an IVUS-guided RA PCI technique is effective and safe. It can also lower the volume of contrast and perhaps the incidence of contrast-related AKI.

Application of transcriptomics and proteomics in pulmonary arterial hypertension.

The onset and progression of pulmonary arterial hypertension (PAH), a malignant disease, are associated with environmental and epigenetic factors. Recent advancements in transcriptomics and proteomics technology have provided new insights into PAH and identified novel gene targets involved in the development of the disease. Transcriptomic analysis has led to the discovery of possible novel pathways, such as miR-483 targeting several PAH-related genes and a mechanistic link between the increase in HERV-K mRNA and protein. Proteomic analysis has revealed crucial details, including the loss of SIRT3 activity and the significance of the CLIC4/Arf6 pathway in PAH pathogenesis. Gene profiles and protein interaction networks of PAH have been analyzed, clarifying the roles of differentially expressed genes or proteins in the occurrence and development of PAH. This article discusses these recent advances.

Electrostatic Self-Assembly of MXene on Ruthenium Dioxide-Modified Carbon Cloth for Electrochemical Detection of Kaempferol.

A superior composite material consisting of MXene and ruthenium dioxide-modified carbon cloth is synthesized by pulsed laser deposition and electrostatic self-assembly, which is further utilized to construct a class of novel electrochemical (EC) sensors for kaempferol (KA) detection. The carbon-cloth-based electrodes modified by ruthenium dioxide and then MXene are characterized by X-ray diffraction, scanning electron microscope, and X-ray photoemission spectroscopy. The EC process on the modified electrodes is analyzed by cyclic voltammetry, EC impedance spectroscopy, and differential pulse voltammetry. It is found that positively charged RuO2 not only possesses the remarkable electrical conductivity and electrocatalysis activity but also hampers the restacking of MXene, which accordingly enhances the exposure of the active surface area and greatly boosts the electrocatalysis activity of the entire composite. Consequently, this newly developed composite-based EC sensor exhibits a high sensitivity, selectivity, and remarkable stability to detect KA with two linear ranges of 0.06-1 and 1-15 µM. The inferred limit of detection is 0.039 µM via differential pulse voltammetry. More importantly, this novel EC sensor is found to be applicable for detecting KA in practical traditional Chinese medicines.

Multi-mycotoxin detection and human exposure risk assessment in medicinal foods.

Mycotoxin contamination in medicinal foods has attracted increasing global attention. In this study, a simple and sensitive ultrasonication assisted one-step extraction based ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method was developed for simultaneous detection of multi-mycotoxins in five kinds of medicinal foods rich in starch. Under optimal conditions, the developed technique displayed excellent analytical performances. Limits of detection and quantitation for the six mycotoxins were 0.04-0.25 ng/mL and 0.10-0.67 ng/mL, respectively. Average recoveries at three fortified levels ranged from 75.33 % to 118.0 %. Real-world application in 103 batches of medicinal foods displayed that 58 samples were positive with one or more mycotoxins at an occurrence rate of 56.31 % (58/103). Coix seed gave the highest positive rate of 96.15 %, followed by Lily (90 %), Chinese yam (50 %), Lotus seed (34.04 %) and Malt (30 %). Zearalenone had the highest positive rate of 28.16 % with contents in 5 Coix seeds exceeding the maximum residue limit (MRL), followed by aflatoxin B1 of 27.18 % (28/103) with contents in 7 Coix seed and 10 Lotus seeds over its MRL, and ochratoxin A (OTA) of 11.65 % with contents in 1 Lotus seed and 5 Lily samples greater than its MRL. Exposure risk assessment indicated that Coix seed and Lotus seeds that were susceptible to aflatoxins posed great threats to human health. Long-term consumption of Lily that was easily contaminated with OTA were also harmful. This work provides a robust platform for multi-mycotoxin monitoring in medicinal foods to protect the consumers from potential health risks.

Ultrasensitive electrochemical aptasensor with Nafion-stabilized f-MWCNTs as signal enhancers for OTA detection.

In this study, an ultrasensitive electrochemical (EC) aptasensor with Nafion-stabilized functionalized multi-walled carbon nanotubes (f-MWCNTs) as signal enhancers was established for ochratoxin A (OTA) determination. Herein, f-MWCNTs were prepared through functionalization with nitric acid. The incorporation of Nafion promoted a good dispersion of f-MWCNTs and prevented their leaching on the electrode, making a robust stability of the aptasensor. The Nafion-f-MWCNTs composites were used as the sensing substrates to largely enhance the electroactive surface area and the conductivity of the electrode, realizing a significant signal amplification. Carboxyl groups on the surface of f-MWCNTs readily exposed from Nafion membrane to couple with streptavidin, facilitating the immobilization of biotinylated aptamers to achieve selective recognition towards OTA. When OTA existed, aptamers preferentially combined with it, causing a noticeable decline in the current response. Under optimum conditions, a good linear relationship between the current changes and the logarithm of OTA concentration was observed from 0.005 ng/mL to 10 ng/mL, with a limit of detection low to 1 pg/mL for OTA. The specific, sensitive, and reproducible aptasensor succeeded in application in malt samples, confirming a great promise for more contaminants and providing a universal platform in complex matrices by simply replacing the corresponding aptamers.

Development of a Nafion-MWCNTs and in-situ generated Au nanopopcorns dual-amplification electrochemical aptasensor for ultrasensitive detection of OTA.

Trace detection of ochratoxin A (OTA) in foods is essential to mitigate risks to human health. Herein, a label-free electrochemical (EC) aptasensor based on dual-signal amplification of Nafion dispersed multi-walled carbon nanotubes (Nafion-MWCNTs) and Au nanopopcorns was developed for ultrasensitive detection of OTA. Nafion solution prevented the leaching of MWCNTs, and the Nafion-MWCNTs modified screen-printed carbon electrode (SPCE) acted as the sensing substrate which facilitated the uniform distribution of the electrodeposited Au nanopopcorns. The in-situ generated Au nanopopcorns could not only load a large amount of aptamers for specific identification of OTA, but also promote the electron transfer of the sensing platform. The incorporation of Nafion-MWCNTs and Au nanopopcorns realized dual-amplification of the aptasensor due to the enhanced conductivity and the increased electroactive surface area of the electrode. The modified electrodes were characterized through scanning electron microscopy, X-ray photoelectron spectroscopy and EC evaluation. Under optimal conditions, the electrochemical impedance spectroscopy (EIS) was measured for the determination of OTA. The as-fabricated Au nanopopcorns/Nafion-MWCNTs impedimetric aptasensor displayed excellent sensitivity with a detection limit as low as 1 pg/mL and a wide linear range of 1 pg/mL-10 ng/mL for OTA. Practical application of the aptasensor in the spiked malt samples achieved satisfactory recoveries of 89.82-95.65 %, which was also successfully verified to detect OTA in eleven batches of actual malt samples collected from the local market. The creative aptasensor is simple, cost-effective, sensitive, and accurate, showing great promise for on-site monitoring of other trace contaminants in foods by simply replacing the aptamers.

Role of gut microbiota in postoperative complications and prognosis of gastrointestinal surgery: A narrative review.

Gastrointestinal surgery is often challenging because of unexpected postoperative complications such as pouchitis, malabsorption, anastomotic leak, diarrhea, inflammatory responses, and life-threatening infections. Moreover, the gut microbiota has been shown to be associated with the complications described above. Major intestinal reconstruction, such as Roux-en-Y gastric bypass (RYGB) and ileal pouch-anal anastomosis surgery, could result in altered gut microbiota, which might lead to some of the benefits of these procedures but could also contribute to the development of postsurgical complications. Moreover, postsurgical reestablishment of the gut microbiota population is still poorly understood. Here, we review evidence outlining the role of gut microbiota in complications of gastrointestinal surgery, especially malabsorption, anastomotic leak, pouchitis, and infections. In addition, this review will evaluate the risks and benefits of live biotherapeutics in the complications of gastrointestinal surgery.

Vasodilatory effects of betaine on isolated rat pulmonary artery rings.

The aim of this study was to investigate the vasodilatory effects of betaine, an alkaloid isolated from Lycium barbarum, on isolated pulmonary artery rings in rats and its possible mechanisms. Pulmonary vessels of normal Sprague-Dawley rats were isolated and pre-contracted using norepinephrine. Then, betaine was cumulatively added in differing concentrations (0.02-0.14 mg/mL), and the tension curve was observed and recorded. Changes in the tension of the pulmonary artery rings with an intact endothelium and a dissected endothelium were recorded. The interactions among betaine and NG-nitro-L-arginine methyl ester, indomethacin, 4-aminopyridine, barium chloride, and glibenclamide were evaluated. The experimental results show that betaine can relax the pulmonary artery rings pre-contracted by norepinephrine. Furthermore, pre-incubation with NG-nitro-L-arginine methyl ester and indomethacin did not inhibit betaine vasodilation, demonstrating that vasodilation by betaine is endothelium-dependent. Additionally, pretreatment of pulmonary artery rings with 4-aminopyridine and glibenclamide had no effect on betaine. However, pretreatment of pulmonary artery rings with barium chloride attenuated the effects of betaine. In conclusion, the vasodilatory effects of betaine on pulmonary artery rings is associated with inward rectifier potassium channels.

Betaine alleviates right ventricular failure via regulation of Rho A/ROCK signaling pathway in rats with pulmonary arterial hypertension.

Pulmonary vascular remodeling was shown to lead to pulmonary arterial hypertension (PAH), further trigger excessive apoptosis of cardiomyocytes, and ultimately cause right ventricular failure (RVF), which involves the activation of Rho A/ROCK signaling pathway. Betaine has been found efficacious for attenuating PAH through its anti-inflammatory effects in our previous research while its effects on RVF due to PAH remains inconclusive. Thus, we attempted to elucidate the protective effects of betaine on PAH, RVF due to PAH as well as the potential mechanisms. To this end, male Sprague Dawley rats received a single subcutaneous injection of monocrotaline (50 mg/kg) to imitate PAH and RVF, and subsequently oral administration of betaine (100, 200, and 400 mg/kg/day). Betaine treatment improved the hemodynamics and histomorphological parameters and echocardiographic changes. Moreover, betaine also alleviated the pulmonary vascular remodeling and cardiomyocyte apoptosis. The mechanisms study revealed that administration of betaine significantly increased the expression of Rho A, ROCK1, and ROCK2. Furthermore, betaine alleviated the changes of its downstream molecules P53, Bcl-2, Bax, phosphorylated MYPT1 (p-MYPT1), total MYPT1 (t-MYPT1), p27kip1, and Cleaved Caspase-3. According to what we observed, this study indicated that betaine treatment could protect RVF due to PAH, which may be achieved through an altered Rho A/ROCK signaling pathway.

Protective effects of 18ß-glycyrrhetinic acid on pulmonary arterial hypertension via regulation of Rho A/Rho kinsase pathway.

PURPOSE: Excessive proliferation, migration and anti-apoptosis of pulmonary artery smooth muscle cells (PASMCs) are the basis for the development of pulmonary vascular remodeling, and it is the driving force for pulmonary arterial hypertension (PAH). 18ß-glycyrrhetinic acid (18ß-GA) is the main active substance extracted from Chinese herbal medicine licorice, with outstanding anti-inflammatory, anti-oxidation and anti-proliferative effects. Our team found in previous studies that 18ß-GA has protective effects on monocrotaline-induced PAH in rats. However, the anti-angiogenic effect of 18ß-GA on PAH remains unclear. Therefore, in order to further investigate whether the beneficial effects of 18ß-GA on PAH are related to its antiproliferative effect, we conducted experiments in vivo and in vitro. METHODS AND RESULTS: In vivo, 18ß-GA relieved mean pulmonary arterial pressure, right ventricular systolic pressure, and right ventricular hypertrophy index, improving pulmonary remodeling. In vitro, 18ß-GA significantly inhibited PDGF-BB-induced proliferation and DNA synthesis of HPASMCs, blocking the progression of G0/G1 to S phase of the cell cycle. Furthermore, after treatment with 18ß-GA, the expression of Rho A, ROCK1, ROCK2 was decreased and ROCK activity was inhibited in HPASMC. In addition, 18ß-GA also attenuated PDGF-induced changes in p27kip1, Bax and Bcl-2. CONCLUSIONS: In summary, these results indicate that 18ß-GA regulates the activity of RhoA-ROCK signaling pathway, inhibits the proliferation of HPASMCs, and has potential value in the treatment of PAH.

Protective Effects of 18ß-Glycyrrhetinic Acid on Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats.

Pulmonary arterial hypertension (PAH) is a destructive and rare disorder characterized by a progressive increase in pulmonary artery pressure and vasoconstriction, ultimately leading to right ventricular failure and death. 18ß-Glycyrrhetinic acid (18ß-GA) is an active ingredient in the commonly used Chinese herbal medicine radix glycyrrhizae, and it possesses antioxidant, anti-inflammatory, anti-tumor, and other pharmacological properties. This study aimed to determine whether 18ß-GA has protective effects against monocrotaline (MCT)-induced PAH and whether it is associated with oxidative stress. The PAH of rats was induced by MCT (60 mg/kg) and oral administration of 18ß-GA (100, 50, or 25 mg/kg/day), sildenafil (30 mg/kg), or saline for 21 consecutive days. The development of PAH was evaluated by hemodynamic parameters and right ventricular hypertrophy index. Hematoxylin and eosin staining, Masson trichrome staining, and electron microscopy were used to determine the degree of vascular remodeling and proliferation in lung tissue. Moreover, the antioxidant capacity and malondialdehyde levels in the lungs were measured according to the instructions provided by the test kits, and the expression levels of nicotinamide adenine dinucleotide phosphate oxidase-2 (Nox2) and Nox4 were detected through Western blot analysis. Results of our study indicated that 18ß-GA treatment significantly improved the hemodynamic and pathomorphological data of the rats, reduced the changes in oxidative stress biomarkers, and inhibited Nox2 and Nox4 expression. Our research indicated that 18ß-GA has a protective effect against MCT-induced PAH by inhibiting oxidative stress in rats.

Protective effects of low-dose rosuvastatin on isoproterenol-induced chronic heart failure in rats by regulation of DDAH-ADMA-NO pathway.

AIMS: Cardiovascular disease is the leading cause of death with high morbidity and mortality, and chronic heart failure is the terminal phase of it. This study aimed to investigate the protective effects of the low-dose rosuvastatin on isoproterenol-induced chronic heart failure and to explore the possible related mechanisms. METHODS: Male Sprague Dawley rats were given isoproterenol 5 mg/kg once a day for 7 days to establish heart failure model by subcutaneous injection. Simultaneously, low-dose rosuvastatin (5 mg/kg) was orally administrated from day 1 to day 14. Protective effects were evaluated by hemodynamic parameter, histopathological variables, serum asymmetric dimethylarginine (ADMA), cardiac troponin I (cTnI), brain natriuretic peptide (BNP) and myocardial nitric oxide (NO), and the levels of dimethylarginine dimethylaminohydrolase 2 (DDAH2), arginine methyltransferases 1 (PRMT1) and endothelial nitric oxide synthase (eNOS) expression were analyzed. RESULTS: Therapeutic rosuvastatin (5 mg/kg) significantly attenuated isoproterenol-induced hypertrophy, remodeling and dysfunction of ventricle, reduced the increased serum content of ADMA, cTnI, and BNP, and elevated myocardial NO in rats (P<.05). Besides, rosuvastatin also significantly inhibited fibrosis of myocardium, normalized the increased PRMT1 and decreased DDAH2 expression. CONCLUSIONS: Low-dose rosuvastatin exerted cardioprotective effects on isoproterenol-induced heart failure in rats by modulating DDAH-ADMA-NO pathway, and it may present the new therapeutic value in ameliorating chronic heart failure.

Oxymatrine attenuated isoproterenol-induced heart failure in rats via regulation of COX-2/PGI2 pathway.

Oxymatrine (OMT) is an active constituent of traditional Chinese herb Sophora japonica Ait which has been shown to exert potent anti-inflammatory,anti-oxidant and anti-fibrosis properties. Our previous studies have demonstrated that OMT has protective effects on isoproterenol-induced heart failure in rats through regulation of DDAH/ADMA metabolism pathway.In this study,we further investigated whether OMT could attenuate isoproterenol-induced heart failure through the regulation of COX-2/PGI2 pathway. Heart failure was induced in Sprague-Dawley rats by 5mg/kg isoproterenol subcutaneous injection for 7days. The rats were maintained on normal diet and randomly divided into five groups: control, isoproterenol, isoproterenol with OMT (50, 100mg/kg), and OMT alone groups (n=12 in each group). Serum brain natruretic peptide (BNP, a heart failure biomarker), histopathological variables, expression of Cytosolic phospholipase A2 (cPLA2), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and Prostacyclin synthase (PGIS) were analysed. Administration of OMT significantly reduced the increased BNP in plasm of isoproterenol-induced rats, attenuated cardiac fibrosis,suppressed overexpression of myocardial COX-1 expression, up-regulated COX-2 and PGIS expression, but had no effects on isoproterenol-induced elevated protein cPLA2. And compared with control group, any indexes in sham rats treated with OMT (100mg/kg) alone were unaltered. These results demonstrated that OMT has cardioprotective effects on isoproterenol-induced heart failure in rats by regulating COX-2/PGI2 pathway.

Cardioprotective effects of oxymatrine on isoproterenol-induced heart failure via regulation of DDAH/ADMA metabolism pathway in rats.

The present study was designed to investigate whether oxymatrine could attenuate isoproterenol-induced heart failure via regulation of asymmetric dimethylarginine (ADMA) metabolism in rats. Heart failure model was established by once daily subcutaneous injection of isoproterenol (5 mg/kg/d) to rats for 7 days. Simultaneously, oral administration of oxymatrine (25, 50 and 100 mg/kg/d) was started from day 1 to day 7, or with vehicle as corresponding controls. After continuous preventive administration of oxymatrine for 7 days, significant isoproterenol-induced heart failure characterized by hypertrophy and dysfunction of left ventricle, and elevation of brain natruretic peptide (BNP, a heart failure biomarker) and cardiac troponin I (cTn-I, a cardiac injury biomarker) was observed. Preventive oxymatrine significantly ameliorated the cardiac hypertrophy, improved the left ventricular dysfunction and reduced the increased BNP and cTn-I in serum of isoproterenol-treated rats. And obvious changes with decrease of systolic blood pressure and increase of heart rate were present in isoproterenol group and normalized by oxymatrine. Besides, prevention with oxymatrine significantly up-regulated the dimethylarginine dimethylaminohydrolase 2 (DDAH2) expression, which was followed by decreased serum ADMA, but it had no effect on protein arginine methyltransferase1 (PRMT1) expression that is up-regulated in isoproterenol-induced heart failure rats. These results manifested that preventive oxymatrine could ameliorate the hypertrophy and dysfunction of left ventricle of rats with heart failure, which is attributed to modulation of DDAH/ADMA metabolism pathway by oxymatrine.

[Protective effect of oxymatrine on chronic heart failure and ADMA metabolism pathway in isoproterenol-induced chronic heart failure in rats].

OBJECTIVE: To investigate the protective effects of oxymatrine on chronic heart failure induced by isoproterenol (ISO) and to observe its effects on ADMA metabolism pathway in ISO-induced chronic heart failure in rats. METHOD: Male Sprague-Dawley rats were given oxymatrine (100,50 mg kg-1) orally for 14 days. Heart failure was induced in rats by subcutaneous injection of isoproterenol (5 mg kg-1 d-1 ) at the 8th day for 1 week. Serum parameters, haemodynamic parameters, Heart weight, and histopathological variables were analysed. Expression of protein levels were measured by Western blot. RESULT: Oxymatrine (100,50 mg kg-1) significantly attenuated serum content of cTn I, improved left ventricle systolic and diastolic function and left ventricular remodeling, reduced the ISO-induced myocardial pathological changes compared with ISO group. In addition, oxymatrine (100,50 mg kg-1) significantly reduced serum level of ADMA (P <0. 01), normalize the reduced dimethylarginine dimethylaminohydrolase 2 (DDAH2) expression (P <0. 01) , but had no effect on the isoproterenol-induced upregulated protein arginine methyltransferases 1 expression. CONCLUSION: Oxymatrine could ameliorate the experimental ventricular remodeling in ISO-induced chronic heart failure in rats and the mechanism involved in reducing serum content of ADMA and increased DDAH2 expression.