A stable atmospheric-pressure plasma for extreme-temperature synthesis.

Plasmas can generate ultra-high-temperature reactive environments that can be used for the synthesis and processing of a wide range of materials1,2. However, the limited volume, instability and non-uniformity of plasmas have made it challenging to scalably manufacture bulk, high-temperature materials3-8. Here we present a plasma set-up consisting of a pair of carbon-fibre-tip-enhanced electrodes that enable the generation of a uniform, ultra-high temperature and stable plasma (up to 8,000 K) at atmospheric pressure using a combination of vertically oriented long and short carbon fibres. The long carbon fibres initiate the plasma by micro-spark discharge at a low breakdown voltage, whereas the short carbon fibres coalesce the discharge into a volumetric and stable ultra-high-temperature plasma. As a proof of concept, we used this process to synthesize various extreme materials in seconds, including ultra-high-temperature ceramics (for example, hafnium carbonitride) and refractory metal alloys. Moreover, the carbon-fibre electrodes are highly flexible and can be shaped for various syntheses. This simple and practical plasma technology may help overcome the challenges in high-temperature synthesis and enable large-scale electrified plasma manufacturing powered by renewable electricity.

Circular RNA circFGD4 suppresses gastric cancer progression via modulating miR-532-3p/APC/ß-catenin signalling pathway.

BACKGROUND: Mounting evidence has displayed critical roles of circular RNAs (circRNAs) in multiple cancers. The underlying mechanisms by which circFGD4 contributed to gastric cancer (GC) are still unclear. METHODS: The levels and clinical values of circFGD4 in GC patients were detected and analysed by quantitative real-time PCR. The biological roles of circFGD4 in GC were assessed in vitro and in vivo experiments. Dual-luciferase reporter, fluorescence in situ hybridization, RNA immunoprecipitation, biotin-coupled RNA pull-down, and TOP/Flash and FOP/Flash reporter gene assays were employed to evaluate the effects of circFGD4 on miR-532-3p-mediated adenomatous polyposis coli (APC)/ß-catenin signalling in GC cells. RESULTS: circFGD4 expression was down-regulated the most in human GC tissues and cell lines. Low expression of circFGD4 was correlated with poor tumour differentiation, lymphatic metastasis, and poor prognosis of GC patients. circFGD4 suppressed GC cell viability, colony formation, migration, induced epithelial-mesenchymal transition (EMT), and tumorigenesis and metastasis in vivo. Next, we validated that circFGD4 acted as a sponge of miR-532-3p to relieve the tumour-promoting effects of miR-532-3p on its target APC. The mechanistic analysis demonstrated that the circFGD4 suppressed GC cell viability, migration, and EMT by modulating the miR-532-3p/APC axis to inactivate the ß-catenin signalling. CONCLUSION: circFGD4 suppressed GC progression through sponging miR-532-3p and enhancing APC expression to inactivate the ß-catenin signalling. Thus circFGD4 provides a novel potential biomarker and valuable therapeutic strategy for GC.

The application of a lateral flow immunographic assay to rapidly test for dexamethasone in commercial facial masks.

Dexamethasone (DE) is a synthetic glucocorticoid that is frequently added to cosmetic products for its good short-term effects, especially in facial masks, but long-term use is hazardous to the health. The abuse of DE in whitening and acne cosmetic products is currently a serious problem in China. It is necessary to establish a rapid method of detecting illegal DE addition in cosmetics. In the present study, a monoclonal antibody (mAb) against DE, 2D5-3D12, was developed that displayed cross-reactivities of 124.5%, 38.8%, 6.7%, 0.9%, 1.1%, 1.82%, and 2.39% with prednisolone, betamethasone, prednisone, beclomethasone, hydrocortisone, triamcinolone, and flumetasone, respectively. A colloidal gold-based lateral flow immunographic assay based on mAb 2D5-3D12 was established and used to determine the DE contents of commercial facial masks. The indicator range of the immunographic assay for DE was 100-200 ng/mL, and the results were consistent with those afforded by LC-MS. This novel method provides the advantages of simple sample treatment, a user-friendly procedure, and rapid detection. Graphical abstract.

Synthesis of 2-substituted 3-chlorobenzofurans via TMSCl-mediated nucleophilic annulation of isatin-derived propargylic alcohols.

A TMSCl-mediated cascade annulation of isatin-derived propargylic alcohols for the synthesis of 2-substituted 3-chlorobenzofurans is now reported. Mechanistic investigations showed that this proceeded through a sequential Meyer-Schuster rearrangement/nucleophilic addition/intramolecular annulation. TMSCl not only acts as a promoter, but also acts as a chlorine source in this protocol.

Differentiation therapy: sesamin as an effective agent in targeting cancer stem-like side population cells of human gallbladder carcinoma.

BACKGROUND: Recent studies have demonstrated that side population (SP) cells isolated from various cancer cell lines and primary tumors possess stem cell-like properties. Sesamin, a food-derived agent, possesses anti-cancer activities both in vitro and in vivo. The present study was designed to determine whether sesamin also have effects on cancer stem-like SP cells from gallbladder cancer (GBC). METHODS: In this study, we sorted SP cells by flow cytometry. SP cells were cultured and treated with sesamin. Tumor-sphere formation, colony formation, Matrigel invasion and tumorigenic potential were determined. Expression of nuclear NF-κB, IL-6, p-Stat3, Twist, E-cadherin and Vimentin was measured by Western blot, immunofluorescence staining or RT-PCR analysis. Nuclear NF-κB activity and IL-6 protein level were assessed with ELISA. Xenograft tumors were generated in nude mice. RESULTS: After treated with sesamin, SP cells differentiated into cells expressing the epithelial marker (E-cadherin). Sesamin effectively affected SP cells stem cell-like characteristics (i.e., tumor-sphere formation, colony-formation, Matrigel invasion), weakened the drug-resistance of SP cells and inhibited tumor growth both in vitro and in vivo. Treatment with sesamin significantly reduced the expression of nuclear NF-κB, IL-6, p-Stat3, Twist and Vimentin (a mesenchymal marker) in SP cells. Nuclear NF-κB activity and IL-6 level were also decreased after treatment with sesamin. CONCLUSION: Food-derived sesamin directs the epithelial differentiation of cancer stem-like SP cells from GBC, which is associated with attenuation of NF-κB-IL-6-Stat3-Twist signal pathway.

Sesamin ameliorates nonalcoholic steatohepatitis through inhibiting hepatocyte pyroptosis in vivo and in vitro.

Sesamin (Ses) is a natural lignan abundantly present in sesame and sesame oil. Pyroptosis, a newly identified type of pro-inflammatory programmed necrosis, contributes to the development of non-alcoholic steatohepatitis (NASH) when hepatocyte pyroptosis is excessive. In this study, Ses treatment demonstrated an improvement in hepatic damage in mice with high-fat, high-cholesterol diet-induced NASH and palmitate (PA)-treated mouse primary hepatocytes. Notably, we discovered, for the first time, that Ses could alleviate hepatocyte pyroptosis both in vivo and in vitro. Furthermore, treatment with phorbol myristate acetate, a protein kinase Cδ (PKCδ) agonist, increased PKCδ phosphorylation and attenuated the protective effects of Ses against pyroptosis in PA-treated mouse primary hepatocytes. Mechanistically, Ses treatment alleviated hepatocyte pyroptosis in NASH, which was associated with the regulation of the PKCδ/nod-like receptor family CARD domain-containing protein 4/caspase-1 axis. This study introduces a novel concept and target, suggesting the potential use of functional factors in food to alleviate liver damage caused by NASH.

Metformin improves nonalcoholic fatty liver disease in db/db mice by inhibiting ferroptosis.

Nonalcoholic fatty liver disease (NAFLD) is the primary complication of type 2 diabetes (T2DM)-related liver disease, lacking effective treatment options. Metformin (Met), a widely prescribed anti-hyperglycemic medication, has been found to protect against NAFLD. Ferroptosis, a newly discovered form of cell death, is associated with the development of NAFLD. Despite this association, the extent of Met's protective effects on NAFLD through the modulation of ferroptosis has yet to be thoroughly investigated. In the present study, the administration of erastin or Ras-selective lethal 3 (RSL3), both known ferroptosis inducers, resulted in elevated cell mortality and reduced cell viability in AML12 hepatocytes. Notably, Met treatment demonstrated the capacity to mitigate these effects. Furthermore, we observed increased ferroptosis levels in both AML12 hepatocytes treated with palmitate and oleate (PA/OA) and in the liver tissue of db/db mice. Met treatment demonstrated significant reductions in iron accumulation and lipid-related reactive oxygen species production, simultaneously elevating the glutathione/glutathione disulfide ratio in both PA/OA-treated AML12 hepatocytes and the liver tissue of db/db mice. Interestingly, the anti-ferroptosis effects of Met were significantly reversed with the administration of RSL3, both in vitro and in vivo. Mechanistically, Met treatment regulated the glutathione peroxidase 4/solute carrier family 7 member 11/acyl-CoA synthetase long-chain family member 4 axis to alleviate ferroptosis in NAFLD hepatocytes. Overall, our findings highlight the crucial role of ferroptosis in the development of T2DM-related NAFLD and underscore the potential of Met in modulating key factors associated with ferroptosis in the context of NAFLD.

Response of the soil microbial community to imazethapyr application in a soybean field.

The objective of this study was to determine the effects of imazethapyr on soil microbial communities combined with its effect on soybean growth. A short-term field experiment was conducted, and imazethapyr was applied to the soil at three different doses [1-fold, 10-fold, and 50-fold of the recommended field rate (H1, H10, H50)] during the soybean seedling period (with two leaves). Soil sampling was performed after 1, 7, 30, 60, 90, and 120 days of application to determine the imazethapyr concentration and microbial community structure by investigating phospholipid fatty acids (PLFA) and microbial biomass carbon (MBC). The half-lives of the imazethapyr in the field soil varied from 30.1 to 43.3 days. Imazethapyr at H1 was innocuous to soybean plants, but imazethapyr at H10 and H50 led to a significant inhibition in soybean plant height and leaf number. The soil MBC, total PLFA, and bacterial PLFA were decreased by the application of imazethapyr during the initial period and could recover by the end of the experiment. The ratio of Gram-negative/Gram-positive (GN/GP) bacteria during the three treatments went through increases and decreases, and then recovered at the end of the experiment. The fungal PLFA of all three treatments increased during the initial period and then declined, and only the fungal PLFA at H50 recovered by the end of the treatment. A principal component analysis (PCA) of the PLFA clearly separated the treatments and sampling times, and the results demonstrate that imazethapyr alters the microbial community structure. This is the first systemic study reporting the effects of imazethapyr on the soil microbial community structure under soybean field conditions.

The content and effectiveness of physical activity for cancer-related fatigue among colorectal cancer survivors: Systematic review and meta-analysis.

AIMS: To review the content and efficacy of physical activity (PA) for cancer-related fatigue (CRF) among colorectal cancer survivors. DESIGN: Systematic review. METHODS: A comprehensive search for randomized controlled trials from inception to April 1, 2022, of the following database was performed: EMBASE, PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data and China Biology Medicine (CBM). RevMan5.4 software was used for performing meta-analysis. RESULTS: A total of eight qualified randomized controlled trials that included 542 survivors were included. PA interventions significantly reduced the CRF (SMD = -0.46; 95% CI: [-0.76, -0.15], Z = 2.67, p = 0.003); Subgroup analysis showed that fatigue was significantly improved when the length of interventions was at least 6 months and the weekly duration of PA was less than 150 min/week (SMD = -0.54; 95% CI: [-0.81, -0.27], Z = 3.87 and p = 0.0001; SMD = -0.67; 95% CI: [-1.15, -0.19], Z = 2.74 and p = 0.006); PA intervention with the length of <6 months and the volume of ≥150 min/week did not reduce fatigue (p > 0.05).

Protective effects of metformin on pancreatic ß-cell ferroptosis in type 2 diabetes in vivo.

Metformin (Met) is the recommended first-line therapeutic drug for type 2 diabetes mellitus (T2DM) and exerts protective effects on ß-cell damage. Ferroptosis, a new form of cell death, is associated with pancreatic islet injury in patients with T2DM. However, the protective effects of Met treatment against ß-cell damage through ferroptosis modulation remain under-reported. This study investigated the in vivo effects of Met treatment on pancreatic ß-cell ferroptosis using two different diabetic mouse models, namely, low-dose streptozotocin (STZ) and high-fat diet (HFD)-induced diabetic mice and db/db mice. Met treatment significantly restored insulin release, reduced cell mortality, and decreased the overproduction of lipid-related reactive oxygen species in the islets of both STZ/HFD-induced diabetic mice and db/db mice. Administration of the Ras-selective lethal 3 injection significantly attenuated the antiferroptosis effects of Met. Mechanistically, Met treatment alleviated ß-cell ferroptosis in T2DM, which was associated with the regulation of the GPX4/ACSL4 axis in the islets. In conclusion, our findings highlight the significance of ferroptosis in T2DM ß-cell damage and provide novel insights into the protective effects of Met against islet ß cells.

Metformin alleviates glucolipotoxicity-induced pancreatic ß cell ferroptosis through regulation of the GPX4/ACSL4 axis.

Ferroptosis, a new type of cell death, is associated with pancreatic ß cell damage. However, the role of glucolipotoxicity in inducing ß cell ferroptosis remains unclear. Metformin (Met), exenatide (Exe), and saxagliptin (Sax) are frequently used anti-hyperglycaemic drugs. However, their protective effects on ß cells through ferroptosis modulation are not well-established. In this study, we observed significant ferroptosis in NIT-1 cells and primary mouse islets after exposure to high glucose and palmitate (HG/PA). Compared to Exe and Sax, Met significantly alleviated glucolipotoxicity-induced pancreatic ß cell ferroptosis. Blocking the activity of glutathione peroxidase 4 (GPX4) with Ras-selective lethal 3 or inhibiting its expression by small interfering RNA transfection significantly attenuated the anti-ferroptosis effects of Met. Mechanistically, Met alleviates HG/PA-induced ß cell ferroptosis by regulating the GPX4/ACSL4 axis. Collectively, our findings highlight the significance of ferroptosis in pancreatic ß cell glucolipotoxicity-induced injury and provide novel insights into the protective effects of Met on islet ß cells.

Portal vein aneurysm combined with intrahepatic portosystemic venous shunt diagnosed by multimodal imaging techniques: A case report.

INTRODUCTION: Portal vein aneurysms (PVA) and intrahepatic portosystemic venous shunts are rarely diagnosed clinically. PATIENT CONCERNS: A 75-year-old female was admitted to our hospital for evaluation of significant weight loss, diabetes, and an irregularly shaped cystic lesion in the left lateral lobe of the liver. DIAGNOSIS: The patient was diagnosed with a portal vein aneurysm combined with an intrahepatic portosystemic venous shunt using multiple imaging techniques. INTERVENTIONS: The patient had no relevant clinical symptoms of PVA with concurrent intrahepatic portosystemic venous shunt; hence, no interventions were performed. Ultrasonography was suggested to be performed every 3 months. OUTCOMES: The patient did not visit the hospital after discharge; however, 4 telephonic follow-up evaluations showed that the patient was well. LESSONS: Multimodal imaging techniques should be used to evaluate the source of blood flow, presence or absence of shunts, and the course, number, and location of the shunts to prevent misdiagnosis of this disease.

Quality Assessment of the Clinical Practice Guidelines of Ostomy Care Based on the AGREE II Instrument.

Objectives: To assess the quality of clinical practice guidelines (CPGs) of ostomy care, and to analyze the status quo and challenges of guideline development. Methods: CPGs of ostomy care were systematically searched in relevant guideline websites and electronic databases, including PubMed, ProQuest, Web of Science, CNKI, VIP, WANFANG, and SinoMed, from January 1, 2012, to November 24, 2021. Two appraisers used the Appraisal of Guidelines for Research and Evaluation, 2nd edition (AGREE II) instrument to assess the quality of the included CPGs independently and objectively. The consistency of assessment was calculated using intraclass correlation coefficients (ICC). Results: A total of 5 CPGs relevant to ostomy care were assessed by AGREE II and the general quality of them was good. There were two CPGs of grade A and three CPGs of grade B. The domain scope and purpose (87.78%) had the highest scores, followed by the clarity of presentation (87.22%), the rigor of development (69.17%), stakeholder involvement (68.33%), and editorial independence (65.00%), and the lowest was applicability (55.42%). The overall assessment score was 5.40. All the ICCs for the AGREE II appraisal conducted by the two appraisers were >0.75. Conclusions: The five CPGs of ostomy care have the potential to be adopted in clinical practice. However, they still have some room for improvement, especially in the applicability domain. The development of ostomy care CPGs should follow the evidence-based progress and methodology of guideline formulation specifications while considering the effects of the CPGs and the practical issues.

Applications for natural deep eutectic solvents in Chinese herbal medicines.

Chinese herbal medicines (CHMs), with a wide range of bioactive components, are considered to be an important source for new drug discovery. However, the process to isolate and obtain those bioactive components to develop new drugs always consumes a large amount of organic solvents with high toxicity and non-biodegradability. Natural deep eutectic solvents (NADES), a new type of green and designable solvents composed of primary plant-based metabolites, have been used as eco-friendly substitutes for traditional organic solvents in various fields. Due to the advantages of easy preparation, low production cost, low toxicity, and eco-friendliness, NADES have been also applied as extraction solvents, media, and drug delivery agents in CHMs in recent years. Besides, the special properties of NADES have been contributed to elucidating the traditional processing (also named Paozhi in Chinese) theory of CHMs, especially processing with honey. In this paper, the development process, preparation, classification, and applications for NADES in CHMs have been reviewed. Prospects in the future applications and challenges have been discussed to better understand the possibilities of the new solvents in the drug development and other uses of CHMs.

An electrochemically stable homogeneous glassy electrolyte formed at room temperature for all-solid-state sodium batteries.

All-solid-state sodium batteries (ASSSBs) are promising candidates for grid-scale energy storage. However, there are no commercialized ASSSBs yet, in part due to the lack of a low-cost, simple-to-fabricate solid electrolyte (SE) with electrochemical stability towards Na metal. In this work, we report a family of oxysulfide glass SEs (Na3PS4-xOx, where 0 < x ≤ 0.60) that not only exhibit the highest critical current density among all Na-ion conducting sulfide-based SEs, but also enable high-performance ambient-temperature sodium-sulfur batteries. By forming bridging oxygen units, the Na3PS4-xOx SEs undergo pressure-induced sintering at room temperature, resulting in a fully homogeneous glass structure with robust mechanical properties. Furthermore, the self-passivating solid electrolyte interphase at the Na|SE interface is critical for interface stabilization and reversible Na plating and stripping. The new structural and compositional design strategies presented here provide a new paradigm in the development of safe, low-cost, energy-dense, and long-lifetime ASSSBs.

Market access for Chinese herbal medicinal products in Europe-A ten-year review of relevant products, policies, and challenges.

BACKGROUND: With increased consumer demand in Europe for natural and efficacious health products, the use of herbal products in the market is rising. Products of Chinese herbal medicine (CHM) could greatly expand European consumer options; however, only seven herbal medicinal products (HMPs) based on CHM formulae have been registered in the European Union (EU) since 2012. PURPOSE: This study reviews the ten-year registration status of HMPs based on CHM formulae in Europe and identifies major challenges and possible solutions for pharmaceutical companies seeking market access for new HMPs. METHODS: An overview of relevant EU regulations identifies pathways to market access in EU countries for CHM products. A discussion of successful attempts to register HMPs based on CHM formulae since 2012 highlights specific challenges that applicants can expect to face. RESULTS: CHM products can enter the EU market as HMPs through the full or well-established use marketing authorization, or through the simplified registration procedure. Alternatively, some CHM products have entered the market as dietary supplements, nutritional foods, and agricultural products; however, under these categories, claims for medicinal use cannot be advertised. Since the registration of the first CHM product, Diao Xin Xue Kang (with the single component of Dioscorea nipponica rhizome), in 2012, only six other HMPs based on CHM formulae have been successfully registered. Among these, four are mono-component products. The remaining two products contain combinations of several herbal ingredients. It is more difficult to register combination products than mono-component products, due to their more complex composition and differences in registration requirements (esp. concerning establishing indications) in China and Europe. CONCLUSIONS: To promote the successful registration of CHM products in Europe, pharmaceutical companies are advised to: demonstrate full control of, and the ability to test, their supply chain and manufacturing procedures following the guidance of European competent authorities; carefully adhere to all steps of the registration process and advices from European competent authorities; take the medication habits and pharmaceutical needs of European market into consideration; and establish collaboration with European local organizations, as appropriate.

Steamed Panax notoginseng and its Saponins Inhibit the Migration and Induce the Apoptosis of Neutrophils in a Zebrafish Tail-Fin Amputation Model.

Panax notoginseng (PN) is a Chinese medicinal herb that is traditionally used to treat inflammation and immune-related diseases. Its major active constituents are saponins, the types and levels of which can be changed in the process of steaming. These differences in saponins are causally relevant to the differences in the therapeutic efficacies of raw and steamed PN. In this study, we have prepared the extracts of steamed PN (SPNE) with 70% ethanol and investigated their immunomodulatory effect using a zebrafish tail-fin amputation model. A fingerprint-effect relationship analysis was performed to uncover active constituents of SPNE samples related to the inhibitory effect on neutrophil number. The results showed that SPNE significantly inhibited the neutrophil number at the amputation site of zebrafish larvae. And SPNE extracts steamed at higher temperatures and for longer time periods showed a stronger inhibitory effect. Ginsenosides Rh1, Rk3, Rh4, 20(S)-Rg3, and 20(R)-Rg3, of which the levels were increased along with the duration of steaming, were found to be the major active constituents contributing to the neutrophil-inhibiting effect of SPNE. By additionally investigating the number of neutrophils in the entire tail of zebrafish larvae and performing TUNEL assays, we found that the decreased number of neutrophils at the amputation site was due to both the inhibition of their migration and apoptosis-inducing effects of the ginsenosides in SPNE on neutrophils. Among them, Rh1 and 20(R)-Rg3 did not affect the number of neutrophils at the entire tail, suggesting that they only inhibit the migration of neutrophils. In contrast, ginsenosides Rk3, Rh4, 20(S)-Rg3, and SPNE did not only inhibit the migration of neutrophils but also promoted neutrophilic cell death. In conclusion, this study sheds light on how SPNE, in particular the ginsenosides it contains, plays a role in immune modulation.

[Proof of solid state cathodoluminescence by using brightness waveform].

Three different inorganic-organic hetero-junctions (A: ITO/SiO2/Alq3/Al, B: ITO/Alq3/SiO2/Al and C: ITO/SiO2/Alq3/SiO2/Al) were fabricated. The emission can be observed only under positive bias in devices A and B, but under both biases in device C according to their brightness waveforms. With increasing voltage, the increase in blue emission in devices B and C is faster than that in green emission. This is because that the recombination of hot electrons and holes, i.e., electron-hole pairs, produced blue emission in devices B and C, and the recombination of electrons injected from Al with the accumulated holes, which are excited by hot electrons, produced green emission in device A. Hence, the emissions of the devices are attributed to not only the recombination of electrons and accumulated holes, but also the cathodoluminescence-like (CL-like) emission.

A novel self-assembled targeted nanoparticle platform based on carboxymethylcellulose co-delivery of anticancer drugs.

Single-drug therapy for cancer is greatly hampered by its non-specific delivery to the target tissue, limited efficacies, poor tolerability, and resistance profiles. In order to overcome these limitations, we developed a new targeted nanoparticle platform for co-delivery of two different anticancer drugs. A conjugate based on carboxymethylcellulose (CMC) was first synthesized by introducing hydrophilic molecules (PEG), target molecules (folate), and drug molecules (betulinic acid) into CMC. Then another anticancer drug hydroxycamptothecine (HCPT) was encapsulated into the nanoparticles from the conjugate using a simple nanoprecipitation method. The obtained nanoparticles possessed appropriate size (∼180 nm), high drug loading efficiency (∼23 wt% BA, 21.15 wt% HCPT), a slow drug release rate, higher blood circulation half-time of free BA (6.4-fold) and HCPT (6.0-fold), and high synergetic activity of BA and HCPT toward cancer cells. Furthermore, the targeted nanoparticles showed rapid cellular uptake by tumor cells. The antitumor effect of the nanoparticles in a mouse tumor xenograft model exhibited a much better tumor inhibition efficacy and fewer side effects than that of BA and HCPT, strongly supporting their application as efficient carriers for anticancer therapy.

Sesamin enhances nitric oxide bioactivity in aortas of spontaneously hypertensive rats.

BACKGROUND: The blood pressure lowering effect of sesamin has been demonstrated to be associated with the increase in vascular nitric oxide (NO) biological activity by our previous studies and others. The present study was designed to explore the underlying mechanisms involved in the effect of sesamin on aortic NO bioactivity in spontaneously hypertensive rats (SHRs). METHODS: Sesamin was orally administered for 8 consecutive weeks in SHRs. Systolic blood pressure (SBP) was measured using the tail-cuff method. The aortas were isolated and in vitro vascular reactivity studies were performed. Superoxide anion production in carotid arteries was assessed by dihydroethidium fluorescence staining. The protein expression of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (P-eNOS), dihydrofolate reductase (DHFR), nicotinamide adenine dinucleotide phosphate oxidase subunit p47phox, and copper, zinc superoxide dismutase (Cu/Zn-SOD) in aortas was detected by Western blotting. The dimeric form of eNOS in aortas was determined by low-temperature sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Aortic level of nitrotyrosine and activities of antioxidant enzymes, namely, total SOD (T-SOD), glutathione peroxidase (GPx) and catalase were also detected. RESULTS: In SHRs, sesamin treatment reduced SBP, improved vascular relaxation induced by acetylcholine and enhanced aortic NO bioactivity. Sesamin treatment enhanced NO biosynthesis in SHR aortas was due to upregulated P-eNOS and suppressed eNOS uncoupling, and the latter effect might be attributed to decreased nitrotyrosine and upregulated DHFR. Sesamin also reduced the NO oxidative inactivation and decreased the superoxide anion production through downregulation of p47(phox) and amelioration of eNOS uncoupling. In addition, sesamin treatment did not alter the levels of GPx and catalase activity but obviously reduced the compensatory elevated T-SOD activity and Cu/Zn-SOD protein expression. CONCLUSION: Chronic treatment with sesamin could reduce hypertension and improve endothelial dysfunction through enhancement of NO bioactivity in SHR aortas.