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JOURNAL OF NANOBIOTECHNOLOGY · 2024 ·Vol. 22 ·期 1 ·1-15 · IF 10.6

NOS-like activity of CeO2 nanozymes contributes to diminishing the vascular plaques

Sun Yuxiang,Xu Tianze,Qian Yike,Chen Qiaoyun,Xiong Fei,Du Wenxian,Xu Li

Ceria nanoparticles (CeO 2 NPs) exhibit great potential in cardiovascular disease and nonalcoholic fatty liver disease due to its excellent antioxidant capacity. However, the profitable effect of CeO 2 NPs on many diseases is almost all attributed to the regulation of ROS. Apart from the general antioxidant function, there seems to be no more distinct mechanism to reflect its unique multi-disease improvement effect. Here, we for the first time reveal a new discovery of CeO 2 NPs in mimicking nitric oxide synthase (NOS) by catalyzing L-arginine (L-Arg) to produce nitric oxide (NO) or the derivatives. NOS-like activity of CeO 2 NPs is original and associated with multiple factors like substrate concentration, pH, temperature and time, etc. where oxygen vacancy ratio plays a more critical role. Meanwhile, NOS-like activity of CeO 2 NPs successfully elevates NO secretion in endothelial cells and macrophages without expanding eNOS/iNOS expression. Importantly, NOS-like activity of CeO 2 NPs and the responsive endogenous NO promote the re-distribution of blood lipids and stabilize eNOS expression but suppress iNOS, thus collectively alleviate the accumulation of vascular plaque. Altogether, we provide a new angle of view to survey the outstanding potential of CeO 2 NPs, apart from the inevitable antioxidant capacity, the covert but possible and more critical NOS-like enzymatic activity is more noteworthy.

研究领域: 生物医学工程 · 心血管疾病研究 · 纳米医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Communications Biology · 2026 · IF 5.8

OGT-mediated PIN O-GlcNAcylation drives depression-like behaviors by impairing NOS-stargazin-GluA1 signaling

Gu Xunhu,Liu Xu,Xiong Yong,Chen Xuefen,Zhang Yancai,Zheng Li-Li,Wang Wei

Major depressive disorder is associated with impaired excitatory synaptic transmission, but the molecular mechanisms linking chronic stress to altered AMPA receptor trafficking remain incompletely understood. Here we show that chronic mild stress increases OGT-mediated O-GlcNAcylation of PIN at serine 88, which stabilizes PIN and enhances its interaction with nitric oxide synthase. This suppresses nitric oxide synthase activity, reduces stargazin S-nitrosylation, weakens stargazin-GluA1 binding, and impairs GluA1-containing AMPA receptor trafficking. Genetic or pharmacological inhibition of OGT restores this signaling pathway and alleviates stress-induced depression-like behaviors in mice. These findings identify the OGT-PIN-NOS-stargazin axis as a regulator of stress-induced synaptic dysfunction and suggest that targeting OGT may help restore AMPA receptor trafficking in depression-related conditions.

✓ 已验证 DOI PubMed 高影响因子
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BIOMATERIALS · 2020 · IF 10.317

Biomimetic nano-NOS mediated local NO release for inhibiting cancer-associated platelet activation and disrupting tumor vascular barriers

Zhifang Ma,Shi Liu,Yue Ke,Haozheng Wang,Runhai Chen,Zehong Xiang,Zhigang Xie,Qiang Shi,Jinghua Yin

Platelets attribute to the hypercoagulation of blood and maintenance of the tumor vascular integrity, resulting in limited intratumoral perfusion of nanoparticle into solid tumors. To overcome these adversities, we herein present an antiplatelet strategy based on erythrocyte membrane-enveloped proteinic nanoparticles that biomimic nitric oxide synthase (NOS)with co-loading of l -Arginine (LA) and photosensitizer IR783 for local NO release and inhibition of the activation of tumor-associated platelets specifically, thereby enhancing vascular permeability and accumulation of the nanoparticles in tumors. A cRGD-immobolized membrane structure is constructed to actively target platelets and cancer cells respectively, through overexpressed integrin receptors such as integrin α IIb β 3 and α v β 3 , accelerating the inhibition of platelet activation and endocytosis of nanoparticles by tumor cells. Bio-mimicking the arginine/NO pathway in vivo , synergistical delivery of LA and IR783 enables LA molecules readily oxidize to NO with O 2 that is mediated by activated IR783, the resulted NO not only retards the activity of platelets to disrupt the vascular integrity of tumor but also enhances toxicity to cancer cells. In addition, NIR-controlled release localizes the NO spatiotemporally to tumor-associated platelets and prevents undesirable systemic bleeding substantially. The reduction of the hypercoagulable state is further demonstrated by the down-regulation of tissues factor (TF) expression in tumor cells. Our study describes a promising approach to combat cancer, which advances the biomimetic NOS system as the potent therapeutic forces toward clinic applications.

研究领域: 癌症治疗 · 纳米技术 · 药理学 · 仿生学 · 分子生物学
✓ 已验证 DOI PubMed 高影响因子
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MEAT SCIENCE · 2020 · IF 3.644

Nitrosylmyoglobin formation in meat by Lactobacillus fermentum AS1.1880 is due to its nitric oxide synthase activity

Huiting Luo,Peijun Li,Hongwei Zhang,Xinping Diao,Baohua Kong

The objective of this study was to clarify whether formation of nitrosylmyoglobin (MbFe II NO) by Lactobacillus fermentum AS1.1880 in meat is due to nitric oxide synthase (NOS) activity. Confocal laser scanning microscopy exhibited strong green fluorescence in the L . fermentum sample treated with a nitric oxide (NO)-specific probe, directly indicating that NO was produced. Furthermore, determination of NOS activity based on the presence of NO metabolites indicated the existence of NOS in L.fermentum . A NOS inhibitor, N G -nitro-L-arginine methyl ester, significantly inhibited the activity of NOS in L.fermentum ( P  < 0.05). Futhermore, NOS protein was detected in L.fermentum by Western blot analysis. L-arginine addition largely increased the NOS activity of L.fermentum ( P  < 0.05). In meat batters , the redness of a sample inoculated with L.fermentum was higher than that of the control and colour was significantly improved with the addition of L-arginine ( P  < 0.05), indicating that more MbFe II NO was formed.

CAS / MDL: 74-79-3 50903-99-6
研究领域: 食品科学 · 微生物学 · 生物化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF HAZARDOUS MATERIALS · 2020 · IF 9.038

Selective stress of antibiotics on microbial denitrification: Inhibitory effects, dynamics of microbial community structure and function

Zhi-Ling Li,Rui Cheng,Fan Chen,Xiao-Qiu Lin,Xiao-Jing Yao,Bin Liang,Cong Huang,Kai Sun,Ai-Jie Wang

Antibiotics commonly exist in municipal, livestock and industrial wastewaters . However, the response of key microbiota performance in wastewater treatment plants to antibiotic exposure lacks systematic research. In this study, the short-term acute stress of four commonly used antibiotics (sulfamethoxazole, chlortetracycline, ciprofloxacin, and amoxicillin) on microbial denitrification performance was systematically investigated. All tested antibiotics exhibited the inhibitory effects in varying degrees by repeated addition for six cycles. The nitrate removal efficiencies ( NrE ) decreased to 7.98–26.80%, accompanied by the significant decrease of the expressed nar G gene, by exposure to sulfamethoxazole, chlortetracycline or amoxicillin. Nitrite reduction was inhibited more severely than nitrate reduction , which was further verified by the low- or non-expressed nir S and nos Z genes. Furthermore, a higher antibiotic concentration made stronger inhibitory effect. Except for chlortetracycline, 2.09–6.80 times decrease of k value was commonly observed as concentration increased from 10 to 50 or 100 mg L −1 . Even in a short period (24 h), antibiotics largely decreased the abundance of the dominant denitrifying bacterial genera ( Thauera , Comamonas , etc.), while, some unclassified populations ( Labrenzia , Longilinea, etc.) were enriched. This study provides theoretical researches on the microbial denitrification behaviors influenced by exposure to different antibiotics.

研究领域: 环境微生物学 · 废水处理 · 生态毒理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Evidence-based Complementary and Alternative Medicine · 2020 · IF 1.813

Oroxylin A Reduces Vasoconstriction in Rat Aortic Rings through Promoting NO Production and NOS Protein Expression via Estrogen Receptor Signal Pathway

Jingtian Qu,Fang Liu,Xuezhu Zhang,Jialong Wang

Oroxylin A, a flavonoid, is naturally produced in many medicinal plants. Our previous study identified it as a phytoestrogen. Based on this, the present study investigated its vasoconstriction reducing effects and whether the action was mediated by the estrogen receptor (ER) signal pathway. Long-term in vitro treatment with oroxylin A reduced Ach-induced vasorelaxation and NE-mediated or KCl-mediated contractile responses in rat aortic rings. These effects were interfered by an ER inhibitor ICI 182,780. Rat cardiac microvascular endothelial cells (CMECs) and aortic vascular smooth muscle cells (VSMCs) were used to study the possible underlying mechanisms. Oroxylin A activated the ER signal pathway. In CMECs, it increased NO production and eNOS protein expression. In VSMCs, it promoted NO production and iNOS protein expression. These effects were also inhibited by ICI 182,780. Besides, oroxylin A stimulated ERα and ERβ protein expression in CMECs and VSMCs. All these findings suggest that the ER signal pathway takes part in the vasoconstriction reducing effects of oroxylin A.

研究领域: 药理学 · 心血管研究 · 分子生物学
✓ 已验证 DOI PubMed 高影响因子
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ANALYTICAL BIOCHEMISTRY · 2020 · IF 2.877

Colorimetric biosensing of nopaline synthase terminator using Fe3O4@Au and hemin-functionalized reduced graphene oxide

Xiaodong Cao,Zihao Xia,Wuwen Yan,Shudong He,Xuan Xu,Zhaojun Wei,Yongkang Ye,Haisong Zheng

In this paper, we present a simple and label-free colorimetric biosensor for detection of the nopaline synthase (NOS) terminator in genetically modified (GM) plants. The “signal on” colorimetric biosensor was developed using a nanocomposite consisted of gold nanoparticles doped magnetic Fe 3 O 4 nanoparticles (Fe 3 O 4 @Au NP), capture probe DNA (cDNA), and hemin-functionalized reduced graphene oxide nanosheets (H-GN). The nanocomposite was successfully prepared by means of Au–S bonds and the strong π interactions between cDNA and H-GN. The sensing approach is based on the excellent peroxidase-mimicking activity of H-GN and its different electrostatic interactions with single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). In presence of the target NOS, the cDNA in the nanocomposite will hybridize with its complementary sequence, and form dsDNA structure. Due to the weak π interactions between dsDNA and H-GN, a portion of H-GN will be released from the surface of Fe 3 O 4 @Au NPs and transferred into solution. After magnetic separation was performed, the supernatant was incubated with 3,3′,5,5′-tetramethylbenzidine (TMB) in the presence of H 2 O 2 . The released H-GN can catalyze the oxidation reaction of TMB and turn the colorless solution blue. This “signal-on” colorimetric biosensor shows a broad linear range of 0.5–100 nM for the target NOS, with a 0.19 nM detection limit. The application of the biosensor for determination of NOS segments in samples of GM and non-GM tomatoes shows that it can discriminate between GM and non-GM plants. The reliability of the method for samples of NOS-spiked GM tomato suggests satisfactory recoveries in the range of 93.6%–94.2%.

研究领域: 生物化学 · 纳米技术 · 农业科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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APPLIED MICROBIOLOGY AND BIOTECHNOLOGY · 2023 ·Vol. 107 ·期 11 ·3745-3761 · IF 5

Heat stress enhanced perylenequinones biosynthesis of Shiraia sp. Slf14(w) through nitric oxide formation

Xu Chenglong,Lin Wenxi,Chen Yunni,Gao Boliang,Zhang Zhibin,Zhu Du

Perylenequinones (PQs) are a class of natural polyketides used as photodynamic therapeutics. Heat stress (HS) is an important environmental factor affecting secondary metabolism of fungi. This study investigated the effects of HS treatment on PQs biosynthesis of Shiraia sp. Slf14(w) and the underlying molecular mechanism. After the optimization of HS treatment conditions, the total PQs amount reached 577 ± 34.56 mg/L, which was 20.89-fold improvement over the control. Also, HS treatment stimulated the formation of intracellular nitric oxide (NO). Genome-wide analysis of Shiraia sp. Slf14(w) revealed iNOSL and cNOSL encoding inducible and constitutive NOS-like proteins (iNOSL and cNOSL), respectively. Cloned iNOSL in Escherichia coli BL21 showed higher nitric oxide synthase (NOS) activity than cNOSL, and the expression level of iNOSL under HS treatment was observably higher than that of cNOSL , suggesting that iNOSL is more responsible for NO production in the HS-treated strain Slf14(w) and may play an important role in regulating PQs biosynthesis. Moreover, the putative biosynthetic gene clusters for PQs and genes encoding iNOSL and nitrate reductase (NR) in the HS-treated strain Slf14(w) were obviously upregulated. PQs biosynthesis and efflux stimulated by HS treatment were significantly inhibited upon the addition of NO scavenger, NOS inhibitor, and NR inhibitor, indicating that HS-induced NO, as a signaling molecule, triggered promoted PQs biosynthesis and efflux. Our results provide an effective strategy for PQs production and contribute to the understanding of heat shock signal transduction studies of other fungi. Key points • PQs titer of Shiraia sp. Slf14(w) was significantly enhanced by HS treatment . • HS-induced NO was first reported to participate in PQs biosynthetic regulation . • Novel inducible and constitutive NOS-like proteins (iNOSL and cNOSL) were obtained and their NOS activities were determined .

CAS / MDL: 14402-89-2
研究领域: 微生物学 · 分子生物学 · 药理学 · 生物技术
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CHEMICAL ENGINEERING JOURNAL · 2021 · IF 13.273

Enhanced nitrate removal by biochar supported nano zero-valent iron (nZVI) at biocathode in bioelectrochemical system (BES)

Siqi Zhang,Ziang Kong,Han Wang,Qun Yan,Dimitris V. Vayenas,Guangsheng Zhang

In this study, activated biochar (BC), nano zero-valent iron (nZVI) and biochar supported nano zero-valent iron (BC-nZVI) were used to remove cathodic nitrate in bioelectrochemical system (BES). With an initial NO 3 – -N concentration of 100 mg/L, it was found that the complete nitrate removal could be observed within 28 h for the group of BC-nZVI, whereas the accumulated ammonia reached 63.33 mg/L. Meanwhile, nitrate removal reaction rate constants reached 0.171, 0.110, 0.023 and only 0.010 h −1 for BC-nZVI, nZVI, BC and the Control groups, respectively. Besides, enzymatic activity of nicotinamide adenine dinucleotide (NADH) and nitrous oxide reductase (NOS) of the BC-nZVI group reached the peak faster than three other groups. As a carrier for nZVI, loading of nZVI onto BC could increase the surface area of BC-nZVI other than nZVI for microbial aggregation, while embedded nZVI would contribute to the granulation of sludge and nitrate reduction. Moreover, Cyclic Voltammetry (CV) and chronoamperometry (CA) indicated that BC-nZVI group obtain better electrochemical performances. Importantly, it was found that not only abundances of microbial genus, but relative abundances of those iron mediated enzymes responsible for electro-consuming, hydrogen production and preferential ammonia accumulated nitrate removal could all be enriched. Therefore, BC-nZVI could be implemented to enhance the nitrate removal at biocathode in BES.

CAS / MDL: 16940-66-2
研究领域: 环境工程 · 电化学 · 微生物学 · 水处理
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JOURNAL OF ETHNOPHARMACOLOGY · 2020 · IF 3.69

Enzymatic preparation of Crassostrea oyster peptides and their promoting effect on male hormone production

Wanwan Zhang,Yifang Wei,Xiaoxiao Cao,Kaixin Guo,Qiangqiang Wang,Xiaochun Xiao,Xufeng Zhai,Dingding Wang,Zebo Huang

Ethnopharmacological relevance Crassostrea gigas Thunberg and other oysters have been traditionally used in China as folk remedies to invigorate the kidney and as natural aphrodisiacs to combat male impotence. Aim of the study Erectile dysfunction (ED) has become a major health problem for the global ageing population. The aim of this study is therefore to evaluate the effect of peptide-rich preparations from C. gigas oysters on ED and related conditions as increasing evidence suggests that peptides are important bioactive components of marine remedies and seafood. Materials and methods Crassostrea oyster peptide (COP) preparations COP1, COP2 and COP3 were obtained from C. gigas oysters by trypsin, papain or sequential trypsin-papain digestion, respectively. The contents of testosterone, cyclic adenosine monophosphate (cAMP) and nitric oxide (NO) and the activity of nitric oxide synthase (NOS) in mice and/or cells were measured by enzyme-linked immunosorbent assays. Real-time PCR was used to assess the expression of genes associated with sex hormone secretion pathways. The model animal Caenorhabditis elegans was also used to analyze the gene expression of a conserved steroidogenic enzyme. In silico analysis of constituent peptides was performed using bioinformatic tools based on public databases. Results The peptide-rich preparation COP3, in which >95% peptides were <3000 Da, was found to increase the contents of male mouse serum testosterone and cAMP, both of which are known to play important roles in erectile function, and to increase the activity of mouse penile NOS, which is closely associated with ED. Further investigation using mouse Leydig-derived TM3 cells demonstrates that COP3 was able to stimulate the production of testosterone as well as NO, a pivotal mediator of penile erection. Real-time PCR analysis reveals that COP3 up-regulated the expression of Areg and Acvr2b , the genes known to promote sex hormone secretion, but not Fst , a gene involved in suppressing follicle-stimulating hormone release. Furthermore, COP3 was also shown to up-regulate the expression of let-767 , a well-conserved C. elegans gene encoding a protein homologous to human 17-β-hydroxysteroid dehydrogenases. Preliminary bioinformatic analysis using the peptide sequences in COP3 cryptome identified 19 prospective motifs, each of which occurred in more than 10 peptides. Conclusions In this paper, Crassostrea oyster peptides were prepared by enzymatic hydrolysis and were found for the first time to increase ED-associated biochemical as well as molecular biology parameters. These results may help to explain the ethnopharmacological use of oysters and provide an important insight into the potentials of oyster peptides in overcoming ED-related health issues.

CAS / MDL: 9002-07-7
研究领域: 药理学 · 生物化学 · 分子生物学 · 民族药理学 · 海洋生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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