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JOURNAL OF ELECTROANALYTICAL CHEMISTRY · 2016 · IF 2.822

Electrochemical behavior of metribuzin based on l-Norvaline modified electrode and its sensitive determination

Donglin Jia,Lu Wang,Yudong Gao,Lina Zou,Baoxian Ye

The electro-polymerization of l -Norvaline was investigated for the first time on glassy carbon electrode. The polymeric conditions and mechanism were discussed in detail. The electrochemical behaviors of metribuzin were studied systematically at this sensor and the dynamic parameters of electrode process were calculated. This electrochemical sensor, fabricated simply and very easy surface update, showed good response for metribuzin with a wide linear range from 6.43   ×   10 −   3 to 1.07   μg/mL and a low detection limit of 2.14   ×   10 −   3   μg/mL (S/N   =   3). The proposed method was successfully applied to determine metribuzin in soil sample with satisfactory results. This work promoted the potential applications of amino acid materials in electrochemical sensors.

CAS / MDL: 21087-64-9 6600-40-4
研究领域: 分析化学 · 环境科学 · 生物传感技术
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BIOMEDICINE & PHARMACOTHERAPY · 2019 · IF 3.743

Combination of L-Arginine and L-Norvaline protects against pulmonary fibrosis progression induced by bleomycin in mice

Lu Gao,Jia-Hua Zhang,Xiao-Xu Chen,Hui-Li Ren,Xiu-Ling Feng,Jia-Ling Wang,Jun-Hua Xiao

Pulmonary fibrosis (PF) progression may be involved with arginine (Arg) metabolism and immune balance. The present study aimed to explore the effects of L-Arginine (L-Arg) and L-Norvaline (L-Nor) on bleomycin (BLM)-induced PF in mice, meanwhile, and observe dynamic changes of Arg metabolism, immune balance and crosstalk between them in PF progression. Followed intratracheal instillation of BLM or saline, Kunming mice were treated orally with saline, L-Arg, L-Nor and L-Arg + L-Nor three times a day. And the mice were sacrificed on Day 3, 14 and 28 after treatment. Changes of body weight, lung index, lung hydroxyproline and histopathology were analyzed to evaluate the PF degree. Peripheral blood Arg, Citrulline (Cit), Ornithine (Orn) and Proline (Pro), lung NO, NOS and arginase were analyzed to evaluate the Arg metabolism. Peripheral blood Tregs, Th17 and γδT cells were analyzed to evaluate the immune balance. Our data showed that combination of L-Arg and L-Nor dynamically reversed the weight loss, decreased lung index and hydroxyproline, and improved lung histopathological damages induced by BLM. The combination dynamically and significantly rectified Tregs, Th17, γδT and Tregs/Th17 abnormal changes. Meanwhile, these disorders of peripheral blood Arg, Cit, Orn, Pro, Orn/Cit and Pro/Orn, and lung NO, iNOS and TNOS were also improved accordingly. These results demonstrated that combination of L-Arg and L-Nor had inhibitory effects on BLM-induced PF progression, possibly due to their corrective action on immune imbalance, Arg metabolism disorder and crosstalk abnormality in the progression of PF.

CAS / MDL: 327-57-1
研究领域: 药理学 · 免疫学 · 肺病学
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CHEMICAL ENGINEERING JOURNAL · 2023 · IF 15.1

A hydrogel-enabled cascade amplification of radiosensitization and immune activation for cancer radiotherapy

Qingxu Song,Gongde Lan,Qian Li,Yang Lin,Xin Chen,Hong Liu,Yufeng Cheng,Yuxia Luan

Hypofractionated radiotherapy (HRT) is a promising approach for tumor treatment, owing to its straightforward elimination of tumor cells and stimulation of immunogenic cell death. However, clinical application of HRT is hindered by the inherent radio-resistance and inadequate immune activation. Herein, an injectable hydrogel platform was reported, enabling a cascade amplification of radiosensitization and immune activation to potentiate HRT. The hydrogel with encapsulated TLR7/8 agonist R848 is in situ constructed in tumor via L-norvaline-based polymer (LNP, a gelator). During HRT, the released L-norvaline from LNP suppresses L-arginine consumption through arginase 1 (ARG1) pathway, sparing adequate L-arginine that was used for radiosensitizer nitric oxide (NO) production by inducible NO synthase (iNOS). Meanwhile, R848 repolarizes tumor-associated macrophages (TAMs) from M2 type with rich ARG1 to M1 type with rich iNOS, reinforcing NO production and disrupting M2-type TAMs-induced radio-resistance and immunosuppression. Therefore, the hydrogel demonstrates a cascade regulation of radio-sensitization and immune activation, achieving powerful inhibition of tumor growth and tumor metastasis. This hydrogel provides a novel approach to potentiate HRT, holding great promise in clinical application.

研究领域: 肿瘤学 · 放射肿瘤学 · 免疫疗法
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JOURNAL OF CONTROLLED RELEASE · 2024 · IF 10.5

Nanodrugs mediate TAMs-related arginine metabolism interference to boost photodynamic immunotherapy

Yi Chen,Xian Shu,Jia-Yi Guo,Yun Xiang,Shi-Yu Liang,Jin-Mei Lai,Jia-Yi Zhou,Li-Han Liu,Ping Wang

As a potential treatment strategy for low immunogenic triple negative breast cancer (TNBC), photodynamic therapy (PDT) induced antitumor immunotherapy is greatly limited by the immunosuppressive tumor microenvironment (ITM), especially the M2 phenotype tumor-associated macrophages (TAMs). The balance of arginine metabolism plays an important role in TAMs polarization. Herein, a multifunctional nanoplatform (defined as HN-HFPA) was employed to burst the anti-tumor immunity of TNBC post PDT by reeducating TAMs through interfering the TAMs-associated arginine metabolism. The L -arginine ( L -Arg) was loaded in the hollow cavity of HN-HFPA, which could not only generate nitric oxide (NO) for tumor therapy, but also serve as a substrate of arginine metabolism pathway. As an inhibitor of arginases-1 (Arg-1) of M2 TAMs, L -norvaline ( L -Nor) was modified to the hyaluronic acid (HA), and coated in the surface of HFPA. After degradation of HA by hyaluronidase in tumor tissue and GSH-mediated disintegration, HN-HFPA depleted intracellular GSH, produced remarkable reactive oxygen species (ROS) under light irradiation and released L -Arg to generate NO, which induced tumor immunogenic cell death (ICD). Real-time ultrasound imaging of tumor was realized taking advantage of the gas feature of NO. The L -Nor suppressed the Arg-1 overexpressed in M2, which skewed the balance of arginine metabolism and reversed the ITM with increased ratios of M1 and CD8 + T cells , finally resulted in amplified antitumor immune response and apparent tumor metastasis inhibition . This study remodeled ITM to strengthen immune response post PDT, which provided a promising treatment strategy for TNBC.

研究领域: 癌症生物学 · 免疫学 · 药学 · 生物医学工程
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JOURNAL OF INDUSTRIAL AND ENGINEERING CHEMISTRY · 2022 · IF 6.76

Additive-assisted preferential crystallization of racemic component: A case of norvaline

Jie Sun,Yaping Wang,Zhenguo Gao,Junbo Gong,Weiwei Tang

Herein, we report a successful resolution of L-norvaline, a racemic compound system, performed near the eutectic composition by coupling preferential crystallization with tailor-made additives. The structures of enantiomer and racemate were characterized by PXRD, DSC , and the enantiomeric purity were measured by Chiral HPLC. The preferential crystallization process was designed and established from binary melting phase diagram and ternary solution phase diagram. The effects of supersaturation, solution enantiomer composition, and seed quantity on the preferential crystallization process were investigated. However, the significant improvements of enantiomeric purity and product yield were demonstrated by additive-assisted preferential crystallization approach using tailor-made additives. These additives bearing similar structure motifs to norvaline a highly selective binding to the racemate rather than enantiomer and remarkably suppress nucleation of DL-norvaline, the key factor determining the resultant enantiomer purity and separation efficiency. The underly inhibition principle was revealed due to the centrosymmetric packing of the racemate while the polarity of enantiomer leads to only partial or slight crystallization suppression. The interesting inhibition mode by tailor-made additives is also believed to be applicable for other racemic crystallization systems. Our established additive-assisted preferential crystallization has showed great potential in the development of separation technology and resolution of enantiomer from racemic compounds.

研究领域: 化学 · 材料科学 · 药学
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