MOLECULES
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2022
·Vol. 28
·期 1
·295
·
IF 4.927
Mengyu Li,Hui Luo,Zhen Huang,Jin Qi,Boyang Yu
Erdong Gao (EDG), consisting equally of roots of Asparagi Radix and Ophiopogonis Radix, is a well-known traditional Chinese formulation that has been used to treat cough and throat pain for centuries. However, the bioactive components in EDG remain to be elucidated. In this study, a rapid and effective method involving live cell bio-specific extraction and HPLC-Q-TOF-MS/MS was established to rapidly screen and identify the anti-inflammatory compounds of an EDG extract. One hundred and twenty-four components were identified in EDG extract using HPLC-Q-TOF-MS/MS analysis. After co-incubation with 16HBE, HPAEpiCs and HUVECs, which have been validated as the key target cells for pulmonary diseases, sixteen components were demonstrated to exhibit an affinity for binding to them. Furthermore, fifteen components were subsequently verified to exert anti-inflammatory effects on lipopolysaccharide (LPS)-induced 16HBE, HPAEpiCs and HUVECs via inhibiting the release of TNF-α and IL-6, indicating that nine steroidal saponins may possess potential for the treatment of lung-related diseases. Taken together, our study provides evidence that live cell biospecific extraction combined with the HPLC-Q-TOF-MS/MS technique was an efficient method for rapid screening potential bioactive components in traditional Chinese medicines and the structure activity relationship of steroidal saponins in EDG was summarized for the first time.Keywords:Erdong Gao;anti-inflammatory;steroidal saponins;structure activity relationship;cell extraction
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CARBOHYDRATE POLYMERS
·
2019
·
IF 6.044
Wen-Na Zhang,Ri-Na Su,Li-Li Gong,Wei-Wei Yang,Juan Chen,Rui Yang,Ya Wang,Wen-Juan Pan,Yong-Ming Lu,Yan Chen
In this research, a polysaccharide fraction (EFSP-1) was obtained from the seeds of Euryale ferox Salisb. by DEAE sepharose FF and Superdex ™ 75 gel chromatography. The average molecular weight (Mw) of EFSP-1 was 8.75 kDa. Monosaccharides composition analysis indicated that EFSP-1 was a glucan. The structure of EFSP-1 was characterized by analysis of FT-IR, GC–MS and NMR, which indicated that the backbone of EFSP-1 was mainly composed of (1→4)- α -D-Glc p with branches substituted at O-6 and terminated with T- α -D-Glc p . Moreover, the hypoglycemic effect of EFSP-1 was investigated by establishing insulin resistance HepG2 and 3T3-L1 cells. The results showed that EFSP-1 could increase glucose consumption by up-regulating the expression of GLUT-4 via activating PI3K/Akt signal pathway in IR cells. Hence, EFSP-1 could be a potential functional food to ameliorate insulin resistance for diabetes therapy.
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ACS Biomaterials Science & Engineering
·
2018
·
IF 4.432
Xing Zhang,Xianyong Yin,Jianjun Luo,Xin Zheng,Huiying Wang,Jin Wang,Zhongqian Xi,Xianjiu Liao,Jeremiah Ong’achwa Machuki,Kaijin Guo,Fenglei Gao
Nanomaterials based on hybrid scaffolds have shown a high potential to promote osteointegration and bone regeneration. In this study, a novel nanocomposite scaffold was synthesized via a cross-linking/hydrothermal/freeze-drying method, resulting in layer-by-layer structures with functional and structural properties mimicking the natural bone. The hierarchical structures of the scaffold were reinforced with nitrogen-doped multiwalled carbon nanotubes (N-MWCNTs), cellulose, and nanohydroxyapatite. The N-MWCNT/Cel/nHA scaffolds were characterized and evaluated in terms of structure, morphology, biocompatibility, cellular responses, and bone repair efficiency in vivo. The resulting scaffolds showed that incorporation of 1 wt % N-MWCNTs into the hybrid scaffold with micropores (∼5 μm) significantly improved its mechanical properties, although the surface morphology of the scaffold tended to be rough and porous. Importantly, the resulting scaffolds supported in vitro cellular attachment, proliferation, viability, and mineralization of bone mesenchymal stem cells (BMSCs). On the other hand, incorporation of N-MWCNTs into the scaffold induced preferential differentiation of BMSCs to osteogenic lineage accompanied by increased alkaline phosphatase activity and expression of key osteogenic genes. Furthermore, 12 weeks after implantation, the 1%N-MWCNT/Cel/nHA porous scaffolds successfully cicatrized a distal femoral condyle critical size defect in rabbit without obvious inflammatory responses, as indicated by the results of the Micro-CT and histological analyses. In vitro and in vivo experiments confirmed that the scaffolds not only improved the interface bonding with bone tissue but also accelerated the new bone formation and regeneration by up-regulating signaling molecules that are involved in cell proliferation and differentiation. These results indicated that the novel N-MWCNT/Cel/nHA scaffold is an efficient platform for osteogenesis research and bone regeneration medicine.
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JOURNAL OF NANOBIOTECHNOLOGY
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2018
·Vol. 16
·期 1
·1-14
·
IF 5.294
Li Shujuan,Chen Li,Wang Guokang,Xu Lexing,Hou Shanshan,Chen Ziwei,Xu Xiaoling,Wang Xiaojuan,Liu Fuhe,Du Yong-Zhong
Background Acute lung injury (ALI) is a life-threatening clinical syndrome without effective treatment. Targeting delivery of glucocorticoid to lung shows potential efficacy for ALI based on their anti-inflammatory and anti-fibrotic properties, breaking through their clinical application limitation due to systemic side effects. This work was aimed to establish lung-targeted dexamethasone (DEX) loaded nanostructured lipid carriers (NLCs) with opposite surface charge and investigate their therapeutic effects on lipopolysaccharide (LPS)-induced ALI mice.Results The diameter of anionic anti-intercellular adhesion molecule 1 (anti-ICAM-1) antibody-conjugated DEX-loaded NLCs (ICAM/DEX/NLCs) and the cationic ones with octadecylamine (ODA) modification (ICAM/DEX/ODA-NLCs) was about 249.9 and 235.9 nm. The zeta potential of ICAM/DEX/NLCs and ICAM/DEX/ODA-NLCs was about − 30.3 and 37.4 mV, respectively. Relative to the non-targeted control and ICAM/DEX/ODA-NLCs, ICAM/DEX/NLCs exhibited higher in vitro cellular uptake in LPS-activated human vascular endothelial cell line EAhy926 after CAM-mediated endocytosis, and stronger in vivo pulmonary distribution in the ALI model mice. In vivo i.v. administration of ICAM/DEX/NLCs significantly attenuated pulmonary inflammatory cells infiltration, and the production of pro-inflammatory cytokine TNF-α and IL-6 in ALI mice. H&E stain also revealed positive histological improvements by ICAM/DEX/NLCs.Conclusion sICAM/DEX/NLCs may represent a potential pulmonary endothelium targeted device, which facilitate translation of DEX into clinical ALI treatment.
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ACS Applied Bio Materials
·
2018
·
IF 0
Jianjun Luo,Xing Zhang,Jeremiah Ong’achwa Machuki,Chengbai Dai,Yang Li,Kaijin Guo,Fenglei Gao
Composite biomaterials with hierarchical structures have emerged as new approaches for bone-tissue engineering. In this study, a biomimetic, osteoconductive tricomposite scaffold made of N-doped graphene–hydroxyapatite (NG–HA) hybrids blended with an agarose (AG) matrix was prepared via a facile hydrothermal/cross-linking/freeze-drying method. The structure and composition of AG/NG–HA were examined by scanning electron microscopy, X-ray photoelectron spectroscopy, X-ray diffraction, Fourier transform infrared, Raman spectroscopy, and thermogravimetric analysis. The as-prepared scaffolds showed hierarchical pore architecture and an organic–inorganic composition, which simulated the composition and structure of natural bone tissue. The effect of AG/NG–HA on bone mesenchymal stem cells (MSCs) osteoblast proliferation, differentiation, and mineralization was tested in vitro. The expression of osteogenic-related genes was determined by real-time polymerase chain reaction. Our results showed that the introduction of N-graphene into the hybrid scaffold significantly improved its mechanical properties, an effect that promoted the proliferation and viability of MSCs. Moreover, the scaffolds triggered selective differentiation of MSCs to osteogenic lineage while conferring good cell adhesion, enhanced alkaline phosphatase activity, and mineralization. A distal femoral condyle critical size defect in rabbits was used as a platform to confirm the effect of AG/NG–HA on bone regeneration in vivo. Our experiments show that the AG/NG–HA hybrid scaffolds provided a favorable environment for new bone formation. The results presented in this study suggest that the AG/NG–HA hybrid scaffolds have potential in bone-tissue regeneration engineering.
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Nanoscale
·
2018
·Vol. 10
·期 26
·12788-12796
·
IF 7.233
Shuang E,Quan-Xing Mao,Xiao-Li Yuan,Xiao-Lei Kong,Xu-Wei Chen,Jian-Hua Wang
Organelles play crucial roles in cellular activities and the functions of organelles are related greatly to the pH values, therefore, the bio-imaging of targeted organelles and their related pH sensing is of great importance in biological assays. Herein we report the fluorescence imaging of specific organelles, i.e., lysosomes and endoplasmic reticulum, and their pH sensing with surface regulated carbon dots (CDs). Carbon dots functionalized with amine groups (ACDs) are first prepared by hydrothermal treatment of citric acid and urea, and then laurylamine functionalized CDs (LCDs) are obtained via the conjugation of laurylamine with ACDs. The as-prepared ACDs and LCDs provide clear and bright imaging results for the lysosome and endoplasmic reticulum, respectively. The subcellular targeting features of the two CDs are attributed to their surface chemistries and cellular uptake pathways. Moreover, both the CDs are pH responsive within a certain pH range, i.e., 4.0–5.4 for ACDs and 6.2–7.2 for LCDs. The ACDs and LCDs are thus successfully applied to visualize the pH fluctuations of the lysosome and endoplasmic reticulum in MCF-7 cells.
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Royal Society Open Science
·
2018
·Vol. 5
·期 3
·
IF 2.504
Chang Shu,Tengfei Li,Wen Yang,Duo Li,Shunli Ji,Li Ding
The present work is focused on the design and development of novel amphotericin B (AmB)-conjugated biocompatible and biodegradable polypeptide hydrogels to improve the antifungal activity. Using three kinds of promoting self-assembly groups (2-naphthalene acetic acid (Nap), naproxen (Npx) and dexamethasone (Dex)) and polypeptide sequence (Phe-Phe-Asp-Lys-Tyr, FFDKY), we successfully synthesized the Nap-FFDK(AmB)Y gels, Npx-FFDK(AmB)Y gels and Dex-FFDK(AmB)Y gels. The AmB-conjugated hydrogelators are highly soluble in different aqueous solutions. The cryo-transmission electron microscopy and scanning electron microscopy micrographs of hydrogels afford nanofibres with a width of 20–50 nm. Powder X-ray diffraction analyses demonstrate that the crystalline structures of the AmB and Dex are changed into amorphous structures after the formation of hydrogels. Circular dichroism spectra of the solution of blank carriers and the corresponding drug deliveries further help elucidate the molecular arrangement in gel phase, indicating the existence of turn features. The in vitro drug releases suggest that the AmB-conjugated hydrogels are suitable as drug-controlled release vehicles for hydrophobic drugs. The antifungal effect of AmB-conjugated hydrogels significantly exhibits the antifungal activity against Candida albicans. The results of the present study indicated that the AmB-conjugated hydrogels are suitable carriers for poorly water soluble drugs and for enhancement of therapeutic efficacy of antifungal drugs.
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Frontiers in Pharmacology
·
2018
·
IF 3.831
Li Zhuo-Qing,Jiang Li-Long,Zhao Dong-Sheng,Zhou Jing,Wang Ling-Li,Wu Zi-Tian,Zheng Xian,Shi Zi-Qi,Li Ping,Li Hui-Jun
Dictamni Cortex (DC) has been reported to be associated with acute hepatitis in clinic and may lead to a selective sub-chronic hepatotoxicity in rats. Nevertheless, the potent toxic ingredient and the underlying mechanism remain unknown. Dictamnine (DTN), the main alkaloid from DC, possesses a furan ring which was suspected of being responsible for hepatotoxicity via metabolic activation primarily by CYP3A4. Herein, the present study aimed to evaluate the role of CYP3A4 in DTN-induced liver injury. The in vitro results showed that the EC50 values in primary human hepatocytes (PHH), L02, HepG2 and NIH3T3 cells were correlated with the CYP3A4 expression levels in corresponding cells. Furthermore, the toxicity was increased in CYP3A4-induced PHH by rifampicin, and CYP3A4 over-expressed (OE) HepG2 and L02 cells. Contrarily, the cytotoxicity was decreased in CYP3A4-inhibited PHH and CYP3A4 OE HepG2 and L02 cells inhibited by ketoconazole (KTZ). In addition, the hepatotoxicity of DTN in enzyme induction/inhibition mice was further investigated in the aspects of biochemistry, histopathology, and pharmacokinetics. Administration of DTN in combination with KTZ resulted in attenuated liver injury, including lower alanine transaminase and aspartate transaminase activities and greater AUC and Cmax of serum DTN, whereas, pretreatment with dexamethasone aggravated the injury. Collectively, our findings illustrated that DTN-induced hepatotoxicity correlated well with the expression of CYP3A4, namely inhibition of CYP3A4 alleviated the toxicity both in vitro and in vivo, and induction aggravated the toxicity effects.
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Nanoscale
·
2018
·Vol. 10
·期 30
·14705-14711
·
IF 7.233
Qian Qian Zhang,Tong Yang,Rong Sheng Li,Hong Yan Zou,Yuan Fang Li,Jian Guo,Xi Dong Liu,Cheng Zhi Huang
Lysosomes, which can be easily targeted by molecules with abundant amino groups, play critical roles in endocytosis, autophagy, and phagocytosis; thus, it is important to accurately characterize lysosomes, including lysosomal pH, in living cells to understand their physiological and pathological functions. Herein, a new type of highly photoluminescent (PL) emerald carbon dots (CDs) was easily prepared through a functional preservation strategy (FPS) by simply mixing p-benzoquinone and ethanediamine at room temperature. The as-prepared CDs possessed abundant amino groups preserved from ethanediamine owing to FPS, and they exhibited excellent photostability as compared to the commercial LysoTracker probes. Consequently, they actively targeted lysosomes to sensitively respond to lysosomal pH in vitro owing to their abundant amino groups and good hydrophilicity. Thus, we could successfully monitor lysosomal pH dynamics during apoptosis in live cells.
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Natural Products and Bioprospecting
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2019
·Vol. 9
·期 3
·201-208
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IF 0
Liu Qi,Chi Quan,Fan Ru-Ting,Tian Hui-Dong,Wang Xian
Abstract A sensitive and rapid high performance liquid chromatography–mass spectrometry (HPLC–MS) method was developed and validated for simultaneous quantification of ten steroid hormones, including estrogens, androgens, progesterones, and corticosteroids four classes of steroids. The following ten steroid hormones were analyzed: progesterone, 21-deoxycortisol, estrone, 4-androstenedione, testosterone, dihydro-testosterone, androstenone, dehydroepiandrosterone, corticosterone and cortisone. Stable deuterated isotopes were used as internal standards for quantification. Sample preparation with and without derivatization were performed after liquid–liquid extraction, and the corresponding results were compared according to sensitivity and selectivity. Hydroxylamine derivatization was found to improve the ionization efficiency of the analytes for electrospray ionization MS analysis. The gradient of mobile phase and experimental parameters for HPLC separation were optimized. The lower limits of quantification were in the range of 0.05–5 ng mL −1 with wide linear range for the ten steroid hormones. The intra-day precision < 11.1% and recovery of 84.5–120% with negligible matrix effect were achieved, where within the acceptance limits of the FDA guideline. Total HPLC–MS analysis time was 6 min. This method enables simultaneous quantification of steroids in human serum. It will be helpful for the serum steroid profiling in order to understand various endocrinology diseases. Graphical Abstract
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JOURNAL OF CHROMATOGRAPHY A
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2019
·
IF 3.858
Yanxia Li,Xiaoman Chen,Ling Xia,Xiaohua Xiao,Gongke Li
In this work, magnetic metal-organic frameworks-101 functionalized with graphite-like carbon nitride material (Fe 3 O 4 /g-C 3 N 4 /MIL-101) has been simply prepared for the efficient enrichment of glucocorticoids in cosmetics. Due to the introduction of g-C 3 N 4 , the water stability of MIL-101 has been greatly improved. This composite material also showed better selectivity for glucocorticoids than those for polycyclic aromatic hydrocarbons and benzene compounds due to the hydrogen bonding effect with g-C 3 N 4 and the size-matching effect with MIL-101. When the prepared material was used as the sorbents in magnetic solid-phase extraction (MSPE) and coupled with ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS), a sensitive MSPE-UPLC-MS/MS method was developed. Under the optimal conditions, the calibration curves were linear over the concentration ranging from 0.01 to 2 μg/L with correlation coefficients (R 2 ) between 0.9915 and 0.9995. The limit of detection (LOD) was as low as 2 ng/L with the RSDs lower than 5.5%. The recoveries ranged from 77.3% to 113%. The LOD of glucocorticoids in real samples analysis was improved by nearly three orders of magnitude compared to current literature records. The results indicated that Fe 3 O 4 /g-C 3 N 4 /MIL-101 could be used as MSPE extractant to determine glucocorticoids in complex cosmetics matrix.
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JOURNAL OF SEPARATION SCIENCE
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2017
·Vol. 40
·期 22
·4311-4319
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IF 2.557
Nani Wang,Qiaoyan Zhang,Hailiang Xin,Dan Shou,Luping Qin
A method using osteoblast membrane chromatography coupled with liquid chromatography and time-of-flight mass spectrometry was developed to recognize and identify the specific active components from traditional Chinese medicines. Primary rat osteoblasts were used for the preparation of the stationary phase in the cell chromatography method. Retention components from the cell chromatography were collected and analyzed by liquid chromatography with time-of-flight mass spectrometry. This method was applied in screening active components from extracts of four traditional Chinese medicines. In total, 24 potentially active components with different structures were retained by osteoblast cell chromatography. There were five phenolic glucosides and one triterpenoid saponin from Curculigo orchioides Gaertn, two organic acids and ten flavonoids from Epimedium sagittatum Maxim, one phthalide compound and one organic acid from Angelica sinensis Diels, and two flavonoids and two saponins from Anemarrhena asphodeloides Bunge. Among those, four components (icariin, curculigoside, ferulaic acid, and timosaponin BII) were used for in vitro pharmacodynamics validation. They significantly increased the osteoblast proliferation, alkaline phosphatase activity, levels of bone gla protein and collagen type 1, and promoted mineralized nodule formation. The developed method was an effective screening method for finding active components from complex medicines that act on bone diseases.
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