Nanoscale
·
2018
·Vol. 10
·期 30
·14705-14711
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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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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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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
·
2017
·
IF 4.4
Liu Qing,Xiao Xu-Hui,Hu Liu-Bing,Jie Hui-Yang,Wang Ying,Ye Wen-Cai,Li Man-Mei,Liu Zhong
Anemone flaccida Fr. Schmidt (Ranunculaceae) (Di Wu in Chinese) is used to treat punch injuries and rheumatoid arthritis (RA). Our previous report has shown that crude triterpenoid saponins from Anemone flaccida exhibited anti-arthritic effects on type II collagen-induced arthritis in rats. Furthermore, anhuienoside C (AC), a saponin compound isolated from A. flaccida, was observed to suppress the nitric oxide production in lipopolysaccharide (LPS)-treated macrophage RAW 264.7 cells. In this study, we examined the effects of AC on the prevention and treatment of collagen-induced arthritis in a mouse model and evaluated the potential mechanisms involved. We observed that oral administration of AC significantly suppressed the paw swelling and arthritic score, decreased the body weight loss, and decreased the spleen index. Improvement in the disease severity was accompanied by the reduction of cluster of differentiation 68 (CD68)-positive cells in the ankle joint and inhibition of the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α) in the synovium of the joint. Mechanistic studies indicated that AC exerted its anti-inflammatory activity by inhibiting the mRNA expression levels of inducible nitric oxide synthase, cyclooxygenase-2, TNF-α, interleukin (IL)-1β, and IL-6 and by suppressing the production of inflammatory cytokines such as TNF-α, IL-1β, and IL-6 in LPS-treated RAW 264.7 cells. AC also blocked the LPS-induced activation of the extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase pathways. Additionally, the LPS-induced activation of nuclear factor kappa-B (NF-κB) was significantly suppressed by AC treatment, as indicated by down-regulation of TLR4 and inhibition of the nuclear translocation of NF-κB p65 and by activation and degradation of the inhibitor of kappa B. These findings indicated that AC has a great potential to be developed as a therapeutic agent for human RA.
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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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CARBON
·
2017
·
IF 6.337
Wei Nie,Cheng Peng,Xiaojun Zhou,Liang Chen,Weizhong Wang,Yanzhong Zhang,Peter X. Ma,Chuanglong He
Three-dimension (3D) porous reduced graphene oxide (RGO) scaffold has attracted increasing attention in bone tissue engineering due to its favorable osteoinductivity. In this paper, a 3D porous RGO composite was prepared from graphene oxide (GO) and nano-hydroxyapatite (nHA) via self-assembly, thus constructing biomimetic scaffold for bone defect reparation. Detailed studies were performed to evaluate its structure, cellular responses, biocompatibility and in vivo bone repair efficiency, emphasizing the influences of the composite on in vivo bone cell growth and mineralization. The as-prepared scaffold was found to significantly enhance the proliferation, alkaline phosphatase activity (ALP) and osteogenic gene expression of rat bone mesenchymal stem cells (rBMSCs). Further in vivo experiment demonstrated that the circular calvarial defects with 4 mm diameter in rabbit were successfully healed by 20% nHA incorporated RGO ( [email protected] ) porous scaffold after 6 weeks implanting, which was visibly quicker than the RGO one. The computed tomography (CT) and histological analysis showed the improved collagen deposition, cell proliferation and new bone formation occurred in the 20% [email protected] treated group. These results indicated that the as-prepared porous scaffold has a promising capacity to stimulate mineralization and promote the in vivo defect healing.
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2017
·
IF 3.255
Yuan Huang,Zhiqun Zheng,Liying Huang,Hong Yao,Xiao shan Wu,Shaoguang Li,Dandan Lin
A rapid, simple, cost-effective dispersive liquid-phase microextraction based on solidified floating organic drop (SFOD-LPME) was developed in this study. Along with high-performance liquid chromatography, we used the developed approach to determine and enrich trace amounts of four glucocorticoids, namely, prednisone, betamethasone, dexamethasone, and cortisone acetate, in animal-derived food. We also investigated and optimized several important parameters that influenced the extraction efficiency of SFOD-LPME. These parameters include the extractant species, volumes of extraction and dispersant solvents, sodium chloride addition, sample pH, extraction time and temperature, and stirring rate. Under optimum experimental conditions, the calibration graph exhibited linearity over the range of 1.2–200.0 ng/ml for the four analytes, with a reasonable linearity(r 2 : 0.9990–0.9999). The enrichment factor was 142–276, and the detection limits was 0.39–0.46 ng/ml (0.078–0.23 μg/kg). This method was successfully applied to analyze actual food samples, and good spiked recoveries of over 81.5%–114.3% were obtained.
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RSC Advances
·
2017
·Vol. 7
·期 5
·2753-2765
·
IF 3.108
Weizong Weng,Wei Nie,Qirong Zhou,Xiaojun Zhou,Liehu Cao,Fang Ji,Jin Cui,Chuanglong He,Jiacan Su
Infected bone defects (IBD) are a challenging problem in orthopedic practice. Biomaterials have attracted attention as a novel approach to overcome this challenge instead of using conventional strategies. Graphene, a two-dimensional carbon allotrope, has been shown to possess multiple advantages, such as osteogenesis-promoting activity, a large surface area for drug delivery, and antibacterial activities. However, these attractive merits have not been entirely explored or introduced for the management of IBD. Herein, a novel approach using a vancomycin-laden, self-assembled, graphene-based material against IBD was developed, and the approach uses a single-stage bone graft instead of multiple procedures. Owing to the π–π bonding with graphene, vancomycin can be promptly delivered in the initial stage, followed by a sustained release, which ensures the rapid elimination of an infection and provides a durable pathogen revival inhibition via the inherent antibacterial activity of graphene. Moreover, the 3D porous structure incorporated with nano-hydroxyapatite (nHA) provided a biomimetic microenvironment favored by cell adhesion and osteogenic differentiation. Further evaluation of this system in an IBD animal model demonstrated prompt control of infection and promotion of bone regeneration. These results revealed the potential of this approach to be an effectual solution for IBD treatment and a new area of graphene application in the future.
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ACS Applied Materials & Interfaces
·
2017
·
IF 7.504
Yi Hou,Nan Jiang,Li Zhang,Yubao Li,Yuezhong Meng,Dongmei Han,Chen Chen,Yuan Yang,Songsong Zhu
To effectively repair irregular shaped bone defects by a minimally invasive procedure, the exploration of an injectable gel to fill the defect is desirable. Herein, positively and negatively charged polyurethane microspheres (PU-A and PU-B) with adjustable zeta potentials as well as the hydroxyapatite-loaded PU microsphere (PU-A/HA) and the dexamethasone-loaded PU microsphere (PU-B/Dex) were successfully prepared, and the oppositely charged microspheres could self-assemble into injectable gels with 3D structures by a mutually electrostatic attraction. The self-assembly PU-A/HA+PU-B/Dex gel exhibited a much higher elastic modulus (about 0.20 MPa) and excellent shear-thinning and self-recovery behaviors, which would allow the gel to be injected through a fine syringe to fill the irregular defect. The in vitro and in vivo experiments demonstrated that the coexistence of HA and Dex in PU-A/HA+PU-B/Dex gel had a synergistic effect on cell differentiation and accelerating new bone formation, displaying a good prospect as an injectable gel for bone repair in minimally invasive surgery.
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Molecular Medicine Reports
·
2017
·Vol. 16
·期 4
·5121-5128
·
IF 1.692
Hongzhang Cui,Shu Li,Caiming Xu,Jingwen Zhang,Zhongwei Sun,Hailong Chen
The present study aimed to evaluate the protective effects of emodin on severe acute pancreatitis (SAP)‑associated acute lung injury (ALI), and investigated the possible mechanism involved. SAP was induced in Sprague‑Dawley rats by retrograde infusion of 5% sodium taurocholate (1 ml/kg), after which, rats were divided into various groups and were administered emodin, FK866 [a competitive inhibitor of pre‑B‑cell colony‑enhancing factor (PBEF)] or dexamethasone (DEX). DEX was used as a positive control. Subsequently, PBEF expression was detected in polymorphonuclear neutrophils (PMNs) isolated from rat peripheral blood by reverse transcription‑quantitative polymerase chain reaction and western blotting. In addition, histological alterations, apoptosis in lung/pancreatic tissues, apoptosis of peripheral blood PMNs and alterations in the expression of apoptosis‑associated proteins were examined by hematoxylin and eosin staining, terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labeling assay, Annexin V/propidium iodide (PI) assay and western blotting, respectively. Serum amylase activity and wet/dry (W/D) weight ratios were also measured. An in vitro study was also conducted, in which PMNs were obtained from normal Sprague‑Dawley rats and were incubated with emodin, FK866 or DEX in the presence of lipopolysaccharide (LPS). Apoptosis of PMNs and the expression levels of apoptosis‑associated proteins were examined in cultured PMNs in vitro by Annexin V/PI assay and western blotting, respectively. The results demonstrated that emodin, FK866 and DEX significantly downregulated PBEF expression in peripheral blood PMNs. In addition, emodin, FK866 and DEX reduced serum amylase activity, decreased lung and pancreas W/D weight ratios, alleviated lung and pancreatic injuries, and promoted PMN apoptosis by regulating the expression of apoptosis‑associated proteins: Fas, Fas ligand, B‑cell lymphoma (Bcl)‑2‑associated X protein, cleaved caspase‑3 and Bcl‑extra‑large. In addition, the in vitro study demonstrated that emodin, FK866 and DEX significantly reversed the LPS‑induced decrease of apoptosis in PMNs by regulating the expression of apoptosis‑associated proteins. In conclusion, the present study demonstrated that emodin may protect against SAP‑associated ALI by decreasing PBEF expression, and promoting PMN apoptosis via the mitochondrial and death receptor apoptotic pathways.
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