NEUROMOLECULAR MEDICINE
·
2021
·Vol. 24
·期 2
·224-231
·
IF 3.843
Wei Guangxin,Li Shengjun,Wang Pengcheng,Wang Shouxian,Zhao Yujing
Glioma is a kind of brain tumor with low overall survival and treatment success rates in the advanced stage. Evidence has shown microRNA-575 (miR-575) plays an important role in the generation and development of various cancers. This study aimed to explore the function of miR-575 in the prognosis and cell biological behavior of glioma. qRT-PCR was used to evaluate the expression of miR-575 in glioma tissues and cells, Kaplan–Meier survival analysis and Cox regression analysis were used to evaluate the prognostic value. The proliferation ability of glioma cells was determined by MTT assay; the invasion and migration abilities were determined by transwell assays. Compared with normal brain tissues, the expression of miR-575 in glioma tissue cells was significantly up-regulated ( P < 0.001). The survival rate of patients in the miR-575 high expression group was significantly lower than that in the low expression group ( P = 0.020). In addition, the overexpression of miR-575 promoted the proliferation, migration, and invasion of glioma cells. The results of this study suggested that miR-575 may be a new biomarker for the prognosis of glioma.
✓ 已验证
DOI
PubMed
高影响因子
Cell Death & Disease
·
2023
·Vol. 14
·期 10
·1-17
·
IF 9
Deng Huan,Chen Yamei,Wang Li,Zhang Yibi,Hang Qingqing,Li Peijing,Zhang Peng,Ji Jing,Song Hai,Chen Ming,Jin Ying
Our previous study revealed that PI3K/AKT/mTOR signaling was associated with SCLC radioresistance. SBC2 cells were used as primary radioresistance models, while H446 cells were continuously exposed to ionizing radiation (IR) to develop acquired radioresistance. Cell viability and apoptosis assays were used to investigate synergistic effects of BEZ235/GSK2126458 and IR in vitro, while immunoblotting, metabolite quantitative analysis and bioinformatic analyses were utilized to explore the underlying mechanism. Both genetically engineered mouse models (GEMM) and subcutaneous tumor models were used to confirm the synergistic effect in vivo. Key molecules of PI3K/AKT/mTOR signaling were upregulated after IR, which was correlated with primary radioresistance, and they were more expressed in acquired radioresistant cells. BEZ235/GSK2126458 effectively enhanced the cytotoxic effects of IR. BEZ235/GSK2126458 plus IR elevated γ-H2AX and p-Nrf2 expression, suggesting DNA and oxidative stress damage were intensified. Mechanistically, BEZ235/GSK2126458 plus IR significantly reduced the expression of G6PD protein, the rate-limiting enzyme of the pentose phosphate pathway (PPP). In detail, PI3K/mTOR inhibitors reinforced interaction between G6PD and HSPA8/HSC70, and G6PD was degraded by chaperone-mediated autophagy processes. Their metabolites (NADPH and R-5P) were decreased, and ROS levels were indirectly elevated, both of which exacerbated cell death. PI3K/AKT/mTOR signaling activator, insulin, enhanced SCLC radioresistance, while the synergistic effect of BEZ235/GSK2126458 and IR can be attenuated by N-acetylcysteine, and enhanced by 6-amino niacinamide. GEMM and allograft transplantation assays further confirmed their synergistic effect in vivo. This study provided insights into the connection between PI3K/AKT/mTOR signaling and the PPP underlying radioresistance and provided evidence of mechanisms supporting PI3K/mTOR inhibitors as possible therapeutic strategies to abrogate SCLC radioresistance.
✓ 已验证
DOI
PubMed
高影响因子
Journal of Occupational Medicine and Toxicology
·
2015
·Vol. 10
·期 1
·1-16
·
IF 1.621
Nattrass C.,Horwell C. J.,Damby D. E.,Kermanizadeh A.,Brown D. M.,Stone V.
Background Diatomaceous earth (DE) is mined globally and is potentially of occupational respiratory health concern due to the high crystalline silica content in processed material. DE toxicity, in terms of variability related to global source and processing technique, is poorly understood. This study addresses this variability using physicochemical characterisation and in vitro toxicology assays. Methods Nineteen DE samples sourced from around the world, comprising unprocessed, calcined and flux-calcined DE, were analysed for chemical and mineral composition, particle size and morphology, and surface area. The potential toxicity of DE was assessed by its haemolytic capacity, and its ability to induce cytotoxicity or cytokine release by J774 macrophages. Results The potential toxicity of DE varied with source and processing technique, ranging from non-reactive to as cytotoxic and haemolytic as DQ12. Crystalline silica-rich, flux-calcined samples were all unreactive, regardless of source. The potential toxicity of unprocessed and calcined samples was variable, and did not correlate with crystalline silica content. Calcium-rich phases, iron content, amorphous material, particle size and morphology all appeared to play a role in sample reactivity. An increased surface area was linked to an increased reactivity in vitro for some sample types. Conclusions Overall, no single property of DE could be linked to its potential toxicity, but crystalline silica content was not a dominant factor. Occlusion of the potentially toxic crystalline silica surface by an amorphous matrix or other minerals and impurities in the crystal structure are suggested to pacify toxicity in these samples. In vivo verification is required, but these data suggest that crystalline silica content alone is not a sufficient indicator of the potential DE hazard.
✓ 已验证
DOI
PubMed
高影响因子
ARCHIVES OF PHARMACAL RESEARCH
·
2016
·Vol. 39
·期 6
·762-770
·
IF 2.49
Wang Nan,Cui Cheng-Bin,Li Chang-Wei
A novel cyclic dipeptide, named penicimutide ( 1 ), and four known cyclic dipeptides, cyclo( l -Val- l -Pro) ( 2 ), cyclo( l -Ile- l -Pro) ( 3 ), cyclo( l -Leu- l -Pro) ( 4 ) and cyclo( l -Phe- l -Pro) ( 5 ), were isolated from a neomycin-resistant mutant of the marine-derived fungus Penicillium
purpurogenum G59. The structure of 1 , including the absolute configuration, was determined by spectroscopic and chemical methods, especially NMR and Marfey’s analysis. An unusual amino acid in 1 , 4,5-didehydro- l -leucine, was found for the first time occurring in nature. HPLC–ESI–MS analysis evidenced that 1 – 3 were produced only in the mutant strain, but 4 and 5 were produced in both the mutant and parental strains, indicating that the introduction of neomycin-resistance in the mutant activated pathways of 1 – 3 biosynthesis that were silent in the parental strain. Compound 1 selectively inhibited HeLa cells (among five tested human cancer cell lines) with an inhibition rate (IR %) of 39.4 % at 100 µg/mL, a similar inhibition intensity to that of the positive control 5-fluorouracil (IR % of 41.4 % at 100 µg/mL against HeLa cells). The present work exemplifies the effectiveness of our previous DMSO-mediated method for introducing drug-resistance in fungi to activate silent biosynthetic pathways to obtain new bioactive compounds.
✓ 已验证
DOI
PubMed
高影响因子
CELL AND TISSUE BANKING
·
2021
·Vol. 22
·期 3
·443-451
·
IF 1.522
Kang Bo Kyoung,Yu Zheyuan,Chen Weiming,Jiang Taoran,Shim Yoong-hun,Gao Jiaman,Zhou Guangdong,Cao Dejun
Engineered cartilage has several applications in treating cartilage ossification, however, its use is restricted clinically. We explored the feasibility of engineered cartilage in constructing tissues using gelatin/curcumin nano-fiber membranes as scaffolds in subcutaneous models. We constructed cartilage with gelatin nano-fiber membrane (control group) and gelatin/curcumin nano-fiber membrane (experimental group) as scaffolds. After the material was implanted into the back of BALB/c mice, gross view observation was performed. Histological examination was performed 3 and 12 weeks after implantation in vivo, and cartilage formation at different time points was compared. Gross observation showed that compared to the control group, the vascularization of nearby tissues in the experimental group was significantly inhibited. The Scanning electron microscope observation showed that the chondrocytes in both groups adhered well. The growth curve of the chondrocytes showed that curcumin had no significant effect on cell growth. Histological observation showed that the cell-material complexes in both groups had cartilage lacuna formation at 3 and 12 weeks. However, compared with that of the control group, the experimental group showed obvious absorption and thicker cartilage matrix with more homogenization. Gelatin/curcumin scaffolds were successfully used to construct engineered cartilage tissues in subcutaneous animal models. Our findings demonstrate that curcumin-loaded scaffolds have great clinical applications.
✓ 已验证
DOI
PubMed
高影响因子
Frontiers of Materials Science
·
2023
·Vol. 17
·期 2
·1-13
·
IF 2.7
Fan Yongyong,Yin Anlin,Li Yunhuan,Gu Qi,Zhou Yan,Zhou Junlong,Zhao Ruibo,Zhang Kuihua
In order to provide a biomimetic natural extracellular matrix microenvironment with excellent mechanical capacity for tissue regeneration, a novel porous hybrid glycidyl methacrylate-modified silk fibroin/poly(L-lactic acid-ε-caprolactone)-polyethylene glycol diacrylate (SFMA/P(LLA-CL)-PEGDA) hybrid three-dimensional (3D) nanofibrous scaffolds was successfully fabricated through the combination of 3D nanofibrous platforms and divinyl PEGDA based photocrosslinking, and then further improved water resistance by ethanol vapor post-treatment. Scanning electron microscopy and micro-computed tomography results demonstrated significant PEGDA hydrogel-like matrices bonded nanofibers, which formed a 3D structure similar to that of “steel bar (nanofibers)–cement (PEGDA)”, with proper pore size, high porosity, and high pore connectivity density. Meanwhile, the hybrid 3D nanofibrous scaffolds showed outstanding swelling properties as well as improved compressive and tensile properties. Furthermore, these hybrid 3D nanofibrous scaffolds could provide a biocompatible microenvironment, capable of inducing the material–cell hybrid and regulating human umbilical vein endothelial cells proliferation. They thus present significant potential in tissue regeneration.
✓ 已验证
DOI
高影响因子
CHEMICAL RESEARCH IN CHINESE UNIVERSITIES
·
2017
·Vol. 33
·期 4
·611-622
·
IF 1.024
Zhang Lei,Zhou Fan,Zhang Laitao,Peng Lizhi,Guo Cuiping,Luo Cheng,Chen Heru
Ten memantine(Mema)-dihydroartemisinin(DHA) ligands were designed and synthesized. Three types of isomers including α , β , and a defined γ isomer were found in each intermediates( 1a—1e ). Type γ isomer was firstly reported here and confirmed as a less stable eclipsed conformation. The bonding of Mema with DHA through different carbon chains generally makes the new entities more cytotoxic than either Mema or artemisinin(Arte). The β Mema/DHA ligands are a little bit more cytotoxic than α ligands. By applying corticosterone(Cort)-impaired PC12 cells models, it was found that Mema and those ligands with more than 3 carbon chains showed weak or no neuro-protective activities against the insults. However, two ligands, 2 a( β ) and 2 b( β ) showed better effects than either Arte or their combination(Mema/Arte in 1:1 molar ratio) at a dose of 5 µmol/L. Furthermore, ligands 2a ( β ), 2b ( β ) and 2c ( β ) were confirmed as mild N -methyl- D -aspartate(NMDA) antagonists, and their corresponding α isomers are weak NMDA antagonists. All the data indicate that the bonding of Mema/DHA in compacted β conformation mode results in enhanced effects against Cort-induced insults in PC12 cells and might reverse memantine as an anti-depression NMDA antagonist.
✓ 已验证
DOI
高影响因子
ARCHIVES OF MICROBIOLOGY
·
2022
·Vol. 204
·期 3
·1-14
·
IF 2.667
Chen Sha,Ding Zhexu,Chen Jinyuan,Luo Jun,Ruan Xiaofang,Li Zongpei,Liao Fengfeng,He Jing,Li Ding
Bacterial non-enzymatic Mn(II) oxidation involving reactive oxygen species (ROS) (i.e., indirect oxidation), initially discovered from a marine alpha-proteobacterium, is believed to be of importance in controlling biogeochemical cycles. For soil-borne bacteria, however, evidence of indirect Mn(II) oxidation remains unclear. In this study, the indirect Mn(II) oxidation was evidenced in a soil-borne bacterium, Providencia sp. LLDRA6. First, with and without 50 mM of Mn(II) exposure for LLDRA6, 300 differentially expressed genes were found to be linked to Mn(II) exposure via transcriptome sequencing. Among them, an operon, responsible for phenylacetic acid catabolism, was sharply upregulated in transcription, drawing us a special attention, since its transcriptional upregulation has recently shown to be important for withstanding ROS. Next, a fluorometric probe, 2′,7′-Dichlorofluorescin diacetate (DCFDA), was used to qualitatively detect ROS from cells, showing a distinct increase in fluorescence intensities of ROS during Mn(II) exposure. Furthermore, concentrations of superoxide and hydrogen peroxide from cells were detected, respectively, with and without Mn(II) exposure, exhibiting that when Mn(II) oxidation occurred, superoxide concentration significantly increased but hydrogen peroxide concentration significantly decreased. Particularly, superoxide produced by LLDRA6 was proven to be the oxidant for Mn(II) in the formation of Mn oxides. Finally, we predicted links between phenylacetic acid metabolism pathway and ROS during Mn(II) exposure, proposing that the excessive ROS, generated in response to Mn(II) exposure, transcriptionally activate phenylacetic acid catabolism presumably by increasing concentrations of highly reactive oxepins.
✓ 已验证
DOI
PubMed
高影响因子
Nano Research
·
2022
·Vol. 15
·期 9
·8214-8227
·
IF 10.269
Ding Yifan,Wang Huan,Wang Yunyun,Li Long,Ding Jiahui,Yuan Caiyan,Xu Tao,Xu Haoran,Xie Hui,Zhu Ning,Hu Xin,Fang Huang,Tan Songwei
Intervertebral disc degeneration (IDD) is closely related to inflammation and imbalance of synthesis/catabolism of extracellular matrix (ECM) in intervertebral disc (IVD). Considering this, luteolin (LUT), a kind of natural flavonoid with good anti-inflammatory effect and TGF-β1 (a gene that promotes the regeneration of ECM) plasmid was co-loaded and co-delivered to nucleus pulposus cells (NPCs). Reactive oxygen species (ROS) responsive cationic copolymer, poly(β-amino ester)-poly(ε-caprolactone) (PBC), with high plasmid DNA (pDNA) compression affinity was synthesized. It can self-assemble into nano-sized polyplexes (pDNA@PBC) with virus-inspired structure and function through which it can transfect pDNA into NPCs with very high efficiency and negligible cytotoxicity. LUT was encapsulated in the hydrophobic core of pDNA@PBC. The co-delivery system, LUT-pTGF-β1@PBC, could enhance the cellular uptake of NPCs and manifest excellent sustained drug release in IVD. Real time quantitative polymerase chain reaction (RT-qPCR) and Western blot experiments reveal that the co-delivery system could inhibit inflammation in NPCs and restore the balance of anabolism and catabolism in vitro by activating TGF/SMAD3 and inhibiting NF- k B/p65. Moreover, LUT-pTGF-β1@PBC retards IDD in vivo as detected by radiological and histological methods with good biosafety in rats. LUT-pTGF-β1@PBC may be a promising option for the treatment of IDD.
✓ 已验证
DOI
高影响因子
Nano Research
·
2019
·Vol. 12
·期 4
·877-887
·
IF 8.515
Pei Qing,Hu Xiuli,Zheng Xiaohua,Xia Rui,Liu Shi,Xie Zhigang,Jing Xiabin
Inspired by the clinically approved albumin based PTX formulation (Abraxane) and high-drug-loading dimeric prodrug tactics, herein we report a theranostic “Abraxane-like” prodrug formulation, which is comprised of human serum albumin (HSA), a paclitaxel (PTX) dimer bridged with thioether liner (PTX 2 -S), and photosensitizer IR780 iodide. Nanoparticles (NPs) with PTX 2 -S and IR780 as the core and HSA as the stealth shell are formed. Compared with HSA-based PTX clinical formulation (Abraxane), the dimeric molecules not only constitute the bulk structure of the particles, but also act as crossing agent, thus realizing drug loading content increasing from 6.6 wt.% to 48.7 wt.% with high loading efficiency (> 90%) and excellent stability in biological conditions. Importantly, the thioether linkage dually responds to the tumor redox heterogeneity and the NPs gradually releases the parent drug PTX for chemotherapy. Meanwhile, PTX 2 -S facilitates the encapsulation of IR780 iodide due to their π-π stacking interaction and IR780 iodide generates spatio-temporal hyperthermia under light irradiation to kill cancer cells for photothermal therapy. The described craft integrates the biomimetic trait of HSA, high drug loading, tumor redox heterogeneity-initiated on-demand drug release, and combination therapy into one formulation and the developed nanoparticles are promising for cancer treatment.
✓ 已验证
DOI
高影响因子
MICROCHIMICA ACTA
·
2026
·Vol. 193
·期 11
·747
·
IF 5.4
Zhang Zhilin,Pu Jin,Peng Yong,Tan Hongliang,Xu Fugang
A noble-metal-free, aggregation-independent surface-enhanced Raman scattering (SERS) platform is reported based on a bifunctional α-MoO 3−x -CuCl 2 nanocomposite for the sensitive and selective detection of phosphate species. The defect-rich α-MoO 3−x provides strong SERS enhancement, and the introduction of CuCl 2 not only enhances its peroxidase like activity, but also endows it selective response to phosphate species. The composite α-MoO 3−x -CuCl 2 can efficient catalytic oxidation of colorless tetramethylbenzidine (TMB) to blue oxidized TMB (ox-TMB), which yields a strong SERS signal. At the assay pH of 4.0, the protonated phosphate species (mainly H 2 PO 4 ⁻) selectively coordinate with Cu 2+ , suppressing the nanozyme activity and causing a dose-dependent decrease in both colorimetric and SERS responses. Under optimized conditions, the method exhibits a linear detection range from 8.0 × 10 − 9 M to 8.0 × 10 − 5 M and a limit of detection as low as 2.0 × 10 − 9 M. The platform also demonstrates good anti-interference capability against common coexisting ions and satisfactory recoveries (103.75%–107.5%) in spiked lake water and tap water samples. This work provides a low-cost, reliable, and reproducible strategy for indirect SERS detection of phosphate species without reliance on noble metals or nanoparticle aggregation. Graphical abstract
✓ 已验证
DOI
高影响因子
BMC PLANT BIOLOGY
·
2017
·Vol. 17
·期 1
·1-20
·
IF 3.964
Guo Xiaoou,Xu Jingjing,Cui Xiaohui,Chen Hao,Qi Hongyan
Background Oriental melon is one of the most popular crops for its nutritional and flavour quality. Components that determine melon quality, such as sugar, colour, texture, flavour and aroma, among other factors, accumulate in different developmental stages. Thus, correlating the proteomic profiles with the biochemical and physiological changes occurring in the oriental melon is very important for advancing our understanding of oriental melon quality in the ripening processes.Results iTRAQ-based protein profiling was conducted on ‘YuMeiren’ oriental melon fruit at different developmental stages. Physiological quality indices, including firmness, rind colour, soluble solids content (SSC), ethylene production, sugar content and volatile compounds were also characterized during four maturity periods of the melon, including 5, 15, 25 and 35 days after anthesis (DAA). A principal component analysis (PCA) revealed that the aroma volatiles at 5 DAA and 15 DAA were similar and separated from that of 35 DAA. More than 5835 proteins were identified and quantified in the two biological repeats and divided into 4 clusters by hierarchical cluster analysis. A functional analysis was performed using Blast2GO software based on the enrichment of a GO analysis for biological process, molecular function and cellular components. The main KEGG pathways, such as glycolysis, α-linolenic acid and starch and sucrose metabolism, were analyzed.The gene family members corresponding to differentially expressed proteins, including lipoxygenase (CmLOX01-18) and alcohol acetyltransferase (CmAAT1-4) involved in the α-linolenic acid metabolic pathway, were verified with real-time qPCR. The results showed that the expression patterns of 64.7% of the genes were consistent with the expression patterns of the corresponding proteins.Conclusion sThis study combined the variation of the quality index and differentially expressed proteins of oriental melon at different developmental stages that laid the foundation for the subsequent protein and gene function validation.
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）