Frontiers in Endocrinology
·
2023
·
IF 5.2
Zhao Qingsong,Xu Jinmei,Han Xu,Zhang Zheqi,Qu Jiahui,Cheng Zhifeng
Background: Diabetic foot ulcer (DFU) represents a highly-prevalent complication of diabetes mellitus (DM). Herein, the current study sought to identify the role of growth differentiation factor 10 (GDF-10) in wound healing in DFU via regulation of the transforming growth factor-beta 1 (TGF-β1)/Smad3 pathway.Methods: DM- and DFU-related microarray datasets GSE29221 and GSE134431 were firstly retrieved, and weighted gene co-expression network analysis (WGCNA) was carried out to construct a co-expression network affecting wound healing in DFU, followed by differential analysis. A protein-protein interaction (PPI) network of the DFU-related genes was subsequently constructed, and the core genes and signaling pathways in DFU were screened with the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional analyses. A DFU rat model was constructed for mechanism verification of the effect of GDF-10 on wound healing in DFU.Results: WGCNA screened five co-expression modules, and the brown module was most closely-related to DM. Clustering analysis screened 4417 candidate genes, of which 175 differential genes were associated with wound healing, further involved in TGF-β1/Smad3 signaling pathway regulation of wound healing in DFU. The PPI network analysis predicted that GDF-10 might regulate the TGF-β1/Smad3 signaling pathway to participate in DFU development. Results of animal experimentation showed that the wound healing rates of NFU, DFU, DFU + GDF and GDF + SIS3 groups on the 22nd day were (87.66 ± 6.80)%, (56.31 ± 7.29)%, (71.64 ± 9.43)% and (55.09 ± 7.13)%, respectively. Besides, the expression of TGF-β1 in NFU, DFU, DFU + GDF and GDF + SIS3 groups was 0.988 ± 0.086, 0.297 ± 0.036, 0.447 ± 0.044, and 0.240 ± 0.050, respectively, and that of Smad3 was 1.009 ± 0.137, 0.145 ± 0.017, 0.368 ± 0.048, and 0.200 ± 0.028, respectively. Specifically, GDF-10 exerted a significant diminishing effect on fasting blood glucose level, and promoted wound healing in DFU rats, in addition to up-regulation of VEGF, FGF, Ang-1, TGF-β1, Smad3 and enhancement of IL-1b, IL-6, TNF-a and MMP-9, thereby promoting fibroblast proliferation, collagen deposition and angiogenesis.Conclusions: Our findings highlight that GDF-10 may promote angiogenesis by activating TGF-β1/Smad3 signaling, thereby promoting wound healing in DFU rats.
研究领域:
糖尿病
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF HYDROGEN ENERGY
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2022
·
IF 7.139
Zhaojie Yang,Minghua Zhang,Zhixin Zhao,Wenting Lan,Xi Zhang,Minmin Fan
To avoid the detrimental effect of aryl ethers on the alkali stability of anion exchange membrane (AEM), elaborately designed and synthesized poly(styrene- co -4-vinyl pyridine) (PS4VP) copolymer without aryl ether linkages is used to prepare AEMs. By introducing commercialized polyquaternium-10 (PQ-10) as the main ion-conducting molecule, the fully-interpenetrating polymer network quaternized PS4VP/PQ-10 (F-IPN QPS4VP/PQ-10) AEMs are prepared by cross-linking PS4VP and PQ-10, respectively. The as-prepared F-IPN QPS4VP/PQ-10 AEMs have obvious nanoscale microphase-separated morphologies, which ensure the membranes have good mechanical properties and dimensional stability. With optimized component ratios, F-IPN QPS4VP/PQ-10 AEM exhibits high ionic conductivity (74.29 mS/cm at 80 °C) and power density (111.83 mW/cm 2 at 60 °C), as well as excellent chemical stabilities (94.36% retaining of initial mass after immersion in Fenton reagent at 30 °C for 10 days, and 92.28% retaining of original ionic conductivity after immersion in 1 M NaOH solution at 60 °C for 30 days), which are greater than those of semi-interpenetrating polymer network QPS4VP/PQ-10 AEM. In summary, a combination of fully-interpenetrating polymer network and stable polymer chains and ion-conducting moieties is found to effectively overcome the trade-off between high ionic conductivity and good dimensional/chemical stabilities.
研究领域:
材料科学
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化学工程
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产品关联
DOI
高影响因子
Acta Pharmaceutica Sinica B
·
2022
·
IF 14.903
Zhejie Chen,Wei Hao,Caifang Gao,Yangyang Zhou,Chen Zhang,Jinming Zhang,Ruibing Wang,Yitao Wang,Shengpeng Wang
With the development of synthesis technology, modified messenger RNA (mRNA) has emerged as a novel category of therapeutic agents for a broad of diseases. However, effective intracellular delivery of mRNA remains challenging, especially for its sensitivity to enzymatic degradation. Here, we propose a polyphenol-assisted handy delivery strategy for efficient in vivo delivery of IL-10 mRNA. IL-10 mRNA binds to polyphenol ellagic acid through supramolecular binding to yield a negatively charged core, followed by complexing with linear polyetherimide and coating with bilirubin-modified hyaluronic acid to obtain a layer-by-layer nanostructure. The nanostructure specifically up-regulated the level of IL-10, effectively inhibited the expression of inflammatory factors, promoted mucosal repair, protected colonic epithelial cells against apoptosis, and exerted potent therapeutic efficacy in dextran sulfate sodium salt-induced acute and chronic murine models of colitis. The designed delivery system without systemic toxicity has the potential to facilitate the development of a promising platform for mRNA delivery in ulcerative colitis treatment.
研究领域:
药学
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分子生物学
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纳米技术
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炎症性肠病
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-18
·
IF 16.6
Wu Yandi,Huang Tongsheng,Li Xinghui,Shen Conghui,Ren Honglin,Wang Haiping,Wu Teng,Fu Xinlu,Deng Shijie,Feng Ziqi,Xiong Shijie,Li Hui,Gao Saifei,Yang Zhenyu,Gao Fei,Dong Lele,Cheng Jianding,Cai Weibin
Diabetic cardiomyopathy is a primary myocardial injury induced by diabetes with complex pathogenesis. In this study, we identify disordered cardiac retinol metabolism in type 2 diabetic male mice and patients characterized by retinol overload, all-trans retinoic acid deficiency. By supplementing type 2 diabetic male mice with retinol or all-trans retinoic acid, we demonstrate that both cardiac retinol overload and all-trans retinoic acid deficiency promote diabetic cardiomyopathy. Mechanistically, by constructing cardiomyocyte-specific conditional retinol dehydrogenase 10-knockout male mice and overexpressing retinol dehydrogenase 10 in male type 2 diabetic mice via adeno-associated virus, we verify that the reduction in cardiac retinol dehydrogenase 10 is the initiating factor for cardiac retinol metabolism disorder and results in diabetic cardiomyopathy through lipotoxicity and ferroptosis. Therefore, we suggest that the reduction of cardiac retinol dehydrogenase 10 and its mediated disorder of cardiac retinol metabolism is a new mechanism underlying diabetic cardiomyopathy.
研究领域:
心脏病学
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内分泌学
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代谢学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INDUSTRIAL CROPS AND PRODUCTS
·
2025
·
IF 6.2
Tengteng Yang,Wenquan Wang,Xiaoli Wang,Qiaowei Miao,Junhai Liu,Hansheng Wang,Lun Liu,Xiaohui Ji,Chenyang Wei
Camptothecin (CPT) has significant biological activity and has been extensively studied. This study established an efficient and green ultrasonic-assisted deep eutectic solvent (UAE-DES) and combined it with macroporous resin purification technology to extract and purify CPT and 10-hydroxycamptothecin (HCPT) from Camptotheca acuminata fruit. In total, 33 natural DES were prepared, among which choline chloride-1,4-butanediol was the most effective. The single-factor and response surface optimization extraction experiments were carried out to determine optimal conditions as follows: ultrasonic time = 27 min, solid-liquid ratio = 1:35 g/mL, ultrasonic temperature = 70 °C, DES moisture content, = 29 %, and total extraction rate = 0.1318 %. Furthermore, the scanning electron microscopy revealed that the UAE-DES treatment significantly disrupted the cell-wall structure of C. acuminata fruits, promoting the release of the target constituents. Moreover, AB-8-type macroporous resin was employed to optimize adsorption and desorption, which optimized 63.4 % and 77.3 % adsorption and desorption of CPT and HCPT, respectively. Density functional theory (DFT) was employed for assessing electrostatic potential (ESP), complexation energy, and reduced density gradient (RDG), to identify the non-covalent interactions between DES, conventional solvent ethanol, and CPT-like compounds during the extraction process. This study comprehensively explained the extraction mechanism and confirmed that DES had better extraction potential and good biocompatibility. These findings provide a theoretical basis and technical support for the green and efficient extraction and purification of CPT-like compounds.
研究领域:
天然产物化学
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药物分析
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植物药学
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绿色化学
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分子互作机制
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产品关联
DOI
高影响因子
Cell Communication and Signaling
·
2023
·Vol. 21
·期 1
·1-18
·
IF 8.4
Liao Zhaohong,Lan Haiqiang,Jian Xiaoting,Huang Jingwen,Wang Han,Hu Jijie,Liao Hua
Background To explore the role of skeletal muscle specific TGF-β signaling on macrophages efferocytosis in inflamed muscle caused by Cardiotoxin (CTX) injection. Methods CTX myoinjury was manipulated in TGF-βr2 flox/flox (control) mice or transgenic mice with TGF-β receptor 2 (TGF-βr2) being specifically deleted in skeletal muscle (SM TGF-βr2 −/− ). Gene levels of TGF-β signal molecules, special inflammatory mediators in damaged muscle or in cultured and differentiated myogenic precursor cells (MPC-myotubes) were monitored by transcriptome microarray or qRT-PCR. TGF-β pathway molecules, myokines and embryonic myosin heavy chain in regenerating myofibers, the phenotype and efferocytosis of macrophages were evaluated by immunofluorescence, immunoblotting, Luminex, or FACS analysis. In vitro apoptotic cells were prepared by UV-irradiation. Results In control mice, TGF-β-Smad2/3 signaling were significantly up-regulated in regenerating centronuclear myofibers after CTX-myoinjury. More severe muscle inflammation was caused by the deficiency of muscle TGF-β signaling, with the increased number of M1, but the decreased number of M2 macrophages. Notably, the deficiency of TGF-β signaling in myofibers dramatically affected on the ability of macrophages to conduct efferocytosis, marked by the decreased number of Annexin-V − F4/80 + Tunel + macrophages in inflamed muscle, and the impaired uptake of macrophages to PKH67 + apoptotic cells transferred into damaged muscle. Further, our study suggested that, the intrinsic TGF-β signaling directed IL-10-Vav1-Rac1 efferocytosis signaling in muscle macrophages. Conclusions Our data demonstrate that muscle inflammation can be suppressed potentially by activating the intrinsic TGF-β signaling in myofibers to promote IL-10 dependent-macrophages efferocytosis.
Video Abstract
研究领域:
免疫学
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肌肉生物学
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细胞信号传导
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炎症
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产品关联
DOI
PubMed
高影响因子
THERMOCHIMICA ACTA
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2012
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IF 1.805
Yang Lu,Juan Han,Chengzhuo Sheng,Ping Yu,Zhenjiang Tan,Yongsheng Yan
The phase diagrams for the systems containing polyoxyethylene (10) lauryl ether (POELE10) and three salts (KOH, K 2 CO 3 and K 3 PO 4 ) have been determined experimentally. Three experiential equations were used to correlate the binodal data. The liquid–liquid equilibrium data of these systems were obtained by experimental method and calculated method using lever rule. The tie-line data were correlated by using Othmer-Tobias and Bancroft and simple Setschenow-type equations. Furthermore, the effect of salt on the binodal curve for the studied systems has been discussed by means of salting-out coefficient, effective excluded volume (EEV) and Gibbs free energy of hydration of the ions (Δ G hyd ). It was found that the salts composed of anion with a higher valence are better salting-out agents than those with a lower valence. The order of salting-out abilities of salts is K 3 PO 4 > K 2 CO 4 > KOH for the investigated systems. Finally, the phase-separation ability of POELE10 is more powerful compared with that of other polymers and two-phase can easily form at the lower concentration, which indicates that lower cost is a remarkable advantage of POELE10–salt ATPSs.
研究领域:
化学
·
生物学
✓ 已验证
DOI
高影响因子
MOLECULES
·
2022
·Vol. 27
·期 12
·3940
·
IF 4.927
Dongge Yin,Xueling Hu,Mengru Cai,Kaixin Wang,Hulinyue Peng,Jie Bai,Yvchen Xv,Tingting Fu,Xiaoxv Dong,Jian Ni,Xingbin Yin
Curcumin (CUR) has a bright future in the treatment of cancer as a natural active ingredient with great potential. However, curcumin has a low solubility, which limits its clinical application. In this study, IRMOF-10 was created by the direct addition of triethylamine, CUR was loaded into IRMOF-10 using the solvent adsorption method, and the two were characterized using a scanning electron microscope (SEM), X-ray diffraction (XRD), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TG) methods, and Brunauer–Emmett–Teller (BET) analysis. We also used the MTT method, 4′,6-diamidino-2-phenylindole (DAPI) staining, the annexin V/PI method, cellular uptake, reactive oxygen species (ROS), and the mitochondrial membrane potential (MMP) to perform a safety analysis and anticancer activity study of IRMOF-10 and[email protected]on HepG2 cells. Our results showed that[email protected]had a CUR load of 63.96%, with an obvious slow-release phenomenon. The CUR levels released under different conditions at 60 h were 33.58% (pH 7.4) and 31.86% (pH 5.5). Cell experiments proved that IRMOF-10 was biologically safe and could promote curcumin entering the nucleus, causing a series of reactions, such as an increase in reactive oxygen species and a decrease in the mitochondrial membrane potential, thereby leading to cell apoptosis. In summary, IRMOF-10 is an excellent drug carrier and[email protected]is an effective anti-liver cancer sustained-release preparation.Keywords:MOFs;IRMOF-10;curcumin;HepG2 cells
研究领域:
药学
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纳米技术
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癌症研究
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材料科学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL SCIENCES
·
2015
·
IF 2.59
Ruixin Li,Chang Shu,Wei Wang,Xiaoliang Wang,Hui Li,Danke Xu,Wenying Zhong
ABSTRACT 10-Hydroxy camptothecin (HCPT) has been proven to be a cell cycle-specific chemotherapeutic agent, which is a necessary choice to inhibit tumor residue growth and prevent tumor metastasis after surgery. But it suffers from light decomposition, poor solubility, relatively low bioavailability, and some side effects, which are the major obstacles toward its clinical use. Integration of hydrophobic HCPT with hydrophilic hydrogel is a facile approach to change the disadvantageous situation of HCPT. In this study, a novel supramolecular hydrogelator with improved synthetic strategy was triggered by chemical hydrolysis, and then self-assembled to hydrogel. Taking advantage of the high-equilibrium solubility of HCPT in hydrogelator solution, this hydrogel was utilized to load HCPT via encapsulation as an effective carrier. HCPT hydrogels were characterized by several techniques including transmission electronic microscopy , rheology, and UV spectroscopy. In vitro release experiment indicated HCPT hydrogel could maintain long term and sustained release of HCPT at high accumulated rate. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay showed that HCPT hydrogel had an optimized anticancer efficacy. Besides, with prominent physical properties of carrier, HCPT hydrogel possessed satisfactory stability, syringeability, and recoverability, demonstrating itself as a potential localized injectable drug delivery system . © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:2266–2275, 2015
研究领域:
药学
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药物递送系统
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癌症治疗
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材料科学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
APPLIED THERMAL ENGINEERING
·
2025
·
IF 6.9
Yiran Zhang,Xufeng Li,Yongsheng Guo,Junjie Ding,Shu Yan,Wenjun Fang
Water-emulsified fuel represents a promising alternative fuel due to its potential to improve combustion efficiency through micro-explosions. In this work, a novel amphiphilic cetylated hyperbranched polyethyleneimine (CHPEI) was designed and synthesized as a surfactant for formulating a high energy-density JP-10 emulsified fuel, marking the first application of CHPEI in such a fuel system. The resulting emulsion demonstrates high stability at a low surfactant concentration, indicating exceptional emulsification efficiency. Single-droplet experiments revealed intense micro-explosions of emulsions during both evaporation and combustion. As a typical result, the emulsion droplets with 10% water exhibited a 43.9% reduction in evaporation lifetime compared to neat JP-10. The characteristics of micro-explosions were found to depend strongly on fuel composition: surfactant-only systems produced weaker (an intensity of 0.48 compared with 14.42) and less frequent (a frequency of 1 compared with 23) micro-explosions than the emulsion containing 10% water. Furthermore, increasing water content from 1% to 15% linearly enhanced the micro-explosion intensity. An optimal water content of 5% was identified, effectively balancing micro-explosion enhancement and the heat sink effect of water, which resulted in the shortest combustion lifetime. The emulsion with 5% water achieved a combustion energy release rate of 65.43 J·s −1 , which is 90.4% higher than that of neat JP-10 (34.36 J·s −1 ) and exceeded those of conventional fuels, including RP-3 (29.31 J·s −1 ), EHF-1 (32.69 J·s −1 ), and decalin (31.37 J·s −1 ). This work provides a practical design strategy to achieve high energy-density emulsified fuels with significantly enhanced combustion performance, offering valuable guidance for future fuel development.
研究领域:
燃料化学
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燃烧学
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能源材料
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界面科学
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热物理
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产品关联
DOI
高影响因子
RSC Advances
·
2018
·Vol. 8
·期 72
·41368-41375
·
IF 2.936
Liangliang He,Jinjin Xu,Qi Wang,Yezi Zhang,Zifei Qin,Yang Yu,Zhengming Qian,Zhihong Yao,Xinsheng Yao
Shogaols, mainly [6]-shogaol (6S), [8]-shogaol (8S) and [10]-shogaol (10S), the predominant and characteristic pungent phytochemicals in ginger, are responsible for most of its beneficial effects. However, poor oral bioavailability owing to extensive glucuronidation limits their application. The present study aimed to characterize the glucuronidation pathways of 6S, 8S and 10S by using pooled human liver microsomes (HLM), human intestine microsomes (HIM) and recombinant human UDP-glucosyltransferases (UGTs). The rates of glucuronidation were determined by incubating shogaols with uridine diphosphate glucuronic acid-supplemented microsomes. Kinetic parameters were derived by appropriate model fitting. Reaction phenotyping assays, activity correlation analyses and relative activity factors were performed to identify the main UGT isoforms. As a result, one mono-4′-O-glucuronide was detected after incubating each shogaol with HLM and HIM. Enzymes kinetic analysis demonstrated that glucuronidation of shogaols consistently displayed the substrate inhibition profile, and the liver showed higher metabolic activity for shogaols (CLint = 1.37–2.87 mL min−1 mg−1) than the intestine (CLint = 0.67–0.85 mL min−1 mg−1). Besides, reaction phenotyping assays revealed that UGT2B7 displayed the highest catalytic ability (CLint = 0.47–1.17 mL min−1 mg−1) among all tested UGTs. In addition, glucuronidation of shogaols was strongly correlated with AZT glucuronidation (r = 0.886, 0.803 and 0.871 for glucuronidation of 6S, 8S and 10S, respectively; p < 0.01) in a bank of individual HLMs (n = 9). Furthermore, UGT2B7 contributed to 40.8%, 34.2% and 36.0% for the glucuronidation of 6S, 8S and 10S in HLM, respectively. Taken altogether, shogaols were efficiently metabolized through the glucuronidation pathway, and UGT2B7 was the main contributor to their glucuronidation.
研究领域:
药理学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioresource Technology Reports
·
2018
·
IF 0
Bing-Qian Wang,Bo Peng,Jian-Fei Sun,Chu Wang,Ke Jiang,Jing-Hao Ma,Peng-Qi Zhang,Yu-Cai He
An effecti v e combination pretreatment of bamboo shoot shell (BSS) using Emulsifier OP-10 (0.5%, w/v) in the acidified media (pH 4.0) by autoclaving (120 °C, 40 min) was conducted. After BSS slurry without detoxification was enzymatically hydrolyzed for 96 h, glucose (25.2 g/L) and xylose (7.5 g/L) were obtained from 50 g/L BSS at high yields. HPLC results showed that no potential inhibitors (furfural and 5-hydroxymethylfurfural) formed. In the hydrolysates , an effective biocatalytic synthesis of ethyl ( S )-4-chloro-3-hydroxybutanoate (100% yield; >99% e.e. ) from 1000 mM ethyl 4-chloro-3-oxobutanoate was developed without the extra addition of cofactors within 24 h. In summary, this combination strategy involving biomass pretreatment, enzymatic saccharification , and bioreduction can be developed for producing chiral alcohols.
研究领域:
生物质预处理
·
酶解糖化
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生物催化
·
手性醇合成
✓ 已验证
DOI
危险品化学品经营许可证（带存储）