CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
·
2019
·Vol. 47
·期 9
·1182-1197
·
IF 3.411
Chaoyang Zhang,Hai Xie,Qian Yang,Yiting Yang,Weiye Li,Haibin Tian,Lixia Lu,Fang Wang,Jing-Ying Xu,Furong Gao,Juan Wang,Caixia Jin,Guoxu Xu,Guo-Tong Xu,Jingfa Zhang
Purpose To explore the mechanisms of erythropoietin (EPO) in maintaining outer blood-retinal barrier (BRB) in diabetic rats. Methods Sprague-Dawley rats were rendered diabetic with intraperitoneal injection of streptozotocin, and then followed by intravitreal injection of EPO. Two and four weeks later, the permeability of outer BRB was examined with FITC-dextran leakage assay, following a method to demarcate the inner and outer retina based on retinal blood supply. The glyoxal-treated ARPE-19 cells, incubated with EPO, soluble EPO receptor (sEPOR), Gö6976, or digoxin, were studied for cell viability and barrier function. The expressions of ZO-1, occludin, VEGFR2, HIF-1α, MAPKs, and AKT were examined with Western blot and immunofluorescence. Results The major Leakage of FITC-dextran was detected in the outer nuclear layer in both 2- and 4-week diabetic rats. The leakage was largely ameliorated in EPO-treated diabetic rats. The protein expressions of ZO-1 and occludin in the RPE-Bruch's membrane choriocapillaris complex were significantly decreased, whereas HIF-1α and JNK pathways were activated, in 4-week diabetic rats. These changes were prevented by EPO treatment. The in vitro study with ARPE-19 cells confirmed these changes, and the protective effect of EPO was abolished by sEPOR. Gö6976 and digoxin rescued the tight junction and barrier function in glyoxal-treated ARPE-19 cells. Conclusions In early diabetic rats, the outer BRB might be more severely damaged and its breakdown is the major factor for retinal oedema. EPO maintains the outer BRB integrity through down-regulation of HIF-1α and JNK signallings, and thus up-regulating ZO-1 and occludin expressions in RPE cells.
✓ 已验证
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2019
·
IF 6.044
Ding Qu,Mengying Jiao,Haijiao Lin,Chunli Tian,Guowei Qu,Jingwei Xue,Lingjing Xue,Caoyun Ju,Can Zhang
Controlled release and tumor-selective distribution are highly desirable for anticancer nanomedicines. Here, we design and synthesize an anisamide-conjugated N -octyl- N,O -maleoyl- O -phosphoryl chitosan (a-OMPC) which can form amphiphilic micelles featuring pH-responsive release and high affinity to sigma-1 receptor-overexpressed tumors for paclitaxel (PTX) delivery. Thereinto, maleoyl and phosphoryl groups cooperatively contribute to pH-responsive drug release due to a conversion from hydrophile to hydrophobe in the acidic microenvironment of endo/lysosomes. We demonstrated that PTX-loaded a-OMPC micelles (PTX-aM) enhanced the cellular internalization via the affinity between anisamide and sigma-1 receptor, rapidly released drug in endo/lysosomes and elevated the cytotoxicity against PC-3 cells. The in vivo studies further verified that PTX-aM could largely accumulate at the tumor site even after 24 h of administration, resulting in obvious inhibition effect and prolonged survival period in PC-3 tumor xenograft-bearing mice. Moreover, OMPC showed no obvious hemolytic and acute toxicity. Collectively, this chitosan derivate holds a promising potential in application of prostate cancer-targeted drug delivery system.
✓ 已验证
DOI
PubMed
高影响因子
ANTIVIRAL RESEARCH
·
2015
·
IF 3.938
Shaoyang Zhang,Limei Zhong,Bing Chen,Ting Pan,Xue Zhang,Liting Liang,Qianwen Li,Ziying Zhang,Hui Chen,Jie Zhou,Haihua Luo,Hui Zhang,Chuan Bai
HIV-1 Vif protein is one of the most crucial accessory proteins for viral replication. It efficiently counteracts the important host restriction factor APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G, A3G) which is lethal to HIV-1 by causing G to A mutation of viral genome. Vif protein mediates degradation of APOBEC3G via the complicated protein–protein interactions of Vif, APOBEC3G, Elongin C/B and Cullin 5. The importance of Vif–APOBEC3G complex makes it a good potential target to develop new therapeutics of HIV-1. We identified a potent HIV-1 replication inhibitor (ZBMA-1, IC 50 = 1.01 μM) that efficiently protected APOBEC3G protein by targeting Vif–APOBEC3G complex. The co-immunoprecipitation and docking studies indicated that compound ZBMA-1 affected the binding of Elongin C with Vif protein.
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF INFECTIOUS DISEASES
·
2008
·Vol. 197
·期 1
·117-125
·
IF 6.035
Michaëlsson Jakob,Long Brian R.,Loo Christopher P.,Lanier Lewis L.,Spotts Gerald,Hecht Frederick M.,Nixon Douglas F.
Natural killer (NK) cells are believed to play a role in human immunodeficiency virus type 1 (HIV-1) disease progression, and NK cell levels are reduced in individuals with chronic HIV-1 infection. Interleukin (IL)-2 therapy results in an expansion of CD4+ T cells as well as NK cells; however, little is known about the detailed effects of IL-2 therapy on NKcells in HIV-1 infection in general and in early infection in particular. Here, we investigated the effects of combined IL-2 therapy and antiretroviral therapy (ART) on the number, frequency, phenotype, and interferon (IFN)-γ production of NK cells in individuals with early HIV-1 infection. Patients randomized to receive combined ART and IL-2 therapy predominantly expanded CD56dim NK cells, and the expansion was greater than in patients randomized to receive ART alone. Importantly, NK cell receptor expression and IFN-γ production were maintained over time. This reconstitution ofNKcells may be useful in helping contain viremia if patients discontinue therapy or develop drug resistance.
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF INORGANIC BIOCHEMISTRY
·
2023
·
IF 3.9
Xiaoting Dong,Wenli Liu,Yuxuan Dong,Kun Wang,Kewei Li,Liujiao Bian
Metallo-β-lactamases (MβLs) are the primary mechanism of resistance to carbapenem antibiotics. To elucidate how MβLs have evolved with the introduction and use of antibiotics, the mutation and evolution of SMB-1 from Serratia marcescens were investigated in microbial evolution plates containing discontinuous meropenem (MEM) concentration gradients. The results revealed 2-point mutations, A242G and S257R; 1 double-site mutation, C240G/E258G; and 3 frameshift mutations , M5, M12, and M13, which are all missense mutations situated at the C-terminus. Compared with that of the wild-type (WT), the minimum inhibitory concentrations (MICs) of MEM for A242G, C240G/E258G, M5, M12, and M13 increased at least 120-fold, and that of S257R increased 8-fold. The catalytic efficiency k cat /K m increased by 365% and 647%, respectively. Concerning the structural changes, the structure at the active site changed from an ordered structure to an unordered conformation. Simultaneously, the flexibility of loop 1 was enhanced. These changes increased the volume of the active site cavity; thus, this was more conducive to exposing the Zn 2+ site, facilitating substrate binding and conversion to products. In A242G, structural changes in Gly-242 can be transmitted to the active region via a network of interactions between the side chains of Gly-242 and the amino acid side chains near the active pocket. Together, these results pointed to the process of persistent drug tolerance and resistance, the SMB-1 enzyme evolved into a more exquisite structure with increased flexibility and stability, and stronger hydrolysis activity via genetic mutations and structural changes.
✓ 已验证
DOI
PubMed
高影响因子
RSC Advances
·
2020
·Vol. 10
·期 48
·28746-28754
·
IF 3.119
Yuan Ma,Ming Luo,Yingping Xu,Yingjia Liu,Xiaocui Liu,Xiufang Bi,Yiping Yuan,Fan Su,Xiaocui Yin
Thaumatin-like protein-1 (TLP-1), a protein displaying high polyphenol oxidase (PPO) action and a member of the pathogenesis-related (PR) protein family, has a considerable influence on the enzymatic browning of Prunus mume (Chinese plum). In this assay, TLP-1 was identified and extracted from Prunus mume to investigate the protein's properties and better understand its contribution to the fruit's browning during storage or processing. The extracted TLP-1 was purified to apparent homogeneity using a procedure involving citrate phosphate buffer solution (CPBS) extraction, (NH4)2SO4 precipitation, dialysis in a cellulose bag, and ion exchange chromatography using a DEAE Sepharose Fast Flow column, while a Sephadex G-75 column was employed to facilitate gel filtration chromatography. Moreover, the enzyme was characterized in terms of its optimal pH and stability, isoelectric point (pI), molecular weight, optimal temperature and stability, enzyme kinetic parameters and substrate specificity, as well as inhibitor stability. This study indicated that the pI and molecular weight of TLP-1 was approximately 4.4 and 28 kDa, respectively, while 30 °C and 7.5 represented the respective optimal temperature and pH level for PPO catalysis. TLP-1 showed high affinity to catechol and pyrogallol, with Km values of 24.40 mM and 26.23 mM, respectively. Sodium bisulfite significantly inhibited TLP-1 activity. These findings on the properties of TLP-1 can contribute significantly to the search for ways to minimize the losses caused by fruit browning during the storage and processing of Prunus mume.
✓ 已验证
DOI
PubMed
高影响因子
Anti-Cancer Agents in Medicinal Chemistry
·
2022
·Vol. 22
·期 17
·3009-3024
·
IF 2.527
Zhu Yuting,Wang Huai,Yu Mingjun,Li Chao,Meng Xiaoming,He Meng,Yao Risheng
Background: GRPR is over-expressed in cancer cells and is a potential drug target for the treatment of cancer. PD176252, as the most representative non-peptide inhibitor of GRPR, can inhibit the growth of cancer cells, but its low selectivity to cancer cells and normal cells limits
its further application. Objective: The aim of this study was to design and synthesize novel GRPR inhibitor with stronger anti-cancer activity and higher affinity with GRPR than the lead compound PD176252. Methods: A series of 1, 3, 4-oxadiazole derivatives as PD176252 analogues
(4a-4j, 6a-6q) were synthesized and their cytotoxic activity was investigated on four cancer lines with high expression of GRPR (gastric (HGC-27), colon (HCT- 116), prostate (PC-3), and lung (A549)) and one human cell line (gastric mucosal epithelial (GES-1)) by MTT assay. Flow cytometry analysis
and Western Blot were used to determine whether the compound induced programmed apoptosis of cancer cells. Competitive binding experiment was used to verify the affinity between GRPR and the optimal compound. Results: Compound 6m exhibited significant growth inhibition on all tested cancer
cell lines, especially gastric cancer cells (HGC-27 cellular IC50 0.37 ± 0.04μM). Also, the selectivity of 6m to HGC-27 was much higher than that of PD176252. Flow cytometric analysis and Western Blot proved that 6m significantly promoted the apoptosis of HGC-
27 cells. Moreover, competitive binding experiment confirmed the close binding of 6m with GRPR, which indicated 6m with a higher affinity than lead compound PD176252. Conclusion: Our results suggested that 6m, as a novel GRPR inhibitor, had a higher affinity with GRPR and potential anti-cancer
effect than PD176252, which can be used as a template for further optimization.
✓ 已验证
DOI
PubMed
高影响因子
mSystems
·
2020
·
IF 6.633
Yougui Li,Wenyi Xu,Fang Zhang,Shi Zhong,Yuqing Sun,Jinxi Huo,Jianxun Zhu,Chongming Wu
Hyperlipidemia is a worldwide epidemic with an obvious gender disparity in incidence. Modulations on gut microbiota by traditional Chinese medicines (TCM) are emerging as a potential rationale governing the profitable effects of drugs on hyperlipidemia. However, it is unclear how gut microbes regulate the progression of hyperlipidemia. Here, we found that mulberry leaf extract (MLE) and its active component 1-deoxynojirimycin (DNJ) diminished hyperglycemia and hypertriglyceridemia with similar efficacy in male and female mice but preferentially alleviated hypercholesterolemia in female mice. Further investigations showed that DNJ sex-specifically downregulated the expression of lipogenic genes, especially cholesterol-biosynthetic genes. Oral administration of DNJ imposed more profound modulation on gut microbiota in female mice than in male ones, as estimated by 16S rRNA metatranscriptomic analysis. DNJ markedly enriched Akkermansia and Clostridium group XIVa and promoted the production of indole-3-propionic acid (IPA) in a sexually dimorphic way. Importantly, IPA tightly associates with the antihyperlipidemic effect of DNJ and exhibited a potent lipid-lowering effect both in vitro and in vivo. Together, our results have established a regulatory mechanism by which DNJ sex-specifically improves hyperlipidemia, offering an in-depth theoretical basis for therapeutic exploitation of DNJ as a sex-specific intervention against hyperlipidemia.IMPORTANCE Hyperlipidemia has been intensively focused on by researchers around the world owing to its major contribution to cardiovascular diseases. Various evidence reveals that women are more susceptible than male counterparts to dyslipidemia, making sex-dependent therapeutic strategies and drugs urgently needed. In the present work, we demonstrate that DNJ, the main active component of mulberry leaves, exerts an obvious female-preferential antihyperlipidemic effect through specifically enriching Akkermansia and Clostridium XIVa and elevating an active microbial metabolite, indole-3-propionic acid (IPA), in female mice. Moreover, we have corroborated the potent lipid-lowering efficacy of IPA both in vitro and in vivo. These findings not only indicate a potential mechanism by which gut microbes and their metabolites confer the beneficial role of DNJ in ameliorating hyperlipidemia but also provide an in-depth theoretical basis for therapeutic exploitation of DNJ as a female-specific intervention against hyperlipidemia.
✓ 已验证
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2020
·
IF 10.257
Guojuan Zhang,Zhiguang Liu,Lifang Fan,Yujie Han,Yujing Guo
A dual signal and label-free electrochemical aptasensor for mucin 1 was constructed based on hemin/ [email protected] nanocomposite ( [email protected] ). Hemin attached on the graphene surface not only improves the solubility of graphene and acts as an in-situ electrochemical probe but also exhibits excellent peroxidase-like properties to electrocatalyze the reduction of H 2 O 2 . PdPtNPs also show outstanding catalytic capacity to the reduction of H 2 O 2 and provide numerous binding sites for loading dDNA (mucin 1 aptamer and cDNA) to form the sensing interface. In the presence of mucin 1, due to the specific affinity between aptamer and mucin 1, double helix would be induced dissociation and the aptamer would be pulled off from the electrode. As a result, the electrochemical signals of hemin and H 2 O 2 were recovered. Based on these properties, the label-free and sensitive dual signal electrochemical biosensor for mucin 1 detection has been developed. The one is differential pulse voltammetry (DPV) signal of hemin and the other is chronoamperometry signal arisen from the catalytic reduction of H 2 O 2 . The linear ranges for mucin 1 were 8.0 pg mL −1 to 80 ng mL −1 and 0.8 pg mL −1 to 80 ng mL −1 with the limit of detection 2.5 pg mL −1 and 0.25 pg mL −1 by DPV and chronoamperometry, respectively. The recovery of mucin 1 in human blood serum samples was from 95.0% to 104.2%. The detection platform does not need signal labeling which greatly reduced the sophisticated and expensive procedures. The aptasensor provide a promising strategy for the determination of mucin 1 in clinical diagnostics.
✓ 已验证
DOI
PubMed
高影响因子
RSC Advances
·
2023
·Vol. 13
·期 16
·10523-10541
·
IF 3.9
Delong Wang,Min Li,Jing Li,Yali Fang,Zhijia Zhang
In an effort to exploit the bioactive natural scaffold 3,4-dihydroisoquinolin-1(2H)-one for plant disease management, 59 derivatives of this scaffold were synthesized using the Castagnoli–Cushman reaction. The results of bioassay indicated that their antioomycete activity against Pythium recalcitrans was superior to the antifungal activity against the other 6 phytopathogens. Compound I23 showed the highest in vitro potency against P. recalcitrans with an EC50 value of 14 μM, which was higher than that of the commercial hymexazol (37.7 μM). Moreover, I23 exhibited in vivo preventive efficacy of 75.4% at the dose of 2.0 mg/pot, which did not show significant differences compared with those of hymexazol treatments (63.9%). When the dose was 5.0 mg per pot, I23 achieved a preventive efficacy of 96.5%. The results of the physiological and biochemical analysis, the ultrastructural observation and lipidomics analysis suggested that the mode of action of I23 might be the disruption of the biological membrane systems of P. recalcitrans. In addition, the established CoMFA and CoMSIA models with reasonable statistics in the three-dimensional quantitative structure–activity relationship (3D-QSAR) study revealed the necessity of the C4-carboxyl group and other structural requirements for activity. Overall, the above results would help us to better understand the mode of action and the SAR of these derivatives, and provide crucial information for further design and development of more potent 3,4-dihydroisoquinolin-1(2H)-one derivatives as antioomycete agents against P. recalcitrans.
✓ 已验证
DOI
PubMed
高影响因子
Biomolecules
·
2026
·Vol. 16
·期 10
·1507
·
IF 5.6
Ting Ge,Yifan Wen,Jiale Zhao,Wenjia Wang,Wenwen Xu,Bo Li,Yibing Wang,Weihua Zhang,Enping Zhang
Litter size is a critical trait determining the economic efficiency of sheep production. Ferritin heavy chain 1 (FTH1), a key iron-storage protein, plays an important role in regulating cellular susceptibility to ferroptosis. Based on our previous observation that ferroptosis-related pathways differ between ovaries from single-lamb and multi-lamb Hu ewes, this study investigated the role ofFTH1in regulating ferroptosis and granulosa cell (GC) function in sheep.FTH1expression was examined in ovarian tissues and GCs from Hu sheep with different reproductive phenotypes and follicular developmental stages using RT-qPCR. An erastin-induced ferroptosis model was established in sheep GCs, andFTH1function was evaluated through overexpression and interference experiments. Ferroptosis-related indicators, including ROS, C11-BODIPY 581/591, Fe2+, malondialdehyde (MDA), reduced glutathione (GSH), ferroptosis-associated genes, and GPX4 protein expression, were analyzed. Steroidogenic function was assessed by measuring the expression ofSTAR,CYP11A1,HSD17B1, and3β-HSD, as well as estradiol (E2) and progesterone (P4) secretion. RNA sequencing was performed to identify transcriptional changes associated withFTH1overexpression in erastin-treated GCs.FTH1expression was higher in ovaries from multiparous sheep and healthy follicles.FTH1overexpression alleviated erastin-induced ferroptosis by enhancing GPX4 expression and reducing Fe2+accumulation, ROS production, and lipid peroxidation, whereasFTH1knockdown aggravated ferroptosis damage. Furthermore,FTH1maintained steroidogenic function by promotingSTARexpression and preserving E2and P4synthesis under ferroptosis stress. Ferrostatin-1 (Fer-1) partially rescued GC viability and steroidogenic capacity, and attenuated erastin-induced apoptosis. Under erastin treatment, transcriptome analysis identified 297 differentially expressed mRNAs and 92 lncRNAs betweenFTH1-overexpressing GCs and the corresponding vector control. These differentially expressed transcripts represent candidate regulatory relationships that require further functional validation. Enrichment analysis highlighted cytokine signaling and ROS-related pathways, suggesting potential processes associated with the effects ofFTH1under these conditions. Collectively, these findings support thatFTH1protects sheep GCs against ferroptosis-induced injury and supports steroidogenic function, providing new insights into the role of iron homeostasis in follicular development.
✓ 已验证
DOI
高影响因子
Chemosensors
·
2026
·Vol. 14
·期 11
·243
·
IF 4.4
Jiahua Su,Wei Qu,Chengjun Qiu,Yuan Zhuang,Yi Qu,Muzhi Li,Huili Hao,Zizi Zhao
1-Aminopyrene, as a transformation product of the priority pollutant 1-nitropyrene, has raised increasing concerns due to its carcinogenic, mutagenic, and bioaccumulative properties in marine environments. A rapid and sensitive method for trace 1-aminopyrene detection in seawater is essential for marine environmental monitoring and public health protection. In this paper, a novel electrochemical immunosensor was fabricated based on an NH2-functionalized multi-walled carbon nanotubes-chitosan (NH2-MWCNTs/CS) nanocomposite film loaded with anti-1-aminopyrene antibody on a glassy carbon electrode. The NH2-MWCNTs/CS composite served as a conductive and biocompatible matrix that facilitated interfacial electron transfer and provided a suitable surface for adsorption-based antibody immobilization. Potassium ferricyanide was employed as an electrochemical probe to generate voltammetric signals, and the immune response was investigated by differential pulse voltammetry. Under optimized experimental conditions, the peak current change was inversely proportional to the 1-aminopyrene concentration in the range of 0.5 ng·mL−1to 110 ng·mL−1, with a detection limit of 0.36 ng·mL−1. The immunosensor demonstrated good selectivity, stability, and anti-interference capability in complex sample matrices. It was successfully applied to the determination of 1-aminopyrene in real seawater samples, with recovery rates ranging from 97.53% to 99.30% and relative standard deviations below 0.92%. The results indicate that the proposed immunosensor offers a simple, cost-effective, and environmentally friendly alternative to conventional chromatographic methods, and holds great potential for on-site monitoring of trace PAH metabolites in marine environments.
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）