FREE RADICAL BIOLOGY AND MEDICINE
·
2016
·
IF 5.784
Bowen Wu,Hao Yu,Yifan Wang,Zongfu Pan,Yihan Zhang,Tong Li,Lu Li,Weichen Zhang,Lijun Ge,Ying Chen,Choe Kyong Ho,Danyan Zhu,Xin Huang,Yijia Lou
Protein nitrosylation is a ubiquitous post-translational modification in almost all biological systems. However, its function on stem cell biology is so far incompletely understood. Here, we demonstrated that peroxiredoxin 2 (Prdx-2) nitrosylation was involved in cardiomyocyte differentiation of mouse embryonic stem (ES) cells induced by S -nitrosoglutathione (GSNO). We found that temporary GSNO exposure could promote ES cell-derived cardiomyogenesis. Using a stable isotope labeling by amino acids in cell culture (SILAC)-based proteomics approach, coupled with biotin switch technique, a total of 104 nitrosylated proteins were identified. Specifically, one of the antioxidant enzymes , Prdx-2, was abundantly nitrosylated and temporarily reduced in antioxidant activity , causing transient endogenous hydrogen peroxide (H 2 O 2 ) accumulation and subsequent X-box binding protein-1s/phosphatidylinositol 3-kinase pathway activation. The present study reveals the mechanism in which GSNO favors cardiomyocyte differentiation. Prdx-2 nitrosylation could be a potent strategy to affect the pluripotent stem cell-derived cardiomyogenesis.
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American Journal of Cancer Research
·
2022
·
IF 5.942
Yuxin Zhuang,Guang Yang,Shaoyu Wu,Jianjun Chen,Jiayin Guo,Dongling Quan,Tingting Zhang,Zichao Yang,Shaobin Tan,Yuheng Ji,Zhipeng Chen,Lin Lv
The composition of microtubules involving several steps, including the polymerization and depolymerization of α-tubulin and β-tubulin heterodimers. Microtubule-targeting agents can increase or inhibit microtubule polymerization, thereby disrupting the dynamic process and stalling cells in G2/M phase. Microtubule-targeting agents are generally cytotoxic, which neurological toxicity being one of the significant adverse events associated. We recently reported a novel 5-arylalkynyl-2-benzoyl thiophene (PST-3) that exhibited broad-spectrum cellular cytotoxicity and in vivo potency with high safety. PST-3 was a substrate of p-gp, which could not cross the blood-brain barrier and lead to less neurotoxicity. The antitumor activities in vitro demonstrated that PST-3 combined with the colchicine-binding site on microtubule, induces morphological changes, disrupts microtubule networks, inhibits polymerization of tubulin, arrests breast cancer cells in the G2/M phase of the cell cycle and induces apoptosis. Evaluation of the antitumor effect in vivo demonstrated that PST-3 elicited MDA-MB-468 tumor %T/C of 11.75%, whereas elicited MCF7 tumor %T/C of 44.38% in breast cancer xenograft models. Besides, in vivo experiments of a higher dose (60 mg/kg) of PST-3 treatment for 21 days did not produce any significant neurotoxicity. These results provide evidence that PST-3 might possess the potential to be developed into a new microtubule inhibitor without neurological toxicity.
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NEW JOURNAL OF CHEMISTRY
·
2022
·Vol. 46
·期 22
·10637-10643
·
IF 3.925
Juan-Juan Hu,Zhong-Ying Ma,Xin-Rui He,Yi-Gang Wu,Qian Chen,Xue-Qing Song,Guan-Yuan Wang,Yi-Han Li,Jing-Yuan Xu
Gastric adenocarcinomas present elevated cyclooxygenase-2 (COX-2) expression compared to non-neoplastic mucosa. Four oxaliplatin (L-OHP)-based Pt(IV) complexes, CP-L-OHP (1), ED-L-OHP (2), KP-L-OHP (3), and SL-L-OHP (4), were synthesized with the non-steroidal anti-inflammatory drugs (COX inhibitors) carprofen, etodolac, ketoprofen and sulindac, respectively, as axial ligands to inhibit BGC-823 gastric cancer cells. Complexes 1–4 displayed comparable cytotoxicity to L-OHP, of which 1 displayed the lowest IC50 value and best selectivity in BGC-823 cells compared to normal liver cells (LO2). Complex 1 significantly enhanced Pt accumulation, DNA damage and apoptosis in BGC-823 cells. Overexpression of COX-2 can lead to a more aggressive behavior in gastric cancer, inducing metastatic and invasive processes. The wound-healing assay displayed that 1 could significantly delay BGC-823 cell metastasis with the lowest wound-healing rate compared to L-OHP and carprofen after treatment for 24 h. Interestingly, few 1-treated cells were observed to adhere to Matrigel, while the cell adhesion was hardly affected by the other treatment groups such as carprofen in cell adhesion experiments. Immunofluorescence studies indicated that 1 exhibited a longer-acting COX-2 response than carprofen alone. Carprofen (20 μM) effectively inhibited COX-2 at 1 and 5 h of treatment in BGC-823 cells, but did not work at 24 h. In contrast, 1 could retain the high inhibitory activity against COX-2 up to 24 h at least.
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ENVIRONMENTAL TOXICOLOGY
·
2018
·Vol. 34
·期 2
·141-149
·
IF 2.491
Xia Wang,Baida Kong,Bingnan He,Lai Wei,Jianbo Zhu,Yuanxiang Jin,Yudong Shan,Weitao Wang,Chunqiang Pan,Zhengwei Fu
8:2 Fluorotelomer alcohol (8:2 FTOH) is widely used in houseware and industrial goods and is ubiquitous in the surrounding environment. 8:2 FTOH has been linked to hepatoxicity, nephrotoxicity, and reproductive toxicity, as well as endocrine-disrupting effects. However, as of yet, the research regarding immunotoxicity of 8:2 FTOH remains largely limited. In the present study, adult male C57BL/6 mice were administered with 10, 30, and 100 mg/kg/d 8:2 FTOH by gavage for 28 days to investigate its immunotoxicity in vivo. The results showed that exposure to 8:2 FTOH caused increases in liver weight and histological changes in the liver, including vacuolation, cell swelling, immune cell infiltration, karyopyknosis and nuclear swelling. No histological change in either the spleen or the thymus was observed after administration of 8:2 FTOH. In addition, exposure to 8:2 FTOH reduced the concentration of IL-1β in serum, and mRNA levels of IL-1β, IL-6 , and TNF-α in both the thymus and spleen. CXCL-1 mRNA expression was downregulated in both the liver and thymus after 8:2 FTOH administration, while only IL-1β mRNA expression was upregulated in the liver. Moreover, the exposure of primary cultured splenocytes to 8:2 FTOH inhibited the ConA-stimulated proliferation of splenocytes at concentrations of 30 and 100 μM, and the LPS-stimulated proliferation of splenocytes at 100 μM. Furthermore, 8:2 FTOH inhibited the level of secreted IFN-γ in ConA-stimulated splenocytes. The results obtained in the study demonstrated that 8:2 FTOH posed potential immunotoxicity and liver injury in mice. Our findings will provide novel data for the health risk assessment of 8:2 FTOH.
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BIOSENSORS & BIOELECTRONICS
·
2019
·
IF 9.518
Xiaoxi Guo,Shuping Liu,Minghui Yang,Huitong Du,Fengli Qu
Photoelectrochemical (PEC) biosensor for highly sensitive detection of breast cancer biomarker human epidermal growth factor receptor-2 (HER2) is reported utilizing a dual signal amplification strategy. The biosensor was prepared based on tungsten sulfide nanowire array on Ti mesh (WS 2 NW/TM). Such WS 2 NW/TM electrode can generate photoelectric signal under visible light excitation . The HER2 aptamer was wrapped onto the nanowire array surface for specific binding with HER2 molecules, and gold nanoparticles (Au NPs) that modified with glucose oxidase (GOx) and HER2 binding peptide was utilized for signal amplification. The H 2 O 2 that generated by GOx catalyzed glucose reaction and localized surface plasmon resonance of Au NPs can both enhance the PEC current intensity of the biosensor, leading to dual signal amplification. The PEC current intensity is enhanced linearly with HER2 concentration in the 0.5–10 ng/mL range with limit of detection of 0.36 ng/mL. Such biosensor was applied for the detection of HER2 in breast cancer serum samples with detection results in good agreement with commercial ELISA results.
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MICROCHIMICA ACTA
·
2014
·Vol. 181
·期 9
·903-910
·
IF 3.719
Wang Jia-Cheng,Wang Yong-Sheng,Rang Wei-Qing,Xue Jin-Hua,Zhou Bin,Liu Lu,Qian Qiu-Mei,Wang Yong-Song,Yin Ji-Cheng
We report on a sensitive and specific method for the visual and colorimetric detection of 8-hydroxy-2′-deoxyguanosine (8-OHdG) in human urine by using the 8-OHdG-aptamer (Apt) as the recognition element. The aptamer was adsorbed on the surface of gold nanoparticles which enhances their stability. On addition of 8-OHdG, the conformation of the aptamer changes to form a G-quadruplex structure, thereby losing the ability to protect the nanoparticles and causing a color change from red to blue. The conformational changes were also studied by circular dichroism. The response is linearly dependent on the concentration of 8-OHdG in the range from 5.6 to 282 nM, the limit of detection is 1.7 nM, the relative standard deviation ranges from 1.1 to 4.2 % (for n = 6), and the recoveries range from 95.9 to 104.9 %. The method paves the way for visual analysis of samples without the use of costly instruments.
8-OHdG-aptamer was adsorbed onto the surface of AuNPs which enhances their stability. On addition of 8-OHdG, the conformation of 8-OHdG-aptamer changes to form a G-quadruplex structure, losing the ability to protect the AuNPs and causing a color change of the system.
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CHINESE SCIENCE BULLETIN
·
2013
·Vol. 59
·期 2
·147-153
·
IF 1.319
Wang Wei,Yan Xiao Li,Zhan Lei,Leng Fei,Yang Xiao Xi,Huang Cheng Zhi
A new type of highly selective aptamer-labeled fluorescent silica nanoparticles [Apt-tris(2,2′-bipyridyl)ruthenium(II)@SiO 2 NPs] were prepared through the reverse microemulsion method by using prolonged fluorescence lifetime ruthenium complexes of tris(2,2′-bipyridyl)ruthenium(II) (Ru(bpy)
2+ 3
) as the source of the fluorescence for cellular prion protein imaging. Investigations showed that the newly prepared Ru(bpy)
2+ 3
@SiO 2 NPs possessed superior advantages of strong fluorescence, low toxicity, and easy surface modification for bioconjugation. Cell imaging experiments indicated that Apt-Ru(bpy)
2+ 3
@SiO 2 NPs had great tendency to human bone marrow neuroblastoma cells (SK-N-SH cells), since they can express large amount of prion protein on the surface of the cell, while in HeLa cells this phenomenon disappeared for the reason that HeLa cells cannot express prion proteins.
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JOURNAL OF MEDICINAL CHEMISTRY
·
2025
·
IF 6.8
Qiuyue Fu,Yue Pan,Peixi Wu,Zhuoxian Cao,Liu Shi,Lan Huang,Kui Cheng,Zhipeng Chen
Capitalizing on the advantages of Toll-like receptor 2 (TLR2) small-molecule agonists combining high potency and low toxicity in cancer therapy, we designed and synthesized a novel series of thiourea-based TLR2 small-molecule agonists and identified a low-toxicity TLR1/2-specific small molecule agonist SMU-C409 (EC50 = 65 ± 3 nM). SMU-C409 incorporates key optimizations: a carbonyl conservation strategy eliminates carboxylesterase-mediated degradation, and a quinoline (N-heterocycle) enables salt formation that boosts solubility by 3.4-fold (free base) and 5.5-fold (hydrochloride) relative to the lead compound SMU-C80 (EC50 = 43 ± 5 nM), while retaining potent agonistic activity and exhibiting superior plasma stability, which is critical for favorable pharmacokinetics and efficacy. Mechanistically, SMU-C409 activates TLR1/2, recruits MyD88, induces NF-κB phosphorylation, and stimulates TNF-α/IL-1β secretion; in vitro studies confirm robust immune cell activation and antitumor immunomodulation. SMU-C409 overcomes core limitations of TLR2 agonists while maintaining high potency, positioning it as a promising candidate for advancing cancer immunotherapy.
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BMC Pulmonary Medicine
·
2022
·Vol. 22
·期 1
·1-11
·
IF 3.32
Zou Liangneng,Hong Dequn,Li Kecong,Jiang Bingyuan
Background Pulmonary fibrosis is a fatal lung disease with complex pathogenesis and limited effective therapies. Salt-inducible kinase 2 (SIK2) is a kinase that phosphorylates CRTCs and regulates many physiological processes. However, the role of SIK2 on pulmonary fibrosis remains unclear, and whether SIK2 inhibitor can attenuate pulmonary fibrosis is unknown.MethodWe subjected human fetal lung fibroblasts (HFLs) to transforming growth factor-β1 (5 ng/mL) for 12 h, and examined the expression of SIK2, CRTCs and pCRTCs in fibroblasts by western-blot. To address the roles of SIK2 and CRTCs involved in the progression of pulmonary fibrosis, HFLs were treated with a small-molecule inhibitor ARN-3236 or by siRNA-mediated knockdown of SIK2 expression. Pulmonary fibrosis model was established with mice by exposing to bleomycin, and assessed by H&E and Masson’s trichrome staining. COL1A and α-SMA distributions were detected in lung tissues by immunohistochemical staining.Results We discovered that SIK2 and phosphorylated-CRTC2 were expressed at a low basal level in normal lung tissues and quiescent fibroblasts, but increased in fibrotic lung tissues and activated fibroblasts. Inhibition of SIK2 by ARN-3236 prevented the fibroblasts differentiation and extracellular matrix expression in HFLs and attenuated bleomycin-induced pulmonary fibrosis in mice. Mechanistically, inactivation of SIK2 resulted in the dephosphorylation and nuclear translocation of CRTC2. Within the nucleus, CRTC2 binds to CREB, promoting CREB-dependent anti-fibrotic actions.Conclusion In conclusion, our results elucidated a previously unexplored role of SIK2 in pulmonary fibrosis, and identified SIK2 as a new target for anti-fibrosis medicines.
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Cell Death & Disease
·
2021
·Vol. 12
·期 6
·1-16
·
IF 8.469
Chi Xiaochun,Luo Weiwei,Song Jiagui,Li Bing,Su Tiantian,Yu Miao,Wang Tianzhuo,Wang Zhenbin,Liu Cheng,Li Zhen,He Huiying,Zhan Jun,Zhang Hongquan
Kindlin-2 is known to play important roles in the development of mesoderm-derived tissues including myocardium, smooth muscle, cartilage and blood vessels. However, nothing is known for the role of Kindlin-2 in mesoderm-derived reproductive organs. Here, we report that loss of Kindlin-2 in Sertoli cells caused severe testis hypoplasia, abnormal germ cell development and complete infertility in male mice. Functionally, loss of Kindlin-2 inhibits proliferation, increases apoptosis, impairs phagocytosis in Sertoli cells and destroyed the integration of blood-testis barrier structure in testes. Mechanistically, Kindlin-2 interacts with LATS1 and YAP, the key components of Hippo pathway. Kindlin-2 impedes LATS1 interaction with YAP, and depletion of Kindlin-2 enhances LATS1 interaction with YAP, increases YAP phosphorylation and decreases its nuclear translocation. For clinical relevance, lower Kindlin-2 expression and decreased nucleus localization of YAP was found in SCOS patients. Collectively, we demonstrated that Kindlin-2 in Sertoli cells is essential for sperm development and male reproduction.
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Journal of Materiomics
·
2025
·
IF 9.6
Qing Li,Wei Deng,Tian-Ci Ma,Changhao Zhao,Mupeng Zheng,Lei Zhao,Qiong Wu,Chaofeng Wu,Fang-Zhou Yao,Wen Gong,Dragan Damjanovic,Mao-Hua Zhang
Complex lead-based perovskites with the general formula Pb(B x ’B 1- x ’’)O 3 , represent an important class of antiferroelectrics beyond the prototypical PbZrO 3 and NaNbO 3 . Depending on the combination of B-site species and the degree of cationic ordering, these materials exhibit a wide range of ferroic behaviors, spanning from antiferroelectric to (relaxor) ferroelectric responses. In this study, we investigate (Pb 1- x Ba x )(Yb 1/2 Nb 1/2 )O 3 polycrystals synthesized via a two-step processing route. Despite displaying antiferroelectric, ferroelectric, or nearly linear dielectric behavior at room temperature, all compositions exhibit double polarization hysteresis loops in proximity to a lower-temperature dielectric anomaly. This dielectric anomaly originates from the competition between antipolar and nanoscale polar regions, and shifts towards lower temperature with increasing Ba content, reflecting the suppression of long-range antiferroelectric ordering. Notably, a composition-invariant temperature scale, T *, is identified and associated with the onset of static correlations among nanoscale polar entities, consistent with behavior reported in other complex Pb-based relaxor ferroelectrics. Superlattice reflections arising from antiparallel Pb 2+ displacements persist above T *, suggesting an intricate cation-ordering landscape requiring further investigation. These findings underscore the coexistence and competition of polar and antipolar instabilities in complex lead-based perovskites, and their pronounced sensitivity to chemical substitution, thermal fluctuations, and external electric fields.
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INTERNATIONAL DENTAL JOURNAL
·
2025
·Vol. 76
·期 1
·109304
·
IF 3.7
Zhaoxia Yu,Shihui Jiang,Xinxin Li,Xingjiao Li,Guanhua Wang,Xiaohua Dai,Xiaoli Lian,Yan Yan,Yue Wang,Zhimou Yang,Huiru Zou
Objectives Enamel matrix derivative (EMD) is widely recognized for its ability to induce osteogenic and odontogenic differentiation. However, the complex composition of EMD frequently results to inconsistent experimental and clinical outcomes. Amelogenin, a key component of EMD, plays crucial roles in tooth germ development as well as in the repair and regeneration of dental tissue. In this study, an amelogenin peptide was investigated on the proliferation and odontogenic differentiation of human dental pulp cells (HDPCs). Methods The amelogenin peptide with the amino acid sequence KWYQNMIR was synthesized using solid-phase techniques. HDPCs were stimulated with various concentrations of the peptide. CCK-8 assays, alkaline phosphatase (ALP) activity measurements, quantitative reverse transcription-polymerase chain reaction, Western blot analysis, Alizarin red staining, and scanning electron microscopy were used to assess the effects. Results The amelogenin peptide concentrations of 100 nM and 1 μM significantly enhanced HDPC proliferation at 5 and 7 days ( P < .01), with 1 μM exhibiting the most pronounced effect. Treatment with 1 μM amelogenin peptide enhanced ALP activity in HDPCs at 7 and 14 days ( P < .01) and markedly upregulated the mRNA expression of DSPP, DMP-1 , and RUNX-2 . Western blot analysis revealed that 1 μM amelogenin peptide enhanced the protein expression of DSPP, DMP-1, and ALP in HDPCs at 7 and 14 days. Additionally, it promoted calcium deposition and mineralized nodule formation at 28 days. Importantly, the amelogenin peptide upregulated the phosphorylation level of ERK1/2 (p-ERK1/2), and the application of an ERK1/2 inhibitor suppressed HDPC differentiation. Conclusions The amelogenin peptide stimulates both the proliferation and odontogenic differentiation of HDPCs via the ERK1/2 pathway. These findings suggest that the amelogenin peptide may have significant implications for regenerative dentistry, particularly in the context of dentine-pulp complex regeneration.
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