Signal Transduction and Targeted Therapy
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2024
·Vol. 9
·期 1
·1-17
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IF 40.8
Fang Lu,Liu Changjie,Jiang Zong-zhe,Wang Mengxiao,Geng Kang,Xu Yangkai,Zhu Yujie,Fu Yiwen,Xue Jing,Shan Wenxin,Zhang Qi,Chen Jie,Chen Jiahong,Zhao Mingming,Guo Yuxuan,Siu K. W. Michael,Chen Y. Eugene,Xu Yong,Liu Donghui,Zheng Lemin
Obesity is a global issue that warrants the identification of more effective therapeutic targets and a better understanding of the pivotal molecular pathogenesis. Annexin A1 (ANXA1) is known to inhibit phospholipase A2, exhibiting anti-inflammatory activity. However, the specific effects of ANXA1 in obesity and the underlying mechanisms of action remain unclear. Our study reveals that ANXA1 levels are elevated in the adipose tissue of individuals with obesity. Whole-body or adipocyte-specific ANXA1 deletion aggravates obesity and metabolic disorders. ANXA1 levels are higher in stromal vascular fractions (SVFs) than in mature adipocytes. Further investigation into the role of ANXA1 in SVFs reveals that ANXA1 overexpression induces lower numbers of mature adipocytes, while ANXA1-knockout SVFs exhibit the opposite effect. This suggests that ANXA1 plays an important role in adipogenesis. Mechanistically, ANXA1 competes with MYC binding protein 2 (MYCBP2) for interaction with PDZ and LIM domain 7 (PDLIM7). This exposes the MYCBP2-binding site, allowing it to bind more readily to the SMAD family member 4 (SMAD4) and promoting its ubiquitination and degradation. SMAD4 degradation downregulates peroxisome proliferator-activated receptor gamma (PPARγ) transcription and reduces adipogenesis. Treatment with Ac2-26, an active peptide derived from ANXA1, inhibits both adipogenesis and obesity through the mechanism. In conclusion, the molecular mechanism of ANXA1 inhibiting adipogenesis was first uncovered in our study, which is a potential target for obesity prevention and treatment.
研究领域:
分子生物学
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内分泌学
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代谢
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肥胖研究
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高影响因子
CHEMICAL ENGINEERING JOURNAL
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2024
·
IF 13.3
Yu Liu,Heng Zhang,Kaiyan Xiang,Chenghao Zeng
Toll-like receptor agonists have been extensively applied as immunostimulatory adjuvants because of their well-defined pharmacological mechanisms, while systemic administration of Toll-like receptor agonists have shown limited efficacy due to their unfavorable pharmacokinetic properties. Here we constructed an albumin-binding Toll-like receptor 7 agonist (Ab1V209) by conjugating the Toll-like receptor 7 agonist 1V209 with truncated Evans Blue for binding to endogenous albumin. The resulting Ab1V209 has the ability to hijack albumin and is retained in tumor tissues for a higher accumulation than 1V209. As monotherapy, the systemic administration of Ab1V209 alters the function of tumor-associated macrophages towards anti-tumor phenotype, and increases the infiltration of CD8 + T cells, leading to controlled tumor growth with minimal systemic toxicity. When used in combination with an mRNA cancer vaccine, the combination therapy activated dendritic cells to provide antigen presentation molecule and co-stimulatory molecule, resulting in a strong T cell activation and expansion. This study presents a strategy for the rational engineering of albumin-binding adjuvants to enhance cancer immunotherapy.
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BIOMEDICINE & PHARMACOTHERAPY
·
2016
·
IF 2.326
Hua-Wen Li,Tang-Bin Zou,Qing Jia,En-Qin Xia,Wen-Jun Cao,Wen Liu,Tai-Ping He,Qin Wang
Background Increasing evidence supports the anticancer effects of morin in vitro and in vivo . However, the role of morin-7-sulphate sodium (NaMoS), a water-soluble flavonoid derivative synthesized from morin remains unclear. The present study investigated the tumor suppression by NaMoS in mouse melanoma cells. Materials and methods We synthesized the flavonoid derivative morin-7-sulphate sodium according to the method described for quercetin-sulphate derivative, and further isolated, purified and identified the compound. Cell proliferation in vitro was assessed using a CCK-8 assay. The wound healing assay was performed to evaluate cell motility , and flow cytometry was used to detect cellular apoptosis . Protein levels of vimentin , matrix metalloproteinase 9 (MMP9), phosphorylation of Akt1/2/3 (p-Akt1/2/3), extracellular signal-regulated kinase 1/2 (p-ERK1/2) and Caspase3 in B16F10 cells were detected by immunohistochemistry and Western blot . Results The results suggest that cell proliferation was markedly decreased in NaMoS-treated groups (1, 10, 25, 50, 100, 500, 1000 μM) in a dose-dependent manner compared with the Control group and the IC 50 was 221.67 μM at 48 h. NaMoS at 200 μM concentration significantly inhibited the invasion and promoted apoptosis of B16F10 cells. Moreover, protein level of Caspase3 increased significantly in B16F10 cells treated by NaMoS. Immunohistochemistry and Western blot further confirmed that NaMoS decreased the expression of vimentin, MMP9, p-Akt1/2/3 and p-ERK1/2 in B16F10 cells. Conclusions This study provides robust evidence that NaMoS, a water-soluble flavonoid, manifests anticancer properties and may act as a signal transduction inhibitor in melanoma cells.
研究领域:
肿瘤学
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药理学
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细胞生物学
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PubMed
高影响因子
Pathogens
·
2026
·Vol. 15
·期 6
·567
·
IF 3.8
Zixiang Wang,Qianwen Deng,Ziyu Huang,Zixing Lin,Haohui Zhu,Janak L. Pathak,Ying Wang,Min Nie
Porphyromonas gingivalis(P. gingivalis) is a primary pathogen in periodontitis, yet its elimination is limited by complex anatomical structures. Photodynamic therapy (PDT) is a promising adjunct, but its antimicrobial efficacy is compromised in the acidic microenvironment induced byP. gingivalis. Given that 2′,4′,5′,7′-tetraiodofluorescein (TIF) exhibits robust and stable photodynamic activity under acidic conditions, this study investigated the antibacterial effect of TIF-mediated PDT (TIF-PDT) againstP. gingivalis.P. gingivalisATCC 33277 was treated with TIF (5, 10, 20, and 40 μM), light (525 nm), or both. Reactive oxygen species (ROS) generation was assessed at pH 4.5 or 7.4. Bacterial viability and membrane integrity were evaluated by colony-forming unit (CFU) assay and LIVE/DEAD staining. CFU assays demonstrated that TIF-PDT groups achieved an approximately 4-log reduction in bacterial viability compared to the DEMI, Light, and TIF groups, with no dark cytotoxicity and light-alone effects. LIVE/DEAD staining revealed bright yellow fluorescence in the TIF-PDT (40 μM), indicating membrane damage and significantly lower survival rates than controls. TIF-PDT at 10, 20, and 40 μM produced ROS under both neutral and acidic conditions, exhibited low dark cytotoxicity, and demonstrated potent antibacterial activity againstP. gingivalisin vitro, suggesting its potential as an acid-tolerant photosensitizer for periodontitis adjunctive therapy.
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高影响因子
JOURNAL OF LUMINESCENCE
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2025
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IF 3.6
Zhiwei Xia,Lan Yao,Xin Pan,Ke Su,Rujun Yang,Yuanhao Jian,Rong-Jun Xie,Lefu Mei
The development of efficient dual-emissive and temperature-sensitive luminescent materials is critical for advancing non-contact optical thermometry. Herein, we employed a co-doping strategy to enhance energy transfer pathways in Ca 9 Ga(PO 4 ) 7 phosphors. Under 331 nm excitation, dual emissions from Eu 2+ (415 nm) and Cr 3+ (696 nm) were achieved, with Zn 2+ enhancing the near-infrared (NIR) of Cr 3+ . The optimal Cr 3+ concentration led to an approximately six-fold increase in NIR emission intensity, attributed to Eu 2+ -induced crystal field modulation and efficient dipole-dipole energy transfer, which are evidenced by comparing the emission spectra and decay curve lifetimes. Temperature-dependent emission spectra revealed that Eu 2+ emission remained stable, while Cr 3+ emission exhibited significant temperature sensitivity in Ca 9 Ga(PO 4 ) 7 :Zn 2+ ,Eu 2+ ,Cr 3+ , enabling precise temperature sensing with a peak sensitivity of 1.256 % K −1 at 298 K. This work offers a novel approach to improving energy transfer efficiency and dual-emission properties, contributing to the development of high-performance, real-time optical thermometry and photonic technologies.
研究领域:
材料科学
·
光学
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高影响因子
Molecular Catalysis
·
2023
·
IF 4.6
Jiang-Tao Xue,Zhi-Neng You,Bing-Yi Yang,Zheng-Yu Huang,Jiang Pan,Chun-Xiu Li,Jian-He Xu
7-Oxo-lithocholic acid (7-oxo-LCA) is a key precursor for the enzymatic synthesis of the therapeutic bile acid ursodeoxycholic acid (UDCA). Chenodeoxycholic acid (CDCA) can be readily converted to 7-oxo-LCA by the 7α-hydroxysteroid dehydrogenase (7α-HSDH). However, the poor substrate tolerance of the current 7α-HSDH limits their practical applications. In this study, a new and natively NAD(+)-dependent Sm 7α-HSDH from Shewanella morhuae was identified, which exhibited a better substrate tolerance compared with other 7α-HSDHs. The purified Sm 7α-HSDH showed a high oxidative activity of 281 U mg −1 protein toward CDCA, with a catalytic efficiency ( k cat /K m ) of 7.47 × 10 3 mM −1 s −1 . In a preparative biotransformation (100 mL scale), 200 mM (∼80 g L −1 ) CDCA was almost completely oxidized to 7-oxo-LCA in 1 h, with a 78% isolated yield and a space-time yield (STY) of up to 1418 g L −1 d −1 , which is so far the highest productivity for biosynthesis of 7-oxo-LCA from CDCA. These results demonstrate the great potential of Sm 7α-HSDH as a promising biocatalyst for UDCA synthesis.
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JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY
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2023
·
IF 4.3
Shijie Wei,Hongcen Zheng,Jia-Jia Zhao,Shouyun Yu,Bingdang Wu,Guoyang Zhang,Shujuan Zhang
Self-sensitized degradation is a typical fate of azo dyes in aquatic systems but its kinetics is far too slow to meet the requirement for a thorough decolorization. Small diketones were found being able to enhance the degradation of dyes under UV irradiation and the introduction of an electron-denoting group at the α -position of the simplest β -diketone (acetylacetone, AA) had a further enhancement effect on the degradation. However, it is unclear whether such enhancement effects exist in the solar-irradiated systems. To clarify this question, the effects of three AA derivatives were investigated with Acid Orange 7 (AO7) as a representative azo dye. Compared with the AA derivatives with a methyl or an ethyl group at the central carbon (AA-CH 3 and AA-CH 2 CH 3 ), 3,5-diacetylheptane-2,6-dione (AA-CH 2 -AA, which is a condensed combination of AA and AA-CH 3 ) showed a >2-fold stronger enhancement effect. The nonstoichiometric enhancement effect of AA-CH 2 -AA on AO7 photodegradation disclosed a novel pathway for dye degradation: AA-CH 2 -AA could enhance the degradation of AO7 by reacting with the photo-sensitized 1 O 2 , whereas AA led to an inhibitory effect on the self-sensitized degradation of AO7 by quenching the excited state of the azo dye. These results demonstrate that small diketones could be designed to regulate the photodegradation of azo dyes in multiple pathways.
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ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Jinyin Lv,Yanwen Cui,Jianhua Yang,Liangqing Li,Xuerong Zhou,Jinming Lu,Gaohong He
Fluorinated metal–organic framework materials (NbOFFIVE-1-Ni, also referred to as KAUST-7) have attracted widespread attention because of their high chemical stability and thermal stability, outstanding tolerance with water and H2S, and high CO2-adsorption selectivity over H2 and CH4. KAUST-7 was expected to be a new membrane material candidate for H2/CO2 separation because of the hindered permeation of CO2 resulting from the interaction between CO2 and (NbOF5)2– of the KAUST-7 framework. A highly H2 perm-selective KAUST-7 membrane was first achieved using a novel strategy of inorganic pillar center-facilitated counterdiffusion (IPCFCD) proposed by us. The IPCFCD method not only effectively avoided the corrosion of hydrofluoric acid to α-Al2O3 tubes in the process of preparing KAUST-7 membranes, but also better reduced grain boundary defects because of the faster nucleation rate and resultant high crystallinity. The KAUST-7 membrane exhibited a high H2/CO2 separation factor (SF) of 27.30 for the 1:1 H2/CO2 binary gas mixture with a high H2 permeance of 5.30 × 10–7 mol m–2 s–1 Pa–1 under ambient conditions and a slight decrease of the H2/CO2 SF with increasing operation temperature and presence of steam. This study highlighted the importance of pre-synthesizing inorganic pillar centers (NiNbOF5 intermediate) and the innovation of a membrane formation process for synthesizing polycrystalline KAUST-7 membranes. Most important of all, our study provided a novel approach to overcome the challenge in fabricating metal–organic framework membranes containing corrosive reactants for the corresponding supports.
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ACS Sustainable Chemistry & Engineering
·
2021
·
IF 8.198
Hai-Peng Li,Zhi-Neng You,Yuan-Yang Liu,Gao-Wei Zheng,Heng Gong,Yiming Mo,Ning Zhu,Yun-Peng Bai,Jian-He Xu
Water-forming NAD(P)H oxidases (NOXs) constitute a clean NAD(P)+ regeneration strategy for NAD(P)+-dependent biotransformations to produce high value-added chemicals because they only consume oxygen and generate water. However, the application of NOXs is still challenging because of limited oxygen transfer in batch reactions. Here, we report an efficient continuous-flow microreactor (CFMR) to improve the oxygen transfer and reaction performance in NAD+-dependent chenodeoxycholic acid oxidation catalyzed by 7α-hydroxysteroid dehydrogenase (7α-HSDH) for the production of 7-oxo-lithocholic acid, a key precursor of ursodeoxycholic acid. The recycling efficiency of NAD+ by NOX from Streptococcus mutans (SmNOX) was significantly improved in this CFMR. Compared with a conventional batch stirred tank reactor, the space–time yield of production of 7-oxo-lithocholic acid was increased by 96-fold. Furthermore, the total turnover number of NAD+ was improved 10-fold, and the enzyme consumption number was decreased 7-fold. Combining the NOX/O2 system with this microreactor technology provides a general platform that enables various NAD(P)+-dependent biotransformations in a green and sustainable manner, which will be helpful in the design of ecofriendly bioprocesses for production of functional chemicals on a large scale.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2021
·
IF 5.875
Wei He,Yawei Du,Tao Wang,Ji Wang,Lei Cheng,Xinsong Li
7-Ethyl-10-hydroxycamptothecin (SN38), a potent camptothecin derivative specifically targeting DNA topoisomerase I cleavage complexes, has shown great potential in the treatment of solid tumors . Because of its poor solubility and chemical and metabolic stability, the clinical application of SN38 is highly limited. To address these problems, a novel redox-responsive SN38 conjugate based liposomal formulation is developed in this report. First, SN38 was conjugated with lysophospholipid by using a cleavable disulfide bond linker. After that, the conjugate (SN38-SS-PC) was assembled into liposomes by thin film method. Dynamic light scattering (DLS) characterization indicated that SN38-SS-PC liposomes possessed a narrow size distribution (172.8 ± 10.5 nm) and negative charged zeta potential (-8.9 ± 0.3 mV). The results of storage and physiological stabilities showed that SN38-SS-PC liposomes was stable under different conditions. More importantly, a reduction responsive release of parent drug SN38 was observed in the medium containing glutathione (GSH). In addition, SN38-SS-PC liposomes had a much more rapid cellular uptake behavior against cancer cells. The enhanced anti-cancer efficacy of SN38-SS-PC liposomes was further demonstrated by in vitro cytotoxicity assay against MCF-7 and A549 cells. Under in vivo evaluation in 4 T1 xenograft tumor model, SN38-SS-PC liposomes were observed to have lower systemic toxicity and higher tumor inhibition rate of 53.3% compared with the commercialized SN38 prodrug Irinotecan (Ir). In summary, SN38-SS-PC liposomes could be a promising redox responsive delivery system of SN38 for cancer therapy.
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高影响因子
NEW JOURNAL OF CHEMISTRY
·
2020
·Vol. 44
·期 11
·4311-4318
·
IF 3.288
Weitao Xu,Xinyu Deng,Xin Xiao,Bing Bian,Qing Chen,Scott J. Dalgarno,Zhu Tao,Carl Redshaw
A benzyl substituted 4-pyrrolidinopyridinium salt (G) with multiple active sites including benzyl, pyridinium and pyrrole groups has been synthesized. The interaction between G and a series of cucurbit[n]urils (TMeQ[6], Q[7], Q[8], Q[10]), has been studied both in aqueous solution and in the solid state. The binding interaction site between G and the Q[n] can be controlled by the size of the cavity of the Q[n]s. In the case of TMeQ[6], the benzyl is accommodated within the cavity, whilst for Q[7] and Q[8], the pyrrole ring and the benzyl are accommodated within the cavity of the Q[7/8], and the latter can shuttle on the guest G in a state of dynamic equilibrium. For the larger cavity of Q[10], the entire G molecule is located within the cavity of the Q[10].
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APPLIED SURFACE SCIENCE
·
2020
·
IF 6.182
Qingdong Qin,Na Qiao,Yahong Liu,Xian Wu
The morphology and structure of heterogeneous catalysts play crucial roles in peroxymonosulfate (PMS) activation by providing much more available active sites and high chemical stability. In this work, spongelike porous CuO (SP-CuO) was synthesized and used as a PMS activator to degrade Acid Orange 7 (AO7) from aqueous solution. The morphology and property of SP-CuO were characterized using various techniques. The results showed that nanoparticles of SP-CuO with uniform in size were agglomerated together to form a porous spongelike texture. In the catalytic experiments, SP-CuO showed highly effective in heterogeneous activation of PMS compared to commercial CuO and Co 3 O 4 . The first-order rate constant of SP-CuO was approximately 3.9 and 4.4 times greater than that of commercial CuO and Co 3 O 4 , respectively. The effects of experimental parameters including PMS dose, AO7 concentration, catalyst dosage, temperature and pH were systematically investigated. The highest degradation rate was achieved at pH 7.0. The activation energy of SP-CuO was obtained as 21.6 kJ mol −1 . Sulfate radical (SO 4 − ), mainly generated through heterogeneous reaction, was the dominant reactive species for AO7 degradation. Moreover, SP-CuO remained good activity and stability after being recycled five times, demonstrating its potential environmental application in the treatment of dye wastewater.
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