MICROCHIMICA ACTA
·
2019
·Vol. 187
·期 1
·1-11
·
IF 5.479
Wang Qian-Long,Huang Wei-Xue,Zhang Pu-Juan,Chen Li,Lio Chon-Kit,Zhou Hua,Qing Lin-Sen,Luo Pei
An ultra-sensitive method is described here for the determination of HIF-1α (an early biomarker for myocardial infarction) in circulating exosomes in serum. Gold nanospheres were functionalized with a HIF-1α-binding aptamer via sulfydryl chemistry. The apt-AuNP-coated gold seeds were grown by seed-mediated growth, and this significantly increased the peroxidase-mimicking property the nanoparticles. A chromogenic system composed of 3,3′5,5′-tetramethylbenzidine and hydrogen peroxide was used. Absorbance at 652 nm increases linearly in the 0.3 to 200 ng L −1 HIF-1α concentration range, and the limit of detection is 0.2 ng L −1 . The method was tested by analyzing rat serum from isoproterenol (ISO)-induced myocardial infarction. It allows HIF-1α to be directly determined in a 25 μL sample without preconcentration. The assay is not interfered by the polydispersity of exosomes released under either health and disease conditions.
Gold nanospheres were functionalized with a HIF-1α-binding aptamer via sulfydryl chemistry. Nanosized gold seed particles were then modified with the functionalized gold nanospheres, and this strongly increases the peroxidase-mimicking activity of the nanomaterial. By using the tetramethylbenzidine/H 2 O 2 chromogenic system, the absorbance at 652 nm increases linearly in the 0.3 to 200 ng L -1 HIF-1α concentration range.
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高影响因子
Pharmaceutics
·
2024
·Vol. 16
·期 9
·1130
·
IF 4.9
Xiao Li,Zhiyin Li,Yue Su,Jia Zhou,Yuxiang Li,Qianqian Zhao,Xia Yang,Leilei Shi,Lingyue Shen
In the present work, we pioneered a coordinated self-assembly approach aimed at fabricating carrier-free hybrid nanoparticles to address the inherent challenges of the anaerobic microenvironment and the oxidative resistance induced by reductive glutathione (GSH) in photodynamic therapy (PDT). In these nanoparticles, protoporphyrin IX (PP), HIF-1α inhibitor ofN, Nʹ-(2,5-Dichlorosulfonyl) cystamine KC7F2 (KC), and the cofactor Fe3+present hydrogen bond and coordination interaction. The nanoparticles exhibited efficient cellular uptake by CAL-27 cells, facilitating their accumulation in tumors by enhanced permeability and retention (EPR) effect. Under irradiation at 650 nm, the formation of cytotoxic singlet oxygen (1O2) would be enhanced by the synergy effect on the Fenton reaction of Fe3+ion and the downregulation of the HIF-1α, leading to the improved PDT efficacy both in vitro and in vivo biological studies. Our work opens a new supramolecular approach to prepare hybrid nanoparticles for effective synergy therapy with PDT against cancer cells.
研究领域:
纳米技术
·
癌症治疗
·
生物医学工程
·
药学
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分子生物学
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PubMed
高影响因子
Molecular Medicine Reports
·
2025
·Vol. 31
·期 3
·1-12
·
IF 3.5
Xiangli Yan,Siqi Quan,Roujia Guo,Zibo Li,Ming Bai,Baoying Wang,Pan Su,Erping Xu,Yucheng Li
Calycosin‑7‑O‑β‑D‑glucoside (CG), a major active ingredient of Astragali Radix, exerts neuroprotective effects against cerebral ischemia; however, whether the effects of CG are associated with mitochondrial protection remains unclear. The present study explored the role of CG in improving mitochondrial function in a HT22 cell model of oxygen‑glucose deprivation/reperfusion (OGD/R). The Cell Counting Kit‑8 assay, flow cytometry, immunofluorescence and western blotting were performed to investigate the effects of CG on mitochondrial function. The results demonstrated that mitochondrial function was restored after treatment with CG, as indicated by reduced mitochondrial reactive oxygen species levels, increased mitochondrial membrane potential and improved mitochondrial morphology. Overactivated mitophagy was revealed to be inhibited by the regulation of proteins involved in fission [phosphorylated‑dynamin‑related protein 1 (Drp1) and Drp1] and mitophagy (LC3, p62 and translocase of outer mitochondrial membrane 20), and mitochondrial biogenesis was demonstrated to be enhanced by increased levels of sirtuin 1 (SIRT1) and peroxisome proliferator‑activated receptor γ coactivator‑1α (PGC‑1α). In addition, neuronal apoptosis was ameliorated by CG, as determined by a decreased rate of apoptosis, and levels of caspase‑3 and Bcl‑2/Bax. In conclusion, the present study demonstrated that CG may alleviate OGD/R‑induced injury by upregulating SIRT1 and PGC‑1α protein expression, and reducing excessive mitochondrial fission and overactivation of mitophagy.
研究领域:
神经科学
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细胞生物学
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药理学
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PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Pan Yongting,Mai Li,He Wenkai,Yang Xuqi,Wu Enting,Zhao Jiayuan,Liu Bailiang,Li Mingyan
Introduction: Peripheral artery disease (PAD) is an increasingly common disease, causing significant complications for patients. Trimetazidine (TMZ) not only improves clinical symptoms in PAD patients but also facilitates angiogenesis in ischemic hind limbs. Our aim was to find the function of TMZ in promoting angiogenesis and tissue perfusion in ischemic rat skeletal muscle.Methods: The rats underwent femoral artery ligation (FAL) and then treated with TMZ and saline. Hematoxylin-eosin and Masson’s trichrome stain in the ischemic gastrocnemius muscle to analyze muscle morphology and atrophy. To identify angiogenesis and the tissue perfusion, CD31 immunohistochemical staining and laser speckle contrast imaging was conducted. Additionally, hind limb motor ability was measured. Finally, qRT-PCR and Western blotting were used to statistically analyze the expression levels of HIF-1α and VEGF.Results: Our study demonstrated significant enhancement in angiogenesis and tissue perfusion after FAL when treated with TMZ compared to the saline group. Histologically, it mitigates ischemia-induced muscle atrophy and inflammation, as well as reduces fibrosis progression in the TMZ group. Additionally, hind limb motor ability improved in rats treated with TMZ during motor experiments.Discussion: It suggests that TMZ can promote angiogenesis and improve tissue perfusion in ischemic skeletal muscle of rats by activating the HIF-1α/VEGF signaling pathway. Additionally, it leads to significant improvement in ischemia-induced motor limitations in the hind limbs of rats.
研究领域:
药理学
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心血管疾病
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肌肉骨骼系统
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分子生物学
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DOI
高影响因子
Advanced Materials Interfaces
·
2023
·
IF 5.4
Weixing Wang,Yifeng Yu,Hao Zhang,Zhiwei Wang,Honglian Dai,Aixi Yu
To solve the problem of tendon adhesion after an operation, an anti-adhesion membrane is designed, which can inhibit the exogenous healing of tendons and promote endogenous healing. Here, poly[3(S)-methyl-morpholine-2,5-dione- co -lactic acid] P(MMD- co -LA) containing alanine units is obtained by melt ring-opening polymerization (ROP). It can effectively reduce the production of acidic degradation products that cause aseptic inflammation. Then a kind of oriented P(MMD- co -LA)/deferoxamine (DFO) anti-adhesion membrane with good mechanical properties, cell adhesion properties, and induced macrophage polarization properties is constructed by electrospinning. In vitro and in vivo studies have shown that oriented fibrous membranes can down-regulate the expression of inflammatory cytokines. In addition, the fibrous membrane can up-regulate the expression of angiogenesis-related genes, namely HIF1-α, SDF-1α, and VEGF, by releasing DFO in situ, thus promoting the revascularization of tendon defects and providing nutritional support for endogenous tendon healing. This method provides a new barrier strategy to reduce tendon adhesion through anti-inflammation combined with vascularization to inhibit exogenous tendon healing while promoting tendon endogenous healing. The results provide essential insights into the corresponding regulation of the tendon healing microenvironment.
研究领域:
生物医学工程
·
组织工程
·
材料科学
·
再生医学
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高影响因子
MOLECULAR AND CELLULAR BIOCHEMISTRY
·
2024
·
IF 3.5
Wang Liwei,Zhang Lu,Yun Yang,Liang Tingting,Yan Chaoqun,Mao Zhuoya,Zhang Jingfang,Liu Baoshe,Zhang Jian,Liang Taigang
Occupational and unintentional exposure of zinc oxide nanoparticles (ZnONPs) raises concerns regarding their neurotoxic potential and there is an urgent need for the development of effective agents to protect against the toxic effects of ZnONPs. Astragalus memeranaceus (AM), a famous Traditional Chinese Medicine, as well as its bioactive components, showing a potential neuroprotective function. This study aims to investigate the neuroprotective effects of bioactive components of AM against ZnONPs-induced toxicity in human neuroblastoma SH-SY5Y cells and its underlying mechanisms. The cell apoptosis, ROS generation, MMP changes, mitochondrial fission/fusion, biogenesis, and mitophagy were assessed. In this study, AM treatment inhibited ZnONPs-induced cell apoptosis and ROS overproduction in SH-SY5Y cells. And astragaloside IV (ASIV) played a dominant role in the attenuation of cytotoxicity after ZnONPs exposure, rather than flavonoids and polysaccharides. ASIV treatment significantly reduced ROS generation and MMP collapse in ZnONPs-exposed cells. Furthermore, the protein expressions of mitochondrial biogenesis (PGC-1α), fusion (Mfn1 and Mfn2), and fission (Drp1) were markedly increased. Meanwhile, the PINK1/Parkin-mediated mitophagy was activated after ASIV administration, which ameliorated ZnONPs-induced SH-SY5Y cell death. Collectively, ASIV administration mitigated ZnONPs-induced cytotoxicity in SH-SY5Y cells through restoring mitochondrial quality control process, which hinted the protective role of ASIV in ZnONPs-induced neurotoxicity. Graphical abstract
研究领域:
药理学
·
毒理学
·
神经科学
·
细胞生物学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Zhao Zhang,Si-Yuan Ma,Xin Yin,Yu-Sang Li,He-Bin Tang
Ethnopharmacological relevance The Chinese traditional medicine frankincense, which can promote blood circulation, is often used to treat skin lesions, including frostbite. Aim of the study To explore the properties of frankincense oil extract (FOE) and its active ingredients and their effect on frostbite wound recovery as an approach to understand the mechanism associated with microcirculation-improvement therapy. Materials and methods The microcirculation-improving effects of FOE and its active ingredients were evaluated using liquid nitrogen-induced frostbite animal models. The rewarming capacity of FOE on the skin was determined through infrared detection, and frostbite wound healing was evaluated following haematoxylin and eosin (H&E) staining and fibre analysis. Moreover, related factors were examined to determine the anti-apoptotic, anti-inflammatory, and microcirculatory properties of FOE and its active ingredients on affected tissue in the context of frostbite. Results FOE and its active ingredients rapidly rewarmed wound tissue after frostbite by increasing the temperature. Moreover, these treatments improved wound healing and restored skin structure through collagen and elastin fibre remodelling. In addition, they exerted anti-apoptotic effects by decreasing the number of apoptotic cells, reducing caspase-3 expression, and eliciting anti-inflammatory effects by decreasing COX-2 and β-catenin expression. They also improved microcirculatory disorders by decreasing HIF-1α expression and increasing CD31 expression. Conclusions FOE and its active components can effectively treat frostbite by enhancing microcirculation, inhibiting the infiltration of inflammatory cells, decreasing cell apoptosis, and exerting antinociceptive effects. These findings highlight FOE as a new treatment option for frostbite, providing patients with an effective therapeutic strategy.
研究领域:
药理学
·
中医
·
伤口愈合
·
微循环
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高影响因子
INTERNATIONAL JOURNAL OF ONCOLOGY
·
2018
·Vol. 53
·期 3
·1055-1068
·
IF 3.333
Yunjie Xu,Weinan Gao,Yong Zhang,Shanshan Wu,Yanan Liu,Xinyue Deng,Lili Xie,Jiayan Yang,Huimei Yu,Jing Su,Liankun Sun
The poor prognosis and high mortality of patients with ovarian cancer result in part from their poor response to platinum-based chemotherapy. However, the precise mechanism behind cisplatin resistance is still not fully understood. In the present study, the authors explored the mechanism of resistance to cisplatin from the perspective of glucose metabolism in human ovarian cancer. The experiments using genetically matched ovarian cancer cell lines SKOV3 (cisplatin-sensitive) and SKOV3/DDP (cisplatin-resistant) in the present study provided some important findings. First, in comparison to SKOV3 cells, SKOV3/DDP cells exhibited decreased dependence on aerobic glycolysis and an increased demand for glucose. Secondly, the stable overexpression of Bcl‑2 and ability to shift metabolism towards oxidative phosphorylation (OXPHOS) in SKOV3/DDP cells were associated with increased oxygen consumption. Furthermore, the metabolic characteristic of elevated OXPHOS primarily comprised most mitochondrial‑derived reactive oxygen species (ROS) and, at least in part, contributed to the slight pro-oxidant state of SKOV3/DDP cells in turn. Thirdly, SKOV3/DDP cells reset the redox balance by overexpressing the key enzyme glucose 6-phosphate dehydrogenase (G6PD) of the pentose phosphate pathway to eliminate the cytotoxicity of highly elevated ROS. Furthermore, the inhibition of Bcl‑2 reduced the OXPHOS and sensitivity of SKOV3/DDP cells to cisplatin in a selective manner. Furthermore, when combined with 2-deoxyglucose (2-DG), the anticancer effect of the Bcl‑2 inhibitor ABT737 was greatly potentiated and hypoxia-inducible factor 1α (HIF‑1α) appeared to be closely associated with Bcl‑2 family members in the regulation of glucose metabolism. These results suggested that the special glucose metabolism in SKOV3/DDP cells might be selectively targeted by disrupting Bcl‑2-dependent OXPHOS.
研究领域:
肿瘤学
·
药理学
·
细胞代谢
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PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2017
·
IF 7.786
Wei Li,Xiaomeng Guo,Fenfen Kong,Hanbo Zhang,Lihua Luo,Qingpo Li,Chunqi Zhu,Jie Yang,Yongzhong Du,Jian You
Photodynamic therapy (PDT) and photothermal therapy (PTT) have captured much attention due to the great potential to cure malignant tumor. Nevertheless, photodynamic resistance of cancer cells has limited the further efficacy of PDT. Unfortunately, the resistance mechanism and efforts to overcome the resistance still have been rarely reported so far. Here, we report a nanosystem with specific tumor targeting for combined PDT and PTT mediated by near-infrared (NIR) light, which was established by covalently conjugating indocyanine green (ICG) and TNYL peptide onto the surface of hollow gold nanospheres (HAuNS). Our nanosystem (TNYL-ICG-HAuNS) was proved to possess significantly increased light stability, reactive oxygen species (ROS) production and photothermal effect under NIR light irradiation, thus presenting a remarkably enhanced antitumor efficacy. The up-regulation of nuclear factor erythroid 2-related factor 2 (NFE2L2, Nrf2) in cancer cells during PDT induced a significant increase of ABCG2 , NQO-1 and HIF-1α expression, causing PDT resistance of the cells. Interestingly, ABCG2 expression could almost keep a normal level in the whole PDT process mediated by TNYL-ICG-HAuNS. After repeated irradiations, TNYL-ICG-HAuNS could still produce almost constant ROS in cells while the Nrf2 expression reduced significantly. Furthermore, PDT resistance induced an obvious decrease of the internalization of free ICG, but didn't influence the cell uptake of TNYL-ICG-HAuNS. Our data explained that TNYL-ICG-HAuNS could overcome the photodynamic resistance of cancer cells, acting as a promising modality for simultaneous photothermal and photodynamic cancer therapy.
研究领域:
癌症治疗
·
纳米技术
·
生物医学工程
·
分子生物学
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高影响因子
RSC Advances
·
2018
·Vol. 8
·期 65
·37117-37128
·
IF 2.936
Guixin Wu,Min Wen,Lin Sun,Huitao Li,Yubei Liu,Rui Li,Feihua Wu,Rong Yang,Yining Lin
Geniposide (GE) is a major component isolated from Gardenia jasminoides Ellis, which has been used to treat cholestasis liver diseases. Our previous study has shown that GE could notably increase mRNA and protein expressions of BSEP in cholestatic rats. BSEP plays a critical role in maintenance of the enterohepatic circulation of bile acids. BSEP could be regulated by the transactivation pathway of farnesoid X receptor (FXR) and nuclear factor erythroid 2-related factor (Nrf2). Here the mechanisms for BSEP regulation by GE were investigated. GE induced the mRNA levels of BSEP in HepG2 cells and cholestatic mice, and knockdown of FXR and Nrf2 reduced the mRNA expression of BSEP at varying degrees after treatment of GE. FXR acts as the major regulator of BSEP transcription. The involvement of FXR regulated BSEP expression by GE was further investigated. An enhancement was observed in FXR-dependent BSEP promoter activation using luciferase assay. ChIP assay further confirmed the interaction between FXR and BSEP after GE treatment. Using siRNA and ChIP assays, we demonstrated that peroxisome-proliferator-activated receptor γ co-activator-1α (PGC-1α) and co-activator-associated arginine methyltransferase 1 (CARM1) were predominantly recruited to the BSEP promoter upon FXR activation by GE. In conclusion, GE regulated the expression of BSEP through FXR and Nrf2 signaling pathway. The FXR transactivation pathway was enhanced by increasing recruitment of coactivators PGC-1α and CARM1 upon GE treatment, coupled with an increased binding of FXR to the BSEP promoter.
研究领域:
药理学
·
分子生物学
·
肝病学
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高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Xin Xiao,Ailian Zhu,Gang He,Seiichi Tokula,YiTing Yang,Yang Qing,Yali Liu,HanWen Hu,Qin Song
A miscellaneous polysaccharide, PAP55–3-1, with a molecular weight of 23.03 kDa, was isolated from Periplaneta americana through extraction with dilute alkali solution, ethanol precipitation, and column chromatography purification. Structural analysis shows that PAP55–3-1 is mainly composed of five monosaccharides: galactosamine hydrochloride, glucosamine hydrochloride, galactose, glucose and mannose. Its main glycosidic bonds are: Manp-(1→, Galp-(1→, →3)-Galp-(1→, →3,6)-Manp-(1→, →2,6)-Manp-(1→, →6)-Manp-(1→, →4)-Galp-(1→, →6-Glcp-(1→, →6)-Galp-(1→, →2)-Manp-(1 →, →3,4)-Glcp-(1→, →3,6)-Galp-(1→. In vitro experiments demonstrated that PAP55–3-1 can effectively inhibit reactive oxygen species (ROS) and O 2 − production following H 2 O 2− induction. After H 2 O 2− induction, HIF-1α (hypoxia-inducible factor) was translocated in mitochondria PAP55–3-1 increased localization of HIF-1α was located on mitochondria to maintain the stability of mitochondrial function stability, thereby effectively inhibiting H 2 O 2 -induced mitochondrial oxidative damage. Additionally, PAP55–3-1 inhibited the M1 polarization of macrophages stimulated by H 2 O 2 and promoted the phenotype polarization of macrophages from M1 to M2, displaying anti-inflammatory and pro-repair properties. In vivo experimental results indicated that PAP55–3-1 promoted wound healing in mice. Immunohistochemical experiments revealed a reduction in CD68 expression and increase in CD206 expression in both positive and the high-dose polysaccharide group control group. This further demonstrated that PAP55–3-1 promotes the phenotype polarization of macrophages from M1 to M2, exerting anti-inflammatory and wound-healing activities.
研究领域:
免疫学
·
药理学
·
生物化学
·
细胞生物学
·
伤口愈合
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PubMed
高影响因子
CELLULAR SIGNALLING
·
2016
·
IF 4.191
Wenjun Zhao,Aiyun Li,Xin Feng,Ting Hou,Kang Liu,Baolin Liu,Ning Zhang
This study aims to investigate the effects of metformin and resveratrol on muscle insulin resistance with emphasis on the regulation of lipolysis in hypoxic adipose tissue. ICR mice were fed with high fat diet (HFD) for 10 days with administration of metformin, resveratrol, or intraperitoneal injection of digoxin . Adipose hypoxia, inflammation and cAMP/PKA-dependent lipolysis were investigated. Moreover, lipid deposition and insulin resistance were examined in the muscle. Metformin and resveratrol attenuated adipose hypoxia, inhibited HIF-1α expression and inflammation in the adipose tissue of HFD-fed mice. Metformin and resveratrol inhibited lipolysis through prevention of PKA/HSL activation by decreasing the accumulation of cAMP via preserving PDE3B . Metformin and resveratrol reduced FFAs influx and DAG accumulation, and thus improved insulin signaling in the muscle by inhibiting PKCθ translocation. This study presents a new view of regulating lipid metabolism to ameliorate insulin resistance and provides the clinical guiding significance for obesity and type 2 diabetes with metformin and resveratrol treatment.
研究领域:
药理学
·
内分泌学
·
代谢学
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PubMed
高影响因子
危险品化学品经营许可证（带存储）