ACS Applied Bio Materials
·
2026
·
IF 5.6
Wenjing Zhang,Xiaoyang Chen,Ziyi Lin,Shangyang Pan,Zufa sabeel,Wenxin Li,Heyun Shen,Zhao Yang
Breast cancer (BC) remains the most prevalent and deadly malignancy among women worldwide. While photothermal therapy (PTT) and chemodynamic therapy (CDT) offer tumor-specific and minimally invasive advantages, their standalone efficacy is limited. Ligustilide (LIG) can exert antitumor effects by generating •O2–, but its bioavailability is poor, thus necessitating improved delivery strategies. Here, we reported a multifunctional nanoplatform (FeD@LIG) integrating PTT, CDT, and chemotherapy for the simultaneous elimination of breast cancer stem cells (BCSCs) and non-BCSCs. FeD@LIG was synthesized via one-step oxidative polymerization of dopamine, co-loading Fe3+ and LIG. The nanospheres exhibited excellent photothermal conversion efficiency (52.8%) and pH/GSH-responsive drug release. Upon near-infrared (NIR) irradiation, FeD@LIG triggered ROS generation via Fenton-like reactions and elevated local temperature, leading to enhanced oxidative stress, apoptosis, and LIG release. In vitro, FeD@LIG reduced cell viabilities of MCF-7 and MDA-MB-231 cells to 12.5 and 7.9%, respectively, and significantly inhibited BCSCs’ self-renewal. In vivo, FeD@LIG achieved a tumor inhibition rate of 92.8% with minimal toxicity. Mechanistic studies revealed activation of the BAX/BCL-2/Caspase-3 pathway and suppression of Hedgehog signaling. Overall, FeD@LIG represents a promising nanotherapeutic strategy for overcoming drug resistance and recurrence by inhibiting both BCSCs and non-BCSCs through multimodal synergistic therapy.
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高影响因子
ANTIVIRAL RESEARCH
·
2026
·
IF 4.3
Pu Wang,Xinchang Liu,Yong Xie,Yingjun Zhang,Baohua Gu,Jing Li,Yunfu Chen
CAM-A (GLS4) rapidly suppresses HBV DNA with delayed HBsAg decline and ALT flares. • CAM-A upregulates ISGs and activates IFN-α/γ pathways in HBV models. • CAM-A induces TUNEL + caspase-3-independent death of HBcAg + hepatocytes. • CAM-A effects persist without adaptive immunity; synergize with innate immunemodulators such as TLR7 agonist. Capsid assembly modulators (CAMs) are promising antiviral agents for chronic hepatitis B virus (HBV) infection. This study investigates the anti-HBV activity and immunomodulatory effects of Class I CAMs (CAM-A) in vitro and in vivo . In HepAD38 cells, CAM-A treatment significantly upregulated the expression of interferon-stimulated genes (IP-10, MX1, OAS1). In AAV-HBV mice, CAM-A (GLS4) induced rapid reductions in HBV DNA and delayed HBsAg decline accompanied by transient ALT elevation, upregulated interferons and Tnfsf10/Tnfrsf10b gene expression, while terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and immunohistochemistry (IHC) experiments indicated caspase-3-independent cell death in HBV-infected hepatocytes. Importantly, the antiviral and HBsAg-lowering effects of CAM-A did not require adaptive immunity. Furthermore, combination of CAM-A with a TLR7 agonist in AAV-HBV mice, or with Peg-IFN-α in primary human hepatocytes (PHH) resulted in synergistic antiviral effects, underscoring the therapeutic potential of these agents to promote sustained HBsAg decline and support functional cure strategies in chronic HBV infection.
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高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2021
·
IF 6.53
Wei-ni Qin,Kai-cheng Zhang,Ting Geng,Fang-fang Cheng,Pei-dong Chen,Wei-feng Yao,Li Zhang,Yu-dan Cao
Euphorbiae pekinensis Radix (EP) is effective in treating various diseases, but it’s toxicity is a major obstacle in use in clinical. Although EP was processed with vinegar to reduce it’s toxicity, the detailed mechanism of toxicity in EP have not been clearly delineated. This study investigate the toxicity attenuation-mechanism of Euphorbiae pekinensis after being processed with vinegar (VEP) and the toxic mechanism of four compounds from EP on zebrafish embryos. The contents of four compounds decreased obviously in VEP. Correspondingly, slower development on embryos can be seen as some symptoms like reduction of heart rate, liver area and gastrointestinal peristalsis after exposed to the compounds. Some obvious pathological signals such as pericardial edema and yolk sac edema were observed. Furthermore, the compounds could increase the contents of MDA and GSH-PX and induce oxidative damage by inhibiting the activity of SOD. Also, four compounds could provoke apoptosis by up-regulating the expression level of p53, MDM2, Bax, Bcl-2 and activating the activity of caspase-3, caspase-9. In conclusion, the four compounds play an important role in the toxicity attenuation effects of VEP, which may be related to the apoptosis induction and oxidative damage. This would contribute to the clinical application and further toxicity-reduction mechanism research.
研究领域:
药理学
·
毒理学
·
发育生物学
·
生物化学
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高影响因子
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
·
2020
·Vol. 47
·期 6
·1083-1091
·
IF 2.456
Zhu Wang,Qianqian Wang,Tao He,Wen Li,Yan Liu,Yuan Fan,Yanping Wang,Qi Wang,Jie Chen
Carboplatin (CBP) is a widely used targeted anticancer therapeutic drug; however, multi-drug resistance induced by the accumulation of CBP eventually causes diseases progression. The anti-malarial drug artesunate (ART) also exerts anticancer effects in various cancers; however, the combined effect of ART and CBP on non-small cell lung cancer (NSCLC) remains unclear. In the present study, the NSCLC cell line A549 was pretreated with various concentrations of CBP, ART and gemcitabine (GEM). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were conducted to detect cell viability. Cell apoptosis was evaluated by both flow cytometry and TUNEL apoptotic assay. The expression profiles of cell cycle-related proteins and apoptotic proteins were determined by western blot. Cell clone numbers were visualized using crystal violet staining. Here, we found that both CBP and ART suppressed cell viability, and promoted cell apoptosis, and the combined application of ART and CBP at a lower concentration exhibited synergistic effects. Specifically, the combination of ART and CBP at a lower concentration suppressed cell clone numbers, promoted cell cycle arrest at the G 2 /M phase, and induced the expression of the cell cycle and apoptosis-related proteins BAX, p21, p53, and Caspase-3, while decreasing Bcl-2 and Cyclin B1 expression. Based on these results, we concluded that combined application of ART and CBP exerts synergistic anti-tumour effects on NSCLC by enhancing cell apoptosis in a mitochondria-dependent manner.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
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高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2022
·
IF 5.999
Fang Pan,Yueping Li,Yujie Ding,Songwei Lv,Rongrong You,Roja Hadianamrei,Mhd Anas Tomeh,Xiubo Zhao
Anticancer peptides (ACPs) have attracted increasing attention in cancer therapy due to their unique mechanism of action on cancer cells. The main challenge is to establish the correlation between their physicochemical properties and their selectivity and anticancer effect, leading to a clear design strategy. In this study, a series of new α-helical short peptides (coded At1-At12) with different anticancer activities were systematically designed with different amphiphilicity based on a natural α-helical antimicrobial peptide (AMP) derived from ant. Three of the designed peptides, At7, At10 and At11, showed considerable anticancer activity with low toxicity to normal skin fibroblasts. The high selectivity of the peptides is attributed to their balanced amphiphilicity and cationic nature which favours binding to the outer membrane of negatively charged cancer cells over the neutral membrane of normal mammalian cells . In addition to rapid membrane penetration, the designed peptides also damaged the mitochondria and induced mitochondrial membrane depolarization. Moreover, these peptides were found to induce apoptosis in cancer cells by up-regulating the expression of apoptotic proteins Bax and Caspase-3, down-regulating the apoptotic protein Bcl-2, and activating the Caspase enzyme-linked reaction. The results of this study reveal the potential of these peptides for clinical applications, and provide a guidance for further development of highly selective anticancer medications.
研究领域:
肿瘤学
·
药学
·
分子生物学
·
细胞生物学
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高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2015
·
IF 2.014
Baoyan Zhang,Zhiping Xu,Yixi Zhang,Xusheng Shao,Xiaoyong Xu,Jiaogao Cheng,Zhong Li
Fipronil is the first phenylpyrazole insecticide widely used in controlling pests, including pyrethroid, organophosphate and carbamate insecticides. It is generally accepted that fipronil elicits neurotoxicity via interactions with GABA and glutamate receptors, although alternative mechanisms have recently been proposed. This study evaluates the genotoxicity of fipronil and its likely mode of action in Drosophila S2 cells, as an in vitro model. Fipronil administrated the concentration- and time-dependent S2 cell proliferation. Intracellular biochemical assays showed that fipronil-induced S2 cell apoptosis coincided with a decrease in the mitochondrial membrane potential and an increase reactive oxygen species generation, a significant decrease of Bcl-2 and DIAP1, and a marked augmentation of Cyt c and caspase-3. Because caspase-3 is the major executioner caspase downstream of caspase-9 in Drosophila , enzyme activity assays were used to determine the activities of caspase-3 and caspase-9. Our results indicated that fipronil effectively induced apoptosis in Drosophila S2 cells through caspase-dependent mitochondrial pathways.
研究领域:
毒理学
·
细胞生物学
·
昆虫学
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高影响因子
BIOLOGICAL TRACE ELEMENT RESEARCH
·
2017
·Vol. 181
·期 1
·62-70
·
IF 2.399
Zhang Hui,Chang Zhenyu,Mehmood Khalid,Abbas Rao Zahid,Nabi Fazul,Rehman Mujeeb Ur,Wu Xiaoxing,Tian Xinxin,Yuan Xiaodan,Li Zhaoyang,Zhou Donghai
Nano-sized copper particles are widely used in various chemical, physical, and biological fields. However, earlier studies have shown that nano copper particles (40–100 μg/mL) can induce cell toxicity and apoptosis. Therefore, this study was conducted to investigate the role of nano copper in mitochondrion-mediated apoptosis in PK-15 cells. The cells were treated with different doses of nano copper (20, 40, 60, and 80 μg/mL) to determine the effects of apoptosis using acridine orange/ethidium bromide (AO/EB) fluorescence staining and a flow cytometry assay. The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in the PK-15 cells were examined using commercially available kits. Moreover, the mRNA levels of the Bax, Bid, Caspase-3, and CYCS genes were assessed by real-time PCR. The results revealed that nano copper exposure induced apoptosis and changed the mitochondrial membrane potential. In addition, nano copper significantly altered the levels of the Bax, Bid, Caspase-3, and CYCS genes at a concentration of 40 μg/mL. To summarize, nano copper significantly ( P < 0.05) decreased the level of SOD and increased the level of MDA in PK-15 cells. Altogether, these results suggest that nano copper can play an important role in inducing the apoptotic pathway in PK-15 cells, which may be the mechanism by which nano copper induces nephrotoxicity.
研究领域:
细胞生物学
·
毒理学
·
分子生物学
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高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2022
·
IF 8.025
Fengshu Li,Xin Hu,Liying Qin,Haoshuai Li,Yan Yang,Xiuli Zhang,Jinren Lu,Yiming Li,Mutai Bao
Although exopolysaccharide (EPS) has been applied to various fields, EPS for UVR-mediated oxidative stress repair still needs further exploration. In this study, a novel EPS was isolated from the fermentation medium of Bacillus sp. QDR3-1 and its yield was 4.8 g/L (pH 8.0, 12 % glucose, 30 °C and 6 % NaCl). The pure fraction (named EPS-M1) was purified by DEAE-cellulose and Sephadex G-100 column. EPS-M1 was a heteropolysaccharide composed of Man, Glc, Gal, and Fuc with a molecular weight of 33.8 kDa. Scanning electron microscopy (SEM) observed a rough surface and reticular structure of EPS-M1, and EPS-M1 formed spherical aggregates in aqueous solution observed in atomic force microscopy (AFM). Thermal analysis revealed that the degradation temperature of EPS-M1 was 306 °C. Moreover, methylation and NMR analysis determined that EPS-M1 was consisted of →3)-Man p -(1→, →2,6)-Man p -(1→, →4,6)-Glc p -(1→, →3)-Glc p -(1→, →4)-Gal p -(1→, →4)-Fuc p -(1→, and T-Man p -(1→. Furthermore, the cytotoxicity and the repair ability of UVR-mediated cell damage of EPS-M1 were studied with L929 cells. The results showed that EPS-M1 had good biocompatibility and it could mitigate UVR-mediated cell damage by regulating the levels of cellular reactive oxygen species (ROS), depolarization of mitochondrial membrane potential (MMP) and Caspase-3/7 activity. Overall, the structure analysis and the protective effects of EPS against L929 cells exposed to UVR provided an experimental basis for EPS in practical applications.
研究领域:
微生物学
·
生物化学
·
药学
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SENSORS AND ACTUATORS B-CHEMICAL
·
2019
·
IF 6.393
Dehua Deng,Yuanqiang Hao,Suling Yang,Qiuyang Han,Lin Liu,Yanrong Xiang,Fanbin Tu,Ning Xia
Caspase-3 is believed to be important for diagnosis and prognosis of apoptosis-relative diseases, serving as a reliable molecular biomarker and therapeutic target. In this work, we reported a simple and sensitive electrochemical method for evaluation of cell apoptosis by determining the activity of caspase-3. Specifically, a peptide substrate specific to caspase-3 was attached on the graphene electrode surface through the hydrophobic and π-stacking interactions. Cleavage of the peptide substrate by caspase-3 resulted in the exposure of an amino terminal Cu(II) and Ni(II)-binding (ATCUN) motif on the electrode surface. The ATCUN peptide fragment can interact with Cu(II) to produce an ATCUN-Cu(II) complex which exhibits good electrocatalytic property toward water oxidation. The catalytic current increased linearly with caspase-3 concentration ranging from 0.5 pg/mL to 2 ng/mL. The method showed a detection limit of 0.2 pg/mL for caspase-3 detection. Finally, the sensor electrode was used to evaluate cell apoptosis induced by four drugs (staurosporine, vitamin C, doxorubicin and cisplatin). This work should be valuable for diagnosis and prognosis of apoptosis-relative diseases and designing of novel protease biosensors.
研究领域:
生物化学
·
分析化学
·
分子生物学
·
电化学
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高影响因子
ANALYTICAL CHEMISTRY
·
2025
·
IF 6.7
Hong Wang,Tong Zhu,Wanying Li,Zhangjun Hu,Xin Yang,Qiong Zhang,Peng Huang,Jiwen Hu,Zhihui Feng
As a key signaling molecule, sulfur dioxide (SO2) plays a crucial role in maintaining physiological homeostasis. In this work, we designed a mitochondria-targeted fluorescent probe (MIC) for independently detect SO2 (short-wavelength) and DNA (long-wavelength) in real time. It is worth noting that our research reveals a dual role of that SO2 in regulating oxidative stress. At appropriate levels, it acts as a modulator, whereas excessive amounts induce apoptosis by reducing mitochondrial membrane potential, upregulating p53/Bax, downregulating Bcl-2, and activating the caspase-3 cascade. The apoptotic process induces mitochondrial membrane permeability changes, triggering the release and nuclear translocation of the probe MIC, which subsequently emits red fluorescence. Using time-resolved fluorescence imaging technology, we further observed a significant increase in the average fluorescence lifetime of the DNA channel. This finding demonstrates that the MIC probe not only enables dual-channel monitoring of mitochondrial SO2 and nuclear DNA but also precisely evaluates the apoptotic process through changes in fluorescence lifetime. This innovative tool provides an important means for in-depth study of the SO2-mediated apoptotic mechanism and opens up new strategies for the diagnosis of mitochondrial-related diseases.
研究领域:
生物化学
·
细胞生物学
·
分子生物学
·
生物物理学
·
医学诊断
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高影响因子
PROTEIN JOURNAL
·
2021
·Vol. 40
·期 5
·709-720
·
IF 2.371
Jiang Xuan,Zhang Xin,Fu Chao,Zhao Ruili,Jin Tianming,Liu Mengyue,Pan Chenhao,Li Liu An,Ma Jifei,Yu Enyuan,YU Xiaoxue,Hu Ye
Malignant melanoma, an increasingly common form of skin cancer, poses a significant threat to public health, especially when the disease progresses past skin lesions to the stage of advanced metastasis. In this work, a new anti-tumor peptide, temporin La (T-La), was selected from a cDNA library generated from bullfrog skin. Two new derivative antitumor peptides, T-La (S) and T-La (FS), were designed by bioinformatics analysis and coupled with the RGD small molecule peptide to create chimeric RGD peptides, (RGD-T-La [S] and RGD-T-La [FS]). Preliminary experiments showed that the new antitumor peptides had significant antitumor effects. After coupling to the chimeric RGD peptide, the targeted treatment of mouse melanoma was significantly improved. Our data demonstrate that the 4 peptides tested herein significantly inhibited the proliferation, migration, and invasion of B16F10 cells; with an increase in polypeptide concentration, the proportion of melanoma cells in the G0/G1 phase decreased or increased significantly, respectively, the reactive oxygen species (ROS) content increased significantly, the mitochondrial membrane potential decreased significantly, and the expression of pro-apoptotic Bax, Caspase-3, and Caspase-9 increased, and anti-apoptotic Bcl-2 decreased significantly. Tyr and MITF genes were significantly downregulated. In conclusion, the use of these new anti-tumor peptides, when combined with a chimeric RGD peptide, may increase ROS levels and decrease mitochondrial membrane potential by inhibiting the activity of mitochondria, thus releasing apoptosis-promoting factors in B16F10 cells. The present study describes a new potential strategy for the application of promising peptides in the treatment of various cancers.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
细胞生物学
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高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2021
·Vol. 47
·期 5
·1-11
·
IF 4.101
Yunsheng Liu,Xiangping Xu,Han Tang,Yuchen Pan,Bing Hu,Guodong Huang
There is a growing evidence that Fyn kinase is upregulated in glioblastoma multiforme (GBM), where it plays a key role in tumor proliferation and invasion. In the present study, the antitumor effects of rosmarinic acid (RA), a Fyn inhibitor, were explored in human‑derived U251 and U343 glioma cell lines. These cells were treated with various concentrations of RA to determine its effects on proliferation, migration, invasion, apoptosis, and gene and protein expression levels. The CCK‑8 assay revealed that RA significantly suppressed cell viability of U251 and U343 cells. Furthermore, RA significantly reduced proliferation rates, inhibited migration and invasion, and decreased the expression levels of invasion‑related factors, such as matrix metalloproteinase (MMP)‑2 and MMP‑9. TUNEL staining revealed that RA resulted in a dose‑dependent increase of U251 and U343 cell apoptosis. In line with this finding, the expression of apoptosis suppressor protein Bcl‑2 was downregulated and that of the pro‑apoptotic proteins Bax and cleaved caspase‑3 was increased. In addition, it was revealed that the phosphatidylinositol 3‑kinase (PI3K)/Akt/nuclear factor‑κB (NF‑κB) signaling pathway was involved in RA‑induced cytotoxicity in U251 and U343 cells. Collectively, the present study suggested RA as a drug candidate for the treatment of GBM.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
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高影响因子
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