ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
·
2024
·Vol. 31
·期 13
·19396-19408
·
IF 0
Pan Enzhuang,Xin Yue,Li Xueqing,Ping Kaixin,Li Xing,Sun Ying,Xu Xuhui,Dong Jingquan
As a broad-spectrum and efficient triazole fungicide, difenoconazole is widely used, which not only pollutes the environment but also exerts toxic effects on non-target organisms. The spleen plays an important role in immune protection as an important secondary lymphoid organ in carp. In this study, we assessed the protective impact of silybin as a dietary additive on spleen tissues of carp during exposure to difenoconazole. Sixty carp were separated into four groups for this investigation including control group, difenoconazole group, silybin group, and silybin and difenoconazole group. By hematoxylin-eosin staining, dihydroethidium staining, immunohistochemical staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay, quantitative real-time PCR assay, Western blot analysis, biochemical assays, and immune function indicator assays, we found that silybin could prevent difenoconazole-induced spleen tissue damage, oxidative stress, and immune dysfunction, and inhibited apoptosis of carp spleen tissue cells by suppressing the formation of p53-driven caspase-9-apoptotic protease activating factor-1-cytochrome C complex. The results suggested that silybin as a dietary additive could improve spleen tissue damage and immune dysfunction induced by difenoconazole in aquaculture carp.
研究领域:
环境毒理学
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免疫学
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水产养殖学
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DOI
Journal of Ocean University of China
·
2026
·Vol. 25
·期 2
·586-598
·
IF 1.6
Zeng Chu,Lyu Likang,Liu Mengqun,Yang Xiaodong,Zhao Hongkui,Wen Haishen,Li Jifang,Qi Xin
Caspase-9, the most intensively studied caspase, plays a crucial role in mitochondrial or intrinsic apoptosis of mammals as a protease. To explore the role of caspase-9 in fish, we cloned casp9 gene from rainbow trout ( Oncorhynchus mykiss ) and studied its characteristic and functions. Our in vivo experiments revealed that casp9 expression was significantly upregulated 24 h after bacterial challenge in the gills, accompanied by notable histopathological changes and apoptosis signals. Gene cloning identified that rainbow trout caspase-9 is a 455 amino acid protein encoded by a 1368 bp gene, characterized by a conserved CARD domain, as well as prominent large (P20) and small (P10) subunits. Functional assays of recombinant rainbow trout caspase-9 (rcaspase-9) showed dose-dependent proteolytic activity, with significantly higher activity at 2 mg/mL than at 0.2 mg/mL. Conversely, the CARD domain-deleted version exhibited minimal activity even at 2 mg/mL, demonstrating that the CARD domain is indispensable for homodimerization and self-activation. Additionally, RT-qPCR results indicated that casp9 was mainly expressed in gills and spleen. In vitro studies demonstrated significant upregulation of casp9, apaf-1 and cyt c , along with downregulation of bcl-2 in primary gill cells in response to LPS, peptidoglycan and poly I:C stimulation. Furthermore, rcaspase-9 induced upregulation of casp6 and casp7 in these cells. These findings underscore the importance of caspase-9 in immune defense and apoptosis triggered by pathogens in rainbow trout.
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产品关联
DOI
高影响因子
TROPICAL JOURNAL OF PHARMACEUTICAL RESEARCH
·
2021
·Vol. 18
·期 12
·2531-2538
·
IF 0.533
Jun Tang,Jingfang Yang
Purpose: To investigate the potential role of curcumin in osteosarcoma (OS) cell migration and invasion, and also to explore the underlying mechanism of action.
Methods: OS cell lines, Saos-2 and U2OS, were treated with various concentrations of curcumin (0, 10, 20, 50 μM) for 48 h. Transwell assay was used to determine the migratory and invasive activities of human OS cells while miR-33b-5p expression levels were measured using quantitative real time polymerase chain reaction (qRT-PCR). Expressions of metastasis-related genes, such as matrix metalloproteinases (MMPs), were quantified by qRT-PCR or western blot. The interaction between miR33b-5p and Sirtuin 6 (SIRT6) was evaluated by luciferase assay.
Results: Curcumin inhibited the migratory and invasive activities of huamn OS cells, and downregulated MMP2 and MMP9 (p < 0.05). Moreover, in curcumin-treated OS cells, miR-33b-5p expression was upregulated while SIRT6 expression was significantly downregulated (p < 0.05). Overexpression of miR-33b-5p downregulated SIRT6 mRNA and protein expression, whereas transfection with miR-33b-5p inhibitor upregulated SIRT6 expression in OS cells (p < 0.05). Furthermore, curcumin suppressed SIRT6 expression by upregulating miR-33b-5p expression in OS cells. Finally, overexpression of SIRT6 or miR-33b-5p inhibitor reversed the suppression of OS cell metastasis induced by curcumin (p < 0.05).
Conclusion: Curcumin inhibits SIRT6 expression via upregulating miR-33b-5p expression, which leads to the inhibition of OS cell migration and invasion. Thus, curcumin is a potential therapeutic agent for the management of OS.
研究领域:
肿瘤学
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分子生物学
·
药理学
✓ 已验证
DOI
高影响因子
NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL
·
2021
·
IF 2.9
Yonglu Li,Yaxuan Wang,Xin Yu,Ting Yu,Xiaodong Zheng,Qiang Chu
Lung cancer with high mortality is regarded as a challenging global problem with unsatisfied curative effects. Clinically, the chemotherapy drugs are often faced with side-effects and tumor resistance. Radix Tetrastigma (RT) is a traditional Chinese herb and now regarded as a kind of functional food. In this study, A549-bearing nude mice control was adopted to evaluate the anti-tumor capacity of RT. Results demonstrated that RT showed excellent anti-tumor ability with no side-effect on mice compared to chemotherapy drug (5-Fu).Further studies proved that RT down-regulated the proliferation-related proteins (PCNA, Ki67) and vascular endothelial growth factor (VEGF). Additionally, RT up-regulated the ratio of Bax/Bcl-2, which caused the over-expression of Caspase-9, leading to the activation of downstream protein caspase-3, eventually resulting in apoptosis of A549 in solid tumor. These results together suggest that RT inhibits the non-small cell lung cancer (NSCLC) via Bax/Bcl2/Caspase-9/Caspase-3 pathway. Furthermore, the anti-A549 abilities of the main flavonoid components from RT were compared, and kaempferol-3-O-rutinoside would play a role in RT’s outstanding anti-NSCLC ability.
研究领域:
肿瘤学
·
药理学
·
中药学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2019
·
IF 9.518
Lin Liu,Hua Zhang,Zhenxin Wang,Daqian Song
In the present work, peptide-functionalized upconversion@silica nanoparticle (termed as UCNP@SiO 2 @Cy5-pep)-based fluorescence resonance energy transfer (FRET) sensing platform has been fabricated for the detection of caspase-9 activity in vitro and in vivo. A Cy5 labeled peptide containing specific motif LEHD for caspase-9 cleavage was designed and conjugated with UCNP@SiO 2 through covalent attachment . The red upconversion luminescence (UCL) emission of UCNP@SiO 2 can be quenched by Cy5 while the green UCL emission of UCNP@SiO 2 remains undisturbed. After the cleavage of LEHD by caspase-9, the Cy5 departed from UCNP@SiO 2 surface, resulting in recovery of red UCL emission of UCNP@SiO 2 . The UCNP@SiO 2 @Cy5-pep has been successfully used to monitoring the changes of caspase-9 activity levels in apoptotic cancerous cells (MG-63 and SW480) by cisplatin-induction. Under same experimental conditions, it is found that the intracellular caspase-9 activity level of cisplatin-treated MG-63 cells is higher than that of cisplatin-treated SW480. This result is consistent with that of commercial caspase-9 activity kits. The UCL signal intensity ratio of red emission to green emission of UCNP (termed as R/G) is linearly dependent on the amount of MG-63 cells within the range of 5 × 10 3 to 1 × 10 6 cells (i.e., 0.5–100 U mL −1 caspase-9) with a limit of detection (LOD) of 675 cells (i.e., 0.068 U mL −1 caspase-9). Furthermore, the practicability of UCNP@SiO 2 @Cy5-pep is demonstrated by detection of caspase-9 activities in tumor tissues in vivo, and satisfactory results are obtained.
研究领域:
生物化学
·
纳米医学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Huang Ruxue,Ding Lulu,Ye Ying,Wang Ke,Yu Wenjing,Yan Bingzhao,Liu Zongping,Wang Jicang
Cadmium (Cd), a heavy metal, has harmful effects on animal and human health, and it can also obviously induce cell apoptosis. Quercetin (Que) is a flavonoid compound with antioxidant and other biological activities. To investigate the protective effect of Que on Cd-induced renal apoptosis in rats. 24 male SD rats were randomly divided into four groups. They were treated as follows: control group was administered orally with normal saline (10 ml/kg); Cd group was injected with 2 mg/kg CdCl2 intraperitoneally; Cd + Que group was injected with 2 mg/kg CdCl2 and intragastric administration of Que (100 mg/kg); Que group was administered orally with Que (100 mg/kg). The experimental results showed that the body weight of Cd-exposed rats significantly decreased and the kidney coefficient increased. In addition, Cd significantly increased the contents of Blood Urea Nitrogen, Creatinine and Uric acid. Cd also increased the glutathione and malondialdehyde contents in renal tissues. The pathological section showed that Cd can cause pathological damages such as narrow lumen and renal interstitial congestion. Cd-induced apoptosis of kidney, which could activate the mRNA and protein expression levels of Cyt-c, Caspase-9 and Caspase-3 were significantly increased. Conversely, Que significantly reduces kidney damage caused by Cd. Kidney pathological damage was alleviated by Que. Que inhibited Cd-induced apoptosis and decreased Cyt-c, Caspase-9 and Caspase-3 proteins and mRNA expression levels. To sum up, Cd can induce kidney injury and apoptosis of renal cells, while Que can reduce Cd-induced kidney damage by reducing oxidative stress and inhibiting apoptosis. These results provide a theoretical basis for the clinical application of Que in the prevention and treatment of cadmium poisoning.
研究领域:
毒理学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYST
·
2014
·Vol. 139
·期 10
·2499-2506
·
IF 3.906
Qingqing Wen,Xi Zhang,Jiye Cai,Pei-Hui Yang
Cytochrome c (cyt c) and caspase-9 were critical biomarkers in mitochondria-mediated apoptosis. A novel electrochemical immunosensor was developed for in situ analysis of cyt c and caspase-9 in the cytosol. Gold nanoparticle–polydopamine (AuNP/PDA) composites were used to fabricate the interface of the sensor. The anti-cyt c or anti-caspase-9 functionalized-immunosensor provided a biomimetic interface for immunosensing of cyt c or caspase-9 in Hela cells during apoptosis. The changes in the expression level of cyt c and caspase-9 in the cytosol upon curcumin-induced apoptosis were detected by using the proposed method, and also the influence of different concentrations and incubation times of curcumin-induced Hela cells was investigated. This method achieved a linear range (0.1–100 μM) for standard cyt c and caspase-9, with a detection limit of 0.03 ± 0.01 μM for standard cyt c and 0.08 ± 0.02 μM for standard caspase-9. Moreover, this method was used to detect cells which could detect as low as 100 cells which expressed cyt c and caspase-9, and also the results are in good agreement with standard flow cytometry analysis. The developed electrochemical immunosensor offered a simple and rapid approach for sensitive evaluation of apoptosis markers with considerable specificity and reproducibility, and also the developed strategy could be of great importance in clinical diagnosis and therapeutic research.
研究领域:
生物化学
·
生物技术
·
癌症研究
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Oncology Letters
·
2018
·Vol. 15
·期 4
·5739-5743
·
IF 1.664
Hua Zhang,Yumei Cao,Yuru Chen,Guangxi Li,Hanshu Yu
The present study investigated the inhibitory effects of apatinib on the proliferation of the SMMC-7721 hepatocellular carcinoma cell line to explore the possible mechanism. The MTT assay was used to detect the inhibitory effects of the different concentrations of apatinib on the proliferation of SMMC-7721 cells. Annexin V/PI double staining was performed to investigate the effects of apatinib on the apoptosis of SMMC‑7721 cells. Expression of the apoptosis-related genes Bcl-2, Bax and caspase-9 after apatinib treatment was detected by reverse transcription‑quantitative PCR (RT-qPCR) and western blot analysis. Expression of the PI3K, p-PI3K, Akt and p-Akt proteins after apatinib treatment was detected using western blot analysis. The MTT results showed that apatinib inhibited the in vitro proliferation of SMMC-7721 cells. Annexin V/PI double staining showed that apatinib induced the apoptosis of SMMC‑7721 cells in a concentration-dependent manner. Results of RT-qPCR and western blot analysis showed that apatinib was able to induce the expression of pro-apoptotic genes Bax and caspase-9 and inhibited the expression of anti-apoptotic gene Bcl-2. In addition, the western blot analysis revealed that p-PI3K and p-Akt was significantly decreased following apatinib treatment, while no significant differences were found in the total protein levels of PI3K and Akt. The results of the present show that apatinib is capable of promoting the apoptosis of SMMC-7721 cells by inhibiting the PI3K/Akt signal transduction pathway, upregulating the expression of pro-apoptotic genes Bax and caspase-9, and downregulating the expression level of the anti-apoptotic gene Bcl-2.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2018
·
IF 2.297
Yunzhi Yin,Yiyue Wang,Jun Zhang,Jing Li,Jingjing Chen,Qi Shen
Docetaxel (DTX) is one kind of well-known anticancer drugs against tumors. GDC0941 was used to inhibit PI3K/Akt signal pathway and improve anti-tumor activity. PLGA-PEG-R7 (poly lactic-co-glycolic acid polyethylene glycol bending with cell penetrating peptide R7)/poly sulfadimethoxine-Folate nanoparticles (R7/PSD-Fol NPs) were made to load DTX and GDC0941 simultaneously. In vitro, the release capacity of DTX and GDC0941 inside nanoparticles was determined and both drugs could release from nanoparticles to 70% within 48h. The result of flow cytometry showed that GDC0941 had no interference on cell uptake and R7/PSD-Fol NPs could enhance MCF-7 cells uptake the most significantly. In cell colony study, GDC0941 could further improve the anti-tumor effect of DTX and inhibit the formation of cell clones on the basis of enhancing the uptake of R7/PSD-Fol NPs. The capability of cell colony formation was as follows: DTX > DTX + GDC0941 > R7 NPs > R7/PSD-Fol NPs. The expression of cell apoptosis proteins treated with R7/PSD-Fol NPs was the lowest. The addition of GDC0941 could decrease the full-length content of apoptotic proteins caspase-3 and caspase-9. In vivo, pharmacokinetic parameters results showed us that GDC0941 had no interference on pharmacokinetic study. Main pharmacokinetic parameters of DTX suspension and R7/PSD-Folate NPs suspension showed significant differences.
研究领域:
肿瘤学
·
药理学
·
纳米技术
·
细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
Food & Function
·
2020
·Vol. 11
·期 7
·6128-6138
·
IF 4.171
Xiao-xiao Hou,Jing-yu Liu,Zhuo-yu Li,Ming-chang Chang,Min Guo,Cui-ping Feng,Jiang-ying Shi
The fruiting bodies of Hericium erinaceus (Bull.) Pers. are commonly used in China in the treatment of digestive system diseases. In this work, the polysaccharides from the fruiting bodies of Hericium erinaceus (HEFPs) were extracted, and their effects on human colorectal cancer cells (HCT-116 and DLD1) were investigated in vitro. Our results showed that HEFPs were mainly composed of arabinose, galactose, glucose, and mannose at a molar ratio of 8.99 : 11.15 : 1.2 : 1.97. They significantly inhibited the growth of these cells by inducing apoptosis by the modulation of Bax and Bcl-2 expression, which in turn induced the loss of mitochondrial membrane potential, leading to the activation of cleaved-caspase-9 and cleaved-caspase-3. These results suggested that HEFPs induced apoptosis via the caspase-9-depedent intrinsic mitochondrial pathway. Furthermore, HEFPs increased the level of reactive oxygen species (ROS) in HCT-116 and DLD1 cells. The addition of the antioxidant N-acetyl-L-cysteine reduced the ability of HEFPs to trigger the intrinsic mitochondrial pathway, indicating the role of ROS generation in the upstream pathway of HEFP-induced apoptosis. Therefore, the results described in this study could be of interest for further studies in finding functional foods or alternative therapeutic agents against colorectal cancer.
研究领域:
肿瘤学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 2
·483
·
IF 4.2
Linlin Cui,Li Zhao,Guanghuan Shen,Dahai Yu,Tian Yuan,Yingyu Zhang,Bo Yang
Cordycepin has good antitumor activity, but its clinical application is limited due to the easy deamination of N6 in structure. In this study, a large lipolysis group was introduced at the cordycepin N6 to improve the problem, cordycepin derivatives (3a–4c) were synthesized, and biological evaluation of compounds was studied. In this study, the vitro antitumor activity of the compounds against MCF7 cells, HepG2 cells and SGC-7901 cells was evaluated by MTT assay. In the results, compound4ashowed the most obvious inhibitory effect on MCF7 cells with an IC50value of 27.57 ± 0.52 μM, which was much lower than cordycepin. Compound4ashowed high selectivity between MCF7 and normal MCF-10A cells. Further biological evaluation showed that compound4apromoted apoptosis and blocked the cell cycle in the G0/G1 phase. Then, Western Blot was used to detect related apoptotic proteins. It was found that Compound4acould down-regulate the expression of Bcl-2 protein and up-regulate the expression of p53, Bax, Caspase-3 and Caspase-9 proteins. The mitochondrial membrane potential decreased continuously and the positive expression rate decreased. It was speculated that compound4ainduced the apoptosis of MCF7 cells through the mitochondrial pathway.Keywords:cordycepin derivatives;antitumor;structural modification
研究领域:
药理学
·
肿瘤学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
PEDIATRIC HEMATOLOGY AND ONCOLOGY
·
2020
·
IF 1.232
Ju Yang,Ping Liu,Dan Ma,Peng Zhao,Yan Zhang,Yinghao Lu,Yanju Li,Yi Huang,Ying Chen,Jishi Wang
Development of chemo‑resistance is ultimately responsible for treatment failure and relapse in B-cell acute lymphoblastic leukemia (B-ALL). However, the mechanism underlying glucocorticoid (GC) resistance remains unclear. This study was performed to identify GC resistance-related genes using the transcriptome chip from the GEO database, and preliminarily analyze drug resistance mechanism in B-ALL. Here, we found that ANXA5 expression was upregulated in B-ALL cells and high-level ANXA5 was associated with dexamethasone (DEX) resistance. Then, small interfering RNA (siRNA) was designed to silence ANXA5 expression in the B-ALL cell lines, and the apoptotic rate of cells treated with DEX was detected by flow cytometry. As a result, cell apoptosis was dramatically promoted in B-ALL cells following silencing of ANXA5 and DEX administration versus that in ANXA5-silenced alone or DEX-treated alone cells. It was further found that down-regulation of ANXA5 in B-ALL cells significantly increased the relative amount of cleaved Caspase 3 and Caspase 9 induced by DEX. Collectively, inhibition of ANXA5 gene expression may represent a novel method to restore the sensitivity of treatment-resistant B-ALL tumors to GC-induced cell death, which is of important clinical significance to overcome drug resistance associated with B-ALL.
研究领域:
肿瘤学
·
血液学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）