ONCOLOGY REPORTS
·
2015
·Vol. 34
·期 6
·3147-3155
·
IF 2.301
Lili Zhang,Jie Zhang,Li Chen,Jianli Wang
Autophagy is an intracellular multi-step catabolic degradation process that involves the degradation and recycling of cellular proteins and cytoplasmic damaged organelles to maintain cellular homeostasis and reduction of metabolic stress. Numerous studies have indicated the importance of autophagy in cancer, but the role of autophagy in human skin squamous cell carcinoma (SSCC) development and response to therapy it is still unclear. In the present study, we investigated the role of autophagy in SSCC and the relationship with chemotherapy sensitivity. The present study demonstrated that autophagy related gene the microtubule-associated protein 1 light chain 3 (LC3) expression was low in SSCC. The negative correlation with Bcl2 and survivin, and the chemotherapy drug 5-FU increased the level of autophagy and the autophagy inhibitor 3-MA inhibited this effect in SSCC cells, time- and dose-dependently. When SSCC cells were treated first with 3-MA and then with 5-FU, the inhibition of proliferation, migration, invasion and apoptosis of SSCC cells was enhanced. Our results suggested the possibility of autophagy as a potential target in SSCC therapy and 3-MA and 5-FU combination treatment may be an effective SSCC therapy via autophagy modulating.
研究领域:
肿瘤学
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细胞生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL RESEARCH IN TOXICOLOGY
·
2025
·
IF 3.8
Yue Feng,Ying Zhang,Jinxin Li,Junzhe Yu,Yuan Tian,Zunjian Zhang,Fengguo Xu,Pei Zhang
Cisplatin (DDP) is widely utilized in the clinical treatment of malignant tumors, but its effectiveness is significantly compromised by the adverse effects of acute kidney injury (AKI). Renal tubular cells are primarily responsible for DDP-induced AKI (DDP-AKI); however, the responses of heterogeneous renal tubular cells to DDP exposure have not been thoroughly explored. In this study, we employed a targeted metabolomics approach to investigate the metabolic responses of renal tubular cells in DDP-AKI rats. Tubular cells were isolated from the renal cortex and outer medulla, and a chemical derivatization-based liquid chromatography–tandem mass spectrometry (LC–MS/MS) metabolomics method was applied. Our findings revealed distinct metabolic profiles in tubular cells from the renal cortex and outer medulla, with outer medullary cells exhibiting greater sensitivity to DDP exposure. Further analyses identified the tryptophan pathway as a critical factor contributing to these regional differences. Additional functional investigations showed that intermediate metabolites of the tryptophan pathway alleviated DDP cytotoxicity in both cortical and outer medullary tubular cells primarily through modulation of the Bcl2/Bax and Caspase-3 pathway. This study enhances our understanding of the metabolic characteristics of tubular cells across heterogeneous renal regions in DDP-AKI and facilitates further exploration of the underlying mechanisms of DDP-induced nephrotoxicity.
研究领域:
药理学
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肾病学
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代谢组学
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毒理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-12
·
IF 16.6
Chen Zhigang,Zhang Yi,Li Wenlu,Gao Chenyi,Huang Fengbo,Cheng Lu,Jin Menglei,Xu Xiaoming,Huang Jian
Fibroadenomas (FAs) are the most common breast tumors in women. No pharmacological agents are currently approved for FA intervention owing to its unclear mechanisms and a shortage of reproducible human models. Here, using single-cell RNA sequencing of human FAs and normal breast tissues, we observe distinct cellular composition and epithelial structural changes in FAs. Interestingly, epithelial cells exhibit hormone-responsive functional signatures and synchronous activation of estrogen-sensitive and hormone-resistant mechanisms ( ERBB2 , BCL2 and CCND1 pathways). We develop a human expandable FA organoid system and observe that most organoids seem to be resistant to tamoxifen. Individualized combinations of tamoxifen with ERBB2, BCL2 or CCND1 inhibitors could significantly suppress the viability of tamoxifen-resistant organoids. Thus, our study presents an overview of human FA at single-cell resolution that outlines the structural and functional differences between FA and normal breast epithelium and, in particular, provides a potential therapeutic strategy for breast FAs.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
·
2024
·
IF 4.1
Qiulu Li,Kaixin Ping,Yannan Xiang,Ying Sun,Zunhan Hu,Shujuan Liu,Xinying Guan,Mian Fu
Avamectin (AVM), a macrolide antibiotic, is widely used in fisheries, agriculture, and animal husbandry, however, its irrational use poses a great danger to aquatic organisms. Ferulic acid (FA) is a natural chemical found in the cell walls of plants. It absorbs free radicals from the surrounding environment and acts as an antioxidant. However, the protective effect of FA against kidney injury caused by AVM has not been demonstrated. In this study, 60 carp were divided into the control group, AVM group (2.404 μg/L), FA+AVM group and FA group (400 mg/kg). Pathological examination, quantitative real-time PCR (qPCR), reactive oxygen species (ROS) and western blot were used to evaluate the preventive effect of FA on renal tissue injury after AVM exposure. Histological findings indicated that FA significantly reduced the swelling and infiltration of inflammatory cells in the kidney tissues of carp triggered by AVM. Dihydroethidium (DHE) fluorescent probe assay showed that FA inhibited the accumulation of kidney ROS. Biochemical results showed that FA significantly increased glutathione (GSH) content, total antioxidant capacity (T-AOC) and catalase (CAT) activity, and decreased intracellular malondialdehyde (MDA) content. In addition, western blot results revealed that the protein expression levels of Nrf2 and p-NF-κBp65 in the carp kidney were inhibited by AVM, but reversed by the FA. The qPCR results exhibited that FA significantly increased the mRNA levels of tgf-β1 and il-10 , while significantly down-regulated the gene expression levels of tnf-α , il-6 and il-1β . These data suggest that FA can reduce oxidative stress and renal tissue inflammation induced by AVM. At the same time, FA inhibited the apoptosis of renal cells induced by AVM by decreasing the transcription level and protein expression level of Bax, and increasing the transcription level and protein expression level of Bcl2, PI3K and AKT. This study provides preliminary evidence for the theory that FA reduces the level of oxidative stress, inflammation response and kidney tissue damage caused by apoptosis in carp, providing a theoretical basis for the prevention and treatment of the AVM.
研究领域:
水生毒理学
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药理学
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生物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2023
·Vol. 15
·期 1
·257
·
IF 5.4
Lixing Xu,Enhe Bai,Yangbo Zhu,Jiayi Qin,Xiao Du,Haiqin Huang
Gastric ulcer is one of the most common gastrointestinal diseases, and natural products have obvious advantages in the treatment of gastrointestinal diseases. Baicalin (Bai) extracted from scutellaria baicalensis exhibits anti-inflammatory, antioxidant, and anti-apoptotic activities. Herein, a pH-responsive sodium alginate/polyaspartate/CaCO3(SA/[email protected]3) in situ hydrogel was established for the oral delivery of Bai. In this study, we detected the gelling properties, mechanical strength, in vitro erosion, and in vitro release behavior of the hydrogels. Meanwhile, the efficiency of Bai/SA/[email protected]3hydrogel on ethanol-induced acute gastric ulcers, acetic acid-induced chronic gastric ulcers, and H2O2-stimulated human gastric epithelial GES-1 cells was explored. The pathological examination revealed that Bai-loaded hydrogel alleviated acute and chronic gastric ulcers. In vivo and in vitro results further confirmed that Bai/SA/[email protected]3in situ hydrogels significantly relieved oxidative stress injury. Moreover, through Western blot assay, Bai/SA/[email protected]3hydrogel was also found to dramatically increase the proteins levels of NRF2, HO-1, and Bcl2, and reduce levels of p-JNK, cleaved-caspase-3 and Bax; through flow cytometry, it was observed to significantly inhibit the H2O2-induced apoptosis of GES-1 cells. Importantly, the Bai/SA/[email protected]3in situ hydrogel system showed better anti-gastric ulcer efficiency than free drug, and could serve as a potential drug delivery system for the clinical treatment of gastric ulcers.Keywords:gastric ulcer;pH-responsive in situ gelation;baicalin;sustained release;oxidative stress
研究领域:
药学
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胃肠病学
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药物递送系统
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL SCIENCES
·
2021
·
IF 3.534
Shanshan Li,Long Zhang,Mingda Li,Jiao Huang,Baocheng Cui,Jie Jia,Zhaoming Guo,Kun Ma,Changhao Cui
B lymphoblastic leukemia (B-LL) is a clonal hematopoietic stem cell neoplasm derived from B-cell progenitors, which mainly occurs in children and adolescents and is one of the main causes of death from malignant tumors in this population. The surface marker CD19 is specifically expressed on the membrane of most malignant B-cells, which is widely used as a marker of B-LL antigen-specific immunotherapy . In this study, mesoporous titanium dioxide nanoparticles (MTNs)-based antibody drug delivery system was designed for B-LL treatment. Anti-CD19 monoclonal antibody was conjugated to PEGylated MTNs, and doxorubicin (DOX) was loaded in the nanoparticle . The CD19-PEG-MTN/DOX nanoparticle could recognize CD19 + B -LL cell lines and induced them apoptosis, but nontoxic for the normal cells. Further, after treated with CD19-PEG-MTN/DOX nanoparticle, pro-apoptotic proteins Bax and Caspase-3 in KOPN 8 and NALM-6 cells were significantly upregulated, but anti-apoptotic proteins Bcl2 , MCL-1, HSP 70, and BAG 3 were downregulated, which indicated the activation of the apoptosis pathway by the nanodrug. By contrast, CD19-PEG-MTN/DOX didn't play a part on CD19 − cell line U937. Besides, the cytotoxicity of CD19-PEG-MTN/DOX was low with good biocompatibility. Collectively, CD19-PEG-MTN/DOX is a promising antitumor nanodrug for the treatment of B-LL.
研究领域:
肿瘤学
·
纳米技术
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药学
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免疫疗法
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomed Research International
·
2019
·
IF 2.197
Dongyu Xie,Ping Zhou,Lin Liu,Wenjing Jiang,Haina Xie,Liang Zhang,Donghao Xie
Suitable content of iron is essential for human body, but iron overload is associated with many kinds of diseases including chronic liver damage. Recently, researchers find that iron overload promotes hepatocyte autophagy and apoptosis. However, the mechanism of iron overload in liver damage remains unclear. In this study, Lo2 cells were selected as the research object, iron dextran was a model drug, and astragaloside IV was a therapeutic drug to explore the role of iron overload. MTT assay and Annexin/PI double staining were used to measure cell viability and apoptosis. Ultrastructure was observed by transmission electron microscopy. The expression levels of apoptosis and autophagy-related proteins were determined by real-time PCR and Western Blot. The results showed that iron dextran could significantly inhibit Lo2 cell viability and increase the apoptosis rate, while astragaloside IV could reverse the inhibition of Lo2 cell viability and decrease the apoptosis rate. Transmission electron microscopy showed a significant increase in the number of autophagosomes after administration of iron dextran, and the application of astragaloside IV reduced the production of autophagosomes. LC3II/I was significantly upregulated in the model group but decreased in the astragaloside IV treatment group, and P62 showed the opposite trend. Iron dextran significantly upregulated the expression of Bax and downregulated Bcl2, while astragaloside IV reversed this trend. Finally, the inhibition of hepcidin caused by iron dextran was counteracted by astragaloside IV. In conclusion, the experimental results show that the iron overload model mainly induces excessive autophagy and apoptosis of hepatocytes, thus causing damage to hepatocytes, but astragaloside IV plays a certain therapeutic role in reversing this damage.
研究领域:
药理学
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肝病学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2023
·
IF 6.1
Yichun Liu,Kaimin Niu,Ruxia Wang,Xiaoxiao Liang,Chong Lin,Xin Wu,Zhenya Zhai
Bile acids, such as taurochenodeoxycholic acid (TCDCA), are considered as functional small molecules involved in nutrition regulation or acting with adjuvant therapeutic effects against metabolic or immune diseases. The homeostasis of the intestinal epithelium depends on the conventional cellular proliferation and apoptosis of cells. Herein, mice and normal intestinal epithelial cells (IPEC-J2, a widely used normal intestinal epithelial cell line derived from porcine) were used as models to explore the regulatory effect of TCDCA on the proliferation of intestinal epithelial cells (IECs). In the mouse study, the oral gavage of TCDCA led to a significant reduction in weight gain, small intestinal weight, and the villus height of the intestinal epithelium while inhibiting the gene expression of Ki-67 in the intestinal epithelial crypts of mice (P < 0.05). TCDCA significantly downregulated the expression of the farnesoid X receptor (FXR) and upregulated the expression of caspase-9 in the jejunum (P < 0.05). The results of real-time quantitative PCR (RT-qPCR) suggested that TCDCA significantly inhibited the expression of tight junction proteins zonula occludens (ZO)-1, occludin, claudin-1, and mucin-2 (P < 0.05). In terms of apoptosis-related genes, TCDCA significantly inhibited the expression of Bcl2 and increased the expression of caspase-9 (P < 0.05). At the protein level, TCDCA decreased the expression of Ki-67 and PCNA, as well as FXR (P < 0.05). Caspase inhibitor Q-VD-OPh and guggulsterone, an FXR antagonist, significantly improved the inhibition of TCDCA-induced cell proliferation. Moreover, guggulsterone enhanced TCDCA-induced cell late apoptosis through flow cytometry and significantly lowered the TCDCA-induced up-regulated gene expression of caspase 9, despite both TCDCA and guggulsterone down-regulating the expression of FXR (P < 0.05). Overall, the effect of TCDCA on the induction of apoptosis is not dependent on FXR, whereas it would function via the activation of the caspase system. This provides a new perspective for the application of TCDCA or bile acid as functional small molecules in food, additives, and medicine.
研究领域:
胃肠病学
·
分子生物学
·
细胞生物学
·
药理学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2019
·
IF 3.845
Lin Xiao-mian,Luo Wu,Wang Heng,Li Rong-zhen,Huang Yi-shan,Chen Lian-kuai,Wu Xiao-ping
The prostaglandin-endoperoxide synthase-2 (PTGS2) plays essential roles in diverse pathological process. Although recent studies implied that PTGS2 was closely related with chemoresistance, the precise roles and the underlying mechanisms of PTGS2 in the developing process of chemoresistance in non-small cell lung cancer (NSCLC) remained elusive. In the present study, we revealed a novel molecular mechanism of PTGS2 implicated in the chemoresistance of NSCLC and proposed a model for the positive feedback regulation of PTGS2 in the process of developing resistance phenotype in NSCLC cells. Our results demonstrated that cisplatin induced PTGS2 expression through the ROS-ERK1/2-NF-κB signaling axis. The prostaglandin E2 (PGE2) derived from PTGS2 catalyzation further strengthened PTGS2 expression via the PGE2-EPs-ERK1/2 positive feedback loop, which induced multidrug resistance of NSCLC cells through up-regulation of BCL2 expression and the subsequent attenuation of cell apoptosis. Consistently, high levels of both PTGS2 and BCL2 were closely associated with poor survival in NSCLC patients. Inhibition of PTGS2 significantly reversed the chemoresistance in the resistant NSCLC in vitro and in vivo. Our results suggested that PTGS2 might be employed as an adjunctive therapeutic target for improving the response to the therapeutic agents in a subset of resistant NSCLC.
研究领域:
肿瘤学
·
分子生物学
·
药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF IMMUNOLOGY
·
2024
·
IF 3.6
Zhu Yiqiang,Zhou Lu,Mo Lengshan,Hong Cansheng,Pan Lingxia,Lin Jie,Qi Yanwei,Tan Simin,Qian Manhongtian,Hu Tengfei,Zhao Yi,Qiu Huaina,Lin Peibin,Ma Xiancai,Yang Quan
Myeloid-derived suppressor cells (MDSCs), the negative immune regulators, have been demonstrated to be involved in immune responses to a variety of pathological conditions, such as tumors, chronic inflammation, and infectious diseases. However, the roles and mechanisms underlying the expansion of MDSCs in malaria remain unclear. In this study, the phenotypic and functional characteristics of splenic MDSCs during Plasmodium yoelii NSM infection are described. Furthermore, we provide compelling evidence that the sera from P. yoelii–infected C57BL/6 mice containing excess IL-6 and granulocyte-macrophage colony-stimulating factor promote the accumulation of MDSCs by inducing Bcl2 expression. Serum-induced MDSCs exert more potent suppressive effects on T cell responses than control MDSCs within both in vivo P. yoelii infection and in vitro serum-treated bone marrow cells experiments. Serum treatment increases the MDSC inhibitory effect, which is dependent on Arg1 expression. Moreover, mechanistic studies reveal that the serum effects are mediated by JAK/STAT3 signaling. By inhibiting STAT3 phosphorylation with the JAK inhibitor JSI-124, effects of serum on MDSCs are almost eliminated. In vivo depletion of MDSCs with anti–Gr-1 or 5-fluorouracil significantly reduces the parasitemia and promotes Th1 immune response in P. yoelii–infected C57BL/6 mice by upregulating IFN-γ expression. In summary, this study indicates that P. yoelii infection facilitates the accumulation and function of MDSCs by upregulating the expression of Bcl2 and Arg1 via JAK/STAT3 signaling pathway in vivo and in vitro. Manipulating the JAK/STAT3 signaling pathway or depleting MDSCs could be promising therapeutic interventions to treat malaria.
研究领域:
免疫学
·
传染病学
·
细胞生物学
·
疟疾
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
·
2024
·
IF 5.2
Min Qiu,Liangyan Cheng,Jianbo Xu,Minwei Jin,Wenhua Yuan,Qinwen Ge,Kaiao Zou,Jiali Chen,Yuliang Huang,Ju Li,Liming Zhu,Bing Xu,Chunchun Zhang,Hongting Jin,Pinger Wang
Aims The main pathological features of osteoarthritis (OA) include the degeneration of articular cartilage and a decrease in matrix synthesis. Chondrocytes, which contribute to matrix synthesis, play a crucial role in the development of OA. Liquiritin, an effective ingredient extracted from Glycyrrhiza uralensis Fisch., has been used for over 1000 years to treat OA. This study aims to investigate the impact of liquiritin on OA and its underlying mechanism. Materials and methods Gait and hot plate tests assessed mouse behavior, while Micro-CT and ABH/OG staining observed joint morphological changes. The TUNEL kit detected chondrocyte apoptosis. Western blot and immunofluorescence techniques determined the expression levels of cartilage metabolism markers COL2 and MMP13, as well as apoptosis markers caspase3, bcl2, P53, and PUMA. KEGG analysis and molecular docking technology were used to verify the relationship between liquiritin and P53. Key findings Liquiritin alleviated pain sensitivity and improved gait impairment in OA mice. Additionally, we found that liquiritin could increase COL2 levels and decrease MMP13 levels both in vivo and in vitro. Importantly, liquiritin reduced chondrocyte apoptosis induced by OA, through decreased expression of caspase3 expression and increased expression of bcl2 expression. Molecular docking revealed a strong binding affinity between liquiritin and P53. Both in vivo and in vitro studies demonstrated that liquiritin suppressed the expression of P53 and PUMA in cartilage. Significance This indicated that liquiritin may alleviate OA progression by inhibiting the P53/PUMA signaling pathway, suggesting that liquiritin is a potential strategy for the treatment of OA.
研究领域:
药理学
·
骨科
·
细胞生物学
·
分子生物学
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
American Journal of Translational Research
·
2022
·
IF 3.94
Hui Yu,Ruxin Zheng,Fei Lei,Wanyue Wang,Weikang Guo,Lu Zhang,Yunduo Liu,Xiuwei Chen,Yaoxian Wang
This study aimed to synthesize silica-coated gold (Au@SiO 2 ) nanoparticles coupled to antibodies against the scavenger receptor class B type I (SR-BI) and investigate their potential ability of visual tracking and treatment of cervical cancer. The fluorescein isothiocyanate (FITC)-labeled Au@SiO 2 -SR-BI antibody was synthesized, followed by characterization determination. The expression and location of SR-BI protein in cervical cancer cells were respectively detected by western blot and immunofluorescence assays. The effects of nanoparticles on cancer cells were determined by adsorption assay and apoptosis detection, respectively. The effects of nanoparticles on tumor formation in nude mice were determined. The particle sizes of Au@SiO 2 ranged from 2-2.5 μm, and the particle size distribution was relatively uniform. MS751 showed the highest expression of SR-BI. SR-BI was located in the cytomembrane. There were more FITC-Au@SiO 2 -SR-BI nanoparticles on the surface of the cells compared to FITC-Au@SiO 2 . Significant apoptosis was observed in the FITC-Au@SiO 2 -SR-BI-treated group in both MS751 and H8 cells. Photothermal ablation of solid tumors was observed when FITC-Au@SiO 2 -SR-BI was activated using 808 nm wave. Expressions of the apoptosis-related markers including BCL2, BCLX, and p-AKT were significantly decreased, while those of caspase 3 and caspase 8 were significantly increased. The study presented a novel antibody-conjugated Au@SiO 2 nanoparticle specifically targeting molecular receptors on cancer cell membranes. Antibody-conjugated Au@SiO 2 nanoparticles may have therapeutic potential for the treatment of cervical cancer.
研究领域:
纳米技术
·
癌症研究
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生物医学工程
·
分子生物学
✓ 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）