380 results on '"Li, Min"'
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2. Acteoside and ursolic acid synergistically protects H2O2-induced neurotrosis by regulation of AKT/mTOR signalling: from network pharmacology to experimental validation
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Yan-Jie Qu, Min-Rui Ding, Chao Gu, Li-Min Zhang, Rong-Rong Zhen, Jin-Fang Chen, Bing Hu, and Hong-Mei An
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Neuroprotection ,apoptosis ,mTOR-dependent autophagy ,Rehmannia glutinosa (Gaetn.) Libosch. ex Fisch. et Mey. ,Cornus officinalis Sieb. et Zucc ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Context Ursolic acid (UA) and acteoside (ATS) are important active components that have been used to treat Alzheimer’s disease (AD) because of their neuroprotective effects, but the exact mechanism is still unclear.Objective Network pharmacology was used to explore the mechanism of UA + ATS in treating AD, and cell experiments were used to verify the mechanism.Materials and methods UA + ATS targets and AD-related genes were retrieved from TCMSP, STITCH, SwissTargetPrediction, GeneCards, DisGeNET and GEO. Key targets were obtained by constructing protein interaction network through STRING. The neuroprotective effects of UA + ATS were verified in H2O2-treated PC12 cells. The subsequent experiments were divided into Normal, Model (H2O2 pre-treatment for 4 h), Control (H2O2+ solvent pre-treatment), UA (5 μM), ATS (40 μM), UA (5 μM) + ATS (40 μM). Then apoptosis, mitochondrial membrane potential, caspase-3 activity, ATG5, Beclin-1 protein expression and Akt, mTOR phosphorylation levels were detected.Results The key targets of UA + ATS-AD network were mainly enriched in Akt/mTOR pathway. Cell experiments showed that UA (ED50: 5 μM) + ATS (ED50: 40 μM) could protect H2O2-induced (IC50: 250 μM) nerve damage by enhancing cells viability, combating apoptosis, restoring MMP, reducing the activation of caspase-3, lessening the phosphorylation of Akt and mTOR, and increasing the expression of ATG5 and Beclin-1.Conclusions ATS and UA regulates multiple targets, bioprocesses and signal pathways against AD pathogenesis. ATS and UA synergistically protects H2O2-induced neurotrosis by regulation of AKT/mTOR signalling.
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- 2022
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3. TFEB, a master regulator of autophagy and biogenesis, unexpectedly promotes apoptosis in response to the cyclopentenone prostaglandin 15d-PGJ2
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Yang, Chuan-bin, Liu, Jia, Tong, Benjamin Chun-Kit, Wang, Zi-ying, Zhu, Zhou, Su, Cheng-fu, Sreenivasmurthy, Sravan Gopalkrishnashetty, Wu, Jia-xi, Iyaswamy, Ashok, Krishnamoorthi, Senthilkumar, Huang, Shi-ying, Cheung, King-ho, Song, Ju-xian, Tan, Jie-qiong, Lu, Jia-hong, and Li, Min
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- 2022
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4. Theranostic Nanodots with Aggregation-Induced Emission Characteristic for Targeted and Image-Guided Photodynamic Therapy of Hepatocellular Carcinoma
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Gao, Yang, Zheng, Qi Chang, Xu, Shidang, Yuan, Youyong, Cheng, Xiang, Jiang, Shuai, Kenry, Yu, Qihong, Song, Zifang, Liu, Bin, and Li, Min
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Medical Biotechnology ,Biomedical and Clinical Sciences ,Nanotechnology ,Rare Diseases ,Digestive Diseases ,Biomedical Imaging ,Cancer ,Bioengineering ,Animals ,Apoptosis ,Carcinoma ,Hepatocellular ,Cell Line ,Tumor ,Cell Survival ,Disease Models ,Animal ,Hepatocytes ,Humans ,Liver Neoplasms ,Mice ,Inbred BALB C ,Mice ,Nude ,Models ,Theoretical ,Nanostructures ,Photochemotherapy ,Radiotherapy ,Image-Guided ,Survival Analysis ,Theranostic Nanomedicine ,Treatment Outcome ,Xenograft Model Antitumor Assays ,aggregation-induced emission ,hepatocellular carcinoma ,photodynamic therapy ,integrin alpha(nu)beta(3) ,theranostics ,integrin ανβ3 ,Oncology and Carcinogenesis ,Oncology and carcinogenesis - Abstract
Photosensitizer (PS) serves as the central element of photodynamic therapy (PDT). The use of common nanoparticles (NPs) for PDT has typically been rendered less effective by the undesirable aggregation-caused quenching (ACQ) effect, resulting in quenched fluorescence and reduced reactive oxygen species (ROS) generation that diminish the imaging quality and PDT efficacy. To overcome the ACQ effect and to enhance the overall efficacy of PDT, herein, integrin ανβ3-targeted organic nanodots for image-guided PDT were designed and synthesized based on a red emissive aggregation-induced emission (AIE) PS. Methods: The TPETS nanodots were prepared by nano-precipitation method and further conjugated with thiolated cRGD (cRGD-SH) through a click reaction to yield the targeted TPETS nanodots (T-TPETS nanodots). Nanodots were characterized for encapsulation efficiency, conjugation rate, particle size, absorption and emission spectra and ROS production. The targeted fluorescence imaging and antitumor efficacy of T-TPETS nanodot were evaluated both in vitro and in vivo. The mechanism of cell apoptosis induced by T-TPETS nanodot mediated-PDT was explored. The biocompatibility and toxicity of the nanodots was examined using cytotoxicity test, hemolysis assay, blood biochemistry test and histological staining. Results: The obtained nanodots show bright red fluorescence and highly effective 1O2 generation in aggregate state. Both in vitro and in vivo experiments demonstrate that the nanodots exhibit excellent tumor-targeted imaging performance, which facilitates image-guided PDT for tumor ablation in a hepatocellular carcinoma model. Detailed analysis reveals that the nanodot-mediated PDT is able to induce time- and concentration-dependent cell death. The use of PDT at a high PDT intensity leads to direct cell necrosis, while cell apoptosis via the mitochondria-mediated pathway is achieved under low PDT intensity. Conclusion: Our results suggest that well-designed AIE nanodots are promising for image-guided PDT applications.
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- 2019
5. Transition of autophagy and apoptosis in fibroblasts depends on dominant expression of HIF-1α or p53
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Li, Min, Su, Yidan, Gao, Xiaoyuan, Yu, Jiarong, Wang, Zhiyong, and Wang, Xiqiao
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- 2022
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6. Toosendanin, a late-stage autophagy inhibitor, sensitizes triple-negative breast cancer to irinotecan chemotherapy
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Zhang, Shuang, Dong, Yu, Chen, Xiuping, TAN, Chris Soon Heng, Li, Min, Miao, Kai, and Lu, Jia-Hong
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- 2022
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7. Ganoderma lucidum Polysaccharide Peptide Alleviates Cyclophosphamide-Induced Male Reproductive Injury by Reducing Oxidative Stress and Apoptosis.
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Zhang, Hang, Li, Nannan, Zhang, Yukun, Xu, Yue, Lu, Feng, Lin, Dongmei, Lin, Shuqian, Li, Min, and Yang, Baoxue
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GENITALIA ,MALE infertility ,GANODERMA lucidum ,PEPTIDES ,LABORATORY mice - Abstract
Chemotherapy is an important factor leading to male infertility. It is crucial to discover safe and effective treatments to prevent male reproductive injury caused by chemotherapy. The Ganoderma lucidum polysaccharide peptide (GLPP) has multiple pharmacological activities. The purpose of this study was to determine whether GLPP could protect the male sperm production from chemotherapeutic injury using a mouse model, with testicular damage induced by cyclophosphamide (CP). CP (50 mg/kg/day) was injected intraperitoneally into male ICR mice gavaged with different doses of GLPP at certain spermatogenic stages. The experimental results showed that GLPP alleviated the CP-induced reduction in reproductive organ coefficients and sperm parameters and reduced the morphological damage of testicular tissues in a dose-dependent manner. GLPP significantly improved the reproductive index, sperm-related parameters, sex hormone levels, and histological testis architecture at different spermatogenic stages. Furthermore, GLPP significantly increased superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), Nrf2, and HO-1, and decreased malondialdehyde (MDA) and Keap-1 in the testicular tissue, indicating reduced oxidative stress. In addition, GLPP limited CP-induced apoptosis via a reduction in Bax expression and increase in Bcl-2 expression. This study suggests that GLPP plays a protective role in spermatogenesis by reducing chemotherapeutic injury and might be developed into drug for male patients receiving chemotherapy. [ABSTRACT FROM AUTHOR]
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- 2024
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8. Up-regulation of miR-125a-5p inhibits proliferation and invasion of acute myeloid leukemia cell lines
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GAO Qiu-ying, XUN Li-ru, LI Lan, HOU Li-min, ZHOU Wei, WANG Hui
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acute myeloid leukemia ,mir-125a-5p ,proliferation ,invasion ,apoptosis ,nf-κb signaling pathway ,Medicine - Abstract
Objective To find the regulatory effect of miR-125a-5p on the growth and invasion of acute myeloid leukemia (AML) cell lines. Methods The expression of miR-125a-5p and TRIM71 in bone marrow specimens of AML patients, AML cell lines (U937 and HL60) and PBMC were examined by RT-qPCR. The U937 and HL60 cells were divided into control group (control), miR-125a-5p mimic group (miR-125a-5p mimic), miRNA negative control group (miR-NC), TRIM71 over-expression plasmid group (pcDNA3.1-TRIM71) and control plasmid group(pcDNA3.1-NC). U937 and HL60 cells were transfected with miR-125a-5p mimic, pcDNA3.1-TRIM71 and negative control using Lipofectamine 2000. Cell proliferation was measured by MTT assay; Cell invasion was measured by Matrigel invasion assay; And cell apoptosis was detected by flow cytometry. The expression of TRIM71, Bax, Bcl-2, NF-κB p65 was detected by RT-qPCR or Western blot. The targeted regulation relationship between miR-125a-5p and TRIM71 was verified by luciferase reporter gene assay. Results Compared with healthy controls or PBMC, miR-125a-5p expression levels in bone marrow samples of AML patients and AML cell lines were significantly reduced (P<0.05). The proliferation and invasion of U937 and HL60 cells in miR-125a-5p mimic group were significantly reduced, while the apoptosis rate was significantly increased (P<0.05). Compared with control group, the proliferation and invasion of U937 and HL60 cells in pcDNA3.1-TRIM71 group significantly were increased(P<0.05). Luciferase reporter gene assay detection showed that miR-125a-5p mimic effectively inhibited the luciferase activity of pGL3-TRIM71-WT. Compared with miR-125a-5p mimic group, the cell viability and cell invasion rate of (miR-125a-5p mimic+pcDNA3.1-TRIM71) group were increased significantly, while the apoptosis rate was decreased significantly(P<0.05). The expression level of nucleus NF-κB p65 protein in (miR-125a-5p mimic+pcDNA3.1-TRIM71) group was significantly increased(P<0.05). Conclusions Up-regulation of miR-125a-5p may inhibit proliferation and invasion of AML cell lines and induce apoptosis by targeting at TRIM71. In addition, miR-125a-5p can inhibit the proliferation of AML cells by inhibiting the activation of the NF-κB signaling pathway.
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- 2021
9. Circ_0038467 targets at miR-182 for regulating S. pneumoniae (Sp)-induced injury of human alveolar epithelial cell line HPAEpiC
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LIU Qing, ZHANG Lei, ZHANG Li-yuan, WANG Shi-feng, ZUO Li-min
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circ_0038467 ,s. pneumoniae ,alveolar epithelial cells ,apoptosis ,endoplasmic reticulum stress ,Medicine - Abstract
Objective To investigate the effect of circular RNA 0038467 (circ_0038467) targeting at miR-182 on apoptosis and endoplasmic reticulum stress of alveolar epithelial cell line(HPAEpiC) induced by S. pneumoniae (Sp). Methods HPAEpiC cells were divided into control (NC) group (without any treatment), Sp group (Sp infection), Sp+si-NC group (Sp infection after transfection by si-NC), Sp+si-circ_0038467 group (Sp infection after transfection by si-circ_0038467), Sp+miR-NC group (Sp infection after transfection of miR-NC), and Sp+miR-182 group (Sp infection after transfection of miR-182 mimics), Sp+si-circ_0038467+anti-miR-NC group (Sp infection after transfection by si-circ_0038467 and anti-miR-NC), Sp+si-circ_0038467+anti-miR-182 group (Sp infection after transfection by si-circ_0038467 and anti-miR-182). The expressions of circ_0038467 and miR-182 were detected by RT-qPCR. Flow cytometry detected cell apoptosis; Western blot analyzed the expression level of B-cell lymphoma (Bcl-2), heavy chain binding protein (BIP), Bcl associated X protein (Bax) and CCAAT enhancer binding protein homologous protein (CHOP), cysteine protease 3 (caspase-3), and cleaved-caspase-3 proteins. The effects of circ_0038467 and miR-182 expression on HPAEpiC cell apoptosis and endoplasmic reticulum stress induced by S. pneumoniae were analyzed. Results The apoptosis rate of HPAEpiC cells, the expression of circ_0038467, Bax, caspase-3, cleaved-caspase-3, BIP and CHOP were significantly increased after Sp infection (P<0.05), whereas the expression of Bcl-2 was significantly decreased(P<0.05). After circ_0038467 inhibition or miR-182 over-expression, the apoptosis rate, expression of circ_0038467, Bax, caspase-3, cleaved-caspase-3, BIP and CHOP were significantly reduced (P<0.05), whereas Bcl-2 expression was significantly increased(P<0.05). miR-182 inhibition can attenuate the effect of circ_0038467 inhibition on Sp induced HPAEpiC apoptosis and endoplasmic reticulum stress (P<0.05). Conclusions Inhibition of circ_0038467 can attenuate Sp induced alveolar epithelial cell apoptosis and endoplasmic reticulum stress, and its mechanism is related to the targeted regulation of miR-182 expression.
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- 2021
10. Recent advances in the potential effects of natural products from traditional Chinese medicine against respiratory diseases targeting ferroptosis.
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Chen, Tian, Ding, Lu, Zhao, Meiru, Song, Siyu, Hou, Juan, Li, Xueyan, Li, Min, Yin, Kai, Li, Xiangyan, and Wang, Zeyu
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THERAPEUTIC use of antioxidants ,THERAPEUTIC use of antineoplastic agents ,BIOTHERAPY ,CHINESE medicine ,ANTI-inflammatory agents ,APOPTOSIS ,HERBAL medicine ,NECROSIS ,RESPIRATORY diseases ,BIOLOGICAL products ,CELLULAR signal transduction ,PLANT extracts ,ALTERNATIVE medicine ,IMMUNOMODULATORS - Abstract
Respiratory diseases, marked by structural changes in the airways and lung tissues, can lead to reduced respiratory function and, in severe cases, respiratory failure. The side effects of current treatments, such as hormone therapy, drugs, and radiotherapy, highlight the need for new therapeutic strategies. Traditional Chinese Medicine (TCM) offers a promising alternative, leveraging its ability to target multiple pathways and mechanisms. Active compounds from Chinese herbs and other natural sources exhibit anti-inflammatory, antioxidant, antitumor, and immunomodulatory effects, making them valuable in preventing and treating respiratory conditions. Ferroptosis, a unique form of programmed cell death (PCD) distinct from apoptosis, necrosis, and others, has emerged as a key area of interest. However, comprehensive reviews on how natural products influence ferroptosis in respiratory diseases are lacking. This review will explore the therapeutic potential and mechanisms of natural products from TCM in modulating ferroptosis for respiratory diseases like acute lung injury (ALI), asthma, pulmonary fibrosis (PF), chronic obstructive pulmonary disease (COPD), lung ischemia–reperfusion injury (LIRI), pulmonary hypertension (PH), and lung cancer, aiming to provide new insights for research and clinical application in TCM for respiratory health. [ABSTRACT FROM AUTHOR]
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- 2024
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11. DGAT1 inhibitors protect pancreatic β-cells from palmitic acid-induced apoptosis
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Huang, Jun-shang, Guo, Bin-bin, Wang, Gai-hong, Zeng, Li-min, Hu, You-hong, Wang, Ting, and Wang, He-yao
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- 2021
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12. Research progress on the mechanism and signalling pathway of ferroptosis and its potential role in dermatosis research.
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Li, Min, Gong, Jian, Liu, Qiao, and Wu, Weiwei
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CELLULAR signal transduction , *APOPTOSIS , *CELL death , *NEUROLOGICAL disorders - Abstract
Ferroptosis is a novel type of cell death that is dependent on lipid peroxidation and iron accumulation, which distinguishes it from other types of programmed cell death. Current research indicates a significant association between ferroptosis and various pathological conditions, including cancer, neurological disorders, and cardiovascular diseases, albeit with a relatively unexplored role in dermatological afflictions. This paper elaborates on the mechanisms and signalling pathways of ferroptosis, summarizing the recent studies on ferroptosis and its related factors in dermatosis. Our objective is to shed light on novel perspectives and therapeutic strategies for dermatosis, enhancing the understanding of this under‐researched area through this comprehensive review. [ABSTRACT FROM AUTHOR]
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- 2024
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13. Protective autophagy enhances antistress ability through AMPK/ULK1 signaling pathway in human immortalized keratinocytes.
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Shi, Zhinan, Wang, Jing, Li, Min, Gu, Li, Xu, Zhiyi, Zhai, Xiaoyu, Zhou, Shu, Zhao, Jingting, Gu, Liqun, Chen, Lin, Ju, Linling, Zhou, Bingrong, and Hua, Hui
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KERATINOCYTE differentiation ,MITOCHONDRIAL membranes ,AUTOPHAGY ,KERATINOCYTES ,CELLULAR signal transduction ,ADENOSINE triphosphate ,REACTIVE oxygen species - Abstract
Keratinocytes, located in the outermost layer of human skin, are pivotal cells to resist environmental damage. Cellular autophagy plays a critical role in eliminating damaged organelles and maintaining skin cell homeostasis. Low‐dose 5‐Aminolevulinic acid photodynamic therapy (ALA‐PDT) has been demonstrated to enhance skin's antistress ability; however, the regulatory mechanisms of autophagy in keratinocytes remain unclear. In this study, we treated immortalized human keratinocytes (HaCaT cells) with low‐dose ALA‐PDT (0.5 mmol/L, 3 J/cm2). Through RNA‐sequencing analysis, we identified that low‐dose ALA‐PDT modulated autophagy‐related pathways in keratinocytes and pinpointed Unc‐51‐like kinase 1 (ULK1) as a key gene involved. Western blot results revealed that low‐dose ALA‐PDT treatment upregulated the expression of autophagy‐related proteins Beclin‐1 and LC3‐II/LC3‐I ratio. Notably, low‐dose ALA‐PDT regulated autophagy by inducing an appropriate level of reactive oxygen species (ROS), transiently reducing mitochondrial membrane potential, and decreasing adenosine triphosphate production; all these processes functioned on the AMP‐activated protein kinase (AMPK)/ULK1 pathway to activate autophagy. Finally, we simulated external environmental damage using ultraviolet B (UVB) at a dose of 60 mJ/cm2 and observed that low‐dose ALA‐PDT mitigated UVB‐induced cell apoptosis; however, this protective effect was reversed when using the autophagy inhibitor 3‐methyladenine. Overall, these findings highlight how low‐dose ALA‐PDT enhances antistress ability in HaCaT cells through controlling ROS generation and activating the AMPK/ULK1 pathway to arouse cellular autophagy. [ABSTRACT FROM AUTHOR]
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- 2024
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14. miRNA-186 improves sepsis induced renal injury via PTEN/PI3K/AKT/P53 pathway
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Li Min, Li Wei, Ren Feng-Qin, and Zhang Ming-li
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mirna-186 ,renal injury ,apoptosis ,Medicine - Abstract
The aim of this study is to explain the effects of miRNA-186 in renal injury induced by sepsis.
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- 2020
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15. Chinese medicine Di-Huang-Yi-Zhi protects PC12 cells from H2O2-induced apoptosis by regulating ROS-ASK1-JNK/p38 MAPK signaling
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Li-Min Zhang, Rong-Rong Zhen, Chao Gu, Tian-Li Zhang, Yue Li, Miao Jin, Bing Hu, and Hong-Mei An
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Alzheimer’s disease ,Oxidative stress ,Chinese herb ,Di-Huang-Yi-Zhi ,PC12 cells ,Apoptosis ,Other systems of medicine ,RZ201-999 - Abstract
Abstract Background Oxidative stress mediates the nerve injury during the pathogenesis of Alzheimer’s disease (AD). Protecting against oxidative stress damage is an important strategy to prevent and treat AD. Di-Huang-Yi-Zhi (DHYZ) is a Chinese medicine used for the treatment of AD, but its mechanism remains unknown. This study is aimed to investigate the effect of DHYZ on H2O2 induced oxidative damage in PC12 cells. Methods PC12 cells were treated with H2O2 and DHYZ. Cell proliferation was detected by Cell counting kit-8 (CCK-8) assay. Cytotoxicity of H2O2 was measured by lactate dehydrogenase (LDH) release assay. Apoptosis were identified by Annexin V-FITC/PI staining. Caspase 3 activity was detected by commercial kit. Mitochondrial membrane potential (MMP) was detected by JC-1 staining. Reactive oxygen species (ROS) was 2′, 7′-Dichlorodihydrofluorescein diacetate (DCFH-DA) staining. Protein expression and phosphorylation was identified by western blot. Results The results showed that DHYZ antagonized H2O2-mediated cytotoxicity and proliferation inhibition. DHYZ reduced ROS production, stabilize mitochondrial membrane potential, inhibit Caspase-3 activity and apoptosis induced by H2O2. In addition, DHYZ inhibited the phosphorylation of ASK1, JNK1/2/3 and p38 MAPK which were up-regulated by H2O2. Conclusions The present study suggested that DHYZ protected PC12 cells from H2O2-induced oxidative stress damage and was related to inhibition of ROS production and ASK1-JNK/p38 MAPK signaling. The present study provides experimental evidence for the application of DHYZ for the management of oxidative stress damage and AD.
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- 2020
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16. Procyanidins inhibit fine particulate matter-induced vascular smooth muscle cells apoptosis via the activation of the Nrf2 signaling pathway
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Li-Min Zhang, Shuai-Shuai Lv, Shi-Rui Fu, Jia-Qi Wang, Lu-Yao Liang, Rui-Qiang Li, Fan Zhang, and Yu-Xia Ma
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Procyanidins ,Fine particulate matter ,Vascular smooth muscle cells ,Apoptosis ,Oxidative stress ,Nrf2 ,Environmental pollution ,TD172-193.5 ,Environmental sciences ,GE1-350 - Abstract
The functional role of procyanidins (PC) in PM2.5-induced cardiovascular diseases (CVD) is largely unexplored. This study aimed to explore the protective effect of PC against PM2.5-induced vascular smooth muscle cells (VSMCs) apoptosis and underlying mechanisms. Sprague Dawley rats were pretreated with three doses of PC (50, 100, and 200 mg/kg) and exposed to 10 mg/kg PM2.5 by intratracheal instillation three times a week. VSMCs were exposed to 5, 10, and 20 μM PC before the addition of 100 μg/mL PM2.5. In vivo, the PM2.5 exposure induced apoptosis in the thoracic aorta of rats. The PM2.5 exposure significantly elevated the reactive oxygen species (ROS) and malondialdehyde (MDA) levels and decreased the superoxide dismutase activity. Also, PC supplementation increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), and its downstream antioxidant genes, i.e., NAD(P)H dehydrogenase (quinine) 1 and heme oxygenase 1, attenuated oxidative stress and vascular apoptosis. In vitro, PM2.5 induced cytotoxicity in VSMCs in a dose-dependent manner. Besides, PC abolished the PM2.5-induced cytotoxicity by activating the Nrf2 signal pathway, alleviating oxidative stress, and decreasing apoptosis. In conclusion, this work is the first study to demonstrate that PC can suppress the PM2.5-induced VSMCs apoptosis via the activation of the Nrf2 signal pathway.
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- 2021
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17. MiR-15a-5p in neutrophil exosomes promotes macrophage apoptosis through targeted inhibition of BCL2L2.
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KE Qiao, HU Long-hui, RUAN Chu-jun, and LI Min
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EXOSOMES ,NEUTROPHILS ,MACROPHAGES ,ELECTRON microscopes ,BINDING sites ,MACROPHAGE inflammatory proteins - Abstract
Objective: To explore the possible mechanism of neutrophil exosomes regulating macrophage apoptosis. Methods: neutrophils were induced by lipopolysaccharide, inflammatory factors were detected by ELISA, the morphology of exosomes was identified by electron microscope, and the expression of mir-15a-5p in exosomes was detected by RT-PCR; Raw267.4 macrophages was treated with neutrophil exosomes and mir-15a-5p mimic respectively, CCK8 to detect cell viability, flow cytometry to detect apoptosis; The binding sites of mir-15a-5p and BCL2L2 were predicted and verified by double luciferase experiment; RT-PCR and Western blot verified that mir-15a-5p regulate the expression of BCL2L2. Results: lipopolysaccharide induced neutrophil inflammatory factors IL-2, IL-6, IL-10 and TNF-a. The morphological characteristics of exosomes were observed by electron microscope. Mir-15a-5p was significantly overexpressed in neutrophil exosomes induced by lipopolysaccharide; Lipopolysaccharide-induced neutrophil exosomes and mir-15a-5p simulants can promote raw267.4 macrophage apoptosis and inhibit its cell viability; Targetscan database predicted that mir-15a-5p and BCL2L2 had binding sites. Double-luciferase experiment verified that mir-15a-5p and BCL2L2 bound through binding sites; Mir-15a-5p mimic was transfected into raw267.4 macrophages which inhibit the expression of BCL2L2 mRNA and protein. Conclusion: inflammatory neutrophils may promote raw267.4 by secreting exosomes containing mir-15a-5p and inhibiting BCL2L2 by targeting macrophage apoptosis. This may provide a theoretical basis for further understanding the molecular mechanism of inflammatory regulation of neutrophils and macrophages. [ABSTRACT FROM AUTHOR]
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- 2023
18. Rictor Activates Cav 1 Through the Akt Signaling Pathway to Inhibit the Apoptosis of Gastric Cancer Cells
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Rui-zhen Cao, Li Min, Si Liu, Ru-yue Tian, Hai-yan Jiang, Juan Liu, Lin-lin Shao, Rui Cheng, Sheng-tao Zhu, Shui-long Guo, and Peng Li
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Rictor ,Cav 1 ,Akt ,Apoptosis ,Gastric cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
BackgroundRapamycin-insensitive companion of mammalian target of rapamycin (Rictor) protein is a core subunit of mammalian target of rapamycin complex 2, and is associated with cancer progression. However, the biological function of Rictor in cancer, particularly its clinical relevance in gastric cancer (GC) remains largely unknown.MethodsRictor expression and its association with clinicopathologic characteristics in GC were analyzed by immunohistochemistry. Effect of Rictor and Caveolin-1 (Cav 1) on GC cells apoptosis was evaluated via overexpression experiment in vitro. Mechanisms of Rictor and Cav 1 in GC were explored through overexpression and knockdown, by immunofluorescence and western blot analyses.ResultsRictor was upregulated in GC, and mainly located in the cytoplasm of cancer cells. Moreover, higher Rictor levels were associated with worse prognosis. Rictor could inhibit GC cell apoptosis and promote cell growth in vitro. The results of immunofluorescence revealed that Cav 1 localized in GC cell membrane but did not co-localize with Rictor. Further, Rictor regulated apoptosis-related proteins, long non-coding RNAs and also activated cellular signaling, thereby positively regulating Cav 1 expression. This effect was attenuated by the Akt inhibitor ly294002. Cav 1 did not significantly affect the ability of Rictor to inhibit tumor cell apoptosis.ConclusionsRictor is upregulated in GC and associated with worse prognosis. It inhibits tumor apoptosis and activates Cav 1 through the Akt signaling pathway to inhibit the apoptosis of GC cells. Rictor is, therefore, a promising prognostic biomarker and possible therapeutic target in GC patients.
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- 2021
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19. Feiyanning Formula Induces Apoptosis of Lung Adenocarcinoma Cells by Activating the Mitochondrial Pathway
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Li-Min Zhu, Hai-Xia Shi, Masahiro Sugimoto, Kenjiro Bandow, Hiroshi Sakagami, Shigeru Amano, Hai-Bin Deng, Qing-Yu Ye, Yun Gai, Xiao-Li Xin, and Zhen-Ye Xu
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FYN ,A549 cells ,apoptosis ,NSCLC ,mitochondrial pathway ,metabolomics analysis ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Feiyanning formula (FYN) is a traditional Chinese medicine (TCM) prescription used for more than 20 years in the treatment of lung cancer. FYN is composed of Astragalus membranaceus, Polygonatum sibiricum, Atractylodes macrocephala, Cornus officinalis, Paris polyphylla, and Polistes olivaceous, etc. All of them have been proved to have anti-tumor effect. In this study, we used the TCM network pharmacological analysis to perform the collection of compound and disease target, the prediction of compound target and biological signal and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. It was found that the activation of mitochondrial pathway might be the molecular mechanism of the anti-lung cancer effect of FYN. The experimental results showed that FYN had an inhibitory effect on the growth of lung cancer cells in a dose-dependent and time-dependent manner. Moreover, FYN induced G2/M cell cycle arrest and apoptotic cell death as early as 6 h after treatment. In addition, FYN significantly induced mitochondrial membrane depolarization and increased calreticulin expression. Metabolomics analysis showed the increase of ATP utilization (assessed by a significant increase of the AMP/ATP and ADP/ATP ratio, necessary for apoptosis induction) and decrease of polyamines (that reflects growth potential). Taken together, our study suggested that FYN induced apoptosis of lung adenocarcinoma cells by promoting metabolism and changing the mitochondrial membrane potential, further supporting the validity of network pharmacological prediction.
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- 2021
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20. β-acetoxyisovalerylalkannin suppresses proliferation and induces ROS-based mitochondria-mediated apoptosis in human melanoma cells.
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Xu, Fang, Li, Min, Qian, Qian, Chen, Ling, Yang, Ying, Ji, Teng-Fei, and Li, Jian-Guang
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IN vitro studies , *FLOW cytometry , *MELANOMA , *MITOCHONDRIA , *RESEARCH funding , *APOPTOSIS , *CELL proliferation , *DESCRIPTIVE statistics , *CELL lines , *REACTIVE oxygen species , *PLANT extracts , *MOLECULAR structure , *WESTERN immunoblotting , *ONE-way analysis of variance , *DATA analysis software - Abstract
β-acetoxyisovalerylalkannin (β-AIVA) is one of shikonin/alkannin derivative, which were mainly extracted from Boraginaceae family. The effects of β-AIVA on human melanoma A375 cells and U918 cells were investigated in vitro. The CCK-8 assay showed that β-AIVA inhibited proliferation of cells. Results from flow cytometry, ROS assay and JC-1 assay showed that β-AIVA increased late apoptosis rate, induced the production of ROS and promoted mitochondrial depolarization in cells. β-AIVA regulated expressions of BAX and Bcl-2 proteins, and increased the expression of cleaved caspase-9 and cleaved caspase-3. These findings suggest that β-AIVA may be a potential therapeutic drug for treating melanoma. [ABSTRACT FROM AUTHOR]
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- 2024
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21. FAM175B promotes apoptosis by inhibiting ATF4 ubiquitination in esophageal squamous cell carcinoma
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Yu Zhao, Yang Yu, Hengcun Li, Zheng Zhang, Shuilong Guo, Shengtao Zhu, Qingdong Guo, Peng Li, Li Min, and Shutian Zhang
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apoptosis ,ATF4 ,ESCC ,FAM175B ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
FAM175B is a reported regulator of p53 and suppresses tumorigenesis in numerous types of cancer, but very little is known about its function in esophageal squamous cell carcinomas (ESCCs), almost 70% of which exhibit mutations in p53. Here, we report that FAM175B expression is downregulated in high‐grade intraepithelial neoplasia (t = 2.44, P = 0.031) and ESCC (t = 5.664, P
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- 2019
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22. Advanced MRI to assess hippocampal injury after incomplete cerebral ischemia‐reperfusion in rats.
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Fu, Lan, Zhang, Li‐Min, Guan, Lin‐Na, Song, Yan‐Cheng, Zhang, Dong‐Xue, Kang, Li‐Qing, and Liu, Feng‐Hai
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CEREBRAL circulation ,MYOCARDIAL reperfusion ,BODY-weight-supported treadmill training ,MAGNETIC resonance imaging ,REPERFUSION ,HEMORRHAGIC shock ,HIPPOCAMPUS (Brain) ,SPIN labels - Abstract
Background and Purpose: The purpose of this study was to evaluate advanced MRI findings in the bilateral hippocampus CA1 region of rats with hemorrhagic shock reperfusion (HSR) and their correlation with histopathological results. Additionally, this study aimed to identify effective MRI examination methods and detection indexes for assessing HSR. Methods: Rats were randomized into the HSR and the Sham groups with 24 rats in each group. MRI examination included diffusion kurtosis imaging (DKI) and 3‐dimensional arterial spin labeling (3D‐ASL). Apoptosis and pyroptosis were evaluated directly from tissue. Results: In the HSR group, cerebral blood flow (CBF) was significantly lower than that of the Sham group, while radial kurtosis (Kr), axial kurtosis (Ka), and mean kurtosis (MK) were all higher. In the HSR group, fractional anisotropy (FA) at 12 and 24 hours and radial diffusivity, axial diffusivity (Da), and mean diffusivity (MD) at 3 and 6 hours were lower than in the Sham group. MD and Da at 24 hours in the HSR group were significantly higher. The apoptosis rate and pyroptosis rate were also enhanced in the HSR group. CBF, FA, MK, Ka, and Kr values in the early stage were strongly correlated with apoptosis rate and pyroptosis rate. The metrics were obtained from DKI and 3D‐ASL. Conclusions: Advanced MRI metrics from DKI and 3D‐ASL, including CBF, FA, Ka, Kr, and MK values, are useful to evaluate abnormal blood perfusion and microstructural changes in the hippocampus CA1 area in the setting of incomplete cerebral ischemia‐reperfusion in rats induced by HSR. [ABSTRACT FROM AUTHOR]
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- 2023
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23. Cold exposure protects against medial arterial calcification development via autophagy.
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Li, Fu-Xing-Zi, Liu, Jun-Jie, Xu, Feng, Shan, Su-Kang, Zheng, Ming-Hui, Lei, Li-Min, Lin, Xiao, Guo, Bei, Li, Chang-Chun, Wu, Feng, Tang, Ke-Xin, Cao, Ye-Chi, Wu, Yun-Yun, Duan, Jia-Yue, Wu, Yan-Lin, He, Si-Yang, Chen, Xi, and Yuan, Ling-Qing
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ARTERIAL calcification ,AUTOPHAGY ,VASCULAR smooth muscle ,APOPTOSIS ,COLD (Temperature) ,REVERSE transcriptase - Abstract
Medial arterial calcification (MAC), a systemic vascular disease different from atherosclerosis, is associated with an increased incidence of cardiovascular events. Several studies have demonstrated that ambient temperature is one of the most important factors affecting cardiovascular events. However, there has been limited research on the effect of different ambient temperatures on MAC. In the present study, we showed that cold temperature exposure (CT) in mice slowed down the formation of vitamin D (VD)-induced vascular calcification compared with room temperature exposure (RT). To investigate the mechanism involved, we isolated plasma-derived exosomes from mice subjected to CT or RT for 30 days (CT-Exo or RT-Exo, respectively). Compared with RT-Exo, CT-Exo remarkably alleviated the calcification/senescence formation of vascular smooth muscle cells (VSMCs) and promoted autophagy by activating the phosphorylation of AMP-activated protein kinase (p-AMPK) and inhibiting phosphorylation of mammalian target of rapamycin (p-mTOR). At the same time, CT-Exo promoted autophagy in β-glycerophosphate (β-GP)-induced VSMCs. The number of autophagosomes and the expression of autophagy-related proteins ATG5 and LC3B increased, while the expression of p62 decreased. Based on a microRNA chip microarray assay and real-time polymerase chain reaction, miR-320a-3p was highly enriched in CT-Exo as well as thoracic aortic vessels in CT mice. miR-320a-3p downregulation in CT-Exo using AntagomiR-320a-3p inhibited autophagy and blunted its anti-calcification protective effect on VSMCs. Moreover, we identified that programmed cell death 4 (PDCD4) is a target of miR-320a-3p, and silencing PDCD4 increased autophagy and decreased calcification in VSMCs. Treatment with CT-Exo alleviated the formation of MAC in VD-treated mice, while these effects were partially reversed by GW4869. Furthermore, the anti-arterial calcification protective effects of CT-Exo were largely abolished by AntagomiR-320a-3p in VD-induced mice. In summary, we have highlighted that prolonged cold may be a good way to reduce the incidence of MAC. Specifically, miR-320a-3p from CT-Exo could protect against the initiation and progression of MAC via the AMPK/mTOR autophagy pathway. [ABSTRACT FROM AUTHOR]
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- 2023
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24. Sevoflurane-Induced Neuroapoptosis in Rat Dentate Gyrus Is Activated by Autophagy Through NF-κB Signaling on the Late-Stage Progenitor Granule Cells
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Dongyi Tong, Zhongliang Ma, Peng Su, Shuai Wang, Ying Xu, Li Min Zhang, Ziyi Wu, Kun Liu, and Ping Zhao
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sevoflurane ,dentate gyrus ,apoptosis ,autophagy ,NF-κB ,differentiation ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
ObjectiveThe mechanisms by which exposure of the late-stage progenitor cells to the anesthesia sevoflurane alters their differentiation are not known. We seek to query whether the effects of sevoflurane on late-stage progenitor cells might be regulated by apoptosis and/or autophagy.MethodsTo address the short-term impact of sevoflurane exposure on granule cell differentiation, we used 5-bromo-2-deoxyuridine (BrdU) to identify the labeled late-stage progenitor granule cells. Male or female rats were exposed to 3% sevoflurane for 4 h when the labeled granule cells were 2 weeks old. Differentiation of the BrdU-labeled granule cells was quantified 4 and 7 days after exposure by double immunofluorescence. The expression of apoptosis and autophagy in hippocampal dentate gyrus (DG) was determined by western blot and immunofluorescence. Western blot for the expression of NF-κB was used to evaluate the mechanism. Morris water maze (MWM) test was performed to detect cognitive function in the rats on postnatal 28–33 days.ResultsExposure to sevoflurane decreased the differentiation of the BrdU-labeled late-stage progenitor granule cells, but increased the expression of caspase-3, autophagy, and phosphorylated-P65 in the hippocampus of juvenile rats and resulted in cognitive deficiency. These damaging effects of sevoflurane could be mitigated by inhibitors of autophagy, apoptosis, and NF-κB. The increased apoptosis could be alleviated by pretreatment with the autophagy inhibitor 3-MA, and the increased autophagy and apoptosis could be reduced by pretreatment with NF-κB inhibitor BAY 11-7085.ConclusionThese findings suggest that a single, prolonged sevoflurane exposure could impair the differentiation of late-stage progenitor granule cells in hippocampal DG and cause cognitive deficits possibly via apoptosis activated by autophagy through NF-κB signaling. Our results do not preclude the possibility that the affected differentiation and functional deficits may be caused by depletion of the progenitors pool.
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- 2020
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25. Thymoquinone induces cytotoxicity and reprogramming of EMT in gastric cancer cells by targeting PI3K/Akt/mTOR pathway
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Feng, Li-Min, Wang, Xue-Feng, and Huang, Qing-Xian
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- 2017
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26. Hsc70 Interacts with β4GalT5 to Regulate the Growth of Gliomas
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Sun, Guan, Cao, Ying, Dai, Xueliang, Li, Min, and Guo, Jun
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- 2019
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27. RETRACTED ARTICLE: Chinese medicine Di-Huang-Yi-Zhi protects PC12 cells from H2O2-induced apoptosis by regulating ROS-ASK1-JNK/p38 MAPK signaling
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Zhang, Li-Min, Zhen, Rong-Rong, Gu, Chao, Zhang, Tian-Li, Li, Yue, Jin, Miao, Hu, Bing, and An, Hong-Mei
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- 2020
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28. Global publication trends and research trends of necroptosis application in tumor: A bibliometric analysis.
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Yun-Yun Wu, Chang-chun Li, Xiao Lin, Feng Xu, Su-Kang Shan, Bei Guo, Fu-Xing-Zi Li, Ming-Hui Zheng, Qiu-Shuang Xu, Li-Min Lei, Jia-Yue Duan, Ke-Xin Tang, Ye-Chi Cao, and Ling-Qing Yuan
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BIBLIOMETRICS ,INTERNATIONAL cooperation ,APOPTOSIS ,SCHOLARLY periodicals ,CELL death - Abstract
Introduction: Necroptosis is an alternative, caspase-independent programmed cell death that appears when apoptosis is inhibited. A gowing number of studies have reflected the link between necroptosis and tumors. However, only some systematical bibliometric analyses were focused on this field. In this study, we aimed to identify and visualize the cooperation between countries, institutions, authors, and journals through a bibliometric analysis to help understand the hotspot trends and emerging topics regarding necroptosis and cancer research. Methods: The articles and reviews on necroptosis and cancer were obtained from the Web of Science Core Collection on 16 September 2022. Countries, institutions, authors, references, and keywords in this field were visually analyzed by CtieSpace 5.8.R3, VOSviewer 1.6.18, and R package "bibliometrix." Results: From 2006 to 2022, 2,216 qualified original articles and reviews on necroptosis in tumors were published in 685 academic journals by 13,009 authors in 789 institutions from 75 countries/regions. Publications focusing on necroptosis and cancer have increased violently in the past 16 years, while the citation number peaked around 2008-2011. Most publications were from China, while the United States maintained the dominant position as a "knowledge bridge" in necroptosis and cancer research; meanwhile, Ghent University and the Chinese Academy of Sciences were the most productive institutions. Moreover, only a tiny portion of the articles were multiplecountry publications. Peter Vandenabeele had the most significant publications, while Alexei Degterev was most often co-cited. Peter Vandenabeele also gets the highest h-index and g-index in this research field. Cell Death and Disease was the journal with the most publications on necroptosis and cancer, which was confirmed to be the top core source by Bradford's Law. At the same time, Cell was the leading co-cited journal, and the focus area of these papers was molecular, biology, and immunology. High-frequency keywords mainly contained those that are molecularly related (MLKL, NF-kB, TNF, RIPK3, RIPK1), pathological process related (necroptosis, apoptosis, cell-death, necrosis, autophagy), and mechanism related (activation, expression, mechanisms, and inhibition). Conclusion: This study comprehensively overviews necroptosis and cancer research using bibliometric and visual methods. Research related to necroptosis and cancer is flourishing. Cooperation and communication between countries and institutions must be further strengthened. The information in our paper would provide valuable references for scholars focusing on necroptosis and cancer. [ABSTRACT FROM AUTHOR]
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- 2023
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29. Repeated treatments of Capan-1 cells with PARP1 and Chk1 inhibitors promote drug resistance, migration and invasion
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Ne Guo, Meng-Zhu Li, Li-Min Wang, Hua-Dong Chen, Shan-Shan Song, Ze-Hong Miao, and Jin-Xue He
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Pharmacology ,Cancer Research ,Drug Resistance ,Poly (ADP-Ribose) Polymerase-1 ,Apoptosis ,Poly(ADP-ribose) Polymerase Inhibitors ,CXCL3-ERK1/2 signaling ,PARP1 ,migration and invasion ,G2 Phase Cell Cycle Checkpoints ,resistance ,Oncology ,Cell Line, Tumor ,Humans ,Phthalazines ,Molecular Medicine ,Combination therapy ,Protein Kinase Inhibitors ,Research Article ,Research Paper - Abstract
PARP1 and Chk1 inhibitors have been shown to be synergistic in different cancer models in relatively short time treatment modes. However, the consequences of long-term/repeated treatments with the combinations in cancer models remain unclear. In this study, the synergistic cytotoxicity of their combinations in 8 tumor cell lines was confirmed in a 7-day exposure mode. Then, pancreatic Capan-1 cells were repeatedly treated with the PARP1 inhibitor olaparib, the Chk1 inhibitor rabusertib or their combination for 211–214 days, during which the changes in drug sensitivity were monitored at a 35-day interval. Unexpectedly, among the 3 treatment modes, the combination treatments resulted in the highest-grade resistance to Chk1 (~14.6 fold) and PARP1 (~420.2 fold) inhibitors, respectively. Consistently, G2/M arrest and apoptosis decreased significantly in the resulting resistant variants exposed to olaparib. All 3 resistant variants also unexpectedly obtained enhanced migratory and invasive capabilities. Moreover, the combination treatments resulted in increased migration and invasion than olaparib alone. The expression of 124 genes changed significantly in all the resistant variants. We further demonstrate that activating CXCL3-ERK1/2 signaling might contribute to the enhanced migratory capabilities rather than the acquired drug resistance. Our findings indicate that repeated treatments with the rabusertib/olaparib combination result in increased drug resistance and a more aggressive cell phenotype than those with either single agent, providing new clues for future clinical anticancer tests of PARP1 and Chk1 inhibitor combinations.
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- 2022
30. Some Macrophages With High Expression of CHOP Undergo Necroptosis in Chronic Rhinosinusitis.
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Li, Min, Fu, Ziming, Qi, Chenglin, Wang, Qinying, Xie, Hui, and Li, Huabin
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SINUSITIS ,NASAL mucosa ,ENDOSCOPIC surgery ,CELL death ,NASAL polyps ,MACROPHAGES - Abstract
Background: Endoplasmic reticulum stress (ER stress) is activated in chronic sinusitis with nasal polyps (CRSwNP) and leads to increased expression of C/EBP homologous protein (CHOP). However, the role of CHOP in the pathogenesis of CRSwNP remains unclear. Methods: CHOP expression was detected by immunohistochemistry staining in nasal mucosa of control and CRSwNP patients. Co-localization of CHOP and cleaved caspase3, p-MLKL, and CD68 was detected by immunofluorescence staining in CRSwNP patients. TNFα, IFNγ, IL1β, LPS, and tunicamycin were added to primary dispersed nasal polyp cells (DNPCs) to explore their roles in cell death. Western blot, CCK8 assay, and flow cytometry were employed to detect cell death. Results: CHOP was specifically activated in CRSwNP compared to controls. It was mainly macrophages that highly expressed CHOP, some of which underwent apoptosis and the other underwent necroptosis. IL1β induced increased CHOP and apoptosis, and a slight p-MLKL. In addition, ER stress could also promote p-MLKL expression. Whereas classical TNFα plus IFNγ and LPS did not induce increased necroptosis in DNPCs. Conclusion: IL1β induced the apoptotic pathway and minor necroptosis. And ER stress also plays a role in the occurrence of necroptosis in CRSwNP. [ABSTRACT FROM AUTHOR]
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- 2023
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31. Acteoside and ursolic acid synergistically protects H2O2-induced neurotrosis by regulation of AKT/mTOR signalling: from network pharmacology to experimental validation.
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Yan-Jie Qu, Min-Rui Ding, Chao Gu, Li-Min Zhang, Rong-Rong Zhen, Jin-Fang Chen, Bing Hu, and Hong-Mei An
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URSOLIC acid ,ALZHEIMER'S disease ,MEMBRANE potential ,MITOCHONDRIAL membranes ,PHARMACOLOGY ,CELL death ,APOPTOSIS - Abstract
Context: Ursolic acid (UA) and acteoside (ATS) are important active components that have been used to treat Alzheimer's disease (AD) because of their neuroprotective effects, but the exact mechanism is still unclear. Objective: Network pharmacology was used to explore the mechanism of UAþATS in treating AD, and cell experiments were used to verify the mechanism. Materials and methods: UAþATS targets and AD-related genes were retrieved from TCMSP, STITCH, SwissTargetPrediction, GeneCards, DisGeNET and GEO. Key targets were obtained by constructing protein interaction network through STRING. The neuroprotective effects of UAþATS were verified in H2O2-treated PC12 cells. The subsequent experiments were divided into Normal, Model (H2O2 pre-treatment for 4 h), Control (H2O2þ solvent pre-treatment), UA (5 lM), ATS (40 lM), UA (5 lM) þ ATS (40 lM). Then apoptosis, mitochondrial membrane potential, caspase-3 activity, ATG5, Beclin-1 protein expression and Akt, mTOR phosphorylation levels were detected. Results: The key targets of UAþATS-AD network were mainly enriched in Akt/mTOR pathway. Cell experiments showed that UA (ED50: 5lM) þ ATS (ED50: 40lM) could protect H2O2-induced (IC50: 250lM) nerve damage by enhancing cells viability, combating apoptosis, restoring MMP, reducing the activation of caspase-3, lessening the phosphorylation of Akt and mTOR, and increasing the expression of ATG5 and Beclin-1. Conclusions: ATS and UA regulates multiple targets, bioprocesses and signal pathways against AD pathogenesis. ATS and UA synergistically protects H2O2-induced neurotrosis by regulation of AKT/mTOR signalling. [ABSTRACT FROM AUTHOR]
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- 2022
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32. T4 reduces cisplatin resistance by inhibiting AEG-1 gene expression in lung cancer cells
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Tian-Jiao, Song, Xiao-Hong, Lin, Ping-Ting, Huang, Yu-Qing, Chen, and Li-Min, Chen
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Lung Neoplasms ,Multidisciplinary ,endocrine system diseases ,Gene Expression ,Membrane Proteins ,RNA-Binding Proteins ,Antineoplastic Agents ,Apoptosis ,Phenanthrenes ,respiratory system ,respiratory tract diseases ,Drug Resistance, Neoplasm ,Humans ,Cisplatin ,Diterpenes ,Transcription Factors - Abstract
BackgroundLung cancer is one of the deadliest diseases in the world. Most lung cancer patients are resistant to chemotherapy drugs. In our study, we investigated whether T4 can reduce the resistance of lung cancer cells to chemotherapeutic drugs through the action of AEG-1.Materials and Methods1.A549 and A549/DDP cells were respectively transfected with overexpressing AEG-1 and knockdown AEG-1 plasmid. A549 and A549/DDP cells were added 0、25、50、100、200nM T4 respectively. 200nM T4 was selected for following experiments. A549/DDP cells were divided into A549/DDP empty group, T4 group, T4+AEG-1 overexpressing group. CCK8 assay was used to detect the proliferation of cells in each group. RT-qPCR and Western blotting were used to detect the expression of AEG-1 and MDR-1.ResultsAs expected, the expression of AEG-1 in A549 and A549/DDP cells is positively correlated with cisplatin resistance. When AEG-1 protein was overexpressed in A549 cells, the lethal effect of cisplatin on A549 cells was attenuated (all P
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- 2022
33. Overactivation of corticotropin-releasing factor receptor type 1 and aquaporin-4 by hypoxia induces cerebral edema
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Chen, Shao-Jun, Yang, Jia-Fang, Kong, Fan-Ping, Ren, Ji-Long, Hao, Ke, Li, Min, Yuan, Yuan, Chen, Xin-Can, Yu, Ri-Sheng, Li, Jun-Fa, Leng, Gareth, Chen, Xue-Qun, and Du, Ji-Zeng
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- 2014
34. Asporin represses gastric cancer apoptosis via activating LEF1-mediated gene transcription independent of β-catenin
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Shutian Zhang, Zheng Zhang, Yu Zhao, Li Min, Si Liu, Shengtao Zhu, Lei Chen, Qingdong Guo, Hengcun Li, and Peng Li
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0301 basic medicine ,Cancer Research ,Gene knockdown ,Lymphoid Enhancer-Binding Factor 1 ,Cell growth ,Wnt signaling pathway ,Asporin ,Apoptosis ,Promoter ,Biology ,Cell biology ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Stomach Neoplasms ,030220 oncology & carcinogenesis ,Catenin ,embryonic structures ,Cancer cell ,Genetics ,Humans ,Ectopic expression ,Molecular Biology - Abstract
Asporin (ASPN) presents in the tumor microenvironment and exhibits a cancer-promoting effect as a stroma protein. Even though ASPN has already been observed inside cancer cells, the functions of intracellular ASPN and its underlying mechanisms remain unknown. Here we reported that ASPN was upregulated in different stages of gastric cancer (GC), and associated with a poor prognosis. Moreover, we found that ASPN markedly inhibited GC cell apoptosis and promoted cell growth in vitro and in vivo. Further mechanism investigations revealed that ASPN directly binding to lymphoid enhancer-binding factor 1 (LEF1) and promoted LEF1-mediated gene transcription independent of β-catenin, the classic co-factor in the Wnt/LEF1 pathway. We also demonstrated that ASPN selectively facilitated LEF1 binding to and activating the promoters of PTGS2, IL6, and WISP1 to promote their transcription. The suppression of cell apoptosis by ASPN overexpression could be attenuated by LEF1 knockdown or 100 µM aspirin (PTGS2 inhibitor), and siASPN mediated apoptosis could be rescued by LEF1 ectopic expression or adding recombinant IL6. Therefore, we concluded that ASPN repressed GC cell apoptosis via activating LEF1-mediated gene transcription independent of β-catenin, which could serve as a potential prognostic biomarker in GC patients.
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- 2021
35. Regulation of HepG2 cell apoptosis by hepatitis C virus (HCV) core protein via the sirt1–p53–bax pathway
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Feng, Shenghu, Li, Min, Zhang, Jinqian, Liu, Shunai, Wang, Qi, Quan, Min, Zhang, Mengran, and Cheng, Jun
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- 2015
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36. Patient-Derived Tumor Xenografts Plus Ex Vivo Models Enable Drug Validation for Tenosynovial Giant Cell Tumors
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Xin He, Fan Tang, Chongqi Tu, Yi Luo, Xiawei Wei, Jingyun Yang, Yong Zhou, Li Min, Houhui Shi, Siyuan Chen, Yan Tie, and Weiqi Hong
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business.industry ,Monocyte ,Histology ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Oncology ,Apoptosis ,Surgical oncology ,In vivo ,030220 oncology & carcinogenesis ,Cancer research ,medicine ,030211 gastroenterology & hepatology ,Surgery ,Giant Cell Tumors ,Receptor ,business ,Ex vivo - Abstract
Tenosynovial giant cell tumor (TGCT) is a locally aggressive tumor with colony-stimulating factor 1 receptor (CSF1R) signal expression. However, there is a lack of better in vivo and ex vivo models for TGCT. This study aims to establish a favorable preclinical translational platform, which would enable the validation of efficient and personalized therapeutic candidates for TGCT. Histological analyses were performed for the included patients. Fresh TGCT tumors were collected and sliced into 1.0–3.0 mm3 sections using a sterilized razor blade. The tumor grafts were surgically implanted into subrenal capsules of athymic mice to establish patient-derived tumor xenograft (PDTX) mouse models. Histological and response patterns to CSF1R inhibitors evaluations were analyzed. In addition, ex vivo cultures of patient-derived explants (PDEs) with endpoint analysis were used to validate TGCT graft response patterns to CSF1R inhibitors. The TGCT tumor grafts that were implanted into athymic mice subrenal capsules maintained their original morphological and histological features. The “take” rate of this model was 95% (19/20). Administration of CSF1R inhibitors (PLX3397, and a novel candidate, WXFL11420306) to TGCT-PDTX mice was shown to reduce tumor size while inducing intratumoral apoptosis. In addition, the CSF1R inhibitors suppressed circulating nonspecific monocyte levels and CD163-positive cells within tumors. These response patterns of engrafts to PDTX were validated by ex vivo PDE cultures. Subrenal capsule supports the growth of TGCT tumor grafts, maintaining their original morphology and histology. This TGCT-PDTX model plus ex vivo explant cultures is a potential preclinical translational platform for locally aggressive tumors, such as TGCT.
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- 2021
37. Nanostructured Dihydroartemisinin Plus Epirubicin Liposomes Enhance Treatment Efficacy of Breast Cancer by Inducing Autophagy and Apoptosis
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Ying-Jie Hu, Jing-Ying Zhang, Qian Luo, Jia-Rui Xu, Yan Yan, Li-Min Mu, Jing Bai, and Wan-Liang Lu
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dihydroartemisinin ,liposomes ,autophagy ,apoptosis ,breast cancer ,Chemistry ,QD1-999 - Abstract
The heterogeneity of breast cancer and the development of drug resistance are the relapse reasons of disease after chemotherapy. To address this issue, a combined therapeutic strategy was developed by building the nanostructured dihydroartemisinin plus epirubicin liposomes. Investigations were performed on human breast cancer cells in vitro and xenografts in nude mice. The results indicated that dihydroartemisinin could significantly enhance the efficacy of epirubicin in killing different breast cancer cells in vitro and in vivo. We found that the combined use of dihydroartemisinin with epirubicin could efficiently inhibit the activity of Bcl-2, facilitate release of Beclin 1, and further activate Bax. Besides, Bax activated apoptosis which led to the type I programmed death of breast cancer cells while Beclin 1 initiated the excessive autophagy that resulted in the type II programmed death of breast cancer cells. In addition, the nanostructured dihydroartemisinin plus epirubicin liposomes prolonged circulation of drugs, and were beneficial for simultaneously delivering drugs into breast cancer tissues. Hence, the nanostructured dihydroartemisinin plus epirubicin liposomes could provide a new therapeutic strategy for treatment of breast cancer.
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- 2018
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38. The Janus-faced role of TRPM2-S in retroperitoneal liposarcoma via increasing ROS levels
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Xiangji Li, Fanqin Bu, Shixiang Ma, Ferdinando Cananzi, Yu Zhao, Mengmeng Xiao, Li Min, and Chenghua Luo
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Oxidative Stress ,TRPM Cation Channels ,Apoptosis ,Calcium ,Cell Biology ,Hydrogen Peroxide ,Liposarcoma ,Retroperitoneal Neoplasms ,Reactive Oxygen Species ,Molecular Biology ,Biochemistry - Abstract
Background Retroperitoneal liposarcoma (RPLS) is a specific soft tissue sarcoma with a high recurrence rate. The short isoform of transient receptor potential cation channel subfamily M member 2 (TRPM2-S) plays an important role in the regulation of reactive oxygen species (ROS). However, the association between TRPM2-S and RPLS and its underlying mechanisms remains unclear. Methods The expression of both TRPM2-S and TRPM2-L in RPLS tissues was verified by kimmunohistochemistry (IHC). The regulation on Ca2+ influx by TRPM2-S was evaluated by Fluo-4 AM staining. The effect of TRPM2-S on cell proliferation and apoptosis was tested by 5-Ethynyl-2′-deoxyuridine (EdU) staining and Flow cytometry respectively. The level of cellular ROS was assessed by the DCFH-DA probe. Different concentrations of H2O2 were used to provide oxidative stress on RPLS cells. The underlying mechanisms were further explored by Western blotting. Results The IHC assays showed that TRPM2-S, but not TRPM2-L, was prognostic in RPLS. Low TRPM2-S level was associated with poor disease-free survival (DFS). Calcium influx signal intensity was significantly decreased under TRPM2-S overexpression, which resulted in a decrease in the levels of FOXO3a and PTEN. Correspondingly, the levels of pERK, pAKT, pP65, pGSK-3β, Bcl-2, and β-catenin were upregulated, and cellular ROS was gently increased under TRPM2-S overexpression. Moreover, TRPM2-S slightly promoted cell proliferation and inhibited apoptosis of RPLS cell lines under normoxia, but largely increased apoptosis rates under oxidative stress. The cleaved caspase3 was significantly upregulated by TRPM2-S overexpression under oxidative stress. N-Acetyl-l-cysteine (NAC), a small molecule antioxidant, could largely rescue RPLS cells from the apoptosis induced by H2O2. Conclusion TRPM2-S exerts Janus-faced effects in RPLS by increasing the ROS levels via inhibition on FOXO3a, which promotes cell proliferation under normoxia but induces apoptosis under oxidative stress.
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- 2022
39. Post-shock Mesenteric Lymph Drainage Ameliorates Cellular Immune Function in Rats Following Hemorrhagic Shock
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Liu, Hua, Zhao, Zi-Gang, Xing, Li-Qiang, Zhang, Li-Min, and Niu, Chun-Yu
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- 2015
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40. Up-regulation of SKIP relates to retinal ganglion cells apoptosis after optic nerve crush in vivo
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Wu, Yu, Xu, Fan, Huang, Hui, Chen, Lifei, Wen, Meidan, Jiang, Li, Lu, Lu, Li, Li, Song, Di, Zeng, Siming, Li, Li, and Li, Min
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- 2014
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41. Upregulation of Gem relates to retinal ganglion cells apoptosis after optic nerve crush in adult rats
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Xu, Fan, Huang, Hui, Wu, Yu, Lu, Lu, Jiang, Li, Chen, Lifei, Zeng, Siming, Li, Li, and Li, Min
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- 2014
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42. Polydatin exerts anti-tumor effects against renal cell carcinoma cells via induction of caspase-dependent apoptosis and inhibition of the PI3K/Akt pathway
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Li-Min Xin, Chang-Chun Zhou, Yu Ren, and Yi-Li Jin
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0301 basic medicine ,renal cell carcinoma ,Resveratrol ,PI3K ,OncoTargets and Therapy ,Caspase-Dependent Apoptosis ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Downregulation and upregulation ,polydatin ,Pharmacology (medical) ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Original Research ,Chemistry ,Cell growth ,Akt/PKB signaling pathway ,Akt ,apoptosis ,Retraction ,030104 developmental biology ,Oncology ,Apoptosis ,030220 oncology & carcinogenesis ,Cancer research - Abstract
Yi-Li Jin,1 Li-Min Xin,2 Chang-Chun Zhou,1 Yu Ren2 1Department of Urology, Dongyang People’s Hospital, Wenzhou Medical University, Dongyang, Zhejiang 322100, People’s Republic of China; 2Laboratory of kidney Carcinoma, Ningbo Urology and Nephrology Hospital, Urology and Nephrology Institute of Ningbo University, Ningbo 315000, Zhejiang Province, People’s Republic of China Purpose: Polydatin, a stilbenoid glucoside of a resveratrol derivative, has many biological functions, including antitumor effects. However, the antitumor effects of polydatin in renal cell carcinoma (RCC) have not been investigated. Materials and methods: In the current study, MTT assays, transwell invasion assays and wound healing assays were performed to examine cell proliferation, invasion and migration. An apoptosis nucleosome ELISA was used to measure apoptosis. Caspase activity assays were applied to measure the activities of caspase-3/9. A Western blot assay was used to measure the change in protein levels. Results: Our data demonstrated that polydatin inhibited the proliferation of RCC cells but not normal renal epithelial cells in a time- and dose-dependent manner. Polydatin also triggered apoptosis in a caspase-dependent manner. Moreover, polydatin treatment also led to the downregulation of Bcl-2 and Mcl-1 and to activation of Bax. Ectopic expression of Bcl-2 and Mcl-1 or silencing of Bax could repress the apoptosis that was induced by polydatin. Moreover, incubation with polydatin also suppressed the PI3K/Akt signaling pathway in RCC cells. Conclusion: Taken together, our data indicated that polydatin may be applied as a potent agent against RCC. Keywords: polydatin, renal cell carcinoma, apoptosis, PI3K, Akt
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- 2018
43. miR-18b attenuates cerebral ischemia/reperfusion injury through regulation of ANXA3 and PI3K/Akt signaling pathway
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Xiao-li Min, Ying Shi, Ling Xie, Xiao-jia Ma, He Mu, and Cao Yi
- Subjects
Male ,0301 basic medicine ,Ischemia ,Pharmacology ,Neuroprotection ,Brain Ischemia ,Proinflammatory cytokine ,Mice ,Phosphatidylinositol 3-Kinases ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,Animals ,Humans ,Medicine ,Annexin A3 ,PI3K/AKT/mTOR pathway ,TUNEL assay ,business.industry ,Akt/PKB signaling pathway ,General Neuroscience ,medicine.disease ,Mice, Inbred C57BL ,MicroRNAs ,030104 developmental biology ,Apoptosis ,Reperfusion Injury ,business ,Proto-Oncogene Proteins c-akt ,Reperfusion injury ,030217 neurology & neurosurgery ,Signal Transduction - Abstract
Recent, research has displayed that the disorders of miR-18b are related to ischemic stroke. Here, we aimed to investigate the underlying neuroprotective mechanism of miR-18b in cerebral ischemia/reperfusion (I/R) injury. Oxygen-glucose deprivation/reperfusion (OGDR) model in vitro and middle cerebral artery occlusion (MCAO) model in vivo were established to simulate cerebral I/R injury. RT-PCR, western blotting, CCK-8, TUNEL, and TTC staining assays were applied in this study to explore the effect of miR-18b on cerebral I/R injury. Results displayed that miR-18b expression was reduced after cerebral I/R injury. Besides, miR-18b showed neuroprotective effects on cerebral I/R injury both in vitro and in vivo, These neuroprotective effects included promoting cell viability, decreasing cell apoptosis, reducing the production of inflammatory cytokines in SH-SY 5Y cells after OGDR and depressing MCAO-induced infarct size, neurological deficits and apoptotic cells in mice. Moreover, miR-18b negatively regulated ANXA3 expression, and its neuroprotection on cerebral I/R injury was overturned by ANXA3. Additionally, increasing miR-18b or decreasing ANXA3 promoted the activation of the PI3K/Akt signaling pathway in SH-SY 5Y cells after cerebral I/R injury. In conclusion, these data indicate that miR-18b protects against cerebral I/R injury by inhibiting ANXA3 and activating PI3K/Akt pathway, which provides a promising therapeutic target for ischemic stroke therapy.
- Published
- 2020
44. Intracellular matrix Gla protein promotes tumor progression by activating JAK2/STAT5 signaling in gastric cancer
- Author
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Qingdong Guo, Lei Chen, Shuilong Guo, Li Min, Rui Wei, Shengtao Zhu, Shutian Zhang, Shengquan Zhu, Mizhu Wang, and Yu Chen
- Subjects
0301 basic medicine ,Male ,Cancer Research ,Carcinogenesis ,JAK2/STAT5 pathway ,Apoptosis ,0302 clinical medicine ,Cell Movement ,Matrix gla protein ,Databases, Genetic ,STAT5 Transcription Factor ,RNA, Small Interfering ,Research Articles ,Extracellular Matrix Proteins ,biology ,Chemistry ,General Medicine ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Prognosis ,Immunohistochemistry ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,Oncology ,030220 oncology & carcinogenesis ,Molecular Medicine ,Female ,Signal transduction ,Intracellular ,Research Article ,Signal Transduction ,Immunoprecipitation ,lcsh:RC254-282 ,03 medical and health sciences ,Stomach Neoplasms ,Cell Line, Tumor ,Genetics ,Gene silencing ,Humans ,Neoplasm Invasiveness ,Gene Silencing ,Aged ,Cell Proliferation ,Cell Nucleus ,Cell growth ,gastric cancer ,matrix Gla protein ,Tumor Suppressor Proteins ,Calcium-Binding Proteins ,nutritional and metabolic diseases ,Janus Kinase 2 ,Molecular biology ,030104 developmental biology ,Cell culture ,Tumor progression ,biology.protein ,Interleukin-2 ,progression - Abstract
Matrix Gla protein (MGP) has been widely reported as an extracellular matrix protein with abnormal expression in various types of cancer. However, the function of intracellular MGP in gastric cancer (GC) cells remains largely unknown. Here, we demonstrated aberrantly high expression of intracellular MGP in GC as compared to adjacent normal tissues by immunohistochemistry. Moreover, The Cancer Genome Atlas (TCGA) dataset analysis suggested a positive correlation between MGP overexpression and unfavorable prognosis. MGP silencing reduced cell proliferation, migration, invasion, and survival in GC cell lines. Gene set enrichment analysis of TCGA dataset indicated significant enrichment of the IL2–STAT5 signaling in MGP‐high GC patients. Immunofluorescence staining and immunoprecipitation showed that MGP binds to p‐STAT5 in the nuclei of GC cells. Furthermore, ChIP‐qPCR and luciferase reporter assays indicated that MGP acts as a transcriptional co‐activator through the enhancement of STAT5 binding to target gene promoters. Use of STAT5 inhibitor revealed that the oncogenic functions of intracellular MGP mainly depend on the JAK2/STAT5 signaling pathway. Taken together, our results indicate that intracellular MGP promotes proliferation and survival of GC cells by acting as a transcriptional co‐activator of STAT5. The detected aberrant, high MGP expression in GC tissues highlights MGP as a potential new prognostic biomarker in patients with GC., Matrix Gla protein is a novel transcriptional co‐activator of STAT5 by interacting with phospho‐STAT5 in the nuclei, which facilitates STAT5 binding to target gene promoters and subsequently promotes gastric cancer cell proliferation, migration, invasion and survival.
- Published
- 2020
45. RBBP8/CtIP suppresses P21 expression by interacting with CtBP and BRCA1 in gastric cancer
- Author
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Shutian Zhang, Li Min, Shengtao Zhu, Yang Yu, Guiping Zhao, Qingdong Guo, Lei Chen, Hengcun Li, and Peng Li
- Subjects
Cyclin-Dependent Kinase Inhibitor p21 ,0301 basic medicine ,Cancer Research ,DNA Repair ,Apoptosis ,Hydroxamic Acids ,03 medical and health sciences ,0302 clinical medicine ,Cyclin D1 ,Stomach Neoplasms ,Biomarkers, Tumor ,Tumor Cells, Cultured ,Genetics ,medicine ,Humans ,DNA Breaks, Double-Stranded ,Promoter Regions, Genetic ,Molecular Biology ,Cell Proliferation ,Regulation of gene expression ,Endodeoxyribonucleases ,biology ,BRCA1 Protein ,Cell Cycle ,Acetylation ,Cell cycle ,Prognosis ,Cell biology ,Gene Expression Regulation, Neoplastic ,Histone Deacetylase Inhibitors ,Survival Rate ,030104 developmental biology ,Histone ,Trichostatin A ,Case-Control Studies ,030220 oncology & carcinogenesis ,biology.protein ,Histone deacetylase ,Chromatin immunoprecipitation ,medicine.drug - Abstract
RB Binding Protein 8 (RBBP8) was previously reported being involved in DNA double-strand break (DSB) repair in cancers. However, there is no systematic study about the specific functions and related mechanisms of RBBP8 in gastric carcinogenesis. Through immunohistochemistry staining of paired gastric cancer (GC) tissues, adjacent high-grade intraepithelial neoplasia (HGIEN) tissues, and non-cancerous tissues, we found RBBP8 expression was upregulated in both HGIEN and GC tissues. Functional experiments showed the knockdown of RBBP8 inhibited cell proliferation and colony formation ability. This is mainly achieved through the role of RBBP8 in facilitating G1/S transition and promoting Cyclin D1 and CDK4 level. Then the interaction between RBBP8, BRCA1, and CtBP was revealed by co-immunoprecipitation (co-IP) and immunofluorescence confocal imaging. Moreover, we found RBBP8 acted as an adapter in this complex and RBBP8 overexpression enhanced the nucleus location of BRCA1. RBBP8 overexpression could inhibit P21 expression and HDAC (histone deacetylase) inhibitor Trichostatin A (TSA) eliminated this effect. The HDAC activity of CtBP-RBBP8-BRCA1 complex was also further verified by HDAC activity assay. Through Chromatin immunoprecipitation (ChIP), we found RBBP8 could induce P21 promoter histone deacetylation and inhibit P21 transcription. In conclusion, we found RBBP8 could promote the G1/S transition of GC cells by inhibiting P21 level. Moreover, we revealed the chromatin modification role of RBBP8, which could suppress the histone acetylation level of P21 promoter by recruiting CtBP co-repressor complex to BRCA1 binding site.
- Published
- 2019
46. Adiponectin receptor agonist AdipoRon relieves endotoxin-induced acute hepatitis in mice
- Author
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Wen-Ze Xiao, Li Zhang, and Li-Min Chen
- Subjects
Lipopolysaccharides ,Male ,Agonist ,medicine.medical_specialty ,AdipoRon ,medicine.drug_class ,lcsh:Medicine ,Adipokine ,Apoptosis ,Galactosamine ,Lipopolysaccharide ,Hepatitis ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Piperidines ,Internal medicine ,medicine ,Animals ,Acute hepatitis ,Receptor ,Adiponectin receptor 1 ,Mice, Inbred BALB C ,Adiponectin ,business.industry ,lcsh:R ,Original Articles ,General Medicine ,Transforming Growth Factor alpha ,medicine.disease ,Disease Models, Animal ,Endocrinology ,chemistry ,Caspases ,030220 oncology & carcinogenesis ,Acute Disease ,Hepatocytes ,Tumor necrosis factor alpha ,Receptors, Adiponectin ,D-galactosamine ,business ,030217 neurology & neurosurgery - Abstract
Background: Adiponectin is the most abundant adipokines that plays critical roles in the maintenance of energy homeostasis as well as inflammation regulation. The half-life of adiponectin is very short and the small-molecule adiponectin receptor agonist has been synthesized recently. In the present study, the potential roles of AdipoRon, an adiponectin receptor agonist, in a mouse model of lipopolysaccharide (LPS)/D-galactosamine (D-Gal)-induced acute hepatitis was explored. Methods: BALB/c mice (n = 144, male) were divided into three sets. In set 1, 32 mice were randomized into four groups: the control group, the AdipoRon group, the LPS/D-Gal group, and the AdipoRon + LPS/D-Gal group. The mice in set 1 were sacrificed after LPS/D-Gal treatment, and the plasma samples were collected for detection of tumor necrosis factor-alpha (TNF-α). In set 2, the 32 mice were also divided into four groups similar to that of set 1. The mice were sacrificed 6 h after LPS/D-Gal injection and plasma samples and liver were collected. In set 3, 80 mice (divided into four groups, n = 20) were used for survival observation. The survival rate, plasma aminotransferases, histopathological damage were measured and compared between these four groups. Results: AdipoRon suppressed the elevation of plasma aminotransferases (from 2106.3 ± 781.9 to 286.8 ± 133.1 U/L for alanine aminotransferase, P < 0.01; from 566.5 ± 243.4 to 180.1 ± 153.3 U/L for aspartate aminotransferase, P < 0.01), attenuated histopathological damage and improved the survival rate (from 10% to 60%) in mice with LPS/D-Gal-induced acute hepatitis. Additionally, AdipoRon down-regulated the production of TNF-α (from 328.6 ± 121.2 to 213.4 ± 52.2 pg/mL, P < 0.01), inhibited the activation of caspase-3 (from 2.04-fold to 1.34-fold of the control), caspase-8 (from 2.03-fold to 1.31-fold of the control), and caspase-9 (from 2.14-fold to 1.43-fold of the control), and decreased the level of cleaved caspase-3 (0.28-fold to that of the LPS/D-Gal group). The number of terminal deoxynucleotidyl transferase-mediated nucleotide nick-end labeling-positive apoptotic hepatocytes in LPS/D-Gal-exposed mice also reduced. Conclusions: These data indicated that LPS/D-Gal-induced acute hepatitis was effectively attenuated by the adiponectin receptor agonist AdipoRon, implying that AdipoRon might become a new reagent for treatment of acute hepatitis. Key words: AdipoRon; Lipopolysaccharide; D-galactosamine; Acute hepatitis; Apoptosis
- Published
- 2019
47. Dual-responsive nanoparticles based on chitosan for enhanced breast cancer therapy
- Author
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Jianrong Wu, Hong Zheng, Xia Chen, Xuejing Zhang, Shiwei Niu, Li-Min Zhu, and Gareth R. Williams
- Subjects
Paclitaxel ,Polymers and Plastics ,Apoptosis ,Breast Neoplasms ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Rats, Sprague-Dawley ,Chitosan ,Mice ,chemistry.chemical_compound ,Breast cancer ,Cell Line, Tumor ,Hyaluronic acid ,Human Umbilical Vein Endothelial Cells ,Materials Chemistry ,medicine ,Animals ,Humans ,Viability assay ,Hyaluronic Acid ,Drug Carriers ,Organic Chemistry ,021001 nanoscience & nanotechnology ,medicine.disease ,Antineoplastic Agents, Phytogenic ,Xenograft Model Antitumor Assays ,0104 chemical sciences ,Drug Liberation ,chemistry ,Drug delivery ,Cancer cell ,Cancer research ,Methacrylates ,Nanoparticles ,Ethylene Glycols ,Female ,0210 nano-technology ,Ethylene glycol - Abstract
In this study, we report a novel pH and temperature responsive paclitaxel-loaded drug delivery system based on chitosan and di(ethylene glycol) methyl ether methacrylate. This was functionalized with hyaluronic acid to permit active targeting of CD44-overexpressing human breast cancer cells. The resultant HA-CS-g-PDEGMA-PTX nanoparticles (NPs) have small and uniform sizes (˜170 nm), a high drug loading (13.6 ± 1.3%) and high encapsulation efficiency (76.2 ± 8.5%). Cell viability and confocal microscopy experiments demonstrated that the NPs could effectively target and kill MDA-MB-231 human breast cancer cells, but were much less toxic to healthy human umbilical vein endothelial cells. In vivo biodistribution studies in mice showed that the NPs accumulated in the tumor site, while free drug was distributed more widely and rapidly cleared from the body. Histopathological studies revealed that the NPs led to enhanced apoptosis in the tumor site, which resulted in reduced tumor growth. The NPs prepared in this work have great potential for the treatment of breast cancers, and further offer a platform with which to target other cancers.
- Published
- 2019
48. [Inhibition Effect of Eriodictyol to Growth of DG-75 Cells and the Related Action Mechanism]
- Author
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Bin, Liu, Dao, Wang, Xia, Sun, Xi-Xi, Zhao, Ming-Li, Xiang, Li-Min, Jin, Na, Li, and Shao-Qiong, Niu
- Subjects
Phosphatidylinositol 3-Kinases ,Flavanones ,Apoptosis ,Signal Transduction - Abstract
To explore the effects of Eriodictyol to the growth, apoptosis and oxidative stress of Burkitt lymphoma (BL) cells and phosphorylation of protein kinase B (AKT) in children.The effects of Eriodictyol (0, 1.25, 2.5, 5, 10, 20, 40, 80, 160, 320 μmol/L) to viability of BL cell line DG-75 cells were detected by CCK-8. The effects of Eriodictyol (0, 10, 20, 40 μmol/L) to the proliferation activity of DG-75, apoptosis rate, levels of apoptosis-related proteins, oxidative stress indexes [superoxide dismutase (SOD), malondialdehyde (MDA)], mitochondrial membrane potential (MMP) and phosphorylation level of phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycinm (mTOR) were detected by clony formation assay and Wester blot.When the treatment concentration of Eriodictyol was 20 μmol/L, the proliferation activity of the cells was decreased (P0.05). The concentrations at 10, 20, 40 μmol/L were selected for subsequent experiments. Compared with 0 μmol/L Eriodictyol, the proliferation activity of DG-75, SOD activity, MMP, phosphorylation levels of PI3K, AKT and mTOR in 20 and 40 μmol/L Eriodictyol treatment groups were significantly decreased (P0.05), while cells apoptosis rate, Cleaved-Caspase-3/Caspase-3, Bax/Bcl-2 and MDA level were significantly increased (P0.05).Eriodictyol may promote the mitochondrial apoptosis pathway by inhibiting the abnormal activation of PI3K/AKT/mTOR to reduce the proliferation activity of DG-75, and inhibit oxidative stress response to increase the apoptosis rate and play anti-tumor roles.圣草酚对DG-75细胞生长的抑制作用及相关作用机制研究.探讨圣草酚(Eriodictyol)对儿童伯基特淋巴瘤(BL)细胞生长、凋亡和氧化应激的调节以及蛋白激酶B(AKT)磷酸化的影响.CCK-8法检测圣草酚 0、1.25、2.5、5、10、20、40、80、160、320 μmol/L对BL细胞系DG-75细胞活力的影响;克隆形成实验和流式细胞术等方法检测圣草酚 0、10、20、40 μmol/L对DG-75细胞增殖活性、凋亡率、凋亡相关蛋白水平、氧化应激指标[超氧化物歧化酶(SOD)、丙二醛(MDA)]、线粒体膜电位、磷脂酰肌醇激酶(PI3K)/蛋白激酶B(AKT)/雷帕霉素靶蛋白(mTOR)磷酸化水平的影响.圣草酚处理浓度为20 μmol/L时,细胞增殖活性降低(P0.05),选取10、20、40 μmol/L用于后续试验。与圣草酚 0 μmol/L处理组比较,圣草酚 20、40 μmol/L处理组DG-75细胞的增殖活性、SOD活性、线粒体膜电位、PI3K、AKT、mTOR磷酸化水平均明显降低(P0.05),细胞凋亡率、Cleaved-Caspase-3/Caspase-3比率、Bax/Bcl-2比率、MDA水平均明显升高(P0.05).圣草酚可能通过抑制PI3K/AKT/mTOR异常活化来促进线粒体凋亡途径使DG-75增殖活性降低,并抑制氧化应激反应,细胞凋亡率升高,从而发挥抗肿瘤作用.
- Published
- 2021
49. Circular RNA circ_GLIS2 suppresses hepatocellular carcinoma growth and metastasis
- Author
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Li-Min Chen, Xue-Fei Cui, Zhen-Guo Liu, Hao-Ye Zhang, Peng-Cheng Zhou, Wu Xing, and Yang-Mei Zhou
- Subjects
Messenger RNA ,Carcinoma, Hepatocellular ,Hepatology ,medicine.diagnostic_test ,biology ,Cell growth ,Liver Neoplasms ,RNA, Circular ,medicine.disease ,biology.organism_classification ,digestive system diseases ,Flow cytometry ,Metastasis ,Blot ,Mice ,MicroRNAs ,Nude mouse ,Apoptosis ,Hepatocellular carcinoma ,Cell Line, Tumor ,medicine ,Cancer research ,Animals ,Humans ,Cell Proliferation - Abstract
BACKGROUND & AIMS Hepatocellular carcinoma (HCC) is one of the leading causes of tumour-related death. Here, we investigated the molecular mechanism of HCC by studying the function of circ_GLIS2. METHODS Human HCC specimens and cell lines were used. Sanger sequencing, actinomycin D and RNase R treatment were performed to validate circular RNA features of circ_GLIS2. qRT-PCR, western blotting, immunostaining, and IHC were employed to examine levels of circ_GLIS2, GLIS2 mRNA, and EMT-related markers. CCK-8, colony formation, flow cytometry, wound healing assay, and transwell assays were performed to evaluate cancer cell proliferation, apoptosis, migration, and invasion. RIP and RNA pull-down assay were used to validate EIF4A3/GLIS2 mRNA interaction. MSP was performed to measure the methylation status of GLIS2 promoter. Nude mouse xenograft model was used to examine tumour growth and metastasis in vivo. RESULTS Circ_GLIS2 and linear GLIS2 mRNA were reduced in human HCC tissues and cells. Their low levels correlated with a poor survival rate of HCC patients. Overexpression of circ_GLIS2 and GLIS2 suppressed HCC cell proliferation, migration, and invasion but promoted cell apoptosis. GLIS2 promoter region was hypermethylated in HCC cells. EIF4A3 was directly bound with GLIS2 mRNA and promoted circ_GLIS2/GLIS2 expression. Moreover, overexpression of circ_GLIS2 restrained HCC tumour growth and metastasis in vivo. CONCLUSION Circ_GLIS2 suppresses HCC growth and metastasis by inhibiting cell proliferation, migration, and invasion, but promoting cell apoptosis. These findings provide molecular insights into the mechanism of HCC and indicate that circ_GLIS2 could serve as a diagnosis marker or therapeutic target for HCC.
- Published
- 2021
50. CircRNAPTK2 Promotes Cardiomyocyte Apoptosis in Septic Mice by Competitively Binding to miR-29b-3p with BAK1
- Author
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Hui Xiao, Quanzhu Fu, and Li Min
- Subjects
Mice ,MicroRNAs ,bcl-2 Homologous Antagonist-Killer Protein ,Sepsis ,Immunology ,Immunology and Allergy ,Animals ,Apoptosis ,Myocytes, Cardiac ,General Medicine ,RNA, Circular ,RNA, Messenger - Abstract
Objective: Sepsis is a predominant reason for the growing morbidity and mortality in the world. The role of circular RNAs (CircRNAs) is actively researched in sepsis. In this study, we attempt to find out the effect of CircRNA protein tyrosine kinase 2 (circPTK2) on cardiomyocyte apoptosis in septic mice. Methods: Septic mouse model was established by cecal ligation and puncture. Then circPTK2 expression was detected and the role of circPTK2 in myocardial damage was assessed after circPTK2 expression was silenced using Ad-sh-circHIPK3. The subcellular localization of circPTK2 was analyzed. Besides, the binding relation between circPTK2 and microRNA (miR)-29b-3p and between miR-29b-3p and BCL2 antagonist/killer 1 (BAK1) was verified. The expression of miR-29b-3p and BAK1 in the myocardium was detected. Functional rescue was conducted to evaluate the role of miR-29b-3p and BAK1 in cardiomyocyte apoptosis in septic mice. Results: CircPTK2 was highly expressed in the myocardium of septic mice, while circPTK2 silencing relieved the cardiac function and reduced inflammatory reaction and cardiomyocyte apoptosis of septic mice. Mechanically, circPTK2 competitively bound to miR-29b-3p to upregulate BAK1 mRNA level. Inhibition of miR-29b-3p and BAK1 overexpression could counteract the protective role of circPTK2 silencing in the myocardium of septic mice. Conclusion: CircPTK2 is overexpressed in the myocardium of septic mice. CircPTK2 competitively bound to miR-29b-3p to upregulate BAK1 mRNA level, to promote cardiomyocyte apoptosis, inflammatory response, and myocardial damage of the myocardium of septic mice.
- Published
- 2021
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