المؤلفون: Rui Jin, Xuan Zhou, Xiaofeng Yao, Qiang Zhang, Ping Li, Chao Jing, Yu Wang, Wenchao Zhang, Yuansheng Duan, Xudong Wang, Yingjie Tao

المصدر: Cancer Letters. 432:38-46

مصطلحات موضوعية: 0301 basic medicine, Cancer Research, Epithelial-Mesenchymal Transition, Lung Neoplasms, Adenoid cystic carcinoma, Perineural invasion, Mice, Nude, Motility, Apoptosis, medicine.disease_cause, Metastasis, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cell Movement, Tumor Cells, Cultured, medicine, Animals, Humans, Cell Proliferation, Mice, Inbred BALB C, Mutation, business.industry, Liver Neoplasms, NF-kappa B, Zinc Finger E-box-Binding Homeobox 1, NF-κB, Prognosis, Salivary Gland Neoplasms, medicine.disease, Carcinoma, Adenoid Cystic, Xenograft Model Antitumor Assays, Gene Expression Regulation, Neoplastic, Survival Rate, Insulin-Like Growth Factor Binding Protein 2, 030104 developmental biology, Oncology, chemistry, Lymphatic Metastasis, 030220 oncology & carcinogenesis, Cancer research, Signal transduction, business, Nuclear localization sequence, Signal Transduction

الوصف: Metastasis is a major cause of poor prognosis in patients suffered with salivary adenoid cystic carcinoma (SACC), in which many factors are implicated. In this study, we identified that IGFBP2, overexpressed in SACC, correlated positively with perineural invasion or metastasis and indicated worse outcome. Moreover, IGFBP2 overexpression could dramatically improve motility and invasion capacity of SACC cells in vitro. Mechanically, IGFBP2 enhanced expression of ZEB1 in a NF-κB (p65)-dependent manner and then promoted epithelial-mesenchymal transition (EMT) in SACC. In addition, IGFBP2 mutation in the nuclear localization signal could impede nuclear translocation of p65, lower ZEB1 expression, and abrogate the EMT process. In xenograft models, IGFBP2 overexpression promoted lung and liver metastases of SACC cells; while if nuclear IGFBP2 was reduced, the formation of metastases in lung and liver was weakened. Together, these results for the first time demonstrate that IGFBP2 plays an important role in invasion and metastasis of SACC through the NF-κB/ZEB1 signaling pathway and IGFBP2 may be a novel biomarker and target for SACC.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3d4ac1ce9543ace508a445463d56d618Test
https://doi.org/10.1016/j.canlet.2018.06.008Test

المؤلفون: Chengyan Geng, Junjie Mei, Xiaofeng Yao, Zhiguo Li, Qiujuan Li, Jun Cao, Liping Jiang

المصدر: International journal of medicinal mushrooms. 21(6)

مصطلحات موضوعية: 0106 biological sciences, Antioxidant, Asia, genetic structures, medicine.medical_treatment, Apoptosis, Pharmacology, Mitochondrion, Polysaccharide, 01 natural sciences, Applied Microbiology and Biotechnology, 010608 biotechnology, Drug Discovery, medicine, Humans, chemistry.chemical_classification, Membrane Potential, Mitochondrial, Reactive oxygen species, biology, Chemistry, Cytochrome c, Basidiomycota, Fungal Polysaccharides, Hep G2 Cells, biology.organism_classification, Mitochondria, Tacrine, biology.protein, Inonotus obliquus, Medicine, Traditional, Reactive Oxygen Species, medicine.drug

الوصف: Tacrine is the first drug licensed for the treatment of Alzheimer disease. Unfortunately, reversible hepatotoxicity limits its clinical use. In our previous study, we found that tacrine induced apoptosis in HepG2 cells by reactive oxygen species (ROS) formation and mitochondria dysfunction. Inonotus obliquus is a mushroom traditionally used as a folk medicine in Asia. In this study, the possible protective effect of polysaccharides from I. obliquus was investigated. The results showed that I. obliquus polysaccharides (IOP) reduced tacrine-induced apoptosis in HepG2 cells. Inhibition of tacrine-induced ROS generation, 8-OHdG formation in mitochondrial DNA, and loss of the mitochondrial transmembrane potential by IOP were also observed. Furthermore, IOP decreased the cytochrome c release and activation of caspase-3 induced by tacrine. These data suggest that IOP could inhibit tacrine-induced apoptosis in HepG2 cells. The protection is mediated by an antioxidant protective mechanism. Consumption of IOP may be a plausible way to prevent tacrine-induced hepatotoxicity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7aa2be95e17d3fea9a9d0d85c55c3d9fTest
https://pubmed.ncbi.nlm.nih.gov/31679230Test

المؤلفون: Ming Sun, Cong Zhang, Xiance Sun, Liping Jiang, Xiaofeng Yao, Shaopeng Wang, Xueyan Wu, Guang Yang, Yueran Bai, Xiaofang Liu, Qian Chu

المصدر: Chemico-Biological Interactions. 288:24-31

مصطلحات موضوعية: 0301 basic medicine, Programmed cell death, animal structures, Down-Regulation, Antineoplastic Agents, Apoptosis, Toxicology, Patulin, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Autophagy, Humans, Viability assay, Cytotoxicity, Membrane Potential, Mitochondrial, Membrane potential, chemistry.chemical_classification, Reactive oxygen species, Chemistry, TOR Serine-Threonine Kinases, Liver Neoplasms, RNA-Binding Proteins, Hep G2 Cells, General Medicine, Acetylcysteine, Up-Regulation, Cell biology, 030104 developmental biology, 030220 oncology & carcinogenesis, Toxicity, Reactive Oxygen Species, Microtubule-Associated Proteins, Proto-Oncogene Proteins c-akt

الوصف: Patulin (PAT) is a secondary metabolite produced by certain species of Penicillium, Byssochlamys and Aspergillus. It has been shown to induce liver toxicity, but the possible molecular mechanisms are not completely elucidated. In our study, we treated Human Hepatoma G2 (HepG2) cells by 3-methyladenine (3-MA), an autophagosome formation inhibitor, and rapamycin, an autophagosome formation stimulator. The results showed that 3-MA protected the HepG2 cells against PAT cytotoxicity, while rapamycin decreased the cell viability. Thus, autophagy may play an important role in PAT-induced toxicity. To uncover the mechanism by which cells decrease proliferation and activation of autophagy, we found that collapses of mitochondrial membrane potential (ΔΨm) and reactive oxygen species (ROS) level were increased under treatment with PAT. Further, we elucidated that the expression of p-Akt1 and p-MTOR was inhibited during this process. N-acetyl-l-cysteine (NAC), a ROS inhibitor, protected against PAT-induced cytotoxicity, decreased the protein expression of LC3-II, and up-regulated the level of p-Akt1 and p-MTOR. These findings suggested that PAT-induced autophagic cell death was ROS-dependent in HepG2 cells. In conclusion, it is possible that PAT elicited autophagy through ROS-Akt1-MTOR pathway in the HepG2 cells.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::10e37e3f74769ac0811f1466158d10b9Test
https://doi.org/10.1016/j.cbi.2018.03.018Test

المؤلفون: Liping Jiang, Chengyan Geng, Ming Sun, Guang Yang, Xiance Sun, Xiaofeng Yao, Yueran Bai, Jing Li, Xiaofang Liu, Cong Zhang, Shaopeng Wang, Bo Wang, Qiujuan Li

المصدر: Journal of agricultural and food chemistry. 66(46)

مصطلحات موضوعية: 0301 basic medicine, animal structures, animal diseases, PINK1, Apoptosis, Cathepsin B, Patulin, 03 medical and health sciences, chemistry.chemical_compound, fluids and secretions, 0302 clinical medicine, Mitophagy, Autophagy, Humans, Membrane potential, biology, Chemistry, Cytochrome c, Cytochromes c, General Chemistry, Hep G2 Cells, Cell biology, Mitochondria, 030104 developmental biology, Liver, 030220 oncology & carcinogenesis, cardiovascular system, biology.protein, General Agricultural and Biological Sciences, Lysosomes, Reactive Oxygen Species

الوصف: Patulin (PAT) is a compound produced by fungi including those of the Aspergillus, Penicillium, and Byssochlamys species. PAT has been linked with negative outcomes in certain microorganisms and animal species, but how it causes hepatotoxicity is poorly understood. In this study, we determined that, by treating HepG2 cells using PAT, these cells could be induced to rapidly undergo autophagy, and this was followed within 12 h of treatment by lysosomal membrane permeabilization (LMP) and cathepsin B release. We were able to block these outcomes if cells were treated with 3-methyladenine (3MA), an inhibitor of autophagy, prior to PAT treatment. Moreover, PAT-induced collapse of mitochondrial membrane potential (ΔΨm) depended both on cathepsin B and autophagy. 3MA was further able to reduce the induction of apoptosis in response to PAT, suggesting that autophagy is a driving mechanism for this apoptotic induction. Inhibiting cathepsin B using CA-074 Me further reduced PAT-induced collapses of ΔΨm, mitochondiral cytochrome c release, and apoptosis. We also found that extended treatment of HepG2 cells using PAT over a period of 24 h led to the impairment of mitophagy such that morphologically swollen mitochondria accumulated within cells, and PINK1 failed to colocalize with LC3. Together these data reveal that PAT treatment can promote the induction of apoptosis in HepG2 cells in a manner dependent upon autophagy that progresses via the lysosomal-mitochondrial axis. This study thereby affords new insights into the mechanisms by which PAT drives hepatotoxicity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::33672e3c40240f215a133919a55b906cTest
https://pubmed.ncbi.nlm.nih.gov/30392375Test

المؤلفون: Xiaoxia Shi, Jun Cao, Chengyan Geng, Zhiguo Li, Yong Liu, Xiaofeng Yao, Qiujuan Li, Liping Jiang, Wei Lv

المصدر: Free radical biologymedicine. 130

مصطلحات موضوعية: Autophagy-Related Proteins, Apoptosis, Mitochondrion, medicine.disease_cause, Biochemistry, Downregulation and upregulation, Physiology (medical), medicine, Autophagy, Humans, Inducer, A549 cell, Membrane Potential, Mitochondrial, Chemistry, Caspase 3, Caspase 9, Cell biology, Mitochondria, Gene Expression Regulation, Neoplastic, Crosstalk (biology), Cysteine Endopeptidases, Proto-Oncogene Proteins c-bcl-2, A549 Cells, Beclin-1, Carcinogenesis, Cadmium

الوصف: Cadmium (Cd) is a highly ubiquitous detrimental metal in the environment. It is a well-known inducer of tumorigenesis, but the mechanism is not clear. In our previous study, we found that ROS-dependent Atg4B upregulation mediated Cd-induced autophagy and autophagy played an important role in Cd-induced proliferation and invasion in A549 cells. In this study, we found that Cd induced both apoptosis and autophagy in A549 cells, and apoptosis preceded autophagy. Z-VAD-FMK repressed Cd-induced LC3 and Beclin1, indicating that apoptosis was essential for Cd-induced autophagy. 3MA destroyed the recovery of mitochondrial membrane potential and increased Cd-induced CL-CASP9 and CL-CASP3 expression, suggesting that Cd-induced autophagy prevented A549 cells from apoptosis. Further study showed that Atg4B upregulation was mediated by mitochondrial dysfunction and conversely affected mitochondrial function by decreasing Bcl-2 protein expression and its localization in mitochondria, and played an important role in Cd-induced apoptosis. Moreover, Bcl-2 was involved in Cd-induced autophagy. Co-IP assay showed that Atg4B could directly bind to Bcl-2, and consequently promote disassociation of Bcl-2-Beclin1 and released autophagic protein Beclin1 to activate autophagic pathway. Taken together, our results demonstrated that the interaction of Atg4B and Bcl-2 might play an important role in Cd-induced crosstalk between apoptosis and autophagy through disassociation of Bcl-2-Beclin1. Cd-induced autophagy is apoptosis-dependent and prevents apoptotic cell death to ensure the growth and proliferation of A549 cells.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b138bcb16e006f225ed0791caf2718f8Test
https://pubmed.ncbi.nlm.nih.gov/30458278Test

المؤلفون: Chengyan Geng, Hong Ge, Jun Cao, Liping Jiang, Xiaofeng Yao, Qiujuan Li, Yong Liu, Xiaoxia Shi, Zhiguo Li

المصدر: Chemico-biological interactions. 298

مصطلحات موضوعية: 0301 basic medicine, Chromium, Programmed cell death, Apoptosis, Mitochondrion, Toxicology, Amino Acid Chloromethyl Ketones, 03 medical and health sciences, 0302 clinical medicine, Autophagy, Humans, Endoplasmic Reticulum Chaperone BiP, Carcinogen, A549 cell, Membrane Potential, Mitochondrial, Chemistry, Endoplasmic reticulum, General Medicine, Endoplasmic Reticulum Stress, Phenylbutyrates, Cell biology, 030104 developmental biology, A549 Cells, 030220 oncology & carcinogenesis, Unfolded protein response, Microtubule-Associated Proteins

الوصف: Hexavalent chromium [Cr (VI)], which is widely found in occupational environments, is a recognized human carcinogen. In this study, the role of endoplasmic reticulum (ER) stress in Cr (VI)-induced crosstalk of apoptosis and autophagy was investigated. Cr (VI) resulted in ER stress by upregulating the expression of GRP78 and p-PERK. 4-Phenylbutyric acid (4PBA), an inhibitor of ER stress, reduced both Cr (VI)-induced apoptosis and autophagy, suggesting that ER stress played an important role in Cr (VI)-induced apoptosis and autophagy in A549 cells. Furthermore, Cr (VI)-induced apoptosis preceded autophagy. Z-VAD-FMK, the suppressor of apoptosis, repressed Cr (VI)-induced autophagy. Pretreatment with 3-MA, the inhibitor of autophagy, increased Cr (VI)-induced apoptosis. Exposure to Cr (VI) significantly reduced mitochondrial membrane potential (MMP) during Cr (VI) treatment for 6–12 h. However, Cr (VI)-reduced MMP rescued significantly after treatment with Cr (VI) for 24 h compared with that of 6 h and 12 h groups, suggesting that Cr (VI)-induced autophagy at 24 h might rescue Cr (VI)-induced decrease of MMP through engulfing damaged mitochondria and then inhibit apoptosis in A549 cells. Above all, our results indicated that Cr (VI)-induced ER stress plays an important role in the crosstalk between apoptosis and autophagy. The autophagy might be apoptosis-dependent and subsequently prevents apoptosis cell death to keep A549 cells resistant to Cr (VI)-induced further toxicity. This maybe underlies the mechanism of Cr (VI)-induced carcinogenesis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::195b72f8e92f618dfbbc065095b96bbeTest
https://pubmed.ncbi.nlm.nih.gov/30416085Test

المؤلفون: Jian Kang, Jun Cao, Xiaofeng Yao, Yuexia Wang, Yufang Ma, Xiance Sun, Min Chen, Shanshan Sha, Liping Jiang

المصدر: Toxicological Sciences. 153:198-211

مصطلحات موضوعية: 0301 basic medicine, Autophagosome, Fluorocarbons, Gene knockdown, Chemistry, ATG5, Autophagy, Mitophagy, Cathepsin D, Apoptosis, PINK1, Hep G2 Cells, Toxicology, Cell biology, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Alkanesulfonic Acids, 030220 oncology & carcinogenesis, Humans, RNA Interference

الوصف: Lysosomal membrane permeabilization (LMP) and subsequently impaired autophagosome degradation was induced in HepG2 cells after treatment with perfluorooctane sulfonate (PFOS) for 24 h in our previous studies. We found that treatment of HepG2 cells with PFOS-induced autophagosome formation at earlier stage (6 h) of treatment in this study. The autophagosome formation inhibitor 3-methyladenine (3-MA) was able to relieve PFOS-induced LMP and release of cathepsin D in HepG2 cells. Knockdown of Spinster 1, a lysosomal membrane permease, attenuated PFOS-induced LMP in HepG2 cells. We proposed that Spinster 1 might work as a specific molecule that linked autophagy with LMP. PFOS-induced collapse of mitochondrial transmembrane potential was cathepsin D and autophagy dependent. Addition of 3-MA relieved PFOS-induced apoptosis, which was evidenced by Hoechst assay, AV/PI staining and caspase-3 activity assay. Inhibition of autophagosome formation by Atg5 siRNA attenuated PFOS-induced apoptosis. Treatment of HepG2 cells with PFOS for 24 h impaired mitophagy, as evidenced by an increase of cells with giant mitochondria and impairment of colocalization of PINK1 with light chain 3. In summary, we report that PFOS induces autophagy-dependent apoptosis in HepG2 cells through the lysosomal-mitochondrial axis and impairment of mitophagy, suggesting that autophagy is a primary target for PFOS toxicity. These findings provide new mechanistic insights into PFOS-induced hepatotoxicity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e8ab302c73b8b608ef72a0153ff8270eTest
https://doi.org/10.1093/toxsci/kfw118Test

المؤلفون: Zhaoqing Li, Sinan Wang, Na Ye, Jiabin Dong, Xuan Zhou, Minghui Zhao, Yansheng Wu, Yu Wang, Xudong Wang, Yu Ren, Xin Qu, Qiang Shen, Linhgping Kong, Kailiang Zhang, Yu Qiao, Chao Zhang, Shanshan Sun, Xiaofeng Yao, Wenyu Guo, Rui Jin, Lun Zhang, Haiying Chen, Chao Jing, Jia Zhou

مصطلحات موضوعية: 0301 basic medicine, STAT3 Transcription Factor, Cancer Research, medicine.medical_specialty, Beta-catenin, Cell Survival, Cell, Antineoplastic Agents, Salicylanilides, Article, 03 medical and health sciences, Mice, 0302 clinical medicine, Internal medicine, Cell Line, Tumor, medicine, Animals, Humans, STAT3, beta Catenin, Cell Proliferation, biology, Cell growth, Squamous Cell Carcinoma of Head and Neck, Cell cycle, Xenograft Model Antitumor Assays, Gene Expression Regulation, Neoplastic, MicroRNAs, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, Oncology, Apoptosis, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Catenin, Cancer research, biology.protein, Carcinoma, Squamous Cell, Niclosamide, Signal transduction, Signal Transduction

الوصف: Signal transducer and activator of transcription 3 (STAT3) is involved in the tumor growth and metastasis of human head and neck squamous cell carcinoma (HNSCC) and is therefore a target with therapeutic potential. In this study, we show that HJC0152, a recently developed anticancer agent and a STAT3 signaling inhibitor, exhibits promising antitumor effects against HNSCC both in vitro and in vivo via inactivating STAT3 and downstream miR-21/β-catenin axis. HJC0152 treatment efficiently suppressed HNSCC cell proliferation, arrested the cell cycle at the G0–G1 phase, induced apoptosis, and reduced cell invasion in both SCC25 and CAL27 cell lines. Moreover, HJC0152 inhibited nuclear translocation of phosphorylated STAT3 at Tyr705 and decreased VHL/β-catenin signaling activity via regulation of miR-21. Loss of function of VHL remarkably compromised the antitumor effect of HJC0152 in both cell lines. In our SCC25-derived orthotopic mouse models, HJC0152 treatment significantly abrogated STAT3/β-catenin expression in vivo, leading to a global decrease of tumor growth and invasion. With its favorable aqueous solubility and oral bioavailability, HJC0152 holds the potential to be translated into the clinic as a promising therapeutic strategy for patients with HNSCC. Mol Cancer Ther; 16(4); 578–90. ©2017 AACR.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ce55a0ac3093153620dc592d3f16ec7fTest
https://europepmc.org/articles/PMC5380531Test/

المؤلفون: Xiaofang Liu, Shaopeng Wang, Liping Jiang, Nairong Liu, Yueran Bai, Xiance Sun, Guang Yang, Xiaofeng Yao, Xingyue Zhai, Xueyan Wu

المصدر: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 106

مصطلحات موضوعية: 0301 basic medicine, Cell Survival, Caspase 3, Apoptosis, Mitochondrion, Toxicology, Cathepsin B, Cell Line, 03 medical and health sciences, Diethylhexyl Phthalate, Autophagy, Humans, Cathepsin, Membrane Potential, Mitochondrial, TUNEL assay, biology, Cytochrome c, Cytochromes c, Endothelial Cells, General Medicine, Cell biology, Mitochondria, 030104 developmental biology, biology.protein, Lysosomes, Food Science

الوصف: Mono(2-ethylhexyl) phthalate (MEHP), the active metabolite of di(2-ethylhexyl) phthalate (DEHP), has been known to have adverse effects on the reproductive system, urologic systems, hepatic, developmental toxicities and carcinogenicity. However, the effect of MEHP on cardiovascular toxicity remains unclear. Therefore, we aimed to evaluate the cytotoxic effects of MEHP and the possible molecular mechanism. We found that treatment of EA.hy 926 cells with MEHP induced autophagy at earlier time (6 h) in this study. Lysosomal membrane permeabilization (LMP) occurred, after treatment with MEHP for 12 h, followed by the release of cathepsin B. Autophagy inhibitor 3-methyladenine (3MA) attenuated MEHP-induced LMP and the release of cathepsin B in EA.hy 926 cells. Additionally, MEHP induced collapse of mitochondrial transmembrane potential, which was evidenced by JC-1 staining. Addition of 3MA relieved MEHP-induced apoptosis as assessed by the expression of caspase 3 and TUNEL assay, indicating that MEHP-induced apoptosis was autophagy-dependent. Cathepsin B inhibitor, CA-074 Me, suppressed MEHP-induced the mitochondria release of cytochrome c and apoptosis as well. In summary, our results suggest that MEHP induced autophagy-dependent apoptosis in EA.hy 926 cells through the lysosomal-mitochondrial axis. This study provides new mechanistic insights into MEHP-induced cardiovascular toxicity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c192c5b41bbb558efbe9d4a304e71760Test
https://pubmed.ncbi.nlm.nih.gov/28579546Test

المؤلفون: Jun Cao, Chengyan Geng, Yue Ding, Xiaofeng Yao, Laifu Zhong, Liping Jiang, Chunpeng Gao

المصدر: Toxicology in Vitro. 28:667-674

مصطلحات موضوعية: Cell Survival, Apoptosis, Mitochondrion, Toxicology, medicine.disease_cause, Cathepsin B, Lysosome, medicine, Humans, Cathepsin, biology, Cytochrome c, Hydrazones, Cytochromes c, Dipeptides, Hep G2 Cells, General Medicine, Mitochondria, Cell biology, medicine.anatomical_structure, Nitroimidazoles, Tacrine, biology.protein, Cholinesterase Inhibitors, Lysosomes, Reactive Oxygen Species, Oxidative stress, medicine.drug

الوصف: Tacrine (THA) is a competitive inhibitor of cholinesterase. Administration of THA for the treatment of Alzheimer’s disease results in a reversible hepatotoxicity in 30–50% of patients, as indicated by elevated alanine aminotransferase levels. However, the intracellular mechanisms have not yet been elucidated. In our previous study, we found that THA induced cytotoxicity and mitochondria dysfunction by ROS generation and 8-OHdG formation in mitochondrial DNA in HepG2 cells. In this study, the mechanism underlying was further investigated. Our results demonstrated that THA induced dose-dependent apoptosis with cytochrome c release and activation of caspase-3. THA-induced apoptosis was inhibited by treating cells with a ROS inhibitor, YCG063. In addition, we observed that THA led to an early lysosomal membrane permeabilization and release of cathepsin B. Pretreatment with CA-074Me, a specific cathepsin B inhibitor resulted in a significant but not complete decrease in tacrine-induced apoptosis. These data suggest that tacrine-induced cell apoptosis involves both mitochondrial damage and lysosomal membrane destabilization, and ROS is the critical factor that integrates tacrine-induced mitochondrial and lysosomal death pathways.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3ab2e7bd26ce279f3d17549ea6b0c595Test
https://doi.org/10.1016/j.tiv.2014.02.001Test