Experimental and Therapeutic Medicine
·
2019
·Vol. 18
·期 2
·1285-1290
·
IF 1.448
Hanchun Chen,Qiong Lu,Chao Chen,Yunhai Di,Ya'nan Li,Weijie Min,Zhengquan Yu,Dongwei Dai
Mutations of the β‑catenin gene are common in various cancer types. MicroRNA (miR)‑24 suppresses gene expression during the cell cycle. However, the effects of miR‑24 on the cell viability and autophagy of glioma cells, and how these biological processes are regulated by β‑catenin are largely unclear. The current study aimed to investigate the role of β‑catenin in regulating the effects of miR‑24 on the cell viability and autophagy of glioma cells. The expression levels of microtubule‑associated proteins 1A/1B light chain 3B (LC3B) and Beclin1 were detected by immunohistochemistry and western blotting. Glioma C6 cells were transfected with miR‑24 mimics, miR‑24 inhibitors and negative control miRNAs. C6 cells transfected with miR‑24 mimics or negative control miRNAs were treated with the β‑catenin inhibitor, XAV‑939. An MTT assay was utilized to evaluate the viability of C6 cells. The expression of miR‑24 and mRNA expression of autophagy related 4a cysteine peptidase (ATG4A) were detected by quantitative polymerase chain reaction analysis. The protein expression of LC3B and Beclin1 decreased significantly in glioma tissue and glioma C6 cells compared with normal brain tissue. Compared with the negative control group, C6 cells transfected with miR‑24 mimics exhibited significantly higher cell viability at 24 and 48 h, and those transfected with miR‑24 inhibitors exhibited significantly lower cell viability at 48 h. XAV‑939 decreased the stimulatory effects of miR‑24 mimics on the viability of C6 cells. The expression of miR‑24 significantly decreased and ATG4A mRNA significantly increased in C6 cells transfected with XAV‑939 compared with those transfected with the negative control miRNA. XAV‑939 attenuated the miR‑24‑induced decrease of the protein expression of LC3B and Beclin1, and decreased the stimulatory effects of miR‑24 mimics on cell viability. In addition, XAV‑939 attenuated the miR‑24‑induced decrease of autophagy marker expression by attenuating miR‑24 expression and increasing ATG4A mRNA expression in glioma C6 cells. To the best of our knowledge, the present study is the first to demonstrate whether β‑catenin regulates the intracellular effects of miR‑24 on the viability and autophagy of glioma cells. The results also provide some mechanistic basis to the pharmaceutical targeting of WNT signaling in high grade glial tumors.
研究领域:
癌症生物学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Antioxidants
·
2026
·Vol. 15
·期 7
·824
·
IF 8.2
Xiaoqing Feng,Xiao Zhou,Shushan Jia,Jingzhen Chen,Peiwang Li,Yan Yang,Wei Wu,Lijuan Jiang,Wenbin Zeng,Changzhu Li,Qiang Liu,Yunzhu Chen
Camelliasaponins, bioactive constituents abundant in the by-products ofCamellia oleiferaoil production, exhibit diverse biological activities. However, their potential in regulating neuroprotective mitophagy remains largely unexplored. This study identifies camelliasaponin B1 (CSB1) as an abundant component inC. oleiferaseeds and investigates its cytoprotective mechanisms against oxidative stress. Using an in vitro model of H2O2-induced oxidative damage in PC12 cells, we found that CSB1 pretreatment significantly alleviated oxidative stress, as evidenced by reduced reactive oxygen species (ROS) accumulation and enhanced antioxidant enzyme activities (SOD, CAT, GSH-Px). CSB1 also preserved mitochondrial function, restoring membrane potential (ΔΨm), ultrastructure, and respiratory capacity. Mechanistically, CSB1 reduces the expression of BNIP3/NIX-LC3B pathway-related proteins, suggesting a modulatory effect on mitophagy, as supported by transcriptomic analysis, Western blotting, and immunofluorescence. Molecular docking computationally predicted potential interactions between CSB1 and BNIP3/NIX proteins, which require experimental validation. Collectively, these findings suggest that CSB1 acts as a cytoprotective agent that enhances antioxidant defenses, safeguards mitochondrial integrity, and is associated with reduced BNIP3/NIX-LC3B expression and co-localization, offering a potential molecular basis for its development as a neuroprotective agent targeting oxidative stress-related mitochondrial dysfunction.
✓ 已验证
DOI
高影响因子
FITOTERAPIA
·
2023
·
IF 3.4
Saijuan Li,Fangge Wu,Pengcheng Gao,Can Jin,Yuyong Wang,Wenfeng Liao,Kan Ding
The accumulation of amyloid β (Aβ) containing senile plaques is one of the key histopathological hallmarks of Alzheimer's disease (AD). Increasing evidences demonstrated the important role of autophagy in Aβ clearance. Recent studies implied that extracts from Semiaquilegia adoxoides (DC.) Makino could ameliorate the memory of D-galactose induced aging mice. However, the bioactive substance and underlying mechanism remains unknown. Thus, the present study sought to explore the effects of a novel homogenous peptidoglycane on Aβ 42 secretion and the underlying mechanism. Briefly, we extracted a novel peptidoglycan named SA02C using hot water extraction and alcohol precipitation with the Mw of 13.72 kDa. SA02C contains 73.33% carbohydrate and 27.83% protein. The structure characterization revealed that its glycan part might mainly composed of galacturonic acid with minor rhamnose in backbone, and branched with glucose, galactose, arabinose, xylose and galacturonic acid. The protein or peptide moiety in SA02C was bonded to the polysaccharide via threonine. Bioactivities test showed that SA02C could reduce Aβ 42 production in a dose dependent manner with no obvious cytotoxicity. Mechanism study demonstrated that SA02C could modulate APP processing by upregulating the expression of ADAM10, sAPPα and downregulating BACE1, sAPPβ. Furthermore, SA02C also could stimulate autophagy by promoting the expression of the markers of autophagy such as LC3B and ATG5, resulting in the promotion of Aβ 42 phagocytosis.
研究领域:
药理学
·
神经科学
·
分子生物学
·
植物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Yuan Yuan,Li Jinmeng,Chen Yanhong,Cai Qingshan,Xu Yingying,Lin Luting,Lang Yazhen,Guo Suhang,Zhang Ruoying,Cai Xinjun
Multidrug-resistant tuberculosis (MDR-TB) remains a main global health concern as there is no comprehensive therapeutic intervention yet and numerous adverse effects follow the therapeutic process. In recent years, linezolid has been frequently used for treating MDR-TB. However, peripheral neuropathy associated with linezolid has reduced patient compliance. The current study explored the mechanism underlying linezolid-induced peripheral neuropathy in MDR-TB. Autophagy plays a neuroprotective role against peripheral nerve injury. We hypothesized that autophagy might also play a neuroprotective role against linezolid-induced peripheral neuropathy. In this study, we collected 12 questionnaires from MDR-TB patients in our hospital, and 10 of them developed linezolid-induced pain. The pain is mainly concentrated in the feet and accompanied by numbness. Subsequently, we used Sprague-Dawley (SD) rats and Schwann cells (SCs) to explore the mechanism. We found that linezolid causes a sparse arrangement of sciatic nerve tissue with associated loss of neurons, myelin sheaths, and down-regulation of LC3B expression. These results were also confirmed by in vitro experiments, showing that linezolid inhibited the proliferation of SCs. And the expression of P-AKT and P62 was elevated, and the expression of LC3B declined compared with the control group. Moreover, chloroquine (CQ), an autophagy inhibitor, also exhibited experimental results similar to linezolid. In summary, we conclude that linezolid-induced peripheral neuropathy is associated with the inhibition of autophagy flux.
研究领域:
药理学
·
神经科学
·
传染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2021
·Vol. 22
·期 5
·1-12
·
IF 2.447
Yiqiang Li,Mingwei Zhu,Xuemei Lin,Jingchun Li,Zhe Yuan,Yanhan Liu,Hongwen Xu
Neurofibromatosis type I (NF1) is an autosomal dominant genetic disease that is caused by mutations in the NF1 gene. Various studies have previously demonstrated that the mTOR complex 1 signaling pathway is essential for the NF1‑modulated osteogenic differentiation of bone mesenchymal stem cells (BMSCs). Additionally, the mTOR signaling pathway plays a notable role in autophagy. The present study hypothesized that NF1 could modulate the osteogenic differentiation of BMSCs by regulating the autophagic activities of BMSCs. In the present study, human BMSCs were cultured in an osteogenic induction medium. The expression of the NF1 gene was either knocked down or overexpressed by transfection with a specific small interfering RNA (siRNA) targeting NF1 or the pcDNA3.0 NF1‑overexpression plasmid, respectively. Autophagic activities of BMSCs (Beclin‑1, P62, LC3B I, and LC3B II) were determined using western blotting, electron microscopy, acridine orange (AO) staining and autophagic flux/lysosomal detection by fluorescence microscopy. In addition, the autophagy activator rapamycin (RAPA) and inhibitor 3‑methyladenine (3‑MA) were used to investigate the effects of autophagy on NF1‑modulated osteogenic differentiation in BMSCs. Inhibiting NF1 with siRNA significantly decreased the expression levels of autophagy markers Beclin‑1 and LC3B‑II, in addition to osteogenic differentiation markers osterix, runt‑related transcription factor 2 and alkaline phosphatase. By contrast, overexpressing NF1 with pcDNA3.0 significantly increased their levels. Transmission electron microscopy, AO staining and autophagic flux/lysosomal detection assays revealed that the extent of autophagosome formation was significantly decreased in the NF1‑siRNA group but significantly increased in the NF1‑pcDNA3.0 group when compared with the NC‑siRNA and pcDNA3.0 groups, respectively. In addition, the activity of the PI3K/AKT/mTOR pathway [phosphorylated (p)‑PI3K, p‑AKT, p‑mTOR and p‑p70S6 kinase] was significantly upregulated in the NF1‑siRNA group compared with the NC‑siRNA group, and significantly inhibited in the NF1‑pcDNA3.0 group, compared with the pcDNA3.0 group. The knockdown effects of NF1‑siRNA on the autophagy and osteogenic differentiation of BMSCs were reversed by the autophagy activator RAPA, while the overexpression effects of NF1‑pcDNA3.0 on the autophagy and osteogenic differentiation of BMSCs were reversed by the autophagy inhibitor 3‑MA. In conclusion, results from the present study suggest at the involvement of autophagy in the NF1‑modulated osteogenic differentiation of BMSCs. Furthermore, NF1 may partially regulate the autophagic activity of BMSCs through the PI3K/AKT/mTOR signaling pathway.
研究领域:
医学遗传学
·
细胞生物学
·
干细胞研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2023
·
IF 13.6
Qinggele Borjihan,Xuefang Liang,Ting Chen,Douxin Xiao,Yanling Zhang,Haixia Wu,Qing Zhang,Alideertu Dong
ABSTRACT The growing incidence of thyroid disease triggered by excess iodine uptake poses a severe health threat throughout the world. Extracellular interference therapies impede iodine transport across the sodium-iodide symporter (NIS) membrane protein and thus prevent excessive iodine uptake by thyroid cells, which may lessen the occurrence of disease. Herein, we for the first time utilized nano-starch particles (St NPs) to regulate iodine transport across the NIS protein of thyroid cells by using extracellular interference therapy. By precisely encapsulating iodine within the cavity of a glucan α-helix via hydrogen bonding, extracellular St NPs prevented excess iodine uptake by thyroid cells in vitro and in vivo ; this down-regulated the expression of NIS protein (0.06-fold) and autophagy protein LC3B-II (0.35-fold). We also found that St NPs regulated the metabolic pathway of iodine in zebrafish. We believe this proposed strategy offers a novel insight into controlling iodine uptake by the thyroid and indicates a new direction for preventing iodine-induced thyroid disease.
研究领域:
内分泌学
·
纳米技术
·
治疗学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RENAL FAILURE
·
2022
·
IF 3.222
Qi Xiao
Background To prove the internal connection, we deciphered the effect of cinnamaldehyde on kidney senescence through establishing animal and cell models.Methods In vivo, a rat senescence model was constructed using D-galactose (D-gal), and the modeled rats were further treated with cinnamaldehyde. In vitro, rat renal tubular epithelial cells (NRK-52E) were transfected with miR-155 mimic or inhibitor and then treated with cinnamaldehyde, D-gal or PI3K inhibitor (LY294002). The serum levels of blood urea nitrogen (BUN) and serum creatinine (Scr) of the rats were measured by an automatic biochemical analyzer. Pathological changes of kidney were determined by hematoxylin-eosin staining. The senescence and viability of NRK-52E cells were assessed by SA-β-gal staining and CCK-8 assay, respectively. The levels of miR-155, p-PI3K/PI3K, p-Akt/Akt, LC3B (LC3-II and LC3-I) and Beclin1 were detected by qRT-PCR, immunohistochemistry, or western blot.Results D-gal elevated the levels of BUN, Scr and miR-155 in the kidney, induced the renal pathological damage, inhibited the cell viability, increased the numbers of SA-β-gal-, LC3B- and Beclin1-positive cells and upregulated the levels of LC3-II/LC3-I and Beclin1 both in the kidney and cells. Cinnamaldehyde reversed D-gal-induced effects on the kidney and cells, and moreover, the cinnamaldehyde-induced anti-D-gal effects on cells could be suppressed by miR-155 mimic but promoted by miR-155 inhibitor. LY294002 potentiated D-gal-induced effects, and reversed cinnamaldehyde- and miR-155 inhibitor-caused impacts on the PI3K/Akt pathway and LC3-II/LC3-I level in D-gal-induced cells.Conclusion Cinnamaldehyde attenuates kidney senescence and injury through PI3K/Akt pathway-mediated autophagy via downregulating miR-155.
研究领域:
药理学
·
分子生物学
·
肾病学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2024
·
IF 4.2
Minghui Cai,Qiuyuan Li,Yang Cao,Yujia Huang,Haixu Yao,Chen Zhao,Jiao Wang,Hui Zhu
Autophagy is closely related to the aging of various organ systems, including ovaries. Quercetin has a variety of biological activities , including potential regulation of autophagy. However, whether quercetin-regulated autophagy activity affects the process of ovarian aging and injury has not been clarified yet. This study explores whether quercetin can resist H 2 O 2 -induced aging and injury of granulosa cells by regulating autophagy and its related molecular mechanisms in vitro experiments. The cell viability , endocrine function, cell aging , and apoptosis were detected to evaluate the effects of quercetin and autophagy regulators like 3-methyladenine and rapamycin . The levels of autophagy markers Atg5, Atg12, Atg16L, Lc3B II/I, and Beclin1 were determined by Western blot to assess the effects of quercetin, 3-methyladenine and rapamycin on autophagy. Our results showed quercetin resisted H 2 O 2 -induced granulosa cell aging and injury by activating protective autophagy. The treatment of 3-methyladenine and rapamycin confirmed the protective function of autophagy in H 2 O 2 -induced granulosa cells. 3-methyladenine treatment inhibited the expression of autophagy markers Atg5, Atg12, Atg16L, Lc3B II/I, and Beclin1 and abolished the positive effects on cell viability , estradiol secretion, and cell apoptosis activated by quercetin. In conclusion, quercetin activates autophagy by upregulating the expression of autophagy-related proteins to resist H 2 O 2 -induced aging and injury, which is crucial for stabilizing the function of granulosa cells under oxidative injury conditions and delaying aging. This study may explain the protective effects of quercetin on ovarian aging and injury from the perspective of regulating autophagy.
研究领域:
生殖生物学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2021
·
IF 10.588
Caiying Zhang,Zhisheng Hu,Ruiming Hu,Shaoxing Pi,Zejing Wei,Chang Wang,Fan Yang,Chenghong Xing,Gaohui Nie,Guoliang Hu
Pyroptosis and autophagy are two different biological processes that determine cell fates. Our previous studies revealed that pyroptosis and autophagy were involved in cytotoxicity co-induced by molybdenum (Mo) and cadmium (Cd) in duck renal tubular epithelial cells, but crosstalk between them is unclear. Hence, the cells were treated with 500.0 μM Mo, 4.0 μM Cd, 10.0 μM Z-YVAD-fluoromethylketone (YVAD), 2.5 μM 3-methyladenine (3-MA) and 10.0 μM chloroquine (CQ) alone or in combination for 12 h (CQ for the last 4 h). Under Mo and Cd co-stress, data evidenced that YVAD addition decreased the number of autophagosomes, LC3 puncta, and AMPKα-1, Atg5, Beclin-1, LC3A, LC3B mRNA levels and LC3-II/LC3-I, Beclin-1 protein levels, and increased p62 expression levels. Besides, both 3-MA and CQ addition increased NLRP3, Caspase-1, NEK7, ASC, GSDMA, GSDME, IL-1β, IL-18 mRNA levels, NLRP3, Caspase-1 p20, ASC, GSDMD protein and ROS levels, and NO, LDH, IL-1β, IL-18 releases. Collectively, our results revealed that pyroptosis and autophagy co-induced by Mo and Cd were interrelated in duck renal tubular epithelial cells, and inhibiting pyroptosis might attenuate Mo and Cd co-induced autophagy, but inhibiting autophagy might promote Mo and Cd co-induced pyroptosis.
研究领域:
细胞生物学
·
毒理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2023
·
IF 4.3
Kaiyuan Chen,Yahui Tang,Linhua Lan,Mengxuan Li,Zhongqiu Lu
Acute kidney injury (AKI) induced by diquat (DQ) progresses rapidly, leading to high mortality, and there is no specific antidote for this chemical. Our limited knowledge of the pathogenic toxicological mechanisms of DQ has hindered the development of treatments against DQ poisoning. Pyroptosis is a form of programmed cell death and was recently identified as a novel molecular mechanism of drug-induced AKI. To explore the role of pyroptosis in HK-2 cells exposed to DQ, the plasma membrane damage of the cells was detected by LDH release assay. Western blot was performed to detect the cleavage of GSDME. Proteomics analysis was performed to explore the mechanism of DQ induced nephrotoxicity . FerroOrange probe was used to measure the intracellular Fe 2+ levels. Herein, we show that DQ induces pyroptosis in HK-2 cells. Mechanistically, DQ induces the accumulation of mitochondrial ROS and initiates the cleavage of gasdermin E (GSDME) in an intrinsic mitochondrial pathway. Knockout of GSDME attenuated DQ-induced cell death. Further analysis revealed that loss of FTH1 induces Fe 2+ accumulation, contributing to DQ-induced pyroptosis. Knockdown LC3B could help restore the expression of FTH1 and improve cell viability . Moreover, we found DFO , an iron chelator , could reduce cellular Fe 2+ levels and inhibit pyroptosis. Collectively, these findings suggest an unrecognized mechanism for GSDME-dependent pyroptosis in DQ-induced AKI.
研究领域:
毒理学
·
细胞生物学
·
肾脏病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
·
2024
·Vol. 51
·期 4
·e13845
·
IF 2.4
Wen-Cong Gao,Tie-Hua Yang,Bin-Bao Wang,Qian Liu,Qing Li,Xiao-Huan Zhou,Chang-Bo Zheng,Peng Chen
Abnormalities in vascular smooth muscle cells (VSMCs) are pivotal in the pathogenesis of cardiovascular pathologies such as atherosclerosis and hypertension. Scutellarin (Scu), a flavonoid derived from marigold flowers, exhibits a spectrum of biological activities including anti-inflammatory, antioxidant, antitumor, immunomodulatory and antimicrobial effects. Notably, Scu has demonstrated the capacity to mitigate vascular endothelial damage and prevent atherosclerosis via its antioxidative properties. Nevertheless, the influence of Scu on the formation of VSMC-derived foam cells remains underexplored. In this study, Scu was evidenced to efficaciously attenuate oleic acid (OA)-induced lipid accumulation and the upregulation of adipose differentiation-associated protein Plin2 in a dose- and time-responsive manner. We elucidated that Scu effectively diminishes OA-provoked VSMC foam cell formation. Further, it was established that Scu pretreatment augments the protein expression of LC3B-II and the mRNA levels of Map1lc3b and Becn1, concurrently diminishing the protein levels of the NLRP3 inflammasome compared to the OA group. Activation of autophagy through rapamycin attenuated NLRP3 inflammasome protein expression, intracellular lipid droplet content and Plin2 mRNA levels. Scu also counteracted the OA-induced decrement of LC3B-II levels in the presence of bafilomycin-a1, facilitating the genesis of autophagosomes and autolysosomes. Complementarily, in vivo experiments revealed that Scu administration substantially reduced arterial wall thickness, vessel wall cross-sectional area, wall-to-lumen ratio and serum total cholesterol levels in comparison to the high-fat diet model group. Collectively, our findings suggest that Scu attenuates OA-induced VSMC foam cell formation through the induction of autophagy and the suppression of NLRP3 inflammasome activation.
研究领域:
心血管疾病
·
药理学
·
细胞生物学
·
炎症
✓ 已验证
DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2024
·
IF 7.1
Chaojuan Wen,Xinyue Yu,Jingya Zhu,Jingshu Zeng,Xielan Kuang,Youao Zhang,Shiyu Tang,Qingjiong Zhang,Jianhua Yan,Huangxuan Shen
Age-related macular degeneration (AMD), the leading cause of irreversible blindness in the elderly, is primarily characterized by the degeneration of the retinal pigment epithelium (RPE). However, effective therapeutic options for dry AMD are currently lacking, necessitating further exploration into preventive and pharmaceutical interventions. This study aimed to investigate the protective effects of gastrodin on RPE cells exposed to oxidative stress. We constructed an in vitro oxidative stress model of 4-hydroxynonenal (4-HNE) and performed RNA-seq, and demonstrated the protective effect of gastrodin through mouse experiments. Our findings reveal that gastrodin can inhibit 4-HNE-induced oxidative stress, effectively improving the mitochondrial and lysosomal dysfunction of RPE cells. We further elucidated that gastrodin promotes autophagy and phagocytosis through activating the PPARα-TFEB/CD36 signaling pathway. Interestingly, these outcomes were corroborated in a mouse model, in which gastrodin maintained retinal integrity and reduced RPE disorganization and degeneration under oxidative stress. The accumulation of LC3B and SQSTM1 in mouse RPE-choroid was also reduced. Moreover, activating PPARα and downstream pathways to restore autophagy and phagocytosis, thereby countering RPE injury from oxidative stress. In conclusion, this study demonstrated that gastrodin maintains the normal function of RPE cells by reducing oxidative stress, enhancing their phagocytic function, and restoring the level of autophagic flow. These findings suggest that gastrodin is a novel formulation with potential applications in the development of AMD disease.
研究领域:
眼科学
·
药理学
·
细胞生物学
·
分子生物学
·
神经科学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）