CARBOHYDRATE POLYMERS
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2018
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IF 5.158
Chunyan Hou,Hu Bai,Zhaojie Wang,Yuanhao Qiu,Li-Li Kong,Feifei Sun,Dongdong Wang,Hong Yin,Xiaoli Zhang,Haibo Mu,Jinyou Duan
Accompanied by overproduction of oxidants and reduction of pH, inflammation is closely related to many diseases such as cancer, atherosclerosis, and asthma. Besides chemotherapeutic agents, the potential regulative role of autophagy in inflammation is being actively investigated. RNA interference (RNAi)-based gene therapy is widely explored for clinical therapy but seriously restricted by lack of suitable carriers. In this study, we synthesized a hyaluronan-based ROS-sensitive polymer which was expected to release loaded chemical drugs in inflammatory environment and further developed a stable and nontoxic co-delivery nanosystem of siRNA targeting autophagy suppressive gene and chemotherapeutic agents. The in vitro transfection study of this nanosystem revealed improved intracellular accumulation of siRNA and excellent gene silencing efficacy comparable to that of conventional cationic liposome. Moreover, the mRNA expression of inflammatory cytokines was remarkably decreased by our nanosystem. Considering its biocompatibility, transfection efficacy, and anti-inflammatory capability, this co-delivery nanosystem proclaimed to be a promising combined therapeutic strategy for enhanced anti-inflammatory therapy.
研究领域:
药学
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纳米技术
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分子生物学
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炎症研究
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产品关联
DOI
PubMed
高影响因子
PLoS One
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2023
·Vol. 18
·期 2
·e0281845
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IF 3.7
Hao Tang,Shida Zhu,Kai Chen,Shujie Yuan,Junzu Hu,Hongkai Wang
Bone is a frequent target of tumor metastasis, with high incidence rate and poor prognosis. Osteoclasts play a key role in the process of tumor bone metastasis. Interleukin-17A (IL-17A) is an inflammatory cytokine, highly expressed in a variety of tumor cells, that can alter the autophagic activity of other cells, thereby causing corresponding lesions. Previous studies have shown that low concentration IL-17A can promote osteoclastogenesis. The aim of this study was to clarify the mechanism of low concentration IL-17A promoting osteoclastogenesis by regulating autophagic activity. The results of our study showed that IL-17A could promote the differentiation of osteoclast precursors (OCPs) into osteoclasts in the presence of RANKL, and increase the mRNA levels of osteoclast-specific genes. Moreover, IL-17A increased the expression of Beclin1 by inhibiting the phosphorylation of ERK and mTOR, leading to enhanced autophagy of OCPs, accompanied by decreased OCP apoptosis. Furthermore, knockdown of Beclin1 and suppression of autophagy by 3-methyladenine (3-MA) significantly attenuated the enhanced osteoclastogenesis induced by IL-17A. In summary, these results indicate that low concentration IL-17A enhances the autophagic activity of OCPs through the ERK/mTOR/Beclin1 pathway during osteoclastogenesis, and further promotes osteoclast differentiation, suggesting that IL-17A may serve as a potential therapeutic target for cancer-related bone resorption in cancer patients.
研究领域:
肿瘤学
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免疫学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
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2019
·Vol. 20
·期 1
·529-538
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IF 1.851
Shasha Chen,Feng Cai,Jirong Wang,Zhouxin Yang,Chi Gu,Guofu Wang,Genxiang Mao,Jing Yan
The abnormal aggregation of α‑synuclein (α‑syn), which is an important pathological feature of Parkinson's disease (PD), is cytotoxic to dopaminergic neurons and causes cellular damage and apoptosis. Salidroside (SAL) is the main active component of the traditional Chinese medicine Rhodiola rosea. Previous research has demonstrated that SAL exerts cellular protection against cell senescence and neurodegeneration. However, the role and mechanism of action of SAL in PD remain unclear. The present study used overexpression of the wild‑type and the A53T mutation of α‑syn to induce a neuronal model of PD in SH‑SY5Y cells, which led to neuronal toxicity and a reduced cell proliferation index. SAL increased the cell proliferation index of both PD model groups in a dose‑dependent manner. Additionally, SAL alleviated pathogenic phosphorylated (Ser129) α‑syn expression as well as the ratio of microtubule‑associated proteins 1A/1B light chain 3 (LC3)‑I to LC3‑II expression, which is related to autophagic function. Furthermore, the results suggested that the underlying mechanism for the SAL‑induced protection of PD model neurons may involve the preservation of autophagy, which attenuates the phosphorylation of α‑syn in neurons predominantly via mTOR/p70S6K, and is independent of the PI3K/Akt signaling pathway.
研究领域:
神经科学
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
TISSUE & CELL
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2023
·
IF 2.6
Ying Wang,Yongjun Li,Dongxia Liu
Background This study aimed to investigate role of erythropoietin in atherosclerosis and explore whether underlying mechanism is associated with PI3K/AKT/mTOR pathway. Methods High-fat-diet-induced atherosclerosis model was established in apolipoprotein E knockout mice (C57BL/6 genetic background). Mice were randomly divided into the control group and the EPO group. Hematoxylin-eosin was performed for the determination of atherosclerotic lesions. The expression levels of related proteins were detected by western blot analysis . Results Erythropoietin significantly enhanced the incidence of hemorrhage in atherosclerotic plaques compared with the control group. The proteins’ expression signaling pathways (including PI3K , AKT, and mTOR) and angiogenesis-related proteins (VEGF, COX-2, and HIF-1α) were proved to be up-regulated by erythropoietin. Additionally, erythropoietin significantly enhanced the incidence of hemorrhage in the atherosclerotic plaques compared with the control group. The vitro experiments were conducted in macrophages at 21% O 2 or 1% O 2 . The data showed that expression of p -PI3K, p -AKT, p -mTOR, VEGF, COX-2, and HIF-1α related proteins increased in 1% O 2 group than 21% O 2 group. Moreover, compared with control group, protein expression including p -PI3K, p -AKT, p -mTOR, VEGF, COX-2, and HIF-1α was markedly increased in EPO group, decreased in inhibitors group, and similar results were observed in EPO+ inhibitors group. Conclusion The present study demonstrated that erythropoietin might promote angiogenesis in atherosclerotic vulnerable by activating PI3K/AKT/mTOR signaling pathway in atherosclerotic, providing a novel therapeutic target for atherosclerotic targeted therapy.
研究领域:
心血管疾病
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分子生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
MATERIALS TECHNOLOGY
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2024
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IF 2.9
Menglan Wang,Lewei Li,Wu Zhong,Zheda Liu,Zehui Fan,Shiyang Fu,Xiaojun Tao,Yanjuan He,Chunlian He
Advanced osteosarcoma (OS) has low responsiveness to treatment regimens. Methotrexate (MTX), the first-line chemotherapeutic agent for advanced OS, frequently suffers from severe side effects that lead to chemotherapy interruption. To improve the efficacy and reduce the toxic side effects, we constructed a PF@MTX NP nano-delivery system using MTX-ss-γPGA polymer as a drug carrier loaded with PF. The average size of PF@MTX NPs was approximately 171.9 ± 2.13 nm with a zeta potential of approximately -32.91 ± 0.03 mV, uniformly distributed. We found that the nano showed a significant slowdown in MTX and PF release within 48 h and exhibited GSH-responsive pH sensitivity. In addition, the results of cellular uptake assay, toxicity, scratch and AO/EB staining assays showed that the PF@MTX NPs nanoparticles were able to enter the cells and induced 143B cell death and migration. Thus, the PF@MTX NPs nano-delivery system provides an effective strategy for the combined treatment of solid osteosarcoma.
研究领域:
肿瘤学
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药学
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纳米技术
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产品关联
DOI
高影响因子
Biomed Research International
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2021
·
IF 3.411
Fengqin Wang,Hanzhong Zhang,Zhigang Cheng
EPHA2 is a member of the ephrin receptor tyrosine kinase family and is closely related to the malignant tumor progression. The effect of EPHA2 on OSCC is not clear. This study explored the role of EPHA2 and AKT/mTOR signaling pathways in Cal-27 cell invasion and migration. The expression of EPHA2 and EPHA4 in human OSCC and normal oral tissue was detected by immunohistochemistry. EPHA2-overexpressing and EPHA2-knockdown Cal-27 cells were established, and the cells were treated with an AKT inhibitor (MK2206) and mTOR inhibitor (RAD001). The expression of EPHA2 was detected by qRT-PCR, cell proliferation was evaluated by MTT assay, cell migration and invasion were examined by scratch and Transwell assay, and cell morphology and apoptosis were assessed by Hoechst 33258 staining. Western blot was performed to detect the expression of proteins related to AKT/mTOR signaling, cell cycle, and pseudopod invasion. EPHA2 and EPHA4 were highly expressed in clinical human OSCC. Overexpression of EPHA2 promoted the proliferation, migration, and invasion of Cal-27 cells, inhibited cell cycle blockage and apoptosis, and enhanced the activity of the AKT/mTOR signaling pathway. MK2206 (AKT inhibitor) and RAD001 (mTOR inhibitor) reversed the effect of EPHA2 overexpression on the biological behavior of Cal-27 cells. EPHA2 promotes the invasion and migration of Cal-27 human OSCC cells by enhancing the AKT/mTOR signaling pathway.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
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2023
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IF 4.3
Eun-Ji Han,Eun-Young Choi,Su-Ji Jeon,Sang-Woo Lee,Jun-Mo Moon,Soo-Hyun Jung,Bumseok Kim,Sung-Dae Cho,Jeong-Seok Nam,Changsun Choi,Jeong-Hwan Che,Ji-Youn Jung
Natural products are continuously being researched to develop safe and effective treatment options for cervical cancer , the fourth most common cancer in women. Piperlongumine (PL), an amide alkaloid mainly present in long pepper , exhibits neuroprotective and anti-cancer properties. However, the specific effect of PL in cervical cancer and the relationship between the anti-cancer pathway and autophagy remain unclear. Therefore, we aimed to investigate PL-induced apoptosis in KB human cervical cancer cells and the relationship between apoptosis and autophagy therein. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and wound-healing assays showed that PL treatment suppressed KB cell viability and proliferation. Apoptosis was identified through 4′,6-diamidino-2-phenylindole and annexin V-propidium iodide staining, increased cleaved-poly (ADP-ribose) polymerase and Bcl-2 associated X levels, and decreased B cell lymphoma 2 levels. Acridine orange staining and increased microtubule-associated protein 1A/1B-light chain 3-II and Beclin-1 levels confirmed autophagy. We determined that KB cell-related autophagy exerted cytoprotective effects using the autophagy inhibitors 3-methyladenine and hydroxychloroquine . PL treatment promoted apoptosis by inhibiting the phosphatidylinositol-3-kinase (PI3K)/protein kinase B/mammalian target of rapamycin pathway in KB cells; inhibiting the pathway using PI3K inhibitors increased autophagy. We suggest that PL is a potential natural anticancer agent for cervical cancer treatment.
研究领域:
肿瘤学
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药理学
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细胞生物学
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天然产物化学
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DOI
PubMed
高影响因子
MEDIATORS OF INFLAMMATION
·
2024
·
IF 4.4
Shuyu Ge,Zhenghong Guo,Ting Xiao,Pingping Sun,Bo Yang,Yin Ying
As an interstitial fibrosis disease characterized by diffuse alveolitis and structural alveolar disorders, idiopathic pulmonary fibrosis (IPF) has high lethality but lacks limited therapeutic drugs. A hospital preparation used for the treatment of viral pneumonia, Qingfei Tongluo mixture (QFTL), is rumored to have protective effects against inflammatory and respiratory disease. This study aims to confirm whether it has a therapeutic effect on bleomycin-induced IPF in rats and to elucidate its mechanism of action. Male SD rats were randomly divided into the following groups: control, model, CQ + QFTL (84 mg/kg chloroquine (CQ) + 3.64 g/kg QFTL), QFTL-L, M, H (3.64, 7.28, and 14.56 g/kg, respectively) and pirfenidone (PFD 420 mg/kg). After induction modeling and drug intervention, blood samples and lung tissue were collected for further detection. Body weight and lung coefficient were examined, combined with hematoxylin and eosin (H&E) and Masson staining to observe lung tissue lesions. The enzyme-linked immunosorbent assay (ELISA) and the hydroxyproline (HYP) assay kit were used to detect changes in proinflammatory factors (transforming growth factor-β (TGF-β), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β)) and HYP. Immunohistochemistry and Western blotting were performed to observe changes in proteins related to pulmonary fibrosis (α-smooth muscle actin (α-SMA) and matrix metalloproteinase 12 (MMP12)) and autophagy (P62 and mechanistic target of rapamycin (mTOR)). Treatment with QFTL significantly improved the adverse effects of bleomycin on body weight, lung coefficient, and pathological changes. Then, QFTL reduced bleomycin-induced increases in proinflammatory mediators and HYP. The expression changes of pulmonary fibrosis and autophagy marker proteins are attenuated by QFTL. Furthermore, the autophagy inhibitor CQ significantly reversed the downward trend in HYP levels and α-SMA protein expression, which QFTL improved in BLM-induced pulmonary fibrosis rats. In conclusion, QFTL could effectively attenuate bleomycin-induced inflammation and pulmonary fibrosis through mTOR-dependent autophagy in rats. Therefore, QFTL has the potential to be an alternative treatment for IPF in clinical practice.
研究领域:
药理学
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肺病学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Journal of Biomaterials and Tissue Engineering
·
2018
·Vol. 8
·期 3
·426-432
·
IF 0.781
Hu Jinghui,Wang Li,Shen Heping,Huang Yujie,Zhao Wei
The elevated expression of mammalian target of rapamycin (mTOR) is associated with the occurrence, progression, and drug resistance of various tumors. Studies have shown overexpression of mTOR and reduced expression of miR-101 in cervical cancer tissues. Bioinformatic analysis has revealed
that a targeting binding site exists between miR-101 and the 3'-UTR of mTOR mRNA. In this study we determined whether miR-101 played a role in regulating mTOR expression and influencing the proliferation, apoptosis, and drug resistance to cisplatin (DDP) of CC cells. The regulatory relationship
between miR-101 and mTOR was validated by dual-luciferase reporter gene assay. The DDP resistance cell line, CaSki/DDP, was established, and the expressions of miR-101, mTOR, p-mTOR, and p-4EBP1 in the CaSki/DDP cell line and parental CaSki cells. The effect of DDP treatment on the proliferation
and apoptosis of the two cell lines were detected by flow cytometry. CaSki/DDP cells were divided into the following four transfection groups: miR-NC group; miR-101 mimic group; si-NC group; and si-mTOR group. The expression of miR-101, MTOR, p-mTOR, and p-4EBP1 was determined, and the effect
of DDP treatment on the proliferation and apoptosis of the two cell lines we detected by flow cytometry. There was a targeted regulatory relationship between miR-101 and mTOR. The expression and apoptosis rate of miR-101 in CaSki/DDP cells were significantly lower than CaSki cells, while the
expression and proliferation of mTOR, p-mTOR, and p-4EBP1 in CaSki/DDP cells were significantly higher than CaSki cells. The transfection of miR-101 mimic or si-mTOR significantly reduced the expression of mTOR, p-mTOR, and p-4EBP1 in CaSki/DDP cells and weakened the cell proliferation ability.
DDP treatment significantly increased the apoptosis rate. The decreased expression of miR-101 is associated with CaSki/DD cell resistance to DDP. Overexpression of miR-101 can reduce the resistance of cervical cancer CaSki/DDP cells to DDP by targeted inhibition of the expression of mTOR.
研究领域:
肿瘤学
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分子生物学
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癌症研究
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DOI
高影响因子
ENVIRONMENTAL POLLUTION
·
2022
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IF 9.988
Wenjing Pu,Xuesheng Chu,Huiling Guo,Gang Huang,Ting Cui,Bingyan Huang,Xueyan Dai,Caiying Zhang
Cadmium (Cd) and excess molybdenum (Mo) have multiple organ toxicity, and testis is one of their important target organs, but the reproductive toxicity of Mo and Cd combined treatment is still unclear. To explore the effects of Mo and Cd co-exposure on DNA damage and autophagy from the insight of ATM/AMPK/mTOR axis in duck testes, we randomly assigned 40 healthy 8-day-old ducks to control, Mo (100 mg/kg Mo), Cd (4 mg/kg Cd), and Mo + Cd groups for 16 weeks. Results found that Mo and/or Cd exposure caused trace elements imbalance, oxidative stress with a decrease in the activities of GSH-Px, CAT , T-SOD and GSH content, an increase in the concentrations of H 2 O 2 and MDA and pathological damage. Additionally, Mo and/or Cd markedly raised DNA damage-related factors expression levels and 8-OHdG content, caused G1/S arrest followed by decreasing CDK2 and Cyclin E protein levels and increasing CDK1 and Cyclin B protein levels, and activated ATM/AMPK/mTOR axis by enhancing p-ATM/ATM, p-AMPK/AMPK and reducing p-mTOR/mTOR protein levels, eventually triggered autophagy by elevating LC3A, LC3B, Atg5, Beclin-1 mRNA levels and LC3II/LC3I, Beclin-1 protein levels and reducing P62, Dynein, mTOR mRNA levels and P62 protein level. Moreover, these changes were most apparent in the combined group. Altogether, the results reveal that autophagy caused by Mo and/or Cd may be associated with activating the DNA damage-mediated ATM/AMPK/mTOR axis in duck testes, and Mo and Cd co-exposure exacerbates these changes.
研究领域:
毒理学
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生殖生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2020
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IF 4.225
Sun Xiaowei,Wang Dongyan,Zhang Tingting,Lu Xuejian,Duan Fangfang,Ju Lili,Zhuang Xiaotong,Jiang Xicheng
Eugenol, as an active compound isolated from Acorus gramineus, has been shown to protect against cerebral ischemia-reperfusion (I/R) injury. Nonetheless, the detailed neuroprotective mechanisms of eugenol in cerebral I/R injury have not been elaborated. In the present study, cerebral I/R injury model was established by middle cerebral artery occlusion (MCAO) in rats. HT22 cells were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) to mimic cerebral I/R injury in vitro. The results showed that eugenol pre-treatment relieved cerebral I/R injury as evidenced by improving neurological deficits and reducing infarct volume. Autophagy was induced by MCAO, which was further promoted by eugenol administration. Moreover, rapamycin, an activator of autophagy, promoted eugenol-induced decreases in neurological score, infarct volume, brain water content, and apoptosis. However, pretreatment with 3-MA, an inhibitor of autophagy, led to the opposite results. Similarly, eugenol pretreatment increased the viability and restrained apoptosis of OGD/R-challenged HT22 cells. OGD/R-induced autophagy was strengthened by eugenol. Mechanically, eugenol promoted autophagy through regulating AMPK/mTOR/P70S6K signaling pathway in vivo and in vitro. In conclusion, pretreatment with eugenol attenuated cerebral I/R injury by inducing autophagy via AMPK/mTOR/P70S6K signaling pathway.
研究领域:
神经科学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
·
IF 6.2
Xinyuan Wu,Dan Su,Jiaxin Xu,Ge Ge,Yongzhen Zhang,Bingjian Wu,Kun Hu,Jie Ren,Hao Yang
Alzheimer’s disease (AD), the most prevalent neurodegenerative disorder among older adults, significantly impairs behavioral and cognitive functions, posing a severe threat to patients’ health and quality of life. The Tricetin (TRN), a natural flavonoid found in wheat, pomegranate, and eucalyptus honey, has demonstrated anti-inflammatory, antitumor, and neuroprotective properties. However, its role in the context of AD has not been previously explored. This study investigated the antineuroinflammatory and autophagic protective effects of TRN in lipopolysaccharide (LPS)-induced BV2 cells and D-galactose/sodium nitrite/aluminum chloride (D-gal/NaNO2/AlCl3)-induced AD mice. The RNA sequencing examined the underlying mechanisms by which TRN ameliorates AD-related pathologies. Our research findings revealed that TRN significantly improved memory and mobility in AD mice, reduced Aβ deposition, and inhibited Tau protein phosphorylation. Furthermore, TRN regulated enzyme activities and reduced pathological markers associated with AD. Moreover, it modulated inflammatory mediators, inhibited the nuclear translocation of NF-κB in LPS-induced BV2 cells, and exerted anti-inflammatory and autophagic protective effects via the PI3K/Akt/mTOR signaling pathway. In conclusion, TRN demonstrated robust neuroprotective effects in vitro and in vivo AD models by regulating the PI3K/Akt/mTOR signaling pathway. These findings highlight its potential as a promising therapeutic agent for treating AD.
研究领域:
神经科学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）