Bioengineered
·
2021
·
IF 3.269
Ji Wu,Yang Fu,Ying-xing Wu,Zu-xiang Wu,Zhen-hua Wang,Ping Li
Alleviating cardiac dysfunction improves the prognosis of heart failure patients. Lycorine is an alkaloid with several beneficial biological properties. Here, we used mice to evaluate the effect of lycorine on cardiac dysfunction elicited by isoproterenol. Mice were divided into four groups: control, lycorine, isoproterenol, and isoproterenol + lycorine. Mice in the combined group were treated daily with 10 mg/kg isoproterenol intraperitoneally for 2 weeks and 5 mg/kg lycorine was given simultaneously intraperitoneally for 4 weeks. Cardiac structure and function were assessed by echocardiography, hematoxylin and eosin staining, and Masson’s trichrome staining. Isoproterenol-induced cardiac dysfunction and histopathological injury that was significantly improved by treatment with lycorine. Western blotting and the quantitative real-time polymerase chain reaction were used to explore the molecular mechanisms of these effects. Levels of the inflammatory cytokines, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, were increased by treatment with isoproterenol; these increases were significantly reduced by lycorine, with involvement of the NF-κB signaling pathway. The fibrotic factors, collagen I and collagen III, were increased by isoproterenol and decreased by treatment with lycorine through inhibiting activation of the Smad signaling pathway. In addition, lycorine alleviated oxidative stress as evidenced by a reduction in total reactive oxygen species in the isoproterenol + lycorine group compared to the isoproterenol group. Lycorine exerted an anti-apoptotic effect as evidenced by upregulating Bcl-2 and downregulating Bax. Overall, our findings demonstrate that lycorine protects against cardiac dysfunction induced by isoproterenol by inhibiting inflammation, fibrosis, oxidative stress, and apoptosis.
研究领域:
药理学
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心脏病学
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分子生物学
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DOI
PubMed
高影响因子
Neural Regeneration Research
·
2021
·
IF 5.135
Rui Zhao,Xue Wu,Xue-Yuan Bi,Hao Yang,Qian Zhang
Baicalin is a natural active ingredient isolated from Scutellariae Radix that can cross the blood-brain barrier and exhibits neuroprotective effects on multiple central nervous system diseases. However, the mechanism behind the neuroprotective effects remains unclear. In this study, rat models of spinal cord injury were established using a modified Allen's impact method and then treated with intraperitoneal injection of Baicalin. The results revealed that Baicalin greatly increased the Basso, Beattie, Bresnahan Locomotor Rating Scale score, reduced blood-spinal cord barrier permeability, decreased the expression of Bax, Caspase-3, and nuclear factor κB, increased the expression of Bcl-2, and reduced neuronal apoptosis and pathological spinal cord injury. SH-SY5Y cell models of excitotoxicity were established by application of 10 mM glutamate for 12 hours and then treated with 40 μM Baicalin for 48 hours to investigate the mechanism of action of Baicalin. The results showed that Baicalin reversed tight junction protein expression tendencies (occludin and ZO-1) and apoptosis-related protein expression (Bax, Bcl-2, Caspase-3, and nuclear factor-κB), and also led to up-regulation of PI3K and Akt phosphorylation. These effects on Bax, Bcl-2, and Caspase-3 were blocked by pretreatment with the PI3K inhibitor LY294002. These findings suggest that Baicalin can inhibit blood-spinal cord barrier permeability after spinal cord injury and reduce neuronal apoptosis, possibly by activating the PI3K/Akt signaling pathway. This study was approved by Animal Ethics Committee of Xi’an Jiaotong University on March 6, 2014.
研究领域:
神经科学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2023
·Vol. 24
·期 6
·1-17
·
IF 3.3
Cao Xia,Deng Tianwen,Zhu Qin,Wang Jianping,Shi Wenwan,Liu Qi,Yu Qintong,Deng Wenwen,Yu Jiangnan,Wang Qilong,Xiao Gao,Xu Ximing
Emodin is applied as an antitumor drug in many tumor therapies. However, its pharmacology performances are limited due to its low solubility. Herein, we fused erythrocyte and macrophage to form a hybrid membrane (EMHM) and encapsulated emodin to form hybrid membrane-coated nanoparticles. We employed glycyrrhizin to increase the solubility of emodin first and prepared the hybrid membrane nanoparticle-coated emodin and glycyrrhizin (EG@EMHM NPs) which exhibited an average particle size of 170 ± 20 nm and encapsulation efficiency of 98.13 ± 0.67%. The half-inhibitory concentrations (IC50) of EG@EMHM NPs were 1.166 μg/mL, which is half of the free emodin. Based on the photosensitivity of emodin, the reactive oxygen species (ROS) results disclosed that ROS levels of the photodynamic therapy (PDT) section were higher than the normal section ( P < 0.05). Compared to the normal section, PDT-mediated EG@EMHM NPs could induce an early stage of apoptosis of B16. The western blot and flow cytometry results verified that PDT-mediated EG@EMHM NPs can significantly improve the solubility of emodin and perform a remarkably antitumor effect on melanoma via BAX and BCL-2 pathway. The application of the combined chemical and PDT therapy could provide an improving target therapy for cutaneous melanoma and also may offer an idea for other insoluble components sources of traditional Chinese medicine. Graphical abstract
Schematic of EG@EMHM NPs formulation
研究领域:
癌症治疗
·
纳米技术
·
药理学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
OncoTargets and Therapy
·
2023
·
IF 4
Gang Wang,Yue Jing,Lingsen Cao,Changchang Gong,Zhunan Gong,Xiangrong Cao
Activation of the transcription factor, signal transducers and activators of transcription 3 (STAT3), has been linked to the proliferation and migration of a variety of human cancer cells. These actions occur via the upregulation or downregulation of cell survival and tumor suppressor genes, respectively. Importantly, agents that can suppress STAT3 activation have the potential for use in the prevention and treatment of various cancers. In this study, an Asiatic acid (AA) derivative, N-(2α,3β,23-acetoxyurs-12-en-28-oyl)-l-proline methyl ester (AA-PMe), is reported to dose dependently suppress constitutive STAT3 activation in gastric cancer cells. This inhibition was mediated by blockade of Janus-activated kinase 2. Additionally, AA-PMe regulated the expression of STAT3-modulated gene products, including cyclin D1, Bax, Bcl-2, c-Myc, and matrix metalloproteinase (MMP)-2 and MMP-9. Finally, transfection with both a STAT3 mimic and an inhibitor reversed the AA-PMe-driven modulation of STAT3 downstream gene products. Overall, these results suggest that AA-PMe is a novel blocker of STAT3 activation and has the potential for the prevention and treatment of gastric cancer.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Showkat Ali Ganie,Rayees Ahmad Naik,Ovas Ahmad Dar,Luqman Jameel Rather,Mohammed A. Assiri,Qing Li
We developed a facile method for the fabrication of a biodegradable delivery system composed of two blocks: curdlan and curcumin. This was achieved by chemical functionalization of curdlan through tosylation, amination followed by complexation with curcumin. A comprehensive evaluation of structural characterization and component stability showed that cur-cum complex exhibited better anticancer properties with enhanced thermal properties. The cur-cum complex shows pH sensitive sustained release behaviour with higher release at acidic pH and kinetic data of drug release follows the Korsmeyer-Peppas model. The cur-cum complex has ability to block the proliferation of the MCF-7 cell line as revealed by MTT assay which showed increased toxicity of cur-cum complex against these cell lines. The results obtained from western blot analysis demonstrated that the co-administration of cur and cum effectively induced apoptosis in MCF-7 cells. This effect was observed by a considerable upregulation of the Bcl-2/Bax ratio, a decline in mRNA expression of LDHA, level of lactate and LDH activity. The results clearly depict the role of functionalized curdlan as efficient carrier for curcumin delivery with prolonged, sustained release and enhanced bioavailability, thereby improving the overall anticancer activity.
研究领域:
药学
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生物医学工程
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癌症研究
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Aging-US
·
2020
·
IF 4.831
Zhenteng Liu,Fenghua Li,Jingwen Xue,Meimei Wang,Shoucui Lai,Hongchu Bao,Shunzhi He
Follicular atresia is one of the main processes for the loss of granulosa cells and oocytes from the mammalian ovary and any impairment to premature ovarian failure. Large numbers of studies have demonstrated that granulosa cell apoptosis causes follicular atresia, yet the rescue of these cells remains elusive. We aimed to use Esculentoside A (3-O-b-D-glucopyranosyl-1, 4-b-D-xylopyranosyl) phytolaccagenin, a saponin extracted from Phytolacca esculenta roots, as a potential rescue agent for the apoptosis of granulosa cells. Our results revealed the rescue of normal body and ovary weights, normal ovarian histo-architecture of ovaries, and hormones levels with regular estrus cycle. Consistently, the expression of proliferating and anti-apoptotic markers, i.e. KI67 and BCL-2 in granulosa cells, was enhanced. Meanwhile, the expressions of pro-apoptotic markers, which were BAX and CASPASEs (CASPASE-9 and CASPASE-3), were prominently reduced in Esculentoside A-induced premature ovarian failure mice. Additionally, PPARγ, a potential therapeutic target, has also rescued its expression by treating the premature ovarian failure mice with Esculentoside A. Our results advocated that Esculentoside A could restore folliculogenesis in premature ovarian failure mice. Furthermore, it has the potential to be investigated as a therapeutic agent for premature ovarian failure.
研究领域:
生殖生物学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
MOLECULAR NEUROBIOLOGY
·
2025
·
IF 4.3
Li Xinying,Li Weiran,Xie Xinying,Fang Ting,Yang Jingwen,Shen Yue,Wang Yicheng,Wang Hongyan,Tao Liqing,Zhang Heng
Rotenone, a plant-derived natural insecticide, is widely used to induce Parkinson’s disease (PD) models. However, the mechanisms of rotenone-induced cell death remain unclear. Here, we found that rotenone (0.01, 0.1, or 1 μmol/L) suppressed SH-SY5Y dopamine neuron viability and led to PD-like pathological changes, such as reduced tyrosine hydroxylase (TH) but increased α-synuclein. Rotenone increased the levels of intracellular reactive oxygen species (ROS) and mitochondrial ROS, as well as the levels of the antioxidants nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), ultimately resulting in oxidative stress. Moreover, rotenone significantly downregulated the expression of GPX4 and xCT but upregulated the expression of COX2 and NCOA4, which are markers of ferroptosis. Furthermore, rotenone decreased phosphorylated mTOR level but increased Beclin-1, ATG5, LC3 and p62 expression, suggesting that rotenone enhances autophagy and reduces autophagy flux. Additionally, rotenone reduced Bcl-2 levels and the mitochondrial membrane potential (MMP) while promoting BAX and Caspase-3 expression, thus initiating cell apoptosis. N-acetylcysteine (NAC), a ROS scavenger, and ferrostatin-1 (Fer-1) and deferoxamine (DFO), two ferroptosis inhibitors, significantly eliminated rotenone-induced autophagy and apoptosis. Moreover, ML385, a specific inhibitor of Nrf2, suppressed rotenone-induced ferroptosis. Our results demonstrated that ROS might mediate rotenone-induced PD-like pathological changes by regulating iron death, autophagy, and apoptosis. Inhibiting ferroptosis blocked the rotenone-induced increase in autophagy and apoptosis. Thus, the ability of ROS to regulate rotenone-induced death through autophagy and apoptosis is dependent on ferroptosis. The findings require validation in multiple neuronal cell lines and in vivo.
研究领域:
神经科学
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药理学
·
细胞生物学
·
帕金森病研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF FOOD SCIENCE
·
2024
·
IF 3.2
Jianping Chen,Xuehua Chen,Anqi Tang,Zhuo Wang,Kit-Leong Cheong,Xiaofei Liu,Saiyi Zhong
This study aimed to evaluate the anti-cervical cancer activity of chondroitin sulfate–functionalized selenium nanoparticles (SeCS) and to elucidate their action mechanism. Cytotoxic effect of SeCS on HeLa cells was assessed by MTT assay. Further molecular mechanism of SeCS was analyzed by flow cytometric assay and western blotting. The results showed that treatment with SeCS resulted in a dose- and time-dependent inhibition in the proliferation of HeLa cells. The data obtained from flow cytometry demonstrated that SeCS inhibited HeLa cell growth via the induction of S-phase arrest and cell apoptosis. Further mechanism analysis found that SeCS down-regulated expression levels of cyclin A and CDK2 and up-regulated p21 expression, which contributed to S arrest. Moreover, SeCS increased the level of Bax and decreased the expression of Bcl-2, resulting in the release of cytochrome C from mitochondria and activating caspase-3/8/9 for caspase-dependent apoptosis. Meanwhile, intracellular reactive oxygen species (ROS) levels were elevated after SeCS treatment, suggesting that ROS might be upstream of SeCS-induced S-phase arrest and cell apoptosis. These data show that SeCS has anti-tumor effects and possesses the potential to become a new therapeutic agent or adjuvant therapy for cancer patients. Practical Application In our previous study, we used chondroitin sulfate to stabilize nano-selenium to obtain SeCS to improve the bioactivity and stability of nano-selenium. We found that it possessed an inhibitory effect on HeLa cells. However, the molecular mechanism remains unclear. This study elucidated the mechanism of SeCS damage to HeLa cells. SeCS has the potential to become a new therapeutic agent or adjuvant therapy for cancer patients.
研究领域:
肿瘤学
·
纳米技术
·
细胞生物学
·
药学
✓ 已验证
DOI
PubMed
高影响因子
American Journal of Translational Research
·
2022
·
IF 3.94
Zheng Xu,Luwei Xu,Yuzheng Ge,Hongbin Sun,Jiageng Zhu,Quanliang Dou,Ruipeng Jia
Background: Cabazitaxel has been applied to the treatment of castration-resistant prostate cancer (CRPC), but the molecular mechanism remained to be fully understood. Methods: After treatment with Cabazitaxel alone or in combination with ionizing radiation (IR), CRPC cell viability, proliferation and apoptosis were determined by Cell Counting Kit-8 (CCK-8) assay, colony formation, and flow cytometry, respectively. Tumor volume was measured after the establishment of animal xenograft model. Relative expressions of proteins related to apoptosis (B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and cleaved caspase 3) and phosphoinositide 3-kinase (PI3K)/AKT pathway were measured by Western blot, and the phosphorylated-PI3K/PI3K and p-AKT/AKT ratios were determined as well. Results: Cell viability and proliferation were suppressed, and apoptosis was promoted in CRPC cells after Cabazitaxel treatment alone, accompanied with upregulated expressions of Bax and cleaved caspase 3 and downregulated Bcl-2 expression. Also, a single treatment with Cabazitaxel resulted in suppression of PI3K/AKT pathway activation, along with downregulated expressions of p-PI3K and p-AKT and a reduced ratio of p-PI3K/PI3K to p-AKT/AKT. Meanwhile, Cabazitaxel enhanced the effects of IR on suppressing survival and promoting apoptosis in CRPC cells through downregulating Bcl-2 and upregulating Bax and cleaved caspase 3. However, Cabazitaxel suppressed IR-induced PI3K/AKT pathway activation via downregulating p-PI3K and p-AKT, leading to a reduced ratio of p-PI3K/PI3K to p-AKT/AKT. Furthermore, Cabazitaxel further promoted the effects of IR on suppressing tumor growth in vivo . Conclusion: Cabazitaxel inhibited the proliferation and promoted the apoptosis and radiosensitivity of CRPC cells, which is related to the suppression of PI3K/AKT pathway, providing a therapeutic method for CRPC in clinical practice.
研究领域:
肿瘤学
·
分子生物学
·
药理学
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产品关联
DOI
PubMed
高影响因子
International Journal of Medical Sciences
·
2017
·
IF 2.399
Lin Yu,Xiaofeng Wu,Min Chen,Huarong Huang,Yan He,Huaqian Wang,Dongli Li,Zhiyun Du,Kun Zhang,Susan Goodin,Xi Zheng
Background : Docetaxel is the first-line treatment for castration-resistant prostate cancer (CRPC). The limited survival benefit associated with the quick emergence of resistance and systemic toxicity diminishes its efficacy in high-dose monotherapy. YK-4-279 is a small molecule inhibitor of ETV1 that plays an important role in the progression of prostate cancer. The aim of this study was to evaluate the hypothesis that the combination of docetaxel and YK-4-279 will have a synergistic effect on inhibiting growth and accelerating apoptosis in human prostate cancer cells. Methods : Cell growth assessed using CCK-8 and trypan blue exclusion assays. Cell apoptosis was determined by morphological assessment in cells stained with propidium iodide. Standard scratch migration and Matrigel-coated transwell invasion assays were used to assess cell migration and invasion, respectively. Western blotting was used to investigate the levels of ETV1, AR, PSA, p-STAT3, survivin, Bcl-2, and p-Akt in prostate cancer cells. Results : The combination of low-dose docetaxel and YK-4-279 synergistically inhibited growth and induced apoptosis in human prostate cancer cells. The combination also more efficiently suppressed the migration and invasion of LNCaP and PC-3 cells. The combination of low-dose docetaxel and YK-4-279 caused a stronger decrease in the levels of ETV1, AR, PSA, p-STAT3, survivin, Bcl-2, and p-Akt in LNCaP cells and of p-Akt, Bcl-2, and p-STAT3 in PC-3 cells compared with either drug alone. Conclusions : These data suggest that the combination of docetaxel and YK-4-279 may be an effective approach for inhibiting the growth and metastasis of prostate cancer. This could permit a decrease in the docetaxel dose necessary for patients with CRPC and thereby lower its systemic toxicity.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2018
·
IF 3.977
Qiang Chu,Lushuang Yu,Zihuan Zheng,Meng Chen,Zheng Hua,Miaojia Hang,Yonglu Li,Xixi Li,Yangyang Liu,Yunyun Yang,Xiaodong Zheng
Since flavonoids are antioxidant compounds, they could beneficially affect neurodegenerative diseases where reactive oxygen species are involved. In this study, we firstly isolated and identified fourteen compounds from the flowers of Apios americana Medik. Then, we tested whether Apios americana Medik flowers water extract (AFWE) exerts a protective effect on H 2 O 2 induced PC12 cells injure. As expected, pretreatment with AFWE inhibited cytotoxicity and DNA condensation in H 2 O 2 induced PC12 cells. Exposure of PC12 cells to H 2 O 2 resulted in reactive oxygen species accumulation and mitochondrial dysfunction, while AFWE alleviated these damages. AFWE obviously reversed the alternations as H2O2 increased Caspase-3 and decreased the ratio of Bcl-2/Bax expressions. Furthermore, autophagy in PC12 cells was further activated by AFWE, which was beneficial to resisting adversity. These results manifest that AFWE prevents H 2 O 2 induced damage via regulating autophagy.
研究领域:
神经科学
·
药理学
·
细胞生物学
·
生物化学
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DOI
PubMed
高影响因子
ANTI-CANCER DRUGS
·
2019
·Vol. 30
·期 1
·46-55
·
IF 1.801
Lin Fuxing,Yang Jie,Muhammad Umair,Sun Jing,Huang Zhenghua,Li Wei,Lv Fengxia,Lu Zhaoxin
Bacillomycin D can inhibit the growth of Aspergillus ochraceus in food samples. In addition, it can induce apoptosis in and inhibit the proliferation of cancer cells, although the details of this mechanism are unknown. In this study, we separated bacillomycin D-C14, D-C15, D-C16
monomers from the Bacillus subtilis strain fmbJ. The bacillomycin D monomers containing longer fatty acid chains better induced apoptosis in Bgc-823, Sgc-7901, and Hgc-27 gastric cancer cells. The Bgc-823 cell line was the most sensitive. Acridine orange-ethidium bromide staining indicated
that bacillomycin D-C16-induced Bgc-823 cell death by triggering apoptosis, characterized by membrane blebbing, cellular shrinkage, and DNA fragmentation. Flow cytometric analysis showed a bacillomycin D-C16 dose-dependent trigger of Bgc-823 apoptosis. Bacillomycin D-C16-induced the mitochondrial
pathway, as indicated by a reduced Bcl-2/Bax expression ratio, enhanced cytochrome C release, and higher levels of cleaved caspase-3. Furthermore, bacillomycin D-C16 effectively repressed phosphorylation of the serine–threonine protein kinase Akt at Ser-473 and increased the levels of
the FoxO3a protein. The combination of the PI3K/Akt-inhibitor BEZ235 with bacillomycin D-C16 enhanced the apoptosis of Bgc-823 cells. Together, these findings indicated that bacillomycin D-C16 induces apoptosis through the PI3K/Akt and FoxO3a signaling pathways.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）