LIFE SCIENCES
·
2025
·
IF 5.1
Kang Wei,Yiran Shi,Min Wang,Lu He,Huanhuan Xu,Haijie Wang,Langjie Chai,Ling Zhou,Yi Zou,Liang Guo
Keloids (KD) are noncancerous fibroproliferative tumors exhibiting cancer-like traits, encompass aggressive unregulated growth, absence of natural regression, and a significantly high rate of recurrence. The precise molecular mechanisms underlying KD pathology remain poorly understood. In this study, we employed single-cell sequencing to examine the characteristics of cells in KD and normal scar (NS) tissue. We evaluated Schwann cells and their secretory protein IGFBP5 function in KD. Then, the recombinant IGFBP5 protein was employed to elucidate the regulatory roles of IGFBP5 in the proliferation, migration, invasion, angiogenesis, and cell cycle of keloids fibroblasts (KF). The rabbit ear scar model was utilized to ascertain the function of IGFBP5 in vivo. We demonstrated that in KD, the proportion of Schwann cells was 4.13 times that of NS. Besides, the IGFBP5 gene exhibited an expression level that was 8.02 times higher in KD Schwann cells compared to those in NS Schwann cells. High IGFBP5 expression was positively associated with the cell proliferation, migration, invasion, angiogenesis, and cell cycle of KF. Additionally, the p53/p21/Cyclin D1 pathway regulated cell cycle and promoted cell proliferation, which was suppressed after rIGFBP5 administration. These findings suggest that Schwann cells infiltrate in KD and secrete IGFBP5 protein to promote KD growth, and targeting IGFBP5 or Schwann cell infiltration could offer novel therapeutic strategies for KD.
研究领域:
皮肤病学
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分子生物学
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细胞生物学
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肿瘤生物学
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DOI
PubMed
高影响因子
3 Biotech
·
2021
·Vol. 11
·期 8
·1-11
·
IF 2.406
Wang Dekang,Hu Aili,Peng Hao,Li Dongbo,Zhang Li
Glioma is the most common primary brain tumor in adults with an adverse prognosis and obscure pathogenesis. PICALM interacting mitotic regulator protein (PIMREG) functions as an oncogene in multiple types of cancer, but its function in glioma remains unknown. The Gene Expression Profiling Interactive Analysis 2 (GEPIA2, http://gepia2.cancer-pku.cn/#index ) showed that PIMREG expression in the glioma tissues was higher than that in normal brain tissues. Herein, cell counting kit-8 assay and flow cytometry analysis exhibited that overexpression of PIMREG significantly promoted the proliferation of glioma cells and the transition from G1 phase of the cell cycle to S phase. Wound-healing and transwell assays showed that overexpression of PIMREG markedly enhanced the migration and invasion of glioma cells. Western blot analysis revealed that overexpression of PIMREG increased the expression of cyclin D1, cyclin E, Vimentin, matrix metalloproteinase (MMP)-2, and MMP-9, but reduced the expression of E-cadherin. In addition, overexpression of PIMREG activated the β-catenin signaling pathway, as evidenced by the increased total and nuclear expression of β-catenin and the up-regulated expression of its downstream target c-myc. Furthermore, immunofluorescence staining further indicated the increased nuclear translocation of β-catenin in PIMREG-overexpressing cells. However, knockdown of PIMREG exerted opposite effects on glioma cells. Blockade of the β-catenin signaling by ICG-001 markedly impeded the promoting effects of PIMREG on glioma cell proliferation and invasion. In conclusion, PIMREG acts as a tumor promoter in glioma at least partly via activating the β-catenin signaling pathway. This study provides new insights into the molecular mechanism for glioma pathogenesis and treatment.
研究领域:
肿瘤学
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神经科学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2018
·Vol. 42
·期 1
·61-70
·
IF 2.784
Yuhuan Ma,Wenwei Zheng,Houhuang Chen,Xiang Shao,Pingdong Lin,Xianxiang Liu,Xihai Li,Hongzhi Ye
The present study investigated the mechanism underlying the effects of glucosamine (GlcN) on the proliferation of chondrocytes isolated from the knee cartilage of Sprague‑Dawley rats. Chondrocytes were treated with various concentrations of GlcN or without GlcN. The effects of GlcN on chondrocyte proliferation were determined using reverse transcription‑polymerase chain reaction, western blot analysis and immunohistochemistry. The results indicated that GlcN significantly improved chondrocyte viability, accelerated G1/S transition during progression of the cell cycle and promoted the expression of cell cycle regulatory proteins, including cyclin D1, cyclin‑dependent kinase (CDK)4 and CDK6, thus indicating that GlcN may promote chondrocyte proliferation. Furthermore, GlcN upregulated the expression levels of Wnt‑4, Frizzled‑2 and β‑catenin, and downregulated the expression of glycogen synthase kinase‑3. GlcN also promoted β‑catenin translocation; β‑catenin is able to activate numerous downstream target genes, including cyclin D1. To determine the role of the Wnt/β‑catenin signaling pathway in chondrocyte proliferation, the Wnt/β‑catenin signaling pathway was inhibited using Dickkopf‑1 (DKK‑1), after which chondrocytes were treated with GlcN. The results demonstrated that the expression levels of β‑catenin and cyclin D1 were decreased in chondrocytes treated with DKK‑1 and GlcN. These results suggested that GlcN may promote chondrocyte proliferation via the Wnt/β‑catenin signaling pathway.
研究领域:
药理学
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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
OncoTargets and Therapy
·
2022
·
IF 4.345
Yue Jing,Gang Wang,Ying Ge,Minjie Xu,Shuainan Tang,Zhunan Gong
Asiatic acid (AA; 2α,3β,23-trihydroxyurs-12-ene-28-oic acid) is widely used for medicinal purposes in many Asian countries due to its various bioactivities. A series of AA derivatives has been synthesized in attempts to improve its therapeutic potencies. Herein we investigated the anti-tumor activities of N-(2α,3β,23-acetoxyurs-12-en-28-oyl)-l-proline methyl ester (AA-PMe), a novel AA derivative. AA-PMe exhibited a stronger anti-cancer activity than its parent compound AA. AA-PMe inhibited the proliferation of SGC7901 and HGC27 human gastric cancer cells in a dose-dependent manner but had no significant toxicity in human gastric mucosa epithelial cells (GES-1). AA-PMe induced cell cycle arrest in G0/G1 phase and blocked G1-S transition, which correlated well with marked decreases in levels of cyclin D1, cyclin-dependent kinase CKD4, and phosphorylated retinoblastoma protein, and increase in cyclin-dependent kinase inhibitor P15. Further, AA-PMe induced apoptosis of human gastric cancer cells by affecting Bcl-2, Bax, c-Myc, and caspase-3. Moreover, AA-PMe suppressed the migration and invasion of human gastric cancer cells (SGC7901 and HGC27) cells by downregulating the expression of MMP-2 and MMP-9. Overall, this study investigated the potential anti-cancer activities of AA-PMe including inducing apoptosis and suppressing proliferation, migration and invasion of gastric cancer cells, as well as the underlying mechanisms, suggesting that AA-PMe is a promising anti-cancer drug candidate in gastric cancer therapy.
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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分子生物学
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产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
·
2023
·
IF 8.8
Zhen-Ning Zhang,Dan-Lei Yang,Hai Liu,Jue Bi,Ya-Bo Bao,Jiao-Yang Ma,Qin-Xiang Zheng,Dao-Lei Cui,Wei Chen,Ping Xiang
Tris(2-chloroisopropyl) phosphate (TCPP) and Tris(2-chloroethyl) phosphate (TCEP) are the widely used organophosphorus flame retardants indoors and easily accessible to the eyes as the common adhesive components of dust and particle matter, however, hardly any evidence has demonstrated their corneal toxicity. In this study, the adverse effects of TCPP, TCEP, and TCPP + TCEP exposure on human corneal epithelial cells (HCECs) were investigated. The cell viability and morphology, intracellular reactive oxygen species (ROS), cell cycle, and the expressions of cell cycle and pyroptosis-related genes were assessed to explain the underlying mechanisms. Compared to individual exposure, co-exposure to TCPP 20 +TCEP 20 showed higher cytotoxicity with a sharp decrease of >30% in viability and more serious oxidative damage by increasing ROS production to 110.92% compared to the control group. Furthermore, the cell cycle arrested at the S phase (36.20%) was observed after combined treatment, evidenced by the upregulation of cyclin D1 , CDK2 , CDK4 , CDK6 , p21, and p27 . Interestingly, pyroptosis-related genes GSDMD , Caspase-1 , NLRP3 , IL-1β , IL-18 , NLRP1, and NLRC4 expressions were promoted with cell swelling and glowing morphology. Oxidative stress and cell cycle arrest probably acted as a key role in TCPP 20 +TCEP 20 -induced cytotoxicity and pyroptosis in HCECs. Our results suggested that TCPP 20 +TCEP 20 co-exposure induced severer corneal damage, further illustrating its significance in estimating indoor health hazards to humans.
研究领域:
毒理学
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细胞生物学
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眼科学
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环境健康
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DOI
PubMed
高影响因子
CELL BIOLOGY INTERNATIONAL
·
2023
·
IF 3.9
Hongyang Xie,Junyu Chen,Changyan Ma,Jingjing Zhao,Manhua Cui
Dysregulation of the deubiquitinating protease, UBP43, has been implicated in many human diseases, including cancer. Here, we evaluated the functional significance and mechanism of action of UBP43 in epithelial ovarian cancer. We found that UBP43 was significantly upregulated in the tumor tissues of patients with epithelial ovarian cancer. Similar results were observed in OVCAR-3, Caov-3, TOV-112D, A2780, and SK-OV-3 cells. Furthermore, in vitro functional assays of A2780 and TOV-112D cells demonstrated that UBP43 overexpression promoted cell proliferation, migration, and invasion. Upregulation of UBP43 might result in epithelial–mesenchymal transition by inducing the nuclear transport of β-catenin, which was accompanied by enhanced N-cadherin but decreased E-cadherin expression. These malignant phenotypes were reversed by UBP43 silencing. Further investigation revealed that the knockdown of UBP43 inhibited cell proliferation by inducing a cell cycle arrest at the G2/M phase. The oncogenic characteristics of UBP43 were validated in a subcutaneous xenograft mouse model. In vivo, tumor growth was delayed in the UBP43-silenced group but accelerated after UBP43 overexpression. Finally, we demonstrated that β-catenin is a key protein in the UBP43-mediated malignant development of epithelial ovarian cancer. Specifically, overexpression of UBP43 decreased the ubiquitination degradation of β-catenin and enhanced its protein stability. Also, we observed that the downstream genes of beta-catenin such as cyclin D1, MMP2, and MMP9 were upregulated due to UBP43 overexpression. Thus, we concluded that UBP43 promoted epithelial ovarian cancer tumorigenesis and metastasis through activation of the β-catenin pathway, suggesting that UBP43 may be a potential therapeutic target for this intractable disease.
研究领域:
肿瘤学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
Journal of Integrative Medicine-JIM
·
2020
·
IF 2.446
Tian Fang,Ze-sheng Xue,Jia-xuan Li,Jia-kuan Liu,Di Wu,Mei-qian Li,Yu-ting Song,Shi-feng Yun,Jun Yan
Objective Herbal medicine is an important therapeutic option for benign prostatic hyperplasia (BPH), a common disease in older men that can seriously affect their quality of life. Currently, it is crucial to develop agents with strong efficacy and few side effects. Herein we investigated the effects of the extract of Rauwolfia vomitoria , a shrub grown in West Africa, on BPH. Methods Rats with testosterone-induced BPH were treated with R. vomitoria . Prostates were histologically analyzed by Hematoxylin and eosin staining. Proliferation index and the expression levels of androgen receptor and its associated proteins were quantified through immunohistochemistry and immunoblotting. Androgen receptor target genes were examined by quantitative real-time polymerase chain reaction. The sperm count and body weight of rats were also measured. Results The oral administration of R. vomitoria extract significantly reduced the prostate weight and prostate weight index in BPH rats, supported by the decreased thickness of the prostate epithelial layer and increased lumen size. Similar effects were observed in the BPH rats treated with the reference drug, finasteride. R. vomitoria extract significantly reduced the testosterone-induced proliferation markers, including proliferating cell nuclear antigen and cyclin D1 , in the prostate glands of BPH rats; it also reduced levels of androgen receptor, its associated protein steroid 5α-reductase 1 and its downstream target genes ( FK506-binding protein 5 and matrix metalloproteinase 2 ). Notably, compared with the finasteride group, R. vomitoria extract did not significantly reduce sperm count. Conclusion R. vomitoria suppresses testosterone-induced BPH development. Due to its milder side effects, R. vomitoria could be a promising therapeutic agent for BPH.
研究领域:
药理学
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泌尿学
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草药医学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6.8
Zekun Li,Mochen Guo,Mingxiao Gu,Zhongtian Cai,Qiuyu Wu,Jia Yu,Meilun Tang,Chenxi He,Yuxuan Wang,Piaoyang Sun,Qidong You,Lei Wang
The serine/threonine phosphatase family is important in tumor progression and survival. Due to the high conserved catalytic domain, designing selective inhibitors is challenging. Herein, we obtained compound 28a with 38-fold enhanced PP5 selectivity (PP2A/5 IC50 = 33.8/0.9 μM) and improved drug-like properties (favorable stability and safety, F = 82.0%) by rational drug design based on a phase II PP2A/5 dual target inhibitor LB-100. Importantly, we found the spatial conformational restriction of the 28a indole fragment was responsible for the selectivity of PP5. Thus, 28a activated p53 and downregulated cyclin D1 and MGMT, which showed potency in cell cycle arrest and reverse temozolomide (TMZ) resistance in the U87 MG cell line. Furthermore, oral administration of 28a and TMZ was well tolerated to effectively inhibit tumor growth (TGI = 87.7%) in the xenograft model. Collectively, these results implicate 28a could be a drug candidate by reversing TMZ resistance with a selective PP5 inhibition manner.
研究领域:
药理学
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肿瘤学
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药物化学
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癌症生物学
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产品关联
DOI
PubMed
高影响因子
Nano Research
·
2020
·Vol. 13
·期 8
·2106-2117
·
IF 8.183
Li Zhongtao,Tang Jiaoqing,Wu Hongfeng,Ling Zhixin,Chen Siyu,Zhou Yong,Guo Bo,Yang Xiao,Zhu Xiangdong,Wang Lin,Tu Chongqi,Zhang Xingdong
Melanoma is a highly malignant skin tumor which is prone to recurrence and metastasis. Hydroxyapatite nanoparticles (nHAPs) were reported to possess a suppressive effect on proliferation of various tumor cells in vitro. This study aimed to assess in vitro and in vivo anti-tumor ability and biosafety of the nHAPs used in the treatment of melanoma. Three types of nHAPs with different morphology and crystallinity were synthesized. In vitro cell viability and proliferation studies demonstrated that all three types of nHAPs can inhibit viability and proliferation of A375 and SK-MEL-28 melanoma cells in a concentration-dependent manner. In addition, the rod-shape nHAPs with a crystallinity of 45.60% had the most prominent suppressive effect on the two melanoma cells tested. An important positive regulator of G1/S phase transition in cell cycle, Cyclin D1 protein, was reduced by nHAPs treatment in vivo. We further discovered that the migration ability of the nHAPs treated melanoma cells was greatly decreased. RNA sequencing result revealed that melanoma metastasis related genes were down-regulated by nHAPs, including MMP2, MMP14, ITGA9, ITGB3, ITGB4 and S100B. High concentration of nHAPs treatment in melanoma-bearing nude mice showed a strong inhibitory effect on tumor size and weight. Most importantly, hemolysis, electrolyte disturbance or inflammation response was not discovered in the experimental animals from nHAPs treated groups. We proved that the nHAPs synthesized in the current study has a selective effect to suppress melanoma tumor proliferation and was safe with regard to normal cells and tissue.
研究领域:
肿瘤学
·
纳米技术
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分子生物学
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药学
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产品关联
DOI
高影响因子
HUMAN GENE THERAPY
·
2023
·
IF 4.2
Dr. Zhiguang Chen,Ms. Qi Zhao,Mr. Ran Zhang,Dr. Lianghong Chen,Mr. Songlan Gao,Dr. Yu Wang,Dr. Tiegang Li,Dr. Jinqi Xue
Substantial advances have been made in understanding the role of partial PDZ and LIM domain (PDLIM) family’s proteins in skeletal-related diseases. Yet, little is known about the effect of Pdlim1 on osteogenesis and fracture repair. This study aimed to investigate whether direct gene delivery using an adenovirus vector carrying Pdlim1 (Ad-oePdlim1) or encoding shRNA-Pdlim1 (Ad-shPdlim1) could affect the osteogenic activity of pre-osteoblastic MC3T3-E1 cells in vitro, and influence the fracture healing of mice in vivo. We found that Ad-shPdlim1 transfection contributed to the calcified nodule formation in MC3T3-E1 cells. Downregulation of Pdlim1 enhanced the alkaline phosphatase (ALP) activity and increased the expression of osteogenic markers (Runx2, Col1A1, osteocalcin and osteopontin). Further analysis indicated that Pdlim1 knockdown could activate β-catenin signaling, as evidenced by the accumulation of β-catenin in the nucleus and the increase levels of downstream regulators such as Lef1/Tcf7, Axin2, Cyclin D1 and Sox9. By contrast, Pdlim1 overexpression resulted in inhibition of the osteogenic activity of MC3T3-E1 cells. In vivo, at day 3 after fracture, Ad-shPdlim1 adenovirus particles were injected into the fracture site of the femur of mice, and the process of fracture healing was evaluated by X-ray, Micro-CT and histological examination. Local injection of Ad-shPdlim1 promoted the early cartilage callus formation, restored bone mineral density and accelerated cartilaginous ossification, with the upregulation of osteogenic gene (Runx2, Col1A1, osteocalcin and osteopontin) expression and activation of β-catenin signaling. Thus, we concluded that inhibition of Pdlim1 contributed to osteogenesis and fracture healing by activating the β-catenin signaling pathway.
研究领域:
分子生物学
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骨科
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再生医学
·
基因治疗
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产品关联
DOI
PubMed
高影响因子
CELL BIOCHEMISTRY AND BIOPHYSICS
·
2014
·Vol. 71
·期 1
·367-373
·
IF 2.38
Gan Maozhou,Yin Xiaodong
This research designed to explore the antitumor activity of puerarin against human mantle cell lymphoma (MCL). Cell proliferation and apoptosis were assessed by MTS and flow cytometry. Caspase-3, -8, and -9 activities were assessed with the colorimetric caspase protease assay. Apoptotic proteins like PARP, cyclin D1, Bcl-2 family, XIAP, and cIAP I were researched by western blot. The PI3K inhibitor LY294002 was used to investigate the possible mechanism relating the PI3K/Akt signaling pathway. Puerarin in vitro inhibited proliferation and induced apoptosis of Z138 cells. Expressions of PI3K and p-Akt were downregulated by puerarin. Puerarin negatively regulated NF-κB activity by inhibiting NF-κB phosphorylation with nuclear translocation inhibition. This kind of effects was correlated with the suppression of expression of cyclin D1, BAX, Bcl-2, XIAP etc. This function was modulated by the PI3K inhibitor. Our results demonstrated that puerarin can induce growth arrest and apoptosis in MCL cells and that the mechanism may involve the NF-κB signaling pathway. Puerarin may have therapeutic applications in the treatment of MCL.
研究领域:
肿瘤学
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药理学
·
细胞生物学
·
信号转导
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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）