MOLECULAR BIOLOGY REPORTS
·
2022
·Vol. 49
·期 6
·4607-4617
·
IF 2.742
Zhang Yimin,Chen Jingqin,Fang Wenxuan,Liang Kaoyun,Li Xiaoning,Zhang Fan,Pang Yuzhou,Fang Gang,Wang Xueni
Purpose Kaempferol is a natural flavonoid that has been reported to be active against many cancers, including prostate cancer, breast cancer and colon cancer. In our previous study, we found kaempferol could act as a selective androgen receptor modulator, thereby suppress development of benign prostatic hyperplasia. This finding inspired us to further explore the effect and the mechanism of action of kaempferol on prostate cancer. Methods Plate clone formation assay was performed to detect the effect of kaempferol on cell proliferation. Flow cytometry was used to detect the impact of kaempferol on cell apoptosis and cell cycle distribution. qPCR, immunofluorescence staining, and enzyme-linked immunosorbent assay were used to detect the expression of gene and protein of Ki67 which is a biomarker of cell proliferation. Results In the present study, we found kaempferol could dramatically suppress androgen-dependent and androgen-independent prostate cancer cells proliferation and induce their apoptosis. Furthermore, we found that kaempferol induced cell cycle to be arrested at G1 phase in 22Rv1 cells but at S and G2 phase in PC-3 cells. In addition, we detected the mRNA and protein of Ki67 which is corresponding to the cell proliferation and found that kaempferol could significantly inhibit Ki67 expression at mRNA level but increase its expression at protein levels in both androgen-dependent and androgen-independent prostate cancer cells. Conclusion Taken together, kaempferol inhibited the proliferation of androgen-dependent and androgen-independent prostate cancer cells by regulating the expression of Ki67. These findings further shed light on the mechanism of action of kaempferol on anti-prostate cancer.
研究领域:
肿瘤学
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药理学
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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
BIOSCIENCE REPORTS
·
2018
·Vol. 38
·期 6
·
IF 2.899
Jing Yue,Yang Yan,Hao Fengyao,Song Yuxian,Zhang Xiaoxin,Zhang Ye,Huang Xiaofeng,Hu Qingang,Ni Yanhong
Background: Ki67 has been a key role for the treatment options and prognosis evaluation in some kinds of tumors; however, the spatial expression of Ki67 in oral squamous cell carcinoma (OSCC) has not been fully-evaluated. Therefore, in the present study, we aimed to elucidate the prognosis value of Ki67 spatial expression including in different cell types and at different compartments of tumor in OSCC patients. Methods: Immunohistochemical expression of Ki67 in tumor cells (TCs) and fibroblast like cells (FLCs) at center of tumor (CT) and invasive front (IF) was evaluated in 109 OSCC patients. Then correlations of Ki67 expressions with clinicopathological parameters were analyzed by Chi-square test, and survival curves were evaluated by Kaplan–Meier methods. Furthermore, univariate and multivariate analysis were performed to assess the diagnostic values of Ki67 expression by the Cox regression model. Results: Ki67 expression in TCs was much higher than in FLCs both at CT and IF compartments, but Ki67 expression in TCs was simultaneously higher at CT than that at IF (P=0.0004), which was converse to Ki67 expression in FLCs (P<0.0001). Additionally, high Ki67 expression in FLCs at IF was significantly associated with poor tumor differentiation (P=0.003), worse depth of invasion (DOI, P=0.027) and worst pattern of invasion (WPOI, P=0.041), but Ki67 expression in TCs had no correlation with clinical parameters no matter at CT or IF. Moreover, patients with higher Ki67 expression in TCs at CT had significantly increased risk for OS (overall survival; HR:1.935, 95% CI: 1.181–4.823, P=0.0395) and DFS (disease-free survival; HR: 2.974, 95% CI:1.189–5.023, P=0.046). On contrary, higher Ki67 expression in FLCs at IF was correlated with better OS (HR: 0.15, 95% CI: 0.018–0.846, P=0.0396) and DFS (HR: 0.15, 95% CI: 0.018–0.947, P=0.0445). Whereas, Ki67 expression both at TCs in IF and at FLCs in CT had no significant prognostic value for OS and DFS. Furthermore, Cox multivariate analysis revealed that Ki67 expression in FLCs at IF could not be an independent prognostic factor for OSCC patients. Conclusion: These results show that higher Ki67 expression in FLCs at IF indicated better clinical outcomes for OSCC patients.
研究领域:
肿瘤学
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病理学
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产品关联
DOI
PubMed
高影响因子
Journal of Toxicologic Pathology
·
2019
·
IF 1.153
Qian Tang,Mei Zhang,Zexuan Hong,Yao Chen,Pan Wang,Jian Wang,Zili Wang,Rendong Fang,Meilan Jin
To clarify the suppressive effects of astragalus injection (AI) on different stages of early hepatocarcinogenesis induced by weak promotion, SD rats initiated with a single intraperitoneal (i.p.) injection of N-diethylnitrosamine (DEN) at 200 mg/kg body weight and promoted with 0.5% piperonyl butoxide (PBO) in diet were repeatedly administered AI at 5 ml/kg body weight/day in the early postinitiation (EPI) or late postinitiation (LPI) period for 2 or 8 weeks, respectively. The number and area of glutathione S-transferase placental form (GST-P)-immunoreactive (+) foci tended to increase in the DEN+PBO group compared with the DEN-alone group. Among the PBO-promoted groups, number and area of GST-P+ foci did not visibly change in the DEN+PBO+AI-EPI group compared with the DEN+PBO group. In contrast, number and area of GST-P+ foci tended to decrease in the DEN+PBO+AI-LPI group compared with the DEN+PBO group. Number of Ki67+ cells was increased in the DEN+PBO group compared with the DEN-alone group and was decreased in both AI-administered groups compared with the DEN+PBO group. Gene expression analysis revealed that the DEN+PBO+AI-LPI group showed increased transcript levels of Ccne1, Cdkn1b, Rb1, Bax, Bcl2, Casp3, and Casp9 compared with the DEN+PBO group; however, the DEN+PBO+AI-EPI group did not show changes in the transcript levels of any genes examined compared with the DEN+PBO. These results suggest that AI administration during the LPI period caused weak suppression of hepatocarcinogenesis under weak promotion with a low PBO dose by the mechanism involving facilitation of cell cycle suppression causing G1/S arrest and apoptosis via the mitochondrial pathway. In addition, the results suggest that AI administration during the EPI period has no effect on weakly promoted hepatocarcinogenesis.
研究领域:
肿瘤学
·
药理学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
·
2024
·
IF 2.7
Yu-Hang Dai,Fang-Li Sun,Rui-Miao Wei,Jia-Ji Guo,De-Li Dong,Zhi-Jie Sun
Psoriasis is a chronic inflammatory skin disease. Topical medicines are the preferred treatment for mild to moderate psoriasis, but the effect of excipients used in semi-solid preparations on psoriasis-like skin inflammation is not fully understood. In the present study, we investigated the effect of stearyl alcohol, a commonly used excipient, on imiquimod (IMQ)-induced psoriasis-like skin inflammation in mice. Psoriasis-like skin inflammation was induced by topical IMQ treatment on the back of mice. Skin lesion severity was evaluated by using psoriasis area and severity index (PASI) scores. The skin sections were stained by haematoxylin–eosin and immunohistochemistry. Stearyl alcohol (20% in vaseline) treatment significantly reduced the IMQ-induced increase of PASI scores and epidermal thickness in mice. IMQ treatment increased the number of Ki67- and proliferating cell nuclear antigen (PCNA)-positive cells in the skin, and the increases were inhibited by stearyl alcohol (20% in vaseline) treatment. Stearyl alcohol treatment (1%, 5%, 10% in vaseline) dose-dependently ameliorated IMQ-induced increase of PASI scores and epidermal thickness in mice. Hexadecanol (20% in vaseline), stearic acid (20% in vaseline) and vaseline treatment had no significant effect on IMQ-induced psoriasis-like skin inflammation in mice. In conclusion, stearyl alcohol has the effect of improving IMQ-induced psoriasis-like skin inflammation in mice.
研究领域:
药理学
·
皮肤病学
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炎症
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产品关联
DOI
PubMed
高影响因子
Heliyon
·
2025
·
IF 3.6
Kan Liu,Jinlong Zhu,Yangyang Bao,Jin Fang,Shuihong Zhou,Jun Fan
Multiple studies have demonstrated a significant association between glucose transporter-1 (GLUT1) and the development and recurrence of adenoid cystic carcinoma (ACC). In this study, we investigated the impact of GLUT1 knockdown on adenoid cystic carcinoma. Our findings revealed that hypoxic conditions promoted the progression and autophagy of SACC83 and SACC-LM cell lines, an effect that was mitigated by GLUT1 knockdown. In vivo experiments showed that the combination of lentivirus-delivered GLUT1 shRNA and autophagy inhibitor chloroquine (CQ) produced the most substantial reduction in tumor volume, weight, Ki67 expression, and autophagy in tumor tissues. In conclusion, hypoxia facilitates ACC progression by upregulating GLUT1 expression. The suppression of GLUT1 expression and autophagy effectively inhibited ACC cell proliferation both in vitro and in vivo .
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
MOLECULAR CARCINOGENESIS
·
2019
·Vol. 58
·期 8
·1481-1491
·
IF 3.411
Yuan-yuan Guo,Chen Xu,Yan Fang,Cai-e Wang,Na Gao,Qiang Wen,Hai-ling Qiao
Cytochrome P450 2E1 (CYP2E1) is an important drug-metabolizing enzyme that has been recognized as one of the risk factors for hepatofibrosis. Macrophages play key roles in regulating hepatofibrosis progression and resolution. However, whether CYP2E1 is involved in the regulation of macrophage polarization during hepatofibrosis is still unclear. Herein, we measured CYP2E1 activity and the expression of CD163 (an M2 marker) and CD68 (a pan-macrophage marker) in hepatofibrotic tissue from HCC patients (n = 26) with comparison to normal liver tissue (n = 26). The relationship of CYP2E1 activity in vivo and the CD163/CD68 ratio (an indicator of M2 polarization), as well as the extent of hepatofibrosis, were evaluated in diethylnitrosamine (DEN)-treated Sprague-Dawley rats. Strikingly, CYP2E1 activity and expression of CD68 increased and the CD163/CD68 ratio decreased, especially in hepatofibrotic tissue with higher CYP2E1 activity. Expression of α-SMA, Ki67, and PCNA were positively correlated with CYP2E1 activity and inversely correlated with the CD163/CD68 ratio. Furthermore, CYP2E1 activity showed an inverse correlation with the CD163/CD68 ratio. Overall, high CYP2E1 activity aggravates hepatofibrosis by restraining M2 macrophage polarization, providing a novel insight for understanding the profibrotic activity of CYP2E1 and a promising avenue for hepatofibrosis therapy.
研究领域:
肝病学
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免疫学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Cancer
·
2022
·
IF 4.478
Shixin Chan,Rui Sun,Xucan Tu,Manyu Guo,Qianqian Yuan,Zhen Yu,Zhenglin Wang,Shaocheng Hong,Wei Han,Bingbing Zou,Zeng Li,Huabing Zhang,Wei Chen
Colorectal cancer (CRC) is a malignant disease that is a serious threat to human health. Rutaecarpine (RUT) is an important bioactive alkaloid of Evodia rutaecarpa. According to previous studies, RUT suppressed the proliferation of several human tumors. However, its role in colorectal tumorigenesis remained unknown. The aim of the present study was to determine the functions of RUT in CRC. Here, we have demonstrated that RUT inhibited the proliferation, migration and invasion of CRC cells in vitro . Further, RUT was found to induce the apoptosis of CRC cells. Mechanistically, RUT decreased the phosphorylation levels of NF-κB and STAT3. Moreover, treatment with RUT upregulated the expression of cleaved-Caspase3 and downregulated the expression of Bcl-2 in CRC. In addition, our findings suggested that RUT inhibited the growth and lung metastasis of CRC Cells in vivo . Based on immunofluorescence analysis, the expression of Ki67 was downregulated while that of cleaved-Caspase3 was upregulated in RUT-treated tumors compared with control-treated tumors. Taken together, our findings indicate that RUT can inhibit the proliferation and migration of CRC cells, and induce the apoptosis of CRC cells by inactivating NF-κB/STAT3 signaling. Our study highlights the potential clinical application of RUT for the treatment of CRC.
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
Frontiers in Pharmacology
·
2023
·
IF 5.6
E. Sun,Xiangqi Meng,Zhaoxia Kang,Huimin Gu,Mingyu Li,Xiaobin Tan,Liang Feng,Xiaobin Jia
Lung cancer is a common malignant tumor in clinical practice, and its morbidity and mortality are in the forefront of malignant tumors. Radiotherapy, chemotherapy, and surgical treatment play an important role in the treatment of lung cancer, however, radiotherapy has many complications and even causes partial loss of function, the recurrence rate after surgical resection is high, and the toxic and side effects of chemotherapy drugs are strong. Traditional Chinese medicine has played a huge role in the prognosis and improvement of lung cancer, among them, Zengshengping (ZSP) has the effect of preventing and treating lung cancer. Based on the “gut-lung axis” and from the perspective of “treating the lung from the intestine”, the purpose of this study was to research the effect of Zengshengping on the intestinal physical, biological, and immune barriers, and explore its role in the prevention and treatment of lung cancer. The Lewis lung cancer and urethane-induced lung cancer models were established in C57BL/6 mice. The tumor, spleen, and thymus were weighed, and the inhibition rate, splenic and thymus indexes analyzed. Inflammatory factors and immunological indexes were detected by enzyme-linked immunosorbent assay. Collecting lung and colon tissues, hematoxylin and eosin staining was performed on lung, colon tissues to observe histopathological damage. Immunohistochemistry and Western blotting were carried out to detect tight junction protein expression in colon tissues and expression of Ki67 and p53 proteins in tumor tissues. Finally, the feces of mice were collected to investigate the changes in intestinal microbiota using 16SrDNA high-throughput sequencing technology. ZSP significantly reduced tumor weight and increased the splenic and thymus indexes. It decreased expression of Ki67 protein and increased expression of p53 protein. Compared with Model group, ZSP group reduced the serum levels of interleukin (IL)-1β, IL-6, tumor necrosis factor α (TNF-α), and ZSP group increased the concentration of secretory immunoglobulin A (sIgA) in the colon and the bronchoalveolar lavage fluid (BALF). ZSPH significantly increased the level of tight junction proteins such as ZO-1, Occludin and Claudin-1. Model group significantly reduced the relative abundance of Akkermansia ( p < 0.05) and significantly promoted the amount of norank_f_ Muribaculaceae, norank_f_ Lachnospiraceae ( p < 0.05) compared with that in the Normal group. However, ZSP groups increased in probiotic strains ( Akkermansia ) and decreased in pathogens ( norank_f_ Muribaculaceae, norank_f_ Lachnospiraceae). Compared with the urethane-induced lung cancer mice, the results showed that ZSP significantly increased the diversity and richness of the intestinal microbiota in the Lewis lung cancer mice. ZSP played an important role in the prevention and treatment of lung cancer by enhancing immunity, protecting the intestinal mucosa and regulating the intestinal microbiota.
研究领域:
肿瘤学
·
药理学
·
免疫学
·
微生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Feng-Ling Tang,Li-Wei Xie,Lin-Feng Tang,Hai-Yan Lu,Rui-Qiu Zhu,Di-Fan Wang,Ye Tian,Shang Cai,Ming Li
The small intestine exhibits remarkable sensitivity to ionizing radiation (IR), which significantly hampers the effectiveness of radiotherapy in the treatment of abdominal and pelvic tumors. Unfortunately, no effective medications are available to treat radiation-induced intestinal damage (RIID). Fraxin (7-hydroxy-6-methoxycoumarin 8-glucoside), is a coumarin derivative extracted from the Chinese herb Cortex Fraxini. Several studies have underscored the anti-inflammatory, antibacterial, antioxidant, and immunomodulatory properties of fraxin. However, the efficacy of fraxin at preventing or mitigating RIID remains unclear. Thus, the present study aimed to investigate the protective effects of fraxin against RIID in vitro and in vivo and to elucidate the underlying mechanisms. The study findings revealed that fraxin markedly ameliorated intestinal injuries induced by 13 Gy whole abdominal irradiation (WAI), which was accompanied by a significant increase in the population of Lgr5 + intestinal stem cells (ISCs) and Ki67 + progeny. Furthermore, fraxin mitigated WAI-induced intestinal barrier damage, and reduced oxidative stress and intestinal inflammation in mice. Transcriptome sequencing of fraxin-treated mice revealed upregulation of IL-22, a pleiotropic cytokine involved in regulating the function of intestinal epithelial cells. Moreover, in both human intestinal epithelial cells and ex vivo cultured mouse intestinal organoids, fraxin effectively ameliorated IR-induced damage by promoting the expression of IL-22. The radioprotective effects of fraxin were partially negated in the presence of an IL-22-neutralizing antibody. In summary, fraxin is demonstrated to possess the ability to alleviate RIID and maintain intestinal homeostasis , suggesting that fraxin might serve as a strategy for mitigating accidental radiation exposure- or radiotherapy-induced RIID.
研究领域:
放射生物学
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药理学
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分子生物学
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免疫学
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胃肠病学
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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
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2022
·
IF 9.417
Hui Zhang,Yanjing Ji,Changqing Yuan,Pei Sun,Quanchen Xu,Dongliang Lin,Zeyu Han,Xinkai Xu,Qihui Zhou,Jing Deng
Oral premalignant lesions (OPL) are one of the most common oral diseases, affecting the quality of life and even leading to oral cancer. Current treatments commonly use steroids/retinoids in mouthwashes, films, or ointments. However, conventional drugs/formulations have significant side effects/limitations. Herein, astaxanthin-loaded polycaprolactone (PCL)/gelatin (GT) nanofiber-based mucoadhesive patches (PGA) with the water‐insoluble PCL nanofiber backing (PCL/PGA) are developed via electrospinning for the management of OPL. The saliva-insoluble PCL backing could greatly prevent drug loss after application in the oral cavity. The prepared PCL/PGA patches exhibit a suitable astaxanthin release rate for achieving high local drug concentration, which permeated into buccal mucosa. In addition, the developed thin patches display excellent wet tissue adhesion and great air permeability due to their high porosity. Notably, the in vivo experiment shows that the bioactive mucoadhesive patches significantly promote the recovery of OPL by suppressing the expression of Ki67 and cyclooxygenase-2 (COX-2), comparable to clinical tretinoin cream formulation. Also, the patches did not induce any side effects (i.e., hair loss and oral ulcers) compared to clinical tretinoin cream formulation. The results demonstrate that this novel electrospun mucoadhesive bilayer patch holds great potential for the treatment of OPL.
研究领域:
药学
·
生物医学工程
·
牙科
·
材料科学
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产品关联
DOI
高影响因子
MOLECULAR BIOTECHNOLOGY
·
2022
·Vol. 65
·期 4
·612-623
·
IF 2.86
Han Ning,Zhang Lihong,Guo Mi,Yu Li
Advanced proliferative diabetic retinopathy (PDR) characterized by aberrant retinal angiogenesis is a leading cause of retinal detachment and blindness. Krüppel-like factor 9 (KLF9), a member of the zinc-finger family of transcription factors, participates in the development of diabetic nephropathy and the promotion of angiogenesis of human umbilical vein endothelial cells. Therefore, we speculate that KLF9 may exert a crucial role in PDR. The current study revealed that KLF9 was highly expressed in the high glucose (HG)-treated human retinal microvascular endothelial cells (HRMECs) and the retinas of oxygen-induced retinopathy (OIR) rats. Knockdown of KLF9 inhibited the proliferation, migratory capability, invasiveness and tube formation of HG-treated HRMECs. Besides, knockdown of KLF9 decreased the expression of yes-associated protein 1 (YAP1) in HG-treated HRMECs. Dual-luciferase reporter assays confirmed that KLF9 transcriptionally upregulated YAP1 expression. Overexpression of YAP1 reversed the KLF9 silencing-induced repression of HRMEC proliferation and tube formation. Further in vivo evidence demonstrated that knockdown of KLF9 reduced the expression of Ki67, CD31 and vascular endothelial growth factor A (VEGFA) in the retinas of OIR rats. Collectively, KLF9 silencing might mitigate the progression of PDR by inhibiting angiogenesis via blocking YAP1 transcription.
研究领域:
糖尿病
·
视网膜
·
分子生物学
·
细胞生物学
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转录因子
·
血管生成
✓ 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）