JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Borui Zhao,Xuan Qin,Rui Fu,Maosen Yang,Xin Hu,Shaorong Zhao,Yange Cui,Qingxiang Guo,Wei Zhou
Chemoresistance to cisplatin remains a significant challenge affecting the prognosis of advanced oral squamous cell carcinoma (OSCC). However, the specific biomarkers and underlying mechanisms responsible for cisplatin resistance remain elusive. Through comprehensive bioinformatic analyses, we identified a potential biomarker, BCL2 associated athanogene-1 (BAG1), showing elevated expression in head and neck squamous cell carcinoma (HNSCC). Since OSCC represents the primary pathological type of HNSCC, we investigated BAG1 expression in human tumor tissues and cisplatin resistant OSCC cell lines, revealing that silencing BAG1 induced apoptosis in cisplatin-resistant cells both in vitro and in vivo . This effect led to impaired cell viability of cisplatin resistant OSCC cells and indicated a positive correlation between BAG1 expression and the G1/S transition during cell proliferation. Based on these insights, the administration of a CDK4/6 inhibitor in combination with cisplatin effectively overcame cisplatin resistance in OSCC through the CDK4/6-BAG1 axis. Additionally, to enable simultaneous drug delivery and enhance synergistic antitumor efficacy, we developed a novel supramolecular nanodrug LEE011-FFERGD/CDDP, which was validated in an OSCC orthotopic mouse model. In summary, our study highlights the potential of a combined administration of CDK4/6 inhibitor and cisplatin as a promising therapeutic regimen for treating advanced or cisplatin resistant OSCC.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
癌症治疗
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DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2020
·
IF 4.96
Xuqian Deng,Jiaqi Zhao,Linlin Qu,Zhiguang Duan,Rongzhan Fu,Chenhui Zhu,Daidi Fan
Ginsenoside Rh4, as a bioactive component obtained from Panax notoginseng , has excellent pharmacological efficacy especially antitumor effects. However, its anticancer effects and target mechanisms in regulating human esophageal cancer are still poorly understood. Here, the results suggested that Rh4 exhibited potent anti-esophageal cancer effects in vivo and in vitro . Flow cytometric analysis and Western Blot showed that Rh4 significantly inhibited the growth by inducing G1 phase arrest. In parallel, Rh4 inhibited aerobic glycolysis in esophageal cancer cells by hindering lactate production, glucose uptake and ATP production; reducing the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR); suppressing aerobic glycolysis-related protein expression. Mechanistic studies demonstrated that AKT is a possible target of Rh4, which suppresses aerobic glycolysis. Rh4 administration resulted in AKT deregulation, whereas treatment with insulin abolished the inhibitory effect of Rh4 on aerobic glycolysis. In contrast, treatment with AKT inhibitors or siRNA that silenced AKT enhanced the inhibitory effect of Rh4 on aerobic glycolysis. Moreover, molecular docking results indicated that Rh4 was able to bind to the interdomain region of AKT. Interestingly, the results revealed that Rh4 also inhibited the expression of PD-L1 via the AKT/mTOR pathway. Taken together, our findings provide important insights into the anti-esophageal cancer effects of Rh4 via suppressing aerobic glycolysis and PD-L1 expression, which indicated Rh4 could be as promising drug for clinical treatment.
研究领域:
肿瘤学
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药理学
·
分子生物学
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DOI
PubMed
高影响因子
FASEB JOURNAL
·
2021
·Vol. 35
·期 10
·e21923
·
IF 5.192
Peiling Wang,Xiangmei Hua,Yang Sun,Hongyu Li,Yuge Han Bryner,Richard P. Hsung,Jun Dai
Our recent studies have shown that haspin, a protein kinase imperative for mitosis, is engaged in the interphase progression of HeLa and U2OS cancer cells. In this investigation, we employed the Fucci reporter system and time-lapse imaging to examine the impact of haspin gene silencing on cell cycle progressions at a single-cell level. We found that the loss of haspin induced multiple cell cycle defects. Specifically, the S/G2 duration was greatly prolonged by haspin gene depletion or inhibition in synchronous HeLa cells. Haspin gene depletion in asynchronous HeLa and U2OS cells led to a similarly protracted S/G2 phase, followed by mitotic cell death or postmitotic G1 arrest. In addition, haspin deficiency resulted in robust induction of the p21 CIP1/WAF1 checkpoint protein, a target of the p53 activation. Also, co-depleting haspin with either p21 or p53 could rescue U2OS cells from postmitotic G1 arrest and partially restore their proliferation. These results substantiate the haspin's capacity to regulate interphase and mitotic progression, offering a broader antiproliferative potential of haspin loss in cancer cells.
研究领域:
癌症生物学
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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
JOURNAL OF THE BRAZILIAN CHEMICAL SOCIETY
·
2019
·Vol. 30
·期 9
·1814-1824
·
IF 1.335
Zhao Jiao,Zhou Yifang,Zhang Yi,Wang Baoling,Ge Dandan
A novel method for the determination of aflatoxins B1, B2, G1, and G2 (AFB1, AFB2, AFG1, AFG2) in animal feed samples based on magnetic solid-phase cleanup and novel pre-column derivatization has been developed. In this work, synthesized polyvinylpyrrolidone-coated Fe3O4 magnetic nanoparticles were applied as adsorbents for rapid cleanup for extracts of animal feed samples. The purified extract was then derivatized with trifluoroacetic acid coupling ultraviolet irradiation which enabled the weakly fluorescent AFB1 and AFG1 transformed into their highly fluorescent hemiacetals derivatives. Afterward aflatoxins were separated and quantified by reverse phase liquid chromatography with fluorescence detection. The results indicated that four AFs presented excellent linear response with correlation coefficients > 0.996 and recoveries ranged from 86.7 to 108.9% with relative standard deviations (RSDs) from 3.6 to 6.4%. The limits of detection (LODs) were 0.0392, 0.2429, 0.0842, 0.4556 ng mL-1 for AFB1, AFB2, AFG1 and AFG2, respectively.
研究领域:
食品安全
·
分析化学
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产品关联
DOI
高影响因子
Aging-US
·
2019
·
IF 5.515
Yanhua Du,Jun Lin,Rulin Zhang,Wanli Yang,Heng Quan,Lijuan Zang,Yaqin Han,Bing Li,Hong Sun,Jun Wu
Globally, epithelial ovarian cancer (EOC) is the most common gynecological malignancy with poor prognosis. The expression and oncogenic roles of ubiquitin specific peptidase 5 (USP5) have been reported in several cancers except EOC. In the current study, USP5 amplification was highly prevalent in patients with EOC and associated with higher mRNA expression of USP5. USP5 amplification and overexpression was positively correlated with poor prognosis of patients of ovarian serous carcinomas. Disruption of USP5 profoundly repressed cell proliferation by inducing cell cycle G0/G1 phase arrest in ovarian cancer cells. Additionally, USP5 knockdown inhibited xenograft growth in nude mice. Knockdown of USP5 decreased histone deacetylase 2 (HDAC2) expression and increased p27 (an important cell cycle inhibitor) expression in vitro and in vivo . The promoting effects of USP5 overexpression on cell proliferation and cell cycle transition, as well as the inhibitory effects of USP5 overexpression on p27 expression were mediated by HDAC2. Moreover, USP5 interacted with HDAC2, and disruption of USP5 enhanced the ubiquitination of HDAC2. HDAC2 protein was positively correlated USP5 protein, and negatively correlated with p27 protein in ovarian serous carcinomas tissues. Collectively, our data suggest the oncogenic function of USP5 and the potential regulatory mechanisms in ovarian carcinogenesis.
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
TISSUE & CELL
·
2021
·
IF 2.466
Jianyun Cao,Xuebing Qiu,Yun Gao,Liangliang Cai
Puerarin regulates the osteoblast differentiation of umbilical cord mesenchymal stem cells. This study, hereby, explored the effects of puerarin on the osteogenic differentiation of dental follicle cells (DFCs) for the first time. Rat DFCs (rDFCs) were isolated and identified. After the rDFCs were treated by Puerarin and cultured in osteogenic induction medium, the viability, osteogenic differentiation, and the activities of alkaline phosphatase (ALP) and nitric oxide (NO) were detected. Besides, the secretion of cyclic guanosine monophosphate (cGMP) and expressions of collagen I, osteocalcin (OC), osteopontin (OPN), runt-related transcription factor 2 (RUNX2), soluble guanylate cyclase (SGC), and protein kinase G 1 (PKG-1) were further determined or quantified. Puerarin enhanced the viability and osteogenic differentiation, and increased the activities of ALP, NO, and cGMP and the expressions of Collagen I, OC, OPN, RUNX2, SGC, and PKG-1 in rDFCs. After the co-treatment with puerarin and L-NMMA (NO synthase inhibitor), the promotive effects of Puerarin on cell viability, osteogenic differentiation, and the expressions of collagen I, OC, OPN, RUNX2, SGC, and PKG-1 in rDFCs were reversed by L-NMMA. Puerarin boosted the osteogenic differentiation of rDFCs by activating the NO pathway.
研究领域:
药理学
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细胞生物学
·
牙科
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2015
·
IF 3.65
Lejiao Jia,Zhenyu Li,Jingyi Shen,Dandan Zheng,Xiaona Tian,Hejian Guo,Ping Chang
The objective of the study is to fabricate multifunctional mesoporous silica nanoparticles for achieving co-delivery of conventional antitumor drug paclitaxel (PTX) and the multidrug resistance reversal agent tetrandrine (TET) expecting to overcome multidrug resistance of MCF-7/ADR cells. The nanoparticles were facile to prepare by self-assemble in situ drug loading approach. Namely, PTX and TET were solubilized in the cetyltrimethylammonium bromide (CTAB) micelles and simultaneously silica resources hydrolyze and condense to form nanoparticles. The obtained nanoparticles, denoted as PTX/TET-CTAB@MSN, exhibited pH-responsive release property with more easily released in the weak acidic environment. Studies on cellular uptake of nanoparticles demonstrated TET could markedly increase intracellular accumulation of nanoparticles. Furthermore, the PTX/TET-CTAB@MSN suppressed tumor cells growth more efficiently than only delivery of PTX (PTX-CTAB@MSN) or the free PTX. Moreover, the nanoparticle loading drugs with a PTX/TET molar ratio of 4.4:1 completely reversed the resistance of MCF-7/ADR cells to PTX and the resistance reversion index was 72.3. Mechanism research showed that both TET and CTAB could arrest MCF-7/ADR cells at G1 phase; and besides PTX arrested cells at G2 phase. This nanocarrier might have important potential in clinical implications for co-delivery of multiple drugs to overcome MDR.
研究领域:
纳米技术
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药物科学
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癌症研究
·
药物递送系统
·
生物医学工程
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2018
·
IF 3.997
De-Sheng Liang,Jian Liu,Tao-Xing Peng,Hui Peng,Feng Guo,Hai-Jun Zhong
Cancer stem cells (CSCs) can resist conventional chemotherapy to lead to cancer recurrence. For complete eradication of cancers, an effective CSCs therapeutic strategy should be developed to combine with conventional chemotherapy. In this work, a novel vitamin E-based redox-sensitive salinomycin (SAL, an inhibitor for CSCs) prodrug nanoparticles (TS NPs) and hyaluronic acid (HA)-coated TS NPs (HTS NPs) were fabricated to deliver paclitaxel (PTX) for cancer-targeted and combined chemotherapy. Both TS and HTS prodrug NPs had mean diameter of about 200 nm with uniform size distribution, excellent drug loading capacity for PTX, and glutathione-triggered SAL and PTX release profiles. The HTS prodrug NPs had enhanced cellular uptake efficiency over TS NPs due to CD44 receptor-mediated endocytosis, hence exerting stronger potency of SAL upon CSCs-enriched mammospheres formation and G 0 /G 1 cell phase arresting. Cytotoxicity and 3D tumor spheroids assays demonstrated that both TS and HTS prodrug NPs themself can synergize with loaded PTX to maximize the chemotherapeutic effect. Obviously, the latter demonstrated a more potent anticancer efficacy due to improved intracellular drug delivery efficiency. These results suggested that the designed TS prodrug NPs, especially the coated HTS NPs can serve as an effective anti-CSCs strategy for cancer targeted and combination treatments.
研究领域:
药学
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纳米技术
·
肿瘤学
·
药物递送系统
·
癌症研究
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产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2022
·Vol. 9
·期 29
·2201541
·
IF 17.521
Jiawei Huo,Jie Li,Yang Liu,Libin Yang,Xinran Cao,Chong Zhao,Yicheng Lu,Wei Zhou,Shumu Li,Jianan Liu,Jiao Li,Xing Li,Jing Wan,Rui Wen,Mingming Zhen,Chunru Wang,Chunli Bai
Malignant proliferation and metastasis are the hallmarks of cancer cells. Aminated [70]fullerene exhibits notable antineoplastic effects, promoting it a candidate for multi-targeted cancer drugs. It is an urgent need to reveal the structure–activity relationship for antineoplastic aminated fullerenes. Herein, three amphiphilic derivatives of [60]fullerene with clarified molecular structures are synthesized: TAPC-4, TAPC-3, and TCPC-4. TAPC-4 inhibits the proliferation of diverse tumor cells via G0/G1 cell cycle arrest, reverses the epithelial–mesenchymal transition, and abrogates the high mobility of tumor cells. TAPC-4 can be excreted from the organism and achieves an in vivo inhibition index of 75.5% in tumor proliferation and 87.5% in metastatic melanoma with a wide safety margin. Molecular dynamics simulations reveal that the amphiphilic molecular structure and the ending amino groups promote the targeting of TAPC-4 to heat shock protein Hsp90-beta, vimentin, and myosin heavy chain 9 (MYH9), probably resulting in the alteration of cyclin D1 translation, vimentin expression, and MYH9 location, respectively. This work initially emphasizes the dominant role of the amphiphilic structure and the terminal amino moieties in the antineoplastic effects of aminated fullerenes, providing fundamental support for their anti-tumor drug development.
研究领域:
肿瘤学
·
药物化学
·
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
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Yinli Li,Jie Ding,Liu Dong,Na Sun,Songyi Lin
Egg is one of the eight major food allergens, and ovalbumin (OVA) is the most abundant allergenic protein in eggs. In this study, the effects of pulsed electric field (PEF)-assisted Alcalase hydrolysis on the spatial conformation and potential allergenicity of OVA were studied, and the mechanism of its inhibiting allergic reactions effect was revealed. PEF-assisted Alcalase hydrolysis increased the degree of hydrolysis, surface hydrophobicity, and free sulfhydryl group content. Moreover, the reduction in the α-helix content, fluorescence intensity, and disulfide bond content suggested that PEF promoted the OVA hydrolysis by Alcalase. Additionally, enzyme-linked immunosorbent assay data indicated that PEF-assisted Alcalase hydrolysis hindered OVA binding to immunoglobulins E and G1. Finally, based on bioinformatics combined with mass spectrometry, PEF-assisted Alcalase reduced OVA-induced allergic reactions by destroying epitopes in OVA. Overall, PEF technology further destroyed the epitopes of allergens by targeting the binding sites of substrates and enzymes to improve the affinity of enzymes and substrates, reducing allergic reactions.
研究领域:
食品科学
·
过敏学
·
生物化学
·
生物技术
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR PHYSIOLOGY
·
2019
·Vol. 235
·期 4
·3612-3625
·
IF 4.522
Liming Wang,Xin Zhang,Yang Liu,Shun Xu
The pivotal roles of long noncoding RNAs have been reported in various cancers. Recently, FBXL19-AS1 was proposed to be involved in tumor progression. However, its role in lung adenocarcinoma (LUAD) remains elusive. In this study, we observed that FBXL19-AS1 was significantly upregulated in LUAD tissues and high FBXL19-AS1 expression in LUAD was associated with a poor prognosis. Nevertheless, miR-203-3p showed the opposite effect. Moreover, cell viability and apoptosis analysis revealed that FBXL19-AS1 knockdown could arrest LUAD cells in G0/G1 phase and inhibit cell proliferation, migration and invasion in vitro and inhibited LUAD tumor progress in vivo. Mechanistically, we identified FBXL19-AS1 could act as a miR-203a-3p sponge using dual-luciferase reporter assay. In addition, we demonstrated that downregulation of miR-203a-3p reversed growth inhibition of LUAD cells caused by FBXL19-AS1 knockdown. Finally, FBXL19-AS1/miR-203a-3p axis was found to associate with baculoviral IAP repeat-containing protein 5.1-A-like (survivin), distal-less homeobox 5, E2F transcription factor 1, and zinc finger E-box binding homeobox 2 to regulate metastasis in LUAD cells. This study reveals a significance and mechanism of FBXL19-AS1 in LUAD proliferation and metastasis and offers a potential prognostic marker and a therapeutic target for patients with LUAD.
研究领域:
癌症生物学
·
分子生物学
·
遗传学
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DOI
PubMed
高影响因子
BIORESOURCE TECHNOLOGY
·
2025
·
IF 9
Ruixue Ma,Jun Cheng,Ying Liu,Dongwei Jia,Jiahao Wang
Given that excessive CO 2 induces reactive oxygen species (ROS) which inhibit photosynthesis and microalgal survival, this study explores how exogenous arginine enhances stress resilience and biomass yield of Nannochloropsis oceanica under high CO 2 stress. Arginine promoted NO synthesis, enhancing antioxidant enzyme activities to combat ROS damage. Transcriptomic analysis revealed that key enzymes in the Calvin cycle (PRK, GAPDH, FBPase and SBPase) and TCA cycle (CS, IDH, SCS and MDH) were significantly up-regulated, supporting carbon fixation and energy metabolism. Arginine also alleviated cell necrosis by extending the G1 phase, promoting DNA replication and protein synthesis, which increased the proportion of viable cells from 47 % to 84 %. Furthermore, the synthesis of chlorophyll a and carotenoid were enhanced, leading to 46 % increase in biomass yield. The results highlighted arginine as a promising metabolic regulator for enhancing stress tolerance and carbon fixation efficiency of N. oceanica under high CO 2 conditions.
研究领域:
藻类学
·
植物生理学
·
分子生物学
·
代谢工程
·
环境胁迫生物学
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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）