Molecular Medicine Reports
·
2023
·Vol. 27
·期 2
·1-10
·
IF 3.4
Cunyang Gu,Feng Gao,Shiqi Zhang,Lihua Kang,Wei Zhang,Xiaojuan Feng,Jinxi Liu,Yuexin Tian,Qun Wei,Yunxia Du,Yujia Xing,Qingjuan Liu,Shuxia Liu
Tubulointerstitial fibrosis (TIF) is an important pathological change that occurs during the development of diabetic kidney disease. The epithelial‑mesenchymal transition (EMT) of renal tubular epithelial cells is a manifestation of TIF. STAT1, a member of the STAT family of transcription factors, can be modified by the small ubiquitin‑related modifier (SUMO), thus affecting the activity of STAT1. The present study investigated the role of STAT1 SUMOylation in high glucose‑induced tubular EMT by western blotting, immunocytochemistry, immunofluorescence, co‑immunoprecipitation and dual luciferase reporter analysis. The results indicated that in the process of high glucose‑induced EMT, STAT1 activation protected the cells from EMT. However, high glucose also increased the SUMOylation of STAT1, which prevented STAT1 from exerting an effective protective role by inhibiting its activity.
研究领域:
分子生物学
·
细胞生物学
·
糖尿病研究
·
肾病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2019
·
IF 3.585
Guangxu Cao,Shuang Li,Hezhan Shi,Peidi Yin,Jialing Chen,Huifeng Li,Ying Zhong,Li-Ting Diao,Bin Du
Tubulointerstitial fibrosis (TIF) is the main pathologic feature of end-stage renal disease. Epithelial-mesenchymal transition (EMT) of proximal tubular cells (PTCs) is one of the most significant features of TIF. MicroRNAs play critical roles during EMT in TIF. However, whether miRNAs can be used as therapeutic targets in TIF therapy remains undetermined. We found that miR-30e, a member of the miR-30 family, is deregulated in TGF-β1-induced PTCs, TIF mice and human fibrotic kidney tissues. Moreover, transcription factors that induce EMT, such as snail, slug, and Zeb2, were direct targets of miR-30e. Using a cell-based miR-30e promoter luciferase reporter system, Schisandrin B (Sch B) was selected for the enhancement of miR-30e transcriptional activity. Our results indicate that Sch B can decrease the expression of snail, slug, and Zeb2, thereby attenuating the EMT of PTCs during TIF by upregulating miR-30e, both in vivo and in vitro. This study shows that miR-30e can serve as a therapeutic target in the treatment of patients with TIF and that Sch B may potentially be used in therapy against renal fibrosis
研究领域:
肾病学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Jiuhong Zhao,Wenjing Zhu,Yuxuan Mao,Guixia Ling,Peng Zhang
The increased uric acid (UA) level is closely related to many diseases. However, the detection of UA remains great challenges due to the pain of blood testing and the complexity of common methods. Therefore, the detection of UA is of great significance for public health. In this paper, a new method for UA detection is proposed. The swellable hydrogel microneedles (hydrogel MNs) can be used for minimally invasive extraction of skin interstitial fluid (ISF). The colorimetric detection of trace UA in ISF can be successfully achieved by virtue of DNAzyme@MOFs with enhanced peroxidase activity. This study provides a powerful tool for minimally invasive, painless, rapid and convenient detection of UA in clinical applications. This study not only avoids the use of expensive and unstable natural enzymes but also expands the applications of DNAzyme@MOFs in biomedical detection.
研究领域:
医学检测
·
生物化学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
Chemical Biology & Drug Design
·
2025
·Vol. 105
·期 1
·e70054
·
IF 3.3
Lichao Ji,Yingjie Chai,Chenhao Tong,Yanxin Hu,Jiandong Li,Baochun Lu,Jianhua Yu
Gallbladder cancer is the most prevalent malignancy of the biliary tract and has a dismal overall survival even in the present day. The development of new drugs holds promise for improving the prognosis of this lethal disease. The possible anti-neoplastic role of morusin was investigated both in vitro and in vivo. Through cell viability and colony formation assays, we observed that morusin inhibited the proliferation of gallbladder cancer cells in vitro. Wound healing and transwell assays revealed that morusin impeded the migration and invasion of gallbladder cancer cells. Given the observed morphological changes, we examined epithelial-mesenchymal transition (EMT) markers. Subsequent investigations demonstrated that morusin treatment, both in vitro and in vivo, downregulated the expression of phospho-STAT3 (Signal transducer and activator of transcription 3) and HIF-1α (Hypoxia-inducible factor 1α) in gallbladder cancer cells. Furthermore, morusin effectively reversed EMT induced by phospho-STAT3 or HIF-1α. Morusin has a reversing effect on the EMT of gallbladder cancer cells by modulating STAT3/HIF-1α signaling.
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2024
·Vol. 15
·期 24
·11990-12006
·
IF 5.1
Xilin Zhao,Songping Wang,Xuelan He,Wentao Wei,Kaipeng Huang
Our previous studies have demonstrated that ubiquitin-specific peptidase 22 (USP22) has the capacity to accelerate renal epithelial-to-mesenchymal transition (EMT) and promote the pathological progression of diabetic tubulointerstitial fibrosis (TIF) by regulating the ubiquitination of Snail1, an EMT transcription factor. Quercetin is a type of flavonol compound widely found in fruits and vegetables that has anti-inflammatory, antioxidant and anti-fibrosis effects. However, whether quercetin promotes the degradation of Snail1 and regulates the pathological progression of TIF by inhibiting USP22 requires further investigation. In this study, we found that quercetin significantly inhibited the expression of USP22 and Snail1 in high glucose (HG)-induced renal tubular epithelial cells (TECs), and reversed the expression of EMT-related proteins and inhibited the overproduction of fibronectin (FN) and Collage Type IV (Collagen IV) induced by high glucose. Additionally, quercetin blocked the deubiquitination of Snail1 mediated by USP22. Further study found that quercetin inhibited the interaction between USP22 and Snail1, thereby reducing the stability of Snail1. Furthermore, quercetin also reduced the protein levels of USP22 and Snail1 in the kidney tissue of diabetic mice and ameliorated renal function, delayed EMT and TIF. In conclusion, quercetin regulates the USP22-Snail1 signal pathway to inhibit the occurrence of EMT both in vitro and in vivo, and ultimately ameliorate the pathological progress of TIF.
研究领域:
肾病学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2025
·
IF 5.2
Lujie Zhang,Qinghua Song,Peijing Yang,Zhanqiang Liu
Microneedle (MN) technology is a promising minimally invasive tool for interstitial skin fluid (ISF) extraction. Hydrogel MN patches enable efficient ISF extraction. However, the traditional polydimethylsiloxane (PDMS) photopolymerization method has limitations in morphology control, accuracy, and susceptibility to process parameter interference, affecting MN strength and functional consistency. To address these challenges, we propose a composite hydrogel MN patch based on Digital Light Processing (DLP) 3D bioprinting of hyaluronic acid methacryloyl (HAMA)/gelatin methacryloyl (GelMA) for high-efficiency ISF transdermal extraction. The structure and performance of the MNs were improved by optimizing the bio-ink ratio and printing parameters. Adjusting the ratio of GelMA and HAMA improved the cross-linking structure, optimizing the mechanical properties and swelling performance of the composite hydrogel. Optimizing the light intensity and exposure time ensured consistent MN morphology, resulting in well-defined and evenly distributed needle tips. Controlled UV exposure avoided defects such as uneven cross-linking or brittleness. The results showed that when the HAMA-to-GelMA ratio was 8:2, the light intensity was 9 mW/cm 2 , and the exposure time was 6 s, the MN patches demonstrated excellent microstructures and mechanical properties, with each MN enduring over 1.28 N and achieving a swelling rate above 1200 %. In vitro experiments verified effective penetration and ISF extraction, obtaining 8.5 mg of PBS in 1 min and successfully quantifying glucose concentration. In summary, this study establishes a robust MN patch with superior swelling performance and enhanced ISF extraction efficiency and provides a promising platform for minimally invasive diagnosis and real-time health monitoring.
研究领域:
生物医学工程
·
材料科学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR PHYSIOLOGY
·
2017
·Vol. 233
·期 6
·4919-4925
·
IF 4.08
Ji Li,Mincheng Zhang,Yong Mao,Yimao Li,Xiaoxia Zhang,Xuehan Peng,Feng Yu
Aristolochic acid I (AA-I), one of the main active components in Aristolochaia herbs, may induce aristolochic acid nephropathy (AAN). Renal interstitial fibrosis is one of the most typical features of AAN. To investigate the mechanism of Aristolochic acid I (AA-I) −induced renal epithelial-mesenchymal transition (EMT) and determine the role of aquaporin-1 (AQP1) in this process, we established an AA-I-induced EMT model in human proximal tubular epithelial cells (HK-2 cells). Morphological examination, MTT assay, and Western blot analysis were performed. Aquaporin 1 (AQP1) and several EMT-related proteins were detected, thereby suggesting the occurrence of AA-I-induced EMT. Two main pathways of transforming growth factor-β (TGF-β) signaling, namely, Smad-dependent and Smad-independent signaling pathways, were also detected. The results showed that the TGF-β / Smad-independent signaling pathways (β-catenin, Ras-Raf-Erk1/2 signaling pathways) were activated, and AQP1 expression was decreased during the AA-I induced EMT on HK-2 cells. With the presence of TGF-β1 receptor inhibitor (LY364947) and Erk1/2 inhibitor (PD98059), AQP1 expression was altered by PD98059, suggested that AQP1 could be adjusted by Erk1/2 signaling. Moreover, the inhibitory effect of AA-I on AQP1 was stronger than that of TGF-β1, suggested that AQP1 may be an important target on AAN clinical therapy.
研究领域:
肾病学
·
细胞生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
·
2025
·
IF 2.3
Qing Li,Zhenyu Zhou,Xiaoying Li,Qiongyu Lan
Background Cervical cancer (CC) is a major cause of morbidity and mortality in women, with complex etiology and progression. Diacylglycerol kinases (DGKs) are pivotal in lipid metabolism. Although diacylglycerol kinase beta (DGKβ) is well-studied in neurology, its role in cancer, especially CC, remains underexplored. This study aimed to explore DGKβ's role and mechanism in CC. Methods Bioinformatics analysis was employed to identify genes differentially expressed in CC, with western blot confirming DGKβ expression in CC cells. The role of DGKβ was examined through small interfering RNA-mediated gene silencing, proliferation tests, migration and invasion assays, and angiogenesis studies. In-depth bioinformatics explored DGKβ-regulated downstream targets and pathways. Pathological assessment elucidated the impact of DGKβ and angiopoietin 4 (ANGPT4) on CC samples. Results Our data identified DGKβ as a promising candidate gene in the context of CC. This conclusion stemmed from the notable observation that DGKβ exhibited a heightened expression in CC cell lines. Notably, the silencing of DGKβ resulted in the suppression of CC cell proliferation, invasion, migration, as well as the epithelial-mesenchymal transition processes. Additional bioinformatics analysis delving into DGKβ-associated genes revealed ANGPT4 as a downstream target gene of DGKβ, which is capable of modulating angiogenesis and possesses multiple cellular functions related to cell survival, proliferation, and migration. Most significantly, our findings also demonstrated that both DGKβ and ANGPT4 were overexpressed in clinical specimens of CC. Conclusion This study uncovered an oncogenic role for DGKβ in CC and identified a potential regulatory link between DGKβ and ANGPT4 in tumor angiogenesis. These findings provided promising directions for developing new diagnostic and therapeutic approaches for CC.
研究领域:
肿瘤学
·
分子生物学
·
生物化学
·
转化医学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACTA HISTOCHEMICA
·
2025
·
IF 2.4
Xiaorui Dong,Xixi Chen,Mengling Xue,Yina Zhang,Peiyue Jiang
Background Cervical cancer (CC) is a common gynecological disease that seriously threatens women’s health. This study aims to explore key genes and pathways related to CC prognosis through bioinformatics, providing new insights for further treatment of CC. Methods CC patient data were analyzed from the public databases. The enrichment analyses explored the roles and pathways of CC-related differentially expressed genes (DEGs). A prognostic key gene was identified using Venn diagrams and subjected to survival analysis. Gene Set Enrichment Analysis (GSEA) was employed to investigate the potential pathways of key genes. Correlations between the key gene and clinical features were examined. The function of the key gene was validated through immunohistochemistry, flow cytometry, transwell, MTT, and Western blot assays in vitro and in vivo . Results Our research identified 2459 upregulated genes among DEGs between healthy and tumor cervical tissues. These DEGs were primarily enriched in the PI3K-AKT and MAPK pathways. Moreover, EFNA1 was recognized as a key prognostic gene in CC, with elevated expression compared to normal tissue. A negative correlation between EFNA1 levels and patient survival rates was corroborated by Kaplan-Meier analysis. Furthermore, EFNA1 expression correlated with the cancer stage and was linked to antigen presentation, folate synthesis, and IL-17 signaling. Knockdown of EFNA1 enhanced apoptosis and reduced migration, invasion, and proliferation in vitro and in vivo , inhibiting EMT and MAPK pathways. Conclusion This study revealed the key signaling pathways in CC progression and identified EFNA1 as a crucial prognostic biomarker, potentially impacting CC treatment.
研究领域:
肿瘤学
·
生物信息学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CURRENT DRUG METABOLISM
·
2024
·Vol. 25
·期 3
·197-204
·
IF 2.1
Xin Lv,Zhen Wang,Zhe Wang,Hang Yin,Yangliu Xia,Lili Jiang,Yong Liu
Background: Avapritinib is the only drug for adult patients with PDGFRA exon 18 mutated unresectable or metastatic gastrointestinal stromal tumor (GIST). Although avapritinib has been approved by the FDA for four years, little is known about the risk of drug-drug interactions (DDIs) via UDP-glucuronyltransferases (UGTs) inhibition. Objective: The aim of the present study was to systematically evaluate the inhibitory effects of avapritinib against UGTs and to quantitatively estimate its potential DDIs risk in vivo. Methods: Recombinant human UGTs were employed to catalyze the glucuronidation of substrates in a range of concentrations of avapritinib. The kinetics analysis was performed to evaluate the inhibition types of avapritinib against UGTs. The quantitative prediction of DDIs was done using in vitro-in vivo extrapolation (IVIVE). Results: Avapritinib had a potent competitive inhibitory effect on UGT1A1. Quantitative prediction results showed that avapritinib administered at clinical doses might result in a 14.85% increase in area under the curve (AUC) of drugs primarily cleared by UGT1A1. Moreover, the Rgut value was calculated to be 18.44. Conclusion: Avapritinib has the potential to cause intestinal DDIs via the inhibition of UGT1A1. Additional attention should be paid when avapritinib is coadministered with UGT1A1 substrates.
研究领域:
药理学
·
临床医学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Zining Hao,Yuchu He,Jing Wang,Xuwu Zhang,Fei Ye,Ze Guan,Xiaokang Liu,Zhenhe Ma,Yi Yuan,Hongming Lou,Dawei Gao
Tumor interstitial solid phase-induced physical obstacles and fluid phase-induced hydrostatic pressure are regarded as the two main intractable barriers of drug delivery, leading to the survive of deep-seated tumor stem cells. Herein, a rational strategy is presented based on near-infrared light-stimuli enzymolysis and photocatalysis to decompose the tumor interstitial solid and fluid phases for boosting the tumor penetration of nanomedicine. In detail, a cuprous oxide/sliver nano-photocatalyst (Cu 2 O/Ag) is designed, which is covered with the thermosensitive papain-loaded tumor-homing homologous cytomembrane to form the nanomedicine (Cu 2 O/ [email protected] ). With the light irradiation, the heat generated by Cu 2 O/Ag promote the enzymolysis of extracellular matrix by papain, which eliminate the physical obstacles. Moreover, the photocatalytic water splitting of Cu 2 O/Ag reduce the volume of tumor interstitial fluid, which decrease the elevated hydrostatic pressure to boost the tumor penetration of nanomedicine. Additionally, during the intratumoral delivery, Cu 2 O/ [email protected] is able to realize anti-tumor photothermal therapy and chemotherapy. The results indicate that the Cu 2 O/ [email protected] decompose a majority of tumor extracellular matrix and interstitial fluid under light irradiation. The tumor interstitial hydrostatic pressure is reduced by 69.7%. The tumor penetration of Cu 2 O/ [email protected] + L treated group is 5.03-fold than the Cu 2 O/ [email protected] −L group, leading to the 95.19% of tumor inhibition rate.
研究领域:
生物医学工程
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
Biosensors-Basel
·
2023
·Vol. 13
·期 5
·537
·
IF 5.4
Qingya Zeng,Mengxin Xu,Weilun Hu,Wenyu Cao,Yujie Zhan,Yuxin Zhang,Qingqing Wang,Tao Ma
Though monitoring blood glucose (BG) is indispensable for regulating diabetes, the frequent pricking of the finger by the commonly used fingertip blood collection causes discomfort and poses an infection risk. Since glucose levels in skin interstitial fluid (ISF) correlate with blood glucose levels, monitoring glucose in the skin ISF can be a viable alternative. With this rationale, the present study developed a biocompatible porous microneedle capable of rapid sampling, sensing, and glucose analysis in ISF in a minimally invasive manner, which can improve patient compliance and detection efficiency. The microneedles contain glucose oxidase (GOx) and horseradish peroxidase (HRP), and a colorimetric sensing layer containing 3,3′,5,5′-tetramethylbenzidine (TMB) is on the back of the microneedles. After penetrating rat skin, porous microneedles harvest ISF rapidly and smoothly via capillary action, triggering the production of hydrogen peroxide (H2O2) from glucose. In the presence of H2O2, HRP reacts with TMB contained in the filter paper on the back of microneedles, causing an easily visible color shift. Further, a smartphone analysis of the images quickly quantifies glucose levels in the 50–400 mg/dL range using the correlation between color intensity and glucose concentration. The developed microneedle-based sensing technique with minimally invasive sampling will have great implications for point-of-care clinical diagnosis and diabetic health management.Keywords:porous microneedle;interstitial fluid;glucose;colorimetric detection;diabetes
研究领域:
生物医学工程
·
糖尿病管理
·
即时诊断
✓ 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）