PHYTOMEDICINE
·
2025
·
IF 8.3
XiaoMing Zhou,ChenXi Zhang,Wen Shen,RuiFei Zhuang,ShenLin Liu,JinDi Liu
Background Curzerene, a bioactive compound from Curcuma zedoaria, exhibits anticancer effects, but its role in gastric precancerous lesions remains poorly understood. This study investigates the potential of Curzerene in inhibiting gastric precancerous lesions progression by regulating the long non-coding RNA (LncRNA) AFAP1-AS1 and the Hippo/YAP signaling pathway. Methods In vitro, a gastric precancerous cell model (MC cells) was established by treating GES-1 cells with MNNG. The effects of Curzerene on cell proliferation, migration, and EMT were assessed using CCK-8, scratch assays, RT-PCR, and Western blot. In vivo, a gastric precancerous mouse model was induced by MNU, and the therapeutic effects of Curzerene (14 mg/kg and 28 mg/kg) were evaluated through histological and molecular analysis. Results Curzerene treatment significantly inhibited MC cell proliferation, migration, and EMT, downregulating LncRNA AFAP1-AS1 and YAP while upregulating E-cadherin and downregulating N-cadherin. In vivo, Curzerene alleviated gastric mucosal damage, reduced cancer markers (P53 and CD133), and improved histopathology. Transcriptomic analysis identified the Hippo/YAP pathway as a key mediator of Curzerene’s effects. YAP activation reversed Curzerene’s inhibitory effects on EMT, confirming the involvement of this pathway. Conclusion Curzerene effectively inhibits gastric precancerous lesion progression by targeting the YAP signaling and the following LncRNA AFAP1-AS1 to suppress EMT. These findings suggest Curzerene’s novel potential as a promising therapeutic agent for early intervention and prevention of gastric cancer.
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
COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING
·
2024
·
IF 1.6
Jianghong Wang,Xiaoyuan Wang,Yanru Song,Zilin Huang,Han Wu,Liang Chang,Bingjie Huo,Guanwei Fan
Background: The Precancerous Lesion of Gastric Cancer (PLGC) is an early stage in the development of gastric cancer. The clinical application of HPXLD has been found to be effective in treating PLGC, but the mechanism of how HPXLD acts on PLGC is still unclear. Objective: The objectives of this study were to reveal the molecular mechanism of how HPXLD can be used to treat PLGC and investigate this mechanism through bioinformatics and experimental validation. Methods: PLGC-associated target genes were identified through bioinformatics analysis. A rat model of PLGC was induced using N-methyl-N'-nitro-N-nitrosoquanidine (MNNG) in combination with ranitidine, hot saline, ethanol, and intermittent fasting, with interventions by HPXLD. The pathological alterations in gastric mucosa were assessed through Hematoxylin-eosin staining (HE). Immunohistochemistry (IHC) and Western blot analyses were employed to evaluate the changes in expression levels of inflammation-related proteins. Results: After conducting bioinformatics analysis, it was found that there were 23 HPXLDPLGC crossover genes, which were significantly enriched in the IL-17 signaling pathway, TNF signaling pathway, and NF-kappa B signaling pathway. The results of HE showed that HPXLD was effective in improving gastric mucosal histopathological changes. Additionally, the IHC results demonstrated that HPXLD was able to downregulate the expression of IL-6, COX-2, MCP- 1, and MMP-9. Furthermore, Western blot analysis revealed that HPXLD was able to downregulate the expressions of IL-6, IL-17RA, ACT1, NF-κB, and TNF-α. Conclusion: HPXLD has been shown to improve PLGC by reducing the expression of inflammation- related proteins. This suggests that HPXLD may potentially be a treatment option for PLGC.
研究领域:
肿瘤学
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中医药学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Oncology
·
2021
·
IF 6.244
Liang Dongxin,Tuo Xiaoqian,Wang Qing,Zhao Lanbo,Zhang Kailu,Wang Yiran,Feng Xue,Yin Panyue,Guo Lin,Liu Yu,Wang Lei,Han Lu,An Ruifang,Li Qiling
The lack of cytopathologists delays the advancement of screening for endometrial cancer. It was urgent to develop a new dye for rapid diagnosis. Our study aimed to synthesize a targeted folate receptor-α near-infrared (NIR) fluorescent agent, folic acid-zwitterionic NIR fluorophore (ZW-FA), and explore the feasibility for screening of endometrial cancer and precancerous change. Folic acid was conjugated with zwitterionic NIR fluorophore. The preparation of ZW-FA was validated by 1H NMR, mass spectrometric, ultraviolet spectra and fluorescence spectra. ZW-FA was incubated with endometrial cytology samples obtained from patients who underwent dilation and curettage or total hysterectomy. Diagnostic utility was calculated by applying laser confocal microscope, Image-J and statistical models, such as enumeration, receiver operating characteristic curve, logistic regression, support vector machine and decision tree were used. The purity of ZW-FA was > 95% determined by 1H NMR. ZW-FA had the strongest absorption peak at 633 nm in ultraviolet spectra. Photostability of ZW-FA was over 8 hours. In clinical validation, a total of 92 patients were enrolled. The cut-off value of ZW-FA was 49 in enumeration, which was used to distinguish the type of samples. Indicators about diagnostic utility are as follows: sensitivity 90.77%, specificity 62.96%, false-positive rate 37.04%, false-negative rate 9.23%, positive predictive value 85.51% and negative predictive value 73.91%. The samples processed by ZW-FA did not affect further Hematoxylin-Eosin staining and pathological diagnosis. It was an effective cytologic strategy for in vitro diagnosis of endometrial cancer and precancerous change by using ZW-FA.Clinical Trial Registration: http://www.chictr.org.cn/index.aspx, identifier ChiCTR1800020123.
研究领域:
肿瘤学
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医学影像学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2023
·Vol. 37
·期 4
·e5589
·
IF 1.8
Chenchen Liu,Huiling Chen,Yida Zhang,Meng Li,Qiyao Jiang,Zhendong Wang,Liangwen Yu,Qi Wang,Huafeng Pan,Yue Zhuo
Li-Zhong-Xiao-Pi granules (LZXP) are effective for treating gastric precancerous lesions (GPL) in traditional Chinese medicine. However, the active compounds of LZXP and their potential therapeutic mechanism in GPL remained unclarified. The purpose of this study is to investigate the chemical composition and potential targets of LZXP. Based on the accurate masses, ion fragments, and literature data, a total of 128 compounds were identified in the LZXP sample using ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (UPLC–Q-TOF–MS) in both positive and negative ion modes, and 28 of these compounds were exactly determined by comparison with authentic reference standards. Meanwhile, 11 typical components were quantified via UPLC during a 24 min period. The linearity, accuracy, stability and recovery of the method were all proven. Through the network pharmacological analysis, six chemicals (quercetin, 4′-hydroxywogonin, sinensetin, 5, 7, 8, 3′, 4′-pentamethoxyflavanone, 8-gingerdione and quercetin) were identified as the active ingredients, and five LZXP targets (AKT1, CYP1B1, PTGS2, MMP9 and EGFR) were found to be the crucial molecules in the treatment of GPL. This study provides a systematic and applicable method for the rapid screening and identification of the chemical constituents from LZXP, and an effective understanding the mechanism of LZXP in the treatment of GPL.
研究领域:
中药学
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药理学
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分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2024
·
IF 4.7
Lan Liang,Chenming He,Xue Han,Jia Liu,Liuhong Yang,Fengjiao Chang,Yami Zhang,Jie Lin
Background Precancerous lesions of gastric cancer (PLGC) represent critical stages in gastric cancer progression, with a high risk of malignancy. Current treatments, such as Helicobacter pylori eradication, show limited efficacy in reversing precancerous molecular changes. Zuojin Pill (ZJP), a traditional Chinese medicine, has demonstrated potential for treating digestive disorders and may offer a promising approach for PLGC intervention.Objective This study aims to investigate the therapeutic effects and mechanisms of ZJP in treating PLGC, focusing on its active components, target pathways, and molecular interactions. By using advanced analytical techniques, we provide a scientific foundation for ZJP’s potential application in early gastric cancer intervention.Methods Using ultra-high performance liquid chromatography-quadrupole orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap HRMS), we identified active components in ZJP. A network pharmacology approach was then applied to construct a “ZJP-compound-target-disease” network. Molecular docking and molecular dynamics simulations were conducted to analyze the stability and interactions of the main active components of ZJP with core protein targets in PLGC. Animal experiments were used to validate significant targets and pathways in vivo.Results Tangeritin, Isorhamnetin, Caffeic Acid, Azelaic Acid, and Adenosine were identified as the main active components of ZJP in the treatment of PLGC, with key targets including PIK3R1, MAPK3, SRC, JAK2, STAT3, and PIK3CA. Molecular docking and molecular dynamics simulations further confirmed the relationship between compounds and target proteins. The potential molecular mechanism of ZJP predicted by network pharmacology analysis was confirmed in PLGC rats. ZJP downregulated IL-6, TNF-α, c-myc, p-MEK1 and p-ERK1/2, effectively reversing the progression of PLGC.Conclusion ZJP can reverse MNNG-induced PLGC, potentially through inhibition of the MEK/ERK/c-myc pathway and regulation of cellular proliferation and apoptosis.
研究领域:
中药学
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肿瘤学
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生物信息学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioengineering & Translational Medicine
·
2025
·
IF 5.7
Qunshan Zhu,Gaoyang Chen,Lei Fu,Dawei Cao,Zhenguang Wang,Yan Yang,Wei Wei
Colorectal precancerous lesions (CRP) are early signs of cancer development, and early detection helps prevent progression to colorectal cancer (CRC), reducing incidence and mortality rates. This study developed a serum detection platform integrating surface-enhanced Raman scattering (SERS) with machine learning (ML) for early detection of CRP. Specifically, a microarray chip with Au/SnO 2 nanorope arrays (Au/SnO 2 NRAs) substrate was designed for SERS spectral measurement of serum. The Principal Component Analysis (PCA)-Optimal Class Discrimination and Compactness Optimization (OCDCO) model was proposed to identify CRP spectra. The results demonstrated that the microarray chip exhibited superior portability, SERS activity, stability, and uniformity. Through PCA-OCDCO, the serum samples from healthy controls, CRP patients, and CRC patients were effectively classified, and several key spectral features for distinguishing different groups were identified. The established PCA-OCDCO model achieved outstanding performance, with an accuracy of 97%, a sensitivity of 95%, a specificity of 97%, and an AUC of 0.96. This study suggests that the platform, integrating SERS with the PCA-OCDCO model, holds potential for the early detection of CRP, providing an approach for CRP prevention and clinical diagnostics.
研究领域:
医学
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生物信息学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BMC Complementary Medicine and Therapies
·
2023
·Vol. 23
·期 1
·1-11
·
IF 3.9
Yi Zhirong,Jia Qingling,Wang Yujiao,Zhang Yuqin,Xie Tianyi,Ling Jianghong
Background Precancerous lesions of gastric cancer (PLGC) refer to a kind of histopathological changes in the gastric mucosa that can progress to gastric cancer. Elian granules (ELG), a Chinese medicinal prescription, have achieved satisfactory results in the treatment of PLGC. However, the exact mechanism underlying the therapeutic effect of ELG remains unclear. Here, this study aims to explore the mechanism of ELG alleviating PLGC in rats.Methods The chemical ingredients of ELG were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS). Specific Pathogen Free SD rats were randomly assigned to 3 groups: the control, model, and ELG groups. The 1-Methyl-3-nitro-1-nitrosoguanidine (MNNG) integrated modeling method was adopted to construct the PLGC rat model in groups except for the control group. Meanwhile, normal saline was used as an intervention for the control and model groups, and ELG aqueous solution for the ELG group, lasting 40 weeks. Subsequently, the stomach of rats was harvested for further analysis. Hematoxylin-eosin staining of the gastric tissue was conducted to assess the pathological changes. Immunofluorescence was carried out for the expression of CD68, and CD206 proteins. Real-time quantitative PCR combined with Western blot was conducted to analyze the expression of arginase-1(Arg-1), inducible nitric oxide synthase (iNOS), p65, p-p65, nuclear factor inhibitor protein-α (IκBα), and p-IκBα in gastric antrum tissue.Results Five chemical ingredients including Curcumol, Curzerenone, Berberine, Ferulic Acid, and 2-Hydroxy-3-Methylanthraquine were identified in ELG. The gastric mucosal glands of rats treated with ELG were orderly arranged, with no intestinal metaplasia and no dysplasia. Furthermore, ELG decreased the percentage of M2-type TAMs marked with CD68 and CD206 proteins, and the ratio of Arg-1 to iNOS in the gastric antrum tissue of rats with PLGC. In addition, ELG could also down-regulate the protein and mRNA expression of p-p65, p65, and p-IκBα, but up-regulate the expression of IκBα mRNA in rats with PLGC.Conclusion sThe results showed that ELG attenuates PLGC in rats by suppressing the M2-type polarization of tumor-associated macrophages (TAMs) through NF-κB signaling pathway.
研究领域:
药理学
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肿瘤学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmaceuticals
·
2025
·Vol. 18
·期 6
·791
·
IF 4.8
Xiaojie Wang,Miaomiao Chang,Kun Feng,Qingyue Wang,Bowen Li,Weijuan Gao
Background:Chronic atrophic gastritis precancerous lesions (PL-CAG) are characterized by the atrophy of gastric mucosal glands, often accompanied by intestinal metaplasia or dysplasia. Timely intervention and treatment can effectively reverse its malignant progression and prevent the onset of gastric cancer. Bombyx Batryticatus (BB) exhibits a range of pharmacological effects, including anticoagulation, antiepileptic properties, anticancer activity, and antibacterial effects. However, the pharmacological basis and mechanisms underlying BB’s efficacy in treating PL-CAG remain unclear.Methods:A three-factor modeling approach was implemented to develop a rat PL-CAG model, while the MNNG-induced PLGC (precancerous lesions of gastric cancer) cell model was served as a cell PL-CAG model. UPLC-QE-Orbitrap-MS/MS (Ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry) was utilized to perform an in-depth analysis of the components in the plasma extract of BB. Leveraging network pharmacology, molecular docking analyses, and experimental validation, we initially elucidated the potential mechanisms through which BB mediates its therapeutic effects on PL-CAG at both in vivo and in vitro levels.Results:Prototype compounds of 42 blood-entering components were identified by UPLC-QE-Orbitrap-MS/MS analysis. Network pharmacology analysis and molecular docking studies indicate that the core targets are primarily enriched in the PI3K-Akt signaling pathway, and the key components, including Nepitrin, Quercetin 3-O-neohesperidoside, Rutin, and others, exhibited stable docking conformations with the first eleven pivotal targets. Both in vivo and in vitro experiments validated that BB may effectively treat PL-CAG via modulation of the PI3K-Akt signaling pathway.Conclusions:The therapeutic efficacy of BB in the management of PL-CAG may be achieved through the synergistic interaction of multiple components and targets, which may be more closely related to the inhibition of the PI3K/AKT signaling pathway. This approach will establish a solid experimental foundation and provide essential data for the clinical application of BB in treating PL-CAG, while also facilitating further research initiatives.
研究领域:
药理学
·
肿瘤学
·
胃肠病学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Yichong Wang,Danyan Li,Luqing Zhao,Jixiang Liu,Dan Dou,Nian Liu,Yudi Zhuo,Shengsheng Zhang
Ethnopharmacological relevance Yinxu Weitong Capsule (YXWTC) is a Chinese patent medicine used to treat chronic gastritis. However, its efficacy and mechanisms of action in treating precancerous lesions of gastric cancer (PLGC) remain unclear. Aim of the study To evaluate the effects of YXWTC on PLGC and explore the underlying mechanisms. Materials and methods YXWTC components were identified using ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole-exactive orbitrap mass spectrometry. A PLGC animal model was established and the protective effects of YXWTC on the gastric mucosa in PLGC rats were evaluated using hematoxylin and eosin (H&E), Alcian blue-periodic acid-Schiff and Alcian blue-high iron diamine staining, and transmission electron microscopy (TEM). The vital organs of the rats were examined using H&E staining to evaluate biosafety. Network pharmacology identified potential targets and pathways of YXWTC in PLGC treatment, followed by molecular docking validation. Various techniques, including enzyme-linked immunosorbent assay, real-time quantitative reverse transcription PCR, Western blotting, immunohistochemistry, apoptosis detection, and reactive oxygen species fluorescence staining were employed to elucidate the underlying mechanisms. Results In total, 340 YXWTC components were identified. YXWTC effectively improves gastric mucosal pathology in rats with PLGC. Network pharmacology identified 403 targets common to PLGC and YXWTC. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses identified 2,323 biological processes and 206 signaling pathways, respectively. Molecular docking revealed that the primary target proteins and major drug molecules exhibited strong binding affinities. Animal studies demonstrated that YXWTC inhibited the IL-6/STAT3 pathway, promoted mitochondrial apoptosis, and induced ROS release. Conclusions We verified the pharmacodynamic effects of YXWTC in PLGC. In summary, the effects are mediated by inhibition of the IL-6/STAT3 pathway, promotion of mitochondrial apoptosis, and induction of ROS release.
研究领域:
药理学
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肿瘤学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Yuhui Fu,Lijuan Dai,Sisi Wei,Yuxin Fang,Zhe Zhang,Hongtao Zhu,Tongwei Zhang,Lianmei Zhao,Baoen Shan
Esophageal squamous cell carcinoma (ESCC) represents a globally prevalent malignancy characterized by a poor prognosis, largely due to the challenges that patients face in tolerating invasive diagnostic procedures. Therefore, it is imperative to explore strategies to enhance the early diagnostic rate for patients with ESCC. Based on the property of H-chain ferritin-based magnetic ferritin nanoparticles (M-HFn) as contrast agents that can target cluster of differentiation 71 (CD71), this study provides a comprehensive evaluation of the expression levels and diagnostic potential of CD71 to investigate the feasibility of utilizing M-HFn for non-invasive diagnosis. Following the synthesis and the characterization of M-HFn, an orthotopic mouse model is developed to simulate the progression of ESCC. Subsequently, magnetic resonance imaging (MRI) scans are conducted after administering M-HFn to the mice. The results indicate a progressive increase of CD71 expression in tissues, transitioning from normal epithelium to esophageal squamous precancerous lesions (ESPL) and ultimately to ESCC. M-HFn injected into the mice selectively target cells with heightened CD71 expression, resulting in accumulation at the lesion sites. Consistent with pathological diagnoses, MRI images demonstrate a reduction in signal intensity at the lesion site in T 2 -weighted sequences, thereby facilitating the visualization of ESCC and ESPL. CD71 demonstrates high accuracy and specificity as a diagnostic target, positioning M-HFn-mediated targeted diagnostic strategy as a promising approach for the early detection of ESCC, with the potential to significantly improve patient prognosis.
研究领域:
肿瘤学
·
纳米医学
·
诊断影像学
·
分子靶向治疗
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TISSUE & CELL
·
2024
·
IF 2.7
Lei Zhu,Qingxin Cai,Gang Li,Xiaoming Zou
Objective Gastric precancerous lesions (GPL), characterized by intestinal metaplasia and dysplasia, marks a pivotal juncture in the transformation from gastritis to gastric cancer. Research on GPL could offer fresh perspectives on preventing cancer occurrence. Methods This study employed 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) to establish GPL rat models and knocked BRD4 down in vivo to assess its impact on the lesions and macrophage morphology. Following that, the impacts of BRD4 knockdown on the malignant phenotypes of human gastric epithelial GES-1 cells were determined. Moreover, conditioned medium from macrophage was gathered and used for GES-1 cell culture. The involvement of macrophage polarization in the BRD4 regulatory mechanism in GES-1 cells was assessed. Results This study elucidated that MNNG induced an increase level of BRD4 in the rat models. BRD4 knockdown reduced lesions based on pathological sections and immunohistochemistry to detect proliferative antigens. Western blotting and immunofluorescence showed that BRD4 knockdown suppressed epithelial-mesenchymal transition and macrophage M2 polarization. In in vitro experiments, BRD4 knockdown inhibited the malignant phenotype of GES-1 cells and the differentiation of THP-1 cells into M2 macrophages, respectively. The conditioned medium from M2 macrophages with BRD4 knockdown was co-incubated with GES-1 cells, which attenuated the malignant phenotypes compared with the medium from M2 macrophages. Conclusion: Through in vivo and in vitro experiments, BRD4 upregulation was found to already occur during GPL, affecting macrophage polarization and epithelial cell cancerization. This finding provides an experimental basis for strategies targeting BRD4 inhibition at this critical stage.
研究领域:
肿瘤学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
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
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）