CANCER BIOLOGY & THERAPY
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2020
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IF 3.659
Chunhua Zhou,Wencheng Kong,Tongfa Ju,Qi Xie,Lulu Zhai
Background Studies showed that microRNAs (miRNAs) are important regulators in drug resistance. The current study investigated the role of miR-185-3p and its predicted target gene AQP5 in 5-FU-insensitive colorectal cancer (CRC) cells.Methods Quantitative real-time polymerase chain reaction (qRT-PCR) and Spearman’s correlation analysis were conducted to determine the correlation of expression levels of miR-185-3p and AQP5 from CRC tissues. HCT-116 and HCT-8 cells were treated by gradient concentration of 5-FU to construct 5-FU-resistant CRC model. The inhibition and viability of 5-FU-resistant cells were detected by MTT assay, and cell migration and invasion ability were determined by wound healing and transwell assay. The expressions of miR-185-3p and AQP5 were measured by qRT-PCR. StarBase and dual-luciferase reporter assay were used to predict and confirm the interaction between miR-185-3p and AQP5. Further experiments were performed to explore the function of miR-185-3p in 5-FU-resistant cells through regulating aquaporin-5 (AQP5). The levels of EMT-associated markers and AQP5 were determined by conducting Western Blot and qRT-PCR.Results We found that 5-FU-resistant CRC cells showed a lower inhibition rate, and higher migration and invasion abilities. MiR-185-3p was low-expressed in CRC tissues and 5-FU-resistance cells, and it targeted and regulated the expression of AQP5, which was found up-regulated in CRC and 5-FU-resistance CRC cells (r = −0.29, P < .05). Furthermore, miR-185-3p mimic enhanced the chemo-sensitivity of 5-FU-resistant cells, while overexpressed AQP5 reversed such an effect produced by miR-185-3p mimic.Conclusion MiR-185-3p mimic enhances the chemosensitivity of CRC cells via AQP5. Our research provides a potential therapeutic target for 5-FU-resistant CRC cells.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2025
·
IF 5.1
Fangbin Liu,Jiyuan Chen,Chunai Gong,Minyan Chen,Gang Yang,Chun Chen,Ru Yao,Shengnan Li,Rong Wang,Yongfang Yuan
Introduction Xerostomia, commonly caused by Sjögren disease (SjD) or head and neck radiotherapy, significantly impairs patients’ quality of life, yet effective treatments remain limited. Traditional Chinese Medicine (TCM) offers promising alternatives due to its favourable efficacy and low toxicity. Shatai Heji (STHJ), a compound TCM formulation designed to nourish yin and invigorate qi, shows therapeutic potential for xerostomia. This study aimed to establish quality control standards for STHJ and evaluate its pharmacodynamics, safety, and mechanisms of action in models of xerostomia.Methods A qualitative identification method was developed for the twelve herbal components of STHJ, with quantification of active constituents, focusing on quality markers for Astragalus and Rehmannia. Xerostomia was induced in Sprague–Dawley (SD) rats using a muscarinic receptor antagonist, and in BALB/c mice with SjD. Histological examination of major organs and salivary glands was performed, and aquaporin-5 (AQP5) expression in submandibular glands was assessed via Western blotting and immunohistochemistry. Therapeutic effects were evaluated through salivary secretion, glandular weight, and biochemical markers. In SjD mice, submandibular gland immunofluorescence and ELISA were used to assess inflammatory cytokines (TNF-α, TNF-β, IFN-γ, IL-6) and autoantibodies (anti-SSA/Ro, anti-SSB/La). Western blotting was used to analyse NF-κB and MAPK p38 pathway activation. Acute toxicity was assessed in SD rats.Results STHJ significantly improved xerostomia symptoms, increased salivary output, upregulated AQP5, and preserved glandular morphology. It reduced fibrosis, suppressed inflammatory cytokine expression, and inhibited immune cell infiltration. Mechanistically, STHJ attenuated activation of NF-κB and MAPK p38 pathways. No acute toxicity was observed.Conclusion This is the first study to establish quality control standards for STHJ and to demonstrate its anti-inflammatory and immunomodulatory effects in xerostomia models. The findings suggest that STHJ may serve as a safe and effective therapeutic option for xerostomia associated with SjD and other conditions.
研究领域:
药理学
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免疫学
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中医中药
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分子生物学
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风湿病学
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产品关联
DOI
PubMed
高影响因子
TROPICAL JOURNAL OF PHARMACEUTICAL RESEARCH
·
2022
·Vol. 21
·期 10
·2139-2146
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IF 0.523
Limei Du,Xinglan Huo,Ying Liu
Purpose: To study the influence of resveratrol on chronic obstruction in Aspergillus fumigatus infection-induced chronic lung disease (COPD) in rats, and the process involved.
Methods: Seventy-five Sprague Dawley SD) rats were assigned to blank control, COPD model, Aspergillus fumigatus-infected COPD model, low (100 mg/kg) and high-dose (200 mg/kg) resveratrol groups, with 15 rats in each group. Enzyme-linked immunosorbent assay (ELISA) was used to assay IL-6, IL-8 and TNF-α in bronchoalveolar lavage fluid (BALF), while lung protein concentrations of AMPK and PGC-1α were assayed by immunoblotting.
Results: In low- and high-dose resveratrol groups, inflammatory factor levels were significantly lower than the corresponding levels in COPD model and Aspergillus fumigatus-infected COPD model (p < 0.05), while lung tissue proteins of AMPK, PGC-1α, and AQP5 of the rats given high-dose resveratrol were significantly raised, relative to corresponding levels in rats given low-dose resveratrol (p < 0.05).
Conclusion: Resveratrol modulates expression levels of secretory factors and surface markers in alveolar macrophages in COPD model rats infected with Aspergillus fumigatus. Resveratrol exerts this effect through the regulation of AMPK/PGC-1α signaling pathway.
研究领域:
药理学
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免疫学
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呼吸医学
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产品关联
DOI
高影响因子
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