Frontiers in Immunology
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2025
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IF 5.9
Jingwei Liu,Tong Shu,Yiheng Mu,Wanlin Zheng,Xiaohuan Lu,Hong Tao
Background: Human papillomavirus (HPV) infection is a worldwide reproductive system disease. Baofukang suppository, a traditional herbal preparation that includes curdione and borneol, has been reported to treat bacterial vaginosis (BV) and HPV infection in China. However, the therapeutic mechanism is still unknown. This study aims to explore the molecular mechanisms of curdione and borneol in treating HPV infection.Methods: We conducted a retrospective cohort analysis of medical records from a single-center study involving 205 HPV patients, focusing on the correlation between HPV clearance and co-infection with other pathogens, confirming the efficacy of Baofukang suppository. Bioinformatics and network pharmacology approaches were employed to identify therapeutic targets of Baofukang suppository for BV/HPV co-infections. qRT-PCR, Western blot, immunofluorescence staining, and flow cytometry were utilized to validate the therapeutic targets of curdione and borneol, along with the associated immune molecular changes. Finally, the molecular mechanisms and therapeutic efficacy of curdione and borneol were confirmed in vivo using an LPS/TC-1 cervical orthotopic injection model.Results: Curdione and borneol selectively inhibit the secretion of interleukin-6 (IL-6) and interleukin-1β (IL-1β) by macrophages. The reduction in IL-6 and IL-1β levels effectively inhibits the expression of CD274 (Programmed death ligand 1, PD-L1) in infected epithelial cells by inhibiting STAT3 phosphorylation, thereby suppressing their immune evasion capabilities. Furthermore, curdione and borneol enhance the expression of tumor necrosis factor α (TNF-α) and caspase 1 (CASP1) in macrophages, as well as the expression of interleukin 12 (IL-12) and interleukin 23 (IL-23) in dendritic cells (DCs). The expression of these inflammatory factors effectively promotes the migration and differentiation of T cells to the site of infection, completing the clearance of infected epithelial cells.Conclusion: The main components of Baofukang suppository, curdione and borneol, inhibit the progression of HPV infection and the occurrence of cervical cancer by modulating the communication between innate and adaptive immunity, promoting the recruitment and recognition of CD8+ T cells to eliminate HPV-infected epithelial cells.
研究领域:
医学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2025
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IF 4.6
Xiaoli Zhang,Zhaoguang Wang,Jing Yang,Yingying Li,Cheng Lu,Yanqiang Hao,Guanbo He,Yongjian Zhang,Qifang Song,Jun Long,Jiajie Liang,Yong Tang
Currently, producing NPSH after HPV infection of cells has been confirmed. These NPSH-containing substances accumulate around the urethral opening and are subsequently washed out with urine. Therefore, indirect detection of HPV infection by assessing NPSH levels in urine is feasible, but it has not been reported in detail so far. Here, an assay using phosphotungstic acid to oxidise and produce colour changes by NPSH in urine was developed. This assay enabled the rapid, non-invasive identification of HPV infection by detecting the metabolic byproduct NPSH produced by HPV-infected cells. Employing a smartphone-based device, developed using an ambient light sensor, reduces the cost and simplifies the operation associated with the colourimetric assay. The colourimetric assay was used to detect L-cysteine and L-ascorbic acid standard substance (as NPSH mimics), the limited of detection were 0.12 mM and 31.25 μM, respectively, with high reproducibility and stability. When this colourimetric assay was used to evaluate urine samples from individuals suspected of HPV infection, along with other at-home self-screening methods for HPV nucleic acid detection in urine, showed comparable sensitivity and specificity. Compared with nucleic acid detection in urine, this colourimetric assay is cost-effective, user-friendly, amenable to self-sampling, and enables testing at one’s convenience and location of choice, which is more suitable for home self-testing or population self-screening.
研究领域:
医学检验
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生物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2020
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IF 7.727
Xueqin Gao,Zhuang Jin,Xiangyu Tan,Chong Zhang,Chenming Zou,Wei Zhang,Jiahui Ding,Bhudev C. Das,Konstantin Severinov,Inga Isabel Hitzeroth,Priya Ranjan Debata,Dan He,Xin Ma,Xun Tian,Qinglei Gao,Jun Wu,Rui Tian,Zifeng Cui,Weiwen Fan,Zhaoyue Huang,Chen Cao,Yuxian Bao,Songwei Tan,Zheng Hu
Persistent high-risk HPV infection is the main factor for cervical cancer . HPV E7 oncogene plays an important role in HPV carcinogenesis. Down-regulation of E7 oncogene expression could induce growth inhibition in HPV-positive cells and thus treats HPV related cervical cancer. Here we developed a non-virus gene vector based on poly(amide-amine)-poly(β-amino ester) hyperbranched copolymer (hPPC) for the delivery of CRISPR/Cas9 system to specifically cleave HPV E7 oncogene in HPV-positive cervical cancer cells. The diameter of polyplex nanoparticles (NPs) formed by hPPCs/linear poly(β-amino ester) (PBAE) and plasmids were approximately 300 nm . These hPPCs/PBAE-green fluorescence protein plasmids polyplex NPs showed high transfection efficiency and low toxicity in cells and mouse organs. By cleaving HPV16 E7 oncogene, reducing the expression of HPV16 E7 protein and increasing intracellular retinoblastoma 1 (RB1) amount, hPPCs/PBAE-CRISPR/Cas9 therapeutic plasmids polyplex NPs, especially highly branched hPPC1-plasmids polyplex NPs, exhibited strong growth inhibition of cervical cancer cells in vitro and xenograft tumors in nude mice . Together, the hPPCs/PBAE polyplex NPs to deliver HPV16 E7 targeted CRISPR/Cas9 system in this study could potentially be applied to treat HPV-related cervical cancer.
研究领域:
癌症研究
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基因治疗
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纳米技术
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子