The effects of metabolites from three vaginal bacteria on the Syndecan-1 of cervical epithelial cells.

This study aims to explore the impact of metabolites from three vaginal bacteria on the expression of Syndecan 1 (SDC-1). Human cervical epithelial cells (HcerEpic) were separately incubated with the cell-free supernatants of Lactobacillus crispatus (LCS group), Gardnerella vaginalis (GVS group), and Atopobium vaginalis (AVS group). LCS showed a proliferative effect on HcerEpic, with the most significant effect observed at a concentration of 30 % (P < 0.001). GVS and AVS exhibited some cytotoxicity, with significant growth inhibitory effects observed at concentrations of 30 % and 40 % (P < 0.01). Therefore, subsequent experiments were conducted using 30 % LCS, 40 % GVS, and 40 % AVS. In terms of cellular morphology, compared to the Control group, the LCS group showed more frequent fusion of cell sheets, with no obvious changes in the morphology of individual cells. In the GVS and AVS groups, some individual cells became round and smaller, with reduced protrusions and even a small amount of floating cells. The metabolic products of the three vaginal bacteria significantly upregulated the expression of IL-1ß, IL-6, and TNF-α in HcerEpic (P < 0.05). In the GVS and AVS groups, the level of SDC-1 on the surface of HcerEpic was significantly decreased (P < 0.01), while the concentration of SDC-1 in the cell culture supernatant was significantly increased (P < 0.0001). Additionally, the level of SDC-1 mRNA was significantly downregulated (P < 0.01). In the LCS group, no significant changes were observed in SDC-1 protein and mRNA expression (P > 0.05). LCS promotes HcerEpic proliferation, without significant impact on SDC-1 expression and shedding. This provides molecular evidence for LCS as a protective factor against human papillomavirus infection in the cervix. Metabolites of GV and AV inhibit HcerEpic proliferation, induce cytokine secretion, suppress SDC-1 transcription and expression, and promote SDC-1 shedding.

Halostachys caspica pathogenesis-related protein 10 acts as a cytokinin reservoir to regulate plant growth and development.

Pathogenesis-related class 10 (PR-10) proteins play a role in plant growth and development, but the underlying molecular mechanisms are unclear. Here, we isolated a salt-induced PR-10 gene from the halophyte Halostachys caspica and named it HcPR10. HcPR10 was constitutively expressed during development and HcPR10 localized to the nucleus and cytoplasm. HcPR10-mediated phenotypes including bolting, earlier flowering, increased branch number and siliques per plant are highly correlated with increased cytokinin levels in transgenic Arabidopsis. Meanwhile, increased levels of cytokinin in plants is temporally correlated with HcPR10 expression patterns. Although the expression of cytokinin biosynthesis genes validated was not upregulated, cytokinin-related genes including chloroplast-related genes, cytokinin metabolism and cytokinin responses genes and flowering-related genes were significantly upregulated in the transgenic Arabidopsis compared to the wild type by transcriptome deep sequencing. Analysis of the crystal structure of HcPR10 revealed a trans-zeatin riboside (a type of cytokinin) located deep in its cavity, with a conserved conformation and protein-ligand interactions, supporting HcRP10 acts as a cytokinin reservoir. Moreover, HcPR10 in Halostachys caspica predominantly accumulated in vascular tissue, the site of long-distance translocation of plant hormones. Collectively, we draw that HcPR10 as a cytokinin reservoir induces cytokinin-related signal transduction in plants, thereby promoting plant growth and development. These findings could provide intriguing insights into the role of HcPR10 proteins in phytohormone regulation in plants and advance our understanding of cytokinin-mediated plant development and could facilitate the breeding of transgenic crops with earlier mature, higher yielding agronomic traits.

Clinical indocyanine green-based silk fibroin theranostic nanoprobes for in vivo NIR-I/II fluorescence imaging of cervical diseases.

Cervical diseases such as lymph node disease and tubal obstruction have threatened women's health. However, the traditional diagnostic methods still have shortcomings. NIR-II fluorescence imaging with advantages of low scattering, negligible autofluorescence, and high spatial resolution could be an ideal option. To obtain high quality NIR-II fluorescence imaging, selecting appropriate nanoprobes becomes the important issue. As a small molecular photothermal agent, extensive applications of ICG are rather limited because of its drawbacks. Herein, natural silk fibroin (SF) was synthesized and encapsulated ICG molecules to form SF@ICG nanoparticles (NPs). After detailed analysis, SF@ICG NPs showed excellent stability and long circulation time, as well as strong NIR-II fluorescence emission, well photo-stability, biocompatibility and well photothermal property under 808 nm laser irradiation. Furthermore, SF@ICG NPs were utilized for NIR-II fluorescence imaging of lymph node/lymphangiography and angiography of fallopian tubes. The process of fallopian tubes could be detected with high resolution and high sensitivity.

Polydopamine encapsulated new indocyanine green theranostic nanoparticles for enhanced photothermal therapy in cervical cancer HeLa cells.

Photothermal therapy (PTT) has attracted extensive attention in cancer treatment due to its non-invasiveness, high efficiency, and repeatability in recent years. Photothermal agents (PTAs) are the key factor for PTT. Recently, although an increasing number of PTAs have been developed, there is still a great demand for optimized photothermal nanoparticles (NPs) with low toxicity, bio-safety and stability. Herein, new indocyanine green (IR820) with near-infrared (NIR:700-1,700 nm) fluorescence emission was selected as a photothermal agent (PTA). To enhance the PTT property, IR820 was encapsulated with another kind of PTA, polydopamine (PDA) under alkaline conditions. Furthermore, to improve the biocompatibility of the NPs, methoxy polyethylene glycol amine (mPEG-NH2) was modified via a Michael addition to form a novel kind of IR820@PDA@PEG NPs. After detailed characterization and analysis, the obtained IR820@PDA@PEG NPs showed a spherical shape with an average diameter of ∼159.6 nm. Meanwhile, the formed IR820@PDA@PEG NPs exhibited better photostability and lower cytotoxicity than free IR820 molecules. The photothermal performance of IR820@PDA@PEG NPs was further analyzed in vitro, and the temperature of IR820@PDA@PEG NPs (100 µg/ml) reached 54.8°C under 793 nm laser irradiation. Afterwards, the cellular uptake of IR820@PDA@PEG NPs was evaluated via confocal laser scanning fluorescence microscopic imaging. Then, PTT experiments on HeLa cells demonstrated that IR820@PDA@PEG NPs can hyperthermal ablate cancer cells (∼49.1%) under 793 nm laser irradiation. Therefore, IR820@PDA@PEG NPs would be a promising PTA for the treatment of cervical cancer HeLa cells.

A highly efficient polydopamine encapsulated clinical ICG theranostic nanoplatform for enhanced photothermal therapy of cervical cancer.

Photothermal therapy (PTT) is a safe and efficient anti-tumor treatment. A photothermal agent (PTA) with good biocompatibility and strong photothermal properties is of great importance for PTT. In this study, near-infrared (NIR) excitable clinical indocyanine green (ICG) was utilized as a PTA and further encapsulated by another PTA polydopamine (PDA) to form highly stable and efficient ICG@PDA nanoparticles (NPs). Then the ICG@PDA NPs were modified with methoxy polyethylene glycol amine (mPEG2000-NH2) to form biocompatible ICG@PDA@PEG NPs. ICG@PDA@PEG NPs showed good water solubility and a spherical shape with an average size of 140 nm. Furthermore, the photothermal properties of ICG@PDA@PEG NPs were studied and excellent photothermal performance with a photothermal conversion efficiency of 43.7% under 808 nm laser irradiation was achieved. Then, the PTT properties of ICG@PDA@PEG NPs were confirmed on HeLa cells with an efficiency of 86.1%. Meanwhile, the in vivo biocompatibility and toxicity of ICG@PDA@PEG NPs were evaluated. No apparent in vivo toxicity was observed in 24 hours and 7 days. Next, in vivo PTT analysis was conducted for cervical tumor-bearing nude mice under 808 nm laser excitation. It showed a good anti-tumor effect in vivo. Thus, ICG@PDA@PEG NPs exhibited great potential for safe and efficient photothermal therapy in anti-tumor therapy.

Indocyanine Green-Based Theranostic Nanoplatform for NIR Fluorescence Image-Guided Chemo/Photothermal Therapy of Cervical Cancer.

PURPOSE: Indocyanine green (ICG) is a favorable fluorescence nanoprobe for its strong NIR-I fluorescence emission and good photothermal capabilities. However, the stability and tumor targeting ability of ICG is poor, which limits its further applications. To further improve the photothermal and therapeutic efficiency of ICG, bovine serum albumin (BSA) was utilized to encapsulate the ICG and the chemotherapeutic drug doxorubicin (DOX) was loaded to form the BSA@ICG-DOX theranostic nanoplatform. METHODS: In this study, ICG-loaded BSA nanoparticles (NPs) and the BSA@ICG-DOX NPs were fabricated using reprecipitation methods. Next, the tumour inhibition ability and biocompatibility of the NPs were evaluated. A subcutaneous xenografted nude mice model was established and imaging guided synergetic therapy was performed with the assistance of BSA@ICG-DOX NPs under 808 nm laser irradiation. RESULTS: The BSA@ICG NPs exhibited strong NIR-I fluorescence emission, excellent photothermal properties, biocompatibility, and tumor targeting ability. To further improve the therapeutic efficiency, the chemotherapeutic drug doxorubicin (DOX) was loaded into the BSA@ICG NPs to form the BSA@ICG-DOX theranostic nanoplatform. The BSA@ICG-DOX NPs were spherical with an average size of ~194.7 nm. The NPs had high encapsulation efficiency (DOX: 19.96% and ICG: 60.57%), and drug loading content (DOX: 0.95% and ICG: 3.03%). Next, excellent NIR-I fluorescence and low toxicity of the BSA@ICG-DOX NPs were verified. Targeted NIR-I fluorescence images were obtained after intravenous injection of the NPs into the subcutaneous cervical tumors of the mice. CONCLUSION: To improve the anti-tumor efficiency of the ICG@BSA NPs, the chemotherapeutic drug DOX was loaded into the BSA@ICG NPs. The NIR excitation/emission and targeted BSA@ICG-DOX NPs enables high-performance diagnosis and chemo/photothermal therapy of subcutaneous cervical tumors, providing a promising approach for further biomedical applications.