Mengjiao Xu’s research while affiliated with Tongji Hospital and other places

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Publications (5)


Hypoxic Preconditioned ADSC Exosomes Enhance Vaginal Wound Healing via Accelerated Keratinocyte Proliferation and Migration Through AKT/HIF‑1α Axis Activation
  • Article

September 2024

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1 Read

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3 Citations

Cellular and Molecular Bioengineering

Xiaoyun Yang

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Shasha Zhang

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Kewei Chen

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[...]

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Xiaowen Tong

Accelerating wound healing is a main consideration in surgery. The three stages of wound healing are inflammatory response, tissue repair and cell proliferation. Much research has focused on epidermal cell proliferation and migration because this is an essential step in wound healing. The current study discovered that exosomes from Adipose-derived stem cell (ADSC) following hypoxic preconditioning (HExo) have a greater promotional effect on vaginal wound healing. Protein kinase B (AKT)/hypoxia-inducible factor 1-alpha (HIF-1α) play an important role in HExo-mediated HaCaT cell migration and proliferation. The promotional effect of HExo on rat wound healing was reversed by both, HIF‑1α and AKT inhibition. Phosphorylation of AKT (p-AKT) or HIF‑1α suppression reversed the protective effect of HExo on vaginal wound healing. Taken together, our study found that hypoxic preconditioning of adipose MSC exosomes enhances vaginal wound healing via accelerated keratinocyte proliferation and migration through AKT/HIF‑1α axis activation.


Bivariate relationships between CUMD and AGD-AC measure in the non-overweight subjects.
Characteristic of the study population (n = 117).
Clitoris to Urethral Meatus Distance, an Assumed Marker of Prenatal Androgen Exposure is not Correlated with the Obesity Compared to the Anogenital Distance
  • Article
  • Full-text available

June 2022

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248 Reads

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2 Citations

Background The distance between clitoris and urethral meatus (CUMD) for women has been considered to likely reflect the extent of prenatal androgen exposure, being similar to the anogenital distance (AGD) and the digit length ratio. But no published work has examined the association between CUMD and AGD or digit ratio, and the effects of body weight on the CUMD and AGD. Methods The CUMD and two AGD measurements, including the anus to the anterior clitoris (AGD-AC) and the anus to the posterior fourchette (AGD-AF), were taken in 117 Chinese women (18–45 years), using a digital caliper. The digit ratios were measured from photos by a digital camera. Meanwhile, data of their height, weight, and body mass index (BMI) were collected. Results In bivariate correlation analyses of all 117 subjects, two AGD measurements (AGD-AC and AGD-AF) were moderately correlated with one another (r = 0.474, p < 0.001), but the correlation between AGD-AC and CUMD was weak (r = 0.172, p = 0.063). Both AGD-AC and AGD-AF were notably correlated with weight (r = 0.290, p = 0.002 and r = 0.189, p = 0.041; respectively) and BMI (r = 0.341, p < 0.001 and r = 0.204, p = 0.027; respectively), whereas the CUMD did not differ based on weight or BMI. Exclusion of obese individuals, the CUMD of 86 non-overweight subjects was correlated with the AGD-AC (r = 0.236, p = 0.028). Conclusions These results indicated that the CUMD, as an assumed marker of prenatal androgen exposure, was not affected by the body weight, thus being superior to AGD-AC or AGD-AF.

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Engineering of Neutrophil Membrane Camouflaging Nanoparticles Realizes Targeted Drug Delivery for Amplified Antitumor Therapy

February 2021

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107 Reads

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33 Citations

Purpose Although the neutrophil membrane (NM)-based nanoparticulate delivery system has exhibited rapid advances in tumor targeting stemmed from the inherited instinct, the antitumor effect requires further improvement due to inefficient cellular internalization in the absence of specific interactions between NM-coated nanoparticles and tumor cells. Methods Herein, we fabricated drug-paclitaxel loaded NM camouflaging nanoparticles (TNM-PN) modified with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), favorable for the cellular internalization. Results The results showed that TNM-PN exerted a significant cytotoxicity to tumor cells by TRAIL-mediated endocytosis and strong adhesion to inflamed endothelial cells in vitro. Due to TRAIL modification as well as the adhesive interactions between neutrophil and inflamed tumor vascular endothelial cells, tumors in TNM-PN group exhibited almost 2-fold higher fluorescence intensities than that of NM camouflaging nanoparticles and 3-fold higher than that of bare nanoparticles, respectively. Significant tumor inhibition and survival rates of mice were achieved in TNM-PN group as a consequence of prolonged blood circulations to 48 h and preferential tumor accumulations, which was ascribed to targeting adhesion originated from NM to immune evasion and subsequent excellent cellular internalization. Conclusion The research unveiled a novel strategy of amplifying cellular internalization based on NM coating nanotechnology to boost antitumor efficacy.


Targeted chimera delivery to ovarian cancer cells by heterogeneous gold magnetic nanoparticle

December 2016

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32 Reads

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32 Citations

Efficient delivery of small interfering RNAs (siRNAs) to the targeted cells has remained a significant challenge in clinical applications. In the present study, we developed a novel aptamer-siRNA chimera delivery system mediated by cationic Au-Fe3O4 nanoparticles (NPs). The chimera constructed by VEGF RNA aptamer and Notch3 siRNA was bonded with heterogeneous Au-Fe3O4 nanoparticles by electrostatic interaction. The obtained complex exhibited much higher silencing efficiency against Notch3 gene compared with chimera alone and lipofectamine-siRNA complex, and improved the antitumor effects of the loaded chimera. Moreover, the efficient delivery of the chimera by Au-Fe3O4 NPs could reverse multi-drug resistance (MDR) of ovarian cancer cells against the chemotherapeutic drug cisplatin, indicating its potential capability for future targeted cancer therapy while overcoming MDR.


Figure 1. Immunofluorescence staining of isolated VSMCs. VSMCs were stained with an α-SMA antibody and a fluorescein isothiocyanate-conjugated secondary antibody and counterstained with 4',6-diamidino-2-phenylindole. The majority of cells were positive for α-SMA, and exhibited discernible fiber filaments and a well-formed spindle shape, verifying the high purity of isolated VSMCs. Magnification, x20. VSMCs, vascular smooth muscle cells; α-SMA, smooth muscle α-actin.
Figure 2. Effect of Iso and CGA on cytotoxicity and vascular smooth muscle cell viability. Cell viability was determined using an 3‑(4,5‑dimethylthi‑ azol‑2‑yl)‑2,5‑diphenyltetrazolium bromide assay, which determined the absorbance of cells following treatment with various concentrations of (A) Iso and (B) CGA. The percentage of cell viability was calculated relative to control wells designated as 100% viable, for (C) Iso‑and (D) CGA‑treated cells. Iso, isoproterenol; CGA, chlorogenic acid.  
Figure 3. DNA damage following treatment of vascular smooth muscle cells with Iso, in the presence or absence of CGA pretreatment, as determined by western blot analysis. (A) Alterations in the protein expression levels of the nuclear protein γ‑H2AX. TBP served as a loading control. (B) Alterations in the protein expression levels of p‑ATR, p‑ATM, BRCA‑1 and Chk2. GAPDH served as a loading control. The western blot represents one of at least three independent experiments that demonstrated similar results. * P<0.05 vs. control. Iso, isoproterenol; CGA, chlorogenic acid; γ‑H2AX, γ‑H2A histone family member X; TBP, TATA binding protein; p, phosphorylated; ATR, Rad3‑related protein; ATM, ataxia telangiectasia mutated; BRCA1, breast cancer 1; Chk2, C‑terminal Src homologous kinase 2; GAPDH, glyceraldehyde 3‑phosphate dehydrogenase.  
Chlorogenic acid prevents isoproterenol-induced DNA damage in vascular smooth muscle cells

September 2016

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101 Reads

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23 Citations

Molecular Medicine Reports

Numerous clinical therapeutic agents have been identified as DNA damaging. The present study revealed that isoproterenol (Iso) resulted in DNA damage in vascular smooth muscle cells (VSMCs) and increased the levels of intracellular oxygen free radicals. Administration of chlorogenic acid (CGA) inhibited this effect. Pretreatment with CGA abrogated the increase in protein expression levels of γ‑H2A histone family member X, phosphorylated ataxia telangiectasia mutated, phosphorylated Rad3‑related protein, breast cancer 1 and C‑terminal Src homologous kinase induced by Iso. In addition, the increase in levels of intracellular reactive oxygen species (ROS) induced by Iso was inhibited by CGA pretreatment in a dose‑dependent manner. The results of the present study suggest that CGA may inhibit Iso‑induced VSMC damage via the suppression of ROS generation. Therefore, CGA may be a novel agent for the treatment of vascular diseases.

Citations (4)


... Notably, the activation of the PI3K/Akt pathway is critical in this context, as it mediates the protective and regenerative effects of MSC-secreted factors. This pathway promotes cell survival, growth, and metabolism, further enhancing the therapeutic efficacy of MSCs in diabetic wound healing by facilitating tissue repair and modulating inflammatory responses [16][17][18]. Additionally, the application of various biomaterials, including hydrogels, has been shown to enhance the therapeutic effects of MSCs by providing a supportive environment that promotes cell retention, regulates the release of bioactive factors, and improves overall wound healing outcomes [19][20][21]. ...

Reference:

Mesenchymal stem cells from perinatal tissues promote diabetic wound healing via PI3K/AKT activation
Hypoxic Preconditioned ADSC Exosomes Enhance Vaginal Wound Healing via Accelerated Keratinocyte Proliferation and Migration Through AKT/HIF‑1α Axis Activation
  • Citing Article
  • September 2024

Cellular and Molecular Bioengineering

... Likewise, neutrophil membrane-coated nanoparticles (TNM-PN) contribute to immune activation by promoting tumor-infiltrating T cells and increasing survival rates in tumor-bearing mice ( Figure 4F) [141]. These strategies all converge on the idea of transforming the TME from an immune-suppressive state to an immune-reactive one, boosting both innate and adaptive anti-cancer responses. ...

Engineering of Neutrophil Membrane Camouflaging Nanoparticles Realizes Targeted Drug Delivery for Amplified Antitumor Therapy

... Recently, to overcome Notch3-induced MDR, anticancer drugs and Notch3 siRNA codelivery has been explored as important and influential method. Chen et al. used Notch3 siRNA and VEGF RNA aptamer to create a novel chimeric delivery system using Au-Fe3O4 cationic NPs [145]. They codelivered this structure with cisplatin to both the SKOV-3 cell line and cisplatin-resistant SKOV-3/cis-diamminedichloroplatinum(II) cells, significantly suppressing Notch3 expression. ...

Targeted chimera delivery to ovarian cancer cells by heterogeneous gold magnetic nanoparticle

... Moreover, in the presence of trace amounts of chlorogenic acid, caspase-3 activity is reduced, but DNA fragmentation persists. This may be in line with Wang et al. (2016) and Yamagata et al. (2018), who proposed that chlorogenic acid may activate alternative caspases or non-caspase pathways, resulting in DNA cleavage without fully triggering the classic apoptotic pathway. Higher concentrations of chlorogenic acids in green coffee extracts could more effectively prevent ROS overproduction by enhancing antioxidant capacity through the activation of Nrf2/HO-1 under disuse conditions. ...

Chlorogenic acid prevents isoproterenol-induced DNA damage in vascular smooth muscle cells

Molecular Medicine Reports