Publications by authors named "X Zhao"

37,296 Publications

Circular RNA BIRC6 depletion promotes osteogenic differentiation of periodontal ligament stem cells via the miR-543/PTEN/PI3K/AKT/mTOR signaling pathway in the inflammatory microenvironment.

Stem Cell Res Ther 2022 Aug 13;13(1):417. Epub 2022 Aug 13.

Stomatological Hospital, Southern Medical University, Guangzhou, 510280, China.

Background: Periodontal ligament stem cells (PDLSCs) are the ideal seed cells for periodontal tissue regeneration. It is well established that persistent inflammation significantly impairs the osteogenic differentiation capability of PDLSCs. Therefore, maintaining PDLSC osteogenic potential under the inflammatory microenvironment is important for treating bone loss in periodontitis. The aim of our study was to explore the potential role of circular RNA BIRC6 (circBIRC6) in regulating osteogenic differentiation of PDLSCs in the inflammatory conditions.

Methods: Alkaline phosphatase staining, Alizarin Red staining, quantitative real-time polymerase chain reaction, western blotting and immunofluorescence staining were used to evaluated the effects of circBIRC6 on the osteogenic differentiation of PDLSCs. RNA pull-down and luciferase assays were performed to explore the interaction between circBIRC6 and miR-543. Then, the downstream signaling pathway affected by circBIRC6/miR-543 axis was further investigated.

Results: The expression level of circBIRC6 was higher in PDLSCs exposed to inflammatory stimulus and in periodontitis tissues compared to the respective controls. Downregulation of circBIRC6 enhanced the osteogenic potential of PDLSCs under the inflammatory conditions, and upregulation of circBIRC6 led to opposite findings. Mechanistically, we found that circBIRC6 modulated PDLSC osteogenic differentiation through sponging miR-543. More importantly, we have demonstrated that circBIRC6/miR-543 axis regulated the mineralization capacity of PDLSCs via PTEN/PI3K/AKT/mTOR signaling pathway in the inflammatory microenvironment.

Conclusions: In summary, the expression of miR-543 is significantly increased following circBIRC6 downregulation, leading to inhibition of PTEN and subsequently activation of PI3K/AKT/mTOR signaling pathway. Therefore, targeting circBIRC6 might represent a potential therapeutic strategy for improving bone loss in periodontitis.
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http://dx.doi.org/10.1186/s13287-022-03093-7DOI Listing
August 2022

The association between DNA methylation of 6p21.33 and AHRR in blood and coronary heart disease in Chinese population.

BMC Cardiovasc Disord 2022 Aug 13;22(1):370. Epub 2022 Aug 13.

Military Translational Medicine Lab, Medical Innovation Research Division, Chinese PLA General Hospital, Beijing, 100853, China.

Background: Early detection could significantly improve the prognosis of coronary heart disease (CHD). In-invitro diagnostic technique may provide a solution when sufficient biomarkers could be identified. Pertinent associations between blood-based aberrant DNA methylation and smoking, the pathogenesis of atherosclerosis, and CHD have been robustly demonstrated and replicated, but that studies in Chinese populations are rare. The blood-based methylation of aryl-hydrocarbon receptor repressor (AHRR) cg05575921 and 6p21.33 cg06126421 has been associated with cardiovascular mortality in Caucasians. Here, we aim to investigate whether the AHRR and 6p21.33 methylation in the blood is associated with CHD in the Chinese population.

Methods: In this case-control study, 180 CHD patients recruited at their first registration in our study center, and 184 controls randomly selected from the people who participated in the annual health examination were enrolled. Methylation intensities of 19 CpG sites, including AHRR cg05575921, 6p21.33 cg06126421, and their flanking CpG sites, were quantified by mass spectrometry. The association between methylation intensities and CHD was estimated by logistic regression analyses adjusted for covariant.

Results: Compared to the controls, lower methylation of 6p21.33_CpG_4.5/cg06126421 was independently associated with increased odds of being a CHD patient (OR per - 10% methylation = 1.42 after adjustment for age, gender, and batch effect; p = 0.032 by multiple testing corrections). No association between blood-based AHRR methylation and CHD was found.

Conclusions: 6p21.33 methylation exhibits a significant association with CHD. The combination of 6p21.33 methylation and conventional risk factors might be an intermediate step towards the early detection of CHD.
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http://dx.doi.org/10.1186/s12872-022-02766-8DOI Listing
August 2022

Ultralight, highly flexible in situ thermally crosslinked polyimide aerogels with superior mechanical and thermal protection properties via nanofiber reinforcement.

J Colloid Interface Sci 2022 Jul 27;628(Pt A):829-839. Epub 2022 Jul 27.

Research Institute of Textile and Clothing Industries, Zhongyuan University of Technology, Zhengzhou, Henan Province 450007, China. Electronic address:

Hypothesis: Advanced thermal-insulation materials for human use in high-temperature and ultra-low-temperature environments have received extensive attention. However, facile synthesis of aerogels with excellent mechanical and thermal properties via freeze-drying or electrospinning alone is still challenging. We hypothesized that a polyimide aerogel with high mechanical strength and good thermal-insulation performance and suitability for various applications at high and low temperatures could be prepared facilely using a simple and novel preparation strategy that combines electrospinning, freeze-drying, and in situ thermal crosslinking.

Experiments: Polyamideimide (PAI) nanofibers loaded with bismaleimide (BMI) were electrospun and dispersed into a polyamic acid aqueous solution. PAI/BMI-nanofiber-reinforced polyimide (IBNR-PI) aerogels with an interpenetrating network structure were prepared by freeze-drying and heat treatment.

Findings: The IBNR-PI aerogels possessed extremely low volume density (26 mg cm) and high porosity (94.92%). Most importantly, they showed high tensile strength and good compressive fatigue resistance with plastic deformation of only 7% after 1000 compression cycles. The aerogels also showed a significantly low thermal conductivity (30.06 mW m K) and excellent thermal insulation over a wide temperature range. Thus, the IBNR-PI aerogels are excellent candidates for thermal-insulation materials at high and low temperatures.
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http://dx.doi.org/10.1016/j.jcis.2022.07.144DOI Listing
July 2022

Establishment of an epithelioid sarcoma PDCs and PDX to evaluate drug sensitivity.

Biochem Biophys Res Commun 2022 Aug 6;625:140-146. Epub 2022 Aug 6.

OriCell Therapy Co. Ltd, No.1227, Zhangheng Rd, Pudong, Shanghai, China.

Epithelioid sarcoma (ES) is a very rare mesenchymal malignancy. Its oncogenesis remains unknown, and few therapies are available for advanced patients. Improved therapies, such as combined therapies, are urgently needed for the treatment of advanced ES. To identify precision drugs for advanced ES patients, the sensitivity of the drugs must be screened and evaluated before they are used for treatment. In the present study, tumour tissue from an ES patient was subjected to NGS sequencing, cell culture and the construction of a PDX model. Using the early generations of tumour-derived cells, we performed a screen and found that the combined drugs ADM and trametinib exhibited coefficiency in tumour inhibition. This conclusion was further confirmed in experiments with later generations of cells and PDX models. Therefore, we suggest that early generations of tumour-derived cells be used to test the sensitivity of ES tumours to candidate drugs. Moreover, we speculate that trametinib may be combined with chemotherapy in ES patients to prolong the duration of the chemotherapeutic response.
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http://dx.doi.org/10.1016/j.bbrc.2022.07.052DOI Listing
August 2022

NRAS p.Q61R/K allele load is correlated to different phenotypes of congenital melanocytic naevi.

Clin Exp Dermatol 2022 Aug 13. Epub 2022 Aug 13.

The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Regional Medical Center for Children, Hangzhou, Zhejiang, China.

Background: Congenital melanocytic naevi (CMN) are known to be associated with mosaic NRAS or BRAF variants. However, the exact correlations of the allele load of mosaic variants in CMN with phenotypic characteristics have not been determined.

Objectives: To determine the correlation of variants allele load and different phenotypes of CMN.

Methods: A panel of genes in RAS/RAF/MAPK signaling pathway was selected for sequencing in 110 patients with CMN. Correlations between variant allele load and clinical phenotypes including anatomic localization, projected adult size of the lesion, satellites, subcutaneous nodules, surface rugosity, color heterogeneity, hypertrichosis were analyzed.

Results: Besides the predominant NRAS p.Q61R/K (61.8%) and BRAF p.V600E variants (10%) in patients, we also detected additional variants of NRAS p. G13R and p.M72fs; BRAF p.D22N; MAP2K1 p.I107fs, p.F209fs, p.Q354H, and p.G91_L92insHDQARRLVGDLEHHKPSG. Furthermore, the higher allele load of NRAS p.Q61R/K was indicated in extremities and trunks, and also in larger size, higher color variation, the more significant hypertrichosis, surface rugosity and asymmetry phenotypes of CMN.

Conclusions: We discovered more genetic variants and established the correlation of allele load of NRAS p.Q61R/K and various phenotypes in CMN. The findings of this study potentially facilitates a more accurate and comprehensive classification of CMN in addition to the phenotypic or pathological characteristics in clinical practice.
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http://dx.doi.org/10.1111/ced.15369DOI Listing
August 2022
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