1.Application progress of collagen membranes in oral medicine.
Yiqin WANG ; Junliang WEN ; Xinhang YU ; Jun CHEN ; Wenjie LI
Journal of Central South University(Medical Sciences) 2025;50(6):1088-1098
Collagen membrane has attracted much attention from researchers due to its excellent properties such as wide source, degradable absorption, and low immunogenicity. However, they are limited by poor mechanical stability and rapid degradation. To enhance their physicochemical properties and biological functions, researchers have developed various strategies, including cross-linking, incorporation of growth factors or drugs, combination with other biomaterials, optimization of composition and structure, and substitution with marine-derived collagen. These advances aim to expand the clinical applications of collagen membranes in oral medicine. With the urgent demand for high-performance biomaterials in oral medicine, summarizing recent progress on collagen membranes provides valuable insights into their mechanisms, clinical efficacy, and limitations, offering reference for optimized design and broader clinical use. Furthermore, further trends may include integrating advanced manufacturing technologies to develop personalized collagen membranes, which could significantly improve therapeutic outcomes in oral diseases.
Collagen/therapeutic use*
;
Humans
;
Biocompatible Materials/chemistry*
;
Membranes, Artificial
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Oral Medicine/methods*
;
Tissue Engineering/methods*
2.Orally deliverable biomimetic nucleic acid therapies for targeted treatment of atherosclerosis.
Chenwen LI ; Yidan CHEN ; Yuan LI ; Huan LIU ; Shengqian YANG ; Yongyao LIN ; Yuantong QI ; Songling HAN ; Yin DOU ; Gaoxing LUO ; Yingxue HAO ; Jianxiang ZHANG
Acta Pharmaceutica Sinica B 2025;15(11):6052-6069
Accumulating evidence has demonstrated that nucleic acid-based therapies are promising for atherosclerosis. However, nearly all nucleic acid delivery systems developed for atherosclerosis necessitate injection, which results in rapid elimination and poor patient compliance. Consequently, oral delivery strategies capable of targeting atherosclerotic plaques are imperative for nucleic acid therapeutics. Herein we report the development of yeast-derived capsules (YCs) packaging an antisense oligonucleotide (AM33) targeting microRNA-33 (miR-33) for the oral treatment of atherosclerosis. YCs provide stability for AM33, preventing its premature release in the gastrointestinal tract. AM33-containing YCs, defined as YAM33, showed high transfection in macrophages, thus promoting cholesterol efflux and inhibiting foam cell formation by regulating the target genes/proteins of miR-33. Orally delivered YAM33 effectively accumulated within atherosclerotic plaques in ApoE -/- mice, primarily by transepithelial absorption via M cells in Peyer's patches and subsequent translocation via macrophages through the lymphatic system. Inhibition of miR-33 by oral YAM33 significantly delayed the progression of atherosclerosis. Moreover, oral treatment with YCs co-delivering AM33 and atorvastatin afforded significantly enhanced anti-atherosclerotic effects. Our findings suggest that yeast-based microcapsules represent an effective carrier for oral delivery of nucleic acids, either alone or in combination with existing drugs, offering a promising approach for precision therapy of atherosclerotic diseases.
3.Prenatal diagnosis of a rare case of complete ring chromosome 15
Hongrui CHEN ; Pengwei JING ; Songling YANG ; Ling LEI ; Xueqi LI
Chinese Journal of Perinatal Medicine 2024;27(1):74-77
This article reported a prenatally diagnosed case of complete ring chromosome 15. A 38-year-old woman who conceived by in vitro fertilization and frozen embryo transfer underwent amniocentesis for prenatal diagnosis at 18 +5 weeks of gestation due to advanced maternal age. The result of G-banding karyotyping was mos 46,XX,r(15)[88]/45,X,-15[11]/46,XX,r(15;15)[1]. No numerical abnormalities of chromosomes or definite pathogenic copy number variations (CNVs) were detected by chromosomal microarray analysis. Amniocentesis was performed again at 31 +6 weeks of gestation. The result of genome copy number variation sequencing indicated no pathogenic CNV and fluorescence in situ hybridization on cultured amniocytes revealed nuc ish(15q)×1[15]/(15q)×3[5]/(15q)×2[80]. Based on all the prenatal diagnosis results, it was suggested that the fetus carried a complete ring chromosome 15. As the peripheral blood chromosomes of the couple were normal and no obvious abnormalities were detected by the prenatal ultrasound either in our hospital or another hospital, the pregnant woman decided to continue the pregnancy after genetic counseling and delivered a baby girl at 41 weeks of gestation. The girl showed no physical abnormalities during a seven-month follow-up.
4.Research progress in periodontally accelerated osteogenic orthodontics.
Yichen XIONG ; Jun CHEN ; Wenjie LI
Journal of Central South University(Medical Sciences) 2024;49(12):2005-2015
Periodontally accelerated osteogenic orthodontics (PAOO) is an adjunctive technique in orthodontic treatment, based on the principle of the regional acceleratory phenomenon (RAP). It aims to shorten orthodontic treatment duration by enhancing osteoclast activity. In recent years, the surgical approach of PAOO has been gradually optimized with the development of techniques such as piezosurgical corticotomy and alveolar micro-osteoperforations. The materials used have also improved, including novel grafting materials such as bioactive glass and new barrier membranes like platelet-rich fibrin. Thanks to these clinical innovations, PAOO is evolving toward a trend of minimal pain, low invasiveness, and high efficacy. However, clinical research on PAOO remains limited, large-sample, multicenter randomized controlled trials are still needed to evaluate the clinical effectiveness of different surgical techniques and grafting materials in PAOO.
Humans
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Osteogenesis/physiology*
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Orthodontics/methods*
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Orthodontics, Corrective/methods*
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Piezosurgery/methods*
5.Anti-PD-L1 antibody enhances curative effect of cryoablation via antibody-dependent cell-mediated cytotoxicity mediating PD-L1highCD11b+ cells elimination in hepatocellular carcinoma.
Jizhou TAN ; Ting LIU ; Wenzhe FAN ; Jialiang WEI ; Bowen ZHU ; Yafang LIU ; Lingwei LIU ; Xiaokai ZHANG ; Songling CHEN ; Haibiao LIN ; Yuanqing ZHANG ; Jiaping LI
Acta Pharmaceutica Sinica B 2023;13(2):632-647
Cryoablation (CRA) and microwave ablation (MWA) are two main local treatments for hepatocellular carcinoma (HCC). However, which one is more curative and suitable for combining with immunotherapy is still controversial. Herein, CRA induced higher tumoral PD-L1 expression and more T cells infiltration, but less PD-L1highCD11b+ myeloid cells infiltration than MWA in HCC. Furthermore, CRA had better curative effect than MWA for anti-PD-L1 combination therapy in mouse models. Mechanistically, anti-PD-L1 antibody facilitated infiltration of CD8+ T cells by enhancing the secretion of CXCL9 from cDC1 cells after CRA therapy. On the other hand, anti-PD-L1 antibody promoted the infiltration of NK cells to eliminate PD-L1highCD11b+ myeloid cells by antibody-dependent cell-mediated cytotoxicity (ADCC) effect after CRA therapy. Both aspects relieved the immunosuppressive microenvironment after CRA therapy. Notably, the wild-type PD-L1 Avelumab (Bavencio), compared to the mutant PD-L1 atezolizumab (Tecentriq), was better at inducing the ADCC effect to target PD-L1highCD11b+ myeloid cells. Collectively, our study uncovered the novel insights that CRA showed superior curative effect than MWA in combining with anti-PD-L1 antibody by strengthening CTL/NK cell immune responses, which provided a strong rationale for combining CRA and PD-L1 blockade in the clinical treatment for HCC.
6. Effect of fractionated radiotherapy of transplanted hepatocellular carcinoma on the splenic immune cells in mice
Dan YAO ; Junling ZHANG ; Wang ZHENG ; Qianping CHEN ; Songling HU ; Yan PAN ; Chunlin SHAO
Chinese Journal of Radiological Medicine and Protection 2020;40(2):82-87
Objective:
To investigate the effect of fractionated radiotherapy on the immune system of mice with subcutaneously transplanted hepatocellular carcinoma.
Methods:
Logarithmic growth of mouse hepatocellular carcinoma cells Hepa 1-6 were inoculated subcutaneously on the right side of C57BL/6 J mice (1×107 cells /mice). The tumor-bearing mice were randomly divided into control group (Ctrl) and irradiation group (IR), 20 mice in each group. Additionally, 10 healthy mice were set as normal control group. Local fractionated X-ray irradiation of 8 Gy×3 fraction was given to the subcutaneous tumors, and the dose rate was 0.883 Gy/min. At 7 and 14 d after irradiation, the tumor organ index, spleen organ index, spleen pathological changes, and splenic T lymphocyte subsets, B lymphocyte subsets, and NK cells were detected.
Results:
Compared with Ctrl, at 7 and 14 d after irradiation, the tumor organ index decreased (
7.The regulatory mechanisms of IGF1 in the osteogenic differentiation of canine MSMSCs via BMP2⁃Smad 1/5 signaling pathway
LIAO Chunhui ; LI I Mingfei ; YE Jinmei ; PENG Wei ; CHEN Songling
Journal of Prevention and Treatment for Stomatological Diseases 2020;28(1):16-23
Objective:
To investigate the role of the bone morphogenetic protein 2 (BMP2)⁃Smad1/5 and p38MAPK
signaling pathways in the osteogenic differentiation of MSMSCs by insulin⁃like growth factor 1 (IGF1).
Methods :
A re⁃
combinant adenovirus (RAD) and IGF1 expressing IGF1 gene were constructed. After osteogenic induction, qRT⁃PCR
and Western blot were used to detect the phosphorylation level of Smad1/5 and the expression of the BMP⁃2 protein in
the BMP⁃Smad signaling pathway; immunohistochemistry was used to observe the nuclear translocation of Smad1/5; qRT⁃PCR and Western blot were used to detect IGF with Noggin and SB203580, inhibitors of the p38MAPK signaling path⁃
way 1⁃mediated osteogenic differentiation of MSMSCs
Results:
The recombinant IGF1 adenovirus was constructed suc⁃
cessfully. MSMSCs were cultured in inductive medium after infection with different concentrations of Ad⁃IGF1, and
then, the protein levels of BMP2 and p⁃Smad1/5 increased. IGF1 can also induce nuclear translocation of Smad1/5. In
addition, Noggin significantly reduced the phosphorylation level of Smad1/5 and the formation of mineralized nodules in
the MSMSCs. The mRNA levels of Runx2, OPN and ALP also decreased. In contrast, SB203580 decreased neither the
phosphorylation level of p38 nor the mRNA expression of Runx2, OPN and ALP in the Ad⁃IGF1 MSMSCs
Conclu⁃sion
IGF1 can promote the osteogenic differentiation of MSMSCs via the BMP2⁃Smad1/5 signaling pathway. In con⁃
trast, IGF1 may not promote the osteogenic differentiation of MSMSCs via the p38MAPK signaling pathway.
8.The role of the membrane of the maxillary sinus in space osteogenesis under the sinus floor after elevation of the sinus floor
Journal of Prevention and Treatment for Stomatological Diseases 2020;28(8):477-486
With the continuous development of maxillary sinus floor elevation technology, the osteogenesis mechanism of maxillary sinus floor elevation has always been a concern of scholars. The membrane of the maxillary sinus is an indispensable physiological structure in the process of space osteogenesis under the sinus floor after elevation of the sinus floor. In recent years, the role of the maxillary sinus floor mucosa in sinus floor space osteogenesis has been a research hotspot. Recent studies have found that the maxillary sinus floor membrane plays a role as a natural biological barrier membrane in the process of sinus floor space osteogenesis after maxillary sinus floor elevation; in addition, it has the ability to undergo osteogenesis. It has also been found that maxillary sinus membrane stem cells (MSMSCs) derived from the maxillary sinus floor membrane have characteristics of mesenchymal stem cells, which can differentiate into osteoblasts and participate in sinus floor space osteogenesis after maxillary sinus floor elevation. New studies have also found that small RNAs such as microRNAs, long noncoding RNAs and circular RNAs can regulate the osteogenic differentiation of MSMSCs, which may be important biological targets for promoting osteogenesis in the sinus floor space. In this paper, the relationship between the maxillary sinus floor mucosa and bone formation after maxillary sinus floor elevation, the barrier and osteogenic function of the maxillary sinus floor mucosa, the sources of osteoblasts involved in osteogenesis of the sinus floor space, and the molecular regulatory mechanisms of stem cells derived from maxillary sinus mucosa will be elucidated step by step.
9.Role of miR-27a in the osteogenic differentiation of beagle maxillary sinus membrane stem cells
ZHANG Jing ; ZHU Shuangxi ; RONG Qiong ; PENG Wei ; LI Xiang ; CHEN Songling
Journal of Prevention and Treatment for Stomatological Diseases 2018;26(8):484-490
Objective:
To detect the expression level of miR-27a during the osteogenic differentiation of beagle maxillary sinus membrane stem cells (MSMSCs) and explore the role of miR-27a in the osteogenic differentiation of MSMSCs.
Methods:
Beagle MSMSCs were cultured in vitro. The expression level of miR-27a was detected via RT-PCR after an osteogenic inductive culture was prepared. The mRNA expression levels of Runx2 and OPN were examined via RT-PCR, and the protein expression levels of Runx2 and OPN were examined via Western blot after the cells were transfected with pre-miR-27a or anti-miR-27a. Finally, osteoprogenitor cells transfected with pre-miR-27a were composited with Bio-Oss particles and subcutaneously implanted into nude mice to form ectopic bone formation models, and then the inhibition of bone formation from miR-27a was observed in vivo.
Results:
The expression level of miR-27a in the beagle MSMSCs decreased after osteogenic inductive culturing. The relative miR-27a levels were significantly decreased at day 1 (t=3.795, P=0.023), day 3 (t=4.493, P=0.011), day 7 (t=11.591, P < 0.001), day 14 (t=12.542, P < 0.001), and day 21 (t=5.621, P=0.008) compared with day 0. In addition, the expression levels of Runx2 mRNA (t=4.923, P=0.007) and protein (t=4.425, P=0.008) were reduced after the cells were transfected with pre-miR-27a. The expression levels OPN mRNA (t=5.253, P=0.006) and protein (t=5.132, P=0.006) were also reduced. In contrast, the mRNA expression levels of Runx2 (t=3.925, P=0.013) and OPN (t=3.712, P=0.019) were increased after the cells were transfected with anti-miR-27a, and bone formation was observed after the subcutaneous implantation of beagle MSMSCs composited with Bio-Oss in nude mice. Nevertheless, ectopic bone formation was inhibited by pre-miR-27a-transfected beagle MSMSCs composited with Bio-Oss (t=7.219, P=0.0020).
Conclusion
MiR-27a negatively regulates the osteogenic differentiation of MSMSCs.
10.Culture and identification of the osteogenic properties of beagle maxillary sinus membrane stem cells
ZHANG Jing ; ZHU Shuangxi ; PENG Wei ; LI Xiang ; RONG Qiong ; CHEN Songling
Journal of Prevention and Treatment for Stomatological Diseases 2018;26(7):422-427
Objective:
To investigate the osteogenic properties of maxillary sinus membrane stem cells (MSMSCs).
Methods :
Beagle maxillary sinus mucosa was collected, immunomagnetic bead method was applied for isolation of CD146+ cells, and MSMSCs were harvested and cultured from the canine maxillary sinus floor mucosa. The levels of the cell surface antigens CD44, CD146, and CD34 were determined at passage one by flow cytometry. Cells at passage one were cultured in basal medium and osteogenic inductive medium. Real-time PCR, immunohistochemical staining, alkaline phosphatase activity, alizarin red staining and Von Kossa staining were used to investigate the osteogenic properties in vitro.
Results:
The canine MSMSCs were cultured successfully. The results of flow cytometry were positive for CD146 and CD44 expression but negative for CD34 expression. The relative mRNA expression of runt-related transcription factor 2 (RUNX2) (t = 14.44,P < 0.001), osteopontin (OPN) (t = 7.85,P = 0.001) and alkaline phosphatase alkaline phosphatase (t = 14.27,P < 0.001) was apparently higher in the osteoinductive medium group than in the basal medium group, the differences in relative mRNA expression between the groups were significant. The protein levels of RUNX2 and OPN increased in the osteoinductive medium group. The alkaline phosphatase activity of the MSMSCs increased when the cells were cultured in osteoinductive medium; the activity increased to a level that was significantly higher than that in basal medium, particularly at days 3 (t = 8.79, P < 0.001), 7 (t = 9.75,P < 0.001), 14 (t = 12.14,P < 0.001), 21 (t = 19.62,P < 0.001) and 28 (t = 17.53,P < 0.001). Obvious mineralized nodules were observed by alizarin red staining or Von Kossa staining.
Conclusion
Maxillary sinus membrane stem cells exhibit osteogenic ability.


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