1.Hydrogels:role and problems in the repair of oral and maxillofacial defects
Zhixin WU ; Wenwen JIANG ; Jianhui ZHAN ; Yangshurun LI ; Wenyan REN ; Yiyu WANG
Chinese Journal of Tissue Engineering Research 2025;29(10):2178-2188
BACKGROUND:Hydrogels have become a research hotspot due to their unique advantages in the biomedical field due to their superior mechanical and biological properties.At present,related research involves tissue engineering,wound dressing and so on. OBJECTIVE:To review the advantages and properties of hydrogels and the research progress of their application in the repair of oral and maxillofacial defects,discuss the current limitations and challenges of hydrogels in application and promotion,and provide new ideas for future research directions. METHODS:Relevant literature was searched in PubMed,CNKI,and WanFang database by computer.The search terms were"hydrogel,oral and maxillofacial defects,mechanical properties,tissue engineering,wound dressing"in Chinese and"hydrogel,oral and maxillofacial defects,mechanical properties,guided tissue regeneration,wound dressing"in English.Preliminary screening was carried out by reading titles and abstracts,and articles not related to the topic of the article were excluded.According to the inclusion and exclusion criteria,108 articles were finally included for the result analysis. RESULTS AND CONCLUSION:(1)The hydrogel has good biological activity,mechanical controllability,and stimulation response.(2)Polymer,metal,and ceramic hydrogel composites have appropriate mechanical properties,biodegradability,and controlled release rate,which are suitable for maxillofacial bone tissue engineering.(3)Fibrin-based hydrogel could fill the hollow nerve conduit through the nerve defect area and promote the regeneration and growth of axons to restore the function of maxillofacial nerve.(4)Controlling the interaction between nanomaterials and hydrogels can improve the formation of muscle fiber oriented structure to promote maxillofacial muscle tissue regeneration.(5)Polysaccharide hydrogel has gradually become the first choice for repairing irregular periodontal defects due to its ability to control drug delivery,carry bioactive molecules,and combine with other materials to produce the best scaffold matching the extracellular matrix.(6)Calcium phosphate or calcium carbonate-based hydrogels can be used to fill irregular or fine tissue defects and remineralize hard tissues.The self-assembled hydrogels are simple to prepare and have good biological activity.(7)Salivary gland-derived extracellular matrix-like gel is expected to participate in the treatment of many salivary gland diseases.(8)Hydrogels can be used as wound dressings in combination with biological adhesives,acellular biomaterials,antimicrobials,antioxidants,or stem cells to treat various wounds.(9)Fibrin-based hydrogel has the most potential in the repair of oral and maxillofacial defects.It has excellent biocompatibility,flexibility,and plasticity.It can combine with cells,extracellular matrix proteins,and various growth factors,and promote the osteogenic differentiation of mesenchymal stem cells,axon regeneration and growth,angiogenesis,myotube differentiation,salivary gland tissue regeneration,and periodontal tissue regeneration.It has a broad prospect in the repair of oral and maxillofacial defects.However,its therapeutic effect depends on the function of the substance carried.The complex preparation process,its safety and long-term efficacy,and the special anatomical oral and maxillofacial structure is the problem that hinders its promotion,which also provides directions for future research.
2.Inhibitory Effects of the Slit Guidance Ligand 1-3’ Untranslated Region on the Fibrotic Phenotype of Cardiac Fibroblasts
Ya WANG ; Huayan WU ; Yuan GAO ; Rushi WU ; Peiying GUAN ; Hui LI ; Juntao FANG ; Zhixin SHAN
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(3):466-474
ObjectiveTo study the regulatory effect of the partial sequence within the 3’ untranslated region (3’UTR) of slit guidance ligand 1 (Slit1) (Slit1-3’UTR) on the fibrotic phenotypes of cardiac fibroblasts (CFs) and its potential mechanism. MethodsThe adenovirus vector was used to overexpress the 1526nt sequence of Slit1-3’UTR in ICR neonatal mouse CFs (mCFs). The expression of fibrosis-related genes in mCFs, such as collagen type 1 alpha1(COL1A1), collagen type 3 alpha3 (COL3A1) and alpha smooth muscle actin (α-SMA) were detected by Western blot assay. The effect of Slit1-3’UTR 1526nt on the proliferation and migration of mCFs was assessed by EdU staining and Trans-well assays. Angiotensin Ⅱ (Ang Ⅱ) was used to treat mCFs, and the impact of Slit1-3’UTR 1526nt on the fibrotic phenotypes of Ang Ⅱ-induced mCFs was evaluated. After overexpression of Slit1-3’UTR 1526nt, miR-34a-5p mimic was transfected into mCFs, followed by actinomycin D treatment to detect the mRNA stability of Slit1-3’UTR 1526nt, and the levels of miR-34a-5p and its target gene SIRT1(si-SIRT1) in mCFs were determined. The effects of miR-34a-5p and small interfering RNA targeting SIRT1 on the Slit1-3’UTR 1526nt-mediated regulation of fibrotic phenotypes were also determined. ResultsAdenovirus-mediated overexpression of Slit 1-3’UTR 1526nt was achieved in mCFs. Overexpression of Slit 1-3’UTR 1526nt markedly inhibited the expression of the fibrosis-related genes, proliferation and migration of mCFs and fibrotic phenotypes of Ang Ⅱ. The results of actinomycin D assay showed that miR-34a-5p inhibited the stability of Slit1-3’UTR 1526nt in mCFs, while the level of miR-34a-5p was reduced in mCFs with overexpression of Slit1-3’UTR 1526nt. Transfection of miR-34a-5p promoted the fibrotic phenotypes, and reversed the inhibitory effect of Slit1-3’UTR 1526nt on the fibrotic phenotypes of mCFs. Overexpression of Slit1-3’UTR 1526nt significantly increased the level of miR-34a-5p target gene SIRT1 in mCFs. Transfection of miR-34a-5p and si-SIRT1 consistently reversed the inhibitory effects of Slit1-3’UTR 1526nt on the fibrotic phenotypes of mCFs. ConclusionSlit1-3’UTR1526nt inhibits the fibrotic phenotypes of mCFs by binding to miR-34a-5p and increasing the expression of its target gene of SIRT1.
3.IDH3A Inhibits Cardiomyocyte Hypertrophy via Elevating α-Ketoglutarate Level
Huayan WU ; Yihong WEN ; Hengli ZHAO ; Yuan GAO ; Chuanmeng ZHOU ; Ya WANG ; Jiening ZHU ; Zhixin SHAN
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(2):275-283
ObjectiveTo investigate the regulatory effect and potential mechanisms of isocitrate dehydrogenase 3A (IDH3A) on cardiomyocyte hypertrophy. MethodsThe expression of IDH3A in the myocardium of healthy volunteers (n=10) and patients with heart failure (HF) (n=10), and in the myocardium of mice subjected to transverse aortic constriction (TAC) surgery and sham operation, as well as in phenylephrine (PE)-induced neonatal rat ventricular cardiomyocytes (NRVCs), was assessed by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot assay. The effect of adenovirus-mediated overexpression of IDH3A on the expression of hypertrophy-related genes in PE-induced NRVCs was also evaluated. The effect of IDH3A on NRVCs area was examined by phalloidin staining assay. A mutant of IDH3A with abolished enzymatic activity, IDH3A_D208A, was generated through site-directed mutagenesis. The impact of this IDH3A mutant on the hypertrophic phenotype, ATP and ROS levels in NRVCs was evaluated to investigate whether the regulatory role of IDH3A in cardiomyocyte hypertrophy was dependent on its enzymatic activity. The effect of exogenous α-ketoglutaric acid (AKG) on cardiomyocyte hypertrophy was also detected by Western blot and phalloidin staining assay, respectively. ResultsIDH3A was significantly decreased in the myocardium of HF patients, in the myocardium of TAC-operated mice, and in PE-induced NRVCs (P = 0.005 2,P = 0.026 6,P = 0.041 3 and P = 0.006 6, respectively). Overexpression of IDH3A markedly suppressed the expression of hypertrophy-related genes and the increase of cell size of PE-induced NRVCs (P < 0.000 1, P = 0.000 1 and P = 0.000 2, respectively). The ATP and ROS analysis indicated that IDH3A inhibited the increases of ATP and ROS levels in PE-induced NRVCs (P = 0.001 2 and P<0.000 1, respectively), whereas the enzymatically inactive IDH3A mutant lacked this effect. Exogenous AKG provision could, but overexpression of IDH3A mutant failed to suppress PE-induced NRVCs hypertrophy. ConclusionIDH3A inhibits cardiomyocyte hypertrophy via elevating AKG level, providing scientific evidence for study on IDH3A-based treatment of cardiac hypertrophy.
4.Research progress on the treatment of ischemia-reperfusion injury with human umbilical cord mesenchymal stem cells and their derivatives
Ru NIE ; Yunlong DUAN ; Mingquan PANG ; Zhixin WANG ; Haining FAN
Organ Transplantation 2025;16(4):516-525
Ischemia-reperfusion injury (IRI) can lead to organ dysfunction and tissue necrosis in the liver, kidney, myocardium and spinal cord, and there is currently a lack of effective treatment options. Human umbilical cord mesenchymal stem cell (HUC-MSC) and their derivatives have anti-inflammatory, anti-apoptotic, reactive oxygen species scavenging, mitochondrial and endothelial function improvement properties, and are ideal gene therapy carrier cells, providing new possibilities for the treatment of IRI in different organs. This article reviews the concept and mechanisms of IRI, the biological characteristics of HUC-MSC and their derivatives and their comparison with mesenchymal stem cells from other sources, and the mechanisms of HUC-MSC in treating IRI in different organs. It also summarizes and analyzes the advantages and disadvantages of HUC-MSC in protecting different organs from IRI, and prospects future research directions to explore more valuable research paths.
5.Efficacy and Safety of Acupuncture Combined with Levodopa in the Treatment of Parkinson's Disease: A Randomized Controlled Trial
Jingyun ZHU ; Xiyan GAO ; Linlin WANG ; Zhixin REN ; Guiling WANG ; Jing GUO ; Yanrong WU
Journal of Traditional Chinese Medicine 2025;66(14):1456-1462
ObjectiveTo evaluate the clinical efficacy and safety of acupuncture combined with levodopa in the treatment of Parkinson's disease(PD). MethodsA total of 60 patients with PD were enrolled and randomly assigned to test group or control group, with 30 patients in each group. The control group received levodopa only, starting at 100 mg per dose, three times daily, with gradual increases not exceeding a maximum daily dose of 800 mg. The test group received acupuncture three times per week in addition to levodopa. Both groups were treated for 12 weeks. Assessments were conducted before treatment, after 6 and 12 weeks treatment, using the Unified Parkinson's Disease Rating Scale(UPDRS), Wearing-Off Questionnaire-9(WOQ-9), Montreal Cognitive Assessment(MoCA), Mini-Mental State Examination(MMSE), Depression Rating Scale(DRS), Hamilton Depression Scale(HAMD), Hamilton Anxiety Scale(HAMA), PD Questionnaire-39(PDQ-39), and Pittsburgh Sleep Quality Index(PSQI). Repeated measures ANOVA was utilized to evaluate the effects of time, group, and their interaction on each index. Spearman correlation analysis was conducted to examine the relationships between combined treatment and outcome scores. Adverse events in both groups were recorded throughout the study. ResultsBoth groups showed significant improvements after 6 and 12 weeks treatment, with decreases in UPDRS total score, WOQ-9 total score, DRS score, HAMD score, HAMA score, PDQ-39 score, and PSQI score, and increases in MoCA and MMSE scores(P<0.05). Compared with the control group, the test group demonstrated significantly greater improvements in all the above indicators after 6 and 12 weeks (P<0.05). Repeated measures ANOVA showed significant time main effects, group main effects, and their interaction across all outcome measures(P<0.01). Spearman correlation analysis revealed that combined therapy was significantly negatively correlated with UPDRS, WOQ-9, DRS, HAMD, HAMA, PDQ-39, and PSQI scores, while positively correlated with MoCA and MMSE scores after 12 weeks of treatment(P<0.05). Both groups did not experience any serious adverse events and did not affect treatment. ConclusionAcupuncture combined with levodopa is more effective than levodopa alone in improving motor function, non-motor symptoms, cognitive function, depression and anxiety, quality of life, and sleep quality in patients with PD, with good safety.
6.Research progress of Faricimab in the treatment of macular edema associated with retinal vascular diseases
Xinyi HOU ; Haoran WANG ; Chunhua DAI ; Jing ZHANG ; Meng XIN ; Zhixin GUAN ; Shu LIU
International Eye Science 2025;25(8):1267-1273
Intravitreal injection of anti-vascular endothelial growth factor(VEGF)agents has become the primary treatment for macular edema associated with retinal vascular disease such as diabetic retinopathy and retinal vein occlusion, but there are limitations such as variable treatment efficacy and insufficient durability of therapeutic effects. As the first bispecific antibody applied in ophthalmic treatment, Faricimab achieves favorable outcomes by simultaneously targeting both VEGF-A and angiopoietin-2(Ang-2)pathways. Based on evidence from recent clinical trials and real-world studies, this article reviews the research progress on Faricimab for the treatment of diabetic macular edema(DME), retinal vein occlusion-associated macular edema(RVO-ME)and refractory macular edema compared to the therapeutic effects of other agents. Additionally, based on Faricimab's safety characteristics and future potential, its therapeutic prospects for macular edema associated with retinal vascular diseases are discussed. This review aims to provide evidence-based references for optimizing clinical treatment strategies, thereby contributing to mitigating the risk of vision loss due to macular edema.
7.Characteristics of gut microbiota determine effects of specific probiotics strains in patients with functional constipation.
Haohao ZHANG ; Lijuan SUN ; Zhixin ZHAO ; Yao ZHOU ; Yuyao LIU ; Nannan ZHANG ; Junya YAN ; Shibo WANG ; Renlong LI ; Jing ZHANG ; Xueying WANG ; Wenjiao LI ; Yan PAN ; Meixia WANG ; Bing LUO ; Mengbin LI ; Zhihong SUN ; Yongxiang ZHAO ; Yongzhan NIE
Chinese Medical Journal 2024;137(1):120-122
8.Current status of ex vivo liver resection and autotransplantation in treatment of benign liver lesions
Shuai ZHANG ; Fazhu FEI ; Zhixin WANG ; Haining FAN ; Haijiu WANG ; Lizhao HOU
Journal of Clinical Hepatology 2024;40(12):2543-2547
Benign liver lesions mainly include hepatic hemangioma, focal nodular hyperplasia of the liver, hepatocellular adenoma, and hepatic angiomyolipoma. Hepatic alveolar echinococcosis is a type of parasitic disease, and since it mainly occurs in the liver, it is also a benign lesion of the liver. The clinical treatment of benign liver lesions is mainly based on follow-up observation, supplemented by surgical resection. For patients with end-stage diseases, liver transplantation can be performed due to the large volume of the lesion, the invasion of a number of surrounding large vessels, unclear anatomic location, and the possibility of intraoperative rupture and massive hemorrhage. Since patients with poor liver function based on the liver allocation score for organ donation are more likely to get donor liver, it is difficult for patients with benign liver lesions to obtain the corresponding donor liver resources due to the growth pattern of benign liver lesions, thereby leading to the limited application of allogeneic liver transplantation. Since its emergence in the 1980s, ex vivo liver resection and autotransplantation (ELRA) has brought a new way for the treatment of such patients. This article summarizes the current application of ELRA in benign liver lesions, in order to provide a reference for diagnosis and treatment by clinical medical staff.
9.Progress in diagnosis and treatment of hepatic alveolar echinococcosis
Zhixin WANG ; Yunfei LIU ; Hao WANG ; Haijiu WANG ; Haining FAN
Organ Transplantation 2024;15(2):171-177
Hepatic echinococcosis is a chronic parasitic disease, which is caused by the larvae of Echinococcus multilocularis. It has a high risk of disability and mortality, which is also known as "parasite cancer". In clinical practice, hepatic echinococcosis can be divided into hepatic alveolar echinococcosis and hepatic cystic echinococcosis. Hepatic echinococcosis is widely prevalent worldwide. It mainly occurs in the populations residing agricultural and pastoral areas in western China, posing significant threats to the quality of life of local residents. At present, surgery is the main treatment for hepatic echinococcosis in clinical settings. With rapid development of surgical diagnosis and treatment technology and deepening understanding of hepatic echinococcosis, diagnosis and treatment regimens have also been constantly improved. In this article, research progresses on the diagnosis and treatment of hepatic alveolar echinococcosis were reviewed, aiming to provide reference for clinicians, deliver early diagnosis and treatment, mitigate adverse effects of this disease upon patients and improve clinical prognosis.
10.Evaluation of Simulated Weightlessness Model of Hindlimb Unloading Miniature Pigs and Their Tissue Damage
Yingxin TU ; Yilan JI ; Fei WANG ; Dongming YANG ; Dongdong WANG ; Zhixin SUN ; Yuexin DAI ; Yanji WANG ; KAN GUANGHAN ; Bin WU ; Deming ZHAO ; Lifeng YANG
Laboratory Animal and Comparative Medicine 2024;44(5):475-486
Objective To establish a weightlessness simulation animal model using miniature pigs, leveraging the characteristic of multiple systems’ tissue structures and functions similar to those of humans, and to observe pathophysiological changes, providing a new method for aerospace research. Methods Nine standard-grade miniature pigs were selected and randomly divided into an experimental group (n=7) and a control group (n=2). The experimental group was fixed using customized metal cages, with canvas slings suspending their hind limbs off the ground, and the body positioned at a -20° angle relative to the ground to simulate unloading for 30 days (24 hours a day). Data on body weight, blood volume, and blood biochemistry indicators were collected at different time points for statistical analysis of basic physiological changes. After the experiment, the miniature pigs were euthanized and tissue samples were collected for histopathological observation of the cardiovascular, skeletal and muscle systems HE and Masson staining. Statistical analysis was also conducted on the thickness of arterial vessels and the diameter of skeletal muscle fibers. Additionally, western blotting was employed to detect the expression levels of skeletal muscle atrophy-related proteins, including muscle-specific RING finger protein 1 (MuRf-1) and muscle atrophy F-box (MAFbx, as known as Atrogin-1), while immunohistochemistry was used to detect the expression of glial fibrillary acidic protein (GFAP), an indicator of astrocyte activation in the brain, reflecting the pathophysiological functional changes across systems. Results After hindlimb unloading, the experimental group showed significant decreases in body weight (P<0.001) and blood volume (P<0.01). During the experiment, hemoglobin, hematocrit, and red blood cell count levels significantly decreased (P<0.05) but gradually recovered. The expression levels of alanine aminotransferase and γ-glutamyltransferase initially decreased (P<0.05) before rebounding, while albumin significantly decreased (P<0.001) and globulin significantly increased (P<0.01). Creatinine significantly decreased (P<0.05). The average diameter of gastrocnemius muscle fibers in the experimental group significantly shortened (P<0.05), with a leftward shift in the distribution of muscle fiber diameters and an increase in small-diameter muscle fibers. Simultaneously, Atrogin-1 expression in the gastrocnemius and paravertebral muscles significantly increased (P<0.05). These changes are generally consistent with the effects of weightlessness on humans and animals in space. Furthermore, degenerative changes were observed in some neurons of the cortical parietal lobe, frontal lobe, and hippocampal regions of the experimental group, with a slight reduction in the number of Purkinje cells in the cerebellar region, and a significant enhancement of GFAP-positive signals in the hippocampal area (P<0.05). Conclusion Miniature pigs subjected to a -20° angle hind limb unloading for 30 days maybe serve as a new animal model for simulating weightlessness, applicable to related aerospace research.

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