1.The Role of NEAT1 in Bone and Cartilage Metabolism and Bone Diseases
Rui-Ming WEN ; Rui-Qi HUANG ; Yi-Xing CHANG ; Ke XU ; Xue-Jie YI
Progress in Biochemistry and Biophysics 2025;52(4):930-945
In the process of maintaining the steady state of bone tissue, the transcription network and signal pathway of the body play a vital role. These complex regulatory mechanisms need precise coordination to ensure the balance between bone formation and bone absorption. Once this balance is broken, it may lead to pathological changes of bone and cartilage, and then lead to various bone diseases. Therefore, it is of great significance to understand these regulatory mechanisms for the prevention and treatment of bone diseases. In recent years, with the deepening of research, more and more lncRNA has been found to be closely related to bone health. Among them, nuclear paraspeckle assembly transcript 1 (NEAT1), as an extremely abundant RNA molecule in mammalian nuclei, has attracted extensive attention. NEAT1 is mainly transcribed from a specific site in human chromosome 11 by RNA polymerase II (RNaseP), which can form two different subtypes NEAT1_1 and NEAT1_2. These two subtypes are different in intracellular distribution and function, but they participate in many biological processes together. Studies have shown that NEAT1 plays a specific role in the process of cell growth and stress response. For example, it can regulate the development of osteoblasts (OB), osteoclasts (OC) and chondrocytes by balancing the differentiation of bone marrow mesenchymal stem cells (BMSCs), thus maintaining the steady state of bone metabolism. This discovery reveals the important role of NEAT1 in bone development and remodeling. In addition, NEAT1 is closely related to a variety of bone diseases. In patients with bone diseases such as osteoporosis (OP), osteoarthritis (OA) and osteosarcoma (OS), the expression level of NEAT1 is different. These differential expressions may be closely related to the pathogenesis and progression of bone diseases. By regulating the level of NEAT1, it can affect a variety of signal transduction pathways, and then affect the development of bone diseases. For example, some studies show that by regulating the expression level of NEAT1, the activity of osteoclasts can be inhibited, and the proliferation and differentiation of osteoblasts can be promoted, thus improving the symptoms of osteoporosis. It is worth noting that NEAT1 can also be used as a key sensor for the prevention and treatment of bone diseases. When exercising or receiving some natural products, the expression level of NEAT1 will change, thus reflecting the response of bones to external stimuli. This feature makes NEAT1 an important target for studying the prevention and treatment strategies of bone diseases. However, although the role of NEAT1 in bone biology and bone diseases has been initially recognized, its specific mechanism and regulatory relationship are still controversial. For example, the expression level, mode of action and interaction with other molecules of NEAT1 in different bone diseases still need further in-depth study. This paper reviews the role of NEAT1 in maintaining bone and cartilage metabolism, and discusses its expression and function in various bone diseases. By combing the existing research results and controversial points, this paper aims to provide new perspectives and ideas for the prevention and treatment of bone diseases, and provide useful reference and enlightenment for future research.
2.Adolescent Smoking Addiction Diagnosis Based on TI-GNN
Xu-Wen WANG ; Da-Hua YU ; Ting XUE ; Xiao-Jiao LI ; Zhen-Zhen MAI ; Fang DONG ; Yu-Xin MA ; Juan WANG ; Kai YUAN
Progress in Biochemistry and Biophysics 2025;52(9):2393-2405
ObjectiveTobacco-related diseases remain one of the leading preventable public health challenges worldwide and are among the primary causes of premature death. In recent years, accumulating evidence has supported the classification of nicotine addiction as a chronic brain disease, profoundly affecting both brain structure and function. Despite the urgency, effective diagnostic methods for smoking addiction remain lacking, posing significant challenges for early intervention and treatment. To address this issue and gain deeper insights into the neural mechanisms underlying nicotine dependence, this study proposes a novel graph neural network framework, termed TI-GNN. This model leverages functional magnetic resonance imaging (fMRI) data to identify complex and subtle abnormalities in brain connectivity patterns associated with smoking addiction. MethodsThe study utilizes fMRI data to construct functional connectivity matrices that represent interaction patterns among brain regions. These matrices are interpreted as graphs, where brain regions are nodes and the strength of functional connectivity between them serves as edges. The proposed TI-GNN model integrates a Transformer module to effectively capture global interactions across the entire brain network, enabling a comprehensive understanding of high-level connectivity patterns. Additionally, a spatial attention mechanism is employed to selectively focus on informative inter-regional connections while filtering out irrelevant or noisy features. This design enhances the model’s ability to learn meaningful neural representations crucial for classification tasks. A key innovation of TI-GNN lies in its built-in causal interpretation module, which aims to infer directional and potentially causal relationships among brain regions. This not only improves predictive performance but also enhances model interpretability—an essential attribute for clinical applications. The identification of causal links provides valuable insights into the neuropathological basis of addiction and contributes to the development of biologically plausible and trustworthy diagnostic tools. ResultsExperimental results demonstrate that the TI-GNN model achieves superior classification performance on the smoking addiction dataset, outperforming several state-of-the-art baseline models. Specifically, TI-GNN attains an accuracy of 0.91, an F1-score of 0.91, and a Matthews correlation coefficient (MCC) of 0.83, indicating strong robustness and reliability. Beyond performance metrics, TI-GNN identifies critical abnormal connectivity patterns in several brain regions implicated in addiction. Notably, it highlights dysregulations in the amygdala and the anterior cingulate cortex, consistent with prior clinical and neuroimaging findings. These regions are well known for their roles in emotional regulation, reward processing, and impulse control—functions that are frequently disrupted in nicotine dependence. ConclusionThe TI-GNN framework offers a powerful and interpretable tool for the objective diagnosis of smoking addiction. By integrating advanced graph learning techniques with causal inference capabilities, the model not only achieves high diagnostic accuracy but also elucidates the neurobiological underpinnings of addiction. The identification of specific abnormal brain networks and their causal interactions deepens our understanding of addiction pathophysiology and lays the groundwork for developing targeted intervention strategies and personalized treatment approaches in the future.
3. Analysis of cerebral gray matter structure in multiple sclerosis and neuromyelitis optica
Xiao-Li LIU ; Ai-Xue WU ; Ru-Hua LI ; An-Ting WU ; Cheng-Chun CHEN ; Lin XU ; Cai-Yun WEN ; Dai-Qian CHEN
Acta Anatomica Sinica 2024;55(1):17-24
Objective The volume and cortical thickness of gray matter in patients with multiple sclerosis (MS) and neuromyelitis optica (NMO) were compared and analyzed by voxel⁃based morphometry (VBM) and surface⁃based morphometry (SBM), and the differences in the structural changes of gray matter in the two diseases were discussed. Methods A total of 21 MS patients, 16 NMO patients and 19 healthy controls were scanned by routine MRI sequence. The data were processed and analyzed by VBM and SBM method based on the statistical parameter tool SPM12 of Matlab2014a platform and the small tool CAT12 under SPM12. Results Compared with the normal control group (NC), after Gaussian random field (GRF) correction, the gray matter volume in MS group was significantly reduced in left superior occipital, left cuneus, left calcarine, left precuneus, left postcentral, left central paracentral lobule, right cuneus, left middle frontal, left superior frontal and left superior medial frontal (P<0. 05). After family wise error (FWE) correction, the thickness of left paracentral, left superiorfrontal and left precuneus cortex in MS group was significantly reduced (P<0. 05). Compared with the NC group, after GRF correction, the gray matter volume in the left postcentral, left precentral, left inferior parietal, right precentral and right middle frontal in NMO group was significantly increased (P<0. 05). In NMO group, the volume of gray matter in left middle occipital, left superior occipital, left inferior temporal, right middle occipital, left superior frontal orbital, right middle cingulum, left anterior cingulum, right angular and left precuneus were significantly decreased (P<0. 05). Brain regions showed no significant differences in cortical thickness between NMO groups after FWE correction. Compared with the NMO group, after GRF correction, the gray matter volume in the right fusiform and right middle frontal in MS group was increased significantly(P<0. 05). In MS group, the gray matter volume of left thalamus, left pallidum, left precentral, left middle frontal, left middle temporal, right pallidum, left inferior parietal and right superior parietal were significantly decreased (P<0. 05). After FWE correction, the thickness of left inferiorparietal, left superiorparietal, left supramarginal, left paracentral, left superiorfrontal and left precuneus cortex in MS group decreased significantly (P<0. 05). Conclusion The atrophy of brain gray matter structure in MS patients mainly involves the left parietal region, while NMO patients are not sensitive to the change of brain gray matter structure. The significant difference in brain gray matter volume between MS patients and NMO patients is mainly located in the deep cerebral nucleus mass.
4.Study on the Effect of Liuwei Dihuang Pills on Regulating the Antigen Cross-Presenting Ability of Dendritic Cells by Interfering with Gap Junctional Communication Function
Yue SONG ; Man-Si XU ; Xue-Ying ZHONG ; Wen-Jing ZHANG ; Xiao-Yi CHEN ; Biao-Yan DU ; Jian-Yong XIAO ; Kun WANG
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(1):169-177
Objective To investigate whether Liuwei Dihuang Pills enhances the antigen cross-presenting ability of dendritic cell(DC)by increasing gap junctional intercellular communication(GJIC),and to explore the mechanisms involved.Methods Western Blot and immunofluorescence were used to observe the effects of Liuwei Dihuang Pills-containing serum on the expression and membrane localisation of gap junction protein connexin43(Cx43)in mouse melanoma cells(B16);Calcein-AM/DiI fluorescence tracer assay was used to observe the effects of Liuwei Dihuang Pills-containing serum on the function of GJIC in B16 cells;flow cytometry was used to observe the role of GJIC in the enhancement of DC antigen presenting ability by Liuwei Dihuang Pills-containing serum;and propidium iodide(PI)/Hoechst staining assay was used to observe the immunocidal effect of CD8+ T-lymphocytes.Results Western Blot and immunofluorescence experiments showed that Liuwei Dihuang Pills-containing serum led to the up-regulation of Cx43 expression;fluorescence tracer experiments proved that the GJIC function of B16 cells was significantly enhanced by Liuwei Dihuang Pills-containing serum;flow cytometry analyses showed that the DC antigen-presenting ability was enhanced by Liuwei Dihuang Pills-containing serum;and the results of PI/Hoechst staining showed that the immuno-killing effect of CD8+T-cells was more significant after the intervention of Liuwei Dihuang Pills-containing serum in B16-OVA.Conclusion Liuwei Dihuang Pills improve the GJIC function by up-regulating the Cx43 expression of melanoma cells,and then enhance the cross-presenting ability of DCs thus activating stronger CD8+ T-cell immunocidal responses.
5.BMP7 overexpression lentiviral vector construction and its effect on calcification of mouse aortic smooth muscle cells
Shi-Lin FU ; Xue-Jiao YI ; Wen-Xu PAN ; Chun YIN ; Hua-Li KANG ; De-Hui QIAN
Journal of Regional Anatomy and Operative Surgery 2024;33(2):95-99
Objective To construct a lentiviral vector for overexpression of bone morphogenetic protein 7(BMP7)in mice,and the effect of BMP7 overexpression on the expression of Jagged1 in mouse aortic endothelial cells and the calcification of the co-cultured vascular smooth muscle cells(VSMCs)were analyzed.Methods According to the target gene information Mouse-BMP7(NM_007557.3)and plasmid information pLVX-zsGreen-C1,gene sequence synthesis was carried out to construct BMP7 overexpression lentivirus.The efficiency of BMP7 overexpression lentivirus infection was detected by qPCR;the expression of Jagged1 protein in aortic endothelial cells from infected mice was detected by Western blot.The endothelial cells with lentivirus overexpressing BMP7 were co-cultured with VSMCs,and the calcification of VSMCs was observed by alizarin red staining.Results BMP7 overexpression lentiviral vector was successfully constructed and transfected into aortic endothelial cells.qPCR test results showed that the expression level of BMP7 mRNA was significantly increased in the BMP7 overexpression group than that in the normal control group(P<0.01),while there was no significant difference in the expression of BMP7 mRNA between the empty vector control group and the normal control group(P>0.05).Western blot results showed that the expression level of Jagged1 protein in endothelial cells of mouse in the BMP7 overexpression group was significantly lower than that in the normal control group(P<0.01),while there was no significant difference in the expression level of Jagged1 protein in endothelial cells between the empty vector control group and the normal control group(P>0.05).The results of alizarin red staining showed that the calcification of VSMCs was significantly increased after co-cultured with endothelial cells infected with BMP7 lentivirus.Conclusion Mouse BMP7 overexpression lentiviral vector was successfully constructed,and overexpression of BMP7 can reduce the expression of Jagged1 in mouse aortic endothelial cells and promote the calcification of co-cultured VSMCs.
6.Analysis of obesity factors among public primary school students in a town, Minhang District, Shanghai
Danhong MO ; Weizhong ZHAO ; Duojun XU ; Bing LI ; Xiaosa WEN ; Qi ZHAO ; Wenhao XUE
Shanghai Journal of Preventive Medicine 2024;36(1):84-89
ObjectiveTo identify and analyze the possible influencing factors of obesity among public primary school students in Minhang District, Shanghai. MethodsBasic data, collected through questionnaire stars, was imported with merged physical examination data into Excel to form a database. Data were collected by questionnaire and analyzed by SPSS 22.00. Independent sample t-test was used for the data with normal distribution. Nonparametric test was used for the data with non-normal distribution. χ2 test was used for the quantitative data. Logistic regression was used for univariate and multivariate analysis
7.Wnt/β-catenin Signaling Cascades in Cardiovascular Diseases
Yan-Fei QI ; Yan-Ping LIU ; Wen-Qing XU ; Xiao-Xue YAN
Progress in Biochemistry and Biophysics 2024;51(10):2328-2339
Cardiovascular diseases are a group of disorders of the heart and blood vessels, primarily including coronary heart disease, stroke, and other diseases. It is the world’s leading cause of death, and its incidence is increasing yearly. Hypertension is a major risk factor for cardiovascular disease. Wnt signaling comprises a series of highly conservative cascading events controlling fundamental biological processes. Wnt signaling pathways include the canonical Wnt pathway (or Wnt/β-catenin pathway), the non-canonical planar cell-polarity pathway, and the non-canonical calcium-dependent pathways. Abnormal Wnt signaling promotes cell proliferation and differentiation, cardiac malformations, various malignancies, so drugs targeting Wnt signaling play a great therapeutic potential. Wnt/β‑catenin pathway is involved in the occurrence and development of cardiovascular diseases such as atherosclerosis and stroke by regulating cell proliferation, migration, apoptosis, blood-brain barrier permeability, inflammation, oxidative stress, and immune response. Based on the latest research progress, this review summarizes the role of Wnt/β‑catenin signaling in cardiovascular diseases, in order to provide new ideas for the prevention and treatment of cardiovascular diseases.
8.Clinical trial of sodium hyaluronate combined with recombinant human epidermal growth factor in the treatment of patients with dry eye after cataract operation
Jing-Sen QIU ; Xin-Hua WANG ; Wen-Chao DONG ; Wan-Li DIAO ; Xue-Jun XU
The Chinese Journal of Clinical Pharmacology 2024;40(18):2621-2625
Objective To evaluate the effect of sodium hyaluronate combined with recombinant human epidermal growth factor(rhEGF)in the treatment of dry eye after cataract surgery.Methods Patients with dry eye after cataract surgery were divided into treatment group and control group.The control group was treated with sodium hyaluronate eye drops via dropping into the conjunctival sac,a drop per dose,tid,for 4 weeks.On this basis,the treatment group was treated with rhEGF eye drops via dropping into the conjunctival sac,1-2 drops per dose,tid,for 4 weeks.The two groups were compared on overall clinical efficacy,dry eye symptoms before treatment and after 4 weeks of treatment.Tear-film breakup time(BUT),basic tear secretion test(schirmer Ⅰ test,SⅠT),corneal fluorescein staining(CFS)score,meibomian gland yield secretion score(MGYSS),and the levels of tear inflammatory factors were compared between two groups before treatment and after 4 weeks of treatment.The safety was evaluated.Results Finally,41 cases and 39 cases were included in the treatment group and the control group,respectively.After treatment,the total effective rates in the treatment group and the control group were 95.12%and 79.49%,with statistically significant difference(P<0.05).After 4 weeks of treatment,dry eye symptom scores of the treatment group and control group were 1.42±0.18 and 2.31±0.26;BUT were(11.89±1.26)and(10.46±1.27)s;SⅠT were(10.12±1.35)and(8.45±0.87)mm;CFS scores were 0.83±0.11 and 1.94±0.25;MGYSS scores were 10.85±1.17 and 12.43±1.56;interleukin-1β levels in tears were(35.26±3.53)and(74.12±7.55)ng·L-1;interleukin-6 levels were(8.35±0.86)and(12.41±12.56)pg·mL-1.Compared with the control group,the above indexes in the treatment group were statistically significant(all P<0.05).The incidence rates of adverse drug reactions in the treatment group and the control group were 12.20%and 10.26%,without statistically significant difference between the groups(P>0.05).Conclusion Sodium hyaluronate combined with rhEGF can significantly improve dry eye symptoms after cataract surgery,enhance the stability of tear film,reduce tear inflammatory factors,and protect the integrity of meibomian gland.
9.Association of Cytokines with Clinical Indicators in Patients with Drug-Induced Liver Injury
Hua Wei CAO ; Ting Ting JIANG ; Ge SHEN ; Wen DENG ; Yu Shi WANG ; Yu Zi ZHANG ; Xin Xin LI ; Yao LU ; Lu ZHANG ; Yu Ru LIU ; Min CHANG ; Ling Shu WU ; Jiao Yuan GAO ; Xiao Hong HAO ; Xue Xiao CHEN ; Ping Lei HU ; Jiao Meng XU ; Wei YI ; Yao XIE ; Hui Ming LI
Biomedical and Environmental Sciences 2024;37(5):494-502
Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.
10.The correlation between cytokines and arginine metabolism in bronchoalveolar lavage fluid of aged mice infected with the influenza A virus
Juanjuan ZHOU ; Shiyang LIU ; Xue LI ; Xinxin YANG ; Junlian YANG ; Shengdong LUO ; Weiwei CHEN ; Wen XU ; Fusheng WANG
Chinese Journal of Experimental and Clinical Virology 2024;38(4):422-431
Objective:To explore the role of arginine metabolism in the inflammatory response to influenza A virus (FluA) infection.Methods:Eighteen-month-old mice were infected with FluA via nasal drip, with samples collected on the 6th day post-infection. The concentration of cytokines was determined by the Luminex multifactor assay, while the metabolites in bronchoalveolar lavage fluid (BALF) were analyzed using targeted metabolomic method. Correlation analysis was employed to examine the correlation between cytokines and metabolites. Macrophages were infected with FluA at a multiplicity of infection (MOI) of 1 and cultured with different concentrations of arginine for 24 h. The mRNA and protein expression levels of interleukin (IL)-1β, IL-6, tumor necrosis factor α (TNF-α) and IL-10 were detected by real time fluorescence quantitative RT-PCR (qRT-PCR) and Cytometric Bead Array (CBA).Results:In comparison to the control group, the levels of surfactant protein D (SP-D), TNF-α, monocyte chemotactic protein-1 (MCP-1), IL-1α, IL-6, IL-10, recombinant S100 calcium binding protein (S100) A9, interferon inducible protein 10 (IP-10), macrophage inflammatory protein-1α (MIP-1α), matrix metalloprotein-9 (MMP-9), and Complement Factor D in BALF of FluA infection exhibited a significant elevation. The concentrations of arginine, aspartate, citrulline, glutamic acid, ornithine, proline, creatine, and sarcosine in arginine metabolism were up-regulated, which was correlated with most of elevated cytokine levels. The supplementation of arginine after FluA infection significantly decreased the levels of IL-1β, IL-6, and TNF-α, but increased the level of IL-10 in macrophages.Conclusions:Arginine reduces the inflammatory response induced by FluA infection in macrophages, suggesting that it may be a potential intervention target for severe pulmonary inflammation following FluA infection.

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