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.Clinical significance of digital measurement of occipital condyle and foramen magnum in children
Kun LI ; Zheyuan ZHOU ; Jian WANG ; Yan ZHANG ; Yan ZHAO ; Xuetong HE ; Ke LI ; Simin CHEN ; Xingyu WU ; Xing WANG ; Shaojie ZHANG
Chinese Journal of Tissue Engineering Research 2024;28(18):2830-2834
BACKGROUND:Due to the young age of children,the occipital condyle and foramen magnum are not fully developed,and they are prone to various diseases and injuries in the occipitocervical junction,which requires surgical treatment in severe cases.However,anatomical parameters for the development of the occipital condyle and foramen magnum in children are lacking. OBJECTIVE:To measure the morphological structure of the occipital condyle and foramen magnum by three-dimensional reconstruction technique,and to provide important anatomical parameters for occipitocervical junction lesions,related surgical procedures and forensic identification. METHODS:Imaging data of 389 cases of primitive children and adolescents involved in skull base undergoing spiral CT scanning(247 males and 142 females)aged 1-18 years were collected and divided into 1-3-year-old group,4-6-year-old group,7-9-year-old group,10-12-year-old group,13-15-year-old group,and 16-18-year-old group according to their age.Mimics 16.0 software was used to reconstruct the skull base and measure the length and width of the foramen magnum.A formula was used to calculate the area and index of the foramen magnum.We measured the length,width and height of the occipital condyle,the angle between the long axis and the sagittal axis of the occipital condyle(O-S angle),the included angle between the midpoint of the front and back edges of the foramen magnum and the connection between the back edge of occipital condyle and the intersection point of the foramen magnum(F-O angle),and the included angle between the midpoint of the front and back edges of the foramen magnum and the midpoint of the back wall of the sublingual neural tube(F-H angle).Gender,side and age differences were analyzed among the indicators. RESULTS AND CONCLUSION:(1)In foramen magnum measurement,there was no significant difference between sexes in the index of the foramen magnum(P>0.05),but there were significant differences in length,width and area of the foramen magnum(P<0.05).(2)The O-S angle,F-O angle and F-H angle of the occipitral condyle were not significantly different between genders(P>0.05),but length,width and height of the occipital condyle were significantly different between genders(P<0.05).(3)There were no significant differences in the length of the occipital condyle among different groups(P>0.05),but there were significant differences in the width and height of the occipital condyle,O-S angle,F-O angle and F-H angle among different groups(P<0.05).(4)Length,width and area of the foramen magnum,length,width and height of the occipital condyle showed a wavy increasing trend with the increase of age,while O-S,F-O and F-H angles showed a wavy decreasing trend with the increase of age,while the index of the foramen magnum showed no significant change.(5)In conclusion,there are gender and lateral differences in the morphological indexes of the foramen magnum and the occipital condyle in children.These differences can provide an important reference for clinical surgical approach selection and forensic examination.
3.Neurobiology of N-glycosylation modification and its roles in neurological disorders
Ke-Xing XU ; Meng-Xuan WANG ; Xue-Kun LI
Acta Anatomica Sinica 2024;55(2):241-246
Neurodevelopment and neuronal function are modulated by multiple factors including environment,genetics and epigenetics.As a post-translational modification,N-glycosylation is catalyzed by glycosyltransferase and involves in diverse biological processes.N-glycosylation is abundant in neuronal system,regulates the development and maturation of synapse,and inflammatory response of glial cells.The dysregulation of N-glycosylation induces neurological disorders including Alzheimer's disease,congenital disorders of glycosylation,schizophrenia and epilepsy.In the present review,we have summarized the progresses of N-glycosylation in regulating neuronal and astrocytic function,and its roles in neurological disorders and related mechanisms.
4.Effects of vecuronium bromide down-regulation of lncRNA FGD5-AS1 on the proliferation and apoptosis of gastric cancer cell HGC-27
Bin FU ; Ke ZHANG ; Xing LIU ; Chuan-Xing DAI ; Zu-Qi CHEN ; De-Liang QIU
The Chinese Journal of Clinical Pharmacology 2024;40(2):205-209
Objective To investigate the effect of vecuronium bromide on the malignant biological behavior of gastric cancer cells and its molecular mechanism.Methods Gastric cancer cells HGC-27 were divided into control group,experimental-L,-M,-H groups,si-NC group,si-FGD5-AS1 group,pcDNA-FGD5-AS1 group,pcDNA group,experimental-H+pcDNA group,experimental-H+pcDNA-FGD5-AS1 group.The control group was cultured conventionally;experimental-L,-M,-H groups were treated with 5,10 and 20μmol·mL-1 vecuronium bromide,respectively;si-FGD5-AS1 group and the si-NC group were transfected with lncRNA FGD5-AS1 interference expression vector and negative control plasmid,respectively;pcDNA-FGD5-AS1 group and pcDNA group were transfected with lncRNA FGD5-AS1 overexpression vector and negative control plasmid,respectively;lncRNA FGD5-AS1 overexpression vector and negative control plasmid were transfected into HGC-27 cells in the experimental-H+pcDNA-FGD5-AS1 group and experimental-H+pcDNA group,and then treated with 20 μmuol·mL-1 vecuronium bromide.Methyl thiazolyl tetrazolium(MTT),flow cytometry and real-time fluorescent quantitative polymerase chain reaction(RT-qPCR)were applied to dectect cell viability,apoptosis and lncRNA FGD5-AS1 expression.Results The cell activity of control group,experimental-L,-M,-H groups,si-NC group,si-FGD5-AS1 group,pcDNA group,PCDNA-FGD5-AS1 group,experimental-H+pcDNA group and experimental-H+PCDNA-FGD5-AS1 group were 1.31±0.07,0.58±0.03,1.31±0.06,0.51±0.03,1.29±0.08,1.68±0.15,0.59±0.03 and 1.16±0.06;the apoptosis rates were(6.49±0.44)%,(23.52±0.98)%,(6.42±0.44)%,(26.75±0.97)%,(6.72±0.38)%,(2.56±0.19)%,(23.56±1.04)%and(11.65±0.47)%;the expression levels of lncRNA FGD5-AS1 were 1.00±0.05,0.37±0.02,0.99±0.05,0.21±0.02,1.00±0.03,2.98±0.12,0.38±0.02 and 0.87±0.05,respectively.The above indexes were compared with the control group and experimental-H group,those in the si-FGD5-AS1 group were compared with the si-NC group,those in the pcDNA-FGD5-AS1 group were compared with the pcDNA group,and those in the experimental-H+pcDNA-FGD5-AS1 group were compared with the experimental-H+pcDNA group,the differences were statistically significant(all P<0.05).Conclusion Vecuronium bromide may inhibit the proliferation of HGC-27 cells and promote cell apoptosis by down-regulating lncRNA FGD5-AS1.
5.Research status of quercetin-mediated MAPK signaling pathway in prevention and treatment of osteoporosis
Ke-Xin YUAN ; Xing-Wen XIE ; Ding-Peng LI ; Yi-Sheng JING ; Wei-Wei HUANG ; Xue-Tao WANG ; Hao-Dong YANG ; Wen YAN ; Yong-Wu MA
The Chinese Journal of Clinical Pharmacology 2024;40(9):1375-1379
Quercetin can mediate the activation of mitogen-activated protein kinase(MAPK)signaling pathways to prevent osteoporosis(OP).This paper comprehensively discusses the interrelationship between MAPK and osteoporosis-related cells based on the latest domestic and international research.Additionally,it elucidates the research progress of quercetin in mediating the MAPK signaling pathway for OP prevention.The aim is to provide an effective foundation for the clinical prevention and treatment of OP and the in-depth development of quercetin.
6.Non-bifurcating cervical carotid artery:a case report and literature review
Ke XU ; Haiying XING ; Weiping SUN ; Wei SUN ; Yong'an SUN ; Yining HUANG ; Haiqiang JIN
Chinese Journal of Cerebrovascular Diseases 2024;21(3):184-187
Non-bifurcating cervical carotid artery(NBCCA)is a very rare anatomical variation of the cervical carotid artery,which may be related to the abnormal development of internal carotid artery(ICA)and external carotid artery in embryonic period.Neither carotid bulb nor a true carotid bifurcation can be observed on the ultrasound of carotid artery while a"stump-like"change was showed at the expected bifurcation level of carotid artery on DSA.Few cases has been reported in China and abroad so far.This article reported a middle-aged male with a history of hypertension and type 2 diabetes and was admitted to the hospital due to dizziness for one month.The left NBCCA accompanied with severe stenosis of the right ICA was confirmed by cerebral angiography.The patient received the right ICA stent implantation surgery as well as antihypertensive and glucose-control treatment and was discharged as his symptoms improved.Clinical data of this case and related literatures were reviewed,in order to improve clinicians'especially imaging diagnostic physicians'understanding on NBCCA to avoid misdiagnosis and related complications.
7.Investigation of metabolites of 2-methyl-dechloroketamine in vitro
Jun-hui RU ; Feng HUANG ; Hao WU ; Min-hao WANG ; Xing KE ; Jian-hong GAO ; Yi-lei FAN
Acta Pharmaceutica Sinica 2024;59(5):1357-1363
The abuse of novel phenylcyclohexylpyridine drugs poses a significant threat to societal safety. The novel psychoactive substance 2-methyl-deschloroketamine (2-MDCK), belonging to the phenylcyclohexylpyridine class, has recently surfaced as a new compound. However, there is a lack of understanding regarding its metabolic pathways and the identification of suitable biomarkers. In this study, a human liver microsomal model was established, and ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) technology was applied to investigate the
8.Pharmacokinetic study of a novel SHP2 derivative NC-55-122 in rats and its metabolites in vivo
Ying ZHANG ; Xing CUI ; Lei TANG ; Wei-ke LIAO
Acta Pharmaceutica Sinica 2024;59(5):1422-1429
To investigate the pharmacokinetic characteristics and metabolites of Src homology 2 region-containing protein tyrosine phosphatase 2 (SHP2) protein inhibitor in SD rats, a triazole quinolinone based derivative NC-55-122 was utilized. Firstly, rats were randomly divided into groups and given compound NC-55-122 intragastric and intravenous administration, respectively. Blood samples were collected at different time points. Taking carbmazepine as the internal standard, ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to determine the concentration of NC-55-122 in rats, and the methodology was verified. DAS 2.0 software was used to calculate the main pharmacokinetic parameters, and GraphPad Prism 8.0.1 software was used to plot the blood concentration-time curve. At the same time, UPLC-Q-TOF/MS was established to analyze plasma samples, and UNIFI metabolite prediction software was used to analyze metabolites after oral gavage and intravenous injection. The linear range of the mass concentration of compound NC-55-122 was from 1 ng·mL-1 to 1 600 ng·mL-1, and the linear relationship was good. The matrix effect, extraction recovery, precision, accuracy and stability were investigated in this linear range, which met the requirements of biological analysis. Secondly, the analysis of pharmacokinetic parameters showed that the oral bioavailability of the compound was low, with
9.Effect of IL-22 Activating Nrf2 Pathway on the Colonic Barrier in Mice with Liver Fibrosis
Xing LIU ; Xiaojuan XU ; Yanfang WEI ; Hongyou YAN ; Junyan HUO ; Ke LI ; Cuiping XU
Herald of Medicine 2024;43(11):1733-1739
Objective To study the effect of IL-22 on the colonic barrier and its relationship with Nrf2 pathway in liver fibrosis mice.Methods The mice were divided into four groups:the control group(CON group),the model group(MOD group),the interleukin-22 group(IL-22 group),and the IL-22+ML385 group(ML385,an inhibitor of Nrf2),with 10 mice in each group,and the modeling cycle was 8 weeks.Liquid feed containing alcohol and carbon tetrachloride olive oil were given intraperitoneally in all groups except the CON group;IL-22 was given on top of this in the IL-22 group;and ML385 was injected intraperitoneally in the IL-22+ML385 group one hour before IL-22 treatment.At the end of modeling,the livers were stained with HE and Masson staining to clarify whether fibrosis occurred in the mice;the feces were collected to detect the cocci to bacillus ratio and observe the growth of intestinal flora;the colons were stained with HE staining,immunofluorescence and immunohistochemistry,and analyzed for the expression of tight junction proteins ZO-1,Occludin,and the Nrf2 pathway proteins(Nrf2,HO-1,and NQO1).The expression of these proteins was analyzed by immunohistochemistry.Results Compared with the CON group,mice in the MOD group showed significant fibrosis in the liver tissue,inflammatory cell infiltration in the colon tissue,and decreased expression of tight junction proteins(P<0.05).No overgrowth of various pathogenic bacteria was seen in fecal media.And there was no significant difference in the bulb-to-bar ratio.Compared with the MOD group,both liver and colon histopathologic damage were reduced in the IL-22 group,and tight junction protein expression was elevated,in addition,the expression levels of Nrf2,NQO1,and HO-1 were also elevated(P<0.05),whereas there was no significant change in the IL-22+ML385 group.Conclusion IL-22 improved the colonic barrier function in liver fibrosis mice,and the mechanism was related to the activation of Nrf2 anti-oxidative stress pathway.
10.Correlation analysis between patient stature-based optimization of image acquisition parameters and low-dose coronary angiography
Hai QIAN ; Yu-Qin ZHANG ; Ke-Nan LOU ; De-Xing HU
Chinese Journal of Interventional Cardiology 2024;32(4):191-196
Objective To explore the correlation among image acquisition parameter optimization,coronary angiography radiation dose and image quality.Methods 60 patients scheduled for elective percutaneous coronary angiography from January 2022 to January 2024 in our hospital were selected.Basic information and body measurements were collected.Patients were divided into three groups based on BMI,and patients in each BMI group were randomly assigned to the conventional mode group(coronary mode image acquisition:Cardiac Left Coronary,15fps)and the optimized mode group(electrophysiology mode image acquisition:Cardiac EP,7.5fps).Radiation dose data were collected.Image quality was evaluated using an image quality scoring table.Independent sample t-tests,Mann-Whitney U tests,and one-way ANOVA were used for comparisons between groups.Pearson analysis was used for correlations.Results Higher BMI and larger chest circumference were associated with higher radiation doses in a positive linear correlation.Within each BMI group,all radiation dose data(Dose-Area Product,Air Kerma and Chest skin dose)were lower in the optimized mode group than in the conventional mode group(all P<0.05,reduction rate 48.95%-70.59%).The difference in image quality scores between two groups was not statistically significant(P>0.05),and all images were of the required quality.Conclusions The radiation dose of percutaneous coronary angiography is affected by the patient's body size,image acquisition parameters,exposure time and many other factors.Optimizing the image acquisition parameters can ensure the quality of the image while realizing the low dose of radiation and reducing the radiation hazards to the patient and the operator.

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