Bone is a highly calcified and vascularized tissue. The vascular system plays a vital role in supporting bone growth and repair, such as the provision of nutrients, growth factors, and metabolic waste transfer. Moreover, the additional functions of the bone vasculature, such as the secretion of various factors and the regulation of bone-related signaling pathways, are essential for maintaining bone health. In the bone microenvironment, bone tissue cells play a critical role in regulating angiogenesis, including osteoblasts, bone marrow mesenchymal stem cells (BMSCs), and osteoclasts. Osteogenesis and bone angiogenesis are closely linked. The decrease in osteogenesis and bone angiogenesis caused by aging leads to osteoporosis. Long noncoding RNAs (lncRNAs) are involved in various physiological processes, including osteogenesis and angiogenesis. Recent studies have shown that lncRNAs could mediate the crosstalk between angiogenesis and osteogenesis. However, the mechanism by which lncRNAs regulate angiogenesis‒osteogenesis crosstalk remains unclear. In this review, we describe in detail the ways in which lncRNAs regulate the crosstalk between osteogenesis and angiogenesis to promote bone health, aiming to provide new directions for the study of the mechanism by which lncRNAs regulate bone metabolism.
RNA, Long Noncoding/physiology* ; Osteogenesis/physiology* ; Humans ; Neovascularization, Physiologic/genetics* ; Bone and Bones/metabolism* ; Animals ; Mesenchymal Stem Cells ; Signal Transduction ; Osteoblasts ; Osteoclasts ; Angiogenesis

BACKGROUND: Periodontitis is characterized by alveolar bone resorption, aggravated by osteoblast dysfunction, and associated with intracellular oxidative stress linked to the nuclear factor erythroid 2-related factor 2 (NRF2) level. We evaluated the molecular mechanism of periodontitis onset and development and the role of NRF2 in osteogenic differentiation. METHODS: Primary murine mandibular osteoblasts were extracted and exposed to Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) or other stimuli. Reactive oxygen species (ROS) and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining were used to detect intracellular oxidative stress. Alkaline phosphatase staining and alizarin red S staining were used to detect the osteogenic differentiation of osteoblasts. Immunofluorescence and western blotting were used to determine the changes in the mitogen-activated protein kinase (MAPK) pathway and related molecule activities. Immunofluorescence colocalization and co-immunoprecipitation were performed to examine the nuclear translocation of NRF2 and its interaction with dual-specific phosphatase 1 (DUSP1) in cells. RESULTS: Ligated tissue samples showed higher alveolar bone resorption rate and lower NRF2 level than healthy periodontal tissue samples. Pg-LPS increased intracellular oxidative stress levels and inhibited osteogenic differentiation, whereas changes in NRF2 expression were correlated with changes in the oxidative stress and osteogenesis rate. NRF2 promoted the dephosphorylation of the MAPK pathway by nuclear translocation and the upregulation of DUSP1 expression, thus enhancing the osteogenic differentiation capacity of mandibular osteoblasts. The interaction between NRF2 and DUSP1 was observed. CONCLUSIONS: NRF2 and its nuclear translocation can regulate the osteogenic differentiation of mandibular osteoblasts under Pg-LPS conditions by interacting with DUSP1 in a process linked to the MAPK pathway. These findings form the basis of periodontitis treatment.
Animals ; NF-E2-Related Factor 2/physiology* ; Lipopolysaccharides/pharmacology* ; Osteoblasts/drug effects* ; Mice ; Porphyromonas gingivalis/chemistry* ; Cell Differentiation ; Osteogenesis ; Dual Specificity Phosphatase 1/metabolism* ; Mandible/cytology* ; Reactive Oxygen Species/metabolism* ; Oxidative Stress ; Periodontitis/metabolism* ; Cells, Cultured ; Male ; Cell Nucleus/metabolism*

Objective: To analyze the association of participation in non-sports extracurricular tutoring classes with the prevalence of screening myopia, axial length (AL) and axial length to corneal radius ratio (AL/CR) among primary school students, so as to provide evidences for formulating myopia prevention and control policies. Methods: In December 2024, combination of convenience and cluster sampling method was used to select 2 273 students from two primary schools in Hefei City, Anhui Province. Ophthalmic examinations and questionnaire surveys were conducted to obtain information on myopia, AL, AL/CR and participation in various types of extracurricular tutoring. A binary Logistic regression model was used to analyze the association between non-sports tutoring and screening myopia, and multiple linear regression models were used to examine the associations between non-sports tutoring and AL and AL/CR. Results: Among the surveyed students, the participation rate in non-sports extracurricular tutoring classes was 64.9% , and the overall prevalence of screening myopia was 39.1%. The average AL and AL/CR were (23.60± 1.01 ) mm and (3.00±0.12), respectively. Univariate analysis showed that students who attended non-sports, music, or academic tutoring classes for ≥2 h per week had higher risks of screening myopia and greater AL/CR values than non-participants (screening myopia: OR =1.38, 1.82, 1.55; AL/CR: β =0.01, 0.03, 0.03; all P <0.05). After adjusting for sex, grade, and participation in sports tutoring, multivariate analysis indicated that participation in non-sports and musical instrument tutoring classes for ≥2 h per week remained significantly associated with higher risks of screening myopia ( OR =1.26, 1.49, both P <0.05). Multiple linear regression showed that participation in musical instrument tutoring for ≥2 h per week was positively correlated with AL ( β=0.14, P < 0.05). Conclusions Participation in non-sports extracurricular tutoring is common among primary school students. Attending non-sports tutoring classes for ≥2 h per week increases the risk of screening myopia.

OBJECTIVE: Exploring the formation and aggregation of human islet amyloid polypeptide (hIAPP) (amylin) fibers is significant for promoting the prevention and treatment of type II diabetes mellitus (T2DM). Flavones in pomelo peel have visible biological activity in the anti-diabetes aspect. The present study aimed to investigate the effects of five flavones [naringin (NRG), narirutin (NRR), nobiletin (NOB), sinensetin (SIN), and neohesperidin (NHP)] in pomelo peel on peptide aggregation and explore its possible mechanisms. The cell viability of flavones against peptide aggregation was also evaluated. METHODS: The thioflavin T (ThT) assay and transmission electron microscopy (TEM) were used for evaluating the inhibition and disaggregation of flavones on peptide aggregation. The interaction mechanism was analyzed by endogenous fluorescence, molecular dynamics (MD) simulations, ultraviolet spectroscopy (UV) and isothermal titration calorimetry (ITC) experiments. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and immune assays were performed to characterize the cell viability of flavones against peptide aggregation. RESULTS: The five flavones showed a decrease in fluorescence intensity, fiber number and size under incubation with different molar ratios of hIAPP. The compounds can bind to the aromatic tyrosine (Tyr) residueTyr 37, resulting in the intrinsic fluorescence quenching of the peptides. Five flavones can form hydrogen bonds with hIAPP, which is likely to be based on their phenolic hydroxyl structure. They showed strong binding affinity with peptides. The reaction system of NRG and NRR observed an exothermic reaction, and the others were endothermic reactions. The absorption peaks of the compounds with hIAPP changed and showed hypochromic effects, indicating that there may be π-π stacking interaction. Flavones noticeably increased the cell viability in the presence of amyloid peptides and reduced the absorption intensity induced by peptide oligomers. CONCLUSION A total of five flavones in pomelo peel have inhibitory and depolymerization effects on amyloid fibrils, and can significantly protect cells from the toxic effect of hIAPP and reduce the production of toxic oligomers.

Objective: To understand the prevalence of school bullying and the comorbidity of anxiety and depressive symptoms among middle school students and their association, so as to provide a basis for developing related intervention strategies. Methods: From September to December 2023, a multistage random cluster sampling was employed to select 107 851 middle school students across 104 counties in Anhui Province. The Center for Epidemiological Studies Depression Scale (CES-D) and the Generalized Anxiety Disorder-7 (GAD-7) Scale were used to assess depressive and anxiety symptoms. Logistic regression analysis was utilized to examine the correlations between experiences of school bullying and the comorbidity of anxiety and depressive symptoms. Results: The findings revealed that 2.80% of middle school students had experienced school bullying in the past 30 days. Additionally, 27.03% exhibited potential symptoms of depression, 8.94% showed signs of anxiety symptom, and the comorbidity rate of anxiety and depressive symptoms was 8.04%. Logistic regression analysis showed that statistically significant correlations were identified between experiences of school bullying and increased risks of depressive symptoms (OR=6.42, 95%CI=5.93-6.94, P<0.01), anxiety symptoms (OR=5.94, 95%CI=5.47-6.44, P<0.01), and their comorbidity (OR=6.38, 95%CI=5.88-6.93, P<0.01). Compared with those who did not suffer from school bullying, junior high school students, ordinary senior high school students, vocational senior high school students, boys and girls who suffered from school bullying all had increased risks of comorbidity of anxiety and depressive symptoms (OR=7.25, 5.55, 4.80, 6.42, 6.27, P＜0.01). Conclusions The study underscores the significant impact of school bullying on increasing the risk of comorbidity of anxiety and depressive symptoms among middle school students. It is important to pay attention to the psychological health of bullied students and implement timely psychological intervention measures.

Objective:To analyze the risk factors for asparaginase-associated pancreatitis (AAP) in children with acute lymphoblastic leukemia (ALL) after treatment with pegaspargase and evaluate the predictive value of pediatric sequential organ failure assessment (SOFA) score, pediatric acute pancreatitis severity (PAPS) score, Ranson′s score and pediatric Ministry of Health, Labour and Welfare of Japan (JPN) score for severe AAP.Methods:Cross-sectional study.The clinical data of 328 children with ALL who received pegaspargase treatment in the Department of Pediatric Hematology, Zhujiang Hospital, Southern Medical University from January 2014 to August 2021, as well as their clinical manifestations, laboratory examinations, and imaging examinations were collected.The SOFA score at the time of AAP diagnosis, PAPS score and Ranson′s score at 48 hours after AAP diagnosis, and JPN score at 72 hours after AAP diagnosis were calculated, and their predictive value for severe AAP was evaluated by the receiver operating characteristic (ROC) curve.Results:A total of 6.7%(22/328) of children had AAP, with the median age of 6.62 years.AAP most commonly occurred in the induced remission phase (16/22, 72.7%). Three AAP children were re-exposed to asparaginase, and 2 of them developed a second AAP.Among the 22 AAP children, 16 presented with mild symptoms, and 6 with severe symptoms.The 6 children with severe AAP were all transferred to the Pediatric Intensive Care Unit (PICU). There were no significant differences in gender, white blood cell count at first diagnosis, immunophenotype, risk stratification, and single dose of pegaspargase between the AAP and non-AAP groups.The age at diagnosis of ALL in the AAP group was significantly higher than that in the non-AAP group ( t=2.385, P=0.018). The number of overweight or obese children in the AAP group was also higher than that in the non-AAP group ( χ2=4.507, P=0.034). The areas under the ROC curve of children′s JPN score, SOFA score, Ranson′s score, and PAPS score in predicting severe AAP were 0.919, 0.844, 0.731, and 0.606, respectively.The JPN score ( t=4.174, P=0.001) and the SOFA score ( t=3.181, P=0.005) showed statistically significant differences between mild and severe AAP. Conclusions:AAP is a serious complication in the treatment of ALL with combined pegaspargase and chemotherapy.Older age and overweight or obesity may be the risk factors for AAP.Pediatric JPN and SOFA scores have predictive value for severe AAP.

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

Objective To explore the role of MAPK4 in cervical squamous cell carcinoma(CSCC)for the identification of candidate prognostic prediction biomarkers and molecular therapeutic targets.Methods The TCGA cohort was subjected to Kaplan-Meier survival analysis.Immunohistochemistry experiments were conducted on clinical samples to explore the correlation between MAPK4 and patient prognosis.A nomogram was constructed based on MAPK4 mRNA levels.Western blot,CCK-8,colony formation,and Transwell cell function experiments were performed to clarify the abnormal expression and role of MAPK4 in CSCC.DIA proteome sequencing was used to identify effector molecules regulated by MAPK4.Combined with the above cell function experiments,the knockdown of MAPK4 and the overexpression of effector molecules revealed that MAPK4 regulated effector molecules to mediate tumor progression.Results CSCC patients with elevated MAPK4 mRNA levels and high protein expression have a worse prognosis.The constructed nomogram based on MAPK4 can accurately predict the 1-,3-,and 5-year survival rates of patients.Compared with that in normal cervical tissues,MAPK4 protein expre-ssion was up-regulated in tumors.MAP-K4 knockdown substantially inhibited the proliferation,colony formation,mig-ration,and invasion of CSCC ME180 and SiHa cells.SLC3A2 is a downs-tream effector molecule of MAPK4.Overexpression SLC3A2 can weaken the inhibitory effect of MAPK4 knockdown on cell proliferation,colony formation,migration,and invasion.Conclusion MAPK4 is a candidate prognostic biomarker for patients with CSCC.MAPK4 positively regulates SLC3A2 protein expression and accelerates tumor progression,making it a potential molecular therapeutic target for patients with CSCC.

Non-small cell lung cancer (NSCLC) is the most important histological type of lung cancer. This disease affects a large number of patients, and the prognosis of advanced patients is poor. Although great progress has been achieved for existing treatment methods, challenges still exist. Cancer is a genetic disease, and its occurrence is accompanied by substantial genomic-sequence instability. (GT/CA)_n repeat sequence is a common microsatellite sequence serving as transcriptional function-related regions, DNA-methylation modification sites, and other functional sites. Its polymorphism is closely related to the expression of EGFR, HO-1, and HIF-1α in NSCLC patients. (GT/CA)_n repeat sequence is the breakthrough point to explore the molecular mechanism of NSCLC occurrence and development, develop molecular markers for diagnosis and prognosis and epigenetics research. This paper summarizes the studies on (GT/CA)_n repeat polymorphisms in NSCLC with the aim of providing references for relevant NSCLC research.

Objective To explore whether voluntary wheel running affects liver oxidative stress by regulating the Nrf2/HO-1 pathway,thereby alleviating HFFC diet-related lipid deposition in the liver.Methods Eight-week-old C57BL/6J mice were randomly divided into a normal diet group(NC group,n=10)and high-fat,fructose,and cholesterol diet group(HFFC group,n=20)after 1 week of adaptive feeding.Ten weeks of feeding later,mice in the HFFC group were divided into a quiet group(HFFC group,n=10)and HFFC combined with exercise group(HFFC+EX group,n=10).HFFC+EX group mice were caged with voluntary running wheels for free movement,and the number of running wheels was recorded every day for 8 weeks.After the last treatment,the mice were sacrificed by fasting for 12 hours at an interval of 24 hours,and the blood and liver were collected for analysis.Results(1)Body weight,liver weight,and liver index of mice fed the HFFC diet were significantly higher than those of the NC group,which significantly decreased after exercise(P＜0.05).(2)Compared with the NC group,HDL-C and LDL-C in the HFFC group were significantly increased,and the LDL-C level was significantly decreased after 8 weeks of exercise(P＜0.05).(3)The liver fat droplet area and liver TG content in the HFFC group were significantly higher than those in the NC group,whereas those in HFFC+EX group were significantly decreased(P＜0.05).(4)Compared with the NC group,the content of oxidase MDA in the HFFC group were significantly increased,and nuclear translocation and gene expression of Nrf2 were significantly decreased.After exercise,the activities of SOD and T-AOC were significantly increased,and the nuclear translocation and gene expression of Nrf2 and expression levels of HO-1 and SOD-1 were significantly increased(P＜0.05).(5)The number of apoptotic hepatocytes and CHOP expression in the HFFC diet group were significantly higher than those in the NC group,whereas the number of apoptotic hepatocytes,and CHOP and Bax/Bcl-2 expression in the exercise group were significantly lower than those in the NC group(P＜0.05).Conclusions Voluntary wheel can alleviate HFFC diet induced liver lipid deposition by regulating the Nrf2/HO-1 pathway,thereby alleviating oxidative stress and reducing apoptosis in liver cells.