BACKGROUND:Dental mesenchymal stem cells are considered a promising source for bone tissue repair due to their high proliferation potential,osteogenic differentiation capacity,and immunomodulatory properties.However,some allogeneic applications of stem cells still have potential carcinogenic effects and immune rejection risks.Recently,studies have highlighted the paracrine effects mediated by secretions from dental mesenchymal stem cells in bone tissue repair.These secretions include the soluble factors and extracellular vesicles.OBJECTIVE:To review the research progress of dental mesenchymal stem cells in repairing bone defects through paracrine effects.METHODS:Using search terms"dental mesenchymal stem cell,paracrine,osteogenesis,conditioned medium,extracellular vesicle"in Chinese and English,relevant literature published between 2019 and 2024 was retrieved from databases including CNKI,PubMed,and Elsevier ScienceDirect.A total of 104 studies were ultimately selected for this review.RESULTS AND CONCLUSION:(1)Dental mesenchymal stem cells-conditioned medium contains multiple bioactive factors beneficial for bone repair.These factors directly promote bone formation through regulatory agents such as osteocalcin,osteopontin,bone morphogenetic protein,and dentin sialophosphoprotein.They also play an indirect promoting role in bone tissue repair through neurotrophic factors,vascular endothelial growth factor,and immunomodulatory and anti-inflammatory agents.(2)Dental derived mesenchymal stem cell-derived extracellular vesicles not only contain some cytokines from dental conditioned medium,but also various miRNAs,which promote bone repair by directly promoting osteogenesis,angiogenesis,regulating immune cells,and inflammation control.These extracellular vesicles can be engineered within different scaffold materials to achieve controlled or sustained release,enhancing therapeutic efficacy.

BACKGROUND:Dental mesenchymal stem cells are considered a promising source for bone tissue repair due to their high proliferation potential,osteogenic differentiation capacity,and immunomodulatory properties.However,some allogeneic applications of stem cells still have potential carcinogenic effects and immune rejection risks.Recently,studies have highlighted the paracrine effects mediated by secretions from dental mesenchymal stem cells in bone tissue repair.These secretions include the soluble factors and extracellular vesicles.OBJECTIVE:To review the research progress of dental mesenchymal stem cells in repairing bone defects through paracrine effects.METHODS:Using search terms"dental mesenchymal stem cell,paracrine,osteogenesis,conditioned medium,extracellular vesicle"in Chinese and English,relevant literature published between 2019 and 2024 was retrieved from databases including CNKI,PubMed,and Elsevier ScienceDirect.A total of 104 studies were ultimately selected for this review.RESULTS AND CONCLUSION:(1)Dental mesenchymal stem cells-conditioned medium contains multiple bioactive factors beneficial for bone repair.These factors directly promote bone formation through regulatory agents such as osteocalcin,osteopontin,bone morphogenetic protein,and dentin sialophosphoprotein.They also play an indirect promoting role in bone tissue repair through neurotrophic factors,vascular endothelial growth factor,and immunomodulatory and anti-inflammatory agents.(2)Dental derived mesenchymal stem cell-derived extracellular vesicles not only contain some cytokines from dental conditioned medium,but also various miRNAs,which promote bone repair by directly promoting osteogenesis,angiogenesis,regulating immune cells,and inflammation control.These extracellular vesicles can be engineered within different scaffold materials to achieve controlled or sustained release,enhancing therapeutic efficacy.

Objective:To discuss the changes of adenosine deaminase 2(ADA2)activity in the serum of the systemic lupus erythematosus(SLE)patients,and to clarify its clinical value in the diagnosis and disease assessment of the SLE patients.Methods:According to the inclusion and exclusion criteria,69 SLE patients(SLE group)and 69 healthy controls(control group)were enrolled as study subjects.The disease activity of SLE patients was evaluated by SLE Disease Activity Index(SLEDAI).The ADA2 activity in the serum of the subjects in both groups was detected.The patients were further divided into subgroups based on the presence or absence of the following clinical symptoms:arthritis,myositis,hematuria,proteinuria,pyuria,alopecia,new rash,mucosal ulcer,pleuritis,hypocomplementemia,elevated anti-double-stranded DNA(anti-dsDNA)antibody,thrombocytopenia,and leukopenia.The differences in serum ADA2 activity between joint symptomatic group and joint asymptomatic group were analyzed.The diagnostic efficacy of serum ADA2 activity was evaluated by receiver operating characteristic(ROC)curve analysis.The correlation between ADA2 activity and disease activity in the SLE patients was analyzed by Spearman correlation analysis.Results:Compared with control group,the ADA2 activity in the serum of the patients in SLE group was significantly increased(P<0.01).The ROC analysis results showed that when the cut-off value of ADA2 activity was set at 8.5 U·L-1,the diagnostic performance was optimal,with an area under the curve(AUC)of 0.879(95%CI:0.817-0.940),the specificity was 89.86%,and the sensitivity was 75.36%.The serum ADA2 activity was positively correlated with disease activity in the SLE patients(r=0.32,P=0.007).The subgroup analysis of clinical symptoms results showed that the serum ADA2 activity in the SLE patients with symptoms was significantly higher than that in the SLE patients without symptoms(P<0.01).No significant differences were observed in serum ADA2 activity between the SLE patients with and without myositis,hematuria,proteinuria,pyuria,alopecia,new rash,mucosal ulcer,pleuritis,hypocomplementemia,elevated anti-dsDNA antibody,thrombocytopenia,or leukopenia(P>0.05).Conclusion:The serum ADA2 activity is increased in the SLE patients and can serve as a diagnostic marker for SLE.Serum ADA2 activity is positively correlated with disease activity and is associated with arthritis in the SLE patients,suggesting its potential as an indicator for disease assessment and monitoring.

Objective To find out whether photobiomodulation(PBM)can mitigate cognitive dysfunction caused by chronic stress by affecting levels of adenosine triphosphate(ATP)and adenosine receptors.Methods Twenty-four C57BL/6J mice were randomly divided into a control group,a stress group,and a treatment group.Chronic unpredictable mild stress was used to establish a mouse model of stress.Six weeks into modeling,the treatment group was subjected to one week of PBM interventions.Behavioral tests were conducted to observe behavioral changes in the mice.Western blotting(WB)was used to detect the expressions of A1,A2B,and A3 adenosine receptors in the hippocampus and prefrontal cortex of mice in the three groups.Twelve C57BL/6J mice were randomly divided into a control group and an intervention group.The intervention group received a week of PBM interventions and underwent behavioral testing.WB was used to detect the expression changes of A1,A2B,and A3 adenosine receptors in the hippocampus and prefrontal cortex in both groups.Immunofluorescence assay was adopted to detect the expression of c-Fos in the hippocampus of mice in the two groups.The ATP assay kit made by Beyotime Biotechnology Co.,Ltd.was used to measure changes in ATP contents in the hippocampus and prefrontal cortex tissues of mice.Cell experiments were conducted to verify the effect of PBM on intracellular ATP contents.Results Mice in the stress group covered a similar distance to the control group,but finished far fewer platform crossings.There was no significant difference between the treatment group and the control group in the number of times of platform crossings,but compared favorably with the stress group where the levels of adenosine receptors in the hippocampus and prefrontal cortex were lower,but were increased by PBM.After PBM interventions in normal mice,platform crossings were increased significantly compared to the control group.PBM also raised adenosine receptor levels and ATP contents in the hippocampus and prefrontal cortex,and increased hippocampal c-Fos expressions.In vitro,PBM elevated intracellular ATP levels.Conclusion PBM may improve chronic stress-induced cognitive dysfunction by regulating ATP levels and adenosine receptor expressions,thereby modulating neuronal responsiveness in the hippocampus.

Piezo is a newly discovered mechanosensitive ion channel (MSC) in mammals, characterized by a unique homotrimeric three-leaf propeller-shaped structure that converts mechanical signals into biological and electrical signals, thus participating in the regulation of various physiological and pathological processes. In recent years, an increasing number of studies have demonstrated the crucial role of Piezo channel in renal physiology and pathophysiology. This article aims to provide new perspectives and targets for the prevention and treatment of renal diseases by reviewing the recent research advances in the structure, kinetics and pharmacology of Piezo channel, especially their expression and physiopathologic roles in the kidney.

Piezo is a newly discovered mechanosensitive ion channel (MSC) in mammals, characterized by a unique homotrimeric three-leaf propeller-shaped structure that converts mechanical signals into biological and electrical signals, thus participating in the regulation of various physiological and pathological processes. In recent years, an increasing number of studies have demonstrated the crucial role of Piezo channel in renal physiology and pathophysiology. This article aims to provide new perspectives and targets for the prevention and treatment of renal diseases by reviewing the recent research advances in the structure, kinetics and pharmacology of Piezo channel, especially their expression and physiopathologic roles in the kidney.

Objectives To understand the quality status of disinfection products in the market in Shaanxi Province, and to provide a basis for taking targeted management measures. Methods From 2020 to 2023, in accordance with the national disinfection product management regulations and standards, the physicochemical and microbial tests of disinfection products in Shaanxi Province were carried out through supervised sampling, and the test results were analyzed according to the active ingredients, illegal addition, stability, and bactericidal or bacteriostatic performance. Results The overall qualification rate of the active ingredient content of disinfectants sampled in Shaanxi Province was 90.48%, with the lowest qualification rate in 2023 (84.38%). The overall qualification rate of quantitative sterilization test of disinfectants was 90.12%, showing a decreasing trend year by year (P=0.272). The overall qualification rate of anti-bacterial products was 88.59%, and the bactericidal test results of 20 antibacterial products were all qualified. The overall qualification rate of bacteriostatic performance testing for bacteriostatic products was 86.17%, with the pass rate of bacteriostatic product germicidal efficacy testing of different components in descending order being quaternary ammonium salt/silver ion > guanidine > others > lysozyme, and there was statistically significant difference (P=0.004). The detection rate of illegal additives in antimicrobial products was 7.07%, with the main detection indicators being miconazole nitrate, clobetasol propionate, and dexamethasone acetate. Conclusion The qualified rate of disinfection products in Shaanxi Province is relatively high, but there is a downward trend. It is necessary to continue to strengthen the daily supervision and product testing of disinfection product manufacturers, and promote the continuous improvement of disinfection product quality.

AIM:Bone morphogenetic protein 7(BMP7)reduces the expression of Yes-related protein 1(YAP1)by down-regulating Ajuba level and decreasing extracellular matrix(ECM)deposition.This study aimed to inves-tigate the influence of these factors on modifying the degree of renal fibrosis in rats with diabetic nephropathy.METH-ODS:Eighteen Sprague-Dawley(SD)rats were randomly divided into three groups:the normal control(NC)group,the diabetes mellitus(DM)group,and the DM group treated with BMP7 overexpressing adeno-associated virus(DM+rAAV-BMP7).Each group consisted of six rats.Diabetic kidney disease(DKD)was established in the DM and DM+rAAV-BMP7 groups by injecting 55 mg/kg streptozotocin(STZ)via the tail vein.NRK-52E cells were divided into three groups:the normal glucose(NG)group,the high glucose(HG)group,and the high glucose group treated with recombinant hu-man BMP7(HG+rhBMP7)group.Pathological changes in renal tissues were observed using hematoxylin and eosin(HE)and Sirius red staining.Immunohistochemical staining was performed to examine the expression sites of Ajuba and YAP1 in the renal cortex.Western blot analysis was conducted to determine the expression levels of BMP7,Ajuba,YAP1,colla-gen type Ⅲ(Col-Ⅲ),and fibronectin(FN)in the rat renal cortex and NRK-52E cells.RT-qPCR was used to measure the mRNA levels of Ajuba and YAP1 in the rat renal cortex.RESULTS:Biochemical indices revealed significantly ele-vated levels of blood glucose,serum creatinine,triglycerides,total cholesterol,and 24-hour urinary protein in the DM group compared to the NC group(P<0.05).In the DM+rAAV-BMP7 group,the levels of serum creatinine,24-hour uri-nary protein,triglycerides,and total cholesterol were lower than those in the DM group(P<0.05).Pathological staining demonstrated that the renal interstitium of the DM group exhibited inflammatory cell infiltration,fibrous tissue,collagen fi-ber deposition,disordered renal tubule arrangement,atrophy,and vacuolar degeneration,which were ameliorated in the DM+rAAV-BMP7 group.Immunohistochemistry revealed that Ajuba and YAP1 were mainly expressed in the cytoplasm and nucleus,with high expression in the cytoplasm of the DM group,which was significantly decreased in the DM+rAAV-BMP7 group.Western blot results indicated that the protein levels of FN,Col-Ⅲ,Ajuba,and YAP1 were up-regulated in the DM and the HG groups(P<0.05),but significantly down-regulated in the DM+rAAV-BMP7 group(P<0.05).RT-qP-CR results demonstrated that the mRNA levels of Ajuba and YAP1 were higher in the DM group and significantly lower in the DM+rAAV-BMP7 group(P<0.05).CONCLUSION:The overexpression of BMP7 can ameliorate renal fibrosis in rats with DKD.This effect is likely mediated by the down-regulation of Ajuba,reduction of YAP1 expression,and subse-quent inhibition of ECM deposition.

Objective:To explore the role and molecular mechanism of Shikonin(SKN) in inhibiting the growth of anaplastic thyroid carcinoma(ATC) cells.Methods:The effect of SKN on ferroptosis in ATC cell lines CAL-62 was detected by flow cytometry; the expression levels of NF-κB, ferroptosis-related genes glutathione peroxidase 4(GPX4) and selenoprotein thioredoxin reductase 1(TXNRD1), glucose metabolism-related genes pyruvate kinase isoform 2(PKM2) and glucose transporter protein 1(GLUT1) were detected by Western blotting; real-time fluorescence quantitative(qPCR) to detect changes in the expression levels of GPX4, PKM2 and GLUT1; reactive oxygen species(ROS) fluorescent probe to detect changes in intracellular ROS positivity; glucose and lactic acid assay kit to detect the levels of glucose, the raw material of glucose metabolism(GLU), and lactate(LD), the product of glucose metabolism; and establishment of a subcutaneous tumour model in BALB/c nude mice to analyse the inhibitory effect of SKN on ATC in vivo.Results:Compared to the control group, after SKN treatment, the protein expression levels of NF-κB, GPX4, TXNRD1, GLUT1, and PKM2 in CAL-62 cells decreased( P=0.004, P=0.012, P=0.043, P=0.001, P=0.018); the mRNA expression of GPX4, GLUT1, and PKM2 also decreased( P<0.001, P=0.029, P<0.001). Additionally, ROS production increased( P=0.041). After treatment with the ferroptosis inhibitor Liproxstatin-1(L-1), the proportion of cell death was reversed to a certain extent, and there was no statistically significant difference in cell death proportion after L-1 treatment. Intracellular ferroptosis occurred( P<0.001), with reduced levels of glutamate(GLU) uptake and lipid peroxidation(LD) generation( P<0.001). SKN inhibited ATC tumor growth in vivo( P=0.016). Conclusion:SKN promotes intracellular ferroptosis in ATC cells, inhibits glycolysis and glucose uptake, and suppresses ATC cell growth.

Kidney is a highly energy-demanding organ rich in mitochondria. Numerous studies have indicated that mitochondria play a crucial role in maintaining normal kidney function and in the pathogenesis of various kidney diseases. Mitochondrial DNA is the exclusive genome of mitochondria. Damage to mtDNA not only leads to mitochondrial dysfunction and degradation of mitochondrial quality, but also acts as an endogenous inflammatory molecule, activating various inflammatory pathways, which contribute to cellular damage and the progression of kidney diseases. This article reviews the mechanisms of mitochondrial DNA damage and its significant role in triggering inflammatory injury in kidney diseases. Additionally, it summarizes the current research progress on various intervention strategies targeting this type of damage.