BACKGROUND: The protective effect of mesenchymal stem cells (MSCs) on cardiac ischemia-reperfusion (I/R) injury has been widely reported. Dental pulp-derived mesenchymal stem cells (DP-MSCs) have therapeutic effects on various diseases, including diabetes and cirrhosis. This study aimed to determine the therapeutic effects of DP-MSCs on I/R injury and elucidate the underlying mechanism. METHODS: Myocardial I/R injury model mice were treated with DP-MSCs or a miR-19a-3p mimic. The infarct volume, fibrotic area, pyroptosis, inflammation level, and cardiac function were measured. Cardiomyocytes exposed to hypoxia-reoxygenation were transfected with the miR-19a-3p mimic, miR-19a-3p inhibitor, or negative control. Pyroptosis and protein expression in the interferon regulatory factor 8/mitogen-activated protein kinase (IRF-8/MAPK) pathway were measured. RESULTS: DP-MSCs protected cardiac function in cardiac I/R-injured mice and inhibited cardiomyocyte pyroptosis. The upregulation of miR-19a-3p protected cardiac function, inhibited cardiomyocyte pyroptosis, and inhibited IRF-8/MAPK signaling in cardiac I/R-injured mice. DP-MSCs inhibited cardiomyocyte pyroptosis and the IRF-8/MAPK signaling by upregulating the miR-19a-3p levels in cardiomyocytes injured by I/R. CONCLUSION DP-MSCs protected cardiac function by inhibiting cardiomyocyte pyroptosis through miR-19a-3p under I/R conditions.
Animals ; MicroRNAs/metabolism* ; Pyroptosis/genetics* ; Mesenchymal Stem Cells/metabolism* ; Myocytes, Cardiac/cytology* ; Mice ; Male ; Mice, Inbred C57BL ; Dental Pulp/cytology* ; Myocardial Reperfusion Injury/therapy* ; MAP Kinase Signaling System/physiology*

Objective To investigate the effects of salidroside(Sal)on inflammatory response,lung injury,and high mobility group protein B1/Toll-like receptor 4/nuclear factor kappa B(HMGB1/TLR4/NF-κB)signaling pathway in mice with mycoplasmal pneumonia(MP).Methods An MP mouse model was constructed and randomly assigned into a Model group,a positive control-Azithromycin group(Azithromycin group),low and high dose salidroside groups(Sal-L,Sal-H groups),and high dose salidroside+pathway activator group(Sal-H+rHMGB1 group),with 12 mice in each group.Another 12 healthy mice were included as the control group.The total number of inflammatory cells and levels of inflammatory factors(IL-1β,TNF-α,and IL-6)in mice bronchoalveolar lavage fluid(BALF),levels of inflammatory factors in serum,levels of oxidative stress factors in lung tissue(ELISA),degree of lung tissue injury(HE staining),apoptosis of lung tissue cells(TUNEL staining),and expression levels of HMGB1/TLR4/NF-κB signaling pathway related proteins(Western blot)were measured.Results The lung tissue of mice in the Model group showed obvious pathological injury and infiltration of inflammatory cells,the total inflammatory cell count,inflammatory cytokine levels in BALF,the serum inflammatory cytokine levels,the MDA and NO levels in lung tissue,apoptosis rate,HMGB1 and Bax protein expression levels and p-TLR4/TLR4,p-NF-κB p65/NF-κB p65 values were obviously higher,while the SOD and GSH-Px activities,and the Bel-2 protein expression level in lung tissue were obviously lower(P＜0.05).Compared with the Model group,with the increase of Sal dose,the degree of lung tissue injury and the infiltration of inflammatory cells were reduced in the Sal-L,Sal-H,and Azithromycin groups,the total cell count,inflammatory cytokine levels in BALF,the MDA and NO levels in lung tissue,apoptosis rate,HMGB1 and Bax protein expression levels and p-TLR4/TLR4,p-NF-κB p65/NF-κB p65 values were obviously lower,while the SOD and GSH-Px activities,and the Bcl-2 protein expression level in lung tissue were obviously higher(P＜0.05).Compared with the Sal-H group,the mice in the Sal-H+rHMGB1 group showed severe lung tissue injury,the total inflammatory cell count,inflammatory cytokine levels in BALF,the serum inflammatory cytokine levels,the MDA and NO levels in lung tissue,apoptosis rate,HMGB1 and Bax protein expression levels and p-TLR4/TLR4,p-NF-κB p65/NF-κB p65 values were obviously higher,while the SOD and GSH-Px activities,and the Bcl-2 protein expression level in lung tissue were obviously lower(P＜0.05).Conclusion Sal can inhibit inflammation and oxidative stress responses,improve lung tissue injury in MP mice,and its effect may be related to the inhibition of HMGB1/TLR4/NF-κB signaling pathway activation.

This article reports a case of membranous nephropathy in an adolescent accompanied by monoclonal IgG1-κ deposition. The 16-year-old female patient was hospitalized for experiencing proteinuria and hematuria for more than 20 days. The patient had a history of mycoplasma infection and acute kidney injury, and renal pathology revealed glomerular membrane lesions accompanied by crescent formation. Electron microscopy showed electron dense deposits in the subepithelial and mesangial regions, and immunofluorescence demonstrated monotypic IgG1-κ deposits in the glomerulus. Bone marrow examination did not find any abnormal plasma cells, nor were there significant abnormalities in serum or urine free light chain κ/λ ratio. The diagnosis was proliferative glomerulonephritis characterized by membranous lesions with monoclonal IgG1-κ deposits. This disease is rare in children and adolescents, and currently there is limited understanding of its mechanism, with limited clinical treatment experience. This article aims to provide clinical insights through case analysis and literature review.

Objective To investigate the effects of salidroside(Sal)on inflammatory response,lung injury,and high mobility group protein B1/Toll-like receptor 4/nuclear factor kappa B(HMGB1/TLR4/NF-κB)signaling pathway in mice with mycoplasmal pneumonia(MP).Methods An MP mouse model was constructed and randomly assigned into a Model group,a positive control-Azithromycin group(Azithromycin group),low and high dose salidroside groups(Sal-L,Sal-H groups),and high dose salidroside+pathway activator group(Sal-H+rHMGB1 group),with 12 mice in each group.Another 12 healthy mice were included as the control group.The total number of inflammatory cells and levels of inflammatory factors(IL-1β,TNF-α,and IL-6)in mice bronchoalveolar lavage fluid(BALF),levels of inflammatory factors in serum,levels of oxidative stress factors in lung tissue(ELISA),degree of lung tissue injury(HE staining),apoptosis of lung tissue cells(TUNEL staining),and expression levels of HMGB1/TLR4/NF-κB signaling pathway related proteins(Western blot)were measured.Results The lung tissue of mice in the Model group showed obvious pathological injury and infiltration of inflammatory cells,the total inflammatory cell count,inflammatory cytokine levels in BALF,the serum inflammatory cytokine levels,the MDA and NO levels in lung tissue,apoptosis rate,HMGB1 and Bax protein expression levels and p-TLR4/TLR4,p-NF-κB p65/NF-κB p65 values were obviously higher,while the SOD and GSH-Px activities,and the Bel-2 protein expression level in lung tissue were obviously lower(P＜0.05).Compared with the Model group,with the increase of Sal dose,the degree of lung tissue injury and the infiltration of inflammatory cells were reduced in the Sal-L,Sal-H,and Azithromycin groups,the total cell count,inflammatory cytokine levels in BALF,the MDA and NO levels in lung tissue,apoptosis rate,HMGB1 and Bax protein expression levels and p-TLR4/TLR4,p-NF-κB p65/NF-κB p65 values were obviously lower,while the SOD and GSH-Px activities,and the Bcl-2 protein expression level in lung tissue were obviously higher(P＜0.05).Compared with the Sal-H group,the mice in the Sal-H+rHMGB1 group showed severe lung tissue injury,the total inflammatory cell count,inflammatory cytokine levels in BALF,the serum inflammatory cytokine levels,the MDA and NO levels in lung tissue,apoptosis rate,HMGB1 and Bax protein expression levels and p-TLR4/TLR4,p-NF-κB p65/NF-κB p65 values were obviously higher,while the SOD and GSH-Px activities,and the Bcl-2 protein expression level in lung tissue were obviously lower(P＜0.05).Conclusion Sal can inhibit inflammation and oxidative stress responses,improve lung tissue injury in MP mice,and its effect may be related to the inhibition of HMGB1/TLR4/NF-κB signaling pathway activation.

OBJECTIVES: To explore the therapeutic mechanism of compound Centella asiatica formula (CCA) for alleviating Schistosoma japonicum (Sj)-induced liver fibrosis in mice. METHODS: The active components and targets of CCA were identified using the TCMSP database with cross-analysis of Sj-related liver fibrosis targets. A "drug-component-target-pathway-disease" network was constructed using Cytoscape 3.9.1. Functional enrichment analysis (GO/KEGG) was performed using DAVID. Molecular docking study was carried out to validate interactions between the core targets and the key compounds. For experimental validation of the results, 36 mice were divided into control group, Sj-infected model group, and CCA-treated groups. In the latter two groups, liver fibrosis was induced via abdominal infection with Sj cercariae for 8 weeks, followed by 8 weeks of daily treatment with CCA decoction or saline. Hepatic pathology of the mice was assessedwith HE and Masson staining, and hepatic expressions of collagen-I and collagen-III were detected using immunohistochemistry; serum IL-6 and TNF-α levels were determined with ELISA. Hepatic expressions of TLR4 and MyD88 proteins were analyzed with Western blotting. RESULTS: We identified a total of 107 bioactive CCA components and 791 targets, including 37 intersection targets linked to Sj-induced fibrosis. The core targets included TNF, TP53, JUN, MMP9, and CXCL8, involving the IL-17 signaling, lipid metabolism, TLR4/MyD88 axis, and cancer pathways. Molecular docking study confirmed strong binding affinity between quercetin (a primary CCA component) and TNF/TP53/JUN/MMP9. In Sj-infected mouse models, CCA treatment significantly attenuated hepatic inflammatory cell infiltration, reduced collagen-I and collagen-III deposition, improved tissue architecture, reduced serum IL-6 and TNF-α levels, and downregulated TLR4 and MyD88 expressions in the liver. CONCLUSIONS CCA mitigates Sj-induced liver fibrosis by targeting TNF, TP53, JUN, and MMP9 to modulate the TLR4/MyD88 pathway, thereby suppressing pro-inflammatory cytokine release, inhibiting hepatic stellate cell activation, reducing collagen deposition, and preventing granuloma formation in the liver.
Animals ; Toll-Like Receptor 4/metabolism* ; Mice ; Myeloid Differentiation Factor 88/metabolism* ; Schistosoma japonicum ; Liver Cirrhosis/parasitology* ; Schistosomiasis japonica ; Signal Transduction ; Molecular Docking Simulation ; Inflammation ; Centella/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Tumor Necrosis Factor-alpha/metabolism*

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis

Melanoma is characterized by high malignancy, ranking the third among skin malignancies, and is associated with lack of specific treatment options and poor prognosis. Therefore, the development of effective therapies for melanoma is imperative. A critical challenge in addressing subcutaneous disease lies in overcoming the skin barrier. In this study, we engineered a microneedle (MN) system that integrates chemotherapy, photothermal therapy (PTT), and targeted therapy to enhance anti-tumor efficacy while effectively penetrating the skin barrier. In vitro studies have demonstrated that the MN drug delivery system (DDS) can effectively penetrate the stratum corneum of the skin, deliver therapeutics to subcutaneous tumor sites, and establish a drug reservoir at these locations to exert anti-tumor effects. Cellular experiments indicated that the engineered PTT chemotherapy-targeted MNs can be internalized by tumor cells, exhibiting enhanced cytotoxicity against them. In vivo pharmacological investigations revealed that the combination of PTT and chemotherapy delivered via this MN DDS produced synergistic anti-tumor effects, achieving a tumor inhibition rate of up to 98.15%. This in situ DDS minimizes involvement with other organs, significantly reducing chemotherapy-related side effects. In summary, the PTT chemotherapy-targeted MNs developed in this study demonstrate promising application potential by enhancing anti-tumor efficacy while minimizing adverse effects.

Objective Based on the assumption of spatial heterogeneity,the distribution pattern and risk characteristics of health poverty in middle-aged and elderly people with chronic diseases are described from the perspective of spatial differentiation.In order to providing a theoretical basis for the optimization of subsequent poverty reduction policies and a model policy for other countries.Methods It used factor detector and interaction detector to capture the role of single-factor and multi-factor interactions on the spatial differentiation of health poverty,and risk detectors were utilized to explore the high-risk factors in risky areas Results The single factor explanation of medical assistance and health education activities is prominent,and the factors such as PM2.5,old-age dependency ratio and urban unemployment rate have strong interaction.Furthermore,it identified high-risk factor characteristics in areas at high risk of health poverty.Conclusion The spatial differentiation pattern of health poverty among the middle-aged and elderly chronic disease population in China is the result of the synergistic driving effect of multidimensional factors,and there is variability in the risk characteristics among regions.The government should establish a contextual optimization strategy and pay attention to the joint effect of multiple factors to establish a synergistic management system.

Objective:To investigate the differences of the glymphatic system (GS) function between patients with mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) and healthy controls and between different seizure types by using diffusion tensor imaging along perivascular space (DTI-ALPS), and to analyze the correlation between GS function and the course of disease, as well as the efficacy of predicting the surgical outcome.Methods:This study was a cross-sectional study. A total of 171 patients with mTLE-HS (mTLE-HS group) and 75 healthy volunteers (HC group) were retrospectively enrolled from July 2009 to July 2021 at Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University. The general information of all subjects, such as seizure type (partial seizure, secondary generalized seizure), surgical outcome, etc., was analyzed. The 3D magnetization prepared rapid gradient echo T 1WI and DTI sequence images were collected. The VBM analysis method was used to segment cerebrospinal fluid and calculate the volume. The ALPS index of the bilateral brain was calculated using the Atlas-based DTI-ALPS method. Independent sample t-test or paired t test were used to compare the ALPS index between the mTLE-HS group and HC group, and between patients with different seizure types. Pearson correlation analysis was used to analyze the correlation between bilateral ALPS index and disease duration in mTLE-HS group. The predictive value of the ALPS index for surgical outcomes was evaluated by receiver operating characteristics curve and area under the curve. Results:Among the 171 mTLE-HS patients, 98 patients were mTLE with left-side HS (mTLE-LHS) and 73 patients were mTLE with right-side HS (mTLE-RHS); 37 patients underwent surgical treatment, including 27 with good prognosis and 10 with poor prognosis. Compared with the HC group, the left-side ALPS index of mTLE-LHS and mTLE-RHS were both decreased ( P<0.05). The right-side ALPS index in mTLE-RHS was lower than that in the HC group ( P<0.001). There was no significant difference in the right-side ALPS index between mTLE-LHS and HC group ( P=0.080). The ALPS index on the affected side of patients with secondary generalized seizures was significantly lower than that of patients with only partial seizures (all P<0.05), but the difference in ALPS index on the healthy side was not statistically significant( P>0.05). The left-side and right-side ALPS index in mTLE-LHS were negatively correlated with disease duration ( r=-0.272, P=0.007; r=-0.307, P=0.002), but no significant correlation was found between the left-side or right-side ALPS index in mTLE-RHS (all P>0.05). The DTI-ALPS index on the affected side in mTLE-HS patients exhibited good diagnostic accuracy for surgical outcome classification, with an area under the curve of 0.778. Conclusions:The patients with mTLE-HS exhibit dysfunction of the GS, and the degree of impairment is related to the type of seizure and the course of epilepsy. The ALPS index, which characterizes the function of GS, demonstrates good diagnostic accuracy for classifying surgical outcomes.

Objective To explore the value of serum Annexin A2(ANXA2),vasohibin-1(VASH1)and caveolin-1(CAV-1)in evaluating pregnancy outcomes in patients with hypertensive disorders of pregnancy(HDP).Methods From June 2020 to April 2023,125 patients with HDP admitted to Qingdao Women's and Children's Hospital were regarded as the research group,according to the pregnancy outcomes,they were separated into a good pregnancy outcome group(n=77)and a poor pregnancy outcome group(n=48).In addition,100 normal pregnant women who underwent pregnancy tests during the same period were regarded as the control group.Enzyme-linked immunosorbent assay(ELISA)was used to detect serum levels of ANXA2,VASH1,and CAV-1.Binary logistic regression was used to analyze the influencing factors of pregnancy outcomes in pregnant women with HDP,and receiver operating characteristic(ROC)curves were drawn to analyze the diagnostic value of serum ANXA2,VASH1,and CAV-1 in the diagnosis of HDP patients pregnancy outcome.Correlation of serum ANXA2,VASH1 and CAV-1 with 24-h urine protein content and blood pressure indices analyzed by Pearson's method.Results Compared with the healthy group,the serum ANXA2(353.19±37.31 μg/L vs 415.32±42.65 μg/L)and CAV-1(6.05±0.64 μg/L vs 6.89±0.73 μg/L)levels in the case group were greatly reduced(t=11.644,9.188),while VASH1(615.48±62.46 ng/L vs 528.63±54.39 ng/L)level was greatly increased(t=10.969),and the differences were statistically significant(all P<0.05).The serum NXA2(322.54±34.24 μg/L vs 372.29±39.23 μg/L)and CAV-1(5.56±0.59 μg/L vs 6.38±0.67 μg/L)levels in poor pregnancy outcomes group were greatly lower than those in good pregnancy outcomes group(t=7.323,6.706),while VASH1(660.29±67.34 ng/L vs 587.56±59.42 ng/L)level was greatly higher(t=6.321),and the differences were statistically significant(all P<0.05).24h urine protein level,VASH1 were risk factors affecting adverse pregnancy outcomes in patients with HDP(P<0.05),serum ANXA2 and CAV-1 were protective factors affecting adverse pregnancy outcomes in patients with HDP,and the differences were statistically significant(P<0.05).ROC curve results showed that the Area under the curve(AUC)of ANXA2,VASH1,CAV-1,and their combination in predicting pregnancy outcomes in HDP patients was 0.809,0.747,0.775 and 0.909,respectively.The AUC predicted by the combination of ANXA2,VASH1,and CAV-1 were greatly better than those predicted by ANXA2,VASH1 and CAV-1 alone(Z=2.720,3.334,3.320,all P＜0.05).ANXA2,VASH1 was negatively correlated with 24h urine protein level and systolic and diastolic blood pressure(r=-0.435～-0.406,all P<0.05),and CAV-1 was positively correlated with 24h urine protein level and systolic and diastolic blood pressure(r=0.428,0.409,0.421,P<0.05).Conclusion The serum ANXA2 and CAV-1 levels in HDP patients decreased,while Ang1 level increased,which has certain auxiliary predictive value for the diagnosis of HDP and the evaluation of pregnancy outcomes.