ObjectiveTo investigate the effects of atorvastatin （ATV） on the proliferation and differentiation of rat bone marrow mesenchymal stem cells （BMSCs）， periodontal ligament stem cells （PDLSCs）， and dental pulp stem cells （DPSCs） in vitro， and to validate the regulatory effect of ATV on periodontal bone formation and tooth movement using a rat orthodontic tooth movement （OTM） model. MethodsThe effects of ATV on the proliferation and osteogenic/odontogenic differentiation of rat BMSCs， PDLSCs， and DPSCs were assessed in vitro. CCK-8 assay was used to detect the proliferation of the three types of cells. Alkaline phosphatase （ALP） staining and Alizarin Red staining were employed to evaluate osteogenic differentiation capacity. Western blot was used to detect the expression of osteogenesis-related proteins ［collagen type I （COL-I）， Runt-related transcription factor 2 （Runx2）， bone morphogenetic protein-2 （BMP-2）， osteocalcin （OCN）］ and the odontogenesis-related protein dentin sialophosphoprotein （DSPP） in BMSCs， PDLSCs and DPSCs. An OTM rat model was established， with rats randomly assigned to an ATV gavage group and a control group. The ATV gavage group received daily oral administration of ATV at a dose of 20 mg/kg， while the control group received an equal volume of solvent by gavage. Tooth movement distance was measured via Micro-CT on days 7， 14， and 21. Histomorphology of periodontal tissues was observed using Hematoxylin and Eosin （HE） staining and Masson staining. The gene and protein expression levels of osteogenic markers （BMP-2， Runx2， OCN） on the tension side of the first molar were detected by qRT-PCR and immunohistochemistry， respectively. ResultsATV at concentrations of 1×10⁻⁶ mol/L and 1×10⁻⁷ mol/L significantly promoted the proliferation and osteogenic/odontogenic differentiation of BMSCs， PDLSCs， and DPSCs， manifested as enhanced ALP activity， increased mineralized nodule formation， and up-regulated expression of osteogenic/odontogenic proteins COL-I， Runx2， BMP-2， OCN， and DSPP （P<0.001）. In the OTM model， compared with the control group， the ATV gavage group showed a significant reduction in tooth movement distance （P<0.05）， enhanced osteogenic activity in periodontal tissues， and significantly increased gene （P<0.001） and protein （P<0.05） expression of BMP-2， Runx2， and OCN on the tension side of the first molar. ConclusionATV enhances periodontal osteogenesis by promoting osteogenic/dentinogenic differentiation， thus inhibiting tooth movement.

Objective: To construct a Family with sequence similarity 50 member A(FAM50A) gene knockout mouse insulinoma pancreatic β-cell line Beta-TC-6 using CRISPR/Cas9 gene editing technology and to prepare polyclonal antibodies specifically recognizing FAM50A. Methods: Two guide RNAs(sgRNAs) targeting the FAM50A gene were designed,and a recombinant plasmid expressing blue fluorescent protein(BFP) was constructed for gene knockout.The successfully constructed plasmid was transfected into Beta-TC-6 cells,and BFP-positive single cells were isolated for clonal expansion.The expanded monoclonal cell lines were genotyped by Sanger sequencing,and FAM50A protein expression was assessed by Western blot.Purified human recombinant FAM50A protein was used to immunize New Zealand rabbits for the preparation of a polyclonal antibody.The specificity of the prepared antibody was then validated using the successfully established FAM50A knockout cell line. Results: A monoclonal cell line with a successful knockout of the FAM50A gene was identified.Sanger sequencing confirmed base deletions at the target site.Western blot analysis showed a complete absence of FAM50A protein expression in this cell line.The prepared polyclonal antibody successfully recognized endogenous murine FAM50A protein in wild-type Beta-TC-6 cells and in hTERT-RPE1 cells overexpressing human FAM50A-GFP fusion protein,while no signal was detected in the FAM50A knockout cells. Conclusion This study successfully established a FAM50A gene knockout Beta-TC-6 cell model and generated a FAM50A polyclonal antibody,providing powerful tools for future research.

Noise-induced hearing loss is a worldwide public health issue that is characterized by temporary or permanent changes in hearing sensitivity. This condition is closely linked to inflammatory responses, and interventions targeting the inflammatory gene tumor necrosis factor-alpha (TNFα) are known to mitigate cochlear noise damage. TNFα-induced proteins (TNFAIPs) are a family of translucent acidic proteins, and TNFAIP6 has a notable association with inflammatory responses. To date, there have been few reports on TNFAIP6 levels in the inner ear. To elucidate the precise mechanism, we generated transgenic mouse models with conditional knockout of Tnfaip6 (Tnfaip6 cKO). Evaluation of hair cell morphology and function revealed no significant differences in hair cell numbers or ribbon synapses between Tnfaip6 cKO and wild-type mice. Moreover, there were no notable variations in hair cell numbers or hearing function in noisy environments. Our results indicate that Tnfaip6 does not have a substantial impact on the auditory system.
Animals ; Mice, Knockout ; Hair Cells, Auditory, Inner/pathology* ; Mice ; Mice, Transgenic ; Hearing Loss, Noise-Induced ; Evoked Potentials, Auditory, Brain Stem/physiology*

Neuroendocrine carcinoma (NEC) represents a category of malignant tumors originating from neuroendocrine cells. Given that NEC cells exhibit characteristics of both neural and endocrine cells, they can hijack neuronal signaling pathways and dynamically regulate the expression of neuronal lineage markers during tumor metastasis, thereby constructing a microenvironment conducive to tumor growth and metastasis. Conversely, alterations in the tumor microenvironment can enhance the interactions between neurons and tumor cells, ultimately synergistically promoting the metastasis of NEC. This review highlights recent advancements in the field of cancer neuroscience, uncovering neuronal lineage markers in NEC that facilitate tumor dissemination through mediating crosstalk, bidirectional communication, and synergistic interactions between tumor cells and the nervous system. Consequently, the latest findings in tumor neuroscience have enriched our understanding of the biological mechanisms underlying tumor metastasis, opening new research avenues for a deeper comprehension of the complex biological processes involved in tumor metastasis, particularly brain metastasis. This review provides a comprehensive review of the crosstalk between tumor cells and neural signaling in the metastasis of NEC.
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Humans ; Carcinoma, Neuroendocrine/metabolism* ; Signal Transduction ; Animals ; Neoplasm Metastasis ; Neurons/pathology* ; Tumor Microenvironment ; Cell Communication

MRGPRX2 antagonists possess the potential for the treatment of allergic rhinitis, atopic dermatitis, and chronic urticaria. Previously, we identified a class of diaryl urea (DPU) MRGPRX2 antagonists with sub-micromolar IC₅₀ values in vitro. However, the structure-activity relationship remains unclear. Herein, we adopted a "relative symmetry with electronegativity of different key-groups" strategy for further modification of DPUs to achieve a promising MRGPRX2 antagonist with higher activity and safety. Electrostatic potential energy analysis and biological evaluation revealed that B-1023 and B-5023, that possess relatively symmetric electron-withdrawing substituents, remarkable inhibited mast cell degranulation at a sub-micromolar IC₅₀ in vitro and alleviated anaphylactic symptoms. Furthermore, B-1023, mitigated antigen-induced pulmonary inflammation (AIPI) in mice and competitively bonded to MRGPRX2. In summary, the "relative symmetry with electronegativity of different key-groups" strategy provided a drug design pattern for MRGPRX2 antagonists and identified promising antiallergic precursors for AIPI treatment.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.

Objectives:To investigate the effect of interferon-γ(IFN-γ)on the repair of dental pulp injury.Methods:hDPSCs were isolated and cultured,and the hDPSCs were divided into control group,0.05 ng/mL IFN-γ group,0.5 ng/mL IFN-γ group,5 ng/mL IFN-γ group and 0.5 ng/mL IFN-γ+PDTC group.Transwell was used to detect the effect of IFN-γ on the migration abil-ity of human dental pulp stem cells,alizarin red staining was used to evaluated the influence of IFN-γ on the osteogenic differentia-tion of hDPSCs,and the expression of protein related to Wnt/β-catenin signaling pathway in cells was detected by Western blot.The rat dental pulp mechanical injury model was established,and the 3D cultured hDPSCs cell mass and hDPSCs cell mass with 0.5 ng/mL IFN-γ were placed in the cavity of the established rat dental pulp injury model.The cavity was filled with glass ionomer,and HE staining was used to compare the repair of dental pulp tissue in each group of rats.Results:The number of migrating cells in dif-ferent concentrations of IFN-γ groups was significantly higher than that in the control group,and the difference was statistically signif-icant(P＜0.05),and the number of migrated cells in the 0.5 ng/mL IFN-γ group was more than that in the 0.05 ng/mL IFN-γgroup and the 5 ng/mL IFN-γ group(P＜0.05).Compared with the control group,the mineralized nodules and osteoblastic differ entiation of hDPSCs in different concentrations IFN-γgroups were significantly inhibited(P＜0.05).Compared with the 0.5 ng/mL IFN-γ group,the mineralized nodule formation and osteogenic differentiation of hDPSCs in the 0.5 ng/mL IFN-γ+PDTC group were enhanced(P＜0.05).Compared with the control group,the ALP activity of IFN-γ group and IFN-γ+PDTC group was significantly lower(P＜0.05),and the ALP activity of IFN-γ+PDTC group was higher than that of IFN-γgroup,and the difference between groups was statistically significant(P＜0.05).Compared with the control group,the protein ex-pression levels of Wnt1,β-catenin,RUNX2,CyclinD1 and OCN in the IFN-γ group and IFN-γ+PDTC group were significantly decreased,while the GSK-3β and p-GSK-3β had increased,and the difference between the groups was statistically significant(P＜0.05),the protein expressions of Wnt1,β-catenin,RUNX2,CyclinD1 and OCN in the IFN-γ+PDTC group were significantly higher than those in the IFN-γ group,while the protein expression levels of p-GSK-3β and GSK-3β were lower than those in the IFN-γ group,and the differences between the groups were statistically significant(P＜0.05).Compared with the control group,the inflammatory response in the dental pulp mechanical injury model of the IFN-γ group was aggravated,and the dentin formation was significantly inhibited.Conclusion:IFN-γ can promote the migration of hDPSCs and inhibit the osteogenic differentiation of hDP-SCs,and IFN-γ has an inhibitory effect on the formation of restorative dentin after pulp injury,which may be related to the expres-sion regulation of Wnt signaling pathway.

Objective To investigate the mechanisms through which Qinggan Yipi formula(QgYp)may alleviate liver fibrosis by integrating network pharmacology with experiments.Methods The active ingredients and gene targets of QgYp,associated with liver fibrosis,were sourced from several databases,including the Traditional Chinese Medicine Systems Pharmacology Database(TCMSP),various professional chemical databases,the HERB database,the GeneCards database,and the Online Mendelian Inheritance in Man(OMIM)database.Protein-protein interaction(PPI)networks were developed using the STRING database and visualized through Cytoscape software.Furthermore,GO enrichment analysis and KEGG pathway analysis were conducted with the Metascape database,alongside molecular docking studies using the CB-DOCK 2 platform.HSC-T6 cells were used as the research model,and the MTT assay along with Western blotting were applied to evaluate cell proliferation and protein expression levels,and the expression of related proteins was also detected in the animal experiment.Results A total of 22 bioactive components and 124 gene targets were identified within the formula.Enrichment analyses revealed 896 GO entries and 123 signaling pathways,notably including the IL-7,TNF,Toll-like receptor,and NF-kappa B pathways.Molecular docking indicated that the key components of the formula exhibited a strong binding affinity with proteins involved in the TLR4/NF-κB signaling pathway.Additionally,experiments confirmed that QgYp effectively inhibited the proliferation of HSC-T6 cells induced by LPS,and the expression of α-SMA,COL-1,TLR4,IκB-α,and NF-κB p65 proteins in both HSC-T6 cells and rats with liver fibrosis decreased.Conclusion QgYp can effectively inhibit the TLR4/NF-κB signaling pathway and has a suppressive effect on the fibrosis process in hepatic stellate cells,offering a theoretical basis for its clinical application in treating liver fibrosis.

Objective:To explore the effects of workload factors and social psychological factors on work-related musculoskeletal disorders (WMSDs) , construct a preventive decision-assisted ensemble learning model, and propose screening methods with clinical significance.Methods:In October 2022, 1071 workers from optoelectronic enterprises were selected as the research subjects by cluster sampling method. The general situation of workers, workload factors, social psychological factors and the occurrence of WMSDs were collected by using questionnaires. logistic regression, Extreme Gradient Boosting (XGBoost) , ensemble learning and classification chain model were adopted to explore the key factors influencing WMSDs, and the area under curve (AUC) was used to evaluate the model performance.Results:The incidence of WMSDs among workers in optoelectronic enterprises in the past year was 47.7% (511/1071) , among which the incidence of multi-site WMSDs was 54.4% (278/511) . logistic regression analysis showed that prolonged sitting, personnel shortage and forward neck tilt were risk factors for the occurrence of WMSDs in workers ( P<0.05) . XGBoost identified the key social psychological factors influencing WMSDs as low mood, mental tension, perceived happiness level, psychological calmness and tranquility. The integrated classification chain model based on the ordered label order had certain efficacy (AUC>0.7) when analyzing WMSDs at the neck, waist, shoulder, back, elbow and hip positions. Conclusion:Workload factors are the main risk factors for the occurrence of WMSDs among workers in optoelectronic enterprises, and social psychological factors also have potential influences. The construction of a classification chain model can accurately identify the occurrence of WMSDs in multiple parts. The alternating prevention strategy of workload factors and social psychological factors has important public health significance.

WDFY1 is a member of the protein family containing the WD repeat and FYVE structural domains,acting as a junction that assists the recruitment of downstream molecules by Toll-like receptor 3/4(TLR3/TLR4)and promotes the body's natural anti-viral and anti-bacterial immune response.In recent years,the role of WDFY1 has been successively reported in various disease models,such as neurological diseases,autophagy and tumors.This paper aims to provide a comprehensive review of the current state of WDFY1 research,encompassing its expression distribution,cell biological function and its role in disease development,and take a prospect on the potential of WDFY1 as a target in rheumatoid arthritis.