Xinwen Zhang

Aim: To explore the potential roles of mitochondrial dysfunction in the initiation of inflammation in periodontal macrophages and to determine the mechanism underlying the involvement of dynamin‐related protein 1 (Drp1) in macrophage inflammatory responses through its interaction with hexokinase 1 (HK1). Materials and Methods: Gingival tissues were collected from patients diagnosed with periodontitis or from healthy volunteers. Drp1 tetramer formation and phosphorylation were analysed using western blot. THP‐1 macrophages and RAW264.7 cells were stimulated with Porphyromonas gingivalis ( Pg ) or Pg lipopolysaccharide ( Pg LPS), respectively. Alterations in proteins associated with mitochondrial dynamics were scrutinized via western blot. Immunofluorescence was used to evaluate mitochondrial damage and mitochondrial permeability transition pore (mPTP) opening. Western blot was used to examine the inflammatory markers NLRP3, caspase‐1, IL‐1β and GSDMD. Protein interactions involving Drp1 were verified through immunoprecipitation. Results: In periodontitis patient samples, Pg LPS‐treated RAW264.7 cells, and Pg ‐stimulated THP‐1 macrophages, over‐activated Drp1 was able to drive NLRP3 inflammasome activation and the subsequent release of inflammatory factors. A direct interaction between Drp1 and HK1 was observed, facilitating excessive mPTP opening and subsequent mitochondrial dysfunction. Conclusion: In the inflammatory milieu of periodontal tissues, Drp1 hyperactivation in the macrophages is implicated in inflammation induction. Modulation of the inflammatory response in periodontal macrophages by Drp1 appears to facilitate mPTP opening.

Background: The selection of post-core material holds significant importance in endodontically treated teeth, influencing stress distribution in the dental structure after restoration. The use of computer-aided design/computer-aided manufacturing (CAD/CAM) glass fiber post-core possesses a better adaptation for different root canal morphologies, but whether this results in a more favorable stress distribution has not been clearly established. Materials and methods: This study employed finite element analysis to establish three models of post-core crown restoration with normal, oversized, and dumbbell-shaped root canals. The three models were restored using three different materials: CAD/CAM glass fiber post-core (CGF), prefabricated glass fiber post and resin core (PGF), and cobalt-chromium integrated metal post-core (Co-Cr), followed by zirconia crown restoration. A static load was applied and the maximum equivalent von Mises stress, maximum principal stress, stress distribution plots, and the peak of maximum displacement were calculated for dentin, post-core, crown, and the cement acting as the interface between the post-core and the dentin. Results: In dentin of three different root canal morphology, it was observed that PGF exhibited the lowest von Mises stresses, while Co-Cr exhibited the highest ones under a static load. CGF showed similar stress distribution to that of Co-Cr, but the stresses were more homogeneous and concentrated apically. In oversized and dumbbell-shaped root canal remnants, the equivalent von Mises stress in the cement layer using CGF was significantly lower than that of PGF. Conclusions: In oversized root canals and dumbbell-shaped root canals, CGF has shown good performance for restoration of endodontically treated teeth. Clinical relevance: This study provides a theoretical basis for clinicians to select post-core materials for residual roots with different root canal morphologies and should help to reduce the occurrence of complications such as root fracture and post-core debonding.

Background: This study aimed to evaluate stomatological students’ learning efficacy and their attitude towards Lecture-Team-Based Learning (LTBL) on topics regarding the design of removable partial dentures via in-class, online, and both in combination.Methods: Students from seven distinct grades participated in the course in their fourth academic year (Years 2015, 2016, 2017, 2018, 2019, 2020, and 2021). Students of Years 2015–2019 attended in-class LTBL, students of Year 2020 attended online LTBL, and students of Year 2021 attended the combination mode. The scores of three examinations were compared, namely, individual readiness assessment test, team readiness assurance test, and individual application test. Visual Analog Scales (VAS) were used for students to self-assess their mastery of prosthodontics knowledge before and after the course. Anonymous questionnaires were delivered to evaluate their satisfaction with LTBL via a Likert scale.Results: In each academic year, the three exam scores were significantly improved as the course progressed and VAS-post scores were significantly higher than VAS-pre scores. The three examination and VAS scores of students in Year 2020 were significantly lower than those in Years 2019 and 2021. Students were highly satisfied with the LTBL course based on the three parameters of knowledge acquisition, teamwork, and classroom atmosphere.Conclusion: Students were highly satisfied with the LTBL course and their learning performance was improved as the course progressed both in-class and online. Online LTBL could be adopted when students have to study online, while in-class LTBL could perform better when combined with video records of an online LTBL course.

Objective: To determine the critical roles of PU.1/cathepsin S activation in regulating inflammatory responses of macrophages during periodontitis.Background: Cathepsin S (CatS) is a cysteine protease and exerts important roles in the immune response. Elevated CatS has been found in the gingival tissues of periodontitis patients and is involved in alveolar bone destruction. However, the underlying mechanism of CatS‐driven IL‐6 production in periodontitis remains unclear.Methods: Western blot was applied to measure mature cathepsin S(mCatS) and IL‐6 expression in gingival tissues from periodontitis patients and RAW264.7 cells exposed to lipopolysaccharide from Porphyromonas gingivalis (P.g. LPS). Immunofluorescence was applied to confirm the localization of PU.1, and CatS in the gingival tissues of periodontitis patients. ELISA was performed to determine IL‐6 production by the P.g. LPS‐exposed RAW264.7 cells. Knockdown by shRNA was used to determine the effects of PU.1 on p38/ nuclear factor (NF)‐κB activation, mCatS expression and IL‐6 production in RAW264.7 cells.Results: The expressions mCatS and IL‐6 were significantly upregulated in gingival macrophages. In cultured RAW264.7 cells, increased mCatS and IL‐6 protein paralleled the activation of p38 and NF‐κB after exposure to P.g. LPS. CatS knockdown by shRNA significantly decreased P.g. LPS‐induced IL‐6 expression and p38/NF‐κB activation. PU.1 was significantly increased in P.g. LPS‐exposed RAW264.7 cells, and PU.1 knockdown dramatically abolished the P.g. LPS‐induced upregulation of mCatS and IL‐6 and the activation of p38 and NF‐κB. Furthermore, PU.1 and CatS colocalized in macrophages within the gingival tissues of periodontitis patients.Conclusion: PU.1‐dependent CatS drives IL‐6 production in macrophages by activating p38 and NF‐κB in periodontitis.

Background: Where the gene is expressed determines the function of the gene. Neuregulin 1 (Nrg1) encodes a tropic factor and is genetically linked with several neuropsychiatry diseases such as schizophrenia, bipolar disorder and depression. Nrg1 has broad functions ranging from regulating neurodevelopment to neurotransmission in the nervous system. However, the expression pattern of Nrg1 at the cellular and circuit levels in rodent brain is not full addressed. Methods: Here we used CRISPR/Cas9 techniques to generate a knockin mouse line (Nrg1 ^Cre/+ ) that expresses a P2A-Cre cassette right before the stop codon of Nrg1 gene. Since Cre recombinase and Nrg1 are expressed in the same types of cells in Nrg1 ^Cre/+ mice, the Nrg1 expression pattern can be revealed through the Cre-reporting mice or adeno-associated virus (AAV) that express fluorescent proteins in a Cre-dependent way. Using unbiased stereology and fluorescence imaging, the cellular expression pattern of Nrg1 and axon projections of Nrg1-positive neurons were investigated. Results: In the olfactory bulb (OB), Nrg1 is expressed in GABAergic interneurons including periglomerular (PG) and granule cells. In the cerebral cortex, Nrg1 is mainly expressed in the pyramidal neurons of superficial layers that mediate intercortical communications. In the striatum, Nrg1 is highly expressed in the Drd1-positive medium spiny neurons (MSNs) in the shell of nucleus accumbens (NAc) that project to substantia nigra pars reticulata (SNr). In the hippocampus, Nrg1 is mainly expressed in granule neurons in the dentate gyrus and pyramidal neurons in the subiculum. The Nrg1-expressing neurons in the subiculum project to retrosplenial granular cortex (RSG) and mammillary nucleus (MM). Nrg1 is highly expressed in the median eminence (ME) of hypothalamus and Purkinje cells in the cerebellum. Conclusions: Nrg1 is broadly expressed in mouse brain, mainly in neurons, but has unique expression patterns in different brain regions.

Considerable evidence indicates that the semiautonomous organelles mitochondria play key roles in the progression of many neurodegenerative disorders. Mitochondrial DNA (mtDNA) encodes components of the OXPHOS complex but mutated mtDNA accumulates in cells with aging, which mirrors the increased prevalence of neurodegenerative diseases. This accumulation stems not only from the misreplication of mtDNA and the highly oxidative environment but also from defective mitophagy after fission. In this review, we focus on several pivotal mitochondrial proteins related to mtDNA maintenance (such as ATAD3A and TFAM), mtDNA alterations including mtDNA mutations, mtDNA elimination, and mtDNA release-activated inflammation to understand the crucial role played by mtDNA in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. Our work outlines novel therapeutic strategies for targeting mtDNA.

Yao L, et al. J Breast Cancer. 2023 Mar;26:e12. https://doi.org/10.4048/jbc.2023.26.e12

After bone defects reach a certain size, the body can no longer repair them. Tantalum, including its porous form, has attracted increasing attention due to good bioactivity, biocompatibility, and biomechanical properties. After a metal material is implanted into the body as a medical intervention, a series of interactions occurs between the material’s surface and the microenvironment. The interaction between cells and the surface of the implant mainly depends on the surface morphology and chemical composition of the implant’s surface. In this context, appropriate modification of the surface of tantalum can guide the biological behavior of cells, promote the potential of materials, and facilitate bone integration. Substantial progress has been made in tantalum surface modification technologies, especially nano-modification technology. This paper systematically reviews the progress in research on tantalum surface modification for the first time, including physicochemical properties, biological performance, and surface modification technologies of tantalum and porous tantalum.