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Ginsenoside Rh2 is one of rare panaxidiols extracted from Panax ginseng and a potential estrogen receptor ligand that exhibits moderate estrogenic activity. However, the effect of Rh2 on growth inhibition and its underlying molecular mechanism in human breast cells are not fully understood. In this study, we tested cell viability by MTT and colony formation assays. Cell growth and cell cycle were determined to investigate the effect of ginsenoside Rh2 by flow cytometry. The expressions of estrogen receptors (ERs), TNFα, and apoptosis-related proteins were detected by qPCR and western blot analysis. The mechanisms of ERα and ERβ action were determined using transfection and inhibitors. Antitumor effect of ginsenoside Rh2 against MCF-7 cells was investigated in xenograft mice. Our results showed that ginsenoside Rh2 induced apoptosis and G1/S phase arrest in MCF-7 cells. Treatment of cells with ginsenoside Rh2 down-regulated protein levels of ERα, and up-regulated mRNA and protein levels of ERβ and TNFα. We also found that ginsenoside Rh2-induced TNFα over-expression is through up-regulation of ERβ initiated by ginsenoside Rh2. Furthermore, ginsenoside Rh2 induced MCF-7 cell apoptosis via estrogen receptor β-TNFα pathway in vivo. These results demonstrate that ginsenoside Rh2 promotes TNFα-induced apoptosis and G1/S phase arrest via regulation of ERβ.

Bacterial infection severely limits the effectiveness of biomaterials for tissue repair, posing a major challenge to modern medicine. Despite advances in novel antibiotics and their application in treatment, challenges remain in clinical practice. To address this issue, biomaterials are engineered to achieve desirable anti-infective performance and compatibility via adjusting their surface physicochemical properties. Recently, numerous studies on piezoelectric materials have been performed for anti-infective and regenerative therapies, but a comprehensive review is still lacking. This article provides a brief overview of the different types of piezoelectric materials and their characteristics. Building on this understanding, this review highlights the antibacterial mechanisms including orchestrating electric field and optimizing piezoelectric catalysis, which promote infective tissue regeneration, as well as discusses the anti-infective bioapplication of piezoelectric materials. Furthermore, this review concludes with perspectives into the challenges and future research directions of piezoelectric biomaterials. [ABSTRACT FROM AUTHOR]

Objective: Sjögren's syndrome (SS) is a systemic autoimmune disease, and T cells play an important role in the initiation and perpetuation of the disease. In this study, we developed an immunotherapy for NOD/LtJ mice with SS‐like symptoms by combining a transient depletion of CD4+ T cells with the administration of autoantigen‐specific peptide Ro480. Methods: NOD/LtJ mice were treated with single anti‐CD4 monoclonal antibody (mAb) followed 2 days later by a series of 6 intraperitoneal injections of Ro480–494 every other day. Salivary flow rates were determined pre‐ and posttreatment once a week. Mice were euthanized 6 weeks after the initial anti‐CD4 mAb treatment, salivary glands (SGs) were collected for analyses of histologic disease scores and inflammatory cell infiltration, polymerase chain reaction determination of genes was conducted, and flow cytometry analysis including major histocompatibility complex class II tetramer staining of immune cells was performed. In addition, adoptive transfer of Treg cells was administrated to investigate the function of the newly generating Treg cells in vivo. Results: The combination of anti‐CD4 mAb with autoantigen‐specific peptide Ro480 generated SSA/Ro antigen–specific Treg cells in vivo, which can suppress interferon‐γ production of CD4+ T cells and inflammation infiltration in SGs and maintain the function of SGs. Conclusion: Our findings provide a new approach to generating antigen‐specific Treg cells in vivo for SS treatment, which may have implications for potential therapy for patients with SS. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral health is increasingly recognized as an important part of overall health. Tooth loss is a contributor to overall musculoskeletal frailty and is closely associated with increased morbidity in the elderly population. Limited intervention exists to alleviate tooth loss associated with periodontitis, other than antibiotics. Mounting evidence suggests that targeting cellular senescence could slow down the fundamental aging process, and thus alleviate a wide range of age-related tissue dysfunctions, likely including tooth loss. Therefore, we feel it might be valuable to review the current understanding of the role and potential mechanisms of senescent cells in oral health with aging. Periodontitis is a chronic inflammatory disease which increases in prevalence and severity in the older population. Aging is a leading risk factor for periodontitis, which exacerbates alveolar bone loss and results in tooth loss in the elderly. However, the mechanism by which aging affects periodontitis is not well understood. There is considerable evidence to suggest that targeting cellular senescence could slow down the fundamental aging process, and thus alleviate a series of age-related pathological conditions, likely including alveolar bone loss. Recently, it has been discovered that the senescent cells accumulate in the alveolar bone and promote a senescence-associated secretory phenotype (SASP). Senescent cells interacting with bacteria, together with secreted SASP components altering the local microenvironment and inducing paracrine effects in neighboring cells, exacerbate the chronic inflammation in periodontal tissue and lead to more alveolar bone loss. This review will probe into mechanisms underlying excessive alveolar bone loss in periodontitis with aging and discuss potential therapeutics for the treatment of alveolar bone loss targeting cellular senescence and the SASP. Inspecting the relationship between cellular senescence and periodontitis will lead to new avenues of research in this field and contribute to developing potential translatable clinical interventions to mitigate or even reverse the harmful effects of aging on oral health. [ABSTRACT FROM AUTHOR]

With aging, a portion of cells, including mesenchymal stem cells (MSCs), become senescent, and these senescent cells accumulate and promote various age-related diseases. Therefore, the older age group has become a major population for MSC therapy, which is aimed at improving tissue regeneration and function of the aged body. However, the application of MSC therapy is often unsatisfying in the aged group. One reasonable conjecture for this correlation is that aging microenvironment reduces the number and function of MSCs. Cellular senescence also plays an important role in MSC function impairment. Thus, it is necessary to explore the relationship between senescence and MSCs for improving the application of MSCs in the elderly. Here, we present the influence of aging on MSCs and the characteristics and functional changes of senescent MSCs. Furthermore, current therapeutic strategies for improving MSC therapy in the elderly group are also discussed. [ABSTRACT FROM AUTHOR]

Successful implant–bone integration remains a formidable challenge in osteoporotic patients, because of excessive inflammatory reactions and osteoclastogenesis around the peri-implant bone tissue. This study designed biomimetic micro/sub-micro hierarchical surfaces on titanium implants based on natural bone hierarchical structures to mitigate macrophage-mediated inflammatory reactions, osteoclastogenesis, and osteogenesis in vitro, as well as promote early osseointegration in vivo. It was found that the biomimetic hierarchical surfaces inhibited M1 macrophage-mediated inflammatory reactions via suppression of the TLR2/NF-κB signaling pathway in vitro. Subsequently, osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was observed to be significantly enhanced on hierarchical surfaces in the presence of macrophage conditional media. Furthermore, osteoclast formation was also decreased by inhibiting the osteoclastogenesis regulatory factor NFATc-1 expression on hierarchical surfaces. In vivo, the implant with a micro/sub-micro hierarchical surface underwent rapid and early osseointegration, with the newly formed bone being tightly integrated with the implants. Hence, the hierarchical surface mitigated the inflammatory microenvironment around the implant, thereby inhibiting osteoclastogenesis. This study thus offers a novel biomimetic strategy for designing surface hierarchical topography to facilitate implant–bone osseointegration in osteoporotic patients. [ABSTRACT FROM AUTHOR]

In the last decade, numerous circRNAs were discovered by virtue of the RNA-Seq technique. With the deepening of experimental research, circRNAs have brought to light the key biological functions and progression of human diseases. CircRNA ITCH has been demonstrated to be a tumor suppressor in numerous cancers, and recently it was found to play an important role in bone diseases, diabetes mellitus, and cardiovascular diseases. However, the functions of circ-ITCH have not been completely understood. In this review, we comprehensively provide a conceptual framework to elucidate circ-ITCH biological functions of cell proliferation, apoptosis and differentiation, and the pathological mechanisms of inflammation, drug resistance/toxicity, and tumorigenesis. Finally, we summarize its clinical applications in various diseases. This research aimed at clarifying the role of circ-ITCH, which could be a promising therapeutic target. [ABSTRACT FROM AUTHOR]

Maxillofacial-derived mesenchymal stem cells (MFSCs) are a particular collective type of mesenchymal stem cells (MSCs) that originate from the hard and soft tissue of the maxillofacial region. Recently, many types of MFSCs have been isolated and characterized. MFSCs have the common characteristics of being extremely accessible and amazingly multipotent and thus have become a promising stem cell resource in tissue regeneration. However, different MFSCs can give rise to different cell lineages, have different advantages in clinical use, and regulate the immune and inflammation microenvironment through paracrine mechanisms in different ways. Hence, in this review, we will concentrate on the updated new findings of all types of MFSCs in tissue regeneration and also introduce the recently discovered types of MFSCs. Important issues about proliferation and differentiation in vitro and in vivo, up-to-date clinical application, and paracrine effect of MFSCs in tissue regeneration will also be discussed. Our review may provide a better guide for the clinical use of MFSCs and further direction of research in MFSC regeneration medicine. [ABSTRACT FROM AUTHOR]

The use of the C-expander is an effective treatment modality for maxillary skeletal deficiencies which can cause ailments and significantly reduce life expectancy in late adolescents and young adults. However, the morphological and dynamic effects on the nasal airway have not been reported. The main goal of this study was to evaluate the nasal airway changes after the implementation of a C-expander. A sample of nine patients (8 females, 1 male, age range from 15 to 29 years) was included. The morphology parameters and nasal airway ventilation parameters of pretreatment and posttreatment were measured. All study data were normally distributed. A paired t -test was used to evaluate the changes before and after treatment. After expansion, the mean and standard deviation values of intercanine maxillary width (CMW) and intermolar maxillary width (MMW) increased from 35.75 ± 2.48 mm and 54.20 ± 3.17 mm to 37.87 ± 2.26 mm (P < 0.05) and 56.65 ± 3.10 mm (P < 0.05), respectively. The nasal cavity volume increased from 20320.00 ± 3468.25 mm3 to 23134.70 ± 3918.84 mm3 (P < 0.05). The nasal pressure drop decreased from 36.34 ± 3.99 Pa to 30.70 ± 3.17 Pa (P < 0.05), while the value of the maximum velocity decreased from 6.50 ± 0.31 m/s to 5.85 ± 0.37 m/s (P < 0.05). Nasal resistance dropped remarkably from 0.16 ± 0.14 Pa/ml/s to 0.08 ± 0.06 Pa/ml/s (P < 0.05). The use of C-expander can effectively broaden the area and volume of the nasal airway, having a positive effect in the reduction of nasal resistance and improvement of nasal airway ventilation. For patients suffering from maxillary width deficiency and respiratory disorders, a C-expander may be an alternative method to treat the disease. [ABSTRACT FROM AUTHOR]

Interleukin (IL)‐33, a member of the IL‐1 superfamily, functions as an alarm signal, which is released upon cell injury or tissue damage to alert the immune system. It has emerged as a chief orchestrator in immunity and has a broad pleiotropic action that influences differentiation, maintenance and function of various immune cell types via the ST2 receptor. Although it has been strongly associated with immunopathology, critically, IL‐33 is involved in host defence, tissue repair and homeostasis. In this review, we provide an overview of the signalling pathway of IL‐33 and highlight its regulatory functions in immune cells. Furthermore, we attempt a broader discussion of the emerging functions of IL‐33 in host defence, tissue repair, metabolism, inflammatory disease and cancer, suggesting potential avenues to manoeuvre IL‐33/ST2 signalling as treatment options. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the changes of maxillary expansion and upper airway structure after microimplant assisted rapid palatal expansion (MARPE) using cone-beam computed tomography (CBCT). METHODS: This retrospective study included 19 subjects (15 females and 4 males) aged 15–29 years old (mean, 19.95±4.39 years) with maxillary transverse deficiency treated with MARPE. CBCT was performed at the initial diagnosis and 3 months after MARPE treatment. Measurements were taken to evaluate the amount of total expansion, skeletal expansion, and dental expansion at the maxillary first premolar (P1), second premolar (P2), first molar (M1), second molar (M2) regions and upper airway changes. RESULTS: After MARPE treatment, the maxillary skeletal base expansion, skeletal expansion, alveolar expansion and dental expansion were achieved at the P1, P2, M1, M2 region. The nasopharyngeal volume significantly increased 8.48% after MARPE treatment compared with that before the treatment (P < 0.05). The change of nasal lateral width (NLW) was also significantly different before and after MARPE (P < 0.05). However, there were no statistically significant change in the oropharyngeal, palatopharyngeal, glossopharyngeal and airway total volume (all P > 0.05). CONCLUSIONS: MARPE can produce more transverse bone expansion, relieve maxillary transverse deficiency and improve upper airway ventilation. [ABSTRACT FROM AUTHOR]

Objectives: Mesenchymal stem cells (MSCs) could regulate the function of various immune cells. It remains unclear whether MSCs additionally possess immunostimulatory properties. We investigated the impact of human MSCs on the responsiveness of primary natural killer (NK) cells in terms of induction of anti‐inflammatory purinergic signalling. Material and Methods: We obtained human bone marrow mesenchymal stem cells (BMMSCs) and dental pulp stem cells (DPSCs). NK cells were isolated from peripheral blood of healthy volunteers. Activated NK cells were cultured with MSCs. Proliferation assay, apoptosis analysis, activating or inhibitory receptor expression and degranulation assay were used to explore NK cells' function. High‐performance liquid chromatography was used to investigate the purinergic signalling in activated NK cells. Results: Both DPSCs and BMMSCs could impair proliferation and promote apoptosis of activated NK cells. Also, activated NK cells could cause DPSCs to lyse. Furthermore, the expression of activating NK cells' receptors was decreased, but inhibitory receptors of NK cells were elevated following co‐cultivation. NK cells acquired CD73 expression, while MSCs could release ATP into the extracellular space where nucleotides were converted into adenosine (ADO) following co‐culture system. Under the existence of exogenous 2‐chloroadenosine (CADO), the cytotoxic capacity of NK cells was remarkably depressed in a concentration‐dependent manner. Conclusions: DPSCs and BMMSCs could depress NK cells' function by hydrolysing ATP to ADO using CD39 and CD73 enzymatic activity. Our data suggested that DPSCs might represent a new strategy for treating immune‐related diseases by regulating previously unrecognized functions in innate immune responses. [ABSTRACT FROM AUTHOR]

The mitogen-activated protein kinase (MAPK) signaling pathway is associated with tumor cell proliferation, differentiation, apoptosis, angiogenesis, invasion and metastasis. The present review assesses the involvement of the MAPK signaling pathway in oral cancer progression and invasion based on analysis of individual sub-pathways and their mechanisms of action. The regulation of this pathway for targeted oral cancer therapy is explored and the challenges confronting this, as well as corresponding potential solutions, are discussed. Exploring this pathway with an emphasis on its components, subfamilies, sub-pathways, interactions with other pathways and clinical practice modes may improve oral cancer treatment. [ABSTRACT FROM AUTHOR]

Introduction: Dental pulp stem cell (DPSC)-mediated dental pulp regeneration is considered a promising method for the treatment of deep caries with pulpitis. However, mesenchymal stem cell (MSC) senescence is an adverse factor from the perspective of cell-based therapies. In this study, we investigated the characteristics and expression profiles of DPSCs from young and old donors. Methods: DPSCs from young and old donors were cultured in differentiation medium, and their differentiation potentials were assessed. Long noncoding RNA (LncRNA) microarray assays and a bioinformatic analysis were performed to investigate differences in LncRNA and mRNA expression profiles between DPSCs from young and old donors. Results: We found that DPSCs from young donors exhibited more powerful proliferation ability and greater osteogenic and adipogenic differentiation potentials than DPSCs from old donors. In DPSCs from young donors, numerous LncRNAs were significantly up-(n = 389) or down-regulated (n = 172) compared to DPSCs from old donors. Furthermore, 304 mRNAs were differentially expressed, including 247 up-regulated genes and 57 downregulated genes in DPSCs from young donors. The bioinformatic analysis identified that several pathways may be associated with DPSC characteristics, such as those involved in the cell cycle and RNA transport, and revealed nuclear transcription factor Y subunit β, general transcription factor IIB, and nuclear receptor subfamily 3 group C member 1 as core regulatory factors and FR249114, FR299091, and ENST00000450004 as core LncRNAs. Conclusions: Our results indicated that senescence impaired the proliferation and differentiation potentials of DPSCs and that donor age is an important factor that affects their use for tooth regeneration. We also provide insight into the mechanisms responsible for senescence in DPSCs. [ABSTRACT FROM AUTHOR]

Rapid prototyping (RP) technologies have found many uses in dentistry, and especially oral and maxillofacial surgery, due to its ability to promote product development while at the same time reducing cost and depositing a part of any degree of complexity theoretically. This paper provides an overview of RP technologies for maxillofacial reconstruction covering both fundamentals and applications of the technologies. Key fundamentals of RP technologies involving the history, characteristics, and principles are reviewed. A number of RP applications to the main fields of oral and maxillofacial surgery, including restoration of maxillofacial deformities and defects, reduction of functional bone tissues, correction of dento-maxillofacial deformities, and fabrication of maxillofacial prostheses, are discussed. The most remarkable challenges for development of RP-assisted maxillofacial surgery and promising solutions are also elaborated. [ABSTRACT FROM AUTHOR]

Periodontal ligament stem cells (PDLSCs) have provided novel cell sources for tooth and periodontal tissue regeneration. Allogeneic PDLSCs can reconstruct periodontal ligament tissue that has been damaged by periodontal diseases and regulate T-cell immunity. However, the effect of PDLSCs on B cells remains unknown. Here, we treated periodontitis in a miniature pig model using allogeneic PDLSCs and showed a reduction in humoral immunity in the animals. When cocultured with normal B cells, human PDLSCs (hPDLSCs) had similar effects as bone marrow mesenchymal stem cells in suppressing B cell proliferation, differentiation, and migration, while intriguingly, hPDLSCs increased B cell viability by secreting interleukin-6. Mechanistically, hPDLSCs suppressed B cell activation through cell-to-cell contact mostly mediated by programmed cell death protein 1 and programmed cell death 1 ligand 1. Our data revealed a previously unrecognized function of PDLSCs in regulating humoral immune responses, which may represent a novel therapeutic strategy for immune-related disorders. S TEM C ells 2013;31:1371-1382 [ABSTRACT FROM AUTHOR]

Electrophoretic deposition (EPD) is an effective technique to construct coatings onto the surface of medical devices. These coatings can act as reservoirs for local delivery of therapeutic agents, including metal ions and metal-free drugs. This manuscript presents a comprehensive overview of the fundamentals and application of EPD coatings for local delivery of therapeutic agents, with a specific focus on the mechanism and control over loading and release of therapeutic agents. After a brief introduction of the EPD coating process, the matrices that are most commonly deposited using EPD for drug delivery purposes are summarized including the mechanism of their deposition without additives and co-deposition with additives. Subsequently, three strategies towards loading therapeutic agents are discussed, including i) co-deposition of therapeutic agents with coating matrices, ii) pre-loading therapeutic agents into microcarriers, and iii) post-loading therapeutic agents into prepared coatings. Furthermore, factors influencing loading (e.g., EPD processing parameters and additives) are identified. Subsequently, the release mechanisms as well as the influence of both intrinsic (e.g., additives, layered structures, building blocks, and microcarrier properties) and extrinsic processing parameters (e.g., pH, electric, magnetic and photothermal stimuli) used to tune the release kinetics are presented. Additionally, the applications of therapeutic agent loaded EPD coatings are summarized. Finally, the remaining challenges and future perspectives related to the use of EPD coatings for drug delivery purposes are reviewed. [ABSTRACT FROM AUTHOR]

Periodontitis is an inflammation of the alveolar bone and soft tissue surrounding the teeth. Although mesenchymal stem cells (MSCs) have been implicated in periodontal regeneration, the mechanisms by which they promote osteogenesis remain unclear. We examined whether epigenetic modifications mediated by the long-noncoding RNA (lncRNA) NR&#95;045147, which plays a crucial role in cancer, influence the osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Alkaline phosphatase staining, alizarin red staining, and western blotting were used to detect the effects of NR&#95;045147 on PDLSC osteogenic differentiation. Scratch migration and transwell chemotaxis assays were used to evaluate the effects of NR&#95;045147 on PDLSC migration. Mitochondrial function was evaluated via Seahorse XF analysis to measure changes in cellular respiration upon manipulation of NR&#95;045147 expression. Ubiquitination assays were performed to examine the protein stability and degradation pathways affected by the NR&#95;045147-MDM2 interaction. An in vivo nude rat calvarial defect model was established and gene-edited PDLSCs were re-implanted to examine the osteogenic effects of NR&#95;045147. NR&#95;045147 significantly reduced PDLSC osteogenic differentiation and migration ability both in vitro and in vivo. Under inflammatory conditions, the loss of NR&#95;045147 rescued osteogenesis. NR&#95;045147 significantly blocked the expression of integrin beta3-binding protein (ITGB3BP). Mechanistically, NR&#95;045147 promoted the ITGB3BP-MDM2 interaction, thus increasing ITGB3BP ubiquitination and degradation. NR&#95;045147 regulated PDLSC mitochondrial respiration and ITGB3BP upregulation efficiently promoted their osteogenic differentiation and migration ability. Concluding, NR&#95;045147 downregulation enhances PDLSC osteogenic differentiation and migration, connects changes in cellular metabolism to functional outcomes via mitochondrial respiration, and promotes ITGB3BP degradation by mediating its interaction with MDM2., (© The Author(s) 2024. Published by Oxford University Press.)

Mitophagy is a highly precise process of selective autophagy, primarily aimed at eliminating excess or damaged mitochondria to maintain the stability of both mitochondrial and cellular homeostasis. In recent years, with in-depth research into the association between mitophagy and fibrotic diseases, it has been discovered that this process may interact with crucial cellular biological processes such as oxidative stress, inflammatory responses, cellular dynamics regulation, and energy metabolism, thereby influencing the occurrence and progression of fibrotic diseases. Consequently, modulating mitophagy holds promise as a therapeutic approach for fibrosis. Currently, various methods have been identified to regulate mitophagy to prevent fibrosis, categorized into three types: natural drug therapy, biological therapy, and physical therapy. This review comprehensively summarizes the current understanding of the mechanisms of mitophagy, delves into its biological roles in fibrotic diseases, and introduces mitophagy modulators effective in fibrosis, aiming to provide new targets and theoretical basis for the investigation of fibrosis-related mechanisms and disease prevention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cui, Zhou, Tu, Wu, Zhou, Yi, Liu and Dai.)

Modeling and remodeling are essential processes in the development and refinement of maxillofacial bones. Dysregulated bone modeling during the developmental stage may lead to maxillofacial bone malformations and malocclusion. Bone remodeling under mechanical loading serves as the biological basis for orthodontic treatment. Although previous reviews have indicated the significance of microRNAs (miRNAs) in bone metabolism, their roles in orchestrating maxillofacial bone modeling and remodeling remain unclear. This review aims to discuss the mechanisms by which miRNAs regulate the morphogenesis and development of maxillofacial bones, as well as their implications for maxillofacial malformations and malocclusion. Moreover, miRNAs participating in maxillofacial bone remodeling and their impacts on cell mechanosensing are also summarized. Given the intricate interplay of cells and signaling pathways, exosomal miRNAs emerge as the orchestrators of the modeling and remodeling processes. The diagnostic and therapeutic potentials of miRNAs are also highlighted in this review for future clinical applications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Zhang and Liu.)

Oral submucous fibrosis is a chronic, inflammatory and potentially malignant oral disease. Local delivery of triamcinolone to lesion site is a commonly used therapy. The existing methods for local drug delivery include topical administration and submucosal injection. However, in the wet and dynamic oral microenvironment, these methods have drawbacks such as limited drug delivery efficiency and injection pain. Therefore, it is urgently needed to develop an alternative local drug delivery system with high efficiency and painlessness. Inspired by the structure of band-aid, this study proposed a novel double-layered mucoadhesive microneedle patch for transmucosal drug delivery. The patch consisted of a mucoadhesive silk fibroin/tannic acid top-layer and a silk fibroin microneedle under-layer. When applying the annealing condition for the medium content of β-sheets of silk fibroin, the microneedles in under-layer displayed both superior morphology and mechanical property. The mechanical strength of per needle (0.071N) was sufficient to penetrate the oral mucosa. Sequentially, the gelation efficiency of silk fibroin and tannic acid in top-layer was maximized as the weight ratio of tannic acid to silk fibroin reached 5:1. Moreover, in vitro results demonstrated the double-layered patch possessed undetectable cytotoxicity. The sustained release of triamcinolone was observed from the double-layered patch for at least 7 days. Furthermore, compared with other commercial buccal patches, the double-layered patch exhibited an enhanced wet adhesion strength of 37.74 kPa. In addition, ex vivo mucosal tissue penetration experiment confirmed that the double-layered patch could reach the lamina propria, ensuring effective drug delivery to the lesion site of oral submucous fibrosis. These results illustrate the promising potential of the drug-loaded mucoadhesive microneedle patch for the treatment of oral submucous fibrosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cheng, Yang, Liao, Yi, Zhou, Dai, Liu and Liu.)

A large number of studies in China and other countries have confirmed that circularHIPK3 (circHIPK3) plays an important role in the pathophysiological processes of various diseases. Through the action of sponge miRNA (miR), circHIPK3 regulates cell proliferation, differentiation, and migration, and plays a key role in disease processes. By referring to a large number of research reports, this article explores the specific functional role of circHIPK3 in fibrotic diseases, cancer, and other diseases. This review aims to clarify the role of circHIPK3 in disease processes in order to aid further studies into the specific pathogenesis and clinical diagnosis of various diseases and provide new ideas for treatments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhou, Wang, Bin, Xie, Li, Liu and Tang.)

It has been proven that the surface topographic cues of fiber arrangement can induce osteogenic differentiation of mesenchymal stem cells. However, this effect alone is weak and insufficient to meet the needs of regenerative medicine. In this work, electroactivity concept was introduced to enhance the osteoinductivity of fibrous scaffolds. The randomly oriented and aligned electroactive fibrous scaffolds of poly-(l-lactic acid) (PLLA) with incorporation of ferroelectric ceramic BaTiO 3 (BTO) nanoparticles (NPs) were fabricated by electrospinning. Physicochemical properties, including fiber morphology, microstructure, composition, thermal stability, surface roughness, and surface wettability, of these fibrous scaffolds were studied. The dielectric properties of the scaffolds were evaluated. The results showed that the randomly oriented BTO/PLLA composite fibrous scaffolds had the highest dielectric permittivity of 1.19, which is of the same order of magnitude as the natural bone. The combined effects of fiber orientation and electrical activity on the osteogenic responses of bone marrow mesenchymal stem cells (BM-MSCs) were specifically investigated. Randomly oriented composite fibrous scaffolds significantly promoted polygonal spreading and encouraged early osteogenic differentiation in BM-MSCs, whereas aligned composite fibrous scaffolds promoted cell elongation and discouraged osteogenic differentiation. These results evidenced that randomly fiber orientation and biomimetic electric activity have combining effects on osteogenic differentiation of BM-MSCs. Our findings indicate that coupling effects of multi-physical properties should be paid more attention to mimic the microenvironment for enhancing osteogenic differentiation of BM-MSCs., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Purpose: Squamous cell carcinoma (SCC) is the most prevalent malignant neoplasm of the oral cavity and oral verrucous carcinoma (OVC) is a verrucous variant of SCC. The purpose of this study was to examine the clinical classification of OVC and see for any difference in the biological behavior between OVC and CSS., Methods: OVC and SCC were divided into 5 groups: the exogenic type of OVC (eOVC), cystoid type of OVC (cOVC) and infiltrative type of OVC (iOVC); well differentiated SCC (wdSCC), and medium/poorly differentiated SCC (m/pdSCC). A normal mucosa (NM) group was also created and studied. Stereology was used to measure and describe the morphological parameters of the nucleus to cytoplasm ratio (Vnp), desmosomes, mitochondria, etc. Analysed were also the nucleus volume density (Vv), Vnp, desmosomes and intracellular desmosomes number density (Nv), which were observed by stereology., Results: We noticed some statistically significant differences in the morphological parameters among the 6 groups including the Vv (p<0.05), the Vnp (p<0.05), the number density of desmosomes (p<0.05), and the Nv (p<0.05)., Conclusion: This study provides a theoretical basis for the clinical diagnosis and therapy of OVC.

αB-crystallin, a member of the small heat shock protein family, acts as a molecular chaperone. αB-crystallin has been found to be overexpressed in a number of cancer tissues, including head and neck cancers. Overexpression of αB-crystallin in cancer tissue may be related to its anti-apoptotic properties; however, its mechanism of action remains unclear. The aim of this study was to investigate the anti-apoptotic role of αB-crystallin in oral verrucous carcinoma (OVC). Since oral squamous cell carcinoma (OSCC) is the most common tumor of the oral cavity, we selected OSCC as a control group. Immunohistochemical staining was used to evaluate the expression levels. The results showed that the expression of αB-crystallin was detected in OVC, OSCC and normal oral mucosa (NM). The expression in OVC was higher compared to that of NM, but lower compared to OSCC, indicating that OVC was less aggressive than OSCC with respect to malignancy potential. Furthermore, we found that in OVC, the increased expression of αB-crystallin coincided with the decreased expression of activated caspase-3. The results indicated that αB-crystallin may play an anti-apoptotic role via inhibition of the activation of caspase-3 in OVC.