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1.
Am J Pathol ; 2024 May 16.
Article in English | MEDLINE | ID: mdl-38762116

ABSTRACT

Duchenne muscular dystrophy (DMD), caused by loss-of-function mutations in the dystrophin gene, results in progressive muscle weakness and early fatality. Impaired autophagy is one of the cellular hallmarks of DMD, contributing to the disease progression. Molecular mechanisms underlying the inhibition of autophagy in DMD are not well understood. In the current study, the DMD mouse model mdx is used for the investigation of signaling pathways leading to suppression of autophagy. Mammalian target of rapamycin complex 1 (mTORC1) is found to be hyperactive in the DMD muscles, accompanying muscle weakness and autophagy impairment. Surprisingly, Akt, a well-known upstream regulator of mTORC1, is not responsible for mTORC1 activation or the dystrophic muscle phenotypes. Instead, leucyl-tRNA synthetase (LeuRS) is found to be overexpressed in mdx muscles compared with the wild type. LeuRS is known to activate mTORC1 in a noncanonical mechanism that involves interaction with RagD, an activator of mTORC1. Disrupting LeuRS interaction with RagD by the small-molecule inhibitor BC-LI-0186 reduces mTORC1 activity, restores autophagy, and ameliorates myofiber damage in the mdx muscles. Furthermore, inhibition of LeuRS by BC-LI-0186 improves dystrophic muscle strength in an autophagy-dependent manner. Taken together, our findings uncover a noncanonical function of the housekeeping protein LeuRS as a potential therapeutic target in the treatment of DMD.

2.
J Cachexia Sarcopenia Muscle ; 14(4): 1880-1893, 2023 08.
Article in English | MEDLINE | ID: mdl-37311604

ABSTRACT

BACKGROUND: Duchenne muscular dystrophy (DMD), caused by dystrophin deficiency, leads to progressive and fatal muscle weakness through yet-to-be-fully deciphered molecular perturbations. Emerging evidence implicates RhoA/Rho-associated protein kinase (ROCK) signalling in DMD pathology, yet its direct role in DMD muscle function, and related mechanisms, are unknown. METHODS: Three-dimensionally engineered dystrophin-deficient mdx skeletal muscles and mdx mice were used to test the role of ROCK in DMD muscle function in vitro and in situ, respectively. The role of ARHGEF3, one of the RhoA guanine nucleotide exchange factors (GEFs), in RhoA/ROCK signalling and DMD pathology was examined by generating Arhgef3 knockout mdx mice. The role of RhoA/ROCK signalling in mediating the function of ARHGEF3 was determined by evaluating the effects of wild-type or GEF-inactive ARHGEF3 overexpression with ROCK inhibitor treatment. To gain more mechanistic insights, autophagy flux and the role of autophagy were assessed in various conditions with chloroquine. RESULTS: Inhibition of ROCK with Y-27632 improved muscle force production in 3D-engineered mdx muscles (+25% from three independent experiments, P < 0.05) and in mice (+25%, P < 0.001). Unlike suggested by previous studies, this improvement was independent of muscle differentiation or quantity and instead related to increased muscle quality. We found that ARHGEF3 was elevated and responsible for RhoA/ROCK activation in mdx muscles, and that depleting ARHGEF3 in mdx mice restored muscle quality (up to +36%, P < 0.01) and morphology without affecting regeneration. Conversely, overexpressing ARHGEF3 further compromised mdx muscle quality (-13% vs. empty vector control, P < 0.01) in GEF activity- and ROCK-dependent manner. Notably, ARHGEF3/ROCK inhibition exerted the effects by rescuing autophagy which is commonly impaired in dystrophic muscles. CONCLUSIONS: Our findings uncover a new pathological mechanism of muscle weakness in DMD involving the ARHGEF3-ROCK-autophagy pathway and the therapeutic potential of targeting ARHGEF3 in DMD.


Subject(s)
Dystrophin , Muscular Dystrophy, Duchenne , Animals , Mice , Dystrophin/genetics , Dystrophin/metabolism , Mice, Inbred mdx , Muscle Weakness/metabolism , Muscle, Skeletal/pathology , Muscular Dystrophy, Duchenne/genetics , Muscular Dystrophy, Duchenne/pathology
3.
Sci Robot ; 8(74): eadd1053, 2023 01 25.
Article in English | MEDLINE | ID: mdl-36652505

ABSTRACT

Bioengineering approaches that combine living cellular components with three-dimensional scaffolds to generate motion can be used to develop a new generation of miniature robots. Integrating on-board electronics and remote control in these biological machines will enable various applications across engineering, biology, and medicine. Here, we present hybrid bioelectronic robots equipped with battery-free and microinorganic light-emitting diodes for wireless control and real-time communication. Centimeter-scale walking robots were computationally designed and optimized to host on-board optoelectronics with independent stimulation of multiple optogenetic skeletal muscles, achieving remote command of walking, turning, plowing, and transport functions both at individual and collective levels. This work paves the way toward a class of biohybrid machines able to combine biological actuation and sensing with on-board computing.


Subject(s)
Robotics , Robotics/methods , Muscle, Skeletal/physiology , Electronics , Walking
4.
APL Bioeng ; 6(3): 036103, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36035771

ABSTRACT

Biohybrid robots, composed of cellular actuators and synthetic scaffolds, have garnered much attention in recent years owing to the advantages provided by their biological components. In recent years, various forms of biohybrid robots have been developed that are capable of life-like movements, such as walking, swimming, and gripping. Specifically, for walking or crawling biorobots, there is a need for complex functionality and versatile and robust fabrication processes. Here, we designed and fabricated multi-actuator biohybrid walkers with multi-directional walking capabilities in response to noninvasive optical stimulation through a scalable modular biofabrication process. Our new fabrication approach provides a constant mechanical strain throughout the cellular differentiation and maturation process. This maximizes the myotube formation and alignment, limits passive bending, and produces higher active forces. These demonstrations of the new fabrication process and bioactuator designs can pave the way for advanced multi-cellular biohybrid robots and enhance our understanding of the emergent behaviors of these multi-cellular engineered living systems.

5.
Foods ; 11(13)2022 Jun 28.
Article in English | MEDLINE | ID: mdl-35804740

ABSTRACT

This study aims to determine the immunomodulatory effects of a polysaccharide fraction from fermented M. citrifolia L. (FMP) in RAW 264.7 macrophages and Balb/c mice. M. citrifolia was fermented for 72 h using Lactobacillus brevis; polysaccharides were extracted using ethanol precipitation. The RAW 264.7 cells exposed to FMP (50, 100, and 200 µg/mL) for 24 h showed increased NO production, proinflammatory cytokine (IL-1ß, IL-6, and TNF-α) release, and COX-2 and iNOS protein expression. FMP (100, 200 mg/kg) and deacetylasperulosidic acid (DAA) (20 mg/kg) administered orally to Balb/c mice for 14 days upregulated NO production and NK cytotoxicity in abdominal cavity and spleen, respectively. Th1 and Th2 cytokines production and immune cell numbers increased in spleen, mesenteric lymph nodes (MLN), peritoneal exudate cells (PEC), Peyer's patches (PP), and peripheral blood mononuclear cells (PBMC). Therefore, FMP containing DAA can be used as materials for health functional foods to enhance immune responses.

6.
J Korean Assoc Oral Maxillofac Surg ; 48(2): 79-84, 2022 Apr 30.
Article in English | MEDLINE | ID: mdl-35491138

ABSTRACT

Objectives: The purpose of this study was to evaluate risk factors and symptoms in cemento-osseous dysplasia (COD) patients. Materials and Methods: In this study, 62 patients who were diagnosed histologically with COD were investigated from 2010 to 2020 at the author's institution. We compared clinical and radiological characteristics of symptomatic and asymptomatic patients. The factors were sex, age, lesion size, site, radiologic stage of lesion, apical involvement, sign of infection, and history of tooth extraction. Statistical analysis was performed using Fisher's exact test and the chi-square test. Results: COD was more prevalent in female patients. With the exception of three cases, all were focal COD. The majority of patients presented with symptoms when the lesion was smaller than 1.5 cm in size. Symptoms were observed when the apex of the tooth was included in the lesion or there was a local infection around the lesion. The history of tooth extraction and previous endodontic treatment were evaluated, and history was not a significant predictor for the onset of symptoms. Conclusion: In this study, risk factors associated with symptomatic patients were size of lesion, apical involvement, and local infection.

7.
Arch Orthop Trauma Surg ; 142(2): 219-226, 2022 Feb.
Article in English | MEDLINE | ID: mdl-33170353

ABSTRACT

INTRODUCTION: We compared the angle of the humerus and plate and to assess compatibility of a plate to the proximal humerus using three-dimensional (3D) printed models. MATERIALS AND METHODS: A total of 120 cases were included, who underwent anteroposterior shoulder radiographs. From these, 30 cases with 3D shoulder computed tomography scans were randomly selected to print 3D model. The lateral angle between the lateral cortex of the humeral shaft and lateral border of the greater tuberosity (GT), neck-shaft angle, and height from the most proximal point of the GT to the angular point were measured. When the plates were applied on the 3D models, the gap from the most proximal point of the GT to the proximal rim of the plate was measured. RESULTS: The mean lateral angle in plain radiographs was 12.9 ± 2.2° and height from the most proximal point of the GT to the angular point was 44.4 ± 4.7 mm. The bending angles of the three plates were 8° and 10°. Height from the proximal rim of the plate to the bending point was 42.4, 42.0 and 43.8 mm. In 98% of cases, the lateral angle of the humerus was larger than all three plates. In 43% of cases, height of the GT was smaller than height of plates. When plates were applied to the 3D model, the mean gap from GT to plate was 4.8 ± 2.8 mm. CONCLUSIONS: There was large variation in the lateral angle of the proximal humerus, which was not correlated with the neck-shaft angle. The lateral angle of the humerus was larger than the plates and prone to varus reduction and medial collapse. LEVEL OF EVIDENCE OR CLINICAL RELEVANCE: Basic science study.


Subject(s)
Shoulder Fractures , Shoulder , Bone Plates , Fracture Fixation, Internal , Humans , Humerus/diagnostic imaging , Humerus/surgery , Shoulder Fractures/diagnostic imaging , Shoulder Fractures/surgery
8.
J Korean Assoc Oral Maxillofac Surg ; 47(5): 360-364, 2021 Oct 31.
Article in English | MEDLINE | ID: mdl-34713810

ABSTRACT

OBJECTIVES: The purpose of this study was to evaluate the clinical and radiographic characteristics of idiopathic bone cavity (IBC) to determine the effect of surgical intervention on the process of healing. MATERIALS AND METHODS: All cases diagnosed with IBC during the period of 2011 to 2020 at our Department of Oral and Maxillofacial Surgery were searched. Ninety cases were retrieved. The features evaluated were sex, age, contour of the lesion, number of teeth involved, site, history of trauma, and postoperative healing pattern. The significance of differences was assessed by Mann-Whitney U test and chi-square test. RESULTS: The female:male ratio showed no predilection toward either sex (0.9:0.8). The mean age of the collected sample was 22.05±14.38 years, and the age ranged from 10 to 58 years. All cases presented in the mandible and showed well-circumscribed radiolucency. Margins were either scalloped or round in shape, and the size varied from one tooth to six teeth involvement. Seventy cases involved three or fewer roots. Three cases showed bilateral lesion. Four cases had a history of trauma at the area of the lesion. Fifty-one cases were followed for six months after surgery, and all showed increased bone density at the lesion. CONCLUSION: There is no definitive radiological or clinical feature of IBC. Considering the diversity of clinical and radiological features, such a diagnosis relies primarily on surgical findings of an empty bone cavity with no epithelial lining. Our data suggest that surgical intervention be the first choice of treatment as opposed to observation.

9.
Proc Natl Acad Sci U S A ; 118(19)2021 05 11.
Article in English | MEDLINE | ID: mdl-33941674

ABSTRACT

Tissue-on-chip systems represent promising platforms for monitoring and controlling tissue functions in vitro for various purposes in biomedical research. The two-dimensional (2D) layouts of these constructs constrain the types of interactions that can be studied and limit their relevance to three-dimensional (3D) tissues. The development of 3D electronic scaffolds and microphysiological devices with geometries and functions tailored to realistic 3D tissues has the potential to create important possibilities in advanced sensing and control. This study presents classes of compliant 3D frameworks that incorporate microscale strain sensors for high-sensitivity measurements of contractile forces of engineered optogenetic muscle tissue rings, supported by quantitative simulations. Compared with traditional approaches based on optical microscopy, these 3D mechanical frameworks and sensing systems can measure not only motions but also contractile forces with high accuracy and high temporal resolution. Results of active tension force measurements of engineered muscle rings under different stimulation conditions in long-term monitoring settings for over 5 wk and in response to various chemical and drug doses demonstrate the utility of such platforms in sensing and modulation of muscle and other tissues. Possibilities for applications range from drug screening and disease modeling to biohybrid robotic engineering.


Subject(s)
Cell Culture Techniques, Three Dimensional/methods , Imaging, Three-Dimensional/methods , Muscles/metabolism , Tissue Engineering/methods , Tissue Scaffolds/chemistry , Acetylcholine/pharmacology , Actinin/metabolism , Animals , Caffeine/pharmacology , Cell Culture Techniques, Three Dimensional/instrumentation , Cell Differentiation , Cell Line , Dantrolene/pharmacology , Mice , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Myoblasts/cytology , Myoblasts/metabolism , Myosins/metabolism , Tissue Engineering/instrumentation , Vasodilator Agents/pharmacology
10.
J Korean Assoc Oral Maxillofac Surg ; 47(1): 47-50, 2021 Feb 28.
Article in English | MEDLINE | ID: mdl-33632977

ABSTRACT

Untreated adult or elderly cleft lip and palate patients are rarely seen, but studies on delayed primary palatal closure have been performed in the less developed Asian and African countries, where access to medical care is difficult. A 64-year-old woman visited our clinic with untreated cleft palate with a 40×20-mm-wide defect in the medial palate. Two-flap palatoplasty under general anesthesia was performed to close the cleft palate. After 1 month, the result was favorable without any complications including oronasal fistula. Cleft palate primary repair in an elderly patient is rare and has some surgical problems that are associated with a wide range of defects, but good results can be obtained if surgery is performed well with appropriate considerations.

11.
Maxillofac Plast Reconstr Surg ; 43(1): 5, 2021 Feb 10.
Article in English | MEDLINE | ID: mdl-33566201

ABSTRACT

BACKGROUND: Stability of the grafted bone volume is one of the important factors to the success of alveolar bone grafts. For this, platelet-rich plasma (PRP) or fibrin sealant is mixed with the bone graft material. Bio-Oss® is a protein-free bovine mineral commonly used in bone graft procedures. The grafting particles are commonly combined with a standard fibrin sealant (Tisseel®) to fabricate a plastic implantable product. The purpose of this experiment was to evaluate the efficacy of fibrin sealant (Tisseel®) in bone regeneration performance in a rabbit maxillary sinus model. METHODS: A total of five 3.5 kg weight New Zealand white rabbits were used for the study. After elevating the sinus membrane in both maxillary sinus cavities, Bio-Oss® mixed with normal saline (group 1) was filled into the right side, and Tisseel® mixed Bio-Oss® (group 2) was inserted into the other side. The bone mineral density and bone volume were analyzed with microscopic computed tomography (micro-CT) and histomorphometric 12 weeks after application. RESULTS: Histologically, new bone formation rate was 14.8%, and grafted bone rate was 70.5% in group 1. In group 2, they were 18.5% and 60.4%, respectively. According to micro-CT analysis, bone mineral density (mg/cm3, BMD) was 2.5% larger in group 1. CONCLUSIONS: The findings from this study suggest that, although the difference in the bone formation between group 1 and group 2 appears to be insignificant, group 2 had an advantage in using smaller amount of bone substances to achieve the reliable bone formation.

12.
Dent Traumatol ; 37(3): 430-435, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33421357

ABSTRACT

BACKGROUND/AIMS: Teeth in a jaw fracture line, because of the presence of the periodontal ligament, may communicate with the oral cavity. There are no guidelines for the management of teeth in mandibular fracture lines. The aim of this study was to investigate the factors related to dental problems with teeth involved in mandibular fracture lines and to determine the best treatment option. MATERIAL AND METHODS: This retrospective study was based on the medical and radiographic records of patients with mandibular fractures. The relationships among the patient's age, gender, smoking history, amount of bony displacement, surgery, trauma-surgery period, apical involvement, tooth mobility, and periodontal status were investigated. Group comparisons were performed using the chi-squared test, Fisher's exact test, and Mann-Whitney U-test. RESULT: A total of 238 patients (247 fracture lines) with mandibular fractures including a tooth in the line of the fracture were examined. Post-operative dental complications occurred in 42 cases (17.0%). Extraction of related teeth occurred in 34 cases (80.9%) compared to eight cases (19.0%) related to root canal therapy. This study defined "dental problem" as "a case with a tooth extracted or endodontically treated after trauma." The variables associated with an increased risk of dental problems were the amount of bony displacement (p < .01), tooth mobility (p < .01), and pre-existing marginal alveolar bone loss (p = .027). CONCLUSION: The prognosis of teeth in mandibular fracture lines was related to tooth mobility, periodontal state, and the amount of bony displacement.


Subject(s)
Mandibular Fractures , Tooth Fractures , Tooth Mobility , Tooth , Humans , Mandibular Fractures/complications , Mandibular Fractures/diagnostic imaging , Prognosis , Retrospective Studies
13.
Int J Mol Sci ; 23(1)2021 Dec 25.
Article in English | MEDLINE | ID: mdl-35008651

ABSTRACT

The prevalence of atopic dermatitis (AD), a disease characterized by severe pruritus, immune imbalance, and skin barrier dysfunction, is rapidly increasing worldwide. Deacetylasperulosidic acid (DAA) has anti-atopic activity in the three main cell types associated with AD: keratinocytes, mast cells, and eosinophils. Our study investigated the anti-atopic activity of DAA in 2,4-dinitrochlorobenzene-induced NC/Nga mice. DAA alleviated the symptoms of AD, including infiltration of inflammatory cells (mast cells and eosinophils), epidermal thickness, ear thickness, and scratching behavior. Furthermore, DAA reduced serum IgE, histamine, and IgG1/IgG2a ratio and modulated the levels of AD-related cytokines and chemokines, namely interleukin (IL)-1ß, IL-4, IL-6, IL-9, IL-10, IL-12, tumor necrosis factor-α, interferon-γ, thymic stromal lymphopoietin, thymus and activation-regulated chemokine, macrophage-derived chemokine, and regulated on activation the normal T cell expressed and secreted in the serum. DAA restored immune balance by regulating gene expression and secretion of Th1-, Th2-, Th9-, Th17-, and Th22-mediated inflammatory factors in the dorsal skin and splenocytes and restored skin barrier function by increasing the expression of the pro-filaggrin gene and barrier-related proteins filaggrin, involucrin, and loricrin. These results suggest DAA as a potential therapeutic agent that can alleviate the symptoms of AD by reducing pruritus, modulating immune imbalance, and restoring skin barrier function.


Subject(s)
Dermatitis, Atopic/chemically induced , Dermatitis, Atopic/drug therapy , Dinitrochlorobenzene/adverse effects , Immunity/drug effects , Plant Extracts/pharmacology , Pruritus/drug therapy , Skin/drug effects , Animals , Anti-Inflammatory Agents/pharmacology , Chemokines/metabolism , Dermatitis, Atopic/metabolism , Filaggrin Proteins/metabolism , Inflammation/drug therapy , Inflammation/metabolism , Keratinocytes/drug effects , Keratinocytes/metabolism , Male , Mast Cells/drug effects , Membrane Proteins/pharmacology , Mice , Protein Precursors/pharmacology , Pruritus/metabolism , Skin/metabolism , T-Lymphocytes/drug effects , T-Lymphocytes/metabolism
14.
Int J Mol Sci ; 21(21)2020 Nov 09.
Article in English | MEDLINE | ID: mdl-33182361

ABSTRACT

Letrozole is a reversible nonsteroidal aromatase inhibitor that is widely used in postmenopausal breast cancer patients. It is well established that letrozole decreases bone density owing to estrogen depletion; however, few studies have reported its direct effect on bone cells in vitro. Therefore, we investigated the effect of letrozole on bone metabolism, focusing on osteoclastogenesis. Letrozole did not affect the viability, proliferation, or migration of bone marrow-derived macrophages (BMMs); however, it reduced the multinucleation of immature osteoclasts and subsequent bone resorption in vitro. Overall, letrozole inhibited the expression of dendritic cell-specific transmembrane protein (DC-STAMP), tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K. Among them, the reduced expression of DC-STAMP was the most prominent. However, this downregulation of DC-STAMP expression following letrozole treatment was not related to the inhibition of major osteoclastogenesis pathways, such as the nuclear factor-κB (NF-κB), c-Fos, and nuclear factor of activated T cell c1 (NFATc1) pathways, but was attributed to the inhibition of p38, which is known to reside upstream of DC-STAMP expression. Notably, the anti-osteoclastogenic effect of letrozole was abolished following treatment with the p38 activator anisomycin. Contrary to our expectations, these results strongly suggest a previously unknown anti-osteoclastogenic activity of letrozole, mediated by the downregulation of the p38/DC-STAMP pathway.


Subject(s)
Dendritic Cells/drug effects , Letrozole/pharmacology , Membrane Proteins/metabolism , Osteoclasts/drug effects , Signal Transduction/drug effects , p38 Mitogen-Activated Protein Kinases/metabolism , Animals , Bone Resorption/drug therapy , Bone Resorption/metabolism , Cell Differentiation/drug effects , Cell Fusion/methods , Cell Proliferation/drug effects , Dendritic Cells/metabolism , Down-Regulation/drug effects , Macrophages/drug effects , Macrophages/metabolism , Mice , Mice, Inbred ICR , NF-kappa B/metabolism , NFATC Transcription Factors/metabolism , Osteoclasts/metabolism , Osteogenesis/drug effects , Proto-Oncogene Proteins c-fos/metabolism
15.
Sci Rep ; 10(1): 12803, 2020 07 30.
Article in English | MEDLINE | ID: mdl-32733047

ABSTRACT

Biophysical studies on single cells have linked cell mechanics to physiology, functionality and disease. Evaluation of mass and viscoelasticity versus cell cycle can provide further insights into cell cycle progression and the uncontrolled proliferation of cancer. Using our pedestal microelectromechanical systems resonant sensors, we have developed a non-contact interferometric measurement technique that simultaneously tracks the dynamic changes in the viscoelastic moduli and mass of adherent colon (HT-29) and breast cancer (MCF-7) cells from the interphase through mitosis and then to the cytokinesis stages of their growth cycle. We show that by combining three optomechanical parameters in an optical path length equation and a two-degree-of-freedom model, we can simultaneously extract the viscoelasticity and mass as a function of the nano-scaled membrane fluctuation of each adherent cell. Our measurements are able to discern between soft and stiff cells across the cell cycle and demonstrated sharp viscoelastic changes due to cortical stiffening around mitosis. Cell rounding before division can be detected by measurement of mechanical coupling between the cells and the sensors. Our measurement device and method can provide for new insights into the mechanics of single adherent cells versus time.


Subject(s)
Breast Neoplasms/pathology , Cell Cycle/physiology , Colonic Neoplasms/pathology , Viscosity , Breast Neoplasms/physiopathology , Colonic Neoplasms/physiopathology , Elasticity , Female , HT29 Cells , Humans , MCF-7 Cells , Male , Mitosis
16.
Article in English | MEDLINE | ID: mdl-32386819

ABSTRACT

OBJECTIVES: The purpose of this study was to identify the characteristics of supernumerary teeth, analyze the associated complications, and to present new clinical knowledge on surgical interventions for supernumerary teeth. STUDY DESIGN: This retrospective cohort study was based on the medical records and radiographic records of patients who underwent surgical extraction of supernumerary teeth. The relationships among the patient's age, gender, anatomic features of supernumerary teeth, and presence and type of complications (i.e., spacing, rotation, delayed eruption of the adjacent tooth, cyst formation.) were investigated. The groups were compared by using the Mann-Whitney U test, the Kolmogorov-Smirnov test, and multiple logistic regression analysis (P < .05). RESULTS: The study population consisted of 705 participants who underwent extraction for 1036 supernumerary teeth. The mean age of the participants was 11.5 years, and 73.5% of the participants were males. The complication rate was 55.6%. Variables associated with an increased risk of complications were the patient's age, dentition, tuberculate shape, and horizontal direction of eruption (P < .05). CONCLUSIONS: An increase in the patient's age or abnormalities in the shape and direction of eruption of supernumerary teeth was associated with complications. These parameters should be considered while formulating the treatment plan.


Subject(s)
Tooth, Supernumerary , Child , Humans , Male , Research Design , Retrospective Studies , Tooth Eruption
17.
Int J Med Sci ; 17(5): 647-656, 2020.
Article in English | MEDLINE | ID: mdl-32210715

ABSTRACT

Connective tissue growth factor (CTGF), an extracellular matrix protein with various biological functions, is known to be upregulated in multiple chronic diseases such as liver fibrosis and congestive heart failure, but the mechanism it undertakes to cause alveolar bone loss in periodontitis remains elusive. The present study therefore investigates the pathways involving CTGF in chronic periodontitis. RNA sequencing revealed a notable increase in the expression of CTGF in chronic periodontitis tissues. Also, TRAP staining, TRAP activity and bone resorption assays showed that osteoclast formation and function is significantly facilitated in CTGF-treated bone marrow-derived macrophages (BMMs). Interestingly, western blotting and immunofluorescence staining results displayed that CTGF had little effect on the osteoclastogenic differentiation mediated by the positive regulators of osteoclastogenesis such as nuclear factor of activated T cells 1 (NFATc1). However, following results showed that both the mRNA and protein expressions of B cell lymphoma 6 (Bcl6), a transcriptional repressor of "osteoclastic" genes, were significantly downregulated by CTGF treatment. Moreover, CTGF upregulated the expressions of v-ATPase V0 subunit d2 (ATP6v0d2) and Dendritic cell-specific transmembrane protein (DC-STAMP) which are osteoclastic genes specifically required for osteoclast cell-cell fusion in pre-osteoclasts. Findings from this study suggest that CTGF promotes the fusion of pre-osteoclasts by downregulating Bcl6 and subsequently increasing the expression of DC-STAMP in periodontitis. Understanding this novel mechanism that leads to increased osteoclastogenesis in periodontitis may be employed for the development of new therapeutic targets for preventing periodontitis-associated alveolar bone resorption.


Subject(s)
Alveolar Bone Loss/etiology , Connective Tissue Growth Factor/metabolism , Osteogenesis , Periodontitis/metabolism , Proto-Oncogene Proteins c-bcl-6/metabolism , Alveolar Bone Loss/metabolism , Animals , Case-Control Studies , Female , Humans , Membrane Proteins/metabolism , Mice , Mice, Inbred ICR , Osteoclasts/metabolism , Periodontitis/complications
18.
Cells ; 9(1)2020 01 12.
Article in English | MEDLINE | ID: mdl-31940881

ABSTRACT

Dental pulp plays an important role in the health of teeth. The aging of teeth is strongly related to the senescence of dental pulp cells. A novel adipokine, visfatin, is closely associated with cellular senescence. However, little is known about the effect of visfatin on the senescence of human dental pulp cells (hDPCs). Here, it was found that in vivo visfatin levels in human dental pulp tissues increase with age and are upregulated in vitro in hDPCs during premature senescence activated by H2O2, suggesting a correlation between visfatin and senescence. In addition, visfatin knockdown by small interfering RNA led to the reduction in hDPC senescence; however, treatment with exogenous visfatin protein induced the senescence of hDPCs along with increased NADPH consumption, which was reversed by FK866, a chemical inhibitor of visfatin. Furthermore, visfatin-induced senescence was associated with both the induction of telomere damage and the upregulation of senescence-associated secretory phenotype (SASP) factors as well as NF-κB activation, which were all inhibited by FK866. Taken together, these results demonstrate, for the first time, that visfatin plays a pivotal role in hDPC senescence in association with telomere dysfunction and the induction of SASP factors.


Subject(s)
Cellular Senescence , Cytokines/metabolism , Dental Pulp/cytology , Dental Pulp/metabolism , Nicotinamide Phosphoribosyltransferase/metabolism , Adult , Cells, Cultured , Female , Humans , Male , Middle Aged , Young Adult
19.
Adv Healthc Mater ; 9(4): e1901137, 2020 02.
Article in English | MEDLINE | ID: mdl-31944612

ABSTRACT

Integration of conductive electrodes with 3D tissue models can have great potential for applications in bioelectronics, drug screening, and implantable devices. As conventional electrodes cannot be easily integrated on 3D, polymeric, and biocompatible substrates, alternatives are highly desirable. Graphene offers significant advantages over conventional electrodes due to its mechanical flexibility and robustness, biocompatibility, and electrical properties. However, the transfer of chemical vapor deposition graphene onto millimeter scale 3D structures is challenging using conventional wet graphene transfer methods with a rigid poly (methyl methacrylate) (PMMA) supportive layer. Here, a biocompatible 3D graphene transfer method onto 3D printed structure using a soft poly ethylene glycol diacrylate (PEGDA) supportive layer to integrate the graphene layer with a 3D engineered ring of skeletal muscle tissue is reported. The use of softer PEGDA supportive layer, with a 105 times lower Young's modulus compared to PMMA, results in conformal integration of the graphene with 3D printed pillars and allows electrical stimulation and actuation of the muscle ring with various applied voltages and frequencies. The graphene integration method can be applied to many 3D tissue models and be used as a platform for electrical interfaces to 3D biological tissue system.


Subject(s)
Graphite , Electric Conductivity , Electrodes , Muscle, Skeletal , Polymers
20.
Maxillofac Plast Reconstr Surg ; 41(1): 49, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31815113

ABSTRACT

BACKGROUND: The purpose of this study was to review the clinical features of oromaxillofacial infections in patients presenting to a hospital emergency ward, to identify the key factors affecting the requirement for hospitalization, and the potential risk factors predisposing to a prolonged length of hospital stay. METHODS: A retrospective medical record review of the 598 patients treated for oromaxillofacial infection from 2013 to 2017 at the oral and maxillofacial surgery department, Yangsan Pusan National University Hospital, was conducted. The following information was collected from each patient: sex, age, past medical history, site of infection, etiology, admission or outpatient care, level of C-reactive protein (mg/dL), fascial spaces involved, treatment method, and duration of hospitalization. Chi-squared tests were used to identify risk factors, which were further analyzed using multivariable logistic regression. RESULTS: A total of 606 patients were eligible for inclusion in the study, of which eight were excluded due to having incomplete charts; thus, 598 patients were included: 55% were male, mean patient age was 47.1 ± 19.9 years, and 12.9% of patients were diabetic. Furthermore, 71.2% of patients had infection originating in the mandible; the most common tooth of origin was lower posterior, and 29.8% of patients were hospitalized. Risk factors for hospital admission were elderly patients with concurrent disease, elevated C-reactive protein level, and multiple-space infection in the oromaxillofacial area. The duration of hospitalization was correlated with both diabetes and age. CONCLUSIONS: The requirement for hospital admission is determined by the severity of the infection; even severe infections, once treated with appropriate surgery, have no relation to the length of hospital stay. The important risk factors for increased duration of hospitalization are diabetes mellitus and older age. The understanding of risk factors associated with a prolonged hospital stay during the treatment of oromaxillofacial infection will aid in treatment planning as well as highlight the importance of adequate diabetes control in patients at risk of such infection.

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