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1.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1006866

ABSTRACT

Objective@#To explore an accurate method to obtain an intraoral model of patients with specific limited mouth opening (microstomia) due to systemic scleroderma.@*Methods@#This study followed medical ethics, and informed consent has been obtained from patients. A case of Ken's Type I mandibular dentition defect scleroderma with limited mouth opening was addressed with digital technology as the leading method combined with the traditional impression method of segmental impression. Individual trays were made based on the patient's left and right mandibular dentition, and segmented molds were obtained. Simultaneously, intraoral scanning was performed to obtain the morphological data of both the soft and hard tissues of the upper and lower mandibles. After each part of the model was obtained, the mandibular model was scanned and digitally aligned to form the final denture model, and the final removable partial denture was designed and made by computer aided design/computer aided manufacturing (CAD/CAM) technology. At the same time, combined with the literature, the diagnosis and treatment of removable partial denture in patients with limited mouth opening were retrospectively analyzed.@*Results@#The denture was well retained and achieved a good repair effect. The patients expressed satisfaction with the mastication efficiency and other functions of the denture. The findings of the literature review show that the integration of digital technology with the traditional impression method, along with computer fitting, can accurately obtain the patient's oral model and facilitate successful follow-up repairs. However, when the anterior mandibular dentition of the patient is absent, the margin of error is increased in this procedure, which deserves further exploration.@*Conclusion@#Utilizing digital technology as the leading method, combined with the traditional impression method of segmental impression, for the repair of dental defects in patients with limited mouth opening, has proven to be effective. Thus, patients report a positive medical experience with high satisfaction, indicating that this approach is worthy of clinical promotion.

2.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1003446

ABSTRACT

Objective@#To investigate the effect of the socket-shield technique (SST) concurrent with immediate implant placement and provisionalization (IIPP) in the aesthetic restoration of anterior teeth.@*Methods@#A case of maxillary anterior tooth stumps with a thin labial bone wall was treated with SST for preservation of labial soft and hard tissue fullness, combined with an immediate implant placement and immediate provisional crown for restoring the shape of the tooth and gingival molding@*Results@#Immediate implant placement and provisionalization restored the morphology and function of the affected tooth in the shortest possible time. The patient's labial soft and hard tissue contours in the affected tooth area were well preserved in the 18-month follow-up after the application of the SST, which presented a better aesthetic result. The literature review indicates that the indications for SST are unrestorable maxillary anterior teeth, whose dental, periodontal and periapical tissues are healthy and intact. In the esthetic zone, root shielding is effective in maintaining the soft and hard tissue contour on the labial side of the implant. However, there is no consensus on the technical details of SST, such as the ideal coronal height and thickness of the shield, and the management of the gap between the shield and the implant. Thus, more clinical studies and histologic evidence are needed to provide a reference for clinical decision-making. In addition, digital technology can improve the accuracy of implant placement and shield preparation.@*Conclusion@#The correct application of SST combined with IIPP in the esthetic zone can ensure esthetic results. However, more high-quality evidence-based medical evidence is needed for its long-term efficacy, and indications should be strictly controlled during clinical application.

3.
Biomaterials ; 303: 122355, 2023 12.
Article in English | MEDLINE | ID: mdl-37948855

ABSTRACT

Diabetic infectious microenvironment (DIME) frequently leads to a critical failure of osseointegration by virtue of its main peculiarities including typical hyperglycemia and pathogenic infection around implants. To address the plaguing issue, we devise a glucose-primed orthopedic implant composed of polyetheretherketone (PEEK), Cu-chelated metal-polyphenol network (hauberk coating) and glucose oxidase (GOx) for boosting diabetic osseointegration. Upon DIME, GOx on implants sostenuto consumes glucose to generate H2O2, and Cu liberated from hauberk coating catalyzes the H2O2 to highly germicidal •OH, which massacres pathogenic bacteria through photo-augmented chemodynamic therapy. Intriguingly, the catalytic efficiency of the coating gets greatly improved with the turnover number (TON) of 0.284 s-1. Moreover, the engineered implants exhibit satisfactory cytocompatibility and facilitate osteogenicity due to the presence of Cu and osteopromotive polydopamine coating. RNA-seq analysis reveals that the implants enable to combat infections and suppress pro-inflammatory phenotype (M1). Besides, in vivo evaluations utilizing infected diabetic rat bone defect models at week 4 and 8 authenticate that the engineered implants considerably elevate osseointegration through pathogen elimination, inflammation dampening and osteogenesis promotion. Altogether, our present study puts forward a conceptually new tactic that arms orthopedic implants with glucose-primed antibacterial and osteogenic capacities for intractable diabetic osseointegration.


Subject(s)
Diabetes Mellitus , Osseointegration , Rats , Animals , Glucose/pharmacology , Hydrogen Peroxide/pharmacology , Polyethylene Glycols/pharmacology , Benzophenones/pharmacology , Ketones/pharmacology , Anti-Bacterial Agents/pharmacology , Osteogenesis , Diabetes Mellitus/drug therapy , Surface Properties
4.
FASEB J ; 37(8): e23046, 2023 08.
Article in English | MEDLINE | ID: mdl-37389546

ABSTRACT

Metabolic diseases are considered the primary culprit for physical and mental health of individuals. Although the diagnosis of these diseases is relatively easy, more effective and convenient potent drugs are still being explored. Ca2+ across the inner mitochondrial membrane is a vital intracellular messenger that regulates energy metabolism and cellular Ca2+ homeostasis and is involved in cell death. Mitochondria rely on a selective mitochondrial Ca2+ unidirectional transport complex (MCU complex) in their inner membrane for Ca2+ uptake. We found that the channel contains several subunits and undergoes dramatic transformations in various pathological processes, especially in metabolic diseases. In this way, we believe that the MCU complex becomes a target with significant potential for these diseases. However, there is no review linking the two factors, thus hindering the possibility of new drug production. Here, we highlight the connection between MCU complex-related Ca2+ transport and the pathophysiology of metabolic diseases, adding understanding and insight at the molecular level to provide new insights for targeting MCU to reverse metabolism-related diseases.


Subject(s)
Metabolic Diseases , Mitochondria , Humans , Biological Transport , Cell Death , Energy Metabolism
5.
J Histotechnol ; 46(3): 139-150, 2023 09.
Article in English | MEDLINE | ID: mdl-37184352

ABSTRACT

Diabetes and periodontitis are prevalent diseases that considerably impact global economy and diabetes is a major risk factor of periodontitis. Mitochondrial dynamic alterations are involved in many diseases including diabetes and this study aims to evaluate their relevance with diabetes aggravated periodontitis. Sixty mice are randomly divided into 4 groups: control, periodontitis, diabetes and diabetic periodontitis. Periodontitis severity is evaluated by alveolar bone loss, inflammation and oxidative stress status. Mitochondrial structural and functional defects are evaluated by the mitochondrial fission/fusion events, mitochondrial reactive oxygen species (ROS) accumulation, complex activities and adenosine triphosphate (ATP) production. Advanced glycation end product (AGE) and Porphyromonas gingivalis are closely related to periodontitis occurrence and development. Human gingival fibroblast cells (HGF-1) are used to investigate the AGE role and lipopolysaccharide (LPS) from Porphyromonas gingivalis (P-LPS) in aggravating diabetic periodontitis by mitochondrial dynamic and function alterations. In vivo, diabetic mice with periodontitis show severe bone loss, increased inflammation and oxidative stress accumulation. Among mice with periodontitis, diabetic mice show worse mitochondrial dynamic perturbations than lean mice, along with fusion protein levels inducing more mitochondrial fission in gingival tissue. In vitro, AGEs and P-LPS co-treatment causes severe.


Subject(s)
Diabetes Mellitus, Experimental , Periodontitis , Mice , Humans , Animals , Mitochondrial Dynamics , Diabetes Mellitus, Experimental/complications , Lipopolysaccharides/metabolism , Lipopolysaccharides/pharmacology , Periodontitis/etiology , Periodontitis/metabolism , Inflammation , Porphyromonas gingivalis/chemistry , Porphyromonas gingivalis/metabolism
6.
J Nanobiotechnology ; 21(1): 119, 2023 Apr 05.
Article in English | MEDLINE | ID: mdl-37020301

ABSTRACT

BACKGROUND: Sustained release of bioactive BMP2 (bone morphogenetic protein-2) is important for bone regeneration, while the intrinsic short half-life of BMP2 at protein level cannot meet the clinical need. In this study, we aimed to design Bmp2 mRNA-enriched engineered exosomes, which were then loaded into specific hydrogel to achieve sustained release for more efficient and safe bone regeneration. RESULTS: Bmp2 mRNA was enriched into exosomes by selective inhibition of translation in donor cells, in which NoBody (non-annotated P-body dissociating polypeptide, a protein that inhibits mRNA translation) and modified engineered BMP2 plasmids were co-transfected. The derived exosomes were named ExoBMP2+NoBody. In vitro experiments confirmed that ExoBMP2+NoBody had higher abundance of Bmp2 mRNA and thus stronger osteogenic induction capacity. When loaded into GelMA hydrogel via ally-L-glycine modified CP05 linker, the exosomes could be slowly released and thus ensure prolonged effect of BMP2 when endocytosed by the recipient cells. In the in vivo calvarial defect model, ExoBMP2+NoBody-loaded GelMA displayed great capacity in promoting bone regeneration. CONCLUSIONS: Together, the proposed ExoBMP2+NoBody-loaded GelMA can provide an efficient and innovative strategy for bone regeneration.


Subject(s)
Exosomes , Hydrogels , Bone Regeneration , Delayed-Action Preparations/metabolism , Exosomes/metabolism , Hydrogels/pharmacology , Osteogenesis , RNA, Messenger/metabolism , Bone Morphogenetic Protein 2/metabolism
7.
RSC Adv ; 13(3): 1558-1566, 2023 Jan 06.
Article in English | MEDLINE | ID: mdl-36688070

ABSTRACT

Hydrogels are crosslinked hydrophilic polymer networks of high-water content. Although they have been widely investigated, preparing hydrogels with excellent mechanical properties and biocompatibility remains a challenge. In the present work, we developed a novel GelMA/κ-carrageenan (GelMA/KC) double network (DN) hydrogel through a dual crosslinking strategy. The three-dimensional (3D) microstructure of KC is the first network, and covalently crosslinked on the κ-carrageenan backbone is the second network. The GelMA/KC hydrogel shows advantages in physical properties, including higher compression strength (10% GelMA/1% KC group, 130 kPa) and Young's modulus (10% GelMA/1% KC group, 300), suggesting its excellent elasticity and compressive capability. When using a higher concentration of GelMA, the hybrid hydrogel has even higher mechanical properties. In addition, the GelMA/KC hydrogel is favorable for cell spreading and proliferation, demonstrating its excellent biocompatibility. This study provides a new possibility for a biodegradable and high-strength hydrogel as a new generation material of orthopedic implants.

8.
Exp Physiol ; 108(3): 398-411, 2023 03.
Article in English | MEDLINE | ID: mdl-36648334

ABSTRACT

NEW FINDINGS: What is the topic of this review? In this review, we consider the key role of mitochondria in the peri-implant milieu, including the regulation of mitochondrial reactive oxygen species and mitochondrial metabolism in angiogenesis, the polarization of macrophage immune responses, and bone formation and bone resorption during osseointegration. What advances does it highlight? Mitochondria contribute to the behaviours of peri-implant cell lines based on metabolic and reactive oxygen species signalling modulations, which will contribute to the research field and the development of new treatment strategies for improving implant success. ABSTRACT: Osseointegration is a dynamic biological process in the local microenvironment adjacent to a bone implant, which is crucial for implant performance and success of the implant surgery. Recently, the role of mitochondria in the peri-implant microenvironment during osseointegration has gained much attention. Mitochondrial regulation has been verified to be essential for cellular events in osseointegration and as a therapeutic target for peri-implant diseases in the peri-implant microenvironment. In this review, we summarize our current knowledge of the key role of mitochondria in the peri-implant milieu, including the regulation of mitochondrial reactive oxygen species and mitochondrial metabolism in angiogenesis, the polarization of macrophage immune responses, and bone formation and resorption during osseointegration, which will contribute to the research field and the development of new treatment strategies to improve implant success. In addition, we indicate limitations in our current understanding of the regulation of mitochondria in osseointegration and suggest topics for further study.


Subject(s)
Bone Resorption , Bone and Bones , Humans , Reactive Oxygen Species , Osteogenesis/physiology , Osseointegration/physiology , Mitochondria
9.
Nanoscale ; 15(2): 609-624, 2023 Jan 05.
Article in English | MEDLINE | ID: mdl-36503969

ABSTRACT

The treatment of festering pathogenic bacteria-induced skin wounds with increased inflammation is an ongoing challenge. The traditional antibacterial photothermal therapy always results in localized hyperthermia (over 50 °C), which inevitably delays tissue recovery. To address this serious issue, we devise a novel photonic hydrogel by integrating urchin-like Bi2S3 nano-heterojunctions (nano-HJs) into double-network hydrogels for infected skin regeneration. The synergy of NIR-triggered heat and ROS enables the hydrogels to achieve a rapid germicidal efficacy against bacteria within 15 min at mild temperature (below 50 °C). In vitro cell analysis results revealed that the photonic hydrogels exhibit superior cytocompatibility even after NIR illumination. More importantly, an in vivo study demonstrated that the photonic hydrogel dressings have a robust ability of accelerating contagious full-thickness wound regeneration through debriding abscesses, eliminating pathogens, improving collagen deposition, promoting angiogenesis, and adjusting the inflammation state. This photonic hydrogel system provides a general management strategy for the remedy of infectious wounds, where the incorporation of nano-HJs endows the hydrogels with the photodisinfection ability; in addition, the multifunctional hydrogels alleviate the damage from overwhelming heat towards surrounding tissues during phototherapy and steer the inflammation during the process of tissue regeneration. Accordingly, this work highlights the promising application of the photonic hydrogels in conquering refractory pathogen-invaded infection.


Subject(s)
Bacteria , Hydrogels , Humans , Hydrogels/pharmacology , Phototherapy , Inflammation/therapy , Anti-Bacterial Agents/pharmacology , Bandages
10.
Am J Physiol Cell Physiol ; 323(4): C1149-C1160, 2022 Oct 01.
Article in English | MEDLINE | ID: mdl-36036451

ABSTRACT

High-mobility group box 1 (HMGB1) not only induces cell proliferation and migration but also promotes cell apoptosis and autophagy. Abnormal expression of HMGB1 in plasma or body fluids could be detected in the occurrence and development of inflammation, cardiovascular disease, immune diseases, and cancer. In recent years, the accumulating research on lncRNAs had led us to the important role of lncRNAs in finely regulating the expression of molecules. Nevertheless, the roles of lncRNAs in upregulating HMGB1 and its receptors remain elusive. This article systematically summarizes the lncRNAs related to HMGB1 and its essential receptors such as RAGE. Multiple lncRNAs, such as lncRNA MALAT1 were proposed to regulate HMGB1 and its receptors upstream. As HMGB1-related diseases were summarized, we also expected predictable application prospects of both HMGB1 and related lncRNAs. The in-depth research focusing on lncRNAs behind HMGB1 and its receptors might provide a novel foundation for therapeutic treatment of HMGB1-related disorders, together with targets regarding HMGB1.


Subject(s)
HMGB1 Protein , MicroRNAs , RNA, Long Noncoding , Cell Proliferation/genetics , HMGB1 Protein/genetics , MicroRNAs/genetics , Molecular Biology , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism
11.
J Nanobiotechnology ; 20(1): 385, 2022 Aug 23.
Article in English | MEDLINE | ID: mdl-35999549

ABSTRACT

BACKGROUND: Exosomes are recognized as effective platforms for targeted delivery for their high physicochemical stability and biocompatibility. However, most of the exosomes are inevitably and rapidly cleared by mononuclear phagocytic system (MPS) during cancer therapy. How to engineer exosome to enhance the delivery efficiency is being intensively explored. In this study, we have constructed mPEG2000-TK-CP05 decorated exosomes as effective delivery platforms to achieve enhanced photodynamic/chemical cancer therapy. RESULTS: Exosomes were coated with CP05-TK-mPEG2000, in which CP05 is a peptide with high affinity to exosomal CD63 and TK could be cleaved by ROS. The resulted exosomes, namely stealth Exo, were electroporated to load RB (photosensitizer Rose Bengal) and Dox (Doxorubicin). We verified that the Stealth Exo@RB (Stealth Exo additionally loaded with RB) could escape MPS while accumulate in the tumor region efficiently in the xenograft model when laser irradiation conducted locally. Additionally, we revealed that the Stealth Exo serves as an efficient platform for Dox delivery. Dox, together with the RB mediated photodynamic therapy induce tumor cell damage synergistically in the tumor region. Moreover, the proposed switchable stealth exosomes minimized the dose of toxic Dox and thus allowed robust tumor immune response. CONCLUSIONS: Our results indicated that the proposed Stealth Exo greatly improves both the accessibility and efficiency of drug delivery, with minimal chemical or genetic engineering. The proposed Stealth Exo serve as a promising and powerful drug delivery nanoplatform in cancer treatment.


Subject(s)
Exosomes , Neoplasms , Photochemotherapy , Cell Line, Tumor , Doxorubicin , Drug Delivery Systems , Humans , Neoplasms/drug therapy , Reactive Oxygen Species
12.
Oxid Med Cell Longev ; 2022: 7702681, 2022.
Article in English | MEDLINE | ID: mdl-35571239

ABSTRACT

The M2 isoform of pyruvate kinase (PKM2) is one isoform of pyruvate kinase (PK). PKM2 is expressed at high levels during embryonic development and tumor progression and is subject to complex allosteric regulation. PKM2 is a special glycolytic enzyme that regulates the final step of glycolysis; the role of PKM2 in the metabolism, survival, and apoptosis of cancer cells has received increasing attention. Mitochondria are directly or indirectly involved in the regulation of energy metabolism, susceptibility to oxidative stress, and cell death; however, the role of PKM2 in mitochondrial functions remains unclear. Herein, we review the related mechanisms of the role of PKM2 in the regulation of mitochondrial functions from the aspects of metabolism, reactive oxygen species (ROS), dynamic, and apoptosis, which can be highlighted as a target for the clinical management of cardiovascular and metabolic diseases.


Subject(s)
Mitochondria , Pyruvate Kinase , Apoptosis , Glycolysis/physiology , Mitochondria/metabolism , Oxidative Stress , Protein Isoforms/metabolism , Pyruvate Kinase/metabolism
13.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-923483

ABSTRACT

Objective@# To investigate the adverse reactions of resin cement used for dentin bonding and its influencing factors.@*Methods@# Patients with dental defects treated with resin cement dentin adhesive for direct composite resin repair or full crown indirect repair were selected as the research objects. The occurrence and causes of adverse reactions, such as dental pulp lesions, soft tissue adverse reactions, and restoration loosening and falling off 7 days, 1 month, 3 months, 6 months, and 1 year after treatment, were analyzed retrospectively.@*Results @# Among the 14 776 teeth of 5 971 patients who used resin cement dentin adhesive, 580 cases (3.93%) had adverse reactions. Univariate analysis showed that the incidence of adverse events was highest in teeth with the "full crowns (fixed partial dentures)" restoration type at 7 days, 1 month, and 12 months after treatment. At 7 days after treatment, the incidence of adverse events was the highest in teeth with a preparation depth of "near pulp after preparation". At 7 days and 3 months after treatment, the incidence of adverse events was the highest in teeth with " dentin conditioner-adhesive-resin" treatment of the bonding surface. Multivariate analysis indicated that pulp perforation and pulp capping after tooth preparation were risk factors for adverse events 7 days after treatment (OR=2.610), and the “dentin primer-adhesive-resin” bonding surface treatment method was a protective factor for adverse events 7 days and 3 months after treatment (OR<1). @*Conclusion@#affect the occurrence of adverse events. pulp perforation, and pulp capping after tooth preparation, and self-etching bonding may contribute to adverse reactions.

14.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-904735

ABSTRACT

Objective@#To explore the application effect of a four-dimensional smile design as the leading and facial streamline as the reference system in the aesthetic restoration of anterior teeth.@*Methods@# A case of scattered space in anterior teeth was treated with a four-dimensional smile design and digital aesthetic restoration with ultrathin porcelain veneer. The digital information of the patients was obtained through oral and facial scanning, and a four-dimensional smile design and prediction were carried out. After the treatment plan was jointly determined by doctors and patients, minimally invasive abutment preparation was carried out, and ultrathin porcelain veneer was made and bonded in place. After the operation, the esthetic degree and marginal fit were observed and reexamined one year after the repair.@* Results @#The edges of the ultrathin ceramic veneers were naturally tight, and the color was coordinated, with satisfying pink and white esthetics. The face was more harmonious and natural when smiling. One year after the restoration, the facial aesthetics were wonderful, the abutment teeth and periodontal tissues were healthy, and the patients were satisfied. The results of the literature review showed that the fitting of temporal facial scanning and intraoral scanning data can accurately predict four-dimensional smile aesthetics, simulate the real state of the dynamic smile and pronunciation process, and combine it with facial streamlines to design a natural and coordinated personalized smile for patients with asymmetric faces. However, for patients with occlusal changes, unstable occlusion or temporomandibular joint disorder, it is necessary to add data fitting, such as electronic facial arch and cone beam CT, to more accurately simulate postoperative mandibular movement.@*Conclusion@# With a four-dimensional smile design as the leading and facial streamline as the reference system, the whole process digital design assisted the restoration of asymmetric anterior teeth with ultrathin porcelain veneer and had a good effect. The postoperative smiling of patients is harmonious and beautiful, which is in line with the expected effect. Patient participation and satisfaction are high; thus, this method is worthy of clinical promotion.

15.
Small ; 17(50): e2103993, 2021 12.
Article in English | MEDLINE | ID: mdl-34713567

ABSTRACT

Phototherapy has recently emerged as a competent alternative for combating bacterial infection without antibiotic-resistance risk. However, owing to the bacterial endogenous antioxidative glutathione (GSH), the exogenous reactive oxygen species (ROS) generated by phototherapy can hardly behave desired antibacterial effect. To address the daunting issue, a quad-channel synergistic antibacterial nano-platform of Ti3 C2 MXene/MoS2 (MM) 2D bio-heterojunctions (2D bio-HJs) are devised and fabricated, which possess photothermal, photodynamic, peroxidase-like (POD-like), and glutathione oxidase-like properties. Under near-infrared (NIR) laser exposure, the 2D bio-HJs both yield localized heating and raise extracellular ROS level, leading to bacterial inactivation. Synchronously, Mo4+ ions can easily invade into ruptured bacterial membrane, arouse intracellular ROS, and deplete intracellular GSH. Squeezed between the "ROS hurricane" from both internal and external sides, the bacteria are hugely slaughtered. After being further loaded with fibroblast growth factor-21 (FGF21), the 2D bio-HJs exhibit benign cytocompatibility and boost cell migration in vitro. Notably, the in vivo evaluations employing a mouse-infected wound model demonstrate the excellent photonic disinfection towards bacterial infection and accelerated wound healing. Overall, this work provides a powerful nano-platform for the effective regeneration of bacteria-invaded cutaneous tissue using 2D bio-HJs.


Subject(s)
Molybdenum , Titanium , Animals , Bacteria , Disinfection , Intercellular Signaling Peptides and Proteins , Mice , Regeneration
16.
J Periodontal Res ; 56(6): 1163-1173, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34591326

ABSTRACT

BACKGROUND: Sirtuin 3 (SIRT3), a mitochondrial NAD+ -dependent deacetylase, has received much attention for its effect on metabolism and aging. However, the role of SIRT3 in periodontal disease remains unknown. OBJECTIVE: This study aimed to investigate the functional role of SIRT3 in age-related periodontal disease and underlying mechanisms. METHODS: Sixteen mice were randomly assigned into four groups: the young wild type (WT), the aged WT, the young SIRT3-knockout (KO), and the aged SIRT3-KO. SIRT3 and cyclophilin D (CypD) expression and protein lysine acetylation levels in alveolar bones were detected by western blot. The bone architecture and the distance of CEJ-ABC were assessed using micro-CT and HE staining. The osteoclast number was observed through tartrate-resistant acid phosphatase (TRAP) staining. Mitochondrial morphology in SIRT3 knockdown MC3T3-E1 osteoblastic cells was analyzed by Immunofluorescence staining. In gingival tissues, the NAD+ /NADH ratio was measured, and oxidative stress was detected by MitoSOX staining, HO-1 staining, and MnSOD expression. Mitochondrial biogenesis was measured by PGC-1α expression and oxygen consumption rate (OCR). RESULTS: In parallel with the imbalanced NAD+ /NADH ratio, the SIRT3 expression was significantly decreased in the alveolar bones of the aged mice, accompanied by a global elevation of protein acetylation levels. The aged SIRT3-KO group showed the highest rate of bone resorption and the largest number of TRAP-positive osteoclasts among the four groups. Moreover, the reactive oxygen species level was up-regulated in the young and the aged SIRT3-KO groups. SIRT3 deficiency promoted mitochondrial fission and increased the CypD expression. Furthermore, the lack of SIRT3 reduced the PGC-1α expression in gingival tissues and exhibited a significant reduction in maximal OCR. CONCLUSION: Reduced SIRT3 abundance contributes to aged-related periodontal disease via the exacerbation of oxidative stress and mitochondrial dysfunction.


Subject(s)
Periodontal Diseases , Sirtuin 3 , Animals , Mice , Mitochondria , Oxidative Stress , Periodontal Diseases/metabolism , Reactive Oxygen Species/metabolism , Sirtuin 3/genetics , Sirtuin 3/metabolism
17.
Adv Sci (Weinh) ; 8(20): e2101778, 2021 10.
Article in English | MEDLINE | ID: mdl-34396715

ABSTRACT

As a chronic metabolic disease, diabetes mellitus (DM) creates a hyperglycemic micromilieu around implants, resulting inthe high complication and failure rate of implantation because of mitochondrial dysfunction in hyperglycemia. To address the daunting issue, the authors innovatively devised and developed mitochondria-targeted orthopedic implants consisted of nutrient element coatings and polyetheretherketone (PEEK). Dual nutrient elements, in the modality of ZnO and Sr(OH)2 , are assembled onto the sulfonated PEEK surface (Zn&Sr-SPEEK). The results indicate the synergistic liberation of Zn2+ and Sr2+ from coating massacres pathogenic bacteria and dramatically facilitates cyto-activity of osteoblasts upon the hyperglycemic niche. Intriguingly, Zn&Sr-SPEEK implants are demonstrated to have a robust ability to recuperate hyperglycemia-induced mitochondrial dynamic disequilibrium and dysfunction by means of Dynamin-related protein 1 (Drp1) gene down-regulation, mitochondrial membrane potential (MMP) resurgence, and reactive oxygen species (ROS) elimination, ultimately enhancing osteogenicity of osteoblasts. In vivo evaluations utilizing diabetic rat femoral/tibia defect model at 4 and 8 weeks further confirm that nutrient element coatings substantially augment bone remodeling and osseointegration. Altogether, this study not only reveals the importance of Zn2+ and Sr2+ modulation on mitochondrial dynamics that contributes to bone formation and osseointegration, but also provides a novel orthopedic implant for diabetic patients with mitochondrial modulation capability.


Subject(s)
Diabetes Mellitus/therapy , Hyperglycemia/therapy , Osseointegration/drug effects , Prostheses and Implants , Animals , Benzophenones/chemistry , Benzophenones/pharmacology , Diabetes Mellitus/metabolism , Diabetes Mellitus/pathology , Disease Models, Animal , Femur/drug effects , Femur/growth & development , Femur/pathology , Humans , Hyperglycemia/metabolism , Hyperglycemia/pathology , Membrane Potential, Mitochondrial/drug effects , Mitochondria/drug effects , Mitochondria/genetics , Mitochondrial Dynamics/drug effects , Nutrients/chemistry , Nutrients/pharmacology , Osteoblasts/drug effects , Osteogenesis/drug effects , Polyethylene Glycols/chemistry , Polyethylene Glycols/pharmacology , Polymers/chemistry , Polymers/pharmacology , Rats , Reactive Oxygen Species/metabolism , Surface Properties/drug effects , Tibia/drug effects , Tibia/growth & development , Zinc Oxide/chemistry , Zinc Oxide/pharmacology
18.
Exp Physiol ; 106(8): 1752-1761, 2021 08.
Article in English | MEDLINE | ID: mdl-34143536

ABSTRACT

NEW FINDINGS: What is the central question of this study? Does leptin have an effect on hypoxia-induced apoptosis in human periodontal ligament cells (hPDLCs), and what is the potential underlying mechanism? What is the main finding and its importance? Hypoxia induces cell apoptosis and leptin expression in hPDLCs through the induction of hypoxia-inducible factor-1α and accumulation of reactive oxygen species (ROS). Leptin shows feedback inhibition on hypoxia-induced ROS-mediated apoptosis in hPDLCs, suggesting a new application of leptin for hypoxic damage in periodontal diseases. ABSTRACT: Hypoxia-induced apoptosis of human periodontal ligament cells (hPDLCs) is an important contributor to the progression of various periodontal diseases. Although leptin has been shown to protect connective tissue cells against hypoxia-induced injury, whether it might do so by attenuating hypoxia-induced apoptosis in hPDLCs remains unclear. Here, using CoCl2 treatment, we simulated hypoxic conditions in hPDLCs and explored whether apoptosis and reactive oxygen species (ROS) levels were related to hypoxia. After small interfering RNA (siRNA) inhibition of leptin and hypoxia-inducible factor-1α (HIF-1α), the levels of apoptosis, ROS and leptin expression were measured. We showed that in CoCl2 -treated hPDLCs, significantly higher cell apoptosis rates and ROS accumulation were observed. Cobalt chloride also increased leptin and HIF-1α expression in hPDLCs. Further investigation of the pathway demonstrated that inhibition of ROS attenuated hypoxia-induced cell apoptosis and leptin expression, whereas siRNA inhibition of leptin aggravated hypoxia-induced cell apoptosis and ROS accumulation. Hypoxia induces cell apoptosis and leptin expression in hPDLCs through the induction of ROS and HIF-1α pathways, and leptin shows feedback inhibition on ROS-mediated apoptosis in hPDLCs. These findings suggest a new application of leptin for hypoxic damage in periodontal diseases.


Subject(s)
Hypoxia-Inducible Factor 1, alpha Subunit , Periodontal Ligament , Apoptosis , Cell Hypoxia/physiology , Humans , Hypoxia/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Leptin/metabolism , Periodontal Ligament/metabolism , Reactive Oxygen Species/metabolism
19.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 39(1): 115-120, 2021 Feb 01.
Article in English, Chinese | MEDLINE | ID: mdl-33723947

ABSTRACT

Many patients with large-area tooth defect need cast post-core crown restoration. However, the color defect of the cast post-core will affect the final restorative result, especially that of the anterior teeth. A new technology of color masking by applying CERAMAGE polymeric porcelain to the cast metal post-core surface improves the color of a full-ceramic restoration of anterior teeth and may provide a new alternative for the aesthetic repair of anterior teeth with a large area of defective tooth.


Subject(s)
Dental Porcelain , Post and Core Technique , Ceramics , Crowns , Esthetics, Dental , Humans
20.
J Physiol Biochem ; 77(2): 227-235, 2021 May.
Article in English | MEDLINE | ID: mdl-33635525

ABSTRACT

High mobility group box-1 (HMGB1) participates actively in oxidative stress damage, and the latter relates closely to diabetes and diabetic complications including osteoporosis, though the underlying mechanisms are elusive. This study aimed to investigate the effect of high glucose on bone marrow stromal cells (BMSCs) apoptosis and the role of HMGB1 in this process. BMSCs were isolated from 2-week-old Sprague-Dawley rats and cultured in medium containing normal glucose (NG), high glucose (HG), high glucose + glycyrrhizin (HMGB1 inhibitor, HG+GL), and high glucose + glycyrrhizin + dorsomorphin (AMPK inhibitor, HG+GL+Dm), respectively. Cell apoptosis, expression of HMGB1, AMPK, apoptotic markers, and mitochondrial functions were detected. By these approaches, we demonstrated that HG treatment significantly upregulated the expression of HMGB1 in BMSCs, which could be attenuated by GL treatment. Inhibiting HMGB1 by GL improved AMPK activation, decreased mitochondrial ROS levels, increased mitochondrial membrane potential, normalized mitochondrial fission/fusion balance, and consequently reduced apoptosis of BMSCs under HG condition. The addition of AMPK inhibitor dorsomorphin hampered this protective effect. Taken together, our data show that inhibition of HMGB1 can be an effective approach to alleviate HG-induced BMSCs apoptosis by activation of AMPK pathway and relieving mitochondrial dysfunction.


Subject(s)
AMP-Activated Protein Kinases/genetics , Apoptosis/drug effects , Glucose/pharmacology , Glycyrrhizic Acid/pharmacology , HMGB1 Protein/genetics , Osteoblasts/drug effects , AMP-Activated Protein Kinases/metabolism , Animals , Apoptosis/genetics , Cell Differentiation , Culture Media/chemistry , Culture Media/pharmacology , Gene Expression Regulation , Glucose/antagonists & inhibitors , HMGB1 Protein/antagonists & inhibitors , HMGB1 Protein/metabolism , Male , Membrane Potential, Mitochondrial/drug effects , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Mitochondria/drug effects , Mitochondria/metabolism , Osteoblasts/cytology , Osteoblasts/metabolism , Primary Cell Culture , Pyrazoles/pharmacology , Pyrimidines/pharmacology , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Signal Transduction
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