Agaricus blazei Murrill Polysaccharide Attenuates Periodontitis via H2 S/NRF2 Axis-Boosted Appropriate Level of Autophagy in PDLCs.

SCOPE: Periodontitis is one of the most prevalent chronic inflammatory diseases with impaired autophagy. Agaricus blazei Murrill polysaccharide (ABMP) shows beneficial effects in various inflammatory diseases. However, whether ABMP is involved in autophagy regulation and periodontitis attenuation remains to be elucidated. METHODS AND RESULTS: This study firstly shows the dynamic changes in inflammatory and autophagy levels in silk ligature periodontitis model. Then the positive regulation effect of autophagy on inflammation and its vital role in ABMP inhibiting PDLCs inflammatory response are testified in LPS-treated PDLCs. Secondly, the Micro-CT, quantitative RT-PCR, Western Blot, TRAP, and immunofluorescence staining analysis are performed to assess the effects of ABMP on periodontitis and autophagy. The data show the augmented autophagy and alleviated gingival recession, inflammatory cell infiltration, alveolar bone resorption, and reduced osteoclasts in periodontitis by ABMP treatment. Further experiments using chemical inhibitors demonstrate the vital role of H2 S/NRF2 axis in ABMP-induced appropriate level of autophagy augmentation against periodontitis. CONCLUSIONS: Collectively, the findings not only reveal the unrecognized capacity and mechanism of ABMP as an effective and potential dietary intake against periodontitis, but also suggest the possibility for ABMP to be used in the treatment of other autophagy-related diseases.

Application of a standardized early activity program on enhanced recovery after surgery in patients after surgery for pulmonary nodules.

BACKGROUND: Early postoperative activity, an important part of enhanced recovery after surgery (ERAS) in clinical practice, is considered to be a significant component of postoperative quality care. OBJECTIVE: To evaluate the effect of a standardized early activity program on ERAS in patients after surgery for pulmonary nodules. METHODS: A total of 100 patients with pulmonary nodules who underwent a single-port thoracoscopic segmental resection or a wedge resection of the lung were selected for the present study. These patients were divided into a control group (n= 50) and an intervention group (n= 50) by a digital random method. The patients in the control group received routine perioperative nursing intervention for thoracic surgery due to lung cancer, and those in the intervention group received an intervention using a standardized early activity program along with routine nursing care. The evaluation indexes in both groups included postoperative indwelling time of the closed chest drainage tube, the time to the first off-bed activity after surgery, the incidence of postoperative pulmonary complications, the length of postoperative hospital stay, and patient satisfaction. RESULTS: The postoperative indwelling time of the closed chest drainage tube and the time to the first off-bed activity in the intervention group were less than in the control group. The length of the postoperative hospital stay in the intervention group was shorter than in the control group, and the patient satisfaction in the intervention group was higher than in the control group. The difference for these evaluation indexes were statistically significant (P< 0.05). The number of cases of postoperative complications was four and eight in the intervention group and the control group, respectively, and the difference was not statistically significant (P> 0.05). CONCLUSION: A standardized early activity program is a safe and effective nursing measure for ERAS for patients after surgery for pulmonary nodules, which can promote earlier off-bed activity, shorten the postoperative indwelling time of the closed chest drainage tube, shorten the postoperative hospital stay, improve patient satisfaction, and promote rapid recovery.

A new frontier in temporomandibular joint osteoarthritis treatment: Exosome-based therapeutic strategy.

Temporomandibular joint osteoarthritis (TMJOA) is a debilitating degenerative disease with high incidence, deteriorating quality of patient life. Currently, due to ambiguous etiology, the traditional clinical strategies of TMJOA emphasize on symptomatic treatments such as pain relief and inflammation alleviation, which are unable to halt or reverse the destruction of cartilage or subchondral bone. A number of studies have suggested the potential application prospect of mesenchymal stem cells (MSCs)-based therapy in TMJOA and other cartilage injury. Worthy of note, exosomes are increasingly being considered the principal efficacious agent of MSC secretions for TMJOA management. The extensive study of exosomes (derived from MSCs, synoviocytes, chondrocytes or adipose tissue et al.) on arthritis recently, has indicated exosomes and their specific miRNA components to be potential therapeutic agents for TMJOA. In this review, we aim to systematically summarize therapeutic properties and underlying mechanisms of MSCs and exosomes from different sources in TMJOA, also analyze and discuss the approaches to optimization, challenges, and prospects of exosome-based therapeutic strategy.

Effect of an Early Oral Food Intake Strategy on the Quality of Life of Postoperative Patients With Esophageal Cancer.

Objective: To explore the early oral food intake on the quality of life of postoperative patients with esophageal cancer. Methods: A total of 100 patients with esophageal cancer were randomized into an observation group and a control group, with 50 patients in each group. The patients in the control group were routinely indwelt with a gastric tube and fasted for seven days. If no abnormality was found in examinations, the patients were instructed to attempt drinking water and gradually try eating liquid, semi-liquid, and common foods. The patients in the observation group were subjected to the early oral food intake strategy. The recovery and gastrointestinal symptoms of the patients were evaluated using the six-minute walk test and gastrointestinal symptom rating scale (GSRS) at discharge. The quality of life of patients was evaluated using the QLQ-C30 scale and QLQ-OES18 scale during the return visit to the hospital one month after discharge. Results: The GSRS score of the observation group was markedly lower than that of the control group. The six-minute walk distance in the observation group was significantly higher than that in the control group; the difference was statistically significant (P < 0.01). In comparing the QLQ-C30 scores of the two groups, the scores in physical function, emotional function, and general health condition in the observation group were higher than those in the control group. In comparing the QLQ-OES18 scores of the two groups, the scores in dysphagia, eating, reflux, pain domains, and choking symptoms in the observation group were lower than those in the control group; the differences were statistically significant (P < 0.01), and there were no statistically significant differences in other symptoms and related functions between the two groups (P > 0.05). Conclusion: The early oral food intake strategy can reduce gastrointestinal symptoms, promote recovery of postoperative patients with esophageal cancer, and improve quality of life.

Gli1+ Mesenchymal Stem Cells in Bone and Teeth.

Mesenchymal stem cells (MSCs) are remarkable and noteworthy. Identification of markers for MSCs enables the study of their niche in vivo. It has been identified that glioma-associated oncogene 1 positive (Gli1+) cells are mesenchymal stem cells supporting homeostasis and injury repair, especially in the skeletal system and teeth. This review outlines the role of Gli1+ cells as MSC subpopulation in both bones and teeth, suggesting the prospects of Gli1 an + cells in stem cell- based tissue engineering.

Comparison and applicability of three induction methods of temporomandibular joint osteoarthritis in murine models.

BACKGROUND: Temporomandibular joint osteoarthritis (TMJ-OA) causes severe symptoms such as chewing difficulties, acute pain and even maxillofacial deformity. However, there is hardly any effective disease-curing strategy because of uncertainty in aetiology. Animal model is an excellent tool to investigate the mechanism, prevention and treatment on diseases. Currently, although several TMJ-OA animal models have been established, there are almost no comparative studies on different models, which poses a great challenge for selecting suitable models. OBJECTIVE: To compare three TMJ-OA induction methods and assess their applicability considering pathological changes in the cartilage, subchondral bone, osteoclasts, and synovium. METHODS: Murine models were employed and followed for 3 and 6 weeks after experimental procedures (surgery, injection, crossbite). The TMJ changes were evaluated by Safranin-O/Fast green staining, immunofluorescence staining, micro-CT, TRAP staining, and HE staining. RESULTS: In the Surgery group, a pronounced drop in bone volume fraction was observed. In the Injection group, chondrocytes were mostly disordered or arranged in clusters and a substantial increase in the OARSI score and osteoclasts was found. The OARSI score and osteoclasts also increased significantly in the Crossbite group, although to a lower extent compared with injection. CONCLUSION: Osteoarthritis-like changes were observed in all models. Concerning the applicability of the different induction methods, surgery might be an important resource for the assessment of post-traumatic TMJ-OA and subchondral bone changes in early stages. Injection induces a severe end-stage osteoarthritis in a short time and provides model basis for advanced TMJ-OA. Crossbite might be more reasonable model to explore the pathogenesis mechanism of temporomandibular arthritis due to occlusal disorders.

HO-1 in Bone Biology: Potential Therapeutic Strategies for Osteoporosis.

Osteoporosis is a prevalent bone disorder characterized by bone mass reduction and deterioration of bone microarchitecture leading to bone fragility and fracture risk. In recent decades, knowledge regarding the etiological mechanisms emphasizes that inflammation, oxidative stress and senescence of bone cells contribute to the development of osteoporosis. Studies have demonstrated that heme oxygenase 1 (HO-1), an inducible enzyme catalyzing heme degradation, exhibits anti-inflammatory, anti-oxidative stress and anti-apoptosis properties. Emerging evidence has revealed that HO-1 is critical in the maintenance of bone homeostasis, making HO-1 a potential target for osteoporosis treatment. In this Review, we aim to provide an introduction to current knowledge of HO-1 biology and its regulation, focusing specifically on its roles in bone homeostasis and osteoporosis. We also examine the potential of HO-1-based pharmacological therapeutics for osteoporosis and issues faced during clinical translation.

D-mannose alleviates osteoarthritis progression by inhibiting chondrocyte ferroptosis in a HIF-2α-dependent manner.

OBJECTIVES: Chondrocyte ferroptosis contributes to osteoarthritis (OA) progression, and D-mannose shows therapeutic value in many inflammatory conditions. Here, we investigated whether D-mannose interferes in chondrocyte ferroptotic cell death during osteoarthritic cartilage degeneration. MATERIALS AND METHODS: In vivo anterior cruciate ligament transection (ACLT)-induced OA mouse model and an in vitro study of chondrocytes in an OA microenvironment induced by interleukin-1ß (IL-1ß) exposure were employed. Combined with Epas1 gene gain- and loss-of-function, histology, immunofluorescence, quantitative RT-PCR, Western blot, cell viability and flow cytometry experiments were performed to evaluate the chondroprotective effects of D-mannose in OA progression and the role of hypoxia-inducible factor 2 alpha (HIF-2 α) in D-mannose-induced ferroptosis resistance of chondrocytes. RESULTS: D-mannose exerted a chondroprotective effect by attenuating the sensitivity of chondrocytes to ferroptosis and alleviated OA progression. HIF-2α was identified as a central mediator in D-mannose-induced ferroptosis resistance of chondrocytes. Furthermore, overexpression of HIF-2α in chondrocytes by Ad-Epas1 intra-articular injection abolished the chondroprotective effect of D-mannose during OA progression and eliminated the role of D-mannose as a ferroptosis suppressor. CONCLUSIONS: D-mannose alleviates osteoarthritis progression by suppressing HIF-2α-mediated chondrocyte sensitivity to ferroptosis, indicating D-mannose to be a potential therapeutic strategy for ferroptosis-related diseases.

Muscone Promotes The Adipogenic Differentiation Of Human Gingival Mesenchymal Stem Cells By Inhibiting The Wnt/ß-Catenin Signaling Pathway.

OBJECTIVES: This study was performed to evaluate the effects of muscone on the proliferation, migration and differentiation of human gingival mesenchymal stem cells (GMSCs) and to explore the relevant mechanisms. MATERIALS AND METHODS: We performed studies to determine the effects and mechanisms of muscone on GMSC proliferation, migration and differentiation. We conducted CCK-8, colony formation, transwell chamber, scratch wound, alkaline phosphatase (ALP) staining and activity, and alizarin red and oil red O staining assays, as well as real-time quantitative polymerase chain reaction (qRT-PCR), to ascertain the effects of muscone on GMSC proliferation, migration and differentiation in vitro. The mechanism by which muscone influences the osteogenic and adipogenic differentiation of GMSCs was elucidated by qRT-PCR and Western blotting. RESULTS: We found that muscone significantly promoted GMSC proliferation, chemotaxis, wound healing and fat droplet formation and inhibited ALP activity and mineral deposition. Notably, we observed that the Wnt/ß-catenin pathway was closely related to the ability of muscone to inhibit the osteogenic differentiation and promote the adipogenic differentiation of GMSCs. The effect of muscone on the multidirectional differentiation capacity of GMSCs was significantly reversed by the agonist lithium chloride through the Wnt/ß-catenin signaling pathway. CONCLUSION: Muscone effectively increased the proliferation and migration, promoted the adipogenic differentiation and inhibited the osteogenic differentiation of GMSCs by inhibiting the Wnt/ß-catenin signaling pathway. These results may provide a theoretical basis for the application of GMSCs and muscone in tissue engineering and regenerative medicine.

[Effect of osthole on periodontal remodeling during orthodontic tooth movement in rats].

PURPOSE: To investigate the effect of osthole on periodontal remodeling during orthodontic tooth movement (OTM) in rats. METHODS: Seventy two 8-week-old male SD rats were randomly equally divided into 3 groups: two experimental groups of osthole with low (20 mg/kg) and high (40 mg/kg) concentration and the control group. Models of OTM were routinely established. Rats in the experimental groups were respectively given osthole by intragastric administration, while rats in the control group received the same volume of solvent. The rats were sacrificed on 7th, 14th, 21st and 28th day after orthodontic treatment, and the maxilla was harvested and the distance between the first and second molar was measured in each stage. Hematoxylin-eosin (H-E) staining, tartrate resistant acid phosphatase (TRACP) staining were performed. The results were analyzed with SPSS 20.0 software package for one-way analysis of variance. RESULTS: The mesio-moving distance of the three groups successively increased gradually. On the 7th day, there was no difference between the low concentration group and the control group (P>0.05); at other time point, the experimental groups exhibited significant differences from the control group(P<0.05), and the high concentration group had more obviously mesio-movement than the low concentration group(P<0.05). Histological observation showed that in the tension side, osteoblast appeared, but more apparent in the experimental groups than in the control group. In the pressure side, the number of osteoclast reached the peak at the 7th day, and much more osteoclasts were seen in the experimental groups than in the control group (P<0.05), in high concentration group than in low concentration group (P<0.05). The number of osteoclast decreased subsequently, but significant difference existed between the experimental groups and the control group (P<0.05) on the 14th day. At other time points, there was no significant difference among the three groups(P>0.05). CONCLUSIONS: Osthole could increase the number of osteoclast in periodontium and promote bone remodeling at the early stage of treatment, its effect is dose-dependence during OTM.