A Portable Nucleic Acid Testing Platform with Photosensitization, a Three-Dimensionally Printed Multipiece Chip, and Digital Color Sensing.

Portable nucleic acid testing (NAT) holds great promise for point-of-care disease diagnosis and field-based applications but remains difficult to achieve. Herein, we describe a portable NAT that streamlines loop-mediated isothermal amplification with photosensitization-based color development in a fully sealed 3D-printed multipiece chip. Using a smartphone accessory and an APP, we also introduce a calibration-free quantification approach via digital color sensing and library matching. With these innovative approaches, our detection platform is highly accessible, allowing for rapid and sensitive NAT without requiring sophisticated instruments and well-trained personnel. The field applicability of our NAT platform was demonstrated by detecting tuberculosis infections in clinical sputum samples and food adulteration in commercial salmon meat products.

Construction of Zwitterionic Coatings with Lubricating and Antiadhesive Properties for Invisible Aligner Applications.

Invisible aligners have been widely used in orthodontic treatment but still present issues with plaque formation and oral mucosa abrasion, which can lead to complicated oral diseases. To address these issues, hydrophilic poly(sulfobetaine methacrylate) (polySBMA) coatings with lubricating, antifouling, and antiadhesive properties have been developed on the aligner materials (i.e., polyethylene terephthalate glycol, PETG) via a simple and feasible glycidyl methacrylate (GMA)-assisted coating strategy. Poly(GMA-co-SBMA) is grafted onto the aminated PETG surface via the ring-opening reaction of GMA (i.e., "grafting to" approach to obtain G-co-S coating), or a polySBMA layer is formed on the GMA-grafted PETG surface via free radical polymerization (i.e., "grafting from" approach to obtain G-g-S coating). The G-co-S and G-g-S coatings significantly reduce the friction coefficient of PETG surface. Protein adsorption, bacterial adhesion, and biofilm formation on the G-co-S- and G-g-S-coated surfaces are significantly inhibited. The performance of the coatings remains stable after storage in air or artificial saliva for 2 weeks. Both coatings demonstrate good biocompatibility in vitro and is not caused irritation to the oral mucosa of rats in vivo over 2 weeks. This study proposes a promising strategy for the development of invisible aligners with improved performance, which is beneficial for oral health treatment.

The coordination of bimaxillary alveolar arch widths in subjects with normal occlusion or posterior crossbite: A CBCT retrospective study.

OBJECTIVES: To propose a method for evaluating the coordination of maxillomandibular alveolar arch in transverse dimension with cone-beam computed tomography (CBCT) and to apply this method to subjects with normal occlusion at different dentition stages or transverse discrepancy. MATERIALS AND METHODS: Digital data of 130 patients with normal occlusion at different dentition stages or transverse discrepancy were collected for three-dimensional reconstruction. The patients with normal occlusion were divided into Group 1 (>16 years) and Group 2 (≤16 years) based on their age. Adult patients with posterior crossbite were divided into the Group 3. According to the proposed method, the average alveolar arch coordination angle (AACA) and other parameters were analysed in each group. Group 1 was considered as the control group and compared with Group 2 and Group 3. RESULTS: Significant differences were observed in the maxillary posterior segment width among patients with normal occlusion. Group 3 demonstrated increased AACA and mandibular alveolar arch width compared with the normal occlusion group. Pearson correlation analysis indicated a positive relationship between maxillomandibular alveolar arch widths in the normal occlusion groups, with a strong correlation between AACA and the disparity in maxillomandibular widths. CONCLUSION: Adults with normal occlusion exhibit significantly wider maxillary posterior alveolar arches than adolescents, with no marked difference in mandibular widths. The posterior crossbite group showed broader mandibular alveolar arches. There was a strong correlation between AACA and the difference in maxillomandibular widths. This study's method shows potential value for orthodontic transverse diagnosis.

Evaluation of modified clear Twin Block aligner in treating adolescents with skeletal class II malocclusion: A two-centre cephalometric study.

INTRODUCTION: The purpose of this study was to evaluate the therapeutic effect of modified clear Twin Block (CTB) aligner and traditional twin block (TB) appliance from skeletal, dentoalveolar and soft tissue changes in adolescents with skeletal class II malocclusion. METHODS: A total of 80 adolescents, included in this study from two medical centres, were distributed into CTB group, TB group and control group based on the treatment they received. Lateral cephalograms at pre-treatment (T1) and post-treatment (T2) were measured by modified Pancherz's cephalometric analysis, and dentoskeletal and soft tissue changes were analysed by independent-sample t-test, paired-sample t-test, ANOVA test and Scheffe's Post Hoc test. RESULTS: Seventy-five adolescents completed the study, including 32 in the CTB group, 32 in the TB group and 11 in the control group. Both CTB and TB treatment showed significant differences in most dentoskeletal and soft tissue measurements. Compared with the control group, improvements were observed in class II molar relationship through significant different in S Vert/Ms-S Vert/Mi in the CTB group (P < .01) and the TB group (P < .001), as well as deep overjet through significant different in S Vert/Is-S Vert/Ii in the CTB group (P < .001) and the TB group (P < .001). Besides, the CTB group also showed less protrusion of lower incisors and resulted in a more significant improvement in profile with fewer adverse effects on speaking, eating and social activities. CONCLUSIONS: For adolescents with skeletal class II malocclusion, CTB appliance was as effective as TB on improving dentoskeletal and soft tissue measurements, featuring more reliable teeth control and patient acceptance.

The complex of tannic acid and cetylpyridinium chloride: An antibacterial and stain-removal cleaner for aligners.

INTRODUCTION: Effective aligner hygiene is recognized as an important part of orthodontic treatments and oral hygiene. However, there is no effective cleansing method for removable aligners. METHODS: In this study, we incorporated tannic acid (TA) with cetylpyridinium chloride (CPC) to develop the TA-CPC complex. The antibacterial properties of 15.8 mg/mL TA-CPC against Escherichia coli and Staphylococcus aureus were evaluated in vitro, which were compared with 5.1 mg/mL TA, 10.7 mg/mL CPC, a commercial denture cleansing solution (YA; 15 mg/mL), and water. As for the assessment of stain-removal ability, the aligners stained by coffee were soaked in cleansing solutions, and the color changes (ΔE∗) were calculated on the basis of the CIE L∗a∗b∗ color system, and the National Bureau of Standards system was used for the clinical interpretation of the color change. Atomic force microscope examination, tensile property assessment, and wavelength dispersive x-ray fluorescence analysis were performed to investigate the material compatibility of TA-CPC, and Cell Counting Kit-8 assay and live/dead assay were used to test the cytotoxicity of TA-CPC. RESULTS: The results showed that TA-CPC had a positive zeta-potential, and cation-π interaction changed the chemical environments of the phenyl group in TA-CPC, resulting in greater inhibition zones of S. aureus and E. coli than other cleaners. The quantification of the biofilm biomass and the fluorescent intensities also reflected that the TA-CPC solution exhibited better antibacterial ability. As for the ability of stain removal, ΔE∗ value of group TA-CPC was 2.84 ± 0.55, whereas those of stained aligners immersed with deionized distilled water, TA, YA, and CPC were 10.26 ± 0.04, 9.54 ± 0.24, 5.93 ± 0.36, and 4.69 ± 0.35, respectively. The visual inspection and National Bureau of Standards ratings also showed that the color of stained aligners cleansed by TA-CPC was much lighter than those of the other groups. Meanwhile, TA-CPC had good compatibility with the aligner material and cells. CONCLUSIONS: TA-CPC is a promising strategy to inhibit the formation of biofilms and remove the stains on the aligners safely, which may disinfect the aligners to improve oral health and help keep the transparent appearances of aligners without impacting the morphology and mechanical properties.

Bibliometric and visualized analysis of randomized controlled trials in orthodontics between 1991 and 2022.

INTRODUCTION: In many evidence-based approaches to orthodontic research, randomized controlled trials (RCTs) represent authoritative evidence to identify rational therapeutics. This study aimed to perform mappings of bibliometric networks on orthodontic RCTs and summarize visual characteristics between 1991 and 2022. METHODS: The articles were retrieved from the Web of Science Core Collection in October 2022 without an initial time limit. Only orthodontic RCTs were eligible. Some bibliometric tools (HistCite, VOSviewer, SCImago Graphica, and CiteSpace) were applied for visualized analysis. Data such as geography, productive institutions, hot articles, journals, authors, references, and keywords were extracted and summarized for analysis. RESULTS: A total of 1122 orthodontic RCTs were searched. A total of 3841 authors from 1157 institutions in 65 countries published orthodontic RCTs. The United States (149) was the most prolific country, and the University of Sao Paulo (35) was the most productive institution. The American Journal of Orthodontics and Dentofacial Orthopedics (206) was the most popular journal for scholars. The visualization results of keyword co-occurrence identified 5 clusters: (1) tooth movement and auxiliary measures, (2) appliances and oral health, (3) orthodontic discomfort and symptomatic therapy, (4) periodontal disease in orthodontics and health maintenance, and (5) retention and relapse. CONCLUSIONS: Over the past 31 years, publications and citations on orthodontic RCTs from the Web of Science Core Collection have increased notably across many countries, authors, and institutions. Recently, there has been a significant increase in the attention to orthodontic RCTs that focus on accelerating tooth movement.

Dynamic biomechanical changes of clear aligners during extraction space closure: Finite element analysis.

INTRODUCTION: Clear aligners (CAs) have recently become popular and widely used orthodontic appliances. Research on CA biomechanics has become a focal point in orthodontics to improve the efficiency of CA treatment and address challenging issues, such as extraction. The biomechanical characteristics of CAs in space closure have been reported. However, previous studies have mainly focused on static biomechanical analysis that cannot demonstrate the dynamic biomechanical changes in CAs during space-closing. Given that these biomechanical changes can be significant and have considerable clinical value, this study aimed to investigate these characteristics. METHODS: Sequential extraction space-closing models were derived from included patient data and refined using modeling and CA design software. A finite element analysis was performed to obtain biomechanical raw data. This study introduced a dual coordinate system and space geometry analysis to demonstrate the biomechanical properties accurately. RESULTS: As space closure progressed, the instantaneous tooth displacements increased, indicating an enhanced space closure force because of the increased strain in the CA extraction area. Meanwhile, the central axis of rotation of the anterior teeth continuously moved toward the labial-apical direction, showing a gradually enhanced vertical and torque control effect. CONCLUSIONS: During space closure, CAs undergo specific biomechanical changes, including increased contraction and control forces on both sides of the gap. These biomechanical effects are beneficial to alleviate the roller coaster effect gradually. Meanwhile, more reasonable staging design strategies can be proposed on the basis of this biomechanical mechanism.

Metagenomic analysis of oral and intestinal microbiome of patients during the initial stage of orthodontic treatment.

INTRODUCTION: This prospective study analyzed changes in the oral and intestinal microbiomes in patients before and after fixed orthodontic treatment, elucidating the impacts of fixed orthodontic treatment on patient health and metabolism. METHODS: Metagenomic analysis was conducted on stool, dental plaque, and saliva samples from 10 fixed orthodontic patients. All the samples were sequenced with Illumina NovaSeq 6000 with a paired-end sequencing length of 150 bp. Identification of taxa in metagenomes and functional annotation of genes of the microbiota were performed using the data after quality control. Clinical periodontal parameters, including the gingiva index, plaque index, and pocket probing depth, were examined at each time point in triplicates. Patients also received a table to record their oral hygiene habits of brushing, flossing, and dessert consumption frequency over 1 month. RESULTS: The brushing and flossing times per day of patients were significantly increased after treatment compared with baseline. The number of times a patient ate dessert daily was also fewer after treatment than at baseline. In addition, the plaque index decreased significantly, whereas the pH value of saliva, gingiva index, and pocket probing depth did not change. No significant differences were observed between the participants before and after orthodontic treatment regarding alpha-diversity analysis of the gut, dental plaque, or saliva microbiota. However, on closer analysis, periodontal disease-associated bacteria levels in the oral cavity remain elevated. Alterations in gut microbiota were also observed after orthodontic treatment. CONCLUSIONS: The richness and diversity of the microbiome did not change significantly during the initial stage of fixed orthodontic treatment. However, the levels of periodontal disease-associated bacteria increased.

Assessing the impact of occlusal plane rotation on facial aesthetics in orthodontic treatment: a machine learning approach.

BACKGROUND: Adequate occlusal plane (OP) rotation through orthodontic therapy enables satisfying profile improvements for patients who are disturbed by their maxillomandibular imbalance but reluctant to surgery. The study aims to quantify profile improvements that OP rotation could produce in orthodontic treatment and whether the efficacy differs among skeletal types via machine learning. MATERIALS AND METHODS: Cephalometric radiographs of 903 patients were marked and analyzed by trained orthodontists with assistance of Uceph, a commercial software which use artificial intelligence to perform the cephalometrics analysis. Back-propagation artificial neural network (BP-ANN) models were then trained based on collected samples to fit the relationship among maxillomandibular structural indicators, SN-OP and P-A Face Height ratio (FHR), Facial Angle (FA). After corroborating the precision and reliability of the models by T-test and Bland-Altman analysis, simulation strategy and matrix computation were combined to predict the consequent changes of FHR, FA to OP rotation. Linear regression and statistical approaches were then applied for coefficient calculation and differences comparison. RESULTS: The regression scores calculating the similarity between predicted and true values reached 0.916 and 0.908 in FHR, FA models respectively, and almost all pairs were in 95% CI of Bland-Altman analysis, confirming the effectiveness of our models. Matrix simulation was used to ascertain the efficacy of OP control in aesthetic improvements. Intriguingly, though FHR change rate appeared to be constant across groups, in FA models, hypodivergent group displayed more sensitive changes to SN-OP than normodivergent, hypodivergent group, and Class III group significantly showed larger changes than Class I and II. CONCLUSIONS: Rotation of OP could yield differently to facial aesthetic improvements as more efficient in hypodivergent groups vertically and Class III groups sagittally.

Nano porous polycarbonate membranes stimulating cell adhesion and promoting osteogenic differentiation and differential mRNA expression.

Tissue engineering is thought to be the ideal therapy for bone defect reconstructive treatment. In this study, we present a method of utilizing micro/nano porous polycarbonate membranes (PCMs) as the extracellular matrix to cultivate the human periodontal ligament cells (hPDLCs) and investigate the osteogenic differentiation of those cells. We also compared the osteogenic enhancing abilities of different pore size PCMs. The pore diameters of the candidate membranes are 200 nm, 800 nm, 1200 nm, and 10 µm respectively, and their physical properties are identified. After seeding and cultivating on the PCMs, hPDLCs can be stimulated to undergo osteogenic differentiation, in which the 200 nm PCM is proved to have the most optimal osteo-induction ability. The results of in vivo experiments provide strong evidence suggesting that the hPDLCs stimulated by 200 nm PCM greatly accelerates the healing of bone reconstruction in mice skull defects, as well as promote the process of ectopic osteogenesis. RNA-sequencing was conducted to determine the differential mRNA expression profile during the osteogenesis process of hPDLCs on PCMs. GO and KEGG enrichment analysis were conducted to study the regulatory mechanisms, in which osteogenic marker expression such as Hippo, TGF-ß, and PI3K-Akt signaling pathways were significantly up-regulated. The up-regulation indicates the promising potential of nano porous PCMs for promoting osteogenesis for bone regeneration applications. Ultimately, signaling pathways that promote osteogenesis warrants further exploration.

miR-20a-5p regulated SMAD6 to inhibit chondrogenesis of hDPSCs.

OBJECTIVES: Chondrogenic differentiation of human dental pulp stem cells (hDPSCs) is highly promising for cartilage repair. The specific mechanism, however, still needs to be explicated. MATERIALS AND METHODS: In this study, we isolated hDPSCs and transfected cells with lentiviruses containing an over-expression, knock-down, or negative control of miR-20a-5p. Three-D pellet cultures of hDPSCs were used for the chondrogenic induction. Following the pellet culture period, chondrogenesis was assessed by histological and immunohistochemical analysis and expression of chondrogenic-related genes. Dual-luciferase report assay was performed to determine potential targeted genes of miR-20a-5p, and the phosphorylation levels of P65 and IκBα were explored. Animal experiments were performed to determine the effect of miR-20a-5p on cartilage regeneration. RESULTS: miR-20a-5p was showed to repress the expression of SMAD6 to inhibit the chondrogenic differentiation of hDPSCs. Accordingly, the knock-down of miR-20a-5p promoted cartilage regeneration in the osteochondral defects of rats. Mechanically, it is indicated that NF-κB signaling is the potential down-stream network of miR-20a-5p/Smad6 crosstalk during chondrogenic differentiation. CONCLUSIONS: miR-20a-5p could target SMAD6 to activate NF-κB signaling pathway, and thus inhibit chondrogenesis of hDPSCs, which provided promising therapeutic target for cartilage defects clinically.

Down-regulation of hsa-circ-0107593 promotes osteogenic differentiation of hADSCs via miR-20a-5p/SMAD6 signaling.

OBJECTIVES: Increasing evidence indicated circRNAs were involved in stem cells osteogenesis differentiation. Herein, we aimed to clarify the role of hsa-circ-0107593 during the osteogenesis process of human adipose-derived stem cells (hADSCs) and the underlying mechanisms. METHODS: The ring structure of hsa-circ-0107593 was confirmed using RNase R treatment and Sanger sequencing. Nucleoplasmic separation and fluorescence in situ hybridization detected hsa-circ-0107593 distribution. Lentivirus and siRNA were used to modulate the expression of hsa-circ-0107593, and the binding relationship between hsa-circ-0107593 and miR-20a-5p was verified by luciferase assay and RNA immunoprecipitation. We detected the osteogenic activity of hADSCs through alkaline phosphatase staining, alizarin red S staining, real-time polymerase chain reaction (RT-PCR), western blot, and cellular immunofluorescence experiment. In vivo, micro-computed tomography was performed to analyze bone formation around skull defect. RESULTS: RT-PCR results exhibited that hsa-circ-0107593 was downregulated while miR-20a-5p was upregulated during hADSCs osteogenesis. In vivo and in vitro experiments results indicated that knocking down hsa-circ-0107593 promoted the osteogenic differentiation of hADSCs, while overexpression of hsa-circ-0107593 showed an inhibitory effect on hADSCs osteogenic differentiation. In vitro experiment results showed hsa-circ-0107593 acted as a hADSCs osteogenic differentiation negative factor for it inhibited the suppressing effect of miR-20a-5p on SMAD6. CONCLUSION: Knocking down hsa-circ-0107593 acts as a positive factor of the osteogenic differentiation of hADSCs via miR-20a-5p/SMAD6 signaling.

mTOR Signaling Pathway in Bone Diseases Associated with Hyperglycemia.

The interplay between bone and glucose metabolism has highlighted hyperglycemia as a potential risk factor for bone diseases. With the increasing prevalence of diabetes mellitus worldwide and its subsequent socioeconomic burden, there is a pressing need to develop a better understanding of the molecular mechanisms involved in hyperglycemia-mediated bone metabolism. The mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that senses extracellular and intracellular signals to regulate numerous biological processes, including cell growth, proliferation, and differentiation. As mounting evidence suggests the involvement of mTOR in diabetic bone disease, we provide a comprehensive review of its effects on bone diseases associated with hyperglycemia. This review summarizes key findings from basic and clinical studies regarding mTOR's roles in regulating bone formation, bone resorption, inflammatory responses, and bone vascularity in hyperglycemia. It also provides valuable insights into future research directions aimed at developing mTOR-targeted therapies for combating diabetic bone diseases.

Different biomechanical effects of clear aligners in closing maxillary and mandibular extraction spaces: Finite element analysis.

INTRODUCTION: Compared with fixed treatments, clear aligners (CAs) have the advantages of comfort, esthetics, and hygiene, and are popular among patients and orthodontists. However, CAs exhibit control deficiencies in extraction patients because of insufficient root control and retention effects. These deficiencies can magnify biomechanical differences in bimaxillary dentition, further causing different orthodontic requirements between maxillary and mandibular dentition. This study aimed to elaborate on the biomechanical characteristics of bimaxillary dentition in extraction space closure and provided feasible biomechanical compensation strategies for use in clinical practice. METHODS: We constructed a 3-dimensional (3D) bimaxillary model based on patient data. Several 3D modeling-related software was used to generate a standard first premolar extraction model, CAs, and attachments. Subsequently, finite element analysis was performed to demonstrate the biomechanical effects. RESULTS: The maxillary and mandibular dentition showed a roller coaster effect during space closure. Compared with the maxillary dentition, the mandibular posterior teeth exhibited stronger relative anchorage causing greater anterior teeth retraction. The tipping and vertical movements of the anterior teeth were related to tooth length. The longer the anterior tooth, the less tipping and greater vertical displacement occurred. Generally, when having the same retraction distance, the mandibular dentition exhibited greater retroclination and fewer extrusions. Both mechanical and retention compensations should be considered to prevent these unwanted tipping movements. Adding specific attachments to bimaxillary dentitions compensated for the retention and root control deficiencies of CAs. CONCLUSIONS: When applying CAs to extraction patients, different biomechanical effects can present in the bimaxillary dentition because of specific dentition morphologies. To effectively treat these patients, mechanical compensation through overcorrection of the target position should be designed on the basis of bimaxillary control deficiencies, and retention compensation by adding specific attachments should also be considered according to the overcorrections.

Finite element analysis of the biomechanical effect of clear aligners in extraction space closure under different anchorage controls.

INTRODUCTION: Clear aligners (CAs) have attracted increasing attention from patients and orthodontists because of their excellent esthetics and comfort. However, treating tooth extraction patients with CAs is difficult because their biomechanical effects are more complicated than those of traditional appliances. This study aimed to analyze the biomechanical effect of CAs in extraction space closure under different anchorage controls, including moderate, direct strong, and indirect strong anchorage. It could provide several new cognitions for anchorage control with CAs through finite element analysis, further directing clinical practice. METHODS: A 3-dimensional maxillary model was generated by combining cone-beam computed tomography and intraoral scan data. Three-dimensional modeling software was used to construct a standard first premolar extraction model, temporary anchorage devices, and CAs. Subsequently, finite element analysis was performed to simulate space closure under different anchorage controls. RESULTS: Direct strong anchorage was beneficial for reducing the clockwise occlusal plane rotation, whereas indirect anchorage was conducive for anterior teeth inclination control. In the direct strong anchorage group, an increase in the retraction force would require more specific anterior teeth overcorrection to resist the tipping movement, mainly including lingual root control of the central incisor, followed by distal root control of the canine, lingual root control of the lateral incisor, distal root control of the lateral incisor, and distal root control of the central incisor. However, the retraction force could not eliminate the mesial movement of the posterior teeth, possibly causing a reciprocating motion during treatment. In indirect strong groups, when the button was close to the center of the crown, the second premolar presented less mesial and buccal tipping but more intrusion. CONCLUSIONS: The 3 anchorage groups showed significantly different biomechanical effects in both the anterior and posterior teeth. Specific overcorrection or compensation forces should be considered when using different anchorage types. The moderate and indirect strong anchorages have a more stable and single-force system and could be reliable models in investigating the precise control of future tooth extraction patients.

Abaloparatide and teriparatide enhance mandibular growth in adolescent rats with site-specific and mechano-related effects.

OBJECTIVE: Teriparatide (TPTD) and abaloparatide (ABL) are two osteoanabolic drugs targeting parathyroid hormone (PTH)1R signalling. This study aimed to investigate the effects of TPTD and ABL on the adolescent mandibular growth. METHOD: In total, 70 4-week-old male Sprague-Dawley rats were randomly divided into 14 groups, treated with intermittent TPDT or ABL at various doses, accompanied by mandibular advancement (MA) or not. 3D printing was used to fabricate an innovative splint for MA. After a 4-week treatment, morphological measurement, histological and immunohistochemical analysis were performed. Mandibular condylar chondrocytes (MCCs) were treated with TPTD or ABL, followed by CCK-8 assay, alcian blue staining, real time-PCR and immunofluorescent staining. RESULT: In vivo, TPTD or ABL alone increased the condylar length and cartilage thickness, with up-regulated SOX9 and COL II, whilst down-regulated COL X; however, when combined with MA, the promotive effects were attenuated. TPTD or ABL alone increased the mandibular body height and mandibular angle width, whilst increased the mandibular body length and alveolar bone width when combined with MA. In vitro, TPTD or ABL enhanced the MCC proliferation, glycosaminoglycan synthesis, COL II and SOX9 expression, whilst down-regulated COL X, Ihh and PTH1R expression. CONCLUSION: Both ABL and TPTD enhance mandibular growth in adolescent rats with site-specific and mechano-related effects, including propelling chondrogenesis at the condylar cartilage and promoting bone apposition at other mechano-responsive sites. They behave as promising drugs for mandibular growth modification, and in general ABL seems more potent than TPTD in this context.

CircRNA-miRNA networks in regulating bone disease.

Circular RNA (circRNA) is a class of endogenous noncoding RNA (ncRNA), presenting as a special covalent closed loop without a 5' cap or 3' tail, maintaining resistance to RNA exonuclease and keeping high stability. Although lowly expressed in most situations, circRNA makes an active difference in regulating physiological or pathological processes by modulating gene expression by regulation of transcription, protein, and miRNA functions through various mechanisms in particular tissues. Recent studies have demonstrated the roles of the miRNA-circRNA network in the development of several bone diseases such as osteoporosis, a multiple-mechanism disease resulting from defective bone quality and low bone mass, osteoarthritis, whose main pathomechanism is inflammation and articular cartilage degradation, as well as osteosarcoma, known as one of the most common bone cancers. However, the specific mechanism of how circRNA along with miRNA influences those diseases is not well documented, showing potential for the development of new therapies for those bone diseases.

Hyaluronan injection versus oral glucosamine and diclofenac in the treatment of temporomandibular joint osteoarthritis.

OBJECTIVES: This study was aimed to compare the effects of 4 biweekly hyaluronan (HA) injection with glucosamine and diclofenac oral administration on TMJ OA patients. MATERIALS AND METHODS: This retrospective cohort study included TMJ OA patients who had the treatment of 4 biweekly HA injection (group HA) or oral glucosamine hydrochloride for 3 months and diclofenac sodium for 2 weeks (group G/D), and had complete data at first-visit, 3 months, 6 months, and 12 months. Clinical signs and symptoms were scored by anamnestic dysfunction index (Ai) and clinical dysfunction index (Di), and condylar bone changes were evaluated by CBCT scoring system. RESULTS: We included 22 patients in group HA and 20 patients in group G/D. After HA injection, Ai was decreased from 4.3 to 1.6(CI [- 4.0, - 1.4]) at 3-month follow-up, which was smaller than that in group G/D significantly. Di in group HA was declined significantly from 8.1 at first-visit to 3.6 at 3-month follow-up, while Di in group G/D scarcely changed until at 6- and 12-month follow-up. Neither HA injection nor oral glucosamine/diclofenac showed positive effect on the bone of TMJs during follow-ups with statistical significance. CONCLUSIONS: HA injection alleviated signs and symptoms of TMJ OA rapidly and presented superior clinical effects over oral glucosamine with diclofenac. However, both treatments did not limit the bone destruction of TMJs significantly. CLINICAL RELEVANCE: This cohort study provides knowledge on the symptom relief and bone changes of TMJ OA patients when treated with HA injection or glucosamine and diclofenac oral administration.

The vital role of Gli1+ mesenchymal stem cells in tissue development and homeostasis.

The hedgehog (Hh) signaling pathway plays an essential role in both tissue development and homeostasis. Glioma-associated oncogene homolog 1 (Gli1) is one of the vital transcriptional factors as well as the direct target gene in the Hh signaling pathway. The cells expressing the Gli1 gene (Gli1+ cells) have been identified as mesenchymal stem cells (MSCs) that are responsible for various tissue developments, homeostasis, and injury repair. This review outlines some recent discoveries on the crucial roles of Gli1+ MSCs in the development and homeostasis of varieties of hard and soft tissues.

Exploring the oncostatin M (OSM) feed-forward signaling of glioblastoma via STAT3 in pan-cancer analysis.

BACKGROUND: Oncostatin M (OSM) has been reported to be a key regulating factor in the process of tumor development. Previous studies have demonstrated both the promotion and inhibition effects of OSM in tumors, therefore inspiring controversies. However, no systematic assessment of OSM across various cancers is available, and the mechanisms behind OSM-related cancer progression remain to be elucidated. METHODS: Based on The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, we conducted a pan-cancer analysis on OSM to explore its tumor-related functions across cancers as well as its correlations with specific molecules, cells in the tumor microenvironment. Considering the results of pan-cancer analysis, we chose the specific tumor glioblastoma multiforme (GBM) to screen out the OSM-induced signaling pathways and intercellular communications in tumor progression. Wound scratch assay, invasion assay and qRT-PCR were performed to verify the biological effects of OSM on glioblastoma cells. RESULTS: Higher OSM level was found in most tumor tissues compared with corresponding normal tissues, and the enhanced OSM expression was observed to be strongly related to patients' poor prognosis in several cancers. Moreover, the expression of OSM was associated with stromal and immune cell infiltration in the tumor microenvironment, and OSM-related immune checkpoint and chemokine co-expression were also observed. Our results suggested that OSM could communicate extensively with the tumor microenvironment. Taking GBM as an example, our study found that two critical signaling pathways in OSM-related tumor progression by KEGG enrichment analysis: Jak-STAT and NF-κB pathways. Single-cell RNA sequencing data analysis of GBM revealed that OSM was mainly secreted by microglia, and cell-cell interaction analysis proved that OSM-OSMR is an important pathway for OSM to stimulate malignant cells. In vitro, OSM treatment could facilitate the migration and invasion of glioblastoma cells, meanwhile promote the proneural-mesenchymal transition. The administration of STAT3 inhibitors effectively suppressed the OSM-mediated biological effects, which proved the key role of STAT3 in OSM signaling. CONCLUSION: Taken together, our study provides a comprehensive understanding with regard to the tumor progression under the regulation of OSM. OSM seems to be closely related to chronic inflammation and tumor development in the tumor microenvironment. As an important inflammatory factor in the tumor microenvironment, OSM may serve as a potential immunotherapeutic target for cancer treatment, especially for GBM.