Proteomic Analysis of the Supernatant from Bone Marrow Mesenchymal Stem Cells under High Glucose Conditions.

Diabetes mellitus hinders the process of bone regeneration by inhibiting the function of mesenchymal stem cells (MSCs) through elevated glucose levels, thereby impeding osteointegration. The stem cell niche (SCN) plays a crucial role in determining the fate of stem cells by integrating various signals. However, the precise mechanism by which high glucose levels affect the SCN and subsequently influence the function of MSCs remains unclear. In this study, we employed proteomic analysis to identify proteins with altered expression in the extracellular matrix (ECM), aiming to elucidate the underlying mechanism. Three cell supernatants were collected from bone marrow mesenchymal stem cells (BMSCs) or BMSCs stimulated with high glucose (BMSCs+Hg). A total of 590 differentially expressed proteins were identified, which were found to be associated with the ECM, including aging, autophagy, and osteogenic differentiation. The findings of our study indicate that elevated glucose levels exert an influence on the molecular aspects of the SCN, potentially contributing to a better comprehension of the underlying mechanism.

Untargeted Metabolomics Analysis of Gingival Tissue in Patients with Severe Periodontitis.

The purpose of this study was to determine potential metabolic biomarkers and therapeutic drugs in the gingival tissue of individuals with periodontitis. Liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) were used to analyze the gingival tissue samples from 20 patients with severe periodontitis and 20 healthy controls. Differential metabolites were identified using variable important in projection (VIP) values from the orthogonal partial least squares discrimination analysis (OPLS-DA) model and then verified for significance between groups using a two-tailed Student's t test. In total, 65 metabolites were enriched in 33 metabolic pathways, with 40 showing a significant increase and 25 expressing a significant decrease. In addition, it was found that patients with severe periodontitis have abnormalities in metabolic pathways, such as glucose metabolism, purine metabolism, amino acid metabolism, and so on. Furthermore, based on a multidimensional analysis, 12 different metabolites may be the potential biomarkers of severe periodontitis. The experiment's raw data have been uploaded to the MetaboLights database, and the project number is MTBLS8357. Moreover, osteogenesis differentiation characteristics were detected in the selected metabolites. The findings may provide a basis for the study of diagnostic biomarkers and therapeutic metabolites in severe periodontitis.

Phthalate exposure aggravates periodontitis by activating NFκB pathway.

BACKGROUND: Phthalates are widely used plasticizers, which were identified as risk factors in the development of many human diseases. However, the effects of phthalates in the periodontitis are unknown. We aimed to investigated the relationship of periodontitis and phthalate exposure as well as the underlying mechanisms. MATERIALS AND METHODS: Univariate and multivariate logistic regressions were employed to evaluate the association between phthalate metabolites and periodontitis. The generalized additive model and piecewise logistic regression were conducted to investigate the dose-response relationship. Cell and animal models were used to explore the role and mechanism of DEHP in the development of periodontitis. Transcriptome sequencing, bioinformatics analysis, western blot, immunofluorescence and mice model of periodontitis were also employed. RESULTS: MEHP (OR 1.14, 95% CI 1.05-1.24), MCPP (OR 1.08, 95% CI 1.00-1.17), MEHHP (OR 1.18, 95% CI 1.08-1.29), MEOHP (OR 1.18, 95% CI 1.07-1.29), MiBP (OR 1.15, 95% CI 1.04-1.28), and MECPP (OR 1.20, 95% CI 1.09-1.32) were independent risk factors. And MEHHP, the metabolite of DEHP, showed the relative most important effects on periodontitis with the highest weight (0.34) among all risk factors assessed. And the increase of inflammation and the activation of NFκB pathway in the periodontitis model mice and cells were observed. CONCLUSION: Exposure to multiple phthalates was positively associated with periodontitis in US adults between 30 and 80 years old. And DEHP aggravated inflammation in periodontitis by activating NFκB pathway.

Accumulative Rolling Mg/PLLA Composite Membrane with Lamellar Heterostructure for Enhanced Bacteria Inhibition and Rapid Bone Regeneration.

Developing composite materials with optimized mechanics, degradation, and bioactivity for bone regeneration has long been a crucial mission. Herein, a multifunctional Mg/Poly-l-lactic acid (Mg/PLLA) composite membrane based on the "materials plain" concept through the accumulative rolling (AR) method is proposed. Results show that at a rolling ratio of 75%, the comprehensive mechanical properties of the membrane in the rolling direction are self-reinforced significantly (elongation at break ≈53.2%, tensile strength ≈104.0 MPa, Young's modulus ≈2.13 GPa). This enhancement is attributed to the directional arrangement and increased crystallization of PLLA molecular chains, as demonstrated by SAXS and DSC results. Furthermore, the AR composite membrane presents a lamellar heterostructure, which not only avoids the accumulation of Mg microparticles (MgMPs) but also regulates the degradation rate. Through the contribution of bioactive MgMPs and their photothermal effect synergistically, the membrane effectively eliminates bacterial infection and accelerates vascularized bone regeneration both in vitro and in vivo. Notably, the membrane exhibits outstanding rat skull bone regeneration performance in only 4 weeks, surpassing most literature reports. In short, this work develops a composite membrane with a "one stone, four birds" effect, opening an efficient avenue toward high-performance orthopedic materials.

Accuracy of dental implant placement with a robotic system in partially edentulous patients: A prospective, single-arm clinical trial.

OBJECTIVES: This clinical study aimed to assess the accuracy of implant positions using a robotic system in partially edentulous patients. MATERIALS AND METHODS: Twenty-eight partially edentulous patients received 31 implants using the robotic system. Deviations between the planned and placed implants were calculated after surgery. The deviations were compared with objective performance goals (OPGs) from reported studies of fully guided static computer-assisted implant surgery (CAIS) and dynamic CAIS. A multiple linear regression analysis was performed to investigate the possible effects of the type and side of the arch, implant location, and implant dimensions on the deviations. RESULTS: The evaluation of 31 implants resulted in a mean angle deviation of 2.81 ± 1.13° (95% confidence interval (CI): 2.40-3.23°), while the 3D deviations at the implant shoulder and apex were 0.53 ± 0.23 mm (95% CI 0.45-0.62 mm) and 0.53 ± 0.24 mm (95% CI 0.44-0.61 mm), respectively. The upper limits of the 95% CI of 3D deviations were lower than those of the corresponding OPGs; however, the angle deviation was similar to that of the OPG. No statistically significant differences were found for the type and side of the arch, implant location, and implant dimensions to the deviations (p > .05). CONCLUSIONS: The robotic system appears to achieve higher accuracy in implant positions than static and dynamic CAIS in partially edentulous patients (Chinese Clinical Trial Registry ChiCTR2300067587).

Calcium phytate reverses high glucose-inhibited osteogenesis of BMSCs via the MAPK/JNK pathway.

OBJECTIVES: Diabetes mellitus (DM) induces oxidative tissue impairment and suppresses bone formation. Some studies have shown that phytic acid has antioxidant and anti-diabetic properties. This study aimed to investigate the potential of calcium phytate (Ca-phytate) to reverse inhibited osteogenesis of human bone marrow mesenchymal stem cells (hBMSCs) in a high glucose (HG) environment and to determine the underlying mechanism. MATERIALS AND METHODS: hBMSCs were exposed to HG and palmitic acid to simulate DM in vitro. Osteogenic differentiation was measured using alkaline phosphatase staining and activity assay, alizarin red S staining, qRT-PCR, Western blot and immunofluorescence staining. A critical-size cranial defect model of type 2 diabetes mellitus (T2DM) rats was established to evaluate bone regeneration. A specific pathway inhibitor was used to explore whether the MAPK/JNK pathway was involved. RESULTS: Treatment with 34 µM Ca-phytate had the highest effect on osteogenic differentiation in HG. Ca-phytate improved cranial bone defect healing in T2DM rats. The long-term HG environment inhibited the activation of the MAPK/JNK signalling pathway, which was restored by Ca-phytate. Blocking the JNK pathway reduced the Ca-phytate-mediated osteogenic differentiation of hBMSCs. CONCLUSION: Ca-phytate induced bone regeneration in vivo and reversed HG-inhibited osteogenesis of hBMSCs in vitro via the MAPK/JNK signalling pathway.

Comparison of alveolar bone width and sagittal tooth angulation of maxillary central incisors in Class I and Class III canine relationships: a retrospective study using CBCT.

BACKGROUND: Canine relationship is a key reference identifying anterior malocclusion and an important implication for evaluating preimplantation bone morphology at maxillary esthetic zone. This study aimed to compare the differences of maxillary central incisor-related measurements (alveolar bone thickness and tooth sagittal angulation) between Class I and Class III canine relationship and further explore the risk factors for immediate implant placement in the anterior maxilla based on cone beam computed tomography (CBCT) data. METHODS: CBCT digital imaging and communications in medicine (DICOM) files of 107 patients (54 with Class I canine relationship and 53 with Class III canine relationship) were collected and the alveolar bone thickness at mid-root (mid-root buccal thickness/MBT; palatal/MPT), apical regions (apical buccal thickness/ABT; palatal/APT) and sagittal angulation (SA) of the maxillary central incisor at the examined side were measured on the mid-sagittal observation plane. Descriptive statistical analysis and frequency distributions of the measurements based on Class I or Class III canine relationship were established. Statistical analyses were performed using Fisher's exact test, independent samples t test and Pearson correlation test with the significance level set at p < 0.05. RESULTS: The frequency distributions of maxillary central incisors' MPT, ABT, APT and SA showed significant differences between Class I and Class III canine relationships (p = 0.030, 0.024, 0.000 and 0.000, respectively). MPT (2.48 ± 0.88 mm vs. 3.01 ± 1.04 mm, p = 0.005), APT (6.79 ± 1.65 mm vs. 8.47 ± 1.93 mm, p = 0.000) and SA (12.23 ± 5.62° vs. 16.42 ± 4.49°, p = 0.000) were significantly smaller in patients with Class III canine relationship. Moreover, SA showed a strong positive correlation with APT (R = 0.723, p = 0.000) and a moderate negative correlation with ABT (R = - 0.554, p = 0.000). CONCLUSIONS: In populations with Class III canine relationship, maxillary central incisors were significantly more labially inclined and have a thinner palatal bone plate at the apex compared with Class I relationship. Clinicians should avoid palatal perforation during immediate implantation at sites of originally protrusive maxillary incisors.

Interdisciplinary treatment with implant-supported prostheses for an adolescent with ectodermal dysplasia: A clinical report.

This clinical report describes interdisciplinary treatments for a 17-year-old girl with ectodermal dysplasia. The treatment was initiated with orthodontic therapy. After the remaining primary teeth had been extracted, 6 implants were placed in the maxilla with bilateral sinus floor elevations, and 6 implants were placed in the mandible. Immediate restorations were provided. Definitive restorations included screw-retained partial dental prostheses and ceramic crowns.

Periostin promotes migration, proliferation, and differentiation of human periodontal ligament mesenchymal stem cells.

OVERVIEW: Periostin (POSTN) is critical to bone and dental tissue morphogenesis, postnatal development, and maintenance; however, its roles in tissue repair and regeneration mediated by human periodontal ligament mesenchymal stem cells (PDLSCs) remain unclear. The present study was designed to evaluate the effects of POSTN on hPDLSCs in vitro. MATERIALS AND METHODS: hPDLSCs were isolated and characterized by their expression of the cell surface markers CD44, CD90, CD105, CD34, and CD45. Next, 100 ng/mL recombinant human POSTN protein (rhPOSTN) was used to stimulate the hPDLSCs. Lentiviral POSTN shRNA was used to knockdown POSTN. The cell counting kit-8 (CCK8) and scratch assay were used to analyze cell proliferation and migration, respectively. Osteogenic differentiation was investigated using an alkaline phosphatase (ALP) activity assay, alizarin staining, and quantitative calcium analysis and related genes/protein expression assays. RESULTS: Isolated hPDLSCs were positive for CD44, CD90, and CD105 and negative for CD34 and CD45. In addition, 100 ng/mL rhPOSTN significantly accelerated scratch closure, and POSTN-knockdown cells presented slower closure at 24 h and 48 h. Furthermore, the integrin inhibitor Cilengitide depressed the scratch closure that was enhanced by POSTN at 24 h. The CCK8 assay showed that 100 ng/mL rhPOSTN promoted hPDLSC proliferation. Moreover, 100 ng/mL rhPOSTN increased the expression of RUNX2, OSX, OPN, OCN, and VEGF and enhanced ALP activity and mineralization. POSTN silencing decreased the expression of RUNX2, OSX, OPN, OCN, and VEGF and inhibited ALP activity and mineralization. CONCLUSIONS: POSTN accelerated the migration, proliferation, and osteogenic differentiation of hPDLSCs.

Effect of titanium ions on the Hippo/YAP signaling pathway in regulating biological behaviors of MC3T3-E1 osteoblasts.

Titanium (Ti) and its corresponding alloys have been widely applied in dental and orthopedic implants. Owing to abrasion and corrosion of implants in the unfavorable electrolytic aqueous environment of the host body, Ti ions could be released from implants and accumulated in local tissues. Recent studies have found that excessive Ti ions were toxic to osteoblasts in adjacent bone tissues and subsequently influenced long-term effects on implant prostheses. However, the potential molecular mechanisms underlying the damage to osteoblasts induced by Ti ions remained unclear. Hippo signaling has been confirmed to be involved in organ size and tissue regeneration in many organs, while its roles in osteoblasts differentiation and bone repair remained elusive. Therefore, we hypothesize that YAP, a regulator of Hippo pathway, inhibited osteoblast growth, skeletal development and bone repair, as well as excessive Ti ions promoted the progression of YAP activation. This study aimed to explore the role of Hippo/YAP signaling pathway in the biotoxicity effect of Ti ions on osteoblast behaviors. Here, we confirmed that 10 ppm Ti ions, a minimum concentration gradient previously reported that was capable of suppressing osteoblasts growth, induced nuclear expression of YAP in osteoblasts in our study. Furthermore, 10 ppm Ti ion-induced YAP activation was found to downregulate osteogenic differentiation of MC3T3-E1 cells. Most importantly, the hypothesis we proposed that knockdown of YAP did reverse the inhibitory effect of 10 ppm Ti ions on osteogenesis has been verified. Taken together, our work provides insights into the mechanism of which YAP is involved in regulating osteoblast behaviors under the effect of Ti ions, which may help to develop therapeutic applications for Ti implant failures and peri-implantitis.

Immediate implant placement and complete mouth rehabilitation with CAD-CAM titanium frameworks and cemented crowns for a patient with severe periodontal disease: A clinical report.

The technique of immediate implantation has been widely used to reduce treatment time and bone loss after extraction. However, immediate implant placement in infected extraction sockets is generally contraindicated. This clinical report describes a treatment protocol for immediate implantation after the extraction of teeth with generalized chronic periodontitis. The technique used for the oral rehabilitation used computer-assisted design and computer-assisted manufacturing (CAD-CAM) titanium frameworks and cemented zirconia crowns. The titanium frameworks overcame suboptimal implant position and the cemented crowns provided excellent function and esthetics despite the locations of screw-access openings. No clinical complications occurred during a 13-month follow-up.

[Study on inhibitory effect of EGCG on Calcium oxalate nephrolithiasis in rats and its related mechanism].

In the study, the inhibitory effect of epigallocatechin gallate (EGCG) on Calcium oxalate nephrolithiasis and its possible mechanism were investigated. The rat Calcium oxalate nephrolithiasis model was induced through the combined oral administration of ethylene glycol and ammonium chloride, which was intervened with EGCG. Rat blood samples were collected to detect blood creatinine (Cr), blood urea nitrogen (BUN) and blood calcium. Rat urine samples were collected to observe and compare 24-hour urine volume, oxalic acid (Ox) and calcium in urine. Renal samples were collected to prepare tissue slices and observe the pathological changes in Calcium oxalate nephrolithiasis. The expression of osteopontin (OPN) in renal tissues was evaluated by Real-time PCR and Western blot. According to the results, compared with normal rats, rats in the nephrolithiasis model showed significant increases in Cr, BUN, urine Calcium, urine Ox and renal OPN expression (P < 0.05), but obvious decrease in 24-hour urine volume (P < 0.05); Compared with rats with nephrolithiasis, those processed with EGCG revealed remarkable declines in Cr, BUN, urine Calcium and urine Ox (P < 0.05), with significant rise in 24-hour urine volume (P < 0.05) in a concentration-dependent manner. Additionally, compared with the control group, nephrolithiasis rats showed significant pathological changes in Calcium oxalate calculus. After ECCG treatment, the renal pathological changes and OPN expression attenuated significantly in a concentration-dependent manner. The results showed that EGCG inhibits the formation of calcium oxalate nephrolithiasis in rats and shows a notable protective effect on renal functions.

Dentin matrix proteins (DMPs) enhance differentiation of BMMSCs via ERK and P38 MAPK pathways.

Dentin, the predominant mineralized tissue of the tooth, comprises an extracellular matrix of collagen and a heterogeneous mixture of non-collagenous components, many of which have cellular signaling properties. These properties may be important in signaling stem cell involvement in tissue regeneration following injury and the present study investigates their morphogenic effects on differentiation of Bone Marrow Stromal Stem Cells (BMMSCs) in vitro. Non-collagenous dentin matrix proteins (DMPs) were isolated from healthy human teeth and their effects on BMMSCs behavior examined during in vitro culture. In vitro, DMPs enhanced alkaline phosphatase activity and mineralization in BMMSCs cultures as well as increasing the expression of dentinogenic and osteogenic differentiation markers (including runt-related transcription factor 2, osterix, bone sialoprotein, dentin sialophosphoprotein and osteocalcin) at both transcript and protein levels, with 10 µg/mL DMPs being the optimal stimulatory concentration. Expression of phosphor-ERK/phosphor-P38 in BMMSCs was up-regulated by DMPs and, in the presence of the ERK1/2- and p38-specific inhibitors, the differentiation of BMMSCs was inhibited. These data indicate that DMPs promote the dentinogenic/osteogenic differentiation of BMMSCs via the ERK/p38 MAPK pathways.

The effect of platform switching on stress distribution in implants and periimplant bone studied by nonlinear finite element analysis.

STATEMENT OF PROBLEM: It is unknown whether dental implant systems with a platform-switched configuration have better periimplant bone stress distribution and lead to less periimplant bone level changes. PURPOSE: The purpose of this study was to quantitatively investigate interfacial stress and stress distribution in implant bone in 2 implant abutment designs (platform-switched design and conventional diameter matching) by using a nonlinear finite element analysis method. MATERIAL AND METHODS: A finite element simulation study was applied to 2 commercially available dental implant systems: the Ankylos implant system with a reduced-diameter abutment (platform-switched implant) and the Anthogyr implant system with an abutment of the same diameter (regular platform implant). These 2 dental implant systems were positioned in a bone block, which was constructed based on a cross-sectional image of a human mandible in the molar region. In simulation, a single vertical load of 50 N, 100 N, or 150 N and horizontal loads of 50 N and 100 N were applied to the occlusal surface of the abutment. RESULTS: The finite element analysis found that the Ankylos implant system has a higher maximum von Mises stress in the implant abutment connection section and a lower maximum von Mises stress in the periimplant bone. The opposite results were found in the Anthogyr implant system. CONCLUSIONS: Lower stress levels in the periimplant bone with a more uniform stress distribution were found for the Ankylos implant system with a platform-switched configuration. Although relatively higher stress was found in the abutment, premature implant failure is not anticipated because of the high strength of titanium alloy.

Dosimetric Effect of Target Position Accuracy on Single-Isocenter Multiple Liver Metastases SBRT.

Purpose: To evaluate the dosimetric effects of intrafraction baseline shifts combined with rotational errors on Four-dimensional computed tomography-guided stereotactic body radiotherapy for multiple liver metastases (MLMs). Methods: A total of 10 patients with MLM (2 or 3 lesions) were selected for this retrospective study. Baseline shift errors of 0.5, 1.0, and 2.0 mm; and rotational errors of 0.5°, 1°, and 1.5°, were simulated about all axes. All of the baseline shifts and rotation errors were simulated around the planned isocenter using a matrix transformation of 6° of freedom. The coverage degradation of baseline shifts and rotational errors were analyzed according to the dose to 95% of the planning target volume (D95) and the volume covered by 95% of the prescribed dose (V95), and related changes in gross tumor volume were also analyzed. Results: At the rotation error of 0.5° and the baseline offset of less than 0.5 mm, the D95 and V95 values of all targets were >95%. For rotational errors of 1.0° (combined with all baseline shift errors), 36.3% of targets had D95 and V95 values of <95%. Coverage worsened substantially when the baseline shift errors were increased to 1.0 mm. D95 and V95 values were >95% for about 77.3% of the targets. Only 11.4% of the D95 and V95 values were >95% when the baseline shift errors were increased to 2.0 mm. When the rotational error was increased to 1.5° and baseline shift errors increased to 1.0 mm, the D95 and V95 values were >95% in only 3 cases. Conclusions: The multivariate regression model analysis in this study showed that the coverage of the target decreased further with reduced target volume, increasing the baseline drift, the rotation error, and the distance to the target.

Phytic acid improves osteogenesis and inhibits the senescence of human bone marrow mesenchymal stem cells under high-glucose conditions via the ERK pathway.

Hyperglycaemia causes impairment of osteogenic differentiation and accelerates stem cell senescence, resulting in weakened osteogenesis and disordered bone metabolism. Phytic acid (PA) is an antioxidant that is reportedly beneficial to bone homeostasis. The present study aims to clarify how PA affects the osteogenic capacity and cellular senescence of bone marrow mesenchymal stem cells (BMSCs) exposed to high-glucose environments, as well as the potential molecular mechanisms. Our results indicate that osteogenic differentiation in BMSCs cultivated in high-glucose conditions is enhanced by PA, as evidenced by increased alkaline phosphatase activity and staining, Alizarin Red S staining, osteogenic marker in in vitro studies, and increased osteogenesis in animal experiments. PA also prevented high-glucose-induced senescence of BMSCs, as evidenced by the repression of reactive oxygen species production, senescence-associated ß-galactosidase staining, and P21 and P53 expression. Furthermore, it was found that PA rescued the high-glucose-inhibited expression of phosphorylated extracellular regulated protein kinases (p-ERK). The inhibition of ERK pathway by the specific inhibitor PD98059 blocked the PA-enhanced osteogenesis of BMSCs and promoted cell senescence. Our results revealed that PA enhances osteogenic differentiation and inhibits BMSC senescence in a high-glucose environment. In addition, the activation of the ERK pathway seems to mediate the beneficial effects of PA. The findings provide novel insights that could facilitate bone regeneration in patients with diabetes.

Dosimetric evaluation of different planning strategies for hypofractionated whole-breast irradiation technique.

Purpose.The dose hotspot areas in hypofractionated whole-breast irradiation (WBI) greatly increase the risk of acute skin toxicity because of the anatomical peculiarities of the breast. In this study, we presented several novel planning strategies that integrate multiple sub-planning target volumes (sub-PTVs), field secondary placement, and RapidPlan models for right-sided hypofractionated WBI.Methods.A total of 35 cases of WBI with a dose of 42.5 Gy for PTVs using tangential intensity-modulated radiotherapy (IMRT) were selected. Both PTVs were planned for simultaneous treatment using the original manual multiple sub-PTV plan (OMMP) and the original manual single-PTV plan (OMSP). The manual field secondary placement multiple sub-PTV plan (m-FSMP) with multiple objects on the original PTV and the manual field secondary placement single-objective plan (m-FSSP) were initially planned, which were distribution-based of V105 (volume receiving 105% of the prescription dose). In addition, two RapidPlan-based plans were developed, including the RapidPlan-based multiple sub-PTVs plan (r-FSMP) and the RapidPlan-based single-PTV plan (r-FSSP). Dosimetric parameters of the plans were compared, and V105 was evaluated using multivariate analysis to determine how it was related to the volume of PTV and the interval of lateral beam angles (ILBA).Results.The lowest mean V105 (5.64 ± 6.5%) of PTV was observed in m-FSMP compared to other manual plans. Upon validation, r-FSSP demonstrated superior dosimetric quality for OAR compared to the two other manual planning methods, except for V5(the volume of ipsilateral lung receiving 5 Gy) of the ipsilateral lung. While r-FSMP showed no significant difference (p = 0.06) compared to r-FSSP, it achieved the lowest V105 value (4.3 ± 4.5%), albeit with a slight increase in the dose to some OARs. Multivariate GEE linear regression showed that V105 is significantly correlated with target volume and ILBA.Conclusions.m-FSMP and r-FSMP can substantially enhance the homogeneity index (HI) and reduce V105, thereby minimizing the risk of acute skin toxicities, even though there may be a slight dose compromise for certain OARs.

Quantify the Effect of Air Gap Errors on Skin Dose for Breast Cancer Radiotherapy.

Purpose: Determining the impact of air gap errors on the skin dose in postoperative breast cancer radiotherapy under dynamic intensity-modulated radiation therapy (IMRT) techniques. Methods: This was a retrospective study that involved 55 patients who underwent postoperative radiotherapy following modified radical mastectomy. All plans employed tangential IMRT, with a prescription dose of 50 Gy, and bolus added solely to the chest wall. Simulated air gap depth errors of 2 mm, 3 mm, and 5 mm were introduced at depression or inframammary fold areas on the skin, resulting in the creation of air gaps named Air2, Air3, and Air5. Utilizing a multivariable GEE, the average dose (Dmean) of the local skin was determined to evaluate its relationship with air gap volume and the lateral beam's average angle (AALB). Additionally, an analysis was conducted on the impact of gaps on local skin. Results: When simulating an air gap depth error of 2 mm, the average Dmean in plan2 increased by 0.46 Gy compared to the initial plan (planO) (p < .001). For the 3-mm air gap, the average Dmean of plan3 was 0.51 Gy higher than that of planO (p < .001). When simulating the air gap as 5 mm, the average Dmean of plan5 significantly increased by 0.59 Gy compared to planO (p < .001). The TCP results showed a similar trend to those of Dmean. As the depth of air gap error increases, NTCP values also gradually rise. The linear regression of the multivariable GEE equation indicates that the volume of air gaps and the AALB are strong predictors of Dmean. Conclusion: With small irregular air gap errors simulated in 55 patients, the values of skin's Dmean, TCP, and NTCP increased. A multivariable linear GEE regression model may effectively explain the impact of air gap volume and AALB on the local skin.

Phytic acid promotes high glucose-mediated bone marrow mesenchymal stem cells osteogenesis via modulating circEIF4B that sponges miR-186-5p and complexes with IGF2BP3.

Diabetes-related hyperglycemia inhibits bone marrow mesenchymal stem cell (BMSC) function, thereby disrupting osteoblast capacity and bone regeneration. Dietary supplementation with phytic acid (PA), a natural inositol phosphate, has shown promise in preventing osteoporosis and diabetes-related complications. Emerging evidence has suggested that circular (circ)RNAs implicate in the regulation of bone diseases, but their specific regulatory roles in BMSC osteogenesis in hyperglycemic environments remain elucidated. In this study, in virto experiments demonstrated that PA treatment effectively improved the osteogenic capability of high glucose-mediated BMSCs. Differentially expressed circRNAs in PA-induced BMSCs were identified using circRNA microarray analysis. Here, our findings highlight an upregulation of circEIF4B expression in BMSCs stimulated with PA under a high-glucose microenvironment. Further investigations demonstrated that circEIF4B overexpression promoted high glucose-mediated BMSC osteogenesis. In contrast, circEIF4B knockdown exerted the opposite effect. Mechanistically, circEIF4B sequestered microRNA miR-186-5p and triggered osteogenesis enhancement in BMSCs by targeting FOXO1 directly. Furthermore, circEIF4B inhibited the ubiquitin-mediated degradation of IGF2BP3, thereby stabilizing ITGA5 mRNA and promoting BMSC osteogenic differentiation. In vivo experiments, circEIF4B inhibition attenuated the effectiveness of PA treatment in diabetic rats with cranial defects. Collectively, our study identifies PA as a novel positive regulator of BMSC osteogenic differentiation through the circEIF4B/miR-186-5p/FOXO1 and circEIF4B/IGF2BP3/ITGA5 axes, which offers a new strategy for treating high glucose-mediatedBMSCosteogenic dysfunction and delayed bone regeneration in diabetes.

Dual Mg-Reinforced PCL Membrane with a Janus Structure for Vascularized Bone Regeneration and Bacterial Elimination.

Commercially available guided bone regeneration (GBR) membranes often exhibit limited mechanical properties or bioactivity, leading to poor performance in repairing bone defects. To surmount this limitation, we developed a Janus structural composite membrane (Mg-MgO/PCL) reinforced by dual Mg (Mg sheets and MgO NPs) by using a combined processing technique involving casting and electrospinning. Results showed that the addition of Mg sheets and MgO NPs enhanced the mechanical properties of the composite membrane for osteogenic space maintenance, specifically tensile strength (from 10.2 ± 1.2 to 50.3 ± 4.5 MPa) and compression force (from 0 to 0.94 ± 0.09 N mm-1), through Mg sheet reinforcement and improved crystallization. The dense cast side of the Janus structure membrane displayed better fibroblast barrier capacity than a single fiber structure; meanwhile, the PCL matrix protected the Mg sheet from severe corrosion due to predeformation. The porous microfibers side supported preosteoblast cell adhesion, enhanced osteogenesis, and angiogenesis in vitro, through the biomimetic extracellular matrix and sustainable Mg2+ release. Furthermore, the Mg-MgO/PCL membrane incorporating 2 wt % MgO NPs exhibited remarkable antimicrobial properties, inducing over 88.75% apoptosis in Staphylococcus aureus. An in vivo experiment using the rat skull defect model (Φ = 5 mm) confirmed that the Mg-MgO/PCL membrane significantly improved new bone formation postsurgery. Collectively, our investigation provides valuable insights into the design of multifunctional membranes for clinical oral GBR application.