LncRNA JHDM1D-AS1 promotes osteogenic differentiation of periodontal ligament cells by targeting miR-532-5p to activate IGF1R signaling.

OBJECTIVE: The aim of this study was to explore the mechanism underlying periodontal ligament cells (PDLCs) osteogenic differentiation. BACKGROUND: Periodontitis causes damage to tooth-supporting apparatus and eventually leads to tooth loss. PDLCs hold great promise in periodontal regeneration due to their osteogenic features. METHODS: The expression of osteogenic markers, lncRNA JHDM1D-AS1, miR-532-5p and IGF1R was examined. For osteogenic differentiation, primary human PDLCs (hPDLCs) were cultured in an osteogenic medium, and it was assessed by ALP activity and Alizarin Red staining. The interaction between JHDM1D-AS1, miR-532-5p and IGF1R was analyzed via dual luciferase, RIP and RNA pull-down assays. RESULTS: JHDM1D-AS1 was up-regulated during osteogenic differentiation and its silencing inhibited hPDLC osteogenic differentiation. JHDM1D-AS1 worked as a miR-532-5p sponge in hPDLCs. miR-532-5p directly targeted IGF1R to suppress its expression, and miR-532-5p knockdown facilitated osteogenic differentiation of hPDLCs. Overexpression of IGF1R promoted osteogenic differentiation of hPDLCs via activating Notch/HES1 signaling in hPDLCs. CONCLUSION: JHDM1D-AS1 promotes osteogenic differentiation of hPDLCs via sponging miR-532-5p to facilitate IGF1R expression and activate Notch/HES1 signaling.

Dentoperiodontal and skeletal changes induced by miniscrew-assisted rapid maxillary expansion (C-expander) treatment in adults: A retrospective clinical trial.

INTRODUCTION: The objective of this study was to evaluate the dental periodontal and skeletal response to ≥5 mm of expansion width achieved by C-expander treatment with posterior miniscrews placed between the first and second molars in adults. METHODS: A total of 28 patients aged 21.91 ± 3.20 years with maxillary transverse deficiency underwent C-expander treatment. Anterior miniscrews were positioned between the first and second premolars, whereas posterior miniscrews were positioned between the first and second molars. Cone-beam computed tomography records were obtained before expansion and 3 months after expansion. The dental periodontal and skeletal changes for all patients were recorded. RESULTS: The C-expander treatment expanded the palatal suture with slight buccal alveolar bone inclination. An increase in the nasal cavity width and a greater increase in the maxillary base bone width were observed after maxillary expansion. The expansion at the posterior nasal spine (3.78 mm) was approximately 85.7% of that at the anterior nasal spine (4.41 mm). No significant buccal dehiscence occurred after expansion, whereas the mesiobuccal alveolar bone thickness of the first molars was decreased at the 8 mm level with respect to the cementoenamel junction. The first molar showed decreased inclination (right, -0.45°; left, -0.38°, P >0.05), whereas the expansion at the apical level was less than that at the crown level. Age and the skeletal/dental expansion ratio had no discernible relationship. CONCLUSIONS: Miniscrew-assisted C-expander treatment can be effective for adults with maxillary transverse deficiency. Rearward placement of the miniscrews may create an approximately parallel expansion. Most maxillary expansion was derived from skeletal expansion with slight alveolar bone buccal inclination.

A Chewing Gum Residue-Based Gel with Superior Mechanical Properties and Self-Healability for Flexible Wearable Sensor.

Chewing gum residue is hard to decompose and easy to cause pollution, which is highly desirable to realize recycling. In this paper, a chewing gum gel with enhanced mechanical properties and self-healing properties is prepared by using polyvinyl alcohol (PVA) as the backbone in chewing gum residue. The hydrogen bond and the borax ester bond are employed to construct reversible interaction to enhance the self-healing ability. The physical crosslinking is realized by further freeze-thaw treatment to improve its mechanical properties. The gel demonstrates high elongation at break of 610% and strength of 0.11 MPa, as well as excellent self-healing performance and recyclable properties. In particular, the gel with a fast signal response is successfully applied as a wearable strain sensor to monitor different types of human motion. The gel as a sensor exhibits self-healing properties suggesting superior safety and stability, and displays wide linear sensitivity (the gauge factor is 0.417 and 0.170). The gel can be further served to explore temperature changes, implying the application in temperature monitoring. This study develops a novel approach for the recycle and reuse of chewing gum residue. The obtained gel may be a promising candidate for the fabrication of flexible wearable sensor.

Doxorubicin and lapatinib combination nanomedicine for treating resistant breast cancer.

Our objective was to design a polymeric micelle-based doxorubicin and lapatinib combination therapy for treating multidrug resistant (MDR) breast cancers. Poly(ethylene glycol)-block-poly(2-methyl-2-benzoxycarbonylpropylene carbonate) (PEG-PBC) polymers were synthesized for preparing doxorubicin and lapatinib loaded micelles using a film dispersion method. Micelles were characterized by determining critical micelle concentration (CMC), particle size distribution, and drug loading. The anticancer effects were determined in vitro with MTT assays as well as with lactate dehydrogenase (LDH) release studies. In addition, the cellular uptake of drug-loaded micelles was determined with fluorescence microscopy and flow cytometry. Finally, in vivo anticancer activity and tolerance of developed formulations were evaluated in resistant breast tumor bearing mice. PEG5K-PBC7K polymer synthesized in this study had a low CMC value (1.5 mg/L) indicating an excellent dynamic stability. PEG-PBC micelles could efficiently load both doxorubicin and lapatinib drugs with a loading density of 21% and 8.4%, respectively. The mean particle size of these micelles was 100 nm and was not affected by drug loading. The use of lapatinib as an adjuvant sensitized drug resistant MCF-7/ADR cells to doxorubicin treatment. Cellular uptake studies showed enhanced doxorubicin accumulation in MCF-7/ADR cells in the presence of lapatinib. The doxorubicin and lapatinib combination therapy showed a significant decrease in tumor growth compared to doxorubicin monotherapy. In conclusion, we have developed PEG-PBC micelle formulations for the delivery of doxorubicin and lapatinib. The combination therapy of doxorubicin plus lapatinib has a great potential for treating MDR breast cancer.

The freeze-thaw cycle exacerbates the ecotoxicity of polystyrene nanoplastics to Secale cereale L. seedlings.

In the context of global climate change, recurrent freeze-thaw cycles (FTC) and concurrent exposure to polystyrene nanoplastics (PSNPs) directly impact crop growth and indirectly affect resilience to abiotic stress. In January 2023, experiments at the Environmental Biology Laboratory, Jilin University, Changchun, China, exposed rye seedlings to 100 nm PSNPs at concentrations of 0, 10, 50, and 100 mg/L for seven days, followed by three FTC. Scanning electron microscopy (SEM) demonstrated that PSNPs migrated from the roots to the leaves, with FTC significantly exacerbating their accumulation within plant tissues. Transmission electron microscopy (TEM) observations showed that FTC disrupted normal cell division, and combined stress from NPs damaged plant organs, particularly chloroplasts, thereby substantially inhibiting photosynthesis. FTC delayed plant phenological stages. Under combined stress, malondialdehyde (MDA) accumulation in plant tissues increased by 15.6%, while hydrogen peroxide (H2O2) content decreased. Simultaneously, the activities of peroxidase (POD) and catalase (CAT) increased by 34.2% and 38.6%, respectively. Molecular docking unveiled that PSNPs could bind to the active center of POD/CAT through hydrogen bonding or hydrophobic interactions. The Integrated Biomarker Response (IBR) index highlighted FTC as a crucial determinant for pronounced effects. Moreover, an apparent dose-dependent effect was observed, with antioxidant enzyme activities in rye seedlings induced by low pollutant concentrations and inhibited by high concentrations. These results indicate that FTC and PSNPs can disrupt plant membrane systems and cause severe oxidative damage. Overall, this study provides compelling scientific evidence of the risks associated with NPs exposure in plants subjected to abiotic stress.

Bio-based alginate and Si-, P- and N-containing compounds cooperate toward flame-retardant modification of polyester fabrics.

Imparting flame retardancy to polyester fabrics is still a pressing issue for the textile industry. To this end, a composite coating was developed by phosphite, pentamethyldisiloxane, urea and sodium alginate, and then applied together with calcium chloride to prepare flame-retardant polyester fabrics. The optimized polyester fabrics named PF-HUSC exhibited a rough surface with P, Si, N and Ca element distributions, as observed by scanning electron microscope (SEM) and energy dispersive X-ray spectrometer (EDX). Flame retardancy evaluations showed that the damaged length of PF-HUSC with a limiting oxygen index (LOI) value of 35.3 ± 0.3 % was reduced from the contrastive 17.6 ± 0.4 cm to 4.6 ± 0.2 cm after vertical burning test. Thermogravimetric (TG) test confirmed that PF-HUSC retained a char residue as high as 35.1 % at 700 °C. Cone calorimetry test displayed that the total heat release (THR) and total smoke production (TSP) values of PF-HUSC were reduced to 3.1 MJ/m2 and 1.1 m2, respectively, as compared to those of pure polyester fabrics. More importantly, PF-HUSC still exhibited higher LOI value than that of pure polyester fabrics after 25 washing cycles. Hence, the coating scheme is considered as a new method to expand the preparation of flame-retardant polyester fabrics.

Nomograms for Predicting Cancer-Specific Survival of Patients with Gingiva Squamous Cell Carcinoma: A Population-Based Study.

OBJECTIVE: The use of the traditional American Joint Committee on Cancer (AJCC) staging system alone has limitations in predicting the survival of gingiva squamous cell carcinoma (GSCC) patients. We aimed to establish a comprehensive prognostic nomogram with a prognostic value similar to the AJCC system. METHODS: Patients were identified from SEER database. Variables were selected by a backward stepwise selection method in a Cox regression model. A nomogram was used to predict cancer-specific survival rates for 3, 5 and 10 years in patients with GSCC. Several basic features of model validation were used to evaluate the performance of the survival model: consistency index (C-index), receiver operating characteristic (ROC) curve, calibration chart, net weight classification improvement (NRI), comprehensive discriminant improvement (IDI) and decision curve analysis (DCA). RESULTS: Multivariate analyses revealed that age, race, marital status, insurance, AJCC stage, pathology grade and surgery were risk factors for survival. In particular, the C-index, the area under the ROC curve (AUC) and the calibration plots showed good performance of the nomogram. Compared to the AJCC system, NRI and IDI showed that the nomogram has improved performance. Finally, the nomogram's 3-year and 5-year and 10-year DCA curves yield net benefits higher than traditional AJCC, whether training set or a validation set. CONCLUSION: We developed and validated the first GSCC prognosis nomogram, which has a better prognostic value than the separate AJCC staging system. Overall, the nomogram of this study is a valuable tool for clinical practice to consult patients and understand their risk for the next 3, 5 and 10 years.

Polymer-Assisted Metallization of Mammalian Cells.

Developing biotemplating techniques to translate microorganisms and cultured mammalian cells into metallic biocomposites is of great interest for biosensors, electronics, and energy. The metallization of viruses and microbial cells is successfully demonstrated via a genetic engineering strategy or electroless deposition. However, it is difficult to transform mammalian cells into metallic biocomposites because of the complicated genes and the delicate morphological features. Herein, "polymer-assisted cell metallization" (PACM) is reported as a general method for the transformation of mammalian cells into metallic biocomposites. PACM includes a first step of in situ polymerization of functional polymer on the surface and in the interior of the mammalian cells, and a subsequent electroless deposition of metal to convert the polymer-functionalized cells into metallic biocomposites, which retain the micro- and nanostructures of the mammalian cells. This new biotemplating method is compatible with different cell types and metals to yield a wide variety of metallic biocomposites with controlled structures and properties.

Redox sensitive PEG controlled octaarginine and targeting peptide co-modified nanostructured lipid carriers for enhanced tumour penetrating and targeting in vitro and in vivo.

To strengthen the anti-tumour efficacy and weaken the side effects, a nano targeted drug delivery system was constructed. The nanostructured lipid carriers (NLCs) were prepared by the melt-emulsification method. Modified with the octaarginine, thiolytic cleavable polyethylene glycol (PEG) and targeting peptide simultaneously on the surface, this multifunctional NLC could not only actively target to tumour tissues, but also control the cell penetration effect of the octaarginine easily by a safe reducing agent l-cysteine (l-Cys). In the present study, the pharmaceutical characteristics, the cytotoxicity and cellular uptake on NCI-H1299 cells in vitro, the biodistribution and targeting effect and anti-tumour ability in vivo were employed to evaluate the formulations. As the results revealed, various NLCs had a mean particle size of about 40 nm and a positive zeta potential of about 10 mV. The optimum density of cleavable PEG was confirmed as 10% and the best concentration of l-cysteine was determined as 20 mM via the qualitative and quantitative cellular uptake study. Based on these outcomes, the multiply decorated NLC manifested a great cell growth inhibition with the increased concentration of paclitaxel (PTX). Moreover, it preferred to accumulate at tumours, but not normal organs in vivo. Compared with Taxol®, this preparation demonstrated stronger anti-tumour efficacy and better security. Therefore, the multifunctional NLC can be considered as a promising drug delivery system targeting to tumours.

Polyarginine and PEG-AEYLR comodified nanostructured lipid carrier: 10mol% uncleavable PEG-AEYLR showed no shielding effect to polyarginine in vitro while maintaining good tumor targeting in vivo.

We constructed a dual ligands-modified nanostructured lipid carrier (NLC) called PAR-NLC, in which the epidermal growth factor receptor (EGFR)-targeted small peptide AEYLR was attached to the distal end of PEG2000 anchored on the NLC surface naming PEG-AEYLR, and poly-arginine (R8) as a classic cell-penetrating peptide was attached directly to the NLC surface. PAR-NLC was near-spherical particle with average size ∼50 nm and zeta potential at +14.09 mV; the cellular uptake of PAR-NLC showed synergistic effect of the two peptides, presented as significant superior cellular uptake in EGFR-positive cells NCI-H1299 and S180 over EGFR-negative cell K562. In the animal optical imaging study, 2 h after the administration of the Dir-loaded PAR-NLC, maximum Dir signal appeared in tumor tissue, indicating prompt tumor targeting effect, as time prolonged to 48 h, the Dir signal attenuated in the organs except tumor, suggesting constant clearance from the body. In the in vivo antitumor study, in premise of the same dose, paclitaxel-loaded PAR-NLC exhibited better antitumor and safety effect than Taxol, the body weight of the mice was more stable and tumor size was smaller. In summary, PAR-NLC was a potential drug carrier to deliver anticancer drugs safely and effectively.

Expression of matrix metalloproteinases-8 and -9 and their tissue inhibitor in the condyles of diabetic rats with mandibular advancement.

The present study aimed to evaluate the effects of type 1 diabetes mellitus on the condylar response during treatment with a functional appliance. Sprague-Dawley rats were divided into 3 groups, normal (NG), diabetes (DG) and diabetes with insulin-treatment (TG). Bite-jumping appliances were fitted to the rats in the experimental groups. At 7, 14, 21 and 28 days following fitting, animals were sacrificed and condyles were excised and processed using routine histological techniques. The expression of matrix metalloproteinase (MMP)-8, MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) was detected using immunohistochemical analysis. Mandibular advancement increased the expression levels of MMP-8 (peaked on day 28), MMP-9 (peaked on day 21), TIMP-1 (peaked on days 21 and 28) and the ratio of MMP-8 to TIMP-1 and MMP-9 to TIMP-1. In the DG, diabetes decreased the expression levels of MMP-8 and MMP-9 induced by mandibular advancement and increased the expression levels of TIMP-1 compared with that of the NG. The ratio of MMP-8 to TIMP-1 and MMP-9 to TIMP-1 also showed a significant decrease in the DG compared with that of the NG. A recovery of these parameters was observed in the TG. Diabetes significantly altered the condylar response, which was triggered by mandibular advancement, and weakened subsequent bone deposition. The results from the TG were not significantly different from that of the NG.

Low-molecular-weight protamine-modified PLGA nanoparticles for overcoming drug-resistant breast cancer.

Multidrug resistance (MDR) is a major challenge for cancer therapy. Herein, we report a simple yet effective system, cell-penetrating peptide (CPP)-assisted poly(lactic-co-glycolic acid nanoparticles (PLGA NPs), for improving doxorubicin (DOX) delivery and overcoming MDR cancer. We selected the naturally derived CPP low-molecular-weight protamine (LMWP) to modify PLGA NP for enhanced drug delivery. We demonstrated that multiple mechanisms ("synergistic multipronged delivery") were responsible for the anti-MDR effects of LMWP/PLGA NP. This delivery system could boost intracellular and intranuclear delivery, thereby circumventing drug efflux. Use of a P-glycoprotein inhibitor did not further increase the efficiency of intracellular delivery of LMWP/PLGA/DOX NP, suggesting that delivery of LMWP-based NP was not affected by transporter-mediated drug efflux. Importantly, enhanced uptake and penetration within the tumor was found in mice given LMWP-based NP. LMWP/PLGA NP effectively arrested tumor growth in mice harboring drug-resistant breast tumors, thereby improving treatment outcomes without detectable toxicities. These data suggest that our system could provide effective yet safe anti-MDR cancer therapy based on a synergistic, multipronged drug-delivery strategy.

[A pilot study of repair of periodontal bone defects with carbonated phosphate bone cement modified with synthesized peptides in dogs].

OBJECTIVE: To explore the possibility of repairing periodontal defects with carbonated calcium phosphate bone cement (CCPBC) modified with synthesized peptides. METHODS: Periodontal bone defects in 4 dogs were surgically created and then restored directly with hydroxyapatite (HA), Perioglass, CCPBC and CCPBC modified with peptides. The results were compared at different levels. RESULTS: Bone replacement materials were lost in HA and Perioglass groups. In the HA group defects were restored with connective tissue. Perioglass group had only a little new bone around materials by alveolar bone. CCPBC could firmly stay in bone defects to maintain the space of bone defects even without membrane use. CCPBC modified with peptides was superior to HA, Perioglass, and CCPBC, surrounded by a great deal of new bone. CONCLUSION: Under limitation of this study, CCPBC modified with peptides has some osteoinuctive activity and may have good prospect for the clinical application in periodontal defect repair.