Knowledge and awareness of early gastrointestinal cancer screening in Sunan Yugur Autonomous County in Gansu, China.

OBJECTIVE: We aimed to assess the level of knowledge and awareness regarding the need for screening of early gastrointestinal cancer among residents of Sunan Yugur Autonomous County in China. METHODS: In this cross-sectional study, we conducted a survey among permanent residents of Sunan Yugur Autonomous County from January 2020 to January 2023 using a questionnaire to obtain data on knowledge regarding early gastrointestinal cancer screening. RESULTS: The survey included 12,000 residents. Among participants, 62.30% (7476/12,000) were aware of the need for early gastrointestinal cancer screening. Awareness about the need for early gastrointestinal cancer screening differed significantly based on participants' sex, age, level of education, area of residence, and ethnicity. CONCLUSION: The level of awareness regarding the need for early gastrointestinal cancer screening was relatively low in our study population. The government and medical institutions should provide information and promote early gastrointestinal cancer screening in the region to improve the health status and quality of life among the Yugur people.

Porous Organic Materials in Tissue Engineering: Recent Advances and Applications for Severed Facial Nerve Injury Repair.

The prevalence of facial nerve injury is substantial, and the restoration of its structure and function remains a significant challenge. Autologous nerve transplantation is a common treatment for severed facial nerve injury; however, it has great limitations. Therefore, there is an urgent need for clinical repair methods that can rival it. Tissue engineering nerve conduits are usually composed of scaffolds, cells and neurofactors. Tissue engineering is regarded as a promising method for facial nerve regeneration. Among different factors, the porous nerve conduit made of organic materials, which has high porosity and biocompatibility, plays an indispensable role. This review introduces facial nerve injury and the existing treatment methods and discusses the necessity of the application of porous nerve conduit. We focus on the application of porous organic polymer materials from production technology and material classification and summarize the necessity and research progress of these in repairing severed facial nerve injury, which is relatively rare in the existing articles. This review provides a theoretical basis for further research into and clinical interventions on facial nerve injury and has certain guiding significance for the development of new materials.

Endothelium dysfunction and thrombosis in COVID-19 with type 2 diabetes.

SARS-CoV-2 can directly or indirectly damage endothelial cells. Endothelial injury, especially phosphatidylserine (PS) exposure on the outer membrane of cells, can more easily promote thrombosis. Type 2 diabetes(T2D) patients were more susceptible to COVID-19, they had more severe symptoms, higher risk of thrombotic complications, and longer duration of post-COVID-19 sequelae. This review provided a detailed overview of the mechanisms underlying endothelial dysfunction in T2D patients with COVID-19 (including long COVID), which may be influenced by hyperglycemia, hypoxia, and pro-inflammatory environments. The mechanisms of thrombosis in T2D patients with COVID-19 are also explored, particularly the effects of increased numbers of PS-exposing particles, blood cells, and endothelial cells on hypercoagulability. Given the high risk of thrombosis in T2D patients with COVID-19, early antithrombotic therapy can both minimize the impact of the disease on patients and maximize the chances of improvement, thereby alleviating patient suffering. We provided detailed guidance on antithrombotic drugs and dosages for mild, moderate, and severe patients, emphasizing that the optimal timing of thromboprophylaxis is a critical factor in influencing prognosis. Considering the potential interactions between antidiabetic, anticoagulant, and antiviral drugs, we proposed practical and comprehensive management recommendations to supplement the incomplete efficacy of vaccines in the diabetic population, reduce the incidence of post-COVID-19 sequelae, and improve patient quality of life.

Effects of photodynamic therapy on Streptococcus mutans and enamel remineralization of multifunctional TiO2-HAP composite nanomaterials.

BACKGROUND: As photosensitizer and photocatalyst, titanium dioxide (TiO2) can produce a photodynamic reaction for antibacterial treatment. This study aims to explore a Titanium dioxide/nano-hydroxyapatite (TiO2-HAP) composite combined with the dental curing lamp (385-515 nm) in clinical which could inhibit the dental plaque biofilm formed by Streptococcus mutans (S. mutans) and promote the enamel surface remineralization simultaneously. METHODS: X-ray Diffraction (XRD) and high resolution transmission electron microscope (HRTEM) were used to detect the characterization of TiO2-HAP composite nanomaterials. Photodynamic properties of TiO2-HAP were detected by Diffuse reflectance spectrum (DRS) and fluorescence spectroscopy. Bacterial growth was measured by reading the absorbance of bacterial cultures and confocal microscope was used to observe the biofilm removal ability of nanomaterials. The ability of TiO2-HAP to promote enamel remineralization was measured by Scanning electron microscope (SEM). RESULTS: The OD 600 of S. mutans was 0.76 in the control group and 0.13 in group of TiO2-HAP with exposure to light-emitting diode (LED) (150 mW/cm2) for 5 min, suggesting its sustained antibacterial potency and inhibition of the metabolic activity of dental plaque microcosm biofilm. Also, the release of calcium and phosphorus ions in TiO2-HAP can promote enamel mineralization simultaneously. After 15 days of remineralization, the Ca/P ratio of demineralized enamel surface increased from 1.28 to 1.67, which was similar to that of normal enamel. CONCLUSIONS: The TiO2-HAP exhibit a promising anti-bacterial activity and remineralization capacity which can prevent the occurrence of caries to the greatest extent and promote the biomimetic mineralization of dental tissues.

Identifying Common Genes and Pathways Associated with Periodontitis and Aging by Bioinformatics Analysis.

Background: This work used bioinformatic analysis to identify the relationship between periodontitis (PD) and aging, which could lead to new treatments for periodontal disease in the elderly. Method: Four microarray datasets were obtained from the Gene Expression Omnibus (GEO) database and analyzed in R language to identify differentially expressed genes (DEGs). The common DEGs of PD and aging were evaluated as key genes in this investigation by a Venn diagram. These common DEGs were analyzed through additional experiments and analysis, such as pathway analysis and enrichment analysis, and a network of protein-protein interactions (PPIs) was constructed. Cytoscape was used to visualize hub genes and critical modules based on the PPI network. Interaction of TF-genes and miRNAs with hub genes is identified. Result: 84 common DEGs were found between PD and aging. Cytohubba was performed on the PPI network obtained from STRING tool, and the top 10 genes (MMP2, PDGFRB, CTGF, CD34, CXCL12, VIM, IL2RG, ACTA2, COL4A2, and TAGLN) were selected as hub genes. VIM may be a potential biomarker in the analysis of linked hub gene regulatory networks, and hsa-mir-21 and hsa-mir-125b are predicted to be associated in PD and aging. Conclusion: This study investigated the key genes and pathways interactions between PD and aging, which may help reveal the correlation between PD and aging. The current research results are obtained by prediction, and follow-up biological experiments are required for further verification.

Expert consensus on dental caries management.

Dental Caries is a kind of chronic oral disease that greatly threaten human being's health. Though dentists and researchers struggled for decades to combat this oral disease, the incidence and prevalence of dental caries remain quite high. Therefore, improving the disease management is a key issue for the whole population and life cycle management of dental caries. So clinical difficulty assessment system of caries prevention and management is established based on dental caries diagnosis and classification. Dentists should perform oral examination and establish dental records at each visit. When treatment plan is made on the base of caries risk assessment and carious lesion activity, we need to work out patient­centered and personalized treatment planning to regain oral microecological balance, to control caries progression and to restore the structure and function of the carious teeth. And the follow-up visits are made based on personalized caries management. This expert consensus mainly discusses caries risk assessment, caries treatment difficulty assessment and dental caries treatment plan, which are the most important parts of caries management in the whole life cycle.

Silencing integrin α6 enhances the pluripotency-differentiation transition in human dental pulp stem cells.

OBJECTIVES: Although integrins have been shown to be associated with proliferation and differentiation in some stem cells, the regulatory effect of integrin α6 (ITGα6) on the human dental pulp stem cells (hDPSCs) has not been reported. Here, we detected the roles of ITGα6 in hDPSCs. MATERIALS AND METHODS: Attached to Cytodex 3 microcarriers, hDPSCs grown under stimulated microgravity (SMG) or conventional culture conditions were measured the proliferation and different gene expression. Further, ITGα6 was silenced in hDPSCs, and its effect on proliferation, differentiation, and cytoskeletal organization was analyzed. RESULTS: SMG conditions increased the number of Ki67-positive hDPSCs and progression into S phase of cell cycle. WB analysis showed the expression of ITGα6 was upregulated in hDPSCs under SMG conditions. Knockdown of ITGα6 decreased the expression of stemness markers, CD105 and STRO-1 in hDPSCs, but promoted the osteogenic and odontogenic differentiation by increased ALP expression and Alizarin Red nodules. Moreover, RNA-seq demonstrated that RHO/ROCK signaling pathway upregulated silencing ITGα6-hDPSCs. Treatment with Y-27632 inhibited the effect of ITGα6 depletion on hDPSCs stemness, rearranged the cytoskeleton, promoted the pluripotency, proliferation ability, and inhibited the differentiation. CONCLUSION: ITGα6 promotes hDPSCs stemness via inhibiting RHO/ROCK and restoring cytoskeleton.

Microvesicles, blood cells, and endothelial cells mediate phosphatidylserine-related prothrombotic state in patients with periodontitis.

BACKGROUND: Phosphatidylserine (PS) is essential for inflammation-associated thrombogenesis, but the exact effect of PS on the prothrombotic state in periodontitis is uncertain. This study aimed to determine the PS-related procoagulant state in patients with periodontitis. METHODS: A total of 138 patients with periodontitis were examined compared with 42 healthy controls. PS-exposing cells and microvesicles in blood samples were detected by confocal microscopy and flow cytometry. The clotting time assay and prothrombinase complex formation assay were used to measure the procoagulant activity of microvesicles, blood cells and endothelial cells. Periodontal clinical parameters and laboratory characteristics of patients with severe periodontitis were recorded and analyzed at baseline and 6 months after non-surgical periodontal therapy. RESULTS: Total PS-positive (PS+ ) microvesicles and the percentage of PS+ blood cells increased in patients with severe periodontitis compared with patients with moderate/mild periodontitis or healthy controls. Endothelial cells cultured in serum from patients with severe periodontitis expressed more PS compared with those cultured in serum from healthy controls. Specifically, PS exposure on blood cells and endothelial cells significantly decreased after inhibiting the effect of inflammatory cytokines. The elevated levels of PS+ cells and microvesicles in severe periodontitis shortened clotting time and led to increased prothrombinase complex formation. Non-surgical periodontal therapy significantly attenuated the release of microvesicles and the PS exposure of blood cells in severe periodontitis. CONCLUSIONS: The prothrombotic state of patients with periodontitis is mediated by PS+ cells and microvesicles stimulated by elevated levels of inflammatory cytokines.

Chitosan Tubes Prefilled with Aligned Fibrin Nanofiber Hydrogel Enhance Facial Nerve Regeneration in Rabbits.

Facial nerves are fragile and easily injured, for example, by traffic accidents or operations. Facial nerve injury drastically reduces the quality of life in affected patients, and its treatment presents clinical challenges. A promising therapeutic strategy includes nerve conduits with appropriate fillers capable of guiding nerve regeneration. In this study, a three-dimensional hierarchically aligned fibrin nanofiber hydrogel (AFG) assembled via electrospinning and molecular self-assembly was first used to mimic the architecture of the native fibrin cable, which is similar to the nerve extracellular matrix (ECM). AFG as a substrate in chitosan tubes (CST) was used to bridge a 7 mm-long gap in a rabbit buccal branch facial nerve defect model. The results showed that AFG and CST showed good compatibility to support the adhesion, activity, and proliferation of Schwann cells (SCs). Further morphological, histological, and functional analyses demonstrated that the regenerative outcome of AFG-prefilled CST was close to that of autologous nerve grafts and superior to that of CST alone or CSTs prefilled with random fibrin nanofiber hydrogel (RFG), which indicated that AFG-prefilled CST markedly improved axonal regeneration with enhanced remyelination and functional recovery, thus showing great potential for clinical application for facial nerve regeneration treatments.

Effects of graphene on the proliferation, migration and morphology of dental pulp stem cells / 口腔疾病防治

Objective@# To investigate the effects of graphene on the proliferation, migration and cell morphology of dental pulp stem cells (DPSCs).@*Methods@#Graphene powder was prepared by the oxidation-reduction method, and a 0.5 mg/mL graphene dispersion was prepared. Raman spectroscopy and atomic force microscopy were used to characterize the structure and surface morphology of graphene. DPSCs were isolated and cultured in vitro. MTT assay was used to detect the effects of different concentrations of graphene dispersions (0, 1, 5, 10, 20, 50, 100 μg/mL) on the proliferation and wound healing assay was used to detected the migration abilities of DPSCs. The effects of graphene on the morphology of DPSCs were observed by immunofluorescence staining. @*Results @# In the present study, compared with the control group (0 μg/mL), the proliferation of DPSCs in the 100 μg/mL group was inhibited at 72 h (P < 0.05), and the proliferation of DPSCs in the other groups was not significantly affected (P > 0.05). Graphene dispersions at 10 and 20 μg/mL promoted the migration of DPSCs (P < 0.05). After being cultured in 20 μg/mL graphene dispersions for 3 days, the DPSCs showed a large and orderly cytoskeletal structure, and the spread area of cells was not significantly different from that of the control group (0 μg/mL) (P > 0.05), while some cells had the morphological characteristics of nerve cells.@* Conclusion @# Graphene has good biocompatibility and is expected to be a suitable material for tissue engineering within fitting concentration.

Computational fluid dynamics analysis of the flow of ultrasonic irrigations in root canal / 口腔疾病防治

Objective@#To study the computational fluid dynamics (CFD) characteristics of ultrasonic root canal irrigation when the file was placed at a certain depth in the root canal, to provide a reference for clinical application.@*Methods @#First, scanning laser vibrometry (SLV) was utilized to analyze the characteristics of vibrational ultrasonic files under specific power. Then ICEM CFD 18.0 software was used to establish the root canal ultrasonic irrigation model. The insertion position of the ultrasonic working tip was set 1 mm away from the physiological apical foramen, and cloud images of the results were obtained by FLUENT 18.0 software. Volume fraction, flow velocity and pressure in the root canal were evaluated after setting the computing conditions.@*Results@#The vibration of the ultrasonic working tip was mainly transverse vibration with slight longitudinal vibration. The amplitude of transverse vibration of each part of the working tip was different. Maximum values were observed at the apical end area of the file, and the closer to the base of the file, the smaller the amplitude. The area where the cavitation volume fraction of the rinsing fluid was greater than 0 was concentrated around the working point. The flow rate of the irrigating fluid was up to 2 m/s, within the area 0.2 mm in front of the working tip, the velocity of the irrigating fluid was greater than 0.1 m/s, while within the area 0.8 mm from the root tip, the velocity of the irrigating fluid was small or even zero. The apical pressure value was non-positive when the tip of the file was 1 mm away from the apical foramen in this model.@*Conclusion@# Based on the experimental results, it appears that when the ultrasonic working tip was placed 1 mm short of the working length, the ultrasonic irrigating flow did not overflow the root apical foramen and the irrigation process was relatively safe; the irrigation fluid had a strong irrigation effect within approximately 0.2 mm in front of the working tip.

Pathogenesis and multidisciplinary management of medication-related osteonecrosis of the jaw.

Medication-related osteonecrosis of the jaw (MRONJ) is a serious side effect of bone-modifying agents and inhibits angiogenesis agents. Although the pathogenesis of MRONJ is not entirely clear, multiple factors may be involved in specific microenvironments. The TGF-ß1 signalling pathway may have a key role in the development of MRONJ. According to the clinical stage, multiple variables should be considered when selecting the most appropriate treatment. Therefore, the prevention and management of treatment of MRONJ should be conducted in patient-centred multidisciplinary team collaborative networks with oncologists, dentists and dental specialists. This would comprise a closed responsibility treatment loop with all benefits directed to the patient. Thus, in the present review, we aimed to summarise the pathogenesis, risk factors, imaging features, clinical staging, therapeutic methods, prevention and treatment strategies associated with MRONJ, which may provide a reference that can inform preventive strategies and improve the quality of life for patients in the future.

A Customized Self-Assembling Peptide Hydrogel-Wrapped Stem Cell Factor Targeting Pulp Regeneration Rich in Vascular-Like Structures.

Pulp regeneration is to replace the inflamed/necrotic pulp tissue with regenerated pulp-like tissue to rejuvenate the teeth. Self-assembling peptide hydrogels RADA16-I (Ac-(RADA16-I)4-CONH2) can provide a three-dimensional environment for cells. The stem cell factor (SCF) plays a crucial role in homing stem cells. Combining these advantages, our study investigated the effects of SCF-RADA16-I on adhesion, proliferation, and migration of human dental pulp stem cells (DPSCs) and the angiogenesis of human umbilical vein endothelial cells (HUVECs). The ß-sheet and grid structure were observed by circular dichroism (CD), scanning electron microscopy (SEM), and atomic force microscopy (AFM). Cytoskeleton staining, living cell staining, cell viability, cell migration, angiogenesis, and western blot assays were performed, and the results indicated that all the SCF groups were superior to the corresponding non-SCF groups in cell adhesion, proliferation, migration, and angiogenesis. RADA16-I provided a three-dimensional environment for DPSCs. Besides, the SCF promoted HUVECs to form more vascular-like structures and release more vascular endothelial growth factor A. In summary, the SCF-loaded RADA16-I scaffold improved adhesion, proliferation, and migration of DPSCs and the formation of more vascular-like structures of HUVECs. SCF-RADA16-I holds promise for guided pulp regeneration, and it can potentially be applied widely in tissue engineering and translational medicine in the future.

Human Umbilical Cord Mesenchymal Stem Cell Differentiation Into Odontoblast-Like Cells and Endothelial Cells: A Potential Cell Source for Dental Pulp Tissue Engineering.

OBJECTIVES: Dental pulp regeneration is considered an ideal approach for treating dental pulp disease. Because pulp is composed of various cells, determining the proper seed cells is critical. We explored the potential of human umbilical cord mesenchymal stem cells (hUCMSCs) as seed cells for dental pulp regeneration. METHODS: Liquid extract of human treated dentin matrix (LE-TDM) was acquired to culture hUCMSCs. Odontoblast-specific markers were detected by western blot, qRT-PCR, and immunofluorescence assays. Endothelial differentiation of hUCMSCs was examined according to VEGF induction by western blot, qRT-PCR, and Matrigel assays. hUCMSCs and VEGF-induced hUCMSCs (V-hUCMSCs) were also cocultured in vivo for the Matrigel plug assay and in vitro for RNA-sequencing (RNA-seq). Finally, encapsulated mono-cultured hUCMSCs or cocultured hUCMSCs and V-hUCMSCs in scaffolds were injected into the root segments and transplanted into immunodeficient mice for dental pulp regeneration. RESULTS: Under LE-TDM induction, hUCMSCs expressed specific odontoblast markers (DSPP, DMP-1, DSP). Under VEGF induction, hUCMSCs expressed functional endothelial markers (CD31, eNOs, vWF). In vivo, the Matrigel plug assay indicated that cocultured hUCMSCs and V-hUCMSCs formed extensive vessel-like structures. RNA-seq results indicated that cocultured V-hUCMSCs exhibited high Hif-1 signaling pathway activity. Both the hUCMSCs mono-culture and coculture groups showed pulp-like tissue regeneration. The cocultured group showed more extracellular matrix and vascularization than the mono-cultured group in vivo. CONCLUSION: hUCMSCs can differentiate into odontoblast-like cells and functional endothelial cells. Cocultured hUCMSCs and V-hUCMSCs formed vessel-like structures and regenerated dental pulp-like tissue. Therefore, hUCMSCs can be used as an alternative seed cell source for angiogenesis and dental pulp regeneration.

Tuftelin-derived peptide facilitates remineralization of initial enamel caries in vitro.

With the gradual discovery of functional domains in natural proteins, several biologically inspired peptides have been designed for use as biomaterials for hard tissue regeneration and repair. In this study, we designed a tuftelin-derived peptide (TDP) and tested its effects on hydroxyapatite crystallization and remineralization of initial enamel carious lesions in vitro. Using circular dichroism spectroscopy, we found that TDP contained 36.1% ß-sheets and ß-turns, which could be influenced by calcium ions. We verified the ability of TDP to crystallize hydroxyapatite using transmission electron microscopy and its ability to bind to the enamel surface and hydroxyapatite using confocal laser scanning microscopy and Langmuir adsorption isotherms (K = 881.56, N = 1.41 × 10-5 ). Artificial enamel lesions were generated on human enamel blocks and subjected to a 12-day pH cycling model and were treated with 25 µM TDP, 1 g/L sodium fluoride (NaF), or deionized water. We analyzed the results of remineralization by surface microhardness testing, polarized light microscopy, and transverse microradiography. The TDP group showed significantly higher surface microhardness recovery (49.21 ± 1.66%), shallower lesions (34.89 ± 4.05 µm), and less mineral loss (871.33 ± 81.49 vol%·µm) after pH cycling than the deionized water group (p < .05). There were no significant differences between the TDP and NaF groups. Our experiment indicated that TDP could regulate hydroxyapatite crystallization and promote remineralization of enamel caries in vitro.

Antibacterial Effect of Caffeic Acid Phenethyl Ester on Cariogenic Bacteria and Streptococcus mutans Biofilms.

Dental caries is the most common disease in the human mouth. Streptococcus mutans is the primary cariogenic bacterium. Propolis is a nontoxic natural product with a strong inhibitory effect on oral cariogenic bacteria. The polyphenol-rich extract from propolis inhibits S. mutans growth and biofilm formation, as well as the genes involved in virulence and adherence, through the inhibition of glucosyltransferases (GTF). However, because the chemical composition of propolis is highly variable and complex, the mechanism of its antimicrobial action and the active compound are controversial and not completely understood. Caffeic acid phenethyl ester (CAPE) is abundant in the polyphenolic compounds from propolis, and it has many pharmacological effects. In this study, we investigated the antibacterial effects of CAPE on common oral cariogenic bacteria (Streptococcus mutans, Streptococcus sobrinus, Actinomyces viscosus, and Lactobacillus acidophilus) and its effects on the biofilm-forming and cariogenic abilities of S. mutans CAPE shows remarkable antimicrobial activity against cariogenic bacteria. Moreover, CAPE also inhibits the formation of S. mutans biofilms and their metabolic activity in mature biofilms. Furthermore, CAPE can inhibit the key virulence factors of S. mutans associated with cariogenicity, including acid production, acid tolerance, and the bacterium's ability to produce extracellular polysaccharides (EPS), without affecting bacterial viability at subinhibitory levels. In conclusion, CAPE appears to be a new agent with anticariogenic potential, not only via inhibition of the growth of cariogenic bacteria.

Remineralization of enamel caries by an amelogenin-derived peptide and fluoride in vitro.

Dental caries is one of the most common oral diseases in the world. This study was tantamount to investigate the combinatory effects of an amelogenin-derived peptide (called QP5) and fluoride on the remineralization of artificial enamel caries. The peptide QP5 was synthesized and characterized, and the binding capability of the peptide on hydroxyapatite (HA) and demineralized tooth enamel surface was analysed. Then, the mineralization function of the peptide and fluoride was studied through the spontaneous mineralization testing and remineralization on enamel caries in vitro. First, the novel peptide QP5 could bind on the hydroxyapatite and demineralized tooth enamel surfaces. Second, QP5 can transitorily stabilize the formation of amorphous calcium phosphate and direct the transformation into hydroxyapatite crystals alone and in combination with fluoride. In addition, compared to blocks treated by peptide QP5 alone or fluoride, the sample blocks showed significantly higher surface microhardness, lower mineral loss and shallower lesion depth after treatment with a combination of QP5 and fluoride at high or low concentrations. The peptide QP5 could control the crystallization of hydroxyapatite, and combinatory application of peptide QP5 and fluoride had a potential synergistic effect on the remineralization of enamel caries.

Cotransplantation of human umbilical cord mesenchymal stem cells and endothelial cells for angiogenesis and pulp regeneration in vivo.

AIMS: To explored the potential of human umbilical cord mesenchymal stem cells (hUCMSCs) as seed cells for dental pulp regeneration and the possibility of cotransplantation hUCMSCs and endothelial cells (ECs) for angiogenesis and pulp regeneration in vivo. MATERIALS AND METHODS: hUCMSCs and human umbilical vein endothelial cells (HUVECs) were cocultured for matrigel angiogenesis assay in vitro and Matrigel plug assay in vivo. Next, we used the transwell coculture system to coculture hUCMSCs and HUVECs in vitro for RNA- sequencing (RNA-seq). Last, encapsulated hUCMSCs and HUVECs in scaffolds were injected into the root segments, and transplanted into immunodeficient mice for dental pulp regeneration. KEY FINDINGS: In vitro Matrigel angiogenesis assay and in vivo Matrigel plug assay indicated that cocultured hUCMSCs and HUVECs promote vascular formation of HUVECs, especially in 1:5 (hUCMSCs:HUVECs) coculture group. The RNA-seq result indicated that cocultured HUVECs exhibited high Hif-1 signaling pathway activity. We performed the cell transfection assay to knock down HIF1A-AS2 in HUVECs and then coculture with hUCMSCs, and the expression of VEGFA, HIF1A and PECAM1 were reduced. In pulp regeneration assay, Cotransplantation of hUCMSCs and HUVECs (1,5) group showed pulp-like tissue regeneration. SIGNIFICANCE: Cocultured hUCMSCs and HUVECs can promote vascular formation of HUVECs, and the optimal coculture ration is 1:5 (hUCMSCs:HUVECs). hUCMSCs promote angiogenesis of HUVECs through the long noncoding RNA HIF1A-AS2-activation of the Hif-1 signaling pathway. Cotransplantation of hUCMSCs and HUVECs can regenerate dental pulp-like tissue in vivo.

Comparative investigations of in vitro and in vivo bioactivity of titanium vs. Ti-24Nb-4Zr-8Sn alloy before and after sandblasting and acid etching.

To avoid the failure of clinical surgery due to "stress shielding" and the loosening of an implant, a new type of alloy, Ti-24Nb-4Zr-8Sn (TNZS), with a low Young's modulus acted as a new implant material in this work. Meanwhile, the surface characteristics, MC3T3-E1 cell behavior and in vivo osseointegration of the titanium and TNZS before and after sandblasting and acid etching were studied comparatively. TNZS and Ti had the same microstructure based on the transmission electron microscopy results. Meanwhile, the TNZS alloy had a lower Young's modulus and surface nanohardness compared with pure titanium. However, the corrosion resistance of Ti was better than that of the TNZS sample in simulated body fluid solution. In addition, the TNZS alloy after sandblasting and acid etching (SLATNZS) had excellent cell adhesion, proliferation, differentiation, ALP activity and in vivo osseointegration ability such as there being almost no soft tissue as compared with other implants. Based on the current results, the new type of Ti-24Nb-4Zr-8Sn alloy showed good potential and promising application prospects in its biochemical aspects.

PEP06 polypeptide 30 is a novel cluster-dissociating agent inhibiting α v integrin/FAK/Src signaling in oral squamous cell carcinoma cells.

Collectively migrating tumor cells have been recently implicated in enhanced metastasis of epithelial malignancies. In oral squamous cell carcinoma (OSCC), αv integrin is a crucial mediator of multicellular clustering and collective movement in vitro; however, its contribution to metastatic spread remains to be addressed. According to the emerging therapeutic concept, dissociation of tumor clusters into single cells could significantly suppress metastasis-seeding ability of carcinomas. This study aimed to investigate the anti-OSCC potential of novel endostatin-derived polypeptide PEP06 as a cluster-dissociating therapeutic agent in vitro. Firstly, we found marked enrichment of αv integrin in collectively invading multicellular clusters in human OSCCs. Our study revealed that metastatic progression of OSCC was associated with augmented immunostaining of αv integrin in cancerous lesions. Following PEP06 treatment, cell clustering on fibronectin, migration, multicellular aggregation, anchorage-independent survival and colony formation of OSCC were significantly inhibited. Moreover, PEP06 suppressed αv integrin/FAK/Src signaling in OSCC cells. PEP06-induced loss of active Src and E-cadherin from cell-cell contacts contributed to diminished collective migration of OSCC in vitro. Overall, these results suggest that PEP06 polypeptide 30 inhibiting αv integrin/FAK/Src signaling and disrupting E-cadherin-based intercellular junctions possesses anti-metastatic potential in OSCC by acting as a cluster-dissociating therapeutic agent.