[Effect of collagen sponge on the healing process of alveolar fossa after tooth extraction in rats].

PURPOSE: To investigate the effect of collagen sponge on early bone healing process of alveolar fossa after tooth extraction in rats. METHODS: A total of 16 healthy female SD rats were selected. Animal models with tooth extraction were established. The right alveolar fossa inserted with collagen sponge was as the experimental group, and the left alveolar fossa was as the control group with treatment. The rats were sacrificed 1, 2, 4 and 8 weeks after tooth extraction, and the osteogenesis of alveolar fossa was observed. Real-time quantitative PCR (qt-PCR) was used to detect the changes of osteogenesis related gene expression. SPSS 19.0 software package was used for statistical analysis. RESULTS: After surgery, alveolar cavity healing was significantly better in the experimental group than in the control group. Osterix, Runx2 and Vegf genes were expressed in the experimental group and the control group, and the expression levels of related genes in the experimental group were significantly higher than the control group 1, 2, 4 and 8 weeks after surgery(P＜0.05). CONCLUSIONS: Collagen sponge could promote early alveolar bone healing, possibly related to the expression level of osteogenic genes regulated by collagen sponge.

Lower lip recurrent keratoacanthoma: A case report.

BACKGROUND: This paper introduces a case of recurrent keratoacanthoma (KA). KA is a self-healing disease. Recurrence after surgical resection is rare. In this case, the local application of retinoic acid ointment after the second operation achieved a good prognosis after 2 years of follow-up. CASE SUMMARY: A 76-year-old male patient was admitted to the hospital for "lower lip rupture and scab for 3 mo". Treatment: A rectangular incision was made in the healthy tissue about 3 mm outside the periphery of the lower lip mass, and a modified Bernard sliding flap was designed to completely remove the mass. Pathology showed (lower lip) KA. When the patient returned 6 mo after surgery, the middle mucosa of the lower lip had a bulge with a diameter of about 0.5 cm. The boundary was still clear, the surface was ulcerated. A recurrence of lower lip KA was suspected and a fan-shaped incision was performed in the healthy tissue about 5 mm outside the lesion to completely resect. Pathological showed lower lip KA had recurred. Topical application of tretinoin cream was applied once a day for 3 mo. The lower lip wounds were clean at the 2-year postoperative follow-up and the mucosa was normal. CONCLUSION: Adjuvant retinoic acid treatment after KA surgical resection can achieve good results.

[Effect of ipriflavone on reconstruction of periodontal tissues during recurrence of orthodontic teeth in rats].

PURPOSE: To investigate the effect of ipriflavone on reconstruction of periodontal tissues during recurrence of orthodontic teeth. METHODS: Twenty-four male SD rats were randomized into 2 groups, ipriflavone group(IP group) and control group, there were 12 rats in each group. The model of recurrence after movement of orthodontic teeth in rats was established. After continuous loading for 10 days, the loading devices were removed. Rats in ipriflavone group (IP group) were given ipriflavone intragastrically for 10 mg/(kg·d) after the devices were removed, while rats in the control group were given an equivalent amount of normal saline after the devices were removed. On the 0th, 1st, 3rd, 7th, and 10th day of administration, the rat maxillary impression and plaster model of two groups were prepared under local anesthesia, the distance between maxillary first molar lingual sulcus point and third molar in lingual groove point was measured to evaluate the relapse distance. After drug infusion for 10 days, the collected tissue specimens were stained with H-E to observe periodontal reconstruction, and expression of bone morphogenetic protein-2(BMP-2) was detected by immunohistochemical staining. Software Image-Pro 6.0 was used to analyze the optical density values of the stained sections. The data were analyzed with SPSS 22.0 software package. RESULTS: After removing the orthopaedic devices for 10 days , there was a significant recurrence of the movement of the orthodontic teeth in both groups. The recurrent distance of IP group was significantly smaller than that of the control group, and still significantly smaller than that of the control group at 10 d. H-E staining and immunohistochemical staining results showed that the IP group had more new bone formation and more BMP-2 expression in the periodontal tissues compared to the control group in vivo. CONCLUSIONS: In the process of recurrence of orthodontic tooth movement, ipriflavone can promote the expression of BMP-2 in periodontal tissue, improve bone remodeling of periodontal tissue, and effectively reduce the recurrent rate of orthodontic tooth movement.

The effects of binge alcohol exposure on tooth movement and associated root resorption in rats.

BACKGROUND: Considering the increasing prevalence of alcohol use and the growing number of orthodontic patients, some orthodontic patients might engage in binge drinking during treatment. Nevertheless, little is known about the effect of alcohol use on orthodontic treatment. METHODS: Male Wistar rats were divided into ethanol and control groups (n = 32). The rats received a single daily intraperitoneal injection of 20% (vol/vol) ethanol/saline solution at a dose of 3 g/kg of ethanol or saline for three consecutive days, and no injection was given during the remaining four days each week. All rats received orthodontic appliances to draw the maxillary first molar mesially. The rats were sacrificed at days 14 and 28, respectively. The amount of tooth movement was measured. Root resorption area was evaluated by scanning electron microscope. Hematoxylin and eosin (H&E) staining and tartrate-resistant acid phosphatase (TRAP) staining were conducted. Immunohistochemistry staining was performed to evaluate the expressions of nuclear factor kappa B ligand (RANKL), osteoprotegerin (OPG), and inducible nitric oxide synthase (iNOS). RESULTS: There were no significant differences in tooth movement and root resorption between ethanol and control groups. The number of TRAP-positive cells was significantly higher in the ethanol group. The expression of RANKL was statistically increased in the ethanol group. In contrast, the expression of OPG was remarkably decreased in rats injected with ethanol. Moreover, the iNOS level was significantly up-regulated in the ethanol group. CONCLUSION: The tooth movement and root resorption in rats were not affected by binge alcohol exposure.

Inhibitory effects of resveratrol on orthodontic tooth movement and associated root resorption in rats.

OBJECTIVE: To investigate the effect of resveratrol (RSV) on orthodontic tooth movement (OTM) and orthodontic induced root resorption (OIRR) in rats. METHODS: Thirty-six male Wistar rats used in this study were randomly divided into three groups of 12 animals each. All test subjects underwent a 50 g orthodontic force each, generated from a nickel-titanium closed-coil spring. The control group were fed carboxymethylcellulose (CMC) while rats in other two groups were fed 5 mg/kg/d RSV or 10 mg/kg/d RSV (dissolved in CMC). After 14 days of OTM, all rats were sacrificed, after which each group was randomly divided into two subgroups (6 test subjects in each subgroup). One subgroup was used to measure the amount of OTM and assessed by hematoxylin and eosin (HE) staining, tartrate-resistant acid phosphatase (TRAP) staining, and immunohistochemistry staining of Receptor Activator of Nuclear Factor-κ B Ligand (RANKL), Osteoprotegerin (OPG), Runt-related transcription factor 2 (RUNX2), as well as Osteocalcin (OCN). The second subgroup was used to analyze OIRR via scanning electron microscopy. RESULTS: Compared with the control group, the RSV groups showed a significant decrease in the distance of OTM and the OIRR ratio (p＜0.05). The number of TRAP positive osteoclasts and the expression of RANKL in periodontal tissue of the RSV groups were significantly inhibited (p＜0.01) while the expression of OPG, RUNX2, and OCN were remarkably promoted (p＜0.05). The effect of 10 mg/kg/d RSV group was more obvious than that of 5 mg/kg/d RSV group (p＜0.05). CONCLUSIONS: RSV could reduce the extent of OTM and root resorption areas.

Effects Of Triptolide On Tooth Movement And Root Resorption In Rats.

PURPOSE: The aim of this study was to investigate the effects of triptolide on the tooth movement and root resorption in rats during orthodontic treatment. MATERIAL AND METHODS: A total of 48 male Wistar rats were divided into three groups of 16 each. The right maxillary first molars of rats were drawn mesially by closed coil nickel-titanium spring with a force of 50 g. The two experimental groups received intraperitoneal injections of triptolide for 14 days at a dose of 15 µg/kg/day and 30 µg/kg/day, respectively. The control group received vehicle injections. After 14 days, the rats were humanely killed. The amount of tooth movement was measured. Eight rats from each group were randomly chosen for analysis of the percentage of root resorption area by scanning electron microscopy. For the remaining eight rats in each group, the H&E staining, tartrate-resistant acid phosphatase (TRAP) staining and immunohistochemistry analysis were performed. RESULTS: The amount of tooth movement and the ratio of root resorption area were significantly decreased in the triptolide-treated rats. The number of TRAP-positive cells was significantly lower in triptolide-treated groups. Moreover, the expression of nuclear factor kappa B ligand (RANKL) was reduced. In contrast, the expression of osteoprotegerin was significantly up-regulated. In the tension side, the expressions of runt-related transcription factor 2 and osteocalcin were significantly enhanced by triptolide injection. CONCLUSION: Triptolide injection could arrest orthodontic tooth movement and reduce root resorption in rats via inhibition of osteoclastogenesis. In addition, triptolide may exert a positive effect on osteoblastogenesis.

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

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

Erythropoietin enhances osteogenic differentiation of human periodontal ligament stem cells via Wnt/ß-catenin signaling pathway.

OBJECTIVES: The aim of this study is to examine the roles of erythropoietin (EPO) in regulating proliferation and osteogenic differentiation of periodontal ligament stem cells (PDLSCs) and analyze the underlying signaling of these processes. MATERIALS AND METHODS: PDLSCs were isolated and characterized. The PDLSCs were transfected with ß-catenin shRNA. qRT-PCR and Western blot analysis were used to examine the osteogenic effects of EPO on the expression of osteogenic-related genes and protein (Runx2, OCN and Osterix) in PDLSCs. Alizarin Red-S staining was used to detect mineralized nodule formation. In addition, the relationship between the Wnt/ß-catenin pathway and the effect of EPO on the osteogenesis of PDLSCs was investigated. RESULTS: The results suggested that EPO exerts positive osteogenic effects on PDLSCs. The results showed that EPO decreased the growth of PDLSCs slightly and increased alkaline phosphatase activity and calcium deposition in a dose-dependent manner. The expression of Runx2, Osterix and OCN was increased after EPO administration. EPO increases ß-catenin and Cyclin D1 in PDLSCs. After transfected with ß-catenin shRNA, the osteogenic effect of EPO on PDLSCs was attenuated. CONCLUSION: EPO promotes osteogenic differentiation of PDLSCs. The underlying mechanism may be activating Wnt/ß-catenin signaling pathway.

Microglia-derived TNF-α mediates endothelial necroptosis aggravating blood brain-barrier disruption after ischemic stroke.

Endothelium (EC) is a key component of blood-brain barrier (BBB), and has an important position in the neurovascular unit. Its dysfunction and death after cerebral ischemic/reperfusion (I/R) injury not only promote evolution of neuroinflammation and brain edema, but also increase the risk of intracerebral hemorrhage of thrombolytic therapies. However, the mechanism and specific interventions of EC death after I/R injury are poorly understood. Here we showed that necroptosis was a mechanism underlying EC death, which promoted BBB breakdown after I/R injury. Treatment of rats with receptor interacting protein kinase 1 (RIPK1)-inhibitor, necrostatin-1 reduced endothelial necroptosis and BBB leakage. We furthermore showed that perivascular M1-like microglia-induced endothelial necroptosis leading to BBB disruption requires tumor necrosis factor-α (TNF-α) secreted by M1 type microglia and its receptor, TNF receptor 1 (TNFR1), on endothelium as the primary mediators of these effects. More importantly, anti-TNFα (infliximab, a potent clinically used drug) treatment significantly ameliorate endothelial necroptosis, BBB destruction and improve stroke outcomes. Our data identify a previously unexplored role for endothelial necroptosis in BBB disruption and suggest infliximab might serve as a potential drug for stroke therapy.

Berberine improves advanced glycation end products­induced osteogenic differentiation responses in human periodontal ligament stem cells through the canonical Wnt/ß­catenin pathway.

The aim of the present study was to investigate the effects of advanced glycation end products (AGEs) and berberine hydrochloride (BBR) on the osteogenic differentiation ability of human periodontal ligament stem cells (hPDLSCs) in vitro, and their underlying mechanisms. hPDLSCs were subjected to osteogenic induction and were treated with AGEs or AGEs + BBR. Following varying numbers of days in culture, alkaline phosphatase (ALP) activity assays, ALP staining, alizarin red staining, ELISAs, and reverse transcription­quantitative polymerase chain reaction (RT­qPCR) and western blot analyses were performed to determine the osteogenic differentiation ability of hPDLSCs; RT­qPCR, western blot analysis, and immunofluorescence staining were conducted to investigate the underlying mechanisms. The canonical Wnt/ß­catenin pathway inhibitor XAV­939 and agonist CHIR­99021 were used to determine the contribution of the canonical Wnt/ß­catenin pathway to differentiation. Treatment with AGEs resulted in reduced ALP activity and Collagen I protein levels, decreased ALP staining, fewer mineralized nodules, and downregulated expression of osteogenic­specific genes [Runt­related transcription factor 2 (Runx2), Osterix, ALP, osteopontin (OPN), Collagen I and osteocalcin (OCN)] and proteins (Runx2, OPN, BSP and OCN); however, BBR partially rescued the AGE­induced decrease in the osteogenic potential of hPDLSCs. Furthermore, AGEs activated the canonical Wnt/ß­catenin signaling pathway and promoted the nuclear translocation of ß­catenin; BBR partially attenuated this effect. In addition, XAV­939 partially rescued the AGE­induced reduction in the osteogenic potential of hPDLSCs, whereas CHIR­99021 suppressed the BBR­induced increase in the osteogenic potential of hPDLSCs. The present study indicated that AGEs attenuated the osteogenic differentiation ability of hPDLSCs, in part by activating the canonical Wnt/ß­catenin pathway; however, BBR attenuated these effects by inhibiting the canonical Wnt/ß­catenin pathway. These findings suggest a role for BBR in periodontal regeneration induced by hPDLSCs in patients with diabetes mellitus.

Erythropoietin attenuates high glucose-induced oxidative stress and inhibition of osteogenic differentiation in periodontal ligament stem cell (PDLSCs).

Diabetes mellitus and periodontitis have long been considered to be biologically linked. Erythropoietin (EPO) has multiple biological functions, such as stimulating the proliferation and differentiation of erythroid progenitor cells and reducing glucose-induced oxidative stress via different mechanisms, acting as a direct antioxidant. The purposes of the study to examine the anti-oxidative effect of EPO on reducing high glucose-induced oxidative stress of hPDLSCs and provide a better understanding of the mechanism of these processes. PDLSCs were induced by highglucose (HG, 30 mM) in the presence or absence of EPO. Cell proliferation was measured by MTT assay. The reactiveoxygen species (ROS) level, malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were detected to evaluate oxidative stress. qRT-PCR and western blot analysis were used to examine the expression of osteogenic related genes and protein (Runx2 and Osterix). Alizarin Red-S staining was used to detect mineralized nodule formation. The results showed that EPO promote the proliferation of PDLSCs, which was suppressed by high glucose (30 mM). Moreover, EPO attenuated high glucose (30 mM) induced oxidative stress by reducing the levels of ROS and MDA, and increasing the SOD activity. Furthermore,EPO alleviate high glucose(30 mM) induced suppression of osteogenic differentiation ability in PDLSCs, as evidenced by the up-regulated mRNA and protein expression of Runx2 and Osterix and increased ALP activity. In conclusion, EPO attenuates high glucose-induced oxidative stress, inhibitory effect of proliferation and inhibition of osteogenic differentiation in periodontal ligament stem cell (PDLSCs).

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

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

[Effect of psoralen on the stability after orthodontic tooth movement in rats].

PURPOSE: This study was designed to investigate the effect of psoralen on periodontal tissue reconstruction after orthodontic tooth movement(OTM) in rats. METHODS: Thirty-six male 6-week-old Wistar rats were randomly divided into 2 groups: the experimental group and the control group. The experimental group and the control group were all installed between the central incisor and the left maxillary first molars to pull the first molars away from the force device; after 21 days, the force was removed and the rats in 2 groups were given drug gavage. Rats in the experimental group were given a gavage of psoralen 8 mg/kg per day, while rats in the control group were given the same amount of 0.9% sodium chloride everyday. Maxillary casts were made every week during the experimental and were scanned by 3D Scanner to measure relapse distance, and histologic examination was conducted. After 28 days, the rats were sacrificed and rats' upper jaw was separated. The remaining sections were immunohistochemically stained with BMP2 and BMP4. SPSS 19.0 software package was used for statistical analysis. RESULTS：Both groups had relapse after the force device was removed. Significant decrease of relapse percentage was observed in the experimental group compared with the control group at day 7，day 14，day 21 and day 28（P<0.05）. The speed of relapse of both groups were fastest in the first week and slowed down in the second, third and fourth week gradually. The speed of relapse in the experimental group in the first week was significantly less than in the control group(P<0.05).The expression of BMP2 and BMP4 within periodontal membrane and alveolar bone was significantly higher in the experimental group than in the control group(P<0.05). CONCLUSIONS: Psoralen can accelerate the reconstruction of periodontal tissues of orthodontic tooth and reduce relapse.

[Effect of akebiasaponin D with different concentrations on orthodontic tooth movement in rats].

PURPOSE: This study investigated the effect of local injection of akebiasaponin D (ASD) with different concentrations on the rate of orthodontic tooth movement in rats. METHODS: Forty 6-week-old female Wistar rats were randomly divided into 4 groups with 10 rats in each group. Animal model for orthodontic tooth movement was established. The upper first molars of the rats were moved mesially by coil springs（force=40 g）. ASD solution at the concentration of 5 mg/kg was locally injected in ASD1 group, and ASD solution at the concentration of 10 mg/kg was locally injected in ASD2 group. The rats of group PGE2 were injected PGE2 solution at the concentration of 25 µg/kg. The same amount of normal saline was injected in the control group. The rats were sacrificed in batch on the 3rd, 7th, 14th, 21st and 28th days after orthodontic treatment. The distance between upper first molar and second molar was measured. H-E straining was performed to observe the changes of periodontal tissue and the amount of osteoclast. SPSS13.0 software package was used for statistical analysis. RESULTS: The distance between the first and second molar was successively increased compared with the control group. On day 3, there was significant difference between PGE2 group and the control group (P＜0.05). On day 7, the distance between the first and second molar in PGE2 group and ASD2 group was significantly increased compared with the control group (P＜0.05). The amount of tooth movement was significantly increased (P＜0.05) in ASD1 group, ASD2 group and PGE2 group, compared with the control group on the 14th, 21st and 28th day. However, there was no significant difference (P＞0.05) between ASD2 group and PGE2 group. Under microscope, the number of osteoclast was increased on the tension side, reaching a peak on day 21st, and decreased later. CONCLUSIONS: Local injection of ASD solution may accelerate orthodontic tooth movement. ASD solution at the dose of 10 mg/kg can accelerate orthodontic tooth movement efficiently similar to PGE2 solution, while ASD solution at the dose of 5 mg/kg is not as effectual as PGE2 solution.

[Influence of fixed orthodontic treatment on oral health-related quality of life in adolescent and adult: a comparative study].

PROPOSE: To compare the changes in oral health-related quality of life(OHRQoL) among adolescent patients and adult patients during orthodontic treatment. METHODS: The clinical data were collected from 81 patients (aged 15 to 25 years old) who underwent comprehensive orthodontic treatment. The participants were divided into 2 groups: adolescent patients (n=43) and adult patients (n=38) by age. OHRQoL was assessed using the Oral Health Impact Profile (OHIP-14). All subjects were examined and interviewed at baseline and the end of 3 stages during orthodontics treatment. Friedman 2-way analysis of variance (ANOVA) and Wilcoxon signed rank tests were used to compare the relative changes of OHRQoL among different time points with SPSS 20.0 software package. RESULTS: The scores of OHIP-14 and all domains except communication disorder and social disability domain in adolescent and adult patients showed significant changes as well as a decrease trend. Only adults showed significant changes in communication disorder.Both groups had no significant difference. CONCLUSIONS: The impact of comprehensive orthodontic treatment on patients' OHRQoL is quite different. Orthodontists should pay attention to the differences and guide the patients accordingly.

Sema3E/PlexinD1 inhibition is a therapeutic strategy for improving cerebral perfusion and restoring functional loss after stroke in aged rats.

Brain tissue survival and functional recovery after ischemic stroke greatly depend on cerebral vessel perfusion and functional collateral circulation in the ischemic area. Semaphorin 3E (Sema3E), one of the class 3 secreted semaphorins, has been demonstrated to be a critical regulator in embryonic and postnatal vascular formation via binding to its receptor PlexinD1. However, whether Sema3E/PlexinD1 signaling is involved in poststroke neovascularization remains unknown. To determine the contribution of Sema3E/PlexinD1 signaling to poststroke recovery, aged rats (18 months) were subjected to a transient middle cerebral artery occlusion. We found that depletion of Sema3E/PlexinD1 signaling with lentivirus-mediated PlexinD1-specific-shRNA improves tissue survival and functional outcome. Sema3E/PlexinD1 inhibition not only increases cortical perfusion but also ameliorates blood-brain barrier damage, as determined by positron emission tomography and magnetic resonance imaging. Mechanistically, we demonstrated that Sema3E suppresses endothelial cell proliferation and angiogenic capacity. More importantly, Sema3E/PlexinD1 signaling inhibits recruitment of pericytes by decreasing production of platelet derived growth factor-BB in endothelial cells. Overall, our study revealed that inhibition of Sema3E/PlexinD1 signaling in the ischemic penumbra, which increases both endothelial angiogenic capacity and recruitment of pericytes, contributed to functional neovascularization and blood-brain barrier integrity in the aged rats. Our findings imply that Sema3E/PlexinD1 signaling is a novel therapeutic target for improving brain tissue survival and functional recovery after ischemic stroke.

Effects of Btbd7 knockdown on the proliferation of human dental pulp cells and expression of Dspp.

BTB/POZ domain-containing protein 7 (Btbd7) is recognized as a regulatory gene that promotes epithelial tissue remodeling and branching morphogenesis. In cancer cells, it is involved in epithelial-mesenchymal transition and cell invasion. However, the role of Btbd7 in human dental pulp cells (hDPCs) is not clear. The aim of this study is to explore the function of Btbd7 in hDPCs. Expression of Btbd7 in hDPCs was examined by immunocytochemical staining. Lentiviral vectors expressing small interfering RNA (siRNA)-Btbd7 were used to knockdown expression of Btbd7 in hDPCs. Proliferation of Btbd7 knockdown hDPCs was determined using a cell counting Kit-8 assay, and expression of dentin sialophosphoprotein (Dspp) was assessed using real-time quantitative reverse transcription-PCR and Western blot. Btbd7 was mainly expressed in the cytoplasm and nucleus of hDPCs. Suppression of Btbd7 temporarily promoted hDPC proliferation and significantly inhibited expression of Dspp in hDPCs. Our results show that Btbd7 plays a role in hDPC proliferation, and possibly participates in odontoblast differentiation of hDPCs and dentin formation by regulating the expression of Dspp.

Sema4D/PlexinB1 inhibition ameliorates blood-brain barrier damage and improves outcome after stroke in rats.

The inflammatory process in stroke is the major contributor to blood-brain barrier (BBB) breakdown. Previous studies indicated that semaphorin 4D (Sema4D), an axon guidance molecule, initiated inflammatory microglial activation and disrupted endothelial function in the CNS. However, whether Sema4D disrupts BBB integrity after stroke remains unclear. To study the effect of Sema4D on BBB disruption in stroke, rats were subjected to transient middle cerebral artery occlusion and targeted injection of lentivirus-mediated clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene disruption of PlexinB1. We found that Sema4D synchronously increased with BBB permeability and accumulated in the perivascular area after stroke. Suppressing Sema4D/PlexinB1 signaling in the periinfarct cortex significantly decreased BBB permeability as detected by MRI and fibrin deposition, and thereby improved stroke outcome. In vitro, we confirmed that Sema4D disrupted BBB integrity and endothelial tight junctions. Moreover, we found that Sema4D induced pericytes to acquire a CD11b-positive phenotype and express proinflammatory cytokines. In addition, Sema4D inhibited AUF1-induced proinflammatory mRNA decay effect. Taken together, our data provides evidence that Sema4D disrupts BBB integrity and promotes an inflammatory response by binding to PlexinB1 in pericytes after transient middle cerebral artery occlusion. Our study indicates that Sema4D may be a novel therapeutic target for treatment in the acute phase of stroke.-Zhou, Y.-F., Li, Y.-N., Jin, H.-J., Wu, J.-H., He, Q.-W., Wang, X.-X., Lei, H., Hu, B. Sema4D/PlexinB1 inhibition ameliorates blood-brain barrier damage and improves outcome after stroke in rats.

Upper airway asymmetry in skeletal Class III malocclusions with mandibular deviation.

The purpose of this study was to investigate the relationship between bilateral differences of upper airway and mandibular morphologic patterns in subjects with skeletal Class III mandibular deviation. 47 skeletal Class III (ANB < 0°) adult patients with and without mandibular deviation were divided into 2 groups. Bilateral differences of minimum cross-sectional area, mean cross-sectional area, volume of subdivisions (nasopharynx, palatopharynx, glossopharynx, hypopharynx) were assessed paired t test. Stepwise linear regression analysis and Pearson correlation coefficients were computed between a significant pair of upper airway variables and a pair of mandibular deviation variables to examine the quantitative relationship between the upper airway asymmetry and mandibular deviation. The mean cross-sectional area and the volume of palatopharynx on the deviated side in mandibular deviated group was significantly smaller than non-deviated side. The asymmetry index of the palatopharyngeal volume showed significant correlations with CRA asymmetry (r = 0.49) and Ramus asymmetry (r = 0.54). However, in the glossopharyngeal and hypopharyngeal segment, the mandibular deviated group showed significant asymmetry, characterized by larger mean cross-sectional area and volume in deviated side. The asymmetry index of the glossopharyngeal volume and hypopharyngeal volume showed significant correlations with CRA asymmetry (r = 0.42), Me-s (r = 0.72) and Me-s (r = 0.67) respectively.

Report: Small cell neuroendocrine carcinoma (SCNEC) of the tongue: A case report.

Small cell neuroendocrine carcinoma (SCNEC) of the tongue is very rare. We here present a SCNEC impatient with distant metastasis. A 74-year-old Chinese male went to hospital to treat a tongue tumor, which was founded at a conventional physical examination in Weifang Stomatology Hospital. The check of positron emission tomography-computer tomography (PET-CT) by Weifang people's hospital revealed a tumor in the right root of tongue, and distant metastasis in the right submandibular area, neck, mediastinum, right hilar, abdominal, retroperitoneal multiple lymph nodes, left thyroid, right lower lung, right scapula and bilateral adrenal. The patient was diagnosed tongue SCNEC by the pathological analysis of the tissue section. Conforming to the diagnosis of tongue SCNEC, the patient received adjuvant chemotherapy for 6 cycles with etoposide and carboplatin, and is alive now 9 months after the diagnosis.