Alveolar Bone Morphologic Predictors for Guided Bone Regeneration Outcome in Anterior Maxilla.

OBJECTIVES: This study aimed to explore the influence of alveolar bone morphologic variables on the outcome of guided bone regeneration (GBR) in the anterior maxilla region. METHODS: Twenty-eight patients who received single maxillary anterior tooth delayed implant placed simultaneously with GBR were recruited. Baseline data including age, gender, implant site, implant brand, and bone graft materials were recorded. The resorption rate of the grafted bone (RRGB), labial bone width at 0 mm, 2 mm, and 4 mm apical to the implant platform at Tn (LBW0Tn, LBW2Tn, LBW4Tn), implant angulation (IA), maximum bone graft thickness (MBGT), bone graft volume (BGV), and the initial bone morphologic variables bone concavity depth (BCD) and bone concavity angulation (BCA) were measured. The Pearson correlation analysis, analysis of variance (ANOVA), and optimal binning method were used to explore the potential predictors for GBR. RESULTS: Among 28 patients, the labial bone width of implant and bone graft volume decreased significantly when measured 6 months after surgery. The mean percentage of RRGB was 49.78%. RRGB was not correlated with gender, age, bone graft material, IA, MBGT, bone graft volume at T1, implant site, and implant brand (P > .05). BCD and BCA were each moderately correlated with RRGB (r = -0.872 [P < .001] and r = 0.686 [P < .001], respectively). A BCD ≥1.03 mm and a BCA <155.30° resulted in a significantly lower percentage of RRGB (P < .001). CONCLUSIONS: A significant grafted bone materials volume reduction was detected after GBR with collagen membrane and deproteinized bovine bone mineral (DBBM). The initial bone morphology can influence GBR outcome, and a bone concavity with a depth ≥1.03 mm and an angulation <155.30° led to a lower RRGB. BCD and BCA can be used as variables to predict the outcome of GBR.

Protective effects of different anti­inflammatory drugs on tracheal stenosis following injury and potential mechanisms.

Tracheal stenosis following injury cannot be effectively treated. The current study compared the protective effects of different anti­inflammatory drugs on tracheal stenosis and investigated their possible mechanisms. Rabbit tracheal stenosis models following injury were constructed and confirmed using hematoxylin and eosin (H&E) staining. A total of 30 rabbits were divided into the control (CON), penicillin (PEN), erythromycin (ERY), budesonide (BUD) and PEN + ERY + BUD groups (n=6). Stenotic tracheal tissue, serum and bronchoalveolar lavage fluid (BALF) were collected 10 days after continuous treatment. Pathological changes in the tracheas were observed by H&E staining. Histone deacetylase 2 (HDAC2) expression in tracheal tissues was detected by immunofluorescence. Immunohistochemistry was performed to detect collagen I (Col­I) and collagen III (Col­III) levels in tracheal tissues. Transforming growth factor ß1 (TGF­ß1), vascular endothelial growth factor (VEGF) and interleukin 8 (IL­8) levels in serum and BALF samples were determined using ELISA kits. Western blotting detected HDAC2, IL­8, TGF­ß1 and VEGF levels in tracheal tissues. H&E staining demonstrated that tracheal epithelial hyperplasia and fibroblast proliferation in the ERY and PEN + ERY + BUD groups markedly improved compared with the CON group. Furthermore, in tracheal tissues, HDAC2 expression was significantly increased and IL­8, TGF­ß1, VEGF, Col­I and Col­III levels were significantly decreased in the ERY and PEN + ERY + BUD groups compared with the CON group. Additionally, the results for the PEN + ERY + BUD were more significant compared with the ERY group. In serum and BALF samples, IL­8, TGF­ß1 and VEGF levels in the ERY and PEN + ERY + BUD groups were significantly lower compared with the CON group, with the results of the PEN + ERY + BUD group being more significant compared with the ERY group. There were no significant differences between the PEN, BUD and CON groups. ERY inhibited tracheal granulation tissue proliferation and improved tracheal stenosis following injury and synergistic effects with PEN and BUD further enhanced these protective effects. The mechanism may involve HDAC2 upregulation and inhibition of local airway and systemic inflammatory responses.

Expression of histone deacetylase 2 in tracheal stenosis models and its relationship with tracheal granulation tissue proliferation.

The current treatments for benign tracheal stenosis are inefficient. The present study examined the expression of histone deacetylase 2 (HDAC2) in different tracheal stenosis models and explored its association with the proliferation of tracheal granulation tissue and its ability to constitute a potential therapy for tracheal stenosis. Animal tracheal stenosis models were established, as indicated by hematoxylin and eosin (H&E) staining. A total of 24 New Zealand White rabbits were randomly divided into control, erythromycin, budesonide and vorinostat groups. Stenotic tracheal tissues were collected on day 11 after drug administration for 10 days. The degree of tracheal stenosis in each group was calculated, and pathological alterations were observed using H&E staining. The mRNA expression of HDAC2, interleukin-8 (IL-8), transforming growth factor-ß1 (TGF-ß1) and vascular endothelial growth factor (VEGF) was examined via reverse transcription-quantitative PCR. The protein expression of HDAC2 was examined via immunofluorescence, while the expression of type I and type III collagen was assessed using immunohistochemistry. The results of the present study demonstrated that tracheal epithelial hyperplasia in the erythromycin group was improved, the degree of hyperplasia being the lowest among all groups, and tracheal stenosis was reduced compared with the control group. In the vorinostat group, tracheal epithelial tissue hyperplasia was aggravated and stenosis was increased. The HDAC2 mRNA and protein levels were increased and decreased in the erythromycin and vorinostat groups, respectively. In contrast, the IL-8 mRNA expression levels were decreased and increased in the erythromycin and vorinostat groups, respectively. TGF-ß1, VEGF, type I and type III collagen expression was decreased in the erythromycin group, while TGF-ß1, VEGF and type III collagen expression was increased in the vorinostat group. Compared with the control, the budesonide group did not exhibit any alterations in all of the indicators examined, including TGF-ß1, VEGF, IL-8, HDAC2 and collagen. Erythromycin treatment upregulated the expression of HDAC2, inhibited the inflammatory responses and reduced the proliferation of tracheal granulation tissue. In contrast, vorinostat treatment downregulated HDAC2 expression, promoted the inflammatory responses and increased the proliferation of tracheal granulation tissue. These results suggest that regulating HDAC2 may be used as a potential treatment for benign tracheal stenosis.

Nintedanib ameliorates tracheal stenosis by activating HDAC2 and suppressing IL-8 and VEGF in rabbit.

Acquired tracheal stenosis is a common disease occurring after endotracheal intubation or tracheotomy. Currently, surgery is the main option to treat the stenosis. This study investigated therapeutic effect and possible mechanism of nintedanib on tracheal stenosis. The rabbit models of tracheal stenosis were established and were administered with nintedanib and budesonide. The damage and repair of the tracheal tissue were determined using hematoxylin and eosin (HE) staining. The expression of histone deacetylase 2 (HDAC2), interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF) was detected by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western Blot and immunofluorescence assay. The expression of collagens I and III was assayed immunohistochemically. Remarkable tracheal stenosis was observed after the trachea was brushed in the rabbit model. Compared with control, the stenosis was improved after nintedanib treatment. The mRNA of HDAC2 was increased and that of IL-8 and VEGF was decreased significantly in the tracheal tissue following nintedanib treatment. Western blot analysis showed that HDAC2 increased to the level similar to that of control while VEGF remained unchanged following nintedanib treatment. Budesonide treatment also resulted in increased HDAC2 expression and decreased IL-8 and VEGF expression. Immunofluorescence assays also showed an increased HDAC2 expression following nintedanib treatment. Collagens I and III decreased significantly after nintedanib treatment in the tracheal tissues of models. Therefore, it is concluded that nintedanib alleviates the acquired tracheal stenosis by activating HDAC2 expression and suppressing IL-8 and VEGF expression, and may offer new option to medical treatment for the disease.

Role of Erythromycin-Regulated Histone Deacetylase-2 in Benign Tracheal Stenosis.

Objective: This study aims to explore the role of erythromycin-regulated histone deacetylase-2 in benign tracheal stenosis. Methods: The rabbit model of tracheal stenosis was established. The rabbits were randomly divided into 8 groups. Histone deacetylase-2 (HDAC2) expression was detected by immunofluorescence. The expression of type I collagen and type III collagen was detected by immunohistochemical method. The expression of TGF-ß1, VEGF and IL-8 in serum and alveolar lavage fluid was detected by ELISA. The expression of HDAC2, TGF-ß1, VEGF and IL-8 in serum and alveolar lavage fluid was detected by ELISA. The expression of HDAC2, TGF. Results: In Erythromycin (ERY) group, ERY + Budesonide group, ERY + Vorinostat group and ERY + Budesonide + Vorinostat group, the degree of bronchial stenosis was alleviated, and the mucosal epithelium was still slightly proliferated. The effect of ERY combined with other drugs was more obvious. The HDAC2 protein expression increased significantly in ERY group, ERY + Budesonide group and ERY + Budesonide + Vorinostat group and decreased significantly in Vorinostat group, the expression of collagen I and III decreased significantly in ERY group, ERY + Budesonide group and ERY + Budesonide + Vorinostat group (P < 0.05). The TGF-ß1, VEGF and IL-8 in serum and alveolar lavage fluid was detected by ELISA. The expression of HDAC2, TGF-P < 0.05). The TGF. Conclusions: Erythromycin inhibited inflammation and excessive proliferation of granulation tissue after tracheobronchial mucosal injury by up-regulating the expression of HDAC2, it promoted wound healing and alleviated tracheobronchial stenosis. When combined with budesonide, penicillin and other glucocorticoids and antibiotics, it had a good synergistic effect. However, vorinostat could attenuate erythromycin's effect by down-regulating the expression of HDAC2. It may have good clinical application prospects in the treatment of tracheal stenosis.

microRNA-1908-5p inhibits proliferation and promotes apoptosis by targeting PP5 in NSCLC.

MicroRNA-1908 is involved in the occurrence and development of various tumors. However, the mechanism of microRNA-1908-5p in the pathogenesis of non-small cell lung cancer (NSCLC) is not thoroughly studied. Protein phosphatase 5 catalytic subunit (PP5), a member of the protein phosphatase catalytic subunit family, may be a target of the microRNA-1908-5p. In order to further explore the mechanism of microRNA-1908-5p, real-time PCR was used to detect the expression of microRNA-1908-5p in non-small cell lung cancer tissues, and analyze the relationship between the expression of microRNA-1908-5p and clinical characteristics of lung cancer patients. The target of microRNA-1908-5p was predicted by bioinformatics and verified by Dual-luciferase assay. The effects of microRNA-1908-5p on the proliferation and apoptosis of lung cancer cells were examined at the cellular level. Nude mice tumorigenesis experiment was used to study the effect of microRNA-1908-5p on cancer cells. Western blot was used to detect the expression of related proteins. The results showed that the expression of microRNA-1908-5p in lung cancer tissues was significantly lower than that in adjacent tissues. The expression of microRNA-1908-5p in the non-metastatic lung cancer tissues was significantly higher than that in the metastatic lung cancer tissues, and the expression of microRNA-1908-5p was closely related to the survival rate of patients. Bioinformatics analysis combined with double luciferase assay showed that PP5 was a significant target of microRNA-1908-5p. Our results suggest that microRNA-1908-5p can regulate the pathogenesis of NSCLC by inhibiting PP5.