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Silk sericin is a degumming product used by the silk industry. The degumming process can affect the protein structure and molecular weight of silk sericin. The present study examined how pretreatment with 4-hexylresorcinol (4HR) affects the biomedical properties of silk sericin. Before the degumming process, silkworm cocoons were treated with 4HR solution. The protein structure of the final degumming product was evaluated by Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy. Untreated silk sericin (S) and silk sericin pretreated with 4HR (S+4HR) were added to RAW264.7 cells, and the expression of BMP-2 was determined. The bone-regenerating capacity of S+4HR was evaluated using the critical-sized rat calvarial defect model. Compared with S, S+4HR showed an increase in β-sheet structures. Administration of S+4HR to RAW264.7 cells increased expression of BMP-2, mainly via the TLR-mediated signaling pathway. Bone volume, as measured by micro-computerized tomography, was significantly greater in the S+4HR group than in the S, gelatin alone, and unfilled control groups (p < 0.05 each). Expression of BMP-2 and runx2 in tissue specimens was significantly higher following treatment with S+4HR than with S (p < 0.05). Taken together, these findings show that 4HR pretreatment before the degumming process increased the β-sheet structure of silk sericin, as well as inducing BMP-2 expression and bone regeneration ability.

BackgroundCompared to the conventional approach, including preoperative orthodontic preparation, the so-called surgery-first approach (SFA) seems to reduce the overall treatment time in the correction of skeletal class III dentofacial deformity. However, there have been controversies about postoperative skeletal stability with SFA. Therefore, we investigated the long-term stability and the overall treatment time after maxillomandibular surgery for skeletal class III correction with or without preoperative orthodontic preparation.MethodsThis retrospective study included eight patients who underwent maxillomandibular surgery for class III correction with the SFA (SFA group) and 20 patients who underwent the conventional approach (CA group). A comparative study of the change in the maxillary and mandibular position on preoperative (T1), 1-day (T2), 6-month (T3), and 2-year (T4) postoperative lateral cephalograms. We calculated the overall treatment time for each group.ResultsAt the presurgical stage (T1), there was no bias in the skeletal features between the two groups. In the surgical change from T1 to T2, the mandible (point B) of the CA group was significantly moved superiorly. Short-term changes from T2 to T3 revealed that the mandible moved forward in both groups, whereas the maxillary position showed no significant changes. Long-term changes from T3 to T4 demonstrated that none of the measured parameters showed any significant differences. Finally, the average of overall treatment time was 15.1 months in the SFA group and 26.0 months in the CA group.ConclusionsThese findings suggest that SFA in bimaxillary orthognathic surgery for skeletal class III correction leads to predictable long-term skeletal stability, similar to surgery with CA. Furthermore, SFA reduced the overall treatment time compared to CA.

The p53 mutation is inherent in over 50% of human cancers. In head and neck squamous cell carcinoma, the p53 mutation is associated with a poor prognosis. 4‑Hexylresorcinol (4HR) is a pharmacologic chaperone. The present study aimed to investigate the effect of 4HR on p53 transcriptional activity in oral carcinoma cells with p53 mutations. To identify conformational changes induced by 4HR administration, peptides including the DNA‑binding domain from mutant and wild‑type p53 were synthesized, and Fourier transform infrared spectroscopy was performed. To determine the effect of 4HR on p53 mutant carcinoma cells, western blot analysis, p53 transcriptional activity analysis, MTT assay and apoptosis immunocytochemistry were performed. The YD‑15 cell line has a mutation in the DNA binding domain of p53 (Glu258Ala). When p53 Ala‑258 was coupled by 4HR, the p53 Ala‑258 structure lost its original conformation and approached a conformation similar to that of p53 Glu‑258. In the cell experiments, 4HR administration to p53 mutant cells increased p53 transcriptional activity and the expression levels of apoptosis‑associated proteins such as B‑cell lymphoma 2 (BCL2), BCL2‑associated X (BAX) and BCL2‑associated agonist of cell death (BAD). Accordingly, 4HR administration on YD‑15 cells decreased cell viability and increased apoptosis. In conclusion, 4HR is a potential substance for use in the recovery of loss‑of‑function in mutant p53 as a pharmacologic chaperone.

Bone morphogenic protein-2/4 (BMP-2/4) is an osteoinductive protein that accelerates osteogenesis when administered to bony defects. Sericin is produced by silkworms, and has a biological activity that differs depending on the degumming method used. Our results indicated that the high molecular weight fraction of silk sericin (MW > 30 kDa) obtained via sonication had a more abundant β-sheet structure than the low molecular weight fraction. Administration of the β-sheet structure silk sericin increased BMP-2/4 expression in a dose-dependent manner in RAW264.7 cells and human monocytes. This sericin increased the expression levels of toll-like receptor (TLR)-2, TLR-3, and TLR-4 in RAW264.7 cells. Application of a TLR-2 antibody or TLR pathway blocker decreased BMP-2/4 expression following sericin administration. In the animal model, the bone volume and BMP-2/4 expression were higher in rats treated with a sericin-incorporated gelatin sponge than in rats treated with a gelatin sponge alone or a sponge-incorporated with denatured sericin. In conclusion, sericin with a more abundant β-sheet structure increased BMP-2/4 expression and bone formation better than sericin with a less abundant β-sheet structure.

The main flaw of silkworm cocoon originated membranes for guided bone regeneration (GBR) techniques is that the maximum size of the membrane is determined by the size of the cocoon. Flatwise-spun silk does not have any limitation to its production size. The objective of this study was to compare flatwise-spun silk mats with cocoon-derived silk mats for a GBR technique. Tensile strength, scanning electron microscopy, Fourier transform infrared (FT-IR) spectroscopy and sericin contents analysis were done for in vitro test. Bone regeneration ability was tested in the critical sized defect of the animal model. In this study, flatwise-spun silk mats showed lower tensile strength and similar tensile strain to a cocoon-derived commercialized silk mat (TDI). Compared to TDIs, the flatwise-spun silk mats showed a similar second derivative spectrum, but they showed an increased abundance of the random coil and helix structures in the FT-IR spectra because of a higher content of sericin. In animal model experiments, the bone volume (BV) after the application of a flatwise-spun silk mat was similar to the volume observed after the application of a TDI. Both groups showed a significantly higher BV compared to an unfilled control group (P

There is an association between diabetes and impaired bone healing. The purpose of this study was to determine whether sericin had a positive effect on bone regeneration with streptozotocin-induced diabetes in a rat model. Sprague Dawley rats (n = 21) were assigned to one of three groups. A critical-sized bone defect was created on the calvaria. In the sericin group (S group, n = 7), the bone defect was filled with a sericin–gelatin combination, whereas in the gelatin group (G group, n = 7), only gelatin sponge was used. The control group (N group, n = 7) did not receive any graft. New bone formation was evaluated by micro-computerized tomogram and histological analysis. The regenerated bone volume in group S was the highest among the three groups (3.87 ± 2.51 mm3), followed by group N (1.71 ± 1.65 mm3) and group G (1.24 ± 1.05 mm3). The application of sericin in combination with a gelatin sponge enhanced the process of bone regeneration in streptozotocin-induced type I diabetes animal model.

4-Hexyl resorcinol (4HR) is an organic compound and has been used in skin care application. 4HR is an M2-type macrophage activator and elevates vascular endothelial growth factor (VEGF) expression via the hypoxia-inducible factor (HIF)-independent pathway. As endothelial cells are important in wound healing, the human umbilical vein endothelial cells (HUVECs) were treated with 4HR, and changes in VEGF-A, -C, and transforming growth factor-&beta, 1 (TGF-&beta, 1) expression were investigated. The administration of 4HR increased the expression level of VEGF-A, -C, and TGF-&beta, 1. The application of TGF-&beta, 1 protein also increased the expression level of VEGF-A and -C. Knockdown with small interfering RNA (siRNA) targeting to TGF-&beta, 1 and the selective chemical inhibition (A83-01) to ALK5 confirmed the involvement of the TGF-&beta, signaling pathway in the 4-HR-mediated VEGFs expression. 4HR application in a burn model of diabetic rats demonstrated an increased level of angiogenic proteins with wound healing. Compared to sericin application, the 4HR application group showed more prominent capillary regeneration. Collectively, 4HR activated TGF-&beta, 1/ALK5/VEGFs signaling in endothelial cells and induced vascular regeneration and remodeling for wound healing.

4-Hexylresorcinol (4HR) has been used as a food additive and antiseptic. The aim of this study was to evaluate whether the application of 4HR in breast cancer cells and ovariectomized rats showed estrogen-like effects. MCF-7 and SK-BR-3 cells were treated by solvent, 1&ndash, 100 &micro, M bisphenol-A (BPA), or 1&ndash, M 4HR, respectively. 3-(4, 5-Dimethylthiazole-2-yl)- 2,5-diphenyltetrazolium bromide (MTT) assay and Western blot for extracellular signal-regulated kinase-1/-2 (ERK1/2), phosphorylated ERK1/2 (p-ERK1/2), estrogen receptor-&alpha, (ER&alpha, ), and ER&beta, were done. As an in vivo study, ovariectomized rats (n = 15) received solvent, 125 mg/kg of 4HR, or 10 &micro, g of 17-&beta, estradiol via daily subcutaneous injection for 7 days. Blood samples were obtained for evaluation of prolactin levels. Pituitary glands and uteruses were biopsied for histological evaluation and Western blot analysis. Compared with the control group, the application of 4HR decreased the proliferation of MCF-7 and SK-BR-3 cells, while the application of BPA increased (p &lt, 0.05). The application of BPA increased the expression of ER&alpha, ER&beta, and p-ERK1/2, but 4HR did not change the expression of ER&alpha, or p-ERK1/2 in MCF-7 cells. In an animal model, the 4HR group showed similar levels of ER&alpha, and prolactin expression in the pituitary gland compared to the solvent only group, while the estradiol group showed higher levels. Serum prolactin levels were similar between the 4HR and solvent only groups. Taken together, 1&ndash, M 4HR did not show BPA-like behavior in MCF-7 cells, and 125 mg/kg of 4HR daily subcutaneous injection for 7 days did not demonstrate estradiol-like effects in ovariectomized rats. Collectively, 4HR has no estrogen-like effects on both ER&alpha, positive cells and estrogen-deficient rat models.

Background Class II malocclusion patients with hyperdivergent facial types are characterized by short mandibular body lengths and anterior open bite. Accordingly, the treatment for hyperdivergent skeletal class II malocclusion is a lengthening of the mandibular body length and a counterclockwise rotation of the mandible. To prevent post-operative relapse, botulinum toxin-A (BTX-A) injection can be a retention modality. Case presentation A class II open-bite patient received BTX-A injection to the anterior belly of her digastric muscle for the prevention of post-operative relapse. The relapse was evaluated via a clinical examination and a lateral cephalometric radiograph after the completion of post-surgical orthodontic treatment. The patient showed stable occlusion without any signs of relapse at 15 months post-operatively. Conclusion In this case presentation, a single injection into the anterior belly of the digastric muscle was sufficient for the prevention of post-operative open bite.

Background Botulinum toxin-A (BTX-A) injection into muscle reduces muscular power and may prevent post-operative complication after orthognathic surgery. The purpose of this study was (1) to evaluate BTX-A injection into the masseter muscle on the prevention of plate fracture and (2) to compare post-operative relapse between the BTX-A injection group and the no injection group. Methods Sixteen patients were included in this study. Eight patients received BTX-A injection bilaterally, and eight patients served as control. All patients received bilateral sagittal split ramus osteotomy for the mandibular setback and additional surgery, such as LeFort I osteotomy or genioplasty. Post-operative plate fracture was recorded. SNB angle, mandibular plane angle, and gonial angle were used for post-operative relapse. Results Total number of fractured plates in patients was 2 out of 16 plates in the BTX-A injection group and that was 8 out of 16 plates in the no treatment group (P = 0.031). However, there were no significant differences in post-operative changes in SNB angle, mandibular plane angle, and gonial angle between groups (P > 0.05). Conclusions BTX-A injection into the masseter muscle could reduce the incidence of plate fracture.

Background The objective of this study was to evaluate xenograft degradation velocity when treated with 4-hexylresorcinol (4HR). Methods The scapula of a cow was purchased from a local grocery, and discs (diameter 8 mm, thickness 1 mm) were prepared by trephine bur. Discs treated with 4HR were used as the experimental group. Untreated discs were used as the control. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), antibacterial test, endotoxin test, and scanning electron microscopy (SEM) were performed on the discs. In vivo degradation was evaluated by the rat calvarial defect model. Results The XRD and FT-IR results demonstrated successful incorporation of 4HR into the bovine bone. The experimental disc showed antibacterial properties. The endotoxin test yielded results below the level of endotoxin contamination. In the SEM exam, the surface of the experimental group showed needle-shaped crystal and spreading of RAW264.7 cells. In the animal experiments, the amount of residual graft was significantly smaller in the experimental group compared to the control group (P = 0.003). Conclusions In this study, 4HR was successfully incorporated into bovine bone, and 4HR-incorporated bovine bone had antibacterial properties. In vivo experiments demonstrated that 4HR-incorporated bovine bone showed more rapid degradation than untreated bovine bone.