Therapeutic Potential of 4-Hexylresorcinol in Preserving Testicular Function in Streptozotocin-Induced Diabetic Rats.

It is known that many diabetic patients experience testicular atrophy. This study sought to investigate the effect of 4-hexylresorcinol (4HR) on testicular function in rats with streptozotocin (STZ)-induced diabetes, focusing on testicular weight, sperm motility, histological alterations, and serum testosterone levels to understand the efficacy of 4HR on testes. Our findings reveal that 4HR treatment significantly improves testicular health in diabetic rats. Notably, the STZ group exhibited a testicular weight of 1.22 ± 0.48 g, whereas the STZ/4HR group showed a significantly enhanced weight of 1.91 ± 0.26 g (p < 0.001), aligning closely with the control group's weight of 1.99 ± 0.17 g and the 4HR group's weight of 2.05 ± 0.24 g, indicating no significant difference between control and 4HR groups (p > 0.05). Furthermore, the STZ/4HR group demonstrated significantly improved sperm motility compared to the STZ group, with apoptotic indicators notably reduced in the STZ/4HR group relative to the STZ group (p < 0.05). These results underscore the therapeutic potential of 4HR for maintaining testicular function under diabetic conditions.

The optimal scaffold for silk sericin-based bone graft: collagen versus gelatin.

BACKGROUND: Silk sericin is an active ingredient in bone grafts. However, the optimal scaffold for silk sericin has yet to be identified. METHOD: A critical-sized bone defect model in rat calvaria was used to evaluate bone regeneration. Silk sericin from Yeonnokjam, Bombyx mori, was incorporated into gelatin (group G, n = 6) and collagen (group C, n = 6). Bone regeneration was evaluated using micro-computed tomography (mCT) and histology. RESULTS: Group C showed a larger bone volume than group G in the mCT analysis (P = 0.001). Histological analysis showed a larger area of bony defects in group G than in group C. The bone regeneration area in group C was significantly larger than that in group G (P = 0.003). CONCLUSION: Compared with gelatin, collagen shows better bone regeneration in silk sericin-based bone grafts.

Porous silicon surface modification via a microwave-induced in situ cyclic disulfide (S-S) cleavage and Si-S bond formation.

Porous silicon (pSi) materials have gained a great deal of attention from various research fields, and their surface-functionalization is one of the critical points for their applications. In this study, a new surface modification method of Si-H-terminated pSi materials via microwave-induced Si-S bond formation is disclosed. The silicon hydride (Si-H) functionality on the pSi surface could react with the 5-membered cyclic disulfide (S-S) compound (DL-α-lipoic acid in this study) by microwave-induced in situ S-S bond cleavage and Si-S bond formation. This surface chemistry is fast responsive (<10 min) and more efficient than other methods such as vortexing, heating stirring, or ultrasonication. The reaction maintains the primary porous structure of pSi materials including pSi wafer, pSi rugate filer, and pSi nanoparticles. An additional functional group such as carboxylic acid is demonstrated to be readily introducible on the pSi surface for further applications. Overall, this study has successfully demonstrated the porous silicon surface modification via a microwave-induced in situ cyclic disulfide (S-S) cleavage and Si-S bond formation.

MicroRNA-18a regulates the metastatic properties of oral squamous cell carcinoma cells via HIF-1α expression.

BACKGROUND: Rapid metastasis of oral squamous cell carcinoma (OSCC) is associated with a poor prognosis and a high mortality rate. However, the molecular mechanisms underlying OSCC metastasis have not been fully elucidated. Although deregulated expression of microRNA (miRNA) has a crucial role in malignant cancer progression, the biological function of miRNA in OSCC progression remains unclear. This study aimed to investigate the function of miRNA-18a in OSCC metastatic regulation via hypoxia-inducible factor 1α (HIF-1α). METHODS: miRNA-18a-5p (miRNA-18a) expressions in patients with OSCC (n = 39) and in OSCC cell lines (e.g., YD-10B and HSC-2 cells) were analyzed using quantitative real-time polymerase chain reaction. HIF-1α protein expressions in OSCC cells treated with miRNA-18a mimics or combined with cobalt chloride were analyzed using western blotting. The miRNA-18a expression-dependent proliferation and invasion abilities of OSCC cells were analyzed using MTT assay, EdU assay, and a Transwell® insert system. RESULTS: miRNA-18a expression was significantly lower in OSCC tissue than in the adjacent normal tissue. In OSCC cell lines, HIF-1α expression was significantly decreased by miRNA-18a mimic treatment. Furthermore, the migration and invasion abilities of OSCC cells were significantly decreased by miRNA-18a mimics and significantly increased by the overexpression of HIF-1α under hypoxic conditions relative to those abilities in cells treated only with miRNA-18a mimics. CONCLUSIONS: miRNA-18a negatively affects HIF-1α expression and inhibits the metastasis of OSCC, thereby suggesting its potential as a therapeutic target for antimetastatic strategies in OSCC.

Development of a fluorescent nanoprobe based on an amphiphilic single-benzene-based fluorophore for lipid droplet detection and its practical applications.

Lipid droplets (LDs) are crucial biological organelles connected with metabolic pathways in biological systems and diseases. To monitor the locations and accumulation of LDs in lipid-related diseases, the development of a visualization tool for LDs has gained importance. In particular, LD visualization using fluorescent probes has gained attention. Herein, a new fluorescent nanoprobe, BMeS-Ali, is developed that can sense LDs based on an amphiphilic single benzene-based fluorophore (SBBF). BMeS-Ali consists of hydrophilic (-NH2) and hydrophobic (-C12H25) moieties and exists as a micelle nanostructure in aqueous media. BMeS-Ali has a weak fluorescence, but its emission was dramatically enhanced upon exposure to the LD components such as oleic acids (OA) by reassembling its nano-formulation. BMeS-Ali showed a selective LD staining ability and great biocompatibility in cells (cancer cells and stem cells). It also showed a practical sensing ability towards biologically derived lipids and can be applied to the visualization of human fingerprints. We found that the nanoprobe BMeS-Ali has significant potential to serve as a practical dye and sensor for lipids, especially for LD imaging in the biomedical research area and broader industrial applications.

Optical Detection of Copper Ions via Structural Dissociation of Plasmonic Sugar Nanoprobes.

Heavy metal ions are known to cause environmental pollution and several human diseases because of their inherent toxicity. Among them, Cu2+ is an essential element for the human body, but its continuous exposure and accumulation may cause adverse effects. Thus, copper ion levels in aquatic environments are strictly regulated by international standards. Herein, we demonstrate a simple optical method for detecting Cu2+ using plasmonic sugar nanoprobes (PSNs) composed of gold nanoparticles and polysaccharides. Gold precursors were reduced to nanoparticles and spontaneously embedded in the sugar-based polymeric network with the sulfated residues of carrageenan during the polymerization procedure. Owing to the abundant functional residues of PSNs and their affinity toward Cu2+, we observed the Cu2+-mediated preferential dissociation of the PSNs, resulting in absorbance spectral shifts and scattering shifts of the PSNs. Based on these plasmon band shifts, Cu2+ below the EPA regulation level of 20 µM can be easily detected by the optimized experimental condition. Additionally, the reaction mechanism between the PSNs and Cu2+ was elucidated by indepth spectroscopic analyses, which revealed that the increased binding of Cu2+ to the sulfate groups in the PSNs induces the eventual decomposition of the PSNs.

Evaluation of postoperative changes in condylar positions after orthognathic surgery using balanced orthognathic surgery system.

BACKGROUND: Many studies on maintaining the condyle in a normal or anatomical position during orthognathic surgery have been conducted to stabilize surgical outcomes and prevent iatrogenic temporomandibular joint complications. The aim of this study is to evaluate the changes in condylar positions after orthognathic surgery using virtual surgical planning via the balanced orthognathic surgery (BOS) system. METHODS: Postoperative changes in condylar position were retrospectively evaluated in 22 condyles of 11 patients with skeletal class III malocclusion who underwent orthognathic surgery using virtual surgical planning via the BOS system. The center point coordinates of the condylar head before and after orthognathic surgery were analyzed using voxel-based registration. RESULTS: Changes in the condylar position mainly occurred downward in the y-axis (-1.09 ± 0.62 mm) (P < 0.05). The change in the x-axis (0.02 ± 0.68 mm) and z-axis (0.01 ± 0.48 mm) showed no significant difference between before and after orthognathic surgery. CONCLUSION: These results indicate that the changes in the condylar positions after orthognathic surgery using virtual surgical planning via the BOS system mainly occurred downward in the y-axis, with slight changes in the x- and z-axes. The change in the condylar position after orthognathic surgery using the BOS system is clinically acceptable.

A Deep Dive: SIWV Tetra-Peptide Enhancing the Penetration of Nanotherapeutics into the Glioblastoma.

Glioblastoma multiforme (GBM) is the most aggressive malignant tumor. It is difficult to regulate GBM using conventional chemotherapy-based methods due to its anatomical structure specificity, low drug targeting ability, and limited penetration depth capability to reach the tumor interior. Numerous approaches have been proposed to overcome such issues, including nanoparticle-based drug delivery system (DDS) with the development of GBM site targeting and penetration depth enhancing moieties (e.g., peptides, sugars, proteins, etc.). In this study, we prepared four different types of nanoparticles, which are based on porous silicon nanoparticles (pSiNPs) incorporating polyethylene glycol (PEG), iRGD peptide (well-known cancer targeting peptide), and SIWV tetra-peptide (a recently disclosed GBM-targeting peptide), and analyzed their deep-tumor penetration abilities in cell spheroids, in GBM patient-derived tumoroids, and in GBM xenograft mice. We found that SIWV tetra-peptide significantly enhanced the penetration depth of pSiNPs, and its therapeutic formulation (temozolomide-loaded/SIWV-functionalized pSiNPs) showed a higher anticancer efficacy compared with other formulations. These findings hold great promise for the development of nanotherapeutics and peptide-conjugated drugs for GBM.

4-Hexylresorcinol Treatment before Degumming Increases the ß-Sheet Structure of Silk Sericin and BMP-2 Expression in RAW264.7 Cells.

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 ß-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 ß-sheet structure of silk sericin, as well as inducing BMP-2 expression and bone regeneration ability.

Thermally induced silane dehydrocoupling on porous silicon nanoparticles for ultra-long-acting drug release.

Here, we report an ultra-long-acting drug release nano-formulation based on porous silicon nanoparticles (pSiNPs) that are prepared by thermally induced silane dehydrocoupling and lipid-coating. This robust formulation offers the ability to release an anticancer drug, for up to 2 weeks, in various biological environments; pH 7.4 buffer, cancer cells, and tumor xenograft model.

Silk sericin application increases bone morphogenic protein-2/4 expression via a toll-like receptor-mediated pathway.

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 ß-sheet structure than the low molecular weight fraction. Administration of the ß-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 ß-sheet structure increased BMP-2/4 expression and bone formation better than sericin with a less abundant ß-sheet structure.

Effects of 4-Hexylresorcinol on Craniofacial Growth in Rats.

4-Hexylresorcinol (4HR) has been used as a food additive, however, it has been recently demonstrated as a Class I histone deacetylase inhibitor (HDACi). Unlike other HDACi, 4HR can be taken through foods. Unfortunately, some HDACi have an influence on craniofacial growth, therefore, the purpose of this study was to evaluate the effects of 4HR on craniofacial growth. Saos-2 cells (osteoblast-like cells) were used for the evaluation of HDACi and its associated activities after 4HR administration. For the evaluation of craniofacial growth, 12.8 mg/kg of 4HR was administered weekly to 4 week old rats (male: 10, female: 10) for 12 weeks. Ten rats were used for untreated control (males: 5, females: 5). Body weight was recorded every week. Serum and head samples were collected at 12 weeks after initial administration. Craniofacial growth was evaluated by micro-computerized tomography. Serum was used for ELISA (testosterone and estrogen) and immunoprecipitation high-performance liquid chromatography (IP-HPLC). The administration of 4HR (1-100 µM) showed significant HDACi activity (p < 0.05). Body weight was significantly different in male rats (p < 0.05), and mandibular size was significantly smaller in 4HR-treated male rats with reduced testosterone levels. However, the mandibular size was significantly higher in 4HR treated female rats with increased growth hormone levels. In conclusion, 4HR had HDACi activity in Saos-2 cells. The administration of 4HR on growing rats showed different responses in body weight and mandibular size between sexes.

Recent advances in single-benzene-based fluorophores: physicochemical properties and applications.

Fluorescence-based materials and associated techniques (analytical, imaging, and sensing techniques) have been highlighted over the last century throughout various basic research fields and industries. Organic molecule-based fluorophores, in particular, have ushered in a new era in biology and materials science. To date, hundreds of organic fluorophores have been developed, and many studies have introduced new rationales for the fluorophore design and the analysis of the relationship between its structure and photophysical properties both in the solution- and solid-state. In this review, we summarize the recent advances (mainly from 2015 to 2020) in single-benzene-based fluorophores (SBBFs), which have an electron-donor (D)-acceptor (A) type dipolar structure within a compact benzene backbone. We also present a systematic outline of the physicochemical properties of SBBFs and representative examples of their applications, which will provide useful context for the development of new SBBF derivatives in fluorophore-related materials science fields.

Natural Bone Healing In Compromised Sockets After Tooth Extraction: Digital Measurement Methods With Cone-Beam Computed Tomography.

This study aimed to evaluate bone regeneration within infected extraction sockets with bone defects using cone-beam computed tomography (CBCT) at a 1-year follow-up after implant placement in a prosthetically driven implant position. Forty-eight patients requiring premolar or molar tooth extraction due to bone defects caused by periodontal diseases were included. Vertical and horizontal bone volumes were assessed by overlapping the CBCT scan images with the full digital process. At 1-year post-extraction, a prosthetically-driven implant was planned using virtual implant planning software. At 1 year after extraction, CBCT revealed significant horizontal and vertical bone gains; an overall mean buccolingual bone width gain of 5.46 ± 2.87 mm, and an overall mean vertical bone gain of 0.27 ± 1.28 mm for the lingual bone plate level and 3.50 ± 1.81 mm for the buccal bone plate level were observed. Except for 4 (out of 48) sites, implants were virtually positioned in the center of the edentulous spaces. In summary, despite the dimensional changes after tooth extraction in compromised posterior sockets, there was sufficient bone for placing an implant using the prosthetically driven approach.

Increased Level of Vascular Endothelial Growth Factors by 4-hexylresorcinol is Mediated by Transforming Growth Factor-ß1 and Accelerates Capillary Regeneration in the Burns in Diabetic Animals.

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-ß1 (TGF-ß1) expression were investigated. The administration of 4HR increased the expression level of VEGF-A, -C, and TGF-ß1. The application of TGF-ß1 protein also increased the expression level of VEGF-A and -C. Knockdown with small interfering RNA (siRNA) targeting to TGF-ß1 and the selective chemical inhibition (A83-01) to ALK5 confirmed the involvement of the TGF-ß 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-ß1/ALK5/VEGFs signaling in endothelial cells and induced vascular regeneration and remodeling for wound healing.

Stress Distribution on the Prosthetic Screws in the All-on-4 Concept: A Three-Dimensional Finite Element Analysis.

The all-on-4 concept, which is used to rehabilitate edentulous patients, can present with mechanical complications such as screw loosening and fracture. The purpose of this study was to evaluate the stress patterns induced in the prosthetic screws by the different prosthetic screw and abutment designs in the all-on-4 concept using finite element analysis. Von Mises stress values on 6 groups of each screw type, including short and narrow screw, short abutment; short and wide screw, short abutment; long and wide screw, short abutment; short and narrow screw, long abutment; short and wide screw, long abutment; and long and wide screw, long abutment, were compared under a cantilever loading of 200 N that was applied on the farther posterior to the position of the connection between the distal implant and the metal framework. Posterior prosthetic screws showed higher stress values than anterior prosthetic screws. The stress values in posterior prosthetic screws decreased as the length and diameter increased. In conclusion, the long and wide screw design offers advantages in stress distribution when compared with the short and narrow design.

Retrospective comparative clinical study for silk mat application into extraction socket.

BACKGROUND: Silk mats have been approved for clinical trials by the Korean Food and Drug Administration as membranes for guided tissue regeneration (GTR). In this study, silk mat application was compared to high-density polytetrafluoroethylene (dPTFE) membrane application or no membrane group. METHODS: To compare the silk mat group to the dPTFE group or the no membrane group, a retrospective sample collection was conducted. Bony defects were measured at the time of extraction (T0) and then at 3 months (T1) and 6 months after extraction (T2) on a digital panoramic view. Bone gain (BG) was calculated by subtracting from the bony defect at T0 to the bony defect at each follow-up. RESULTS: The BG at T2 was 2.44 ± 2.49 mm, 4.18 ± 1.80 mm, and 4.24 ± 2.05 mm in the no membrane group, silk mat group, and dPTFE group, respectively. Both membrane groups had significantly higher BG than BG in the no membrane group at T2 (P < 0.05). CONCLUSIONS: Both membrane groups showed higher BG than the no membrane group.

A digital technique for fabricating an interim implant-supported fixed prosthesis immediately after implant placement in patients with complete edentulism.

The conversion of a denture into an interim implant-supported, screw-retained restoration has become the standard method for immediate interim restoration in patients with complete edentulism. The most critical steps of the denture conversion process are the creation of appropriate denture access holes to prevent displacement of the denture by the interim cylinders and removal of the denture flanges to facilitate both good esthetics and accessibility for oral hygiene after the denture is connected to the interim cylinders. This article presents a digital technique for designing and fabricating an interim implant-supported, fixed prosthesis for edentulous patients. The interim prosthesis has cylinder access holes that are digitally prefabricated and a denture flange part that is designed to be easily sectioned. This technique facilitates more straightforward and efficient immediate restoration for edentulous patients after implant placement.

Anatomical repair of a bilateral Tessier No. 3 cleft by midfacial advancement.

BACKGROUND: Bilateral Tessier number 3 clefts are extremely rare, and their surgical treatments have not been well established. CASE PRESENTATION: The authors describe the case of a patient with a right Tessier number 3, 11 facial cleft with microphthalmia, a left Tessier number 3 facial cleft with anophthalmia, and cleft palate. We repaired simultaneously the bilateral soft tissue clefts by premaxillary repositioning, cleft lip repair, facial cleft repair by nasal lengthening, midfacial advancement, and an upper eyelid transposition flap with repositioning both the medial canthi. Postoperatively, the patient showed an esthetically acceptable face without unnatural scars. CONCLUSIONS: We achieved good results functionally and esthetically by midfacial advancement with facial muscle reposition instead of traditional interdigitating Z-plasties. The surgical modality of our anatomical repair and 3 months follow-up results are presented.

Recent advances in the reconstruction of cranio-maxillofacial defects using computer-aided design/computer-aided manufacturing.

With the development of computer-aided design/computer-aided manufacturing (CAD/CAM) technology, it has been possible to reconstruct the cranio-maxillofacial defect with more accurate preoperative planning, precise patient-specific implants (PSIs), and shorter operation times. The manufacturing processes include subtractive manufacturing and additive manufacturing and should be selected in consideration of the material type, available technology, post-processing, accuracy, lead time, properties, and surface quality. Materials such as titanium, polyethylene, polyetheretherketone (PEEK), hydroxyapatite (HA), poly-DL-lactic acid (PDLLA), polylactide-co-glycolide acid (PLGA), and calcium phosphate are used. Design methods for the reconstruction of cranio-maxillofacial defects include the use of a pre-operative model printed with pre-operative data, printing a cutting guide or template after virtual surgery, a model after virtual surgery printed with reconstructed data using a mirror image, and manufacturing PSIs by directly obtaining PSI data after reconstruction using a mirror image. By selecting the appropriate design method, manufacturing process, and implant material according to the case, it is possible to obtain a more accurate surgical procedure, reduced operation time, the prevention of various complications that can occur using the traditional method, and predictive results compared to the traditional method.