Background: Traditionally, dental implants require a healing period of 4 to 9 months for osseointegration, with longer recovery times considered when bone grafting is needed. This retrospective study evaluates the clinical efficacy of demineralized dentin matrix (DDM) combined with recombinant human bone morphogenetic protein-2 (rhBMP-2) during dental implant placement to expedite the osseointegration period for early loading. Methods: Thirty patients (17 male, 13 female; mean age 55.0 ± 8.8 years) requiring bone grafts due to implant fixture exposure (more than four threads; ≥ 3.2 mm) were included, with a total of 96 implants placed. Implants were inserted using a two-stage protocol with DDM/rhBMP-2 grafts. Early loading was initiated at two months postoperatively in the mandible and three months in the maxilla. Clinical outcomes evaluated included primary and secondary stability (implant stability quotient values), healing period, bone width, and marginal bone level assessed via cone-beam computed tomography. Results: All implants successfully supported final prosthetics with a torque of 50Ncm, without any osseointegration failures. The average healing period was 69.6 days in the mandible and 90.5 days in the maxilla, with significantly higher secondary stability in the mandible (80.7 ± 6.7) compared to the maxilla (73.0 ± 9.2, p < 0.001). Histological analysis confirmed new bone formation and vascularization. Conclusion DDM/rhBMP-2 grafting appears to significantly reduce the healing period, enabling early loading with stable and favorable clinical outcomes.

Background: Traditionally, dental implants require a healing period of 4 to 9 months for osseointegration, with longer recovery times considered when bone grafting is needed. This retrospective study evaluates the clinical efficacy of demineralized dentin matrix (DDM) combined with recombinant human bone morphogenetic protein-2 (rhBMP-2) during dental implant placement to expedite the osseointegration period for early loading. Methods: Thirty patients (17 male, 13 female; mean age 55.0 ± 8.8 years) requiring bone grafts due to implant fixture exposure (more than four threads; ≥ 3.2 mm) were included, with a total of 96 implants placed. Implants were inserted using a two-stage protocol with DDM/rhBMP-2 grafts. Early loading was initiated at two months postoperatively in the mandible and three months in the maxilla. Clinical outcomes evaluated included primary and secondary stability (implant stability quotient values), healing period, bone width, and marginal bone level assessed via cone-beam computed tomography. Results: All implants successfully supported final prosthetics with a torque of 50Ncm, without any osseointegration failures. The average healing period was 69.6 days in the mandible and 90.5 days in the maxilla, with significantly higher secondary stability in the mandible (80.7 ± 6.7) compared to the maxilla (73.0 ± 9.2, p < 0.001). Histological analysis confirmed new bone formation and vascularization. Conclusion DDM/rhBMP-2 grafting appears to significantly reduce the healing period, enabling early loading with stable and favorable clinical outcomes.

Background: Traditionally, dental implants require a healing period of 4 to 9 months for osseointegration, with longer recovery times considered when bone grafting is needed. This retrospective study evaluates the clinical efficacy of demineralized dentin matrix (DDM) combined with recombinant human bone morphogenetic protein-2 (rhBMP-2) during dental implant placement to expedite the osseointegration period for early loading. Methods: Thirty patients (17 male, 13 female; mean age 55.0 ± 8.8 years) requiring bone grafts due to implant fixture exposure (more than four threads; ≥ 3.2 mm) were included, with a total of 96 implants placed. Implants were inserted using a two-stage protocol with DDM/rhBMP-2 grafts. Early loading was initiated at two months postoperatively in the mandible and three months in the maxilla. Clinical outcomes evaluated included primary and secondary stability (implant stability quotient values), healing period, bone width, and marginal bone level assessed via cone-beam computed tomography. Results: All implants successfully supported final prosthetics with a torque of 50Ncm, without any osseointegration failures. The average healing period was 69.6 days in the mandible and 90.5 days in the maxilla, with significantly higher secondary stability in the mandible (80.7 ± 6.7) compared to the maxilla (73.0 ± 9.2, p < 0.001). Histological analysis confirmed new bone formation and vascularization. Conclusion DDM/rhBMP-2 grafting appears to significantly reduce the healing period, enabling early loading with stable and favorable clinical outcomes.

Background: Traditionally, dental implants require a healing period of 4 to 9 months for osseointegration, with longer recovery times considered when bone grafting is needed. This retrospective study evaluates the clinical efficacy of demineralized dentin matrix (DDM) combined with recombinant human bone morphogenetic protein-2 (rhBMP-2) during dental implant placement to expedite the osseointegration period for early loading. Methods: Thirty patients (17 male, 13 female; mean age 55.0 ± 8.8 years) requiring bone grafts due to implant fixture exposure (more than four threads; ≥ 3.2 mm) were included, with a total of 96 implants placed. Implants were inserted using a two-stage protocol with DDM/rhBMP-2 grafts. Early loading was initiated at two months postoperatively in the mandible and three months in the maxilla. Clinical outcomes evaluated included primary and secondary stability (implant stability quotient values), healing period, bone width, and marginal bone level assessed via cone-beam computed tomography. Results: All implants successfully supported final prosthetics with a torque of 50Ncm, without any osseointegration failures. The average healing period was 69.6 days in the mandible and 90.5 days in the maxilla, with significantly higher secondary stability in the mandible (80.7 ± 6.7) compared to the maxilla (73.0 ± 9.2, p < 0.001). Histological analysis confirmed new bone formation and vascularization. Conclusion DDM/rhBMP-2 grafting appears to significantly reduce the healing period, enabling early loading with stable and favorable clinical outcomes.

Background: Traditionally, dental implants require a healing period of 4 to 9 months for osseointegration, with longer recovery times considered when bone grafting is needed. This retrospective study evaluates the clinical efficacy of demineralized dentin matrix (DDM) combined with recombinant human bone morphogenetic protein-2 (rhBMP-2) during dental implant placement to expedite the osseointegration period for early loading. Methods: Thirty patients (17 male, 13 female; mean age 55.0 ± 8.8 years) requiring bone grafts due to implant fixture exposure (more than four threads; ≥ 3.2 mm) were included, with a total of 96 implants placed. Implants were inserted using a two-stage protocol with DDM/rhBMP-2 grafts. Early loading was initiated at two months postoperatively in the mandible and three months in the maxilla. Clinical outcomes evaluated included primary and secondary stability (implant stability quotient values), healing period, bone width, and marginal bone level assessed via cone-beam computed tomography. Results: All implants successfully supported final prosthetics with a torque of 50Ncm, without any osseointegration failures. The average healing period was 69.6 days in the mandible and 90.5 days in the maxilla, with significantly higher secondary stability in the mandible (80.7 ± 6.7) compared to the maxilla (73.0 ± 9.2, p < 0.001). Histological analysis confirmed new bone formation and vascularization. Conclusion DDM/rhBMP-2 grafting appears to significantly reduce the healing period, enabling early loading with stable and favorable clinical outcomes.

Background: Cytoplasmic polyadenylation element binding (CPEB) proteins are sequencespecific RNA-binding proteins that control translation via cytoplasmic polyadenylation. We previously reported that CPEB1 or CPEB4 knockdown suppresses TAK1 and SMAD signaling in an in vitro study. Objective: This study aimed to investigate whether suppression of CPEB1 or CPEB4 expression inhibits scar formation in a mice model of acute dermal wound healing. Methods: CPEB1 and CPEB4 expression levels were suppressed by siRNA treatment. Skin wounds were created by pressure-induced ulcers in mice. Images of the wound healing were obtained using a digital camera and contraction was measured by ImageJ. mRNA and protein expression was analyzed using quantitative real time polymerase chain reaction and western blotting, respectively. Results: Wound contraction was significantly decreased by pre-treatment with CPEB1 or CPEB4 siRNA compared to the control. Suppression of CPEB1 or CPEB4 expression decreased TAK1 signaling by reducing the levels of TLR4 and TNF-α, phosphorylated TAK1, p38, ERK, JNK, and NF-κB-p65. Decreased levels of phosphorylated SMAD2 and SMAD3 indicated a reduction in SMAD signaling as well. Consequently, the expression of α-SMA, fibronectin, and type I collagen decreased. Conclusion CPEB1 siRNA or CPEB4 siRNA inhibit scar formation by modulating the TAK1 and SMAD signaling pathways. Our study highlights CPEB1 and CPEB4 as potential therapeutic targets for the treatment of scar formation.

Background: Stem cell therapies can be a new therapeutic strategy that may rebalance anabolic and anti-resorptive effects in osteoporosis patients. Tonsil-derived mesenchymal stem cells (TMSCs) can be an alternative therapeutic source for chronic degenerative diseases including osteoporosis. MSCs acquire immune regulatory function under the inflammatory cytokines. Since interleukin (IL) 1β is known to be one of inflammatory cytokines involved in osteoporosis progression, treatment of IL1β with TMSCs may enhance immunomodulatory function and therapeutic effects of TMSCs in osteoporosis. Methods: For IL1β priming, TMSCs were cultured in the presence of the medium containing IL1β for 1 day. Characteristics of IL1β priming TMSCs such as multipotent differentiation properties, anti-inflammatory potential, and suppression of osteoclast differentiation were assessed in vitro. For in vivo efficacy study, IL1β priming TMSCs were intravenously infused twice with ovariectomized (OVX) osteoporosis mouse model, and blood serum and bone parameters from micro computed tomography images were analyzed. Results: IL1β priming TMSCs had an enhanced osteogenic differentiation and secreted factors that regulate both osteoclastogenesis and osteoblastogenesis. IL1β priming TMSCs also suppressed proliferation of peripheral blood mononuclear cells (PBMCs) and decreased expression of Receptor activator of nuclear factor kappa-Β ligand (RANKL) in PHA-stimulated PBMCs. Furthermore, osteoclast specific genes such as Nuclear factor of activated T cells c1 (NFATc1) were effectively down regulated when co-cultured with IL1β priming TMSCs in RANKL induced osteoclasts. In OVX mice, IL1β priming TMSCs induced low level of serum RANKL/osteoprotegerin (OPG) ratio on the first day of the last administration. Four weeks after the last administration, bone mineral density and serum Gla-osteocalcin were increased in IL1β priming TMSC-treated OVX mice. Furthermore, bone formation and bone resorption markers that had been decreased in OVX mice with low calcium diet were recovered by infusion of IL1β priming TMSCs. Conclusion IL1β priming can endow constant therapeutic efficacy with TMSCs, which may contribute to improve bone density and maintain bone homeostasis in postmenopausal osteoporosis. Therefore, IL1β priming TMSCs can be a new therapeutic option for treating postmenopausal osteoporosis.

Background: Stem cell therapies can be a new therapeutic strategy that may rebalance anabolic and anti-resorptive effects in osteoporosis patients. Tonsil-derived mesenchymal stem cells (TMSCs) can be an alternative therapeutic source for chronic degenerative diseases including osteoporosis. MSCs acquire immune regulatory function under the inflammatory cytokines. Since interleukin (IL) 1β is known to be one of inflammatory cytokines involved in osteoporosis progression, treatment of IL1β with TMSCs may enhance immunomodulatory function and therapeutic effects of TMSCs in osteoporosis. Methods: For IL1β priming, TMSCs were cultured in the presence of the medium containing IL1β for 1 day. Characteristics of IL1β priming TMSCs such as multipotent differentiation properties, anti-inflammatory potential, and suppression of osteoclast differentiation were assessed in vitro. For in vivo efficacy study, IL1β priming TMSCs were intravenously infused twice with ovariectomized (OVX) osteoporosis mouse model, and blood serum and bone parameters from micro computed tomography images were analyzed. Results: IL1β priming TMSCs had an enhanced osteogenic differentiation and secreted factors that regulate both osteoclastogenesis and osteoblastogenesis. IL1β priming TMSCs also suppressed proliferation of peripheral blood mononuclear cells (PBMCs) and decreased expression of Receptor activator of nuclear factor kappa-Β ligand (RANKL) in PHA-stimulated PBMCs. Furthermore, osteoclast specific genes such as Nuclear factor of activated T cells c1 (NFATc1) were effectively down regulated when co-cultured with IL1β priming TMSCs in RANKL induced osteoclasts. In OVX mice, IL1β priming TMSCs induced low level of serum RANKL/osteoprotegerin (OPG) ratio on the first day of the last administration. Four weeks after the last administration, bone mineral density and serum Gla-osteocalcin were increased in IL1β priming TMSC-treated OVX mice. Furthermore, bone formation and bone resorption markers that had been decreased in OVX mice with low calcium diet were recovered by infusion of IL1β priming TMSCs. Conclusion IL1β priming can endow constant therapeutic efficacy with TMSCs, which may contribute to improve bone density and maintain bone homeostasis in postmenopausal osteoporosis. Therefore, IL1β priming TMSCs can be a new therapeutic option for treating postmenopausal osteoporosis.

BACKGROUND: Melanogenesis is a biological process resulting in the production of melanin pigment, which plays an important role in the prevention of sun-induced skin injury and determines the hair and skin color. Melanin has the ability to block ultraviolet radiation and scavenge free oxygen radicals, thus protecting the skin from their harmful effects. Agents that increase melanin synthesis in melanocytes may reduce the risk of photodamage and skin cancer. Hence, various approaches have been proposed to increase the synthesis of melanin. METHODS: The current study aimed to develop a three-dimensional hair follicle-like tissue (HFLT) model with human dermal papilla, melanocytes, and outer root sheaths cells. This model showed enhanced melanogenesis-related protein expression after rice bran ash extract (RBE) treatment. Next, we investigated the melanogenic effect of RBE in the HFLT and compared the results to those of hair follicle (HF) organ culture model. RESULTS: RBE was found to significantly increase the expression of microphthalmia-associated transcription factor, a key transcription factor involved in melanin production, in both HFLT and organ culture models. Results showed that melanogenesis-related protein expression levels were higher in the RBE group compared to those in the control group. Similar results were obtained by immunohistochemistry. CONCLUSION Our data suggested that RBE promotes melanin biosynthesis. Taken together, this simple in vitro HFLT model system has the potential to provide significant insights into the underlying molecular mechanisms of HF melanogenesis, and hence can be used for controlled evaluation of the efficacy of new materials for melanogenesis.

Background: Recently, a study comprising adult patients with sepsis admitted in the intensive care unit (ICU) was conducted. The patients were treated with high doses of intravenous ascorbic acid, thiamine, and hydrocortisone; the clinical outcomes demonstrated significant therapeutic benefits. The mortality rate in children with sepsis is approximately 25%. However, the effects of additional treatment with ascorbic acid and thiamine (“vitamin protocol”) in children are rarely investigated. Methods: A retrospective analysis was performed using medical records of patients diagnosed with sepsis and admitted to the pediatric ICU (PICU) between September 2016 and June 2019. The control group received treatment only as per sepsis protocol, whereas the treated group received both sepsis protocol and the vitamin protocol. The primary endpoint was change in Vasoactive-Inotropic Score (VIS) for 5 days. The secondary endpoints included the length of stay in the PICU, duration of using mechanical ventilators and vasopressors, and mortality rate. Results: The number of patients in the treated and control groups was 33 and 24, respectively. The treated group showed greater decrease in their VIS for 5 days than the control group (44.4 vs 18.6); however, the difference was not statistically significant. The length of stay in the PICU was significantly longer for the treated group than for the control group [10.0 days (Interquartile range (IQR), 6-18) vs 4.5 days (IQR, 4-10.3); p=0.004]. Conclusions No significant treatment benefits were observed following vitamin protocol administration to the pediatric patients with sepsis. Further studies are necessary for improving the efficacy and safety of the vitamin protocol.