Kaempferia parviflora extract and its component polymethoxyflavones suppress adipogenic differentiation of human bone marrow-derived mesenchymal stem cells via the AMPK pathway.

BACKGROUND: Kaempferia parviflora Wall. ex. Baker (KP) has been reported to exhibit anti-obesity effects. However, the detailed mechanism of the anti-obesity effect of KP extract (KPE) is yet to be clarified. Here, we investigated the effect of KPE and its component polymethoxyflavones (PMFs) on the adipogenic differentiation of human mesenchymal stem cells (MSCs). METHODS AND RESULTS: KPE and PMFs fraction (2.5 µg/mL) significantly inhibited lipid and triacylglyceride accumulation in MSCs; lipid accumulation in MSCs was suppressed during the early stages of differentiation (days 0-3) but not during the mid (days 3-7) or late (days 7-14) stages. Treatment with KPE and PMFs fractions significantly suppressed peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancer binding protein α (C/EBPα), and various adipogenic metabolic factors. Treatment with KPE and PMFs fraction induced the activation of AMP-activated protein kinase (AMPK) signaling, and pretreatment with an AMPK signaling inhibitor significantly attenuated KPE- and PMFs fraction-induced suppression of lipid formation. CONCLUSIONS: Our findings demonstrate that KPE and PMFs fraction inhibit lipid formation by inhibiting the differentiation of undifferentiated MSCs into adipocyte lineages via AMPK signaling, and this may be the mechanism underlying the anti-obesity effects of KPE and PMFs. Our study lays the foundation for the elucidation of the anti-obesity mechanism of KPE and PMFs.

Relationships Between Test Results for Oral Hypofunction, Subjective Frailty Symptoms and Oral Health-Related Quality of Life of Japanese Dental Outpatients: A Multicentre, Cross-Sectional Study.

BACKGROUND: Oral hypofunction is the stage before oral dysfunction. The subjective symptoms of poor oral function and the decline in oral health-related quality of life (OHRQoL) that occur in the oral hypofunction stage can be missed. OBJECTIVE: This multicentre cross-sectional study was performed to examine the relationships between the test results for oral hypofunction, subjective frailty symptoms and OHRQoL of outpatients in dental clinics. METHODS: The basic characteristics and oral function test results of 637 dental clinic outpatients were evaluated. The subjective symptoms of physical and oral frailty were investigated using a questionnaire. OHRQoL was assessed using the Japanese short version of the Oral Health Impact Profile (OHIP-JP16) and OHRQoL dimension score. RESULTS: The overall prevalence of oral hypofunction was 37.8%, with no significant difference between men and women. No significant differences in the presence or absence of subjective symptoms of frailty and a high OHIP score were observed based on sex. However, the prevalence of oral hypofunction was significantly different among the age groups and increased with age. The subjective symptoms of frailty score, OHIP score and OHRQoL dimension score were significantly higher in patients with versus without oral hypofunction. Age, number of underlying diseases, total score for subjective symptoms of frailty, total score for OHIP and OHRQoL dimension score were significantly associated with oral hypofunction. CONCLUSION: Oral hypofunction may affect the subjective symptoms of frailty and OHRQoL in older adults.

DO ORAL CARE AND REHABILITATION IMPROVE COGNITIVE FUNCTION? A SYSTEMATIC REVIEW OF CLINICAL STUDIES.

OBJECTIVES: An increasing number of studies have identified an association between oral health status and cognitive function. However, the effect of oral interventions, including oral health care, dental treatment and oral motor exercises, on cognitive function remains unclear. This systematic review examined whether oral interventions contribute to the long-term improvement of cognitive status. METHODS: Four databases were searched (MEDLINE, Web of Science, Cochrane Library, and ICHUSHI Web) to identify randomized and nonrandomized controlled trial studies and prospective cohort studies from inception until 1 September 2023, published in English or Japanese. The Cochrane risk of bias tool for randomized controlled trials and the risk of bias assessment tool for nonrandomized studies were used to assess bias risk. RESULTS: A total of 20 articles were included in the qualitative analysis; 13 articles were published in English, and 7 were published in Japanese. The implemented interventions were oral care in 8 studies, dental treatment in 8 studies, and oral motor exercise in 4 studies. One study found a significant effect on attention following oral care intervention. Some dental treatments influenced cognitive function, although a clear positive effect was not determined. In 1 study, attention and working memory improved in the chewing exercise group. CONCLUSIONS: Several studies verified the improvement effects of oral interventions, such as oral care, dental treatment, and oral motor exercise, on cognitive function or impairment. However, there was still a lack of conclusive evidence that such an intervention clearly improved cognitive function. To clarify the effects of oral interventions on cognitive function, it is necessary to examine participants, interventions, and outcome measures in detail.

Role of reactive oxygen species (ROS) in the regulation of adipogenic differentiation of human maxillary/mandibular bone marrow-derived mesenchymal stem cells.

BACKGROUND: Maxillary/mandibular bone marrow-derived mesenchymal stem cells (MBMSCs) exhibit a unique property of lower adipogenic potential than other bone marrow-derived MSCs. However, the molecular mechanisms regulating the adipogenesis of MBMSCs remain unclear. This study aimed to explore the roles of mitochondrial function and reactive oxygen species (ROS) in regulating the adipogenesis of MBMSCs. METHODS AND RESULTS: MBMSCs exhibited significantly lower lipid droplet formation than iliac BMSCs (IBMSCs). Moreover, the expression levels of CCAAT/enhancer-binding protein ß (C/EBPß), C/EBPδ, and early B cell factor 1 (Ebf-1), which are early adipogenic transcription factors, and those of peroxisome proliferator-activated receptor-γ (PPARγ) and C/EBPα, which are late adipogenic transcription factors, were downregulated in MBMSCs compared to those in IBMSCs. Adipogenic induction increased the mitochondrial membrane potential and mitochondrial biogenesis in MBMSCs and IBMSCs, with no significant difference between the two cell types; however, intracellular ROS production was significantly enhanced only in IBMSCs. Furthermore, NAD(P)H oxidase 4 (NOX4) expression was significantly lower in MBMSCs than in IBMSCs. Increased ROS production in MBMSCs by NOX4 overexpression or treatment with menadione promoted the expression of early adipogenic transcription factors but did not induce that of late adipogenic transcription factors or lipid droplet accumulation. CONCLUSIONS: These results suggest that ROS may be partially involved in the process of MBMSC adipogenic differentiation from undifferentiated cells to immature adipocytes. This study provides important insights into the tissue-specific properties of MBMSCs.

Rare earth element identification and quantification in millimetre-sized Ryugu rock fragments from the Hayabusa2 space mission.

Millimetre-sized primordial rock fragments originating from asteroid Ryugu were investigated using high energy X-ray fluorescence spectroscopy, providing 2D and 3D elemental distribution and quantitative composition information on the microscopic level. Samples were collected in two phases from two sites on asteroid Ryugu and safely returned to Earth by JAXA's asteroid explorer Hayabusa2, during which time the collected material was stored and maintained free from terrestrial influences, including exposure to Earth's atmosphere. Several grains of interest were identified and further characterised to obtain quantitative information on the rare earth element (REE) content within said grains, following a reference-based and computed-tomography-assisted fundamental parameters quantification approach. Several orders of magnitude REE enrichments compared to the mean CI chondrite composition were found within grains that could be identified as apatite phase. Small enrichment of LREE was found for dolomite grains and slight enrichment or depletion for the general matrices within the Ryugu rock fragments A0055 and C0076, respectively. Supplementary Information: The online version contains supplementary material available at 10.1186/s40623-022-01705-3.

On the origin and evolution of the asteroid Ryugu: A comprehensive geochemical perspective.

Presented here are the observations and interpretations from a comprehensive analysis of 16 representative particles returned from the C-type asteroid Ryugu by the Hayabusa2 mission. On average Ryugu particles consist of 50% phyllosilicate matrix, 41% porosity and 9% minor phases, including organic matter. The abundances of 70 elements from the particles are in close agreement with those of CI chondrites. Bulk Ryugu particles show higher δ18O, Δ17O, and ε54Cr values than CI chondrites. As such, Ryugu sampled the most primitive and least-thermally processed protosolar nebula reservoirs. Such a finding is consistent with multi-scale H-C-N isotopic compositions that are compatible with an origin for Ryugu organic matter within both the protosolar nebula and the interstellar medium. The analytical data obtained here, suggests that complex soluble organic matter formed during aqueous alteration on the Ryugu progenitor planetesimal (several 10's of km), <2.6 Myr after CAI formation. Subsequently, the Ryugu progenitor planetesimal was fragmented and evolved into the current asteroid Ryugu through sublimation.

Lipoteichoic Acid and Lipopolysaccharides Are Affected by p38 and Inflammatory Markers and Modulate Their Promoting and Inhibitory Effects on Osteogenic Differentiation.

Lipoteichoic acid (LTA) and lipopolysaccharide (LPS) are cell wall components of Gram-positive and Gram-negative bacteria, respectively. Notably, oral microflora consists of a variety of bacterial species, and osteomyelitis of the jaw caused by dental infection presents with symptoms of bone resorption and osteosclerosis. However, the effects of LTA and LPS on osteogenic differentiation have not yet been clarified. We examined the effects of LTA and LPS on osteoblasts and found that LTA alone promoted alizarin red staining at low concentrations and inhibited it at high concentrations. Additionally, gene expression of osteogenic markers (ALP, OCN, and OPG) were enhanced at low concentrations of LTA. High concentrations of LPS suppressed calcification potential, and the addition of low concentrations of LTA inhibited calcification suppression, restoring the gene expression levels of suppressed bone differentiation markers (ALP, BSP, and OCN). Moreover, the suppression of p38, a signaling pathway associated with bone differentiation, had opposing effects on gene-level expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), suggesting that mixed LTA and LPS infections have opposite effects on bone differentiation through concentration gradients, involving inflammatory markers (TNF-α and IL-6) and the p38 pathway.

Human cathelicidin antimicrobial peptide LL-37 promotes lymphangiogenesis in lymphatic endothelial cells through the ERK and Akt signaling pathways.

LL-37, the only member of the cathelicidin family of cationic antimicrobial peptides in humans has been shown to exhibit a wide variety of biological actions in addition to its antimicrobial activity. However, the lymphangiogenic effect of LL-37 has not been elucidated yet. In this study, we examined the effects of LL-37 on lymphangiogenesis and evaluated the underlying molecular mechanisms. LL-37 treatment significantly increased the migration and tube-like formation of human dermal lymphatic microvascular endothelial cells (HDLECs) and promoted the expression of lymphangiogenic factor in HDLECs. Treatment with LL-37 increased phosphorylation of ERK and Akt proteins in HDLECs, and pretreatment with ERK and Akt inhibitors significantly blocked the LL-37-induced HDLEC migration and tube-like formation. Furthermore, to investigate the involvement of formyl peptide receptor-like 1 (FPRL1) signaling in LL-37-induced lymphangiogenesis, HDLECs were treated with an FPRL1 antagonist. Pretreatment with the FPRL1 antagonist inhibited LL-37-induced phosphorylation of ERK and Akt proteins and attenuated LL-37-induced HDLEC migration and tube-like formation. These data indicated that LL-37 induces lymphangiogenesis in lymphatic endothelial cells via FPRL1, and the activation of the ERK and Akt-dependent signaling pathways.

Effects of Storage Temperature and pH on the Antifungal Effects of Commercial Oral Moisturizers against Candida Albicans and Candida Glabrata.

Background and objectives: Oral moisturizers have been used to treat dry mouth. This study aimed to investigate the effects of storage temperature and pH on the antifungal effects of oral moisturizers against Candida albicans and Candida glabrata. Materials and Methods: Thirty-one oral moisturizers and amphotericin B (AMPH-B) were stored at 25 and 37 °C for 1 week. Subsequently, they were added to cylindrical holes in 50% trypticase soy agar plates inoculated with C. albicans and C. glabrata (107 cells/ml). The antifungal effects were evaluated based on the sizes of the growth-inhibitory zones formed. Two-way analysis of variance was used to determine the effects of storage temperature and pH on the growth-inhibitory zones. Results: Significant differences in the effects of storage temperature and pH of the moisturizers were observed against C. albicans and C. glabrata. The growth-inhibitory zones of samples stored at 37 °C and with neutral pH were significantly larger than those stored at 25 °C and with acidic pH, respectively. The sizes of the zones formed by most of the oral moisturizers were larger than those formed by AMPH-B (concentration, 0.63 µg/ml). Conclusion: The antifungal effects of oral moisturizers against C. albicans and C. glabrata were affected by their storage temperature and pH.

Vascular endothelial growth factor-C promotes human mesenchymal stem cell migration via an ERK-and FAK-dependent mechanism.

Vascular endothelial cell growth factor-C (VEGF-C) is a member of the VEGF family and plays a role in various biological activities. VEGF-C enhances proliferation and migration of lymphatic endothelial cells and vascular endothelial cells through VEGF receptor 2 (VEGFR2) and/or receptor 3 (VEGFR3), and thereby induces lymphangiogenesis or angiogenesis. However, it remains unclear whether VEGF-C promotes the migration of mesenchymal stem cells (MSCs). Here, we investigated the effects of VEGF-C on the migration of MSCs and evaluated the underlying molecular mechanisms. VEGF-C treatment significantly induced the migration of MSCs, which is accompanied by the promotion of actin cytoskeletal reorganization and focal adhesion assembly. VEGF-C treatment enhanced the phosphorylation of VEGFR2 and VEGFR3 proteins in MSCs, and pretreatment with VEGFR2 and VEGFR3 kinase inhibitors effectively suppressed the VEGF-C-induced MSC migration. In addition, VEGF-C treatment promoted phosphorylation of ERK and FAK proteins in MSCs, and inhibition of VEGFR2 and VEGFR3 signaling pathways abolished the VEGF-C-induced activation of ERK and FAK proteins. Furthermore, treatment with ERK and FAK inhibitors suppressed VEGF-C-induced actin cytoskeletal reorganization and focal adhesion assembly, and then significantly inhibited MSCs migration. These results suggest that VEGF-C-induced MSC migration is mediated via VEGFR2 and VEGFR3, and follows the activation of the ERK and FAK signaling pathway. Thus, VEGF-C may be valuable in tissue regeneration and repair in MSC-based therapy.

A Retrospective Cohort Study of the Cumulative Survival Rate of Obturator Prostheses for Marsupialization.

PURPOSE: After marsupialization of benign tumors and jawbone cysts, insertion of an obturator prosthesis maintains the surgical opening and improves hygiene. To date, there have been no reports clarifying the relationship between the obturator design and treatment outcomes. The purpose of this study was to examine the survival rate of three types of obturator, and to investigate the factors that expedite the removal of the obturator. MATERIALS AND METHODS: The subject group comprised 100 patients who had an obturator inserted after marsupialization at Kagoshima University Hospital between May 31, 2012 and March 31, 2015; 73 patients with lesions in the mandible were eligible. Three types of mandibular obturator were designed and inserted, considering the teeth missing, the anteroposterior position of the lesion, and the buccolingual direction of marsupialization. The endpoint of this study was defined as the removal of the obturator. The analyzed predictor values for the endpoint were age, gender, remaining teeth, nature of primary disease, anteroposterior location of primary disease, buccolingual direction of marsupialization, type of obturator, and dates of insertion and removal. RESULTS: No significant differences were found in the cumulative survival rate among the three types of obturator. Early obturator removal was more frequent in patients with cysts, anterior lesions, and/or marsupialization from the occlusal direction CONCLUSIONS: Because obturator design had minimal effect on the ability of the appliance to maintain the surgical opening, it is preferable to use the least invasive design. Our findings also suggest that the follow-up examination should account for the type of primary disease, the anteroposterior location of the lesion, and the buccolingual direction of marsupialization.

Silodosin as second-line α-blocker monotherapy in patients with benign prostatic hyperplasia: A prospective observational study.

OBJECTIVE: To assess the efficacy of silodosin as second-line α-blocker monotherapy in patients with lower urinary tract symptoms as a result of benign prostatic hyperplasia. METHODS: Men who were given an α-blocker other than silodosin for ≥8 weeks, aged ≥50 years, had a total International Prostate Symptom Score ≥13 and quality of life index ≥4 were enrolled. After treatment with 8 mg/day silodosin for 8 weeks, symptoms and treatment satisfaction were assessed. If the patients still complained and hoped for readministration of the first-line α-blocker, the previous medication was administered again for 8 weeks in the case of persisting symptoms, and efficacy was again evaluated. RESULTS: A total of 73 patients were enrolled and analyzed at 8 weeks. Silodosin administration significantly improved the International Prostate Symptom Score and Overactive Bladder Symptom Score. The quality of life index was improved by at least 1 point in 49.3% patients, and its mean change was significantly greater in the group with previous naftopidil treatment than in those with tamsulosin. A total of 59 patients hoped to continue silodosin, and 13 requested administration of the first-line α-blocker. Previously taking naftopidil and having a shorter duration of prior α-blocker treatment at baseline were associated with silodosin continuation. Although prior α-blocker readministration in the 13 patients did not show significant efficacy, six preferred to continue the previous α-blocker. CONCLUSIONS: Silodosin represents an effective second-line α-blocker monotherapy, even in those who still have moderate lower urinary tract symptoms.

Impact of Type and Duration of Application of Commercially Available Oral Moisturizers on Their Antifungal Effects.

PURPOSE: To examine the impact of oral moisturizer type and application time on antifungal effects. MATERIALS AND METHODS: Seventeen oral moisturizers (7 liquids, 10 gels) and amphotericin B (AMPH-B) were tested. Antifungal effects were evaluated with newly opened moisturizer samples (0 hour) and with samples incubated for 8 hours to simulate contact during sleep. Candida albicans samples (108 cells/ml) were placed into cylindrical holes in 50% trypticase soy agar plates. Antifungal effects were evaluated based on growth-inhibitory zones after 24 hours. Equal quantities of moisturizers showing growth-inhibitory zones were mixed as additional samples. The effects of moisturizer type and application time on growth-inhibitory zones were evaluated with ANOVA. Growth-inhibitory zone sizes were compared with multiple comparisons. RESULTS: Growth-inhibitory zones were found with two liquids, one gel, moisturizer mixtures, and AMPH-B. Significant differences in antifungal effects were found among different moisturizer types and between the 0- and 8-hour groups. The growth-inhibitory zones of the 8-hour group were significantly smaller than those of the 0-hour group. In both the 0- and 8-hour groups, the growth-inhibitory zones of the liquid-gel mixtures were significantly larger than those of other moisturizer types, and were the same size as those of AMPH-B at two concentrations (1.25 and 2.5 µg/ml). Growth-inhibitory zones of individual moisturizers and liquid-liquid mixtures were the same size as those of lower AMPH-B concentrations (0.16, 0.31, and 0.63 µg/ml). CONCLUSION: Our findings suggest that mixing liquid and gel moisturizers improves their antifungal efficiency.

Vascular endothelial growth factor-C induces osteogenic differentiation of human mesenchymal stem cells through the ERK and RUNX2 pathway.

Vascular endothelial cell growth factor C (VEGF-C) is a member of the VEGF family and plays a role in a variety of biological activities including lymphangiogenesis, angiogenesis, and neurogenesis through VEGF receptor 2 (VEGFR2) and 3 (VEGFR3). However, it has not been elucidated whether VEGF-C promotes osteogenic differentiation. Herein, we investigated the effects of VEGF-C on osteogenic differentiation in human mesenchymal stem cells (MSCs) and evaluated the underlying molecular mechanisms. VEGF-C treatment significantly increased RUNX2 expression, and led to the promotion of osteogenic marker gene expression and mineralization of MSCs. VEGF-C treatment induced the phosphorylation of VEGFR2 and VEGFR3 in MSCs. Treatment with the VEGFR3-specific ligand VEGF-C156S also promoted MSC mineralization. Furthermore, co-treatment with VEGFR2 and VEGFR3 kinase inhibitors blocked VEGF-C-induced MSC mineralization. VEGF-C treatment activated ERK signaling in MSCs, and inhibition of ERK signaling effectively suppressed VEGF-C-induced RUNX2 expression and mineralization. These results indicate that VEGF-C-induced MSC osteogenesis is mediated through VEGFR2 and VEGFR3, and followed the activation of the ERK/RUNX2 signaling pathway.

Low-serum culture with novel medium promotes maxillary/mandibular bone marrow stromal cell proliferation and osteogenic differentiation ability.

OBJECTIVES: The purpose of this study was to evaluate the effect of low-serum STK2 medium on the isolation and osteogenic differentiation of human maxillary/mandibular bone marrow stromal cells (MBMSCs). MATERIALS AND METHODS: Human MBMSCs were obtained from patients undergoing dental implant treatment. These cells were cultured in serum-free medium or STK2 medium containing 1  % fetal bovine serum (low-serum) or α-MEM containing 10  % fetal bovine serum (control). Proliferation on the culture surface, cell surface antigen expression, and mRNA levels of neural crest and osteogenic markers were examined. Alkaline phosphatase assay and Alizarin red staining were used to assess osteogenic differentiation potential. Immunoblotting analysis was performed to detect ERK phosphorylation. RESULTS: Low-serum and control MBMSCs were positive for CD73, CD90, and CD105 and negative for CD14, CD34, CD45, CD271, and HLA-DR. CD140a was absent in low-serum cells but present in control cells. Low-serum MBMSCs proliferated more than control MBMSCs. After induction of osteogenic differentiation, alkaline phosphatase activity and osteocalcin mRNA levels were higher in low-serum MBMSCs than in control cells, and Alizarin red staining was stronger in low-serum MBMSCs than in control cells. Low-serum culture promoted ERK phosphorylation. CONCLUSIONS: MBMSCs precultured in low-serum medium exhibited a greater cumulative cell number and a higher osteogenic differentiation capacity than those cultured in control medium. CLINICAL RELEVANCE: These findings indicate that low-serum STK2 culture might be useful to promote MBMSC proliferation and osteogenic differentiation. This method requires less autologous blood collection for cell expansion than conventional methods, thus reducing the burden on patients.

Impact of Types of Moisturizer and Humidity on the Residual Weight and Viscosity of Liquid and Gel Oral Moisturizers.

PURPOSE: Oral moisturizers need to be selected based on their material properties. The purpose of this study was to investigate the effects of moisturizer type and humidity on the residual weight and viscosity of oral moisturizers. MATERIALS AND METHODS: The weight and viscosity of 17 oral moisturizers (7 liquid and 10 gel) at baseline and after 8 hours were measured using an incubator maintained at 37°C at either 85% or 40% relative humidity (RH). The rate of change in weight (RCW) and the rate of change in viscosity (RCV) were calculated. Data were analyzed with two-way analysis of variance (ANOVA) and Scheffe's test to evaluate the effect of the type of moisturizer (liquid or gel) and humidity (85% or 40% RH) on RCW and RCV. Pearson's correlation coefficient was used to evaluate the relationship between RCW and RCV. RESULTS: Two-way ANOVA results indicated that the type of moisturizer and RH had a significant effect on RCW and RCV (p < 0.05); however, the interaction between them was not significant. The results of multiple comparisons showed that gel moisturizers had a significantly lower RCW and higher RCV than liquid moisturizers (p < 0.05). The RCW and RCV at 40% RH were significantly higher than those at 85% RH (p < 0.05). There was no correlation between RCW and RCV in the liquid moisturizer group, but a significant negative correlation was found in the gel moisturizer group (pp = 0.01). CONCLUSION: Because viscosity of gel moisturizers increases as weight decreases, selecting gel moisturizers with a minimal change in weight and viscosity would be preferable in the case of a long-time application and severe dry mouth.

Vildagliptin stimulates endothelial cell network formation and ischemia-induced revascularization via an endothelial nitric-oxide synthase-dependent mechanism.

Dipeptidyl peptidase-4 inhibitors are known to lower glucose levels and are also beneficial in the management of cardiovascular disease. Here, we investigated whether a dipeptidyl peptidase-4 inhibitor, vildagliptin, modulates endothelial cell network formation and revascularization processes in vitro and in vivo. Treatment with vildagliptin enhanced blood flow recovery and capillary density in the ischemic limbs of wild-type mice, with accompanying increases in phosphorylation of Akt and endothelial nitric-oxide synthase (eNOS). In contrast to wild-type mice, treatment with vildagliptin did not improve blood flow in ischemic muscles of eNOS-deficient mice. Treatment with vildagliptin increased the levels of glucagon-like peptide-1 (GLP-1) and adiponectin, which have protective effects on the vasculature. Both vildagliptin and GLP-1 increased the differentiation of cultured human umbilical vein endothelial cells (HUVECs) into vascular-like structures, although vildagliptin was less effective than GLP-1. GLP-1 and vildagliptin also stimulated the phosphorylation of Akt and eNOS in HUVECs. Pretreatment with a PI3 kinase or NOS inhibitor blocked the stimulatory effects of both vildagliptin and GLP-1 on HUVEC differentiation. Furthermore, treatment with vildagliptin only partially increased the limb flow of ischemic muscle in adiponectin-deficient mice in vivo. GLP-1, but not vildagliptin, significantly increased adiponectin expression in differentiated 3T3-L1 adipocytes in vitro. These data indicate that vildagliptin promotes endothelial cell function via eNOS signaling, an effect that may be mediated by both GLP-1-dependent and GLP-1-independent mechanisms. The beneficial activity of GLP-1 for revascularization may also be partially mediated by its ability to increase adiponectin production.

ß-Amyrin induces angiogenesis in vascular endothelial cells through the Akt/endothelial nitric oxide synthase signaling pathway.

ß-Amyrin is a pentacyclic triterpene found in various plants and has a variety of biological and pharmacological activities. However, the angiogenic effects of ß-amyrin in vascular endothelial cells have not been elucidated. Herein, we investigated the effects of ß-amyrin on angiogenesis and evaluated the underlying molecular mechanisms. ß-Amyrin treatment had no cytotoxic effect on cultured human umbilical vein endothelial cells (HUVECs). It promoted the formation of tube-like structures and enhanced HUVEC migration and the phosphorylation of Akt and endothelial nitric oxide synthase (eNOS) in HUVECs. Pre-treatment with a PI3 kinase or NOS inhibitor blocked ß-amyrin-induced phosphorylation of Akt and eNOS. ß-Amyrin treatment significantly induced nitric oxide (NO) production in HUVECs. Furthermore, pre-treatment with a PI3 kinase or NOS inhibitor significantly inhibited ß-amyrin-induced tube-like structures formation of vascular endothelial cells and HUVEC migration. These data indicate that ß-amyrin-induced angiogenesis in vascular endothelial cells may be mediated by Akt-eNOS signaling-dependent mechanisms. These findings suggest that ß-amyrin could be a novel therapeutic agent for ischemic vascular diseases.

Fabrication of a movable obturator following maxillary reconstruction with slit-shaped fenestration.

Extensive maxillary resection has generally been reconstructed with free skin flaps. Because drooping of the transferred flap causes instability of the obturator prosthesis, maxillary reconstruction often incorporates a slit-shaped oronasal fenestration. Although obturator prostheses for edentulous patients are stabilized with the help of oronasal slits, those for dentate patients are unstable because of flap mobility, resulting in a harmful lateral force exerted on the abutment teeth, causing dislodging of the denture. This report evaluates the benefits of a movable obturator prosthesis for a 60-year-old dentulous patient with maxillary sinus carcinoma. The patient underwent left-sided total maxillectomy, and the defect was reconstructed with a slit-shaped fenestration using a rectus abdominis flap. A conventional obturator prosthesis was inserted; however, drooping of the flap caused instability of the obturator, resulting in nasal regurgitation and fracture of the clasp. To solve this problem, we designed an obturator prosthesis with a movable connection consisting of a ball attachment (patrix) in the metal base and a socket (matrix) in the obturator, which acted as a stress breaker against the harmful force exerted by the flap. Application of this movable obturator prosthesis was a useful solution for a compromising situation created by the surgical procedure. No clinical disorders were observed at the 3-year follow-up.