Oleanane-type saponins from Lysimachia laxa Baudo and their anti-bacterial activities.

Seven new oleanane-type triterpene saponins, lysimaponins A-G, were isolated from aerial parts of Lysimachia laxa Baudo. Their chemical structures have been elucidated by analysis of spectroscopic and chemical methods. All compounds were evaluated for their anti-bacterial effects against Microcystis aeruginosa, Vibrio parahaemolyticus, V. harveyi, V. vulinificus, V. cholerae, and V. alginolyticus. All compounds showed potent anti-bacterial activities against the cyanobacteria M. aeruginosa with IC50 values ranging from 14.4 ± 1.2 to 35.3 ± 2.2 µg/mL. Compounds 1, 2, 4-7 inhibited V. parahaemolyticus with MIC values ranging from 64 to 256 µg/mL. The results suggested that saponins from L. laxa could be potential anti-cyanobacteria agents.

Caffeine-induced protein kinase A activation restores cognitive deficits induced by sleep deprivation by regulating O-GlcNAc cycling in adult zebrafish.

Sleep deprivation (SD) is widely acknowledged as a significant risk factor for cognitive impairment. In this study, intraperitoneal caffeine administration significantly ameliorated the learning and memory (L/M) deficits induced by SD and reduced aggressive behaviors in adult zebrafish. SD led to a reduction in protein kinase A (PKA) phosphorylation, phosphorylated-cAMP response element-binding protein (p-CREB), and c-Fos expression in zebrafish brain. Notably, these alterations were effectively reversed by caffeine. In addition, caffeine mitigated neuroinflammation induced by SD, as evident from suppression of the SD-mediated increase in glial fibrillary acidic protein (GFAP) and nuclear factor-κB (NF-κB) activation. Caffeine restored normal O-GlcNAcylation and O-GlcNAc transferase (OGT) levels while reversing the increased expression of O-GlcNAcase (OGA) in zebrafish brain after SD. Intriguingly, rolipram, a selective phosphodiesterase 4 (PDE4) inhibitor, effectively mitigated cognitive deficits, restored p-CREB and c-Fos levels, and attenuated the increase in GFAP in brain induced by SD. In addition, rolipram reversed the decrease in O-GlcNAcylation and OGT expression as well as elevation of OGA expression following SD. Treatment with H89, a PKA inhibitor, significantly impaired the L/M functions of zebrafish compared with the control group, inducing a decrease in O-GlcNAcylation and OGT expression and, conversely, an increase in OGA expression. The H89-induced changes in O-GlcNAc cycling and L/M dysfunction were effectively reversed by glucosamine treatment. H89 suppressed, whereas caffeine and rolipram promoted O-GlcNAc cycling in Neuro2a cells. Our collective findings underscore the interplay between PKA signaling and O-GlcNAc cycling in the regulation of cognitive function in the brain, offering potential therapeutic targets for cognitive deficits associated with SD.NEW & NOTEWORTHY Our observation highlights the intricate interplay between cAMP/PKA signaling and O-GlcNAc cycling, unveiling a novel mechanism that potentially governs the regulation of learning and memory functions. The dynamic interplay between these two pathways provides a novel and nuanced perspective on the molecular foundation of learning and memory regulation. These insights open avenues for the development of targeted interventions to treat conditions that impact cognitive function, including SD.

Evaluating smile aesthetic satisfaction and related smile characteristics in dental students.

Aim: This study aimed to assess the association between self-rated smile satisfaction and the smile dimensions among dental students. Method: An analytical cross-sectional study was conducted on 216 Vietnamese dental students. A standardized photograph was taken of each student with their frontal social smiles to assess aesthetic dimensions. A single-session self-administered questionnaire containing five questions about smile aesthetic satisfaction related to various aspects was administered to all students. Differences in smile characteristics and satisfaction scores between the two genders were evaluated. The impact of smile characteristics on satisfaction scores was assessed using multiple linear regression models. Results: Most dental students had a high smile line, parallel smile arcs, an upward upper lip curvature, a non-touching labiodental relationship, a dental midline that coincided with the midline of the face, and eight teeth displayed during smile. Most participants were satisfied with their smiles, and the self-rated satisfaction score was 67 out of 100. Self-perceived overall smile satisfaction was associated with the "smile arc", the "upper lip curvature", the "number of teeth displayed during smile", and the "dental midline". Female students had a statistically significant correlation between self-perception and smile characteristics, such as upper lip curvature, dental midline shift, and smile line. Conclusions: The smile arc, upper lip curvature, and dental midline shift affected self-perceived satisfaction among dental students. Female students showed an association between the smile parameters and self-perceived satisfaction.

REM Sleep Deprivation Impairs Learning and Memory by Decreasing Brain O-GlcNAc Cycling in Mouse.

Rapid eye movement (REM) sleep is implicated learning and memory (L/M) functions and hippocampal long-term potentiation (LTP). Here, we demonstrate that REM sleep deprivation (REMSD)-induced impairment of contextual fear memory in mouse is linked to a reduction in hexosamine biosynthetic pathway (HBP)/O-GlcNAc flux in mouse brain. In mice exposed to REMSD, O-GlcNAcylation, and O-GlcNAc transferase (OGT) were downregulated while O-GlcNAcase was upregulated compared to control mouse brain. Foot shock fear conditioning (FC) induced activation of protein kinase A (PKA) and cAMP response element binding protein (CREB), which were significantly inhibited in brains of the REMSD group. Intriguingly, REMSD-induced defects in L/M functions and FC-induced PKA/CREB activation were restored upon increasing O-GlcNAc cycling with glucosamine (GlcN) or Thiamet G. Furthermore, Thiamet G restored the REMSD-induced decrease in dendritic spine density. Suppression of O-GlcNAcylation by the glutamine fructose-6-phosphate amidotransferase (GFAT) inhibitor, 6-diazo-5-oxo-L-norleucine (DON), or OGT inhibitor, OSMI-1, impaired memory function, and inhibited FC-induced PKA/CREB activation. DON additionally reduced the amplitude of baseline field excitatory postsynaptic potential (fEPSP) and magnitude of long-term potentiation (LTP) in normal mouse hippocampal slices. To our knowledge, this is the first study to provide comprehensive evidence of dynamic O-GlcNAcylation changes during the L/M process in mice and defects in this pathway in the brain of REM sleep-deprived mice. Our collective results highlight HBP/O-GlcNAc cycling as a novel molecular link between sleep and cognitive function.

Effect of Two Nonsurgical Periodontal Treatment Modalities in Type 2 Diabetes Mellitus Patients with Chronic Periodontitis: A Randomized Clinical Trial.

AIM AND OBJECTIVE: The current study aimed to investigate the effect of two nonsurgical periodontal treatment modalities on clinical periodontal parameters and glycemic control. MATERIALS AND METHODS: A randomized clinical trial was conducted with a sample of 64 type 2 diabetes mellitus (T2DM) patients with chronic periodontitis. Subjects were randomly assigned into two groups. Group I received oral hygiene instructions (OHI) at baseline and each recall visit. Group II received one-stage full-mouth scaling and root planning (SRP) combining OHI. At baseline, third month, and sixth month the plaque index (PlI), gingival index (GI), probing pocket depth (PPD), clinical attachment loss (CAL), and glycated hemoglobin (HbA1c) were recorded and analyzed. RESULTS: After treatment, two groups showed significant differences for all parameters at both assessed times (p <0.05). The OHI alone only demonstrated a slight reduction in GI in third month, with no significant changes for PlI and PPD indexes. However, Group I recorded the increased HbA1c and CAL values at 6-month follow-up (p <0.05). The combination of OHI and SRP exhibited a significant improvement in all periodontal values (p <0.05). Also, the HbA1C levels of Group II showed a significant reduction after treatment and were lower than those of Group I. CONCLUSIONS: Oral hygiene instructions only resulted in a better gingival condition of diabetic patients in the initial time. The nonsurgical periodontal therapy by combining SRP and OHI significantly improved both periodontal health and glycemic control. CLINICAL SIGNIFICANCE: Diabetic patients should be supplied with an effective OHI modality and a professional dental debridement.

Cytotoxic components from the leaves of Erythrophleum fordii induce human acute leukemia cell apoptosis through caspase 3 activation and PARP cleavage.

Cassaine diterpenoids as erythrofordins A-C (1-3), pseudo-erythrosuamin (4), and erythrofordin U (5) isolated from the leaves of Vietnamese Erythrophleum fordii Oliver were tested cytotoxic activity against human leukemia cancer cells. The results showed that these metabolites exhibited dose-dependent cytotoxicity against human leukemia HL-60 and KG cells with IC50 values ranging from 15.2 ± 1.5 to 42.2 ± 3.6 µM. Treatment with erythrofordin B led to the apoptosis of HL-60 and KG cells due to the activation of caspase 3, caspase 9, and poly (ADP-ribose) polymerase (PARP). Erythrofordin B significantly increased Bak protein expression, but downregulated the anti-apoptotic protein Bcl-2, in HL-60 cells. In silico results demonstrated that erythrofordin B can bind to both the procaspase-3 allosteric site and the PARP-1 active site, with binding energies of -7.36 and -10.76 kcal/mol, respectively. These results indicated that the leaves of Vietnamese E. fordii, which contain cassaine diterpenoids, can induce the apoptosis of human leukemia cancer cells.

In vitro wear behavior between enamel cusp and three aesthetic restorative materials: Zirconia, porcelain, and composite resin.

PURPOSE: The aim of this study was to identify the effects of three aesthetic restorative materials on the wear between tooth and restoration by a pin-on-disk manner. MATERIALS AND METHODS: Six aesthetic restorative materials were used to prepare disk specimens for wear test, which were Lava Zirconia as zirconia group, Vintage MP and Cerabien ZR as veneering porcelain group, Gradia Direct microhybrid composite containing prepolymerized fillers, Filtek Z250 microhybrid composite containing zirconia glass and colloidal silica particles, and Filtek Z350 nanocomposite as composite resin group. Vertical loss of the worn cusp, change of the surface roughness of the restoration materials, and the surface topography were investigated after wear test under 9.8-N contact load. RESULTS: The porcelain groups (Vintage MP and Cerabien ZR) caused the largest vertical loss of teeth when compared with those of the composite resin and zirconia groups, and Filtek Z250 microhybrid composite results in the second-largest vertical loss of teeth. The surface of Filtek Z350 nanocomposite was deeply worn out, but visible wear on the surface of the zirconia and Gradia Direct microhybrid composite was not observed. When the zirconia surface was roughened by sand-blasting, vertical loss of teeth considerably increased when compared with that in the case of fine polished zirconia. CONCLUSION: It was identified that microhybrid composite resin containing a prepolymerized filler and zirconia with reduced surface roughness by polishing were the most desirable restorative materials among the tested materials to prevent the two-body wear between aesthetic restorative material and tooth.

In vivo bone regeneration by differently designed titanium membrane with or without surface treatment: a study in rat calvarial defects.

The current objective was to evaluate six groups of titanium membranes in a rat calvarial defect model, regarding the surface treatment with or without calcium-phosphate coating and surface topography with no, small, or large holes. Critical size defects (Ф = 8 mm, n = 42) were surgically created in rat calvaria, and then were treated by one of the six groups. Biopsies were obtained at 4 weeks (n = 5 per group) for micro-computed tomography and histomorphometric analyses. Fluorochrome bone markers were injected in two rats each group at 1 (Alizarin red), 3 (Calcein green) and 5 weeks (Oxytetracyclin yellow), followed by histological examination at 7 weeks to assess bone regeneration dynamic. At 4 weeks, the highest bone volume was observed in no-hole groups independent of surface treatment (p < 0.05). Treated groups with no-hole and large-hole membranes showed increased bone mineral density than with respective non-treated groups (p < 0.05). Histology exhibited an intimate bone formation onto the treated membranes, whereas non-treated ones demonstrated interposition of connective tissue, which was confirmed through bone contact percentages. The results suggest that occlusive membranes showed more bone formation than other perforated ones, and calcium-phosphate treatment induces intimate bone formation toward the membrane.

Effect of strontium doping on the biocompatibility of calcium phosphate-coated titanium substrates.

BACKGROUND:: Titanium biomedical devices coated with strontium-doped calcium phosphate ceramics can support desirable bone regeneration through anabolic and anti-catabolic effects of strontium and the compositions close to that of natural mineral tissue. METHODS:: Strontium was doped into the calcium phosphate coating using the cyclic pre-calcification method on the anodized titanium plate. The effects of the different concentration of strontium in treatment solution and cycle numbers of the pre-calcification treatment on the biocompatibility were investigated in terms of the changes in morphology and chemical composition of coating, ion release pattern and cytocompatibility in vitro. RESULTS:: At a high substitution ratio of strontium in the calcium phosphate coating, the size of precipitated particles was decreased and the solubility of the coating was increased. ASH55 group, which was coated by pre-calcification treatment of 20 cycles in coating solution with Sr:Ca molar ratio of 5:5, exhibited superior cellular attachment at 1 day and proliferation after 7 days of culturing in comparison with the non-doped surface and other doped surfaces. CONCLUSION:: Sufficient strontium doping concentrations in calcium phosphate coating can enhance cell adhesion and proliferation on the titanium biomedical devices for bone regeneration.

Osteogenesis-Related Gene Expression and Guided Bone Regeneration of a Strontium-Doped Calcium-Phosphate-Coated Titanium Mesh.

Guided bone regeneration using a perforated titanium membrane is actively used in oral and orthopedic surgeries to provide space for the subsequent filling of a new bone in the case of bone defects and to achieve proper bone augmentation and reconstruction. The surface modification of a titanium membrane using a strontium-substituted calcium phosphate coating has become a popular trend to provide better bioactivity and biocompatibility on the membrane for improving the bone regeneration because strontium can stimulate not only the differentiation of osteoblasts but also inhibit the differentiation of osteoclasts. The strontium-doped calcium phosphate coating on the titanium mesh was formed by the cyclic precalcification method, and its effects on bone regeneration were evaluated by in vitro analysis of osteogenesis-related gene expression and in vivo evaluation of osteogenesis of the titanium mesh using the rat calvarial defect model in this study. It was identified that the strontium-doped calcium phosphate-treated mesh showed a higher expression of all genes related to osteogenesis in the osteoblast cells and resulted in new bone formation with better osseointegration with the mesh in the rat calvarial defect, in comparison with the results of untreated and calcium phosphate-treated meshes.

In vitro wear behavior between enamel cusp and three aesthetic restorative materials: Zirconia, porcelain, and composite resin

PURPOSE: The aim of this study was to identify the effects of three aesthetic restorative materials on the wear between tooth and restoration by a pin-on-disk manner. MATERIALS AND METHODS: Six aesthetic restorative materials were used to prepare disk specimens for wear test, which were Lava Zirconia as zirconia group, Vintage MP and Cerabien ZR as veneering porcelain group, Gradia Direct microhybrid composite containing prepolymerized fillers, Filtek Z250 microhybrid composite containing zirconia glass and colloidal silica particles, and Filtek Z350 nanocomposite as composite resin group. Vertical loss of the worn cusp, change of the surface roughness of the restoration materials, and the surface topography were investigated after wear test under 9.8-N contact load. RESULTS: The porcelain groups (Vintage MP and Cerabien ZR) caused the largest vertical loss of teeth when compared with those of the composite resin and zirconia groups, and Filtek Z250 microhybrid composite results in the second-largest vertical loss of teeth. The surface of Filtek Z350 nanocomposite was deeply worn out, but visible wear on the surface of the zirconia and Gradia Direct microhybrid composite was not observed. When the zirconia surface was roughened by sand-blasting, vertical loss of teeth considerably increased when compared with that in the case of fine polished zirconia. CONCLUSION: It was identified that microhybrid composite resin containing a prepolymerized filler and zirconia with reduced surface roughness by polishing were the most desirable restorative materials among the tested materials to prevent the two-body wear between aesthetic restorative material and tooth.

Effects of Titanium Mesh Surfaces-Coated with Hydroxyapatite/ß-Tricalcium Phosphate Nanotubes on Acetabular Bone Defects in Rabbits.

The management of severe acetabular bone defects in revision reconstructive orthopedic surgery is challenging. In this study, cyclic precalcification (CP) treatment was used on both nanotube-surface Ti-mesh and a bone graft substitute for the acetabular defect model, and its effects were assessed in vitro and in vivo. Nanotube-Ti mesh coated with hydroxyapatite/ß-tricalcium phosphate (HA/ß-TCP) was manufactured by an anodizing and a sintering method, respectively. An 8 mm diameter defect was created on each acetabulum of eight rabbits, then treated by grafting materials and covered by Ti meshes. At four and eight weeks, postoperatively, biopsies were performed for histomorphometric analyses. The newly-formed bone layers under cyclic precalcified anodized Ti (CP-AT) meshes were superior with regard to the mineralized area at both four and eight weeks, as compared with that under untreated Ti meshes. Active bone regeneration at 2-4 weeks was stronger than at 6-8 weeks, particularly with treated biphasic ceramic (p < 0.05). CP improved the bioactivity of Ti meshes and biphasic grafting materials. Moreover, the precalcified nanotubular Ti meshes could enhance early contact bone formation on the mesh and, therefore, may reduce the collapse of Ti meshes into the defect, increasing the sufficiency of acetabular reconstruction. Finally, cyclic precalcification did not affect bone regeneration by biphasic grafting materials in vivo.

The effect of APH treatment on surface bonding and osseointegration of Ti-6Al-7Nb implants: an in vitro and in vivo study.

This study investigated the effects of anodization-cyclic precalcification-heat (APH) treatment on the bonding ability of Ca-P coating to the parent metal and osseointegration of Ti-6Al-7Nb implants. Eighteen Ti-6Al-7Nb discs, 9 untreated and 9 APH-treated, were cultured with osteoblast cells in vitro, and the cellular differentiation ability was assayed at 1, 2, and 3 weeks. For in vivo testing, 28 Ti-6Al-7Nb implants (14 implants of each group) were inserted to rat tibias, and after each 4 and 6 weeks of implantation, bone bonding, and osseointegration were evaluated through removal torque and histological analysis. Osteoblast-culturing showed twice as much of the alkaline phosphatase activity on the treated surface at 3 weeks than on the untreated surface (p < 0.05). The treated implants exhibited higher removal torque values than the untreated ones (15.5 vs. 1.8 Ncm at 4 weeks and 19.7 vs. 2.6 Ncm at 6 weeks, p < 0.05). Moreover, the excellent bonding quality of coats was confirmed by the existence of cohesive fractures on the surface of removed APH implants (field emission scanning electron microscopy and histological observation). Within the limits of this study, it can be concluded that the APH treatment significantly enhanced osseointegration of the Ti-6Al-7Nb implant, with the stable bonding between the coating and the implant surface.

Phylogeny of the Cyrtodactylus irregularis species complex (Squamata: Gekkonidae) from Vietnam with the description of two new species.

The number of described species of bent-toed geckos of the Cyrtodactylus irregularis species complex in Vietnam has increased from one to eight in the last six years. We combined morphological and molecular analyses to explore phylogenetic relationships among all described species in the group. The phylogeny required the description of two new species, Cyrtodactylus phuocbinhensis sp. nov. and Cyrtodactylus taynguyenensis sp. nov. Further, the tree resolved two additional undescribed clades that may also be new species. The species C. bugiamapensis and C. ziegleri were found to require redefinition. Cyrtodactylus phuocbinhensis sp. nov. is characterized by a series of enlarged femoral scales separated from preanal scales while Cyrtodactylus taynguyenensis sp. nov. does not possess enlarged femoral scales. Both new species are distinguished from other congeners by a combination of the following characters: small subcaudal scales, not transversely enlarged; presence (C. phuocbinhensis sp. nov.) or absence (C. taynguyenensis sp. nov.) of enlarged femoral scales; number of preanal pores; and dorsal pattern. Genetic distances between described species and new species were 16.5% and 2.0% in COI and RPL35, respectively, for C. phuocbinhensis sp. nov., and these distances were 18.8% and 2.2% for C. taynguyenensis sp. nov., respectively.