Hispidulin Inhibits the Vascular Inflammation Triggered by Porphyromonas gingivalis Lipopolysaccharide.

Hispidulin is a natural bioactive flavonoid that has been studied for its potential therapeutic properties, including its anti-inflammatory, antioxidant, and neuroprotective effects. The aim of this study was to explore whether hispidulin could inhibit the endothelial inflammation triggered by Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS). The adhesion of monocytes to the vascular endothelium was evaluated through in vitro and ex vivo monocyte adhesion assays. We analyzed the migration of monocytes across the endothelial layer using a transmigration assay. The results showed that treatment with hispidulin decreased the P. gingivalis LPS-induced adhesion of monocytes to endothelial cells and their migration by suppressing the P. gingivalis LPS-triggered expression of intercellular adhesion molecule-1 (ICAM-1) through downregulating nuclear factor-қB (NF-қB). In addition, hispidulin inhibited P. gingivalis LPS-induced mitogen-activated protein kinases (MAPKs) and AKT in endothelial cells. Altogether, the results indicate that hispidulin suppresses the vascular inflammation induced by P. gingivalis LPS. Mechanistically, it prevents the adhesion of monocytes to the vascular endothelium and migration and inhibits NF-қB, MAPKs, and AKT signaling in endothelial cells.

Naringenin stimulates osteogenic/odontogenic differentiation and migration of human dental pulp stem cells.

Background/purpose: Naringenin, a naturally occurring flavanone in citrus fruits, regulates bone formation by bone marrow-derived mesenchymal stem cells. The purpose of this study was to characterize the effects of naringenin on some biological behaviors of human dental pulp stem cells (HDPSCs). Materials and methods: HDPSCs were cultured in osteogenic differentiation medium and osteo/odontogenic differentiation and mineralization were analyzed by alkaline phosphatase (ALP) staining and Alizarin Red S (ARS) staining. The migration of HDPSCs was evaluated by transwell chemotactic migration assays and scratch wound healing migration assay. Using tooth slice/scaffold model, we assessed the in vivo odontogenic differentiation potential of HDPSCs. Results: We have demonstrated that naringenin increases the osteogenic/odontogenic differentiation of HDPSCs through regulation of osteogenic-related proteins and the migratory ability of HDPSCs through stromal cell derived factor-1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4) axis. Moreover, naringenin promotes the expression of dentin matrix acidic phosphoprotein-1 (DMP-1) and dentin sialophosphoprotein (DSPP) in HDPSCs seeded on tooth slice/scaffolds that are subcutaneously implanted into immunodeficient mice. Conclusion: Our present study suggests that naringenin promotes migration and osteogenic/odontogenic differentiation of HDPSCs and may serve as a promising candidate in dental tissue engineering and bone regeneration.

Inhibition of the Semaphorin 4D-Plexin-B1 axis prevents calcification in vascular smooth muscle cells.

Vascular calcification is common in cardiovascular diseases including atherosclerosis, and is associated with an increased risk of pathological events and mortality. Some semaphorin family members play an important role in atherosclerosis. In the present study, we show that Semaphorin 4D/Sema4D and its Plexin-B1 receptor were significantly upregulated in calcified aorta of a rat chronic kidney disease model. Significantly higher Sema4D and Plexin-B1 expression was also observed during inorganic phosphate-induced calcification of vascular smooth muscle cells. Knockdown of Sema4D or Plexin-B1 genes attenuated both the phosphate-induced osteogenic phenotype of vascular smooth muscle cells, through regulation of SMAD1/5 signaling, as well as apoptosis of vascular smooth muscle cells, through modulation of the Gas6/Axl/Akt survival pathway. Taken together, our results offer new insights on the role of Sema4D and Plexin-B1 as potential therapeutic targets against vascular calcification. [BMB Reports 2023; 56(3): 160-165].

Effects of Integrative Autism Therapy on Multiple Physical, Sensory, Cognitive, and Social Integration Domains in Children and Adolescents with Autism Spectrum Disorder: A 4-Week Follow-Up Study.

This study aimed to compare the effects of conventional autism therapy (CAT) and integrative autism therapy (IAT) in children and adolescents with autism spectrum disorder (ASD). A convenience sample of 24 children with ASD was recruited and underwent either CAT or IAT for 60 min/day, twice a week, for 20 sessions over 10 weeks. Outcome measures included the following: (1) physical domain (pediatric balance scale, PBS), (2) sensory domain (short sensory profile), (3) cognitive domains (functional independence measure, FIM; and childhood autism rating scale), and (4) social integration domain (Canadian occupational performance measure, COPM; short falls efficacy scale; and pediatrics quality of life questionnaire). Two-way repeated analysis of variance (ANOVA) was used to determine the intervention-related changes in the four domains across the pre-test, post-test, and follow-up test at p < 0.05. ANOVA showed significant interaction effects on the PBS, FIM, and COPM (p < 0.05) variables. Moreover, time main effects (p < 0.05) were observed in all four domain variables, but no group main effect was noted. This study provides promising evidence that IAT is more effective than CAT for managing children and adolescents with ASD.

Comparative effects of community-based family-child-centered care and conventional pediatric rehabilitation for cerebral palsy.

BACKGROUND: While the transdisciplinary-based rehabilitation provided ample evidence on improving impairment (body structure and functions) levels, the therapeutic effects on the international classification of functioning, disability, and health (ICF) domains are unknown in cerebral palsy (CP). OBJECTIVE: To compare the effects of the community-based family-child-centered care (CFC) and conventional pediatric rehabilitation (CPR) on the physical, cognitive, sensory, and social integration domains in children and adolescents with CP. METHODS: Twenty-six participants with CP (mean age = 9.37±5.24, 14 females) were assigned into either CPR or CFC groups. Clinical outcomes included gross motor function measure (GMFM-66), Pediatric Balance Scale (PBS), fine motor area of Bruininks-Oseretsky Test of Motor Proficiency-2 (BOT-2), Functional Independence Measure (FIM) cognition area, Short Sensory Profile (sSP), COPM, Pediatrics Quality of Life (PedsQL) questionnaire, Short Falls Efficacy Scale (sFES), and Dynamic Postural Instability (DPI). An analysis of variance (ANOVA) and an analysis of covariance (ANCOVA) was conducted at P < 0.05. RESULTS: ANOVA revealed the superior effects of CFC in GMFM-66, PBS, BOT-2, FIM, and PedsQL compared to CPR (P < 0.05). ANCOVA showed the superior effects of CFC in Z-axis of DPI than CPR (P < 0.05). CONCLUSIONS: Our results provide novel, promising clinical evidence that CFC was more effective than CPR at improving impairment, activity, as well as participation levels in participants with CP.

Neuromedin B modulates phosphate-induced vascular calcification.

Vascular calcification is the heterotopic accumulation of calcium phosphate salts in the vascular tissue and is highly correlated with increased cardiovascular morbidity and mortality. In this study, we found that the expression of neuromedin B (NMB) and NMB receptor is upregulated in phosphate-induced calcification of vascular smooth muscle cells (VSMCs). Silencing of NMB or treatment with NMB receptor antagonist, PD168368, inhibited the phosphate-induced osteogenic differentiation of VSMCs by inhibiting Wnt/ß-catenin signaling and VSMC apoptosis. PD168368 also attenuated the arterial calcification in cultured aortic rings and in a rat model of chronic kidney disease. The results of this study suggest that NMB-NMB receptor axis may have potential therapeutic value in the diagnosis and treatment of vascular calcification. [BMB Reports 2021; 54(11): 569-574].

Comparative parenting stress measures between segmental and community-based rehabilitation services in parents of children and adolescents with intellectual and developmental disabilities (IDD): A cross-sectional survey.

BACKGROUND: There is a dearth of information on the effects of different types (Segmental rehabilitation service (SRS) vs Community-based rehabilitation service (CRS)) on the parenting stress and family quality of life in parents of children who have individuals with intellectual and developmental disabilities (IDD). OBJECTIVE: This paper is to compare the effects of SRS and CRS on parenting stress and family quality of life in parents of individuals with IDD. METHODS: A cross-sectional design was used to examine parenting stress and family quality life in cohorts of 120 fathers and mothers of children with IDD who had received either SRS or CRS participated in the survey. The outcome measures included the modified Parenting Stress Index (PSI) and the modified Beach Center Family Quality of Life Scale (mBCFQLS). The Mann-Whitney U test was performed at P< 0.05. RESULTS: A significant difference was observed in social stress in PSI between the SRS and CRS groups (P= 0.03). The child rearing, emotional well-being, and physical and material well-being variables in mBCFQLS were different between the SRS and CRS groups (P< 0.05), indicating superior benefits from CRS than SRS. CONCLUSIONS: These findings provide important information and about parenting stress and family quality of life in children with IDD, for developing effective rehabilitation programs and services for these parents.

Prevalence of Sarcopenia in Community-Dwelling Older Adults According to Simplified Algorithms for Sarcopenia Consensus Based on Asian Working Group for Sarcopenia.

PURPOSE: This study sought to identify the prevalence of sarcopenia in community-dwelling Korean older adults and validate two simplified diagnostic algorithms based on the Asian Working Group for Sarcopenia (AWGS) algorithm for identifying sarcopenia. PATIENTS AND METHODS: Patients (n = 338) aged ≥65 years participated in this cross-sectional study. Muscle strength was measured by hand grip strength, physical performance by gait speed, and muscle mass by the skeletal muscle mass index (SMI). Sarcopenia was assessed using the AWGS-recommended algorithm and two simplified algorithms (A and B). Algorithms A and B were validated with respect to the AWGS-recommended algorithm using the chi-square test, and the sensitivity and specificity were obtained. RESULTS: Sarcopenia prevalence, determined using the AWGS-recommended algorithm, was 40.3% and 41.3% in men and women, respectively. The overall prevalence of sarcopenia was 41.0% by the AWGS-recommended algorithm, 37.6% by algorithm A, and 37.6% by algorithm B; 111 participants were diagnosed with sarcopenia using all three methods (p = 0.157). CONCLUSION: We established sarcopenia prevalence among rural community-dwelling adults in Korea and confirmed that the simplified algorithms were suitable for the identification of sarcopenia in rural community-dwelling older adults in Korea. Further studies are needed to assess whether these simplified algorithms are applicable to older Asian adults with functional and/or cognitive impairment and nursing home residents.

Infection of Porphyromonas gingivalis Increases Phosphate-Induced Calcification of Vascular Smooth Muscle Cells.

Accumulating evidence suggests a link between periodontal disease and cardiovascular diseases. Vascular calcification is the pathological precipitation of phosphate and calcium in the vasculature and is closely associated with increased cardiovascular risk and mortality. In this study, we have demonstrated that the infection with Porphyromonas gingivalis (P. gingivalis), one of the major periodontal pathogens, increases inorganic phosphate-induced vascular calcification through the phenotype transition, apoptosis, and matrix vesicle release of vascular smooth muscle cells. Moreover, P. gingivalis infection accelerated the phosphate-induced calcium deposition in cultured rat aorta ex vivo. Taken together, our findings indicate that P. gingivalis contributes to the periodontal infection-related vascular diseases associated with vascular calcification.

Inhibition of Gastrin-Releasing Peptide Attenuates Phosphate-Induced Vascular Calcification.

Vascular calcification is the pathological deposition of calcium/phosphate in the vascular system and is closely associated with cardiovascular morbidity and mortality. Here, we investigated the role of gastrin-releasing peptide (GRP) in phosphate-induced vascular calcification and its potential regulatory mechanism. We found that the silencing of GRP gene and treatment with the GRP receptor antagonist, RC-3095, attenuated the inorganic phosphate-induced calcification of vascular smooth muscle cells (VSMCs). This attenuation was caused by inhibiting phenotype change, apoptosis and matrix vesicle release in VSMCs. Moreover, the treatment with RC-3095 effectively ameliorated phosphate-induced calcium deposition in rat aortas ex vivo and aortas of chronic kidney disease in mice in vivo. Therefore, the regulation of the GRP-GRP receptor axis may be a potential strategy for treatment of diseases associated with excessive vascular calcification.

Pentraxin-3 Modulates Osteogenic/Odontogenic Differentiation and Migration of Human Dental Pulp Stem Cells.

Pentraxin-3 (PTX3) is recognized as a modulator of inflammation and a mediator of tissue repair. In this study, we characterized the role of PTX3 on some biological functions of human dental pulp stem cells (HDPSCs). The expression level of PTX3 significantly increased during osteogenic/odontogenic differentiation of HDPSCs, whereas the knockdown of PTX3 decreased this differentiation. Silencing of PTX3 in HDPSCs inhibited their migration and C-X-C chemokine receptor type 4 (CXCR4) expression. Our present study indicates that PTX3 is involved in osteogenic/odontogenic differentiation and migration of HDPSCs, and may contribute to the therapeutic potential of HDPSCs for regeneration and repair.

MESIA: Magnetic force-assisted electrochemical sandwich immunoassays for quantification of prostate-specific antigen in human serum.

We propose a new immunoassay technique, called magnetic-force assisted electrochemical sandwich immunoassay (MESIA), where serum biomarkers can be determined by magnetic actuation and electrochemical detection of gold-coated iron oxide nanoparticles as probes for immunocomplex formation. In MESIA, neither washing buffer nor fluidic parts are necessary, because the formation of immunocomplexes and the removal of unbound probes are controlled by magnetic forces. Electrochemical pretreatment and measurement of the gold-coated magnetic probes allows highly sensitive, precise, and robust system for quantification of target analytes. Using MESIA, the concentration of prostate-specific antigen (PSA) in 10 µl of human serum is determined within 5 min. The limit of detection is 0.085 ng/mL, and the average coefficient of variance is 8.85% for five different PSA concentrations ranging from 0 to 25 ng/mL. This method shows good precision and reproducibility (<10%) and high correlation with cobas e 801 (r = 0.997) for clinical patient samples. We believe this technique to be useful in the development of a point-of-care testing platform for diagnosis and prognosis of various diseases, such as cancer, based on quantification of biomarkers in a drop of blood.

Involvement of Gastrin-Releasing Peptide Receptor in the Regulation of Adipocyte Differentiation in 3T3-L1 Cells.

Gastrin-releasing peptide (GRP), a member of bombesin-like peptides, and its receptor (GRP-R) play an important role in various physiological and pathological conditions. In this work, we investigated the role of GRP-R on adipogenesis in 3T3-L1 adipocytes. The expression of GRP-R was significantly increased during the adipocyte differentiation of 3T3-L1 cells. The inhibition of GRP-R by the antagonist RC-3095 affected adipogenesis in 3T3-L1 cells, which reduced lipid accumulation and regulated the expression of adipogenic genes. Moreover, cyclic AMP response element-binding protein (CREB) directly bound to the GRP-R promoter upon exposure to adipogenic stimuli. The down-regulation of GRP-R by the knockdown of CREB inhibited adipocyte differentiation of 3T3-L1 cells. Together these results suggest that the regulation of GRP-R activity or expression has an influence on adipogenesis through regulating adipogenic related genes.

Pentraxin 3 Modulates the Inflammatory Response in Human Dental Pulp Cells.

INTRODUCTION: Pentraxin 3 (PTX3) has been suggested as a novel inflammatory biomarker in inflammation-associated diseases. The aim of this study was to examine the role of PTX3 in the inflammatory response of human dental pulp cells (HDPCs). METHODS: HDPCs were treated with tumor necrosis factor alpha (TNF-α), and total RNA and protein were extracted. PTX3 messenger RNA and protein expression levels were analyzed using reverse transcription polymerase chain reaction and Western blotting, respectively. For PTX3 knockdown, HDPCs were transfected with a small interfering RNA against human PTX3. Macrophage chemotaxis after PTX3 silencing in HDPCs was assessed by transwell migration assays. RESULTS: TNF-α increased PTX3 messenger RNA and protein levels in HDPCs. TNF-α-induced PTX3 expression was mediated by extracellular signal-regulated kinase 1/2 and nuclear factor kappa B. PTX3 knockdown decreased the expression levels of interleukin 6, interleukin 8, and monocyte chemoattractant protein 1 after stimulation with TNF-α in HDPCs. Moreover, PTX3 silencing in HDPCs significantly decreased the chemotactic migration of macrophages. CONCLUSIONS: Our findings indicate PTX3 plays a critical role in the regulation of pulp inflammatory processes and reveal its underlying molecular mechanism.

CTCF Regulates Otic Neurogenesis via Histone Modification in the Neurog1 Locus.

The inner ear is a complex sensory organ responsible for hearing and balance. Formation of the inner ear is dependent on tight regulation of spatial and temporal expression of genes that direct a series of developmental processes. Recently, epigenetic regulation has emerged as a crucial regulator of the development of various organs. However, what roles higher-order chromatin organization and its regulator molecules play in inner ear development are unclear. CCCTC-binding factor (CTCF) is a highly conserved 11-zinc finger protein that regulates the three-dimensional architecture of chromatin, and is involved in various gene regulation processes. To delineate the role of CTCF in inner ear development, the present study investigated inner ear-specific Ctcf knockout mouse embryos (Pax2-Cre; Ctcffl/fl ). The loss of Ctcf resulted in multiple defects of inner ear development and severely compromised otic neurogenesis, which was partly due to a loss of Neurog1 expression. Furthermore, reduced Neurog1 gene expression by CTCF knockdown was found to be associated with changes in histone modification at the gene's promoter, as well as its upstream enhancer. The results of the present study demonstrate that CTCF plays an essential role in otic neurogenesis by modulating histone modification in the Neurog1 locus.

The effects of shoulder stabilization exercises and pectoralis minor stretching on balance and maximal shoulder muscle strength of healthy young adults with round shoulder posture.

[Purpose] The purpose of this study was to analyze the effects of pectoralis minor stretching and shoulder strengthening with an elastic band on balance and maximal shoulder muscle strength in young adults with rounded shoulder posture. [Subjects and Methods] Nineteen subjects with rounded shoulder posture were randomly divided into 2 groups: a shoulder stabilization exercise group and a stretching exercise group. The groups performed each exercise for 40 minutes, 3 times a week, for 4 weeks. Static balance (eyes open and closed), dynamic balance (the limits of stability in 4 directions) and shoulder muscle strength in 5 directions were measure before and after the exercises. [Results] The stretching exercise demonstrated a significant difference between the pre- and post-exercise in the static balance with eyes closed and extension and horizontal abduction strength while the stabilization exercise demonstrated significant difference in the left and right directions between the pre- and post-exercise of the dynamic balance and flexion strength. The stabilization exercise demonstrated significant differences shown in the flexion between the pre- and post-test. [Conclusion] The shoulder stabilization and stretching exercises improved the static balance, dynamic balance, and muscle strength.

Effects of open and closed kinetic-chain exercises on the muscle strength and muscle activity of the ankle joint in young healthy women.

[Purpose] The purpose of this study was to analyze the effects of open and closed chain exercise on the muscle strength and muscle activity of the ankle joint. [Subjects and Methods] Twenty women in their 20s were randomly assigned to two groups: the open kinetic-chain group and the closed kinetic-chain group. Each group performed 5 sets 3 times per week for 4 weeks. Exercise intensity was increased once after two weeks. The muscle activity of the tibialis anterior, gastrocnemius, tibialis posterior, and peroneus longus muscles were measured. The collected data were analyzed with two-way repeated measures ANOVA. [Results] In the results for muscle strength, both groups showed significant differences in dorsiflexion and plantar flexion between the pre-test and post-test. In the results for muscle activity, no significant differences were noted for either group. [Conclusion] Open and closed kinetic-chain exercises can help to improve muscle strength.

Gastrin-releasing peptide promotes the migration of vascular smooth muscle cells through upregulation of matrix metalloproteinase-2 and -9.

Gastrin-releasing peptide (GRP) has been reported to be implicated in the pathogenesis of inflammatory disorders. The migration and proliferation of vascular smooth muscle cells (VSMCs) are key components of vascular inflammation that leads to the development of atherosclerosis. The present study aimed to investigate the molecular effect of GRP on VSMC proliferation and migration. We report that GRP significantly enhanced the proliferation and migration of rat VSMCs. GRP increased mRNA and protein expression of matrix metalloproteinase- 2 and -9 (MMP-2/9) in VSMCs. The induction of MMP-2/9 by GRP was regulated by the activation of the signal transducer and activator of transcription-3 (STAT3). In addition, STAT3-knockdown of VSMCs by siRNA or blockade of the GRP receptor inhibited GRP-induced migration of VSMCs. Taken together, our findings indicate that GRP promotes the migration of VSMCs through upregulation of MMP-2/9 via STAT3 activation. [BMB Reports 2017; 50(12): 628-633].

The effect of shoe type on static and dynamic balance during treadmill walking in young healthy women.

[Purpose] The purpose of this study was to analyze the effect of various shoes on the static and dynamic balance of young women in their 20s. [Subjects and Methods] The subjects of the study were 15 healthy young women and repeated measured design. The subjects walked on the treadmill at a speed of 4 km/h for 30 minutes wearing three types of shoes: sneaker, rain boots, and combat boots. Balance was measured by a Romberg test and a limits of stability test. One-way ANOVA was used for statistical analysis. [Results] As the results of the Romberg test, the main effect of time was shown in the EO-COG area, EO-COG length, and EO-COG velocity. As the results of the limits of stability test, the main effects of time in LT, RT, FW, and total. There were significant differences in the LT in the sneaker group, the rain boots group, and the LT and RT in the combat boots group between the pre- and post-test. [Conclusion] The characteristics of shoes such as the materials, hardness, and thickness of the soles, the coefficient of friction of the outsoles, and the collar height affected the static and dynamic balance.

CCCTC-binding factor is essential to the maintenance and quiescence of hematopoietic stem cells in mice.

Hematopoiesis involves a series of lineage differentiation programs initiated in hematopoietic stem cells (HSCs) found in bone marrow (BM). To ensure lifelong hematopoiesis, various molecular mechanisms are needed to maintain the HSC pool. CCCTC-binding factor (CTCF) is a DNA-binding, zinc-finger protein that regulates the expression of its target gene by organizing higher order chromatin structures. Currently, the role of CTCF in controlling HSC homeostasis is unknown. Using a tamoxifen-inducible CTCF conditional knockout mouse system, we aimed to determine whether CTCF regulates the homeostatic maintenance of HSCs. In adult mice, acute systemic CTCF ablation led to severe BM failure and the rapid shrinkage of multiple c-Kithi progenitor populations, including Sca-1+ HSCs. Similarly, hematopoietic system-confined CTCF depletion caused an acute loss of HSCs and highly increased mortality. Mixed BM chimeras reconstituted with supporting BM demonstrated that CTCF deficiency-mediated HSC depletion has both cell-extrinsic and cell-intrinsic effects. Although c-Kithi myeloid progenitor cell populations were severely reduced after ablating Ctcf, c-Kitint common lymphoid progenitors and their progenies were less affected by the lack of CTCF. Whole-transcriptome microarray and cell cycle analyses indicated that CTCF deficiency results in the enhanced expression of the cell cycle-promoting program, and that CTCF-depleted HSCs express higher levels of reactive oxygen species (ROS). Importantly, in vivo treatment with an antioxidant partially rescued c-Kithi cell populations and their quiescence. Altogether, our results suggest that CTCF is indispensable for maintaining adult HSC pools, likely by regulating ROS-dependent HSC quiescence.