Tubular dentin formation by TGF-ß/BMP signaling in dental epithelial cells.

OBJECTIVES: This study aimed to identify formation of tubular dentin induced by transforming growth factor-ß (TGF-ß) and bone morphogenic protein (BMP) signaling pathway in dental epithelial cells. METHODS: We collected conditioned medium (CM) of rTGF-ß1/rBMP-2-treated HAT-7 and treated to MDPC-23 cells. The expression levels of odontoblast differentiation markers, KLF4, DMP1, and DSP were evaluated by real-time PCR and Western blot analysis. To evaluate whether CM of rTGF-ß1/rBMP-2 induces tubular dentin formation, we made a beagle dog tooth defect model. RESULTS: Here, we show that Cpne7 is regulated by Smad4-dependent TGF-ß1/BMP2 signaling pathway in dental epithelial cells. CM of rTGF-ß1/rBMP-2 treated HAT-7 or rCPNE7 raises the expression levels of KLF4, DMP1, and DSP in MDPC-23 cells. When rTGF-ß1 or rBMP-2 is directly treated to MDPC-23 cells, however, expression levels of Cpne7-regulated genes remain unchanged. In a beagle dog defect model, application of rTGF-ß1/BMP2-treated CM resulted in tubular tertiary dentin mixed with osteodentin at cavity-prepared sites, while rTGF-ß1 group exhibited homogenous osteodentin. CONCLUSIONS: Taken together, Smad4-dependent TGF-ß1/BMP2 signaling regulates Cpne7 in dental epithelial cells, and CPNE7 protein secreted from pre-ameloblasts mediates odontoblast differentiation via epithelial-mesenchymal interaction.

Impacts of COVID-19 on bike-sharing usages in Seoul, South Korea.

The COVID-19 pandemic and social distancing restrictions have had a significant impact on urban mobility. As micro mobility offers less contact with other people, docked or dockless e-scooters and bike-sharing have emerged as alternative urban mobility solutions. However, little empirical research has been conducted to investigate how COVID-19 might affect micro mobility usage, especially in a major Asian city. This research aims to study how COVID-19 and other related factors have affected bike-sharing ridership in Seoul, South Korea. Using detailed urban telecommunication data, this study explored the spatial-temporal patterns of a docked bike-sharing system in Seoul. Stepwise negative binomial panel regressions were conducted to find out how COVID-19 and various built environments might affect bike-sharing ridership in the city. Our results showed that open space areas and green infrastructure had statistically significant positive impacts on bike-sharing usage. Compared to registered population factors, real-time telecommunication floating population had a significant positive relationship with both bike trip count and trip duration. The model showed that telecommunication floating population has a significant positive impact on bike-sharing trip counts and trip duration. These findings could offer useful guidelines for emerging shared mobility planning during and after the COVID-19 pandemic.

A Paradigm Shift in Nuclear Chromatin Interpretation: From Qualitative Intuitive Recognition to Quantitative Texture Analysis of Breast Cancer Cell Nuclei.

Assessing the pattern of nuclear chromatin is essential for pathological investigations. However, the interpretation of nuclear pattern is subjective. In this study, we performed the texture analysis of nuclear chromatin in breast cancer samples to determine the nuclear pleomorphism score thereof. We used three different algorithms for extracting high-level texture features: the gray-level co-occurrence matrix (GLCM), gray-level run length matrix (GLRLM), and gray-level size zone matrix (GLSZM). Using these algorithms, 12 GLCM, 11 GLRLM, and 16 GLSZM features were extracted from three scores of breast carcinoma (Scores 1-3). Classification accuracy was assessed using the support vector machine (SVM) and k-nearest neighbor (KNN) classification models. Three features of GLCM, 11 of GLRLM, and 12 of GLSZM were consistent across the three nuclear pleomorphism scores of breast cancer. Comparing Scores 1 and 3, the GLSZM feature large zone high gray-level emphasis showed the largest difference among breast cancer nuclear scores among all features of the three algorithms. The SVM and KNN classifiers showed favorable results for all three algorithms. A multiclass classification was performed to compare and distinguish between the scores of breast cancer. Texture features of nuclear chromatin can provide useful information for nuclear scoring. However, further validation of the correlations of histopathologic features, and standardization of the texture analysis process, are required to achieve better classification results. © 2021 The Authors. Cytometry Part A published by Wiley Periodicals LLC on behalf of International Society for Advancement of Cytometry.

Notch1-mediated inflammation is associated with endothelial dysfunction in human brain microvascular endothelial cells upon particulate matter exposure.

Exposure to atmospheric particulate matter (PM) is an emerging risk factor for the pathogenesis of several diseases in humans, including cerebrovascular diseases. However, the mechanisms underlying PM-induced endothelial dysfunction are currently unclear. In this study, we examined how PM leads to endothelial dysfunction in human brain microvascular endothelial cells (HBMECs). We demonstrated that PM10 exposure (up to 25 µg/mL) increase Notch1 cleavage, and it regulates endothelial dysfunction through NICD-mediated inflammation and senescence. PM10-induced NICD signaling causes increased expression of interleukin-1 beta (IL-1ß) and enhances characteristics of cellular senescence, which leads to increased endothelial permeability in HBMECs. Knockdown of Notch1 by siRNA blocks PM10-induced endothelial dysfunction via the suppression of inflammation and senescence. Furthermore, we found that Notch1-mediated inflammation accelerates endothelial senescence, which eventually leads to endothelial dysfunction. Altogether, our data suggest that Notch1 and NICD are potential target regulators for the prevention of cerebrovascular endothelial dysfunction induced by ambient air pollutants such as PM.

Osteopontin heptamer peptide containing the RGD motif enhances the phagocytic function of microglia.

Osteopontin (OPN) is a phosphorylated glycoprotein expressed in various tissues, including brain, and mediates a wide range of cellular activities. In our previous studies, we reported recombinant OPN and RGD and SLAY-containing OPN-peptide icosamer (OPNpt20) exhibited robust neuroprotective activities in an animal model of transient focal ischemia, and attributed these effects to the anti-inflammatory, pro-angiogenic, and phagocytic functions of OPNpt20. In the present study, we truncated OPNpt20 to 13 or 7 amino acid peptides containing RGD (R) and/or SLAY (S) motif (OPNpt13RS, OPNpt7R, OPNpt7RS, and OPNpt7S) and their cell motility and migration inducing activities were examined in BV2 cells (a microglia cell line). All four peptides significantly enhanced BV2 cell motility and migration, but OPNpt7R, an RGD-containing 7-amino-acid OPN peptide (VPNGRGD), was found to be most potent and its potency was comparable to OPNpt20. Phagocytic activity and F-actin polymerization were also significantly enhanced in OPNpt7R-treated BV2 cells. Importantly, studies using two mutant peptides (OPNpt7R-RAA and OPNpt7R-RAD, wherein RGD in OPNpt7R was replaced with RAA or RAD, respectively) revealed that all these effects of OPNpt7R, motility, migration, F-actin polymerization, and phagocytosis induction, were RGD-dependent. Furthermore, the Erk, Fak, and Akt signaling pathways appeared to be involved in the induction of phagocytic activity by OPNpt7R. Co-treating cells with OPNpt7R and D98059 or wortmannin (pharmacological inhibitors of Erk and Akt, respectively) significantly suppressed OPNpt7R-mediated phagocytosis induction. These results indicate the RGD-containing OPN heptamer OPNpt7R triggers microglial motility, migration, and phagocytic activity and that the RGD motif plays a critical role in these activities.

Altered COVID-19 receptor ACE2 expression in a higher risk group for cerebrovascular disease and ischemic stroke.

Coronavirus disease 2019 (COVID-19) is a worldwide pandemic. It has a high transmission rate among humans, and is a threat to global public health. However, there are no effective prophylactics or therapeutics available. It is necessary to identify vulnerable and susceptible groups for adequate protection and care against this disease. Recent studies have reported that COVID-19 has angiotensin-converting enzyme 2 (ACE2) as a functional receptor, which may lead to the development of severe cerebrovascular diseases (CVD), including strokes, in patients with risk factors for CVD such as diabetes and smoking. Thus, the World Health Organization (WHO) advised caution against COVID-19 for smokers and patients with underlying clinical symptoms, including cardiovascular diseases. Here, we observed ACE2 expression in the brain of rat middle cerebral artery occlusion (MCAO) model and evaluated the effects of cigarette smoke extract (CSE) and diabetes on ACE2 expression in vessels. We showed that the levels of ACE2 expression was increased in the cortex penumbra after ischemic injuries. CSE treatment significantly elevated ACE2 expression in human brain vessels. We found that ACE2 expression was upregulated in primary cultured human blood vessels with diabetes compared to healthy controls. This study demonstrates that ACE2 expression is increased in ischemic brains and vessels exposed to diabetes or smoking, makes them vulnerable to COVID-19 infection.

Assessment of suicidal risk using Minnesota multiphasic personality inventory-2 restructured form.

BACKGROUND: Suicide is a major social issue, affected by both social and psychopathological factors. This study investigated suicide risk assessment using the Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF). METHODS: Data were collected from 7824 college students using the MMPI-2-RF. The participants were classified into high-, moderate-, and low-risk for suicide groups based on their scores on the structured Mini-International Neuropsychiatric Interview (MINI) for comparative analysis. The relationships between scores on the Restructured Clinical (RC) Scales of the MMPI-2-RF and suicide risk level were investigated using a multiple logistic regression. RESULTS: Out of the 7824 participants, 964 (12.3%) were identified as being at risk of suicide. There were 553 participants considered low-risk, 312 moderate-risk, and 99 at high-risk. Suicide risk in the participants tended to increase as RC scale scores increased. Out of the nine RC scales, the Demoralization (RCd) and Negative Emotions (RC7) scale scores were highest across all risk groups. The results of a multiple logistic regression indicated that the Demoralization (RCd) scores were significantly elevated in all three suicide risk groups. Antisocial Behavior (RC4) and Aberrant Experiences (RC8) scale scores were significantly elevated for the low-risk group, whereas Somatic Complaints (RC1) scores were elevated for the moderate-risk group, and Somatic Complaints (RC1), Low Positive Emotions (RC2), Antisocial Behavior (RC4), and Ideas of Persecution (RC6) scale scores were elevated for the high-risk group. CONCLUSIONS: Compared to the healthy control group, all three suicide risk groups showed elevated scores on the RC Scales overall, suggesting that various psychopathological factors are involved in the etiology of suicide. More psychopathologic factors were found to influence suicide-related issues in the higher risk groups than lower risk groups, suggesting that more risk factors are involved in higher suicide risk groups. Compared to healthy controls, even the low-risk group showed a significant elevation in emotional factors and antisocial behaviors. While the healthy controls and those at risk of suicide differed significantly on both the Demoralization (RCd) and Negative Emotions (RC7) scales, only the Demoralization (RCd) scale appeared to be able to screen for high suicide risk.

Progressing super-enhancer landscape during mammary differentiation controls tissue-specific gene regulation.

The mammary luminal lineage relies on the common cytokine-sensing transcription factor STAT5 to establish super-enhancers during pregnancy and initiate a genetic program that activates milk production. As pups grow, the greatly increasing demand for milk requires progressive differentiation of mammary cells with advancing lactation. Here we investigate how persistent hormonal exposure during lactation shapes an evolving enhancer landscape and impacts the biology of mammary cells. Employing ChIP-seq, we uncover a changing transcription factor occupancy at mammary enhancers, suggesting that their activities evolve with advancing differentiation. Using mouse genetics, we demonstrate that the functions of individual enhancers within the Wap super-enhancer evolve as lactation progresses. Most profoundly, a seed enhancer, which is mandatory for the activation of the Wap super-enhancer during pregnancy, is not required during lactation, suggesting compensatory flexibility. Combinatorial deletions of structurally equivalent constituent enhancers demonstrated differentiation-specific compensatory activities during lactation. We also demonstrate that the Wap super-enhancer, which is built on STAT5 and other common transcription factors, retains its exquisite mammary specificity when placed into globally permissive chromatin, suggesting a limited role of chromatin in controlling cell specificity. Our studies unveil a previously unrecognized progressive enhancer landscape where structurally equivalent components serve unique and differentiation-specific functions.

A structural model for quality of life of alcoholics.

AIMS: To investigate the factors affecting the quality of life of alcoholics and to identify the relationships between these factors to establish and verify a hypothetical model for the quality of life of alcoholics. DESIGN: Covariance structure analysis using structural equation model. METHODS: Participants were 223 adults who were hospitalized at alcohol addiction treatment centre after being diagnosed with alcoholism in Gyunggi-do, South Korea. Data included the general characteristics of study participants, depression, abstinence self-efficacy, stress level, stress coping strategy, social support and quality of life. Data were collected from March - 28 May 2016 and were analysed using SPSS 22.0 and AMOS 22.0. RESULTS: The factors affecting the quality of life of alcoholics included alcohol abstinence self-efficacy (ß = 0.37, t = 4.56), stress copying strategy (ß = 0.23, t = 2.37), stress level (ß = -0.20, t = -2.08) and social support (ß = 0.14, t = 2.52). Factor analysis and statistical significance level was used for model coefficients and t-value estimation. CONCLUSION: This study suggested that to improve the quality of life of alcoholics, their alcohol abstinence self-efficacy should be increased, measures to improve their stress coping strategy and ability should be prepared, their stress level should be lowered and the social support system perceived by them should be strengthened. Health professionals need to pay attention to the affecting factors to improve the quality of life of alcoholics. IMPACT: Alcoholism is emerging as a social problem, not just an individual problem. Alcohol abstinence self-efficacy had the greatest direct effect on the quality of life of alcoholics, followed by stress coping strategy, stress level and social support, which had significant direct effects. Depression had significant indirect effect on the quality of life of alcoholics. Health professionals need to pay attention to the affecting factors to improve the quality of life of alcoholics in clinical practice or community fields.

Adenosine Triphosphate Accumulated Following Cerebral Ischemia Induces Neutrophil Extracellular Trap Formation.

In ischemic stroke, neutrophils infiltrate damaged brain tissue immediately following the ischemic insult and aggravate inflammation via various mechanisms which include neutrophil extracellular traps (NETs) formation. In the present study, we showed that adenosine triphosphate (ATP), a DAMP molecule, accumulates in the brain and induces NETosis in brain parenchyma and in circulating neutrophils (PMNs) isolated from a murine model of stroke induced by middle cerebral artery occlusion (MCAO). Expression of peptidylarginine deiminase-4 (PAD4), which induces citrullination of histones H3 (CitH3) and initiates NETosis, was significantly enhanced in brain parenchyma and blood PMNs following MCAO. ATP or BzATP (a prototypic P2X7R agonist) significantly enhanced the inductions of PAD4 and CitH3 in a P2X7R-dependent manner and intracellular Ca2+ influx, PKCα activation, and NADPH oxidase-dependent reactive oxygen species (ROS) production play critical roles in this ATP-P2X7R-mediated NETosis. In our MCAO animal model, NETosis was markedly suppressed by treatment with apyrase, an enzyme hydrolyzing ATP, but enhanced by co-treatment of BzATP, confirming ATP-P2X7R-mediated NETosis. Since ATP not only induced NETosis but was also extruded after NETosis, our results indicate that ATP accumulated in the ischemic brain induces NETosis, mediating a cross-talk linking NETosis with neuronal damage that might aggravate inflammation and brain damage.

Effects of a Korean version of the metacognitive training program for outpatients with schizophrenia on theory of mind, positive symptoms, and interpersonal relationships.

BACKGROUND: Since the significance of metacognition as the theoretical basis of a psychological intervention for schizophrenia first emerged, there have been ongoing attempts to restore or strengthen patients' metacognitive abilities. AIM: A Korean version of the metacognitive training (MCT) program was developed, and its effects on theory of mind, positive and negative symptoms, and interpersonal relationships were examined in stable outpatients with schizophrenia. METHOD: A pre-test-post-test design with a control group was used. The participants were 59 outpatients (30 in experimental group, 29 in control group) registered at five mental health facilities in a city in South Korea. The developed MCT program was applied for a total of 18 sessions, 60 min per session, over a period of 14 weeks. The hinting task, false belief task, Scale for the Assessment of Positive and Negative Symptoms, and Relationship Change Scale were used to verify the effects of this program. Data were analysed by the chi-square test, t-test, and Mann-Whitney U-test using the SPSS/PASW 18.0 statistics program. RESULTS: The general characteristics, intelligence, and outcome variables of the two groups were homogeneous. After the intervention, the experimental group showed significant improvements in theory of mind, positive and negative symptoms and interpersonal relationships compared with the control group. CONCLUSION: These results suggest that the MCT program can be a complementary psychotherapy that contributes to symptom relief and interpersonal functioning in patients with schizophrenia, and is effective in the Korean culture, beyond the Western context.

Functional assessment of CTCF sites at cytokine-sensing mammary enhancers using CRISPR/Cas9 gene editing in mice.

The zinc finger protein CTCF has been invoked in establishing boundaries between genes, thereby controlling spatial and temporal enhancer activities. However, there is limited genetic evidence to support the concept that these boundaries restrict the search space of enhancers. We have addressed this question in the casein locus containing five mammary and two non-mammary genes under the control of at least seven putative enhancers. We have identified two CTCF binding sites flanking the locus and two associated with a super-enhancer. Individual deletion of these sites from the mouse genome did not alter expression of any of the genes. However, deletion of the border CTCF site separating the Csn1s1 mammary enhancer from neighboring genes resulted in the activation of Sult1d1 at a distance of more than 95 kb but not the more proximal and silent Sult1e1 gene. Loss of this CTCF site led to de novo interactions between the Sult1d1 promoter and several enhancers in the casein locus. Our study demonstrates that only one out of the four CTCF sites in the casein locus had a measurable in vivo activity. Studies on additional loci are needed to determine the biological role of CTCF sites associated with enhancers.

Anti-Zn2+-Toxicity of 4-Hydroxybenzyl Alcohol in Astrocytes and Neurons Contribute to a Robust Neuroprotective Effects in the Postischemic Brain.

4-Hydroxybenzyl alcohol (4-HBA) is an important phenolic constituent of Gastrodia elata (GE) Blume, which is used as a traditional herbal medicine in East Asia. Many activities have been reported to underlie the beneficial effects of 4-HBA in brain, such as, anti-oxidative, anti-inflammatory, anti-excitotoxic, and anti-apoptotic effects in neurons and microglia. Here, the authors demonstrate the robust neuroprotective effects of 4-HBA in rat middle cerebral artery occlusion (MCAO) model of stroke, and showed anti-Zn2+ toxicity in neurons and astrocytes as a molecular mechanism contributing to these effects. Intraperitoneal administration of 4-HBA (20 mg/kg) in Sprague-Dawley rats 1 h after MCAO reduced infarct volumes to 27.1 ± 9.2% of that of MCAO controls and significantly ameliorated motor impairments and neurological deficits. Significant suppressions of Zn2+-induced cell death, ROS generation, and PARP-1 induction by 4-HBA were observed in primary cortical cultures. 4-HBA also protected astrocytes from Zn2+-induced toxicity and suppressing ROS generation by employing slightly different molecular mechanisms, i.e., suppressing PARP-1 induction and NAD depletion under acute Zn2+-treatment and suppressing p67 NADPH oxidase subunit induction under chronic Zn2+-treatment. Results indicate that the protective effects of 4-HBA against Zn2+-toxicity in neurons and astrocytes contribute to its robust neuroprotective effects in the postischemic brain. Considering the pleiotropic effects of 4-HBA, which have been reported in previous reports and added in the present study, it has therapeutic potential for the amelioration of ischemic brain damage.

Odontogenic ameloblast-associated protein (ODAM) in gingival crevicular fluid for site-specific diagnostic value of periodontitis: a pilot study.

BACKGROUND: Odontogenic Ameloblast-Associated Protein (ODAM) in gingival crevicular fluid (GCF) can provide evidence of the detachment of junctional epithelium from the tooth surface by periodontitis. This study sought to investigate the ability of ODAM to reflect the severity of periodontitis at a site-specific level; thus whether there was a relationship between clinical diagnostic parameters and the value of ODAM in GCF was analyzed. METHODS: Eight periodontitis patients with various severities were enrolled, and the clinical parameters and samples of GCF were obtained from 44 to 60 sites of each subject. The ODAM concentration was quantified by enzyme-linked immunosorbent assay. Correlation analyses between clinical parameters and ODAM values and unadjusted and adjusted (linear) mixed model analyses were performed. The accuracy of ODAM to reflect sites having a probing depth (PD) ≥ 5 mm and a positive bleeding on probing (BOP) was evaluated by receiver-operating characteristic analysis. RESULTS: A total of 424 GCF samples were collected. The mean ODAM concentration from each patient varied from 0.2 to 1.52 ng/ml. Correlations between PD or clinical attachment level (CAL) and ODAM values were found (p <  0.0001). An adjusted linear mixed model showed that PD or CAL were associated with ODAM values (p <  0.05). The area under the curve of ODAM, which reflected sites with PD ≥ 5 mm and positive BOP, was 0.661 (p <  0.0001). CONCLUSION: This result shows the possibility of GCF ODAM as a site-specific biomarker for periodontal tissue destruction.

Odontogenic Ameloblast-associated Protein (ODAM) Mediates Junctional Epithelium Attachment to Teeth via Integrin-ODAM-Rho Guanine Nucleotide Exchange Factor 5 (ARHGEF5)-RhoA Signaling.

Adhesion of the junctional epithelium (JE) to the tooth surface is crucial for maintaining periodontal health. Although odontogenic ameloblast-associated protein (ODAM) is expressed in the JE, its molecular functions remain unknown. We investigated ODAM function during JE development and regeneration and its functional significance in the initiation and progression of periodontitis and peri-implantitis. ODAM was expressed in the normal JE of healthy teeth but absent in the pathologic pocket epithelium of diseased periodontium. In periodontitis and peri-implantitis, ODAM was extruded from the JE following onset with JE attachment loss and detected in gingival crevicular fluid. ODAM induced RhoA activity and the expression of downstream factors, including ROCK (Rho-associated kinase), by interacting with Rho guanine nucleotide exchange factor 5 (ARHGEF5). ODAM-mediated RhoA signaling resulted in actin filament rearrangement. Reduced ODAM and RhoA expression in integrin ß3- and ß6-knockout mice revealed that cytoskeleton reorganization in the JE occurred via integrin-ODAM-ARHGEF5-RhoA signaling. Fibronectin and laminin activated RhoA signaling via the integrin-ODAM pathway. Finally, ODAM was re-expressed with RhoA in regenerating JE after gingivectomy in vivo. These results suggest that ODAM expression in the JE reflects a healthy periodontium and that JE adhesion to the tooth surface is regulated via fibronectin/laminin-integrin-ODAM-ARHGEF5-RhoA signaling. We also propose that ODAM could be used as a biomarker of periodontitis and peri-implantitis.

Temperament and characteristics related to attention deficit/hyperactivity disorder symptoms.

OBJECTIVE: Adult attention deficit/hyperactivity disorder (ADHD) exhibits symptoms, such as attention deficit and impulsivity, that make it difficult for patients to manage social activities. In this study, we investigated the association of adult ADHD symptoms with temperament and character dimensions, taking into account possible sex interactions. METHOD: A total of 2917 (1462 males and 1455 females) college students completed the 140 5-point Likert items on the Temperament and Character Inventory-Revised Short version (TCI-RS) and the Attention Deficit/Hyperactivity Disorder Self-Rated Scale (ASRS). According to the ASRS score, subjects were classified into the control group, the inattentive ADHD symptom (IA) group, or the hyperactive/impulsive ADHD symptom (HI) group. Additionally, the scores of the four temperament dimensions and the three character dimensions were compared. RESULTS: In the IA and HI groups, the NS and HA levels of the temperament dimension were high and the PS level was low compared with the control group. In the character dimension, the levels of SD and CO were significantly lower in the ADHD groups than in the control group (P<0.001). Meanwhile, the ST level in the HI group was significantly higher than in the control group. In the regression analysis after age and gender correction, NS and SD in the IA group and NS, CO, and ST in the HI group were associated with adult ADHD symptoms. CONCLUSION: The current findings suggest that high novelty seeking may be related to adult ADHD symptoms in the temperament dimension. Furthermore, some character dimensions were associated with adult ADHD symptoms.

Robust neuroprotective effects of intranasally delivered iNOS siRNA encapsulated in gelatin nanoparticles in the postischemic brain.

The therapeutic efficacy of intranasal iNOS siRNA delivery was investigated in the postischemic rat brain after encapsulating on in gelatin nanoparticles (GNPs; diameter 188.0 ± 60.9 nm) cross-linked with 0.0667% glutaraldehyde (GA). Intranasally delivered GNPs were found in extracellular and intracellular compartments of many brain regions, including the olfactory bulb, cerebral cortex, and striatum at 1 hour after infusion and continued to be detected for days. Infarct volumes were markedly suppressed (maximal reduction to 42.1 ± 2.6%) at 2 days after 60 minutes of middle cerebral artery occlusion (MCAO) when iNOS siRNA/GNPs were delivered at 6 hours post-MCAO. In addition, this protective effect was manifested by reductions in neurological and behavioral deficits that were sustained for 2 weeks. Therapeutic potency of iNOS siRNA/GNPs was significantly greater and sustained longer than that of bare siRNA and prolonged and efficient iNOS by iNOS siRNA/GNP is responsible for the robust neuroprotective effect.

Effects of Multivitamin Supplements on Cognitive Function, Serum Homocysteine Level, and Depression of Korean Older Adults With Mild Cognitive Impairment in Care Facilities.

PURPOSE: To examine effects of multivitamin supplements on cognitive function, serum homocysteine level, and depression of Korean older adults with mild cognitive impairment (MCI) in care facilities. DESIGN: A quasi-experimental pretest-posttest control group design was employed. METHODS: Forty-eight adults 65 years of age and older with MCI (experimental, n = 24; control, n = 24) who were living in care facilities in Gyeong-gi-do, Korea, were recruited. Multivitamin supplements as experimental treatment consisted of vitamin B6, B12, and folic acid. Multivitamin supplements were taken at a dosage of one pill every day for 12 weeks through the oral route. Measures were Mini Mental State Examination-Korean, serum homocysteine level, and Geriatric Depression Scale Short Form Korea Version. Collected data were analyzed using SPSS version 21.0 statistical software (SPSS Inc., Chicago, IL, USA). FINDINGS: There were significant effects of multivitamin supplements on cognitive function (F = 3.624, p = .021), serum homocysteine level (F = 6.974, p = .001), and depression (F = 10.849, p = .001). CONCLUSIONS: Multivitamin supplements increased cognitive function, and decreased serum homocysteine level and depression of Korean older adults with MCI in care facilities. CLINICAL RELEVANCE: Multivitamin supplements can be utilized for improving cognitive ability and for decreasing depression of Korean older adults with MCI in care facilities.

Nuclear factor I-C (NFIC) regulates dentin sialophosphoprotein (DSPP) and E-cadherin via control of Krüppel-like factor 4 (KLF4) during dentinogenesis.

Odontoblasts are a type of terminally differentiated matrix-secreting cells. A number of molecular mechanisms are involved in the differentiation of odontoblasts. Several studies demonstrated that Krüppel-like factor 4 (KLF4) promotes odontoblast differentiation via control of dentin sialophosphoprotein (DSPP). Because nuclear factor I-C (NFIC) is also known to control DSPP, we investigated the relationship between NFIC and KLF4 during odontoblast differentiation. Klf4 mRNA expression was significantly decreased in Nfic(-/-) pulp cells compared with wild type cells. In immunohistochemistry assays, dentin matrix protein 1 (Dmp1), and DSP protein expression was barely observed in Nfic(-/-) odontoblasts and dentin matrix. Nfic bound directly to the Klf4 promoter and stimulated Klf4 transcriptional activity, thereby regulating Dmp1 and DSPP expression during odontoblast differentiation. Nfic or Klf4 overexpression promoted mineralized nodule formation in MDPC-23 cells. In addition, Nfic overexpression also decreased Slug luciferase activity but augmented E-cadherin promoter activity via up-regulation of Klf4 in odontoblasts. Our study reveals important signaling pathways during dentinogenesis: the Nfic-Klf4-Dmp1-Dspp and the Nfic-Klf4-E-cadherin pathways in odontoblasts. Our results indicate the important role of NFIC in regulating KLF4 during dentinogenesis.