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1.
Genomics ; 115(6): 110710, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37734486

RESUMO

DNA-based prediction of externally visible characteristics (EVC) with SNPs is one of the research areas of interest in the forensic field. Based on a previous study performing GWAS on facial traits in a Korean population, herein, we present results stemming from GWA analysis with KoreanChip and novel genetic loci satisfying genome-wide significant level. We discovered a total of 20 signals and 12 loci were found to have novel associations with facial traits, including six loci located in intergenic regions and six loci located at UBE2O, HECTD2, CCDC108, TPK1, FCN2, and FRMPD1. Additionally, we performed a polygenic score analysis for 33 distance-related traits in facial phenotyping and determined genetic relationships between facial traits and SNPs using the GCTA program. The results of the current study offer an understanding of how facial morphology is influenced by complex genetic structures and provide insights into forensic investigation and population genetics.


Assuntos
Loci Gênicos , Estudo de Associação Genômica Ampla , Humanos , Estudo de Associação Genômica Ampla/métodos , Fenótipo , Genética Populacional , República da Coreia , Polimorfismo de Nucleotídeo Único , Enzimas de Conjugação de Ubiquitina/genética
2.
Hum Genet ; 142(11): 1561-1569, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37728764

RESUMO

Exome and genome sequencing (ES/GS) in genetic medicine and research leads to discovering genomic secondary findings (SFs) unrelated to the purpose of the primary test. There is a lack of agreement to return the SF results for individuals undergoing the test. The aim of this study is to investigate the frequency of actionable secondary findings using GS data obtained from the rare disease study and the Korean Genome and Epidemiology Study (KoGES) in the National Project of Bio Big Data pilot study. Pathogenic (P) or likely pathogenic (LP) variants of 78 SF genes recommended by the American College of Medical Genetics and Genomics (ACMG) were screened in the rare disease study and KoGES. The pathogenicity of SF gene variants was determined according to the ACMG interpretation. The overall SF rate was 3.75% for 280 individuals with 298 P/LP variants of 41 ACMG SF genes which were identified among 7472 study participants. The frequencies of genes associated with cardiovascular, cancer, and miscellaneous phenotypes were 2.17%, 1.22%, and 0.58%, respectively. The most frequent SF gene was TTN followed by BRCA2. The frequency of actionable SFs among participants with rare disease and general population participants in the Korean population presented here will assist in reporting results of medically actionable SFs in genomic medicine.


Assuntos
Big Data , Doenças Raras , Humanos , Projetos Piloto , Genômica , República da Coreia/epidemiologia , Testes Genéticos
3.
Forensic Sci Res ; 8(1): 62-69, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37415797

RESUMO

Human face is a highly heritable and complex trait. Many genome-wide analyses have identified genetic variants influencing facial morphology. Genome-wide association studies (GWASs) investigating facial morphologies of different populations provide a comprehensive insight into the genetic basis of the human face. Here, we report a GWAS of normal facial variation in Koreans using an array optimized for the Korean population (KoreanChip). We found that novel genetic variants encompassing four loci reached the genome-wide significance threshold. They include LOC107984547, UBE2O, TPK1, and LINC01148 loci associated with facial angle, brow ridge protrusion, nasal height, and eyelid curvature. Our results also validated previously published genetic loci, including FAT4, SOX9, and TBX3 loci. All confirmed genetic variants showed phenotypic differences involving each facial trait based on the effect of the minor allele. The present study highlights genetic signals associated with normal human facial variation and provides candidates for functional studies. Key points: GWAS of normal facial variation in the Korean population was conducted using a Korean genome chip.Previously reported genetic signals associated with FAT4, SOX9, and TBX3 loci were replicated in the Korean populations.Genetic signals in UBE2O and TPK1 loci were identified as novel variants for corresponding facial features.

4.
Ann Hum Biol ; 50(1): 187-195, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36876654

RESUMO

BACKGROUND: Hypertension and osteoporosis are the most common types of health problems. A recent study suggested that the fibroblast growth factor receptor-like protein 1 (FGFRL1) gene in giraffes is the most promising candidate gene that may have direct effects on both the skeleton and the cardiovascular system. AIM: Our study purposed to replicate the finding that the FGFR5 gene is related to giraffe-related characteristics (height, hypertension, and osteoporosis), and to assess the associations between genetic variants of the FGFR family and three phenotypes. SUBJECTS AND METHODS: An association study was performed to confirm the connections between hypertension, osteoporosis, and height and the FGFR family proteins (FGFR1 to FGFR5). RESULTS: We identified a total of 192 genetic variants in the FGFR family and found six SNVs in the FGFR2, FGFR3, and FGFR4 genes that were associated with two phenotypes simultaneously. Also, the FGFR family was found to be involved in calcium signalling, and three genetic variants of the FGFR3 gene showed significant signals in the pituitary and hypothalamus. CONCLUSION: Taken together, these findings suggest that FGFR genes are associated with hypertension, height, and osteoporosis. In particular, the present study highlights the FGFR3 gene, which influences two fundamental regulators of bone remodelling.


Assuntos
Hipertensão , Osteoporose , Humanos , Hipertensão/genética , Osteoporose/genética
5.
Pharmaceuticals (Basel) ; 15(12)2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36558966

RESUMO

Inflammatory bowel diseases (IBD) are digestive tract disorders that involve chronic inflammation with frequent recurrences. This study aimed to evaluate the efficacy of two novel histone deacetylase 8 (HDAC8) inhibitors, namely, SPA3052 and SPA3074, against dextran sulfate sodium (DSS)-induced experimental colitis. Male C57BL/6N mice were subjected to two cycles of 1.5% DSS followed by treatment with suberoylanilide hydroxamic acid (SAHA), SPA3052, or SPA3074 for 14 days. Our results showed that SPA3074 administration increased (>50%) the expression of occludin, a tight junction protein, which was significantly decreased (>100%) after DSS treatment. Moreover, SPA3074 upregulated suppressor of cytokine signaling 1 (SOCS1) protein expression, which is known to be a key suppressor of T-helper cell differentiation and pro-inflammatory cytokines expression. Furthermore, we observed a decrease in SOCS1-associated Akt phosphorylation and an increase in lower extracellular signal-regulated kinase 1 and 2 phosphorylation, which contributed to lower nuclear factor-kappa B activation. Th2 effector cytokines, especially interleukin-13, were also downregulated by SPA3074 treatment. This study suggests that HDAC8 might be a promising novel target for the development of IBD treatments and that the novel HDAC8 inhibitor SPA3074 is a new candidate for IBD therapeutics.

6.
PLoS One ; 17(8): e0273237, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35980984

RESUMO

Hypertension and osteoporosis are two major disorders, which interact with each other. Specific genetic signals involving the fibroblast growth factor receptor-like 1 (FGFRL1) gene are related to high blood pressure and bone growth in giraffes. FGFRL1 is associated with cardiovascular system and bone formation. We performed an association study to investigate the role of FGFRL1 in hypertension, osteoporosis, and height determination in humans. In addition, we identified three kinds of phenotypes in fibroblast growth factor (FGF) genes and examined their association with the FGFRL1 gene. We identified 42 SNPs in the FGFRL1 gene associated with each trait. We then analyzed the potential functional annotation of each SNP. The FGFRL1 gene was found to be associated with height, hypertension, and osteoporosis, consistent with the results of a previous study. In addition, the FGF2, FGF4, FGF10, FGF18, and FGF22 genes were found to interact with the FGFRL1 gene. Our study suggests that both FGFRL1 and FGFRL1-related genes may determine the height and the prevalence of osteoporosis and hypertension in the Korean population.


Assuntos
Hipertensão , Osteoporose , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Humanos , Hipertensão/genética , Osteoporose/genética , Receptor Tipo 5 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 5 de Fator de Crescimento de Fibroblastos/metabolismo , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo
7.
Psychol Mark ; 39(4): 694-700, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35465078

RESUMO

Apart from personal- and societal-level factors, we propose that collectivism also plays a role in the spread of COVID-19. Results from six studies using both secondary datasets and laboratory experiments conducted in two different countries demonstrate that collectivism is: (a) negatively associated with the spread of COVID-19 and (b) positively associated with the self-importance/expectation to engage in widely publicized behaviors to prevent the spread of the disease, as well as with greater likelihood to vaccinate against COVID-19. Finally, the higher likelihood of people high (vs. low) in collectivism to engage in preventive behaviors is driven by their belief that others consider it important to engage in such behaviors. The effects were robust and emerged by measuring collectivism both at the country level and at the individual level. We conclude by proposing features of public health campaigns likely to elicit compliance behavior to control the spread of COVID-19.

8.
Br J Pharmacol ; 179(5): 1033-1048, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34610141

RESUMO

BACKGROUND AND PURPOSE: Recently, isoflavone derivatives have been shown to have neuroprotective effects against neurological disorders. For instance, genistein attenuated the neuroinflammation and amyloid-ß accumulation in Alzheimer's disease animal models, suggesting the potential for use to prevent and treat Alzheimer's disease. EXPERIMENTAL APPROACH: Here, 50 compounds, including isoflavone derivatives, were constructed and screened for the inhibitory effects on amyloid-ß42 fibrilization and oligomerization using the high-throughput screening formats of thioflavin T assay and multimer detection system, respectively. The potential neuroprotective effect of t3-(4-hydroxyphenyl)-2H-chromen-7-ol (SPA1413), also known as dehydroequol, idronoxil or phenoxodiol, was evaluated in cells and in 5xFAD (B6SJL) transgenic mouse, a model of Alzheimer's disease. KEY RESULTS: SPA1413 had a potent inhibitory action on both amyloid-ß fibrilization and oligomerization. In the cellular assay, SPA1413 prevented amyloid-ß-induced cytotoxicity and reduced neuroinflammation. Remarkably, the oral administration of SPA1413 ameliorated cognitive impairment, decreased amyloid-ß plaques and activated microglia in the brain of 5xFAD (B6SJL) transgenic mouse. CONCLUSION AND IMPLICATIONS: Our results strongly support the repurposing of SPA1413, which has already received fast-track status from the US Food and Drug Administration (FDA) for cancer treatment, for the treatment of Alzheimer's disease due to its potent anti-amyloidogenic and anti-neuroinflammatory actions.


Assuntos
Doença de Alzheimer , Isoflavonas , Fármacos Neuroprotetores , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Animais , Encéfalo/metabolismo , Modelos Animais de Doenças , Isoflavonas/farmacologia , Camundongos , Camundongos Transgênicos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Placa Amiloide
9.
Front Cell Infect Microbiol ; 11: 695191, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34458160

RESUMO

High-throughput DNA sequencing technologies have facilitated the in silico forensic analysis of human microbiome. Specific microbial species or communities obtained from the crime scene provide evidence of human contacts and their body fluids. The microbial community is influenced by geographic, ethnic, lifestyle, and environmental factors such as urbanization. An understanding of the effects of these external stressors on the human microbiome and determination of stable and changing elements are important in selecting appropriate targets for investigation. In this study, the Forensic Microbiome Database (FMD) (http://www.fmd.jcvi.org) containing the microbiome data of various locations in the human body in 35 countries was used. We focused on skin, saliva, vaginal fluid, and stool and found that the microbiome distribution differed according to the body part as well as the geographic location. In the case of skin samples, Staphylococcus species were higher than Corynebacterium species among Asians compared with Americans. Holdemanella and Fusobacterium were specific in the saliva of Koreans and Japanese populations. Lactobacillus was found in the vaginal fluids of individuals in all countries, whereas Serratia and Enterobacter were endemic to Bolivia and Congo, respectively. This study is the first attempt to collate and describe the observed variation in microbiomes from the forensic microbiome database. As additional microbiome databases are reported by studies worldwide, the diversity of the applications may exceed and expand beyond the initial identification of the host.


Assuntos
Líquidos Corporais , Microbiota , Pele/microbiologia , Líquidos Corporais/microbiologia , Feminino , Ciências Forenses , Geografia , Humanos , RNA Ribossômico 16S/genética , Saliva
10.
Front Genet ; 12: 669215, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34054925

RESUMO

Most previous genome-wide association studies (GWAS) have identified genetic variants associated with anthropometric traits. However, most of the evidence were reported in European populations. Anthropometric traits such as height and body fat distribution are significantly affected by gender and genetic factors. Here we performed GWAS involving 64,193 Koreans to identify the genetic factors associated with anthropometric phenotypes including height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip ratio. We found nine novel single-nucleotide polymorphisms (SNPs) and 59 independent genetic signals in genomic regions that were reported previously. Of the 19 SNPs reported previously, eight genetic variants at RP11-513I15.6 and one genetic variant at the RP11-977G19.10 region and six Asian-specific genetic variants were newly found. We compared our findings with those of previous studies in other populations. Five overlapping genetic regions (PAN2, ANKRD52, RNF41, HGMA1, and C6orf106) had been reported previously but none of the SNPs were independently identified in the current study. Seven of the nine newly found novel loci associated with height in women revealed a statistically significant skeletal expression of quantitative trait loci. Our study provides additional insight into the genetic effects of anthropometric phenotypes in East Asians.

11.
Genes (Basel) ; 12(3)2021 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-33800915

RESUMO

Osteoporosis, characterized by reduced bone mass and increased bone fragility, is a disease prevalent in women. Likewise, breast cancer is a multifactorial disease and considered the major cause of mortality in premenopausal and postmenopausal women worldwide. Our data demonstrated the association of the MYLK gene and PTGS1 gene variants with osteoporosis and benign breast tumor risk and the impact of ovariectomy on osteoporosis in Korean women. We performed a genome-wide association study (GWAS) of women with osteoporosis and benign breast tumors. There were 60 single nucleotide polymorphisms (SNPs) and 12 SNPs in the MYLK and PTGS1 genes, associated with benign breast tumors and osteoporosis. Our study showed that women with homozygous MYLK rs12163585 major alleles had an increased risk of osteoporosis following ovariectomy compared to those with minor alleles. Women carrying the minor PTGS1 rs1213265 allele and not treated via ovariectomy carried a higher risk of osteoporosis than those who underwent ovariectomy with a homozygous genotype at the major alleles. Our results suggest that both the MYLK and PTGS1 genes are genetic factors associated with the phenotypes, and these associations appear to be modulated by ovariectomy.


Assuntos
Neoplasias da Mama/genética , Proteínas de Ligação ao Cálcio/genética , Ciclo-Oxigenase 1/genética , Quinase de Cadeia Leve de Miosina/genética , Osteoporose/genética , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Pessoa de Meia-Idade , Ovariectomia/efeitos adversos , Fenótipo , República da Coreia
13.
Biochem Pharmacol ; 183: 114312, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33130126

RESUMO

Cholestasis is a pathological condition involving blockage of bile flow that results in hepatotoxicity, inflammation, and fibrosis. Although recent studies have shown that histone deacetylases (HDACs) are involved in the progression of fibrosis in various organs, the role of HDAC8 on liver fibrosis has until now remained unexplored. This study presents a newly-synthesized, selective HDAC8 inhibitor SPA3014 composed of a vinyl disulfide-sulfoxide core, and evaluates its therapeutic efficacy against cholestatic liver injury and fibrosis in bile duct-ligated (BDL) mice. We first observed the increase in HDAC8 protein levels in mice with BDL and patients with cholestatic liver disease. Mice with BDL that were pretreated with SPA3014 had lower liver damage and fibrosis, based on gross examination, histopathologic findings, and biochemical analyses, than did vehicle-treated mice. Studies with LX-2 human hepatic stellate cells showed that SPA3014 exerted protective effects by inhibiting TGF-ß-mediated activation of MAPK-Smad2/3 and JAK2-STAT3 pathways and by upregulating PPARγ expression. Overall, these results strongly suggest that HDAC8 inhibition constitutes a new therapeutic strategy for treatment of cholestatic liver injury.


Assuntos
Colestase/tratamento farmacológico , Colestase/enzimologia , Inibidores de Histona Desacetilases/uso terapêutico , Histona Desacetilases/metabolismo , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/enzimologia , Animais , Inibidores de Histona Desacetilases/farmacologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL
14.
Am J Hum Biol ; 33(3): e23489, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32865273

RESUMO

OBJECTIVE: FTO (fat mass and obesity-associated) gene is a well-known genetic risk factor for obesity. We investigated whether physical activity modulates the effect of FTO rs9939609 on obesity in Korean population. METHODS: The study analyzed the correlation between physical activity and obesity in 8840 individuals representing the Korea Association Resource (KARE). The association between obesity-related traits and single-nucleotide polymorphisms (SNPs) was assessed using linear regression models. Physical activity was defined as 3 hours or more of daily intense activity. RESULTS: Participants carrying rs9939609 (AT+AA) genotypes showed higher BMI compared with those carrying the wild-type (TT) homozygote. The highest significant association was observed between obesity-related traits (ß = .334, P value = 1.76 × 10-6 ). FTO rs9939609 (AT+AA) increased the risk of obesity (OR = 1.42, CI [1.13-1.79]), which was correlated with BMI correlations. However, active exercise by subjects carrying the same genotype reduced the risk of obesity by nearly 2-fold (OR = 0.62, CI [0.25-0.84]). In contrast, TT genotype was not statistically significant in reducing the risk of obesity in the active exercise group. CONCLUSIONS: Our results support a previous finding correlating FTO and obesity-related traits and suggest that the interaction with genetic variation and physical activity is an important risk factor for obesity.


Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Exercício Físico , Obesidade/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Prevalência , República da Coreia/epidemiologia
15.
Int J Mol Sci ; 21(21)2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33126415

RESUMO

As a member of the tyrosine protein kinase Tec (TEC) family, Bruton's tyrosine kinase (BTK) is considered a promising therapeutic target due to its crucial roles in the B cell receptor (BCR) signaling pathway. Although many types of BTK inhibitors have been reported, there is an unmet need to achieve selective BTK inhibitors to reduce side effects. To obtain BTK selectivity and efficacy, we designed a novel series of type II BTK inhibitors which can occupy the allosteric pocket induced by the DFG-out conformation and introduced an electrophilic warhead for targeting Cys481. In this article, we have described the structure-activity relationships (SARs) leading to a novel series of potent and selective piperazine and tetrahydroisoquinoline linked 5-phenoxy-2-aminopyridine irreversible inhibitors of BTK. Compound 18g showed good potency and selectivity, and its biological activity was evaluated in hematological tumor cell lines. The in vivo efficacy of 18g was also tested in a Raji xenograft mouse model, and it significantly reduced tumor size, with 46.8% inhibition compared with vehicle. Therefore, we have presented the novel, potent, and selective irreversible inhibitor 18g as a type II BTK inhibitor.


Assuntos
Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Aminopiridinas/química , Descoberta de Drogas , Linfoma/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Animais , Apoptose , Proliferação de Células , Feminino , Humanos , Linfoma/enzimologia , Linfoma/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Modelos Moleculares , Estrutura Molecular , Inibidores de Proteínas Quinases/química , Relação Estrutura-Atividade , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Int J Mol Sci ; 21(21)2020 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-33113810

RESUMO

Bruton's tyrosine kinase (BTK) is an attractive target for treating patients with B cell malignancies and autoimmune diseases. Many BTK inhibitors have been identified; however, like other kinase inhibitors, they lack diversity in their core structures. Therefore, it is important to secure a novel scaffold that occupies the adenine-binding site of BTK. We screened an in-house library of natural products and their analogs via a biochemical assay to identify a novel scaffold for targeting BTK. A pyranochromenone scaffold, derived from a natural active component decursin, was found to be effective at targeting BTK and was selected for further optimization. A series of pyranochromenone analogs was synthesized through the modification of pyranochromenone at the C7 position. Pyranochromenone compounds with an electrophilic warhead exhibited promising BTK inhibitory activity, with IC50 values in the range of 0.5-0.9 µM. A docking study of the representative compound 8 provided a reasonable explanation for compound activity. Compound 8 demonstrated good selectivity over other associated kinases and decreased the production of proinflammatory cytokines in THP cells. Moreover, compound 8 presented significant in vivo efficacy in a murine model of collagen-induced arthritis.


Assuntos
Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Antirreumáticos/farmacologia , Benzopiranos/farmacologia , Produtos Biológicos/farmacologia , Butiratos/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Tirosina Quinase da Agamaglobulinemia/química , Tirosina Quinase da Agamaglobulinemia/metabolismo , Animais , Antirreumáticos/química , Artrite Experimental/prevenção & controle , Benzopiranos/química , Produtos Biológicos/química , Butiratos/química , Humanos , Masculino , Camundongos Endogâmicos DBA , Simulação de Acoplamento Molecular , Estrutura Molecular , Domínios Proteicos , Inibidores de Proteínas Quinases/química , Relação Estrutura-Atividade , Células THP-1
17.
J Microbiol Biotechnol ; 30(11): 1640-1650, 2020 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-32958727

RESUMO

Colorectal cancer (CRC) is the leading cause of common malignant neoplasm worldwide. Many studies have analyzed compositions of gut microbiota associated with various diseases such as inflammatory bowel diseases (IBD) and colon cancer. One of the most representative bacteria involved in CRC is enterotoxigenic Bacteroides fragilis (ETBF), a species belonging to phylum Bacteroidetes. We used ETBF colonized mice with azoxymethane (AOM)/dextran sulphate sodium (DSS) and zerumbone, a compound with anti-bacterial effect, to determine whether zerumbone could restore intestinal microbiota composition. Four experimental groups of mice were used: sham, ETBF colonized AOM/DSS group, ETBF colonized AOM/DSS group zerumbone 60 mg kg-1 (ETBF/AOM/ DSS + Z (60)), and only zerumbone (60 mg kg-1)-treated group. We performed reversible dye terminators-based analysis of 16S rRNA gene region V3-V4 for group comparison. Microbiota compositions of ETBF/AOM/DSS + Z (60) group and ETBF colonized AOM/DSS group not given zerumbone were significantly different. There were more Bacteroides in ETBF/AOM/DSS + Z (60) group than those in ETBF colonized AOM/DSS group, suggesting that B. fragilis could be a normal flora activated by zerumbone. In addition, based on linear discriminant analysis of effect size (LEfSe) analysis, microbial diversity decreased significantly in the ETBF colonized AOM/DSS group. However, after given zerumbone, the taxonomic relative abundance was increased. These findings suggest that zerumbone not only influenced the microbial diversity and richness, but also could be helpful for enhancing the balance of gut microbial composition. In this work, we demonstrate that zerumbone could restore the composition of intestinal microbiota.


Assuntos
Azoximetano/farmacologia , Bacteroides fragilis/crescimento & desenvolvimento , Sulfato de Dextrana/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Sesquiterpenos/farmacologia , Animais , Antibacterianos/farmacologia , Bactérias/classificação , Bactérias/efeitos dos fármacos , Colo/microbiologia , Colo/patologia , Neoplasias do Colo/microbiologia , Neoplasias do Colo/patologia , Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/patologia , Modelos Animais de Doenças , Microbioma Gastrointestinal/genética , Camundongos , RNA Ribossômico 16S
18.
J Bone Miner Metab ; 38(6): 868-877, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32653958

RESUMO

INTRODUCTION: Osteoporosis is a common disorder characterized by decreased bone mineral density (BMD). Interestingly, osteoporosis and obesity have several similar features, including a genetic predisposition and a common bone marrow stem cell. With aging, the composition of bone marrow shifts to adipocytes, osteoclast activity increases, and osteoblast function declines, resulting in osteoporosis. MATERIALS AND METHODS: We performed a genome-wide association study (GWAS) analysis with osteoporosis and body mass index (BMI) and did identify an association in 349 and 384 SNPs by filtering with the significant p values (p < 0.001) of BMI and osteoporosis, respectively. RESULTS: Only three of those SNPs were common (rs2326365, rs7097028, and rs11000205) between the SNPs significantly associated with BMI and/or osteoporosis in Korean Association REsource (KARE) females. Two of the three SNPs belonged to the ASCC1 gene and one to the FAM50B gene. We carried out a minor allele frequency (MAF) analysis of the rs7097028 and rs11000205 SNPs in the ASCC1 gene with a geographic genome variant browser. Both rs7097028 and rs11000205 in the ASCC1 gene were seen mostly in African and Southeast Asian populations. CONCLUSIONS: Our results suggest that the ASCC1 gene is a significant genetic factor for determining the risk for both osteoporosis and obesity in KARE postmenopausal females.


Assuntos
Proteínas de Transporte/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Obesidade/genética , Osteoporose/genética , Polimorfismo de Nucleotídeo Único/genética , Pós-Menopausa/genética , População Branca/genética , Adulto , Idoso , Povo Asiático/genética , Índice de Massa Corporal , Densidade Óssea/genética , Feminino , Frequência do Gene/genética , Geografia , Humanos , Desequilíbrio de Ligação/genética , Masculino , Pessoa de Meia-Idade , República da Coreia
19.
J Korean Assoc Oral Maxillofac Surg ; 46(2): 133-142, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32364353

RESUMO

OBJECTIVES: In this study, we determined the incidence and pattern of screw loosening in patients who received dental implants. MATERIALS AND METHODS: Patients who received implants between January 2008 and October 2013 and completed their prosthetic rehabilitation were evaluated for the incidence, frequency, and onset of screw loosening using dental charts and radiographs. The association between each factor and screw loosening was analyzed using the chi-square test and a multivariate analysis with binary logistic regression models (P<0.05). RESULTS: Total 1,928 implants were placed in 837 patients (448 males, 389 females), whose follow-up period after loading varied from 0.25 to 70 months (mean period, 31.5 months). Screw loosening occurred in 7.2% of implants. Most cases occurred less than six months after loading. Among those, 22.3% experienced recurrent screw loosening. Screw loosening was most common in the molar region (8.5%) and frequently associated with an implant diameter of ≥5 mm (14.2%). External implant-abutment connections (8.9%) and screw-retained implant prostheses (10.1%) showed higher incidence of problems than internal implant-abutment connections and cement-retained implants, respectively. Screw loosening was most common in implant prostheses with single crowns (14.0%). CONCLUSION: Within the limits of the current study, we conclude that the incidence of screw loosening differs significantly according to the position of implant placement, the type of implant and manufacturer, implant diameter, the type of implant-abutment connection, the type of retention in the implant prosthesis, and the type of implant prosthesis.

20.
J Prosthet Dent ; 124(4): 461-467, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31839327

RESUMO

STATEMENT OF PROBLEM: A few studies have compared the accuracy of newly introduced intraoral scanners (IOSs); however, limited evidence is available concerning which system provides the best marginal and internal adaptation of zirconia crowns. PURPOSE: The purpose of this in vitro study was to compare the marginal and internal discrepancies of zirconia crowns fabricated with 4 digital scanners by a silicone replica technique. MATERIAL AND METHODS: A maxillary central incisor was prepared for a ceramic crown and duplicated to form 10 metal abutments. Four groups of zirconia crowns with different scanning methods were produced for each die: 1 laboratory scanner, L (Ceramill Map 400), and 3 different IOSs, CS (CS3600), TR (TRIOS3), and CE (CEREC Omnicam). The marginal and internal discrepancies were measured by a silicone replica technique under a static load of 50 N. The replica specimens were sectioned buccolingually and mesiodistally and then examined by using a stereomicroscope (JTZ-7XT) at ×200 magnification. Fifteen reference points were measured on each specimen. One-way ANOVAs with the Duncan multiple range tests were used for statistical analysis of the data (α=.05). RESULTS: The mean marginal discrepancies of zirconia crowns were 12.7 µm for group L, 12.6 µm for group CS, 14.8 µm for group TR, and 15.8 µm for group CE. No significant differences were found in marginal and incisal discrepancies among 4 groups. However, groups CS and L showed significantly better cervical and axial discrepancies than groups TR and CE. Group TR showed significantly better axial discrepancy than group CE. CONCLUSIONS: Zirconia crowns made by using the CS3600 and the laboratory scanner with a conventional impression showed significantly better internal discrepancies than those made by using TRIOS3 and CEREC Omnicam.


Assuntos
Adaptação Marginal Dentária , Planejamento de Prótese Dentária , Desenho Assistido por Computador , Coroas , Técnica de Moldagem Odontológica , Zircônio
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