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1.
Microorganisms ; 12(5)2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38792778

RESUMO

In order to understand the role of microorganisms in litter decomposition and the nutrient cycle in volcanic forest ecosystems, the dominant forest species Larix gmelinii in the volcanic lava plateau of the Wudalianchi volcano was considered as the research object. We analyzed the response of bacterial community structure and diversity to litter decomposition for 1 year, with an in situ decomposition experimental design using litter bags and Illumina MiSeq high-throughput sequencing. The results showed that after 365 days, the litter quality residual rate of Larix gmelinii was 77.57%, and the litter N, P, C:N, C:P, and N:P showed significant differences during the decomposition period (p < 0.05). The phyla Cyanobacteria and the genus unclassified_o_Chloroplast were the most dominant groups in early decomposition (January and April). The phyla Proteobacteria, Actinobacteriota, and Acidobacteriota and the genera Massilia, Pseudomonas, and Sphingomona were higher in July and October. The microbial communities showed extremely significant differences during the decomposition period (p < 0.05), with PCoa, RDA, and litter QRR, C:P, and N as the main factors driving litter bacteria succession. Microbial functional prediction analysis showed that Chloroplasts were the major functional group in January and April. Achemoheterotrophy and aerobic chemoheterotrophy showed a significant decrease as litter decomposition progressed.

2.
Microorganisms ; 12(4)2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38674601

RESUMO

Volcanic lava is an excellent model of primary succession, in which basalt-associated microorganisms drive the cycling of different elements such as nitrogen, carbon, and other nutrients. Microbial communities in volcanic soils are of particular interest for study on the emergence and evolution of life within special and extreme conditions. The initial processes of colonization and subsequent rock weathering by microbial communities are still poorly understood. We analyzed the soil bacterial and fungal communities and diversities associated with lava (LBL) and kipuka (BK) sites in Wudalianchi using 16S and ITS rRNA Illumina Miseq sequencing techniques. The results showed that soil physical and chemical properties (pH, MC, TOC, TN, TP, AP, DOC, and DON) significantly differed between LBL and BK. The Shannon, Ace, and Pd indexes of fungi in the two sites showed a significant difference (p < 0.05). The dominant bacterial phyla forming communities at LBL and BK sites were Acidobacteria, Proteobacteria, Actinobacteria, and Basidiomycota, and their differences were driven by Gemmatimonadetes and Verrucomicrobia. The dominant fungal phyla of LBL and BK sites were Ascomycota, Zygomycota, and Rozellomcota, which differed significantly between the two sites. The microbial communities showed extremely significant differences (p < 0.05), with MC, pH, and nitrogen being the main influencing factors according to RDA/CCA and correlation analysis. Microbial functional prediction analysis across the two sites showed that the relative abundance of advantageous functional groups was significantly different (p < 0.05). The combined results drive us to conclude that the volcanic soil differences in the deposits appear to be the main factor shaping the microbial communities in Wudalianchi (WDLC) volcanic ecosystems.

3.
Anticancer Drugs ; 35(2): 129-139, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-37615540

RESUMO

Colorectal cancer (CRC) is one of the world's most common and deadly cancers. According to GLOBOCAN2020's global incidence rate and mortality estimates, CRC is the third main cause of cancer and the second leading cause of cancer-related deaths worldwide. The US Food and Drug Administration has approved auranofin for the treatment of rheumatoid arthritis. It is a gold-containing chemical that inhibits thioredoxin reductase. Auranofin has a number of biological activities, including anticancer activity, although it has not been researched extensively in CRC, and the mechanism of action on CRC cells is still unknown. The goal of this research was to see how Auranofin affected CRC cells in vivo and in vitro . The two chemical libraries were tested for drugs that make CRC cells more responsive. The CCK-8 technique was used to determine the cell survival rate. The invasion, migration, and proliferation of cells were assessed using a transwell test and a colony cloning experiment. An electron microscope was used to observe autophagosome formation. Western blotting was also used to determine the degree of expression of related proteins in cells. Auranofin's tumor-suppressing properties were further tested in a xenograft tumor model of human SW620 CRC cells. Auranofin dramatically reduced the occurrence of CRC by decreasing the proliferation, migration, and invasion of CRC cells, according to our findings. Through a mTOR-dependent mechanism, auranofin inhibits the epithelial-mesenchymal transition (EMT) and induces autophagy in CRC cells. Finally, in-vivo tests revealed that auranofin suppressed tumor growth in xenograft mice while causing no harm. In summary, auranofin suppresses CRC cell growth, invasion, and migration. Auranofin inhibits the occurrence and progression of CRC by decreasing EMT and inducing autophagy in CRC cells via a mTOR-dependent mechanism. These findings suggest that auranofin could be a potential chemotherapeutic medication for the treatment of human CRC.


Assuntos
Auranofina , Neoplasias Colorretais , Humanos , Animais , Camundongos , Auranofina/farmacologia , Auranofina/uso terapêutico , Linhagem Celular Tumoral , Serina-Treonina Quinases TOR/metabolismo , Neoplasias Colorretais/patologia , Autofagia , Transição Epitelial-Mesenquimal , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica
4.
J Mol Med (Berl) ; 102(2): 273-284, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38153509

RESUMO

EN1 encodes a homeodomain-containing transcription factor and is a determinant of bone density and fracture. Previous powerful genome-wide association studies (GWASs) have identified multiple single-nucleotide polymorphisms (SNPs) near EN1 at 2q14.2 locus for osteoporosis, but the causal SNPs and functional mechanisms underlying these associations are poorly understood. The target genes regulated by the transcription factor EN1 are also unclear. In this study, we identified rs188303909, a functional CpG-SNP, as a causal SNP for osteoporosis at 2q14.2 through the integration of functional and epigenomic analyses. Functional experiments demonstrated that unmethylated rs188303909 acted as a strong allele-specific distal enhancer to regulate EN1 expression by modifying the binding of transcription factor E2F6, but rs188303909 methylation attenuated the active effect of E2F6 on EN1 expression. Importantly, transcription factor EN1 could differentially bind osteoporosis GWAS lead SNPs rs4869739-T and rs4355801-G to upregulate CCDC170 and COLEC10 expression, thus promoting bone formation. Our study provided a mechanistic insight into expression regulation of the osteoporosis susceptibility gene EN1, which could be a potential therapeutic target for osteoporosis precision medicine. KEY MESSAGES: CpG-SNP rs188303909 is a causal SNP at the osteoporosis susceptibility locus 2q14.2. Rs188303909 distally regulates EN1 expression by modulating DNA methylation and E2F6 binding. EN1 upregulates CCDC170 and COLEC10 expression through osteoporosis GWAS lead SNPs rs4869739 and rs4355801.


Assuntos
Osteoporose , Polimorfismo de Nucleotídeo Único , Humanos , Estudo de Associação Genômica Ampla , Metilação de DNA , Osteoporose/genética , Fatores de Transcrição/genética , Predisposição Genética para Doença , Colectinas/genética , Fator de Transcrição E2F6/genética , Proteínas de Homeodomínio/genética
5.
Artigo em Inglês | MEDLINE | ID: mdl-37782285

RESUMO

In order to comprehensively evaluate the driver's vibration comfort under different vibration conditions, eighteen subjects were required to drive a tractor at different speeds on field and asphalt roads respectively in the real vehicle experiment. The sEMG signals and vibration acceleration signals of the subjects were recorded. And the time-frequency domain analysis of sEMG signals and acceleration signals were used to determine the relationship among the characteristic indexes, tractor speed and road surfaces. The relevance analysis showed that there was a significant correlation between the integral electromyography (iEMG) and median frequency (MF) of the middle scalene muscle, erector spinae muscle and gastrocnemius muscle, the RMS of weighted acceleration (aw) of the neck, waist and legs, and the subjective comfort feelings. It was proven that the tractor speed had a significant impact on human body vibration based on the ANOVA result (p < 0.05). With the increase of running speed, the time domain indexes of sEMG signals including iEMG, RMS and the vibration acceleration signals of the testing body parts increased significantly, while the amplitudes of frequency domain indexes decreased. Therefore, a quantitative regression evaluation model for the comfort of the neck, waist and legs integrating the sEMG and vibration signals was established, and its relative errors were 5.05, 4.38 and 6.12% respectively. This proposed assessment model can combine characteristics of the partial and overall vibration response of human body effectively, predict the tractor driver's vibration comfort accurately, provide a theoretical basis for the evaluation of tractor cab vibration comfort.

6.
Ying Yong Sheng Tai Xue Bao ; 34(7): 1941-1948, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37694478

RESUMO

To understand the role of microorganisms in litter decomposition and nutrient cycling in volcanic forest ecosystem, we conducted in-situ litterbag decomposition experiment and used Illumina MiSeq high-throughput sequencing to analyze the response of bacterial community structure and diversity during the decomposition of litters from Larix gmelinii, Betula platyphylla and Populus davidiana, the dominant tree species in volcanic lava plateau of Wudalianchi. The results showed that mass remaining percentage of litters of three species after 18-month decomposition was 63.9%-68.1%. Litter of B. platyphylla decomposed the fastest, with significant difference in N, C:N, and N:P before and after decomposition. The richness of bacterial species and diversity index differed significantly among the three litters. Proteobacteria, Actinomycetes, and Bacteroidetes were the dominant bacterial groups at the phylum level, while Rhizobium, Sphingomonas, and Pseudomonas were the dominant groups at the genus level, with significant difference among the three litters. After 18 months, the dominant bacterial groups in litter tended to be consistent with those in volcanic lava platform soil. In the volcanic forest ecosystem, bacterial diversity and community structure were mainly affected by P, C:N, and N:P in the litter.


Assuntos
Ecossistema , Florestas , Microbiologia do Solo , Larix/metabolismo , Betula/metabolismo , Populus/metabolismo , Folhas de Planta/metabolismo , Bactérias/metabolismo , Biomassa
7.
Polymers (Basel) ; 15(9)2023 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-37177230

RESUMO

The present paper aims to investigate the buckling load of functionally graded carbon-fiber-reinforced polymer (FG-CFRP) composite laminated plates under in-plane loads in a thermal environment. The effective material properties of the CFRP composite are calculated by the Mori-Tanaka homogenization method. The theoretical formulations are based on classical laminate plate theory (CLPT) and the von Kármán equations for large deflections. The governing equations are derived based on the principle of virtual work and then solved through the Navier solution. Results are obtained for the critical buckling load and temperature effect of a simply supported plate subjected to in-plane loading. A detailed numerical study is conducted to provide important insights into the effects of the functionally graded carbon fiber (CF) distribution pattern and volume fraction, total number of layers, temperature, geometrical dimension and lamination angle on the buckling load of functionally carbon-fiber-reinforced composite plates. Finally, the validation is compared with the Reddy and finite element analyses, which show consistency with each other.

9.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-961114

RESUMO

@#Ferroptosis is a newly discovered method of programmed cell death. Current studies have shown that activation of ferroptosis-related pathways can inhibit the growth and proliferation of tumor cells and reverse their drug resistance. Oral cancer is a common malignant tumor with a high recurrence rate and high drug resistance. Inducing ferroptosis is a potential treatment strategy. There are still many uncertainties in the application of ferroptosis in the treatment of oral cancer, which need to be further explored. This article systematically introduces the mechanism of ferroptosis and its recent progress in oral cancer treatment to provide new mechanisms and methods for the clinical treatment of oral cancer. Current research shows that the mechanism of ferroptosis is mainly related to amino acid metabolism, Fe2+ metabolism, and lipid metabolism. Ferroptosis in oral cancer cells can reverse drug resistance in cancer cells and improve the activity of immune cells. New drugs, such as curcumin analogs and triptolide, can induce ferroptosis in oral cancer, and the development of nanomaterials has improved the utilization rate of drugs. Inhibiting the expression of the ferroptosis-related factors SLC7A11, NF-E2-related factor 2 (Nrf2), and ferritin heavy chain 1 (FTH1) can promote ferroptosis in oral cancer cells. It is a potential target for the clinical treatment of oral cancer, but its translation into clinical practice still needs further research.

10.
Ying Yong Sheng Tai Xue Bao ; 33(2): 378-384, 2022 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-35229511

RESUMO

Taking Deyeuxia angustifolia as the research object, a representative plant of wetland in Sanjiang Plain, we analyzed the variations of individual size and biomass among the habitats of swamp wetlands, swampy meadows, typical meadows and miscellaneous grass meadows, and the relationship between reproductive components and plant biomass. We explored the effects of water level on individual biomass and reproductive allocation of D. angustifolia in different types of wetlands. The results showed that plant biomass, height and the characteristics of sexual reproduction significantly decreased with the increases of water level. The reproductive thresholds of D. angustifolia in miscellaneous grass meadow, typical meadow, swampy meadow, and swamp wetland were 0.245, 0.149, 0.148 and 0.157 g, respectively. There was a significantly negative correlation between plant size and reproductive allocation in three habitats except swampy meadow. Compared with individual size, soil water content had a stronger effect on reproductive allocation of D. angustifolia. The different investment between individual size and reproductive allocation in different habitats was the basic condition that contributes to the good ecological adaptability of D. angustifolia.


Assuntos
Água , Áreas Alagadas , China , Ecossistema , Poaceae , Reprodução
11.
Eur J Polit Econ ; 75: 102180, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35068633

RESUMO

This paper studies the role of local Chinese leaders' career incentives in decisions regarding large-scale crises such as the COVID-19 pandemic. Most local leaders were reluctant to impose lockdowns at the beginning of the pandemic, because their promotions rely on posting strong numbers for economic growth in their region, while lockdowns can suppress growth. Once the nation's top leader warned that local leaders who failed to control the disease would be removed from office, many rapidly implemented resolute measures. However, we find that local leaders with larger promotion incentives were still more likely to downplay the virus by avoiding or minimizing lockdowns.

12.
Shock ; 56(4): 582-592, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34524268

RESUMO

ABSTRACT: Dobutamine (DOB) is recommended as an inotrope for septic patients with low cardiac output, but its long-term impact on sepsis-induced cardiomyopathy remains unclear. This study investigated the long-term effect of DOB on septic myocardial dysfunction and injury. Rats were exposed to cecal ligation and puncture (CLP), the intrinsic myocardial function, other organ functions, hemodynamics, inflammatory response, serum myocardial injury biomarkers, myocardial apoptosis, and vascular permeability were determined. At 6 h after CLP, the left ventricular ±dP/dt were significantly depressed, cardiac tumor necrosis factor-α and vascular cell adhesion molecule-1 expression were increased, but not serum cardiac troponin I (cTnI), N-terminal pro-brain natriuretic peptide (NT-proBNP), heart-type fatty acid-binding protein (H-FABP), creatinine, and urea nitrogen concentrations in CLP group compared with controls. At 9 h after CLP, hepatic dysfunction was present in CLP rats compared with controls. At 6 h after CLP, DOB treatment did not affect hemodynamics, the left ventricular ±dP/dt, cytokine levels in serum and myocardium, as well as cardiomyocyte apoptosis and cardiac vascular hyperpermeability at 20 h after CLP. However, DOB (10.0 µg/kg) increased serum IL-10 level and improved survival in septic rats. These results indicate that the intrinsic myocardial depression occurs earlier than hepatic and renal dysfunction in sepsis and serum cTnI, NT-proBNP, and H-FABP are not suitable as early biomarkers for sepsis-induced myocardial dysfunction. Although DOB treatment (10.0 µg/kg) in the presence of myocardial dysfunction improves survival in septic rats, it neither improves myocardial function and hemodynamics nor attenuates myocardial injury at the later stage of sepsis.


Assuntos
Cardiomiopatias/tratamento farmacológico , Cardiotônicos/uso terapêutico , Dobutamina/uso terapêutico , Traumatismos Cardíacos/tratamento farmacológico , Sepse/complicações , Animais , Cardiomiopatias/etiologia , Citocinas/sangue , Modelos Animais de Doenças , Traumatismos Cardíacos/etiologia , Masculino , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
13.
Bone ; 153: 116165, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34461284

RESUMO

Previous powerful genome-wide association studies (GWASs) and whole-genome sequencing have identified multiple single-nucleotide polymorphisms (SNPs) located over 69 kb upstream of CTNNB1 at 3p22.1 locus associated with osteoporosis. The CTNNB1 gene encodes ß-catenin that is an integral part of adherens junctions and the primary mediator of the canonical Wnt signaling pathway. The causal variants and underlying molecular mechanisms of the osteoporosis susceptibility locus 3p22.1 remains unknown. Through comprehensive computational analyses, including expression quantitative trait locus (eQTL), high-throughput chromatin interaction (Hi-C), epigenomic and functional annotation, four enhancer SNPs (rs9820407, rs9878224, rs454690 and rs9832204) were prioritized as potential causal SNPs at 3p22.1 for osteoporosis. Rs9820407 displayed the strongest enhancer activity in dual-luciferase assays. Specifically, the minor rs9820407-A can preferentially bind transcription factor FOXC1, elevate the enhancer activity and increase CTNNB1 expression. The architectural protein CTCF was presumably involved in long-range chromatin interaction between rs9820407 and CTNNB1. Our study provided a mechanistic insight into how noncoding enhancer SNP rs9820407 distally regulates CTNNB1 expression and modulates osteoporosis risk.


Assuntos
Estudo de Associação Genômica Ampla , Osteoporose , Alelos , Cromatina/genética , Elementos Facilitadores Genéticos/genética , Predisposição Genética para Doença/genética , Humanos , Osteoporose/genética , Polimorfismo de Nucleotídeo Único/genética , beta Catenina/genética
14.
Open Life Sci ; 16(1): 758-765, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34435132

RESUMO

Understanding the response of biomass allocation in current-year twigs is crucial for elucidating the plant life-history strategies under heterogeneous volcanic habitats. We aimed to test whether twig biomass allocation, within-leaf biomass allocation, and the size-number trade-off of Betula platyphylla would be influenced. We measured twig traits of B. platyphylla in Wudalianchi volcanic kipuka, the lava platform, and Shankou lake in northeastern China using standardized major axis analyses. The results showed that the leaf number, total lamina mass (TLAM), stem mass (SM), and twig mass (TM) were significantly different between the three habitats and were greatest in kipuka with abundant soil nutrients. TLAM and SM scaled allometrically with respect to TM, while the normalization constants of the lava platform differ significantly between kipuka and Shankou lake, which showed that under certain TM, leaves gain more biomass in the lava platform. However, within the leaf, individual lamina mass (ILM) scaled isometrically with respect to individual petiole mass (IPM) in kipuka and the lava platform, but ILM scaled allometrically to IPM in Shankou lake. Our results indicated that inhabitats influenced the twig traits and biomass allocation and within-leaf biomass allocation are strategies for plants to adapt to volcanic heterogeneous habitats.

15.
Ecol Evol ; 11(9): 4550-4563, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33976830

RESUMO

BACKGROUND: Some ferns have medicinal properties and are used in therapeutic interventions. However, the classification and phylogenetic relationships of ferns remain incompletely reported. Considering that chloroplast genomes provide ideal information for species identification and evolution, in this study, three unpublished and one published ferns were sequenced and compared with other ferns to obtain comprehensive information on their classification and evolution. MATERIALS AND METHODS: The complete chloroplast genomes of Dryopteris goeringiana (Kunze) Koidz, D. crassirhizoma Nakai, Athyrium brevifrons Nakai ex Kitagawa, and Polystichum tripteron (Kunze) Presl were sequenced using the Illumina HiSeq 4,000 platform. Simple sequence repeats (SSRs), nucleotide diversity analysis, and RNA editing were investigated in all four species. Genome comparison and inverted repeats (IR) boundary expansion and contraction analyses were also performed. The relationships among the ferns were studied by phylogenetic analysis based on the whole chloroplast genomes. RESULTS: The whole chloroplast genomes ranged from 148,539 to 151,341 bp in size and exhibited typical quadripartite structures. Ten highly variable loci with parsimony informative (Pi) values of > 0.02 were identified. A total of 75-108 SSRs were identified, and only six SSRs were present in all four ferns. The SSRs contained a higher number of A + T than G + C bases. C-to-U conversion was the most common type of RNA editing event. Genome comparison analysis revealed that single-copy regions were more highly conserved than IR regions. IR boundary expansion and contraction varied among the four ferns. Phylogenetic analysis showed that species in the same genus tended to cluster together with and had relatively close relationships. CONCLUSION: The results provide valuable information on fern chloroplast genomes that will be useful to identify and classify ferns, and study their phylogenetic relationships and evolution.

16.
Hum Mutat ; 42(1): 37-49, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33058301

RESUMO

Osteoporotic fractures cause major morbidity and mortality in the aging population. Genome-wide association studies (GWAS) have identified USF3 as the novel susceptibility gene of osteoporosis. However, the functional role in bone metabolism and the target gene of the basic helix-loop-helix transcription factor USF3 are unclear. Here, we show that USF3 enhances osteoblast differentiation and suppresses osteoclastogenesis in cultured human osteoblast-like U-2OS cells. Mechanistic studies revealed that transcription factor USF3 antagonistically interacts with anti-osteogenic TWIST1/TCF12 heterodimer in the WNT16 and RUNX2 promoter, and counteracts CREB1 and JUN/FOS in the RANKL promoter. Importantly, the osteoporosis GWAS variant g.1744A>G (rs2908007A>G) located in the WNT16 promoter confers G-allele-specific transcriptional modulation by USF3, TWIST1/TCF12 and TBX5/TBX15, and USF3 transactivates the osteoclastogenesis suppressor WNT16 promoter activity and antagonizes the repression of WNT16 by TWIST1 and TCF12. The risk G allele of osteoporosis GWAS variant g.3260A>G (rs4531631A>G) in the RANKL promoter facilitates the binding of CREB1 and JUN/FOS and enhances transactivation of the osteoclastogenesis contributor RANKL that is inhibited by USF3. Our findings uncovered the functional mechanisms of osteoporosis novel GWAS-associated gene USF3 and lead single nucleotide polymorphisms rs2908007 and rs4531631 in the regulation of bone formation and resorption.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Estudo de Associação Genômica Ampla , Osteoporose , Idoso , Diferenciação Celular/genética , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Humanos , Osteoblastos , Osteoporose/genética , Polimorfismo de Nucleotídeo Único , Ligante RANK/genética , Proteínas com Domínio T/genética , Proteínas Wnt/genética , Proteínas Wnt/metabolismo
17.
Biochem Biophys Res Commun ; 523(3): 658-665, 2020 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-31948755

RESUMO

Genome-wide association studies (GWASs) have successfully identified numerous non-coding genetic variants for type 2 diabetes (T2D), but the functional roles underlying these non-coding variants remain largely unknown. The effects of T2D GWAS lead SNPs on transcriptional factors binding motifs were firstly analyzed via JASPAR, followed by functional validations including dual-luciferase reporter assays, biotin-based DNA pull-down assays, real-time quantitative PCR, and western blotting. The results showed that GWAS SNP rs4430796 conferred T allele specific transcriptional enhancer activity via a PAX6 binding element, and upregulated the expression of HNF1B. GWAS SNP rs4607103 showed a bidirectional modulation of ADAMTS9-AS2 and ADAMTS9 by TCF7L2 in a T allele-specific manner. GWAS SNP rs849135 conferred C allele-specific bidirectional transcriptional enhancer activity via a CREB1 binding element. Our findings have uncovered the functional mechanisms of three T2D GWAS SNPs via affecting the binding of transcription factors, providing new insights into the genetics and molecular pathogenesis of T2D.


Assuntos
Diabetes Mellitus Tipo 2/genética , Polimorfismo de Nucleotídeo Único , Proteína ADAMTS9/genética , Proteína ADAMTS9/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Células HEK293 , Fator 1-beta Nuclear de Hepatócito/genética , Fator 1-beta Nuclear de Hepatócito/metabolismo , Humanos , Fator de Transcrição PAX6/genética , Fator de Transcrição PAX6/metabolismo , Ligação Proteica , Proteína 2 Semelhante ao Fator 7 de Transcrição/genética , Proteína 2 Semelhante ao Fator 7 de Transcrição/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
18.
Hum Mutat ; 41(3): 709-718, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31883164

RESUMO

Upstream transcription factor family member 3 (USF3) c.3781C>A (rs1026364) in the 3'-untranslated region (3'-UTR) has been firmly associated with bone mineral density (BMD) in genome-wide association study (GWAS). However, the molecular mechanism by which it influences BMD and osteoporosis is unknown. Bioinformatics analyses suggested that the risk c.3781A allele creates a target site for hsa-miR-345-5p binding. Luciferase assay validated that the c.3781A allele displayed significantly lower luciferase activities than the c.3781C allele in the human osteoblast cell line hFOB1.19, osteosarcoma cell lines U-2OS and Saos-2, and embryonic kidney cell line 293T. Furthermore, hsa-miR-345-5p regulated USF3 expression on both messenger RNA and protein levels in hFOB1.19 and U937 cells with heterozygous A/C genotype. Transfection of hsa-miR-345-5p antagomiR in heterozygous hFOB1.19 cells significantly increased the expression of osteogenic marker genes RUNX2, OSTERIX, COL1A1, ALP, OPN, OCN, and alkaline phosphatase activity and matrix mineralization level. Importantly, we found that hsa-miR-345-5p also inhibits osteoblast maturation in cell lines U-2OS with hsa-miR-345-5p nonbinding C/C genotype by targeting RUNX3 and SMAD1. Our findings uncovered a novel pathogenetic mechanism of osteoporosis by GWAS variant c.3781C>A-mediated disruption of hsa-miR-345-5p binding at the 3'-UTR of USF3 and the functional role of hsa-miR-345-5p in osteogenic differentiation.


Assuntos
Alelos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , MicroRNAs/genética , Osteoporose/diagnóstico , Osteoporose/genética , Regiões 3' não Traduzidas , Diferenciação Celular/genética , Linhagem Celular , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Genes Reporter , Humanos , Conformação de Ácido Nucleico , Osteoblastos/citologia , Osteoblastos/metabolismo , Interferência de RNA , RNA Mensageiro/genética , Transcriptoma
19.
Hum Genet ; 138(2): 151-166, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30661131

RESUMO

Previous genome-wide linkage and association studies have identified an osteoporosis-associated locus at 1p36 that harbors SNPs rs34920465 and rs6426749. The 1p36 locus also comprises the WNT4 gene with known role in bone metabolism and functionally unknown ZBTB40/lncRNA ZBTB40-IT1 genes. How these might interact to contribute to osteoporosis susceptibility is not known. In this study, we show that lncRNA ZBTB40-IT1 is able to suppress osteogenesis and promote osteoclastogenesis by regulating the expression of WNT4, RUNX2, OSX, ALP, COL1A1, OPG and RANKL in U-2OS and hFOB1.19 cell lines, whereas ZBTB40 plays an opposite role in bone metabolism. Treatment with parathyroid hormone significantly downregulates the expression of ZBTB40-IT1 in U-2OS cell lines. ZBTB40 can suppress ZBTB40-IT1 expression but has no response to parathyroid hormone treatment. Dual-luciferase assay and biotin pull-down assay demonstrate that osteoporosis GWAS lead SNPs rs34920465-G and rs6426749-C alleles can respectively bind transcription factors JUN::FOS and CREB1, and upregulate ZBTB40 and ZBTB40-IT1 expression. Our study discovers the critical role of ZBTB40 and lncRNA ZBTB40-IT1 in bone metabolism, and provides a mechanistic basis for osteoporosis GWAS lead SNPs rs34920465 and rs6426749.


Assuntos
Regulação da Expressão Gênica , Predisposição Genética para Doença , Osteogênese/genética , Osteoporose , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante , Alelos , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/biossíntese , Proteínas de Ligação a DNA/genética , Estudo de Associação Genômica Ampla , Células HEK293 , Humanos , Osteoporose/genética , Osteoporose/metabolismo , Osteoporose/patologia , Hormônio Paratireóideo/metabolismo , Hormônio Paratireóideo/farmacologia , RNA Longo não Codificante/biossíntese , RNA Longo não Codificante/genética
20.
Sci Rep ; 8(1): 16635, 2018 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-30413776

RESUMO

Dryopteris fragrans (L.) Schott is a fern growing on the surface of hot rocks and lava. It is exposed to sunlight directly and bears local hot environment. We sequenced the complete nucleotide sequence of its chloroplast (cp) genome. The cp genome was 151,978 bp in length, consisting of a large single-copy region (85,332 bp), a small single-copy region (31,947 bp) and a pair of inverted repeats (17,314 bp). The cp genome contained 112 genes and 345 RNA editing sites in protein-coding genes. Simple sequence repeats (SSRs) and long repeat structure pairs (30-55 bp) were identified. The number and percent of repeat structures are extremely high in ferns. Thermal denaturation experiments showed its cp genome to have numerous, dispersed and high GC percent repeat structures, which conferred the strongest thermal stability. This repeat-heavy genome may provide the molecular basis of how D. fragrans cp survives its hot environment.


Assuntos
Cloroplastos/genética , Dryopteris/genética , Genes de Cloroplastos , Genoma de Cloroplastos , Repetições de Microssatélites , Temperatura , Sequenciamento Completo do Genoma/métodos , Dryopteris/crescimento & desenvolvimento , Evolução Molecular , Anotação de Sequência Molecular , Filogenia , Edição de RNA
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