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1.
Plant Cell Environ ; 47(3): 871-884, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38164043

RESUMO

Symbiotic nitrogen fixation (SNF) is a crucial process for nitrogen geochemical cycling and plant-microbe interactions. Water-soluble humic acid (WSHM), an active component of soil humus, has been shown to promote SNF in the legume-rhizobial symbiosis, but its molecular mechanism remains largely unknown. To reveal the SNF-promoting mechanism, we conducted transcriptomic analysis on soybean treated with WSHM. Our findings revealed that up- and downregulated differentially expressed genes (DEGs) were mainly involved in plant cell-wall/membrane formation and plant defence/immunity in the early stage, while the late stage was marked by the flavonoid synthesis and ethylene biosynthetic process. Further study on representative DEGs showed that WSHM could inhibit GmBAK1d-mediated immunity and BR signalling, thereby promoting rhizobial colonisation, infection, and nodulation, while not favoring pathogenic bacteria colonisation on the host plant. Additionally, we also found that the ethylene pathway is necessary for promoting the soybean nodulation by WSHM. This study not only provides a significant advance in our understanding of the molecular mechanism of WSHM in promoting SNF, but also provides evidence of the beneficial interactions among the biostimulator, host plant, and soil microbes, which have not been previously reported.


Assuntos
Glycine max , Rhizobium , Nodulação , Substâncias Húmicas , Fixação de Nitrogênio , Etilenos/metabolismo , Imunidade Vegetal , Simbiose , Nódulos Radiculares de Plantas/microbiologia
2.
Plant Dis ; 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39254851

RESUMO

Bacterial blight caused by Pseudomonas syringae pv. glycines (Psg) is a widespread foliar disease. Although four Resistance to Pseudomonas syringae pv. glycinea (Rpg) 1 ~ 4 (Rpg1~4) genes that have been observed to segregate in a Mendelian pattern have been reported to confer resistance to Psg in soybean, the genetic basis of quantitative resistance to bacterial blight in soybean remains unclear. In the present study, the Psg resistance of two soybean association panels consisting of 573 and 213 lines, respectively, were phenotyped in multiple environments in 2014 - 2016. Genome-wide association study (GWAS) were performed using 2 models FarmCPU and BLINK to identify Psg resistance loci. A total of 40 soybean varieties with high level of Psg resistance were identified, and 14 quantitative trait loci (QTLs) were detected on 12 soybean chromosomes. These QTLs were identified for the first time. The majority of the QTLs were only detected in one or the other association panels, while qRPG-18-1 was detected in both association panels for at least one growing season. A total of 46 candidate Psg resistance genes were identified from the qRpg_13_1, qRPG-15-1, and qRPG-18-1 loci based on gene function annotation. In addition, we found the genomic region covering rpg1-b and rpg1-r harbored the synteny with a genomic region on chromosome 15, and identified 16 nucleotide binding site - leucine-rich repeat (NBS-LRR) genes as the candidate Psg resistance genes from the synteny blocks. This study provides new information for dissecting the genetic control of Psg resistance in soybean.

3.
Nucleic Acids Res ; 49(D1): D677-D686, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33095861

RESUMO

Essential genes refer to genes that are required by an organism to survive under specific conditions. Studies of the minimal-gene-set for bacteria have elucidated fundamental cellular processes that sustain life. The past five years have seen a significant progress in identifying human essential genes, primarily due to the successful use of CRISPR/Cas9 in various types of human cells. DEG 15, a new release of the Database of Essential Genes (www.essentialgene.org), has provided major advancements, compared to DEG 10. Specifically, the number of eukaryotic essential genes has increased by more than fourfold, and that of prokaryotic ones has more than doubled. Of note, the human essential-gene number has increased by more than tenfold. Moreover, we have developed built-in analysis modules by which users can perform various analyses, such as essential-gene distributions between bacterial leading and lagging strands, sub-cellular localization distribution, enrichment analysis of gene ontology and KEGG pathways, and generation of Venn diagrams to compare and contrast gene sets between experiments. Additionally, the database offers customizable BLAST tools for performing species- and experiment-specific BLAST searches. Therefore, DEG comprehensively harbors updated human-curated essential-gene records among prokaryotes and eukaryotes with built-in tools to enhance essential-gene analysis.


Assuntos
Bases de Dados Genéticas , Genes Essenciais , Humanos
4.
Int J Mol Sci ; 24(4)2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36835600

RESUMO

Domain of unknown function (DUF) is a general term for many uncharacterized domains with two distinct features: relatively conservative amino acid sequence and unknown function of the domain. In the Pfam 35.0 database, 4795 (24%) gene families belong to the DUF type, yet, their functions remain to be explored. This review summarizes the characteristics of the DUF protein families and their functions in regulating plant growth and development, generating responses to biotic and abiotic stress, and other regulatory roles in plant life. Though very limited information is available about these proteins yet, by taking advantage of emerging omics and bioinformatic tools, functional studies of DUF proteins could be utilized in future molecular studies.


Assuntos
Biologia Computacional , Proteínas , Proteínas/genética , Plantas , Sequência de Aminoácidos , Estresse Fisiológico , Proteínas de Plantas/genética , Regulação da Expressão Gênica de Plantas
5.
J Sep Sci ; 45(9): 1514-1524, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35178864

RESUMO

A magnetic solid phase extraction method based on magnetic covalent organic frameworks (TpBD@Fe3 O4 ; 2,4,6-triformylphloroglucinol (Tp) and benzidine (BD)) combined with high performance liquid chromatography has been developed to detect the sulfonamides including sulfadiazine, sulfamerazine, sulfamethazine, and sulfamethoxazole in milk and meat. TpBD@Fe3 O4 were synthesized at room temperature under mild reaction conditions with a simple and rapid operation. The TpBD@Fe3 O4 exhibited higher extraction efficiency because of the π-π and electrostatic interactions between the benzene ring structure of the TpBD and the sulfonamide molecules. The extraction conditions including the dosage of adsorbents, the type and dosage of eluent, the elution time, and the pH of the sample solution were fully optimized. The detection results showed good linearity over a wide range (50-5 × 104 ng/mL) and low detection limits (3.39-5.77 ng/mL) for the sulfonamide targets. The practicability of this magnetic solidphase extraction-high-performance liquid chromatography method was further evaluated by analyzing milk and meat samples, with recoveries of the targets of 71.6-110.8% in milk and 71.9-109.7% in pork. The successful detection of sulfonamides residues has demonstrated the TpBD@Fe3 O4 excellent practical potential for analyzing pharmaceutical residues in animal-derived foods.


Assuntos
Estruturas Metalorgânicas , Animais , Cromatografia Líquida de Alta Pressão/métodos , Contaminação de Alimentos/análise , Limite de Detecção , Fenômenos Magnéticos , Estruturas Metalorgânicas/química , Extração em Fase Sólida/métodos , Sulfonamidas/análise , Temperatura
6.
Pharmacol Res ; 165: 105457, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33515706

RESUMO

Microglia-mediated neuroinflammatory response and neuron damage are considered as a self-propelling progressive cycle, being strongly implicated in the progression of neurodegeneration in amyotrophic lateral sclerosis (ALS). Diphenyl diselenide (DPDS), a simple organoselenium compound, has been known to possess multiple pharmacological properties. The purpose of this study was to explore the neuroprotective effects of DPDS against microglia-mediated neuroinflammatory injury in ALS models. We found that DPDS pretreatment inhibited LPS-induced activation of IκB/NF-κB pathway and subsequent release of proinflammatory factors from activated primary hSOD1G93A microglia. Moreover, DPDS suppressed NLRP3 inflammasome activation by decreasing protein nitration via reduction in NO and ROS levels, whose low levels are related to NF-κB inhibition responsible for iNOS and NOX2 down-regulations, respectively. Notably, DPDS-mediated ROS attenuation was not linked to Nrf2 activation in this cellular model. Furthermore, in the absence of activated microglia, DPDS has no significant effect on the individual hSOD1G93A-NSC34 cells; however, in in vitro neuron-microglia conditional culture and co-culture experiments, DPDS protected motor neurons from neurotoxic damage caused by LPS or BzATP-stimulated microglia activation. Above observations suggest that DPDS-afforded neuroprotection is linked to inhibition of microglia-mediated neuroinflammation in ALS, which was further verified in vivo as shown by improvements of motor deficits, prolonged survival, and reduction of motor neuron loss and reactive microgliosis in hSOD1G93A transgenic mouse. Altogether, our results show that DPDS elicited neuroprotection in ALS models through inactivation of microglia by inhibiting IκB/NF-κB pathway and NLRP3 inflammasome activation, suggesting that DPDS may be a promising candidate for potential therapy for ALS.


Assuntos
Esclerose Lateral Amiotrófica/prevenção & controle , Derivados de Benzeno/uso terapêutico , Mediadores da Inflamação/antagonistas & inibidores , Microglia/efeitos dos fármacos , Neurônios Motores/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Compostos Organosselênicos/uso terapêutico , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/metabolismo , Animais , Derivados de Benzeno/farmacologia , Linhagem Celular , Células Cultivadas , Relação Dose-Resposta a Droga , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Microglia/metabolismo , Neurônios Motores/metabolismo , Fármacos Neuroprotetores/farmacologia , Compostos Organosselênicos/farmacologia , Superóxido Dismutase-1/genética
7.
Analyst ; 146(6): 1965-1972, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33496685

RESUMO

Among antibacterial nanomaterials, carbon dots (CDs) have attracted much attention because of their unique physical and chemical properties and good biosafety. In this study, kanamycin sulfate (Kan), a broad-spectrum antibiotic, was used to synthesize novel carbon dots (CDs-Kan) by a one-step hydrothermal method. CDs-Kan showed good inhibitory effects on Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. Further, scanning electron microscopy revealed that treatment with CDs-Kan and Kan resulted in the same phenomena. In particular, the morphologies of S. aureus cells treated with CDs-Kan and Kan became smaller and irregular, whereas the surfaces of E. coli cells protruded and formed vesicles. These results indicated that CDs-Kan was shown to retain the good antibacterial activity of Kan as well as its main bactericidal functional groups, namely, the amino sugar and amino cyclic alcohol, We refer to this phenomenon as the "preservation property". We also found that CDs-Kan has good biocompatibility and nontoxic properties. Moreover, CDs-Kan was successfully applied to the biological imaging of fungi and plant cells. In addition, CDs-Kan could be used as a fluorescent probe for the quick, sensitive, and selective detection of Cr6+. Therefore, CDs-Kan not only retained the good bacteriostatic properties of Kan but also expanded its application in bioimaging and biosensors.


Assuntos
Carbono , Pontos Quânticos , Antibacterianos/toxicidade , Escherichia coli , Corantes Fluorescentes , Canamicina/farmacologia , Staphylococcus aureus
8.
Analyst ; 146(2): 683-690, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33210668

RESUMO

Carbon dots (CDs) have excellent application prospects in various fields such as fluorescent dyes, but expanding their application, especially in bioimaging and the detection of organic pollutants, is still a major research objective. In this study, fluorescent CDs were successfully synthesized via the hydrothermal method using Serratia marcescens KMR-3. The platform based on CDs-KMR3 exhibited excellent stability, good biocompatibility, and low biotoxicity, and can be effectively applied to the imaging of bacteria, fungi, plant cells, protozoa and mammalian cells, and can specifically stain the membranes of all tested cells. In this study, for the first time, bacteria-derived CDs were used to image the representative species of organisms ranging from lower-order to higher-order organisms, thereby proving the feasibility of the application of CDs in the fluorescence imaging of Paramecium caudatum. Additionally, CDs-KMR3 can rapidly diffuse into all the parts of the leaf through diffusion into the veins and intercellular interstitium in response to the induction of transpiration. Moreover, the data illustrate that CDs-KMR3 are likely to enter the digestive tracts of microworms by ingestion through the oral cavity and pharynx, and spread to the pseudocoelom and somatic cells, and finally to be excreted from microworms through the anus. Furthermore, this platform can be utilized as fluorescent probes for the rapid and highly selective detection of p-nitrophenol (p-NP). Moreover, this study contributed to the increased application of bacteria-derived CDs in bioimaging and detection of p-NP.


Assuntos
Carbono/química , Corantes Fluorescentes/química , Imagem Molecular/métodos , Nanopartículas/química , Nitrofenóis/análise , Imagem Óptica/métodos , Serratia marcescens/química , Células HeLa , Humanos , Limite de Detecção , Nitrofenóis/química , Nitrofenóis/metabolismo
9.
Analyst ; 146(3): 911-919, 2021 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-33237046

RESUMO

Carbon dots (CDs) and photoluminescent carbon dots (Pn-CDs) are promising nanomaterials due to their bioimaging applications and have attracted considerable attention because of their excellent stability, good biocompatibility, and low biotoxicity. Here, the Pn-CDs and highly fluorescent nitrogen-doped CDs (Pn N-CDs) derived from Panax notoginseng were successfully synthesized by a simple hydrothermal method. Pn N-CDs exhibit optical properties and stability superior to those of Pn-CDs and can be better used as fluorescent dyes and probes in biological imaging. The obtained Pn N-CDs can be effectively applied to the imaging of bacteria, fungi, plant cells, and protozoa. In addition, Pn N-CDs can perform specific staining on the membranes of all tested cells. The in vivo imaging of mice revealed that Pn N-CDs exhibit nontoxicity and good biocompatibility and biodistribution. Furthermore, Pn N-CDs can be utilized as fluorescent probes for the rapid and highly selective detection of Cr6+. Hence, a simple, cost-effective, scalable, and green synthetic approach based on traditional Chinese medicine-derived CDs can be used to develop biolabeling, membrane targeting, and optical sensing probes.


Assuntos
Panax notoginseng , Pontos Quânticos , Animais , Carbono , Corantes Fluorescentes/toxicidade , Camundongos , Nitrogênio , Pontos Quânticos/toxicidade , Distribuição Tecidual
10.
Neurobiol Dis ; 134: 104648, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31676238

RESUMO

Accumulation of DNA damage has been detected in the spinal cord of patients as well as in the G93A mouse model of amyotrophic lateral sclerosis (ALS). Wild-type p53-induced phosphatase 1 (Wip1) is a p53-inducible serine/threonine phosphatase that terminates DNA-damage responses via dephosphorylation of DNA-damage response proteins, namely ataxia-telangiectasia mutated (ATM) kinase, checkpoint kinase 2, and p53, thus enhancing cell proliferation. However, the role of Wip1, DNA-damage responses, and their interaction in ALS development remains to be elucidated. Here, we showed that Wip1 expression levels were substantially decreased in ALS motor neurons compared with wild-type controls both in vivo and in vitro. The DNA-damage response was activated in superoxide dismutase 1 (SOD1) G93A-transfected cells. However, increased expression of Wip1 improved cell viability and inhibited the DNA-damage response in mutated SOD1G93A cells. Further studies demonstrated that decreased Wip1 expression reduced cell viability and further activated the DNA-damage response in chronic H2O2-treated NSC34 cells. In contrast, Wip1 promoted cell survival and suppressed DNA damage-induced apoptosis during persistent DNA damage conditions. Over-expression of Wip1 in the central nervous system (CNS) can delay the onset of disease symptoms, extended the survival, decreased MN loss improved motor function and inhibit the DNA-damage response in SOD1 G93A mice. Furthermore, homeodomain-interacting protein kinase 2 (HIPK2) promoted the degradation of Wip1 via the ubiquitin-proteasome system during chronic stress. These findings indicate that persistent accumulation of DNA damage and subsequent chronic activation of the downstream DNA damage-response ATM and p53 pro-apoptotic signaling pathways may trigger neuronal dysfunction and neuronal death in ALS. Wip1 may play a protective role by targeting the DNA-damage response in ALS motor neurons. Importantly, these findings provide a novel direction for therapeutic options for patients with ALS.


Assuntos
Esclerose Lateral Amiotrófica/patologia , Dano ao DNA/fisiologia , Neurônios Motores/metabolismo , Proteína Fosfatase 2C/metabolismo , Transdução de Sinais/fisiologia , Esclerose Lateral Amiotrófica/metabolismo , Animais , Apoptose/fisiologia , Regulação para Baixo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurônios Motores/patologia
11.
Mol Biol Rep ; 46(6): 6299-6309, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31529340

RESUMO

Abnormally protein aggregation and deposition are key pathological features of ALS, which may related with dysfunctional cellular autophagy. In the current study, we found that, compared with wtSOD1 cells, serum starvation treatment resulted in significant higher percentage of apoptosis in mutSOD1 cells; Lithium treatment exerted protection for those mutSOD1 cells, with decreased GFP-tagged mutant SOD1 protein aggregates deposition; Whereas, pre-treatment with Baf or 3-MA (autophagy inhibitors) blocked protection of lithium for mutant SOD1 cells, and induced increased GFP-tagged mutant SOD1 protein aggregation. Further, Western blots results showed that lithium treatment led to decrease of mutant hSOD1 protein levels in both Triton X-100 soluble and Triton X-100 insoluble fraction of mutSOD1 cells. Besides, improper binding of mutant SOD1 proteins' aggregates with p-CREB (Ser133) (transcription factor) in mutSOD1 cells were demonstrated; whereas lithium treatment attenuated this fault interaction. In conclusion, our results showed that, in mutSOD1 cells, mutSOD1 protein aggregates were related with abnormal autophagic regulation. Lithium treatment could induce autophagy and enhance clearance of protein aggregates, further exerting protection on mutSOD1 cells. More importantly, we uncovered another distinct pathological role of mutSOD1 protein aggregates, that is abnormal binding with p-CREB (Ser133), an important transcription factor, which may play crucial role in the PI3K-Akt-CREB-AEG-1 signaling pathway.


Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Lítio/farmacologia , Mutação , Neurônios/citologia , Superóxido Dismutase-1/metabolismo , Animais , Autofagia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Camundongos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fosforilação , Dobramento de Proteína/efeitos dos fármacos , Transdução de Sinais , Superóxido Dismutase-1/química , Superóxido Dismutase-1/genética , Transfecção
12.
Mol Cell Neurosci ; 90: 1-11, 2018 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-29777762

RESUMO

AEG-1 has received extensive attention on cancer research. However, little is known about its roles in astrogliosis of Amyotrophic lateral sclerosis (ALS). In this study, we detected AEG-1 expression in hSOD1G93A-positive (mut-SOD1) astrocytes and wild type (wt-SOD1) astrocytes, and intend to elucidate its potential functions in ALS related astrogliosis and the always accompanied dysregulated glutamate clearance. Results showed elevated protein and mRNA levels of AEG-1 in mut-SOD1 astrocytes; Also, NF-κB signaling pathway related proteins and inflammatory cytokines were upregulated in mut-SOD1 astrocytes; AEG-1 knockdown attenuated astrocytes proliferation and pro-inflammatory release; also we found that AEG-1 silence inhibited translocation of p65 from cytoplasma to nuclear, which was associated with inhibited NF-κB signaling. Besides, excitatory amino acid transporter-2 (EAAT2) expression levels were significantly decreased, accompanied by impaired glutamate clearance ability, in mut-SOD1 astrocytes; yin yang 1 (YY1), a transcriptional inhibitor for EAAT2, increased in nucleus of mut-SOD1 astrocytes. AEG-1 silence inhibited translocation of YY1 to nucleus, increased EAAT2 expression levels, and enhanced astrocytic ability of glutamate clearance, ultimately exerted the neuronal protection. Findings from this study implicate potential function of AEG-1 in mut-SOD1 related astrogliosis and the accompanied excitatory cytotoxic mechanism in ALS.

13.
J Environ Manage ; 248: 109248, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31310939

RESUMO

Using firm establishment-level data combined with provincial socio-economic characteristic panel data in China for the period of 2011-2015, this study seeks to empirically examine the impact of environmental regulation on location choices of polluting firms. The results of the conditional logit model provide compelling evidence that environmental regulations do affect the location choice of firms in polluting industries. Instead of supporting the pollution haven effect, our results consistently confirm the Porter effect at the country level. This result is robust when taking endogeneity problem into account, adopting various model specifications and estimation strategies, using alternative measurements of environmental regulation and location choices, and subsampling excluding international political events. However, the results also show divergent effect of environmental regulation on location choices for heterogeneous firms. Specifically, polluting firms in eastern region prefer to invest in provinces with stringent environmental policies but those in other regions, especially in northeastern region, choose to locate in provinces with lax environmental regulation. While water-dependent polluting firms with a low level of footlooseness are more likely to enter locations with loose environmental regulation, air pollution-intensive firms tend to locate in provinces with tight environmental legislation. These results have policy implications for transitional China as well as other developing countries with similar experience.


Assuntos
Poluição do Ar , Poluição Ambiental , China , Política Ambiental , Indústrias
14.
Nucleic Acids Res ; 42(Database issue): D574-80, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24243843

RESUMO

The combination of high-density transposon-mediated mutagenesis and high-throughput sequencing has led to significant advancements in research on essential genes, resulting in a dramatic increase in the number of identified prokaryotic essential genes under diverse conditions and a revised essential-gene concept that includes all essential genomic elements, rather than focusing on protein-coding genes only. DEG 10, a new release of the Database of Essential Genes (available at http://www.essentialgene.org), has been developed to accommodate these quantitative and qualitative advancements. In addition to increasing the number of bacterial and archaeal essential genes determined by genome-wide gene essentiality screens, DEG 10 also harbors essential noncoding RNAs, promoters, regulatory sequences and replication origins. These essential genomic elements are determined not only in vitro, but also in vivo, under diverse conditions including those for survival, pathogenesis and antibiotic resistance. We have developed customizable BLAST tools that allow users to perform species- and experiment-specific BLAST searches for a single gene, a list of genes, annotated or unannotated genomes. Therefore, DEG 10 includes essential genomic elements under different conditions in three domains of life, with customizable BLAST tools.


Assuntos
Bases de Dados Genéticas , Genes Essenciais , Proteínas/genética , Animais , Eucariotos/genética , Genoma Arqueal , Genoma Bacteriano , Genômica , Internet , Camundongos , RNA não Traduzido/genética , Sequências Reguladoras de Ácido Nucleico , Alinhamento de Sequência , Software
15.
Int J Mol Sci ; 17(12)2016 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-27999308

RESUMO

BACKGROUND: Mutations in the Cu/Zn superoxide dismutase (SOD1) gene have been linked to amyotrophic lateral sclerosis (ALS). However, the molecular mechanisms have not been elucidated yet. Homer family protein Homer1b/c is expressed widely in the central nervous system and plays important roles in neurological diseases. In this study, we explored whether Homer1b/c was involved in SOD1 mutation-linked ALS. RESULTS: In vitro studies showed that the SOD1 G93A mutation induced an increase of Homer1b/c expression at both the mRNA and protein levels in NSC34 cells. Knockdown of Homer1b/c expression using its short interfering RNA (siRNA) (si-Homer1) protected SOD1 G93A NSC34 cells from apoptosis. The expressions of Homer1b/c and apoptosis-related protein Bax were also suppressed, while Bcl-2 was increased by lithium and valproic acid (VPA) in SOD1 G93A NSC34 cells. In vivo, both the mRNA and protein levels of Homer1b/c were increased significantly in the lumbar spinal cord in SOD1 G93A transgenic mice compared with wild type (WT) mice. Moreover, lithium and VPA treatment suppressed the expression of Homer1b/c in SOD1 G93A mice. CONCLUSION: The suppression of SOD1 G93A mutation-induced Homer1b/c upregulation protected ALS against neuronal apoptosis, which is a novel mechanism of the neuroprotective effect of lithium and VPA. This study provides new insights into pathogenesis and treatment of ALS.


Assuntos
Esclerose Lateral Amiotrófica/terapia , Proteínas de Arcabouço Homer/biossíntese , Lítio/uso terapêutico , Superóxido Dismutase/genética , Ácido Valproico/uso terapêutico , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/patologia , Animais , Apoptose/genética , Linhagem Celular , Predisposição Genética para Doença , Proteínas de Arcabouço Homer/antagonistas & inibidores , Proteínas de Arcabouço Homer/genética , Humanos , Camundongos , Camundongos Transgênicos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Interferência de RNA , RNA Interferente Pequeno/genética
16.
Cardiovasc Diabetol ; 14: 79, 2015 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-26068179

RESUMO

BACKGROUND: As a first-line diabetes drug that is widely prescribed around the world, metformin has been demonstrated to be effective in reducing microvascular risk, in addition to lowering glucose levels. Specifically, metformin use has been shown to be associated with improved lipid profiles, such as increased levels of high-density lipoprotein cholesterol (HDL-C). However, no study has been performed to examine the differential response in HDL-C levels to metformin treatment by race/ethnicity. METHODS: Here, based on a re-analysis of the data from the Diabetes Prevention Program, which involved pre-diabetic participants receiving 850 mg of metformin twice daily, we compared the lipid profile changes following the metformin use. The participants were composed of 602 Whites, 221 African Americans (AAs) and 162 Hispanics. RESULTS: We found that the one-year metformin treatment resulted in a significant increase in HDL-C levels in Whites (p = 0.002) and AAs (p = 0.016), but not in Hispanics. Consistently, both Whites (p = 0.018) and AAs (p = 0.020) had more pronounced changes in HDL-C levels than Hispanics following metformin treatment. CONCLUSION: This result suggests a notion that Whites and AAs are more responsive than Hispanics to one-year metformin use in HDL-C level changes, and that racial and ethnic identity is a factor to consider when interpreting the effects of metformin treatment on lipid profiles.


Assuntos
HDL-Colesterol/sangue , Etnicidade , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Estado Pré-Diabético/tratamento farmacológico , Adulto , Negro ou Afro-Americano , Estudos de Coortes , Feminino , Hispânico ou Latino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Estado Pré-Diabético/sangue , Estado Pré-Diabético/complicações , Comportamento de Redução do Risco , Resultado do Tratamento , População Branca
17.
Nucleic Acids Res ; 41(Database issue): D90-3, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23093601

RESUMO

Replication of chromosomes is one of the central events in the cell cycle. Chromosome replication begins at specific sites, called origins of replication (oriCs), for all three domains of life. However, the origins of replication still remain unknown in a considerably large number of bacterial and archaeal genomes completely sequenced so far. The availability of increasing complete bacterial and archaeal genomes has created challenges and opportunities for identification of their oriCs in silico, as well as in vivo. Based on the Z-curve theory, we have developed a web-based system Ori-Finder to predict oriCs in bacterial genomes with high accuracy and reliability by taking advantage of comparative genomics, and the predicted oriC regions have been organized into an online database DoriC, which is publicly available at http://tubic.tju.edu.cn/doric/ since 2007. Five years after we constructed DoriC, the database has significant advances over the number of bacterial genomes, increasing about 4-fold. Additionally, oriC regions in archaeal genomes identified by in vivo experiments, as well as in silico analyses, have also been added to the database. Consequently, the latest release of DoriC contains oriCs for >1500 bacterial genomes and 81 archaeal genomes, respectively.


Assuntos
Bases de Dados de Ácidos Nucleicos , Genoma Arqueal , Genoma Bacteriano , Origem de Replicação , DNA Arqueal/química , DNA Bacteriano/química , Internet
18.
J Neurooncol ; 119(1): 49-58, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24792491

RESUMO

The Fyn related kinase (FRK) is a noteworthy member of the Src non-receptor tyrosine kinase family for its distinctive tumor suppressive function. Recently, we have shown that FRK plays a protective role against the progression of glioma by suppressing cell migration and invasion. However, it is unclear whether the cell growth of glioma is also regulated by FRK and by which mechanism FRK alters its specific biological functions. In the current study, we found that FRK over-expression significantly suppressed the proliferation of glioma cells. In contrast, FRK knockdown by siRNA promoted glioma cell growth. In addition, FRK over-expression caused G1 phase arrest as well as apoptosis of glioma cells. Further investigation disclosed that FRK-induced G1 arrest was accompanied by down-regulation of hyperphosphorylated retinoblastoma protein (pRb), which led to the consequent suppression of E2F1. More importantly, we found that over-expression of FRK inhibited proper cyclin D1 accumulation in the nucleus of proliferating cells. Taken together, our results demonstrate a combined mechanism for the anti-proliferative effects of FRK by inhibiting cyclin D1 nucleus accumulation and pRb phosphorylation in glioma cells.


Assuntos
Neoplasias Encefálicas/metabolismo , Núcleo Celular/metabolismo , Proliferação de Células/fisiologia , Ciclina D1/metabolismo , Glioma/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Tirosina Quinases/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Regulação para Baixo , Fase G1 , Glioma/patologia , Humanos , Fosforilação , Proteína do Retinoblastoma/metabolismo , Transdução de Sinais/fisiologia
19.
Curr Genomics ; 15(2): 78-94, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24822026

RESUMO

In theoretical physics, there exist two basic mathematical approaches, algebraic and geometrical methods, which, in most cases, are complementary. In the area of genome sequence analysis, however, algebraic approaches have been widely used, while geometrical approaches have been less explored for a long time. The Z-curve theory is a geometrical approach to genome analysis. The Z-curve is a three-dimensional curve that represents a given DNA sequence in the sense that each can be uniquely reconstructed given the other. The Z-curve, therefore, contains all the information that the corresponding DNA sequence carries. The analysis of a DNA sequence can then be performed through studying the corresponding Z-curve. The Z-curve method has found applications in a wide range of areas in the past two decades, including the identifications of protein-coding genes, replication origins, horizontally-transferred genomic islands, promoters, translational start sides and isochores, as well as studies on phylogenetics, genome visualization and comparative genomics. Here, we review the progress of Z-curve studies from aspects of both theory and applications in genome analysis.

20.
Diabetes Metab Syndr Obes ; 17: 2975-2981, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39139740

RESUMO

Introduction: Dyslipidemia commonly complicates type 2 diabetes mellitus, yet the relationship between glycosylated hemoglobin and blood lipid levels remains uncertain. Methods: This retrospective cross-sectional study included 27,158 participants from the People's Hospital of Yuxi. Statistical comparisons for continuous variables utilized analysis of variance (ANOVA), while chi-square analysis was employed for categorical variables. Boxplots assessed the concentration, dispersion, and deviation of total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C) distribution. A linear regression analysis examined the association between HbA1c and lipid profile, complemented by a fitting curve to visualize trends. Results: Participants who developed diabetes exhibited higher age and elevated Body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), TC, TG, LDL-C, and FPG levels compared to those without diabetes (p < 0.001). Linear regression analysis demonstrated significant associations between HbA1c values and TC, TG, LDL-C, and HDL-C (p < 0.001). The plotted curve indicated that as TC, TG, and LDL levels increased, HbA1c levels rose, while HDL levels decreased. Conclusion: HbA1c was positively correlated with TC, TG, LDL-C, and negatively correlated with HDL-C in the population in the central Yunnan Plateau.

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