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1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1566-1569, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34627441

RESUMO

OBJECTIVE: To clarify the significance of inflammasome NLRP3 in children with immune thrombocytopenia (ITP) by detecting its changes before and after treatment. METHODS: Twenty children with ITP diagnosed and treated in Xuzhou Children's Hospital were enrolled as observation group, and 10 healthy children as control group. The mRNA levels of NLRP3, ASC, and Caspase-1 were measured by real-time quantitative PCR (RT-qPCR), the serum levels of IL-18, IL-1ß, and high mobility group protein B1 (HMGB1) were detected by ELISA, and the protein level of NLRP3 was detected by Western blot. RESULTS: In newly diagnosed ITP children, the serum levels of IL-18, IL-1ß and HMGB1 significantly decreased after treatment (P<0.05). After treatment, NLRP3, ASC, and Caspase-1 mRNA levels in peripheral blood mononuclear cells were significantly lower than those before treatment (P<0.05). NLRP3 protein expression decreased significantly after treatment. CONCLUSION: Expression of NLRP3 inflammasome and downstream inflammatory factors are decrease after treatment in children with ITP, which may be used as effective prognostic markers.


Assuntos
Proteína HMGB1 , Púrpura Trombocitopênica Idiopática , Criança , Humanos , Inflamassomos , Leucócitos Mononucleares , Proteína 3 que Contém Domínio de Pirina da Família NLR
2.
Artigo em Inglês | MEDLINE | ID: mdl-34609929

RESUMO

Background: Genome-wide association studies (GWASs) have identified many genetic variants that are risk factors for numerous immune-mediated diseases. In particular, different immune-mediated diseases have been found to share the same susceptibility loci. Therefore, exploring the overlap between atopic dermatitis (AD) and other immune-mediated diseases in more detail may help identify additional common susceptibility loci shared by the common immune-mediated diseases. The latest evidence suggests that the 11q23.3 locus is a susceptibility locus shared between multiple immune-mediated diseases. Objective: This study investigated whether 11q23.3 locus single nucleotide polymorphisms (SNPs) are also associated with AD in the Han Chinese population. Methods: In total, 16 SNPs at 11q23.3 were genotyped using TaqMan genotyping assays in 1012 AD cases and 1362 controls. Among these SNPs, we selected rs638893 with association values of p < 5 × 10-2 for AD for further replication in the independent replication samples (1288 cases and 1380 controls) using the Sequenom MassARRAY system. The combined analyses were performed in two stages using a meta-analytical method. Results: We identified that a common variant at 11q23.3 (rs638893, p = 1.58 × 10-3, OR = 1.22) was significantly associated with AD. The genotype-based association analysis revealed that the recessive model provided the best fit for rs638893. Conclusion: Our study identified a novel variant on chromosome 11q23.3 that confers susceptibility to AD, thereby advancing our understanding of the genetic basis of AD.

3.
Biochem Pharmacol ; : 114793, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34600916

RESUMO

Uveitis is one of the most common blindness-causing ocular disorders. Due to its complicated pathogenesis, the treatment of uveitis has been widely recognized as a challenge for ophthalmologists. Recently, the anti-inflammatory properties of the antibiotic Azithromycin (AZM) have been reported. However, the therapeutic effects of Azithromycin in experimental autoimmune uveitis (EAU), a representative model of human AU, have not been elucidated till date. We conducted this study to examine the therapeutic effects and potential mechanisms of Azithromycin in EAU. We observed that Azithromycin significantly attenuated retinal inflammation in EAU mice at day 14 after immunization along with a significantly decreased inflammatory cell infiltration and cytokine production in the retina. Furthermore, we observed that Azithromycin increased the number of regulatory T cells (Treg) and decreased the number of effector T cells (Teff) in both the draining lymph nodes and spleen of EAU mice. Additionally, Azithromycin suppressed the proliferation and activation of CD4+T cells, and induced the apoptosis of CD4+CD44+ memory T and CD4+CXCR3+ Th1 cells. Mechanistically, we proved that Azithromycin could regulate Teff/Treg balance by inhibiting the phosphorylation of S6 ribosomal protein, a downstream target of mammalian target of rapamycin (mTOR). Together, our findings revealed that Azithromycin alleviated EAU by regulating the Teff/Treg balance through the mTOR signalling pathway, suggesting that Azithromycin could be a promising therapeutic candidate for AU.

4.
BMC Genomics ; 22(1): 682, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34548036

RESUMO

BACKGROUND: BES/BZR family genes have vital roles in plant growth, development, and adaptation to environmental stimuli. However, they have not yet been characterized and systematically analyzed in wheat and foxtail millet. RESULTS: In the current study, five common and two unique BES/BZR genes were identified by genome-wide analysis in wheat and foxtail millet, respectively. These genes were unevenly distributed on 14 and five chromosomes of wheat and foxtail millet, respectively, and clustered in two subgroups in a phylogenetic analysis. The BES/BZR gene family members in each subgroup contained similar conserved motifs. Investigation of cis-acting elements and expression profile analysis revealed that the BES/BZR genes were predominantly expressed in leaf tissues of wheat and foxtail millet seedlings and responded to brassinosteroid, abscisic acid, and NaCl treatments. CONCLUSIONS: Our results provide a basis for future studies on the function and molecular mechanisms of the BES/BZR gene family in wheat, foxtail millet, and other plants.


Assuntos
Setaria (Planta) , Ácidos Alcanossulfônicos , Regulação da Expressão Gênica de Plantas , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Setaria (Planta)/genética , Setaria (Planta)/metabolismo , Triticum/genética , Triticum/metabolismo
5.
Am J Hum Genet ; 108(9): 1647-1668, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34416157

RESUMO

Interpretation of the function of non-coding risk loci for neuropsychiatric disorders and brain-relevant traits via gene expression and alternative splicing quantitative trait locus (e/sQTL) analyses is generally performed in bulk post-mortem adult tissue. However, genetic risk loci are enriched in regulatory elements active during neocortical differentiation, and regulatory effects of risk variants may be masked by heterogeneity in bulk tissue. Here, we map e/sQTLs, and allele-specific expression in cultured cells representing two major developmental stages, primary human neural progenitors (n = 85) and their sorted neuronal progeny (n = 74), identifying numerous loci not detected in either bulk developing cortical wall or adult cortex. Using colocalization and genetic imputation via transcriptome-wide association, we uncover cell-type-specific regulatory mechanisms underlying risk for brain-relevant traits that are active during neocortical differentiation. Specifically, we identified a progenitor-specific eQTL for CENPW co-localized with common variant associations for cortical surface area and educational attainment.


Assuntos
Proteínas Cromossômicas não Histona/genética , Regulação da Expressão Gênica no Desenvolvimento , Neocórtex/metabolismo , Neurogênese/genética , Neurônios/metabolismo , Locos de Características Quantitativas , Alelos , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Diferenciação Celular , Cromatina/química , Cromatina/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Mapeamento Cromossômico , Escolaridade , Feminino , Feto , Predisposição Genética para Doença , Genoma Humano , Estudo de Associação Genômica Ampla , Humanos , Masculino , Neocórtex/citologia , Neocórtex/crescimento & desenvolvimento , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Neurônios/citologia , Neuroticismo , Doença de Parkinson/diagnóstico , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Cultura Primária de Células , Prognóstico , Esquizofrenia/diagnóstico , Esquizofrenia/genética , Esquizofrenia/metabolismo , Transcriptoma
6.
Ocul Surf ; 22: 103-109, 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34333155

RESUMO

PURPOSE: To investigate the safety and feasibility of topical injection of bone marrow derived mesenchymal stem cells (BM-MSCs) in acute severe ocular burns. METHODS: In this open-label,single-arm study, subconjunctival injection of allogenic BM-MSCs combined with standard treatment was given to 16 patients with acute severe ocular burns (Dua's grade IV to VI) within 2 weeks after injury. The primary outcome was efficacy rate which referred to the proportion of complete corneal epithelialization patients without perforation. The secondary outcome was safety, visual acuity, the number of symblephara, and elevated intraocular pressure. RESULTS: One patient was lost to follow-up. During the follow-up period, no corneal perforation was developed. Complete corneal epithelialization was noted 8 (ranged 4-10 weeks) weeks after treatment in 13 eyes (81.3%). The efficacy rate was 87.5% (95% confidence interval, CI: 61.7-98.4). Hypopyon was detected and later well controlled in 1 eye. Partial or total limbal stem cell deficiency (LSCD) was noted in all eyes. Improvement of visual acuity was achieved in 5 out of 16 eyes (31.3%). Seven eyes' visual acuity was reached 0.1. Symblepharon with varied severity was noted in 5 eyes. Two eyes had elevated intraocular pressure. CONCLUSIONS: This study confirms the safety of subconjunctival injection of BM-MSCs as an innovative and convenient procedure in ocular burns. The overall result is promising considering the absence of perforation, the low severity of symblepharon and visual acuity improvement.

7.
Nanoscale Res Lett ; 16(1): 130, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34387780

RESUMO

Water electrolysis is a sustainable and clean method to produce hydrogen fuel via hydrogen evolution reaction (HER). Using stable, effective and low-cost electrocatalysts for HER to substitute expensive noble metals is highly desired. In this paper, by using first-principles calculation, we designed a defect and N-, S-, P-doped penta-graphene (PG) as a two-dimensional (2D) electrocatalyst for HER, and its stability, electronic properties and catalytic performance were investigated. The Gibbs free energy (ΔGH), which is the best descriptor for the HER, is calculated and optimized, the calculation results show that the ΔGH can be 0 eV with C2 vacancies and P doping at C1 active sites, which should be the optimal performance for a HER catalyst. Moreover, we reveal that the larger charge transfer from PG to H, the closer ΔGH is to zero according to the calculation of the electron charge density differences and Bader charges analysis. Ulteriorly, we demonstrated that the HER performance prefers the Volmer-Heyrovsky mechanism in this study.

8.
Ann Palliat Med ; 10(8): 8651-8664, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34328016

RESUMO

BACKGROUND: Drug-induced liver injury (DILI) has become one of the most common and serious adverse drug reactions owing to its high morbidity and leading cause of hepatic failures, which had attracted great attentions worldwide in the past two decades. A need therefore exists to conduct a bibliometric and visualized analysis of the global research trends on DILI with the aim of identifying the status of current research and prioritize the future research areas. METHODS: Publications related to DILI from 1999 to 2019 were extracted through an electronic search of the Web of Science (WoS) and PubMed databases. VOSviewer software was used to perform visualized analysis of bibliographic coupling, co-authorship, co-citation and co-occurrence, and to assess the global trends. RESULTS: Totally of 6,563 publications were identified based on the inclusion criteria. It is noted that the global trends of literatures on DILI showed a significant increase over time and more importantly predict the relevant publications will rise continuously in the coming decades. The United States led in terms of publication numbers with the most citations (the highest H-index). Hepatology made great contributions to the highest H-index and the most citations of publications. University of North Carolina was regarded as the most contributive institution. Notably, after conducting co-occurrence and cluster analysis of keywords and citation networks, it is shown that the pathogenesis, clinical manifestations, diagnosis and risk factors of this field will become the most prominent research hotspots. CONCLUSIONS: The mapping results provides global development trends of publications on DILI from 1999 to 2019. Future studies focused on the diagnosis and predisposing factors of this field will be encouraged.


Assuntos
Bibliometria , Doença Hepática Induzida por Substâncias e Drogas , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Bases de Dados Factuais , Humanos , Estados Unidos
9.
J Anim Ecol ; 2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34245566

RESUMO

Describing the patterns and revealing the underlying mechanisms responsible for variations in community structure remain a central focus in ecology. However, important gaps remain, including our understanding of species abundance. Most studies on abundance-based relationships are from either temperate ecosystems or tropical ecosystems, and few have explicitly tested abundance-based relationships across a temperate to tropical ecotone. Here, we use a comprehensive dataset of breeding birds across elevation spanning a temperate to subtropical gradient in the Himalayas-Hengduan Mountains of China to examine the relationship between species abundance and (a) elevational range size, (b) body size, (c) elevational range centre and (d) endemicity. We tested a priori predictions for abundance-elevational range size relationship, abundance-body size relationship and abundance-elevational range centre relationship, and explored how these relationships change along this temperate to subtropical mountain ecosystem. We found that species abundance was significantly positively correlated with elevational range size across the study sites, demonstrating the key importance of elevational range size towards species abundance. Body size and elevational range centre are weakly correlated with abundance. A novel finding of our study is that the abundance-elevational range size relationship gradually weakened from temperate to subtropical ecosystems, adding to a growing body of evidence suggesting that abundance-elevational range size tracks a temperate to tropical ecotone. Our study demonstrates that abundance range-size relationship can transition across ecotones where faunas of different evolutionary origins converge. Furthermore, measuring abundance relationships across different environmental variables at the same spatial scale with comparable biogeography is a key strategy that can reveal the underlying mechanisms behind abundance patterns.

10.
Hum Genet ; 140(9): 1367-1377, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34255152

RESUMO

Spermatozoa are polarized cells with a head and a flagellum joined together by the connecting piece. Flagellum integrity is critical for normal sperm function, and flagellum defects consistently lead to male infertility. Multiple morphological abnormalities of the flagella (MMAF) is a distinct sperm phenotype consistently leading to male infertility due to a reduced or absent sperm motility associated with severe morphological and ultrastructural flagellum defects. Despite numerous genes recently described to be recurrently associated with MMAF, more than half of the cases analyzed remain unresolved, suggesting that many yet uncharacterized gene defects account for this phenotype. By performing a retrospective exome analysis of the unsolved cases from our initial cohort of 167 infertile men with a MMAF phenotype, we identified one individual carrying a homozygous frameshift variant in CFAP206, a gene encoding a microtubule-docking adapter for radial spoke and inner dynein arm. Immunostaining experiments in the patient's sperm cells demonstrated the absence of WDR66 and RSPH1 proteins suggesting severe radial spokes and calmodulin and spoke-associated complex defects. Using the CRISPR-Cas9 technique, we generated homozygous Cfap206 knockout (KO) mice which presented with male infertility due to functional, structural and ultrastructural sperm flagellum defects associated with a very low rate of embryo development using ICSI. Overall, we showed that CFAP206 is essential for normal sperm flagellum structure and function in human and mouse and that bi-allelic mutations in CFAP206 cause male infertility in man and mouse by inducing morphological and functional defects of the sperm flagellum that may also cause ICSI failures.


Assuntos
Proteínas do Citoesqueleto , Mutação da Fase de Leitura , Homozigoto , Infertilidade Masculina , Cauda do Espermatozoide/metabolismo , Animais , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Humanos , Infertilidade Masculina/genética , Infertilidade Masculina/metabolismo , Masculino , Camundongos
11.
Nat Neurosci ; 24(7): 941-953, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34017130

RESUMO

Common genetic risk for neuropsychiatric disorders is enriched in regulatory elements active during cortical neurogenesis. However, it remains poorly understood as to how these variants influence gene regulation. To model the functional impact of common genetic variation on the noncoding genome during human cortical development, we performed the assay for transposase accessible chromatin using sequencing (ATAC-seq) and analyzed chromatin accessibility quantitative trait loci (QTL) in cultured human neural progenitor cells and their differentiated neuronal progeny from 87 donors. We identified significant genetic effects on 988/1,839 neuron/progenitor regulatory elements, with highly cell-type and temporally specific effects. A subset (roughly 30%) of chromatin accessibility-QTL were also associated with changes in gene expression. Motif-disrupting alleles of transcriptional activators generally led to decreases in chromatin accessibility, whereas motif-disrupting alleles of repressors led to increases in chromatin accessibility. By integrating cell-type-specific chromatin accessibility-QTL and brain-relevant genome-wide association data, we were able to fine-map and identify regulatory mechanisms underlying noncoding neuropsychiatric disorder risk loci.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento/genética , Variação Genética/genética , Transtornos Mentais/genética , Neurônios/fisiologia , Locos de Características Quantitativas/genética , Diferenciação Celular/fisiologia , Cromatina/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Humanos , Células-Tronco Neurais/fisiologia , Neurogênese/genética , Elementos Reguladores de Transcrição/genética , Fatores de Transcrição/genética
12.
Cell Rep ; 35(6): 109114, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33979624

RESUMO

How genes interact with the environment to shape phenotypic variation and evolution is a fundamental question intriguing to biologists from various fields. Existing linear models built on single genes are inadequate to reveal the complexity of genotype-environment (G-E) interactions. Here, we develop a conceptual model for mechanistically dissecting G-E interplay by integrating previously disconnected theories and methods. Under this integration, evolutionary game theory, developmental modularity theory, and a variable selection method allow us to reconstruct environment-induced, maximally informative, sparse, and casual multilayer genetic networks. We design and conduct two mapping experiments by using a desert-adapted tree species to validate the biological application of the model proposed. The model identifies previously uncharacterized molecular mechanisms that mediate trees' response to saline stress. Our model provides a tool to comprehend the genetic architecture of trait variation and evolution and trace the information flow of each gene toward phenotypes within omnigenic networks.

14.
Reproduction ; 162(1): 73-82, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-33989172

RESUMO

Emerging evidence has demonstrated that melatonin (MT) plays a crucial role in regulating mammalian reproductive functions. It has been reported that MT has a protective effect on polycystic ovary syndrome (PCOS). However, the protective mechanisms of MT remain poorly understood. This study aims to explore the effect of MT on ovarian function in PCOS and to elucidate the relevant molecular mechanisms in vivo and in vitro. We first analysed MT expression levels in the follicular fluid of PCOS patients. A significant reduction in MT expression levels was noted in PCOS patients. Intriguingly, reduced MT levels correlated with serum testosterone and inflammatory cytokine levels in follicular fluid. Moreover, we confirmed the protective function of MT through regulating autophagy in a DHEA-induced PCOS rat model. Autophagy was activated in the ovarian tissue of the PCOS rat model, whereas additional MT inhibited autophagy by increasing PI3K--Akt pathway expression. In addition, serum-free testosterone, inflammatory and apoptosis indexes were reduced after MT supplementation. Furthermore, we also found that MT suppressed autophagy and apoptosis by activating the PI3K-Akt pathway in the DHEA-exposed human granulosa cell line KGN. Our study showed that MT ameliorated ovarian dysfunction by regulating autophagy in DHEA-induced PCOS via the PI3K-Akt pathway, revealing a potential therapeutic drug target for PCOS.

15.
PLoS One ; 16(4): e0249431, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33848300

RESUMO

Tonkinacris is a small group in Acrididae. While a few species were occasionally sampled in some previous molecular studies, there is no revisionary research devoted to the genus. In this study, we explored the phylogeny of and the relationships among Chinese species of the genus Tonkinacris using the mitochondrial COI barcode and the complete sequences of ITS1 and ITS2 of the nuclear ribosomal DNA. The phylogeny was reconstructed in maximum likelihood and Bayesian inference frameworks, respectively. The overlap range between intraspecific variation and interspecific divergence was assessed via K2P distances. Species boundaries were delimitated using phylogenetic species concept, NJ tree, K2P distance, the statistical parsimony network as well as the GMYC model. The results demonstrate that the Chinese Tonkinacris species is a monophyletic group and the phylogenetic relationship among them is (T. sinensis, (T. meridionalis, (T. decoratus, T. damingshanus))). While T. sinensis, T. meridionalis and T. decoratus were confirmed being good independent species strongly supported by both morphological and molecular evidences, the validity of T. damingshanus was not perfectly supported by molecular evidence in this study.


Assuntos
Gafanhotos/genética , Filogenia , Animais , Teorema de Bayes , China , Variação Genética
16.
Int Immunopharmacol ; 96: 107580, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33823430

RESUMO

Corneal lymphangiogenesis induced by macrophages played a critical role in corneal allograft rejection (CGR). However, there are few Food and Drug Administration (FDA)-approved drugs that target lymphangiogenesis. The aim of our study is to evaluate the effects of dimethyl fumarate (DMF) on corneal allograft survival in rats. Penetrating corneal transplantation was performed in rats. Subconjunctival injections of dimethyl fumarate (20 µg) were administered at the end of the operation and postoperative day 3 to day 11. The clinical signs of corneal allografts were evaluated. Immunohistochemistry, quantitative real-time PCR (qPCR), flow cytometry and western blot were performed respectively. The effects and mechanism of DMF on RAW264.7 cells were determined by qPCR, enzyme-linked immunosorbent assay (ELISA), and western blot in vitro. The results showed that subconjunctival injections of DMF could significantly inhibit corneal lymphangiogenesis and CGR with decreased corneal macrophage infiltration compared with the vehicle group. Moreover, DMF could reduce the mRNA expression of monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and vascular endothelial growth factor-C (VEGF-C) in the corneal grafts and RAW264.7 macrophages by inhibiting NF-κB activation. Furthermore, compared with the vehicle group, the number of dendritic cells in the ipsilateral cervical lymph nodes of the DMF-treated group was decreased significantly. Collectively, our findings showed that DMF could suppress CGR by inhibiting the macrophage-induced corneal lymphoangiogenesis.

17.
Nano Lett ; 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33914541

RESUMO

Two-dimensional (2D) PtSe2 has emerged as a promising ultrathin electrocatalyst due to its excellent catalytic activity and conductivity. However, the PtSe2 basal plane is inert for the hydrogen evolution reaction (HER), which greatly limits its electrocatalytic performance. Here, in light of theoretical calculations, we designed a facile approach for activating the 2D PtSe2 basal plane for the HER by simultaneously introducing atomic vacancies of Se, Pt, and Pt clusters through a mild Ar plasma treatment. We tracked changes in the structures and catalytic performance of PtSe2 by combining microscopic imaging, spectroscopic mapping, and electrochemical measurements in microcells. The highest performance of the activated PtSe2 basal plane that we obtained was superior to those of other 2D transition metal dichalcogenide-based electrocatalysts measured in microcells in terms of the overpotential, the Tafel slope, and the exchange current density. This study demonstrates the great potential of activated 2D PtSe2 as an ultrathin catalyst for the HER and provides new insights on the rational design of 2D electrocatalysts.

18.
Mol Genet Genomics ; 296(3): 527-539, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33797587

RESUMO

Cis-regulatory sequences play a crucial role in regulating gene expression and are evolutionary hot spots that drive phenotypic divergence among organisms. Sequencing some cis-regulatory regions of interest in many different species is common in comparative genetic studies. For nonmodel organisms lacking genomic data, genome walking is often the preferred method for this type of application. However, applying genome walking will be laborious and time-consuming when the number of cis-regulatory regions and species to be analyzed is large. In this study, we propose a novel method called amplicon genome fishing (AGF), which can isolate and sequence cis-regulatory regions of interest for any organism. The main idea of the AGF method is to use fragments amplified from the target cis-regulatory regions as enrichment baits to capture and sequence the whole target cis-regulatory regions from genomic library pools. Unlike genome walking, the AGF method is based on hybridization capture and high-throughput sequencing, which makes this method rapid and efficient for projects where some cis-regulatory regions have to be sequenced for many species. We used human amplicons as capture baits and successfully sequenced five target enhancer regions of Homo sapiens, Mus musculus, Gallus gallus, and Xenopus tropicalis, proving the feasibility and repeatability of AGF. To show the utility of the AGF method in real studies, we used it to sequence the ZRS enhancer, a cis-regulatory region associated with the limb loss of snakes, for twenty-three vertebrate species (includes many limbless species never sequenced before). The newly obtained ZRS sequences provide new perspectives into the relationship between the ZRS enhancer's evolution and limb loss in major tetrapod lineages.


Assuntos
Genoma/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Hibridização de Ácido Nucleico/métodos , Sequências Reguladoras de Ácido Nucleico/genética , Animais , Galinhas/genética , Elementos Facilitadores Genéticos/genética , Genômica/métodos , Humanos , Camundongos , Xenopus/genética
19.
Int J Biol Macromol ; 180: 458-469, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33711371

RESUMO

Potato resistant starch type 3 (PRS) is helpful for weight-loss. To investigate the regulatory effects of PRS on high-fat diet (HFD)-induced obesity, different doses of PRS (5%, 15% and 25%) were fed to mice for 12 weeks. Metabolic syndrome related to obesity, intestinal microbiota composition and its metabolites as well as the relationship among them were studied. Results showed that PRS could regulate HFD-induced metabolic syndrome in a dose dependent manner; promote the proliferation of intestinal cells and expression of tight junction proteins, such as Occludin and zonula occludens (ZO)-1; reduce the Firmicutes/Bacteroidetes (F/B) rate; regulate the relative abundance of intestinal microbiota, such as Bifidobacterium, Ruminococcus, Bacteroides and Coprococcus; and promote the production of microbial metabolites, such as propionic acid and acetic acid. Besides, the alteration in the intestinal microbiota composition and metabolites were significantly correlated. It could be concluded that propionic acid and acetic acid were the two dominant metabolites of Bifidobacterium, Ruminococcus, Bacteroides, and Coprococcus, which contributed to the anti-obesity potential of PRS, metabolic syndrome alleviation, and intestinal barrier dysfunction.


Assuntos
Bacteroides/metabolismo , Bifidobacterium/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Obesidade/prevenção & controle , Amido Resistente/farmacologia , Solanum tuberosum/química , Ácido Acético/metabolismo , Animais , Bacteroides/efeitos dos fármacos , Bifidobacterium/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Lipídeos/sangue , Masculino , Metabolômica/métodos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/metabolismo , Propionatos/metabolismo , Amido Resistente/administração & dosagem
20.
Clin Lymphoma Myeloma Leuk ; 21(4): e356-e364, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33541793

RESUMO

BACKGROUND: Bone marrow necrosis (BMN) is a rare secondary disorder of many discrepant neoplastic processes. The etiology is diverse, and malignancy is the most common background disease. PATIENTS AND METHODS: Between 2005 and 2019, a total of 23 cases of BMN were detected and analyzed at Zhujiang Hospital and Nanfang Hospital. RESULTS: In our study, the 40-60-year-old age group was the one with the highest incidence of BMN (n = 12, 52.2%). The background diseases of patients with BMN varied. Eighteen (78.3%) of 23 patients were diagnosed with hematologic diseases at the same time, most of which were acute B lymphocytic leukemia (n = 8, 34.8%). The complete blood count of these 23 patients noted a decrease in hemoglobin (100%), a decrease or increase in white blood cells and neutrophils, and thrombocytopenia (78.3%). The levels of lactate dehydrogenase (> 300 U/L) and serum ferritin (> 500 µg/L) were elevated in all patients, and 16 (94.1%) of 17 patients presented with increased d-dimer levels. The 2-week cumulative survival and 2-year cumulative survival of patients with BMN were 56.5% and 47.4%, respectively. The mortality probability within 2 weeks was 43.5%, and the adjusted mortality probability was 26.7% within 2 weeks to 2 years, indicating that patients with BMN had the greatest risk of death within 2 weeks. CONCLUSION: BMN patients with B lymphocytic leukemia as the background disease had a better prognosis than those with other background diseases. BMN of unknown etiology may have an extremely poor prognosis. Therefore, diagnosing the background disease plays an important role in the treatment of BMN.

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