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2.
Atherosclerosis ; 298: 14-26, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32131039

RESUMO

Angiogenesis is the physiological process of new blood vessel formation from existing capillary vessels or posterior capillary veins. Its dysfunction could result in a number of diseases, such as cardiovascular diseases and cancer, contributing to death and disability worldwide. Circular RNAs (circRNAs) are a class of novel identified RNA molecules with a special covalent loop structure without a 5' cap and 3' tail, which can lead to novel back-splicing or skipping events from precursor mRNAs. Accumulating evidence suggests that circRNA play critical roles in diseases; in particular, they are abundantly and abnormally expressed in angiogenesis-related diseases. In this review, we describe the role of circRNA under pathological conditions, discuss the association between circRNA and angiogenesis, classify the regulatory mechanisms and suggest that circRNA can be used as potential therapeutic targets for angiogenesis-related diseases under clinical evaluation.

3.
Atherosclerosis ; 298: 58-69, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32171981

RESUMO

BACKGROUND AND AIMS: The endothelium is crucially involved in the pathogenesis of atherosclerosis according to accumulating evidence. Moreover, recent studies have showed that lncRNAs could serve as biomarkers of cardiovascular diseases, in particular atherosclerosis. However, the underlying mechanism of endothelial dysfunction involving lncRNAs in atherosclerosis remains unknown. This study investigated the mechanism of lncRNA XXYLT1-AS2 in endothelial dysfunction in atherosclerosis. METHODS: The levels of lncRNA XXYLT1-AS2, FUS, VCAM-1, MCP-1, p-AKT, and p-P65 were measured in arteries and HUVEC cell lines via quantitative real-time PCR or Western blot. FISH assay demonstrated that XXYLT1-AS2 and FUS are localized in the nucleus. HUVECs were transfected with si-XXYLT1-AS2 or XXYLT1-AS2 to further assess cell proliferation, migration, and adhesion. Furthermore, bioinformatics analysis, RNA immunoprecipitation and immunofluorescence were performed to investigate the target genes of XXYLT1-AS2 and possible signal pathways. RESULTS: Overexpression of XXYLT1-AS2 inhibited cell proliferation and migration, reduced the expression of adhesion molecules (VCAM-1) and chemoattractant proteins (MCP-1), and restrained monocyte adhesion to endothelial cells. Mechanistic investigations indicated that XXYLT1-AS2 directly interacts with the target gene FUS/cyclin D1 and modulates the proliferation and migration of endothelial cells (ECs). Moreover, XXYLT1-AS2 exerts a protective role against the inflammatory response in atherosclerosis by blocking NF-κB activity. Clinically, the involvement of XXYLT1-AS2/FUS was also observed in human arteries and the results were consistent with the in vitro analysis. CONCLUSIONS: Our study identified a novel long non-coding RNA (XXYLT1-AS2) and suggests that it might act as an underlying therapeutic target in atherosclerosis-related diseases by regulating ECs functions.

4.
Photosynth Res ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32016668

RESUMO

PsbO-D158 is a highly conserved residue of the PsbO protein in photosystem II (PSII), and participates in one of the hydrogen-bonding networks connecting the manganese cluster with the lumenal surface. In order to examine the role of PsbO-D158, we mutated it to E, N or K in Thermosynechococcus vulcanus and characterized photosynthetic properties of the mutants obtained. The growth rates of these three mutants were similar to that of the wild type, whereas the oxygen-evolving activity of the three mutant cells decreased to 60-64% of the wild type. Fluorescence kinetics showed that the mutations did not affect the electron transfer from QA to QB, but slightly affected the donor side of PSII. Moreover, all of the three mutant cells were more sensitive to high light and became slower to recover from photoinhibition. In the isolated thylakoid membranes from the three mutants, the PsbU subunit was lost and the oxygen-evolving activity was reduced to a lower level compared to that in the respective cells. PSII complexes isolated from these mutants showed no oxygen-evolving activity, which was found to be due to large or complete loss of PsbO, PsbV and PsbU during the process of purification. Moreover, PSII cores purified from the three mutants contained Psb27, an assembly co-factor of PSII. These results suggest that PsbO-D158 is required for the proper binding of the three extrinsic proteins to PSII and plays an important role in maintaining the optimal oxygen-evolving activity, and its mutation caused incomplete assembly of the PSII complex.

5.
Biochem Pharmacol ; 174: 113797, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31926936

RESUMO

BX795, a small molecule with an aminopyrimidine backbone, is a potent ATP-competitive inhibitor of phosphoinositide-dependent kinase 1 (PDK1) and TANK-binding kinase 1 (TBK1). BX795 has significant functions in various immune responses and cancer. Few reports on the anti-inflammatory effect of BX795 are available, and its molecular mechanisms have not been fully elucidated. In this study, lipopolysaccharide (LPS)-treated macrophages (RAW264.7 cells), luciferase reporter gene assay, knock-down and overexpression strategies, kinase assay, protein chip, immunoprecipitation, and immunoblotting analyses were employed to clarify the anti-inflammatory mechanism of BX795. BX795 was found to dose-dependently inhibit the production of pro-inflammatory mediators without exhibiting cytotoxicity. Luciferase assay and immunoblotting analysis with nuclear fractions showed that activator protein-1 (AP-1), signal transducer and activator of transcription 1 (STAT1), and interferon regulatory factor 3 (IRF3) are targeted by BX795 rather than nuclear factor (NF)-κB. Moreover, TBK1 and AKT, transforming growth factor activated kinase (TAK)-1/c-Jun N-terminal kinase (JNK)/mitogen-activated protein kinase kinase 4 (MKK4) for AP-1 activation, and Janus kinase 2 (JAK2)/STAT1 were inhibited by BX795. Consistent with these findings, BX795 strongly ameliorated inflammatory symptoms in colitis models. These results suggest that BX795 can suppress inflammatory responses triggered by Gram-positive bacteria by suppressing multiple pathways.

6.
Gynecol Endocrinol ; : 1-5, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31899997

RESUMO

The aim of our study was to test whether there is an association between high expression of milk fat globule EGF factor 8 (MFG-E8) and CD133 presence or clinical outcomes of patients with epithelial ovarian cancer (EOC). MFG-E8 and CD133 expression levels were analyzed by immunohistochemistry in 88 EOC tumor specimens. High expression of MFG-E8 directly and significantly correlated with the presence of CD133 immunostaining (R = 0.353, p=.001), whereas immunostaining of MFG-E8 and CD133 significantly correlated with FIGO stage, tumor grade, debulking status, the dualistic model, ascites status, and nonresponse to chemotherapy (p<.05). It was also found that high expression of MFG-E8 and CD133 presence is a potent predictor of poor clinical outcomes among patients with EOC. Our study is the first to show that high expression of MFG-E8 in EOCs positively correlates with CD133 presence. Further research on MFG-E8 in EOC is needed to determine whether MFG-E8 is a new tumor marker of ovarian cancer and a new target for anticancer therapy as well as whether it can interact with cancer stem cell inhibitors for the treatment of refractory tumors.

7.
Int J Neurosci ; 130(2): 153-160, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31516042

RESUMO

Purpose: Parkinson's disease is a progressive disorder. To investigate the biochemical alterations in the striatum of rats with different stages of Parkinson's disease induced by proteasomal inhibition, we quantified neurochemical profiles of the striatum using proton magnetic resonance spectroscopyusing 9.4 T ultra-high field imaging.Methods: In this study, 10 µg/2 µl lactacystin, a selective proteasome inhibitor, was unilaterally injected stereotaxically into the left substantia nigra pars compacta of rats. An equal volume of saline was injected into the same region and side in the control group. Changes in motor behaviour were observed. The morphological changes of tyrosine hydroxylase-positive cells in substantia nigra pars compacta were visualized using immunohistochemistry. Tyrosine hydroxylase-positive nerve fibers were quantified. Alterations of N-acetylaspartate, choline, creatine, taurine in the different stages of Parkinson's disease rats were detected using proton magnetic resonance spectroscopy.Results: Application of in vivo 1H magnetic resonance spectroscopy was repeated in both the six Parkinson's disease rats and the six control rats across three time points during the first, second and fourth weekend after administration. In Parkinson's disease rats, increased N-acetylaspartate and decreased taurine concentrations were observed in the left striatum at the first week after administration. The increased N-acetylaspartate and choline concentrations were observed at the second weekend. At the fourth weekend, increased creatine concentrations in the left side were observed, while other metabolites were not significantly changed.Conclusions: Neurochemical alterations occurred in the striatum during different stages of the Parkinson's disease model in rats. Also, 9.4 T 1H magnetic resonance spectroscopy may be a useful tool for elucidating the progression of Parkinson's disease through the variation of these metabolites.

8.
Cell Tissue Res ; 379(1): 195-206, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31428875

RESUMO

Liver fibrosis results from collagen fiber deposition. Antler stem cells (ASCs) naturally in vivo differentiate into cartilage, which is only made of Col II in collagen component; whereas liver fibrosis is caused by over-abundance of Col I and III. In addition, ASCs can effectively promote regenerative wound healing in which tissue contains very few collagen fibers (Col I). In this study, we investigate the therapeutic effects of ASCs in a rat model of CCl4-induced liver fibrosis. Rats were treated with ASCs for 4 weeks in vivo, then biochemical and histopathological analyses were performed. Furthermore, we established cell co-culture systems of hepatic stellate cells (HSCs) and ASCs and of M1 macrophages and ASCs in vitro. Mesenchymal stem cells (MSCs) were used as a positive control. The results showed that ASC transplantation alleviated liver fibrosis effectively as evidenced by reduced collagen accumulation, decreased fatty degeneration, increased hepatocyte regeneration, decreased inflammation and significantly enhanced liver function; moreover, ASCs decreased the expression of pro-fibrogenic factors including TGF-ß and α-SMA. Additionally, our study showed that ASCs inhibit HSC activation and proliferation by controlling the expression of MMPs, TIMP1, TGF-ß, α-SMA and COL1A2 involved in these processes. Our results suggested that ASCs alleviate liver fibrosis effectively and inhibit HSC activation. Thus, ASCs may serve as a novel stem cell source for the treatment of liver fibrosis in the clinic.

9.
Chem Biol Interact ; 316: 108921, 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31838053

RESUMO

Hyperproliferation and oxidative stress induced by hyperglycemia in mesangial cells plays crucial roles in the pathological process of diabetic nephropathy. Farrerol, isolated from rhododendron leaves, possesses broad anti-oxidative and anti-inflammatory properties towards several diseases, but its role in diabetic neuropathy remains unclear. The aim of this study was to evaluate the effects of farrerol in high glucose induced mesangial cell injury, and to explore underlying molecular mechanisms. Our results showed that high glucose in vitro conditions significantly stimulated cell proliferation, inflammatory cytokine secretion, extracellular matrix deposition, excessive oxidative stress, and NADPH oxidase activity in mesangial cells. Levels of NADPH oxidase 4 (Nox4) expression, ERK1/2 phosphorylation, and TGF-ß1/Smad2 activation were significantly induced by high glucose conditions in mesangial cells. Inversely, farrerol treatments at 40, 60, and 80 µM concentrations, dose-dependently alleviated this molecular damage by high glucose in mesangial cells. We also found that restoration of Nox4 expression abolished the protective effects of farrerol on high glucose-induced proliferation and reactive oxygen species generation. Furthermore, pretreatment with the Nox4 inhibitor diphenyliodonium or the ERK1/2 pathway inhibitor PD98059, displayed similar ameliorated effects of farrerol on high glucose-induced mesangial cell damage. Taken together, these data suggest that farrerol displays protective effects on high glucose induced mesangial cell injury, partly through the Nox4-mediated ROS/ERK1/2 signaling pathway. These observations may provide novel insights into the application of farrerol as a diabetic neuropathy treatment.


Assuntos
Cromonas/farmacologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , NADPH Oxidase 4/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Glucose/toxicidade , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Células Mesangiais/citologia , Células Mesangiais/efeitos dos fármacos , Células Mesangiais/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Fator de Crescimento Transformador beta/metabolismo
10.
Stem Cell Res Ther ; 10(1): 383, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31843019

RESUMO

BACKGROUND: Radiation dermatitis is a refractory skin injury caused by radiotherapy. Human fetal skin-derived stem cell (hFSSC) is a preferable source for cell therapy and skin tissue regeneration. In the present study, we investigated the repair effect of using hFSSC secretome on a radiation skin injury model in rats. METHODS: We prepared the hFSSC secretome and studied its effects on the proliferation and tube formation of human umbilical vein endothelial cell (HUVEC) in vitro. Furthermore, we used a Sr-90 radiation-induced skin injury model of rats and evaluated the effects of hFSSC secretome on radiation skin injury in vivo. RESULTS: The results showed that hFSSC secretome significantly promoted the proliferation and tube formation of HUVEC in vitro; in addition, hFSSC secretome-treated rats exhibited higher healing quality and faster healing rate than the other two control groups; the expression level of collagen type III α 1 (Col3A1), transforming growth factor ß3 (TGF-ß3), angiotensin 1 (Ang-1), angiotensin 2 (Ang-2), vascular endothelial growth factor (VEGF), and placental growth factor (PLGF) was significantly increased, while collagen type I α 2 (Col1A2) and transforming growth factor ß1 (TGF-ß1) were decreased in hFSSC secretome group. CONCLUSIONS: In conclusion, our results provided the first evidence on the effects of hFSSC secretome towards radiation-induced skin injury. We found that hFSSC secretome significantly enhanced radiation dermatitis angiogenesis, and the therapeutic effects could match with the characteristics of fetal skin. It may act as a kind of novel cell-free therapeutic approach for radiation-induced cutaneous wound healing.

11.
Microorganisms ; 7(11)2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31752202

RESUMO

The composition of the bacterial community affects the intestinal health and growth performance of broiler chickens. The main purpose of this study was to explore the effects of flavomycin and colistin sulfate on the resistance to Salmonella typhimurium infection, ileal bacteria and intestinal health. In total, 396 1-day-old broiler chickens were randomly divided into six groups. Two groups were fed each one of the diets-the control diet (CON), the flavomycin at 10 mg/kg diet (AntiG+), and the colistin sulfate at 40 mg/kg diet (AntiG-), for 5 days. Then, one of each of the two groups was challenged with S. typhimurium on the 8th day; these were named CONS, AntiG+S and AntiG-S, respectively. The results showed that S. typhimurium significantly reduced the feed intake and body weight gain, and increased the feed conversion ratio (p < 0.05). It also increased the inflammatory expressions of NF-κB and MyD88 genes (p < 0.05); and reduced the expressions of claudin-1, occludin and mucin-2 (p < 0.05) tight junction genes in the intestines. S. typhimurium significantly reduced ileal bacterial diversity indexes of observed-species, chao1 and Shannon (p < 0.05). Compared with AntiG+S group, AntiG-S group increased the body weight gain of broiler chickens (p < 0.05), reduced the expression of inflammatory genes (p < 0.05) and intestinal permeability to fluorescein isothiocyanate (p < 0.05). AntiG-S group also improved the ileal bacterial diversity indexes of observed-species and Shannon (p < 0.05). There were many significant correlations between intestinal bacteria, intestinal gene expressions and intestinal morphology (p < 0.05). This study indicated that pre-constructed AntiG- bacteria could against a S. typhimurium infection by inhibiting the expressions of intestinal inflammation genes and increasing the diversity of intestinal bacteria.

12.
BMC Genomics ; 20(1): 851, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31726970

RESUMO

BACKGROUND: Endogenous α-synuclein (α-Syn) is involved in many pathophysiological processes in the secondary injury stage after acute spinal cord injury (SCI), and the mechanism governing these functions has not been thoroughly elucidated to date. This research aims to characterize the effect of α-Syn knockdown on transcriptional levels after SCI and to determine the mechanisms underlying α-Syn activity based on RNA-seq. RESULT: The establishment of a rat model of lentiviral vector-mediated knockdown of α-Syn in Sprague-Dawley rats with T3 spinal cord contusion (LV_SCI group). The results of the RNA-seq analysis showed that there were 337 differentially expressed genes (DEGs) between the SCI group and the LV_SCI group, and 153 DEGs specific to LV_SCI between the (SCI vs LV_SCI) and (SCI vs CON) comparisons. The top 20 biological transition terms were identified by Gene ontology (GO) analysis. The Kyoto Gene and Genomic Encyclopedia (KEGG) analysis showed that the LV_SCI group significantly upregulated the cholinergic synaptic & nicotine addiction and the neuroactive ligand receptor interaction signaling pathway. Enriched chord analysis analyzes key genes. Further cluster analysis, gene and protein interaction network analysis and RT-qPCR results showed that Chrm2 and Chrnb2 together significantly in both pathways. The proliferation of muscarinic cholinergic receptor subtype 2 (Chrm2) and nicotinic cholinergic receptor subtype ß2 (Chrnb2), and the neurogenesis were elevated in the injury site of LV_SCI group by immunofluorescence. Further by subcellular localization, the LV_SCI group enhanced the expression of Chrnb2 at the cell membrane. CONCLUSION: Knockdown of α-Syn after SCI enhance motor function and promote neurogenesis probably through enhancing cholinergic signaling pathways and neuroreceptor interactions. This study not only further clarifies the understanding of the mechanism of knockdown of α-Syn on SCI but also helps to guide the treatment strategy for SCI.

13.
J Biol Chem ; 294(48): 18092-18098, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31624146

RESUMO

Previous work with the classic T4 endonuclease V digestion of DNA from irradiated Drosophila cells followed by Southern hybridization led to the conclusion that Drosophila lacks transcription-coupled repair (TCR). This conclusion was reinforced by the Drosophila Genome Project, which revealed that Drosophila lacks Cockayne syndrome WD repeat protein (CSA), CSB, or UV-stimulated scaffold protein A (UVSSA) homologs, whose orthologs are present in eukaryotes ranging from Arabidopsis to humans that carry out TCR. A recently developed in vivo excision assay and the excision repair-sequencing (XR-Seq) method have enabled genome-wide analysis of nucleotide excision repair in various organisms at single-nucleotide resolution and in a strand-specific manner. Using these methods, we have discovered that Drosophila S2 cells carry out robust TCR comparable with that observed in mammalian cells. Our findings provide critical new insights into the mechanisms of TCR among various different species.

14.
mBio ; 10(5)2019 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-31594817

RESUMO

The presence of an extremely stable latent reservoir of HIV-1 is the major obstacle to eradication, despite effective antiretroviral therapy (ART). Recent studies have shown that clonal expansion of latently infected cells without viral reactivation is an important phenomenon that maintains the long-term stability of the reservoir, yet its underlying mechanism remains unclear. Here we report that a subset of CD4+ T cells, characterized by CD161 expression on the surface, is highly permissive for HIV-1 infection. These cells possess a significantly higher survival and proliferative capacity than their CD161-negative counterparts. More importantly, we found that these cells harbor HIV-1 DNA and replication-competent latent viruses at a significantly higher frequency. By using massive single-genome proviral sequencing from ART-suppressed individuals, we confirm that CD161+ CD4+ T cells contain remarkably more identical proviral sequences, indicating clonal expansion of the viral genome in these cells. Taking the results together, our study identifies infected CD161+ CD4+ T cells to be a critical force driving the clonal expansion of the HIV-1 latent reservoir, providing a novel mechanism for the long-term stability of HIV-1 latency.IMPORTANCE The latent reservoir continues to be the major obstacle to curing HIV-1 infection. The clonal expansion of latently infected cells adds another layer maintaining the long-term stability of the reservoir, but its mechanism remains unclear. Here, we report that CD161+ CD4+ T cells serve as an important compartment of the HIV-1 latent reservoir and contain a significant amount of clonally expanded proviruses. In our study, we describe a feasible strategy that may reduce the size of the latent reservoir to a certain extent by counterbalancing the repopulation and dissemination of latently infected cells.

15.
Sci Total Environ ; 697: 134126, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31491630

RESUMO

Heavy metals in agricultural soil receive much attention because they are easily absorbed by crop into the ecosystem. Managing the discharge of heavy metals from the source is an effective way to prevent and control heavy metals pollution. Grouped principal component analysis (GPCA) and Positive Matrix Factorization (PMF) receptor models were utilized in this study to conduct source apportionment, and the former was optimal because of the accuracy of predicting. Based on the source contribution by GPCA/APCS, heavy metals were evaluated by fuzzy synthetic evaluation model and health risk assessment model. The results of source apportionment showed that heavy metals in Zhangye agricultural soil were mainly affected by steel industry, traffic, agrochemicals, manures, mining activities, leather industry and metal processing industry source. Fuzzy synthetic evaluation showed that the pollution levels of Chromium (Cr) derived by leather industry and metal processing industry and Nickel (Ni) derived by steel industry and traffic source were higher. Health risk assessment revealed that the non-carcinogenic and carcinogenic risks of Cr derived by leather industry and metal processing industry and Lead (Pb) derived by steel industry and traffic source were higher.


Assuntos
Monitoramento Ambiental , Poluição Ambiental/estatística & dados numéricos , Metais Pesados/análise , Poluentes do Solo/análise , China , Lógica Fuzzy , Análise Multivariada , Medição de Risco
16.
Fish Shellfish Immunol ; 93: 567-574, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31394161

RESUMO

HMGB2, a member of the high mobility group box family, plays an important role in host immune responses. However, the mechanism of action of HMGB2 is not well understood. Herein, a homologue from yellow catfish (Pelteobagrus fulvidraco) was cloned and named PfHMGB2. The deduced amino acid sequence of PfHMGB2 possessed a typical tripartite structure (two DNA binding boxes and an acid tail) and shared 90% identity with the predicted HMGB2 from I. punctatus. The mRNA of PfHMGB2 was widely distributed in all 11 tested tissues in healthy fish bodies and was significantly induced in the liver and head kidney when yellow catfish were injected with inactivated Aeromonas hydrophila. Consistently, PfHMGB2 mRNA could also be induced in yellow catfish peripheral blood leucocytes (PBL) by lipopolysaccharide. The recombinant PfHMGB2 protein was purified from E. coli BL21 (DE3):pET-28a/PfHMGB2 and showed DNA-binding affinity. Moreover, rPfHMGB2 improved the phagocytosis and proliferation activity and upregulated the mRNA expression of the pro-inflammatory cytokine TNFα in yellow catfish PBL. These results indicated that PfHMGB2 could protect yellow catfish from pathogen infection by activating PBL.


Assuntos
Peixes-Gato/genética , Peixes-Gato/imunologia , Doenças dos Peixes/imunologia , Regulação da Expressão Gênica/imunologia , Proteína HMGB2/genética , Proteína HMGB2/imunologia , Imunidade Inata/genética , Aeromonas hydrophila/fisiologia , Sequência de Aminoácidos , Animais , Proteínas de Peixes/química , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Perfilação da Expressão Gênica/veterinária , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/veterinária , Proteína HMGB2/química , Leucócitos/imunologia , Fagocitose/imunologia , Filogenia , Alinhamento de Sequência/veterinária
17.
Plants (Basel) ; 8(7)2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31373320

RESUMO

WUSCHEL-related homeobox (WOX) is a family of transcription factors that are unique to plants and is characterized by the presence of a homeodomain. The WOX transcription factor plays an important role in regulating plant growth and development and the response to abiotic stress. Soybean is one of the most important oil crops worldwide. In this study, based on the available genome data of soybean, the WOX gene family was identified by bioinformatics analysis. The chromosome distribution, gene and protein structures, phylogenetic relationship and gene expression patterns of this family were comprehensively compared. The results showed that a total of 33 putative WOX genes in the soybean genome were found and then designated as GmWOX1- GmWOX33, which were distributed across 19 chromosomes except chromosome 16. Multiple sequence analysis of the GmWOX gene family revealed a highly conserved homeodomain. Phylogenetic tree analysis showed that 33 WOX genes could be divided into three major clades (modern/WUS, intermediate and ancient) in soybean. Of these 33 WOX genes, some showed differential expression patterns in the tested tissues (leaves, pods, unopen and open flowers, nodules, seed, roots, root hairs, stems, shoot apical meristems and shoot tips). In addition, the expression profile and qRT-PCR analysis showed that most of the GmWOX genes responded to different abiotic stress treatments (cold and drought). According to the expression pattern of GmWOX genes in the high regeneration capacity soybean material P3, overexpression of GmWOX18 was selected for function analysis. The overexpression of GmWOX18 increased the regeneration ability of clustered buds. The results will provide valuable information for further studies on the roles of WOX genes in regulating soybean growth, development and responses to abiotic stress, as well as a basis for the functional identification and analysis of WOX genes in soybean.

18.
Sci Rep ; 9(1): 12250, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31439882

RESUMO

The genus Allium is one of the largest monocotyledonous genera, containing over 850 species, and most of these species are found in temperate climates of the Northern Hemisphere. Furthermore, as a large number of new Allium species continue to be identified, phylogenetic classification based on morphological characteristics and a few genetic markers will gradually exhibit extremely low discriminatory power. In this study, we present the use of complete chloroplast genome sequences in genome-scale phylogenetic studies of Allium. We sequenced and assembled four Allium chloroplast genomes and retrieved five published chloroplast genomes from GenBank. All nine chloroplast genomes were used for genomic comparison and phylogenetic inference. The chloroplast genomes, ranging from 152,387 bp to 154,482 bp in length, exhibited conservation of genomic structure, and gene organization and order. Subsequently, we observed the expansion of IRs from the basal monocot Acorus americanus to Allium, identified 814 simple sequence repeats, 131 tandem repeats, 154 dispersed repeats and 109 palindromic repeats, and found six highly variable regions. The phylogenetic relationships of the Allium species inferred from the chloroplast genomes obtained high support, indicating that chloroplast genome data will be useful for further resolution of the phylogeny of the genus Allium.

19.
J Biol Chem ; 294(32): 11960-11968, 2019 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-31217280

RESUMO

Cisplatin is the most commonly used chemotherapeutic drug for managing solid tumors. However, toxicity and the innate or acquired resistance of cancer cells to the drug limit its usefulness. Cisplatin kills cells by forming cisplatin-DNA adducts, most commonly the Pt-d(GpG) diadduct. We recently showed that, in mice, repair of this adduct 2 h following injection is controlled by two circadian programs. 1) The circadian clock controls transcription of 2000 genes in liver and, via transcription-directed repair, controls repair of the transcribed strand (TS) of these genes in a rhythmic fashion unique to each gene's phase of transcription. 2) The excision repair activity itself is controlled by the circadian clock with a single phase at which the repair of the nontranscribed strand (NTS) and the rest of the genome takes place. Here, we followed the repair kinetic for long periods genome-wide both globally and at single nucleotide resolution by the Excision Repair-sequencing (XR-seq) method to better understand cisplatin DNA damage and repair. We find that transcription-driven repair is nearly complete after 2 days, whereas weeks are required for repair of the NTS and the rest of the genome. TS repair oscillates in rhythmically expressed genes up to 2 days post injection, and in all expressed genes, we see a trend in TS repair with time from the 5' to 3' end. These findings help to understand the circadian- and transcription-dependent and -independent control of repair in response to cisplatin, and should aid in designing cisplatin chemotherapy regimens with improved therapeutic indexes.

20.
Cell Metab ; 30(3): 508-524.e12, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31204282

RESUMO

Fructose-1,6-bisphosphate (FBP) aldolase links sensing of declining glucose availability to AMPK activation via the lysosomal pathway. However, how aldolase transmits lack of occupancy by FBP to AMPK activation remains unclear. Here, we show that FBP-unoccupied aldolase interacts with and inhibits endoplasmic reticulum (ER)-localized transient receptor potential channel subfamily V, inhibiting calcium release in low glucose. The decrease of calcium at contact sites between ER and lysosome renders the inhibited TRPV accessible to bind the lysosomal v-ATPase that then recruits AXIN:LKB1 to activate AMPK independently of AMP. Genetic depletion of TRPVs blocks glucose starvation-induced AMPK activation in cells and liver of mice, and in nematodes, indicative of physical requirement of TRPVs. Pharmacological inhibition of TRPVs activates AMPK and elevates NAD+ levels in aged muscles, rejuvenating the animals' running capacity. Our study elucidates that TRPVs relay the FBP-free status of aldolase to the reconfiguration of v-ATPase, leading to AMPK activation in low glucose.

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