Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 84
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Small ; 20(11): e2307874, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37890278

RESUMO

Chirality, as one of the most striking characteristics, exists at various scales in nature. Originating from the interactions of host and guest molecules, supramolecular chirality possesses huge potential in the design of functional materials. Here, an overview of the recent progress in structure designs and functions of chiral supramolecular materials is present. First, three design routes of the chiral supramolecular structure are summarized. Compared with the template-induced and chemical synthesis strategies that depend on accurate molecular identification, the twisted-assembly technique creates chiral materials through the ordered stacking of the nanowire or films. Next, chirality inversion and amplification are reviewed to explain the chirality transfer from the molecular level to the macroscopic scale, where the available external stimuli on the chirality inversion are also given. Lastly, owing to the optical activity and the characteristics of the layer-by-layer stacking structure, the supramolecular chirality materials display various excellent performances, including smart response, shape-memorization, superior mechanical performance, and applications in biomedical fields. To sum up, this work provides a systematic review of the helical assemblies, structure design, and applications of supramolecular chirality systems.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38818581

RESUMO

Cetuximab (CET), a human murine chimeric IgG monoclonal antibody and an inhibitor of epidermal growth factor receptor (EGFR), has been shown to be effective in treating various types of cancer. However, its use is hindered by limitations such as resistance development, variability in patient response, side effects, and challenges in biomarker identification. Therefore, CET is often combined with other targeted therapies or chemotherapies to enhance its effectiveness. In this study, we investigate the anticancer effects and underlying mechanisms of the combination of CET, an EGFR inhibitor, and STA9090, an inhibitor of heat shock protein 90 (Hsp90), in both in vitro and in vivo models of non-small cell lung cancer (NSCLC). The results demonstrate significantly stronger effects on NSCLC cells in response to combination therapy than to treatment with either agent alone, indicating that the combination of CET and STA9090 has potential synergistic effects. Additionally, the combination therapy inhibits tumor growth in a xenograft nude mouse model more effectively than treatment with either agent alone, suggesting improved efficacy when used together. Furthermore, the synergistic effects of the combination therapy are likely due to inactivation of the receptor tyrosine kinase (RTK) pathway, which is overly activated in cancer and contributes to tumor growth, angiogenesis, and metastasis. Consequently, our findings suggest that STA9090 has potent direct antitumor activity and synergizes with CET against NSCLC tumors. It is highly likely that these synergistic effects are mediated through RTK pathway inactivation caused by the combination. Therefore, our findings strongly and consistently support the potential synergistic effect of STA9090, an RTK inhibitor, in combination with EGFR-targeting agents.

3.
Genomics ; 115(1): 110540, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36563917

RESUMO

Non-coding RNAs (ncRNAs) induced competing endogenous RNAs (ceRNA) play crucial roles in various biological process by regulating target gene expression. However, the studies of ceRNA networks in the regulation of ovarian ovulation processing of chicken remains deficient compared to that in mammals. Our present study revealed that circEML1 was differential expressed in hen's ovarian tissues at different ages (15 W/20 W/30 W/68 W) and identified as a loop structure from EML1 pre-mRNA, which promoted the expressions of CYP19A1/StAR and E2/P4 secretion in follicular granulosa cells (GCs). Furthermore, circEML1 could serve as a sponge of gga-miR-449a and also found that IGF2BP3 was targeted by gga-miR-449a to co-participate in the steroidogenesis, which possibly act the regulatory role via mTOR/p38MAPK pathways. Meanwhile, in the rescue experiment, gga-miR-449a could reverse the promoting role of circEML1 to IGF2BP3 and steroidogenesis. Eventually, this study suggested that circEML1/gga-miR-449a/IGF2BP3 axis exerted an important role in the steroidogenesis in GCs of chicken.


Assuntos
Galinhas , MicroRNAs , Animais , Feminino , Galinhas/genética , Galinhas/metabolismo , Células da Granulosa , Mamíferos/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Ovário/metabolismo , Esteroides/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo
4.
Mol Hum Reprod ; 27(3)2021 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-33599278

RESUMO

Human zygotes are difficult to obtain for research because of limited resources and ethical debates. Corrected human tripronuclear (ch3PN) zygotes obtained by removal of the extra pronucleus from abnormally fertilized tripronuclear (3PN) zygotes are considered an alternative resource for basic scientific research. In the present study, eight-cell and blastocyst formation efficiency were significantly lower in both 3PN and ch3PN embryos than in normal fertilized (2PN) embryos, while histone H3 lysine 9 trimethylation (H3K9me3) levels were much higher. It was speculated that the aberrant H3K9me3 level detected in ch3PN embryos may be related to low developmental competence. Microinjection of 1000 ng/µl lysine-specific demethylase 4A (KDM4A) mRNA effectively reduced the H3K9me3 level and significantly increased the developmental competence of ch3PN embryos. The quality of ch3PN zygotes improved as the grading criteria, cell number and pluripotent expression significantly increased in response to KDM4A mRNA injection. Developmental genes related to zygotic genome activation (ZGA) were also upregulated. These results indicate that KDM4A activates the transcription of the ZGA program by enhancing the expression of related genes, promoting epigenetic modifications and regulating the developmental potential of ch3PN embryos. The present study will facilitate future studies of ch3PN embryos and could provide additional options for infertile couples.


Assuntos
Blastocisto/enzimologia , Histonas/metabolismo , Histona Desmetilases com o Domínio Jumonji/biossíntese , Zigoto/enzimologia , Blastocisto/patologia , Técnicas de Cultura Embrionária , Desenvolvimento Embrionário , Indução Enzimática , Feminino , Fertilização in vitro , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Histona Desmetilases com o Domínio Jumonji/genética , Masculino , Metilação , Transcrição Gênica , Zigoto/patologia
5.
Funct Integr Genomics ; 20(2): 201-210, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31456133

RESUMO

Soybean is an economically important leguminous crop, and pod dehiscence of soybean could cause huge yield loss. In this study, we measured fruit-cracking forces and percentages of dehisced pods for ten soybean accessions, then separated them into two groups as shattering-sensitive (SS) and shattering-resistant (SR) soybeans. Pod transcriptomes from these two groups were analyzed, and 225 differentially expressed genes (DEGs) were identified between SS and SR soybeans. Some of these DEGs have been previously reported to be associated with pod dehiscence in soybean. The expression patterns of selected DEGs were validated by real-time quantitative reverse transcription PCR, which confirmed the expression changes found in RNA-seq analysis. We also de novo identified 246 soybean pod-long intergenic ncRNAs (lincRNAs), 401 intronic lncRNAs, and 23 antisense lncRNAs from these transcriptomes. Furthermore, genes and lincRNAs co-expression network analysis showed that there are distinct expression patterns between SS and SR soybeans in some co-expression modules. In conclusion, we systematically investigated potential genes and molecular pathways as candidates for differences in soybean pod dehiscence and will provide a useful resource for molecular breeding of soybeans.


Assuntos
Regulação da Expressão Gênica de Plantas , Glycine max/fisiologia , Produtos Agrícolas , Perfilação da Expressão Gênica , Ontologia Genética , Genes de Plantas , Oligonucleotídeos Antissenso/genética , Reação em Cadeia da Polimerase em Tempo Real , Glycine max/genética , Especificidade da Espécie , Estresse Mecânico , Transcriptoma
6.
Int J Mol Sci ; 21(5)2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32120850

RESUMO

Few studies have been conducted regarding the biological function and regulation role of gga-miR-221-5p in the liver. We compared the conservation of miR-221-5p among species and investigated the expression pattern of gga-miR-221-5p, validating the direct target genes of gga-miR-221-5p by dual luciferase reporter assay, the biological function of gga-miR-221-5p in the liver was studied by gga-miR-221-5p overexpression and inhibition. Furthermore, we explored the regulation of gga-miR-221-5p and its target genes by treatment with estrogen and estrogen antagonists in vivo and in vitro. The results showed that miR-221-5p was highly conserved among species, expressed in all tested tissues and significantly downregulated in peak-laying hen liver compared to pre-laying hen liver. Gga-miR-221-5p could directly target the expression of elongase of very long chain fatty acids 6 (ELOVL6) and squalene epoxidase (SQLE) genes to affect triglyceride and total cholesterol content in the liver. 17ß-estradiol could significantly inhibit the expression of gga-miR-221-5p but promote the expression of ELOVL6 and SQLE genes. In conclusion, the highly conservative gga-miR-221-5p could directly target ELOVL6 and SQLE mRNAs to affect the level of intracellular triglyceride and total cholesterol. Meanwhile, 17ß-estradiol could repress the expression of gga-miR-221-5p but increase the expression of ELOVL6 and SQLE, therefore promoting the synthesis of intracellular triglyceride and cholesterol levels in the liver of egg-laying chicken.


Assuntos
Galinhas/metabolismo , Estrogênios/farmacologia , Elongases de Ácidos Graxos/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , MicroRNAs/metabolismo , Esqualeno Mono-Oxigenase/metabolismo , Animais , Linhagem Celular , Galinhas/genética , Colesterol/metabolismo , Estradiol/administração & dosagem , Estradiol/farmacologia , Antagonistas de Estrogênios/farmacologia , Estrogênios/administração & dosagem , Elongases de Ácidos Graxos/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , MicroRNAs/genética , Esqualeno Mono-Oxigenase/genética , Triglicerídeos/metabolismo , Regulação para Cima
7.
BMC Genomics ; 20(1): 743, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615399

RESUMO

BACKGROUND: The distribution and deposition of fat tissue in different parts of the body are the key factors affecting the carcass quality and meat flavour of chickens. Intramuscular fat (IMF) content is an important factor associated with meat quality, while abdominal fat (AbF) is regarded as one of the main factors affecting poultry slaughter efficiency. To investigate the differentially expressed genes (DEGs) and molecular regulatory mechanisms related to adipogenic differentiation between IMF- and AbF-derived preadipocytes, we analysed the mRNA expression profiles in preadipocytes (0d, Pre-) and adipocytes (10d, Ad-) from IMF and AbF of Gushi chickens. RESULTS: AbF-derived preadipocytes exhibited a higher adipogenic differentiation ability (96.4% + 0.6) than IMF-derived preadipocytes (86.0% + 0.4) (p < 0.01). By Ribo-Zero RNA sequencing, we obtained 4403 (2055 upregulated and 2348 downregulated) and 4693 (2797 upregulated and 1896 downregulated) DEGs between preadipocytes and adipocytes in the IMF and Ad groups, respectively. For IMF-derived preadipocyte differentiation, pathways related to the PPAR signalling pathway, ECM-receptor interaction and focal adhesion pathway were significantly enriched. For AbF-derived preadipocyte differentiation, the steroid biosynthesis pathways, calcium signaling pathway and ECM-receptor interaction pathway were significantly enriched. A large number of DEGs related to lipid metabolism, fatty acid metabolism and preadipocyte differentiation, such as PPARG, ACSBG2, FABP4, FASN, APOA1 and INSIG1, were identified in our study. CONCLUSION: This study revealed large transcriptomic differences between IMF- and AbF-derived preadipocyte differentiation. A large number of DEGs and transcription factors that were closely related to fatty acid metabolism, lipid metabolism and preadipocyte differentiation were identified in the present study. Additionally, the microenvironment of IMF- and AbF-derived preadipocyte may play a significant role in adipogenic differentiation. This study provides valuable evidence to understand the molecular mechanisms underlying adipogenesis and fat deposition in chickens.


Assuntos
Gordura Abdominal/citologia , Adipogenia , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Músculos/citologia , Gordura Abdominal/metabolismo , Adipócitos/citologia , Adipócitos/metabolismo , Animais , Diferenciação Celular , Galinhas , Metabolismo dos Lipídeos , Músculos/metabolismo , Análise de Sequência de RNA
8.
J Cell Biochem ; 120(4): 5085-5096, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30259568

RESUMO

20(S)-protopanaxadiol (PPD)-type ginsenosides are generally believed to be the most pharmacologically active components of Panax ginseng. These compounds induce apoptotic cell death in various cancer cells, which suggests that they have anti-cancer activity. Anti-angiogenesis is a promising therapeutic approach for controlling angiogenesis-related diseases such as malignant tumors, age-related macular degeneration, and atherosclerosis. Studies showed that 20(S)-PPD at low concentrations induces endothelial cell growth, but in our present study, we found 20(S)-PPD at high concentrations inhibited cell growth and mediated apoptosis in human umbilical vein endothelial cells (HUVECs). The mechanism by which high concentrations of 20(S)-PPD mediate endothelial cell apoptosis remains elusive. The present current study investigated how 20(S)-PPD induces apoptosis in HUVECs for the first time. We found that caspase-9 and its downstream caspase, caspase-3, were cleaved into their active forms after 20(S)-PPD treatment. Treatment with 20(S)-PPD decreased the level of Bcl-2 expression but did not change the level of Bax expression. 20(S)-PPD induced endoplasmic reticulum stress in HUVECs and stimulated UPR signaling, initiated by protein kinase R-like endoplasmic reticulum kinase (PERK) activation. Total protein expression and ATF4 nuclear import were increased, and CEBP-homologous protein (CHOP) expression increased after treatment with 20(S)-PPD. Furthermore, siRNA-mediated knockdown of PERK or ATF4 inhibited the induction of CHOP expression and 20(s)-PPD-induced apoptosis. Collectively, our findings show that 20(S)-PPD inhibits HUVEC growth by inducing apoptosis and that ATF4 expression activated by the PERK-eIF2α signaling pathway is essential for this process. These findings suggest that high concentrations of 20(S)-PPD could be used to treat angiogenesis-related diseases.


Assuntos
Fator 4 Ativador da Transcrição/metabolismo , Apoptose/efeitos dos fármacos , Fator de Iniciação 2 em Eucariotos/metabolismo , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Sapogeninas/farmacologia , Transdução de Sinais , eIF-2 Quinase/metabolismo , Caspase 3/metabolismo , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Modelos Biológicos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais/efeitos dos fármacos
9.
Int J Mol Sci ; 20(18)2019 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-31500376

RESUMO

Accumulating evidence has shown that miR-34a serves as a posttranscriptional regulatory molecule of lipid metabolism in mammals. However, little studies about miR-34a on lipid metabolism in poultry have been reported until now. To gain insight into the biological functions and action mechanisms of miR-34a on hepatic lipid metabolism in poultry, we firstly investigated the expression pattern of miR-34a-5p, a member of miR-34a family, in liver of chicken, and determined its function in hepatocyte lipid metabolism by miR-34a-5p overexpression and inhibition, respectively. We then validated the interaction between miR-34a-5p and its target using dual-luciferase reporter assay, and explored the action mechanism of miR-34a-5p on its target by qPCR and Western blotting. Additionally, we looked into the function of the target gene on hepatocyte lipid metabolism by gain- and loss-of-function experiments. Our results indicated that miR-34a-5p showed a significantly higher expression level in livers in peak-laying hens than that in pre-laying hens. miR-34a-5p could increase the intracellular levels of triglycerides and total cholesterol in hepatocyte. Furthermore, miR-34a-5p functioned by inhibiting the translation of its target gene, long-chain acyl-CoA synthetase 1 (ACSL1), which negatively regulates hepatocyte lipid content. In conclusion, miR-34a-5p could increase intracellular lipid content by reducing the protein level, without influencing mRNA stability of the ACSL1 gene in chickens.


Assuntos
Galinhas/genética , Galinhas/metabolismo , Colesterol/metabolismo , Coenzima A Ligases/genética , Fígado/metabolismo , MicroRNAs/genética , Triglicerídeos/metabolismo , Animais , Sequência de Bases , Linhagem Celular , Coenzima A Ligases/metabolismo , Expressão Gênica , Metabolismo dos Lipídeos , MicroRNAs/química
10.
Int J Mol Sci ; 20(23)2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31779219

RESUMO

The fatty acid-binding protein (FABP) gene family, which encodes a group of fatty acid-trafficking molecules that affect cellular functions, has been studied extensively in mammals. However, little is known about the gene structure, expression profile, and regulatory mechanism of the gene family in chickens. In the present study, bioinformatics-based methods were used to identify the family members and investigate their evolutionary history and features of gene structure. Real-time PCR combined with in vivo and in vitro experiments were used to examine the spatiotemporal expression pattern, and explore the regulatory mechanism of FABP genes. The results show that nine members of the FABP gene family, which branched into two clusters and shared a conserved FATTYACIDBP domain, exist in the genome of chickens. Of these, seven FABP genes, including FABP1, FABP3-7, and FABP10 were abundantly expressed in the liver of hens. The expression levels of FABP1, FABP3, and FABP10 were significantly increased, FABP5 and FABP7 were significantly decreased, and FABP4 and FABP6 remained unchanged in hens at the peak laying stage in comparison to those at the pre-laying stage. Transcription of FABP1 and FABP3 were activated by estrogen via estrogen receptor (ER) α, whilst FABP10 was activated by estrogen via ERß. Meanwhile, the expression of FABP1 was regulated by peroxisome proliferator activated receptor (PPAR) isoforms, of which tested PPARα and PPARß agonists significantly inhibited the expression of FABP1, while tested PPARγ agonists significantly increased the expression of FABP1, but downregulated it when the concentration of the PPARγ agonist reached 100 nM. The expression of FABP3 was upregulated via tested PPARß and PPARγ agonists, and the expression of FABP7 was selectively promoted via PPARγ. The expression of FABP10 was activated by all of the three tested PPAR agonists, but the expression of FABP4-6 was not affected by any of the PPAR agonists. In conclusion, members of the FABP gene family in chickens shared similar functional domains, gene structures, and evolutionary histories with mammalian species, but exhibited varying expression profiles and regulatory mechanisms. The results provide a valuable resource for better understanding the biological functions of individual FABP genes in chickens.


Assuntos
Biologia Computacional/métodos , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/metabolismo , Animais , Linhagem Celular , Galinhas , Evolução Molecular , Proteínas de Ligação a Ácido Graxo/química , Feminino , Regulação da Expressão Gênica , Fígado/metabolismo , Família Multigênica , Regiões Promotoras Genéticas , Domínios Proteicos , Receptores de Estrogênio/química , Receptores de Estrogênio/metabolismo , Distribuição Tecidual , Ativação Transcricional
11.
Funct Integr Genomics ; 18(6): 613-625, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29754269

RESUMO

Sweet potato (Ipomoea batatas (L.) Lam.) is one of the most important root crops in the world. Initial formation and development of storage roots (SRs) are key factors affecting its yields. In order to study the molecular mechanism and regulatory networks of the SRs development process, we have analyzed root transcriptomes between the high and low starch content sweet potato accessions at three different developmental stages. In this study, we assembled 46,840 unigenes using Illumina paired-end sequencing reads and identified differentially expressed genes (DEGs) between two accessions. The numbers of DEGs were increased with the development of SRs, indicating that the difference between two accessions is enlarging with the maturation. DEGs were mainly enriched in starch biosynthesis, plant hormones regulatory, and genetic information processing pathways. Then, expression patterns of DEGs that are most significant and starch biosynthesis related were validated using qRT-PCR. Our results provide valuable resources to future study on molecular mechanisms of SRs development and candidate genes for starch content improvement in sweet potato.


Assuntos
Regulação da Expressão Gênica de Plantas , Ipomoea batatas/genética , Raízes de Plantas/genética , Amido/genética , Genes de Plantas , Ipomoea batatas/metabolismo , Raízes de Plantas/metabolismo , Amido/biossíntese
12.
Cell Physiol Biochem ; 46(6): 2421-2433, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29742492

RESUMO

BACKGROUND/AIMS: Poultry meat quality is affected by many factors, among which intramuscular fat (IMF) is predominant. IMF content affects the tenderness, juiciness, and favor of chicken. An increasing number of studies are focusing on the functions of microRNAs (miRNAs) during the adipogenic process. However, little is known about miRNAs associated with poultry IMF deposition, especially intramuscular adipocyte differentiation. METHODS: The IMF content of two physiological stages was measured, and miRNA-Seq and RNA-Seq data were integrated and analyzed. A chicken intramuscular adipocyte cell differentiation model was constructed. A luciferase reporter assay, miRNA overexpression, and Oil Red O staining were used to confirm the targets of gga-miR-140-5p. RESULTS: Our results showed that late-laying-period hens, which had a higher IMF content, exhibited lower global expression levels of miRNAs than juvenile hens. A total of 104 differentially expressed (DE) miRNAs were identified between the two groups. Integrated analysis of differentially expressed genes and DE miRNAs identified a total of 378 miRNA-mRNA pairs. Functional enrichment analysis revealed that these intersecting genes are involved in ubiquitin-mediated proteolysis, the peroxisome proliferator-activated receptor signaling pathway, glycerophospholipid metabolism, and fatty acid elongation and degradation pathways. Furthermore, we demonstrated that gga-miR-140-5p promoted intramuscular adipocyte differentiation via targeting retinoid X receptor gamma. CONCLUSION: Our findings may contribute to a more thorough understanding of chicken IMF deposition and the improvement of poultry meat quality.


Assuntos
Adipogenia , Galinhas/genética , Carne , MicroRNAs/genética , Transcriptoma , Animais , Galinhas/metabolismo , Feminino , Qualidade dos Alimentos , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Carne/análise , Redes e Vias Metabólicas , Músculos/metabolismo , RNA Mensageiro/genética
13.
J Stroke Cerebrovasc Dis ; 27(2): 381-390, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29111341

RESUMO

BACKGROUND: Intravenous thrombolysis using tissue plasminogen activator (tPA) improves significantly the neurologic function in patients with acute ischemic stroke (AIS). However, it brings financial burden to patients and is associated with symptomatic intracranial hemorrhage (SICH). Whether low-dose tPA can effectively reduce SICH and has the same efficacy as standard-dose tPA is still controversial. METHODS: We searched for English clinical trials published before March, 2017on the comparison of the efficacy and safety between low and standard dose of tPA in the treatment of AIS using MEDLINE, Embase, and Cochrane Library. The modified Rankin scale (mRS) score was used as the primary efficacy outcome. The mRS1 corresponded to 0-1, whereas mRS2 corresponded to 0-2. The SICH and mortality were adopted as primary safety outcomes. RESULTS: Twelve high-quality studies were selected, including 7686 patients (low-dose: 2888, standard-dose: 4798). With no statistical heterogeneity, the fixed effects model was adopted in the analysis. Similarly to standard doses, low-dose tPA improved the mRS scores (mRS1: odds ratio [OR] = .92, 95% confidence interval [CI] .84-1.02; P = .12; mRS2: OR = .97, 95% CI .88-1.08; P = .57). Compared with standard-dose tPA, low-dose tPA reduced the incidence of SICH (by National Institute of Neurological Disorders and Stroke [NINDS] definition: OR = .71, 95% CI .57-0.89; P = .003; by Safe Implementation of Thrombolysis in Stroke Monitoring Study [SITS-MOST] definition: OR = .64, 95% CI .42-0.99; P = .04), while both reduced mortality (OR = .87, 95% CI .74-1.02; P = .08). CONCLUSIONS: Low-dose tPA is comparable to standard-dose tPA in improving the neurologic function and reducing mortality in AIS patients. Moreover, low-dose tPA can reduce the incidence of SICH compared with standard-dose tPA. Therefore, low-dose tPA is highly recommended in AIS patients.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/administração & dosagem , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/administração & dosagem , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/mortalidade , Isquemia Encefálica/fisiopatologia , Distribuição de Qui-Quadrado , Avaliação da Deficiência , Fibrinolíticos/efeitos adversos , Humanos , Infusões Intravenosas , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/prevenção & controle , Razão de Chances , Recuperação de Função Fisiológica , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/fisiopatologia , Terapia Trombolítica/efeitos adversos , Terapia Trombolítica/mortalidade , Fatores de Tempo , Ativador de Plasminogênio Tecidual/efeitos adversos , Resultado do Tratamento
14.
J Am Chem Soc ; 139(8): 3033-3044, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28166401

RESUMO

RNAi approaches have been widely combined with platinum-based anticancer agents to elucidate cellular responses and to target gene products that mediate acquired resistance. Recent work has demonstrated that platination of siRNA prior to transfection may negatively influence RNAi efficiency based on the position and sequence of its guanosine nucleosides. Here, we used detailed spectroscopic characterization to demonstrate rapid formation of Pt-guanosine adducts within 30 min after coincubation of oxaliplatin [OxaPt(II)] or cisplatin [CisPt(II)] with either guanosine monophosphate or B-cell lymphoma 2 (BCL-2) siRNA. After 3 h of exposure to these platinum(II) agents, >50% of BCL-2 siRNA transcripts were platinated and unable to effectively suppress mRNA levels. Platinum(IV) analogues [OxaPt(IV) or CisPt(IV)] did not form Pt-siRNA adducts but did display decreased in vitro uptake and reduced potency. To overcome these challenges, we utilized biodegradable methoxyl-poly(ethylene glycol)-block-poly(ε-caprolactone)-block-poly(l-lysine) (mPEG-b-PCL-b-PLL) to generate self-assembled micelles that covalently conjugated OxaPt(IV) and/or electrostatically complexed siRNA. We then compared multiple strategies by which to combine BCL-2 siRNA with either OxaPt(II) or OxaPt(IV). Overall, we determined that the concentrations of siRNA (nM) and platinum(II)-based anticancer agents (µM) that are typically used for in vitro experiments led to rapid Pt-siRNA adduct formation and ineffective RNAi. Coincorporation of BCL-2 siRNA and platinum(IV) analogues in a single micelle enabled maximal suppression of BCL-2 mRNA levels (to <10% of baseline), augmented the intracellular levels of platinum (by ∼4×) and the numbers of resultant Pt-DNA adducts (by >5×), increased the cellular fractions that underwent apoptosis (by ∼4×), and enhanced the in vitro antiproliferative activity of the corresponding platinum(II) agent (by 10-100×, depending on the cancer cell line). When combining RNAi and platinum-based anticancer agents, this generalizable strategy may be adopted to maximize synergy during screening or for therapeutic delivery.


Assuntos
Antineoplásicos/farmacologia , Compostos Organoplatínicos/farmacologia , Interferência de RNA , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Células MCF-7 , Micelas , Estrutura Molecular , Compostos Organoplatínicos/química , Relação Estrutura-Atividade , Células Tumorais Cultivadas
15.
Int J Mol Sci ; 18(7)2017 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-28665359

RESUMO

The very long chain fatty acid elongase (ELOVL) plays an important role in the synthesis of long-chain polyunsaturated fatty acids (LCPUFA). Previous studies suggest that chicken could be an alternate source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In this study, we detected that ELOVL5, which plays a key role in the biosynthesis of omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFA), was highly expressed in the liver of laying hens and increased rapidly after sexual maturity. Bioinformatic analysis revealed ELOVL fatty acid elongase 5 (ELOVL5) gene as a putative target of miR-218-5p, miR-19a-3p, miR-19b-3p, miR-30a-5p, miR-30b-5p, and miR-30e-5p. We demonstrated estrogen downregulated microRNA (miRNA), and that ELOVL5 is a direct target of miR-218-5p, which was located in intron 14 of the Slit guidance ligand 2 (SLIT2) gene and co-expressed with the host gene. Overall, estrogen enhanced hepatic synthesis of LCPUFA by functioning as a negative regulator of miRNA thereby augmenting the expression of these miRNA target genes, especially ELOVL5, which plays a key role in the biosynthesis of n-3 and n-6 LCPUFA. This study provides a novel model for the use of estrogen in the poultry industry as an inducer of ELOVL5 expression to enhance hepatic n-3 and n-6 LCPUFA synthesis at the post-transcriptional level.


Assuntos
Acetiltransferases/metabolismo , Estrogênios/farmacologia , Ácidos Graxos Insaturados/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Acetiltransferases/genética , Animais , Galinhas , Biologia Computacional , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/farmacologia , Elongases de Ácidos Graxos , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-6/farmacologia , Feminino , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , MicroRNAs/genética , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo
16.
Plant J ; 80(2): 282-91, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25073546

RESUMO

Heteroduplex DNA (hDNA) generated during homologous recombination (HR) is an important component that shapes genetic diversity in sexually reproducing organisms. However, studies of this process in higher plants are limited. This is because hDNAs are difficult to capture in higher plants as their reproductive developmental model only produces normal gametes and does not preserve the mitotic products of the post-meiotic segregation (PMS) process which is crucial for studying hDNAs. In this study, using the model system for tree and woody perennial plant biology (Populus), we propose a strategy for characterizing hDNAs in higher plants. We captured hDNAs by constructing triploid hybrids originating from a cross between unreduced 2n eggs (containing hDNA information as a result of inhibition chromosome segregation at the PMS stage) with normal male gametes. These triploid hybrids allowed us to detect the frequency and location of persistent hDNAs resulting from HR at the molecular level. We found that the frequency of persistent hDNAs, which ranged from 5.3 to 76.6%, was related to locations of the simple sequence repeat markers at the chromosomes, such as the locus-centromere distance, the surrounding DNA sequence and epigenetic information, and the richness of protein-coding transcripts at these loci. In summary, this study provides a method for characterizing persistent hDNAs in higher plants. When high-throughput sequencing techniques can be incorporated, genome-wide persistent hDNA assays for higher plants can be easily carried out using the strategy presented in this study.


Assuntos
DNA de Plantas/genética , Ácidos Nucleicos Heteroduplexes , Plantas/genética , Recombinação Homóloga
17.
Genome ; 58(2): 81-90, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26053224

RESUMO

Polymorphisms in miRNA genes could potentially alter various biological processes by influencing the processing and (or) target selection of miRNAs. The rs14120863 (C > G) mutation, which we characterized in a Gushi-Anka F2 resource population, resides in the precursor region of miR-1666. Association analysis with chicken carcass and growth traits showed that the SNP was significantly associated with carcass weight, evisceration weight, breast muscle weight, leg muscle weight, and body weight at 8 weeks of age, as well as some body size indexes including shank girth, chest breadth, breast bone length, and body slanting length, in the Gushi-Anka F2 resource population. Quantitative RT-PCR results showed that miR-1666 expression levels in muscle tissues differed within various genotypes. Experiment in DF1 cells further confirmed that the SNP in miR-1666 could significantly alter mature miRNA production. Subsequently, using dual-luciferase report assay, we verified that miR-1666 could perform its function through targeting of the CBFB gene. In conclusion, the SNP in the precursor of miR-1666 could significantly reduce mature miR-1666 production. It may further affect the function of miR-1666 through the target gene CBFB, hence it is associated with chicken growth traits.


Assuntos
Galinhas/genética , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Animais , Peso Corporal/genética , Linhagem Celular , Subunidade beta de Fator de Ligação ao Core/genética , Feminino , Genótipo , Masculino , MicroRNAs/metabolismo , Músculos/metabolismo , Conformação de Ácido Nucleico , Reação em Cadeia da Polimerase Via Transcriptase Reversa
18.
Chem Commun (Camb) ; 60(26): 3511-3514, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38410911

RESUMO

The newly discovered growth self-inhibition phenomenon of tautomeric crystals is now generalized to the demostrope (form B) of irbesartan that displays intra-annular tautomerism in neutral aqueous solutions. The dynamic intra-annular tautomer inter-conversion on the surface is the key factor. Our findings provide implications for producing and engineering tautomeric materials.

19.
Respirol Case Rep ; 12(3): e01328, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38504768

RESUMO

Tracheo-oesophageal fistula (TOF) can arise as a rare complication of malignancy (especially oesophageal or lung cancers) and pose difficult diagnostic and management dilemmas. We explore a challenging case of large malignant TOF below.

20.
Sci Data ; 11(1): 251, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38418828

RESUMO

Livestock constitute the world's largest anthropogenic source of methane (CH4), providing high-protein food to humans but also causing notable climate risks. With rapid urbanization and increasing income levels in China, the livestock sector will face even higher emission pressures, which could jeopardize China's carbon neutrality target. To formulate targeted methane reduction measures, it is crucial to estimate historical and current emissions on fine geographical scales, considering the high spatial heterogeneity and temporal variability of livestock emissions. However, there is currently a lack of time-series data on city-level livestock methane emissions in China, despite the flourishing livestock industry and large amount of meat consumed. In this study, we constructed a city-level livestock methane emission inventory with dynamic spatial-temporal emission factors considering biological, management, and environmental factors from 2010 to 2020 in China. This inventory could serve as a basic database for related research and future methane mitigation policy formulation, given the population boom and dietary changes.


Assuntos
Gado , Metano , Animais , China , Metano/análise , Urbanização
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA