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1.
J Mol Med (Berl) ; 98(4): 555-567, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32072231

RESUMO

Embryo implantation is an essential and complex process in mammalian reproduction. However, little evidence has indicated the involvement of autophagy during embryo implantation. To determine the possible role of autophagy in uterine of pregnant mice during the peri-implantation stage, we first examined the expression of autophagy-related markers ATG5 and LC3 on day 4, 5, and 6 of pregnancy (D4, D5, and D6, respectively). Compared with expression on D4, downregulation of the autophagy-related markers was observed on D5 and D6, the days after the embryo attached to the receptivity endometrium. Further examination showed that autophagy-related markers ATG5, ATG12, LC3, cathepsin B, and P62 at the implantation site were significantly decreased when comparing with the inter-implantation site. Fewer number of autophagosomes at the implantation site were also observed by transmission electron microscopy. To confirm the functional role of autophagy during embryo implantation in mice, we administered the autophagy inhibitor 3-methyladenine and chloroquine to mice. After treated with 3-methyladenine, the expression of decidual markers HOXA10 and progesterone receptor were significantly reduced. Furthermore, a reduction in implantation sites and increase in the HOXA10 and PR protein levels were observed in response to chloroquine treatment. In addition, impaired uterine decidualization and dysregulation of the PR and HOXA10 protein levels was observed after autophagy inhibited by 3-methyladenine and chloroquine in in vivo artificial decidualization mouse model. In the last, LC3 and P62 were also observed in normal human proliferative, secretory, and decidua tissues. In conclusion, endometrial autophagy may be essential for embryo implantation, and it may be associated with endometrial decidualization during early pregnancy. KEY MESSAGE: • Autophagy-related markers were significantly decreased at implantation site. • Autophagy inhibition results in abnormal decidualization. • Autophagy is essential for embryo implantation.

2.
Ann Hematol ; 99(3): 539-547, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31953585

RESUMO

Macrophages within tissues display a strong plastic ability in respond to environmental cues in both physiologic influences and disease. However, the macrophage phenotype and its distribution in the bone marrow biopsies (BMB) samples of human acute leukemia (AL) remain poorly understood. In this study, 97 BMB samples of patients with acute leukemia and 30 iron-deficiency anemias (IDA) as control group were evaluated with immunohistochemistry. In comparison with controls, the counts of CD68+, CD163+, and CD206+macrophages were remarkably increased in BMB samples of acute leukemia (P < 0.01), as well as their infiltration density was roaring up-regulation (P < 0.01). The expression levels of CD68+, CD163+, and CD206+macrophages were decreased in patients with complete remission, but there still existed statistically significant contrast to the control group (P < 0.01). The ratios of the CD163-positive cells or CD206-positive cells to CD68-positive cells were most prevalent in the BMB samples of human acute leukemia compared with the control group (P < 0.01), which support that macrophages were polarized to M2 macrophages.


Assuntos
Antígenos de Diferenciação/metabolismo , Medula Óssea , Leucemia , Macrófagos , Proteínas de Neoplasias/metabolismo , Doença Aguda , Adolescente , Adulto , Idoso , Biópsia , Medula Óssea/metabolismo , Medula Óssea/patologia , Feminino , Humanos , Leucemia/metabolismo , Leucemia/patologia , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade
3.
Biosci Rep ; 39(12)2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31729531

RESUMO

Colorectal cancer (CRC) remains the candidate for one of the typical types of malignant tumors of in gastrointestinal tract all around the world, which leads to tremendous death and ranks as the top leading death of cancer. Recently, microRNAs have emerged as double-edged sword in numerous cancers. This investigation aims to discuss the regulative role of microRNA-574-3p (miR-574-3p), elucidating its molecular mechanism and clinical significance in CRC. Herein, it revealed to us that miR-574-3p was lowly expressed in CRC tissues in comparison with the matched paracarcinoma tissues. In addition, transfection of SW480 and HT29 cells with miR-574-3p mimics prohibited the post-transcriptional expression of Cyclin D2 (CCND2), which then significantly blocked cell growth and cell migration, yet triggered cell apoptosis. Also, dual-luciferase reporter assays proved the role of CCND2 as the targeted gene for miR-574-3p. miR-574-3p overexpression prohibited the activity of CCND2 in SW480 and HT29 cells. Silencing of CCND2 in SW480 and HT29 CRC cell lines leading to reduced cell proliferative and migrative rates, and enhanced apoptotic rate. The suppressive effects of elevation of miR-574-3p on the proliferation of the human CRC cells and promotive effects on cell apoptosis by targeting CCND2 were further illustrated in the in vitro studies. Thus, we hypothesize that miR-574-3p may be served as a prospective therapeutic candidate for CRC.

4.
Molecules ; 24(18)2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31492021

RESUMO

Two new cytochalasans, Chaetomadrasins A (1) and B (2), along with six known analogues (3-8), were isolated from the solid-state fermented culture of desert soil-derived Chaetomium madrasense 375. Their structures were clarified by comprehensive spectroscopic analyses, and the absolute configurations of Compounds 1 and 2 were confirmed by electronic circular dichroism (ECD) and calculated ECD. For the first time, Chaetomadrasins A (1), which belongs to the chaetoglobosin family, is characterized by the presence of all oxygen atoms in the form of Carbonyl. Chaetomadrasin B (2) represents the first example of chaetoglobosin type cytochalasan characterized by a hydroxy unit and carbonyl group fused to the indole ring. Compounds 1 and 2 displayed moderate cytotoxicity against HepG2 human hepatocellular carcinoma cells.


Assuntos
Antineoplásicos/farmacologia , Produtos Biológicos/farmacologia , Chaetomium/química , Citocalasinas/farmacologia , Microbiologia do Solo , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Linhagem Celular , Citocalasinas/química , Citocalasinas/isolamento & purificação , Humanos , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Análise Espectral
5.
Planta Med ; 85(13): 1098-1106, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31250410

RESUMO

In previous studies, crude Houttuynia cordata polysaccharides showed beneficial effects on acute lung injury in vivo, a syndrome in which anti-complementary activities played an important role. Anti-complementary activity-guided fractionation of H. cordata polysaccharides led to the isolation of two highly branched homogeneous polysaccharides, HC-PS1 and HC-PS3, with a molecular weight of 274 530 and 216 384 Da, respectively. The polysaccharides were purified by chromatography on DEAE-cellulose and Superdex columns. Their structural characterization was performed by IR, GC-MS, methylation, NMR, and SEM analysis. Both HC-PS1 and HC-PS3 are composed of eight types of monosaccharides, including rhamnose, arabinose, mannose, glucose, glucuronic acid, galactose, galacturonic acid, and xylose. The main linkages of the sugar residues in HC-PS1 include terminal Rhap, terminal and 1,5-linked Araf; 1,3,6-linked and 1,4,6-linked Manp; terminal, 1,4-linked, 1,3-linked, 1,3,6-linked and 1,4,6-linked and 1,3,4,6-linked Glcp; and terminal, 1,4-linked and 1,6-linked Galp. The main monosaccharide linkages in HC-PS3 are similar to that of HC-PS1, except the additional 1,3,4-linked Manp and the absence of 1,3,6-linked Glcp. HC-PS1 and HC-PS3 were found to inhibit complement activation through both the classical and alternative pathways with 50% inhibition concentrations of 0.272 - 0.318 mg/mL without interfering with the coagulation system. Preliminary mechanism studies indicated that both HC-PS1 and HC-PS3 inhibited the activation of the complement system by interacting with C2, C4, and C5. The results suggest that HC-PS1 and HC-PS3 could be valuable for the treatment of diseases associated with the excessive activation of the complement system.


Assuntos
Proteínas do Sistema Complemento/efeitos dos fármacos , Houttuynia/química , Cromatografia DEAE-Celulose , Ativação do Complemento/efeitos dos fármacos , Humanos , Espectroscopia de Ressonância Magnética , Polissacarídeos/química , Polissacarídeos/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier
6.
Cell Stress Chaperones ; 24(1): 45-58, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30377954

RESUMO

The heat shock protein 90 (Hsp90) and heat shock cognate proteins (Hsc70) have been identified as chaperones of the ecdysone receptor (EcR)/ultraspiracle protein (USP) heterocomplex. However, little is known about the status of Hsp90 and Hsc70 in Polyrhachis vicina Roger. Here, we sequenced the transcriptomes of adult ants in P. vicina for the first time. Clean reads in female, male, and worker ants were annotated into 40,147 transcripts, and 37,488, 28,300, and 33,638 unigenes were assembled in female, male, and worker ants, respectively. According to RPKM, the numbers of differentially expressed genes between female and male ants, between female and worker ants, and between male and worker ants and the common differentially expressed genes were 12,657, 21,630, 15,112 and 3704, respectively. These results reveal that caste differentiation, caste specificity formation, and social divisions of P. vicina ants may be due to gene expression differences. Moreover, PvEcR and PvUSP were also detected as differentially expressed genes in the ants; specifically, PvUSP expression was higher than PvEcR expression in all castes. We speculate that PvUSP may have a role similar to that of juvenile hormone receptor. Four identified PvHsp90 family members and 23 identified PvHsp70 family members were found in the ants, and 2 PvHsp90 genes and 8 PvHsp70 genes were analyzed by qRT-PCR. Among those genes, the expression of 2 PvHsp90 genes and 5 PvHsp70 genes coincided with the expression profiles of PvEcR and PvUSP, which suggest that the characterization of PvHsp90 and PvHsc70 may be as EcR/USP molecular chaperones in P. vicina.


Assuntos
Formigas/genética , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP90/genética , Análise de Sequência de RNA/métodos , Animais , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Ontologia Genética , Genes de Insetos , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Hierarquia Social , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Masculino , Anotação de Sequência Molecular , Filogenia , Transcriptoma
7.
Zhonghua Nan Ke Xue ; 24(7): 589-595, 2018 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-30173440

RESUMO

Objective: To explore the antagonistic effect of vitamin E (VE) on male reproductive toxicity induced by di-2-ethylhexyl phthalate (DEHP) in pubertal SD rats and its underlying mechanisms. METHODS: Thirty 5-week-old male SD rats were randomly divided into five groups of equal number, corn oil control, low-dose (10 mg/kg/d), medium-dose (100 mg/kg/d) and high-dose DEHP exposure (500 mg/kg/d), and VE intervention (high-dose DEHP + VE ï¼»100 mg/kg/dï¼½), and treated respectively for 30 successive days. At 3 days after treatment, the testes of the animals were harvested for determination of the oxidative stress index, serum reproductive hormone levels, cauda epididymal sperm parameters, and expressions of cell apoptosis-related genes and proteins. RESULTS: Compared with the control group, the rats of the medium- and high-dose DEHP groups showed significant decreases in the levels of such serum reproductive hormones as follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T), sperm parameters as average path velocity (VAP), straight line velocity (VSL), curvilinear velocity (VCL), straightness (STR), linearity (LIN) and wobble (WOB), and the activities of superoxide dismutase (SOD) and glutathione peroxide (GSH-Px), but significant increases were observed in the latter two groups in the content of malondialdehyde (MDA)(ï¼»3.32±0.87ï¼½ nmol/mg pro vs ï¼»2.13±0.49ï¼½ nmol/ mg pro), mRNA expressions of Bad, Bax, Cytochrome C, Caspase-3 and the Bax/Bcl-2 ratio, and protein expressions of Cytochrome C and Caspase-3. In comparison with the high-dose DEHP group, the VE intervention group exhibited remarkably increased serum LH and T levels, sperm VAP, VSL, VCL, STR and WOB, and activities of SOD and GSH-Px, but markedly decreased mRNA expressions of Bad, Bax, Cytochrome C, Caspase-3 and the Bax/Bcl-2 ratio as well as the protein expressions of Cytochrome C and Caspase-3 in the testis tissue (P<0.05). CONCLUSIONS: Exposure to DEHP induces androgen secretion disorders, causes oxidative damage to the testicular tissue, activates the mitochondrial apoptosis pathway in the testis, and ultimately reduces the quality of epididymal sperm, while VE can protect the rat testis from DEHP-induced reproductive toxicity.


Assuntos
Antioxidantes/farmacologia , Dietilexilftalato/antagonistas & inibidores , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Vitamina E/farmacologia , Animais , Apoptose/genética , Proteína 5 Relacionada à Autofagia/metabolismo , Caspase 3/metabolismo , Epididimo , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Masculino , Malondialdeído/metabolismo , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Oxirredutases/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Reprodução , Espermatozoides/fisiologia , Superóxido Dismutase/metabolismo , Testosterona/sangue
8.
Gen Comp Endocrinol ; 266: 29-37, 2018 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-29746854

RESUMO

The estrogen-related receptor (ERR) gene is a member of the nuclear receptor subfamily. Previous studies have indicated that ERR plays important roles in regulating insect growth and development. How ERR is associated with ant caste specificities remains unclear. In this study, we attempted to identify the role of ERR in the regulation of different adult caste specificities of Polyrhachis vicina Roger. Significant variations were detected in the ants including PvERR expressions, some physiological indexes and morphological traits including survival rate, body weight, body length, head width and abdominal appearance by different techniques. The results revealed that when PvERR expressions is up-regulated, boundaries of the abdominal segments were indistinct on the ventral side of the abdomen in males. Down-regulation of PvERR expressions caused abdominal swelling in males and a distended ventral abdomen in females and workers. Variation in PvERR expressions led to a remarkable decline in ant survival rates, particularly for males. These results indicated that different caste adults appeared to have different degrees of sensitivity in physiological response and morphological changes caused by variation in PvERR expressions. Thus, our data demonstrate that PvERR plays an important role in regulating the different adult caste specificities of P. vicina.


Assuntos
Envelhecimento/fisiologia , Formigas/anatomia & histologia , Formigas/fisiologia , Hierarquia Social , Receptores Estrogênicos/metabolismo , Administração Oral , Animais , Formigas/genética , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Genisteína/farmacologia , Masculino , Interferência de RNA , RNA de Cadeia Dupla/administração & dosagem , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Estrogênicos/genética
9.
Exp Cell Res ; 367(2): 137-149, 2018 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-29580688

RESUMO

Increasing evidence suggests that mitochondrial respiratory chain complex I participates in carcinogenesis and cancer progression by providing energy and maintaining mitochondrial function. However, the role of complex I in ovarian cancer is largely unknown. In this study we showed that metformin, considered to be an inhibitor of complex I, simultaneously inhibited cell growth and induced mitochondrial-related apoptosis in human ovarian cancer cells. Metformin interrupted cellular energy metabolism mainly by causing damage to complex I that impacted mitochondrial function. Additionally, treatment with metformin increased the activation of sirtuin 3 (SIRT3), a mitochondrial deacetylase. We demonstrated that SIRT3 overexpression aggravated metformin-induced apoptosis, energy stress and mitochondrial dysfunction. Moreover, treatment with metformin or SIRT3 overexpression increased activation of AMP-activated protein kinase (AMPK), a major sensor of cellular energy status. AMPK compensated for energy loss by increasing glycolysis. The impact of this was assessed by reducing glucose levels in the media or by using inhibitors (2-deoxyglucose, Compound C) of glycolysis and AMPK. The combination of these factors with metformin intensified cytotoxicity through further downregulation of ATP. Our study outlines an important role for SIRT3 in the antitumor effect of mitochondrial complex I inhibitors in human ovarian cancer cells. This effect appears to be mediated by induction of energy stress and apoptosis. Strategies that target the mitochondria could be enhanced by modulating glycolysis to further aggravate energy stress that may increase the antitumor effect.


Assuntos
Antineoplásicos/farmacologia , Apoptose , Metformina/farmacologia , Mitocôndrias/efeitos dos fármacos , Neoplasias Ovarianas/metabolismo , Sirtuína 3/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Linhagem Celular Tumoral , Complexo I de Transporte de Elétrons/metabolismo , Feminino , Glucose/metabolismo , Humanos , Mitocôndrias/metabolismo , Neoplasias Ovarianas/patologia , Sirtuína 3/biossíntese , Estresse Fisiológico
10.
Radiat Environ Biophys ; 57(1): 41-54, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29230533

RESUMO

Radiation-induced fibrosis (RIF) is thought to involve the excessive accumulation of collagen and other extracellular matrix components; previously, we reported that ionizing radiation increased the type I collagen expression and that transforming growth factor (TGF)-ß was involved in this increase through activating its downstream mediator, Smad3. A recent study found that microRNAs (miRNAs)-small, noncoding sequences approximately 20 nucleotides long-negatively regulate the gene expression posttranscriptionally, and it has been suggested that miRNAs play essential roles in cellular processes, including fibrosis. However, their role in the development of RIF remains unexplored. In the present study, we examined the effects of miRNA on the expression of type I collagen induced by ionizing radiation and the mechanisms underlying the miRNA expression observed following ionizing radiation. We analyzed the regulation of miRNA following ionizing radiation by an miRNA real-time PCR, and found that miR-29 family members were downregulated in irradiated mouse fibroblasts and directly targeted type I collagen genes by specifically binding to the 3' untranslated region. We also found that the overexpression of miR-29 inhibited the ionizing radiation-induced expression of type I collagen, whereas the knockdown of miR-29 enhanced it. In addition, TGF-ß/Smad-signaling significantly decreased the transcription of miR-29, whereas the inhibition of this signaling pathway cancelled this decrease. In conclusion, miR-29 was involved in the regulation of type I collagen expression through the TGF-ß/Smad-signaling pathway in irradiated cells, suggesting that miR-29 may be an important regulator of RIF.


Assuntos
Colágeno Tipo I/genética , Regulação da Expressão Gênica/genética , Regulação da Expressão Gênica/efeitos da radiação , MicroRNAs/genética , Animais , Sequência de Bases , Regulação para Baixo/genética , Regulação para Baixo/efeitos da radiação , Fibrose , Camundongos , Células NIH 3T3 , Transdução de Sinais/genética , Transdução de Sinais/efeitos da radiação , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/metabolismo
11.
Connect Tissue Res ; 59(3): 263-273, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28829698

RESUMO

AIMS: Col5a1 encodes the α1 chain of type V collagen, a quantitatively minor fibrillar collagen that is critical for the formation and function of the organs in the body. MicroRNAs (miRNAs) are small noncoding RNAs that posttranscriptionally regulate biological functions by binding to the 3'-untranslated region (3'UTR) of specific target mRNA. In this study, we investigated the posttranscriptional regulation of miRNAs on the Col5a1 gene expression. MATERIALS AND METHODS: We cultured osteoblasts and fibroblasts of cell lines. To examine the 3'UTR activity of the Col5a1 gene, chimeric plasmids constructs containing the core promoter and 3'UTR of Col5a1 were generated and luciferase assays were performed. We also evaluated the role of miRNA using constructs that were mutated at the putative binding sites of miRNA. In addition, we evaluated the endogenous mRNA and protein, and luciferase activity of the Col5a1 gene after miRNA overexpression/knockdown or CRISPR/Cas9-induced knockout. RESULTS: The luciferase assay showed a decreased activity of the 3'UTR of Col5a1 gene. However, the expression of the mutant constructs of miRNA-binding sites was restored. The overexpression of miRNA inhibited the Col5a1 gene not only with regard to the luciferase activity and endogenous mRNA but also at the protein level. In contrast, the RNAi-mediated knockdown or CRISPR/Cas9 system increased the expression of the Col5a1 gene. CONCLUSION: These results provided evidence that miR-29b regulates the Col5a1 gene expression through binding to the 3'UTR, which might play an important role in the pathogenesis of disease related to bone metabolism and fibrogenic reactions.


Assuntos
Colágeno/genética , Fibroblastos/metabolismo , Regulação da Expressão Gênica/genética , Expressão Gênica/genética , MicroRNAs/genética , Animais , Linhagem Celular , Células Cultivadas , Colágeno/metabolismo , Camundongos , Osteoblastos/metabolismo , Regiões Promotoras Genéticas/genética
12.
Zhongguo Zhong Yao Za Zhi ; 42(17): 3398-3402, 2017 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-29192453

RESUMO

An Affi-Prep Polymyxin column was combined with a Phenyl Sepharose column and a Sephacryl S-300 column, respectively, to remove the lipopolysaccharides(LPS) in the anti-complementary crude polysaccharides of Houttuynia Herba. The contents of LPS in the polysaccharides were determined by chromogenic tachypleus amebocyte lysate(TAL)method during the procedure of purifying. The anti-complementary activities of the polysaccharides were also compared before and after the removal of LPS. Less remanent LPS was detected after purified using Penyl Sepharose combined with polymyxin column, with the clearance rate of 42.85%. All the columns had no effect on the anti-complementary activity of the polysaccharides. Penyl Sepharose combined with polymyxin column would be sound for LPS removal of the anti-complementary polysaccharides without reducing their bioactivity.


Assuntos
Houttuynia/química , Lipopolissacarídeos/isolamento & purificação , Polissacarídeos/química , Cromatografia , Sefarose
13.
Org Lett ; 19(22): 6208-6211, 2017 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-29090939

RESUMO

Two novel enediyne-derived natural products, amycolamycins A and B (1 and 2), were characterized from a locust-associated actinomycete Amycolatopsis sp. HCa4. Amycolamycins A and B contain a unique 2-(cyclopenta[a]inden-5-yl)oxirane core with suspected enediyne polyketide biosynthetic origin. Sequencing and analysis of the acm biosynthetic gene cluster allowed us to propose the biosynthetic pathway of 1 and 2. Moreover, amycolamycin A (1) was selectively cytotoxic to the M231 breast cancer cell line.


Assuntos
Actinobacteria , Animais , Enedi-Inos , Glucosídeos , Gafanhotos , Estrutura Molecular , Família Multigênica , Pirróis
14.
Sci Rep ; 7(1): 11248, 2017 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-28900140

RESUMO

Seed germination behavior is an important factor in the distribution of species. Many studies have shown that germination is controlled by phylogenetic constraints, however, it is not clear whether phylogenetic constraints or environmental cues explain seed germination of a genus from a common ancestor. In this study, seed germination under different temperature- and water-regimes [induced by different osmotic potentials of polyethylene glycol (PEG)] was investigated in the phylogenetically-related Caragana species that thrive in arid, semiarid, semihumid and humid environments. The results showed that the final percentage germination (FPG) decreased from 95% in species from arid habitats to 0% in species from humid habitats, but with no significant phylogenetic signal. Rather, the response of seed germination to temperature and PEG varied greatly with species from arid to humid habitats and was tightly linked to the ecological niche of the species, their seed coat structure and abscisic acid concentration. The findings are not consistent with the hypothesis that within a family or a genus, seed germination strategies can be a stable evolutionary trait, thus constraining interspecific variation, but the results clearly show that seed germination of Caragana species distributed across a range of habitats has adapted to the environment of that habitat.


Assuntos
Caragana/crescimento & desenvolvimento , Sinais (Psicologia) , Exposição Ambiental , Germinação , Sementes/crescimento & desenvolvimento , Caragana/genética , Clima , Umidade , Pressão Osmótica , Filogenia , Polietilenoglicóis/metabolismo , Sementes/genética , Temperatura
15.
Int J Mol Sci ; 18(7)2017 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-28737710

RESUMO

Recovered blood supply after cerebral ischemia for a certain period of time fails to restore brain function, with more severe dysfunctional problems developing, called cerebral ischemia-reperfusion injury (CIR). CIR involves several extremely complex pathophysiological processes in which the interactions between key factors at various stages have not been fully elucidated. Mitochondrial dysfunction is one of the most important mechanisms of CIR. The mitochondrial deacetylase, sirtuin 3 (SIRT3), can inhibit mitochondrial oxidative stress by deacetylation, to maintain mitochondrial stability. Uncoupling protein 2 (UCP2) regulates ATP (Adenosine triphosphate) and reactive oxygen species production by affecting the mitochondrial respiratory chain, which may play a protective role in CIR. Finally, we propose that UCP2 regulates the activity of SIRT3 through sensing the energy level and, in turn, maintaining the mitochondrial steady state, which demonstrates a cytoprotective effect on CIR.


Assuntos
Encefalopatias/metabolismo , Mitocôndrias/metabolismo , Estresse Oxidativo , Traumatismo por Reperfusão/metabolismo , Sirtuína 3/metabolismo , Proteína Desacopladora 2/metabolismo , Animais , Encefalopatias/patologia , Humanos , Mitocôndrias/patologia , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/patologia
16.
Cancer Sci ; 108(7): 1405-1413, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28498503

RESUMO

Platinum-based therapeutic strategies have been widely used in ovarian cancer treatment. However, drug resistance has greatly limited therapeutic efficacy. Recently, tolerance to cisplatin has been attributed to other factors unrelated to DNA. p62 (also known as SQSTM1) functions as a multifunctional hub participating in tumorigenesis and may be a therapeutic target. Our previous study showed that p62 was overexpressed in drug-resistant ovarian epithelial carcinoma and its inhibition increased the sensitivity to cisplatin. In this study, we demonstrate that the activity of the NF-κB signaling pathway and K63-linked ubiquitination of RIP1 was higher in cisplatin-resistant ovarian (SKOV3/DDP) cells compared with parental cells. In addition, cisplatin resistance could be reversed by inhibiting the expression of p62 using siRNA. Furthermore, deletion of the ZZ domain of p62 that interacts with RIP1 in SKOV3 cells markedly decreased K63-linked ubiquitination of RIP1 and inhibited the activation of the NF-κB signaling pathway. Moreover, loss of the ZZ domain from p62 led to poor proliferative capacity and high levels of apoptosis in SKOV3 cells and made them more sensitive to cisplatin treatment. Collectively, we provide evidence that p62 is implicated in the activation of NF-κB signaling that is partly dependent on RIP1. p62 promotes cell proliferation and inhibits apoptosis thus mediating drug resistance in ovarian cancer cells.


Assuntos
Resistencia a Medicamentos Antineoplásicos/fisiologia , NF-kappa B/metabolismo , Neoplasias Epiteliais e Glandulares/patologia , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo , Neoplasias Ovarianas/patologia , Proteínas de Ligação a RNA/metabolismo , Proteína Sequestossoma-1/metabolismo , Antineoplásicos/farmacologia , Western Blotting , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Cisplatino/farmacologia , Feminino , Citometria de Fluxo , Imunofluorescência , Humanos , Imunoprecipitação , Microscopia Confocal , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Ovarianas/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais
17.
Mol Divers ; 21(2): 293-304, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28144767

RESUMO

A concise, efficient one-pot synthesis of functionalized chromeno[4,3-b]pyridine derivatives via a three-component reaction of 4-oxo-4H-chromene-3-carbaldehydes, malononitrile or cyanoacetates, and aromatic amines under catalyst-free conditions in an environmentally friendly medium (ethanol-water, 3:1 v/v) is described. This synthesis involves a group-assisted purification process, which avoids traditional recrystallization and chromatographic purification methods.


Assuntos
Piridinas/química , Piridinas/síntese química , Técnicas de Química Sintética , Etanol/química , Química Verde , Água/química
18.
Clin J Pain ; 33(4): 369-375, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27518492

RESUMO

BACKGROUND: Transversus abdominis plane (TAP) block reduces opiate requirements and pain scores in abdominal surgery, but the effect has not been evaluated in hernia surgery. The aim of this study was to evaluate the efficacy of TAP block in hernia surgery. METHODS: A meta-analysis of randomized clinical trials (RCTs) evaluating the effect of TAP block in adults undergoing hernia surgery was performed. The primary outcomes were morphine requirements 24 hours after surgery and the number of rescue analgesia patients. Secondary outcomes were pain scores on rest and on movement at 24 hours after surgery, postoperative nausea and vomiting and general postoperative complications. RESULTS: The search strategy yielded 231 articles after duplicates have been removed, and finally 8 RCTs with a total of 791 patients were included. In patients who received a TAP block, the cumulative morphine utilization was significantly reduced at 24 hours (weighted mean difference [WMD] -11.40 mg, -22.41 to -0.39; P=0.04). The number of patients needing a rescue analgesia (relative risk: 0.35, 0.22 to 0.55; P<0.001), the pain scores on rest 24 hours after surgery (WMD: -0.29, -0.55 to -0.04; P=0.02) and the pain scores on movement or coughing 24 hours after surgery (WMD: -0.70, -1.33 to -0.06; P=0.03) were all lower in patients who received a TAP block. There was also significant reduction in the postoperative nausea and vomiting, and the general postoperative complications in TAP block group. CONCLUSIONS: Within a heterogeneous group of RCTs, TAP block reduces postoperative morphine requirements and the severity of pain after hernia surgery.


Assuntos
Herniorrafia , Bloqueio Nervoso , Músculos Abdominais , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Aging Cell ; 16(2): 226-236, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27790859

RESUMO

Methionine (Met) sulfoxide reductase A (MsrA) is a key endogenous antioxidative enzyme with longevity benefits in animals. Only very few approaches have been reported to enhance MsrA function. Recent reports have indicated that the antioxidant capability of MsrA may involve a Met oxidase activity that facilities the reaction of Met with reactive oxygen species (ROS). Herein, we used a homology modeling approach to search the substrates for the oxidase activity of MsrA. We found that dimethyl sulfide (DMS), a main metabolite that produced by marine algae, emerged as a good substrate for MsrA-catalytic antioxidation. MsrA bounds to DMS and promoted its antioxidant capacity via facilitating the reaction of DMS with ROS through a sulfonium intermediate at residues Cys72, Tyr103, and Glu115, followed by the release of dimethyl sulfoxide (DMSO). DMS reduced the antimycin A-induced ROS generation in cultured PC12 cells and alleviated oxidative stress. Supplement of DMS exhibited cytoprotection and extended longevity in both Caenorhabditis elegans and Drosophila. MsrA knockdown abolished the cytoprotective effect and the longevity benefits of DMS. Furthermore, we found that the level of physiologic DMS was at the low micromolar range in different tissues of mammals and its level decreased after aging. This study opened a new window to elucidate the biological role of DMS and other low-molecular sulfides in the cytoprotection and aging.


Assuntos
Biocatálise/efeitos dos fármacos , Caenorhabditis elegans/fisiologia , Drosophila melanogaster/fisiologia , Longevidade/fisiologia , Metionina Sulfóxido Redutases/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Sulfetos/farmacologia , Aminoácidos/metabolismo , Animais , Antioxidantes/farmacologia , Sítios de Ligação , Caenorhabditis elegans/efeitos dos fármacos , Citoproteção/efeitos dos fármacos , Drosophila melanogaster/efeitos dos fármacos , Depuradores de Radicais Livres/metabolismo , Técnicas de Silenciamento de Genes , Longevidade/efeitos dos fármacos , Modelos Biológicos , Células PC12 , Ratos , Espécies Reativas de Oxigênio/metabolismo
20.
Muscles Ligaments Tendons J ; 7(3): 442-448, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29387637

RESUMO

Background: We aimed to investigate the three-dimensional structure of the collagenous fibers of the ligamentum teres (LT) of the human hip and clarify the LT micro-anatomy at the attachment of the femoral head. Methods: Femoral heads and LT were collected during hip arthroplasty. Specimens were cut into 5-10-mm squares, prepared, developed, and observed under a light microscope. Next, specimens were prepared and examined under a scanning electron microscope (SEM). Results: Under optical microscope, LT adhered to the artificial cartilage at the attachment of the femoral head. Under SEM, LT comprised parallelly arranged collagenous fibers and the fine collagenous fibrils were twisted. While the central collagenous fibers of the LT at the attachment of the femoral head penetrated the articular cartilage tissue and reached the ring-shaped bone, fibers at the margin traversed and adhered to the cartilage surface. Conclusion: Articular cartilage and subchondral bone are present at the LT attachment to the femoral head. Although collagenous fibers of the LT show parallel arrangement at the main trunk, they are dispersed at the cartilage surface and not all reach the thin subchondral bone of the femoral head. This could possibly weaken ligament strength at the attachment of the femoral head. Level of evidence: IV.

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