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1.
Lupus ; 33(10): 1059-1068, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39052974

RESUMO

BACKGROUND AND OBJECTIVES: This study aimed to assess the utility of Doppler echocardiography in evaluating left ventricular diastolic function, and prognosis in patients with systemic lupus erythematosus (SLE). PATIENTS AND METHODS: A total of 286 SLE patients were selected along with 100 age- and gender-matched healthy individuals who underwent physical examinations. Clinical baseline characteristics were collected. Various Doppler echocardiographic parameters were measured and analyzed, including left ventricular posterior wall thickness (LVPWT), interventricular septal diameter (IVSD), left ventricular mass (LVM), LVM index (LVMI), and others. RESULTS: Compared to the control group, SLE patients exhibited significantly higher levels of C-reactive protein and lower levels of complement (C) 3 and C4 (p < .001). Doppler echocardiographic parameters showed significant differences between SLE patients and healthy controls, including increased LVPWT, IVSD, LVM, LVMI, peak A, PWI + Tei, E/e', TDI-Tei, and decreased e' and E/A (p < .001). Subgroup analyses indicated more severe ventricular diastolic dysfunction in patients with higher SLE activity and those who experienced cardiovascular events. Correlation analysis revealed positive associations of PWI + Tei, TDI-Tei, and GLS with SLE activity and cardiovascular events (p < .01). Multivariate logistic regression analysis identified LVMI, PWI + Tei, TDI-Tei, and GLS as significant predictors of cardiovascular events (p < .05). CONCLUSION: Doppler echocardiography is a valuable tool for the early diagnosis of left ventricular diastolic dysfunction in SLE patients. Key echocardiographic parameters, including LVMI, PWI + Tei, TDI-Tei, and GLS, are effective in predicting cardiovascular events, underscoring the importance of comprehensive cardiac function assessments in these patients.


Assuntos
Ecocardiografia Doppler , Lúpus Eritematoso Sistêmico , Valor Preditivo dos Testes , Disfunção Ventricular Esquerda , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/fisiopatologia , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Feminino , Masculino , Adulto , Ecocardiografia Doppler/métodos , Pessoa de Meia-Idade , Estudos de Casos e Controles , Prognóstico , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/diagnóstico por imagem , Proteína C-Reativa/análise , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Diástole
2.
Fish Physiol Biochem ; 46(5): 1743-1757, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32514853

RESUMO

Gonadotropin-releasing hormone (GnRH) is a key neuropeptide of the reproductive system. However, little is known about the role of GnRH in the spotted scat (Scatophagus argus). Here, three GnRH subtypes (cGnRH-II, sGnRH, and sbGnRH) were identified in the spotted scat. cGnRH-II and sGnRH were only expressed in the brains and gonads of both male and female fish, exhibiting a tissue-specific expression pattern, while sbGnRH was expressed at different transcription levels in all examined tissues. During ovarian maturation, hypothalamus-associated sbGnRH was upregulated, while the expression of sGnRH was variable and cGnRH-II first increased and then decreased. In vivo experiments showed that sbGnRH significantly promoted the expression of fsh and lh genes in a dose-dependent manner and exhibited a desensitization effect on lh expression at high concentrations. For sGnRH and cGnRH-II, only high concentrations could induce fsh and lh expression. Furthermore, treatment with highly concentrated sbGnRH peptide also induced fsh and lh expression, whereas the sGnRH and cGnRH-II peptides only induced fsh expression in vitro. 17ß-Estradiol (E2) significantly inhibited the expression of sbGnRH mRNA in a dose-dependent manner and did not impact sGnRH and cGnRH-II mRNA levels in vivo or in vitro. The inhibitory effect of E2 on sbGnRH expression was attenuated by the estrogen receptor (ER) broad-spectrum antagonist (fulvestrant) and the ERα-specific antagonist (methyl-piperidinopyrazole), respectively, implying that the feedback regulation on sbGnRH is mediated via ERα. This study provides a theoretical basis for the reproductive endocrinology of the spotted scat by studying GnRH.


Assuntos
Estrogênios/metabolismo , Peixes/fisiologia , Hormônio Liberador de Gonadotropina/metabolismo , Sequência de Aminoácidos , Animais , Clonagem Molecular , DNA Complementar , Estradiol , Feminino , Hormônio Foliculoestimulante/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/genética , Hipotálamo , Hormônio Luteinizante/metabolismo , Ovário/crescimento & desenvolvimento , Filogenia , Receptores de Estrogênio/antagonistas & inibidores , Transcriptoma/efeitos dos fármacos
3.
BMC Cardiovasc Disord ; 19(1): 21, 2019 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-30654760

RESUMO

BACKGROUND: Kawasaki disease (KD) is an acute febrile childhood systemic vasculitis that disturbs coronary arteries. The pathogenesis remains unknown. The study of phosphorylated proteins helps to elucidate the relevant pathophysiological mechanisms of cardiovascular disease. However, few researches explored phosphorylated proteins in KD patients. METHODS: We compared phosphoprotein profiles of HCAECs stimulated by the serum of KD patients and normal children using iTRAQ technology, TiO2 enrichment phosphorylated peptide and MS analysis. Then we conducted the functional analysis by ClueGO and the biological interaction networking analysis by ReactomeFIViz. Western blotting was performed to identify the hub proteins. RESULTS: Our results revealed that phosphorylation of 148 proteins showed different intensities between the two HCAECs groups, which are enriched in MAPK, VEGFR, EGFR, Angiopoietin receptor, mTOR, FAK signaling pathway and so on. Through the Network Analyzer analysis, the hub proteins are CDKN1A, MAPK1 and POLR2A, which were experimentally validated. CONCLUSION: In summary, we provided evidence addressing the valuable phosphorylation signaling that could be useful resource to understand the molecular mechanism and the potential targets for novel therapy of KD.


Assuntos
Vasos Coronários/metabolismo , Células Endoteliais/metabolismo , Síndrome de Linfonodos Mucocutâneos/sangue , Proteínas/metabolismo , Proteômica/métodos , Estudos de Casos e Controles , Células Cultivadas , Pré-Escolar , Cromatografia Líquida de Alta Pressão , Cromatografia de Fase Reversa , Feminino , Humanos , Lactente , Masculino , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Fosforilação , Mapas de Interação de Proteínas , Transdução de Sinais , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem
4.
Molecules ; 24(3)2019 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-30696009

RESUMO

Biomarkers from methane hydrate-bearing sediments can provide vital evidence for microbial activities associated with methanogenesis and their relation to the formation of methane hydrates. However, the former mainly focus on intact polar lipids from these microorganisms, and rarely investigate molecular hydrocarbons such as acyclic isoprenoids and hopanes so far. In this work, the composition of biomarkers in the methane hydrate-bearing sediments in cores SH2B and SH7B from the Shenhu area, the South China Sea (SCS) were identified by gas chromatography-mass spectrometry (GC-MS) and comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry (GC×GC-TOFMS). The occurrence of unresolved complex mixtures (UCMs) and 25-norhopane indicate that the organic matters in methane hydrate-bearing sediments underwent a high degree of biodegradation. Although specific biomarkers for methanogens were not identified, the UCMs, 25-norhopane, pristane, phytane, and hopanes can still indicate the microbial activities associated with methanogenesis. These molecular signals suggest that diverse microorganisms, particularly methanogens, were quite vigorous in the methane hydrate-bearing sediments. Further, the biomarkers identified in this study can also be steadily detected from deep oil/gas reservoirs. Considering numerous adjacent oil/gas reservoir systems, fault systems, and mud diapers occurred in the SCS, it can be inferred that microbial activities and deep oil/gas reservoirs may have jointly contributed to the formation of methane hydrate deposits in the SCS.


Assuntos
Biomarcadores , Sedimentos Geológicos/análise , Sedimentos Geológicos/química , Metano/análise , China , Cromatografia Gasosa-Espectrometria de Massas , Geografia , Sedimentos Geológicos/microbiologia , Microbiota , Oceanos e Mares
5.
Int J Mol Sci ; 19(10)2018 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-30262794

RESUMO

Chemokine receptor Cxcr4 evolved two paralogs in the teleost lineage. However, cxcr4a and cxcr4b have been characterized only in a few species. In this study, we identified two cxcr4 paralogs from the orange-spotted grouper, Epinephelus coioides. The phylogenetic relationship and gene structure and synteny suggest that the duplicated cxcr4a/b should result from the teleost-specific genome duplication (Ts3R). The teleost cxcr4 gene clusters in two paralogous chromosomes exhibit a complementary gene loss/retention pattern. Ec_cxcr4a and Ec_cxcr4b show differential and biased expression patterns in grouper adult tissue, gonads, and embryos at different stages. During embryogenesis, Ec_cxcr4a/b are abundantly transcribed from the neurula stage and mainly expressed in the neural plate and sensory organs, indicating their roles in neurogenesis. Ec_Cxcr4a and Ec_Cxcr4b possess different chemotactic migratory abilities from the human SDF-1α, Ec_Cxcl12a, and Ec_Cxcl12b. Moreover, we uncovered the N-terminus and TM5 domain as the key elements for specific ligand⁻receptor recognition of Ec_Cxcr4a-Ec_Cxcl12b and Ec_Cxcr4b-Ec_Cxcl12a. Based on the biased and divergent expression patterns of Eccxcr4a/b, and specific ligand⁻receptor recognition of Ec_Cxcl12a/b⁻Ec_Cxcr4b/a, the current study provides a paradigm of sub-functionalization of two teleost paralogs after Ts3R.


Assuntos
Bass/genética , Proteínas de Peixes/genética , Receptores CXCR4/genética , Animais , Bass/crescimento & desenvolvimento , Bass/metabolismo , Sítios de Ligação , Proteínas de Peixes/química , Proteínas de Peixes/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Células HEK293 , Humanos , Ligantes , Ligação Proteica , Receptores CXCR4/química , Receptores CXCR4/metabolismo
6.
Int J Mol Sci ; 18(4)2017 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-28333083

RESUMO

Multiple nanos genes have been characterized in several fishes, but the functional implications of their various expression patterns remain unclear. In this study, we identified and characterized four nanos genes from a hermaphroditic fish orange-spotted grouper, Epinephelus coioides. Ecnanos1a and Ecnanos1b show divergent expression patterns, and the dynamic expression change of Ecnanos1a in pituitaries during sex change is associated with testis differentiation and spermatogenesis. Ecnanos2 and Ecnanos3 might be germline stem cells (GSCs) and primordial germ cells (PGCs)-specific markers, respectively. Significantly, Ecnanos3 3'-untranslated region (UTR) is necessary for PGC specific expression, where a non-canonical "GCACGTTT" sequence is required for miR-430-mediated repression of Ecnanos3 RNA. Furthermore, grouper Dead end (Dnd) can relieve miR-430 repression in PGCs by associating with a 23 bp U-rich region (URR) in Ecnanos3 3'-UTR. The current study revealed the functional association of multiple nanos genes with PGC formation and germ cell development in orange-spotted grouper, and opened up new possibilities for developing biotechnologies through utilizing the associations between Ecnanos3 and PGCs or between Ecnanos2 and GSCs in the hermaphroditic fish.


Assuntos
Proteínas de Peixes/genética , Regulação da Expressão Gênica no Desenvolvimento , Perciformes/genética , Proteínas de Ligação a RNA/genética , Regiões 3' não Traduzidas , Animais , Diferenciação Celular , Proteínas de Peixes/metabolismo , Células Germinativas/citologia , Células Germinativas/metabolismo , Organismos Hermafroditas/genética , Organismos Hermafroditas/crescimento & desenvolvimento , Organismos Hermafroditas/metabolismo , Masculino , MicroRNAs/genética , Perciformes/crescimento & desenvolvimento , Perciformes/metabolismo , Proteínas de Ligação a RNA/metabolismo , Testículo/metabolismo
7.
PLoS Genet ; 9(5): e1003494, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23658533

RESUMO

Regulatory T cells expressing the transcription factor Foxp3 play indispensable roles for the induction and maintenance of immunological self-tolerance and immune homeostasis. Genome-wide mRNA expression studies have defined canonical signatures of T cell subsets. Changes in steady-state mRNA levels, however, often do not reflect those of corresponding proteins due to post-transcriptional mechanisms including mRNA translation. Here, we unveil a unique translational signature, contrasting CD4(+)Foxp3(+) regulatory T (T(Foxp3+)) and CD4(+)Foxp3(-) non-regulatory T (TFoxp3-) cells, which imprints subset-specific protein expression. We further show that translation of eukaryotic translation initiation factor 4E (eIF4E) is induced during T cell activation and, in turn, regulates translation of cell cycle related mRNAs and proliferation in both T(Foxp3)- and T(Foxp3+) cells. Unexpectedly, eIF4E also affects Foxp3 expression and thereby lineage identity. Thus, mRNA-specific translational control directs both common and distinct cellular processes in CD4(+) T cell subsets.


Assuntos
Fatores de Transcrição Forkhead/genética , Regulação da Expressão Gênica/imunologia , Tolerância Imunológica/genética , Subpopulações de Linfócitos T , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Fator de Iniciação 4E em Eucariotos/genética , Fatores de Transcrição Forkhead/imunologia , Humanos , RNA Mensageiro/genética , RNA Mensageiro/imunologia , Subpopulações de Linfócitos T/citologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo
8.
Appl Opt ; 54(33): 9688-94, 2015 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-26836524

RESUMO

Using a monochromatic laser beam to illuminate a homogeneous glass bead, some rainbows will appear around it. This paper concentrates on the study of the scattering intensity distribution and the method of measuring the refractive index for glass beads based on the Debye theory. It is found that the first rainbow due to the scattering superposition of backward light of the low-refractive-index glass beads can be explained approximately with the diffraction, the external reflection plus the one internal reflection, while the second rainbow of high-refractive-index glass beads is due to the contribution from the diffraction, the external reflection, the direct transmission, and the two internal reflections. The scattering intensity distribution is affected by the refractive index, the radius of the glass bead, and the incident beam width. The effects of the refractive index and the glass bead size on the first and second minimum deviation angle position are analyzed in this paper. The results of the measurements agree very well with the specifications.

9.
Mar Drugs ; 13(4): 1798-818, 2015 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-25830683

RESUMO

Alginate is a natural polysaccharide extracted from various species of marine brown algae. Alginate-derived guluronate oligosaccharide (GOS) obtained by enzymatic depolymerization has various pharmacological functions. Previous studies have demonstrated that GOS can trigger the production of inducible nitric oxide synthase (iNOS)/nitric oxide (NO), reactive oxygen species (ROS) and tumor necrosis factor (TNF)-α by macrophages and that it is involved in the nuclear factor (NF)-κB and mitogen-activated protein (MAP) kinase signaling pathways. To expand upon the current knowledge regarding the molecular mechanisms associated with the GOS-induced immune response in macrophages, comparative proteomic analysis was employed together with two-dimensional electrophoresis (2-DE), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF MS) and Western blot verification. Proteins showing significant differences in expression in GOS-treated cells were categorized into multiple functional pathways, including the NF-κB signaling pathway and pathways involved in inflammation, antioxidant activity, glycolysis, cytoskeletal processes and translational elongation. Moreover, GOS-stimulated changes in the morphologies and actin cytoskeleton organization of RAW264.7 cells were also investigated as possible adaptations to GOS. This study is the first to reveal GOS as a promising agent that can modulate the proper balance between the pro- and anti-inflammatory immune responses, and it provides new insights into pharmaceutical applications of polysaccharides.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/farmacologia , Desenho de Fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Oligossacarídeos/farmacologia , Polissacarídeos Bacterianos/farmacologia , Alginatos/metabolismo , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/metabolismo , Antioxidantes/química , Antioxidantes/metabolismo , Sequência de Carboidratos , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/imunologia , Núcleo Celular/metabolismo , Tamanho do Núcleo Celular/efeitos dos fármacos , Tamanho Celular/efeitos dos fármacos , Ácido Glucurônico/metabolismo , Ácidos Hexurônicos/metabolismo , Hidrólise , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/citologia , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Peso Molecular , Oligossacarídeos/química , Oligossacarídeos/metabolismo , Mapeamento de Peptídeos , Polissacarídeo-Liases/metabolismo , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/metabolismo , Proteômica/métodos , Células RAW 264.7
10.
Invest New Drugs ; 32(4): 598-603, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24711125

RESUMO

Deranged cap-mediated translation is implicated in the genesis, maintenance and progression of many human cancers including mesothelioma. In this study, disrupting the eIF4F complex by antagonizing the eIF4E-mRNA-cap interaction is assessed as a therapy for mesothelioma. Mesothelioma cells were treated with 4Ei-1, a membrane permeable prodrug that when converted to the active drug, 7-benzyl guanosine monophosphate (7Bn-GMP) displaces capped mRNAs from the eIF4F complex. Colony formation was measured in mesothelioma treated with 4Ei-1 alone or combined with pemetrexed. Proliferation was examined in cells treated with 4Ei-1. Binding to a synthetic cap-analogue was used to study the strength of eIF4F complex activation in lysates exposed to 4Ei-1. 4Ei-1 treatment resulted in a dose dependent decrease in colony formation and cell viability. Combination therapy of 4Ei-1 with pemetrexed further reduced colony number. Formation of eIF4F cap-complex decreased in response to 4Ei-1 exposure. 4Ei-1 is a novel prodrug that reduces proliferation, represses colony formation, diminishes association of eIF4F with the mRNA cap, and sensitizes mesothelioma cells to pemetrexed.


Assuntos
Mesotelioma/tratamento farmacológico , Proteínas Oncogênicas/antagonistas & inibidores , Pró-Fármacos/farmacologia , Biossíntese de Proteínas/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Fator de Iniciação 4E em Eucariotos/antagonistas & inibidores , Fator de Iniciação 4F em Eucariotos/antagonistas & inibidores , Glutamatos/farmacologia , Guanina/análogos & derivados , Guanina/farmacologia , Humanos , Mesotelioma/genética , Proteínas Oncogênicas/genética , Pemetrexede , Biossíntese de Proteínas/genética , RNA Mensageiro/genética
11.
Zhongguo Zhong Yao Za Zhi ; 39(16): 3180-3, 2014 Aug.
Artigo em Zh | MEDLINE | ID: mdl-25509311

RESUMO

To make a thorough investigation of the common She's nationality wild medicinal plants resources in our country, including the species, the distribution, the folk application and the endemic medicinal plant species, Field surveyed was conducted with 25 She people mainly lived area (county, district or city) throughout the country, the folk prescription and treatment cases provided by She's medical personnel, the drug usage and dosage, the commonly used traditional She's medicine and drug samples were collected. And the distribution, growing environment of these plants were investigated, their characteristics, photographs, GPS data and track were record , and the fresh wax leaf or plants specimens were collected. In total 1 600 varieties of folk medicine of She's nationality, 450 disease names and 1 016 prescriptions were collected. 520 kinds of these medicinal plants were commonly used, growing mainly distributed in the southeastern China, about 200 meters above sea level to 1 500 meters. There are 5 First-Grade State protection wild plants (medicinal), 15 second-Grade State protection wild plants (medicinal), and 11 She characteristic medicinal plants in our study, they belong to 144 families, 312 genera 494 species, 2 subspecies, 17 varieties, 3 forms and 1 cultivated varieties of She's nationality. Folk medicine usage is different from the traditional Chinese medicine and ethnic medicine. This survey finds out the common She's nationality wild medicinal plants resources in China, including the species, the distribution, the folk application and commonly used drugs, and found the rare and endangered medicinal plants and the She's nationality endemic medicinal plants, which provides a basis for further development and use the traditional She's medicine resources.


Assuntos
Medicamentos de Ervas Chinesas/análise , Medicina Tradicional Chinesa , Plantas Medicinais/crescimento & desenvolvimento , China/etnologia , Conservação dos Recursos Naturais , Etnicidade , Humanos , Plantas Medicinais/química , Plantas Medicinais/classificação
12.
Front Genet ; 15: 1334473, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38419785

RESUMO

Background: Although previous studies found that inflammatory bowel disease (IBD) and diverticular disease (DD) usually co-exist clinically, studies examining the relationship are spare. Aim: Our study aspires to investigate the causal correlation between the IBD [including ulcerative colitis (UC) and Crohn's disease (CD)] and DD using the Mendelian randomization (MR) analysis. Methods: We conducted a two-sample bidirectional MR analysis using publicly available genome-wide association studies (GWAS) summary data. The single nucleotide polymorphism (SNP) data associated with DD and IBD were obtained from the Finnish Biobank and UK Biobank, respectively. Through secondary data analysis of all GWAS summary data, we systematically screened genetic instrumental variables. To address the impact of horizontal pleiotropy, several methods were employed, including the inverse variance-weighted method (IVW), maximum likelihood method, Egger regression method, weighted median method, and simple median method. These approaches aimed to detect and correct for the potential bias caused by horizontal pleiotropy. Results: Genetically predicted DD did not have a causal effect on IBD (OR 1.06, 95% CI 0.98-1.17, p = 0.15), and had no causal effect on UC (OR 1.10, 95% CI 0.94-1.20, p = 0.36) and CD (OR 1.03, 95% CI 0.92-1.16, p = 0.62) either. Furthermore, in the reverse MR analysis, we did not observe any significant causal effect of IBD on DD. Results of complementary methods showed consistent results with those of the IVW method. Conclusion: This study's findings do not provide evidence for a causal relationship between IBD and DD, which contradicts the majority of observational studies.

13.
ACS Appl Mater Interfaces ; 16(13): 16132-16144, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38511296

RESUMO

The main impediment to the development of zinc-air batteries is the sluggish kinetics of the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER). Transition metal N-doped carbon catalysts offer a promising alternative to noble metal catalysts, with metal-organic framework (MOF)-derived carbon material catalysts being particularly noteworthy. Here, we synthesized MxP-Z-C carbon catalysts by combining two-dimensional (2D) metal porphyrin-based MOFs (MxPMFs, x = Fe, Co, Ni, Mn) and three-dimensional zeolitic imidazole framework-8 (ZIF-8) through electrostatic interaction, followed by carbonization. ZIF-8 was inserted between the layers of MxPMFs to prevent its Π-Π stacking, allowing the active sites to become fully exposed. MxP-Z-C demonstrated an impressive catalytic activity for both the ORR and the OER reactions. Among them, FeP-Z-C showed the best catalytic activity. The half-wave potential for ORR was 0.92 V (vs the reversible hydrogen electrode (RHE)), while the overpotential for the OER was 290 mV. In addition, the zinc-air battery assembled by FeP-Z-C exhibited high power density (133.14 mW cm-2) and significant specific capacity (816 mAh gZn-1), indicating considerable potential as a bifunctional catalyst for electronic devices.

14.
Cell Rep ; 43(7): 114507, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39003742

RESUMO

The oxidative-stress-related protein Kelch-like ECH-associated protein 1 (KEAP1) is a substrate articulator of E3 ubiquitin ligase, which plays an important role in the ubiquitination modification of proteins. However, the function of KEAP1 in breast cancer and its impact on the survival of patients with breast cancer remain unclear. Our study demonstrates that KEAP1, a positive prognostic factor, plays a crucial role in regulating cell proliferation, apoptosis, and cell cycle transition in breast cancer. We investigate the underlying mechanism using human tumor tissues, high-throughput detection technology, and a mouse xenograft tumor model. KEAP1 serves as a key regulator of cellular metabolism, the reprogramming of which is one of the hallmarks of tumorigenesis. KEAP1 has a significant effect on mitochondrial biogenesis and oxidative phosphorylation by regulating HSPA9 ubiquitination and degradation. These results suggest that KEAP1 could serve as a potential biomarker and therapeutic target in the treatment of breast cancer.


Assuntos
Neoplasias da Mama , Proliferação de Células , Proteína 1 Associada a ECH Semelhante a Kelch , Ubiquitinação , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Humanos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Feminino , Animais , Camundongos , Linhagem Celular Tumoral , Biogênese de Organelas , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico HSP70/genética , Proteólise , Camundongos Nus , Mitocôndrias/metabolismo , Apoptose , Camundongos Endogâmicos BALB C , Células MCF-7 , Proteínas Mitocondriais
15.
Mol Pharm ; 10(2): 523-31, 2013 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-23289910

RESUMO

The development of cancer and fibrotic diseases has been shown to be highly dependent on disregulation of cap-dependent translation. Binding protein eIF4E to N(7)-methylated guanosine capped mRNA has been found to be the rate-limiting step governing translation initiation, and therefore represents an attractive target for drug discovery. Our group has found that 7-benzyl guanosine monophosphate (7Bn-GMP) is a potent antagonist of eIF4E cap binding (K(d) = 0.8 µM). Recent X-ray crystallographic studies have revealed that the cap-dependent pocket undergoes a unique structural change in order to accommodate the benzyl group. Unfortunately, 7Bn-GMP is not cell permeable. Recently, we have prepared a tryptamine phosphoramidate prodrug of 7Bn-GMP, 4Ei-1, and shown that it is a substrate for human histidine triad nucleotide binding protein (hHINT1) and inhibits eIF4E initiated epithelial-mesenchymal transition (EMT) by Zebra fish embryo cells. To assess the intracellular uptake of 4Ei-1 and conversion to 7Bn-GMP by cancer cells, we developed a sensitive assay using LC-ESI-MS/MS for the intracellular quantitation of 4Ei-1 and 7Bn-GMP. When incubated with the breast cancer cell line MDA-231 or lung cancer cell lines H460, H383 and H2009, 4Ei-1 was found to be rapidly internalized and converted to 7Bn-GMP. Since oncogenic mRNAs are predicted to have the highest eIF4E requirement for translation, we carried out chemosensitization studies with 4Ei-1. The prodrug was found to chemosensitize both breast and lung cancer cells to nontoxic levels of gemcitabine. Further mechanistic studies revealed that the expressed levels of eIF4E were substantially reduced in cells treated with 4Ei-1 in a dose-dependent manner. The levels of eI4E could be restored by treatment with the proteasome inhibitor MG-132. Taken together, our results demonstrate that 4Ei-1 is likely to inhibit translation initiation by eIF4E cap binding by both antagonizing eIF4E cap binding and initiating eIF4E proteasomal degradation.


Assuntos
Neoplasias da Mama/metabolismo , Desoxicitidina/análogos & derivados , Fator de Iniciação 4E em Eucariotos/metabolismo , Guanosina Monofosfato/análogos & derivados , Guanosina Monofosfato/farmacologia , Neoplasias Pulmonares/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Cristalografia por Raios X , Desoxicitidina/farmacologia , Humanos , Modelos Químicos , Espectrometria de Massas por Ionização por Electrospray , Gencitabina
16.
Ecotoxicol Environ Saf ; 93: 186-90, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23607973

RESUMO

The illegal use of clenbuterol has been an increasingly serious issue in today's livestock products industry. It becomes an important project to develop a reliable approach to detect its content in food animals. A simple and sensitive LC-MS/MS method was developed to detect clenbuterol residue in hair, with the low limit of quantitation (LLOQ) about 0.5ng/g. Hogs fed with 340µg/day of clenbuterol for 2 weeks were found a high clenbuterol residue in their hair approximately at 1-2 months after withdrawal. There remained 3.31ng/g clenbuterol in hog hair approximately 5 months after the last administration, focused on the tip of the hair (mainly in hogs with dark hair). An extensive contamination was observed in twenty investigated market hogs whose dark hair obviously had a higher clenbuterol residue than the light ones (p=0.017, t test). Volunteers (60.3 percent) from Xuhui district (Shanghai) were found to have a detectable amount of clenbuterol in their hair (>0.5ng/g). In conclusion, hair residue detection is a reliable method to evaluate the clenbuterol contamination in animals and humans. Meat supply in the Xuhui district might have serious potential safety risks which should be further investigated and discussed to determine the safety range of clenbuterol residue.


Assuntos
Clembuterol/análise , Cabelo/química , Agonistas Adrenérgicos beta/análise , Agonistas Adrenérgicos beta/metabolismo , Criação de Animais Domésticos , Animais , China , Cromatografia Líquida , Clembuterol/metabolismo , Feminino , Contaminação de Alimentos/análise , Cabelo/metabolismo , Humanos , Gado , Masculino , Carne/análise , Suínos , Espectrometria de Massas em Tandem
17.
Biomed Environ Sci ; 26(11): 894-901, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24331534

RESUMO

OBJECTIVE: To identify the novel species 'Mycobacterium fukienense' sp. nov of Mycobacterium chelonae/abscessus complex from tuberculosis patients in Fujian Province, China. METHODS: Five of 27 clinical Mycobacterium isolates (Cls) were previously identified as M. chelonae/abscessus complex by sequencing the hsp65, rpoB, 16S-23S rRNA internal transcribed spacer region (its), recA and sodA house-keeping genes commonly used to describe the molecular characteristics of Mycobacterium. Clinical Mycobacterium isolates were classified according to the gene sequence using a clustering analysis program. Sequence similarity within clusters and diversity between clusters were analyzed. RESULTS: The 5 isolates were identified with distinct sequences exhibiting 99.8% homology in the hsp65 gene. However, a complete lack of homology was observed among the sequences of the rpoB, 16S-23S rRNA internal transcribed spacer region (its), sodA, and recA genes as compared with the M. abscessus. Furthermore, no match for rpoB, sodA, and recA genes was identified among the published sequences. CONCLUSION: The novel species, Mycobacterium fukienense, is identified from tuberculosis patients in Fujian Province, China, which does not belong to any existing subspecies of M. chelonea/abscessus complex.


Assuntos
Proteínas de Bactérias/genética , DNA Bacteriano/genética , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium/classificação , Tuberculose/microbiologia , Sequência de Bases , China/epidemiologia , Análise por Conglomerados , Humanos , Dados de Sequência Molecular , Mycobacterium/genética , Mycobacterium/isolamento & purificação , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Mycobacterium chelonae/classificação , Mycobacterium chelonae/genética , Mycobacterium chelonae/isolamento & purificação , Filogenia , Alinhamento de Sequência , Tuberculose/epidemiologia
18.
ScientificWorldJournal ; 2013: 637086, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23861656

RESUMO

PURPOSE: Truncated tissue factor (tTF) fusion protein targeting tumor vasculature can induce tumor vascular thrombosis and necrosis. Here, we generated (RGD)3-tTF in which three arginine-glycine-aspartic (RGD) targeting integrin α(v)ß3 and tTF induce blood coagulation in tumor vessels. METHODS: The bioactivities of (RGD)3-tTF including coagulation activity, FX activation, and binding with integrin α(v)ß3 were performed. The fluorescent labeled (RGD)3-tTF was intravenously injected into tumor-bearing mice and traced in vivo. The tumor growth, volume, blood vessel thrombosis, tumor necrosis, and survival time of mice treated with (RGD)3-tTF were evaluated. RESULTS: The clotting time and FX activation of (RGD)3-tTF were similar to that of TF (P > 0.05) but different with that of RGD (P < 0.05). (RGD)3-tTF presented a higher binding with α(v)ß3 than that of RGD and TF at the concentration of 0.2 µmol/L (P < 0.05). (RGD)3-tTF could specifically assemble in tumor and be effective in reducing tumor growth by selectively inducing tumor blood vessels thrombosis and tumor necrosis which were absent in mice treated with RGD or TF. The survival time of mice treated with (RGD)3-tTF was higher than that of mice treated with TF or RGD (P < 0.05). CONCLUSION: (RGD)3-tTF may be a promising strategy for the treatment of colorectal cancer.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Integrina alfaVbeta3/metabolismo , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo , Proteínas Recombinantes de Fusão/farmacocinética , Proteínas Recombinantes de Fusão/uso terapêutico , Inibidores da Angiogênese/uso terapêutico , Animais , Linhagem Celular Tumoral , Neoplasias Colorretais/irrigação sanguínea , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Resultado do Tratamento
19.
Guang Pu Xue Yu Guang Pu Fen Xi ; 33(10): 2637-41, 2013 Oct.
Artigo em Zh | MEDLINE | ID: mdl-24409707

RESUMO

In order to further investigate the utility of near-infrared spectroscopys (NIRS) in rapidly detecting honey adulteration, near-infrared spectroscopy in combination with chemometric methods was investigated for qualitative and quantitative detection of beet syrup adulteration of honey. Total prediction accuracy of testing set was 90.2% by partial least squares-discriminant analysis (PLS-DA) for authentic and adulterated honey samples. Total prediction accuracy of testing sets was all below 33.3% by different discriminant methods for classes of adulteration level. The quantitative analysis of adulteration level by PLS regression gave satisfying results if adulterated honey samples were got from the same one authentic honey sample: correlation coefficient (r)of actual values versus predicted values was 0.9829 and root mean square error of prediction (RMSEP) was 1.394 2 in testing set, otherwise it gave dissatisfying results for the adulterated samples from different botanical origins or the different samples of the same botanical origins. The results showed that NIRS could be applied for rapid detection of authentic and adulterated honey samples, but not for detection of classes of adulteration level and quantification of adulteration level with beet syrup.


Assuntos
Beta vulgaris , Contaminação de Alimentos/análise , Mel , Espectroscopia de Luz Próxima ao Infravermelho , Análise Discriminante , Estudos de Viabilidade , Análise dos Mínimos Quadrados
20.
Artigo em Zh | MEDLINE | ID: mdl-24818389

RESUMO

In order to understand pinworm infection of kindergarten children in Jurong City, Jiangsu Province, a total of 1 088 children were sampled for the survey from September 2011 to October 2012. The cellophane tape swab technique was used to examine pinworm eggs. The infection rate of pinworm was 1.1% (12/1 088). The rate in boys and girls was 1.3% (7/551) and 0.9% (5/537), respectively. Higher infection rate was in the senior class (1.4%, 5/370), and no significant difference was found with gender, as well as among different classes (P > 0.05). Evidently, pinworm prevalence is at a low level in the kindergarten children of Jurong.


Assuntos
Enterobíase/epidemiologia , Animais , Criança , Pré-Escolar , China/epidemiologia , Enterobíase/parasitologia , Enterobius , Feminino , Humanos , Masculino , Contagem de Ovos de Parasitas , Escolas Maternais
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