RESUMO
Lysine crotonylation (Kcr) is a newly identified protein translational modification and is involved in major biological processes including glycolysis, but its role in colorectal cancer (CRC) is unknown. Here, we found that the Kcr of α enolase (ENO1) was significantly elevated in human CRC tissues compared with the paratumoral tissues. CREB-binding protein (CBP) functioned as a crotonyltranferase of ENO1, and SIRT2 was involved in the decrotonylation of ENO1. Using quantitative mass spectrometry for crotonylomics analysis, we further found that K420 was the main Kcr site of ENO1 and ENO1 K420 Kcr promoted the growth, migration, and invasion of CRC cells in vitro by enhancing the activity of ENO1 and regulating the expression of tumor-associated genes. Our study reveals an important mechanism by which ENO1 regulates CRC through crotonylation.
Assuntos
Biomarcadores Tumorais/metabolismo , Proteína de Ligação a CREB/metabolismo , Neoplasias Colorretais/metabolismo , Proteínas de Ligação a DNA/metabolismo , Lisina/metabolismo , Fosfopiruvato Hidratase/metabolismo , Processamento de Proteína Pós-Traducional , Sirtuína 2/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Biomarcadores Tumorais/genética , Proteína de Ligação a CREB/genética , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Proteínas de Ligação a DNA/genética , Humanos , Espectrometria de Massas , Metástase Neoplásica , Fosfopiruvato Hidratase/genética , Sirtuína 2/genética , Proteínas Supressoras de Tumor/genética , Regulação para CimaRESUMO
In-depth analysis on the rambling genes of psoriasis may help to identify the pathologic mechanism of this disease. However, this has seldom been performed. Using bioinformatic approaches, we analyzed four gene expression profiles in gene expression omnibus (GEO) database, identified the differentially expressed genes (DEGs), and found out the overlapping DEGs (common DEGs, CDEGs) in the above four profiles. The CDEGs were further subjected to Gene Ontology (GO) enrichment analysis, Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis and protein-protein interaction (PPI) network analysis, and hub genes were ranked. We identified 139 CDEGs associated with a variety of GO processes including keratinization, immune and inflammatory responses, and type 1 interferon signaling pathway. These CDEGs were enriched in a variety of KEGG processes, including cytokine-cytokine receptor interaction and chemokine signaling. PPI analysis showed that seven genes (HERC6, ISG15, MX1, RSAD2, OAS2, OASL, and OAS3) were likely the novel hub genes of psoriasis. RT-qPCR identified that five (ISG15, MX1, OAS2, OASL, and OAS3) of the seven predicted hub genes were overexpressed in TNF-α stimulated HaCaT cell lines, a result quite consistent with the predictions. The study provides new information in exploring the mechanisms and therapeutic targets of psoriasis.
Assuntos
Mapas de Interação de Proteínas , Psoríase , Biologia Computacional , Ontologia Genética , Humanos , Psoríase/genética , TranscriptomaRESUMO
Two porous coordination polymers, {[Co0.5(TBC)]·2DMF} n (1) and {[Co(TBC)Cl0.5(CH3OH)]·0.5Cl} n (2), were synthesized via the solvothermal reaction of cobalt(II) salts and 3,5-bis(1 H-1,2,4-triazol-1-yl)benzenecarboxylic acid. Single-crystal X-ray diffraction analyses exhibited that complex 1 contains rtl three-dimensional (3D) skeleton and one-dimensional channels with large apertures, while complex 2 displays a novel 2-nodal 3,6-linked 3D structure with a Schläfli sign of {4.82}2{46.89} and contains micropores. Meanwhile, compound 2 shows selective adsorption properties of anionic methyl orange in a water solution. The dye adsorption studies of 1 and 2 revealed that the porous character and charge properties of metal-organic frameworks are two important factors heavily influencing dye adsorption.
RESUMO
An unprecedented cyclic TbIII-radical cluster, [Tb3(hfac)6(4-Me-3-NITtrz)2(OH)3] (1), has been self-assembled from Tb(hfac)3·2H2O and 4-Me-3-NITtrz in the presence of Cu(hfac)2·2H2O. Alternating-current magnetic studies show that the Tb3 cluster displays a dual slow relaxation of magnetization behavior under a zero direct-current (dc) field and a single relaxation process under an induced dc field with an effective energy barrier of 14 K, representing the first triangle 2p-4f cluster with a slow magnetic relaxation property.
RESUMO
Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening disease and currently there is no pharmacological therapy. Sympathetic nerve overactivity plays an important role in the development of TAAD. Sympathetic innervation is mainly controlled by nerve growth factor (NGF, a key neural chemoattractant) and semaphoring 3A (Sema3A, a key neural chemorepellent), while the roles of these two factors in aortic sympathetic innervation and especially TAAD are unknown. We hypothesized that genetically manipulating the NGF/Sema3A ratio by the Ngf -driven Sema3a expression approach may reduce aortic sympathetic nerve innervation and mitigate TAAD progression. A mouse strain of Ngf gene-driven Sema3a expression (namely NgfSema3a/Sema3a mouse) was established by inserting the 2A-Sema3A expression frame to the Ngf terminating codon using CRISPR/Cas9 technology. TAAD was induced by ß-aminopropionitrile monofumarate (BAPN) both in NgfSema3a/Sema3a mice and wild type (WT) littermates. Contrary to our expectation, the BAPN-induced TAAD was severer in NgfSema3a/Sema3a mice than in wild-type (WT) mice. In addition, NgfSema3a/Sema3a mice showed higher aortic sympathetic innervation, inflammation and extracellular matrix degradation than the WT mice after BAPN treatment. The aortic vascular smooth muscle cells isolated from NgfSema3a/Sema3a mice and pretreated with BAPN in vivo for two weeks showed stronger capabilities of proliferation and migration than that from the WT mice. We conclude that the strategy of Ngf -driven Sema3a expression cannot suppress but worsens the BAPN-induced TAAD. By investigating the aortic phenotype of NgfSema3a/Sema3a mouse strain, we unexpectedly find a path to exacerbate BAPN-induced TAAD which might be useful in future TAAD studies.
Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Azidas , Desoxiglucose , Animais , Camundongos , Aminopropionitrilo/efeitos adversos , Aneurisma da Aorta Torácica/genética , Aneurisma da Aorta Torácica/induzido quimicamente , Aneurisma da Aorta Torácica/metabolismo , Desoxiglucose/análogos & derivados , Modelos Animais de Doenças , Fator de Crescimento Neural/genética , Fator de Crescimento Neural/efeitos adversos , Semaforina-3A/genéticaRESUMO
The novel coronavirus disease (COVID-19) outbreak that emerged at the end of 2019 has now swept the world for more than 2 years, causing immeasurable damage to the lives and economies of the world. It has drawn so much attention to discovering how the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated and entered the human body. The current argument revolves around two contradictory theories: a scenario of laboratory spillover events and human contact with zoonotic diseases. Here, we reviewed the transmission, pathogenesis, possible hosts, as well as the genome and protein structure of SARS-CoV-2, which play key roles in the COVID-19 pandemic. We believe the coronavirus was originally transmitted to human by animals rather than by a laboratory leak. However, there still needs more investigations to determine the source of the pandemic. Understanding how COVID-19 emerged is vital to developing global strategies for mitigating future outbreaks.
Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Animais , COVID-19/epidemiologia , COVID-19/veterinária , Pandemias , Zoonoses , Surtos de DoençasRESUMO
Multinuclear hetero-tri-spin complexes based on a methyl-pyrazole nitronyl nitroxide radical, namely, [Ln2Cu3(hfac)12(4-NIT-MePyz)4] (Ln = Gd(1), Tb(2), Dy(3); hfac = hexafluoroacetylacetone; 4-NIT-MePyz = 2-{4-(1-methyl)-pyrazolyl}-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) have been successfully obtained through a one-pot reaction of the radical ligand (4-NIT-MePyz) with Cu(hfac)2 and Ln(hfac)3. These 2p-3d-4f complexes exhibit five-nuclear structures with the sequence [Cu-Rad-Ln-Rad-Cu-Rad-Ln-Rad-Cu], in which each 4-NIT-MePyz radical acting as a bidentate bridging ligand is coordinated to one Ln(hfac)3 unit through one oxygen atom of the NO groups and to one Cu(hfac)2 unit with one nitrogen atom from the pyrazole ring. For complex 1, based on the spin Hamiltonian calculations and MAGPACK program, it is concluded that there exist ferromagnetic couplings between GdIII and NIT radicals, as well as between CuII and free radicals with J1 = 6.8(1) and J3 = 1.3(2) cm-1, respectively, and antiferromagnetic interactions between radical and radical with J2 = -2.8(5) cm-1. Complex 2 shows frequency-dependent out-of-phase signals under a zero or 2000 Oe dc field indicating single-molecule magnetic behavior.
RESUMO
Based on the multifunctional ligand 3-(1H-1,2,4-triazol-1-yl)isophthalic acid (H2TIA), a three-dimensional coordination polymer, namely {[Zn(TIA)]·DMA} n (Zn-1) was synthesized solvothermally. Single-crystal X-ray diffraction analyses confirmed that Zn-1 is a 3D framework composed of binuclear Zn2 paddle wheels with one-dimensional channels long the a direction. Further topological analyses revealed that MOF Zn-1 existed as a (3,6)-connected rtl binodal net {4·62}2{42·610·83}. Furthermore, the luminescence explorations indicate that complex Zn-1 is the first MOF for luminescent probing of phthalate esters (carcinogenic organic pollutants) with a high quenching-efficiency constant and low fluorescence-detection limit.