RESUMEN
Human malignant pleural mesothelioma (hMPM) is an aggressive, rare disease with a poor prognosis. Histologically, MPM is categorized into epithelioid, biphasic, and sarcomatoid subtypes, with the epithelioid subtype generally displaying a better response to treatment. Conversely, effective therapies for the non-epithelioid subtypes are limited. This study aimed to investigate the potential role of FK228, a histone deacetylase inhibitor, in the suppression of hMPM tumor growth. We conducted a comprehensive analysis of the histological and molecular characteristics of two MPM cell lines, CRL-5820 (epithelioid) and CRL-5946 (non-epithelioid). CRL-5946 cells and non-epithelioid patient-derived xenografted mice exhibited heightened growth rates compared to those with epithelioid MPM. Both CRL-5946 cells and non-epithelioid mice displayed a poor response to cisplatin. However, FK228 markedly inhibited the growth of both epithelioid and non-epithelioid tumor cells in vitro and in vivo. Cell cycle analysis revealed FK228-induced G1/S and mitotic arrest in MPM cells. Caspase inhibitor experiments demonstrated that FK228-triggered apoptosis occurred via a caspase-dependent pathway in CRL-5946 but not in CRL-5820 cells. Additionally, a cytokine array analysis showed that FK228 reduced the release of growth factors, including platelet-derived and vascular endothelial growth factors, specifically in CRL-5946 cells. These results indicate that FK228 exhibits therapeutic potential in MPM by inducing cytotoxicity and modulating the tumor microenvironment, potentially benefiting both epithelioid and non-epithelioid subtypes.
Asunto(s)
Apoptosis , Proliferación Celular , Depsipéptidos , Mesotelioma Maligno , Mesotelioma , Ensayos Antitumor por Modelo de Xenoinjerto , Humanos , Animales , Mesotelioma Maligno/tratamiento farmacológico , Mesotelioma Maligno/patología , Línea Celular Tumoral , Ratones , Mesotelioma/tratamiento farmacológico , Mesotelioma/patología , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Depsipéptidos/farmacología , Depsipéptidos/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pleurales/tratamiento farmacológico , Neoplasias Pleurales/patología , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Femenino , Células Epitelioides/patología , Ciclo Celular/efectos de los fármacosRESUMEN
OBJECTIVES: To investigate the expression of CD123 in children with acute lymphoblastic leukemia (ALL) and its effect on the clinical characteristics and prognosis of children with B-lineage acute lymphoblastic leukemia (B-ALL). METHODS: A retrospective analysis was conducted on the clinical data of 251 children with ALL who were admitted to the Department of Hematology and Oncology, Children's Hospital of Kunming Medical University, from December 2019 to June 2022. According to the expression of CD123 at initial diagnosis, the children were divided into CD123+ group and CD123- group, and the two groups were compared in terms of clinical characteristics and treatment outcome. The factors influencing the prognosis were analyzed. RESULTS: Among the 251 children with ALL, there were 146 children (58.2%) in the CD123+ group. The B-ALL group had a significantly higher positive expression rate of CD123 than the acute T lymphocyte leukemia group (P<0.05). Compared with the CD123- group, the CD123+ group had significantly lower peripheral blood leukocyte count and percentage of juvenile cells and a significantly higher proportion of children with high hyperdiploid karyotype or an age of 1-10 years, with a relatively low proportion of children with E2A-PBX1 fusion gene (P<0.05). The multivariate Cox proportional-hazards regression model analysis showed that compared with the >10 years group, the 1-10 years group had a significantly higher overall survival rate (P<0.05), and compared with the high risk group, the moderate risk group had a significantly higher event-free survival rate in children with B-ALL (P<0.05). CONCLUSIONS: CD123 is widely expressed in children with B-ALL, and positive expression of CD123 might be an indicator for good prognosis in children with B-ALL, which is of great significance for evaluating the efficacy of remission induction therapy and survival prognosis of children with B-ALL.
Asunto(s)
Subunidad alfa del Receptor de Interleucina-3 , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Masculino , Femenino , Niño , Preescolar , Subunidad alfa del Receptor de Interleucina-3/análisis , Subunidad alfa del Receptor de Interleucina-3/genética , Pronóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Estudios Retrospectivos , Lactante , AdolescenteRESUMEN
Changing land use systems impact on local edaphic factors and microbial abundance and diversity, however, the information on it in central Myanmar's soils is still lacking. Therefore, soils with four different land uses were analyzed; WAP (soil from perennial tree orchard), PNON (soil from crop rotation of peanut and onion), SESA (soil from mono-crop of sesame) and CHON (soil from mono-crop of onion for 3 years consecutively). Soil organic carbon (SOC), total nitrogen (TN), dissolved organic carbon (DOC), ammonium nitrogen (NH4 +-N) and pH showed the highest in PNON soil, which suggested crop rotation with high fertilizer input and irrigation had positive effect on the edaphic factors of soil. CHON soil showed the lowest in most soil properties and microbial abundance as a result of intensive use of fertilizer and irrigation, no crop rotation and no input of manures. Microbial community composition showed differences among tested soils and relative abundance of Chloroflexi was the highest in CHON soil whereas that of Basidiomycota was the highest in WAP soil. The abundances of bacteria and fungi were significantly affected by Olsen P, whereas the abundances of archaea were influenced by SOC. Our results suggested crop rotation and manure fertilization (PNON soil) enhanced soil properties and microbial abundance although long-time onion mono-crop (CHON soil) reduced soil fertility. This study can provide information to improve soil quality and sustainability of agro-ecosystems using appropriate agricultural management. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02705-y.
RESUMEN
Absorption, fluorescence spectral, cyclic voltammetry and agarose gel electrophoresis studies have been carried out on the interaction of Ni(II) complex with all-trans retinoic acid ([Ni(RA)(2)(H(2)O)(2)] * H(2)O) with DNA. The results indicate that the [Ni(RA)(2)(H(2)O)(2)] * H(2)O can more effectively promote the cleavage of plasmid DNA than that of all-trans retinoic acid (HRA) and Ni(II) at physiological pH and temperature, which may be one of the reasons why the inhibitory effect of [Ni(RA)(2)(H(2)O)(2)] * H(2)O on the human bladder line EJ cells is much greater than that of retinoic acid. It was found that the process of plasmid DNA cleavage was sensitive to ionic strength and pH, however, these radical scavengers almost had no effect on the DNA cleavage reaction. The above results suggested that the cleavage of plasmid DNA by [Ni(RA)(2)(H(2)O)(2)]* H(2)O did not produce diffusible hydroxyl radicals via the Fenton reaction. The results of UV-absorption studies and fluorescence characterization of the interaction of [Ni(RA)(2)(H(2)O)(2)] * H(2)O with Calf thymus DNA show that the [Ni(RA)(2)(H(2)O)(2)] * H(2)O binds to DNA mainly in an intercalating mode.
Asunto(s)
Antineoplásicos/metabolismo , ADN/metabolismo , Níquel/metabolismo , Tretinoina/metabolismo , ADN/química , Concentración de Iones de Hidrógeno , Níquel/química , Concentración Osmolar , Plásmidos/genética , Espectrometría de Fluorescencia , Temperatura , Factores de Tiempo , Tretinoina/químicaRESUMEN
The interaction between the metal complex of hydrazide of podophyllic acid and calf thymus (CT) DNA was studied by using absorption spectra, fluorescence spectra and DNA heat denaturation. It was found that the intensity of the maximal absorption peaks from absorption spectra is weakened in the presence of the metal complex of hydrazide of podophyllic acid compared with that in the absence of the metal complex. All the experimental results show that the intercalation mode was proved to exist between HDPP-Ni complexes and CT DNA.
Asunto(s)
Antibacterianos/química , ADN/química , Podofilotoxina/análogos & derivados , Animales , Bovinos , Podofilotoxina/química , Espectrofotometría UltravioletaRESUMEN
The mechanism of the interaction between hydrazide-podophyllic (HDPP) metal (Me) complexes and calf thymus (ct) DNA in Tris buffer (pH 7.08) was studied by viscosity measurements, electronic absorption, gel electrophoresis, and ethidium bromide (EB) fluorescence spectroscopy. The results from varied experiments show that the intensity of the maximal absorption peaks from absorption spectra is weakened in the presence of DNA compared with that in the absence of DNA. Meanwhile, DNA can remarkably quench the emission intensity of the complex Me-HDPP system. The Me-HDPP complexes can increase the viscosity of ct DNA slightly and catalyze the cleavage of super coiled pBR322 DNA to the nicked form. The complexes of Ni-HDPP and Co-HDPP can be bound to ct DNA mainly by interaction, while the partial interaction of Zn-HDPP and ct DNA is the major modes. The binding constant of Me-HDPP complexes with ct DNA was determined.
Asunto(s)
ADN/química , ADN/metabolismo , ADN Superhelicoidal/química , Hidrazinas/química , Plásmidos/química , Podofilino/química , Espectrometría de FluorescenciaRESUMEN
Intensely luminescent 1,8-naphthyridine-BF2 complexes 1-9 containing terminal bidentate N^N^O and/or N^C^O groups are synthesized and structurally characterized by X-ray diffraction, electrospray ionization mass spectrometry, (1)H and (19)F NMR spectroscopy and elemental analysis. Complexes 1-4 are synthesized from 2-acetamino-1,8-naphthyridine derivatives by a facile route. Selective bonding modes and the chemical stability of complexes 5 and 6 obtained by reacting BF3·Et2O with 1,8-naphthyridine derivatives bearing dual-functional groups (N^C^O and N^N^O) are investigated by crystal structure analysis and time-dependent density functional theory calculations. The products containing a BF2 core bound to a N^C^O chelating group are energetically favorable and can expand the range of derivatives by substitution at the 2-position. In this regard, a free -NH2 group at the 2-position of complex 7 obtained from 5 can be functionalized under a variety of pH conditions to generate complexes 8 and 9, which bear flexible coordination arms that can be used to recognize certain transition metals. The photophysical properties of the complexes are examined in solution and solid state at room temperature. Compared with those of the starting naphthyridine-based compounds, the naphthyridine-BF2 complexes display desirable light-absorbing properties and intense solution and solid-state emission with large Stokes shifts. Complex 4 in solution exhibited an emission quantum yield of 0.98. In complexes 5-9, the binding sites for the BF2 core change from N^N^O to N^C^O, which leads to red shifts of absorption and emission, excellent chemical stability and high emission quantum yields.
RESUMEN
Two new nonanuclear lanthanide(III)-copper(II) complexes of macrocyclic oxamide [NaPr(2)(CuL)(6)(H(2)O)(6)](ClO(4))(6)Cl small middle dot6H(2)O (1) and [NaNd(2)(CuL)(6)(H(2)O)(6)](ClO(4))(6)Cl small middle dot8H(2)O (2) have been synthesized and characterized by means of elemental analysis, IR, and electronic spectra, where L = 1,4,8,11-tetraazacyclotradecanne-2,3-dione. The crystal structures of the two complexes have been determined. The structures of 1 and 2 consist of nonanuclear cations, perchlorate and chloride anions, and water molecules. In the two complexes, each copper(II) ion is connected to lanthanide(III) ion via the exo-cis oxygen atoms of the oxamido macrocyclic ligands, resulting in a tetranuclear subunit. The sodium ion links two tetranuclear subunits via the exo oxygen atoms of the oxamido macrocyclic ligands which results in a novel nonanuclear complex. The magnetic properties of the two complexes have been investigated. Preliminary treatment of the magnetic data by considering Ln(III) as free ion cannot give reasonable results, and accurate models involving both the orbital contribution and ligand field effect have to be developed.