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Chemotherapy is one of the most commonly used methods for treating cancer, but its side effects severely limit its application and impair treatment effectiveness. Removing off-target chemotherapy drugs from the serum promptly through adsorption is the most direct approach to minimize their side effects. In this study, we synthesized a series of adsorption materials to remove the chemotherapy drug doxorubicin by modifying MOF nanosheets with sulfonated azocalix[4]arenes. The strong affinity of sulfonated azocalix[4]arenes for doxorubicin results in high adsorption strength (Langmuir adsorption constant = 2.45-5.73 L mg-1) and more complete removal of the drug. The extensive external surface area of the 2D nanosheets facilitates the exposure of a large number of accessible adsorption sites, which capture DOX molecules without internal diffusion, leading to a high adsorption rate (pseudo-second-order rate constant = 0.0058-0.0065 g mg-1 min-1). These adsorbents perform effectively in physiological environments and exhibit low cytotoxicity and good hemocompatibility. These features make them suitable for removing doxorubicin from serum during "drug capture" procedures. The optimal adsorbent can remove 91% of the clinical concentration of doxorubicin within 5 min.
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BACKGROUND: Cerebral infarction, previously referred to as cerebral infarction or ischemic stroke, refers to the localized brain tissue experiencing ischemic necrosis or softening due to disorders in brain blood supply, ischemia, and hypoxia. The precision rehabilitation nursing model for chronic disease management is a continuous, fixed, orderly, and efficient nursing model aimed at standardizing the clinical nursing process, reducing the wastage of medical resources, and improving the quality of medical services. AIM: To analyze the value of a precise rehabilitation nursing model for chronic disease management in patients with cerebral infarction. METHODS: Patients (n = 124) admitted to our hospital with cerebral infarction between November 2019 and November 2021 were enrolled as the study subjects. The random number table method was used to divide them into a conventional nursing intervention group (n = 61) and a model nursing intervention group (n = 63). Changes in the nursing index for the two groups were compared after conventional nursing intervention and precise rehabilitation intervention nursing for chronic disease management. RESULTS: Compared with the conventional intervention group, the model intervention group had a shorter time to clinical symptom relief (P < 0.05), lower Hamilton Anxiety Scale and Hamilton Depression Scale scores, a lower incidence of total complications (P < 0.05), a higher disease knowledge mastery rate, higher safety and quality, and a higher overall nursing satisfaction rate (P < 0.05). CONCLUSION: The precision rehabilitation nursing model for chronic disease management improves the clinical symptoms of patients with cerebral infarction, reducing the incidence of total complications and improving the clinical outcome of patients, and is worthy of application in clinical practice.
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BACKGROUND: Interleukin-1ß (IL-1)-treated mesenchymal stem cells (MSCs) and IL-1-MSCs-conditioned medium (CM) exert anti-inflammatory roles. Astrocytes are essential for the modulation of synaptic activity and neuronal homeostasis in the brain. Exosomes are the critical mediators in intercellular communication. However, the mechanism underlying the anti-inflammatory effect of IL-1-treated MSCs remains unknown. METHODS: In this study, exosomes (IL-1-Exo) were isolated from IL-1-treated MSCs. In addition, lipopolysaccharide (LPS)-treated hippocampal astrocytes and status epilepticus (SE) mice were treated with IL-1-Exo. Inflammatory activity, astrogliosis, and cognitive performance were measured to determine the effect of IL-1-Exo on inflammation. RESULTS: The results revealed that IL-1-Exo significantly inhibited LPS-induced astrogliosis and inflammatory responses of astrocytes. Also, IL-1-Exo reversed the LPS-induced effect on calcium signaling. The Nrf2 signaling pathway was associated with the effect of IL-1-Exo in LPS-treated astrocytes. Furthermore, IL-1-Exo reduced the inflammatory response and improved the cognitive performance of SE mice. CONCLUSION: The results suggest that IL-1-Exo inhibited LPS-induced inflammatory responses in astrocytes and SE mice and that the effect of IL-1-Exo was primarily mediated through the Nrf-2 signaling pathway. This study provides a new understanding of the molecular mechanism of inflammation-associated brain diseases and an avenue to develop nanotherapeutic agents for the treatment of inflammatory conditions in the brain.
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Astrocitos/patología , Exosomas/metabolismo , Hipocampo/patología , Inflamación/terapia , Interleucina-1beta/farmacología , Células Madre Mesenquimatosas/citología , Factor 2 Relacionado con NF-E2/metabolismo , Transducción de Señal , Animales , Animales Recién Nacidos , Antiinflamatorios/farmacología , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Conducta Animal/efectos de los fármacos , Señalización del Calcio/efectos de los fármacos , Exosomas/efectos de los fármacos , Exosomas/ultraestructura , Humanos , Inflamación/patología , Lipopolisacáridos , Masculino , Células Madre Mesenquimatosas/efectos de los fármacos , Ratones Endogámicos C57BL , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuronas/patología , Transducción de Señal/efectos de los fármacos , Estado Epiléptico/patologíaRESUMEN
OBJECTIVE: The aim was to evaluate the efficacy, safety and completion rate of 3-month, once-weekly rifapentine and isoniazid for tuberculosis (TB) prevention among Chinese silicosis patients. METHODS: Male silicosis patients without human immunodeficiency virus infection, aged 18 years to 65 years, with or without latent TB infection, were randomized 1:1 to receive rifapentine/isoniazid under direct observation (3RPT/INH group) or were untreated (observation group). Active TB incidence was compared between the two groups with 37 months of follow-up. Safety profile and complete rates were evaluated. RESULTS: A total of 1227 adults with silicosis were screened; 513 eligible participants were enrolled and assigned to 3RPT/INH (n = 254) vs. observation (n = 259). Twenty-eight participants were diagnosed with active TB, and 9 and 19 in the 3RPT/INH group and observation groups, respectively. In the intention-to-treat analysis, the cumulative active TB rate was 3.5% (9/254) in the 3RPT/INH group and 7.3% (19/259) in the observation group (log rank p 0.055). On per protocol analysis, the cumulative active TB rates were 0.7% (1/139) and 7.3% (19/259), respectively (log rank p 0.01). Owing to an unexpected high frequency of adverse events (70.4%) and Grade 3 or 4 AEs (7.9%), the completion rate of the 3RPT/INH regimen was 54.7% (139/254). Twenty-six (10.8%) participants had flu-like systemic drug reactions; five (2.1%) experienced hepatotoxicity. DISCUSSION: Weekly rifapentine/isoniazid prophylaxis prevented active TB among Chinese people with silicosis when taken, irrespective of LTBI screening; efficacy was reduced by lack of compliance. The regimen must be used with caution because of the high rates of adverse effects. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number: NCT02430259.
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Antituberculosos/farmacología , Isoniazida/farmacología , Rifampin/análogos & derivados , Silicosis/complicaciones , Tuberculosis Pulmonar/prevención & control , Antituberculosos/administración & dosificación , Área Bajo la Curva , China , Esquema de Medicación , Semivida , Humanos , Isoniazida/administración & dosificación , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Rifampin/administración & dosificación , Rifampin/farmacocinética , Rifampin/farmacología , Tuberculosis Pulmonar/complicacionesRESUMEN
BACKGROUND: Receptor interacting protein kinase 1 (RIPK1)-mediated cell death, including apoptosis and necroptosis, belongs to programmed cell death. It has been reported that RIPK1-mediated necroptosis exists in lesions of cerebral hemorrhage (CH). Electroacupuncture, a treatment derived from traditional Chinese medicine, could improve neurological impairment in patients with brain injury. AIM: To investigate the protective role of cross electro-nape acupuncture (CENA) in CH, and clarify the potential mechanism. METHODS: CH rat models were established, and CENA was applied to the experimental rats. Neurological functions and encephaledema were then measured. Necrotic cells in the brain of rats with CH were evaluated by propidium iodide staining. Necroptosis was assessed by immunofluorescence. Activation of the necroptosis-related pathway was detected by western blot. Extraction of brain tissue, cerebrospinal fluid and serum samples was conducted to measure the expression and secretion of inflammatory cytokines by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: The necroptotic marker p-MLKL was detectable in the brains of rats with CH. Next, we found that CENA could ameliorate neurological functions in rat models of CH. Moreover, the upregulation of RIPK1-mediated necroptosis-related molecules in the brains of rats with CH were inhibited by CENA. Further investigation revealed that CENA partially blocked the interaction between RIPK1 and RIPK3. Finally, in vivo assays showed that CENA decreased the expression of the inflammatory cytokines tumor necrosis factor-α, interleukin-6 and interleukin-8 in CH rat models. CONCLUSION: These findings revealed that CENA exerts a protective role in CH models by inhibiting RIPK1-mediated necroptosis.
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Three iridium(III) polypyridyl complexes [Ir(ppy)2(PYTA)](PF6) (1) (ppy = 2-phenylpyridine), [Ir(bzq)2(PYTA)](PF6) (2) (bzq = benzo[h]quinolone) and [Ir(piq)2(PYTA)](PF6) (3) (piq = 1-phenylisoquinoline, PYTA = 2,4-diamino-6-(2'-pyridyl)-1,3,5-triazine) were synthesized and characterized by elemental analysis, IR, 1H NMR and 13C NMR. The cytotoxic activity of the complexes toward cancer SGC-7901, Eca-109, A549, HeLa, HepG2, BEL-7402 and normal LO2 cell lines was investigated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Complex 3 shows the most effective on inhibiting the above cell growth among these complexes. The complexes locate at the lysosomes and mitochondria. AO/EB, Annex V and PI and comet assays indicate that the complexes can induce apoptosis in SGC-7901 cells. Intracellular ROS and mitochondrial membrane potential were examined under fluorescence microscopy. The results demonstrate that the complexes increase the intracellular ROS levels and induce a decrease in the mitochondrial membrane potential. The complexes can enhance intracellular Ca2+ concentration and cause a release of cytochrome c. The autophagy was studied using MDC staining and western blot. Complexes 1-3 can effectively inhibit the cell invasion with a concentration-dependent manner. Additionally, the complexes target tubules and inhibit the polymerization of tubules. The antimicrobial activity of the complexes against S. aureus, E. coli, Salmonella and L. monocytogenes was explored. The mechanism shows that the complexes induce apoptosis in SGC-7901 cells through ROS-mediated lysosomal-mitochondrial, targeting tubules and damage DNA pathways. Three iridium(III) complexes [Ir(N-C)2(PYTA)](PF6) (N-C = ppy, 1; bzq, 2; piq, 3) were synthesized and characterized. The anticancer activity of the complexes against SGC-7901 cells was studied by apoptosis, comet assay, autophagy, ROS, mitochondrial membrane potential, intracellular Ca2+ levels, release of cytochrome c, tubules and western blot analysis. The antibacterial activity in vitro was also assayed.
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Antibacterianos/farmacología , Antineoplásicos/farmacología , Complejos de Coordinación/farmacología , Iridio/farmacología , Fenazopiridina/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Antineoplásicos/síntesis química , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Escherichia coli/efectos de los fármacos , Humanos , Iridio/química , Listeria monocytogenes/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Fenazopiridina/química , Salmonella/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Relación Estructura-ActividadRESUMEN
A new series of dibenzoxanthene derivatives 4a-4d (4a: 1-oxo-5-bromo-11-cyano-13c-methoxy-1,13c-dihydroxyl-dibenzo[a,kl]xanthene, 4b: 1-oxo-5-bromo-11-cyano-13c-ethoxy-1,13c-dihydroxyl-dibenzo[a,kl]xanthene, 4c: 1-oxo-5-bromo-11-cyano-13c-propoxy-1,13c-dihydroxyl-dibenzo[a,kl]xanthene and 4d: 1-oxo-5-bromo-11-cyano-13c-butoxy-1,13c-dihydroxyl-dibenzo[a,kl]xanthene) were synthesized and the molecular mechanisms of anti-cancer activities were investigated. These compounds showed excellent anti-tumor activity against A549, Eca-109, HeLa, HepG2 and SGC-7901 cell lines. Compounds 4a-4d could effectively inhibit the migration and invasion of HeLa cells in wound healing and transwell assays. Compounds induced the DNA damage and arrested in cell cycle distribution at G0/G1 phase. Apoptosis induced by compounds was detected using morphological observation of nuclear changes and FITC-Annexin V/PI staining. Additionally, compounds also induced the autophagy of HeLa cells through observing AO staining and upregulated the expression of LC3II and Beclin-1 proteins. Furthermore, treatment with autophagy inhibitor 3-methyladenine induced an obvious decrease in apoptotic rate in HeLa cells. This indicated that autophagy further promoted the HeLa cells apoptosis. Compounds 4a-4d enhanced the intracellular Ca2+ and ROS. Then the mitochondrial membrane potential of HeLa cells was depolarized and the cytochrome C was released from mitochondria into cytoplasm. Activities of the apoptotic factors Bcl-2, Bax, caspase-3 were measured using western blotting. After HeLa cells were exposed to compounds, the expressions of PI3K and Akt protein were decreased. Compounds exhibit anti-cancer activity via apoptosis and autophagy through inhibition of PI3K/Akt signaling pathway in HeLa cells.
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Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Xantenos/farmacología , Beclina-1/metabolismo , Caspasa 3/metabolismo , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Células HeLa , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Microscopía Confocal , Proteínas Asociadas a Microtúbulos/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteína X Asociada a bcl-2/metabolismoRESUMEN
A new series of dibenzoxanthenes 4a-4f were synthesized through the nucleophilic substitution and characterized by NMR and MS spectra. Their antitumor activity was screened by MTT assay. Compounds (except 4b and 4c) displayed strong growth inhibitory effects against chosen five tumor cells under light irradiation. The molecular mechanism of compound-induced cell apoptosis was investigated by AO/EB staining, comet assay, DCFH-DA, JC-1 fluorescent probe, and western blotting. Compounds induced the apoptosis of HepG2 cells and DNA damage. Location assay showed that compounds entered the nucleus of tumor cells. Furthermore, it was found that compounds induced loss of mitochondrial membrane potential, acceleration of ROS production, and activation of caspse-3, caspase-7, and caspase-9 proteins. Compounds upregulated the expression of pro-apoptotic Bim and Bax and downregulated the expression of anti-apoptotic Bcl-xl and Bcl-2. These results indicated that compounds induced the apoptosis of HepG2 cells through ROS-mediated mitochondrial pathway. The induction of apoptosis by dibenzoxanthenes may provide an important mechanism for their cancer chemopreventive function.
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Apoptosis/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Xantenos/farmacología , Western Blotting , Espectroscopía de Resonancia Magnética con Carbono-13 , Caspasas/metabolismo , Proliferación Celular/efectos de los fármacos , Cromatografía Liquida , Ensayo Cometa , Daño del ADN , Células Hep G2 , Humanos , Espectrometría de Masas , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Espectroscopía de Protones por Resonancia Magnética , Especies Reactivas de Oxígeno/metabolismo , Sales de Tetrazolio/química , Tiazoles/químicaRESUMEN
A novel polycyclic bridged-ring xanthene 2 was synthesized by nucleophilic substitution followed by Michael addition reaction between parent dibenzoxanthene 1 and acetylacetone. The structure of compound 2 was also confirmed by single-crystal X-ray diffraction. We studied the binding activity of this compound with bovine serum albumin (BSA) by fluorescent and UV-visible spectra. The results showed that compound had strong binding ability with BSA. Cell viability in five tumor cell lines was studied by MTT assay. The cytotoxic effect of bridged-ring xanthene 2 against BEL-7402 cells was examined by morphological analyses and biochemical assays. Significant nuclear damages of BEL-7402 cells were observed after cells were treated with compound in a comet assay. The compound also caused DNA damage and S phase arrest in BEL-7402 cells. The efficient induction of apoptosis by the compound was confirmed by flow cytometry. Additionally, the characteristic nuclear and morphological changes during apoptotic cell death were investigated by fluorescent microscopy. The compound 2 enhanced the reactive oxygen species (ROS) and decreased the mitochondrial membrane potential. Western blot assay indicated that the compound can active caspase-3, caspase-7, down-regulate the level of Bcl-2, Bcl-x, and up-regulate the level of pro-apoptosis protein Bax. The compound 2 induces apoptosis of BEL-7402 cells through a ROS-mediated mitochondrial dysfunction pathway.
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Apoptosis/efectos de los fármacos , Xantenos/farmacología , Western Blotting , Caspasa 3/metabolismo , Caspasa 7/metabolismo , Línea Celular Tumoral , Ensayo Cometa , Cristalografía por Rayos X , Daño del ADN , Regulación hacia Abajo , Activación Enzimática , Citometría de Flujo , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Microscopía Fluorescente , Estructura Molecular , Unión Proteica , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Fase S/efectos de los fármacos , Albúmina Sérica Bovina/química , Espectrometría de Fluorescencia , Espectrometría de Masa por Ionización de Electrospray , Espectrofotometría Ultravioleta , Sales de Tetrazolio , Tiazoles , Xantenos/químicaRESUMEN
Isoliquiritigenin (ISL) has been reported to have a wide range of biological activities. This study evaluated the cytotoxic effect of ISL on norvegicus pheochromocytoma cell line (PC-12 cells) and its possible molecular mechanism. The cytotoxicity in vitro of ISL against PC-12 cells was investigated by MTT assay. The migration and invasion of PC-12 cells were performed by scratch test and transwell assay. Apoptosis was evaluated by microscopy and flow cytometry. The reactive oxygen species (ROS) and mitochondrial membrane potential were studied by fluorescent microscopy. DNA damage of PC-12 cells was analyzed by comet assay. The protein expression of caspase, Bcl-2 family member, autophagy-associated protein Beclin-1, and LC3 was detected by western blot. The autophagy of PC-12 cells was investigated by acridine orange (AO) and monodansylcadaverine (MDC) staining. The IC50 value of ISL against PC-12 cell is 17.8 ± 1.8 µM. ISL could suppress PC-12 cell migration and invasion. AO/ethidium bromide staining and flow cytometry suggested that ISL caused apoptosis of PC-12 cells. Significant DNA damages of PC-12 cells treated with ISL were observed in a comet assay. ISL inhibited the cell growth of PC-12 cells at S phase. Exposure of PC-12 cells to ISL increased the levels of cellular reactive oxygen species (ROS) and decreased the mitochondrial membrane potential. Additionally, ISL trigged the release of cytochrome c from the mitochondria to the cytoplasm. The expression levels of caspase-9, caspase-3, caspase-7, Bax, and Bim were upregulated, whereas the expression levels of Bcl-2 and Bcl-x were downregulated. AO and monodansylcadaverine (MDC) staining assay showed that ISL caused autophagy of PC-12 cells. The upregulation of protein Beclin-1 and LC3 was observed in PC-12 cells. Therefore, the results show that ISL induces apoptosis of PC-12 cells through ROS-mediated activation of the intrinsic mitochondria-cytochrome c-caspase protease mechanism and causes the autophagy of PC-12 cells. Graphical Abstract The in vitro cytotoxicity, apoptosis, comet assay, ROS, mitochondrial membrane potential, cell cycle arrest, autophagy, and western blot induced by ISL were investigated.
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Apoptosis/efectos de los fármacos , Chalconas/farmacología , Citotoxinas/farmacología , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Animales , Beclina-1/metabolismo , Proteínas Asociadas a Microtúbulos/metabolismo , Células PC12 , RatasRESUMEN
We have synthesized dibenzoxanthene derivatives 2a-2i via nucleophilic substitution of methoxyl group and evaluated underlying antitumor molecular mechanism of target compounds. Compounds showed high cytotoxic activities against BEL-7402, A549, HeLa and MG-63 cancer cells in the µM range. These compounds inhibited the cell growth of BEL-7402 cells at S or G2/M phase. The compounds 2a-2i also induced the apoptosis of BEL-7402 cells. In addition, compounds enhanced the level of intramolecular ROS and decreased the mitochondrial membrane potential. Western blot analysis showed caspase-3 were activated and the expression of Bcl-2 and Bcl-xl was down-regulated. According to given results, these dibenzoxanthenes exhibited a broad spectrum of antiproliferative effects on various tumors and therapeutic efficacy. Molecular mechanism indicated that induction of apoptosis was associated with DNA fragmentation, ROS generation, mitochondria dysfunction. Compounds induced apoptosis in BEL-7402 cells through the intrinsic ROS-mediated mitochondrial pathway.
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Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Xantenos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Células HeLa , Humanos , Neoplasias Hepáticas/patología , Estructura Molecular , Relación Estructura-Actividad , Xantenos/síntesis química , Xantenos/químicaRESUMEN
A new ligand PFPIP (PFPIP=2-(2,3,4,5,6-pentafluorophenyl)[4,5-f]imadazo [1,10]phenanthroline) and its four ruthenium(II) polypyridyl complexes [Ru(NN)2(PFPIP)](ClO4)2 (NN=dmb: 4,4'-dimethyl-2,2'-bipyridine, 1; bpy: 2,2'-bipyridine, 2; phen: 1,10-phenanthroline, 3; dmp: 2,9-dimethyl-1,10-phenanthroline, 4) were synthesized and characterized by elemental analysis, IR, 1H NMR, 13C NMR and ESI-MS. The cytotoxic activity in vitro of the ligand and complexes toward BEL-7402, A549, HeLa, HepG2 and MG-63 cell lines was evaluated using MTT method (MTT=(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide). Complexes 1, 3 and 4 show moderate cytotoxic effect on the cell growth in BEL-7402 cells with IC50 values of 32.1±0.9, 37.9±1.7 and 42.1±3.0µM, respectively. The apoptosis in BEL-7402 cell was investigated with AO/EB and Hoechst 33,258 staining methods. The autophagy in BEL-7402 cell induced by complexes was assayed using MDC staining cell nuclei. The cell invasion, reactive oxygen species (ROS), mitochondrial membrane potential, cell cycle arrest, cellular uptake, comet assay and wound healing were studied under a fluorescent microscope. The complexes can cause autophagy and inhibit the cell invasion, and increase the ROS levels and induce a decrease in the mitochondrial membrane potential. The expression of the proteins related with apoptosis induced by the complexes was assayed by western blot analysis.
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Antineoplásicos/farmacología , Compuestos de Rutenio/química , Compuestos de Rutenio/farmacología , Células A549 , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Células HeLa , Células Hep G2 , Humanos , Espectroscopía de Resonancia Magnética , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
Accurate estimation of rice phenology is of critical importance for agricultural practices and studies. However, the accuracy of phenological parameters extracted by remote sensing data cannot be guaranteed because of the influence of climate, e.g. the monsoon season, and limited available remote sensing data. In this study, we integrate the data of HJ-1 CCD and Landsat-8 operational land imager (OLI) by using the ordinary least-squares (OLS), and construct higher temporal resolution vegetation indices (VIs) time-series data to extract the phenological parameters of single-cropped rice. Two widely used VIs, namely the normalized difference vegetation index (NDVI) and 2-band enhanced vegetation index (EVI2), were adopted to minimize the influence of environmental factors and the intrinsic difference between the two sensors. Savitzky-Golay (S-G) filters were applied to construct continuous VI profiles per pixel. The results showed that, compared with NDVI, EVI2 was more stable and comparable between the two sensors. Compared with the observed phenological data of the single-cropped rice, the integrated VI time-series had a relatively low root mean square error (RMSE), and EVI2 showed higher accuracy compared with NDVI. We also demonstrate the application of phenology extraction of the single-cropped rice in a spatial scale in the study area. While the work is of general value, it can also be extrapolated to other regions where qualified remote sensing data are the bottleneck but where complementary data are occasionally available.
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Interpretación de Imagen Asistida por Computador/métodos , Oryza/clasificación , Oryza/crecimiento & desarrollo , Tecnología de Sensores Remotos/instrumentación , Estaciones del Año , Nave Espacial/instrumentación , Algoritmos , Oryza/anatomía & histología , Tecnología de Sensores Remotos/métodos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Integración de SistemasRESUMEN
Two dibenzoxanthene isomers 3 and 4 were synthesized and characterized. The crystal structures of the two compounds were solved by single-crystal X-ray diffraction. Binding of two compounds with calf thymus DNA (CT DNA) and BSA (bovine serum albumin) has been thoroughly investigated by UV-Vis and fluorescence spectroscopy. The DNA-binding constants were determined to be 2.51 (± 0.09) × 10(3) for compound 3 and 4.55 (± 0.10) × 10(3) for compound 4. Two compounds can cleave pBR322 DNA upon irradiation. Significant nuclear damages of BEL-7402 cells were observed with compound treatment in a comet assay. The cytotoxicity in vitro was investigated by MTT method. These compounds have been found to induce nuclear condensation and fragmentation in BEL-7402 cells. The two compounds can enhance intracellular reactive oxygen species and decrease the mitochondrial membrane potential. The compounds activated caspase-3 and caspase-7, down-regulated the expression levels of anti-apoptotic protein Bcl-2, and up-regulated the expression levels of pro-apoptotic protein Bax. These compounds induce apoptosis of BEL-7402 cells through an ROS-mediated mitochondrial dysfunction pathway.
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Apoptosis/efectos de los fármacos , ADN/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Proteínas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Xantenos/química , Xantenos/farmacología , Animales , Bovinos , Línea Celular , ADN/química , Daño del ADN/efectos de los fármacos , Humanos , Concentración 50 Inhibidora , Modelos Moleculares , Estructura Molecular , Plásmidos/química , Plásmidos/metabolismo , Unión Proteica , Proteínas/química , Xantenos/síntesis químicaRESUMEN
The aim of our study was to investigate DNA-binding and cytotoxic activity of the four new Ru(II) polypyridyl complexes [Ru(dmb)2(HMHPIP)](ClO4)2 (1), [Ru(bpy)2(HMHPIP)](ClO4)2 (2), [Ru(phen)2(HMHPIP)](ClO4)2 (3) and [Ru(dmp)2(HMHPIP)](ClO4)2 (4). The complexes interact with DNA through intercalative mode and show relatively high cytotoxic activity against A549 cells, no cytotoxicity toward MG-63 cells. Complexes 1-4 can enhance the levels of ROS in A549 cells and induce the decrease of the mitochondrial membrane potential. These complexes inhibit the cell growth in A549 cells at G0/G1 or S phase. Complex 3 activated caspase 7, and down-regulated the expression of the anti-apoptotic protein Bcl-2. Complexes 1-4 induce apoptosis in A549 cells through ROS-mediated mitochondrial dysfunction pathway.
Asunto(s)
Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Complejos de Coordinación/toxicidad , ADN/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Rutenio/química , Western Blotting , Caspasa 3/metabolismo , Caspasa 7/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , ADN/química , División del ADN/efectos de los fármacos , División del ADN/efectos de la radiación , Humanos , Sustancias Intercalantes/síntesis química , Sustancias Intercalantes/química , Sustancias Intercalantes/toxicidad , Plásmidos/química , Plásmidos/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Rayos UltravioletaRESUMEN
Two new dibenzoxanthenes compounds 1 and 2 have been synthesized and characterized by analytical and spectral methods. The crystal structure of compound 2 informs that the five rings of compound are almost planar. The DNA binding properties of two compounds were studied by absorption titration, viscosity measurement and luminescence. These results indicate that two compounds interact with calf thymus DNA through intercalative mode. Agarose gel electrophoresis experiment shows that PBR 322 DNA can be induced to cleave by two compounds under photoactivated condition. Compound 1 exhibits higher cytotoxicity than compound 2 toward MG-63, BEL-7402 and A549 cells. The apoptosis and cellular uptake of MG-63 cells were studied by fluorescence microscopy. Two compounds can also enhance the level of reactive oxygen species (ROS) and decrease the mitochondrial membrane potential. Compound 1 induces cell cycle arrest in G2/M phase and compound 2 induces cell cycle arrest in G0/G1 phase in MG-63.
Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Xantenos/química , Xantenos/farmacología , Animales , Antineoplásicos/síntesis química , Apoptosis/efectos de los fármacos , Bovinos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , ADN/metabolismo , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Xantenos/síntesis químicaRESUMEN
Three novel aryloxazole compounds 1-3 were synthesized and characterized. The crystal structures of compounds 2 and 3 show that N atom locates at ß-position and O atom at α-position in naphthalene cycle. The DNA binding constants for compounds 1-3 are 4.44 × 10(3), 5.31 × 10(3) and 2.64 × 10(3) M(-1), respectively. The viscosity measurements indicate that these compounds intercalate between the DNA base pairs. Upon irradiation, compounds 1-3 can effectively cleave pBR322 DNA. The cytotoxicity of the compounds against BEL-7402, A549, MG-63 and SKBR-3 were assayed by MTT method. The apoptosis and cell cycle arrest were investigated towards A549 cells. The antioxidant activities of the compounds against hydroxyl radicals were also explored.
Asunto(s)
Apoptosis/efectos de los fármacos , ADN/metabolismo , Oxazoles/síntesis química , Oxazoles/farmacología , Antioxidantes/síntesis química , Antioxidantes/química , Antioxidantes/metabolismo , Antioxidantes/farmacología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Técnicas de Química Sintética , Humanos , Radical Hidroxilo/química , Sustancias Intercalantes/síntesis química , Sustancias Intercalantes/química , Sustancias Intercalantes/metabolismo , Sustancias Intercalantes/farmacología , Oxazoles/química , Oxazoles/metabolismoRESUMEN
The NPR1 gene was an important regulator for a plant disease resistance. The cDNA of NPR1 gene was cloned from peanut cultivar Ri Hua 1 by rapid amplification of cDNA ends-polymerase chain reaction (RACE-PCR). The full length cDNA of Arachis hypogaea NPR1 consisted of 2,078 base pairs with a 1,446 bp open-reading frame encoding 481 amino acids. The predicted NPR1 contained the highly conserved functional domains (BTB/POZ domain from M1 to D116), protein-protein interaction domains (three ankyrin repeats from K158 to L186; N187 to L217 and R221 to D250) and one NPR1-like domain (C262 to S469). The DNA sequence of the NPR1 gene was 2,332 or 2,223 bp. Both two sequences contained three introns and four exons. The NPR1 transcripts were expressed mainly in roots and leaves, while fewer signals were detected in the stems. Amount of the NPR1 transcript was significantly increased 1 h after salicylic acid challenge and was eventually 5.3 times greater than that in the control group. Both the DNA sequence and the coding sequence were obtained from eight cultivars and nine wild species of Arachis. Maximum likelihood analyses of d N/d S ratios for 25 sequences from different species showed that different selection pressures may have acted on different branches.
Asunto(s)
Arachis/genética , Regulación de la Expresión Génica de las Plantas , Inmunidad de la Planta/genética , Proteínas de Plantas/genética , Receptores del Factor Natriurético Atrial/genética , Secuencia de Aminoácidos , Secuencia de Bases , Clonación Molecular , ADN de Plantas/genética , Exones , Intrones , Datos de Secuencia Molecular , Filogenia , Enfermedades de las Plantas/genética , Proteínas de Plantas/metabolismo , Dominios y Motivos de Interacción de Proteínas , Ácido Salicílico/metabolismo , Alineación de Secuencia , Análisis de Secuencia de ADNRESUMEN
A novel naphthoxazole compound 1 was synthesized and characterized. The crystal structure of the compound shows that N atom locates at ß-position and oxygen atom at α-position in naphthalene cycle. The DNA binding was studied by absorption spectroscopy, viscosity and luminescence spectra. The DNA binding constant was determined to be 6.16×10(3). The stoichiometry of compound/DNA is 1:1. The pBR322 DNA cleavage induced by the compound was investigated. The antioxidant activity of the compound against hydroxyl radical was also explored.
Asunto(s)
Antioxidantes/química , Antioxidantes/farmacología , División del ADN/efectos de los fármacos , Oxazoles/química , Oxazoles/farmacología , Antioxidantes/síntesis química , Cristalografía por Rayos X , ADN/química , ADN/metabolismo , Radical Hidroxilo/química , Modelos MolecularesRESUMEN
Signal transduction has been reported to be involved in antidepressant treatment outcomes; however, its mechanisms remain unclear. The aims of this study were to explore the associations between antidepressant remission and single nucleotide polymorphisms (SNPs), haplotypes, and gene-gene interactions in the Ras-Raf-MAPK intracellular signaling pathway. A total of 302 inpatients with major depressive disorder (DSM-IV Axis I) were assessed using the 17-item Hamilton Depression Rating Scale before and after 8 weeks of antidepressant treatment to determine the remission rate in the samples. Twenty-four SNPs at five kinase genes (Ras-Raf-MEK-ERK-RSK), which are a part of the Ras-Raf-MAPK signaling pathway, were identified to investigate a genetic association with antidepressant drug outcome. Correlations between 24 SNPs at the five kinase genes in the Ras-Raf-MAPK signaling pathway and antidepressant drug outcome were not found. The percentage of the CCAGA haplotype that RSK(2/3/4)-RSKL(1/2) gene loci SNPs constructed was markedly lower in the remitter group when compared with the nonremitter group in female depressed patients (P=0.04), whereas the proportion of AAAGGG haplotype that RSK(2/3/4)-RSKL(1/2) gene loci SNPs constructed in the remitter group was significantly greater than that in the nonremitter group in male patients (P=0.02). In addition, MEK1 (rs28730804) and RSK3 (rs2229712) in the Ras-Raf-MAPK signaling pathway showed a gene-gene interaction that affected antidepressant drug outcome in female depressed patients (P=0.041). Although this study did not find that SNPs at the five kinase genes in the Ras-Raf-MAPK signaling pathway are important markers for antidepressant outcome, certain haplotypes that SNPs at the RSK(2/3/4)-RSKL(1/2) gene constructed may be important markers for antidepressant drug efficacy. We observed a gene-gene interaction in this signaling pathway that influenced antidepressant efficacy in female depressed patients. Therefore, it is likely that in female depressed patients, different haplotypes and gene-gene interaction in the Ras-Raf-MAPK signaling pathway are involved in mediating the pharmacological action of an antidepressant, and eventually influence antidepressant efficacy.