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1.
Molecules ; 28(7)2023 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-37049928

RESUMO

In this paper, a series of glycyrrhetic acid derivatives 3a-3f were synthesized via the esterification reaction. The cytotoxicity of these compounds against five tumor cells (SGC-7901, BEL-7402, A549, HeLa and B16) and normal LO2 cells was investigated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The results showed that compound 3a exhibited high antiproliferative activity against HeLa cells (IC50 = 11.4 ± 0.2 µM). The anticancer activity was studied through apoptosis, cloning, and scratching; the levels of the intracellular ROS, GSH, and Ca2+; and the change in the mitochondrial membrane potential, cell cycle arrest and RNA sequencing. Furthermore, the effects of compound 3a on gene expression levels and metabolic pathways in HeLa cells were investigated via transcriptomics. The experimental results showed that this compound can block the cell cycle in the S phase and inhibit cell migration by downregulating Focal adhesion kinase (FAK) expression. Moreover, the compound can reduce the intracellular glutathione (GSH) content, increase the Ca2+ level and the intracellular ROS content, and induce a decrease in the mitochondrial membrane potential, further leading to cell death. In addition, it was also found that the mechanism of compounds inducing apoptosis was related to the regulation of the expression of mitochondria-related proteins B-cell lymphoma-2 (Bcl-2), Bcl-2-Associated X (Bax), and the activation of the caspase proteins. Taken together, this work provides a help for the development of glycyrrhetinic acid compounds as potential anticancer molecules.


Assuntos
Antineoplásicos , Ácido Glicirretínico , Humanos , Células HeLa , Linhagem Celular Tumoral , Ácido Glicirretínico/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Proliferação de Células , Antineoplásicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Apoptose , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
2.
Neurocase ; 28(5): 448-457, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36548914

RESUMO

Numerous studies have analyzed the state of brain activation about anxiety disorders under emotional stimuli. However, there is no meta-analysis to assess the commonality and specificity activation concerning different subtypes of anxiety. Here, we used ALE to assess this. 29 studies revealed increased bilateral amygdala, anterior cingulate gyrus, parahippocampal gyrus activation in anxiety disorders during emotional stimuli. Moreover, we observed decreased activations in the posterior cingulate, lingual gyrus, and precuneus. In sub-analysis, although different anxiety showed dissimilar activations, the principal activations were observed in limbic lobe, which might indicate the limbic circuit was the main neural reflection of anxiety symptoms.


Assuntos
Encéfalo , Imageamento por Ressonância Magnética , Humanos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Emoções , Mapeamento Encefálico , Transtornos de Ansiedade/diagnóstico por imagem
3.
Molecules ; 27(6)2022 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-35335332

RESUMO

Three benzoxanthone derivatives were synthesized through a new photochemical strategy. The in vitro cytotoxic activity of these compounds was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and their partition coefficients (logP) were measured by shake flask method. The pKa values of the compounds were detected by potentionmetric titration. The interaction of the compounds with calf thymus DNA (CT-DNA) was investigated by electronic absorption, luminescence spectra and viscosity. A molecular docking analysis was performed. The antitumor efficacy of the compounds was evaluated by cell apoptosis, cell cycle arrest, intracellular Ca2+ concentrations and reactive oxygen species (ROS) levels. The mitochondrial membrane potential was assayed using JC-1 (5,5',6,6'-tetrachloro-1,1,3',3'-tetraethyl-imidacarbocyanine iodide) as the fluorescence probe. The expression of Bcl-2 family protein, caspase 3 and poly ADP-ribose polymerase (PARP) was explored by western blot. The results showed that the compounds induced apoptosis through a ROS-mediated mitochondrial dysfunction pathway. This work provides an efficient approach to synthesize benzoxanthone derivatives, and is helpful for understanding the apoptotic mechanism.


Assuntos
Neoplasias Gástricas , Pontos de Checagem do Ciclo Celular , Humanos , Potencial da Membrana Mitocondrial , Simulação de Acoplamento Molecular , Espécies Reativas de Oxigênio/metabolismo , Neoplasias Gástricas/tratamento farmacológico
4.
BMC Public Health ; 21(1): 702, 2021 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-33836705

RESUMO

BACKGROUND: The current study examined the change in local government staff's emotional distress over 7 years after the 2008 Wenchuan earthquake, and the influence of earthquake exposure and professional quality of life (ProQOL) on emotional distress. METHODS: This longitudinal study assessed 250 participants at 1 year after the earthquake; 162 (64.8%) were followed up at 7 years. Emotional distress was assessed with the Self-Reporting Questionnaire (SRQ) at both time points. We assessed ProQOL, including compassion satisfaction, burnout, and secondary traumatic stress, and earthquake exposure at 1 year. Wilcoxon signed-rank tests were performed to test longitudinal changes in emotional distress. Hierarchical multiple regression was conducted to examine the effect of earthquake exposure and ProQOL. RESULTS: The positive screening rate of emotional distress (SRQ ≥ 8) was 37.6 and 15.4% at one and 7 years, respectively. Emotional distress scores declined over time (p < 0.001). Earthquake exposure and ProQOL predicted one-year (ps < 0.05) but not seven-year emotional distress, whereas burnout predicted both one-year (p = 0.018) and seven-year (p = 0.047) emotional distress. CONCLUSIONS: Although emotional distress can recover over time, it persists even 7 years later. Actions to reduce burnout during the early stage of post-disaster rescue have long-term benefits to staff's psychological outcomes.


Assuntos
Terremotos , Angústia Psicológica , Transtornos de Estresse Pós-Traumáticos , China/epidemiologia , Humanos , Governo Local , Estudos Longitudinais , Qualidade de Vida , Inquéritos e Questionários
5.
J Biol Inorg Chem ; 24(2): 151-169, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30564887

RESUMO

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.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Irídio/farmacologia , Fenazopiridina/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Escherichia coli/efeitos dos fármacos , Humanos , Irídio/química , Listeria monocytogenes/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Fenazopiridina/química , Salmonella/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Relação Estrutura-Atividade
6.
Phytopathology ; 109(10): 1689-1697, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31188071

RESUMO

Clubroot caused by Plasmodiophora brassicaeis one of the most important diseases in cruciferous crops. The recognition of P. brassicae by host plants is thought to occur at the primary infection stage, but the underlying mechanism remains unclear. Secretory proteins as effector candidates play critical roles in the recognition of pathogens and the interactions between pathogens and hosts. In this study, 33 P. brassicae secretory proteins expressed during primary infection were identified through transcriptome, secretory protein prediction, and yeast signal sequence trap analyses. Furthermore, the proteins that could suppress or induce cell death were screened through an Agrobacterium-mediated plant virus transient expression system and a protoplast transient expression system. Two secretory proteins, PBCN_002550 and PBCN_005499, were found to be capable of inducing cell death associated with H2O2 accumulation and electrolyte leakage in Nicotiana benthamiana. Moreover, PBCN_002550 could also induce cell death in Chinese cabbage. In addition, 24 of the remaining 31 tested secretory proteins could suppress mouse Bcl-2-associated X protein-induced cell death, and 28 proteins could suppress PBCN_002550-induced cell death.


Assuntos
Brassica , Nicotiana , Plasmodioforídeos , Animais , Brassica/parasitologia , Morte Celular , Linhagem Celular , Peróxido de Hidrogênio/metabolismo , Camundongos , Doenças das Plantas/parasitologia , Proteínas de Protozoários/metabolismo , Nicotiana/parasitologia
7.
Immunopharmacol Immunotoxicol ; 41(4): 497-503, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31293216

RESUMO

Background: Osteoarthritis (OA) is a chronic joint-degeneration disease and accounts for the most frequent arthritis in aging people. OA is characterized by the degeneration of articular cartilage, subchondral bone sclerosis and synovitis. Inflammation as an important role in OA progression, in that anti-inflammatory agents could effectively inhibit the development of OA with minimal side effects, therefore developing a nature anti-inflammatory compound will be a promising therapy for treating OA. Methods: We treated patient-derived chondrocytes and mouse models of OA with astragaloside, an effective component of astragalus membranaceus, and measured its effect on pro-inflammatory cytokines and OA progression in mice. Results: In vitro, astragaloside induced a dose-dependent inhibition of IL-1ß-induced the production of inflammatory factors, including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), nitric oxide (NO), prostaglandin E2 (PGE2), expression of MMP 13 and ADAMTS-5, and the activation of NF-κB signaling. In vivo, astragaloside ameliorate the degeneration of cartilage in mouse model of OA. Conclusion: Astragaloside potentially serve as a promising and effective therapeutic agent for treating OA patients.


Assuntos
Anti-Inflamatórios/farmacologia , Condrócitos/efeitos dos fármacos , Inflamação/tratamento farmacológico , Interleucina-1beta/metabolismo , Osteoartrite/tratamento farmacológico , Animais , Células Cultivadas , Condrócitos/metabolismo , Modelos Animais de Doenças , Humanos , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Osteoartrite/metabolismo , Transdução de Sinais/efeitos dos fármacos
8.
Mol Cell Biochem ; 445(1-2): 145-156, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29380241

RESUMO

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.


Assuntos
Apoptose/efeitos dos fármacos , Xantenos/farmacologia , Western Blotting , Caspase 3/metabolismo , Caspase 7/metabolismo , Linhagem Celular Tumoral , Ensaio Cometa , Cristalografia por Raios X , Dano ao DNA , Regulação para Baixo , Ativação Enzimática , Citometria de Fluxo , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Microscopia de Fluorescência , Estrutura Molecular , Ligação Proteica , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fase S/efeitos dos fármacos , Soroalbumina Bovina/química , Espectrometria de Fluorescência , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Ultravioleta , Sais de Tetrazólio , Tiazóis , Xantenos/química
9.
Nanotechnology ; 28(25): 255402, 2017 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-28489016

RESUMO

A nanocomposite of Mn3O4 octahedrons entangled by carbon nanotubes (CNTs) was synthesized by a hydrothermal method assisted with a non-ionic surfactant. The integration of octahedral structure and CNTs could offer many critical features, which are needed for high activity anodes, such as fast ion diffusion, good electronic conductivity, and skeleton supporting function, thus enabling the nanocomposite-based anodes with excellent electrochemical performance. In addition, CNTs can not only serve as the conductive network and structure skeleton to improve the anode performance, but also play an indispensable role in the formation of more uniform Mn3O4 octahedrons. The lithium-ion batteries based on the CNTs-entangled Mn3O4 octahedrons delivered a high capacity of over 800 mAh g-1 at a current density of 0.2 C for 200 cycles, and even as high as 678.4 mAh g-1 when cycled at 0.5 C after 400 cycles, exhibiting a high capability and ultralong cycle life.

10.
Bioorg Chem ; 72: 333-344, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28521246

RESUMO

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.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Xantenos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Neoplasias Hepáticas/patologia , Estrutura Molecular , Relação Estrutura-Atividade , Xantenos/síntese química , Xantenos/química
11.
J Membr Biol ; 248(6): 951-65, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26400779

RESUMO

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.


Assuntos
Apoptose/efeitos dos fármacos , DNA/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Proteínas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Xantenos/química , Xantenos/farmacologia , Animais , Bovinos , Linhagem Celular , DNA/química , Dano ao DNA/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Modelos Moleculares , Estrutura Molecular , Plasmídeos/química , Plasmídeos/metabolismo , Ligação Proteica , Proteínas/química , Xantenos/síntese química
12.
Int J Mol Sci ; 15(5): 8553-69, 2014 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-24830557

RESUMO

Neuronal nitric oxide synthase (nNOS) plays an important role in neurotransmission and smooth muscle relaxation. Selective inhibition of nNOS over its other isozymes is highly desirable for the treatment of neurodegenerative diseases to avoid undesirable effects. In this study, we present a workflow for the identification and prioritization of compounds as potentially selective human nNOS inhibitors. Three-dimensional pharmacophore models were constructed based on a set of known nNOS inhibitors. The pharmacophore models were evaluated by Pareto surface and CoMFA (Comparative Molecular Field Analysis) analyses. The best pharmacophore model, which included 7 pharmacophore features, was used as a search query in the SPECS database (SPECS®, Delft, The Netherlands). The hit compounds were further filtered by scoring and docking. Ten hits were identified as potential selective nNOS inhibitors.


Assuntos
Inibidores Enzimáticos/química , Neurônios/enzimologia , Óxido Nítrico Sintase Tipo I/antagonistas & inibidores , Sítios de Ligação , Bases de Dados de Compostos Químicos , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/metabolismo , Humanos , Análise dos Mínimos Quadrados , Simulação de Acoplamento Molecular , Óxido Nítrico Sintase Tipo I/metabolismo , Ligação Proteica , Estrutura Terciária de Proteína , Relação Quantitativa Estrutura-Atividade
13.
World J Clin Cases ; 12(1): 24-31, 2024 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-38292646

RESUMO

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.

14.
Biosensors (Basel) ; 14(6)2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38920609

RESUMO

Lateral flow immunoassays (LFIAs) are recognized for their practicality in homecare and point-of-care testing, owing to their simplicity, cost-efficiency, and rapid visual readouts. Despite these advantages, LFIAs typically fall short in sensitivity, particularly in detecting viruses such as SARS-CoV-2, thus limiting their broader application. In response to this challenge, we have innovated an approach to substantially enhance LFIA sensitivity. This involves the integration of a water-soluble dextran-methacrylate polymer wall with a 15% grafting degree positioned between the test and control lines on the LFIA strip. This novel modification significantly improved the sensitivity of the assay, achieving detection limits as low as 50 pg mL-1 and enhancing the sensitivity by 5-20-fold relative to existing LFIA kits available on the market. Furthermore, our developed LFIA kit (WSPW-LFIA) demonstrated exceptional specificity for SARS-CoV-2. Coupled with a straightforward fabrication process and robust stability, the WSPW-LFIA represents a promising advancement for real-time in vitro diagnosis across a spectrum of diseases.


Assuntos
COVID-19 , Polímeros , SARS-CoV-2 , SARS-CoV-2/imunologia , Humanos , COVID-19/diagnóstico , Imunoensaio/métodos , Polímeros/química , Técnicas Biossensoriais , Antígenos Virais/análise , Água , Sensibilidade e Especificidade , Limite de Detecção , Teste Sorológico para COVID-19/métodos , Dextranos
15.
Dalton Trans ; 53(36): 15176-15189, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39221457

RESUMO

Cyclometalated iridium(III) compounds have been widely explored due to their outstanding photo-physical properties and multiple anticancer activities. In this paper, three cyclometalated iridium(III) compounds [Ir(ppy)2(DBDIP)]PF6 (5a), [Ir(bzq)2(DBDIP)]PF6 (5b), and [Ir(piq)2(DBDIP)]PF6 (5c) (ppy: 2-phenylpyridine; bzq: benzo[h]quinoline; piq: 1-phenylisoquinoline, and DBDIP: 2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-imidazo[4,5-f][1,10]phenanthroline) were synthesized and the mechanism of antitumor activity was investigated. Compounds photoactivated by visible light show strong cytotoxicity against tumor cells, especially toward A549 cells. Biological experiments such as migration, cellular localization, mitochondrial membrane potential and permeability, reactive oxygen species (ROS) and calcium ion level detection were performed, and they demonstrated that the compounds induced the apoptosis of A549 cells through a mitochondrial pathway. At the same time, oxidative stress caused by ROS production increases the release of damage-related molecules and the expression of porogen gasdermin D (GSDMD), and the content of LDH released from damaged cell membranes also increased. Besides, the content of the lipid peroxidation product, malondialdehyde (MDA), increased and the expression of GPX4 decreased. These indicate that the compounds promote cell death by combining ferroptosis and pyroptosis. The results reveal that cyclometalated iridium(III) compounds 5a-5c may be a potential chemotherapeutic agent for photodynamic therapy of cancers.


Assuntos
Antineoplásicos , Complexos de Coordenação , Ensaios de Seleção de Medicamentos Antitumorais , Irídio , Espécies Reativas de Oxigênio , Humanos , Irídio/química , Irídio/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Espécies Reativas de Oxigênio/metabolismo , Células A549 , Apoptose/efeitos dos fármacos , Luz , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Estrutura Molecular , Cálcio/metabolismo , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Processos Fotoquímicos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/síntese química
16.
Nanomaterials (Basel) ; 14(10)2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38786820

RESUMO

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.

17.
Biosens Bioelectron ; 256: 116262, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38621340

RESUMO

Lateral flow immunoassays (LFIAs) are an essential and widely used point-of-care test for medical diagnoses. However, commercial LFIAs still have low sensitivity and specificity. Therefore, we developed an automatic ultrasensitive dual-color enhanced LFIA (DCE-LFIA) by applying an enzyme-induced tyramide signal amplification method to a double-antibody sandwich LFIA for antigen detection. The DCE-LFIA first specifically captured horseradish peroxidase (HRP)-labeled colored microspheres at the Test line, and then deposited a large amount of tyramide-modified signals under the catalytic action of HRP to achieve the color superposition. A limit of detection (LOD) of 3.9 pg/mL and a naked-eye cut-off limit of 7.8 pg/mL were achieved for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleoprotein. Additionally, in the inactivated virus detections, LOD equivalent to chemiluminescence (0.018 TCID50/mL) was obtained, and it had excellent specificity under the interference of other respiratory viruses. High sensitivity has also been achieved for detection of influenza A, influenza B, cardiac troponin I, and human chorionic gonadotrophin using this DCE-LFIA, suggesting the assay is universally applicable. To ensure the convenience and stability in practical applications, we created an automatic device. It provides a new practical option for point-of-care test immunoassays, especially ultra trace detection and at-home testing.


Assuntos
Técnicas Biossensoriais , COVID-19 , Limite de Detecção , SARS-CoV-2 , Imunoensaio/instrumentação , Imunoensaio/métodos , Humanos , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/imunologia , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , COVID-19/diagnóstico , COVID-19/virologia , Peroxidase do Rábano Silvestre/química , Troponina I/sangue , Troponina I/análise , Testes Imediatos , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Proteínas do Nucleocapsídeo de Coronavírus/análise , Gonadotropina Coriônica/análise , Gonadotropina Coriônica/sangue , Vírus da Influenza A/isolamento & purificação , Vírus da Influenza A/imunologia , Fosfoproteínas
18.
Sensors (Basel) ; 13(12): 16023-50, 2013 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-24287529

RESUMO

Long-term monitoring of regional and global environment changes often depends on the combined use of multi-source sensor data. The most widely used vegetation index is the normalized difference vegetation index (NDVI), which is a function of the red and near-infrared (NIR) spectral bands. The reflectance and NDVI data sets derived from different satellite sensor systems will not be directly comparable due to different spectral response functions (SRF), which has been recognized as one of the most important sources of uncertainty in the multi-sensor data analysis. This study quantified the influence of SRFs on the red and NIR reflectances and NDVI derived from 31 Earth observation satellite sensors. For this purpose, spectroradiometric measurements were performed for paddy rice grown under varied nitrogen levels and at different growth stages. The rice canopy reflectances were convoluted with the spectral response functions of various satellite instruments to simulate sensor-specific reflectances in the red and NIR channels. NDVI values were then calculated using the simulated red and NIR reflectances. The results showed that as compared to the Terra MODIS, the mean relative percentage difference (RPD) ranged from -12.67% to 36.30% for the red reflectance, -8.52% to -0.23% for the NIR reflectance, and -9.32% to 3.10% for the NDVI. The mean absolute percentage difference (APD) compared to the Terra MODIS ranged from 1.28% to 36.30% for the red reflectance, 0.84% to 8.71% for the NIR reflectance, and 0.59% to 9.32% for the NDVI. The lowest APD between MODIS and the other 30 satellite sensors was observed for Landsat5 TM for the red reflectance, CBERS02B CCD for the NIR reflectance and Landsat4 TM for the NDVI. In addition, the largest APD between MODIS and the other 30 satellite sensors was observed for IKONOS for the red reflectance, AVHRR1 onboard NOAA8 for the NIR reflectance and IKONOS for the NDVI. The results also indicated that AVHRRs onboard NOAA7-17 showed higher differences than did the other sensors with respect to MODIS. A series of optimum models were presented for remote sensing data assimilation between MODIS and other sensors.


Assuntos
Monitoramento Ambiental/instrumentação , Monitoramento Ambiental/métodos , Oryza/crescimento & desenvolvimento , Comunicações Via Satélite/instrumentação , Espectroscopia de Luz Próxima ao Infravermelho/instrumentação , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Algoritmos
19.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 38(1): 81-5, 2013 Jan.
Artigo em Zh | MEDLINE | ID: mdl-23406861

RESUMO

OBJECTIVE: To determine the effect of lung protection mechanical ventilation on respiratory function in the elderly undergoing spinal fusion. METHODS: Sixty 70-85 year old patients, ASA class II or III, undergoing spinal fusion were randomly assigned into 2 groups (30 in each group): a protection mechanical ventilation group (group P) and a conventional mechanical ventilation group (group C). Low VT and low level positive end expiratory pressure (PEEP) mechanical ventilation were applied in group P (VT=6mL/kg, RR=12-18 b/min, I:E=1:2, PEEP=10 cmH2O, alveolar recruitment performed once every 15 min), while traditional ventilation was used in group C ( VT=10-12 mL/kg, RR=12 b/min, I:E=1:2). Arterial blood samples were taken and pH, PaO2, PaCO2, PaO2/FiO2, A-aDO2, HR, SBP, DBP and CVP were recorded before the operation (T0), 1 h after tracheal intubation (T1), tracheal extubation immediately (T2), 1 h after tracheal extubation (T3), 1 d, 2 d, and 3 d after the operation (T4, T5, and T6). The pulmonary complication was also examined 1 d after the operation. RESULTS: At T1, T2, T3, T4 and T5, PaO2 and PaO2/FiO2 in group P were higher than those in group C, but A-aDO2 in group P was lower than that in group C. Five patients had bronchitis, 5 had hyoxemia, and 3 had atelectasis in group C, but 2 bronchitis in group P. The incidence of pulmonary complication was 43.3% in group C and 6.6% in group P. There was no significant difference in HR, SBP, DBP and CVP between the 2 groups. CONCLUSION: Lung protection mechanical ventilation improves the arterial oxygenation and accelerates the recovery of respiratory functions in elderly patients after spinal fusion operation, with no influence on hemodynamics.


Assuntos
Respiração com Pressão Positiva/métodos , Complicações Pós-Operatórias/prevenção & controle , Respiração Artificial/métodos , Fusão Vertebral/métodos , Idoso , Idoso de 80 Anos ou mais , Anestesia Geral , Feminino , Humanos , Hipóxia/prevenção & controle , Masculino , Ventilação Pulmonar , Testes de Função Respiratória
20.
Asian J Surg ; 46(10): 4240-4244, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36653293

RESUMO

OBJECTIVE: Exploring the predictive power of frailty combined with nutritional risk on postoperative complications in elderly gastrointestinal malignancies patients. METHODS: Elderly patients who underwent gastrointestinal cancer surgery at Gastrointestinal Surgery Department of the Affiliated Hospital of Binzhou Medical University from August 2021 to June 2022 were selected as the research subjects. The patients' frailty and nutritional status were assessed using the Fried Frailty Scale and the NRS2002 Nutritional Risk Scale within 24 h of admission. Observing and recording the diagnosis and treatment of postoperative complications during the hospitalization. RESULTS: 202 patients were enrolled, including 119 patients (58.91%) with nutritional risk and 89 patients (44.06%) with frailty. Frailty was an independent risk factor for postoperative complications [OR = 5.904, 95%CI (3.103, 11.233)]. The AUC value of frailty assessment was 0.780, which was greater than the AUC value of NRS2002 score of 0.705 (P < 0.01). The AUC value of frailty assessment combined with NRS-2002 score was 0.844, which was significantly higher than that alone (P < 0.01). CONCLUSIONS: The ability of frailty to predict postoperative complications is better than the NRS-2002 score. Frailty combined with nutritional risk assessment can increase the predictive power of postoperative complications in elderly gastrointestinal malignancies patients.


Assuntos
Fragilidade , Neoplasias Gastrointestinais , Humanos , Idoso , Fragilidade/complicações , Fragilidade/diagnóstico , Idoso Fragilizado , Fatores de Risco , Neoplasias Gastrointestinais/complicações , Neoplasias Gastrointestinais/cirurgia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
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