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1.
Int J Clin Pharmacol Ther ; 62(4): 169-177, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38431830

RESUMO

OBJECTIVE: The aim of this clinical study is to obtain evidence for the clinical efficacy of Bu-Shen-Jian-Pi formula (BSJP), a traditional Chinese medicine, used for the treatment of amyotrophic lateral sclerosis, a relatively rare, progressive and usually fatal disease possibly associated with alterations in tissue redox status, hypoxia, and muscular injury. BACKGROUND: The active agents in BSJP formula† causing apoptosis, modulation of redox changes, and alterations in the immune status have been studied previously by us using cell cultures. The findings from these investigations have been incorporated into pharmacology databases employed in our analysis of BSJP using network pharmacology analysis/artifical intelligence. This information has been used here in the design of the investigation and to optimize evaluation of the clinical efficacy and usefulness of this herbal medicine, as far as possible using evidence-based medicine criteria. MATERIALS AND METHODS: The design of the study was a randomized multi-center, controlled clinical trial in 127 patients with confirmed diagnoses of amyotrophic lateral sclerosis. Patients and investigator were double-blinded. Clinical efficacy was determined using the Amyotrophic Lateral Sclerosis Symptom Score in Integrative Treatment Scale (ALS-SSIT) and the Amyotrophic Lateral Sclerosis Rating Scale-Revised (ALSFRS-R), together with tests of limb muscle strength using the manual muscle test (MMT), forced vital capacity (FVC), and clinical chemistry laboratory tests over a 20-week observation period. RESULTS: The scores of ALS-SSIT in the BSJP group increased significantly (22%) after treatment. The ALSFRS-R score in the BSJP group decreased significantly after treatment (19%). The rate of decrease in muscle function (MMT score) in most BSJP patients was lower than that in the control group, where the differences in the scores for the trapezius and triceps brachii were statistically significant compared to the control group. The fall in FVC in the BJSP group was significantly slower than in the control group. There were no marked differences observed in the frequency of side effects. Serum vitamin D3 levels in the BSJP group showed greater increases compared to the control group. CONCLUSION: BSJP treatment reduced the rate of progression of amyotrophic lateral sclerosis according to the ALS-SSITS and ALSFRS scores and significantly reduced the rate of deterioration in muscle function in the limbs of amyotrophic lateral sclerosis patients. The modes of action of BSJP in treating amyotrophic lateral sclerosis are probably diverse and multi targeted, some of which may involve regulation of serum vitamin D3 and alleviation of the impairments in liver and kidney function.


Assuntos
Esclerose Amiotrófica Lateral , Humanos , Esclerose Amiotrófica Lateral/tratamento farmacológico , Esclerose Amiotrófica Lateral/diagnóstico , Medicina Tradicional Chinesa , Farmacologia em Rede , Resultado do Tratamento , Hipóxia , Colecalciferol , Músculos , Progressão da Doença
3.
Biomarkers ; 28(5): 409-415, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37000536

RESUMO

OBJECTIVE: This study aimed to investigate the significance of miRNA expression levels in peripheral blood lymphocytes of patients clinically diagnosed with pulmonary tuberculosis. METHOD: Pulmonary tuberculosis-related datasets in the Gene Expression Omnibus (GEO) database were analyzed, and DE-miRNAs were screened for Gene Ontology (GO) analysis and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment to construct a DE-miRNA-DE-mRNA network. The peripheral blood lymphocytes of 10 patients with pulmonary tuberculosis, 10 patients with rifampicin-resistant tuberculosis and 10 healthy volunteers were selected for validation of RNA expression levels. qRT-PCR was done to verify the expression of DE-miRNA, and western blotting was done to check the expression levels of genes of associated pathways. RESULTS: Differential expression of miR-660 was found in pulmonary tuberculosis through data analysis and literature mining. The differential expression was also confirmed by qRT-PCR in samples from patients and healthy controls. The expression of miR-660 was significantly upregulated (p < 0.01) in patients with pulmonary tuberculosis and rifampicin-resistant pulmonary tuberculosis compared with the healthy controls. According to western blotting results, the expression levels of P-NF-κB and AKT in patients with pulmonary tuberculosis and NF-κB, P-NF-κB, AKT and p-AKT in patients with rifampicin-resistant tuberculosis were significantly upregulated (p < 0.01). CONCLUSION: The high expression levels of miR-660 may activate the AKT/NF-κB signalling pathway and has the potential to serve as a potential biomarker for the diagnosis of pulmonary tuberculosis.


Assuntos
MicroRNAs , Tuberculose Pulmonar , Humanos , NF-kappa B , Proteínas Proto-Oncogênicas c-akt/genética , Rifampina/farmacologia , Perfilação da Expressão Gênica , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/genética , Linfócitos/metabolismo
4.
FEBS Open Bio ; 12(10): 1828-1838, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36062491

RESUMO

Adipose tissue is a major component for the regulation of energy homeostasis by storage and release of lipids. As a core element of RNA-induced silencing complex, argonaute2 (Ago2) plays critical role in maintenance of systemic metabolic demand. Here, we show that high-fat-diet-fed mice exhibit an increase in body mass alongside systematic insulin resistance and altered rate of energy expenditure. Interestingly, Ago2 expression is associated with obesity and an increased amount of adipose tissue. Moreover, increased levels of Ago2 inhibited the expression of AMPKα by promoting its targeting by miR-148a, the most abundant microRNA in adipose tissues. Those results suggested that Ago2-miR-148a-AMPKα signaling pathway play an important function in the developing obesity and adiposity, and will further provide basic research data for the potential clinical treatment of obesity.


Assuntos
MicroRNAs , Proteínas Quinases Ativadas por AMP/metabolismo , Tecido Adiposo/metabolismo , Animais , Proteínas Argonautas , Lipídeos , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Obesidade/genética , Obesidade/metabolismo , Transdução de Sinais
5.
Eur J Pharmacol ; 931: 175184, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35964659

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial pneumonia with limited therapeutic options. Eucalyptol, a terpenoid oxide isolated from eucalyptus species, reportedly exhibits various biological activities such as anti-inflammatory and antioxidant effects. In the present study, we aimed to determine whether eucalyptol could alleviate bleomycin (BLM)-induced pulmonary fibrosis and inhibit interleukin (IL)-13-induced M2 macrophage polarization. Upon treatment with eucalyptol, BLM-induced pulmonary fibrosis and lung inflammation were significantly reduced. The pulmonary neutrophil accumulation and pulmonary permeability were inhibited and the expression of hydroxyproline, alpha-smooth muscle actin, and fibronectin was significantly down-regulated. Eucalyptol also markedly inhibited the expression of arginase-1, Ym-1, IL-13, and transforming growth factor (TGF)-ß1, reduced the production of IL-13, IL-6, tumor necrosis factor (TNF)-α, and attenuated the activity of TGF-ß1 in bronchoalveolar lavage fluid (BALF). Furthermore, the in vitro assay revealed that eucalyptol disturbed M2 macrophage polarization and reduced the macrophage-mediated secretion of the profibrotic factor TGF-ß1. Eucalyptol inhibited the nuclear location of signal transducer and activator of transcription 6 (STAT6) and the phosphorylation of STAT6 and p38 mitogen-activated protein kinase (p38 MAPK), and reduced the expression of their downstream transcription factors, krupple-like factor 4 (KLF4) and peroxisome proliferator-activated receptor gamma (PPAR-γ). These findings indicated that eucalyptol alleviates BLM-induced pulmonary fibrosis by regulating M2 macrophage polarization, which, in turn, inhibits the activation of signaling molecules (e.g., STAT6 and p38 MAPK) and the expression of transcription factors (e.g., KLF4 and PPAR-γ). Thus, eucalyptol might be a potential therapeutic agent for IPF.


Assuntos
Bleomicina , Fibrose Pulmonar , Bleomicina/efeitos adversos , Eucaliptol/farmacologia , Eucaliptol/uso terapêutico , Humanos , Interleucina-13/metabolismo , Pulmão/patologia , Macrófagos/metabolismo , PPAR gama/metabolismo , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/prevenção & controle , Fator de Crescimento Transformador beta1/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
6.
Planta ; 255(5): 102, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35412154

RESUMO

MAIN CONCLUSION: Glandular trichomes of Artemisia argyi H. Lév. & Vaniot are the key tissues for the production of flavonoid and terpenoid metabolites. Artemisia argyi H. Lév. & Vaniot is an herbaceous perennial plant that has been widely used in traditional medicine for thousands of years. Glandular trichomes (GTs) and nonglandular trichomes (NGTs) have been reported on the leaf surface of A. argyi. The aim of this study was to elucidate the morphogenetic process and to analyze the metabolites of trichomes in A. argyi. The morphogenesis of GTs and NGTs was characterized using light, scanning, and transmission electron microscopy. The constituents of GTs were analyzed using laser microdissection combined with gas and liquid chromatography-mass spectrometry. Five developmental stages of two types of GTs and four developmental stages of one type of NGTs were observed. Two types of mature GT and one type of NGT were composed of 10, 5, and 4-6 cells, respectively. A large storage cavity was detected between the cuticle and cell walls in the first type of mature GT. Large nuclei, nucleoli, and mitochondria were observed in the basal and intermediate cells of the second type of GT. In addition, large vacuoles were observed in the basal and apical cells, and large nuclei were observed in the middle cells of NGTs. One monoterpene and seven flavonoids were identified in GTs of A. argyi. We suggest that GTs are the key tissues for the production of bioactive metabolites in A. argyi. This study provides an important theoretical basis and technical approach for clarifying the regulatory mechanisms for trichome development and bioactive metabolite biosynthesis in A. argyi.


Assuntos
Artemisia , Tricomas , Artemisia/metabolismo , Flavonoides/análise , Morfogênese , Folhas de Planta/metabolismo , Terpenos/metabolismo , Tricomas/metabolismo
7.
Talanta ; 238(Pt 1): 123007, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34857340

RESUMO

Oxidative stress is considered to be one of the main contributors of cyclophosphamide (CP)-induced toxicity, and the generation of free radicals will cause the interruption of multiple signal transduction pathways. Peroxynitrite (ONOO-) has strong oxidation and nitrification ability and is considered as an indirect indicator of oxidative stress. Therefore, it is necessary to design a fluorescent probe that can detect ONOO- and monitor CP-induced oxidative stress during chemotherapy. Herein, we synthesized a lipid droplet targeting fluorescent probe SX-1 based on triphenylamine-benzoindocyanine. When ONOO- is added to the probe SX-1, the CC bond in the probe is broken, thereby releasing fluorescence. The good spectral response characteristics enable SX-1 to successfully track the fluctuations of ONOO- in living cells. Most importantly, we provided the first visual evidence that the level of ONOO- in HeLa cells was up-regulated under CP induction. All results indicated that SX-1 has great potential in detecting drug-induced ONOO-, and provided a new detection tool for a deeper understanding of drug-induced organism injury.


Assuntos
Corantes Fluorescentes , Ácido Peroxinitroso , Ciclofosfamida/toxicidade , Células HeLa , Humanos , Estresse Oxidativo
8.
Analyst ; 146(21): 6490-6495, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34559170

RESUMO

Hypochlorous acid (HClO) is an important bactericide, and adjusting the content of HClO helps to improve the host's innate immunity and resist microbial invasion. Aggregation-induced luminescence (AIE) is the opposite of aggregation-induced quenching (ACQ). Compounds with AIE properties emit weakly in a dispersed state in solution and they can emit strong fluorescence in an aggregated state. In this article, we proposed a new AIE fluorescent probe QM-ClO based on the quinoline-malononitrile (QM) fluorophore and dimethylthiocarbamate (DMTC) to detect HClO. The probe QM-ClO showed a fast response time, a low detection limit of 30.8 nM and a large Stokes shift (190 nm). Carbonyl cyanide metachlorophenyl-hydrazone (CCCP) was used to induce cell apoptosis, and then an increase in the HClO content was observed in the cell. It is proved that cell apoptosis can lead to the increase of the HClO content in the cell. This probe provides an effective tool for studying apoptosis-related diseases.


Assuntos
Corantes Fluorescentes , Ácido Hipocloroso , Apoptose , Microscopia de Fluorescência , Imagem Óptica
9.
Biomed Res Int ; 2021: 9939065, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34136575

RESUMO

OBJECTIVE: Driver gene mutation in lung adenocarcinoma patients in Zunyi and its relationship with clinical features were probed in this investigation. METHODS: In total, with 244 patients with lung adenocarcinoma as study subjects, including 141 males and 103 females, amplification-refractory mutation system-polymerase chain reaction (ARMS-PCR) was utilized for detecting multigene mutations. Subsequently, the relationship between gene mutation and clinical characteristics was analyzed. RESULTS: The total mutation rate of driver genes was 65.17%, including 48.36% EGFR, 6.15% KRAS, 5.74% ALK, 2.05% HER-2, 1.23% ROS1, 0.82% RET, 0.41% NRAS, and 0.41% BRAF. Among EGFR mutations, 47.46% were EGFR-19-deletion, 42.37% EGFR-21-L858R mutation, 4.24% EGFR-20-T790M mutation, 2.54% EGFR-21-L861Q mutation, 2.54% EGFR-20-insertion, and 0.85% EGFR-18-G719X mutation. Both female patients and nonsmoking patients with lung adenocarcinoma had a higher rate of EGFR mutation. Additionally, 15 patients with multiple mutations in EGFR, including 13 patients with 2 mutations in EGFR and 2 patients with 3 mutations in EGFR, were found. CONCLUSION: Among driver gene mutations in patients with lung adenocarcinoma in Zunyi, EGFR mutation has the highest incidence, followed by ALK fusion and KRAS mutation. Although both mutations and multisite mutations in the other driver genes account for a low proportion, they still have great clinical significance. Multigene mutation detection contributes to the rapid screening of patients with lung adenocarcinoma who respond to targeted therapy.


Assuntos
Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/genética , Mutação , Idoso , China , Análise Mutacional de DNA , Receptores ErbB/genética , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Oncogenes , Reação em Cadeia da Polimerase , Proteínas Proto-Oncogênicas/genética
10.
Microsc Res Tech ; 84(7): 1400-1413, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33455029

RESUMO

Programmed cell death (PCD) plays a critical role throughout the lives of plants, it is regarded as a highly regulated and active process of plant cell death during the times of biotic or abiotic stress. This study aims to provide developmental anatomical characteristics of the interxylary cork formation in the roots of Astragalus. membranaceus var. mongholicus, and to subsequently show cytomorphological evidence that PCD is involved in the development of rhytidome and interxylary cork. The developmental anatomy of rhytidome and interxylary cork of the perennial fresh main root of A. membranaceus var. mongholicus was studied using light microscopy, whereas the PCD in the development of rhytidome and interxylary cork was studied using fluorescence microscopy and transmission electron microscopy. Histologically, it was observed that the parenchyma cells of secondary phloem and xylem in roots recovered their meristematic ability, and later developed into rhytidome and interxylary cork. Cytologically, ultrastructural characteristics such as nucleus malformation, vacuole disappearance, mitochondrial degeneration, and vesicle filling were observed. In roots, the nucleus of the phloem parenchyma cells were terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive from the pre-rhytidome stage to the formation of rhytidome stage and 4',6-diamidino-2-phenylindole dihydrochloride (DAPI)-negative during the mature rhytidome stage. The TUNEL assay of the xylem parenchyma cells showed positive characteristics from the early stage of interxylary cork formation to the interxylary cork formation stage, whereas DAPI-negative characteristics were observed in the mature interxylary cork. Gel electrophoresis showed that DNA cleavage was random. Our results indicated that the formation of the rhytidome and interxylary cork involved the PCD process.


Assuntos
Astragalus propinquus , Fabaceae , Apoptose , Marcação In Situ das Extremidades Cortadas , Raízes de Plantas , Xilema
11.
Front Pharmacol ; 12: 825425, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35095535

RESUMO

Niemann-Pick disease type C1 (NPC1) is a neurodegenerative disorder characterized by lysosomal storage of free cholesterol. 2-Hydroxypropyl-ß-cyclodextrin (HPßCD) is a cyclic oligosaccharide derivative that is being developed to treat NPC1. Recently, metformin was reported to be beneficial in various neurodegenerative diseases, such as Alzheimer's and Huntington's diseases. In this study, we examined the effects of combined treatment with HPßCD and metformin on Npc1 -/- mice. Unfortunately, body weight and survival rates showed that cotreatment with metformin did not extend survival time and increase the body weight of HPßCD-treated Npc1 -/- mice. However, cotreatment with metformin reduced inflammatory response and inhibited the proinflammatory cytokine release in the brain, liver and spleen of HPßCD-treated Npc1 -/- mice. Furthermore, metformin did not reduce the free cholesterol levels in Npc1 -/- brain tissue or fibroblasts. In conclusion, our results demonstrate that metformin does not show beneficial effects on body weight or survival time but reduced the inflammatory response in a mouse model of NPC1 when combined with HPßCD.

12.
FASEB J ; 34(9): 12197-12213, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-33000506

RESUMO

MHC-II on alveolar type-II (AT-II) cells is associated with immune tolerance in an inflammatory microenvironment. Recently, we found TNF-α upregulated MHC-II in AT-II in vitro. In this study, we explored whether TNF-α-mediated inflammation upregulates MHC-II on AT-II cells to trigger Treg expansion in inflammation-driven lung adenocarcinoma (IDLA). Using urethane-induced mice IDLA model, we found that IDLA cells mainly arise from AT-II cells, which are the major source of MHC-II. Blocking urethane-induced inflammation by TNF-α neutralization inhibited tumorigenesis and reversed MHC-II upregulation on tumor cells of AT-II cellular origin in IDLA. MHC-II-dependent AT-II cells were isolated from IDLA-induced Treg expansion. In human LA samples, we found high expression of MHC-II in tumor cells of AT-II cellular origin, which was correlated with increased Foxp3+ T cells infiltration as well as CXCR-2 expression. CXCR-2 and MHC-II colocalization was observed in inflamed lung tissue and IDLA cells of AT-II cellular origin. Furthermore, at the pro-IDLA inflammatory stage, TNF-α-neutralization or CXCR-2 deficiency inhibited the upregulation of MHC-II on AT-II cells in inflamed lung tissue. Thus, tumor cells of AT-II cellular origin contribute to Treg expansion in an MHC-II-dependent manner in TNF-α-mediated IDLA. At the pro-tumor inflammatory stage, TNF-α-dependent lung inflammation plays an important role in MHC-II upregulation on AT-II cells.


Assuntos
Adenocarcinoma de Pulmão/imunologia , Células Epiteliais Alveolares/imunologia , Antígenos de Histocompatibilidade Classe II/análise , Inflamação/imunologia , Neoplasias Pulmonares/imunologia , Receptores de Interleucina-8B/fisiologia , Linfócitos T Reguladores/fisiologia , Fator de Necrose Tumoral alfa/fisiologia , Animais , Feminino , Antígenos HLA-DR/análise , Antígenos de Histocompatibilidade Classe II/fisiologia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Regulação para Cima
13.
Chem Commun (Camb) ; 56(86): 13217-13220, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33026369

RESUMO

A probe, MITO-TPE, was developed for imaging mitochondrial SO2 with good selectivity, high sensitivity, and a fast response time. Cell imaging indicated that SO2-induced oxidative stress may cause damage to cells through O2˙- bursting. MITO-TPE has here been used to image the misregulation of SO2 levels in mitochondria during heat stroke for the first time.


Assuntos
Corantes Fluorescentes/química , Golpe de Calor/diagnóstico por imagem , Imagem Óptica , Dióxido de Enxofre/análise , Golpe de Calor/metabolismo , Humanos , Células MCF-7 , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Estrutura Molecular , Estresse Oxidativo/efeitos dos fármacos , Espectrometria de Fluorescência , Dióxido de Enxofre/farmacologia
14.
Ann Palliat Med ; 9(5): 3152-3161, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32921122

RESUMO

BACKGROUND: The aim of this study was to clarify the characteristics of gene mutation related to multidrug-resistance (MDR) of tuberculosis (TB) and diabetes in Zunyi. METHODS: A total 763 patients with TB were screened for TB-DNA, TB-RNA, and acid-fast staining (all were positive). They were divided into the tuberculosis (TB) group and the diabetes mellitus-tuberculosis (DM-TB) group. We compared and analyzed the MDR gene rpoB, KatG, and inhA characteristics of gene mutations in the two groups by polymerase chain reaction (PCR)-reverse dot hybridization, and collected relevant clinical data to explore its correlation with the occurrence of multidrug resistance. RESULTS: Multidrug resistance occurred in 32 of the 525 patients in the TB group, and extensive drug resistance occurred in 15 of the 207 patients in the DM-TB group. In the DM-TB group, the mutation rates of ropBS531L and ropB531 (both 53.33%) were lower than those of the TB group (both 59.38%) in rifampicin resistance mutations. Most of the mutations were at the KatG315N site, conferring isoniazid resistance. CONCLUSIONS: The mutation sites of multidrug-resistant patients in Zunyi are mainly ropB531 and ropBS531L mutations, which are prone to co-occurrence; patients with MDR-TB alone are prone to mutations at the KatG315N site, while patients with diabetes and MDR-TB are more likely to have inhA15M site mutations.


Assuntos
Diabetes Mellitus , Mycobacterium tuberculosis , Tuberculose , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , China , Farmacorresistência Bacteriana Múltipla/genética , Humanos , Testes de Sensibilidade Microbiana , Mutação , Mycobacterium tuberculosis/genética , Tuberculose/tratamento farmacológico
15.
Anal Chem ; 92(17): 12002-12009, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32786484

RESUMO

Mercury (Hg) is considered an extremely toxic heavy metal which is extremely harmful to both the human body and environment. In addition, Hg2+-induced oxidative stress also exerts a crucial role to play in pathophysiological mechanisms of mercury toxicity. Thus, efficient and specific fluorescent probes for imaging Hg2+-induced oxidative stress are necessary. In the present study, we rationally design a novel Hg2+-activated and ICT-based NIR emission fluorescent probe NIR-HO for sequentially monitoring the ONOO- level with a "dual-key-and-lock" strategy. The probe NIR-HO showed rapid response and excellent specificity and sensitivity for the detection of Hg2+ and ONOO- in vitro. Cell imaging demonstrated that Hg2+-induced oxidative stress was involved in ONOO- upregulation. Also, GSH, NAC, and EDTA were employed as excellent detoxifying drugs against Hg2+-induced toxicity. Moreover, the probe NIR-HO was successfully used for imaging Hg2+ and ONOO- in vivo. In brief, NIR-HO provides a simple and powerful approach which can be used to image Hg2+-induced oxidative stress in the pathological environment.


Assuntos
Mercúrio/química , Sondas Moleculares/metabolismo , Estresse Oxidativo/fisiologia , Animais , Humanos , Camundongos
16.
Mol Carcinog ; 59(9): 1088-1099, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32673443

RESUMO

Manganese superoxide dismutase (SOD-2), an important primary antioxidant enzyme located in mitochondria, plays a critical role in tumor progression. Reportedly, the proinflammatory cytokine, tumor necrosis factor (TNF)-α, can increase SOD-2 expression in a human lung adenocarcinoma cell line in vitro, indicating that TNF-α-mediated inflammation may regulate SOD-2 expression, which may be related to cancer promotion. Using a urethane-induced inflammation-driven lung adenocarcinoma (IDLA) mice model, we investigated whether and how TNF-α-mediated inflammation upregulated SOD-2 expression in lung adenocarcinoma. Our results showed that SOD-2 was mostly expressed on surfactant protein-C+ AT-II cells (alveolar type II cell) and tumor cells in IDLA mice, which were surrounded by CD68+ macrophages. Blocking TNF-α-dependent inflammation downregulated SOD-2 expression in inflamed lung tissues at the protumor stage and also inhibited SOD-2 expression in tumor cells in the IDLA model. In human lung adenocarcinoma, both the number of infiltrating CD68+ macrophages and TNF-α expression correlated positively with SOD-2 expression, which is related to lymph node metastasis and TNM stage. We collected the conditioned medium from lipopolysaccharide-activated phorbol myristate acetate-induced THP1 (M1) cells to stimulate A549 and H1299 cells and observed that THP1-M1 upregulated SOD-2 by secreting TNF-α. Blocking SOD-2 expression significantly inhibited TNF-α-induced cell proliferation in A549 and H1299 cells in vitro. Thus, TNF-α-mediated lung inflammation can upregulate SOD-2 expression in lung adenocarcinoma, and macrophages contribute to SOD-2 upregulation by secreting TNF-α.


Assuntos
Adenocarcinoma de Pulmão/patologia , Proliferação de Células , Neoplasias Pulmonares/patologia , Pneumonia/complicações , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Uretana/toxicidade , Adenocarcinoma de Pulmão/etiologia , Adenocarcinoma de Pulmão/metabolismo , Animais , Apoptose , Carcinógenos/toxicidade , Citocinas , Feminino , Humanos , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/metabolismo , Macrófagos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pneumonia/induzido quimicamente , Pneumonia/metabolismo , Células Tumorais Cultivadas
17.
Zhongguo Zhong Yao Za Zhi ; 45(11): 2702-2707, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32627506

RESUMO

Gastrodia Rhizoma, as a precious Chinese materia medica, has attracted the attention of Chinese materia medica experts in the past dynasties for the commercial specification and experimental identification, and has gradually formed a wealth of terms concerning commercial specification and experimental identification. Through combing the literatures of successive dynasties, this paper discussed the change of the commercial specification of the Gastrodiae Rhizoma and formation of its identifying terms. It has found that the Gastrodiae Rhizoma mainly came from the dried rhizomes of the Gastrodia elata f.elata before the Qing Dynasty. Since the Qing Dynasty, G. elata in Yunnan and Guizhou gradually arose and become one of sources of mainstream commodities. After that, G. elata f. glauca and G. elata f. elata were becoming the main sources of Gastrodiae Rhizoma. Before the large-scale cultivation of G. elata in the 1970 s, there is only wild G. elata over the country. In terms of commercial specification, they were often classified into Chunma and Dongma according to their harvest time. With the successful promotion of cultivation technology and the endangered wild resources of G. elata, the Dongma became the mainstream in the market. The adulterants of G. elata increased significantly in the 1960 s and 1970 s, in this period, the terms of experimental identification for G. elata also increased obviously. Experimental identification is distinctive in different times, therefore, studying experimental identification of medicinal materials helps to promote the development of the Chinese materia medica.


Assuntos
Medicamentos de Ervas Chinesas , Gastrodia , Materia Medica , China , Rizoma
18.
Zhongguo Zhong Yao Za Zhi ; 45(6): 1334-1341, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32281345

RESUMO

In order to understand the structural characteristics of squalene synthase genes in the triterpenoids biosynthesis pathway of Crataegus pinnatifida, the squalene synthase genes of C. pinnatifida was cloned and analyzed by bioinformatics and prokaryotic expression. Two squalene synthase genes CpSQS1 and CpSQS2 were cloned from C. pinnatifida fruit by RT-PCR. The ORF length of CpSQS1 and CpSQS2 were 1 239 bp and 1 233 bp respectively, encoding 412 aa and 410 aa respectively. CpSQS1 and CpSQS2 were predicted to be stable acidic proteins by online tools. The secondary structure was mainly composed of α-helix structure, and the tertiary structure was predicted by homology modeling. Structural functional domain analysis showed that 35-367 aa of CpSQS1 and CpSQS2 cDNA containing conserved trans-isoprenyl pyrophosphate synthase domains. Transmembrane domain analysis predicted that two transmembrane domains were founded in CpSQS1 and CpSQS2. The squalene synthase amino sequence of C. pinnatifida had higher homology with the known SQS of Salvia miltiorrhiza and Glycyrrhiza glabra. Phylogenetic tree analysis showed that CpSQS1 and CpSQS2 were clustered into one branch of MdSQS1 and MdSQS2, which were consistent with the phylogenetic rule. Prokaryotic expression vector pGEX-4 T-1-CpSQS1 and pGEX-4 T-1-CpSQS2 were transformed into Escherichia coli Transetta(DE3) for induction, and the target protein was successfully expressed at 65 kDa. The expression levels of CpSQS2 were significantly higher than that of CpSQS1 in three different developmental stages of C. pinnatifida. In this study, the full-length cDNA sequences of C. pinnatifida SQS1 and SQS2 were cloned and analyzed for the first time, which provided the foundation for further study on the metabolic pathway of C. pinnatifida triterpenoids.


Assuntos
Crataegus/enzimologia , Farnesil-Difosfato Farnesiltransferase/genética , Proteínas de Plantas/genética , Sequência de Aminoácidos , Clonagem Molecular , Crataegus/genética , Frutas/enzimologia , Filogenia
19.
Org Biomol Chem ; 18(7): 1487-1492, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-32026925

RESUMO

As an important biothiol in living cells, cysteine is closely related to oxidative damage in living organisms. Sulfite from cysteine metabolism in living cells plays a crucial role in maintaining homeostasis in an organism, and the unbalance of sulfite in vivo would lead to multiple diseases. Thus the development of a new fluorescent probe for cysteine metabolism is needed urgently in mitochondria which are the main place of cysteine metabolism. Herein we construct a novel targeting mitochondria fluorescent probe CP-K based on the FRET mechanism to visualize sulfite in living MCF-7 cells. Probe CP-K displays a large Stokes shift of 150 nm, a low detection limit (26.3 nM) and "naked eye" detection after the addition of HSO3-. Importantly, it is appropriate for imaging the endogenous sulfite from cysteine metabolism in living cells.


Assuntos
Cisteína/análise , Transferência Ressonante de Energia de Fluorescência , Corantes Fluorescentes/química , Mitocôndrias/química , Cisteína/metabolismo , Humanos , Células MCF-7 , Mitocôndrias/metabolismo , Estrutura Molecular , Imagem Óptica
20.
Polymers (Basel) ; 11(12)2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31810159

RESUMO

Isotactic polybutylene-1 (iPB) has lots of advantages and is best used as hot water pipe. However, to transform into stable crystal form I, the iPB needs as long as 7 days. In this process, the irreversible damage brings great difficulties to the use of the iPB. The method which convert it directly into crystal I has shortcomings such as being requiring complex operation and being expensive. In this study, an innovative idea was put forward, not paying attention to the crystal transformation of iPB but only focusing on reducing the time it can be applied. In this study, bamboo powder was modified by the silane coupling agent KH570 (KBP) to prepare iPB/KBP composite. The infiltration test and Fourier transform infrared (FTIR) analysis showed that the hydrophilicity of KBP is greatly reduced, which can greatly improve the compatibility of the iPB and KBP. The tensile strength, tensile modulus, flexural strength, and flexural modulus of the composites storage for 3 days is equal to the pure iPB with storage 7 days with the KBP additions of 3%, 3%, 7%, and 5%, respectively. The heat deformation temperature (HDT) of the composite with 3% KBP after 1-day storage reached the value of pure iPB storage for 7 days. This provides more space and possibilities for the industrialization of the iPB. The crystallization behavior of iPB/KBP composites proves that the addition of KBP accelerates the crystallization rate of iPB, but the crystallinity of the iPB/KBP composites is not changed. The SEM photograph of iPB/KBP composites showed that when the KBP addition was low the compatibility between KBP and iPB was good. When the KBP addition was increased the agglomeration of KBP in the iPB was very obvious, which leads to the poor mechanical properties of the composite.

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