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1.
Apoptosis ; 23(5-6): 356-374, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29777330

RESUMO

Recent studies have confirmed that IL-6/GP130 targets are closely associated with tumor growth, metastasis and drug resistance. 5-Fluorouracil (5-FU) is the most common chemotherapeutic agent for colon cancer but is limited due to chemoresistance and high cytotoxicity. Bazedoxifene (BZA), a third-generation selective estrogen receptor modulator, was discovered by multiple ligand simultaneous docking and drug repositioning approaches to have a novel function as an IL-6/GP130 target inhibitor. Thus, we speculated that in colon cancer, the anti-tumor efficacy of 5-FU might be increased in combination with IL-6/GP130 inhibitors. CCK8 assay and colony formation assay were used to detect the cell proliferation and colony formation. We measured the IC50 value of 5-FU alone and in combination with BZA by cell viability inhibition. Cell migration and invasion ability were tested by scratch migration assays and transwell invasion assays. Flow cytometric analysis for cell apoptosis and cell cycle. Quantitative real-time PCR was used to detect Bad, Bcl-2 and Ki-67 mRNA expression and western blotting (WB) assay analyzed protein expression of Bad/Bcl-2 signaling pathway. Further mechanism study, WB analysis detected the key proteins level in IL-6/GP130 targets and JAK/STAT3, Ras/Raf/MEK/ERK, and PI3K/AKT/mTOR signaling pathway. A colon cancer xenograft model was used to further confirm the efficacy of 5-FU and BZA in vivo. The GP130, P-STAT3, P-AKT, and P-ERK expression levels were detected by immunohistochemistry in the xenograft tumor. BZA markedly potentiates the anti-tumor function of 5-FU in vitro and in vivo. Conversely, 5-FU activation is reduced following exogenous IL-6 treatment in cells. Further mechanistic studies determined that BZA treatment enhanced 5-FU anti-tumor activation by inhibiting the IL-6/GP130 signaling pathway and the phosphorylation status of the downstream effectors AKT, ERK and STAT3. In contrast, IL-6 can attenuate 5-FU function via activating IL-6R/GP130 signaling and the P-AKT, P-ERK and P-STAT3 levels. This study firstly verifies that targeting IL-6/GP130 signaling can increase the anti-tumor function of 5-FU; in addition, this strategy can sensitize cancer cell drug sensitivity, implying that blocking IL-6/GP130 targets can reverse chemoresistance. Therefore, combining 5-FU and IL-6/GP130 target inhibitors may be a promising approach for cancer treatment.


Assuntos
Neoplasias do Colo/tratamento farmacológico , Receptor gp130 de Citocina/antagonistas & inibidores , Fluoruracila/uso terapêutico , Indóis/uso terapêutico , Interleucina-6/antagonistas & inibidores , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica , Apoptose , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo , Feminino , Fluoruracila/administração & dosagem , Humanos , Indóis/administração & dosagem , Camundongos , Camundongos Nus , Invasividade Neoplásica , Transdução de Sinais/efeitos dos fármacos , Ensaio Tumoral de Célula-Tronco , Ensaios Antitumorais Modelo de Xenoenxerto
2.
Biochem Biophys Res Commun ; 496(4): 1069-1075, 2018 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-29366790

RESUMO

Recent reports have indicated that circular RNA (circRNA) may regulate Lung adenocarcinoma (LAC) development. Our previous studies showed that hsa_circ_0012673 was up-regulated in a circRNA microarray. However, its expression level in LAC has not been verified, and the underlying molecular mechanisms in LAC are unknown. In this study, we found that the expression of hsa_circ_0012673 was up-regulated in LAC tissues compared to pair-matched adjacent non-tumor tissues (P = 0.0079), and that the expression level was associated with tumour size (P = 0.015). Furthermore, hsa_circ_0012673 was primarily localized in the cytoplasm and promoted cell proliferation of LAC cells by sponging miR-22, which targeted erb-b2 receptor tyrosine kinase 3 (ErbB3) in LAC. Hsa_circ_0012673 promotes LAC proliferation by suppressing miR-22, which targets ErbB3.


Assuntos
Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Proliferação de Células , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , MicroRNAs/metabolismo , RNA/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Ligação Proteica , RNA Circular , Receptor ErbB-3/metabolismo , Regulação para Cima
3.
World J Surg Oncol ; 16(1): 215, 2018 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-30400981

RESUMO

BACKGROUND: Circular RNA (circRNA), as a covalently closed circular RNA molecule, is widely present, which is recognized as a competing endogenous RNA. A large number of differentially expressed circRNAs have been identified and are recognized as potential biomarkers for the diagnosis of tumors. MAIN BODY: CircRNAs play an important role in the regulation of cell signaling pathways. The main biological functions of circRNAs include acting as miRNA sponges, regulating the transcription of the parental genes, and acting as adapters to regulate the interactions between proteins and encoding proteins. Compared with normal tissues, there are differentially expressed circRNAs in lung cancer tissue, and the expression levels of circRNAs are correlated with clinicopathological features of lung cancer. Their roles in pathway regulation are described, and the diagnostic and prognostic values are further evaluated. CONCLUSION: In lung cancer, circRNAs participate in the proliferation, migration, and invasion, acting as a competitive endogenous RNA. Differentially expressed circRNAs may serve as non-invasive diagnostic markers for lung cancers. Further investigation of the roles of circRNAs in the pathogenesis and regulatory pathways is conducive to the development of novel approaches for the diagnosis and accurate treatment of lung cancers.


Assuntos
Pesquisa Biomédica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , RNA/genética , Humanos , Prognóstico , RNA Circular
4.
ScientificWorldJournal ; 2014: 346405, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25485296

RESUMO

Seed dispersal and germination were examined for 70 species from the cold Gurbantunggut Desert in northwest China. Mean and range (3 orders of magnitude) of seed mass were smaller and narrower than those in other floras (5-8 orders of magnitude), which implies that selection favors relatively smaller seeds in this desert. We identified five dispersal syndromes (anemochory, zoochory, autochory, barochory, and ombrohydrochory), and anemochorous species were most abundant. Seed mass (F = 3.50, P = 0.01), seed size (F = 8.31, P < 0.01), and seed shape (F = 2.62, P = 0.04) differed significantly among the five dispersal syndromes and barochorous species were significantly smaller and rounder than the others. There were no significant correlations between seed mass (seed weight) (P = 0.15), seed size (P = 0.38), or seed shape (variance) (P = 0.95) and germination percentage. However, germination percentages differed significantly among the dispersal syndromes (F = 3.64, P = 0.01) and seeds of ombrohydrochorous species had higher germination percentages than those of the other species. In the Gurbantunggut Desert, the percentage of species with seed dormancy was about 80%. In general, our studies suggest that adaptive strategies in seed dispersal and germination of plants in this area are closely related to the environment in which they live and that they are influenced by natural selection forces.


Assuntos
Germinação/fisiologia , Fenômenos Fisiológicos Vegetais , Dispersão de Sementes , Sementes/fisiologia , China , Clima Desértico
5.
ScientificWorldJournal ; 2014: 510343, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24605054

RESUMO

Diaspore characteristics of 22 families, including 102 genera and 150 species (55 represented by seeds and 95 by fruits) from the Gurbantunggut Desert were analyzed for diaspore biological characteristics (mass, shape, color, and appendage type). The diaspore mass and shape were significantly different in phylogeny group (APG) and dispersal syndromes; vegetative periods significantly affected diaspore mass, but not diaspore shape; and ecotypes did not significantly affect diaspore mass and shape, but xerophyte species had larger diaspore mass than mesophyte species. Unique stepwise ANOVA results showed that variance in diaspore mass and shape among these 150 species was largely dependent upon phylogeny and dispersal syndromes. Therefore, it was suggested that phylogeny may constrain diaspore mass, and as dispersal syndromes may be related to phylogeny, they also constrained diaspore mass and shape. Diaspores of 85 species (56.67%) had appendages, including 26 with wings/bracts, 18 with pappus/hair, 14 with hooks/spines, 10 with awns, and 17 with other types of appendages. Different traits (mass, shape, color, appendage, and dispersal syndromes) of diaspore decided plants forming different adapted strategies in the desert. In summary, the diaspore characteristics were closely related with phylogeny, vegetative periods, dispersal syndromes, and ecotype, and these characteristics allowed the plants to adapt to extreme desert environments.


Assuntos
Adaptação Fisiológica , Biodiversidade , Ecologia , Filogenia , Plantas/embriologia , Análise de Variância , China
6.
Front Plant Sci ; 15: 1394409, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38903444

RESUMO

Walnuts have substantial economic value and are of significant interest being a wild-cultivated species. The study has re-sequenced the entire genome of the wild walnut, aligning it with the walnut reference genome, to identify 2,021,717 single nucleotide polymorphisms (SNPs). These were used to examine the genetics of 130 wild walnut samples collected from three countries. Utilizing structural and principal component analysis, the walnut samples from Central Asia were classified into four populations: Ili ah in Xinjiang (I), Dushanbe region in Tajikistan (II), Sary-Chelek, Arslanbob in Kara-Alma regions of Kyrgyzstan (III), and Kok-Tundy region of Kyrgyzstan (IV). The 4 groups showed large differences in nucleotide diversity, population differentiation, and linkage disequilibrium decay, as well as gene flow among them. The present geographic distribution of these populations does not align with the genetic distribution pattern as the populations of Central Asian wild walnuts have experienced similar population dynamics in the past, i.e., the highest effective population size at ca. 6 Ma, two sharp population declines at 6 and 0.2 Ma, and convergence at ca. 0.2 Ma. The genetic distribution patterns are better explained by human activity, notably through archaeological findings of walnut use and the influence of the Silk Road, rather than by current geographic distributions.

7.
Mitochondrial DNA B Resour ; 8(5): 541-545, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37187688

RESUMO

Tamarix L. is of great ecological and economic significance in arid desert ecosystems. This study reports the complete chloroplast (cp) genomic sequences of T. arceuthoides Bunge and T. ramosissima Ledeb., which are currently unknown, by high-throughput sequencing. The cp genomes of T. arceuthoides 1852 and T. ramosissima 1829 were 156,198 and 156,172 bp in length, respectively, and contained a small single-copy region (SSC: 18,247 bp), a large single-copy region (LSC: 84,795 and 84,890 bp, respectively), and a pair of inverted repeat regions (IRs: 26,565 and 26,470 bp, respectively). The two cp genomes possessed 123 genes arranged in the same order, including 79 protein-coding, 36 tRNA, and eight rRNA genes. Of these, 11 protein-coding genes and seven tRNA genes contained at least one intron. The present study found that Tamarix and Myricaria are sister groups with the closest genetic relationship. The obtained knowledge could provide useful information for future phylogenetic, taxonomic, and evolutionary studies on Tamaricaceae.

8.
Plants (Basel) ; 12(14)2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37514284

RESUMO

Ammopiptanthus possesses ancestral traits and, as a tertiary relict, is one of the surviving remnants of the ancient Mediterranean retreat and climate drought. It is also the only genus of super xerophytic, evergreen, broad-leaved shrubs. Ammopiptanthus nanus, one of the two species in this genus, is predominantly found in extremely arid and frigid environments, and is increasingly threatened with extinction. Study of the species' genetic diversity is thus beneficial for its survival and the efficacy of ex situ conservation efforts. Based on transcriptome data, 15 pairs of effective EST-SSR were screened to evaluate A. nanus genetic diversity. In all, 87 samples from three populations were evaluated, the results of which show that ex situ conservation in the Wuqia region needs to be supplemented. Conservation and breeding of individual A. nanus offspring should be strengthened in the future to ensure their progeny continue to exhibit high genetic diversity and variation.

9.
Nurs Open ; 10(1): 241-251, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35997202

RESUMO

AIM: Care dependence has been scarcely investigated in coronary heart disease patients after percutaneous coronary intervention. This study aimed to investigate the association between frailty, self-efficacy, combined effects of frailty and self-efficacy, mental health, and care dependence in coronary heart disease patients after percutaneous coronary intervention. DESIGN: Cross-sectional study. METHODS: Data from 400 patients after percutaneous coronary intervention were collected from 2017-2020. Logistic regression model and mediating analysis were used to identify the association between frailty, self-efficacy, combined effects of frailty and self-efficacy, and care dependence. RESULTS: Patients with frailty and self-efficacy tended to have severe care dependence symptoms. There was no correlation between frailty symptoms, self-efficacy, and care dependence in patients without symptoms of anxiety or depression. But in patients with anxiety or depression symptoms, there is a strong correlation between frailty symptoms, lower self-efficacy, and care dependence. Mental health played an inhibitory effect on frailty and care dependence.


Assuntos
Doença das Coronárias , Fragilidade , Intervenção Coronária Percutânea , Humanos , Estudos Transversais , Fragilidade/diagnóstico , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/psicologia , Doença das Coronárias/cirurgia , Ansiedade
10.
Zhongguo Fei Ai Za Zhi ; 26(5): 400-406, 2023 May 20.
Artigo em Chinês | MEDLINE | ID: mdl-37316450

RESUMO

Lung cancer is one of the most lethal malignancies in the world, with non-small cell lung cancer (NSCLC) accounting for approximately 80%-85% of all pathological types. Approximately 30%-55% of NSCLC patients develop brain metastases. It has been reported that 5%-6% of patients with brain metastases harbor anaplastic lymphoma kinase (ALK) fusion. ALK-positive NSCLC patients have shown significant therapeutic benefits after treatment with ALK inhibitors. Over the past decade, ALK inhibitors have rapidly evolved and now exist in three generations: first-generation drugs such as Crizotinib; second-generation drugs including Alectinib, Brigatinib, Ceritinib, and Ensartinib; and third-generation drugs like Lorlatinib. These drugs have exhibited varying efficacy in treating brain metastases in ALK-positive NSCLC patients. However, the numerous options available for ALK inhibition present a challenge for clinical decision-making. Therefore, this review aims to provide clinical guidance by summarizing the efficacy and safety of ALK inhibitors in treating NSCLC brain metastases.
.


Assuntos
Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Encefálicas/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Crizotinibe
11.
Life (Basel) ; 13(11)2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-38004349

RESUMO

Rare and vulnerable endemic plants represent different evolutionary units that occur at different times, and protecting these species is a key issue in biological protection. Understanding the impact of the history of endangered plant populations on their genetic diversity helps to reveal evolutionary history and is crucial for guiding conservation efforts. Saussurea involucrata, a perennial alpine species mainly distributed in the Tianshan Mountains, is famous for its medicinal value but has become endangered due to over-exploitation. In the present study, we employed both nuclear and chloroplast DNA sequences to investigate the genetic distribution pattern and evolutionary history of S. involucrata. A total of 270 individuals covering nine S. involucrata populations were sampled for the amplification and sequencing of nrDNA Internal Transcribed Spacer (ITS) and chloroplast trnL-trnF, matK and ndhF-rpl32 sequences. Via calculation, we identified 7 nuclear and 12 plastid haplotypes. Among the nine populations, GL and BA were characterized by high haplotype diversity, whereas BG revealed the lowest haplotype diversity. Molecular dating estimations suggest that divergence among S. involucrata populations occurred around 0.75 Ma, coinciding with the uplift of Tianshan Mountains. Our results reveal that both isolation-by-distance (IBD) and isolation-by-resistance (IBR) have promoted genetic differentiation among populations of S. involucrata. The results from the ecological niche modeling analyses show a more suitable habitat for S. involucrata in the past than at present, indicating a historical distribution contraction of the species. This study provides new insight into understanding the genetic differentiation of S. involucrata, as well as the theoretical basis for conserving this species.

12.
Ying Yong Sheng Tai Xue Bao ; 34(10): 2637-2643, 2023 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-37897270

RESUMO

Stem photosynthesis widely presents in desert plants, which increases carbon uptake capacity. In this study, we measured the photosynthetic characteristics of leaves and stems in seven desert woody plants (Populus euphratica, Populus alba var. pyramidalis, Populus pruinose, Haloxylon ammodendron, Calligonum rubicundum, Calligonum caput-medusae, Ammopiptanthus mongolicus) in the same habitat, using a portable Li-6400XT photosynthesis system combined with P-Chamber. We analyzed stem photosynthetic rate and its relationship with leaf photosynthetic rate. We measured the stem functional traits, including water content, stem dry matter content, chlorophyll content, water potential, non-structure carbohydrate (NSC), etc., to find out the main affecting factors of stem photosynthesis. The results showed that stem photosynthetic rate of seven species ranged from 0.72 to 1.71 µmol·m-2·s-1, with the largest of P. pruinose and the smallest of H. ammodendron. Stem photosynthetic rate could offset CO2 of stem respiration by 57%-83%. Leaf photosynthetic rate of the seven sepceis ranged from 12.80 to 22.54 µmol·m-2·s-1, with H. ammodendron and A. mongolicus being lower than those of the other five species. There was a significant positive correlation between leaf photosynthetic rate and stem photosynthetic rate. Stem water use efficiency was 2.2-7.7 times of the leaf. Chlorophyll content, NSC, stem respiration rate, and leaf photosynthetic rate were the main factors affecting stem photosynthesis.


Assuntos
Fabaceae , Fotossíntese , Clorofila , Folhas de Planta , Carboidratos , Água
13.
Genes (Basel) ; 14(12)2023 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-38136974

RESUMO

In order to study the genetics of local adaptation in all main deserts of northwest China, whole genomes of 169 individuals were resequenced, which covers 20 populations of Zygophyllum loczyi (Zygophyllales: Zygophylaceae). We describe more than 15 million single nucleotide polymorphisms and numerous InDels. The expected heterozygosity and PIC values associated with local adaptation varied significantly across biogeographic regions. Variation in environmental factors contributes largely to the population genetic structure of Z. loczyi. Bayesian analysis performed with STRUCTURE defined four genetic clusters, while the results of principle component analysis were similar. Our results shows that the Qaidam Desert group appears to be diverging into two branches characterized by significant geographic separation and gene flow with two neighboring deserts. Geological data assume that it is possible that the Taklamakan Desert was the original distribution site, and Z. loczyi could have migrated later on and expanded within other desert areas. The above findings provide insights into the processes involved in biogeography, phylogeny, and differentiation within the northwest deserts of China.


Assuntos
Zygophyllum , Humanos , Filogenia , Variação Genética/genética , Teorema de Bayes , China
14.
Exp Ther Med ; 25(6): 250, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37153891

RESUMO

Acute respiratory failure and sudden cardiac arrest caused by acute intrathoracic infection is a fatal clinical condition with a low resuscitation success rate. The present study describes the case of a patient with acute empyema secondary to an acute lung abscess rupture, complicated by acute respiratory failure and sudden cardiac arrest caused by severe hypoxemia. The patient recovered well through the administration of multiple therapeutic measures, including medication and closed chest drainage, cardiopulmonary resuscitation, extracorporeal membrane oxygenation combined with continuous renal replacement therapy, and minimally invasive surgical resection of the lung lesion with persistent alveolar fistula as the clinical manifestation. To the best of our knowledge, the treatment of such a severe condition combined with thoracoscopic surgery has rarely been reported before, and the present study may provide insight regarding therapeutic schedules for acute respiratory failure by intrathoracic infection, and excision of ruptured lung abscess.

15.
Appl Microbiol Biotechnol ; 93(6): 2475-82, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22159610

RESUMO

This study was aimed to investigate the effect of a single-chain fragment variable antibody of connective tissue growth factor (anti-CTGF scFv) against the differentiation of fibroblast into myofibroblast. The scFv antibody was firstly expressed in Escherichia coli cells and was then purified by affinity chromatography. The yield scFv protein reached a purity over 95% after purification. Immunoreactivity assay demonstrated that scFv possessed a special affinity toward CTGF. RT-PCR, western blot, and immunofluorescence experiments showed that increased expression of α-smooth muscle actin induced by TGF-ß1 could be suppressed by this scFv antibody through inhibiting the phosphorylation of Akt.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Fator de Crescimento do Tecido Conjuntivo/imunologia , Fibroblastos/citologia , Miofibroblastos/citologia , Anticorpos de Cadeia Única/farmacologia , Actinas/genética , Actinas/metabolismo , Linhagem Celular , Fator de Crescimento do Tecido Conjuntivo/genética , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Miofibroblastos/efeitos dos fármacos , Miofibroblastos/metabolismo , Anticorpos de Cadeia Única/genética , Anticorpos de Cadeia Única/isolamento & purificação , Anticorpos de Cadeia Única/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
16.
ACS Omega ; 7(11): 9796-9807, 2022 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-35350349

RESUMO

Casing deformation is frequent during hydraulic fracturing in the Weirong shale gas field, which impedes shale gas production. We investigated the effect of shale elastic modulus on casing deformation based on shale swelling in this work. According to field data, the silicon content in the Weirong shale gas field has a considerable impact on casing deformation during hydraulic fracturing. Furthermore, the results of the experiment show that the silicon content is positively related to the elastic modulus of shale. We conducted numerical simulations to analyze the casing deformation based on shale swelling. We observed that the shale elastic modulus was negatively correlated with the casing stress without shale swelling; however, the shale elastic modulus was positively correlated to casing stress with shale swelling. Furthermore, when the elastic modulus remained constant, casing stress was positively correlated with shale swelling. The numerical simulation results were validated using field data from the WY23-5 shale well. Moreover, factors such as injection pressure, formation pressure, and cement sheath elastic modulus can increase the impact of the shale elastic modulus on casing deformation with shale swelling. Casing deformation is greatly influenced by the distribution of the stimulated reservoir volume (SRV) area. Different SRV area behaviors result in different types of casing deformation. The symmetric distribution of the SRV area causes casing extrusion deformation, whereas the asymmetric distribution of the SRV area causes casing bending deformation. Moreover, casing stress is positively correlated with the length of the SRV area.

17.
J Healthc Eng ; 2022: 7957121, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35320997

RESUMO

To explore the prognostic potential of AK021443 in non-small-cell lung carcinoma (NSCLC), AK021443 levels in NSCLC specimens were determined by quantitative real-time polymerase chain reaction (qRT-PCR). The correlation between the AK021443 level and pathological factors in NSCLC patients was analyzed. Kaplan-Meier curves were plotted for assessing the prognostic value of AK021443 in NSCLC patients. Potential factors influencing NSCLC prognosis were analyzed by multivariable Cox regression test. AK021443 was upregulated in NSCLC specimens than normal ones. Its level was correlated to histological type, tumor differentiation, TNM staging, and lymphatic metastasis in NSCLC patients. AK021443 was the independent risk factor for the overall survival of NSCLC. AK021443 is highly expressed in NSCLC specimens, which is correlated to histological type, tumor differentiation, TNM staging, and lymphatic metastasis in NSCLC patients. It is the independent prognostic factor for NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/genética , Metástase Linfática
18.
Front Pharmacol ; 13: 837784, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35308251

RESUMO

The tumor-associated macrophage (TAM) serves as an immunosuppressive agent in the malignant tumor microenvironment, facilitating the development and metastasis of lung cancer. The photodynamic effect destabilizes cellular homeostasis owing to the generation of reactive oxygen species (ROS), resulting in the enhanced pro-inflammatory function of immunocytes. In our previous study, the Ce6-mediated photodynamic effect was found to have kept the viability of macrophages and to remodel them into the M1 phenotype. However, the mechanism remains unrevealed. The present study now explores the mechanism of photodynamic therapy (PDT)-mediated reprogramming of macrophages. As expected, Ce6-mediated PDT was capable of generating reactive oxygen species, which was continuously degraded, causing "low intensity" damage to DNA and thereby triggering subsequent DNA damage response in macrophages. The autophagy was thus observed in Ce6-treated macrophages and was shown to protect cells from being photodynamically apoptotic. More importantly, Ce6 PDT could activate the stimulator of interferon genes (STING) molecule, a sensor of DNA damage, which could activate the downstream nuclear factor kappa-B (NF-κB) upon activation, mediating the polarization of macrophages towards the M1 phenotype thereupon. In addition, inhibition of ROS induced by PDT attenuated the DNA damage, STING activation, and M1-phenotype reprogramming. Furthermore, the silence of the STING weakened Ce6 treatment-mediated M1 remodeling of macrophages as well. Altogether, these findings indicate the Ce6-induced photodynamic effect polarizes macrophages into an M1 phenotype through oxidative DNA damage and subsequent activation of the STING. This work reveals the crucial mechanism by which photodynamic therapy regulates the macrophage phenotype and also provides a novel intervenable signaling target for remodeling macrophages into the M1 phenotype.

19.
Sci Rep ; 12(1): 22201, 2022 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-36564433

RESUMO

Metastasis, a major challenge during the treatment of lung cancer, causes deterioration in patient health outcomes. Thus, to address this problem, this study aimed to explore the role and contribution of Cholesterol 25-Hydroxylase (CH25H) as a potential diagnostic and prognostic marker in lung cancer. Online public databases were used to analyze the expression level, prognostic value, gene-pathway enrichment, and immune infiltration of CH25H in lung cancer patients. The Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was used to analyze and detect the CH25H expression levels in leukocytes from lung cancer patients. The expression level of CH25H was significantly reduced in lung adenocarcinoma (LUAD), which is associated with a higher disease stage, but not in lung squamous cell carcinoma (LUSC). Kaplan-Meier survival analysis indicated that LUAD patients with low CH25H expression had a worse prognosis. Mechanistically, our results showed that in LUAD, CH25H may be a regulatory factor affecting the immune cell infiltration level, and the resultant tumor development. Experimental data showed that low expression of CH25H in leukocytes was significantly associated with LUAD metastasis (P < 0.01). Our study suggests that CH25H may function as a prognostic and risk stratification biomarker for LUAD.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Prognóstico , Perfilação da Expressão Gênica , Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Leucócitos/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo
20.
Eur J Pharmacol ; 919: 174797, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35122867

RESUMO

Photodynamic therapy (PDT) is noninvasive, low toxicity, and photo-selective, but may be resisted by malignant cells. A previous study found chlorin e6 (Ce6) mediated PDT showed drug resistance in lung cancer cells (LLC), which may be associated with PDT-induced DNA damage response (DDR). DDR may up-regulate glutathione peroxidase 4 (GPX4), which in turn degrade ROS induced by PDT. However, dihydroartemisinin (DHA) was found to down-regulate GPX4. Accordingly, the DHA was hypothesized to improve the resistance to PDT. The present work explores the mechanism of Ce6 mediated drug resistance and reveals whether DHA can enhance the efficacy of PDT by suppressing GPX4. The in vitro experiments found Ce6 treatment did not inhibit the viability of LLC within 6 h without inducing significant apoptosis, suggesting LLC were resistant to PDT. Further investigation demonstrated PDT could damage DNA and up-regulate GPX4, thus degrading the generated ROS. DHA effectively inhibited the viability of LLC and induced apoptosis. Importantly, DHA displayed a prominent inhibitory effect on the GPX4 expression and thereby triggered ferroptosis. Combining DHA with Ce6 for treatment of LLC resulted in the suppressed GPX4 and elevated ROS. Finally, the findings showed DHA combined with Ce6 exhibited superb anti-lung cancer efficacy. In summary, Ce6 PDT damages DNA, up-regulates GPX4 to degrade ROS, thereby inducing drug resistance. Down-regulation of GPX4 by DHA-triggered ferroptosis significantly enhances the efficacy of PDT. This study provides an outstanding theoretical basis for the regulation of the intratumoral redox system and improving PDT efficacy against lung cancer by herbal monomer DHA.


Assuntos
Artemisininas/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Apoptose/efeitos dos fármacos , Artemisininas/uso terapêutico , Linhagem Celular Tumoral/efeitos dos fármacos , Clorofilídeos/metabolismo , Ferroptose/efeitos dos fármacos , Humanos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo
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