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1.
BMC Oral Health ; 24(1): 718, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38909208

RESUMO

BACKGROUND: Parotid gland carcinoma (PGC) is a rare malignant tumor. The purpose of this study was to investigate the role of immune-inflammatory-nutrition indicators and age-adjusted Charlson comorbidity index score (ACCI) of PGC and develop the nomogram model for predicting prognosis. METHOD: All patients diagnosed with PGC in two tertiary hospitals, treated with surgical resection, from March 2012 to June 2018 were obtained. Potential prognostic factors were identified by univariate and multivariate Cox regression analyses. The nomogram models were established based on these identified independent prognostic factors. The performance of the developed prognostic model was estimated by related indexes and plots. RESULT: The study population consisted of 344 patients with PGC who underwent surgical resection, 285 patients without smoking (82.8%), and 225 patients (65.4%) with mucoepidermoid carcinoma, with a median age of 50.0 years. American Joint Committee on Cancer (AJCC) stage (p < 0.001), pathology (p = 0.019), tumor location (p < 0.001), extranodal extension (ENE) (p < 0.001), systemic immune-inflammation index (SII) (p = 0.004), prognostic nutrition index (PNI) (p = 0.003), ACCI (p < 0.001), and Glasgow prognostic Score (GPS) (p = 0.001) were independent indicators for disease free survival (DFS). Additionally, the independent prognostic factors for overall survival (OS) including AJCC stage (p = 0.015), pathology (p = 0.004), tumor location (p < 0.001), perineural invasion (p = 0.009), ENE (p < 0.001), systemic immune-inflammation index (SII) (p = 0.001), PNI (p = 0.001), ACCI (p = 0.003), and GPS (p = 0.033). The nomogram models for predicting DFS and OS in PGC patients were generated based on these independent risk factors. All nomogram models show good discriminative capability with area under curves (AUCs) over 0.8 (DFS 0.802, and OS 0.825, respectively). Decision curve analysis (DCA), integrated discrimination improvement (IDI), and net reclassification index (NRI) show good clinical net benefit of the two nomograms in both training and validation cohorts. Kaplan-Meier survival analyses showed superior discrimination of DFS and OS in the new risk stratification system compared with the AJCC stage system. Finally, postoperative patients with PGC who underwent adjuvant radiotherapy had a better prognosis in the high-, and medium-risk subgroups (p < 0.05), but not for the low-risk subgroup. CONCLUSION: The immune-inflammatory-nutrition indicators and ACCI played an important role in both DFS and OS of PGC patients. Adjuvant radiotherapy had no benefit in the low-risk subgroup for PGC patients who underwent surgical resection. The newly established nomogram models perform well and can provide an individualized prognostic reference, which may be helpful for patients and surgeons in proper follow-up strategies.


Assuntos
Nomogramas , Neoplasias Parotídeas , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Neoplasias Parotídeas/cirurgia , Neoplasias Parotídeas/patologia , Prognóstico , Idoso , Adulto , Comorbidade , Estudos Retrospectivos , Inflamação , Fatores Etários
2.
BMC Cancer ; 24(1): 730, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877437

RESUMO

BACKGROUND: Oral cavity squamous cell carcinoma (OCSCC) is the most common pathological type in oral tumors. This study intends to construct a novel prognostic nomogram model based on China populations for these resectable OCSCC patients, and then validate these nomograms. METHODS: A total of 607 postoperative patients with OCSCC diagnosed between June 2012 and June 2018 were obtained from two tertiary medical institutions in Xinxiang and Zhengzhou. Then, 70% of all the cases were randomly assigned to the training group and the rest to the validation group. The endpoint time was defined as overall survival (OS) and disease-free survival (DFS). The nomograms for predicting the 3-, and 5-year OS and DFS in postoperative OCSCC patients were established based on the independent prognostic factors, which were identified by the univariate analysis and multivariate analysis. A series of indexes were utilized to assess the performance and net benefit of these two newly constructed nomograms. Finally, the discrimination capability of OS and DFS was compared between the new risk stratification and the American Joint Committee on Cancer (AJCC) stage by Kaplan-Meier curves. RESULTS: 607 postoperative patients with OCSCC were selected and randomly assigned to the training cohort (n = 425) and validation cohort (n = 182). The nomograms for predicting OS and DFS in postoperative OCSCC patients had been established based on the independent prognostic factors. Moreover, dynamic nomograms were also established for more convenient clinical application. The C-index for predicting OS and DFS were 0.691, 0.674 in the training group, and 0.722, 0.680 in the validation group, respectively. Besides, the calibration curve displayed good consistency between the predicted survival probability and actual observations. Finally, the excellent performance of these two nomograms was verified by the NRI, IDI, and DCA curves in comparison to the AJCC stage system. CONCLUSION: The newly established and validated nomograms for predicting OS and DFS in postoperative patients with OCSCC perform well, which can be helpful for clinicians and contribute to clinical decision-making.


Assuntos
Neoplasias Bucais , Nomogramas , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , China/epidemiologia , Neoplasias Bucais/cirurgia , Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Prognóstico , Idoso , Período Pós-Operatório , Adulto , Intervalo Livre de Doença , Estimativa de Kaplan-Meier , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Estadiamento de Neoplasias
3.
World J Surg Oncol ; 22(1): 35, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38279138

RESUMO

BACKGROUND: Lip squamous cell carcinoma (LSCC) was one of the most common cancer types of head and neck tumors. This study aimed to find more predictors of the prognosis in postoperative LSCC patients. METHODS: A total of 147 LSCC patients between June 2012 and June 2018 were collected from two tertiary care institutions. There were 21 clinicopathological factors included and analyzed in our study. The univariate and multivariate Cox regression analyses were performed to find the independent prognostic factors for predicting progression-free survival (PFS) and overall survival (OS) in postoperative LSCC patients. The role of adjuvant radiotherapy in various subgroups was displayed by Kaplan-Meier plots. RESULTS: The 1-, 3-, and 5-year PFS of postoperative LSCC patients were 88.4%, 70.1%, and 57.8%, respectively. Similarly, the 1-, 3-, and 5-year OS of postoperative LSCC patients were 94.6%, 76.9%, and 69.4%, respectively. The results suggested that postoperative LSCC patients with age at diagnosis ≥ 70 years, grade with moderate or poor differentiate, the American Joint Committee on Cancer (AJCC) stage IV, higher systemic immune-inflammation index (SII), surgical margin < 5, and age-adjusted Charlson Comorbidity Index (ACCI) ≥ 5 tend to have a poorer PFS (all P < 0.05). Besides, postoperative LSCC patients with age at diagnosis ≥ 70 years, AJCC stage IV, higher GPS, higher SII, and ACCI ≥ 5 tend to have a worse OS (all P < 0.05). Additionally, postoperative patients with LSCC in the subgroup of ACCI < 5 and AJCC III-IV stage was more likely to benefit from adjuvant radiotherapy, but not for the other subgroups. CONCLUSION: We identified a series of significant immune-inflammation-related and comorbidity-related clinicopathological factors associated with the prognosis of postoperative LSCC patients by local data from two tertiary care institutions in China, which can be helpful for patients and surgeons to pay more attention to nutrition, inflammation, and complications and finally obtained a better prognosis.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Laríngeas , Humanos , Idoso , Prognóstico , Lábio , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Inflamação , Neoplasias Laríngeas/patologia , Estudos Retrospectivos
4.
Phytother Res ; 37(3): 834-847, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36349468

RESUMO

Advanced glycation end products (AGEs) have been identified to transduce fibrogenic signals via inducing the activation of their receptor (RAGE)-mediated pathway. Recently, disrupting AGE-RAGE interaction has become a promising therapeutic strategy for chronic heart failure (CHF). Endothelial-to-mesenchymal transition (EndMT) is close to the cardiac fibrosis pathological process. Our previous studies have demonstrated that knockout RAGE suppressed the autophagy-mediated EndMT, and thus alleviated cardiac fibrosis. Plantamajoside (PMS) is the major bioactive compound of Plantago Asiatica, and its activity of anti-fibrosis has been documented in many reports. However, its effect on CHF and the underlying mechanism remains elusive. Thus, we tried to elucidate the protective role of PMS in CHF from the viewpoint of the AGEs/RAGE/autophagy/EndMT axis. Herein, PMS was found to attenuate cardiac fibrosis and dysfunction, suppress EndMT, reduce autophagy levels and serum levels of AGEs, yet did not affect the expression of RAGE in CHF mice. Mechanically, PMS possibly binds to the V-domain of RAGE, which is similar to the interaction between AGEs and RAGE. Importantly, this competitive binding disturbed AGEs-induced the RAGE-autophagy-EndMT pathway in vitro. Collectively, our results indicated that PMS might exert an anti-cardiac fibrosis effect by specifically binding RAGE to suppress the AGEs-activated RAGE/autophagy/EndMT pathway.


Assuntos
Catecóis , Produtos Finais de Glicação Avançada , Animais , Camundongos , Autofagia , Catecóis/farmacologia , Fibrose , Produtos Finais de Glicação Avançada/metabolismo , Receptor para Produtos Finais de Glicação Avançada , Transição Epitelial-Mesenquimal
5.
Front Cell Infect Microbiol ; 12: 969526, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36051242

RESUMO

The gut dysbiosis has emerged as a prominent player in the pathogenesis and development of colorectal cancer (CRC), which in turn intensifies dysregulated gut microbiota composition and inflammation. Since most drugs are given orally, this dysbiosis directly and indirectly impinges the absorption and metabolism of drugs in the gastrointestinal tract, and subsequently affects the clinical outcome of patients with CRC. Herbal medicine, including the natural bioactive products, have been used traditionally for centuries and can be considered as novel medicinal sources for anticancer drug discovery. Due to their various structures and pharmacological effects, natural products have been found to improve microbiota composition, repair intestinal barrier and reduce inflammation in human and animal models of CRC. This review summarizes the chemo-preventive effects of extracts and/or compounds derived from natural herbs as the promising antineoplastic agents against CRC, and will provide innovative strategies to counteract dysregulated microbiota and improve the lives of CRC patients.


Assuntos
Neoplasias Colorretais , Microbioma Gastrointestinal , Animais , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/prevenção & controle , Disbiose/prevenção & controle , Medicina Herbária , Humanos , Inflamação
6.
Front Cell Infect Microbiol ; 12: 972655, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36118041

RESUMO

N6-methyladenine (m6A) is one of the most common RNA epigenetic modifications in all higher eukaryotes. Increasing evidence demonstrated that m6A-related proteins, acted as oncogenes or tumor suppressors, are abnormally expressed in the cell lines and tissues of non-small cell lung cancer (NSCLC). In addition, lung as the special immune organ contacts with the outer environments and thereby inevitably suffers from different types of microbial pathogen attack. Those microbial pathogens affect the development, progression, and clinical outcomes of NSCLC via altering host m6A modification to disrupt pulmonary immune homeostasis and increase the susceptibility; conversely, host cells modulate m6A modification to repress bacterial colonization. Therefore, m6A harbors the potential to be the novel biomarkers and targets for predicting poor prognosis and chemotherapy sensitivity of patients with lung cancer. In this paper, we provided an overview of the biological properties of m6A-modifying enzymes, and the mechanistic links among lung microbiota, m6A modification and NSCLC. Although the flood of novel m6A-related inhibitors represents many dramatic improvements in NSCLC therapy, their efficacy and toxicity in NSCLC are explored to address these pivotal gaps in the field.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Microbiota , Adenosina/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Metilação , RNA/genética
7.
Front Cell Infect Microbiol ; 12: 937864, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35967848

RESUMO

Recently, chronic obstructive pulmonary disease (COPD) has been considered as a common risk factor of non-small cell lung cancer (NSCLC). However, very few studies have been conducted on the effects of COPD on the lung microbiota in patients with NSCLC. To identify the lung microbiota in patients with COPD and NSCLC (CN), the microbiome of the induced sputa of 90 patients was analyzed using 16S rDNA sequencing. The results showed no significant differences in the bacterial diversities of induced sputa among patients with COPD, NSCLC, and CN and no intrinsic differences among patients with different pathological types of lung cancer. After surgical operation, the diversities of the induced sputa in patients with CN significantly decreased. More remarkably, both the microbial community phenotypes and the components of the induced sputa in patients with CN obviously differed from those in patients with COPD or NSCLC. The relative abundances of Streptococcus, Veillonella, Moraxella, and Actinomyces significantly decreased, but those of Neisseria and Acinetobacter significantly increased in patients with CN compared with those in patients with COPD or NSCLC alone, resulting in increased Gram-negative microbiota and, therefore, in potential pathogenicity and stress tolerance, as well as in enhancement of microbial glycolipid metabolism, amino acid metabolism, and oxidative stress. Although COPD did not affect the number of pulmonary flora species in patients with NSCLC, these significant alterations in the microbial populations, phenotypes, and functions of induced sputa due to COPD would contribute to inflammation-derived cancer progression in patients with CN.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Microbiota , Doença Pulmonar Obstrutiva Crônica , Carcinoma Pulmonar de Células não Pequenas/complicações , Humanos , Pulmão/microbiologia , Neoplasias Pulmonares/complicações , Microbiota/genética , Doença Pulmonar Obstrutiva Crônica/complicações
8.
Phys Rev Lett ; 129(7): 076803, 2022 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-36018691

RESUMO

Overlaying two graphene layers with a small twist angle θ can create a moiré superlattice to realize exotic phenomena that are entirely absent in a graphene monolayer. A representative example is the predicted formation of localized pseudo-Landau levels (PLLs) with kagome lattice in tiny-angle twisted bilayer graphene (TBG) with θ<0.3° when the graphene layers are subjected to different electrostatic potentials. However, this was shown only for the model of rigidly rotated TBG, which is not realized in reality due to an interfacial structural reconstruction. It is believed that the interfacial structural reconstruction strongly inhibits the formation of the PLLs. Here, we systematically study electronic properties of the TBG with 0.075°≤θ<1.2° and demonstrate, unexpectedly, that the PLLs are quite robust for all the studied TBG. The structural reconstruction suppresses the formation of the emergent kagome lattice in the tiny-angle TBG. However, for the TBG around the magic angle, the sample-wide electronic kagome lattices with tunable lattice constants are directly imaged by using a scanning tunneling microscope. Our observations open a new direction to explore exotic correlated phases in moiré systems.

9.
Int J Ophthalmol ; 15(6): 868-875, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35814888

RESUMO

AIM: To investigate the role of procollagen C-proteinase enhancer 1 (PCPE1) in retinal angiogenesis and relevant mechanisms. METHODS: The Pcolce1-knockout (KO) mice were used to explore the effect of PCPE1 on retinal angiogenesis in vivo. Pcolce1 siRNA were designed, cell count kit 8 (CCK8) assays and tube formation assays were performed to investigate the cell proliferation and tube formation abilities of retinal microvascular endothelial cells (hRMECs) in vitro. Mouse embryo fibroblasts (MEF) cells were isolated and cultured to analyze the effect of PCPE1 on enhancing procollagen cleavage. RESULTS: In vivo studies showed that the retinal vascular density of Pcolce1-/- mice was significantly lower than that of the control group. Furthermore, silencing of Pcolce1 inhibited cell proliferation and tube formation abilities of hRMECs in vitro. Additionally, much more pro-collagen was found in Pcolce1-/- MEF cells, compared to wild type MEF cells. CONCLUSION: PCPE1 may promote physiological retinal angiogenesis by regulating the processing of collagen, which may provide a potential therapeutic target of retinal vascular disease.

10.
Artigo em Inglês | MEDLINE | ID: mdl-35900652

RESUMO

PURPOSE: Colchicine, a multipotent anti-inflammatory drug, has been reported to alleviate cardiac remodeling and improve cardiac function after acute myocardial infarction (AMI). However, the underlying mechanism remains incompletely understood. Because neutrophils extracellular traps (NETs) enhance inflammation and participate in myocardial ischemia injury, and colchicine can inhibit NETosis, we thus aimed to determine whether colchicine exerts cardioprotective effects on AMI via suppressing NETs. METHODS: Adult C57BL/6 mice were subjected to permanent ligation of the left anterior descending coronary artery and treated with colchicine (0.1 mg/kg/day) or Cl-amidine (10 mg/kg/day) for 7 or 28 days after AMI. Cardiac function was evaluated by echocardiography, and NETs detected by immunofluorescence. ROS production was detected using 2',7'-dichlorodihydrofluorescein diacetates (DCFH-DA) fluorometry. Intracellular Ca2+ concentration was assessed by a fluorometric ratio technique. RESULTS: We found that colchicine treatment significantly increased mice survival (89.8% in the colchicine group versus 67.9% in control, n = 32 per group; log-rank test, p < 0.05) and improved cardiac function at day 7 (left ventricular ejection fraction (LVEF): 28.0 ± 9.2% versus 12.6 ± 3.9%, n = 8 per group; p < 0.001) and at day 28 (LVEF: 26.2 ± 7.2% versus 14.8 ± 6.7%, n = 8 per group; p < 0.001) post-AMI. In addition, the administration of colchicine inhibited NETs formation and inflammation. Furthermore, colchicine inhibited NETs formation by reducing NOX2/ROS production and Ca2+ influx. Moreover, prevention of NETs formation with Cl-amidine significantly alleviated AMI-induced cardiac remodeling. CONCLUSIONS: Colchicine inhibited NETs and cardiac inflammation, and alleviated cardiac remodeling after acute myocardial infarction.

11.
Int Immunopharmacol ; 104: 108510, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34999393

RESUMO

Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis in young children, but there are few safe and effective treatments for this disease. Platycodonis Radix is widely used as an antitussive and expectorant drug for preventing various diseases in lower respiratory tract, in which the polysaccharides are one of the main bioactivity constituents. In this study, the protective effects of the P. Radix polysaccharides (PRP) against RSV-induced bronchiolitis in juvenile mice and RSV-induced apoptosis of epithelial HEp-2 cells were investigated. The results showed that PRP obviously decreased the levels of IL-1ß, IL-4, IL-6, TNF-α, IFN-γ and TSLP in lung tissues, and reduced the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) of RSV-infected mice. Furthermore, it reduced the apoptosis of RSV-infected HEp-2 cells and remarkably inhibited the mRNA expressions of RSV L gene, which indicated that PRP affected transcription and replication of RSV in host cells. Compared with that in RSV-infected group, miR-181a-5p in the PRP-treated group presented the highest relative abundance and its expression was violently reduced by approximately 30%. Mechanistically, PRP had the similar effects as miR-181a-5p antagomir on RSV-induced apoptosis and inflammation in HEp-2 cells via upregulating BCL2, MLL3 and SIRT1, which could be reversed by miR-181a-5p mimic. Therefore, it demonstrated that PRP not only protected against RSV-induced lung inflammation in mice but also inhibited apoptosis of RSV-infected HEp-2 cells via suppressing miR-181a-5p and transcriptionally activating Hippo and SIRT1 pathways.


Assuntos
Anti-Inflamatórios/uso terapêutico , Extratos Vegetais , Platycodon , Polissacarídeos/uso terapêutico , Hipersensibilidade Respiratória/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/virologia , Feminino , Via de Sinalização Hippo/efeitos dos fármacos , Humanos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Camundongos Endogâmicos BALB C , MicroRNAs , Polissacarídeos/farmacologia , Hipersensibilidade Respiratória/genética , Hipersensibilidade Respiratória/metabolismo , Hipersensibilidade Respiratória/patologia , Infecções por Vírus Respiratório Sincicial/genética , Infecções por Vírus Respiratório Sincicial/metabolismo , Infecções por Vírus Respiratório Sincicial/patologia , Vírus Sinciciais Respiratórios , Sirtuína 1/metabolismo
12.
Int Immunopharmacol ; 94: 107357, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33715980

RESUMO

The increased resistance and toxicity have become the main causes of chemotherapy failure for treating lung cancer. The combination of chemotherapeutic drugs with other agents has been recognized as a promising strategy to overcome these difficulties. Isovitexin (IVT) is a well-known flavone C-glycoside found in many plants and has attracted wide attention due to its obvious antitumor and antioxidant effects. In this study, we investigated the synergistic effects of IVX and cisplatin (DDP) in non-small cell lung cancer (NSCLC) A549 and H1975 cells. The results showed that the combined treatment with IVT and DDP markedly inhibited proliferation and induced apoptosis of the two NSCLC cells. Using a mouse model of A549 xenograft, IVT potentiated the inhibition of DDP on tumor growth, but reduced DDP-induced hepatotoxicity and nephrotoxicity in mice. Remarkedly, IVT promoted lipopolysaccharide (LPS)- and lectin- stimulated splenocyte proliferation, and enhance cytotoxic T lymphocyte (CTL) and natural killer (NK) cell activities as well as the production of IL-2 and TNF-α. Furthermore, IVT significantly reduced glucose uptake, lactate production, and ATP production, and downregulated the protein expressions of pyruvate kinase M2 (PKM2)-mediated pathway in both A549 and H1975 cells. After the over-expression of PKM2 in the NSCLC cells, the synergistic antitumor effect of IVT and DDP was markedly weakened. Therefore, IVT not only inhibited cell proliferation and glucose metabolism via downregulating the expression of PKM2 to enhance the antitumor activity of DDP against lung cancer cells, and improved DDP-induced immunotoxicity in mice. It also presented a novel strategy to enhance the anti-tumor effect of platinum-based chemotherapy against NSCLC.


Assuntos
Antineoplásicos/uso terapêutico , Apigenina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/uso terapêutico , Glucose/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Trifosfato de Adenosina/metabolismo , Animais , Antineoplásicos/farmacologia , Apigenina/farmacologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Proteínas de Transporte/imunologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/farmacologia , Citocinas/imunologia , Regulação para Baixo/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Ácido Láctico/metabolismo , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Proteínas de Membrana/imunologia , Camundongos Nus , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/imunologia , Hormônios Tireóideos/imunologia , Proteínas de Ligação a Hormônio da Tireoide
13.
Int J Biol Macromol ; 158: 542-551, 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32380108

RESUMO

Two polysaccharides (PRP1 and PRP2) were isolated from Platycodonis Radix. Preliminary structural analysis indicated that PRP1 was composed of glucose, fructose, and arabinose in a molar ratio of 1:1.91:1.59 with a molecular weight of 440 kDa, whereas PRP2 was composed of arabinose, fructose, and galactose in a molar ratio of 1:1.39:1.18 with a molecular weight of 2.85 kDa. Compared with PRP2, PRP1 exerted stronger anticancer activity in vitro. Treatment with 5-30 µg/ml of PRP1 significantly inhibited the proliferation of HepG2 cells in vitro, and oral administration at the doses of 75-300 mg/kg also reduced the tumor growth in vivo. The miRNA expression patterns of human liver cancer cells HepG2 in vivo under PRP1 treatment were established, and microRNA-21 (miR-21) as the onco-miRNA was appreciably downregulated. PRP1 repressed the expression of miR-21, which directly targeted and suppressed PTEN (a negative regulator of the PI3K/Akt signaling cascade), and subsequently upregulated the expression of PTEN but downregulated the PI3K/AKT pathway, thereby promoting liver cancer cell apoptosis. These findings indicated that PRP1 inhibited the proliferation and induced the apoptosis of HepG2 mainly via inactivating the miR-21/PI3K/AKT pathway. Therefore, PRP1 could be used as a food supplement and candidate for the treatment of liver cancer.

14.
Huan Jing Ke Xue ; 39(1): 9-17, 2018 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-29965661

RESUMO

Based on one year real-time measurements from a seven-wavelength Aethalometer combined with an Aethalometer model, the measured aerosol absorption coefficients at different wavelengths have been used to apportion the contribution of fossil fuel and biomass burning sources to the total black carbon (BC) mass concentration in the north suburb of Nanjing. Good consistency in the relationship between the Angstrom absorption exponent(α)and the ratio of BC from biomass burning sources to total BC (BB) was obtained during this period. The α was highest in winter and lowest in summer, which indicates the change in the source of the absorbing aerosols and their relative source strength. The BC and the BC from fossil fuel (BCff) and biomass burning (BCbb) mass concentrations exhibit significant diurnal variation, with higher values during 07:00 to 09:00 (local time) and 18:00 to 21:00. The BCff was three to five times higher than the BCbb and contributes greatest to the BC mass concentrations throughout the day. Night time BC values were about a factor of 1.2 higher than day time BC values. Meanwhile, the concentration weighted trajectory (CWT) analysis indicates that the highest value of BC was concentrated in the Zhejiang, Anhui, Jiangxi, and Fujian provinces.

15.
Nephron ; 136(4): 328-338, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28402979

RESUMO

BACKGROUND: The unilateral ureteral obstruction (UUO) model not only induces renal interstitial fibrosis in the obstructed kidney but also induces injury in the contralateral kidney. We hypothesized that activation of the mineralocorticoid receptor (MR) may induce fibrosis in the early stage of UUO. METHODS: Thirty male Sprague-Dawley rats weighting 200 ± 10 g were used in this study and randomly divided into 3 groups: a UUO group, a UUO and eplerenone group, and a sham group. The contralateral kidney and plasma were harvested for further study 10 days after surgery. RESULTS: The level of plasma aldosterone (869.95 ± 55.851 pg/mL) was significantly higher in the UUO group than that in the sham group (478.581 ± 36.186 pg/mL vs. UUO, p < 0.05). The infiltrated inflammatory cells (F4/80) and deposited collagens were increased significantly in the contralateral kidneys in the UUO group compared to those in the sham group, which were decreased by eplerenone. However, proliferating cell nuclear antigen was increased 2.47 times in the UUO group compared to the sham group in the contralateral kidney (p < 0.01), and those changes are attenuated by eplerenone. The expression of SGK-1 protein and mRNA was upregulated in the contralateral kidney in the UUO group, which is suppressed by eplerenone treatment. NF-κB pathway effecters were also changed markedly in the contralateral kidney in the UUO group and partly reversed by eplerenone. CONCLUSION: Aldosterone induces inflammatory cell proliferation via the MR/SGK-1 and NF-κB pathways and eventually leads to fibrosis in the contralateral kidney.


Assuntos
Rim/efeitos dos fármacos , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Espironolactona/análogos & derivados , Obstrução Ureteral/patologia , Actinas/biossíntese , Actinas/genética , Aldosterona/sangue , Animais , Proliferação de Células/efeitos dos fármacos , Colágeno/metabolismo , Eplerenona , Fibrose/induzido quimicamente , Fibrose/patologia , Proteínas Imediatamente Precoces/biossíntese , Proteínas Imediatamente Precoces/genética , Rim/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Antígeno Nuclear de Célula em Proliferação/biossíntese , Proteínas Serina-Treonina Quinases/biossíntese , Proteínas Serina-Treonina Quinases/genética , Ratos , Ratos Sprague-Dawley , Receptores de Mineralocorticoides/efeitos dos fármacos , Espironolactona/farmacologia , Fator de Necrose Tumoral alfa/biossíntese , Regulação para Cima/efeitos dos fármacos
16.
Huan Jing Ke Xue ; 37(9): 3280-3289, 2016 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-29964760

RESUMO

Based on the hourly averaged data of black carbon(BC) aerosol, PM2.5, gaseous pollutants, and meteorological data in the northern suburb of Nanjing from January to October 2015, characteristics and influencing factors of BC concentration variation were analyzed. The mean concentration of BC was found to be (2524±1754) ng·m-3 during the observation period. BC concentrations in Nanjing showed strong seasonality, the highest mean concentration of BC occurred during winter reaching (3468±2455) ng·m-3, and the lowest mean BC concentration was found during spring being (2142±1240) ng·m-3; a distinct diurnal variation of BC with two high peaks occurred, one in the morning during 07:00 to 08:00 and the other in late evening during 21:00 to 22:00 local time. The strong correlation between BC and NOx indicated a greater impact of vehicle emissions on BC concentration, while a lower rate of ΔBC/ΔCO was found in the northern suburb of Nanjing, suggesting that biomass burning emission might be another important source of BC in here. BC concentration increased with decreasing wind speed. BC concentration lower than 2000 ng·m-3 mainly occurred in westerly wind and adjacent wind in all seasons, whereas BC concentration higher than 6000 ng·m-3 more frequently appeared in easterly winds in autumn and winter. BC concentration was higher in hazy and heavy hazy weather, which were 2 and 2.3 times as large as that in non-hazy weather, respectively.

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