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1.
Cancer Treat Res Commun ; 29: 100455, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34619647

RESUMO

BACKGROUND: Varieties of systemic treatments in second-line treatment for metastatic colorectal cancer (mCRC) patients have showed an improvement on survival. In this study, we performed a systematic review with a pairwise and bayesian network meta-analysis to rank the best strategy for mCRC patients in second-line treatment. METHODS: A systematic literature search through 2007 was performed to evaluate the association between several treatment combinations and overall survival (OS), progression-free survival (PFS) and disease control rate (DCR) in mCRC patients. Data were carried out and pooled into a statistical indirect comparison with Bayesian network meta-analysis (NMA). RESULTS: 10 trials totally comprised 4183 patients were included in our study. In NMA, For PFS, Doublet+Bev showed benefits in comparing with Doublet, Doulblet+placebo and Doublet+Ramucirumab. Also, Doublet+Aflibercept demonstrated its superiority in comparing with Doulblet+placebo. For OS, Doublet+Bev represented its superiority when comparing with Double and Doublet+placebo. Doublet+Aflibercept and Doublet+Ramucirumab also done well when opposed to Doublet+placebo. For DCR, Doublet+bev showed unique superiority when compared with Doublet, And Doublet+targeted agent did not represent benefits to each other in DCR. Doublet+bev ranked highest in terms of PFS, OS and DCR followed by Doublet+panitumumab, Doublet+placebo was the lowest in terms of PFS and OS. CONCLUSIONS: Our study shows that Doublet+Bev has the major probability to provide an improvement of survival in patients with mCRC.

2.
Sheng Wu Gong Cheng Xue Bao ; 37(8): 2836-2844, 2021 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-34472301

RESUMO

It has been reported that ODB genes play an important role in homologous recombination-directed DNA repair, suggesting their potential applications in plant breeding. To analyze the expression characteristics of tobacco NtODB gene, the cDNA sequence of NtODB was obtained using in silico cloning technique. The physicochemical properties, signal peptide, and advanced structures of the predicted protein were analyzed using bioinformatics tools. The results showed that the NtODB gene has a 579-bp open reading frame which encodes a protein with 192 amino acid residues. The protein NtODB is predicted to be alkaline and hydrophilic. Real-time quantitative PCR showed that NtODB was constitutively expressed in different tissues. Subcellular localization showed that NtODB was mainly expressed in cell membrane and chloroplast. These results may help us to better understand and elucidate the roles of ODB genes in the homologous recombination-directed DNA repair.


Assuntos
Biologia Computacional , Tabaco , Sequência de Aminoácidos , Sequência de Bases , Clonagem Molecular , Simulação por Computador , DNA Complementar , Filogenia , Melhoramento Vegetal , Tabaco/genética
3.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(3): 445-451, 2021 Jun 30.
Artigo em Chinês | MEDLINE | ID: mdl-34238422

RESUMO

Breast cancer patients with bone,liver and lung metastases tend to have a poor prognosis.According to Paget's "seed and soil" theory,metastatic cancer cell "seeds" must fall on congenial target organ "soil".Studies have shown that myeloid-derived suppressor cells(MDSCs)can be recruited at the site of breast cancer metastasis in advance and play a role in the metastasis of breast cancer cells.This paper reviews the biological characteristics of MDSCs,the roles of MDSCs in peripheral circulation,prometastatic niche,and metastatic site during breast cancer metastasis,as well as the research progress of MDSCs-targeted treatment of breast cancer metastasis.


Assuntos
Neoplasias da Mama , Neoplasias Pulmonares , Células Supressoras Mieloides , Feminino , Humanos , Metástase Neoplásica , Microambiente Tumoral
4.
JCI Insight ; 6(17)2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34264867

RESUMO

A dynamically regulated microenvironment, which is mediated by crosstalk between adipocytes and neighboring cells, is critical for adipose tissue homeostasis and function. However, information on key molecules and/or signaling pathways regulating the crosstalk remains limited. In this study, we identify adipocyte miRNA-182-5p (miR-182-5p) as a crucial antiobesity molecule that stimulated beige fat thermogenesis by promoting the crosstalk between adipocytes and macrophages. miR-182-5p was highly enriched in thermogenic adipocytes, and its expression was markedly stimulated by cold exposure in mice. In contrast, miR-182-5p expression was significantly reduced in adipose tissues of obese humans and mice. Knockout of miR-185-5p decreased cold-induced beige fat thermogenesis whereas overexpression of miR-185-5p increased beiging and thermogenesis in mice. Mechanistically, miR-182-5p promoted FGF21 expression and secretion in adipocytes by suppressing nuclear receptor subfamily 1 group D member 1 (Nr1d1) at 5'-UTR, which in turn stimulates acetylcholine synthesis and release in macrophages. Increased acetylcholine expression activated the nicotine acetylcholine receptor in adipocytes, which stimulated PKA signaling and consequent thermogenic gene expression. Our study reveals a key role of the miR-182-5p/FGF21/acetylcholine/acetylcholine receptor axis that mediates the crosstalk between adipocytes and macrophages to promote beige fat thermogenesis. Activation of the miR-182-5p-induced signaling pathway in adipose tissue may be an effective approach to ameliorate obesity and associated metabolic diseases.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34019186

RESUMO

BACKGROUND: Recent studies have demonstrated that right ventricular pacing (RVP) has deleterious effects on non-synchronized ventricular contraction, while His-bundle pacing (HBP) or left bundle branch area pacing (LBBaP) contribute to improvements in patients' mid- and long-term outcomes. This meta-analysis aimed to compare the safety and efficacy of physiologic pacing (HBP/LBBaP) versus those of RVP. METHODS: A systematic search of PubMed, Cochrane Library, and Embase was conducted for studies that compared the effects of physiologic pacing and RVP. All eligible studies were published before January 1, 2021 and were conducted in humans. STATA software version 15.0 was used for all the data analyses. RESULTS: Twenty articles (n = 2787 patients) were included in this meta-analysis. Compared to RVP, physiologic pacing was associated with a significantly shorter QRS duration and better cardiac function. Physiologic pacing was also correlated with lower rates of mitral regurgitation, pacing-induced cardiomyopathy, death, heart failure hospitalization, and atrial fibrillation, although the above results were not statistically significant. In addition, RVP led to the achievement of higher success rates than physiologic pacing, a shorter fluoroscopic time and mean procedure duration, a lower pacing threshold: the results were statistically significant. Compared with HBP, LBBaP appeared to have some advantages in R wave amplitudes, pacing threshold, fluoroscopic time, procedure time, and success rate, with statistically significant differences. Whereas HBP was associated with fewer surgical complications and shorter QRS duration, the results were not statistically significant. CONCLUSION: Physiologic pacing (HBP/LBBaP) might be a better strategy than RVP and improve long-term clinical outcomes like cardiac function. Although LBBaP appears to have some advantages over HBP, the long-term benefits are still controversial. More large-scale randomized clinical trials are needed for further verification.

6.
Environ Sci Pollut Res Int ; 28(24): 31770-31777, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33611731

RESUMO

The air purification in intensive care units (ICU) involving the removal of smog and volatile organic compounds (VOCs), disinfection, and sterilization are closely linked to important health issues. The environmental photocatalysis technology that could decompose gaseous pollutants into small molecular inorganic substances provides the potential solution. In a chamber of 30-m3 simulated ICU, photocatalytic purifier with ZnSn(OH)6 nanoparticles photocatalyst is set up to treat 10 VOCs with concentration below 2 ppm. Compared with regular purifiers of plasma and activated carbon, the present photocatalytic purifier can completely eliminate 10 varieties of low-concentration irritating VOCs without CO production. The continuous tests show that loading of 600 g ZnSn(OH)6 has capacity to treat large volumes of VOCs and remains high removal efficiencies up to 600-h operation. The results suggest that the photocatalytic purifier could be potentially applied for the treatment of contaminated indoor air particularly ICU. The mechanism of ZnSn(OH)6 photocatalysis is proposed to interpret the high performance and mineralization of the degradation process.


Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Poluição do Ar , Nanopartículas , Compostos Orgânicos Voláteis , Catálise , Unidades de Terapia Intensiva
7.
Nat Commun ; 12(1): 326, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436607

RESUMO

Adipose tissue-resident T cells have been recognized as a critical regulator of thermogenesis and energy expenditure, yet the underlying mechanisms remain unclear. Here, we show that high-fat diet (HFD) feeding greatly suppresses the expression of disulfide-bond A oxidoreductase-like protein (DsbA-L), a mitochondria-localized chaperone protein, in adipose-resident T cells, which correlates with reduced T cell mitochondrial function. T cell-specific knockout of DsbA-L enhances diet-induced thermogenesis in brown adipose tissue (BAT) and protects mice from HFD-induced obesity, hepatosteatosis, and insulin resistance. Mechanistically, DsbA-L deficiency in T cells reduces IFN-γ production and activates protein kinase A by reducing phosphodiesterase-4D expression, leading to increased BAT thermogenesis. Taken together, our study uncovers a mechanism by which T cells communicate with brown adipocytes to regulate BAT thermogenesis and whole-body energy homeostasis. Our findings highlight a therapeutic potential of targeting T cells for the treatment of over nutrition-induced obesity and its associated metabolic diseases.


Assuntos
Dieta Hiperlipídica , Glutationa Transferase/deficiência , Interferon gama/biossíntese , Linfócitos T/metabolismo , Termogênese , Adipócitos Marrons/efeitos dos fármacos , Adipócitos Marrons/metabolismo , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Animais , Regulação para Baixo/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Comportamento Alimentar , Glutationa Transferase/metabolismo , Resistência à Insulina , Interferon gama/administração & dosagem , Interferon gama/farmacologia , Masculino , Camundongos Knockout , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Obesidade/genética , Obesidade/patologia , Linfócitos T/efeitos dos fármacos , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/metabolismo , Termogênese/efeitos dos fármacos , Termogênese/genética , Proteína Desacopladora 1/metabolismo
8.
J Immunol Res ; 2020: 5269787, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33381603

RESUMO

Background: PD-1/PD-L1 inhibitors have made unprecedented progress in the treatment of cancer. Methods: A systemic search was conducted for randomized controlled trials that compared PD-1/PD-L1 inhibitor monotherapy or combination therapy with nonimmunotherapy. Hazard ratios (HRs) of overall survival (OS) according to the sex, age, ECOG PS, smoking status, liver metastasis, PD-L1 expression, EGFR, and KRAS status of patients were analyzed. Results: Totally, 13 studies with monotherapy and 5 with combination regimens were included, and the pooled HRs of OS were 0.74 (P < 0.001) and 0.64 (P < 0.001), respectively. EGFR wild-type patients could benefit from immunotherapy monotherapy (HR, 0.77; P < 0.001) while those of the mutant type had no survival benefit (HR, 1.11; P = 0.54), and the difference was statistically significant (interaction, P = 0.005). KRAS wild-type patients had no survival benefit from monotherapy (HR, 0.89; P = 0.49). For combination therapy, both male and female derived benefits but female had a significantly reduced risk of death (HR, 0.45; P < 0.001) compared with male (HR, 0.73; P < 0.001; interaction, P = 0.004). Nonsmokers derived more survival benefits from combination therapy (HR, 0.29; P < 0.001) than smokers (HR, 0.63; P = 0.001; interaction, P = 0.02). No significant difference was found between age, ECOG PS, liver metastasis, PD-L1 expression, and OS of both PD-1/PD-L1 inhibitor monotherapy and combination therapy. Conclusions: Both PD-1/PD-L1 inhibitor monotherapy and combination therapy significantly prolonged the OS of patients with advanced malignant tumors. EGFR status for monotherapy and sex and smoking status for combination therapy were important predictors of survival benefits.


Assuntos
Neoplasias/mortalidade , Neoplasias/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Humanos , Inibidores de Checkpoint Imunológico/administração & dosagem , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias/tratamento farmacológico , Neoplasias/etiologia , Prognóstico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Modelos de Riscos Proporcionais , Resultado do Tratamento
9.
Oncol Rep ; 44(5): 1997-2008, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000266

RESUMO

Curcumin is the main component of the Chinese herbal plant turmeric, which has been demonstrated to possess antitumor and other pharmacological properties. The aim of the present study was to investigate the effects of curcumin on the viability, migration and apoptosis of human colorectal carcinoma HCT­116 cells, and to explore the underlying molecular mechanisms. In addition, it was investigated whether the antitumor effect of curcumin on HCT­116 cells could match that of the chemotherapeutic drug 5­fluorouracil (5­FU). HCT­116 cells were treated with curcumin (10, 20 and 30 µM) and 5­FU (500 µM), and cell viability and proliferation were detected by Cell Counting Kit­8 and colony formation assays, respectively. The migration and invasion of treated cells were determined using Transwell and carboxyfluorescein succinimidyl amino ester fluorescent labeling assays. Cell cycle distribution and apoptosis rates were detected by flow cytometry. Furthermore, cell morphology changes associated with apoptosis were observed by fluorescence microscopy with acridine orange/ethidium bromide dual staining. To investigate the possible underlying molecular mechanisms, the gene and protein levels of Fas, Fas­associated via death domain (FADD), caspase­8, caspase­3, matrix metalloproteinase (MMP)­9, nuclear factor (NF)­κB, E­cadherin and claudin­3 were detected using quantitative PCR analysis, zymography and western blotting. The results revealed that curcumin markedly inhibited the viability and proliferation of HCT­116 cells in a dose­ and time­dependent manner. The migration, aggregation and invasion of HCT­116 cells into the lungs of mice were decreased by curcumin treatment in a dose­dependent manner. S­phase arrest and gradually increased apoptotic rates of HCT­116 cells were observed with increasing curcumin concentrations. Additionally, the mRNA and protein levels of apoptosis­associated proteins (Fas, FADD, caspase­8 and caspase­3) and E­cadherin in HCT­116 cells were upregulated following treatment with curcumin in a dose­dependent manner. By contrast, the expression of migration­associated proteins, including MMP­9, NF­κB and claudin­3, was downregulated with increasing curcumin concentrations. These data suggested that the inhibitory effect of curcumin on HCT­116 cells may match that of 5­FU. Therefore, curcumin induced cell apoptosis and inhibited tumor cell metastasis by regulating the NF­κB signaling pathway, and its therapeutic effect may be comparable to that of 5­FU.

10.
ACS Appl Mater Interfaces ; 10(1): 1084-1092, 2018 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-29251905

RESUMO

Integration of optical imaging modality with photothermal therapy (PTT) for simultaneously providing oncotherapy and bioimaging enables an optimized therapeutic efficacy and higher treatment accuracy and therefore has emerged as a prospective cancer treatment. However, it remains challenging to develop biocompatible PTT nanoagents capable of imaging, monitoring, and diagnosis. Carbon dots (CDs) possess unique photoluminescent (PL) properties and intrinsic biocompatibility; while Prussian blue nanoparticles (PBNPs) are nontoxic with efficient photothermal conversion capacity for PTT. Herein, a simple, cost-effective, and environmentally benign method was developed to strategically fabricate CD-decorated PBNP (CDs/PBNP) nanocomposites with satellite/core structure. The CDs/PBNPs possess distinct green PL emission and near-infrared photoabsorption with high efficiency and photothermal stability. In vitro and in vivo toxicity tests prove the biocompatibility of the CDs/PBNPs. Moreover, the applicability of CDs/PBNPs as nanotheranostic agents was tested, which suggests that CDs/PBNPs possess promising imaging and effective tumor ablation properties.


Assuntos
Nanocompostos , Carbono , Ferrocianetos , Fototerapia , Estudos Prospectivos
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