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1.
Aging (Albany NY) ; 12(13): 12987-13004, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32609094

RESUMO

Circulating miRNAs have received extensive attention as non-invasive biomarkers for prediction and diagnosis of disease. However, most samples have been obtained from peripheral venous blood. To evaluate whether peripheral venous miRNAs represent circulating miRNAs from all blood vessels under a given condition, such as aging, we compared the miRNA profiles of venous and arterial plasma between young and aged rats by Illumina next-generation sequencing. The DEseq2 tool was used to obtain differentially-expressed miRNAs. We observed 105 aging-related deregulated miRNAs in vein and 62 in artery, which were highly associated with cell survival and inflammation, respectively. On the other hand, the young and aged groups exhibited a unique arterial-venous bias. There were 54 differentially-expressed miRNAs in the young group and 42 in the aged group; only 8 miRNAs were shared. Further transcriptional factors enrichment analysis found that the shared miRNAs could be partially upregulated by NF-κB and SIRT1. These transcriptional factors could be organ-specific and/or regulated in physiological and aging states as possible causal factors. This study suggested the potential application of circulating miRNAs, which reflect the systematic response to certain conditions, such as aging, and the importance of origin selection for candidate circulating miRNAs.

2.
Thorac Cancer ; 11(7): 2023-2030, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32379397

RESUMO

Pembrolizumab, an anti-programmed cell death protein 1 (PD-1) antibody, has been shown to improve survival in patients with non-small cell lung cancer (NSCLC) with high expression of programmed death-ligand 1 (PD-L1). Corticosteroids are the mainstay for most high-grade immune-related adverse events (irAEs) such as pembrolizumab-induced hepatitis. However, the dose and duration of corticosteroid therapy are not well defined. The objective of this case report was to describe a new treatment pattern for severe immune checkpoint inhibitor-associated hepatitis. Here, we report the case of a patient with metastatic lung adenocarcinoma who developed grade 3 immunotherapy-induced hepatitis after the first cycle of pembrolizumab. Alanine aminotransferase (ALT) levels peaked at 233 U/L. Hepatitis was alleviated after the administration of methylprednisolone. Therefore, we retreated the patient with pembrolizumab. However, aminotransferase levels increased again after the initiation of low-dose methylprednisolone or the reuse of pembrolizumab. Finally, hepatitis was controlled with low-dose methylprednisolone plus bicyclol, a Chinese hepatoprotective agent. Although the patient had been on low-dose methylprednisolone therapy for about six months, he showed a prompt response. During this period, we also found a dramatic decrease in the neutrophil-lymphocyte ratio (NLR), senescent T cells (CD8+ CD28- CD57+ ), and myeloid-derived suppressor cells (MDSCs) in the peripheral blood of the patient. To our knowledge, this is the first case report of successful management of grade 3 pembrolizumab-induced hepatitis with a combination of low-dose corticosteroids and bicyclol. The durable clinical response and changes in blood biomarkers indicate that low doses of corticosteroids do not compromise the efficacy of immune checkpoint inhibitors (ICIs). Therefore, this case may provide a new treatment pattern for severe immunotherapy-induced hepatitis.

3.
Aging (Albany NY) ; 12(3): 2530-2544, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-32023551

RESUMO

Circular RNA (circRNA) is a novel class of noncoding RNAs, and the roles of circRNAs in the development of cardiac hypertrophy remain to be explored. Here, we investigate the potential roles of circRNAs in cardiac hypertrophy. By circRNA sequencing in left ventricular specimens collected from 8-week-old mice with isoproterenol hydrochloride-induced cardiac hypertrophy, we found 401 out of 3323 total circRNAs were dysregulated in the hypertrophic hearts compared with the controls. Of these, 303 circRNAs were upregulated and 98 were downregulated. Moreover, the GO and KEGG analyses revealed that the majority of parental gene of differentially expressed circRNAs were not only related to biological process such as metabolic process and response to stimulus, but also related to pathway such as circulatory system and cardiovascular diseases. On the other hand, total 1974 miRNAs were predicted to binding to these differentially expressed circRNAs, and the possible target mRNAs of those miRNAs were also predicted and analyzed in terms of functional annotation. Finally, we identified that ANF and miR-23a are downstream targets of circRNA wwp1, suggesting that circRNA wwp1 exerts inhibitory roles of cardiac hypertrophy via down-regulation of ANF and miR-23a, which underlying the potential mechanisms whereby circRNA regulates cardiac hypertrophy.

4.
Int J Cancer ; 144(5): 933-946, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29992569

RESUMO

Cancer progression is closely related to the tumor microenvironment in which the tumor exists, including surrounding blood vessels, immune cells, fibroblasts, bone marrow-derived inflammatory cells, signaling molecules and the extracellular matrix. Tumors can influence the microenvironment by releasing extracellular signals, promoting tumor angiogenesis and inducing peripheral immune tolerance, while the immune cells in the microenvironment can impact the growth and evolution of cancerous cells. One of major cell components in the tumor microenvironment is myeloid-derived suppressor cells (MDSCs), which promote tumor growth and metastasis directly or indirectly by recognizing other immune cells, producing cytokines and exerting their immunosuppression functions. MDSCs have emerged as major regulators of immune responses in cancer and key targets for treating cancer. There are many limitations and side-effect in approaches of conventional cancer therapy, including radiotherapy. It has grown up to be a burgeoning field that a combination of radiotherapy and immunotherapy applied to cancer therapy. Therefore, it is fundamental to explore the immune mechanism in the process of cancer treatment. Here, we reviewed the recent progress of MDSCs in roles of the tumor microenvironment and tumor radiotherapy.


Assuntos
Células Supressoras Mieloides/patologia , Neoplasias/patologia , Neoplasias/radioterapia , Radioterapia/efeitos adversos , Microambiente Tumoral/fisiologia , Animais , Citocinas/metabolismo , Progressão da Doença , Humanos , Neoplasias/metabolismo
5.
J Cell Physiol ; 234(8): 13252-13262, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30580435

RESUMO

Although cardiac hypertrophy is widely recognized as a risk factor that leads to cardiac dysfunction and, ultimately, heart failure, the complex mechanisms underlying cardiac hypertrophy remain incompletely characterized. The nuclear receptor peroxisome proliferator-activated receptor δ (PPARδ) is involved in the regulation of cardiac lipid metabolism. Here, we describe a novel PPARδ-dependent molecular cascade involving microRNA-29a (miR-29a) and atrial natriuretic factor (ANF), which is reactivated in cardiac hypertrophy. In addition, we identify a novel role of miR-29a, in which it has a cardioprotective function in isoproterenol hydrochloride-induced cardiac hypertrophy by targeting PPARδ and downregulating ANF. Finally, we provide evidence that miR-29a reduces the isoproterenol hydrochloride-induced cardiac hypertrophy response, thereby underlining the potential clinical relevance of miR-29a in which it may serve as a potent therapeutic target for heart hypertrophy treatment.


Assuntos
Fator Natriurético Atrial/metabolismo , Cardiomegalia/metabolismo , Regulação da Expressão Gênica/fisiologia , MicroRNAs/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Animais , Regulação para Baixo , Camundongos , Camundongos Endogâmicos ICR , Miócitos Cardíacos/metabolismo
6.
J Cancer ; 9(12): 2072-2081, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29937925

RESUMO

DNA double-strand breaks (DSBs) are highly toxic lesions that can impair cellular homeostasis and genome stability to result in tumorigenesis for inappropriate repair. Although DSBs are repaired by homologous recombination (HR) or non-homologous end-joining (NHEJ), the related mechanisms are still incompletely unclear. Indeed, more and more evidences indicate that the methylation of histone lysine has an important role in choosing the pathways of DNA repair. For example, tri-methylated H3K36 is required for HR repair, while di-methylated H4K20 can recruit 53BP1 for NHEJ repair. Here, we reviewed the recent progress in the molecular mechanisms by which histone methylation functions in DNA double-strand breaks repair (DSBR). The insight into the mechanisms of histone methylation repairing DNA damage will supply important cues for clinical cancer treatment.

7.
Sci Rep ; 7(1): 10007, 2017 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-28855712

RESUMO

Meiotic recombination is initiated from the formation of DNA double-strand breaks (DSBs). In Arabidopsis, several proteins, such as AtPRD1, AtPRD2, AtPRD3, AtDFO and topoisomerase (Topo) VI-like complex, have been identified as playing important roles in DSB formation. Topo VI-like complex in Arabidopsis may consist of subunit A (Topo VIA: AtSPO11-1 and AtSPO11-2) and subunit B (Topo VIB: MTOPVIB). Little is known about their roles in Arabidopsis DSB formation. Here, we report on the characterization of the MTOPVIB gene using the Arabidopsis mutant alleles mtopVIB-2 and mtopVIB-3, which were defective in DSB formation. mtopVIB-3 exhibited abortion in embryo sac and pollen development, leading to a significant reduction in fertility. The mtopVIB mutations affected the homologous chromosome synapsis and recombination. MTOPVIB could interact with Topo VIA proteins AtSPO11-1 and AtSPO11-2. AtPRD1 interacted directly with Topo VI-like proteins. AtPRD1 also could interact with AtPRD3 and AtDFO. The results indicated that AtPRD1 may act as a bridge protein to interact with AtPRD3 and AtDFO, and interact directly with the Topo VI-like proteins MTOPVIB, AtSPO11-1 and AtSPO11-2 to take part in DSB formation in Arabidopsis.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Proteínas Arqueais/metabolismo , Quebras de DNA de Cadeia Dupla , DNA Topoisomerases Tipo II/metabolismo , DNA de Plantas/metabolismo , Meiose , Recombinação Genética
8.
Inorg Chem ; 56(14): 8036-8044, 2017 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-28653844

RESUMO

Although great progress has been made for charge transfer (CT) compounds of various organic donor-acceptor systems, no CT compounds containing both inorganic chalcogenide cluster anions and organic porphyrin cations have been reported. Herein, a germanium chalcogenide cluster (Ge4S104-) is chosen as an electron donor and a methylated tetrakis(4-pyridyl)porphyrin (5,10,15,20-tetrakis(N-methyl-4-pyridyl)porphyrin, TMPyP) is selected as an electron acceptor to create chalcogenide cluster-porphyrin CT compounds (TMPyP-Ge4S10)·5H2O (1) and (MnTMPyP-Ge4S10)·13H2O (2). Their crystal structures have been characterized by single-crystal X-ray diffraction. Compound 1 is an ionic CT salt assembled through interion interactions, and compound 2 is a neutral CT dyad formed by metal-ligand axial coordination of the chalcogenide cluster with manganese porphyrin. The strong charge transfer properties are revealed by electronic spectra, theoretical calculations, 1H NMR, and ESR. The CT intensity of the chalcogenide cluster-porphyrin system can be modulated by metalation. The fluorescence and photocurrent response properties of 1 and 2 are related to the CT intensity.

9.
Inorg Chem ; 55(18): 9154-7, 2016 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-27603504

RESUMO

A tetrathiafulvalene derivative has been incorporated into a diamond-like structure for the first time. The coordination network shows highly unusual 8-fold interpenetration with redox-active and photoelectric properties.

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