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1.
Nano Lett ; 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35507684

RESUMO

Zn-based aqueous batteries (ZABs) have been regarded as promising candidates for safe and large-scale energy storage in the "post-Li" era. However, kinetics and stability problems of Zn capture cannot be concomitantly regulated, especially at high rates and loadings. Herein, a hierarchical confinement strategy is proposed to design zincophilic and spatial traps through a host of porous Co-embedded carbon cages (denoted as CoCC). The zincophilic Co sites act as preferred nucleation sites with low nucleation barriers (within 0.5 mA h cm-2), and the carbon cage can further spatially confine Zn deposition (within 5.0 mA h cm-2). Theoretical simulations and in situ/ex situ structural observations reveal the hierarchical spatial confinement by the elaborated all-in-one network (within 12 mA h cm-2). Consequently, the elaborate strategy enables a dendrite-free behavior with excellent kinetics (low overpotential of ca. 65 mV at a high rate of 20 mA cm-2) and stable cycle life (over 800 cycles), pushing forward the next-generation high-performance ZABs.

2.
Sci China Life Sci ; 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35471687

RESUMO

Nasopharyngeal carcinoma (NPC) is a malignant tumor that usually occurs in people from Southeast Asia and Southern China. NPC is prone to migration and invasion, leading to poor prognosis. A large number of circular RNAs (circRNAs) exacerbate the process of metastasis in NPC; however, their underlying mechanisms remain unclear. We found that the circular RNA circCCNB1, encoded by the oncogene CCNB1, was downregulated in NPC biopsies and cell lines. In vitro assays show that circCCNB1 inhibits NPC cell migration and invasion. Moreover, circCCNB1 induces a protein, nuclear factor 90 (NF90), to bind and prolong the half-life of tight junction protein 1 (TJP1) mRNA. Upregulation of TJP1 enhances tight junctions between cancer cells and inhibits NPC cell migration and invasion. This study reveals a novel biological function of circCCNB1 in the migration and invasion of NPC by enhancing the tight junctions of cancer cells by binding to NF90 proteins and TJP1 mRNA, and may provide a potential therapeutic target for NPC.

3.
Open Med (Wars) ; 17(1): 661-675, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35434372

RESUMO

Long noncoding RNAs (lncRNAs) are key regulators of hepatic stellate cells (HSCs), yet the role of upregulated lncRNA-NONRATT013819.2 in activated HSCs remains uncertain. In this study, the effects of NONRATT013819.2 on proliferation, apoptosis, migration, and contraction of transforming growth factor (TGF)-ß1-induced HSCs were investigated. The mechanisms of NONRATT013819.2 on the activated HSCs were explored by loss-of-function of NONRATT013819.2 and gain-of-function of the target gene. Here, TGF-ß1 treatment resulted in a gradual increase in the expression of cytoskeleton markers (collagen, α-SMA, and TIMP1), NONRATT013819.2, miR24-3p, and lysyl oxidase (Lox) over time in HSCs. NONRATT013819.2 acted as a sponge of miR24-3p to competitively abolish the inhibition of the lox gene in HSCs. Silencing of NONRATT013819.2 suppressed the expression of cytoskeleton markers, proliferation, and the proportion of cells that entered the S-phase, and promoted apoptosis in TGF-ß1-activated HSCs. These effects were reversed when lox overexpression was introduced simultaneously. Similarly, silencing of NONRATT013819.2 also blocked ECM reconstruction, while recused by lox overexpression in TGF-ß1-activated HSCs. In conclusion, upregulation of NONRATT013819.2 promotes the myofibroblastic transition by competitively binding miR24-3p to release lox in HSCs. Therefore, targeted therapy of NONRATT013819.2 may have the potential for liver fibrosis.

4.
Nanomaterials (Basel) ; 12(6)2022 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-35335799

RESUMO

In this research, we successfully developed a green, economical and effective one-step hydrothermal method for the synthesis of fluorescent nitrogen-doped carbon dots (N-CDs) by utilizing fresh tea leaves and urea as the carbon and nitrogen sources, respectively. The obtained N-CDs were characterized by TEM, XPS and FT-IR. We found that the N-CDs were near-spherical with an average size of about 2.32 nm, and contained abundant oxygen and nitrogen functional groups. The N-CDs exhibited bright blue fluorescence under ultraviolet illumination, with the maximum emission at 455 nm. Meanwhile, the as-prepared N-CDs could be selectively quenched by Fe3+ ions. The quenching of N-CDs is linearly correlated with the concentration of Fe3+ in the range of 0.1-400 µM with a low detection limit of 0.079 µM. Significantly, the N-CDs present excellent biocompatibility and high photostability. The results also depict that multicolor fluorescence is displayed under a fluorescence microscope and successfully applied for the detection of intracellular Fe3+. To sum up, the fluorescent N-CDs are expected to be a sensitive detection probe for Fe3+ in biological systems.

5.
Front Endocrinol (Lausanne) ; 13: 801925, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35282434

RESUMO

Background: The prevalence of thyroid carcinoma (TC) and Hashimoto's thyroiditis (HT) has been increasing dramatically over the past decades. We investigated the relationship between HT and TC. Methods: We followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines for carrying out and reporting this meta-analysis. The literature from January 1, 2010 to December 31, 2020, regardless of region and publication type, was searched comprehensively in PubMed, Embase, Web of Science, and Cochrane Library databases. After careful selection and data extraction, the pooled odds ratio of various clinical characteristics in 39 studies were calculated. Publication bias was analyzed using funnel plots. Results: Meta-analysis of 39 original research articles showed HT to be a risk factor of TC (pooled odds ratio = 1.71; 95% confidence interval, 1.57-1.80; p < 0.00001) and papillary thyroid carcinoma (1.67, 1.51-1.85, <0.00001). Patients with papillary thyroid carcinoma (PTC) combined with HT were more likely to have multifocal carcinomas. The prevalence of an extrathyroidal extension, metastasis, BRAFV600E mutation, and recurrence was significantly lower in patients with PTC combined with HT. Conclusions: HT is a "double-edged sword" in TC patients. HT increases the risk of TC and PTC but is a protective factor against PTC progression.


Assuntos
Carcinoma , Doença de Hashimoto , Neoplasias da Glândula Tireoide , Carcinoma/patologia , Doença de Hashimoto/epidemiologia , Doença de Hashimoto/patologia , Humanos , Mutação , Estudos Observacionais como Assunto , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia
6.
Mol Cancer ; 21(1): 62, 2022 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-35227262

RESUMO

BACKGROUND: Circular RNAs play an important role in tumor genesis and progression, but they have not been sufficiently studied in patients with nasopharyngeal carcinoma (NPC). METHODS: The circular RNA, circCAMSAP1, was screened in NPC cells by RNA sequencing analysis. The expression of circCAMSAP1 in NPC tissues was examined by real-time quantitative polymerase chain reaction (RT-qPCR) and in situ hybridization. Wound-healing, transwell, MTT and flow cytometry assays, and nude mouse tumor models were used to explore the effect of circCAMSAP1 on proliferation and metastasis of NPC in vitro or in vivo. The downstream proteins regulated by circCAMSAP1 were screened using mass spectrometry. The interaction between circCAMSAP1 and the SERPINH1 mRNA was identified using the circular RNA immunoprecipitation method and the luciferase reporter assay. The interaction between SERPINH1 and transcription factor c-Myc was verified through Co-immunoprecipitation (Co-IP) and immunofluorescence. The effect of c-Myc on the generation of circCAMSAP1 was examined through RT-qPCR and chromatin immunoprecipitation. Finally, the splicing factors that promote the production of circCAMSAP1 were explored by RT-qPCR and RNA immunoprecipitation (RIP). RESULTS: We found that circCAMSAP1 was highly expressed in NPC tissues and promoted NPC proliferation and metastasis. Additionally, circCAMSAP1 promoted SERPINH1 expression through improved SERPINH1 mRNA stability by binding to the 3'-untranslated region (3'UTR) of SERPINH1. Highly expressed SERPINH1 reduced the ubiquitination-degradation rate of c-Myc, causing increased tumorigenesis. Meanwhile, c-Myc, cooperating with splicing factor 10 (SRSF10), could also promote CAMSAP1 pre-mRNA transcription and back-splicing, forming a positive feedback of circCAMSAP1 production, resulting in the proliferation and metastasis of NPC. CONCLUSIONS: Our findings revealed that circCAMSAP1 promotes NPC proliferation and metastasis by binding to the 3'UTR of SERPINH1, suggesting that the positive feedback of circCAMSAP1-SERPINH1-c-Myc may serve as a prognostic biomarker or therapeutic target in patients with NPC.


Assuntos
MicroRNAs , Neoplasias Nasofaríngeas , Regiões 3' não Traduzidas , Animais , Carcinogênese/genética , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transformação Celular Neoplásica/genética , Retroalimentação , Regulação Neoplásica da Expressão Gênica , Proteínas de Choque Térmico HSP47 , Humanos , Camundongos , MicroRNAs/genética , Proteínas Associadas aos Microtúbulos , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Fatores de Processamento de RNA/genética , RNA Circular/genética , Proteínas Repressoras , Fatores de Processamento de Serina-Arginina/metabolismo
7.
Plant Cell ; 2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35263433

RESUMO

CONSTITUTIVELY PHOTOMORPHOGENIC1 (COP1), a well-characterized E3 ubiquitin ligase, is a central repressor of seedling photomorphogenic development in darkness. However, whether COP1 is involved in modulating abscisic acid (ABA) signaling in darkness remains largely obscure. Here, we report that COP1 is a positive regulator of ABA signaling during Arabidopsis seedling growth in the dark. COP1 mediates ABA-induced accumulation of ABI5, a transcription factor playing a key role in ABA signaling, through transcriptional and post-translational regulatory mechanisms. We further show that COP1 physically interacts with ABA-hypersensitive DCAF1 (ABD1), a substrate receptor of the CUL4-DDB1 E3 ligase targeting ABI5 for degradation. Accordingly, COP1 directly ubiquitinates ABD1 in vitro, and negatively regulates ABD1 protein abundance in vivo in the dark but not in the light. Therefore, COP1 promotes ABI5 protein stability post-translationally in darkness by destabilizing ABD1 in response to ABA. Interestingly, we reveal that ABA induces the nuclear accumulation of COP1 in darkness, thus enhancing its activity in propagating the ABA signal. Together, our study uncovers that COP1 modulates ABA signaling during seedling growth in darkness by mediating ABA-induced ABI5 accumulation, demonstrating that plants adjust their ABA signaling mechanisms according to their light environment.

8.
Nat Commun ; 13(1): 866, 2022 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-35165282

RESUMO

Epstein-Barr virus (EBV) is reportedly the first identified human tumor virus, and is closely related to the occurrence and development of nasopharyngeal carcinoma (NPC), gastric carcinoma (GC), and several lymphomas. PD-L1 expression is elevated in EBV-positive NPC and GC tissues; however, the specific mechanisms underlying the EBV-dependent promotion of PD-L1 expression to induce immune escape warrant clarification. EBV encodes 44 mature miRNAs. In this study, we find that EBV-miR-BART11 and EBV-miR-BART17-3p upregulate the expression of PD-L1 in EBV-associated NPC and GC. Furthermore, EBV-miR-BART11 targets FOXP1, EBV-miR-BART17-3p targets PBRM1, and FOXP1 and PBRM1 bind to the enhancer region of PD-L1 to inhibit its expression. Therefore, EBV-miR-BART11 and EBV-miR-BART17-3p inhibit FOXP1 and PBRM1, respectively, and enhance the transcription of PD-L1 (CD274, http://www.ncbi.nlm.nih.gov/gene/29126 ), resulting in the promotion of tumor immune escape, which provides insights into potential targets for EBV-related tumor immunotherapy.


Assuntos
Herpesvirus Humano 4/genética , MicroRNAs/genética , Carcinoma Nasofaríngeo/imunologia , Neoplasias Nasofaríngeas/imunologia , Neoplasias Gástricas/imunologia , Evasão Tumoral/imunologia , Antígeno B7-H1/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/metabolismo , Infecções por Vírus Epstein-Barr/virologia , Fatores de Transcrição Forkhead/antagonistas & inibidores , Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Herpesvirus Humano 4/imunologia , Humanos , Linfoma/imunologia , Linfoma/virologia , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/virologia , Proteínas Repressoras/antagonistas & inibidores , Proteínas Repressoras/metabolismo , Neoplasias Gástricas/virologia , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/metabolismo , Evasão Tumoral/genética , Microambiente Tumoral/imunologia
9.
Fungal Biol ; 126(3): 201-212, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35183337

RESUMO

Blue mold caused by Penicillium italicum is a severe postharvest disease in citrus fruits. In this study, the fermentation product (FP-E) of Aspergillus aculeatus GC-09, an endophytic fungus isolated from a citrus plant, was found to exhibit antifungal activity against P. italicum with a MIC of 0.3125 mg/mL. The fungus A. aculeatus GC-09 was identified based on the studies of morphology and ITS nucleotide sequence. FP-E significantly inhibited the spore germination and mycelial growth of P. italicum. Scanning electron microscopy (SEM) results of P. italicum treated with FP-E showed shrunken, distorted and collapsed hyphae and conidiospores, indicative of the cell membrane damage, which was further confirmed by the propidium iodide (PI) fluorescent staining analysis. Consistent with the microscopy observation, FP-E led to the leakage of cellular constituents from P. italicum, which is evident from the increase in electrical conductivity and nucleic acid contents in the mycelial solution incubated with FP-E. In addition, FP-E treatment considerably increased the intracellular reactive oxygen species (ROS) content, and reduced the enzyme activities of both catalase (CAT) and peroxidase (POD) in P. italicum cells. Furthermore, orange fruits treated with FP-E showed fewer disease symptoms compared to the untreated fruits. These results suggested that the antifungal activity of FP-E might be associated with the disruption of cell membrane integrity, the accumulation of ROS level, and the reduction of the antioxidant enzymes activity of P. italicum. Therefore, A. aculeatus GC-09 might be a potential microbial resource for the biocontrol of citrus postharvest blue mold.


Assuntos
Citrus , Penicillium , Aspergillus , Citrus/microbiologia , Frutas/microbiologia , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle
10.
J Org Chem ; 87(5): 2797-2808, 2022 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-35076229

RESUMO

A [3+1+1+1] annulation of arylamines, arylaldehydes, and dimethyl sulfoxide (DMSO) to the pyridine structure in quinolines using DMSO as a nonadjacent dual-methine (═CH-) synthon is disclosed. In this annulation, arylamines provide two carbon atoms and one nitrogen atom, arylaldehydes furnish one carbon atom, and DMSO provides two nonadjacent methines (═CH-) to the pyridine ring in quinoline molecules. This annulation provides a simple approach for the synthesis of 3-arylquinolines from readily available substrates in useful yields. On the basis of the control experiments and the literature, a plausible mechanism is proposed.


Assuntos
Dimetil Sulfóxido , Quinolinas , Aminas , Carbono , Piridinas , Quinolinas/química
11.
Adv Mater ; 34(14): e2110047, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35100662

RESUMO

Aqueous Zn metal batteries have attracted much attention due to their high intrinsic capacity, high safety, and low cost. Nevertheless, uncontrollable dendrite growth and adverse side reactions of Zn anodes seriously hinder their further application. Herein, a three-dimensional (3D) porous graphene-carbon nanotubes scaffold decorated with metal-organic framework derived ZnO/C nanoparticles (3D-ZGC) is fabricated as the host for dendrite-free Zn-metal composite anodes. The zincophilic ZnO/C nanoparticles act as preferred deposition sites with low nucleation barriers to induce homogeneous Zn deposition. The mechanically robust 3D scaffold with high conductivity not only suppresses the formation of dendritic Zn by reducing the local current density and homogenizing Zn2+ ion flux, but also inhibits volume changes during the long-term plating/stripping process. As a result, the 3D-ZGC composite anodes afford unprecedented Zn plating-stripping stability at an ultrahigh current density of 20 mA cm-2 for 1500 cycles with low overpotential (<65 mV) when used in a symmetric cell. When coupled with MnO2 cathodes, the assembled Zn@3D-ZGC//MnO2 full batteries deliver an enhanced cycling stability for up to 6000 cycles at 2000 mA g-1 , demonstrating the potential of the 3D-ZGC composite anode for advanced Zn metal batteries.

12.
Food Chem ; 377: 131965, 2022 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-34979398

RESUMO

Lateral flow immunoassay (LFIA) is the most effective real-time detection method for aflatoxin B1 (AFB1). Here, we constructed a nanozyme-strip based on MnO2 nanosheets (MnO2 NSs) as a catalytic label for detection of AFB1. By taking advantage of the MnO2-TMB catalytic amplified system, the new test achieves rapid detection with high sensitivity and ultrawide range. The limit of detection of the assay was 15 pg mL-1, which was over 100-fold lower than the maximum limit set by the European Union (EU) of AFB1 in foods. In addition, the strip test could offer 7 dynamic detection ranges, spanning 4 orders of magnitude, which could cater to the varieties of limits on AFB1 residues in foods and feeds set by different countries. The estimated recoveries were in the range of 85.67%-106.38% with coefficients of variations (CVs) less than 9.68%. Overall, the developed approach is a rapid, reliable, sensitive and widely available tool for on-site detection of AFB1.


Assuntos
Aflatoxina B1 , Compostos de Manganês , Aflatoxina B1/análise , Imunoensaio , Limite de Detecção , Óxidos
13.
Angew Chem Int Ed Engl ; 61(12): e202115308, 2022 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-35018705

RESUMO

2D nanomaterials with flexibly modifiable surfaces are highly sought after for various applications, especially in room-temperature chemiresistive gas sensing. Here, we have prepared a series of COF 2D nanomaterials (porphyrin-based COF nanosheets (NS)) that enabled highly sensitive and specific-sensing of NO2 at room temperature. Different from the traditional 2D sensing materials, H2 -TPCOF was designed with a largely reduced interlayer interaction and predesigned porphyrin rings as modifiable sites on its surfaces for post-metallization. After post-metallization, the metallized M-TPCOF (M=Co and Cu) showed remarkably improved sensing performances. Among them, Co-TPCOF exhibited highly specific sensing toward NO2 with one of the highest sensitivities of all reported 2D materials and COF materials, with an ultra-low limit-of-detection of 6.8 ppb and fast response/recovery. This work might shed light on designing and preparing a new type of surface-highly-modifiable 2D material for various chemistry applications.

14.
Angew Chem Int Ed Engl ; 61(3): e202113315, 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-34716649

RESUMO

The exploration of new application forms of covalent organic frameworks (COFs) in Li-S batteries that can overcome drawbacks like low conductivity or high loading when typically applied as sulfur host materials (mostly ≈20 to ≈40 wt % loading in cathode) is desirable to maximize their low-density advantage to obtain lightweight, portable, or high-energy-density devices. Here, we establish that COFs could have implications as microadditives of binders (≈1 wt % in cathode), and a series of anthraquinone-COF based hollow tubes have been prepared as model microadditives. The microadditives can strengthen the basic properties of the binder and spontaneously immobilize and catalytically convert lithium polysulfides, as proved by density functional calculations, thus showing almost doubly enhanced reversible capacity compared with that of the bare electrode.

15.
Br J Cancer ; 126(8): 1113-1124, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34750493

RESUMO

Alternative splicing (AS) is a key process in which precursor RNAs produce different mature RNAs, and the disorder of AS is a key factor in promoting cancer development. Compared with coding RNA, studies on the functions of long non-coding RNAs (lncRNAs) are far from enough. In fact, lncRNA is an important participant and regulator in the process of AS. On the one hand, lncRNAs regulate cancer progression as AS products of precursor messenger RNA (mRNA), but on the other hand, precursor lncRNA generates cancer-related abnormal splicing variants through AS. In addition, lncRNAs directly or indirectly regulate the AS events of downstream target genes, thus affecting the occurrence and development of cancer. Here, we reviewed how lncRNAs regulate AS and influence oncogenesis in different ways.


Assuntos
Neoplasias , RNA Longo não Codificante , Processamento Alternativo/genética , Transformação Celular Neoplásica , Humanos , Neoplasias/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro
16.
Oncogene ; 41(2): 233-245, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34725462

RESUMO

Nasopharyngeal carcinoma (NPC) demonstrates significant regional differences and a high incidence in Southeast Asia and Southern China. Bactericidal/permeability-increasing-fold- containing family B member 1 (BPIFB1) is a relatively specific and highly expressed protein in the nasopharyngeal epithelium. BPIFB1 expression is substantially downregulated in NPC and is significantly associated with poor prognosis in patients with NPC. However, the specific molecular mechanism by which BPIFB1 regulates NPC is not well understood. In this study, we found that BPIFB1 inhibits vasculogenic mimicry by regulating the metabolic reprogramming of NPC. BPIFB1 decreases GLUT1 transcription by downregulating the JNK/AP1 signaling pathway. Altered glycolysis reduces the acetylation level of histone and decreases the expression of vasculogenic mimicry-related genes, VEGFA, VE-cadherin, and MMP2, ultimately leading to the inhibition of vasculogenic mimicry. To our knowledge, this is the first report on the role and specific mechanism of BPIFB1 as a tumor suppressor gene involved in regulating glycolysis and vasculogenic mimicry in NPC. Overall, these results provide a new therapeutic target for NPC diagnosis and treatment.


Assuntos
Autoantígenos/metabolismo , Proteínas de Ligação a Ácido Graxo/metabolismo , Transportador de Glucose Tipo 1/metabolismo , Neoplasias Nasofaríngeas/genética , Acetilação , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Camundongos Nus , Neoplasias Nasofaríngeas/patologia , Transfecção
17.
Eur J Pharm Sci ; 168: 106055, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34742834

RESUMO

BACKGROUND: Inhaled formulations are the first choices for treating asthma and chronic obstructive pulmonary disease (COPD), attracting the increasing investment and development in the pharmaceutical industry. Both the equivalence of local and systemic exposures need to be considered when assessing the equivalence of generic inhaled drugs, which has become a dilemma in the development of generic inhaled drugs. There is an urgent need for reliable methods such as physiologically-based pharmacokinetic (PBPK) model to assist in the development of inhaled drugs. METHOD: To test the strategy that in silico simulation is an effective tool in developing inhaled products and further assessing their clinically feasibility, a long-acting beta2-adrenergic agonists indacaterol, which was referred as the first-line therapy for patient with COPD, was selected as a tool drug. The PBPK model was established and the predicted plasma concentration curve was obtained by inputting the physicochemical properties of indacaterol and adjusting model parameters. The accuracy of simulation was verified by an alignment with the actual data. The main factor affecting PK in vivo was investigated by parameter sensitivity analysis. The biological equivalent size of indacaterol was investigated by virtual bioequivalence analysis. RESULTS: The models of indacaterol after intravenous and oral administration were established and confirmed, and used as a background for PBPK model of inhaled administration. All those models showed favorable stability and applicability. Appropriate lung deposition was generated in the PBPK model, and the predicted plasma profile of indacaterol was consistent with the clinical actual observation values. Particle size is the most important factor affecting the PK of indacaterol in vivo. Furthermore, virtual bioequivalence simulation exhibited statistically comparable results between the particle size fluctuates in the range of 3.5-6.5 µm and baseline levels (D90 = 5 µm). CONCLUSIONS: The PBPK model can simulate the pharmacokinetics and lung deposition of indacaterol, which will be a powerful tool to assist the development of inhaled drugs.


Assuntos
Indanos , Quinolonas , Simulação por Computador , Voluntários Saudáveis , Humanos , Modelos Biológicos
18.
Autophagy ; 18(2): 240-253, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33904341

RESUMO

Circular RNAs (circRNAs) are non-coding RNAs that have attracted considerable attention in recent years. Owing to their distinct circular structure, circRNAs are stable in cells. Autophagy is a catabolic process that helps in the degradation and recycling of harmful or inessential biological macromolecules in cells and enables cells to adapt to stress and changes in the internal and external environments. Evidence has shown that circRNAs influence the course of a disease by regulating autophagy, which indicates that autophagy is involved in the onset and development of various diseases and can affect drug resistance (for example, it affects cisplatin resistance in tumors). In this review, we summarized the role of circRNAs in autophagy and their influence on disease onset and progression as well as drug resistance. The review will expand our understanding of tumors as well as cardiovascular and neurological diseases and also suggest novel therapeutic strategies.Abbreviations: ACR: autophagy-related circRNA; ADSCs: adipogenic mesenchymal stem cells; AMPK: AMP-activated protein kinase; ATG: autophagy related; BCL2: BCL2 apoptosis regulator; BECN1: beclin 1; ceRNA: competing endogenous RNA; circRNA: circular RNA; CMA: chaperone-mediated autophagy; EPCs: endothelial progenitor cells; LE/MVBs: late endosomes/multivesicular bodies; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MTOR: mechanistic target of rapamycin kinase; NSCLC: non-small cell lung cancer; PDLSCs: periodontal ligament stem cells; PE: phosphatidylethanolamine; PtdIns: phosphatidylinositol; PtdIns3K: phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate 1,2-dipalmitoyl; PTEN: phosphatase and tensin homolog; RBPs: RNA-binding proteins; SiO2: silicon dioxide; TFEB: transcription factor EB; ULK: unc-51 like autophagy activating kinase 1.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Autofagia/genética , Progressão da Doença , Humanos , Fosfatidilinositóis , Proteínas Proto-Oncogênicas c-bcl-2 , RNA Circular/genética , Dióxido de Silício
19.
Anal Chim Acta ; 1189: 339210, 2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-34815051

RESUMO

Circular Ribonucleic Acid (CircRNA) plays regulatory roles in many biological processes, such as tumors and metabolic diseases. Due to the fact that circRNA is more stable and conservative than linear RNA, circRNA has become a potential biomarker in early clinical diagnosis and biomedical research. Therefore, the quantification of circRNA expression level is of importance for understanding their functions and their applications for disease diagnosis and treatment. Nevertheless, due to the low abundance of circRNA, it is still a challenge for the analysis of circRNA in cells. Herein, we proposed a sensitive detection method for circRNA based on the T7 exonuclease-assisted cycling enzymatic amplification. The fluorescent sensor was constructed by a hairpin molecular beacon and T7 exonuclease. With the cycling enzymatic amplification process, this sensor achieved the limit of detection of 1 pM with a good linear correlation in the range of 0-100 pM (R2 = 0.9891) using circBART2.2 as a model. Furthermore, we applied the proposed method in the determination of circBART2.2 in cell lysates. The results demonstrated that this method has promising applications in early diagnosis of Epstein-Barr virus (EBV) infection-related diseases using circRNA as the biomarker.


Assuntos
Infecções por Vírus Epstein-Barr , RNA Circular , Contagem de Células , Herpesvirus Humano 4 , Humanos , Limite de Detecção , Espectrometria de Fluorescência
20.
J Clin Lab Anal ; 36(2): e24183, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34953004

RESUMO

BACKGROUND: Pulmonary arterial hypertension (PAH) is a hemodynamic state that is characterized by pulmonary vasoconstriction and vascular remodeling, leading to a continuous increase in mean pulmonary arterial pressure, and eventually right heart failure. Mutations of the bone morphogenetic protein type II receptor (BMPR2) gene are the most common genetic cause of PAH. METHODS: A 52-year-old woman was admitted to Shaoxing People's Hospital after suffering from a cough for 2 months. In our hospital, the proband got a thorough medical examination and was diagnosed with PAH following genetic testing. RESULTS: Genetic test showed that the proband carried a novel heterozygous c.1481C>T (p.Ala494Val) mutation in the BMPR2 gene. The new mutation was initially discovered as a potential pathogenic variant by bioinformatics research, but it needed to be functionally verified. CONCLUSIONS: The novel mutation may be related to the development of the PAH. In addition to general examinations, clinicians must thoroughly examine molecular genetics to provide an accurate diagnosis in the clinic, particularly for rare disorders.


Assuntos
Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Hipertensão Arterial Pulmonar/genética , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/ultraestrutura , Análise Mutacional de DNA/métodos , Feminino , Testes Genéticos/métodos , Heterozigoto , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Pessoa de Meia-Idade , Mutação , Estrutura Secundária de Proteína
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