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1.
Food Chem ; 334: 127572, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32721834

RESUMO

In the present work, a rapid, accurate and cost-effective method has been developed for the simultaneous quantification of phenolic compounds in oil using mixed-mode solid-phase extraction (SPE) coupled with chemical labeling UHPLC-MS/MS. Mix-mode SPE weak cation cartridges were selected to enrich and purify phenolic compounds in oil, and hydroxyl moiety was dansylation as stable-isotope internal standard. The major parameters that affected the extraction and chemical labeling efficiency were investigated, and the method was fully validated. The limit of quantifications and the limit of detections were 0.002 µg kg-1 ~ 0.10 µg kg-1 and 0.006 µg kg-1 ~ 0.30 µg kg-1, respectively. The recoveries were 61.2% ~ 129.3% with intra-day and inter-day precision less than 12%. The results for 38 rapeseed oils revealed that 14 phenolic compounds, including canolol, phenolic acids, phenolic alcohols, tyrosol and vanillin from trace levels to relatively high content.

2.
Injury ; 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-33023742

RESUMO

PURPOSE: To repair multiple skin soft tissue defects of one finger is a challenge to hand surgeons. We introduce a method which can be used to repair multiple skin soft tissue defects of one finger with bilateral flaps in parallel pattern flap based on the dorsal branches of the proper digital artery. METHOD: A patient suffered electric injury in her left index finger with two soft tissue defects, and the areas were 1.6 cm × 1.0 cm and 2.2 cm × 1.2 cm, respectively. And who underwent a homodigital parallel flaps based on the dorsal branches of the proper digital artery to repair in January 2018. The donor sites were covered by full-thickness skin grafting. RESULTS: The flaps and the skin grafting survived uneventfully. All incisions achieved primary healing. The follow-up was 19 months, and the shape of the flaps was satisfactory with soft texture and suitable appearance. TAM of the injured finger was 210°, the level was excellent. The score of VAS was 9. CONCLUSION: The homodigital bilateral flaps in parallel pattern based on the dorsal branches of the proper digital artery are a potential treatment in one-stage for multiple skin soft tissue defects of one finger with reliable blood supply, satisfactory results and simple surgical procedure.

3.
Biosens Bioelectron ; 171: 112712, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33045657

RESUMO

DNA methylation is the predominant epigenetic modification that participates in many fundamental cellular processes through posttranscriptional regulation of gene expression. Aberrant DNA methylation is closely associated with a variety of human diseases including cancers. Therefore, accurate and sensitive detection of DNA methylation may greatly facilitate the epigenetic biological researches and disease diagnosis. In recent years, a series of novel biosensors have been developed for highly sensitive detection of DNA methylation, but an overview of recent advances in biosensors for in vitro detection and especially live-cell imaging of DNA methylation is absent. In this review, we summarize the emerging biosensors for in vitro and in vivo DNA methylation assays in the past five years (2015-2020). Based on the signal types, the biosensors for in vitro DNA methylation assay are classified into five categories including fluorescent, electrochemical, colorimetric, surface enhanced Raman spectroscopy, mass spectrometry, and surface plasmon resonance biosensors, while the biosensors for in vivo DNA methylation assay mainly rely on fluorescent imaging. We review the strategies, features and applications of these biosensors, and provide a new insight into the challenges and future directions in this area.

4.
Biomater Sci ; 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33078791

RESUMO

Gallbladder cancer has high incidence and mortality and a low early diagnosis rate and requires rapid and efficient diagnosis. Herein, carboxyl/amino functionalized polymer dots (Pdots) were designed to enhance cellular internalization and tumor accumulation. The prepared Pdots were 40-50 nm in diameter, contained no toxic metal, exhibited long circulation time and high stability, and produced strong NIR emission and photoacoustic signals. Different cellular uptake and distribution of functionalized Pdots in eight gallbladder cell lines were quantitatively investigated using flow cytometry and super-resolution microscopy. In vivo NIR fluorescence imaging showed that the functional Pdots had high accumulation in the tumor after 30 minutes of injection and remained there for up to 6 days. In addition, photoacoustic imaging found that the abundant blood vessels around the tumor microenvironment and Pdots entered the tumor through the blood vessels. Furthermore, a high heterogeneity of vascular networks was visualized in real-time and high resolution by probe-based confocal laser endomicroscopy imaging. These results offer a new avenue for the development of functional Pdots as a probe for multi-modal and multi-scale imaging of gallbladder cancer in small animals.

6.
Nat Commun ; 11(1): 4455, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32901005

RESUMO

Dysregulated alternative splicing (AS) driving carcinogenetic mitosis remains poorly understood. Here, we demonstrate that cancer metastasis-associated antigen 1 (MTA1), a well-known oncogenic chromatin modifier, broadly interacts and co-expresses with RBPs across cancers, contributing to cancerous mitosis-related AS. Using developed fCLIP-seq technology, we show that MTA1 binds abundant transcripts, preferentially at splicing-responsible motifs, influencing the abundance and AS pattern of target transcripts. MTA1 regulates the mRNA level and guides the AS of a series of mitosis regulators. MTA1 deletion abrogated the dynamic AS switches of variants for ATRX and MYBL2 at mitotic stage, which are relevant to mitosis-related tumorigenesis. MTA1 dysfunction causes defective mitotic arrest, leads to aberrant chromosome segregation, and results in chromosomal instability (CIN), eventually contributing to tumorigenesis. Currently, little is known about the RNA splicing during mitosis; here, we uncover that MTA1 binds transcripts and orchestrates dynamic splicing of mitosis regulators in tumorigenesis.


Assuntos
Carcinogênese/genética , Carcinogênese/metabolismo , Montagem e Desmontagem da Cromatina/fisiologia , Mitose/fisiologia , RNA Mensageiro/metabolismo , Proteínas Repressoras/metabolismo , Transativadores/metabolismo , Processamento Alternativo , Animais , Sítios de Ligação/genética , Montagem e Desmontagem da Cromatina/genética , Instabilidade Cromossômica , Feminino , Células HCT116 , Xenoenxertos , Humanos , Camundongos , Camundongos Nus , Mitose/genética , Neoplasias/genética , Neoplasias/metabolismo , Precursores de RNA/genética , Precursores de RNA/metabolismo , Processamento Pós-Transcricional do RNA , RNA Mensageiro/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas Repressoras/antagonistas & inibidores , Proteínas Repressoras/genética , Transativadores/antagonistas & inibidores , Transativadores/genética
7.
Chin J Cancer Res ; 32(4): 476-484, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32963460

RESUMO

Objective: Family caregivers (FCs) of breast cancer patients play a vital role throughout the treatment process. Psychological distress of FCs is common and often ignored. A simple and effective instrument for screening psychological distress would help in selecting those FCs requiring special attention and intervention. Here, the validity of distress thermometer (DT) in FCs of Chinese breast cancer patients receiving postoperative chemotherapy was assessed, and the prevalence of anxiety and depression was evaluated. Methods: We recruited 200 FCs of hospitalized breast cancer patients in this cross-sectional descriptive study. Before the first cycle of adjuvant chemotherapy, the levels of anxiety and depression among FCs were assessed using DT and Hospital Anxiety and Depression Scale (HADS). In total, 191 valid cases were analyzed. HADS was used as the diagnostic standard to assess the effectiveness of DT as a screening tool for anxiety and depression as well as to analyze the diagnostic efficiency of DT at various cutoff points. Results: The definitive prevalence of both anxiety and depression was 8.90%. The mean level of anxiety and depression among FCs was 5.64±3.69 and 5.09±3.85, respectively, both of which were significantly higher than corresponding Chinese norms (P<0.01). The areas under receiver operating characteristic curves of DT for the diagnoses of FCs' anxiety and depression were 0.904 and 0.885, respectively. A cutoff value of 5 produced the best diagnostic effects of DT for anxiety and depression. Conclusions: The levels of both anxiety and depression were higher in the FCs of Chinese breast cancer patients receiving postoperative chemotherapy than the national norm. DT might be an effective tool to initially screen psychological distress among FCs. This process could be integrated into the palliative care of breast cancer patients and warrant further research.

8.
Chin J Cancer Res ; 32(4): 485-496, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32963461

RESUMO

Objective: The objective of this open-label, randomized study was to compare dose-dense paclitaxel plus carboplatin (PCdd) with dose-dense epirubicin and cyclophosphamide followed by paclitaxel (ECdd-P) as an adjuvant chemotherapy for early triple-negative breast cancer (TNBC). Methods: We included Chinese patients with high recurrence risk TNBC who underwent primary breast cancer surgery. They were randomly assigned to receive PCdd [paclitaxel 150 mg/m2 on d 1 and carboplatin, the area under the curve, (AUC)=3 on d 2] or ECdd-P (epirubicin 80 mg/m2 divided in 2 d and cyclophosphamide 600 mg/m2 on d 1 for 4 cycles followed by paclitaxel 175 mg/m2 on d 1 for 4 cycles) every 2 weeks with granulocyte colony-stimulating factor (G-CSF) support. The primary endpoint was 3-year disease-free survival (DFS); the secondary endpoints were overall survival (OS) and safety. Results: The intent-to-treat population included 143 patients (70 in the PCdd arm and 73 in the ECdd-P arm). Compared with the ECdd-P arm, the PCdd arm had significantly higher 3-year DFS [93.9% vs. 79.1%; hazard ratio (HR)=0.310; 95% confidence interval (95% CI), 0.137-0.704; log-rank, P=0.005] and OS (98.5% vs. 92.9%; HR=0.142; 95% CI, 0.060-0.825; log-rank, P=0.028). Worse neutropenia (grade 3/4) was found in the ECdd-P than the PCdd arm (47.9% vs. 21.4%, P=0.001). Conclusions: PCdd was superior to ECdd-P as an adjuvant chemotherapy for early TNBC with respect to improving the 3-year DFS and OS. PCdd also yielded lower hematological toxicity. Thus, PCdd might be a preferred regimen for early TNBC patients with a high recurrence risk.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32940848

RESUMO

PURPOSE: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with poor survival outcomes. Metformin has been shown to have antitumor effects by lowering serum levels of the mitogen insulin and having pleiotropic effects on cancer cell signaling pathways. BMS-754807 is a potent and reversible inhibitor of both insulin-like growth factor 1 receptor (IGF-1R) and insulin receptor (IR). Both drugs have been reported to have some efficacy in TNBC. However, it is unclear whether the combination of the two drugs is more effective than single drug treatment in TNBC. METHODS: We treated a panel of TNBC cell lines with metformin and BMS-754807 alone and in combination and tested cell viability using MTS assays. We used the CompuSyn software to analyze for additivity, synergism, or antagonism. We also examined the molecular mechanism by performing reverse phase protein assay (RPPA) to detect the candidate pathways altered by single drugs and the drug combination and used Western blotting to verify and expand the findings. RESULTS: The combination of metformin and BMS-754807 showed synergy in 11 out of 13 TNBC cell lines tested (85%). RPPA analysis detected significant alterations by the drug combination of multiple proteins known to regulate cell cycle and tumor growth. In particular, the drug combination significantly increased levels of total and phosphorylated forms of the cell cycle inhibitor p27Kip1 and decreased the level of the p27Kip1 E3 ligase SCFSkp2. CONCLUSIONS: We conclude that the combination of metformin and BMS-754807 is more effective than either drug alone in inhibiting cell proliferation in the majority of TNBC cell lines, and that one important mechanism may be suppression of SCFSkp2 and subsequent stabilization of the cell cycle inhibitor p27Kip1. This combination treatment may represent an effective targeted therapy for a significant subset of TNBC cases and should be further evaluated.

10.
Photosynth Res ; 146(1-3): 287-297, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32766997

RESUMO

Photosynthetic organisms use different means to regulate their photosynthetic activity in respond to different light conditions under which they grow. In this study, we analyzed changes in the photosystem I (PSI) light-harvesting complex I (LHCI) supercomplex from a red alga Cyanidioschyzon merolae, upon growing under three different light intensities, low light (LL), medium light (ML), and high light (HL). The results showed that the red algal PSI-LHCI is separated into two bands on blue-native PAGE, which are designated PSI-LHCI-A and PSI-LHCI-B, respectively, from cells grown under LL and ML. The former has a higher molecular weight and binds more Lhcr subunits than the latter. They are considered to correspond to the two types of PSI-LHCI identified by cryo-electron microscopic analysis recently, namely, the former with five Lhcrs and the latter with three Lhcrs. The amount of PSI-LHCI-A is higher in the LL-grown cells than that in the ML-grown cells. In the HL-grown cells, PSI-LHCI-A completely disappeared and only PSI-LHCI-B was observed. Furthermore, PSI core complexes without Lhcr attached also appeared in the HL cells. Fluorescence decay kinetics measurement showed that Lhcrs are functionally connected with the PSI core in both PSI-LHCI-A and PSI-LHCI-B obtained from LL and ML cells; however, Lhcrs in the PSI-LHCI-B fraction from the HL cells are not coupled with the PSI core. These results indicate that the red algal PSI not only regulates its antenna size but also adjusts the functional connection of Lhcrs with the PSI core in response to different light intensities.

11.
Breast ; 53: 172-180, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32836201

RESUMO

BACKGROUND: There is a lack of prognostic models predicting the overall survival (OS) of advanced breast cancer (ABC) patients in China. METHODS: Data from the China National Cancer Center database that recorded 4039 patients diagnosed with breast cancer between 1987 and 2019 were extracted and a total of 2263 ABC participants were enrolled in this study, which were further randomized 3:1 and divided into training (n = 1706) and validation (n = 557) groups. The nomogram was built based on independent predictors identified by univariate and multivariate cox regression analyses. The discriminatory and predictive capacities of the nomogram were assessed by Harrell's concordance index (C-index) and calibration plots. RESULTS: Univariate and multivariate analyses found that age, Eastern Cooperative Oncology Group (ECOG) score, T-stage, N-stage, tumor subtype, the presence of distant lymph node (DLN)/liver/brain metastasis, local therapy, efficacy of first-line therapy and metastatic-free interval (MFI) were significantly related to OS (all P < 0.05). These variables were incorporated into a nomogram to predict the 2-year and 3-year OS of ABC patients. The C-indexes of the nomogram were 0.700 (95% confidence interval [CI]: 0.683-0.717) for the training set and 0.686 (95% CI: 0.652-0.719) for the validation set. The calibration curves revealed satisfactory consistency between actual survival and nomogram prediction in both the internal and external validations. The nomogram was capable of stratifying patients into different risk cohorts. CONCLUSIONS: We constructed and validated a nomogram that might serve as an efficient tool to provide prognostic prediction for ABC patients and guide the physicians to make personalized treatment decisions.

12.
Arch Physiol Biochem ; : 1-8, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32757960

RESUMO

The authors conducted this meta-analysis to robustly estimate relationships between polymorphisms in VDR gene and the risk of osteoporosis by integrating the results of previous works. Medline, Embase, Wanfang, VIP and CNKI were searched thoroughly for eligible studies, and 73 genetic association studies were finally included in this meta-analysis. We noticed that ApaI rs7975232, BsmI rs1544410 and TaqI rs731236 polymorphisms were significantly associated with the risk of osteoporosis in Caucasians. Moreover, BsmI rs1544410 and FokI rs10735810 polymorphisms were significantly associated with the risk of osteoporosis in Asians. In conclusion, this meta-analysis demonstrates that ApaI rs7975232, BsmI rs1544410 and TaqI rs731236 polymorphisms may influence the risk of osteoporosis in Caucasians, while BsmI rs1544410 and TaqI rs731236 polymorphisms may influence the risk of osteoporosis in Asians.

13.
Carcinogenesis ; 2020 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-32860508

RESUMO

Long non-coding RNAs (lncRNAs) regulate a series of biological processes, and their anomalous expression exerts critical roles in progression of multiple malignancies, including colorectal cancer (CRC). The present study was designed to provide new ideas and perspectives for the role of lncRNA MCF2L-AS1 and disclose the underlying mechanism in CRC. Herein, we observed that MCF2L-AS1 expression was enriched in CRC tissues and cell lines. Additionally, silencing of MCF2L-AS1 dramatically impeded cell proliferation, invasion and migration capacities of CRC, and distinctly attenuated the expression of invasion associated targets MMP-2 and MMP-9. Moreover, depletion of MCF2L-AS1 apparently restricted the glucose consumption and lactate production, and downregulated GLUT1 and LDHA expression. More importantly, we predicted and verified that MCF2L-AS1 acted as a molecular sponge for miR-874-3p and inversely regulated miR-874-3p expression. Interesting, FOXM1 was identified as direct target of miR-874-3p, and positively modulated by MCF2L-AS1 through sponging miR-874-3p. Mechanistically, MCF2L-AS1 accelerated cell proliferation, invasion and glycolysis through competitively binding to miR-874-3p, leading to enhance FOXM1 expression. Collectively, these outcomes highlighted that MCF2L-AS1 acted as a motivator by modulating the miR-874-3p/FOXM1 axis, thereby aggravating tumorigenesis and glycolysis progress of CRC, disclosing that MCF2L-AS1 may serve as a valuable and promising therapeutic strategy for CRC.

14.
Sci Adv ; 6(33): eaaz8850, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32851160

RESUMO

Immunoglobulin heavy chain (IgH) genes are assembled by two sequential DNA rearrangement events that are initiated by recombination activating gene products (RAG) 1 and 2. Diversity (DH) gene segments rearrange first, followed by variable (VH) gene rearrangements. Here, we provide evidence that each rearrangement step is guided by different rules of engagement between rearranging gene segments. DH gene segments, which recombine by deletion of intervening DNA, must be located within a RAG1/2 scanning domain for efficient recombination. In the absence of intergenic control region 1, a regulatory sequence that delineates the RAG scanning domain on wild-type IgH alleles, VH and DH gene segments can recombine with each other by both deletion and inversion of intervening DNA. We propose that VH gene segments find their targets by distinct mechanisms from those that apply to DH gene segments. These distinctions may underlie differential allelic choice associated with each step of IgH gene assembly.

15.
Eur J Nutr ; 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32856190

RESUMO

PURPOSE: This study aimed to assess the effects of folic acid (FA) combined with a docosahexaenoic acid (DHA) intervention on the cognitive function and inflammatory cytokines in elderly subjects with mild cognitive impairment (MCI). METHODS: This randomized, double-blind, placebo-controlled trial recruited 240 individuals with MCI in Tianjin, China, and randomly allocated into 4 groups: FA + DHA (FA 800 µg/d + DHA 800 mg/d), FA (FA 800 µg/d), DHA (DHA 800 mg/d), and placebo. Cognitive function, serum folate and homocysteine (Hcy), plasma DHA and inflammatory cytokines levels were measured at baseline and 6 months. RESULTS: Daily oral FA, DHA and their combined use for 6 months significantly improved the full-scale intelligence quotient (FSIQ) and some subtests of Wechsler Adult Intelligence Scale compared to the placebo. The increases of FSIQ, arithmetic, picture completion scores in the FA group and picture completion, block design scores in the DHA group were significantly less than that in the FA combined DHA group (P < 0.05). Meanwhile, daily oral FA, DHA and their combined use for 6 months significantly decreased plasma inflammatory cytokines compared to the placebo. The changes of interleukin-1ß levels in the FA group and interleukin-6 levels in the DHA group were significantly less than that in the FA + DHA group (P < 0.05). CONCLUSIONS: Daily oral FA, DHA and their combined use for 6 months can significantly improve cognitive function and decrease plasma inflammatory cytokines in MCI individuals. The combination of FA and DHA was more beneficial than each individual nutrient on their own.

16.
Breast ; 53: 111-118, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32738630

RESUMO

BACKGROUND: Genome-wide chromosomal instability, instead of specific somatic mutations or copy-number alterations in selected genes, is a significant property of cancer and may suggest a new strategy for treatment. Here we utilized cell-free DNA (cfDNA) sequencing to display the whole picture of chromosomal instability in patients with metastatic breast cancer (MBC), and evaluate its predictive value for patient survival. METHODS: The clinical data of 65 patients who had frozen plasma and planned to change the therapeutic regimen were retrospectively enrolled. Low-coverage whole-genome sequencing of cfDNA was performed to generate the chromosomal instability represented by chromosomal instability (CIN) score. RESULTS: Tumors with diverse status of hormone receptor and HER2 represented diverse chromosomal instability across the whole genome. According to the receiver operating characteristic curve and the statistical distribution, CIN score exceed 3881 was defined as "High". 32 (53.3%) patients with high CIN score had similar clinicopathologic characteristics compared with low CIN score patients. The median overall survival of patients with high CIN score was 21.2 months (95% CI 14.1-28.3), which was significantly inferior to those with low CIN score (not reached, P = 0.006). Regardless of various treatment regimens, the median progression free survival in patients with high CIN score was 7.3 months, which was significantly worse than those in the low CIN score population (11.0 months, P = 0.034). Multivariate analysis revealed that CIN score was an independent prognostic factor, with hazard ratio of 3.563 (P = 0.005). CONCLUSIONS: To our knowledge, this is the first study illustrating the prognostic value of chromosomal instability derived from cfDNA in MBC.

17.
J Phys Chem Lett ; 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32787324

RESUMO

Photo-induced phase segregation (PIPS) of mixed-halide perovskites (MHPs), due to halogen migration, has reaped considerable attentions for its retroaction on film photostability and photovoltaic output. Nevertheless, the original mechanism is still unclear to date. Herein, taking the representative CsPbIBr2 material as an example, confocal laser scanning microscope (CLSM) technique is adopted to track PIPS and dark recovery procedures. Besides the aggregation of iodide-rich (I-rich) domains at grain boundaries (GBs), some sporadic iodide "islands" with a swifter light response also appear throughout the polycrystalline films. It illustrates again that GBs are not essential for iodide aggregation. Furthermore, the iodide "islands" have substantial influence on device's open-circuit voltage (Voc), resulting in an obvious plunge in the first tens of seconds. Results reveal the internal reason for the failure to reach larger Voc outputs, expected from wide-bandgap perovskites. Importantly, this finding can help promote the exploration of efficient means to stabilize MHPs.

18.
Bioinformatics ; 2020 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-32805023

RESUMO

: There are seven known coronaviruses that infect humans: four mild coronaviruses, including HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1, only cause mild respiratory diseases, and three severe coronaviruses, including SARS-CoV, MERS-CoV and SARS-CoV-2, can cause severe respiratory diseases even death of infected patients. Both infection and death caused by SARS-CoV-2 are still rapidly increasing worldwide. In this study, we demonstrate that viral coding proteins of SARS-CoV-2 have distinct features and are most, medium and least conserved with SARS-CoV, MERS-CoV, and the rest four mild coronaviruses (HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1), respectively. Moreover, expression of host responsive genes (HRG), HRG-enriched biological processes, and HRG-enriched KEGG pathways upon infection of SARS-CoV-2 show slightly overlapping with SARS-CoV and MERS-CoV but distinctive to the four mild coronaviruses. Interestingly, enrichment of overactivation of neutrophil by HRGs is only and commonly found in infections of severe SARS-CoV-2, SARS-CoV, and MERS-CoV but not in the other four mild coronaviruses, and the related gene networks show different patterns. Clinical data supports that overactivation of neutrophil for severe patients can be one major factor for the similar clinical symptoms observed in SARS-CoV-2 infection compared to infections of the other two severe coronavirus (SARS-CoV, and MERS-CoV). Taken together, our study provides a mechanistic insight into SARS-CoV-2 epidemic via revealing the conserved and distinct features of SARS-CoV-2, raising the critical role of dysregulation of neutrophil for SARS-CoV-2 infection. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

19.
PLoS Genet ; 16(8): e1008989, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32810129

RESUMO

Drosophila Myc (dMyc), as a broad-spectrum transcription factor, can regulate the expression of a large number of genes to control diverse cellular processes, such as cell cycle progression, cell growth, proliferation and apoptosis. However, it remains largely unknown about whether dMyc can be involved in Drosophila innate immune response. Here, we have identified dMyc to be a negative regulator of Drosophila Imd pathway via the loss- and gain-of-function screening. We demonstrate that dMyc inhibits Drosophila Imd immune response via directly activating miR-277 transcription, which further inhibit the expression of imd and Tab2-Ra/b. Importantly, dMyc can improve the survival of flies upon infection, suggesting inhibiting Drosophila Imd pathway by dMyc is vital to restore immune homeostasis that is essential for survival. Taken together, our study not only reports a new dMyc-miR-277-imd/Tab2 axis involved in the negative regulation of Drosophila Imd pathway, and provides a new insight into the complex regulatory mechanism of Drosophila innate immune homeostasis maintenance.


Assuntos
Proteínas de Ligação a DNA/genética , Proteínas de Drosophila/genética , Imunidade Inata/genética , MicroRNAs/genética , Fatores de Transcrição/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Divisão Celular/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Homeostase/genética , Humanos , Transdução de Sinais/genética , Fatores de Transcrição/metabolismo , Transcrição Genética/genética
20.
Dev Comp Immunol ; 114: 103838, 2020 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-32846160

RESUMO

The signal transducer and activator of transcription (STAT), as an important transcription factor of the Janus kinase (JAK)-STAT signaling pathway, is pivotal for development and immunity and well documented in vertebrates. However, the STAT gene has not been reported in chordate amphioxus (Branchiostoma belcheri). In this study, we firstly identify and characterize two STAT genes from Branchiostoma belcheri (designed as AmphiSTATa and AmphiSTATb). Secondly, our results reveal that AmphiSTATa is clustered with vertebrate STAT1, STAT2, STAT3 and STAT4, whereas AmphiSTATb is grouped with STAT5 and STAT6 based on phylogenetic analysis. Thirdly, AmphiSTATa and AmphiSTATb are found to widely express in five representative tissues of amphioxus (gill, hepatic cecum, intestine, muscle and notochord) by RT-qPCR analysis. Importantly, both AmphiSTATa and AmphiSTATb can be involved in innate immune responses to LPS stimulation. Fourthly, we demonstrate that AmphiSTATa and AmphiSTATb can form homodimers or heterodimers by Co-IP and Native-PAGE assay, and that AmphiSTATa and AmphiSTATb proteins can also distribute in cytoplasm and nucleus by the subcellular localization. Taken together, our findings not only reveal the roles of AmphiSTATa and AmphiSTATb in amphioxus innate immune responses to LPS stimulation, but provide a new insight into further elucidating the evolution and function of STATs in animals.

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