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1.
Mol Cancer ; 20(1): 9, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407516

RESUMO

BACKGROUND: MicroRNAs (miRNAs) show considerable promise as therapeutic agents to improve tumor treatment, as they have been revealed as crucial modulators in tumor progression. However, our understanding of their roles in gastric carcinoma (GC) metastasis is limited. Here, we aimed to identify novel miRNAs involved in GC metastasis and explored their regulatory mechanisms and therapeutic significance in GC. METHODS: The microRNA expression profiles of GC tumors at different stages and at different metastasis statuses were compared respectively using the stomach adenocarcinoma (STAD) miRNASeq dataset in TCGA. Using the above method, miR-4521 was picked out for further study. miR-4521 expression in GC tissues was examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH). Highly and lowly invasive cell sublines were established using a repetitive transwell assay. Gain-of-function and loss-of-function analyses were performed to investigate the functions of miR-4521 and its upstream and downstream regulatory mechanisms in vitro and in vivo. Moreover, we investigated the therapeutic role of miR-4521 in a mouse xenograft model. RESULTS: In this study, we found that miR-4521 expression was downregulated in GC tissues compared with adjacent normal tissues and that its downregulation was positively correlated with advanced clinical stage, metastasis status and poor patient prognosis. Functional experiments revealed that miR-4521 inhibited GC cell invasion and metastasis in vitro and in vivo. Further studies showed that hypoxia repressed miR-4521 expression via inducing ETS1 and miR-4521 mitigated hypoxia-mediated metastasis, while miR-4521 inactivated the AKT/GSK3ß/Snai1 pathway by targeting IGF2 and FOXM1, thereby inhibiting the epithelial-mesenchymal transition (EMT) process and metastasis. In addition, we demonstrated that therapeutic delivery of synthetic miR-4521 suppressed gastric carcinoma progression in vivo. CONCLUSIONS: Our results suggest an important role for miR-4521 in regulating GC metastasis and hypoxic response of tumor cells as well as the therapeutic significance of this miRNA in GC.

2.
Medicine (Baltimore) ; 100(1): e24239, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33429826

RESUMO

RATIONALE: Subarachnoid hemorrhages (SAHs) from ruptured intracranial aneurysms are very rare during pregnancy. Management of ruptured intracranial aneurysms with SAH in pregnancy is often challenging because of the risks to the fetus and the mother. We present the first successful awake endovascular coiling of a dissected intracranial aneurysm in a third trimester twin pregnancy. PATIENT CONCERNS: A 28 years' old pregnant woman was admitted at the obstetric department of our hospital on account of very severe headaches associated with nausea and vomiting. DIAGNOSIS: Emergency obstetric ultrasound scan done confirmed 32 weeks' twin gestation, whereas magnetic resonance imaging established hemorrhage in the suprasellar cistern and the subarachnoid space. Magnetic resonance angiography revealed a dissected aneurysm in the ophthalmic segment of the left internal carotid artery. INTERVENTIONS: Awake cerebral angiography as well as embolization of the aneurysm with coils was done via the transarterial route and the twins were delivered via caesarean section at 37 weeks' gestation. OUTCOMES: Two years' follow-up indicated no complications and children as well as their mother are healthy. LESIONS: Awake endovascular coiling was very beneficial in our case because we avoided general anesthesia and the use of osmotic diuretics which are potentially hazardous during pregnancy.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33387318

RESUMO

The continuous outbreak of haze pollution attracted full attention and became one of the most severe environmental problems in China. Based on the panel data of 266 prefecture-level cities from 2000 to 2016, this paper investigates the effects of haze pollution on China's urban innovation. Results show that (1) haze pollution does not damage urban innovation but forms a crisis-driven effect to stimulate it. (2) Haze pollution enhances the public's environmental awareness, which induces the government to invest more in science and technology, and finally forces the improvement of urban innovation. (3) Haze pollution causes the loss of human capital and leading to a decrease in the number of people who engaged in scientific research, which weakens the city's technological innovation ability. (4) The crisis-driven effect caused by haze pollution boosts the improvement of technological innovation in eastern cities, large cities, and northern cities. This study enriches the evidence on the relationship between haze pollution and urban innovation, which is significant for local governments to formulate green development and innovation-driven strategies.

4.
Bioresour Technol ; 322: 124555, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33352391

RESUMO

A bacterial strain was isolated and identified as Pseudomonas sp. DM02 from an aquaculture system. Strain DM02 showed efficient heterotrophic nitrification-aerobic denitrification capability. Total ammonia nitrogen (TAN, 10 mg/L) could be completely removed by strain DM02 within 12 h under low nutrient condition. Nitrogen mass balance indicated that 70.8% of the initial TAN was translated into gaseous nitrogen and 28.1% was converted into intracellular nitrogen. Various carbon sources can be used for nitrate removal (>95% within 28 h). The optimal conditions for TAN, nitrate and nitrite removal were pH 7 with carbon/nitrogen (C/N) ratios of 8, 12 and 12, respectively. The napA, nirK, and nosZ functional genes were successful amplified from strain DM02. Both bioaugmentation and immobilized technology of strain DM02 present ability (>88%) for continuous treatment of real aquaculture wastewater. This research indicated a great potential for practical application of Pseudomonas sp. DM02 in aquaculture wastewater treatment.


Assuntos
Nitrogênio , Purificação da Água , Aerobiose , Aquicultura , Desnitrificação , Processos Heterotróficos , Nitratos , Nitrificação , Nitritos , Pseudomonas/genética
5.
Talanta ; 221: 121670, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33076176

RESUMO

Tumor-derived extracellular vesicles (TEVs) have emerged as promising sources of diagnostic and prognostic biomarkers for nasopharyngeal carcinoma (NPC). However, the lack of high-sensitivity analytic methods for ultratrace membrane proteins on TEVs hamper their clinical application of TEVs. Herein, by combining aptamers that specifically bind to protein targets on TEVs, PCR-based exponential amplification and CRISPR/Cas12a real-time DNA detection, we developed a novel technique, termed the aptamer-CRISPR/Cas12a assay, to detect CD109+ and EGFR+ TEVs from cell lines and complex biofluids. The platform enables highly sensitive detection of CD109+ and EGFR+ TEVs at as low as 100 particles/mL with a linear range spanning 6 orders of magnitude (102-108 particles/mL), which was found to be sufficient to effectively detect TEV proteins directly in low-volume (50 µl) samples. Furthermore, clinical serum sample analysis verified that the combination of serum CD109+ and EGFR+ TEV levels yielded high diagnostic accuracy, with an AUC of 0.934 (95% CI: 0.868-1.000), a sensitivity of 84.1% and a specificity of 85.0%, in discriminating NPC from healthy controls. Moreover, the dramatic decrease in both biomarkers in responders after radiotherapy indicated their potential roles in radiotherapy surveillance. Given that the aptamer-CRISPR/Cas12a assay rapidly and conveniently detects ultralow concentrations of CD109+ and EGFR+ TEVs directly in serum, it could be useful in NPC diagnosis and prognosis.

6.
Medicine (Baltimore) ; 99(52): e23674, 2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33350748

RESUMO

BACKGROUND: Tuberculosis is an infectious disease caused by mycobacterium tuberculosis. It may occur in multiple parts and organs of the patients body, and the lung is the most common. It is a major health threat worldwide. Hepatotoxicity is a common adverse reaction of commonly used clinical anti-tuberculosis drugs, as well as one of the important factors leading to poor prognosis of tuberculosis. Milk thistle is a traditional Chinese medicine extract derived from the mature fruit of Silybum marianum. Clinical practice shows that milk thistle has a good anti-liver injury effect and can be used to prevent anti-tuberculosis drug-induced liver injury. However, there is a lack of evidence-based medicine. The research carried out in this protocol is to systematically evaluate the efficacy and safety of milk thistle preventive treatment of anti-tuberculosis drug-induced liver injury, and to improve the evidence-based basis for clinical application of milk thistle in the preventive treatment of anti-tuberculosis drug-induced liver injury. METHOD: Computer search of English databases (PubMed, the Cochrane Library, Embase, Web of Science) and Chinese databases (CNKI, VIP, Wanfang, China Biology Medicine disc (CBMdisc)) was performed. From the establishment of database to October 2020, 2 researchers independently extracted and evaluated the data included in the randomized controlled clinical research of milk thistle preventive treatment of anti-tuberculosis drug-induced liver injury, and used RevMan5.3 software to conduct a meta-analysis of the included literature. RESULT: In this research, the efficacy and safety of milk thistle preventive treatment of anti-tuberculosis drug-induced liver injury were evaluated by indicators such as the incidence of liver injury, bilirubin levels, and liver enzyme levels. CONCLUSION: In this research, reliable evidence-based evidence for the clinical application of milk thistle in the preventive treatment of anti-tuberculosis drug-induced liver injury was provided. OSF REGISTRATION NUMBER: DOI: 10.17605/OSF.IO/VC3RM.


Assuntos
Antituberculosos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Medicamentos de Ervas Chinesas/uso terapêutico , Cardo-Mariano , Tuberculose Pulmonar/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Humanos , Resultado do Tratamento
7.
ACS Nano ; 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33295753

RESUMO

Luminescence nanomaterial-based lateral flow assay (LFA) is promising for point-of-care tests. However, the detection sensitivity and accuracy are often affected by the interferences of autofluorescence and photon scattering from nitrocellulose membrane and colored plasma. Here, we describe a near-infrared to near-infrared upconversion nanoparticle (UCNP) immunolabeled LFA for background-free chromatographic detection of sepsis biomarker procalcitonin (PCT) in clinical human plasma. This upconversion immunolabeling enables both light excitation (at ∼980 nm) and anti-Stokes emission (at 800 nm) to be adopted within the first biological window (700-1000 nm), which eliminates background autofluorescence as well as photon scattering interferences, empowering a high-sensitivity detection without complicated procedures. After optimization, the described assay presented a limit of detection reaching down to 0.03 ng/mL, lower than the normal level (0.05 ng/mL), while having a detection range of 0.03-50 ng/mL that covers the clinical PCT level of interest (0.5-10 ng/mL). The assay recoveries in human serum samples were evaluated to be about 95-110%, whereas the inter- and intra-assay coefficient variations were both determined to be below 15%. Importantly, measured PCT concentrations in clinical samples are in good correlation with that of the electrochemiluminescence immunoassay (Roche) widely applied in large clinical settings. This near-infrared to near-infrared upconversion immunolabeling approach has direct implications for ultrasensitive and background-free point-of-care detection of other serum biomarkers in resource-limited clinical settings.

8.
Ann Bot ; 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33252661

RESUMO

BACKGROUND AND AIMS: Cephalotaxus is a paleo-endemic genus in East Asia that consists of ~7-9 conifer species. Despite its great economic and ecological importance, the relationships between Cephalotaxus and related genera, as well as the interspecific relationships within Cephalotaxus, have long been controversial, resulting in contrasting taxonomic proposals in delimitation of Cephalotaxaceae and Taxaceae. Based on plastome data, this study aims to reconstruct a robust phylogeny to infer the systematic placement and the evolutionary history of Cephalotaxus. METHODS: A total of eleven plastomes, representing all species currently recognized in Cephalotaxus and two Torreya species, were sequenced and assembled. Combining these with previously published plastomes, we reconstructed a phylogeny of Cephalotaxaceae and Taxaceae with nearly full taxonomic sampling. Under a phylogenetic framework and molecular dating, the diversification history of Cephalotaxus and allied genera was explored. KEY RESULTS: Phylogenetic analyses of 81 plastid protein-coding genes recovered robust relationships between Cephalotaxus and related genera, as well as providing a well-supported resolution of interspecific relationships within Cephalotaxus, Taxus, Torreya and Amentotaxus. Divergence time estimation indicated that most extant species of these genera are relatively young, although fossil and other molecular evidence consistently show these genera are ancient plant lineages. CONCLUSIONS: Our results justify the taxonomic proposal that recognizes Cephalotaxaceae as a monotypic family, and contribute to a clear-cut delineation between Cephalotaxaceae and Taxaceae. Given that extant species of Cephalotaxus are derived from recent divergence events associated with the establishment of monsoonal climates in East Asia and Pleistocene climatic fluctuations, they are not evolutionary relics.

9.
Chem Commun (Camb) ; 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33140754

RESUMO

To reach the promising potential of circularly polarized luminescence (CPL) emitters, high CPL brightness must be achieved. We describe the synthesis of analogues of the C3-symmetrical Shibasaki's lanthanide complexes (Sm, Tb, Dy) supported by enantiopure 5,5',6,6',7,7',8,8'-octahydro-1,1'-bi-2-naphthol (H8-Binol). The complexes exhibit visible luminescence in solution with exceptionally high quantum yields for Sm (4%) and Dy (17%), and strong circularly polarized luminescence for Sm, Tb, and Dy (|glum| up to 0.44, 0.32, 0.33, respectively). Altogether, these complexes possess amongst the strongest CPL brightness reported to date in lanthanide molecular complexes (up to 782 M-1 cm-1 for Tb).

10.
Transfus Med ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33000534

RESUMO

OBJECTIVE: The COVID-19 epidemic has caused a significant global social and economic impact since December 2019. The objective of this study was to demonstrate the emergency response of a Chinese blood centre on maintaining both the safety and the sufficiency of blood supply during large, emerging, infectious epidemics. MATERIALS AND METHODS: Early on in the outbreak of COVID-19, the Chengdu Blood Center developed strategies and implemented a series of measures, including enhanced recruitment efforts, addition of new donation deferral criteria and notification after donation, optimisation of donor experience, development and implementation of a new coronavirus nucleic acid detection technology platform for blood screening and screening all donations for SARS-CoV-2 RNA to maximumly protect the safety of blood supply during a time of unclear risk. RESULTS: Starting on February 20, the immediate satisfaction rate of blood product orders in Chengdu city's clinical settings reached 100%, and there was no case of blood transfusion infection. CONCLUSION: The recent experience during the outbreak of SARS-CoV-2 reminded us that improvement in the areas of national and international collaborative programmes for dealing with blood availability and safety concerns during early stages of a disaster and regional and national mechanisms for timely communication with the general public on behalf of blood services should help to better prepare us for future disasters.

11.
Nat Commun ; 11(1): 5362, 2020 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-33097710

RESUMO

Human C-terminal binding protein (CtBP)-interacting protein (CtIP) is a central regulator to initiate DNA end resection and homologous recombination (HR). Several studies have shown that post-translational modifications control the activity or expression of CtIP. However, it remains unclear whether and how cells restrain CtIP activity in unstressed cells and activate CtIP when needed. Here, we identify that USP52 directly interacts with and deubiquitinates CtIP, thereby promoting DNA end resection and HR. Mechanistically, USP52 removes the ubiquitination of CtIP to facilitate the phosphorylation and activation of CtIP at Thr-847. In addition, USP52 is phosphorylated by ATM at Ser-1003 after DNA damage, which enhances the catalytic activity of USP52. Furthermore, depletion of USP52 sensitizes cells to PARP inhibition in a CtIP-dependent manner in vitro and in vivo. Collectively, our findings reveal the key role of USP52 and the regulatory complexity of CtIP deubiquitination in DNA repair.


Assuntos
Proteínas de Ligação a DNA/metabolismo , DNA/metabolismo , Endodesoxirribonucleases/metabolismo , Exorribonucleases/metabolismo , Ubiquitinação/fisiologia , Animais , Dano ao DNA , Exorribonucleases/genética , Feminino , Células HEK293 , Recombinação Homóloga , Humanos , Camundongos , Camundongos Nus , Fosforilação , Ligação Proteica , Processamento de Proteína Pós-Traducional , Ensaios Antitumorais Modelo de Xenoenxerto
12.
J Phys Chem Lett ; : 8790-8798, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32985887

RESUMO

Magnesium primary cells are currently experiencing a renaissance following the suggestion of new strategies to boost their performance. The strategies suggested will maintain utilization efficiencies of 30-70%, which is considered to be relatively modest. In this work, the highest ever reported level of utilization efficiency of 82% is achieved for a Mg-based primary cell using a synergistic combination of electrolyte additives. It is demonstrated that the joint use of sodium nitrate and salicylate as electrolyte additives allows us to reach the aforementioned utilization efficiency of 5 mA/cm2 via offering an effective suppression of anode self-corrosion and uniform Mg dissolution under discharge conditions.

13.
Sci Adv ; 6(37)2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32917705

RESUMO

DNA double-strand breaks (DSBs) are highly toxic lesions that can drive genetic instability. These lesions also contribute to the efficacy of radiotherapy and many cancer chemotherapeutics. DNA repair efficiency is regulated by both intracellular and extracellular chemical signals. However, it is largely unknown whether this process is regulated by physical stimuli such as extracellular mechanical signals. Here, we report that DSB repair is regulated by extracellular mechanical signals. Low extracellular matrix (ECM) stiffness impairs DSB repair and renders cells sensitive to genotoxic agents. Mechanistically, we found that the MAP4K4/6/7 kinases are activated and phosphorylate ubiquitin in cells at low stiffness. Phosphorylated ubiquitin impairs RNF8-mediated ubiquitin signaling at DSB sites, leading to DSB repair deficiency. Our results thus demonstrate that ECM stiffness regulates DSB repair efficiency and genotoxic sensitivity through MAP4K4/6/7 kinase-mediated ubiquitin phosphorylation, providing a previously unidentified regulation in DSB-induced ubiquitin signaling.

14.
Theranostics ; 10(22): 10262-10273, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32929347

RESUMO

Tumor-derived extracellular vesicle (TEV) protein biomarkers facilitate cancer diagnosis and prognostic evaluations. However, the lack of reliable and convenient quantitative methods for evaluating TEV proteins prevents their clinical application. Methods: Here, based on dual amplification of hybridization chain reaction (HCR) and CRISPR-Cas12a, we developed the apta-HCR-CRISPR assay for direct high-sensitivity detection of TEV proteins. The TEV protein-targeted aptamer was amplified by HCR to produce a long-repeated sequence comprising multiple CRISPR RNA (crRNA) targetable barcodes, and the signals were further amplified by CRISPR-Cas12a collateral cleavage activities, resulting in a fluorescence signal. Results: The established strategy was verified by detecting the TEV protein markers nucleolin and programmed death ligand 1 (PD-L1). Both achieved limit of detection (LOD) values as low as 102 particles/µL, which is at least 104-fold more sensitive than aptamer-ELISA and 102-fold more sensitive than apta-HCR-ELISA. We directly applied our assay to a clinical analysis of circulating TEVs from 50 µL of serum, revealing potential applications of nucleolin+ TEVs for nasopharyngeal carcinoma cancer (NPC) diagnosis and PD-L1+ TEVs for therapeutic monitoring. Conclusion: The platform was simple and easy to operate, and this approach should be useful for the highly sensitive and versatile quantification of TEV proteins in clinical samples.

15.
Virol J ; 17(1): 127, 2020 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-32831118

RESUMO

BACKGROUND: There has been little published data on estimates of HBV and/or HCV coinfection in HIV-positive patients in China or an understanding of how this coinfection varies with different factors. Therefore, this study aimed to determine, through a systematic review and meta-analysis, the prevalence of HBV and/or HCV in HIV-positive patients in China and explore variations in prevalence. METHODS: The Medicine, Web of Science, Chinese Web of Knowledge, and Wanfang databases were searched using a search strategy combining key words and related disease-specific subject terms to identify relevant cohort or cross-sectional studies published up to April 2019. Included articles were assessed for quality. Pooled prevalence and 95% confidence intervals (CIs) were calculated according to study region and other specific characteristics. RESULTS: Our searches identified 7843 records, but only 66 studies were included in our meta-analysis. The pooled HBsAg prevalence in HIV-positive patients was 13.7% (95% CI 12.3-15.3%), with variations found in terms of age and geographic region. The meta-HCV prevalence was 24.7% (95% CI 19.3-30.5%), which varied over the study period and age. The pooled HBV-HCV coinfection prevalence was 3.5% (95% CI 2.4-4.8%), with variations found in terms of age and geographic region. CONCLUSION: Given the high burden of HBV and HCV coinfections in HIV-positive patients, the incorporation of comprehensive screening, treatment, prevention, and vaccination programs into general HIV management in China is imperative.

16.
Chem Commun (Camb) ; 56(72): 10552-10555, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32785314

RESUMO

A multicomponent catalytic reaction between ketones, Morita-Baylis-Hillman (MBH) carbonates and trifluoromethylthiolating agents is devised for straightforwardly accessing two products, α-trifluoromethylthiolated ketones and α-methylene ß-amino esters in a one pot fashion. Particularly noteworthy is that the trifluoromethylthiolating reagent is employed as both the nitrogen and SCF3 source initiated by DABCO. This mild one pot strategy enjoys atom- and step-economic attractiveness, for direct introduction of an SCF3 group onto a variety of acyclic ketones, which have been considered as less effective and less developed substrates.

17.
Diabetes Metab Res Rev ; : e3394, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32798322

RESUMO

AIMS: Circular RNAs (circRNAs) have recently been shown to exert important effects in human diseases. However, the roles of circRNAs in type 1 diabetes (T1D) are largely unknown. This study is to identify the circRNA expression profiles in the peripheral blood of patients with T1D and predict their potential regulatory mechanisms and coding potential. METHODS: CircRNA expression profiles were detected by Arraystar human circRNA microarray. With real-time PCR validation, multiple bioinformatics approaches were used to explore their biological functions, construct the circRNA-miRNA-mRNA interactions, and predict circRNA coding potential. RESULTS: A total of 93 differentially expressed circular transcripts were identified in T1D compared with controls, among which 30 were upregulated, and 63 were downregulated. Two circRNAs were identified to have significant differences by RT-PCR. Gene ontology analysis enriched terms such as cellular protein metabolic process, cytoplasm and zinc ion binding. The proposed molecular functions of these differentially expressed circRNAs, including cellular protein metabolic process, cytoplasm, and binding, may contribute to T1D. The most enriched pathways for these circRNAs were involved in protein processing in the endoplasmic reticulum. Hsa_circ_0072697 may be involved in 50 circRNA-miRNA-mRNA signalling pathways related to diabetes, such as circ_0072697-miR-15a-UBASH3A network. Furthermore, hsa_circ_0071224, hsa_circ_0002437, hsa_circ_0084429, hsa_circ_0072697, and hsa_circ_0000787 in T1D were considered to have the most coding potential involved in the pathogenesis of T1D. CONCLUSIONS: These results showed that circRNAs are aberrantly expressed in the peripheral blood of patients with T1D and may play potential actions by interactions with miRNA and circRNA-derived peptides in the development of T1D.

18.
Mol Cell ; 79(5): 824-835.e5, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32649882

RESUMO

DNA-protein crosslinks (DPCs) are highly toxic DNA lesions that threaten genomic integrity. Recent findings highlight that SPRTN, a specialized DNA-dependent metalloprotease, is a central player in proteolytic cleavage of DPCs. Previous studies suggest that SPRTN deubiquitination is important for its chromatin association and activation. However, the regulation and consequences of SPRTN deubiquitination remain unclear. Here we report that, in response to DPC induction, the deubiquitinase VCPIP1/VCIP135 is phosphorylated and activated by ATM/ATR. VCPIP1, in turn, deubiquitinates SPRTN and promotes its chromatin relocalization. Deubiquitination of SPRTN is required for its subsequent acetylation, which promotes SPRTN relocation to the site of chromatin damage. Furthermore, Vcpip1 knockout mice are prone to genomic instability and premature aging. We propose a model where two sequential post-translational modifications (PTMs) regulate SPRTN chromatin accessibility to repair DPCs and maintain genomic stability and a healthy lifespan.


Assuntos
Envelhecimento/genética , Reparo do DNA , Proteínas de Ligação a DNA/metabolismo , Acetilação , Envelhecimento/metabolismo , Animais , Linhagem Celular , Dano ao DNA , Proteínas de Ligação a DNA/genética , Enzimas Desubiquitinantes/metabolismo , Endopeptidases/metabolismo , Feminino , Instabilidade Genômica , Células HEK293 , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosforilação , Domínios Proteicos , Processamento de Proteína Pós-Traducional , Ubiquitinação
19.
Mikrochim Acta ; 187(8): 453, 2020 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-32681310

RESUMO

A rapid strategy for the ß-glycosidase (ß-Gal) and Escherichia coli (E. coli) sensing is presented, which is based on selective recognition reactions of QDs using visualization/fluorescence (FL)/atomic fluorescence spectrometry (AFS)/inductively coupled plasma mass spectrometry (ICP-MS) multimode assay. CdTe QDs can selectively recognize Ag+ and Ag NPs with a cation exchange reaction (CER) where Ag+ triggers the release of Cd2+ and quenches the fluorescence signal of QDs. Taking advantage of the fact that ß-Gal can hydrolyze 4-Aminophenyl ß-D-galactopyranoside (PAPG) to produce p-aminophenol (PAP), which has the ability to reduce Ag+ to form Ag NPs. The ß-Gal can be easily detected by visualization or FL in a turn-on manner. Furthermore, combining with the selective separation of Cd2+ by filter membrane, AFS and ICP-MS with higher sensitivity were used for the determination of the enzyme. Under optimized conditions, the system limits of detections (LODs) were 0.01 U/L, 0.03 mU/L, and 0.02 mU/L using FL, AFS, and ICP-MS as the detector, respectively. The relative standard deviations (RSDs, n = 7) for 0.1 U/L ß-Gal were 2.2, 2.0, and 1.3% using FL/AFS/ICP-MS as the detector, respectively. And 0.1 U/L of ß-Gal can be discriminated from the blank solution with the naked eye. In addition, given that the ß-Gal can serve as an indicator of E. coli, we have successfully applied this strategy for the detection of E. coli with a LOD of 25 CFU/mL. Application of the method was demonstrated by analyzing human urine samples and milk samples for ultra-trace detection of E. coli. Graphical abstract The CVG-AFS/ICP-MS/visual/FL multimode ß-Gal and E.coli detection via CER.

20.
Cell Rep ; 32(4): 107952, 2020 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-32726617

RESUMO

A certain number of epithelial cells in intestinal crypts are DNA damage resistant and contribute to regeneration. However, the cellular mechanism underlying intestinal regeneration remains unclear. Using lineage tracing, we show that cells marked by an Msi1 reporter (Msi1+) are right above Lgr5high cells in intestinal crypts and exhibit DNA damage resistance. Single-cell RNA sequencing reveals that the Msi1+ cells are heterogeneous with the majority being intestinal stem cells (ISCs). The DNA damage-resistant subpopulation of Msi1+ cells is characterized by low-to-negative Lgr5 expression and is more rapidly cycling than Lgr5high radiosensitive crypt base columnar stem cells (CBCs). This enables an efficient repopulation of the intestinal epithelium at early stage when Lgr5high cells are not emerging. Furthermore, relative to CBCs, Msi1+ cells preferentially produce Paneth cells during homeostasis and upon radiation repair. Together, we demonstrate that the DNA damage-resistant Msi1+ cells are cycling ISCs that maintain and regenerate the intestinal epithelium.

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