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1.
Ultrasound Med Biol ; 46(1): 180-187, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31582179

RESUMO

This article aims to test a minimally invasive interventional approach by real-time transcranial contrast-enhanced ultrasound (CEUS) through a small bur hole to achieve an early local hemostatic drug therapy in a novel traumatic intracerebral hematoma (ICH) model of pigs with hemostatic abnormalities. The effects of hemostasis in the hemocoagulase atrox (HA) injection group and saline injection group groups were observed by transcranial CEUS at three time points: 0 s, 10 s, 2nd. We successfully established a novel traumatic ICH model of pigs with hemostatic abnormalities by the methods of interventional ultrasound techniques and observed the effect of hemostasis by using HA in a local injection method with the assistance of minimally invasive interventional ultrasound technique. At 0 s, four pigs (100%) were observed that active bleeding was significantly weakened, and the range of hematoma became smaller in the HA group. At 10 s, four pigs (100%) were observed that active bleeding became much weaker, and the range of hematoma became further smaller in the HA group. At 2nd, zero pigs (0/4, 0%) were observed that active bleeding could be clearly identified and four pigs (100%) with ICH could also be observed in the HA group. We believe this useful technique could minimize the invasiveness and be operated at the bedside, which would bring much more benefits for traumatic ICH patients.

2.
Theor Biol Med Model ; 16(1): 19, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31801614

RESUMO

BACKGROUND: Gravity, especially hypergravity, can affect the morphology of membranes, and further influence most biological processes. Since vesicle structures are relatively simple, the vesicle can be treated as a vital model to study the mechanical properties of membranes in most cases. Basic research on membrane tension has become a vital research topic in cellular biomechanics. METHODS: In this study, a new vesicle model is proposed to quantitatively investigate the response of membrane tension to gravity. In the model, the aqueous lumen inside the vesicle is represented by water, and the vesicle membrane is simplified as a closed, thin, linear elastic shell. Then, the corresponding static equilibrium differential equations of membrane tension are established, and the analytical expression is obtained by the semi-inverse method. The model parameters of the equations are accurately obtained by fitting the reported data, and the values calculated by the model agree well with the reported results. RESULTS: The results are as follows: First, both the pseudo-ellipsoidal cap and the pseudo-spherical cap can be used to describe the deformed vesicle model; however, the former can better represent the deformation of the vesicle model because the variance of the pseudo-ellipsoidal cap is smaller. Second, the value of membrane tension is no longer a constant for both models. Interestingly, it varies with the vesicle height under the action of gravity. The closer it is to the substrate, the greater the membrane tension. Finally, the inclination between the tangent and the radial lines at a certain point is nearly proportional to the radius of the cross section in both models. CONCLUSION: These findings may be helpful to study the vesicle model spreading more accurately by taking into account the influence of gravity because it could affect the distribution of membrane tension. Furthermore, it may also provide some guidance for cell spreading and may have some implications for membrane tension-related mechanobiology studies, especially in the hypergravity conditions.

3.
Curr Probl Cancer ; : 100514, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31753315

RESUMO

INTRODUCTION: Debates exist about the effects of peritoneal cytology and its treatment on the survival of early endometrial cancer. This study is to explore the prognostic role of peritoneal cytology and relevant therapy in patients with stage IA endometrial endometrioid carcinomas in a retrospective cohort study. MATERIAL AND METHODS: From June 1, 2010, to June 1, 2017, in a teaching hospital, all the cases of pathologically confirmed stage IA endometrioid endometrial cancer were reviewed. Patients were followed up to February 1, 2019. The survival outcomes were compared among patients with negative peritoneal cytology, positive peritoneal cytology and no peritoneal cytology outcomes. RESULTS: In total, 1284 patients were included in the study, and 754 (58.7%) had peritoneal cytology evaluations with 22 (2.9%) of positive peritoneal cytology. After a median follow-up of 57.4 months, 1257 patients (97.9%) had definite survival outcomes. None of the patients with positive peritoneal cytology had recurrence or mortality. The appearance of positive peritoneal cytology had no impact on the disease-free, overall and cancer-specific overall survivals in univariate and multivariate analyses. No risk factors, including the adjuvant therapy, were found to be relevant with the appearance and survival in patients with positive peritoneal cytology. CONCLUSIONS: In patients with stage IA endometrial endometrioid carcinoma, the prevalence of positive peritoneal cytology was very low without know risk factor. Positive peritoneal cytology did not influence the survival outcomes of whole population, and adjuvant therapy did not influence the survival outcomes of patients with positive peritoneal cytology in such population. Mini Abstract The appearance of positive peritoneal cytology in stage IA endometrial endometrioid carcinomas had no clinical significance and need no adjuvant therapy.

5.
Aging (Albany NY) ; 11(21): 9348-9368, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31715585

RESUMO

Gut dysbiosis and oxidative stress may trigger senile osteoporosis. Fructus Ligustri Lucidi (FLL) has bone-preserving properties and affects the intestinal microecology. However, the mechanism of the anti-osteoporotic effect of FLL and its link to the gut microbiota remains to be elucidated. Here, we demonstrated that sustained exposure of ICR mice to D-galactose / sodium nitrite for 90 days causes aging-related osteoporosis and reduced cognitive performance. The aging phenotype is also characterized by increased oxidative stress in serum. This is likely triggered by abnormal changes in the gut microbiota population of Bifidobacterium and the ratio of Firmicutes/ Bacteroidetes that resulted in increased levels of flavin-containing monooxygenase-3 and trimethylamine-N-oxide (TMAO). Moreover, the increased oxidative stress further accelerated aging by increasing tumor necrosis factor-α levels in serum and reducing Sirtuin 6 (Sirt6) expression in long bones, which prompted nuclear factor kappa-B acetylation as well as over-expression and activation of cathepsin K. FLL-treated aging mice revealed a non-osteoporotic bone phenotype and an improvement on the cognitive function. The mechanism underlying these effects may be linked to the regulation of gut microbiota diversity, antioxidant activity, and the levels of TMAO and Sirt6. FLL may represent a potential source for identifying anti-senile osteoporotic drug candidates.

6.
Environ Int ; 134: 105283, 2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31743806

RESUMO

In the last decade, North China (NC) has been one of the most populated and polluted regions in the world. The regional air pollution has had a serious impact on people's health; thus, all levels of government have implemented various pollution prevention measures since 2013. Based on multi-city in situ environmental and meteorological data, as well as the meteorological reanalysis dataset from 2013 to 2017, regional pollution characteristics and meteorological formation mechanisms were analyzed to provide a more comprehensive understanding of the evolution of PM2.5 in NC. The domain-averaged PM2.5 was 79 ±â€¯17 µg m-3 from 2013 to 2017, with a decreasing rate of 10 µg m-3 yr-1. Two automatic computer algorithms were established to identify 6 daily regional pollution types (DRPTs) and 48 persistent regional pollution events (PRPEs) over NC during 2014-2017. The average PM2.5 concentration for the Large-Region-Pollution type (including the Large-Moderate-Region-Pollution and Large-Severe-Region-Pollution types) was 113 ±â€¯40 µg m-3, and more than half of Large-Region-Pollution days and PRPEs occurred in winter. The PRPEs in NC mainly developed from the area south of Hebei. The number of Large-Region-Pollution days decreased notably from 2014 to 2017, the annual number of days varying between 194 and 97 days, whereas a slight decline was observed in winter. In addition, the averaged PM2.5 concentrations and the numbers and durations of the PRPEs decreased. Lamb-Jenkinson weather typing was used to reveal the impact of synoptic circulations on PM2.5 across NC. Generally, the contributions of the variations in circulation to the reduction in PM2.5 levels over NC between 2013 and 2017 were 64% and 45% in summer and winter, respectively. The three most highly polluted weather types were types C, S and E, with an average PM2.5 concentration of 137 ±â€¯40 µg m-3 in winter. Furthermore, three typical circulation dynamics were categorized in the peak stage of the PRPEs, namely, the southerly airflow pattern, the northerly airflow pattern and anticyclone pattern; the averaged relative humidity, recirculation index, wind speed and boundary layer height were 63%, 0.33, 2.0 m s-1 and 493 m, respectively. Our results imply that additional emission reduction measures should be implemented under unfavorable meteorological situations to attain ambient air quality standards in the future.

7.
Mol Ther Nucleic Acids ; 18: 882-892, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31751911

RESUMO

Circular RNAs (circRNAs) have been reported to participate in the molecular mechanism of human cancers. The PUM1 gene has been confirmed to be closely related to tumorigenesis and progression of ovarian cancer. In the present study, we explored the function and underlying molecular mechanism of circPUM1 in ovarian cancer. qRT-PCR analysis showed upregulation of circPUM1 in ovarian cancer tissues compared with normal ovaries. Gain- and loss-of-function experiments indicated that circPUM1 increased cell proliferation, migration, and invasion and inhibited cell apoptosis. Intraperitoneal injection of circPUM1-knockout tumor cells in nude mice resulted in a decrease in the metastatic ability of the tumor. Bioinformatics analysis and dual-luciferase reporter assays revealed that circPUM1 upregulated the expression of nuclear factor kappa B (NF-κB) and MMP2 by sponging miR-615-5p and miR-6753-5p. Further studies showed that exosomal circPUM1 acted on peritoneal mesothelial cells and increased tumor metastasis. In conclusion, our study indicates that circPUM1 not only promotes ovarian cancer proliferation, migration and invasion, but also acts on the peritoneum and contributes to metastasis of cancer in the form of cancer-derived exosomes.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31689921

RESUMO

Air pollution, including particulate matter (PM2.5) pollution, is extremely harmful to the environment as well as human health. The Beijing-Tianjin-Hebei (BTH) Region has experienced heavy PM2.5 pollution within China. In this study, a six-year time series (January 2013-December 2018) of PM2.5 mass concentration data from 102 air quality monitoring stations were studied to understand the spatio-temporal variation characteristics of the BTH region. The average annual PM2.5 mass concentration in the BTH region decreased from 98.9 µg/m3 in 2013 to 64.9 µg/m3 in 2017. Therefore, China has achieved its Air Pollution Prevention and Control Plan goal of reducing the concentration of fine particulate matter in the BTH region by 25% by 2017. The PM2.5 pollution in BTH plain areas showed a more significant change than mountains areas, with the highest PM2.5 mass concentration in winter and the lowest in summer. The results of spatial autocorrelation and cluster analyses showed that the PM2.5 mass concentration in the BTH region from 2013-2018 showed a significant spatial agglomeration, and that spatial distribution characteristics were high in the south and low in the north. Changes in PM2.5 mass concentration in the BTH region were affected by both socio-economic factors and meteorological factors. Our results can provide a point of reference for making PM2.5 pollution control decisions.

9.
J Control Release ; 316: 404-417, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31678653

RESUMO

Messenger RNA (mRNA) has recently emerged as a promising class of nucleic acid therapy, with the potential to induce protein production to treat and prevent a range of diseases. However, the widespread use of mRNA as a therapeutic requires safe and effective in vivo delivery technologies. Libraries of ionizable lipid nanoparticles (LNPs) have been designed to encapsulate mRNA, prevent its degradation, and mediate intracellular delivery. However, these LNPs are typically characterized and screened in an in vitro setting, which may not fully replicate the biological barriers that they encounter in vivo. Here, we designed and evaluated a library of engineered LNPs containing barcoded mRNA (b-mRNA) to accelerate the screening of mRNA delivery platforms in vivo. These b-mRNA are similar in structure and function to regular mRNA, and contain barcodes that enable their delivery to be quantified via deep sequencing. Using a mini-library of b-mRNA LNPs formulated via microfluidic mixing, we show that these different formulations can be pooled together, administered intravenously into mice as a single pool, and their delivery to multiple organs (liver, spleen, brain, lung, heart, kidney, pancreas, and muscle) can be quantified simultaneously using deep sequencing. In the context of liver and spleen delivery, LNPs that exhibited high b-mRNA delivery also yielded high luciferase expression, indicating that this platform can identify lead LNP candidates as well as optimal formulation parameters for in vivo mRNA delivery. Interestingly, LNPs with identical formulation parameters that encapsulated different types of nucleic acid barcodes (b-mRNA versus a DNA barcode) altered in vivo delivery, suggesting that the structure of the barcoded nucleic acid affects LNP in vivo delivery. This platform, which enables direct barcoding and subsequent quantification of a functional mRNA, can accelerate the in vivo screening and design of LNPs for mRNA therapeutic applications such as CRISPR-Cas9 gene editing, mRNA vaccination, and other mRNA-based regenerative medicine and protein replacement therapies.

10.
Food Res Int ; 126: 108612, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31732041

RESUMO

To shorten the fermentation time and reduce the contamination with heterozygous bacteria during the process of fermenting rice noodles, pure bacterial fermentation combined with semidry flour milling was used to produce fermented rice noodles. The changes in the pH value and microbial community diversity of the rice slurries, the physicochemical properties of the rice flours, and the texture, cooking qualities, sensory qualities and volatile components of the rice noodles prepared with different fermentative methods were investigated. The results showed that the pure bacterial fermentation required 18 h to reach a stable pH value, while the natural fermentation required 54 h. In addition, compared with naturally fermented rice slurry, the bacterial community diversity of the pure bacterial fermented rice slurry was significantly lower, while the fungal community diversity did not differ significantly. Significant differences were observed in the content of the damaged starch, amylose and protein between semidry milled pure bacterial fermented (SP) and wet milled naturally fermented (WN) rice flours (P < .05), while these differences had no significant effect on the texture and cooking qualities of the SP and WN rice noodles (P > .05). In addition, the types of volatile components of the SP noodles were significantly lower than those of other noodles, while the primary volatile component categories of the SP noodles were consistent with that of the WN noodles, and they had a similar flavoring substance.

11.
Blood ; 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31697816

RESUMO

NF-kB and Notch signaling can be simultaneously activated in a variety of B cell lymphomas. Patients with B cell lymphoma occasionally develop clonally-related myeloid tumors with poor prognosis. Whether concurrent activation of both pathways is sufficient to induce B cell transformation and the signaling initiates B-myeloid conversion in a pathological context are largely unknown. Here, we provide genetic evidence that concurrent activation of NF-kB and Notch signaling in committed B cells is sufficient to induce B cell lymphomatous transformation and primes common progenitor cells to convert to myeloid lineage through dedifferentiation, not transdifferentiation. Intriguingly, the converted myeloid cells can further transform, albeitat low frequency, to myeloid leukemia. Mechanistically, coactivation of NF-kB and Notch signaling endows committed B cells with the ability to self-renew. Downregulation of BACH2, a lymphoma and myeloid gene suppressor, but not upregulation of CEBPa and/or downregulation of B cell transcription factors, is one of the early events for both B cell transformation and myeloid conversion. Interestingly, a DNA hypomethylating drug not only effectively eliminated the converted myeloid leukemia cells, but also restored the expression of GFP, which was lost in converted myeloid leukemia cells. Collectively, our results suggest that targeting NF-kB and Notch signaling will not only improve lymphoma treatment, but also prevent the lymphoma-to-myeloid tumor conversion. Importantly, DNA hypomethylating drugs might efficiently treat these converted myeloid neoplasms.

12.
BMJ Open ; 9(10): e027278, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31676643

RESUMO

OBJECTIVES: The aim of this study was to identify the prevalence of peripherally inserted central catheter (PICC) malposition and the influence of guide wire removal on tip location in PICCs and determine whether related factors, including age, sex, side of insertion and brand of catheter, influence the PICC tip location. SETTING: Single-centre research institute in China recruiting patients from the hospital. PARTICIPANTS: A total of 837 adult patients with inserted PICCs were recruited from October 2016 to May 2017. INTERVENTIONS: This was a cross-sectional study aiming to identify the prevalence of PICC malposition and the influence of guide wire removal on tip location in PICCs. A linear regression model and a variance of factorial design analysis were performed. The PICC tip location was documented on a postinsertion chest X-ray. Multivariable analyses were performed based on the following related factors: age, sex, side of insertion and brand of catheter. RESULTS: The tip location moved a mean of 17.4 mm among the 837 included patients. The prevalence of PICC malposition was 83.6% (700/837), while 16.4% (137/837) of PICCs remained in correct location. The mean movement caused by guide wire removal without an adjusted tail end was (-1.95±26.90) mm. The difference between tail end adjustment movement and actual tip position movement in each PICC was (33.0±17.1) mm in type C, which was significantly higher than the findings for type A (12.8±13.3) mm and type B (12.9±12.7) mm. CONCLUSIONS: PICC malposition is a frequent event. Different catheter brands were associated with different ranges of movement in tip location after guide wire removal. The age and sex of the patients and the insertion side did not influence the extent of movement.

13.
Nat Commun ; 10(1): 5051, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31699991

RESUMO

The oncogenic fusion protein AML1-ETO retains the ability of AML1 to interact with the enhancer core DNA sequences, but blocks AML1-dependent transcription. Previous studies have shown that post-translational modification of AML1-ETO may play a role in its regulation. Here we report that AML1-ETO-positive patients, with high histone lysine methyltransferase Enhancer of zeste homolog 1 (EZH1) expression, show a worse overall survival than those with lower EZH1 expression. EZH1 knockdown impairs survival and proliferation of AML1-ETO-expressing cells in vitro and in vivo. We find that EZH1 WD domain binds to the AML1-ETO NHR1 domain and methylates AML1-ETO at lysine 43 (Lys43). This requires the EZH1 SET domain, which augments AML1-ETO-dependent repression of tumor suppressor genes. Loss of Lys43 methylation by point mutation or domain deletion impairs AML1-ETO-repressive activity. These findings highlight the role of EZH1 in non-histone lysine methylation, indicating that cooperation between AML1-ETO and EZH1 and AML1-ETO site-specific lysine methylation promote AML1-ETO transcriptional repression in leukemia.

14.
J Ultrasound Med ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31724216

RESUMO

OBJECTIVES: To determine whether real-time 3-dimensional ultrasound (RT3DUS) could provide additional information on early detection and evaluation in the management of solid abdominal organ trauma based on an animal model. METHODS: Nine bleeding lesions were developed in the livers (n = 3), kidneys (n = 3), and spleens (n = 3) from 9 pigs. An ultrasound contrast agent was administered intravenously (liver, 0.025 mL/kg; kidney, 0.008 mL/kg; and spleen, 0.013 mL/kg) after an unenhanced 2-dimensional ultrasound (2DUS) examination (B-mode and color Doppler). After contrast agent injection, bleeding lesions were imaged by 2DUS and sequentially imaged by 3-dimensional static ultrasound (3DSUS) and RT3DUS to identify active bleeding, observe the relationship between bleeding lesions and peripheral blood vessels, and evaluate the spatial scope of the bleeding lesions in the organs. RESULTS: For the identification of active bleeding, there was no statistical difference in contrast-enhanced 2DUS, 3DSUS, and RT3DUS. For observation of the relationship between bleeding lesions and peripheral blood vessels, RT3DUS performed statistically better than 2DUS (P < .05), as reconstructed RT3DUS could show more information about the relationship. For the evaluation of the spatial scope of the bleeding lesion in the organ, RT3DUS also performed statistically better than 2DUS from the multiplanar observation by postprocessing of the 3-dimensional real-time volumes (P < .05). CONCLUSIONS: Real-time 3-dimensional ultrasound improves early detection and evaluation of solid abdominal organ trauma and provides additional information over the current contrast-enhanced 2DUS.

15.
Leuk Lymphoma ; : 1-11, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31724463

RESUMO

The prognostic significance of loss of the Y chromosome (LOY) in patients with t(8;21)(q22;q22) acute myeloid leukemia (AML) remains poorly understood. To investigate this issue, 226 younger adult male patients with t(8;21) AML from 15 Chinese hematology research centers were retrospectively evaluated, among which, 50.4% had LOY. In patients receiving high-dose cytarabine (HiDAC) consolidation therapy, LOY was associated with a significantly higher cumulative incidence of relapse (CIR, HR = 2.18, p = .048), worse relapse-free survival (RFS, HR = 2.39, p = .026), and worse but not significant overall survival (OS, HR = 2.71, p = .166). A multivariate analysis adjusted for age, WBC, KIT mutations, and minimal residual disease showed LOY to be an independent adverse prognostic factor for relapse in patients on HiDAC consolidation therapy. Our results suggest that LOY may be associated with a high relapse risk in t(8;21) AML patients receiving HiDAC therapy during consolidation.

16.
Lab Invest ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31772313

RESUMO

The mechanisms underlying the lineage switching from prostate adenocarcinoma (AdPC) to lethal neuroendocrine prostate cancer (NEPC) have yet to be completely elucidated. In this study, RNA sequencing data from a unique patient-derived xenograft NEPC model and a clinical NEPC cohort were used to identify the potential genes driving NEPC progression. Enrichr analysis resulted in the identification of SRY-related HMG-box gene 2 (SOX2) as a potential repressor that causes decrease in the expression of AdPC specific genes in NEPC. Assays involving the stable overexpression of SOX2 in LNCaP and CWR22RV1 cells validated this role of SOX2 in vitro. Mechanistic studies showed that the repressor role of SOX2 was attributed to the marked global hypomethylation of histone H3, which was driven by the activation of lysine-specific demethylase 1 (LSD1). Furthermore, Enrichr also predicted SOX2 as a driver gene involved in the upregulation of NEPC specific genes. However, SOX2 alone could only marginally induce the expression of some neuroendocrine markers in vitro, which was consistent with previous reports. Moreover, we also elucidated the molecular features of LNCaP-SOX2 cells that may confer resistance to androgen-deprivation therapy (ADT) and the inclination toward neuroendocrine transdifferentiation. The results of this study reveal a novel mechanism for SOX2 in the progression of NEPC via LSD1-mediated global epigenetic modulation. This discovery suggests that LSD1 may be a selective target for the prevention of NEPC progression.

17.
Zhongguo Zhen Jiu ; 39(11): 1169-72, 2019 Nov 12.
Artigo em Chinês | MEDLINE | ID: mdl-31724351

RESUMO

OBJECTIVE: To observe the effect of grain-moxibustion at Zusanli (ST 36) and Weishu (BL 21) on neutrophil to lymphocyte ratio (NLR) and quality of life (QOL) in patients with advanced gastric cancer. METHODS: Sixty patients with advanced gastric cancer were randomly divided into an observation group and a control group, 30 cases in each one. In the control group, conventional chemotherapy regimen combined with symptomatic treatment,such as antiemetic, acid-suppressive, liver-protecting drugs. On the basis of the treatment in the control group, grain-moxibustion was applied at Zusanli (ST 36) and Weishu (BL 21) in the observation group, 9 cones for each acupoint, once a day for a total of 90 days. The levels of NLR were observed before and after treatment, and the clinical efficacy and quality of life were evaluated in the two groups. RESULTS: After treatment, the value of NLR in the observation group was significantly lower than before treatment (P<0.05), there was no significant difference before and after treatment in the control group (P>0.05), and the descend range of observation group was larger than the control group (P<0.05). The effective rates (RR) were 33.3% (10/30) in the observation group and 36.7% (11/30) in the control group, there was no significant difference between the two groups (P>0.05). After treatment, the QOL in the observation group was improved in diarrhea, loss of appetite, fatigue, nausea and vomiting, general health states (P<0.05), there was no significant difference in the control group before and after treatment in varions scores (P>0.05), and the observation group was superior to the control group in fatigue, sleep disorder, loss of appetite, diarrhea and general health states after treatment (P<0.05). CONCLUSION: Grain-moxibustion at Zusanli (ST 36) and Weishu (BL 21) can decrease NLR and improve QOL of patients with advanced gastric cancer.


Assuntos
Linfócitos/imunologia , Moxibustão , Neutrófilos/imunologia , Qualidade de Vida , Neoplasias Gástricas , Pontos de Acupuntura , Humanos , Moxibustão/métodos , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/psicologia , Neoplasias Gástricas/terapia
18.
Artigo em Inglês | MEDLINE | ID: mdl-31747312

RESUMO

Fluorescence recovery after photobleaching (FRAP) has been useful in delineating cardiac myofilament biology and innovations in fluorophore chemistry have expanded the array of microscopic assays used. However, one assumption in FRAP is the irreversible photobleaching of fluorescent proteins after laser excitation. Here we demonstrate reversible photobleaching regarding the photoconvertible fluorescent protein, mEos3.2. We used CRISPR/Cas9 genome editing in human induced pluripotent stem cells (hiPSC) to knock-in mEos3.2, into the C-terminus of titin to visualize sarcomeric titin incorporation and turnover. Upon cardiac induction, the titin-mEos3.2 fusion protein is expressed and integrated in the sarcomeres of hiPSC-derived cardiomyocytes. STORM imaging shows M-band clustered regions of bound titin-mEos3.2 with few soluble titin-mEos3.2 molecules. FRAP revealed a baseline titin-mEos3.2 fluorescence recovery of 68% and half-life of ~1.2 hours, suggesting a rapid exchange of sarcomeric titin with soluble titin. However, paraformaldehyde fixed and permeabilized titin-mEos3.2 hiPSC-CMs surprisingly revealed a 55% fluorescence recovery. Whole cell FRAP analysis in paraformaldehyde fixed, cycloheximide treated and untreated titin-mEos3.2 hiPSC-CMs displayed no significant differences in fluorescence recovery. FRAP in fixed HEK 293T expressing cytosolic mEos3.2 demonstrates a 58% fluorescence recovery. These data suggest that titin-mEos3.2 is subject to reversible photobleaching following FRAP. Using a mouse titin-eGFP model, we demonstrate that no reversible photobleaching occurs. Our results reveal that reversible photobleaching accounts for the majority of titin recovery in the titin-mEos3.2 hiPSC-CM model and should warrant as a caution in the extrapolation of reliable FRAP data from specific fluorescent proteins in long-term cell imaging.

19.
Chem Commun (Camb) ; 55(93): 14074-14077, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31696869

RESUMO

We discovered that the function of cytochrome C can be modulated by DNA nanoribbons. Meanwhile, the interplay between the DNA nanoribbons and the native cytochrome C and the possible mechanisms are also discussed.


Assuntos
Citocromos c/metabolismo , DNA/metabolismo , Nanoestruturas/química , Peroxidases/metabolismo , Animais , Catálise , Citocromos c/química , DNA/química , Guaiacol/química , Cavalos , Oxirredução , Peroxidases/química , Ligação Proteica
20.
J Cell Mol Med ; 23(12): 8472-8481, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31639291

RESUMO

Ovarian cancer is a leading cause of deaths due to gynaecological malignancy. While endogenous non-coding circular RNAs (circRNAs) in cancer have attracted attention, their roles in ovarian cancer are not known. We used qRT-PCR to quantify expression of circRhoC in ovarian cancer tissues and normal tissues. The effects of overexpressing or destruction of circRhoC on the phenotype of ovarian cancer cells were assessed both in vitro and in vivo. Dual-luciferase reporter assay assesses the microRNA sponge function of circRhoC. Western blotting was used to confirm the effects of circRhoC and microRNA on target gene expression. Our results showed that circRhoC was significantly up-regulated in ovarian cancer tissues compared to normal ovarian tissues. Overexpression of circRhoC in CAOV3 ovarian cancer cell increased cell viability, migration and invasion ability; destroying circRhoC in A2780 had the opposite effects and inhibited ovarian tumour cell A2780 dissemination in the peritoneum in vivo. We confirmed circRhoC functions as a sponge for miR-302e to positively regulate VEGFA; FISH experiments showed that circRhoC could co-focal with miR-302e; besides, overexpression of miR-302e reversed the ability of circRhoC to positively regulate VEGFA, and what's more, RIP assay showed that circRhoC could directly bind with VEGFA; besides, VEGFA expression level in ovarian cancer tissues was positively associated with circRhoC expression. In conclusion, the oncogenic effect of RhoC in ovarian cancer is at least in part due to circRhoC, which functions not only as a miR-302e sponge to positively regulate VEGFA protein expression, but may also directly bind and modulate VEGFA expression.

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