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1.
Artigo em Inglês | MEDLINE | ID: mdl-34902570

RESUMO

BACKGROUND & AIMS: Data on long-term tenofovir alafenamide (TAF) therapy for pregnant women with active chronic hepatitis B (CHB) (immune clearance and reactivation phases, currently and previously diagnosed) and their infants are lacking. METHODS: Pregnant women with active CHB treated with TAF and tenofovir disoproxil fumarate (TDF) were enrolled in this multicenter prospective study, and infants received immunoprophylaxis. The primary outcomes were rates of adverse (safety) events in pregnant women and defects in infants and fetuses. The secondary outcomes were virologic responses in pregnant women, infants' safety, hepatitis B surface antigen (HBsAg) status, and growth conditions. RESULTS: One hundred three and 104 pregnant women were enrolled and 102 and 104 infants were born in the TAF and TDF groups, respectively. In the TAF group, the mean age, gestational age, alanine aminotransferase level, and viral loads at treatment initiation were 29.3 years, 1.3 weeks, 122.2 U/L, and 5.1 log10 IU/mL, respectively. TAF was well-tolerated, and the most common adverse event was nausea (29.1%) during a mean of 2 years of treatment. Notably, 1 (1.0%) TAF-treated pregnant woman underwent induced abortion due to noncausal fetal cleft lip and palate. No infants in either group had birth defects. In the TAF group, the hepatitis B e antigen seroconversion rate was 20.7% at postpartum month 6, infants had normal growth parameters, and no infants were positive for HBsAg at 7 months. The TDF group had comparable safety and effectiveness profiles. CONCLUSIONS: TAF administered throughout or beginning in early pregnancy is generally safe and effective for pregnant women with active CHB and their infants.

3.
Eur J Clin Invest ; : e13714, 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34800290

RESUMO

BACKGROUND: The prognosis of primary bile cholangitis (PBC) is linked to gut microbiota dysbiosis. This study investigated the association between the gut microbiome and elevated total bilirubin (TB) level in PBC patients treated with ursodeoxycholic acid (UCDA). METHODS: A total of 47 PBC patients with 12 months of UCDA treatment were enrolled. Patients were divided into the TB (+) (TB>1× upper limit of the normal range [ULN]; n = 20) and TB(-) (TB≤1× ULN; n = 27) groups. Stool and serum specimens were collected, and microbiota composition and functional characteristics in the 2 groups were evaluated by 16S RNA gene sequencing and bioinformatic analysis. RESULTS: Bacterial diversity was lower in the TB(+) group than in the TB(-) group, although there was no significant difference in bacterial community profile. The phylum Saccharibacteria showed differential abundance in the 2 groups. Meanwhile, the TB(-) group had lower abundance of the Gemmiger, Blautia, Anaerostipes and Coprococcus genera than the TB(+) group, whereas Holdemania was absent. The abundance of Gemmiger formicillis and Coprococcus eutactus was positively correlated with that of Faecalibacterium prausnitzii, while Blautia, Anaerostipes and Coprococcus were negatively correlated with total bile acid level. CONCLUSION: TB level in PBC patients treated for 12 months with UCDA is associated with a distinct gut microbiome profile.

4.
Comput Intell Neurosci ; 2021: 6440338, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34782833

RESUMO

The optimization problems are taking place at all times in actual lives. They are divided into single objective problems and multiobjective problems. Single objective optimization has only one objective function, while multiobjective optimization has multiple objective functions that generate the Pareto set. Therefore, to solve multiobjective problems is a challenging task. A multiobjective particle swarm optimization, which combined cosine distance measurement mechanism and novel game strategy, has been proposed in this article. The cosine distance measurement mechanism was adopted to update Pareto optimal set in the external archive. At the same time, the candidate set was established so that Pareto optimal set deleted from the external archive could be effectively replaced, which helped to maintain the size of the external archive and improved the convergence and diversity of the swarm. In order to strengthen the selection pressure of leader, this article combined with the game update mechanism, and a global leader selection strategy that integrates the game strategy including the cosine distance mechanism was proposed. In addition, mutation was used to maintain the diversity of the swarm and prevent the swarm from prematurely converging to the true Pareto front. The performance of the proposed competitive multiobjective particle swarm optimizer was verified by benchmark comparisons with several state-of-the-art multiobjective optimizer, including seven multiobjective particle swarm optimization algorithms and seven multiobjective evolutionary algorithms. Experimental results demonstrate the promising performance of the proposed algorithm in terms of optimization quality.


Assuntos
Algoritmos , Rotação
5.
Microbiome ; 9(1): 228, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34814945

RESUMO

BACKGROUND: Mesenteric adipose tissue (mAT) hyperplasia, known as creeping fat is a pathologic characteristic of Crohn's disease (CD). The reserve of creeping fat in surgery is associated with poor prognosis of CD patients, but the mechanism remains unknown. METHODS: Mesenteric microbiome, metabolome, and host transcriptome were characterized using a cohort of 48 patients with CD and 16 non-CD controls. Multidimensional data including 16S ribosomal RNA gene sequencing (16S rRNA), host RNA sequencing, and metabolome were integrated to reveal network interaction. Mesenteric resident bacteria were isolated from mAT and functionally investigated both in the dextran sulfate sodium (DSS) model and in the Il10 gene-deficient (Il10-/-) mouse colitis model to validate their pro-inflammatory roles. RESULTS: Mesenteric microbiota contributed to aberrant metabolites production and transcripts in mATs from patients with CD. The presence of mAT resident microbiota was associated with the development of CD. Achromobacter pulmonis (A. pulmonis) isolated from CD mAT could translocate to mAT and exacerbate both DSS-induced and Il10 gene-deficient (Il10-/-) spontaneous colitis in mice. The levels of A. pulmonis in both mAT and mucous layer from CD patients were higher compared to those from the non-CD group. CONCLUSIONS: This study suggests that the mesenteric microbiota from patients with CD sculpt a detrimental microenvironment and promote intestinal inflammation. Video abstract.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34754313

RESUMO

Objective: To evaluate the efficacy of dual-antiplatelet treatment (DAPT) in patients with coronary heart disease (CHD) at high altitude by using thrombelastogram (TEG) and to analyze the related biochemical factors affecting drug reactivity. Methods: Totally 118 CHD patients who admitted to the Qinghai People's Hospital from September 2019 to September 2020 were enrolled in the group. Those people have lived in Qinghai for a long time. Seven days after DAPT, venous blood was collected on an empty stomach in the early morning of the next day; blood routine, coagulation function, and biochemical items were tested. Thrombelastogram (TEG) was used to draw curves to calculate platelet, coagulation and fibrinolysis functions, and drug inhibition rate. Patients were divided into the aspirin resistance (AR) group, clopidogrel resistance (CR) group, dual-antiplatelet drug resistance (DAR) group, and drug-sensitive group according to different inhibition rates. The drug efficacy was analyzed, and the clinical data, biochemical indexes, and TEG parameters of each group were compared to identify the risk factors of drug resistance. Results: Those 118 CHD patients at high altitude were incorporated into the study, ranging from 38 to 84 years of age, including 81 males (68.64%) and 37 females (31.36%). The platelet function and coagulation-fibrinolysis function were detected by TEG, and MATHROMBI, MAADP, and MAAA were higher than the reference range. There were 82 cases (69.49%) of drug resistance, 36 cases (32.53%) of drug sensitivity, 17 cases (14.41%) of AR alone, and 16 cases (12.71%) of CR alone. There was no significant difference in age, gender, BMI, oxygen saturation, TG, GFR, and history of diabetes and hypertension between ACS and CCS groups (P > 0.05). PLT and FIB in the ACS group were higher than those in the CCS group, and the difference was statistically significant (P < 0.05). In addition, MATHROMBIN, MAFIBRIN, E, A, A30, and coagulation composite index were also higher than those in the CCS group, with a statistically significant difference (P < 0.05). Univariate analysis and logistic regression analysis suggested that age, HbA1c, FBG, and diabetes were the main factors of drug resistance. Conclusion: Antiplatelet drugs aspirin and clopidogrel resistance are associated with increased age, elevated HbA1c and FBG, and diabetes. Therefore, it is necessary to take reasonable treatment measures based on the actual situation of patients.

7.
J Exp Clin Cancer Res ; 40(1): 304, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34583750

RESUMO

BACKGROUND: Tumor-associated macrophages (TAMs) are key regulators of the complex interplay between cancer and the immune microenvironment. Tumor cell-derived spondin 2 (SPON2) is an extracellular matrix glycoprotein that has complicated roles in recruitment of macrophages and neutrophils during inflammation. Overexpression of SPON2 has been shown to promote tumor cell migration in colorectal cancer (CRC). However, the mechanism by which SPON2 regulates the accumulation of TAMs in the tumor microenvironment (TME) of CRC is unknown. METHODS: Immunohistochemistry was used to examine SPON2 expression in clinical CRC tissues. In vitro migration assays, transendothelial migration assays (iTEM), and cell adhesion assays were used to investigate the effects of SPON2 on monocyte/macrophage migration. Subcutaneous tumor formation and orthotopic implantation assays were performed in C57 BL/6 mice to confirm the effects of SPON2 on TAM infiltration in tumors. RESULTS: SPON2 expression is positively correlated with M2-TAM infiltration in clinical CRC tumors and poor prognosis of CRC patients. In addition, SPON2 promotes cytoskeletal remodeling and transendothelial migration of monocytes by activating integrin ß1/PYK2 axis. SPON2 may indirectly induce M2-polarization through upregulating cytokines including IL10, CCL2 and CSF1 expression in tumor cells. Blocking M2 polarization and Macrophage depletion inhibited the SPON2-induced tumors growth and invasion. Furthermore, blocking the SPON2/integrin ß1/PYK2 axis impairs the transendothelial migration of monocytes and cancer-promoting functions of TAMs in vivo. CONCLUSIONS: Our findings demonstrate that SPON2-driven M2-TAM infiltration plays an important role during CRC tumor growth and metastasis. SPON2 may be a valuable biomarker guiding the use of macrophage-targeting strategies and a potential therapeutic target in advanced CRC.

8.
Am J Transl Res ; 13(8): 9024-9031, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34540014

RESUMO

OBJECTIVE: To explore the incidence rate of aspirin resistance (AR) in patients with coronary heart disease (CHD) in the plateau, and analyze its correlation with clinical influencing factors and serological indicators. METHODS: In this retrospective study, 90 patients with CHD who had lived in the plateau for a long time (>10 years) and received treatment were selected as the subjects. Patients were divided into the AR group (11-dehydrothromboxane B2 (11-DH-TXB2) >1500 pg/mg) and aspirin sensitivity group (AS group, 11-DH-TXB2 ≤1500 pg/mg) according to the content of 11-DH-TXB2 in the urine. The differences in gender, body weight, blood pressure and heart rate between the two groups were compared, and the correlation of these indexes with the incidence rate of AR was analyzed. Moreover, serum indicators were detected. Multiple variable binary logistic regression was used to detect the independent risk factors for AR. RESULTS: The incidence rate of AR in the enrolled patients with CHD was 27.78% (25/90). The body mass index (BMI) in the AR group was significantly higher than that in the AS group (P<0.05). Patients in the AR group had significantly higher C-reactive protein (CRP) and total bilirubin levels and lower mean corpuscular volume and mean corpuscular hemoglobin compared with the AS group (all P<0.05). Binary logistic regression showed that BMI and CRP were independent factors for AR. CONCLUSION: AR occurs in patients with CHD who take aspirin in the plateau. Patients with high BMI or CRP level have an increased risk of AR. In addition, BMI and CRP are independent factors for AR, and bilirubin can be a predictive factor for AR.

9.
Front Cell Infect Microbiol ; 11: 708827, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34589441

RESUMO

Understanding the dynamics of lung microbiota in tuberculosis patients, especially those who cannot be confirmed bacteriologically in clinical practice, is imperative for accurate diagnosis and effective treatment. This study aims to characterize the distinct lung microbial features between bacteriologically confirmed and negative tuberculosis patients to understand the influence of microbiota on tuberculosis patients. We collected specimens of bronchoalveolar lavage fluid from 123 tuberculosis patients. Samples were subjected to metagenomic next-generation sequencing to reveal the lung microbial signatures. By combining conventional bacterial detection and metagenomic sequencing, 101/123 (82%) tuberculosis patients were bacteriologically confirmed. In addition to Mycobacterium tuberculosis, Staphylococcus aureus, Kluyveromyces lactis, and Pyricularia pennisetigena were also enriched in the bacteriological confirmation group. In contrast, Haemophilus parainfluenzae was enriched in the bacteriologically negative group. Besides, microbial interaction exhibits a different state between bacteriologically confirmed and negative tuberculosis patients. Mycobacterium tuberculosis was confirmed correlated with clinical characteristics such as albumin and chest cavities. Our study comprehensively demonstrates the correlation between unique features of lung microbial dynamics and the clinical characteristics of tuberculosis patients, suggesting the importance of studying the pulmonary microbiome in tuberculosis disease and providing new insights for future precision diagnosis and treatment.


Assuntos
Microbiota , Mycobacterium tuberculosis , Tuberculose , Ascomicetos , Líquido da Lavagem Broncoalveolar , Haemophilus parainfluenzae , Humanos , Kluyveromyces , Pulmão , Metagenômica , Mycobacterium tuberculosis/genética , Staphylococcus aureus , Tuberculose/microbiologia
10.
Curr Mol Med ; 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34325631

RESUMO

OBJECTIVE: Psoriasis is a chronic inflammatory skin disease highly depending on angiogenesis. Our prior results showed that the mRNA and protein of Del-1 in dermal mesenchymal stem cells (dMSCs) was up-regulated from psoriasis. Our aim was further to investigate the role of Del-1 from dMSCs in the pathogenesis of psoriasis and confirm the effect of Del-1 on the pathogenesis of psoriasis. METHODS: We conducted an immunohistochemistry experiment to further investigate the expression of Del-1in psoriatic lesions. In addition, dMSCs with over-expressed Del-1 via the lentiviral vector of Del-1 were co-cultured with ECs, and the protein expression of integrins (αvß3, αvß5 ,and α5ß1) of ECs were detected by western blotting. RESULTS: This research showed that Del-1 was significantly increased in lesions of patients with psoriasis (p< .05, 9.96 vs. 2.18), and Del-1 from dMSCs successfully induced up-regulation of integrins α5ß1 and αvß3 (all p < .05). CONCLUSION: This study demonstrated that Del-1 from dMSCs was involved in the pathogenesis of psoriasis through induced angiogenesis. And Del-1, αvß3 and α5ß1 may be potential new targets for inhibiting angiogenesis in psoriasis.

11.
Ann Transl Med ; 9(2): 153, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33569455

RESUMO

Background: Anti-soluble liver antigen/liver pancreas (anti-SLA/LP) is a highly specific serological marker for the diagnosis of autoimmune hepatitis (AIH). The aim of the present study was to define the clinical characteristics and human leucocyte antigen (HLA) genotypes of Chinese patients with anti-SLA/LP positive AIH. Methods: Ninety-one AIH patients who were anti-SLA/LP positive were enrolled in this case control study. Clinical information was obtained through reviewing patients' clinical notes. High-resolution genotyping of HLA-A, B, C, DRB1, and DQB1 alleles was performed by sequence-based typing polymerase chain reaction on 62 of the 91 patients. Data from 500 healthy patients were used as baseline controls. Results: Anti-SLA/LP-positive AIH patients were characterized as follows: adults (age 20-80 years), female (88%), and frequent anti-nuclear antibody positivity (91%). Genetically, compared with the controls, HLA-B*35:01 and C*08:01 were significantly more frequent in patients. The frequencies of HLA-B*08:01, B*40:02, DRB1*04:01, DRB1*04:05, DRB1*14:01, and DRB1*16:02 increased, and the frequency in DRB1*15:01 decreased in patients, but did not reach significance after Bonferroni's correction. Patients with other autoimmune diseases had a higher DRB1*04:05 and DQB1*04:01 allele carrier frequency than those without. DRB1*04:05 and DQB1*04:01 alleles were found at increased frequency in patients with decompensated liver disease than those with compensated liver disease. Conclusions: Chinese anti-SLA/LP-positive AIH patients have some distinct clinical characteristics than other populations reported in the literature. The presence of certain specific HLA alleles could potentially increase the risk of developing anti-SLA/LP-positive AIH or other autoimmune disease and decompensated liver disease in the Chinese population.

12.
Clin Infect Dis ; 73(9): e3324-e3332, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-33395488

RESUMO

BACKGROUND: Few safety and effectiveness results have been published regarding the administration of tenofovir alafenamide fumarate (TAF) during pregnancy for the prevention of mother-to-child transmission (MTCT) of hepatitis B virus (HBV). METHODS: In this multicenter prospective observational study, pregnant women with HBV DNA levels higher than 200 000 IU/mL who received TAF or tenofovir disoproxil fumarate (TDF) from gestational weeks 24-35 to delivery were 1:1 enrolled and followed until postpartum month 6. Infants received immunoprophylaxis. The primary endpoint was the safety of mothers and infants. The secondary endpoint was the hepatitis B surface antigen (HBsAg)-positive rate at 7 months for infants. RESULTS: In total, 116 and 116 mothers were enrolled, and 117 and 116 infants were born, in the TAF and TDF groups, respectively. TAF was well tolerated during a mean treatment duration of 11.0 weeks. The most common maternal adverse event was nausea (19.0%). One (0.9%), 3 (2.6%), and 9 (7.8%) mothers had abnormal alanine aminotransferase levels at delivery and at postpartum months 3 and 6, respectively. The TDF group had safety profiles that were comparable to those of the TAF group. No infants had birth defects in either group. The infants' physical and neurological development at birth and at 7 months in the TAF group were comparable with those in the TDF group. The HBsAg positive rate was 0% at 7 months in all 233 infants. CONCLUSIONS: Antiviral prophylaxis with TAF was determined to be generally safe for both mothers and infants and reduced the MTCT rate to 0%.


Assuntos
Hepatite B Crônica , Hepatite B , Complicações Infecciosas na Gravidez , Alanina , Antivirais/efeitos adversos , Feminino , Hepatite B/tratamento farmacológico , Hepatite B/prevenção & controle , Hepatite B Crônica/tratamento farmacológico , Humanos , Lactente , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/prevenção & controle , Estudos Prospectivos , Tenofovir/análogos & derivados , Carga Viral
13.
Small ; 17(1): e2005607, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33284504

RESUMO

Diamond-like carbon (DLC) films are capable of achieving superlubricity at sliding interfaces by a rapid running-in process. However, fundamental mechanisms governing the friction evolution during this running-in processes remain elusive especially at the nanoscale, which hinders strategic tailoring of tribosystems for minimizing friction and wear. Here, it is revealed that the running-in governing superlubricity of DLC demonstrates two sub-stages in single-asperity nanocontacts. The first stage, mechanical removal of a thin oxide layer, is described quantitatively by a stress-activated Arrhenius model. In the second stage, a large friction decrease occurs due to a structural ordering transformation, with the kinetics well described by the Johnson-Mehl-Avrami-Kolmogorov model with a modified load dependence of the activation energy. The direct observation of a graphitic-layered transfer film formation together with the measured Avrami exponent reveal the primary mechanism of the ordering transformation. The findings provide fundamental insights into friction evolution mechanisms, and design criteria for superlubricity.

14.
Front Neurol ; 12: 750908, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34975719

RESUMO

Background: Moderate hypobaric hypoxia induces cerebral ischemic tolerance. We investigated the optimal method for applying hypobaric hypoxia preconditioning at 5,000 m to ischemic brain tissue and combined it with proteomics to determine the mechanisms underlying this effect. Methods: Male SD rats were randomly grouped as S (sham, n = 20), M (middle cerebral artery occlusion [MCAO], n = 28), H2M (intermittent hypobaric hypoxia preconditioned MCAO group, 2 h/day, 10 days, n = 20), H6M (intermittent hypobaric hypoxia preconditioned MCAO group, 6 h/day, 10 days, n = 28), and HpM (persistent hypobaric hypoxia preconditioned MCAO group, 10 days, n = 28). The permanent MCAO model was established based on the Zea Longa method. Infarction was assessed with the modified neurological severity score (mNSS) and 2,3,5-triphenyl tetrazolium chloride staining. The total protein expression of the neuron-specific nuclear protein (NeuN), cysteinyl aspartate specific proteinase 3 (caspase-3), cleaved-caspase-3, and interleukin 6 (IL-6) was determined using western blotting. We assessed the peri-infarct cortex's ultrastructural changes. A label-free proteomic study and western blot verification were performed on the most effective preconditioned group. Results: The H6M group showed a lower infarct volume (p = 0.0005), lower mNSS score (p = 0.0009) than the M group. The H2M showed a lower level of IL-6 (p = 0.0213) than the M group. The caspase-3 level decreased in the H2M (p = 0.0002), H6M (p = 0.0025), and HpM groups (p = 0.0054) compared with that in the M group. Cleaved-caspase-3 expression decreased in the H2M (p = 0.0011), H6M (p < 0.0001), and HpM groups (p < 0.0001) compared with that in the M group. The neurons' ultrastructure and the blood-brain barrier in the peri-infarct tissue improved in the H2M and H6M groups. Immunofluorescence revealed increased NeuN-positive cells in the peri-infarct tissue in the H6M group (p = 0.0003, H6M vs. M). Protein expression of Chmp1a, Arpc5, and Hspa2 factors related to endocytosis were upregulated in the H6M compared with those of the M group (p < 0.05 for all) on western blot verification of label-free proteomics. Conclusions: Intermittent hypobaric hypoxia preconditioning exerts a neuroprotective effect in a rat stroke model. Persistent hypobaric hypoxia stimulation exhibited no significant neuroprotective effect. Intermittent hypoxic preconditioning for 6 h/day for 10 days upregulates key proteins in clathrin-dependent endocytosis of neurons in the cortex.

15.
Onco Targets Ther ; 13: 9351-9364, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061423

RESUMO

Background and Aim: Dysexpression of circular RNAs has been identified in multiple types of cancer. Hsa_circ_0004018 was reported to be significantly downregulated in hepatocellular carcinoma (HCC) and to display HCC-stage-specific expression features. However, the role of hsa_circ_0004018 in HCC progression remains unclear. Methods: The expression of hsa_circ_0004018 or microRNA-626 (miR-626) was detected in tumor tissues and paired non-tumor tissues from HCC patients, as well as in one normal human liver cell line and 5 HCC cell lines by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, dye exclusion assay, clonogenic assay, scratch migration assay and transwell assay were used to measure cell proliferation and migration capacity, respectively. Luciferase report assay and RNA pull down assay were performed to explore the regulatory effect of certain molecules on the expression of target genes. Results: We found that the expression of hsa_circ_0004018 was lower in tumor tissues than in their paired non-tumor tissues from 28 out of 41 HCC patients. The difference in the expression between tumor tissues and non-tumor tissues was statistically significant (p<0.001). Further analysis revealed that such lower expression in tumor tissues was much more common in bigger tumor size group (≥5cm) compared with the smaller tumor size group (<5cm) (85% vs 42%, p=0.0007). Similarly, hsa_circ_0004018 was downregulated in HCC cell lines. Additionally, a negative correlation between hsa_circ_0004018 and miR-626 expression was noticed in HCC tissues. Moreover, we observed that hsa_circ_0004018 interacted with miR-626/DKK3 and contributed to HCC cell proliferation and migration through inhibiting Wnt/ß-catenin signaling pathway in vitro. Furthermore, hsa_circ_0004018 blocked xenograft tumor growth in vivo through inhibiting Wnt/ß-catenin signaling pathway by targeting miR-626/DKK3. Conclusion: We revealed that hsa_circ_0004018/miR-626/DKK3 regulatory axis may be a possible novel therapeutic target for HCC.

16.
Sci Rep ; 10(1): 18138, 2020 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-33097753

RESUMO

The earth has been undergoing climate change, especially in recent years, driven by increasing concentration of atmospheric carbon dioxide (CO2) and rising earth-surface temperature, which could reduce N allocation to Bt toxin for transgenic Bt crops (Bt crops), but the N fertilization is considered to be an effective method to enhance the C-N balance in Bt crops in the case of elevated CO2 in future. DNA methylation not only in promoterregion but also in codingregion of transgene plays a critical role in transgene expression regulation and silencing of transgenic crops. Recent research has emphasized the risks of increased transgene silencing of Bacillus thuringiensis (Bt) rice under elevated CO2. In this study, the effects of elevated CO2 (vs. ambient CO2) on exogenous Bt toxins and transgene expression in promoterregion and codingregion of Bt rice during tillering stage (cv. HH1 expressing fused Cry1Ab/Cry1Ac) were evaluated under three nitrogen (N) fertilizer rate (1/4, 1 and 2 N levels). The aboveground and belowground biomass, and foliar Bt protein content of Bt rice were all significantly increased with the augmentation of N-fertilizer. And elevated CO2 significantly increased belowground biomass, total soluble protein content, transgene methylation levels in promoterregion (P1), and in total of promoterregion(P1) and codingregion (P2 + P3) (i.e., P1 + P2 + P3) at 1 N level, and it also increased transgene methylation levels in codingregion (P2), and in total of promoterregion and codingregion (P1 + P2 + P3) at 2 N level. In addition, elevated CO2 decreased foliar Bt protein content at 1 N level. The transgene methylation levels in promoterregion and codingregion were negatively correlated with Bt-transgene expression level. The methylation level of cytosines located at CG sites was higher than those at CHG and CHH sites in P1, P2 and P3 fragments regardless of the CO2 or N-fertilizer level. The correlation of transgene mehtylation in promoterregion with transgene expression is even stronger than that in codingregion. These data indicate that N fertilization supply will increase the Bt toxin content in transgenic Bt rice, especially under elevated CO2.


Assuntos
Toxinas de Bacillus thuringiensis/genética , Dióxido de Carbono/efeitos adversos , Fertilizantes , Oryza/genética , Plantas Geneticamente Modificadas/genética , Mudança Climática , Metilação de DNA/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/genética , Inativação Gênica , Nitrogênio/administração & dosagem , Fases de Leitura Aberta/genética , Regiões Promotoras Genéticas/genética , Transgenes/genética
17.
Cell Res ; 30(11): 950-965, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32901110

RESUMO

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated malignancy with a complex tumor ecosystem. How the interplay between tumor cells, EBV, and the microenvironment contributes to NPC progression and immune evasion remains unclear. Here we performed single-cell RNA sequencing on ~104,000 cells from 19 EBV+ NPCs and 7 nonmalignant nasopharyngeal biopsies, simultaneously profiling the transcriptomes of malignant cells, EBV, stromal and immune cells. Overall, we identified global upregulation of interferon responses in the multicellular ecosystem of NPC. Notably, an epithelial-immune dual feature of malignant cells was discovered and associated with poor prognosis. Functional experiments revealed that tumor cells with this dual feature exhibited a higher capacity for tumorigenesis. Further characterization of the cellular components of the tumor microenvironment (TME) and their interactions with tumor cells revealed that the dual feature of tumor cells was positively correlated with the expression of co-inhibitory receptors on CD8+ tumor-infiltrating T cells. In addition, tumor cells with the dual feature were found to repress IFN-γ production by T cells, demonstrating their capacity for immune suppression. Our results provide new insights into the multicellular ecosystem of NPC and offer important clinical implications.


Assuntos
Perfilação da Expressão Gênica , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , Análise de Célula Única , Microambiente Tumoral/genética , Viroses/genética , Animais , Agregação Celular , Comunicação Celular , Feminino , Fibroblastos/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Imunomodulação , Interferons/metabolismo , Ligantes , Linfócitos do Interstício Tumoral/imunologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Células Mieloides/metabolismo , Neoplasias Nasofaríngeas/imunologia , Neoplasias Nasofaríngeas/virologia , Processos Estocásticos , Células Estromais/metabolismo , Linfócitos T/imunologia
18.
BMC Genomics ; 21(1): 634, 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32928099

RESUMO

BACKGROUND: Chilo suppressalis is a widespread rice pest that poses a major threat to food security in China. This pest can develop resistance to Cry toxins from Bacillus thuringiensis (Bt), threatening the sustainable use of insect-resistant transgenic Bt rice. However, the molecular basis for the resistance mechanisms of C. suppressalis to Cry1C toxin remains unknown. This study aimed to identify genes associated with the mechanism of Cry1C resistance in C. suppressalis by comparing the midgut transcriptomic responses of resistant and susceptible C. suppressalis strains to Cry1C toxin and to provide information for insect resistance management. RESULTS: A C. suppressalis midgut transcriptome of 139,206 unigenes was de novo assembled from 373 million Illumina HiSeq and Roche 454 clean reads. Comparative analysis identified 5328 significantly differentially expressed unigenes (DEGs) between C. suppressalis Cry1C-resistant and -susceptible strains. DEGs encoding Bt Cry toxin receptors, aminopeptidase-P like protein, the ABC subfamily and alkaline phosphatase were downregulated, suggesting an association with C. suppressalis Cry1C resistance. Additionally, Cry1C resistance in C. suppressalis may be related to changes in the transcription levels of enzymes involved in hydrolysis, digestive, catalytic and detoxification processes. CONCLUSION: Our study identified genes potentially involved in Cry1C resistance in C. suppressalis by comparative transcriptome analysis. The assembled and annotated transcriptome data provide valuable genomic resources for further study of the molecular mechanisms of C. suppressalis resistance to Cry toxins.


Assuntos
Toxinas de Bacillus thuringiensis/toxicidade , Endotoxinas/toxicidade , Proteínas Hemolisinas/toxicidade , Resistência a Inseticidas , Lepidópteros/genética , Transcriptoma , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Aminopeptidases/genética , Aminopeptidases/metabolismo , Animais , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Mucosa Intestinal/metabolismo , Lepidópteros/efeitos dos fármacos , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo
19.
Microvasc Res ; 132: 104056, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32795468

RESUMO

The dermal mesenchymal stem cells (DMSCs) from psoriasis display higher expression level of epidermal growth factor-like repeats and discoidin I-like domains 3 (EDIL3), while EDIL3 can bind integrins, including αvß3 and αvß5, to regulate angiogenesis. To assess the role of EDIL3 derived from DMSCs of psoriasis (P-DMSCs) in angiogenesis, in vitro, EDIL3 of DMSCs from psoriasis was silenced by interfering EDIL3. Then the efficacy of silencing EDIL3 was tested by fluorescent flag, qRT-PCR and western blotting. And, in vitro, the relationship of EDIL3 in DMSCs with the angiogenesis of HUVECs were investigated through co-culture system. In vivo, EDIL3 recombinant protein was injected into IMQ cream-induced psoriasis-like skin lesions of mouse and EDIL3-associated tube formation were determined using Image J software. Our results showed the capacity of the adhesion, migration and tube formation of HUVECs in all psoriatic DMSCs groups were significantly higher compared with the control and si-EDIL3 groups (all P<0.05) in vitro. Moreover, under stimulated by EDIL3 recombinant protein, EDIL3-associated tube formation was dramatically elevated in vivo (P<0.01). In this study, EDIL3 could promote the adhesion, migration and tube formation of ECs and participant in the angiogenesis pathogenesis of psoriasis through affecting biological function on ECs both in vitro and in vivo. The results suggest a potential role of the critical pro-angiogenic factor EDIL3 in psoriasis therapy.


Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Moléculas de Adesão Celular/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células-Tronco Mesenquimais/metabolismo , Neovascularização Patológica , Psoríase/metabolismo , Pele/irrigação sanguínea , Animais , Proteínas de Ligação ao Cálcio/genética , Estudos de Casos e Controles , Adesão Celular , Moléculas de Adesão Celular/genética , Movimento Celular , Proliferação de Células , Células Cultivadas , Técnicas de Cocultura , Modelos Animais de Doenças , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Células-Tronco Mesenquimais/patologia , Camundongos Endogâmicos BALB C , Comunicação Parácrina , Psoríase/patologia , Transdução de Sinais
20.
ACS Appl Mater Interfaces ; 12(38): 43167-43172, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32840104

RESUMO

Graphite has been conventionally believed to exhibit an inferior lubricating performance with significantly larger friction coefficient and wear rate in a vacuum environment than in ambient air. Dangling bonds at the edge planes of graphite, accounting for the high friction in inert atmosphere are saturated by chemisorbed vapor molecules in air, which contributes to low surface adhesion and low friction. However, there is still a lack of direct experimental evidence whether basal planes of graphite excluding the negative effects of edges or dangling bonds shows intrinsic lubricity when sliding under ultrahigh vacuum (UHV) conditions. By the interlayer friction measurement enabled by graphite flake-wrapped atomic force microscope tips in UHV, we show a record-low friction coefficient of 4 × 10-5 (slope of friction vs normal force curve) when sliding between graphite layers, which is much lower than that in ambient air. This discrepancy manifests the intrinsic sliding frictional behavior between the graphite basal planes when the tribo-materials and experimental conditions are well-designed and strictly controlled. In addition, the temperature dependence of the kinetic friction between the graphite layers has been investigated under UHV conditions over the temperature range of 125-448 K, which is consistent with the thermally activated process.

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