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1.
Preprint | bioRxiv | ID: ppbiorxiv-437666

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Understanding the influence of mutations in the SARS-CoV-2 gene on clinical outcomes and related factors is critical for treatment and prevention. Here, we analyzed 209,551 high-coverage complete virus sequences and 321 RNA-seq samples to mine the mutations associated with clinical outcome in the SARS-CoV-2 genome. Several important hotspot variants were found to be associated with severe clinical outcomes. Q57H variant in ORF3a protein were found to be associated with higher mortality rate, and was high proportion in severe cases (39.36%) and 501Y.V2 strains (100%) but poorly proportional to asymptomatic cases (10.04%). T265I could change nsp2 structure and mitochondrial permeability, and evidently higher in severe cases (20.12%) and 501Y.V2 strains (100%) but lower in asymptomatic cases (1.43%). Additionally, R203K and G204R could decrease the flexibility and immunogenic property of N protein with high frequency among severe cases, VUI 202012/01 and 484K.V2 strains. Interestingly, the SARS-CoV-2 genome was more susceptible to mutation because of the high frequency of nt14408 mutation (which located in RNA polymerase) and the high expression levels of ADAR and APOBEC in severe clinical outcomes. In conclusion, several important mutation hotspots in the SARS-CoV-2 genome associated with clinical outcomes was found in our study, and that might correlate with different SARS-CoV-2 mortality rates.

2.
Biosens Bioelectron ; 176: 112907, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33349536

RESUMO

Biofuel cells (BFCs)-based self-powered biosensors suffer from the limited stability of bioenzymes. Meanwhile, the poor performance of self-powered biosensors affects the sensitivity of biosensing, thus, it is significant and challenging to improve their stability and sensitivity. In our work, a BFC-based self-powered biosensor, with simultaneously enhanced stability and sensitivity, was constructed utilizing dual metal-organic frameworks (MOFs) as the carriers of the bioenzyme and the electroactive probe, respectively. Anodic enzyme, glucose dehydrogenase (GDH), was encapsulated in zeolitic imidazolate framework-8 (ZIF-8) to form GDH@ZIF-8 composites, enhancing the catalytic activity and stability of GDH. Meanwhile, another zirconium metal-organic frameworks (UiO-66-NH2) loaded with electroactive molecules (K3[Fe(CN)6]) served as nano-enrichment carriers and improved the capability of the cathode to accept electrons from the anode, further improving the sensitivity of the as-proposed biosensor. Herein, the "signal-on" BFC-based self-powered biosensing of exosomes, the model analyte, with excellent stability and outstanding sensitivity was realized with the assistance of dual MOFs, and the detection limit was down to 300 particles mL-1 (based on 3s/k), which was superior to those previously reported in literatures. Furthermore, the developed protocol was capable of detecting exosomes derived from cancer cells in complex biological samples. Overall, in this work the enhancement of both stability and sensitivity has been achieved by utilizing two types of MOFs, which laid the foundation for expanding the applications of BFC-based self-powered biosensors.

3.
Analyst ; 2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33242047

RESUMO

A novel and convenient method for the ratiometric fluorescence detection of alkaline phosphatase (ALP) activity was proposed based on dual emission of bovine serum albumin-templated gold nanoclusters (BSA-AuNCs) and the mechanism of the inner filter effect between BSA-AuNCs and p-nitrophenol (PNP). First, ALP catalyzed the hydrolysis of the substrate p-nitrophenyl phosphate (PNPP) to produce PNP. PNP effectively quenched the emission peak of BSA-AuNCs at 410 nm because of the overlap in absorbance feature of PNP and the fluorescence spectrum of BSA-AuNCs, and the peak at 650 nm was almost unaffected. Thus, a sensitive ratiometric method for detection of ALP activity was developed using the fluorescence intensity of BSA-AuNCs at 650 nm as a reference signal. ALP activity versus the ratio of fluorescence intensities at 410 and 650 nm showed good linearity between 0.2 and 5 mU mL-1 (R2 = 0.9931) and high sensitivity with a detection limit of 0.03 mU mL-1 (S/N = 3). The developed sensing method was successfully applied to investigate ALP inhibitors and detect ALP in serum samples.

4.
Ann Transl Med ; 8(17): 1090, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33145309

RESUMO

Background: Deep vein thrombosis (DVT) is an early postoperative complication. Thrombosis formation, which is potentially life-threatening, seriously affects the rehabilitation of patients after surgery. We aimed to establish a C57 mouse model of DVT and to examine the changes in the expression of Krüppel-like factor 15 (KLF15) and endothelial nitric oxide synthase (eNOS) in venous wall tissues, and we also investigated the regulatory relationship of KLF15 and eNOS in the thrombin-induced human umbilical vein endothelial cell (HUVEC) injury cell model. Methods: The DVT model was established using the inferior vena cava (IVC) stenosis method. The expression levels of KLF15 and eNOS were analyzed using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). In cell experiments, the expression of KLF15 and eNOS was analyzed in the model of thrombin-induced HUVEC injury with KLF15 siRNA. Results: Compared to the control and sham-operated groups, KLF15 in the DVT group was upregulated, while eNOS was downregulated. The results of cell experiments revealed that KLF15 was downregulated in the thrombin+KLF15 siRNA group compared with the thrombin group. Meanwhile, eNOS was upregulated in the thrombin+KLF15 siRNA group compared with the thrombin group. These findings suggested that KLF15 regulated the expression of eNOS in the DVT model. Conclusions: We successfully constructed a DVT mouse model. In the early stage of DVT formation, KLF15 regulated the expression and inhibited the antithrombotic effect of eNOS, resulting in thrombi formation.

5.
Blood Purif ; : 1-9, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33113536

RESUMO

BACKGROUND: Since the outbreak of COVID-19 in December 2019, it has spread rapidly and widely, bringing great psychological pressure to the public. In order to prevent the epidemic, traffic lockdown was required in many areas of China, which led to inconvenience of treatment for dialysis patients. This study was conducted to explore the psychological distress and the psychological demand induced by CO-VID-19 in the patients undergoing dialysis and compare the difference between hemodialysis (HD) and peritoneal dialysis (PD) patients during the traffic lockdown period. METHODS: Questionnaires were given to the dialysis patients in the West China Hospital of Sichuan University. The Impact of Event Scale (IES) was used to investigate the patients' trauma-related distress in response to COVID-19. RESULTS: 232 eligible respondents were enrolled in this cross-section study, consisting of 156 PD patients and 76 HD patients. The median IES score for all the enrolled patients was 8.00 (2.00-19.00), which belonged to the subclinical dimension of post-traumatic stress symptoms (PTSS). HD patients had a significant higher IES score than PD patients (11.50 vs. 8.00) (p < 0.05). HD patients already got more psychological support from the medical staff. According to IES scores, 22.4% HD patients and 13.4% PD patients were classified as having moderate or severe PTSS, which need psychological support (p < 0.05). But more patients of both groups considered psychological support was necessary (HD: 50%, PD: 45.5%) (p > 0.05). In the multivariate regression analysis, we found that dialysis vintage, the impact of COVID-19 on the severity of illness and daily life, and confidence in overcoming the disease contributed to IES score (p < 0.05). CONCLUSIONS: HD patients had more severe trauma-related stress symptoms than PD patients. When major public healthy events occurred, careful psychological estimate and sufficient psychological support should be provided to the dialysis patients, especially to the HD patients.

6.
Front Plant Sci ; 11: 574316, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32983222

RESUMO

Arabidopsis thaliana ENO2 (AtENO2) encodes two proteins AtENO2 (enolase) and AtMBP-1 (c-Myc binding protein 1-like). The loss of AtENO2 function causes the constitutive developmental defects which are correlated with reduced enolase activity, but not AtMBP-1 transcript abundance. However, the regulation mechanism of AtENO2 on the seed properties is still not clear. In this study, we found that the mutation of AtENO2 reduced the seed size and weight. The level of glucose in seed was significantly elevated but that of starch was decreased in AtENO2 mutants compared to WT plants. We also found that AtENO2 mutation reduced the content of cytokinin which resulted in smaller cotyledons. The RNA-seq data showed that there were 1892 differentially expressed genes and secondary metabolic pathways were significantly enriched. Instead of AtMBP-1, AtENO2 protein interacted with AtbZIP75 which may mediate the secondary metabolism. Therefore, ENO2 alters the size and weight of seeds which is not only regulated by the content of cytokinin and secondary metabolism, but may be affected by the interaction of ENO2 and bZIP57. These results are helpful to understand the novel function of AtENO2 which provide a foundation for further exploration of the key candidate genes for crop breeding.

7.
Parasitol Res ; 119(8): 2733-2740, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32617726

RESUMO

Amebiasis is a worldwide parasitic zoonosis, with symptoms of abdominal discomfort, indigestion, diarrhea, and even death. However, limited information about the prevalence of Entamoeba spp. in experimental nonhuman primates (NHPs) in southwestern China is available. The objective of the current study was to investigate the frequency and species identity of Entamoeba to evaluate potential zoonotic risk factors for Entamoeba spp. infection in experimental NHPs. A total of 505 fecal samples were collected from NHPs (macaques) and analyzed by PCR analysis the small subunit rRNA (SSU rRNA) gene of Entamoeba spp. Forty-seven specimens were positive for Entamoeba spp., and the prevalence of Entamoeba spp. was 9.31% (47/505). Significant differences in the prevalence rates among the three breeds (P = 0.002 < 0.01, df = 2, χ2 = 12.33) and feed types (P = 0.001 < 0.01, df = 1, χ2 = 10.12) were observed. Altogether, four Entamoeba species, including E. dispar (57.44%), E. chattoni (29.78%), E. histolytica (6.38%), and E. coli (6.38%), were identified by DNA sequence analysis. The results suggested a low prevalence but high diversity of Entamoeba species in experimental NHPs in Yunnan Province, southwestern China. Results of this study contribute to the knowledge of the genetic characteristics of Entamoeba spp. in NHPs.


Assuntos
Entamoeba/genética , Entamebíase/veterinária , Macaca/parasitologia , Infecções Protozoárias em Animais/epidemiologia , Infecções Protozoárias em Animais/parasitologia , Animais , Animais de Laboratório , China/epidemiologia , DNA de Protozoário/genética , Entamoeba/classificação , Entamoeba/isolamento & purificação , Entamebíase/epidemiologia , Entamebíase/parasitologia , Entamebíase/transmissão , Fezes/parasitologia , Epidemiologia Molecular , Prevalência , Infecções Protozoárias em Animais/transmissão , RNA Ribossômico/genética , Subunidades Ribossômicas Menores/genética , Análise de Sequência de DNA
8.
Acta Parasitol ; 65(4): 1005-1010, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32556839

RESUMO

PURPOSE: Blastocystis is an enteral eukaryote that omnipresent existence in animals and humans global. The objective of the current study investigated the frequency and subtypes to evaluate risk factors for Blastocystis infection in pigs in southwestern China. MATERIALS AND METHODS: The 866 fecal samples were collected from farmed pigs in Yunnan province, which were determined by the molecular method of the nested PCR and phylogenetic analysis established on the small subunit rDNA (SSU rDNA) gene fragment. RESULTS: A total of 433 specimens were detected Blastocystis positive, and the prevalence of is 50.0% (433/866). The significant differences in prevalence were also observed in pigs from regions (P < 0.01, df = 8, χ2 = 29.17) and age groups (P < 0.01, df = 2, χ2 = 66.6). Older pigs had more Blastocystis infection than younger ones. Moreover, three zoonotic subtypes were identified by DNA sequence analysis, included ST1 (7.39%, 32/433), ST3 (4.39%, 19/433) and ST5 (88.22%, 382/433). CONCLUSIONS: The results suggested a high prevalence and diversified subtypes in farmed pigs in Yunnan province, southwestern China, which indicated pigs are most likely to potential reservoirs and zoonotic transmission of Blastocystis for human infection. To our knowledge, the study is the first large-scale systematic statement of Blastocystis colonization in Yunnan province, Southwestern China, which contributed to the in-depth study of genetic characteristics and prevention, control and treatment of Blastocystis in pigs in Yunnan province and other regions.

9.
Plant Sci ; 292: 110378, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32005383

RESUMO

In plants, the organ size is one of the most important features and regulated by an elaborate developmental program involving both internal and external signals. The steroidal hormone brassinosteroid (BR) plays an important role in regulating the organ size. BRASSINAZOLE RESISTANT 1 (BZR1) is one of important transcription factors that regulate organ size in BR signal pathway in Arabidopsis. The function of BZR1 on organ size is well characterized in Arabidopsis, but poorly understood in maize (Zea mays). To understand the mechanism of intrinsic organ size regulated by BZR1 during organogenesis, we identified the maize BZR1 and examined its function in Arabidopsis. Overexpression of ZmBZR1 displayed phenotypes of enlarged cotyledons, rosette leaves, floral organ and seed size in Arabidopsis. The cells in rosette leaves as well as other organs in transgenic ZmBZR1 lines were dramatically larger and longer than those in Col-0. ChIP and RNA-seq analysis showed ZmBZR1 can directly bind to the promoter region of organ size related genes, Germination Repression and Cell Expansion receptor-like kinase (GRACE) and KIP-RELATED PROTEIN6 (KRP6) to regulate their expression, suggesting ZmBZR1 is required for the progressive increase in cells during Arabidopsis development. Collectively, our findings provide significant insights into the mechanisms underlying regulation of organ size mediated by maize BZR1.


Assuntos
Organogênese Vegetal/genética , Proteínas de Plantas/genética , Fatores de Transcrição/genética , Zea mays/fisiologia , Sequência de Aminoácidos , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/fisiologia , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Filogenia , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Plantas Geneticamente Modificadas/fisiologia , Sementes/fisiologia , Alinhamento de Sequência , Fatores de Transcrição/química , Fatores de Transcrição/metabolismo , Zea mays/genética , Zea mays/crescimento & desenvolvimento
10.
Theor Appl Genet ; 133(5): 1467-1489, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31965233

RESUMO

KEY MESSAGE: Epigenetic regulation has been implicated in the control of multiple agronomic traits in maize. Here, we review current advances in our understanding of epigenetic regulation, which has great potential for improving agronomic traits and the environmental adaptability of crops. Epigenetic regulation plays vital role in the control of complex agronomic traits. Epigenetic variation could contribute to phenotypic diversity and can be used to improve the quality and productivity of crops. Maize (Zea mays L.), one of the most widely cultivated crops for human food, animal feed, and ethanol biofuel, is a model plant for genetic studies. Recent advances in high-throughput sequencing technology have made possible the study of epigenetic regulation in maize on a genome-wide scale. In this review, we discuss recent epigenetic studies in maize many achieved by Chinese research groups. These studies have explored the roles of DNA methylation, posttranslational modifications of histones, chromatin remodeling, and noncoding RNAs in the regulation of gene expression in plant development and environment response. We also provide our future prospects for manipulating epigenetic regulation to improve crops.

11.
Drug Des Devel Ther ; 14: 5747-5756, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33408463

RESUMO

Background: To establish a novel delivery system of RGD-conjugated resveratrol human serum albumin (HAS) nanoparticles in ovarian cancer therapy. Methods: The nanoparticles system was characterized for physicochemical properties, the stability in the serum and in vitro release. The comparison between RVT injection, HSA-RVT NPs and RGD-HSA-RVT NPs regarding tissue distributions and pharmacokinetics was also carried out using mice as the animal models. Results: The results showed that RGD-HSA-RVT NPs were characterized of small particle size about 128.2 nm and negative zeta potential about -21.42 mV, and drug controlled to release slowly on a biphasic pattern. Compared with control groups, RGD-HSA-RVT NPs showed the higher cellular uptake and cell inhibition rates. In vivo data showed that RGD-HSA-RVT NPs have good tumor enrichment characteristics and a significant difference in tumor inhibition, compared with the control group. Conclusion: RGD-conjugated resveratrol HSA nanoparticles are an ideal drug delivery system, which can play a role in the treatment of ovarian cancer.

12.
Huan Jing Ke Xue ; 40(12): 5484-5492, 2019 Dec 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854621

RESUMO

Investigating the change of soil quality during reclamation can provide scientific guidance for desalinization, fertilization, etc. Soil samples were collected from natural tidal flat areas (0 years) and coastal tidal flat reclamation areas with different reclamation years (5, 30, 38, and 61 years) to assess the changes in soil quality after 60 years of reclamation. Soil quality was evaluated using a soil quality index (SQI), which was calculated by the selected minimum data set (MDS) and TOPSIS method. The ratio of clay content (CLAY), soil salt content (SSC), soil organic carbon (SOC), total potassium (TK), and bulk density (BD) were selected as soil quality indicators involving soil physical and chemical properties based on the MDS. The results showed that soil particle size tended to refine gradually with the continuous decrease of sand content and increase of silt and clay content. Simultaneously, soil water content (SWC) and soil BD decreased gradually during the reclamation period. Additionally, SSC, pH and sodium adsorption ratio (SAR) decreased significantly with increase in reclamation years, whereas the nutrients and available nutrients were accumulated gradually, such as soil organic matter (SOM), total nitrogen (TN), total phosphorus (TP), available nitrogen (AN), and available phosphorus (AP). However, C/N, TK and available potassium (AK) showed a decrease with increasing reclamation years, and the cation exchange capacity (CEC) showed a trend of first decrease and then increase. Finally, SQI values varied from 24.06 in the bare flat soils to 63.08 in the soils after 63 years of reclamation, and showed that bare flat (20.04±11.48) < reclamation for 5 years (29.33±10.65) < reclamation for 30 years (51.52±8.76) ≈ reclamation for 38 years (49.98±10.75) < reclamation for 61 years (58.37±3.15), which has gone through approximately three stages of "initial stability-rapid improvement-relative stability." Soil CLAY content had the highest obstacle degree towards SQI among the selected MDS indicators, followed by SSC, SOM, TK, and SWC, and thereby the lower clay content and higher salt content were the main obstacle factors for promotion of soil quality in reclamation areas.

13.
Front Plant Sci ; 10: 1031, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31552061

RESUMO

Soybean is an important economic crop for human diet, animal feeds and biodiesel due to high protein and oil content. Its productivity is significantly hampered by salt stress, which impairs plant growth and development by affecting gene expression, in part, through epigenetic modification of chromatin status. However, little is known about epigenetic regulation of stress response in soybean roots. Here, we used RNA-seq and ChIP-seq technologies to study the dynamics of genome-wide transcription and histone methylation patterns in soybean roots under salt stress. Eight thousand seven hundred ninety eight soybean genes changed their expression under salt stress treatment. Whole-genome ChIP-seq study of an epigenetic repressive mark, histone H3 lysine 27 trimethylation (H3K27me3), revealed the changes in H3K27me3 deposition during the response to salt stress. Unexpectedly, we found that most of the inactivation of genes under salt stress is strongly correlated with the de novo establishment of H3K27me3 in various parts of the promoter or coding regions where there is no H3K27me3 in control plants. In addition, the soybean histone modifiers were identified which may contribute to de novo histone methylation and gene silencing under salt stress. Thus, dynamic chromatin regulation, switch between active and inactive modes, occur at target loci in order to respond to salt stress in soybean. Our analysis demonstrates histone methylation modifications are correlated with the activation or inactivation of salt-inducible genes in soybean roots.

14.
Chin Med J (Engl) ; 132(12): 1390-1399, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31205095

RESUMO

BACKGROUND: Mental stress-induced myocardial ischemia (MSIMI) is closely associated with adverse cardiac events in patients with coronary artery disease (CAD) and we aimed to determine whether biomarkers and blood pressure could be potential predictors of MSIMI. METHODS: This study enrolled 82 patients with documented CAD between June 1, 2017 and November 9, 2017. Patient blood samples were obtained at resting period and at the end of mental arithmetic. Then, patients were assigned to MSIMI positive group and MSIMI negative group. The main statistical methods included linear regression, receiver operating characteristic (ROC) curves, and logistic regression. RESULTS: Patients with CAD with MSIMI had significantly greater median resting N-terminal pro-brain natriuretic peptide (NT-proBNP, 141.02 [45.85-202.76] pg/mL vs. 57.95 [27.06-117.64] pg/mL; Z = -2.23, P = 0.03) and mean systolic blood pressure (SBP) (145.56 ±â€Š16.87 mmHg vs. 134.92 ±â€Š18.16 mmHg, Z = -2.13, P = 0.04) when compared with those without MSIMI. After 5-min mental stress task, those who developed MSIMI presented higher elevation of median post-stressor high sensitivity cardiac troponin I (hs-cTnI, 0.020 [0.009-0.100] ng/mL vs. 0.009 [0.009-0.010] ng/mL; Z = -2.45, P = 0.01), post-stressor NT-proBNP (138.96 [39.93-201.56] pg/mL vs. 61.55 [25.66-86.50] pg/mL; Z = -2.15, P = 0.03) compared with those without MSIMI. Using the ROC curves, and after the adjustment for basic characteristics, the multiple logistic regression analysis showed that patients presenting a post-stressor hs-cTnI ≥ 0.015 ng/mL had seven-fold increase in the risk of developing MSIMI (odds ratio [OR]: 7.09; 95% confidence interval [CI]: 1.65-30.48; P = 0.009), a rest NT-proBNP ≥ 80.51 pg/mL had nearly eight-fold increase (OR: 7.85; 95% CI: 1.51-40.82; P = 0.014), a post-stressor NT-proBNP ≥ 98.80 pg/mL had 35-fold increase (OR: 34.96; 95% CI: 3.72-328.50; P = 0.002), a rest SBP ≥ 129.50 mmHg had 11-fold increase (OR: 11.42; 95% CI: 1.21-108.17; P = 0.034). CONCLUSIONS: The present study shows that CAD patients with higher hs-cTnI level, and/or greater NT-proBNP and/or SBP are at higher risk of suffering from MSIMI when compared with those without MSIMI, indicating that hs-cTnI, NT-proBNP, SBP might be potential predictors of MSIMI.


Assuntos
Doença da Artéria Coronariana/complicações , Isquemia Miocárdica/etiologia , Estresse Psicológico/complicações , Idoso , Ansiedade/sangue , Ansiedade/complicações , Biomarcadores/sangue , Pressão Sanguínea/fisiologia , Proteína C-Reativa/metabolismo , Doença da Artéria Coronariana/sangue , Depressão/sangue , Depressão/complicações , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/sangue , Peptídeo Natriurético Encefálico/sangue , Razão de Chances , Fragmentos de Peptídeos/sangue , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Estresse Psicológico/sangue , Tomografia Computadorizada de Emissão de Fóton Único , Troponina I/sangue , Troponina T/sangue
15.
Int J Mol Med ; 44(1): 57-66, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31115494

RESUMO

Cisplatin is one of the primary compounds used in the treatment of nasopharyngeal carcinoma (NPC), and fibroblast growth factor receptor 2 (FGFR2) has emerged to be a promising target for treatment in various tumors. Therefore, the present study aimed to explore whether the expression levels of FGFR2 in NPC tissues and cell lines were altered, and whether the efficiency of cisplatin was increased following the downregulation of FGFR2. The downregulation of FGFR2 was achieved by transfection with a small interfering RNA against FGFR2. Tissues of patients with NPC were analyzed by immunohistochemistry. Cell viability was examined using a Cell Counting Kit­8 assay. Cell cycle analysis was performed using flow cytometry. mRNA and protein levels were measured by reverse transcription quantitative polymerase chain reaction and western blot analysis, respectively. FGFR2 was observed to be overexpressed in cancer tissues of patients with NPC and in the NPC SUNE1, C666­1, 6­10B and HNE­3 cell lines, and resulted in an unfavorable prognosis. Cisplatin treatment decreased cell viability and increased FGFR2 expression. The silencing of FGFR2 was demonstrated to augment the effects of cisplatin treatment, including decreasing the cell viability and inducing cell cycle arrest, which involved the increase and decrease of the durations of G1 and S phases, respectively, and a decrease in the expression levels of cyclin D1 and CDC25A, and increasing the rate of apoptosis via the intrinsic apoptosis pathway, as demonstrated by the upregulation of cleaved caspase­3 and B­cell lymphoma 2 (Bcl­2)­associated X protein and downregulation of Bcl­2, in SUNE1 and C666­1 cell lines. FGFR2 was overexpressed in the cancer tissues of patients with NPC and in NPC cell lines, resulting in an unfavorable prognosis. The downregulation of FGFR2 decreased cell viability via cell cycle arrest at G1 phase, and increased the efficacy of the cisplatin­based induction of apoptosis through the intrinsic apoptosis pathway.


Assuntos
Cisplatino/farmacologia , Regulação para Baixo/efeitos dos fármacos , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/tratamento farmacológico , Proteínas de Neoplasias/biossíntese , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/biossíntese , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Feminino , Fase G1/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Proteínas de Neoplasias/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Fase S/efeitos dos fármacos
16.
Math Biosci Eng ; 16(4): 3094-3110, 2019 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-31137252

RESUMO

To explore the impact of the periodic evolution in habitats on the prevention and control of the infectious disease, we consider a diffusive SIS epidemic model in a heterogeneous and periodically evolving domain. By assuming that the evolving domain is uniform and isotropic, the epidemic model in a evolving domain is converted to the reaction diffusion problem in a fixed domain. The basic reproduction number, which depends on the evolving rate of the domain and spatial heterogeneity, is defined. The driving mechanism of the model is obtained by using the principal eigenvalue and the upper and lower solutions method, and a biological explanation of the impact of regional evolution on disease is given. Our theoretical results and numerical simulations show that small evolving rate benefits the control of the infectious disease.


Assuntos
Epidemias/estatística & dados numéricos , Modelos Biológicos , Número Básico de Reprodução/estatística & dados numéricos , Controle de Doenças Transmissíveis/estatística & dados numéricos , Doenças Transmissíveis/epidemiologia , Simulação por Computador , Ecossistema , Meio Ambiente , Humanos , Conceitos Matemáticos
17.
Genet Test Mol Biomarkers ; 23(4): 246-250, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30986102

RESUMO

AIMS: To determine the diagnostic precision of using different sets of fetal-specific methylation markers with methylation-sensitive restriction enzyme-quantitative polymerase chain reaction (MSRE-qPCR) for detection of trisomy 21 (T21). MATERIALS AND METHODS: The diagnostic value for trisomy 21 of differential methylation of HLCS, C21orf25, and RASSF1A (a fetal-specific internal control) was examined by MSRE-qPCR. RESULTS: The combined marker set of HLCS and RASSF1A achieved accurate quantification of fetal-specific chromosome 21 and was an excellent marker for detecting the presence of three copies of chromosome 21. MSRE-qPCR correctly identified three cases of fetal T21 from 11 clinical samples, which were 100% consistent with karyotyping results. In addition, this method was able to detect fetal-specific, T21-derived, cell-free fetal DNA at concentrations as low as 0.1%. CONCLUSIONS: Evaluation of the HLCS and RASSF1A fetal-specific methylation marker set by MSRE-qPCR could be a highly sensitive, specific, cost-effective, and noninvasive prenatal screening method for T21. This MSRE-qPCR testable marker should be considered as an alternative to next generation sequencing technology for diagnosing fetal T21.


Assuntos
Síndrome de Down/diagnóstico , Síndrome de Down/genética , Biomarcadores/metabolismo , Carbono-Nitrogênio Ligases/genética , Cromossomos Humanos Par 21/genética , Ilhas de CpG , DNA/análise , Metilação de DNA/genética , Epigênese Genética/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Masculino , Reação em Cadeia da Polimerase/métodos , Gravidez , Diagnóstico Pré-Natal/métodos , Trissomia , Proteínas Supressoras de Tumor/genética
18.
Cardiovasc Diabetol ; 17(1): 149, 2018 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-30482197

RESUMO

BACKGROUND: Negative coronary artery remodeling is frequent in patients with diabetes, but its mechanism remains unclear. We here evaluated the association of serum levels of glycated albumin (GA) and endogenous secretory receptor for advanced glycation end products (esRAGE) with coronary artery remodeling in type 2 diabetic patients. METHODS: Serum levels of GA and esRAGE were measured and intravascular ultrasound was performed in 136 consecutive diabetic patients with 143 coronary intermediate lesions. The remodeling index (RI) was calculated as the ratio between external elastic membrane (EEM) area at the lesion site and EEM area at the reference segment. Negative remodeling (NR) was defined as an RI < 0.95 and intermediate or positive remodeling as an RI ≥ 0.95. RESULTS: Mean plaque burden at the lesion site was 70.96 ± 9.98%, and RI was 0.96 ± 0.18. Negative coronary arterial remodeling existed in 81 (56.6%) lesions. RI correlated closely with serum esRAGE level (r = 0.236, P = 0.005) and was inversely related to serum GA level (r = - 0.240, P = 0.004) and plasma low-density lipoprotein cholesterol (LDL-C) (r = - 0.206, P = 0.014) and total cholesterol levels (r = - 0.183, P = 0.028). Generalized estimating equations logistic regression analysis identified esRAGE (OR 0.037; 95% CI 0.012-0.564, P = 0.021), GA (OR 1.093; 95% CI 1.013-1.179, P = 0.018) and LDL-C (OR 1.479; 95% CI 1.072-2.835, P = 0.023) as independent predictors for negative remodeling. CONCLUSIONS: In diabetic patients, negative coronary artery remodeling is associated with increased GA and decreased esRAGE levels in serum.


Assuntos
Doença da Artéria Coronariana/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Diabetes Mellitus Tipo 2/sangue , Hemoglobina A Glicada/metabolismo , Receptor para Produtos Finais de Glicação Avançada/sangue , Ultrassonografia de Intervenção , Remodelação Vascular , Idoso , Biomarcadores/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/patologia , Vasos Coronários/patologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica , Valor Preditivo dos Testes
19.
Plant Physiol ; 178(2): 824-837, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30061119

RESUMO

Perception and transduction of salt stress signals are critical for plant survival, growth, and propagation. Thus, identification of components of the salt stress-signaling pathway is important for rice (Oryza sativa) molecular breeding of salt stress resistance. Here, we report the identification of an apetala2/ethylene response factor transcription factor INDETERMINATE SPIKELET1 (IDS1) and its roles in the regulation of rice salt tolerance. By genetic screening and phenotype analysis, we demonstrated that IDS1 conferred transcriptional repression activity and acted as a negative regulator of salt tolerance in rice. To identify potential downstream target genes regulated by IDS1, we conducted chromatin immunoprecipitation (ChIP) sequencing and ChIP-quantitative PCR assays and found that IDS1 may directly associate with the GCC-box-containing motifs in the promoter regions of abiotic stress-responsive genes, including LEA1 (LATE EMBRYOGENESIS ABUNDANT PROTEIN1) and SOS1 (SALT OVERLY SENSITIVE1), which are key genes regulating rice salt tolerance. IDS1 physically interacted with the transcriptional corepressor topless-related 1 and the histone deacetylase HDA1, contributing to the repression of LEA1 and SOS1 expression. Analyses of histone H3 acetylation status and RNA polymerase II occupation on the promoters of LEA1 and SOS1 further defined the molecular foundation of the transcriptional repression activity of IDS1. Our findings illustrate an epigenetic mechanism by which IDS1 modulates salt stress signaling as well as salt tolerance in rice.


Assuntos
Etilenos/metabolismo , Histona Desacetilases/metabolismo , Oryza/enzimologia , Reguladores de Crescimento de Planta/metabolismo , Fatores de Transcrição/metabolismo , Histona Desacetilases/genética , Oryza/genética , Oryza/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regiões Promotoras Genéticas/genética , Tolerância ao Sal , Estresse Fisiológico , Fatores de Transcrição/genética
20.
Mol Med Rep ; 18(3): 3537-3543, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30066937

RESUMO

Aloe vera is a traditional wound­healing medicine used for the treatment of skin disorders. Aloe polysaccharide (APS) is the main macromolecule of Aloe vera, which contributes to its function. Psoriasis is an immune­mediated chronic inflammatory disease, which affects 2­3% of the general population. The conventional remedies used to treat psoriasis demonstrate limited effects; therefore, natural products, including Aloe vera, are being taken into consideration. However, the effects of APS on the treatment of psoriasis and the underlying mechanisms remain to be elucidated. The human keratinocyte cell line HaCaT was used to determine the effects of APS on psoriasis. Cells were randomly divided into five groups: i) Negative control group; ii) tumor necrosis factor (TNF)­α stimulated psoriasis model group; and iii) APS (20, 40 and 80 µg/ml) pretreated psoriasis groups. Cell viability and proliferation were investigated using the CCK­8 assay. ELISA and western blotting were applied to study the abundance of interleukin (IL)­8 and IL­12 in TNF­α­incubated culture medium and APS­treated HaCaT cells, respectively. In addition, the mRNA expression levels of p65, and the protein expression levels of nuclear factor (NF)­κB inhibitor­α (IκBα) and phosphorylated­p65, were detected by reverse transcription­quantitative polymerase chain reaction and western blotting, respectively. APS was revealed to significantly reduce TNF­α­stimulated elevation of HaCaT cell proliferation in a dose­dependent manner. The expression levels of inflammatory factors, including IL­8 and IL­12, were increased in response to TNF­α. In addition, the mRNA and protein expression levels of p65 were increased following treatment with TNF­α. Notably, treatment with APS was demonstrated to significantly attenuate the aforementioned effects in a dose­dependent manner. Furthermore, IκBα protein expression levels were significantly reduced following treatment with TNF­α, which was significantly reversed following treatment with APS. In conclusion, these results suggested that APS inhibited TNF­α­induced proliferation of keratinocytes and overactivation of the NF­κB signaling pathway.


Assuntos
Aloe/química , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Regulação da Expressão Gênica , Humanos , Mediadores da Inflamação/metabolismo , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , NF-kappa B/metabolismo , Extratos Vegetais/química , Polissacarídeos/química , Psoríase/genética , Psoríase/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia
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