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1.
Artigo em Inglês | MEDLINE | ID: mdl-35001882

RESUMO

OBJECTIVE: To investigate the value of contrast-enhanced ultrasound (CEUS) for the diagnosis of cervical tuberculous lymphadenitis (CTL). METHODS: The cohort study included 203 consecutive patients diagnosed with cervical lymph node. Before pathological or laboratory confirmation, all patients underwent CEUS examination, and the imaging findings were analyzed afterward. The diagnostic efficiency of the CEUS imaging findings of CTL was evaluated. RESULTS: Nighty-seven patients of the 203 (47.8%) were pathologically or laboratory confirmed with a CTL diagnosis while the remainder (52.2%) were diagnosed with non-tuberculous lymphadenitis. Regarding the imaging findings of CEUS, it was more common in CTL patients to find a pattern of heterogeneous enhancement inside the lymph nodes relative to non-tuberculous patients [81.44% (79/97) vs 15.09% (16/106), P <  0.01]. The sensitivity of the feature in diagnosis for CTL was 81.44% and the specificity was 84.91%, resepectively. Furthermore, a pattern of peripheral rim-like enhancement had been notable in CTL patients compared with non-tuberculous patients [86.60% (84/97) vs 12.26% (13/106), P <  0.01], associating with a diagnostic sensitivity of 86.60% and a specificity of 87.74% . When it came to the combination of both imaging findings mentioned above, the features were more prominent in CTL patients than compared with non-tuberculous patients [74.23% (72/97) vs 5.66% (6/106), P <  0.01], with a diagnostic sensitivity of 74.23% and a high specificity of 94.34% . Regarding area under curve (AUC) for the ROC analysis, the feature of internal heterogeneous enhancement, peripheral rim-like enhancement, and both features were 0.832, 0.872, and 0.843. CONCLUSIONS: CEUS patterns of heterogeneous enhancement and peripheral rim-like enhancement of lymph nodes are helpful characteristics for the diagnosis of CTL.

2.
Eur Radiol ; 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35029731

RESUMO

OBJECTIVES: To investigate the clinical characteristics and outcomes on the success of bronchial arterial embolization (BAE) in patients with and without systemic artery-to-pulmonary vessel fistula (SA-PF) and to evaluate the feasibility of CTA in the assessment of SA-PF. METHODS: We retrospectively enrolled 420 consecutive patients that underwent BAE for hemoptysis control in our hospital from September 2011 to May 2019. The clinical characteristics, preprocedural CTA findings, BAE procedural findings, and follow-up outcomes were collected. Patients were divided into two groups according to DSA findings: patients with SA-PF and those without. RESULTS: A total of 184 (43.7%) patients presented with SA-PF. Pneumonia was less likely to be the concomitant condition in patients with SA-PF (p < 0.001). The mean number of culprit arteries per patient was significantly higher in patients with SA-PF compared to that in patients without SA-PF (p = 0.017). The SA-PF patients saw a greater probability of recurrence (HR: 2.782, 95% CI: 1.617-4.784, p < 0.001). SA-pulmonary venous fistula (SA-PVF) favored lower hemoptysis recurrence rate (HR: 0.199, 95%CI: 0.052-0.765, p = 0.019). SA-pulmonary artery fistula (SA-PAF) can be detected by optimized CTA protocol with a detection rate of 65.3% (49/75). CONCLUSIONS: The presence of SA-PF is an independent risk factor predicting early recurrence of hemoptysis after BAE. SA-PVF seems to be a protective factor for longer hemoptysis control compared to SA-PAF. Optimized preprocedural CTA is a reliable examination to identify SA-PAF. KEY POINTS: • The appearance of SA-PF is associated with a greater probability of early recurrent hemoptysis after bronchial artery embolization. • The presence of SA-PVF seems to be a protective factor for longer hemoptysis control after BAE compared to SA-PAF. • Optimized CTA protocol seems to be a promising auxiliary examination to detect SA-PAF.

3.
Bioresour Technol ; 343: 126130, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34655777

RESUMO

Herein, acidic concentrated lithium bromide-water system was efficiently carried out to synthesize levulinic acid (LA) from raw lignocellulose by two-step treatment. Saccharification was processed in 1st step, and 80.96 wt% glucose and 85.60 wt% xylose were yielded based on their theoretical yield from poplar at 110 °C for 20 min. The hydrolysate after solid residual lignin (SRL) separation was converted into LA and furfural by thermal treatment (130 °C) in the 2nd step, where 67.0 wt% LA and 48.0 wt% furfural were yielded. The SRL in 1st step, with high hydrophobicity and uniform dispersity, was used to prepare lignin nanoparticles (LNPs), which showed tailored size (100-200 nm diameters) and morphology in solid or hollow structure with single hole. Additionally, the residue in 2nd step was suggested as biochar. So far, this study offered a simple pathway for utilization of raw lignocellulose in water system, resulting in high yields of LA and LNPs.


Assuntos
Lignina , Água , Brometos , Ácidos Levulínicos , Compostos de Lítio
4.
BMC Surg ; 21(1): 416, 2021 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-34906107

RESUMO

BACKGROUND: To investigate the value of multimodal ultrasonography in differentiating tuberculosis from other lymphadenopathy. METHODS: Sixty consecutive patients with superficial lymphadenopathy treated at our hospital from January 2017 to December 2018 were categorized into four types based on the color Doppler ultrasound, five types based on contrast-enhanced ultrasound, and five types based on elastography. Sensitivity and specificity were calculated of all the three imaging, including color Doppler examination, contrast-enhanced ultrasound and one individual multimodal method, for detecting lymph nodes. RESULTS: A total of 60 patients were included in the final analysis. Of those, Mycobacterium tuberculosis was positive in 38 patients and negative in 22 patients. Among the 38 patients who were positive for Mycobacterium tuberculosis, of which 23 had a history of pulmonary tuberculosis, accounting for 60.53% of the positive cases, and the remaining patients did not combine lesions of other organs. Among the 60 superficial lymph nodes, 63.3% presented with tuberculous lymphadenitis. The sensitivity, specificity, and accuracy of the color Doppler examination were 73.68%, 68.18%, and 71.67%, respectively. The sensitivity, specificity and accuracy of contrast-enhanced ultrasound were 89.47%, 63.64% and 80.00%, respectively. The sensitivity, specificity and accuracy of the elastography were 63.16%, 63.64% and 63.33%, respectively. The sensitivity, specificity and accuracy of one individual multimodal method were 42.11%, 95.45% and 61.67%, respectively. The sensitivity, specificity and accuracy of all modes combined were 100.00%, 27.27% and 73.33%, respectively. CONCLUSION: Multimodal ultrasonography has high predictive value for the differential diagnosis of superficial tuberculous lymphadenitis.


Assuntos
Linfadenite , Linfadenopatia , Tuberculose dos Linfonodos , Diagnóstico Diferencial , Humanos , Linfonodos , Tuberculose dos Linfonodos/diagnóstico por imagem , Ultrassonografia
5.
Front Physiol ; 12: 753914, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34751218

RESUMO

Glyphodes pyloalis Walker (Lepidoptera: Pyralidae) is a destructive mulberry pest, causing great damage to mulberry in China. Heat shock proteins (Hsps) are involved in various signal pathways and regulate lots of physiological processes in insects. The function of Hsps in G. pyloalis, however, has still received less attention. Here, we identified five Hsp genes from G. pyloalis transcriptome dataset including two Hsp70 family genes (GpHsp71.3 and GpHsp74.9) and three Hsp90 family genes (GpHsp82.4, GpHsp89, and GpHsp93.4). Quantitative Real-time PCR validation revealed that all Hsps of G. pyloalis have significant expression in pupal and diapause stage, at which the larvae arrest the development. Expressions of GpHsp71.3 and GpHsp82.4 were increased significantly after thermal treatment at 40°C, and this upregulation depended on heat treatment duration. Furthermore, silencing GpHsp82.4 by RNA interference led to a significant increase in mortality of G. pyloalis larvae under the heat stress compared to the control group. After starvation stress, the expression levels of GpHsp82.4 and GpHsp93.4 were significantly increased. At last, after being parasitized by the parasitoid wasp Aulacocentrum confusum, Hsp70 and Hsp90 genes of G. pyloalis were decreased significantly in the early stage of parasitization and this moderation was affected by time post-parasitization. This study highlights the function of G. pyloalis Hsps in response to environmental stress and provides a perspective for the control of this pest.

6.
Molecules ; 26(22)2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34833921

RESUMO

Panax quinquefolius, a popular medicinal herb, has been cultivated in China for many years. In this work, the region-specific profiles of metabolites in P. quinquefolius from Wendeng was investigated using liquid-chromatography-quadrupole-time-of-flight-(LC-Q-TOF)-based metabolomics analysis. The three most abundant biomarkers, identified as ginsenoside Rb3, notoginsenoside R1, and ginsenoside Rc, were the representative chemical components employed in the network pharmacology analysis. In addition, molecular docking and western blotting analyses revealed that the three compounds were effective binding ligands with Hsp90α, resulting in the inactivation of SRC and PI3K kinase, which eventually led to the inactivation of the Akt and ERK pathways and lung cancer suppression. The outcomes obtained herein demonstrated the intriguing chemical characteristics and potential functional activities of P. quinquefolius from Wendeng.

7.
J Psychiatr Res ; 144: 217-224, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34700209

RESUMO

BACKGROUND: Research on predictors and risk of recurrence after suicide attempt from China is lacking. This study aims to identify risk factors and develop prediction models for recurrent suicidal behavior among suicide attempters using Cox proportional hazard (CPH) and machine learning methods. METHODS: The prospective cohort study included 1103 suicide attempters with a maximum follow-up of 10 years from rural China. Baseline characteristics, collected by face-to-face interviews at least 1 month later after index suicide attempt, were used to predict recurrent suicidal behavior. CPH and 3 machine learning algorithms, namely, the least absolute shrinkage and selection operator, random survival forest, and gradient boosting decision tree, were used to construct prediction models. Model performance was accessed by concordance index (C-index) and the time-dependent area under the receiver operating characteristic curve (AUC) value for discrimination, and time-dependent calibration curve along with Brier score for calibration. RESULTS: The median follow-up time was 7.79 years, and 49 suicide attempters had recurrent suicidal behavior during the study period. Four models achieved comparably good discrimination and calibration performance, with all C-indexes larger than 0.70, AUC values larger than 0.65, and Brier scores smaller than 0.06. Mental disorder emerged as the most important predictor across all four models. Suicide attempters with mental disorders had a 3 times higher risk of recurrence than those without. History of suicide attempt (HR = 2.84, 95% CI: 1.34-6.02), unstable marital status (HR = 2.81, 95% CI: 1.38-5.71), and older age (HR = 1.51, 95% CI: 1.14-2.01) were also identified as independent predictors of recurrent suicidal behavior by CPH model. CONCLUSIONS: We developed four models to predict recurrent suicidal behavior with comparable good prediction performance. Our findings potentially provided benefits in screening vulnerable individuals on a more precise scale.

8.
Chemosphere ; : 132679, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34718007

RESUMO

Poplar trees rapidly yield wood and are therefore suitable as a biofuel feedstock; however, the quality of poplar is modest, and the profitability of poplar cultivation depends on the efficiency of the harvesting process. This study offers a simple and sustainable technique to harvest lignocellulosic resources from poplar for bioethanol production. The proposed two-step pretreatment method increased the surface lignin content and decreased the surface polysaccharide content. The cellulose content increased to 54.9% and the xylan content decreased to 6.7% at 5% AC. The cellulose yield of poplar residues (Populus L.) reached 65.5% by this two-step acetic acid (AC) and sodium sulphite (SS) treatment method. Two-step pretreatment using 5% AC and 4% SS obtained a recovery of nearly 80% of the total available fermentable sugar. The surface characterization showed a higher porosity in treated samples, which improved their hydrolysability. This method decreased the amount of lignin in plant biomass, making it applicable for further wood resource recovery or waste recycling for biorefinery purposes at very low costs.

9.
Ying Yong Sheng Tai Xue Bao ; 32(9): 3127-3135, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34658197

RESUMO

Climate change may lead to biodiversity loss and species extinction. Understanding the impacts of climate change on the distribution pattern of endangered species is of great value to the identification of priority reserves and the formulation of relevant conservation strategies. Based on the distribution data of Marco Polo sheep (Ovis ammon polii) obtained from the field survey in Taxkorgan Nature Reserve (TNR) in Xinjiang during 2017-2018, the maximum entropy (MaxEnt) model was used to predict the distribution pattern of its suitable habitat under climate change. The results showed that the suitable habitat of Marco Polo sheep was mainly distributed in the northwest of the TNR, with temperature as the key factor affecting its suitable habitat distribution. Under the medium and high emission concentration (RCP4.5 and RCP8.5), the suitable habitat area of Marco Polo sheep would decrease in the next two periods (2050s and 2070s), with the loss rate of suitable habitat being as high as 40.5%. The loss of suitable habitat was mainly located in the low-altitude area, while the area of suitable habitat increased correspondingly in the high-altitude area. The area of suitable habitat from low elevation to high elevation increased with the increases of greenhouse gas emission concentration. According to the results of centroid transfer, the suitable habitat was mainly moved to the west, namely Tajikistan, the main distribution country of Marco Polo sheep.


Assuntos
Mudança Climática , Ecossistema , Animais , Biodiversidade , China , Espécies em Perigo de Extinção , Ovinos
10.
Materials (Basel) ; 14(16)2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34442941

RESUMO

Herein, the paper reports an experimental investigation lasting one year on the chloride resistance of polypropylene fiber (PF) reinforced concrete with fly ash (FA). Four influential factors at four levels were studied, viz. water to binder ratio (w/b) (0.53, 0.34, 0.29, and 0.25), PF dosage (0%, 0.06%, 0.08%, and 0.1% in volume basis of the total volume of concrete), FA content (0%, 15%, 25%, and 35% in mass substitution ratio of cement) and concentration of NaCl solution (0%, 3%, 5%, and 7%). Dry-wet cyclic immersion and long-term soaking were taken into consideration in addition to the aforementioned factors. A L16(44) orthogonal table was used to sequence influencing factors and to determine the optimal combination. Results showed that 7% NaCl solution caused the highest chloride content in 0-5 mm depth, whilst the w/b ratio of 0.25 curbed the chloride penetration within 10 mm even for concrete subjected to dry-wet cyclic immersion for 360 d. Subsequently, a respond surface model (RSM) basing on polynomials was constructed to visually evaluate the effect of PF dosage and FA content. Results clarified that a cubic model was more precise and PF dosage and FA content turned out to have the positive facilitation to chloride resistance. The positive effect of PF however is not consistent and commensurate for concrete with varied fly ash content. Finally, a fuzzy logic based nonlinear model accommodating all seven influencing factors was verified to be proper and adaptive in predicting chloride content.

11.
Microbiol Immunol ; 65(10): 410-421, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34101233

RESUMO

Surfactin, an antibacterial peptide, produced by various Bacillus subtilis strains, have broad-spectrum antibacterial and immune-enhancing functions. In this study, we investigated the anti-inflammatory, antioxidant, and hepatoprotective effect of surfactin on zebrafish (Danio rerio) larvae following their exposure to copper sulfate (CuSO4 ). The mature AB wild-type and a transgenic line of zebrafish larvae that expressed enhanced GFP (EGFP) named Tg (Lyz:EGFP) were exposed to 0, 20, 40, and 60 µg/mL surfactin after incubation with 3.2 µg/mL CuSO4 for 2 h from 72 h postfertilization (hpf). Different endpoints, such as migration of GFP-labeled neutrophils, analysis of inflammatory cytokines and transaminases, markers of oxidation, expression of certain genes, and histological changes of liver, were studied to evaluate the function of surfactin. The protein expression levels of NF-κBp65, TNF-α, cyclooxygenase-2 (COX-2), and iNOS were determined in murine macrophage RAW 264.7 cells by western blotting. Our results show that surfactin reduced migration of neutrophils and relieved hepatic injury. In addition, surfactin reduced the index levels of inflammatory factors, oxidative stress response, and improved hepatic function. Surfactin also significantly inhibited the expression of IL-1ß, IL-8, TNF-α, nitric oxide, NF-κBp65, COX-2, and iNOS, and increased the expression of IL-10. Thus, our results demonstrate that surfactin has anti-inflammatory, antioxidant, and hepatoprotective activities. Surfactin has potential as a novel inflammation and immune adjustment.


Assuntos
Sulfato de Cobre , Peixe-Zebra , Animais , Sulfato de Cobre/toxicidade , Inflamação/tratamento farmacológico , Inflamação/prevenção & controle , Fígado , Camundongos , NF-kappa B/metabolismo , Estresse Oxidativo , Peixe-Zebra/metabolismo
12.
Front Plant Sci ; 12: 648026, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34122473

RESUMO

Understanding the roles played by geography and ecology in driving species diversification and in the maintenance of species cohesion is the central objective of evolutionary and ecological studies. The multi-phased orogenesis of Qinghai-Tibetan Plateau (QTP) and global climate changes over late-Miocene has profoundly influenced the environments and evolution of organisms in this region and the vast areas of Asia. In this study, we investigate the lineage diversification of Chrysanthemum-group in subtribe Artemisiinae (tribe Anthemideae, Asteraceae) likely under the effects of climate changes during this period. Using DNA sequences of seven low-copy nuclear loci and nrITS and the coalescent analytical methods, a time-calibrated phylogeny of subtribe Artemisiinae was reconstructed with emphasis on Chrysanthemum-group. The monophyletic Chrysanthemum-group was well resolved into two major clades corresponding to Chrysanthemum and Ajania, two genera which can be well identified by capitulum morphology but have been intermingled in previous plastid and ITS trees. Within Chrysanthemum, a later divergence between Ch. indicum-complex and Ch. zawadskii-complex can be recognized. The time frames of these sequential divergences coincide with the late Cenozoic uplift of the Northern QTP and the concomitant climatic heterogeneity between eastern and inland Asia. Reconstruction of historical biogeography suggested the origin of Chrysanthemum-group in Central Asia, followed by eastward migration of Chrysanthemum and in situ diversification of Ajania. Within Chrysanthemum, Ch. indicum-complex and Ch. zawadskii-complex exhibited contemporary distributional division, the former in more southern and the latter in more northern regions. The geographic structure of the three lineages in Chrysanthemum-group have been associated with the niche differentiation, and environmental heterogenization in Asia interior.

13.
Plant J ; 106(4): 1024-1038, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33638198

RESUMO

Evolutionary shifts among radiate, disciform and discoid flowerheads have occurred repeatedly in a number of major lineages across the Asteraceae phylogeny; such transitions may also appear within evolutionarily young groups. Although several studies have demonstrated that CYC2 genes partake in regulating floral morphogenesis in Asteraceae, the evolution of capitulum forms within a recently diverging lineage has remained poorly understood. Here, we study the molecular regulation of the shift from a radiate to a disciform capitulum within the Chrysanthemum group. This is a recently radiating group mainly comprising two genera, Chrysanthemum and Ajania, that are phylogenetically intermingled but distinct in flowerhead morphology: Chrysanthemum spp. with radiate capitula and Ajania spp. with disciform capitula. We found that the morphogenesis of zygomorphy in the marginal floret in Ajania was disrupted soon after floral primordium emergence; CYC2g, one of the CYC2 copies that was expressed prominently in the ray floret of Chrysanthemum was not expressed in flowerheads of Ajania. Weakening the expression of ClCYC2g in Chrysanthemum lavandulifolium led to the gradual transition of a ray flower toward the disc-like form. Molecular evolutionary analyses indicated that the disciform capitulum might have evolved only once, approximately 8 Mya, arising from dysfunction of the CYC2g orthologs. A 20-nt deletion, including a putative TATA-box of the Ajania-type CYC2g promoter, appeared to inhibit the expression of the gene. Considering the divergent habitats of Chrysanthemum and Ajania, we propose that the shift from radiate to disciform capitulum must have been related to changes in pollination strategies under selective pressure.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33611221

RESUMO

The interaction between a host and its parasitoid is one of the most fascinating relationships of insects. Immune-related genes play crucial roles in this association. Nevertheless, until now, identification of these genes on a large scale has not received much attention. To gain insight into the parasitic effects of the endoparasitoid Aulacocentrum confusum (Hymenoptera: Braconidae) on Glyphodes pyloalis (Lepidoptera: Pyralidae) larva, which is a destructive pest of mulberry (Morus alba L.) trees in China, we presented a transcriptome dataset for uncovering immune-related genes in parasitized G. pyloalis larvae. In total, 91,118,138 and 92,778,814 clean reads were obtained from parasitized and healthy host larvae, respectively, and de novo assembly generated 57,122 unigenes. The transcriptional profile of G. pyloalis larvae was remarkably influenced by parasitism. A total of 3259 differentially expressed genes (DEGs) were identified in parasitized and nonparasitized G. pyloalis larvae and 55 genes related to immune response were screened from these DEGs. Among the 55 DEGs, 37 genes were significantly upregulated, and 18 genes were downregulated. qRT-PCR validated the sequencing results and revealed that the expression levels of selected immune-related genes depended on the parasitization and duration after parasitization. Knocking down the C type lectin gene (CTL) changed the expression of serine proteinase, serine protease inhibitor, antimicrobial peptide, prophenoloxidase activating enzymes and peroxiredoxin in G. pyloalis larvae, suggesting CTL can modulate the immune response after parasitization by A. confusum females. The present study provides a foundation for revealing the molecular mechanisms of immune response in G. pyloalis larvae when they are parasitized by A. confusum and promotes the development of novel biological control practices for G. pyloalis.


Assuntos
Himenópteros/imunologia , Lepidópteros/parasitologia , Morus/parasitologia , Animais , Genes de Insetos , Himenópteros/genética , Imunidade , Larva/imunologia , Larva/parasitologia , Lepidópteros/imunologia , Doenças das Plantas/parasitologia , Transcriptoma
15.
Genes Genomics ; 43(3): 289-294, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33555503

RESUMO

BACKGROUND: Unlike peoples' belief that transposable elements (TEs) are "junk DNAs" or "genomic parasites", TEs are essential genomic elements that bring about genetic diversity and enable evolution of a species. In fact, transposons are major constituent of chromosome in crop genomes, particularly in major cereal crops, the primary type of which is long terminal repeat (LTR) retrotransposon. Since TE mobilization can be controlled by specific environmental stimulation and as the result can generate novel genetic variations, it has been suggested that controlled mobilization of TEs can be a plausible method for crop breeding. To achieve this goal, series of sequencing techniques have been recently established to identify TEs that are active in mobility. These methods target and detect extrachromosomal DNAs (ecDNAs), which are final products of integration. The newly identified TEs by these methods exhibit strong transpositional activity which can generate novel genetic diversity and provide useful breeding resources. CONCLUSIONS: In this mini review, we summarize and introduce ALE-seq, mobilome-seq, and VLP DNA-seq techniques employed to detect active TEs in plants.

16.
J Cancer ; 12(2): 530-538, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33391449

RESUMO

Recently, ample evidence indicated that numerous aberrantly expressed long non-coding RNAs (lncRNAs) participated in the development of multiple malignancies. However, the expression and function of lncRNA LOXL1-AS1 in mediating esophageal squamous cell carcinoma (ESCC) carcinogenesis remains largely elusive. Here we validated that LOXL1-AS1 was significantly upregulated in ESCC tissues compared with the corresponding adjacent non-neoplastic tissues, and LOXL1-AS1 expression was positively correlated with ESCC patients' lymph node metastasis. Besides, LOXL1-AS1 knockdown impaired ESCC cells proliferation, migration and invasion capabilities in vitro. Furthermore, inhibiting LOXL1-AS1 in ESCC cells increased the percentage of cells at the G1 phase, accompanied by reducing in S phase in contrast to scramble control, and silencing of LOXL1-AS1 evoked ESCC cell apoptosis. From high throughput RNA sequencing (RNA-seq) analysis, we identified that differentially expressed in squamous cell carcinoma 1 (DESC1) was a critical downstream target of LOXL1-AS1. Taken together, we demonstrated the function and mechanism of LOXL1-AS1 in contributing ESCC progression for the first time, and indicated LOXL1-AS1 may be a novel therapeutic biomarker of ESCC.

17.
Mol Ther ; 29(5): 1821-1837, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33484966

RESUMO

Growing evidence indicates that N6-methyladenosine (m6A) is the most pervasive RNA modification in eukaryotic cells. However, the specific role of METTL3 in papillary thyroid carcinoma (PTC) initiation and development remains elusive. Here we found that downregulation of METTL3 was correlated with malignant progression and poor prognosis in PTC. A variety of gain- and loss-of-function studies clarified the effect of METTL3 on regulation of growth and metastasis of PTC cells in vitro and in vivo. By combining RNA sequencing (RNA-seq) and methylated RNA immunoprecipitation sequencing (meRIP-seq), our mechanistic studies pinpointed c-Rel and RelA as downstream m6A targets of METTL3. Disruption of METTL3 elicited secretion of interleukin-8 (IL-8), and elevated concentrations of IL-8 promoted recruitment of tumor-associated neutrophils (TANs) in chemotaxis assays and mouse models. Administration of the IL-8 antagonist SB225002 substantially retarded tumor growth and abolished TAN accumulation in immunodeficient mice. Our findings revealed that METTL3 played a pivotal tumor-suppressor role in PTC carcinogenesis through c-Rel and RelA inactivation of the nuclear factor κB (NF-κB) pathway by cooperating with YTHDF2 and altered TAN infiltration to regulate tumor growth, which extends our understanding of the relationship between m6A modification and plasticity of the tumor microenvironment.

18.
J Cancer ; 12(4): 1200-1211, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33442418

RESUMO

Background: Recent researches have pinpointed that long non-coding RNA (lncRNA) was tightly related to the carcinogenesis. However, the function of lncRNA in esophageal cell squamous carcinoma (ESCC) remains to be explored. In the current study, we assessed the expression pattern and the biological function of FAM83A-AS1 in ESCC. Methods: qRT-PCR was used to detect the expression of FAM83A-AS1, miR-214, and CDC25B expression in ESCC tissues and cell lines. CCK-8, transwell, apoptosis and cell cycle assays were performed to define the function of FAM83A-AS1 in ESCC cells. Furthermore, the regulation of miR-214 by FAM83A-AS1 was defined by qRT- PCR and rescue assays. In addition, the association between CDC25B, miR-214, CDC25B was confirmed by qRT-PCR. Results: Here, we discovered that FAM83A-AS1 was strongly expressed in ESCC tissues. FAM83A-AS1 abundance was associated with TNM stages and the differentiation grade of ESCC patients. The receiver operating characteristic curve (ROC) analysis indicated the high accuracy of FAM83A-AS1 in ESCC diagnosis. Functionally, inhibiting FAM83A-AS1 repressed cell proliferation, migration, and invasion in ESCC. In addition, we found that FAM83A-AS1 accelerated the cell cycle while inhibited cell apoptosis. Mechanistically, we found that FAM83A-AS1 regulated miR-214 expression, and there was a negative correlation between miR-214 and FAM83A-AS1 in ESCC. Rescue assay indicated that miR-214 could impair the suppressing effect of cell migration induced by FAM83A-AS1 depletion. Furthermore, CDC25B was a direct target of miR-214, and FAM83A-AS1 enhanced CDC25B expression while miR-214 positively CDC25B expression in ESCC. Conclusions: Collectively, we concluded that FAM83A-AS1 facilitated ESCC progression by regulating the miR-214/CDC25B axis. Our study showed FAM83A-AS1 may act as a promising target for ESCC diagnosis and therapy.

19.
Acta Pharmacol Sin ; 42(1): 68-76, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32457417

RESUMO

Programmed cell death (PCD), including apoptosis, apoptotic necrosis, and pyroptosis, is involved in various organ dysfunction syndromes. Recent studies have revealed that a substrate of caspase-3, gasdermin E (GSDME), functions as an effector for pyroptosis; however, few inhibitors have been reported to prevent pyroptosis mediated by GSDME. Here, we developed a class of GSDME-derived inhibitors containing the core structure of DMPD or DMLD. Ac-DMPD-CMK and Ac-DMLD-CMK could directly bind to the catalytic domains of caspase-3 and specifically inhibit caspase-3 activity, exhibiting a lower IC50 than that of Z-DEVD-FMK. Functionally, Ac-DMPD/DMLD-CMK substantially inhibited both GSDME and PARP cleavage by caspase-3, preventing apoptotic and pyroptotic events in hepatocytes and macrophages. Furthermore, in a mouse model of bile duct ligation that mimics intrahepatic cholestasis-related acute hepatic failure, Ac-DMPD/DMLD-CMK significantly alleviated liver injury. Together, this study not only identified two specific inhibitors of caspase-3 for investigating PCD but also, more importantly, shed light on novel lead compounds for treating liver failure and organ dysfunctions caused by PCD.


Assuntos
Clorometilcetonas de Aminoácidos/uso terapêutico , Caspase 3/metabolismo , Inibidores de Caspase/uso terapêutico , Hepatopatias/prevenção & controle , Oligopeptídeos/uso terapêutico , Substâncias Protetoras/uso terapêutico , Clorometilcetonas de Aminoácidos/química , Animais , Apoptose/efeitos dos fármacos , Ductos Biliares/cirurgia , Inibidores de Caspase/química , Linhagem Celular Tumoral , Humanos , Ligadura , Masculino , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Oligopeptídeos/química , Fragmentos de Peptídeos/química , Substâncias Protetoras/química , Piroptose/efeitos dos fármacos , Receptores de Estrogênio/química
20.
Exp Biol Med (Maywood) ; 246(2): 226-239, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32996350

RESUMO

Restenosis after angioplasty of peripheral arteries is a clinical problem involving oxidative stress. Hydrogen sulfide (H2S) participates in oxidative stress regulation and activates nuclear factor erythroid 2-related factor 2 (Nrf2). This study investigated the effect of H2S and Nrf2 on restenosis-induced arterial injury. Using an in vivo rat model of restenosis, we investigated whether H2S inhibits restenosis after percutaneous transluminal angioplasty (PTA) and the oxidative stress-related mechanisms implicated therein. The involvement of Nrf2 was explored using Nrf2-shRNA. Neointimal formation and the deposition of elastic fibers were assessed histologically. Inflammatory cytokine secretion and the expression of proteins associated with oxidative stress and inflammation were evaluated. The artery of rats subjected to restenosis showed increased arterial intimal thickness, with prominent elastic fiber deposition. Sodium hydrosulfide (NaHS), an H2S donor, counteracted these changes in vivo. Restenosis caused a decrease in anti-oxidative stress signaling. This phenomenon was inhibited by NaHS, but Nrf2-shRNA counteracted the effects of NaHS. In terms of inflammation, inflammatory cytokines were upregulated, whereas NaHS suppressed the induced inflammatory reaction. Similarly, Nrf2 downregulation blocked the effect of NaHS. In vitro studies using aortic endothelial and vascular smooth muscle cells isolated from experimental animals showed consistent results as those of in vivo studies, and the participation of the nuclear factor-kappa B signaling pathway was demonstrated. Collectively, H2S played a role in regulating post-PTA restenosis by alleviating oxidative stress, modulating anti-oxidant defense, and targeting Nrf2-related pathways via nuclear factor-kappa B signaling.


Assuntos
Angioplastia/efeitos adversos , Reestenose Coronária/etiologia , Reestenose Coronária/patologia , Sulfeto de Hidrogênio/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Reestenose Coronária/metabolismo , Hiperplasia , Inflamação/patologia , Masculino , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Oxirredução , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Túnica Íntima/efeitos dos fármacos , Túnica Íntima/patologia
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