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1.
Pediatr Cardiol ; 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33938988

RESUMO

To evaluate the surgical outcomes of total anomalous pulmonary venous drainage focusing on survival, postoperative and pulmonary venous obstruction. Further investigate the role of primary sutureless technique in patients with preoperative pulmonary venous obstruction. Consecutive patients underwent total anomalous pulmonary venous drainage repair in our institution during Jan 2000 to Dec 2019 were enrolled into this retrospective analysis. Since 2016, sutureless repair was regularly applied in patients with preoperative pulmonary venous obstruction. All patients with preoperative pulmonary venous obstruction referred before 2016 had underwent traditional repair. A total of 95 patients were included. During follow-up time of 85 months, main endpoints were documented in 21 patients, including 9 (9.5%) early deaths, 3 (2.3%) late deaths and 9 (9.5%) postoperative pulmonary venous obstructions. Preoperative pulmonary venous obstruction was presented in 26 (27.4%) patients with more emergent surgery (14/26 vs 3/69, P < 0.001) was required. Main endpoints occurred more in patients with preoperative pulmonary venous obstruction (4/26 vs 5/69, P = 0.004). Patients experienced sutureless technique had a lower incidence of postoperative PVO at follow-up (0/11 versus 4/11, P = 0.045). Outcomes of surgical repair for total anomalous venous drainage are satisfactory. However, preoperative pulmonary venous obstruction may be accompanying unfavorable early deaths and postoperative pulmonary venous obstruction. Propensity matching analysis showed that sutureless technique was benefit for postoperative pulmonary venous obstruction without longer cardiopulmonary bypass and aortic cross-clamp time.

2.
Eur J Hum Genet ; 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33824467

RESUMO

Thoracic aortic aneurysm with or without dissection (TAAD) can be broadly categorized as syndromic TAAD (sTAAD) and isolated TAAD (iTAAD). sTAAD and is highly correlated with genetics. However, although the incidence of iTAAD is much higher, its monogenic contribution is not yet clear. Here, we sequenced 15 known TAAD genes for 578 iTAAD cases from four cardiac centers in China and found that 10.6% patients with a pathogenic/likely pathogenic (P/LP) variant. Other 7.27% of patients carried variants of uncertain significance in these target genes. We further investigated the correlations among genetics, clinical features, and long-term outcomes. Genetic patients showed younger onset ages (P = 1.31E-13) and larger aortic diameter (P = 1.00E-6), with the youngest age in patients with FBN1 P/LP variants. Monogenic variants were also associated with more aortic segments involved (P = 0.043) and complicated with initial dissection (P = 4.50E-5), especially for genetic patients with non-FBN1 P/LP variants. MACEs occurred in 14.9% patients during follow-up of median 55 months. Genetic status (P = 0.001) and initial dissection (P = 3.00E-6) were two major risk factors for poor prognosis. Early onset age was associated with MACEs in non-genetic cases without initial dissection (P = 0.005). Our study revealed the monogenic contribution in known TAAD genes to iTAAD patients. The genotype-phenotype correlations may complement the risk stratification of iTAAD patients and identification of higher risk subgroups, as well as assist the development of tailored precision medicine in iTAAD.

3.
BMC Cardiovasc Disord ; 21(1): 172, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33845782

RESUMO

BACKGROUND: Epicardial adipose tissue (EAT) shares the same microcirculation with coronary arteries through coronary arteries branches, and contributes to the development of atherosclerosis. MicroRNAs (miRNAs) are involved in the formation of atherosclerosis. However, the alteration of miRNA profile in EAT during atherosclerosis is still uncovered. METHODS: The miRNA expression profiles of EAT from non-coronary atherosclerosis disease (CON, n = 3) and coronary atherosclerosis disease (CAD, n = 5) patients was performed to detect the differentially expressed miRNA. Then the expression levels of miRNA in other CON (n = 5) and CAD (n = 16) samples were confirmed by realtime-PCR. miR-200b-3p mimic was used to overexpress the miRNA in HUVECs. The apoptosis of HUVECs cells was induced by H2O2 and ox-LDL, and detected by Annexin V/PI Staining, Caspase 3/7 activity and the expression of BCL-2 and BAX. RESULTS: 250 miRNAs were differentially expressed in EAT from CAD patients, which were associated with metabolism, extracellular matrix and inflammation process. Among the top 20 up-regulated miRNAs, the expression levels of miR-200 family members (hsa-miR-200b/c-3p, miR-141-3p and miR-429), which were rich in endothelial cells, were increased in EAT from CAD patients significantly. Upregulation of miR-200 family members was dependent on the oxidative stress. The overexpression of miR-200b-3p could promote endothelial cells apoptosis under oxidative stress by targeting HDAC4 inhibition. CONCLUSIONS: Our study suggests that EAT derived miR-200b-3p promoted oxidative stress induced endothelial cells damage by targeting HDAC4, which may provide a new and promising therapeutic target for AS.

4.
Med Image Anal ; 71: 102031, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33798993

RESUMO

Fundus diseases classification is vital for the health of human beings. However, most of existing methods detect diseases by means of single angle fundus images, which lead to the lack of pathological information. To address this limitation, this paper proposes a novel deep learning method to complete different fundus diseases classification tasks using ultra-wide field scanning laser ophthalmoscopy (SLO) images, which have an ultra-wide field view of 180-200˚. The proposed deep model consists of multi-branch network, atrous spatial pyramid pooling module (ASPP), cross-attention and depth-wise attention module. Specifically, the multi-branch network employs the ResNet-34 model as the backbone to extract feature information, where the ResNet-34 model with two-branch is followed by the ASPP module to extract multi-scale spatial contextual features by setting different dilated rates. The depth-wise attention module can provide the global attention map from the multi-branch network, which enables the network to focus on the salient targets of interest. The cross-attention module adopts the cross-fusion mode to fuse the channel and spatial attention maps from the ResNet-34 model with two-branch, which can enhance the representation ability of the disease-specific features. The extensive experiments on our collected SLO images and two publicly available datasets demonstrate that the proposed method can outperform the state-of-the-art methods and achieve quite promising classification performance of the fundus diseases.

5.
Cardiovasc Toxicol ; 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33929718

RESUMO

Fatty acid-binding protein 5 (FABP5) is an important member of the FABP family and plays a vital role in the metabolism of fatty acids. However, few studies have examined the role of FABP5 in pathological cardiac remodeling and heart failure. The aim of this study was to explore the role of FABP5 in transverse aortic constriction (TAC)-induced pathological cardiac remodeling and dysfunction in mice. Quantitative RT-PCR (qRT-PCR) and western blotting (WB) analysis showed that the levels of FABP5 mRNA and protein, respectively, were upregulated in hearts of the TAC model. Ten weeks after TAC in FABP5 knockout and wild type control mice, echocardiography, histopathology, qRT-PCR, and WB demonstrated that FABP5 deficiency aggravated cardiac injury (both cardiac hypertrophy and fibrosis) and dysfunction. In addition, transmission electron microscopy, ATP detection, and WB revealed that TAC caused severe impairment to mitochondria in the hearts of FABP5-deficient mice compared with that in control mice. When FABP5 was downregulated by siRNA in primary mouse cardiac fibroblasts, FABP5 silencing increased oxidative stress, reduced mitochondrial respiration, and increased the expression of myofibroblast activation marker genes in response to treatment with transforming growth factor-ß. Our findings demonstrate that FABP5 deficiency aggravates cardiac pathological remodeling and dysfunction by damaging cardiac mitochondrial function.

6.
Eur J Clin Invest ; : e13547, 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33782973

RESUMO

BACKGROUND: Our previous studies showed that vitamin D receptor (VDR) depletion promotes lipopolysaccharide (LPS)-induced acute kidney injury (AKI) in mice, and renal VDR is down-regulated in AKI, but the mechanism of VDR down-regulation is unclear. METHODS: Nutritional vitamin D deficiency was induced by feeding mice a vitamin D-deficient (VD-D) diet. Mice were injected intraperitoneally with LPS (20 mg/kg) to establish LPS-induced AKI. Levels of VDR and miR-122 were measured both in vivo and in vitro. The associations between VDR and miR-122 were analysed by dual-luciferase reporter assays. RESULTS: Compared with vitamin D-sufficient (VD-S) mice, VD-D mice developed more severe renal injury following LPS challenge. LPS induced a dramatic decrease in VDR expression and marked induction of miR-122 both in vivo and in vitro. Furthermore, miR-122 hairpin inhibitor alleviated LPS-induced VDR down-regulation whereas miR-122 mimic directly suppressed VDR expression in HK-2 cells. In luciferase reporter assays, miR-122 mimic was able to suppress luciferase activity in 293T cells co-transfected with a luciferase reporter that contains a putative miR-122 target site from 3'UTR of the VDR transcript, but not when this site was mutated. Moreover, miR-122 mimic significantly blocked paricalcitol-induced luciferase activity in 293T cells co-transfected with a VDRE-driven luciferase reporter, whereas miR-122 hairpin inhibitor enhanced paricalcitol's activity to suppress PUMA and caspase 3 activation induced by LPS in HK-2 cells. CONCLUSIONS: Collectively, these studies provide evidence that miR-122 directly targets VDR in renal tubular cells, which strongly suggest that miR-122 up-regulation in the kidney under LPS challenge contributes to kidney injury by down-regulating VDR expression.

7.
Talanta ; 228: 122231, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33773735

RESUMO

A novel solid-phase microextraction coating based on polypyrrole (Ppy) with manganese dioxide modified 6-aminohexanoic acid functionalized graphene (MnO2-fGr) and 1-allyl-3-vinylimidazolium bis(trifluoromethylsulfonyl)imide ([AVIm]NTf2) as dopants (Ppy/MnO2-fGr/[AVIm]NTf2) was successfully prepared by electrochemical method. The composite coating was characterized by scanning electron microscope (SEM), Fourier infrared spectrum (FT-IR) and thermogravimetry (TG). The composite coating showed coarse structure, which could improve the specific surface area of it, and according to the TG curve, it also had good thermal stability. The composite coating was used for the headspace-solid phase microextraction (HS-SPME) and chromatographic analysis of benzoates (i.e. methyl benzoate, ethyl benzoate, propyl benzoate, butyl benzoate),by coupling with gas chromatography with hydrogen flame ionization detector (GC-FID). Under optimal conditions, their enrichment factors were 140-460, linear detection ranges were 25-60000 ng L-1, and detection limits were 2.84-6.42 ng L-1. The standard deviations for five consecutive extractions of 100 µg L-1 analytes were 3.00-10.20%, while the standard deviation for the extractions of 100 µg L-1 analytes with five different coatings were 5.70-13.80%. The proposed method was applied for the detection of the benzoates in cosmetics, and the recoveries for the spiked benzoates were 82.8-116.8%.

8.
PLoS One ; 16(3): e0248872, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33735265

RESUMO

BACKGROUND: The fertility desire of people living with HIV (PLHIV) has been rising in the past decade. However, there are many studies among which the association remains controversial between the fertility desire of HIV-infected persons and antiretroviral therapy (ART), sex, marital status, and educational level. METHODS: We performed a literature search of these meta-analyses in PubMed, the Cochrane Library, Web of Science and ScienceDirect in November 2019. We also reviewed references of eligible studies to complement the search. We used pooled odds ratios (ORs) and 95% confidence intervals (CIs) with a random-effects model and a fixed-effects model to estimate the association between fertility desire among PLHIV and ART, sex, age, marital status, educational level, and number of children. Subgroups with I square values (I2) and sensitivity analyses were performed to assess the heterogeneity and the stability of the overall ORs, respectively. We evaluated publication bias using Egger's test and a visual inspection of the symmetry in funnel plots. RESULTS: In these meta-analyses 50 articles were included with 22,367 subjects. The pooled prevalence of fertility desire among PLHIV was estimated to be 42.04%. The pooled analyses showed that the fertility desire of PLHIV is associated with ART (OR = 1.11, 95% CI:1.00-1.23, P = 0.043), sex (OR = 1.51, 95% CI:1.10-2.09), age (OR = 2.65, 95% CI:2.24-3.14), marital status (OR = 1.34, 95% CI:1.08-1.66), educational level (OR = 0.85, 95% CI:0.73-1.00, P = 0.047) and the number of children (OR = 3.99, 95% CI:3.06-5.20). PLHIV who are on ART, are male, are younger than 30, are married/cohabiting, have received a secondary education or above, and are childless have a higher prevalence of fertility desire. The two factors of age and the number of children, in particular demonstrated a strong significant association with fertility desire. We found moderate heterogeneity in the meta-analyses of age and educational level and high heterogeneity in the meta-analyses of sex, marital status and number of children. Publication bias was detected in the meta-analyses of the association of fertility with sex and educational level. CONCLUSION: This study demonstrates that the prevalence of fertility desire among HIV-infected people is 42.04%, and the fertility desire among PLHIV is associated with ART experience, sex, age, marital status, the number of children, and educational level. Since a majority of PLHIV are of reproductive age, it is necessary to support PLHIV in terms of their needs regarding reproductive decision-making. Through counseling and reproductive health care, further measures to prevent the horizontal and vertical transmission of HIV should be taken.

9.
IEEE Trans Med Imaging ; PP2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33646948

RESUMO

Automatic gastric tumor segmentation and lymph node (LN) classification not only can assist radiologists in reading images, but also provide image-guided clinical diagnosis and improve diagnosis accuracy. However, due to the inhomogeneous intensity distribution of gastric tumor and LN in CT scans, the ambiguous/missing boundaries, and highly variable shapes of gastric tumor, it is quite challenging to develop an automatic solution. To comprehensively address these challenges, we propose a novel 3D multi-attention guided multi-task learning network for simultaneous gastric tumor segmentation and LN classification, which makes full use of the complementary information extracted from different dimensions, scales, and tasks. Specifically, we tackle task correlation and heterogeneity with the convolutional neural network consisting of scale-aware attention-guided shared feature learning for refined and universal multi-scale features, and task-aware attention-guided feature learning for task-specific discriminative features. This shared feature learning is equipped with two types of scale-aware attention (visual attention and adaptive spatial attention) and two stage-wise deep supervision paths. The task-aware attention-guided feature learning comprises a segmentation-aware attention module and a classification-aware attention module. The proposed 3D multi-task learning network can balance all tasks by combining segmentation and classification loss functions with weight uncertainty. We evaluate our model on an in-house CT images dataset collected from three medical centers. Experimental results demonstrate that our method outperforms the state-of-the-art algorithms, and obtains promising performance for tumor segmentation and LN classification. Moreover, to explore the generalization for other segmentation tasks, we also extend the proposed network to liver tumor segmentation in CT images of the MICCAI 2017 Liver Tumor Segmentation Challenge. Our implementation is released at https://github.com/infinite-tao/MA-MTLN.

10.
J Biol Chem ; : 100483, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33647318

RESUMO

Vascular calcification is the ectopic deposition of calcium hydroxyapatite minerals in arterial wall which involves the transdifferentiation of vascular smooth muscle cells (VSMCs) toward an osteogenic phenotype. However, the underlying molecular mechanisms regulating the VSMC osteogenic switch remain incompletely understood. In this study, we examined the roles of microRNAs (miRNAs) in vascular calcification. miRNA-seq transcriptome analysis identified miR-223-3p as a candidate miRNA in calcified mouse aortas. MiR-223-3p knockout aggravated calcification in both medial and atherosclerotic vascular calcification models. Further, RNA-seq transcriptome analysis verified JAK-STAT and PPAR signaling pathways were upregulated in both medial and atherosclerotic calcified aortas. Overlapping genes in these signaling pathways with predicted target genes of miR-223-3p derived from miRNA databases, we identified signal transducer and activator of transcription 3 (STAT3) as a potential target gene of miR-223-3p in vascular calcification. In vitro experiments showed that miR-223-3p blocked interleukin-6 (IL-6)/STAT3 signaling, thereby preventing the osteogenic switch and calcification of VSMCs. In contrast, overexpression of STAT3 diminished the effect of miR-223-3p. Taken together, the results indicate a protective role of miR-223-3p that inhibits both medial and atherosclerotic vascular calcification by regulating IL-6/STAT3 signaling mediated VSMC transdifferentiation.

11.
Cells ; 10(3)2021 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-33673583

RESUMO

Pro-inflammatory cytokines are considered to play a major role in osteoarthritis (OA), yet so far, the specific cytokines involved in the pathology of OA have not been identified. Oncostatin M (OSM) is a cytokine from the interleukin 6 (IL-6) family that has been shown to be elevated in synovial fluid of most rheumatoid arthritis (RA) patients, but only in a limited subset of OA patients. Little is known about OSM in the different joint tissues during OA and how its expression correlates with hallmarks of disease. Here, we mapped OSM expression in the joint tissues of two rat models of arthritis: an acute inflammatory model and an instability-induced osteoarthritic model. OSM expression was correlated with hallmarks of OA, namely cartilage damage, synovitis, and osteophyte formation. Reanalysis of an existing dataset on cytokine profiling of OA synovial fluid was performed to assess pattern differences between patients positive and negative for OSM. In the inflammatory model, OSM expression correlated with synovitis and osteophyte formation but not with cartilage damage. On the contrary, in the instability model of OA, an increase in synovitis, cartilage damage, and osteophyte formation was observed without changes in OSM expression. In line with these findings, synovial fluid of OA patients with detectable OSM contained higher levels of other inflammatory cytokines, namely interferon gamma (IFN-γ), IL-1α and tumor necrosis factor alpha (TNF-α), likely indicating a more inflammatory state. Taken together these data indicate OSM might play a prominent role in inflammatory phenotypes of OA.

12.
Gene ; 784: 145594, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-33766704

RESUMO

Analysing the molecular regulation mechanism of fat deposition in yellow cattle can provide a theoretical basis for the breeding of excellent beef cattle. ANGPTL8 (angiopoietin-like protein 8) promotes the formation of lipid droplets during adipocyte differentiation. To explore the promoter active region of ANGPTL8 and predict potential transcription factors, we further provide a theoretical basis for the functional analysis and regulatory mechanism of ANGPTL8 in adipogenesis. The promoter region of bovine ANGPTL8 was cloned by overlap extension PCR. Online software was used to predict potential transcription factor binding sites, and it identified PPARγ, SREBP1, C/EBPα, and Znf423 transcription factor binding sites in ANGPTL8 promoter region. A luciferase reporter gene vector which contained different deletion fragments of the ANGPTL8 promoter was constructed. Then, the vectors were cotransfected into 293 T cells with the internal control plasmid pRL-TK by cationic liposomes, and the relative fluorescence intensity was detected by a microplate reader. The results of the luciferase activity analysis showed that the core promoter area of ANGPTL8 was in the -885/-227 bp region of the 5' flanking sequence, while just two SREBP1 binding sites occurred in this area. When SREBP1 was knocked down by siRNA, the expression level of ANGPTL8 was reduced, and we speculated that SREBP1 may be an important transcription factor regulating ANGPTL8 transcription.


Assuntos
Proteínas Semelhantes a Angiopoietina/química , Proteínas Semelhantes a Angiopoietina/genética , Biologia Computacional/métodos , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteínas Semelhantes a Angiopoietina/metabolismo , Animais , Sítios de Ligação , Cruzamento , Bovinos , Clonagem Molecular , Regulação da Expressão Gênica , Células HEK293 , Humanos , Regiões Promotoras Genéticas , Software , Fatores de Transcrição/genética
13.
J Cell Mol Med ; 25(7): 3400-3407, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33656264

RESUMO

MicroRNA-122 (miR-122) is known to be up-regulated by inflammation to exert a variety of biological functions in hepatocellular carcinoma (HCC)-derived human cell lines. Vitamin D receptor (VDR) is reported to regulate excessive oral keratinocytes apoptosis which compromises oral epithelial barrier in oral lichen planus (OLP). Although many studies have suggested that miR-122 is capable of regulating cell apoptosis, its effects on the development of OLP and VDR expression are still unclear. Herein, we demonstrate that miR-122 expression is increased in the epithelial layer of OLP. Mechanically, transcription factor nuclear factor-κB (NF-κB) selectively binds with κB element in the promoter of miR-122 to accelerate gene transcription. The up-regulation of miR-122 induces cell apoptosis in human oral keratinocytes (HOKs) by targeting VDR mRNA. In VDR knockout oral keratinocytes, miR-122 fails to improve caspase 3 activity and cleaved caspase 3 and poly(ADP-ribose) polymerase (PARP) levels. Moreover, VDR overexpression is able to reverse lipopolysaccharide (LPS)- or activated CD4+ T cell-induced miR-122 up-regulation and ameliorate miR-122-stimulated caspase 3 activity. Collectively, our results suggest that miR-122 promotes oral keratinocytes apoptosis in OLP through decreasing VDR expression.

14.
Med Image Anal ; 71: 102042, 2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33784600

RESUMO

Paediatric echocardiography is a standard method for screening congenital heart disease (CHD). The segmentation of paediatric echocardiography is essential for subsequent extraction of clinical parameters and interventional planning. However, it remains a challenging task due to (1) the considerable variation of key anatomic structures, (2) the poor lateral resolution affecting accurate boundary definition, (3) the existence of speckle noise and artefacts in echocardiographic images. In this paper, we propose a novel deep network to address these challenges comprehensively. We first present a dual-path feature extraction module (DP-FEM) to extract rich features via a channel attention mechanism. A high- and low-level feature fusion module (HL-FFM) is devised based on spatial attention, which selectively fuses rich semantic information from high-level features with spatial cues from low-level features. In addition, a hybrid loss is designed to deal with pixel-level misalignment and boundary ambiguities. Based on the segmentation results, we derive key clinical parameters for diagnosis and treatment planning. We extensively evaluate the proposed method on 4,485 two-dimensional (2D) paediatric echocardiograms from 127 echocardiographic videos. The proposed method consistently achieves better segmentation performance than other state-of-the-art methods, whichdemonstratesfeasibility for automatic segmentation and quantitative analysis of paediatric echocardiography. Our code is publicly available at https://github.com/end-of-the-century/Cardiac.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33759562

RESUMO

Vitamin D/vitamin D receptor (VDR) signaling is reported to have a protective effect on the onset or progression of inflammatory bowel diseases (IBD) and hypoxia-inducible factor 1α (HIF-1α) activation is demonstrated to be closely associated with chemical-induced colitis. However, the association between vitamin D/VDR signaling and HIF-1α on IBD development remains a mystery. Here, we showed that HIF-1α expression was largely increased in the colonic epithelial cells of diseased tissues from ulcerative colitis (UC) patients. Consistently, HIF-1α activation was also improved in colonic epithelial cells upon TNFα treatment in a NF-κB pathway-dependent manner. HIF-1α inhibitors treatments ameliorated 2,4,6-trinitrobenzenesulfonic acid (TNBS)- or dextran sulfate sodium (DSS)-induced colitis in animal models. In cell or colitis animal models, vitamin D/VDR signaling suppressed HIF-1α overexpression in colonic epithelial cells via regulating NF-κB pathway, resulting in the inhibition of IFNγ and IL-1ß overproductions in these cells. Collectively, these data suggest that vitamin D/VDR signaling relieves colitis development in animal models, at least in part, by suppressing HIF-1α expression in colonic epithelial cells.

16.
BMC Genomics ; 22(1): 176, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33706696

RESUMO

BACKGROUND: Low temperature (LT) often occurs at the seedling stage in the early rice-growing season, especially for direct seeded early-season indica rice, and using flooding irrigation can mitigate LT damage in rice seedlings. The molecular mechanism by which flooding mitigates the damage induced by LT stress has not been fully elucidated. Thus, LT stress at 8 °C, LT accompanied by flooding (LTF) and CK (control) treatments were established for 3 days to determine the transcriptomic, proteomic and physiological response in direct seeded rice seedlings at the seedling stage. RESULTS: LT damaged chloroplasts, and thylakoid lamellae, and increased osmiophilic bodies and starch grains compared to CK, but LTF alleviated the damage to chloroplast structure caused by LT. The physiological characteristics of treated plants showed that compared with LT, LTF significantly increased the contents of rubisco, chlorophyll, PEPCK, ATP and GA3 but significantly decreased soluble protein, MDA and ABA contents. 4D-label-free quantitative proteomic profiling showed that photosynthesis-responsive proteins, such as phytochrome, as well as chlorophyll and the tricarboxylic acid cycle were significantly downregulated in LT/CK and LTF/CK comparison groups. However, compared with LT, phytochrome, chlorophyllide oxygenase activity and the glucan branching enzyme in LTF were significantly upregulated in rice leaves. Transcriptomic and proteomic studies identified 72,818 transcripts and 5639 proteins, and 4983 genes that were identified at both the transcriptome and proteome levels. Differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) were significantly enriched in glycine, serine and threonine metabolism, biosynthesis of secondary metabolites, glycolysis/gluconeogenesis and metabolic pathways. CONCLUSION: Through transcriptomic, proteomic and physiological analyses, we determined that a variety of metabolic pathway changes were induced by LT and LTF. GO and KEGG enrichment analyses demonstrated that DEGs and DEPs were associated with photosynthesis pathways, antioxidant enzymes and energy metabolism pathway-related proteins. Our study provided new insights for efforts to reduce the damage to direct seeded rice caused by low-temperature stress and provided a breeding target for low temperature flooding-resistant cultivars. Further analysis of translational regulation and metabolites may help to elucidate the molecular mechanisms by which flooding mitigates low-temperature stress in direct seeded early indica rice at the seedling stage.

17.
Aging (Albany NY) ; 13(4): 5164-5184, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33535178

RESUMO

The Notch1-mediated inflammatory response participates in the development of abdominal aortic aneurysm (AAA). The vascular endogenous bioactive peptide intermedin (IMD) plays an important role in maintaining vascular homeostasis. However, whether IMD inhibits AAA by inhibiting Notch1-mediated inflammation is unclear. In this study, we found Notch intracellular domain (NICD) and hes1 expression were higher in AAA patients' aortas than in healthy controls. In angiotensin II (AngII)-induced AAA mouse model, IMD treatment significantly reduced AAA incidence and maximal aortic diameter. IMD inhibited AngII-enlarged aortas and -degraded elastic lamina, reduced NICD, hes1 and inflammatory factors expression, decreased infiltration of CD68 positive macrophages and the NOD-like receptor family pyrin domain containing 3 protein level. IMD inhibited lipopolysaccharide-induced macrophage migration in vitro and regulated macrophage polarization. Moreover, IMD overexpression significantly reduced CaCl2-induced AAA incidence and down-regulated NICD and hes1 expression. However, IMD deficiency showed opposite results. Mechanically, IMD treatment significantly decreased cleavage enzyme-a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) level. Pre-incubation with IMD17-47 (IMD receptors blocking peptide) and the phosphatidylinositol 3-kinase/protein kinase b (PI3K/Akt) inhibitor LY294002 reversed ADAM10 level. In conclusion, exogenous and endogenous IMD could inhibit the development of AAA by inhibiting Notch1 signaling-mediated inflammation via reducing ADAM10 through IMD receptor and PI3K/Akt pathway.

18.
Animals (Basel) ; 11(2)2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33578694

RESUMO

In animal breeding, body components and metabolic traits always fall behind body weights in genetic improvement, which leads to the decline in standards and qualities of animal products. Phenotypically, the relative growth of multiple body components and metabolic traits relative to body weights are characterized by using joint allometric scaling models, and then random regression models (RRMs) are constructed to map quantitative trait loci (QTLs) for relative grwoth allometries of body compositions and metabolic traits in chicken. Referred to as real joint allometric scaling models, statistical utility of the so-called LASSO-RRM mapping method is given a demonstration by computer simulation analysis. Using the F2 population by crossing broiler × Fayoumi, we formulated optimal joint allometric scaling models of fat, shank weight (shank-w) and liver as well as thyroxine (T4) and glucose (GLC) to body weights. For body compositions, a total of 9 QTLs, including 4 additive and 5 dominant QTLs, were detected to control the allometric scalings of fat, shank-w, and liver to body weights; while a total of 10 QTLs of which 6 were dominant, were mapped to govern the allometries of T4 and GLC to body weights. We characterized relative growths of body compositions and metabolic traits to body weights in broilers with joint allometric scaling models and detected QTLs for the allometry scalings of the relative growths by using RRMs. The identified QTLs, including their highly linked genetic markers, could be used to order relative growths of the body components or metabolic traits to body weights in marker-assisted breeding programs for improving the standard and quality of broiler meat products.

19.
Sci Rep ; 11(1): 1725, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33462277

RESUMO

In the present work, we constructed nanoscale graphene oxide (NGO) as a drug nanocarrier to improve the process of tumor-targeted drug releases, promote cellular uptake and accumulation of chemotherapy drugs in tumor tissues, and reduce the toxic effects of chemotherapy drugs on normal cells. Hence, great stability was obtained in the biological solution. Moreover, we designed an effective nanoparticle system for the doxorubicin (DOX) delivery targeting the oral squamous cell carcinoma (OSCC) by mediating the HN-1 (TSPLNIHNGQKL) through hydrogen and π-π bonds. DOX@NGO-PEG-HN-1 showed significantly higher cellular uptakes and cytotoxicity in OSCC cells (CAL-27 and SCC-25), compared to free DOX. Moreover, HN-1 showed considerable tumor-targeting and competition inhibition phenomenon. As we expected, the nanocarrier showed pH-responsive drug release. In total, our study represented a good technique to construct OSCC-targeted delivery of nanoparticles and improve the anticancer medicines' efficiency.

20.
Dig Dis Sci ; 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33433800

RESUMO

BACKGROUND: The renin-angiotensin system (RAS) is activated in inflammatory bowel disease (IBD), and vitamin D deficiency aggravates the development of colitis, but the relationship between the local colonic RAS and vitamin D is unclear with regard to the pathogenesis of IBD. AIMS: To investigate whether vitamin D suppresses the local colonic RAS to prevent colonic mucosal inflammation in a mouse model of experimental colitis. METHODS: C57BL/6 mice fed vitamin D-deficient (VDD) diet for 8 weeks were induced to colitis by 2,4,6-trinitrobenzenesulfonic acid (TNBS), with mice fed vitamin D-sufficient (VDS) diet as controls. Colitis severity was assessed by histology, and pro-inflammatory cytokines, RAS components, and signaling pathways were quantified by real-time RT-PCR and Western blotting. RESULTS: C57BL/6 mice fed the VDD diet for 8 weeks exhibited significantly lower serum 25(OH)D3 concentrations compared to mice fed the VDS diet. When these VDD mice were induced to colitis by TNBS, they exhibited more severe colonic inflammation and developed more severe colitis compared to the VDS counterparts. VDD diet feeding resulted in higher production of mucosal pro-inflammatory cytokines, higher activation of the myosin light chain kinase-tight junction regulatory pathway, and greater increases in mucosal permeability. VDD diet feeding also enhanced colonic RAS activation. Treatment with angiotensin II receptor blocker losartan markedly alleviated colitis in TNBS-induced VDD mice. CONCLUSION: Vitamin D deficiency promotes colonic inflammation at least in part due to over activation of the local RAS in the colon.

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