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1.
J Virol ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32999033

RESUMO

Chikungunya virus (CHIKV) is an arthritogenic alphavirus that causes debilitating musculoskeletal disease. CHIKV displays broad cell, tissue, and species tropism, which may correlate with the attachment factors and entry receptors used by the virus. Cell-surface glycosaminoglycans (GAGs) have been identified as CHIKV attachment factors. However, the specific types of GAGs and potentially other glycans to which CHIKV binds and whether there are strain-specific differences in GAG binding is not fully understood. To identify the types of glycans bound by CHIKV, we conducted glycan microarray analyses and discovered that CHIKV preferentially binds GAGs. Microarray results also indicate that sulfate groups on GAGs are essential for CHIKV binding and that CHIKV binds most strongly to longer GAG chains of heparin and heparan sulfate. To determine whether GAG-binding capacity varies among CHIKV strains, a representative strain from each genetic clade was tested. While all strains directly bound to heparin and chondroitin sulfate in ELISAs and depended on heparan sulfate for efficient cell-binding and infection, we observed some variation by strain. Enzymatic removal of cell-surface GAGs and genetic ablation that diminishes GAG expression reduced CHIKV binding and infectivity of all strains. Collectively, these data demonstrate that GAGs are the preferred glycan bound by CHIKV, enhance our understanding of the specific GAG moieties required for CHIKV binding, define strain differences in GAG engagement, and provide further evidence for a critical function of GAGs in CHIKV cell attachment and infection.IMPORTANCE Alphavirus infections are a global health threat, contributing to outbreaks of disease in many parts of the world. Recent epidemics caused by CHIKV, an arthritogenic alphavirus, resulted in more than 8.5 million cases as the virus has spread into new geographic regions, including the Western Hemisphere. CHIKV causes disease in the majority of people infected, leading to severe and debilitating arthritis. Despite the severity of CHIKV disease, there are no licensed therapeutics. Since attachment factors and receptors are determinants of viral tropism and pathogenesis, understanding these virus-host interactions can enhance our knowledge of CHIKV infection. We analyzed over 670 glycans and identified GAGs as the main glycan bound by CHIKV. We defined specific GAG components required for CHIKV binding and assessed strain-specific differences in GAG-binding capacity. These studies provide insight about cell-surface molecules that CHIKV binds, which could facilitate the development of antiviral therapeutics targeting the CHIKV attachment step.

2.
Oncol Rep ; 44(5): 2288-2296, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000264

RESUMO

Triptolide, a triterpene extracted from the Chinese herb Tripterygium wilfordii, has been reported to exert multiple bioactivities, including immunosuppressive, anti­inflammatory and anticancer effects. Although the anticancer effect of triptolide has attracted significant attention, the specific anticancer mechanism in non­small­cell lung cancer (NSCLC) remains unclear. The present study aimed to investigate the anticancer effect of triptolide in the H1395 NSCLC cell line and to determine its mechanism of action. The results revealed that triptolide significantly inhibited the cell viability of NSCLC cells in a dose­dependent manner, which was suggested to be through inducing apoptosis. In addition, triptolide was revealed to activate the calcium (Ca2+)/calmodulin­dependent protein kinase kinase ß (CaMKKß)/AMP­activated protein kinase (AMPK) signaling pathway by regulating the intracellular Ca2+ concentration levels, which increased the phosphorylation levels of AMPK and reduced the phosphorylation levels of AKT, ultimately leading to apoptosis. The CaMKKß blocker STO­609 and the AMPK blocker Compound C significantly inhibited the apoptosis­promoting effect of triptolide. In conclusion, the results of the present study suggested that triptolide may induce apoptosis through the CaMKKß­AMPK signaling pathway and may be a promising drug for the treatment of NSCLC.

3.
J Tradit Chin Med ; 40(5): 870-874, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33000589

RESUMO

OBJECTIVE: To investigate the clinical effects of Xinkeshu combined with levosimendan on perioperative heart failure in oldest-old patients with hip fractures. METHODS: Oldest-old patients over 80 years old with perioperative heart failure and hip fractures were randomly divided into the control and observation groups, with 50 patients in each group. All patients in both groups were treated with conventional anti-heart failure therapy and levosimendan, whereas patients in the observation group additionally received Xinkeshu tablets. Clinical manifestations; left ventricular ejection fraction (LVEF); left ventricular end-diastolic dimension (LVEDD); left ventricular end-systolic dimension (LVESD); B-type natriuretic peptide (BNP), superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), and endothelin-1 (ET-1) levels; and self-rating anxiety scale (SAS) and self-rating depression scale (SDS) scores were compared between before and after treatment to evaluate the curative effects of Xinkeshu combined with levosimendan. RESULTS: After treatment, the efficacy rate was significantly higher in the observation group than in the control group. LVEF and the levels of SOD and NO were higher in the observation group than in the control group after treatment. However, LVEDD; LVESD; BNP, MDA, and ET-1 levels; and the SAS and SDS scores were lower after treatment in the observation group than in the control group. CONCLUSION: Levosimendan combined with Xinkeshu can improve cardiac function, alleviate oxidative stress, and relieve anxiety and depression in oldest-old patients with perioperative heart failure and hip fracture.

4.
Hum Cell ; 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33010000

RESUMO

Severe corneal injury is one of the main causes of loss of visual function. Mesenchymal stem cells (MSCs) have the ability to repair damaged cells in vivo. The present study aimed to explore whether MSCs could function as a cell therapy tool to replace traditional methods to treat corneal injury. CD44 + /CD105 + mesenchymal stem cells isolated from mouse amniotic fluid (mAF-MSCs) were injected into mice after cryoinjury to induce corneal endothelial cell injury. Histopathological assays indicated that mAF-MSCs could promote the growth of corneal epithelial cells, reduce keratitis, and repair the corneal damage caused by low temperature. cDNA microarray analysis revealed that the mAF-MSCs affected the expression patterns of mRNAs related to cell proliferation and differentiation pathways in the mice after transplantation. The results of quantitative real-time PCR and western blotting revealed that NAT12, NAT10, and the ETV4/JUN/CCND2 signaling axis were elevated significantly in the mAF-MSC-transplantation group, compared with those in the phosphate-buffered saline-treated groups. High performance liquid chromatography-mass spectroscopy results revealed that mAF-MSCs could promote mRNA N4-acetylcytidine (ac4C) modification and high expression of N-acetyltransferase in the eyeballs. RNA immunoprecipitation-PCR results showed that a specific product comprising Vegfa, Klf4, Ccnd2, Jun, and Etv4 mRNA specific coding region sites could be amplified using PCR from complexes formed in mAF-MSC-transplanted samples cross-linked with anti-ac4C antibodies. Thus, mouse amniotic fluid MSCs could repair the mouse corneal cold injury by promoting the ETV4/JUN/CCND2 signal axis activation and improving its stability by stimulating N4-acetylcytidine modification of their mRNAs.

5.
Sci Rep ; 10(1): 16307, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004915

RESUMO

Studies on the risk factors for intrahepatic cholestasis of pregnancy (ICP) in a population-based cohort are lacking. We assess the prevalence and risk factors of ICP in a Chinese population. In this study, a cohort study was conducted that included 12,200 eligible pregnant women. The overall incidence of ICP in this cohort was 6.06%. With increasing maternal age, the incidence of ICP decreased in women younger than 30 years of age but increased in those older than 30. With increasing pre-pregnancy BMI, the incidence of ICP decreased if the pre-pregnancy BMI was less than 23 kg/m2 but increased if it was 23 kg/m2 or higher. Further analysis showed that the risk of ICP increased when maternal age was < 25 years (Adjusted RR 2.01; 95% CI 1.64-2.47) or ≥ 35 years (Adjusted RR 1.34; 95% CI 1.02-1.76). Furthermore, an increased risk of ICP was associated with pre-pregnancy underweight (adjusted RR 1.27; 95% CI 1.04-1.56), inadequate gestational weight gain (GWG) (adjusted RR 1.58; 95% CI 1.28-1.96), lower maternal education (adjusted RR 2.96; 95% CI 2.35-3.74), multiparity (adjusted RR 1.54; 95% CI 1.23-1.93), and twin/multiple pregnancies (adjusted RR 2.12; 95% CI 1.25-3.58). Maternal age (< 25 or ≥ 35 years), underweight, inadequate GWG, lower maternal education, multiparity, and twin/multiple pregnancies were identified as risk factors of ICP.

6.
Org Lett ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33021797

RESUMO

A pair of new macrocyclic spermidine alkaloids, (+)-(S)-scocycamide and (-)-(R)-scocycamide, were isolated from the roots of Scopolia tangutica. Their structures were established by extensive spectroscopic data, electronic circular dichroism analyses, and chemical synthesis. They featured a unique 6/18 fused bicyclic framework with spermidine and catechol units, representing a new subtype of natural spermidine alkaloids. A plausible biosynthetic pathway was also proposed. They inhibited butyrylcholinesterase and exhibited antioxidant capacity, suggesting beneficial constituents against Alzheimer's disease and oxidation.

7.
Tissue Eng Part A ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33023406

RESUMO

Fabrication of multifunctional scaffolds with biomimicking physical and biological signals play an important role in enhancing tissue regeneration. Multifunctional features come from composite scaffold with various bioactive molecules. However, simple, biocompatible and controllable hybridization strategy is still lacking. Here, we leverage naturally derived extracellular matrix (ECM) as chemically controllable hydrogel carrier to effectively load functional biomolecules. The use of ECM hydrogel takes advantage of both native functionality of ECM components and tunability of hydrogel in controlling release of loaded molecules. As a proof of concept, porous acellular bone scaffold was selected as the solid pristine scaffold to be composited with BMP-2 and VEGF, which are loaded by spinal cord derived ECM (SC-ECM) hydrogel. Crosslinking degree of SC-ECM hydrogel is tuned by changing genipin concentration, which renders the control over release kinetics of BMP-2 and VEGF. The mechanical strength of scaffold maintained after hybridization and is not significantly decreased in wet condition. In vitro evaluations of scaffolds cocultured with osteoblasts and mesenchymal stem cells (MSCs) demonstrate the biocompatible and bioactive features resulting from the composite scaffolds. Evidenced by alkaline phosphatase test, Immunofluorescence and Real-Time PCR, differentiation of MSCs towards osteoblasts lineage is significantly enhanced by composite scaffolds. Therefore, our strategy in fabricating composite scaffold enabled by biomolecule-loaded ECM hydrogel holds great promise in regenerating diverse tissue types by appropriate combinations of solid pristine scaffolds, ECM, and bioactive molecules.

8.
Biosci Rep ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33026076

RESUMO

Mesenchymal stem cells (MSCs) are multipotent stromal cells which can be a useful source of cells for the treatment of many diseases, including neurologic diseases. The curative effect of MSCs relies mostly on cell's capacity of migration, proliferation and differentiation. MicroRNAs (miRNAs) are small non-coding RNAs which play important roles on regulating various cell behaviors. Here, we report that miRNA-124 (miR124) and miRNA-21-5p (miR21-5p) display different regulatory roles on migration, proliferation and neuron differentiation of MSCs. MiR124 was shown greatly promoting MSCs migration and neuronal differentiation. MiR21-5p could significantly enhance the proliferation and neuronal differentiation ability of MSCs. MiR124 and miR21-5p synergistically promote differentiation of MSCs into neurons. Collectively, miR124 and miR21-5p can functionally regulate cell migration, proliferation and neuronal differentiation of MSCs. Therefore, miR124 and miR21-5p may be promising tools to improve transplantation efficiency for neural injury.

9.
Front Immunol ; 11: 1717, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013823

RESUMO

Vascular endothelial injury caused by post-hemorrhagic shock mesenteric lymph (PHSML) return is an important manifestation during refractory hemorrhagic shock. Using human umbilical vein endothelial cells (HUVECs) and transcriptome analysis, this study sought to investigate the molecular mechanism underlying the adverse effect of PHSML on vascular endothelium. Post-hemorrhagic shock mesenteric lymph was collected from male rats after they underwent hemorrhagic shock and following resuscitation, while normal mesenteric lymph (NML) was harvested from sham rats. Human umbilical vein endothelial cells were incubated with the culture medium containing either 10% phosphate buffered saline (Control), NML, or PHSML for 3 h, and then were harvested for RNA sequencing. In comparison with NML treated cells, 37 genes were differentially expressed in PHSML-treated HUVECs, including 32 upregulated genes and five downregulated genes. These differentially expressed genes were mainly enriched in inflammatory pathways, including signaling pathways for activation of the NOD-like receptors, NF-κB, and TNF. Furthermore, we found that C-C motif chemokine ligand 2 (CCL2) was increased significantly after PHSML treatment, and Bindarit, a CCL2 production inhibitor, attenuated the damage of HUVECs induced by PHSML. The results provide molecular evidence on vascular endothelium damage caused by PHSML. C-C motif chemokine ligand 2 might represent a new target for reducing vascular injury after severe hemorrhagic shock.

10.
J Occup Environ Med ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33021514

RESUMO

OBJECTIVES: To understand the relationship between job burnout and job satisfaction for medical workers and analyse the influencing factors. METHODS: We used two scales to examine medical workers in Hengyang mental hospitals. Multivariate logistic regression and structural equation model were used to evaluate the relevant factors of job satisfaction, and the relationship between job satisfaction and job burnout. RESULTS: The total job satisfaction was at the moderate level. For job burnout was in the middle burnout level. Job satisfaction can have a negative prediction function for job burnout (direct effect -0.684). The relevant factors of job burnout and job satisfaction was as follows: nature of the work, pay, benefits and communication impacted job satisfaction and job burnout. CONCLUSIONS: The current level of job satisfaction is relatively low, job satisfaction has a negative effect on job burnout.

11.
Plant Genome ; 13(2): e20018, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33016611

RESUMO

Callus induction is a dedifferentiation process that accompanies a cell fate transition, and epigenetic regulation plays a crucial role in the process. N6 -methyladenosine (m6A) methylation is an important mechanism in post-transcriptional epigenetic regulation and functions in cell reprogramming. However, the function of m6A methylation during callus induction is still unknown. Here, we performed transcriptome-wide m6A-seq on immature maize embryos after culturing for 2, 4, or 8 days with or without the auxin analogue 2,4-D. A total of 26,794 unique m6A peaks were detected from 17,456 maize genes; and 2,338 specific, 2,4-D-induced m6A peaks (D-specific m6A) were detected only in embryos cultured with 2,4-D. Furthermore, a positive correlation between m6A methylation and mRNA abundance was discovered in the genes with D-specific m6A deposition, especially at the beginning of callus induction. Key genes involved in callus induction, i.e. BABY BOOM and LBD transcription factors, underwent m6A methylation, increasing their transcript levels, thus improving callus induction. These results revealed the importance of m6A methylation during the early stage of callus induction and provided new insights into the molecular mechanism of callus induction at an epitranscriptomic level.

12.
Food Chem Toxicol ; 146: 111803, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33035629

RESUMO

This study aimed to investigate the therapeutic effect of curcumin on type 2 diabetes and its underlying mechanisms. A type 2 diabetes mellitus rat model was established by providing high-fat diet and low doses of streptozotocin. Type 2 diabetes mellitus rats were treated with low dose and high dose of curcumin for 8 weeks. The results showed that high-dose curcumin significantly reduced fasting blood glucose, total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, alanine aminotransferase, and aspartate transaminase, liver coefficient, and malondialdehyde levels, and BCL2-Associated X expression in the type 2 diabetes mellitus rats. High-dose curcumin increased the levels of liver superoxide dismutase, catalase, and glutathione; as well as the expression of liver B-cell lymphoma-2, phosphatidylinositol 3-kinase, phosphorylated phosphatidylinositol 3-kinase, protein kinase B, and phosphorylated protein kinase B in type 2 diabetes mellitus rats. Furthermore, it ameliorated the histological structure of the liver and pancreas in diabetes mellitus model rats. However, low-dose curcumin had no significant effect on diabetes mellitus model rats. The results suggest that adequate doses of curcumin controls type 2 diabetes mellitus development as well as the mechanism involved in its anti-apoptotic actions and phosphatidylinositol 3-hydroxy kinase/protein kinase B signal pathway regulation in the liver.

13.
Plant Cell Physiol ; 2020 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-33035344

RESUMO

Forisomes are protein bodies known exclusively from sieve elements of legumes. Forisomes contribute to the regulation of phloem transport due to their unique Ca2+-controlled, reversible swelling. The assembly of forisomes from sieve element occlusion (SEO) protein monomers in developing sieve elements and the mechanism(s) of Ca2+-dependent forisome contractility are poorly understood because the amino acid sequences of SEO proteins lack conventional protein-protein interaction and Ca2+-binding motifs. We selected amino acids potentially responsible for forisome-specific functions by analyzing SEO protein sequences in comparison to those of the widely distributed SEO-related (SEOR), or SEOR proteins. SEOR proteins resemble SEO proteins closely but lack any Ca2+ responsiveness. We exchanged identified candidate residues by directed mutagenesis of the Medicago truncatula SEO1 gene, expressed the mutated genes in yeast (Saccharomyces cerevisiae) and studied the structural and functional phenotypes of the forisome-like bodies that formed in the transgenic cells. We identified three aspartate residues critical for Ca2+ responsiveness and two more that were required for forisome-like bodies to assemble. The phenotypes observed further suggested that Ca2+-controlled and pH-inducible swelling effects in forisome-like bodies proceeded by different yet interacting mechanisms. Finally, we observed a previously unknown surface striation in native forisomes and in recombinant forisome-like bodies that could serve as an indicator of successful forisome assembly. To conclude, this study defines a promising path to the elucidation of the so-far elusive molecular mechanisms of forisome assembly and Ca2+-dependent contractility.

14.
Psychol Health Med ; : 1-10, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33044837

RESUMO

The purpose of this study was to determine the effect of video-based nursing education on perioperative anxiety and depression. A total of 128 patients scheduled for minimally invasive gastrectomy were randomly divided into intervention (n = 64) and control (n = 64) group. The. The anxiety and depression scores, systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were assessed before the intervention, 1 h before surgery and 24 h after surgery. And the cortisol levels were measured before the intervention and 1 h before surgery. No significant difference was observed in baseline anxiety score, depression score, vital signs and cortisol level (P > 0.05). The anxiety level, depression level, SBP, DBP and HR of patients in intervention group was significantly lower than that in control group at 1 h before surgery and 24 hs after surgery (P < 0.05). The serum cortisol in the intervention group was also significantly lower than that in the control group 1 h before surgery (p < 0.001). Video-based nursing education was effective in decreasing the perioperative anxiety and depression of patients undergoing minimally invasive gastrectomy. It could also keep vital signs and serum cortisol levels in normal limits.

15.
Expert Rev Vaccines ; : 1-9, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33001703

RESUMO

OBJECTIVES: More and more premature infants were born worldwide that are suffering from various complications, vaccination for whom is often delayed in China. We aim to describe current vaccination recommendations in practice, immunization status, and vaccination safety for premature infants in Zhejiang. METHODS: The demographic information, medical records of treatments, and adverse events following immunization (AEFI) history were collected from infants' parents by questionnaire in the Vaccination Consultation Clinic(VCC). Vaccination data were retrieved from Zhejiang Provincial Immunization Information System. The information of AEFI was collected from the Chinese National Adverse Event Following Immunization Information System. RESULTS: A total of 1515 premature infants visiting the VCC were included in the study. The majority (65.94%) of them were under 7 months. 47.59% of premature infants were advised to receive normal vaccinations, while 45.94% were advised to defer a specific vaccination and 6.47% were advised to defer all vaccinations. A total of 807 infants received 7187 vaccine doses were administered and only seven cases experienced mild and self-limiting adverse reactions (9.74/10,000). No uncommon or serious side effects were reported. CONCLUSION: Most premature infants visiting the VCC did not receive vaccines on time. The majority of them can be safely vaccinated according to the national-recommended schedule.

16.
J Biotechnol ; 324: 91-98, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33010308

RESUMO

Enzymes, which provide more efficient and eco-friendly strategies for various functional molecules' construction than traditional chemo-catalysts, were utilized for the synthesis of 4H-pyrimido[2,1-b] benzothiazole derivatives. Reported herein is a trypsin-catalysed three- component Biginelli reaction of aldehyde, ß-ketoester and 2-amino benzothiazole in one pot, affording a streamlined pathway to diverse ring-fused pyrimidines. In addition to using commercially available aromatic aldehydes as substrates, acetaldehyde, the chemical liquid with rather low boiling point and difficult to handle above room temperature, is utilized to further extend the range of substrates. It was verified that most of the tested substrates exhibited satisfactory reactivity. In addition, several substrates indicated AIE (Aggregation-Induced Emission) property and have been investigated as potential biomarkers.

17.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 1766-1769, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018340

RESUMO

Intracranial visual pathway is related to the effective transmission of visual signals to brain. It was not only the target organ of diseases but also the organs at risk in radiotherapy thus its delineation plays an important role in both diagnosis and treatment planning. Traditional manual segmentation method suffered from time- and labor- consuming as well as intra- and inter- variability. In order to overcome these problems, state-of-the-art segmentation models were designed and various features were extracted and utilized, but it's hard to tell their effectiveness on intracranial visual pathway delineation. It's because that these methods worked on different dataset and accompanied with different training tricks. This study aimed to research the contribution of global features and local features in delineating the intracranial visual pathway from MRI scans. The two typical segmentation models, 3D UNet and DeepMedic, were chosen since they focused on global features and local features respectively. We constructed the hybrid model through serially connecting the two mentioned models to validate the performance of combined global and local features. Validation results showed that the hybrid model outperformed the individual ones. It proved that multi scale feature fusion was important in improving the segmentation performance.

18.
Genet Sel Evol ; 52(1): 59, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33036552

RESUMO

BACKGROUND: Genetic analysis of gene expression level is a promising approach for characterizing candidate genes that are involved in complex economic traits such as meat quality. In the present study, we conducted expression quantitative trait loci (eQTL) and allele-specific expression (ASE) analyses based on RNA-sequencing (RNAseq) data from the longissimus muscle of 189 Duroc × Luchuan crossed pigs in order to identify some candidate genes for meat quality traits. RESULTS: Using a genome-wide association study based on a mixed linear model, we identified 7192 cis-eQTL corresponding to 2098 cis-genes (p ≤ 1.33e-3, FDR ≤ 0.05) and 6400 trans-eQTL corresponding to 863 trans-genes (p ≤ 1.13e-6, FDR ≤ 0.05). ASE analysis using RNAseq SNPs identified 9815 significant ASE-SNPs in 2253 unique genes. Integrative analysis between the cis-eQTL and ASE target genes identified 540 common genes, including 33 genes with expression levels that were correlated with at least one meat quality trait. Among these 540 common genes, 63 have been reported previously as candidate genes for meat quality traits, such as PHKG1 (q-value = 1.67e-6 for the leading SNP in the cis-eQTL analysis), NUDT7 (q-value = 5.67e-13), FADS2 (q-value = 8.44e-5), and DGAT2 (q-value = 1.24e-3). CONCLUSIONS: The present study confirmed several previously published candidate genes and identified some novel candidate genes for meat quality traits via eQTL and ASE analyses, which will be useful to prioritize candidate genes in further studies.

19.
J Transl Med ; 18(1): 384, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33036620

RESUMO

BACKGROUND: Autoimmune hepatitis (AIH) is a liver disease characterized by the autoimmune-induced injury of hepatocytes which can lead to cirrhosis and hepatic failure. The diagnosis and disease management of AIH patients remain challenging due to the diversity of clinical phenotypes and the presence of confounders such as alcohol and viruses. Recently, EN-RAGE and sRAGEs have been implicated in inflammatory-immune response. Nonetheless, their natural behaviour and relationship to disease activity as well as clinical predictive values in AIH development or therapy-induced remission have not been reported. METHODS: Sixty-seven AIH patients and thirty gender- and age-matched healthy controls (HC) were enrolled. The serum concentrations of EN-RAGE, sRAGE and their ratio (EN-RAGE/sRAGE) in these subjects were measured by ELISA. Besides, the correlations of three parameters with clinical features and therapeutic response were analyzed, respectively. Furthermore, their potential predictive values for monitoring the AIH progression and therapeutic response were also evaluated. RESULTS: Higher serum EN-RAGE, lower sRAGE and higher EN-RAGE/sRAGE value were observed in AIH patients. EN-RAGE and sRAGE as well as EN-RAGE/sRAGE were correlated with liver necroinflammation parameters, cirrhosis occurrence and therapeutic response. In addition, we identified that EN-RAGE/sRAGE, EN-RAGE and sRAGE had valuable predicting power for AIH patients, AIH patients with normal ALT and cirrhosis incidence, respectively. More importantly, EN-RAGE/sRAGE also exerted predicting power for the remission in AIH patients. CONCLUSIONS: AIH patients rendered distinct patterns of serum EN-RAGE, sRAGE or EN-RAGE/sRAGE compared to healthy controls. Moreover, these three parameters exhibited potentials as novel biomarkers for AIH diagnosis and prognosis evaluation.

20.
BMC Cancer ; 20(1): 998, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33054738

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC), in part because of the high metastasis rate, is one of the most prevalent causes of malignancy-related mortality globally. Ubiquitin specific peptidase 6 N-terminal like (USP6NL) has been unmasked to be implicated in some human cancers. However, the precise biological function of USP6NL in TNBC has not been defined. METHODS: RNA expression was examined by real-time quantitative PCR (RT-qPCR), while USP6NL protein level was tested through western blot. Besides, cell proliferation was assessed by using colony formation assay, whereas cell apoptosis estimated by flow cytometry analysis, JC-1 assay and TUNEL assay. Transwell assays were adopted to detect the migration and invasion of indicated TNBC cells. Immunofluorescence (IF) assay evaluated epithelial-mesenchymal transitions (EMT) progress in TNBC. Further, RNA immunoprecipitation (RIP), RNA pull down and luciferase reporter assays were implemented for measuring the mutual interplay among USP6NL, miR-142-3p and long intergenic non-protein coding RNA 689 (LINC00689). RESULTS: Elevated USP6NL level was uncovered in TNBC cells. RNA interference-mediated knockdown of USP6NL inhibited TNBC cell growth, motility and EMT. Further, USP6NL was proved as the target of a tumor-inhibitor miR-142-3p, and LINC00689 augmented USP6NL expression by absorbing miR-142-3p. Importantly, miR-142-3p deficiency or USP6NL overexpression fully abolished the inhibitory effect of LINC00689 silence on TNBC cellular behaviors. CONCLUSION: All data revealed the important role of USP6NL/LINC00689/miR-142-3p signaling in TNBC. The findings might provide a new and promising therapeutic biomarker for treating patients with TNBC.

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