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1.
BMC Bioinformatics ; 22(1): 185, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33845765

RESUMO

BACKGROUND: Microsatellite instability (MSI) is a common genomic alteration in colorectal cancer, endometrial carcinoma, and other solid tumors. MSI is characterized by a high degree of polymorphism in microsatellite lengths owing to the deficiency in the mismatch repair system. Based on the degree, MSI can be classified as microsatellite instability-high (MSI-H) and microsatellite stable (MSS). MSI is a predictive biomarker for immunotherapy efficacy in advanced/metastatic solid tumors, especially in colorectal cancer patients. Several computational approaches based on target panel sequencing data have been used to detect MSI; however, they are considerably affected by the sequencing depth and panel size. RESULTS: We developed MSIFinder, a python package for automatic MSI classification, using random forest classifier (RFC)-based genome sequencing, which is a machine learning technology. We included 19 MSI-H and 25 MSS samples as training sets. First, we selected 54 feature markers from the training sets, built an RFC model, and validated the classifier using a test set comprising 21 MSI-H and 379 MSS samples. With this test set, MSIFinder achieved a sensitivity (recall) of 1.0, a specificity of 0.997, an accuracy of 0.998, a positive predictive value of 0.954, an F1 score of 0.977, and an area under the curve of 0.999. To further verify the robustness and effectiveness of the model, we used a prospective cohort consisting of 18 MSI-H samples and 122 MSS samples. MSIFinder achieved a sensitivity (recall) of 1.0 and a specificity of 1.0. We discovered that MSIFinder is less affected by a low sequencing depth and can achieve a concordance of 0.993 while exhibiting a sequencing depth of 100×. Furthermore, we realized that MSIFinder is less affected by the panel size and can achieve a concordance of 0.99 when the panel size is 0.5 M (million bases). CONCLUSION: These results indicate that MSIFinder is a robust and effective MSI classification tool that can provide reliable MSI detection for scientific and clinical purposes.

2.
Nat Commun ; 12(1): 2114, 2021 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-33837182

RESUMO

Lack of detailed knowledge of SARS-CoV-2 infection has been hampering the development of treatments for coronavirus disease 2019 (COVID-19). Here, we report that RNA triggers the liquid-liquid phase separation (LLPS) of the SARS-CoV-2 nucleocapsid protein, N. By analyzing all 29 proteins of SARS-CoV-2, we find that only N is predicted as an LLPS protein. We further confirm the LLPS of N during SARS-CoV-2 infection. Among the 100,849 genome variants of SARS-CoV-2 in the GISAID database, we identify that ~37% (36,941) of the genomes contain a specific trio-nucleotide polymorphism (GGG-to-AAC) in the coding sequence of N, which leads to the amino acid substitutions, R203K/G204R. Interestingly, NR203K/G204R exhibits a higher propensity to undergo LLPS and a greater effect on IFN inhibition. By screening the chemicals known to interfere with N-RNA binding in other viruses, we find that (-)-gallocatechin gallate (GCG), a polyphenol from green tea, disrupts the LLPS of N and inhibits SARS-CoV-2 replication. Thus, our study reveals that targeting N-RNA condensation with GCG could be a potential treatment for COVID-19.

3.
Transgenic Res ; 30(2): 185-200, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33792795

RESUMO

Channel catfish (Ictalurus punctatus) is the primary culture species in the US along with its hybrid made with male blue catfish, I. furcatus. In an effort to improve the nutritional value of channel catfish, the masou salmon Δ5-desaturase like gene (D5D) driven by the common carp beta-actin promoter (ßactin) was inserted into channel catfish. The objectives of this study were to determine the effectiveness of ßactin-D5D for improving n-3 fatty acid production in F1 transgenic channel catfish, as well as examine pleiotropic effects on growth, proximate analysis, disease resistance, and other performance traits. Transgenic F1 channel catfish showed a 33% increase in the relative proportion of n-3 fatty acids coupled with a 15% decrease in n-6 fatty acids and a 17% decrease in n-9 fatty acids when compared to non-transgenic full-siblings (P < 0.01, P < 0.01, P < 0.01). However, while the relative proportion of n-3 fatty acids was achieved, the total amount of fatty acids in the transgenic fish decreased resulting in a reduction of all fatty acids. Insertion of the ßactin-D5D transgene into channel catfish also had large effects on the body composition, and growth of channel catfish. Transgenic channel catfish grew faster, were more disease resistant, had higher protein and moisture percentage, but lower fat percentage than full-sib controls. There were sex effects as performance changes were more dramatic and significant in males. The ßactin-D5D transgenic channel catfish were also more uniform in their fatty acid composition, growth and other traits.

4.
Am J Clin Nutr ; 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33829223

RESUMO

BACKGROUND: SCFAs are involved in regulation of body weight and bone health. OBJECTIVES: We aimed to examine whether genetic variations related to butyrate modified the relation between dietary fiber intake and changes in bone mineral density (BMD) in response to weight-loss dietary interventions. METHODS: In the 2-y Preventing Overweight Using Novel Dietary Strategies trial, 424 participants with BMD measured by DXA scan were randomly assigned to 1 of 4 diets varying in macronutrient intakes. A polygenic score (PGS) was calculated based on 7 genetic variants related to the production of butyrate for 370 of the 424 participants. RESULTS: SCFA PGS significantly modified the association between baseline dietary fiber intake and sex on 2-y changes in whole-body BMD (P-interaction = 0.049 and 0.008). In participants with the highest tertile of SCFA PGS, higher dietary fiber intake was related to a greater increase in BMD (ß:  0.0022; 95% CI: 0.0009, 0.0035; P = 0.002), whereas no such association was found for participants in the lower tertiles. In the lowest tertiles of SCFA PGS, men showed a significant increase in whole-body BMD (ß: 0.0280; 95% CI: 0.0112, 0.0447; P = 0.002) compared with women. In the highest tertile, no significant difference was found for the change in BMD between men and women. CONCLUSIONS: Our data indicate that genetic variants related to butyrate modify the relations of dietary fiber intake and sex with long-term changes in BMD in response to weight-loss diet interventions.

5.
Transgenic Res ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33786748

RESUMO

Histamine H2 receptor (HRH2) is closely associated with the development of cardiovascular and cerebrovascular diseases. However, systematic Hrh2 knockout mice did not exactly reflect the HRH2 function in specific cell or tissue types. To better understand the physiological and pathophysiological functions of endothelial HRH2, this study constructed a targeting vector that contained loxp sites flanking the ATG start codon located in Hrh2 exon 2 upstream and a neomycin (Neo) resistance gene flanked by self-deletion anchor sites within the mouse Hrh2 allele. The targeting vector was then electroporated into C57BL/6J embryonic stem (ES) cells, and positively targeted ES cell clones were micoinjected into C57BL/6J blastocysts, which were implanted into pseudopregnant females to obtain chimeric mice. The F1 generation of Hrh2flox/+ mice was generated via crossing chimeric mice with wild-type mice to excise Neo. We also successfully generated endothelial cell-specific knockout (ECKO) mice by crossing Hrh2flox/+ mice with Cdh5-Cre mice that specifically express Cre in endothelial cells and identified that Hrh2 deletion was only observed in endothelial cells. Hrh2flox/+ and Hrh2ECKO mice were normal, healthy and fertile and did not display any obvious abnormalities. These novel animal models will create new prospects for exploring roles of HRH2 during the development and treatment of related diseases.

6.
Genomics ; 113(3): 1438-1447, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33744343

RESUMO

China is a second center of oak diversity but with less intensively systematic studies. Here, with 49 species representing all four sections in China, we firstly gave insight into the comprehensive phylogenetic relationships of Chinese oaks based on 54 complete plastid genomes. Our results recovered a robust phylogenetic framework and provided strong support for most nodes. The phylogenetic tree supported Quercus section Ilex as not monophyletic, in which Quercus section Cyclobalanopsis and Quercus section Cerris were nested. Most likely, incomplete lineage sorting and/or introgression among ancestral lineages in these three sections resulted in this complex pattern. The current distribution, diversification and molecular differentiation of Q. sect. Ilex in China are likely consequences of local adaptation to the geographic and paleoclimatic changes, which were driven by the uplift of Tibetan Plateau, the Hengduan Mountains and the Himalayas.

7.
Biomed Pharmacother ; 138: 111403, 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33714782

RESUMO

Gu-Ben-Fang-Xiao decoction (GBFXD), derived from the traditional Chinese medicine Yu-Ping-Feng-San, is widely used in clinical settings and has obvious curative effects in respiratory diseases. GBFXD regulates cholesterol transport and lipid metabolism in chronic persistent asthma. There is evidence for its beneficial effects in the remission stage of asthma; however, its metabolic regulatory effects and underlying mechanisms during asthma remission are unclear. In the present study, we used liquid chromatography-mass spectrometry (LC-MS) to analyse the metabolic profile of mouse serum during asthma remission. The acquired LC-MS data were subjected to a multivariate analysis for identification of significantly altered metabolites. In total, 42 metabolites were significantly differentially expressed among the control, model, and GBFXD groups. In particular, levels of fatty acids, acylcarnitines, phosphatidylcholines, phosphatidylethanolamines, phosphatidylinositols, triglycerides, and diacylglycerols were altered during asthma remission. GBFXD may maintain lipid homeostasis on the lung surface by modulating lipid metabolism and may thereby alleviate asthma. We further quantified hypogeic acid (FA 16:1) based on targeted metabolomics and found that GBFXD may regulate fatty acid metabolism by activating the AMP-activated protein kinase (AMPK) pathway. These results support the use of GBFXD in patients with asthma remission.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33648986

RESUMO

INTRODUCTION: Insulin-like growth factor-1 (IGF-1) has been implicated in fetal and early-life growth and development of type 2 diabetes (T2D). We aimed to examine the interaction between circulating IGF-1 and birth weight in relation to risk of T2D. RESEARCH DESIGN AND METHODS: We included 181 090 adults, aged 39-70 years in the UK Biobank Study, who were free of diabetes or major cardiovascular diseases at baseline. Serum IGF-1 levels were determined using chemiluminescent immunoassay method. Birth weight was self-reported; a Genetic Risk Score (GRS) was calculated to define the genetically determined birth weight. The outcome was the incidence of T2D. RESULTS: We identified 3299 incident T2D cases over an average of 9.9 years of follow-up. Among the participants with birth weight of ≥2.5 kg, IGF-1 levels were inversely associated with T2D risk in a dose-dependent manner (p-trend<0.001). In contrast, the association was not significant among those with birth weight of <2.5 kg (p-interaction=0.001). The GRS of birth weight did not interact with IGF-1 levels on T2D risk. CONCLUSIONS: Our results indicate that birth weight significantly modifies the relation between adulthood levels of circulating IGF-1 and the risk of T2D. Our findings highlight the importance of early-life risk factors in the development of the lifecourse prevention strategies targeting IGF-1 and T2D.

9.
Aging (Albany NY) ; 132021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33744854

RESUMO

Coronary heart disease (CHD) is one of the leading causes of heart-associated deaths worldwide. This study aimed to investigate the mechanism by which microRNA-363-3p (miR-363-3p) regulates endothelial injury induced by inflammatory responses in CHD. The expression patterns of miR-363-3p, NADPH oxidase 4 (NOX4), and p38 MAPK/p-p38 MAPK were examined in an established atherosclerosis (AS) model in C57BL/6 mice and in isolated coronary arterial endothelial cells (CAECs) after gain- or loss-of-function experiments. We also measured the levels of inflammatory factors (IL-6, ICAM-1, IL-10 and IL-1ß), hydrogen peroxide (H2O2), and catalase (CAT) activity, followed by detection of cell viability and apoptosis. In AS, miR-363-3p was downregulated and NOX4 was upregulated, while miR-363-3p was identified as targeting NOX4 and negatively regulating its expression. The AS progression was reduced in NOX4 knockout mice. Furthermore, miR-363-3p resulted in a decreased inflammatory response, oxidative stress, and cell apoptosis in CAECs while augmenting their viability via blockade of the p38 MAPK signaling pathway. Overall, miR-363-3p hampers the NOX4-dependent p38 MAPK axis to attenuate apoptosis, oxidative stress injury, and the inflammatory reaction in CAECs, thus protecting CAECs against CHD. This finding suggests the miR-363-3p-dependent NOX4 p38 MAPK axis as a promising therapeutic target for CHD.

10.
Eur J Med Chem ; 216: 113322, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33652353

RESUMO

In this paper, the 2,5-disubstituted furan derivatives containing 1,3,4-thiadiazole were synthesized and screened for their inhibitory activity against α-glucosidase and ß-glucuronidases to obtain potent α-glucosidase inhibitor 9 (IC50 = 0.186 µM) and E. coli ß-glucuronidase inhibitor 26 (IC50 = 0.082 µM), respectively. The mechanisms of the compounds were studied. The kinetic study revealed that compound 9 is a competitive inhibitor against α-glucosidase (Ki = 0.05 ± 0.003 µM) and molecular docking simulation showed several key interactions between 9 and the target including hydrogen bond and p-π stacking interaction. Derivative 26 (Ki = 0.06 ± 0.005 µM) displayed uncompetitive inhibition behavior against EcGUS. Furthermore, the result of docking revealed the furan ring of 26 may be a key moiety in obstructing the active domain of EcGUS. In addition, compound 15 exhibited significant inhibitory activity against these two enzymes, with potential therapeutic effects against diabetes and against CPT-11-induced diarrhea. At the same time, their low toxicity against normal liver tissue LO2 cells lays the foundation for in vivo studies and the development of bifunctional drug.

11.
J Infect Chemother ; 27(6): 876-881, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33676844

RESUMO

INTRODUCTION: Coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) swept rapidly throughout the world. So far, no therapeutics have yet proven to be effective. Ribavirin was recommended for the treatment of COVID-19 in China because of its in vitro activity. However, evidence supporting its clinical use with good efficacy is still lacking. METHODS: A total of 208 confirmed severe COVID-19 patients who were hospitalized in Wuhan Union West Campus between 1 February 2020 and 10 March 2020 were enrolled in the retrospective study. Patients were divided into two groups based on the use of ribavirin. The primary endpoint was the time to clinical improvement. The secondary endpoints included mortality, survival time, time to throat swab SARS-CoV-2 nucleic acid negative conversion, and the length of hospital stay. RESULTS: 68 patients were treated with ribavirin while 140 not. There were no significant between-group differences in demographic characteristics, baseline laboratory test results, treatment, and distribution of ordinal scale scores at enrollment, except for coexisting diseases especially cancer (ribavirin group vs no ribavirin group, P = 0.01). Treatment with ribavirin was not associated with a difference in the time to clinical improvement (P = 0.48, HR = 0.88, 95% CI = 0.63-1.25). There were also no significant differences between-group in SARS-CoV-2 nucleic acid negative conversion, mortality, survival time, and the length of hospital stay. CONCLUSIONS: In hospitalized adult patients with severe COVID-19, no significant benefit was observed with ribavirin treatment.

12.
J Am Chem Soc ; 143(14): 5526-5533, 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33787233

RESUMO

Colibactin is a polyketide-nonribosomal peptide hybrid secondary metabolite that can form interstrand cross-links in double-stranded DNA. Colibactin-producing Escherichia coli has also been linked to colorectal oncogenesis. Thus, there is a strong interest in understanding the role colibactin may play in oncogenesis. Here, using the high-colibactin-producing wild-type E. coli strain we isolated from a clinical sample with the activity-based fluorescent probe we developed earlier, we were able to identify colibactin 770, which was recently identified and proposed as the complete form of colibactin, along with colibactin 788, 406, 416, 420, and 430 derived from colibactin 770 through structural rearrangements and solvolysis. Furthermore, we were able to trap the degrading mature colibactin species by converting the diketone moiety into quinoxaline in situ in the crude culture extract to form colibactin 860 at milligram scale. This allowed us to determine the stereochemically complex structure of the rearranged form of an intact colibactin, colibactin 788, in detail. Furthermore, our study suggested that we were capturing only a few percent of the actual colibactin produced by the microbe, providing a crude quantitative insight into the inherent instability of this compound. Through the structural assignment of colibactins and their degradative products by the combination of LC-HRMS and NMR spectroscopies, we were able to elucidate further the fate of inherently unstable colibactin, which could help acquire a more complete picture of colibactin metabolism and identify key DNA adducts and biomarkers for diagnosing colorectal cancer.

13.
Zhongguo Zhong Yao Za Zhi ; 46(5): 1148-1154, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33787109

RESUMO

There is no consensus on the content, accumulation, transformation and content determination methods of phenolic acids in fresh Salvia miltiorrhiza. In order to find out the true content of phenolic acids in fresh S. miltiorrhiza, a variety of treatment me-thods were used in this study to prepare sample solution. The content changes of phenolic acids in S. miltiorrhiza samples with different dehydration rates were investigated during drying and shade drying processes. Polyphenol oxidase(PPO) of S. miltiorrhiza was extracted and purified by ammonium sulfate precipitation and dialysis to investigate the enzymatic properties. The content of rosmarinic acid, lithosperic acid and S. nolic acid B in S. miltiorrhiza was determined by UPLC. The results showed that the content of phenolic acids in fresh S. miltiorrhiza was highest when it was homogenized with 1 mol·L~(-1) HCl solution or 1 mol·L~(-1) HCl methanol solution. There was no significant difference in the content of phenolic acids in S. miltiorrhiza with different dehydration rates, indicating that there was no correlation between phenolic acid content and dehydration rate. The optimum pH of S. miltiorrhiza PPO was 7.6 and the optimum temperature was 40 ℃. With catechol as substrate, S. miltiorrhiza PPO had the enzymatic browning reaction which was in compliance with Michaelis equation, with Michaelis constant K_m of 0.12 mol·L~(-1) and V_(max) of 588.23 U·min~(-1). The inhibitory effect of citric acid, disodium ethylenediamine tetraacetate, ascorbic acid and sodium sulfite on S. miltiorrhiza PPO increased with the increase of inhibitor concentration, and sodium sulfite showed the strongest inhibitory effect. The present study proved that there were a large number of phenolic acids in fresh S. miltiorrhiza, which were the secondary metabolite of primitive accumulation during the growth of S. miltiorrhiza, rather than the induced product of postharvest drying and dehydration stress. This study has reference value and significance for the cultivation, harvest and processing of S. miltiorrhiza.


Assuntos
Salvia miltiorrhiza , Catecol Oxidase , Dessecação , Hidroxibenzoatos , Raízes de Plantas
14.
Sci Adv ; 7(12)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33731342

RESUMO

Adult neurogenesis in the dentate gyrus of the hippocampus is regulated by specific microglia groups and functionally implicated in behavioral responses to stress. However, the role of microglia in hippocampal neurogenesis and stress resilience remains unclear. We identified interleukin 4 (IL4)-driven microglia characterized by high expression of Arg1, which is critical in maintaining hippocampal neurogenesis and stress resistance. Decreasing Arg1+ microglia in the hippocampus by knocking down the microglial IL4R suppressed hippocampal neurogenesis and enhanced stress vulnerability. Increasing Arg1+ microglia in the hippocampus by enhancing IL4 signaling restored hippocampal neurogenesis and the resilience to stress-induced depression. Brain-derived neurotrophic factor (BDNF) was found necessary for the proneurogenesis effects of IL4-driven microglia. Together, our findings suggest that IL4-driven microglia in the hippocampus trigger BDNF-dependent neurogenesis responding to chronic stress, helping protect against depressive-like symptoms. These findings identify the modulation of a specific microglial phenotype as a treatment strategy for mood disorders.

15.
Oncol Rep ; 45(4): 1, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33649840

RESUMO

Radioactive iodine (RAI, 131I) therapy is the main treatment for thyroid carcinoma (TC). Long noncoding RNA (lncRNA)/microRNA (miR) competing endogenous RNA (ceRNA) networks have aroused great interest for their roles in gene expression. The present study aimed to investigate the effect of lncRNA SNHG7 on the growth and 131I resistance of TC. Differentially expressed lncRNAs in TC and paracancerous tissues were analyzed. The binding of miR­9­5p with small nucleolar RNA host gene 7 (SNHG7) and dipeptidyl­peptidase 4 (DPP4) was identified. Gain­ and loss­of­function analyses of SNHG7 and miR­9­5p were performed to determine their effects on the growth and 131I resistance of TC cells. The activity of the PI3K/Akt pathway was evaluated. Consequently, upregulated SNHG7 was revealed in TC tissues and correlated with 131I resistance. Silencing of SNHG7 or overexpressing miR­9­5p inhibited the growth and 131I resistance of TC cells. SNHG7 acted as a ceRNA of miR­9­5p to enhance DPP4 expression. Overexpressed SNHG7 increased DPP4 expression and activated the PI3K/Akt signaling pathway by sponging miR­9­5p. The in vitro results were reproduced in vivo. In summary, the present study provided evidence that the SNHG7/miR­9­5p/DPP4 ceRNA network could promote the growth and 131I resistance of TC cells via PI3K/Akt activation. The present study may offer novel options for TC treatment.

16.
Int J Clin Oncol ; 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33666788

RESUMO

BACKGROUND: The impact of tumor size on account of the long-term survival results in gallbladder cancer (GBC) patients has been controversial. It is urgent necessary to identify the optimal cut-off value of tumor size in resected GBC, and we attempted to integrate tumor size with other prognostic factors into a prognostic nomogram to predict the cancer-specific survival (CSS) of GBC patients. METHODS: 1639 patients with resected GBC were extracted from the Surveillance, Epidemiology and End Results (SEER) database. X-tile program was used to identify the optimal cut-off value of tumor size. A nomogram including tumor size was established to predict 1-, 3- and 5-year CSS based on the independent risk factors chosen by univariate and multivariable cox analyses. The precision of the nomogram for predicting survival was validated with Harrell's concordance index (C-index), calibration curves, and receiver operating characteristic curve (ROC) internally and externally. RESULTS: Patients with GBC were classified into 1-13 mm, 14-63 mm and 64 mm subgroup based on the optimal cut-off for tumor size in terms of CSS. The nomogram according to the independent factors was well calibrated and displayed better discrimination power than 7th tumor-node-metastasis (TNM) stage systems. CONCLUSIONS: The results demonstrated that increased tumor size is closely associated with the worse CSS. Our novel nomogram, which outperforms the conventional TNM staging system, showed satisfactory accuracy and clinically practicality for predicting the outcome of resected GBC patients.

17.
Environ Toxicol ; 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33656234

RESUMO

Fenvalerate (Fen) is an endocrine disruptor, capable of interfering with the activity of estrogen and androgen. Our objective was to explore the molecular mechanisms of Fen on sperm in vivo. Adult male Sprague-Dawley rats were orally exposed to 0, 0.00625, 0.125, 2.5, 30 mg/kg/day Fen for 8 weeks. Sperm morphology, differential proteomics of sperm and testes, bioinformatic analysis, western blotting (WB), and RT-PCR were used to explore the mechanism of Fen on sperm. Data showed that low Fen doses significantly induced sperm malformations. In sperm proteomics, 47 differentially expressed (DE) proteins were enriched in biological processes (BPs) related to energy metabolism, response to estrogen, spermatogenesis; and enriched in cellular components (CCs) relating to energy-metabolism, sperm fibrous sheath and their outer dense fibers. In testicular proteomics, 56 DE proteins were highly associated with mRNA splicing, energy metabolism; and enriched in CCs relating to vesicles, myelin sheath, microtubules, mitochondria. WB showed that the expression of selected proteins was identical to their tendency in 2D gels. Literature indicates that key DE proteins in proteomic profiles (such as Trap1, Hnrnpa2b1, Hnrnpk, Hspa8, and Gapdh) are involved in P53-related processes or morphogenesis or spermatogenesis. Also, P53 mRNA and protein levels were significantly increased by Fen; bioinformatic re-analysis showed that 88.5% DE proteins and P53 formed a complex interacting network, and the key DE proteins were coenriched with P53-related BPs. Results indicate that key DE proteins of proteome underlying sperm malformations of rats exposed to low Fen doses are highly related to P53.

18.
Biofactors ; 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33651487

RESUMO

Head and neck squamous cell carcinoma is a malignant tumor of the upper aerodigestive tract. These RNA-binding proteins (RBPs) influence post-transcriptional in cells and regulate cell physiology, participate in regulating RNA stability, alternative splicing, translation, modification, localization, and apoptosis. We used RNA sequencing data from The Cancer Genome Atlas to display dysfunctional RBPs microenvironments and provide potential useful biomarkers for head and neck squamous cell carcinoma (HNSCC) diagnosis and prognosis. Six RBPs (DNMT1, PCF11, EIF5A2, RNASE10, PSMA6, and IGF2BP2) were selected as independent prognosis factors of HNSCC patients. The Kyoto Encyclopedia of Genes and Genomes were mainly enriched in RNA transport, Spliceosome, RNA degradation, mRNA surveillance pathway, and Epstein-Barr virus infection. cBioPortal results demonstrated that these six genes were altered in 150 samples out of 504 HNSCC patients (30%) and the amplification of IGF2BP2 was the largest frequent copy-number alteration. Based on the online database, we identified novel RBPs markers for the prognosis of HNSCC.

19.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 46(1): 25-31, 2021 Jan 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-33678633

RESUMO

OBJECTIVES: Chondrocyte apoptosis is an important process in the pathogenesis of osteoarthritis. Mangiferin exerts multiple pharmacological effects such as anti-inflammatory and anti-apoptosis. However, the role of mangiferin in chondrocyte apoptosis is not clear. In this study, we aimed to explore the role of mangiferin in IL-1ß-induced chondrocyte apoptosis. METHODS: ATDC5 cells were randomly divided into a control group, a IL-1ß group, a MFN-L group, a MFN-M group, a MFN-H group and a MFN+LY294002 group. Cells in the control group were treated with IL-1ß (10 ng/mL) for 24 h; cells in the MFN-L group, the MFN-M group and the MFN-H group were pretreated with 5, 10 and 20 µmol/L mangiferin for 1 h respectively, and then they were treated with IL-1ß (10 ng/mL) for 24 h; cells in the MFN+LY294002 group were treated with LY294002 (25 µmol/L) for 1 h, then mangiferin (20 µmol/L) and IL-1ß (10 ng/mL) for 1 h and 24 h, respectively. Cell viability was detected by CCK-8 assay and cell apoptosis was measured by flow cytometry. Colorimetric assay was conducted to measure the caspase-3 activity. The protein levels of Bcl-2, Bax, and phosphoinositide 3-kinase (PI3K)/Akt signaling pathway related proteins were detected by Western blotting. RESULTS: Compared to the control group, cell viability was significantly decreased; cell apoptosis, caspase-3 activity and Bax protein expression were significantly increased; the protein levels of Bcl-2, p-PI3K, and p-Akt were significantly decreased in the IL-1ß group (all P<0.05). Compared to the IL-1ß group, cell viability was significantly increased; cell apoptosis, caspase-3 activity and Bax protein expression were significantly decreased; the protein levels of Bcl-2, p-PI3K, and p-Akt were significantly increased in the MFN-L, the MFN-M and the MFN-H groups (all P<0.05). Compared to the MFN-M group, cell apoptosis and the protein level of Bax in the MFN+LY294002 group were significantly increased; the Bcl-2 protein expression was significantly decreased (all P<0.05). CONCLUSIONS: Mangiferin could attenuate IL-1ß-induced apoptosis of the mice chondrocytes, which is mediated by the activation of PI3K/Akt signaling pathway.


Assuntos
Condrócitos , Fosfatidilinositol 3-Quinases , Animais , Apoptose , Interleucina-1beta , Camundongos , Proteínas Proto-Oncogênicas c-akt , Xantonas
20.
Biomed Res Int ; 2021: 8858326, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33728343

RESUMO

Long noncoding RNAs (lncRNAs) are a class of important regulators participating in various pathological processes. Until now, the role of lncRNAs in the occurrence and development of intrahepatic cholestasis of pregnancy (ICP) has rarely been investigated. The data from microarray screening revealed 58 upregulated and 85 downregulated lncRNAs and 47 upregulated and 71 downregulated mRNAs in ICP patients compared to healthy controls. Bioinformatics analysis revealed biological processes focused on lipid metabolism, apoptosis, cell cycle, cell differentiation, and oxidative stress. Furthermore, the expressions of three lncRNAs (ENST00000505175.1, ASO3480, and ENST00000449605.1) chosen for verification were significantly decreased and showed the diagnostic and prognostic value for ICP based on ROC analysis. This is the first study to report the specific role of lncRNAs in ICP, which may be helpful for the diagnosis and prognosis of ICP clinically.

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