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1.
Neural Regen Res ; 18(5): 1147-1153, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36255005

RESUMO

Research has shown that long-chain noncoding RNAs (lncRNAs) are involved in the regulation of a variety of biological processes, including peripheral nerve regeneration, in part by acting as competing endogenous RNAs. c-Jun plays a key role in the repair of peripheral nerve injury. However, the precise underlying mechanism of c-Jun remains unclear. In this study, we performed microarray and bioinformatics analysis of mouse crush-injured sciatic nerves and found that the lncRNA Pvt1 was overexpressed in Schwann cells after peripheral nerve injury. Mechanistic studies revealed that Pvt1 increased c-Jun expression through sponging miRNA-214. We overexpressed Pvt1 in Schwann cells cultured in vitro and found that the proliferation and migration of Schwann cells were enhanced, and overexpression of miRNA-214 counteracted the effects of Pvt1 overexpression on Schwann cell proliferation and migration. We conducted in vivo analyses and injected Schwann cells overexpressing Pvt1 into injured sciatic nerves of mice. Schwann cells overexpressing Pvt1 enhanced the regeneration of injured sciatic nerves following peripheral nerve injury and the locomotor function of mice was improved. Our findings reveal the role of lncRNAs in the repair of peripheral nerve injury and highlight lncRNA Pvt1 as a novel potential treatment target for peripheral nerve injury.

2.
J Affect Disord ; 320: 230-240, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36183821

RESUMO

BACKGROUND: Interpersonal psychotherapy (IPT) has been widely used for depression. However, current studies of IPT have been restricted to depressive symptoms, and the results for improving social functioning were controversial. METHODS: A comprehensive literature search of randomized controlled trials (RCTs) was conducted through eleven databases. Data analysis was performed by RevMan5.3, and effects were summarized by using a random effects model of mean differences with 95 % confidence intervals. RESULTS: From 2443 records, eleven studies met inclusion and exclusion criteria were used for meta-analysis. The results showed that IPT had significant effects on improving social functioning (SMD: -0.53, 95 % CI: -0.80 to -0.26), reducing depression (SMD: -0.49, 95 % CI: -0.80 to -0.19) and anxiety (SMD: -0.90, 95 % CI: -1.28 to -0.52), but the effect on the overall functioning (SMD: -0.37, 95 % CI: -0.73 to -0.01) is not obvious. Moreover, subgroup analysis showed that IPT was effective in improving social functioning in adolescent depression (SMD: -0.35, 95 % CI: -0.58 to -0.13) and perinatal depression (SMD: -1.01, 95 % CI: -1.35 to -0.67), while there was no significant difference in the adult depression group (SMD: -0.39, 95 % CI: -1.05 to 0.27). LIMITATION: The blind method cannot be carried out in most studies due to the particularity of psychotherapy, heterogeneity in some results. CONCLUSION: IPT has a significant effect on improving social functioning and reducing depression and anxiety, while the effect on overall functioning requires further research. Overall, IPT is one of the effective nonpharmacological treatments for depression.


Assuntos
Psicoterapia Interpessoal , Humanos , Adulto , Adolescente , Gravidez , Feminino , Depressão/terapia , Interação Social , Psicoterapia/métodos , Ansiedade
3.
Food Chem ; 403: 134367, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36358067

RESUMO

A pulsed electric field (PEF) induces cell electroporation for solid foods, thereby allowing PEF to be used as a pretreatment method for extraction, drying, peeling, freeze-thawing, and cooking by increasing mass transfer. Currently, popular research mainly focuses on the process and results of the application of PEF to solid food processing. Therefore, this review summarizes the impact of PEF on the quality of solid food, the evaluation techniques of PEF-treated tissues and the characteristics of PEF treatment chambers. Furthermore, other pretreatments, including freezing and peeling, typically used in the meat and vegetable sectors, are also discussed alongside PEF to evaluate the impact on its effects. Finally, this article examined the main obstacles and prospects of PEF in solid food processing. This evaluation is anticipated to expand future PEF research paths in the solid food industry.


Assuntos
Eletricidade , Manipulação de Alimentos , Manipulação de Alimentos/métodos , Indústria de Processamento de Alimentos , Carne/análise , Tecnologia
4.
Food Chem ; 404(Pt A): 134561, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36252379

RESUMO

Xiaoheiyao is the rhizome of Inula nervosa Wall., a traditional spice and medicinal herb in China. In this study, the creatinine inhibitor from Xiaoheiyao extract and also the effects and mechanism on the production of heterocyclic aromatic amines (HAAs) were investigated. Xiaoheiyao extract inhibited the total contents of seven detected HAAs in grilled beef patties, particularly aminoimidazole-azaarenes (AIAs) in a dose-dependent manner, reaching a maximum inhibition rate of 62% for total HAAs and 73% for AIAs. The most effective subfraction of Xiaoheiyao extract (IER80) contained abundant potential creatinine inhibitors, as revealed by immobilized creatinine probe, HPLC and UPLC-MS/MS analyses. Moreover, electrophilic p-coumaric acid derivatives were discovered from IER80 by feature based molecular networking. p-Coumaric acid was demonstrated to inhibit the contents of total HAAs and AIAs in grilled beef patties and model system. Quantitative analyses of the precursor and intermediates of AIAs in model system revealed that p-coumaric acid mainly affected the generation of AIAs by inhibiting creatinine.


Assuntos
Compostos Heterocíclicos , Inula , Bovinos , Animais , Creatinina , Compostos Heterocíclicos/análise , Cromatografia Líquida , Rizoma/química , Espectrometria de Massas em Tandem , Aminas/análise , Extratos Vegetais , Culinária , Carne/análise
5.
J Ethnopharmacol ; 300: 115702, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36099982

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine (TCM) theory, depression is an emotional disease, which is thought to be related to stagnation of liver qi and dysfunction of the spleen in transport. Xiaoyao San (XYS) is considered to have the effects of soothing liver-qi stagnation and invigorating the spleen. The spleen has the function to transport and transform nutrients. The liver has also termed the center of energy metabolism in the body. Therefore, exploring the antidepressant effects of XYS from the perspective of energy metabolism may reveal new findings. AIM OF THE STUDY: Glucose catabolism is an important part of energy metabolism. In recent years, several researchers have found that XYS can exert antidepressant effects by modulating abnormalities in glucose catabolism-related metabolites. The previous research of our research group found that the hippocampus glucose catabolism was disordered in depression. However, the antidepressant potential of XYS through modulating the disorders of hippocampal glucose catabolism and the specific metabolic pathways and targets of XYS action were still unknown. The aim of this study was to address the above scientific questions. MATERIALS AND METHODS: In this research, the CUMS (chronic unpredictable mild stress) model was used as the animal model of depression. The antidepressant effect of XYS was evaluated by behavioral indicators. The specific pathways and targets of XYS modulating the disorders of glucose catabolism in the hippocampus of CUMS rats were obtained by stable isotope-resolved metabolomics. Further, the isotope tracing results were also verified by molecular biology and electron transmission electron microscopy. RESULTS: The results demonstrated that XYS pretreatment could significantly improve the depressive symptoms induced by CUMS. More importantly, it was found that XYS could modulate the disorders of glucose catabolism in the hippocampus of CUMS rats. Stable isotope-resolved metabolomics and enzyme activity tests showed that Lactate dehydrogenase (LDH), Pyruvate carboxylase (PC), and Pyruvate dehydrogenase (PDH) were targets of XYS for modulating the disorders of glucose catabolism in the hippocampus of CUMS rats. The Succinate dehydrogenase (SDH) and mitochondrial respiratory chain complex V (MRCC-Ⅴ) were targets of XYS to improve abnormal mitochondrial oxidative phosphorylation in the hippocampus of CUMS rats. XYS was also found to have the ability to improve the structural damage of mitochondria and nuclei in the hippocampal caused by CUMS. CONCLUSIONS: This study was to explore the antidepressant effect of XYS from the perspective of glucose catabolism based on a strategy combining stable isotope tracing, molecular biology techniques, and transmission electron microscopy. We not only obtained the specific pathways and targets of XYS to improve the disorders of glucose catabolism in the hippocampus of CUMS rats, but also revealed the specific targets of the pathways of XYS compared with VLF.


Assuntos
Medicamentos de Ervas Chinesas , Succinato Desidrogenase , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Comportamento Animal , Depressão/psicologia , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Glucose/farmacologia , Hipocampo/metabolismo , Isótopos/metabolismo , Isótopos/farmacologia , Lactato Desidrogenases/metabolismo , Metabolômica/métodos , Piruvato Carboxilase , Piruvatos/farmacologia , Ratos , Estresse Psicológico/tratamento farmacológico , Succinato Desidrogenase/metabolismo
6.
Nucleic Acids Res ; 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36318242

RESUMO

Alternative splicing (AS) is a fundamental process that governs almost all aspects of cellular functions, and dysregulation in this process has been implicated in tumor initiation, progression and treatment resistance. With accumulating studies of carcinogenic mis-splicing in cancers, there is an urgent demand to integrate cancer-associated splicing changes to better understand their internal cross-talks and functional consequences from a global view. However, a resource of key functional AS events in human cancers is still lacking. To fill the gap, we developed ASCancer Atlas (https://ngdc.cncb.ac.cn/ascancer), a comprehensive knowledgebase of aberrant splicing in human cancers. Compared to extant databases, ASCancer Atlas features a high-confidence collection of 2006 cancer-associated splicing events experimentally proved to promote tumorigenesis, a systematic splicing regulatory network, and a suit of multi-scale online analysis tools. For each event, we manually curated the functional axis including upstream splicing regulators, splicing event annotations, downstream oncogenic effects, and possible therapeutic strategies. ASCancer Atlas also houses about 2 million computationally putative splicing events. Additionally, a user-friendly web interface was built to enable users to easily browse, search, visualize, analyze, and download all splicing events. Overall, ASCancer Atlas provides a unique resource to study the functional roles of splicing dysregulation in human cancers.

7.
Nucleic Acids Res ; 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36318250

RESUMO

DNA methylation, as the most intensively studied epigenetic mark, regulates gene expression in numerous biological processes including development, aging, and disease. With the rapid accumulation of whole-genome bisulfite sequencing data, integrating, archiving, analyzing, and visualizing those data becomes critical. Since its first publication in 2015, MethBank has been continuously updated to include more DNA methylomes across more diverse species. Here, we present MethBank 4.0 (https://ngdc.cncb.ac.cn/methbank/), which reports an increase of 309% in data volume, with 1449 single-base resolution methylomes of 23 species, covering 236 tissues/cell lines and 15 biological contexts. Value-added information, such as more rigorous quality evaluation, more standardized metadata, and comprehensive downstream annotations have been integrated in the new version. Moreover, expert-curated knowledge modules of featured differentially methylated genes associated with biological contexts and methylation analysis tools have been incorporated as new components of MethBank. In addition, MethBank 4.0 is equipped with a series of new web interfaces to browse, search, and visualize DNA methylation profiles and related information. With all these improvements, we believe the updated MethBank 4.0 will serve as a fundamental resource to provide a wide range of data services for the global research community.

8.
Front Oncol ; 12: 968759, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338700

RESUMO

Background: Quantitative contrast-enhanced ultrasonography parameters are affected by various factors. We evaluated corrected quantitative contrast enhanced ultrasonography in differentiating benign adnexal tumors from malignant tumors. Methods: Patients with adnexal masses who underwent conventional and contrast-enhanced ultrasonography were included. Contrast-enhanced ultrasonography parameters such as base intensity, arrival time, peak intensity, time to peak intensity, ascending slope, and descending slope were measured. Corrected (time to peak intensity - arrival time) mass/(time to peak intensity - arrival time) uterus and (peak intensity - base intensity) mass/(peak intensity - base intensity) uterus were calculated. Lesions were confirmed by pathologic examination of surgical specimens. Results: This study included 31 patients with 35 adnexal lesions including 20 (57.10%) benign and 15 (42.90%) malignant lesions. The corrected contrast-enhanced ultrasonography quantitative parameters in lesions were statistically different between malignant and benign groups (P<0.05). The optimal cut-off value for (time to peak intensity - arrival time) mass/(time to peak intensity - arrival time) uterus, ascending slope, and (peak intensity - base intensity) mass/(peak intensity - base intensity) uterus, and descending slope for differentiating malignant adnexal masses from benign tumors were 1.05 (area under curve: 0.93, P<0.05), 1.11 (area under curve: 0.83, P<0.05), 0.82 (area under curve: 0.73, P<0.05), and -0.27 (area under curve: 0.66, P=0.16), with sensitivity and specificity of 93.33% and 85.00%, 86.67% and 75.00%, 86.67% and 60.00%, and 54.55% and 66.67%, respectively. Conclusions: Corrected contrast-enhanced ultrasonography parameters provide practical differential diagnosis value of adnexal lesions with high reliability for sonologists.

9.
Front Oncol ; 12: 870556, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338729

RESUMO

Background: This study aimed to explore the characteristics of optical coherence tomography (OCT) imaging for differentiating between benign and malignant lesions and different pathological types of lung cancer in bronchial lesions and to preliminarily evaluate the clinical value of OCT. Methods: Patients who underwent bronchoscopy biopsy and OCT between February 2019 and December 2019 at the Chinese PLA General Hospital were enrolled in this study. White-light bronchoscopy (WLB), auto-fluorescence bronchoscopy (AFB), and OCT were performed at the lesion location. The main characteristics of OCT imaging for the differentiation between benign and malignant lesions and the prediction of the pathological classification of lung cancer in bronchial lesions were identified, and their clinical value was evaluated. Results: A total of 135 patients were included in this study. The accuracy of OCT imaging for differentiating between benign and malignant bronchial lesions was 94.1%, which was significantly higher than that of AFB (67.4%). For the OCT imaging of SCC, adenocarcinoma, and small-cell lung cancer, the accuracies were 95.6, 94.3, and 92%, respectively. The accuracy, sensitivity, and specificity of OCT were higher than those of WLB. In addition, these main OCT image characteristics are independent influencing factors for predicting the corresponding diseases through logistic regression analysis between the main OCT image characteristics in the study and the general clinical features of patients (p<0.05). Conclusion: As a non-biopsy technique, OCT can be used to improve the diagnosis rate of lung cancer and promote the development of non-invasive histological biopsy.

10.
Nat Prod Res ; : 1-8, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36352349

RESUMO

The establishment of structure activity relationship (SAR) for rakicidin derivatives is pretty vital to develop rakicidins as a new type of anti-cancer agents. Herein, two novel rakicidin derivatives, compounds B1-1 (1) and B1-2 (2), a cyclic depsipeptide and a chain lipopeptide, respectively, were isolated from culture broth of Micromonospora chalcea FIM-R160609, and their structures were elucidated clearly by extensive NMR and HR-ESI-MS analyses. Following, their cytotoxic activities were evaluated against HCT-8 and PANC-1 human cancer cell lines under hypoxic and normoxic conditions. Their activities were significantly decreased when compared with that of rakicidin B1. These results demonstrated that the double bond located on the position 9 and 10 of conjugated diene unit and cycle-type structure plays an important role in keeping the biological activity of rakicidins. Furthermore, the positive effect of double bond and cycle form on the anti-bacterial activities were also confirmed by testing their inhibitory activities against gram positive bacteria. This work will definitely diversify the SAR of rakicidins and provide the guidance for the design of new potent rakicidin analogues.

11.
Nat Commun ; 13(1): 7181, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36418326

RESUMO

Asymmetric cell division (ACD) produces morphologically and behaviorally distinct cells and is the primary way to generate cell diversity. In the model bacterium Caulobacter crescentus, the polarization of distinct scaffold-signaling hubs at the swarmer and stalked cell poles constitutes the basis of ACD. However, mechanisms involved in the formation of these hubs remain elusive. Here, we show that a swarmer-cell-pole scaffold, PodJ, forms biomolecular condensates both in vitro and in living cells via phase separation. The coiled-coil 4-6 and the intrinsically disordered regions are the primary domains that contribute to biomolecular condensate generation and signaling protein recruitment in PodJ. Moreover, a negative regulation of PodJ phase separation by the stalked-cell-pole scaffold protein SpmX is revealed. SpmX impedes PodJ cell-pole accumulation and affects its recruitment ability. Together, by modulating the assembly and dynamics of scaffold-signaling hubs, phase separation may serve as a general biophysical mechanism that underlies the regulation of ACD in bacteria and other organisms.


Assuntos
Caulobacter crescentus , Transdução de Sinais , Divisão Celular Assimétrica , Corpo Celular , Biofísica , Caulobacter crescentus/genética
12.
Front Plant Sci ; 13: 1022273, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36388530

RESUMO

The taxonomic terms "Phlomis" and "Phlomoides" had been used to describe two sections within the genus Phlomis belonging to the Lamiaceae family. Recently, phylogenetic analyses using molecular markers showed that Phlomis and Phlomoides formed two monophyletic clades, and thus they are generally accepted as separate genera. In this study, we assembled the complete chloroplast genome of Phlomis fruticosa, which is the first reported chloroplast genome belonging to Phlomis genus, as well as the complete chloroplast genome of Phlomoides strigosa belonging to Phlomoides genus. The results showed that the length of chloroplast genome was 151,639 bp (Phlomis fruticosa) and 152,432 bp (Phlomoides strigosa), with conserved large single copy regions, small single copy regions, and inverted repeat regions. 121 genes in Phlomis fruticosa and 120 genes in Phlomoides strigosa were annotated. The chloroplast genomes of Phlomis fruticosa, Phlomoides strigosa, and three reported Phlomoides species, as well as those of 51 species from the Lamiaceae family, which covered 12 subfamilies, were subjected to phylogenetic analyses. The Phlomis and Phlomoides species were split into two groups, which were well supported by both maximum likelihood and Bayesian inference tree analyses. Our study provided further evidence to recognize Phlomis and Phlomoides as independent genera.

13.
Nat Commun ; 13(1): 7142, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36414658

RESUMO

Single cell RNA sequencing is a promising technique to determine the states of individual cells and classify novel cell subtypes. In current sequence data analysis, however, genes with low expressions are omitted, which leads to inaccurate gene counts and hinders downstream analysis. Recovering these omitted expression values presents a challenge because of the large size of the data. Here, we introduce a data-driven gene expression recovery framework, referred to as self-consistent expression recovery machine (SERM), to impute the missing expressions. Using a neural network, the technique first learns the underlying data distribution from a subset of the noisy data. It then recovers the overall expression data by imposing a self-consistency on the expression matrix, thus ensuring that the expression levels are similarly distributed in different parts of the matrix. We show that SERM improves the accuracy of gene imputation with orders of magnitude enhancement in computational efficiency in comparison to the state-of-the-art imputation techniques.


Assuntos
Moduladores Seletivos de Receptor Estrogênico , Expressão Gênica
14.
Allergy ; 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36420736

RESUMO

There has been an important change in the clinical characteristics and immune profile of Coronavirus disease 2019 (COVID-19) patients during the pandemic thanks to the extensive vaccination programs. Here, we highlight recent studies on COVID-19, from the clinical and immunological characteristics to the protective and risk factors for severity and mortality of COVID-19. The efficacy of the COVID-19 vaccines and potential allergic reactions after administration are also discussed. The occurrence of new variants of concerns such as Omicron BA.2, BA.4 and BA.5 and the global administration of COVID-19 vaccines have changed the clinical scenario of COVID-19. Multisystem inflammatory syndrome in children (MIS-C) may cause severe and heterogeneous disease but with a lower mortality rate. Perturbations in immunity of T cells, B cells, and mast cells, as well as autoantibodies and metabolic reprogramming may contribute to the long-term symptoms of COVID-19. There is conflicting evidence about whether atopic diseases, such as allergic asthma and rhinitis, are associated with a lower susceptibility and better outcomes of COVID-19. At the beginning of pandemic, the European Academy of Allergy and Clinical Immunology (EAACI) developed guidelines that provided timely information for the management of allergic diseases and preventive measures to reduce transmission in the allergic clinics. The global distribution of COVID-19 vaccines and emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with reduced pathogenic potential dramatically decreased the morbidity, severity, and mortality of COVID-19. Nevertheless, breakthrough infection remains a challenge for disease control. Hypersensitivity reactions (HSR) to COVID-19 vaccines are low compared to other vaccines, and these were addressed in EAACI statements that provided indications for the management of allergic reactions, including anaphylaxis to COVID-19 vaccines. We have gained a depth knowledge and experience in the over 2 years since the start of the pandemic, and yet a full eradication of SARS-CoV-2 is not on the horizon. Novel strategies are warranted to prevent severe disease in high-risk groups, the development of MIS-C and long COVID-19.

15.
Front Immunol ; 13: 1031868, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36405689

RESUMO

Classical swine fever (CSF), caused by the classical swine fever virus (CSFV), is a highly contagious and fatal viral disease, posing a significant threat to the swine industry. Heat shock protein 90 kDa alpha class A member 1 (HSP90AA1) is a very conservative chaperone protein that plays an important role in signal transduction and viral proliferation. However, the role of HSP90AA1 in CSFV infection is unknown. In this study, we found that expression of HSP90AA1 could be promoted in PK-15 and 3D4/2 cells infected by CSFV. Over-expression of HSP90AA1 could inhibit CSFV replication and functional silencing of HSP90AA1 gene promotes CSFV replication. Further exploration revealed that HSP90AA1 interacted with CSFV NS5A protein and reduced the protein levels of NS5A. Since NS5A has an important role in CSFV replication and is closely related to type I IFN and NF-κB response, we further analyzed whether HSP90AA1 affects CSFV replication by regulating type I IFN and NF-κB pathway responses. Our research found HSP90AA1 positively regulated type I IFN response by promoting STAT1 phosphorylation and nuclear translocation processes and promoted the nuclear translocation processes of p-P65. However, CSFV infection antagonizes the activation of HSP90AA1 on JAK/STAT and NF-κB pathway. In conclusion, our study found that HSP90AA1 overexpression significantly inhibited CSFV replication and may inhibit CSFV replication by interacting with NS5A and activating JAK/STAT and NF-κB signaling pathways. These results provide new insights into the mechanism of action of HSP90AA1 in CSFV infection, which abundant the candidate library of anti-CSFV.


Assuntos
Vírus da Febre Suína Clássica , Suínos , Animais , NF-kappa B/metabolismo , Replicação Viral , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo , Transdução de Sinais , Chaperonas Moleculares/metabolismo
16.
Anim Genet ; 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36414135

RESUMO

Joint genomic prediction (GP) is an attractive method to improve the accuracy of GP by combining information from multiple populations. However, many factors can negatively influence the accuracy of joint GP, such as differences in linkage disequilibrium phasing between single nucleotide polymorphisms (SNPs) and causal variants, minor allele frequencies and causal variants' effect sizes across different populations. The objective of this study was to investigate whether the imputed high-density genotype data can improve the accuracy of joint GP using genomic best linear unbiased prediction (GBLUP), single-step GBLUP (ssGBLUP), multi-trait GBLUP (MT-GBLUP) and GBLUP based on genomic relationship matrix considering heterogenous minor allele frequencies across different populations (wGBLUP). Three traits, including days taken to reach slaughter weight, backfat thickness and loin muscle area, were measured on 67 276 Large White pigs from two different populations, for which 3334 were genotyped by SNP array. The results showed that a combined population could substantially improve the accuracy of GP compared with a single-population GP, especially for the population with a smaller size. The imputed SNP data had no effect for single population GP but helped to yield higher accuracy than the medium-density array data for joint GP. Of the four methods, ssGLBUP performed the best, but the advantage of ssGBLUP decreased as more individuals were genotyped. In some cases, MT-GBLUP and wGBLUP performed better than GBLUP. In conclusion, our results confirmed that joint GP could be beneficial from imputed high-density genotype data, and the wGBLUP and MT-GBLUP methods are promising for joint GP in pig breeding.

17.
Genes (Basel) ; 13(11)2022 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-36360196

RESUMO

The epigenome likely interacts with traditional and genetic risk factors to influence blood pressure. We evaluated whether 13 previously reported DNA methylation sites (CpGs) are associated with systolic (SBP) or diastolic (DBP) blood pressure, both individually and aggregated into methylation risk scores (MRS), in 3070 participants (including 437 African ancestry (AA) and 2021 European ancestry (EA), mean age = 70.5 years) from the Health and Retirement Study. Nine CpGs were at least nominally associated with SBP and/or DBP after adjusting for traditional hypertension risk factors (p < 0.05). MRSSBP was positively associated with SBP in the full sample (ß = 1.7 mmHg per 1 standard deviation in MRSSBP; p = 2.7 × 10-5) and in EA (ß = 1.6; p = 0.001), and MRSDBP with DBP in the full sample (ß = 1.1; p = 1.8 × 10-6), EA (ß = 1.1; p = 7.2 × 10-5), and AA (ß = 1.4; p = 0.03). The MRS and BP-genetic risk scores were independently associated with blood pressure in EA. The effects of both MRSs were weaker with increased age (pinteraction < 0.01), and the effect of MRSDBP was higher among individuals with at least some college education (pinteraction = 0.02). In AA, increasing MRSSBP was associated with higher SBP in females only (pinteraction = 0.01). Our work shows that MRS is a potential biomarker of blood pressure that may be modified by traditional hypertension risk factors.


Assuntos
Hipertensão , Aposentadoria , Feminino , Humanos , Idoso , Pressão Sanguínea/genética , Hipertensão/genética , Fatores de Risco , Epigênese Genética
18.
Genes (Basel) ; 13(11)2022 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-36360207

RESUMO

In Chinese pig populations in which crossbreeding is used, these animals show a level of weakness compared with their original purebred ancestors. For instance, in the Lulai pig, a newly developed Chinese breed that is raised on the basis of the Laiwu pig (a Chinese indigenous breed with exceptionally high intramuscular fat content) and the Yorkshire pig using a method of systematic crossbreeding, both their market acceptance and performance are inferior. To reveal the practical role of these admixed breeds and traditional systematic crossbreeding methods at the genomic level, we explored population structure, genetic signatures, and introgression. We conducted this study based on the SNP chip data of 381 Lulai pigs, 182 Laiwu pigs, and 127 Yorkshires, which showed deficient genome coverage during our study. Therefore, we further selected the Genotyping by Genome Reducing and Sequencing (GGRS) method, which has a high density and suitable genome coverage as a supplement. We applied the GGRS data of 38 Lulai pigs, 75 Laiwu pigs, and 75 Yorkshires. In terms of the SNP chip data, by Fst analysis, we detected 782 significantly different genes between Lulai pigs and Yorkshires, including 3 major genes associated with growth (LEPR) and meat quality (SCD and TBC1D1), and we detected 426 significantly different genes between Lulai pigs and Laiwu pigs. With rIBD, we detected 12 genomic regions that included 182 genes that Yorkshires introgressed to Lulai pigs, and we detected 27 genomic regions that included 229 genes with a major gene (SCD) that Laiwu pigs introgressed to Lulai pigs. Regarding the GGRS data, we detected 601 significantly different genes between Lulai pigs and Yorkshires by Fst analysis, including 3 major genes associated with growth and fat deposits (IGF2 and FTO) and with hair color (KIT), and we detected 634 significantly different genes between Lulai pigs and Laiwu pigs, including 3 major genes related to their body composition (MYPN), hair color (KIT), and ear size (PPARD). By rIBD, we detected 94 deep sections that included 363 genes that Yorkshires introgressed to Lulai pigs, and we detected 149 deep sections that included 727 genes with a major gene (ESR1) that Laiwu pigs introgressed to Lulai pigs. Altogether, this study provides both insight into the molecular background of synthesized breeds of Lulai pigs and a reference for the evaluation of systematic crossbreeding in China.


Assuntos
Genoma , Carne , Suínos/genética , Animais , Genoma/genética , Mapeamento Cromossômico , Composição Corporal , Genômica
19.
Sci Rep ; 12(1): 19857, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36400857

RESUMO

Lung adenocarcinoma (LUAD) is one of the most universal types of cancer all over the world and its morbidity continues to rise year by year. Growing evidence has demonstrated that endoplasmic reticulum stress is highly activated in cancer cells and plays a key role in regulating the fate of cancer cells. However, the role and mechanism of endoplasmic reticulum stress in lung adenocarcinoma genesis and development remains unclear. In this research, we developed a prognostic model to predict the overall survival of patients with LUAD utilizing endoplasmic reticulum stress-related genes and screened out potential small molecular compounds, which could assist the clinician in making accurate decisions and better treat LUAD patients. Firstly, we downloaded 419 endoplasmic reticulum stress-related genes (ERSRGs) from Molecular Signatures Database (MSigDB). Secondly, we obtained information about the transcriptome profiling and corresponding clinical data of 59 normal samples and 535 lung adenocarcinoma samples from The Cancer Genome Atlas (TCGA) database. Next, we used the DESeq2 package to identify differentially expressed genes related to endoplasmic reticulum stress. We performed univariate Cox, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis to establish a prognostic model for LUAD patients based on ERSRGs. Then, we carried out univariate and multivariate independent prognostic analysis of endoplasmic reticulum stress-related gene (ERSRG) score and some clinical traits of lung adenocarcinoma. Additionally, we developed a clinically applicable nomogram for predicting survival for LUAD patients over one, three, and five years. Moreover, we carried out a drug sensitivity analysis to identify novel small molecule compounds for LUAD treatment. Finally, we examined the tumor microenvironment (TME) and immune cell infiltrating analysis to explore the interactions between immune and cancer cells. 142 differentially expressed ERSRGs were identified by using the DESeq2 package. A prognostic model was built based on 7 differentially expressed ERSRGs after performing univariate Cox regression, LASSO regression, and multivariate Cox regression analysis. According to the results of univariate and multivariate independent prognostic analysis, we found ERSRG score can be used as an independent prognostic maker. Using the Kaplan-Meier curves, we found low-risk patients had higher survival probability than high-risk patients in both training set and test set. A nomogram was drawn to predict 1-, 3-, and 5-year survival probability. The calibration curves explained good performance of the model for the prediction of survival. Phenformin, OSU-03012, GSK-650394 and KIN001-135 were identified as the drugs most likely to provide important information to clinicians about the treatment of LUAD patients. A prognostic prediction model was established based on 7 differentially expressed ERSRGs (PDX1, IGFBP1, DDIT4, PPP1R3G, CFTR, DERL3 and NUPR1), which could effectively predict the prognosis of LUAD patients and give a reference for clinical doctors to help LUAD patients to make better treatment tactics. Based on the 4 small molecule compounds (Phenformin, OSU-03012, GSK-650394 and KIN001-135) we discovered, targeting endoplasmic reticulum stress-related genes may also be a therapeutic approach for LUAD patients.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Prognóstico , Estresse do Retículo Endoplasmático/genética , Fenformin , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Estimativa de Kaplan-Meier , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Microambiente Tumoral
20.
Nat Commun ; 13(1): 7096, 2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36402769

RESUMO

RIG-I/DDX58 plays a key role in host innate immunity. However, its therapeutic potential for inflammation-related cancers remains to be explored. Here we identify frameshift germline mutations of RIG-I occurring in patients with colon cancer. Accordingly, Rig-ifs/fs mice bearing a frameshift mutant Rig-i exhibit increased susceptibility to colitis-related colon cancer as well as enhanced inflammatory response to chemical, virus or bacteria. In addition to interruption of Rig-i mRNA translation, the Rig-i mutation changes the secondary structure of Rig-i pre-mRNA and impairs its association with DHX9, consequently inducing a circular RNA generation from Rig-i transcript, thereby, designated as circRIG-I. CircRIG-I is frequently upregulated in colon cancers and its upregulation predicts poor outcome of colon cancer. Mechanistically, circRIG-I interacts with DDX3X, which in turn stimulates MAVS/TRAF5/TBK1 signaling cascade, eventually activating IRF3-mediated type I IFN transcription and aggravating inflammatory damage. Reciprocally, all-trans retinoic acid acts as a DHX9 agonist, ameliorates immunopathology through suppression of circRIG-I biogenesis. Collectively, our results provide insight into mutant RIG-I action and propose a potential strategy for the treatment of colon cancer.


Assuntos
Neoplasias do Colo , RNA Helicases DEAD-box , Camundongos , Animais , RNA Helicases DEAD-box/metabolismo , Transdução de Sinais , Imunidade Inata , Inflamação/genética , Neoplasias do Colo/genética
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