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1.
Z Gesundh Wiss ; : 1-7, 2020 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33134036

RESUMO

Aim: The virulence of the novel coronavirus disease (COVID-19) has facilitated its rapid transition towards becoming a pandemic. Hence, this study aims to investigate the association between population migration and the number of confirmed COVID-19 cases in China while investigating its measures for pandemic prevention and control. Subject and methods: A susceptible-exposed-infected-recovered-dormancy (SEIRD) model for the spread of COVID-19 in China was created to theoretically simulate the relationship between the populations migrating from Wuhan and the number of confirmed cases. Data from Baidu's real-time dynamic pandemic monitoring system were elicited to empirically examine the theoretical inferences. Results: Populations migrating from Wuhan to other cities increased the initial number of latently infected cases in these cities, raising the number of confirmed cases. Hence, implementing social distancing between the susceptible and infected populations could effectively lower the number of infected cases. Using data from Baidu's real-time dynamic pandemic monitoring system, the empirical results revealed that an increase of 1000 persons migrating from Wuhan raised the number of confirmed cases by 4.82 persons. Conclusion: This study confirmed the positive association between population migration and the number of confirmed COVID-19 cases. Based on the theoretical and empirical analysis, China's pandemic prevention and control measures are discussed.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33001355

RESUMO

BACKGROUND: Several clinical trials of dapagliflozin in patients with type 2 diabetes mellitus (T2DM) at elevated cardiovascular risk have observed reduced hospitalization for heart failure (HHF). Several studies have also suggested cardiovascular benefits for patients with HF regardless of whether or not they have T2DM. OBJECTIVE: This meta-analysis was conducted to evaluate the therapeutic effects of dapagliflozin in patients with HF. METHODS: The PubMed, Embase, Cochrane Library, and Web of Science databases were systematically searched from database inception to 15 February 2020. Clinical studies of dapagliflozin use in patients with HF were included. Data on HHF, all-cause mortality, cardiovascular death, major adverse cardiovascular events (MACE), systolic blood pressure, body weight, glycated hemoglobin (HbA1c), and adverse events were collected for analysis. RESULTS: Four randomized controlled trials involving 6738 patients with HF were included in this meta-analysis. Patients receiving dapagliflozin showed a significantly lower incidence of HHF [risk ratio (RR) 0.72; P < 0.00001], all-cause mortality (RR 0.83; P = 0.004), cardiovascular death (RR 0.86; P = 0.03), and MACE (RR 0.88; P = 0.03). Moreover, patients receiving dapagliflozin also showed significant improvements in systolic blood pressure and body weight. However, no statistical difference was observed in HbA1c. In addition, hypoglycemia, volume depletion, and renal impairment was not more frequent with dapagliflozin than with placebo. CONCLUSION: This meta-analysis suggests that dapagliflozin could be a therapeutic strategy for patients with HF regardless of the presence or absence of T2DM.

3.
Food Funct ; 11(11): 9776-9788, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33078819

RESUMO

Among all types of cancers, lung cancer ranks first in morbidity and mortality, and non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancer cases. Chemotherapy has shown promising results, but the accompanying side-effects cannot be neglected. Herein, we introduce novel flavones (TVF), which were characterized as 3-caffeoylquinic acid, 5-caffeoylquinic acid, quercetin-3-O-rutinoside, and kaempferol-3-O-rutinoside by UPLC-MS/MS, derived from the vine of Tetrastigma hemsleyanum (TV), a traditional Chinese herb and food. TVF exhibited outstanding anti-cancer abilities at the in vitro and in vivo level, and markedly triggered apoptosis via the Bax/Bcl-2/caspase-9/caspase-3 pathway. The intrinsic mechanism study illustrated that TVF might induce apoptosis by activating autophagy by inhibiting the Akt-mTOR pathway, and the main component of TVF, quercetin-3-O-rutinoside, enabled THR308 site binding to block the phosphorylation of Akt, which was further evidenced by molecular docking computation. Our study reveals the excellent anti-cancer ability and inner mechanism of TVF, suggesting TVF as a potential candidate for clinical drug exploitation or dietary supplementation in cancer medication and prevention, providing a promising strategy for cancer chemotherapy.

4.
Yakugaku Zasshi ; 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33116033

RESUMO

Doxorubicin (DOX) is currently one of the most widely used and effective drugs for the treatment of breast cancer, but drug resistance in breast cancer often leads to poor efficacy. MicroRNAs (miRNAs) are involved in the development and progression of various tumors and increasing number of studies have confirmed that abnormal miR-520b expression is closely associated breast cancer. We analyzed the clinical features, including miR-520b, of 30 patients with breast cancer. Further, we analyzed the interaction between miR-520b and insulin-like growth factor 1 receptor (IGF-1R) in breast cancer cell. miR-520b expression was significantly increased in chemotherapy-sensitive patients and was positively correlated with the chemotherapeutic efficacy in breast cancer. Cell proliferation assay confirmed that miR-520b promotes DOX-induced breast cancer cell apoptosis by regulating the PI3K/AKT signaling pathway. Moreover, bioinformatics method and dual luciferase reporter assay demonstrated that miR-520b negatively regulates IGF-1R, and IGF-1R overexpression and enhanced activity are closely associated with tumor development, progression, metastasis, and chemotherapy resistance. Similarly, cell proliferation assay showed that IGF-1R is negatively correlated with the efficacy of DOX chemotherapy and affects cell apoptosis mediated by the PI3K/AKT signaling pathway. On the contrary, miR-520b can downregulate the expression of IGF-1R. miR-520b increases DOX sensitivity and promotes cell apoptosis in breast cancer by inhibiting IGF-1R expression by the PI3K/AKT signaling pathway.

5.
Int J Mol Sci ; 21(19)2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32998191

RESUMO

Molecular targets play important roles in agrochemical discovery. Numerous pesticides target the key proteins in pathogens, insect, or plants. Investigating ligand-binding pockets and/or active sites in the proteins' structures is usually the first step in designing new green pesticides. Thus, molecular target structures are extremely important for the discovery and development of such pesticides. In this manuscript, we present a review of the molecular target structures, including those of antiviral, fungicidal, bactericidal, insecticidal, herbicidal, and plant growth-regulator targets, currently used in agrochemical research. The data will be helpful in pesticide design and the discovery of new green pesticides.

6.
Cell Death Dis ; 11(9): 764, 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32938905

RESUMO

Abnormal functional changes in pulmonary artery smooth muscle cells are the main causes of many lung diseases. Among, autophagy plays a crucial role. However, the specific molecular regulatory mechanism of autophagy in PASMCs remains unclear. Here, we first demonstrate that BCAT1 played a key role in the autophagy of hypoxic PASMCs and hypoxic model rats. BCAT1-induced activation and accumulation of the autophagy signaling proteins BECN1 and Atg5 by the endoplasmic reticulum (ER) stress pathway. Interestingly, we discovered that BCAT1 bound IRE1 on the ER to activate expression of its downstream pathway XBP-1-RIDD axis to activate autophagy. More importantly, we identified an RNA-binding protein, zinc finger protein 423, which promoted autophagy by binding adenylate/uridylate (AU)-rich elements in the BCAT1 mRNA 3'-untranslated region. Overall, our results identify BCAT1 as a potential therapeutic target for the clinical treatment of lung diseases and reveal a novel posttranscriptional regulatory mechanism and signaling pathway in hypoxia-induced PASMC autophagy.

7.
Ecotoxicology ; 29(9): 1441-1452, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32945976

RESUMO

Ammonia is one of the major aquatic environmental pollutants that can bring detrimental effects to the growth and survival of aquatic organisms. However, the molecular mechanisms of ammonia toxicity and ammonia excretion in marine invertebrates especially mollusks are still poorly understood. Cephalopods are exclusively ammonotelic with high protein metabolism and ammonia excretion rate, making this taxonomic group an ideal specimen to explore the ammonia detoxification mechanism. In this study, comparative transcriptomes were employed to investigate the transcriptional changes of O. minor in responses to acute ammonia exposure. A total of 63,237 unigenes with an average length of 811 bp were discovered and 25,708 unigenes were successfully annotated. The transcription of 1845 genes were significantly changed after ammonia stress, including 315 up-regulated genes and 1530 down-regulated genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis based on differentially expressed genes (DEGs) revealed that 44 GO terms and 55 KEGG pathways were over-represented. Notably, a large number of genes involved in immune defense, citric acid (TCA) cycle, oxidative phosphorylation and amino acid metabolisms were significantly down-regulated, indicating the decelerated energy production and amino acid rate in response to acute ammonia stress. These results provide new insights into the potential molecular mechanism of ammonia detoxification on transcriptomic level and will facilitate further mechanism studies on mollusks.


Assuntos
Amônia/toxicidade , Octopodiformes , Transcriptoma , Poluentes Químicos da Água/toxicidade , Animais , Perfilação da Expressão Gênica , Hemócitos , Estresse Fisiológico
8.
Hum Cell ; 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32930944

RESUMO

Psoriasis is a chronic inflammatory skin disease which mainly involves immune system. This research was to investigate the role of MST1 in the psoriasis, and the detailed mechanism whether related with Th17 and NF-κB. The skin samples and peripheral blood were obtained from psoriasis patients. Skin samples and T cells isolated from peripheral blood of patients were cultured in vitro. The results showed that the level of MST1 in the lesional skin of all three patients was higher than that of un-lesional skin, as well as the amount of CD4, CD8 and IL17 positive T cells. The amount of circulating Th17 was higher than that of control. The level of MST1, IL-17, IL-22 and TNFα was enhanced in activated T cells (p < 0.01), which indicated that MST1 increased markedly in activated T cells. The proliferation and migration of T cells were decreasing in MST1 knockdown cells, while increasing in overexpressed cells, as well as the production of IL-17, IL-22 and TNFα. MST1 enhanced the activation of TLR4-NF-κB signaling pathway, and TLR4 knockdown could reverse the effect of MST1 on NF-κB activation. This research indicated that MST1 could regulate the activation of Th17 in psoriasis partly through TLR4-NF-κB pathway. MST1 may be a target for treatment of psoriasis.

9.
Epigenetics ; : 1-11, 2020 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-32924783

RESUMO

Psoriasis is an autoimmune skin disorder influenced by genetic, epigenetic and environmental factors. We previously found CYP2S1 intragenic DNA methylation cg19430423 site strongly hypomethylated in psoriatic skin tissues. In this study, we performed methylation loci fine-mapping to search the top signals in the entire CYP2S1 gene region, and further carried out gene expression assay, cell proliferation, apoptosis, differentiation and migration in CYP2S1 overexpressed (CYP2S1 over) and silenced (siRNA) human keratinocytes. Target bisulphite conversion sequencing revealed cg19430423 and nearby two loci were the top differentially methylated loci. These three loci located within active enhancer region marked by H3K4Me1 and H3K27AC peaks. Cg19430423 might not bind with ATF1 directly. CYP2S1 over repressed NHEK cell proliferation, but have no confirmed evidence on affecting migration, apoptosis and differentiation. Real-time PCR showed that CYP2S1 inhibited expression of IL1ß, IL8, IL33, IL36, LL37, CXCL10 and CCL20 gene. In summary, CYP2S1 might inhibit keratinocyte proliferation, and modulate immune response through IL-8, IL-33, IL-36, CXCL-10, CCL20, thus contribute to the development of psoriasis.

10.
Nat Prod Res ; : 1-6, 2020 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-32746709

RESUMO

Eight compounds were obtained from the dry fruits of Piper longum L., and their potential vascular relaxant activities were explored. The present study first revealed the access of Rosin (7) and Piperchabaoside (8) in the medicinal plant Piper longum L. The vessel tension studies showed that Piperine (2), (2E,4E,14Z)-N-isobutyleicosa-2,4,14-trienamide (3), and Piperlonguminine (6) exerted significant inhibitory effects on PE-induced mesenteric artery vasoconstriction. Furthermore, Calcium Imaging studies were applied to observe the effect of Piperine on the intracellular calcium in mesenteric artery smooth muscle cells (MASMCs). Piperine (2) was observed to promote the influx of extracellular calcium in MASMCs, and via an endothelium-independent mechanism involving Ca2+ entry. Piper longum L. might have a great potential to be further studied as a vascular relaxant, even to be a drug candidate of anti-hypertension.

11.
Plast Reconstr Surg Glob Open ; 8(6): e2923, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32766070

RESUMO

Background: Before blepharoptosis surgery, simulation of eyelid features, including lid height and crease position, is often performed. However, discrepancies of the simulation and outcome can occur. The purpose of this study was to analyze the pre- and postoperative images and to evaluate factors contributing to the discrepancies. Methods: Forty-one involutional blepharoptosis patients (68.2 ± 7.1 years) underwent levator aponeurosis advancement. A semicircular bent wire was used to push the preoperative ptotic eyelid up to simulate the postoperative appearance of the eyelid. Digital images of the simulation were compared with the appearance at 3 months after the surgery. The ImageJ software was used to analyze the pre- and postoperative margin reflex distance-1 (MRD-1), pretarsal show (PTS), fissure height (FH), and ocular surface area (OSA). Factors with a potential of affecting the predictability of simulation were determined. Results: During simulation, the MRD-1 was 3.6 ± 0.4 mm, the PTS was 3.48 ± 1.2 mm, the FH was 8.5 ± 0.9 mm, and the OSA was 120.7 ± 22.3 mm2. After the surgery, the corresponding values were 3.3 ± 1.2 mm, 3.3 ± 1.5 mm, 8.6 ± 1.4 mm, and 119.1 ± 25.1 mm2, respectively. The postoperative MRD-1 was significantly smaller than that of the simulation (P = 0.005, paired t test). The MRD-1 simulation error was positively correlated with the length and width of the skin resection (all P < 0.05), and the PTS error was positively correlated with the length of the skin resection (r = 0.332, P = 0.031) and negatively correlated with the preoperative OSA (r = -0.588, P = 0.007). Conclusions: The postoperative appearance of the eyelid can be simulated fairly accurately by pushing up the upper eyelid with a curved wire. However, the MRD-1 tended to be overestimated, especially for cases requiring a large skin resection.

12.
Hypertension ; 76(4): 1124-1133, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32772647

RESUMO

Pulmonary hypertension (PH) is a rare and fatal disorder involving the vascular remodeling of pulmonary arteries mediated by the enhanced proliferation of pulmonary artery smooth muscle cells (PASMCs). Long noncoding RNAs are a subclass of regulatory molecules with diverse cellular functions, but their role in PH remains largely unexplored. We aimed to identify and determine the functions of long noncoding RNAs involved in hypoxia-induced PH and PASMC proliferation. RNA sequencing in a hypoxic mouse model identified hypoxia-regulated long noncoding RNAs, including Rps4l. Rps4l expression was significantly reduced in PH-model mice and hypoxic PASMCs. The subcellular localization of Rps4l was detected by RNA fluorescence in situ hybridization and quantification of nuclear/cytoplasmic RNA. Rps4l overexpression rescued pulmonary arterial hypertension features, as demonstrated by right ventricle hypertrophy, right ventricular systolic pressure, hemodynamics, cardiac function, and vascular remodeling. At the cellular level, Rps4l overexpression weakened cell viability and proliferation and suppressed cell cycle progression. Potential Rps4l-binding proteins were identified via RNA pull-down followed by mass spectrometry, RNA immunoprecipitation, and microscale thermophoresis. These results indicated that Rps4l is associated with and affects the stabilization of ILF3 (interleukin enhancer-binding factor 3). Rps41 further regulates the levels of HIF-1α and consequently leads to hypoxia-induced PASMC proliferation and migration. Our results showed that in hypoxic PASMCs, Rps4l expression decreases due to regulation by hypoxia. This decrease affects the proliferation, migration, and cell cycle progression of PASMCs through ILF3/HIF-1α. These results provide a theoretical basis for further investigations into the pathological mechanism of hypoxic PH and may provide insight for the development of novel treatments.

13.
Aging (Albany NY) ; 12(13): 13529-13554, 2020 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-32602849

RESUMO

Skin aging is a specific manifestation of the physiological aging process that occurs in virtually all organisms. In this study, we used data independent acquisition mass spectrometry to perform a comparative analysis of protein expression in volar forearm skin samples from of 20 healthy young and elderly Chinese individuals. Our quantitative proteomic analysis identified a total of 95 differentially expressed proteins (DEPs) in aged skin compared to young skin. Enrichment analyses of these DEPs (57 upregulated and 38 downregulated proteins) based on the GO, KEGG, and KOG databases revealed functional clusters associated with immunity and inflammation, oxidative stress, biosynthesis and metabolism, proteases, cell proliferation, cell differentiation, and apoptosis. We also found that GAPDH, which was downregulated in aged skin samples, was the top hub gene in a protein-protein interaction network analysis. Some of the DEPs identified herein had been previously correlated with aging of the skin and other organs, while others may represent novel age-related entities. Our non-invasive proteomics analysis of human epidermal proteins may guide future research on skin aging to help develop treatments for age-related skin conditions and rejuvenation.

14.
Sci Rep ; 10(1): 11768, 2020 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-32678187

RESUMO

The A(H7N9) virus strain that emerged in 2013 was associated with a high fatality rate and may become a long-term threat to public health. A(H7N9) disease incidence is disproportionate to viral exposure, suggesting that host genetic factors may significantly influence susceptibility to A(H7N9) infection. Human genome variation in conferring risk for A(H7N9) infection in Chinese populations was identified by a two-stage investigation involving 121 A(H7N9) patients and 187 healthy controls using next generation sequencing followed by functional analysis. As a result, a low frequency variant (rs189256251; P = 0.0303, OR = 3.45, 95% CI 1.05-11.35, chi-square test) and three HLA alleles (DQB1*06:01, DQA1*05:05 and C*12:02) were identified in A(H7N9) infected volunteers. In an A549 cell line carrying the rs189256251 variant CT genotype, A(H7N9) infection incidence was elevated 6.665-fold over control cells carrying the CC genotype. Serum levels of interferon alpha were significantly lower in patients with the CT genotype compared to the CC genotype (P = 0.01). The study findings of genetic predisposition to A(H7N9) in the Chinese population may be valuable in systematic investigations of A(H7N9) disease etiology.

15.
Neural Plast ; 2020: 9796419, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32617099

RESUMO

Objectives: Recently, it has been demonstrated that patients with subtle preexisting cognitive impairment were susceptible to delayed neurocognitive recovery (DNR). This present study investigated whether preoperative alterations in gray matter volume, spontaneous activity, or functional connectivity (FC) were associated with DNR. Methods: This was a nested case-control study of older adults (≥60 years) undergoing noncardiac surgery. All patients received MRI scan at least 1 day prior to surgery. Cognitive function was assessed prior to surgery and at 7-14 days postsurgery. Preoperative gray matter volume, amplitude of low-frequency fluctuation (ALFF), and FC were compared between the DNR patients and non-DNR patients. The independent risk factors associated with DNR were identified using a multivariate logistic regression model. Results: Of the 74 patients who completed assessments, 16/74 (21.6%) had DNR following surgery. There were no differences in gray matter volume between the two groups. However, the DNR patients exhibited higher preoperative ALFF in the bilateral middle cingulate cortex (MCC) and left fusiform gyrus and lower preoperative FC between the bilateral MCC and left calcarine than the non-DNR patients. The multivariate logistic regression analysis showed that higher preoperative spontaneous activity in the bilateral MCC was independently associated with a higher risk of DNR (OR = 3.11, 95% CI, 1.30-7.45; P = 0.011). A longer education duration (OR = 0.57, 95% CI, 0.41-0.81; P = 0.001) and higher preoperative FC between the bilateral MCC and left calcarine (OR = 0.40, 95% CI, 0.18-0.92; P = 0.031) were independently correlated with a lower risk of DNR. Conclusions: Preoperative higher ALFF in the bilateral MCC and lower FC between the bilateral MCC and left calcarine were independently associated with the occurrence of DNR. The present fMRI study identified possible preoperative neuroimaging risk factors for DNR. This trial is registered with Chinese Clinical Trial Registry ChiCTR-DCD-15006096.

16.
Gene ; 759: 144964, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-32717308

RESUMO

BACKGROUND: Mucosal melanoma is a tumor caused by the malignant transformation of pigment-producing cells and can arise from any mucosal tissue where melanocytes are present. Due to its rarity, the mucosal melanoma subtype is poorly described, and its genetic characteristics are infrequently studied. The discovery or confirmation of new mucosal melanoma susceptibility genes will provide important insights for the study of its pathogenesis. MATERIALS AND METHODS: We performed deep targeted sequencing of 100 previously reported melanoma-related genes in 39 mucosal melanoma samples and a gene-level loss-of-function (LOF) variant enrichment analysis for mucosal melanoma from different incidence sites. RESULTS: We detected 7,589 variants in these samples, and 484 were LOF variants (gain or loss of a stop codon, missense, and splice site). Four different gene-level enrichment analyses revealed that FSIP1 (fibrous sheath interacting protein 1) is a susceptibility gene for oral mucosal melanoma (OR = 0.33, PChi = 4.05 × 10-2, Pburden = 3.06 × 10-2, Pskat = 3.01 × 10-2, Pskato = 3.01 × 10-2), whereas the different methods did not detect a significant susceptibility gene for the other subtypes. CONCLUSIONS: In our study, a susceptibility gene for oral mucosal melanoma was confirmed in a Chinese Han population, and these findings contribute to a better genetic understanding of mucosal melanoma of different subtypes.


Assuntos
Proteínas de Transporte/genética , Mutação com Perda de Função , Melanoma/genética , Proteínas de Plasma Seminal/genética , Idoso , Feminino , Humanos , Masculino , Melanócitos/metabolismo , Melanócitos/patologia , Melanoma/classificação , Melanoma/patologia , Pessoa de Meia-Idade , Membrana Mucosa/metabolismo , Membrana Mucosa/patologia
17.
Genomics ; 2020 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-32603760

RESUMO

This study presented 96 cox1 and 76 cox3 genes of Amphioctopus neglectus populations. Three distinct lineages were formed from phylogenetic trees and networks constructed using haplotypes. Mitogenomes of A. neglectus-a and A. neglectus-b as the representatives of two lineages separated from population genetics were sequenced to compare with A. neglectus at the genome-level. Amphioctopus neglectus-a showed significant differences with A. neglectus, mainly reflected in gene length, intergenic regions and the secondary structure of tandem repeat motifs. Notably, two sequence deletions in mitogenomes of the two representative species were detected in different positions of major non-coding regions, which were the most distinct differences with A. neglectus. Pairwise genetic distances and the phylogenetic analysis supported the relationship of (A. neglectus-a + (A. neglectus + A. neglectus-b)). This study suggested that A. neglectus-a should be considered as a potential cryptic species of this complex, while A. neglectus-b needed further verification to be defined.

18.
J Dermatol Sci ; 99(1): 23-29, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32522384

RESUMO

BACKGROUND: HLA-Cw*0602 has long been established as one of the most important genetic biomarkers in psoriasis. However, the epigenetic and gene expression differences between HLA-Cw*0602 carriers and non-carriers has not yet been investigated. OBJECTIVE: We aim to explore the whole-genome methylation and gene expression differences between HLA-Cw*0602 carriers and non-carriers. METHODS: HLA imputation was performed to get landscape of variants in this region. Genome-wide DNA methylation was compared between positive and negative HLA-Cw*0602 groups. Eleven methylation loci were selected for further validation in additional 43 cases. For differentially methylated genes, GO and KEGG were used to annotate gene functions. RESULTS: We imputed 29,948 variants based on the constructed HLA reference panels, and obtained 42 HLA-Cw*0602 carriers and 72 non-carriers. Significant methylation differences were detected at 4321 sites (811 hypo- and 3510 hypermethylated). The cg02607779 (KLF7, P = 0.001), cg06936779 (PIP5K1A, P = 0.002), cg03860400 (BTBD10, P = 0.017) and cg26112390 (GOLGA2P5, P = 0.019) were identified and validated to be the significant CpGs contributed to different HLA-C*0602 groups. Among the hypo- and hypermethylated sites, the top CpGs were in gene body and CpG island. CONCLUSION: We performed the first whole-genome study on methylation differences between psoriatic individuals with or without HLA-Cw*0602, and found the key methylation sites which may contribute to the carrying status of HLA-Cw*0602. Methylation loci located in gene body and CpG island are more likely to affect the methylation levels in HLA-Cw*0602 carriers. This integrated analysis shed light on novel insights into the pathogenic mechanisms of genomic methylation in different HLA genotypes of psoriasis.

19.
PLoS One ; 15(6): e0234657, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32530927

RESUMO

Public pension insurance has become a major form of social protection around the world. However, little is known about the association between public pension expansion and individuals' fertility in developing economies. In this paper, we examine the effects of the New Rural Pension Scheme (NRPS) on the fertility of married women in rural China. Using data from the China Family Panel Studies (CFPS), the difference-in-differences approach is employed to estimate the impact of NRPS expansion on fertility outcomes. The robustness of results is checked through additional estimations, including difference-in-differences with propensity score matching, fixed-effects model, and instrumental variable approach. Results show that the NRPS expansion has a significantly negative effect on the number of children, and it reduces the likelihood of having a second child. The fertility-reducing effect of the NRPS is larger for the younger, well-educated women and those in high-income families. Considerations of the fertility effects and their population differences are needed in the impact evaluations of relevant public pension reform.


Assuntos
Fertilidade/fisiologia , Pensões , População Rural , Adulto , China , Características da Família , Feminino , Humanos , Renda , Análise de Regressão
20.
Med Sci Monit ; 26: e923749, 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32425177

RESUMO

BACKGROUND The aim of this study was to investigate STMN1 and MKI67 expression in uterine leiomyosarcoma and their potential roles as biomarkers for diagnosis. MATERIAL AND METHODS The expression of STMN1 and MKI67 mRNA in uterine leiomyosarcoma were investigated in TCGA database. The overall survival (OS) and disease-free survival (DFS) were compared between high and low expression groups. Seventy-two patients who received hysterectomy were included and divided into 4 groups: uterine normal smooth muscle tissue (UNSM=30), uterine leiomyoma (UL=30), uterine cellular leiomyoma (UCL=24), and uterine leiomyosarcoma (ULS=18). The STMN1 and MKI67 protein expression of the 4 groups were examined by immunohistochemistry (IHC) assay. RESULTS The expression level of STMN1 mRNA in cancer tissue was significantly higher than those of normal uterine smooth muscle tissue. The high and low expression of STMN1 and mki67 gene mRNA was not related to the patients' OS and DFS (P>0.05). The positive rate of STMN1 protein in uterine leiomyosarcoma was 100.00%, which was significantly higher than that of the other 3 groups (χ²=11.72, P=0.008). And the positive rate of KIM67 protein in uterine leiomyosarcoma was 77.78%, which was also significantly higher than that of the other 3 groups (χ²=48.89, P=0.000). The diagnostic sensitivity and specificity were 77.78%, 90.74% for STMN1 combined MKI67 with the positive predictive value and negative predictive value of 73.68% and 92.45%, respectively. CONCLUSIONS STMN1 and MKI67 were upregulated in uterine leiomyosarcoma and act as potential biomarkers for uterine leiomyosarcoma diagnosis.

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