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1.
Nutrients ; 13(4)2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33807197

RESUMO

Dietary habits have considerable impact on brain development and mental health. Despite long-standing interest in the association of dietary habits with mental health, few population-based studies of dietary habits have assessed depression and fluid intelligence. Our aim is to investigate the association of dietary habits with depression and fluid intelligence. In total, 814 independent loci were utilized to calculate the individual polygenic risk score (PRS) for 143 dietary habit-related traits. The individual genotype data were obtained from the UK Biobank cohort. Regression analyses were then conducted to evaluate the association of dietary habits with depression and fluid intelligence, respectively. PLINK 2.0 was utilized to detect the single nucleotide polymorphism (SNP) × dietary habit interaction effect on the risks of depression and fluid intelligence. We detected 22 common dietary habit-related traits shared by depression and fluid intelligence, such as red wine glasses per month, and overall alcohol intake. For interaction analysis, we detected that OLFM1 interacted with champagne/white wine in depression, while SYNPO2 interacted with coffee type in fluid intelligence. Our study results provide novel useful information for understanding how eating habits affect the fluid intelligence and depression.

2.
Rev Cardiovasc Med ; 22(1): 167-174, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33792258

RESUMO

Our objective was to systematically evaluate the efficacy and safety of proton pump inhibitors combined with clopidogrel in patients undergoing percutaneous coronary intervention and to provide an evidence basis for clinical treatment decision-making. The database EMBASE, PubMed/Medline, Web of Science, the Cochrane Library and CNKI records from establishment of each database until August 2020 were included. Articles were evaluated for quality. Meta-analysis of selected articles was conducted by RevMan5.3 software. Three RCTs and 4 cohort studies were included, with a total of 9932 patients. Four studies reported gastrointestinal (GI) bleeding events, 3 of which were RCT studies. Overall, there was a significantly lower risk of GI bleeding events in the PPI group compared to the no PPI group [OR = 3.06, 95% CI: 1.89 to 4.95] (P < 0.00001). In 3 RCT studies, there was also a significantly lower risk of GI bleeding events in the PPI group compared to the no PPI group [OR = 3.06, 95% CI: 1.80 to 5.21] (P < 0.0001). Seven studies including 3 RCTs and 4 cohort studies reported MACE. Overall, there was no significant difference in MACE events between PPI group and no PPI group [OR = 1.05, 95% CI: 0.91 to 1.21] (P = 0.50). Both in RCT and cohort studies subgroups, there also was no significant difference in MACE events between the PPI group and the no PPI group [OR = 1.16, 95% CI: 0.87 to 1.53] (P = 0.32), [OR = 1.02, 95% CI: 0.87 to 1.19] (P = 0.84), respectively. For PCI patients taking clopidogrel and PPI therapy, PPI reduced the risk of GI bleeding while having no impact on MACE.

3.
J Ethnopharmacol ; 274: 114070, 2021 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-33785356

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Egg yolk oils (EYO) is a traditional Chinese medicine obtained from Gallus gallus domesticus Brisson, which has been used to treat inflammatory related diseases such as cheilitis, ulceration and acute anal fissure. However, the detailed anti-inflammatory mechanism of EYO is still unknown. AIM OF THE STUDY: The anti-inflammatory activity and mechanism of EYO were investigated in tumor necrosis factor (TNF)-α induced Caco-2 cells. MATERIALS AND METHODS: EYO was obtained by direct-heat extraction (HE), ethanol extraction (EE) and petroleum ether extraction (PE), respectively. Fatty acid compositions of three EYO were measured by gas chromatography (GC). Cell viability, enzyme-linked immunosorbent assay (ELISA), transcriptome, RT-PCR and Western blotting were also performed. RESULTS: Fatty acid compositions of three EYO were different with varied extraction methods. EYO significantly reduced interleukin (IL)-8 secretion. EYO exerted anti-inflammatory effect via coordinating regulation of Nrf2/NF-κB pathways based on the results of transcriptome, Q-PCR and Western blotting. In detail, PE and HE inhibited the NF-κB pathway, whereas EE exerted anti-inflammatory activity via the Nrf2/NF-κB pathways. CONCLUSIONS: The aforementioned results showed the anti-inflammatory mechanism of EYO. These findings might be beneficial to clinical applications of EYO.

4.
Genome Med ; 13(1): 41, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33691767

RESUMO

Genome-wide association studies (GWAS) have uncovered thousands of genetic variants that influence risk for human diseases and traits. Yet understanding the mechanisms by which these genetic variants, mainly noncoding, have an impact on associated diseases and traits remains a significant hurdle. In this review, we discuss emerging experimental approaches that are being applied for functional studies of causal variants and translational advances from GWAS findings to disease prevention and treatment. We highlight the use of genome editing technologies in GWAS functional studies to modify genomic sequences, with proof-of-principle examples. We discuss the challenges in interrogating causal variants, points for consideration in experimental design and interpretation of GWAS locus mechanisms, and the potential for novel therapeutic opportunities. With the accumulation of knowledge of functional genetics, therapeutic genome editing based on GWAS discoveries will become increasingly feasible.

5.
Aging Cell ; 20(3): e13323, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33657282

RESUMO

There is growing interest in studying the genetic contributions to longevity, but limited relevant genes have been identified. In this study, we performed a genetic association study of longevity in a total of 15,651 Chinese individuals. Novel longevity loci, BMPER (rs17169634; p = 7.91 × 10-15 ) and TMEM43/XPC (rs1043943; p = 3.59 × 10-8 ), were identified in a case-control analysis of 11,045 individuals. BRAF (rs1267601; p = 8.33 × 10-15 ) and BMPER (rs17169634; p = 1.45 × 10-10 ) were significantly associated with life expectancy in 12,664 individuals who had survival status records. Additional sex-stratified analyses identified sex-specific longevity genes. Notably, sex-differential associations were identified in two linkage disequilibrium blocks in the TOMM40/APOE region, indicating potential differences during meiosis between males and females. Moreover, polygenic risk scores and Mendelian randomization analyses revealed that longevity was genetically causally correlated with reduced risks of multiple diseases, such as type 2 diabetes, cardiovascular diseases, and arthritis. Finally, we incorporated genetic markers, disease status, and lifestyles to classify longevity or not-longevity groups and predict life span. Our predictive models showed good performance (AUC = 0.86 for longevity classification and explained 19.8% variance of life span) and presented a greater predictive efficiency in females than in males. Taken together, our findings not only shed light on the genetic contributions to longevity but also elucidate correlations between diseases and longevity.

6.
Environ Health ; 20(1): 25, 2021 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-33715628

RESUMO

BACKGROUND: The SIRT1 gene was associated with the lifespan in several organisms through inflammatory and oxidative stress pathways. Long-term air particulate matter (PM) is detrimental to health through the same pathways. METHODS: We used the Chinese Longitudinal Healthy Longevity Survey (CLHLS) to investigate whether there is a gene-environment (G × E) interaction of SIRT1 and air pollution on mortality in an older cohort in China. Among 7083 participants with a mean age of 81.1 years, we genotyped nine SIRT1 alleles for each participant and assessed PM2.5 concentration using 3-year average concentrations around each participant's residence. We used Cox-proportional hazards models to estimate the independent and joint effects of SIRT1 polymorphisms and PM2.5 exposure on all-cause mortality, adjusting for a set of confounders. RESULTS: There were 2843 deaths over 42,852 person-years. The mortality hazard ratio (HR) and 95% confidence interval (CI) for each 10 µg/m3 increase in PM2·5 was 1.08 (1.05-1.11); for SIRT1_391 was 0.77 (0.61, 0.98) in the recessive model after adjustment. In stratified analyses, participants carrying two SIRT1_391 minor alleles had a significantly higher HR for each 10 µg/m3 increase in PM2.5 than those carrying zero minor alleles (1.323 (95% CI: 1.088, 1.610) vs. 1.062 (1.028, 1.096) p for interaction = 0.03). Moreover, the interaction of SIRT1 and air pollution on mortality is significant among women but not among men. We did not see significant relationships for SIRT1_366, SIRT1_773, and SIRT1_720. CONCLUSION: We found a gene-environment interaction of SIRT1 and air pollution on mortality, future experimental studies are warranted to depict the mechanism observed in this study.

7.
Jpn J Ophthalmol ; 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33656708

RESUMO

PURPOSE: To compare the differences between cycloplegic and noncycloplegic refraction as well as associated factors in grade one students of primary schools, and explore the effectiveness of noncycloplegic refraction for refractive error screening. STUDY DESIGN: Cross-sectional study. METHODS: A school-based study of 1856 students was conducted in Lhasa, Tibetan Plateau, China. Cycloplegia was achieved with two drops of 1% cyclopentolate and 1 drop of Mydrin P at a 5-min interval. Autorefraction was performed under both cycloplegic and noncycloplegic conditions. Bland-Altman analysis, receiver operating characteristic curve analysis, univariate and multiple linear regression models were used for analysis. RESULTS: Of the 1856 children enrolled, 1830 (98.60%) completed all procedures. The average age was 6.83 ± 0.46 years. 965 (52.73%) children were boys and 1737 (94.92%) were Tibetan. Overall, there was a significant difference between cycloplegic and noncycloplegic SE of 0.90 ± 0.76D (P < 0.001). However, the intra-class coefficient correlation (ICC) for cylinder between these two methods was high (ICC = 0.941, 95% CI, 0.935-0.946). Larger differences between cycloplegic and noncycloplegic SE were associated with hyperopic RE and higher cylindrical value (P < 0.001). The prevalence of myopia, emmetropia and hyperopia with and without cycloplegia was (3.93% vs 14.59%), (9.95% vs 45.8%) and (86.21% vs 39.56%), respectively. Myopia, emmetropia and hyperopia based on noncycloplegic refraction was defined as SE ≤ - 0.625D, - 0.625 < SE ≤ 0D, and SE > 0D, respectively. CONCLUSIONS: Lack of cycloplegia leads to underestimation of hyperopia, with overestimation of myopia and emmetropia. Larger hyperopic refraction exhibited greater difference between cycloplegic and noncycloplegic refraction.

8.
Int Psychogeriatr ; : 1-10, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33658084

RESUMO

STUDY OBJECTIVES: Based on a cohort from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), we aimed to evaluate the relationship between sleep duration and the incidence of cognitive impairment among older Chinese adults. METHODS: We conducted a prospective analysis based on 3692 participants from the CLHLS at baseline (in 2011), and as a 3-year follow-up (till 2014), 531 participants (14.4%) had cognitive impairment, which was defined as a Mini-Mental State Examination score <24. Sleep duration was classified into three groups: short (≤5 hours/day), normal (>5 but <10 hours), and long (≥10 hours/day). A logistic regression model was used to examine the association between baseline sleep duration and cognitive impairment after adjusting for sociodemographic data, living habits, and health conditions. RESULTS: Five hundred sixty-two participants (15.2%) were in the short-duration group, and 608 participants (16.5%) were in the long-duration group. After adjusting for multiple potential confounders, compared with normal sleep duration, long sleep duration was associated with the incidence of cognitive impairment (OR = 1.309, 95% CI: 1.019-1.683), especially among men (OR = 1.527, 95% CI: 1.041-2.240) and those having a primary and above education level (OR = 1.559, 95% CI: 1.029-2.361). No significant association was observed between short sleep duration and cognitive impairment (OR = 0.860, 95% CI: 0.646-1.145). CONCLUSIONS: Excessive sleep may increase the risk of cognitive impairment in older individuals. It may be a suggestive sign of early neurodegeneration and may be a useful clinical tool to identify those at a higher risk of progressing to cognitive impairment.

9.
Ecotoxicol Environ Saf ; 215: 112174, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33773155

RESUMO

BACKGROUND: Phthalates, which are used as excipients of drugs, have been related to adverse reproductive outcomes. However, the relationships between medication use and phthalate exposure among women undergoing in vitro fertilization (IVF) have not been studied. OBJECTIVE: To investigate the associations between the medication intake and phthalate metabolites in urine and follicular fluid (FF). METHOD: Eight phthalate metabolites were measured in urine and FF samples from 274 women undergoing IVF using liquid chromatography-tandem mass spectrometry. Information on recent medication intake was obtained via interview by trained staff. We constructed generalized linear regression models to examine the associations of medication intake with phthalate metabolite concentrations and dose-response relationships between the number of medicines used and metabolite concentrations in two matrices. RESULTS: Four of 10 drugs were used by more than 10% of the participants, including vitamins (23.0%), traditional Chinese medicine (TCM, 22.3%), antioxidants (12.4%) and amoxicillin (10.2%). Participants who had used TCM had 26.0% (95% CI: 0.0, 58.8%), 32.6% (95% CI: 4.2, 68.8%) and 32.3% (95% CI: 2.6, 70.6%) higher urinary mono-n-butyl phthalate (MBP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) concentrations, respectively, than those who had not. Antioxidant intake was associated with a 30.6% (95% CI: -48.5, -6.6%) decrease in the urinary MBP concentration. Compared with non-users, women who reported the use of medicines had 53.2% (95% CI: 2.7, 128.5%) higher concentrations of MMP and a 37.7% (95% CI: -60.7, -1.5%) lower level of MBP in FF, respectively. CONCLUSION: Our data suggest that the intake of some medications may increase phthalate exposure among women undergoing IVF.

10.
Inflamm Bowel Dis ; 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33749741

RESUMO

BACKGROUND: An excessive postoperative inflammatory response is common after surgery for inflammatory bowel disease (IBD) and may be associated with an increased incidence of postoperative ileus. This study assessed the role of perioperative dexamethasone in postoperative ileus after IBD surgery. METHOD: Patients undergoing elective IBD surgery were randomized to either an intravenous 8-mg dose of dexamethasone (n = 151) or placebo (n = 151) upon induction of anesthesia. The primary outcome was the incidence of prolonged postoperative ileus. Secondary outcomes included incidence of reported nausea or vomiting, time to first passage of flatus and stool, GI-2 recovery, postoperative pain, length of stay, and surgical complications. RESULTS: An intention-to-treat analysis revealed that patients who received dexamethasone exhibited a lower incidence of prolonged postoperative ileus (22.5% vs 38.4%; P = 0.003), shorter time to first passage of stool (28 vs 48 h, P < 0.001), GI-2 recovery (72 vs 120 h; P < 0.001), reduced postoperative length of stay (9.0 vs 10.0 d; P = 0.002), and less postoperative pain (P < 0.05) compared with controls. Moreover, there were no significant differences in postoperative nausea or vomiting (P = 0.531), major postoperative complications (P = 0.165), or surgical site infections (P = 0.337) between the groups. A benefit was only observed in patients with Crohn's disease, restored bowel continuity, colon/rectal resections, and those who underwent open operations. CONCLUSION: A single, intravenous 8-mg dose of dexamethasone upon induction of anesthesia reduced the incidence of prolonged postoperative ileus, the intensity of postoperative pain, and shortened the postoperative length of stay for IBD patients undergoing elective surgery. ClinicalTrials.gov: NCT03456752.

11.
Oral Dis ; 2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33675129

RESUMO

OBJECTIVE: To explore the effect of miR-873-5p on proliferation, apoptosis, migration, and invasion of tongue squamous cell carcinoma (TSCC) by targeting SEC11A. METHODS: Tongue squamous cell carcinoma tissues were collected and performed by qRT-PCR and Western blotting to determine the expression of miR-873-5p and SPC18. SCC9 and CAL-27 cells were transfected and divided into Mock, mimic NC, miR-873-5p mimic, SEC11A, and miR-873-5p mimic + SEC11A groups. Then, a series of experiments including cell count kit 8 (CCK-8), wound healing, Transwell, and flow cytometry were conducted. Besides, Western blotting was used to detect the expression of SPC18 and EGFR pathway-related proteins. RESULTS: MiR-873-5p was downregulated while SPC18 was upregulated in TSCC, and miR-873-5p was negatively correlated with SPC18. Dual luciferase reporter gene assay confirmed SEC11A to be a target of miR-873-5p. Cell proliferation, migration, and invasion of SCC9 and CAL-27 cells in miR-873-5p mimic group were decreased with increased cell apoptosis, presenting with downregulations of SPC18 and EGFR pathway-related proteins, while cells in SEC11A group manifested totally different changes. Moreover, the inhibitory effect of miR-873-5p mimic on TSCC cell growth was abolished by SEC11A overexpression. CONCLUSION: Overexpression of miR-873-5p may suppress cell proliferation, migration, and invasion, but facilitate apoptosis in TSCC via targeting SEC11A.

12.
Environ Int ; 151: 106454, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33676285

RESUMO

BACKGROUND: Although epidemiological studies on the effect of chronic fine particulate matter (PM2.5) exposure on lipid disorders have been conducted, it is unclear if improved air quality is associated with beneficial changes in the blood lipid profile. In China, clean air actions introduced in 2013 have rapidly reduced the concentration of ambient PM2.5. METHODS: We conducted a change-by-change study, based on two waves (2011 and 2015) of a national survey of the same 5111 Chinese adults before and after implementation of the clean air actions. Long-term PM2.5 exposure was assessed using a state-of-the-art estimator at the city level. Based on the within-individual differences between the two waves, we associated PM2.5 changes with the variations of four lipid biomarkers-triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)-using a mixed-effects regression model. The robustness and homogeneity of the association were tested via sensitivity analyses. RESULTS: For each 10 µg/m3 reduction in PM2.5, LDL-C, and TC decreased by 2.71 (95% confidence interval [CI] 0.10-5.32) and 4.16 (95% CI 1.24-7.08)mg/dL, respectively. There was no significant association with HDL-C or TG. The results were robust among models adjusted for different covariates. PM2.5 was a significant risk factor for dyslipidemia with an adjusted relative risk of 1.21 (95% CI 1.09-1.34). The association between PM2.5 and LDL-C was stronger in the elderly or adults who did not take medications. CONCLUSIONS: The results suggest that PM2.5 exert a cardiotoxic effect by increasing the risk of lipid disorders. Improvement of air quality could prevent dyslipidemia by reducing LDL-C and TC levels. Clean air policies should be implemented as public health measures in countries with aging societies, especially developing ones with a high air pollution burden.

13.
Hu Li Za Zhi ; 68(1): 43-53, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33521918

RESUMO

BACKGROUND: Because of the COVID-19 epidemic, people are mostly isolated at home and must seek medical advice over the internet. In addition, government authorities are currently investing greater efforts in developing internet hospitals. PURPOSE: The purpose of this essay was to assess how outpatients feel about online outpatient clinics and to analyze the factors that affect their satisfaction and willingness to return to these clinics. The results provide advice regarding how to more effectively encourage patients to use online outpatient clinics. METHODS: A self-developed questionnaire was used to survey 191 patients who had visited the online outpatient clinic of a tertiary hospital in Sichuan Province from January to July 2019. A descriptive analysis was conducted on the collected data, and factors influencing satisfaction were identified. RESULTS: The majority of the surveyed patients were young or middle-aged (92.7%) and 42.9% held a college degree or higher. Nearly three-quarters (72.2%) expressed feeling satisfied or better with the online outpatient clinic, with 31.4% of these expressing feeling very satisfied. Nearly all (91.1%) expressed the opinion that the online outpatient clinic had improved their awareness of health self-management . Furthermore, 176 (92.1%) were willing to use the online outpatient clinic again. The results of univariate analysis showed that the main factors negatively influencing re-use of the online outpatient clinic were: failure to solve the problem in a timely manner (χ2 = 8.603, p = .045), the complicated process of online registration (χ2 = 8.322, p = .016), the failure of the online physical examination (χ2 = 8.958, p = .015), and unreliable quality (χ2 = 15.373, p = .004). CONCLUSIONS: The participants surveyed in this study reported a lower satisfaction for their online outpatient clinic experience than reported in similar surveys of traditional outpatient services. However, many reported that their health-related self-management awareness had improved after use, indicating that they feel better about the online outpatient clinic. The factors that affected willingness to reuse to the online outpatient clinic related mainly to imperfections related to the clinic and its inability to adequately meet patient needs. Online outpatient clinics should simplify the process of registration, improve functions, and increase service functions such as online examination appointments and follow-up visits to improve patient satisfaction.


Assuntos
Idoso , Instituições de Assistência Ambulatorial , Humanos , Pessoa de Meia-Idade , Satisfação do Paciente , Retratamento , Inquéritos e Questionários
14.
J Pharm Biomed Anal ; 197: 113937, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33609949

RESUMO

Prognosis for esophageal squamous cell carcinoma (ESCC) is poor, so it is essential to develop a more complete understanding of the disease. The purpose of this study was to explore metabolic biomarkers and potential therapeutic targets for ESCC. An ultra-high-performance liquid chromatography coupled with high resolution mass (UPLC/MS)-based metabolomic analysis was performed in 141 ESCC cancerous tissue samples and 70 non-cancerous counterparts. The results showed that 41 differential metabolites were annotated in the training set, and 37 were validated in the test set. Single-metabolite-based receiver operating characteristic (ROC) curves as well as metabolite-based machine learning models, including Partial Least Squares (PLS), Support Vector Machine (SVM), and Random Forest (RF), were investigated for cancerous and non-cancerous tissue classification. Six most prevalent diagnostic metabolites-adenylsuccinic acid, UDP-GalNAc, maleylacetoacetic acid, hydroxyphenylacetylglycine, galactose, and kynurenine-showed testing predictive accuracies of 0.89, 0.95, 0.97, 0.89, 0.84, and 0.84, respectively. Moreover, the metabolite-based models (PLS, SVM, and RF) had testing predictive accuracies of 0.95, 0.95, and 1.00, respectively. Kaplan-Meier survival analysis and Cox proportional hazards regression analysis demonstrated that 2-hydroxymyristoylcarnitine (HR: 0.55, 95 % CI: 0.32 to 0.92), 3-hydroxyhexadecanoylcarnitine (HR: 0.49, 95 % CI: 0.29 to 0.83), and 2,3-Dinor-TXB1 (HR: 0.56, 95 % CI: 0.33 to 0.95) to be significantly associated with OS. Based on the observation of accumulation in amino acids, immunohistochemistry (IHC) staining revealed that the amino acid transporters SLC7A5/LAT1, SLC1A5/ASCT2, and SLC16A10/MCT10 were up-regulated in ESCC cancerous tissues when compared to non-cancerous equivalents. Consistently, the same panel of amino acids were downregulated in cells with SLC1A5 knockdown. Herein, it is concluded that this study not only identified several metabolites with diagnostic and/or prognostic value, but also provided accurate metabolite-based prediction models for ESCC tissue classification. Furthermore, the three up-regulated amino acid transporters were identified as potential therapeutic targets for ESCC, especially SLC1A5.

15.
Cartilage ; : 1947603521990859, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33522290

RESUMO

OBJECTIVE: Our aim is to explore the candidate pathogenesis genes and pathways of developmental dysplasia of hip (DDH). DESIGN: Proliferating primary chondrocytes from hip cartilage were used for total RNA extraction including 5 DDH patients and 5 neck of femur fracture (NOF) subjects. Genome-wide mRNA and microRNA (miRNA) were then sequenced on the Illumina platform (HiSeq2500). Limma package was used for difference analysis of mRNA expression profiles. edgeR was used for difference analysis of miRNA expression profiles. miRanda was used to predict miRNA-target genes. The overlapped DDH associated genes identified by mRNA and miRNA integrative analysis were further compared with the differently expressed genes in hip osteoarthritis (OA) cartilage. RESULTS: Differential expression analysis identified 1,833 differently expressed mRNA and 186 differently expressed miRNA for DDH. Integrative analysis of mRNA and miRNA expression profiles identified 175 overlapped candidate genes (differentially expressed genes, DEGs) for DDH, such as VWA1, TMEM119, and SCUBE3. Further gene ontology enrichment analysis detected 111 candidate terms for DDH, such as skeletal system morphogenesis (P = 4.92 × 10-5) and skeletal system development (P = 8.85 × 10-5). Pathway enrichment analysis identified 14 candidate pathways for DDH, such as Hedgehog signaling pathway (P = 4.29 × 10-5) and Wnt signaling pathway (P = 4.42 × 10-2). Among the identified DDH associated candidate genes, we also found some genes were detected in hip OA including EFNA1 and VWA1. CONCLUSIONS: We identified multiple novel candidate genes and pathways for DDH, providing novel clues for understanding the molecular mechanism of DDH.

16.
Curr Microbiol ; 78(4): 1142-1149, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33608775

RESUMO

One marine bacteria Bacillus pumilus was isolated using allura red as ε-poly-L-lysine (ε-PL) secretion indicator. But actually the product was identified as poly-γ-L-diaminobutanoic acid (γ-PAB) by ionization-time-of-flight mass spectrometry, not coproduced with ε-PL. The polymerization degree of γ-PAB was 4-22, namely short-chain γ-PAB, compared with that in S. celluloflavus, and it exhibited stronger inhibitory activities against yeasts than long-chain γ-PAB but weaker activities against bacteria. The fermentative behavior of B. pumilus was investigated, and the γ-PAB production was 38.6 mg/L in shake flask and was enhanced to 284.2 mg/L in 5-L bioreactor by a pH control strategy. Interestingly, the suitable pH for B. pumilus to produce γ-PAB was 4.8, different from 4.0 for current Streptomyces strains, which suggests a potential new metabolic mechanism in B. pumilus as a novel γ-PAB producer. No studies on short-chain γ-PAB production in bacteria have been reported previously and we considered that this is a new discovery in the field of homopolymer research.

17.
Biochimie ; 184: 8-17, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33556471

RESUMO

Acquired drug-resistance, often involving downregulation or mutations in the target protein, is a major caveat in precision medicine. Understanding mechanisms of resistance to therapeutic drugs may unravel strategies to overcome or prevent them. We previously identified phorbol ester (PE) compounds such as TPA that induce Protein Kinase δ (PKCδ), thereby suppressing leukemogenesis. Here we identified erythroleukemia cell lines that resist PEs and showed that reduced PKCδ protein expression underlies drug resistance. Reduced level of PKCδ in resistant cell lines was due to its phosphorylation followed by protein degradation. Indeed, proteasome inhibition prevented PE-induced loss of PKCδ. Accordingly, a combination of TPA and the proteasome inhibitor ALLN significantly suppressed leukemia in a mouse model of leukemia. PKCδ downregulation by TPA was independent of the downstream MAPK/ERK/P38/JNK pathway. Instead, expression of ubiquitin-associated and SH3 domain-containing protein b (Ubash3b) was induced by TPA, which leads to PKCδ protein dephosphorylation and degradation. This specific degradation was blocked by RNAi-mediated depletion of Ubash3b. In drug-sensitive leukemic cells, TPA did not induce Ubash3b, and consequently, PKCδ levels remained high. A PE-resistant cell line derived from PE-treated sensitive cells exhibited very low PKCδ expression. In these drug resistance cells, a Ubash3b independent mechanism led to PKCδ degradation. Thus, PE compounds in combination with proteasome or specific inhibitors for Ubash3b, or other factors can overcome resistance to TPA, leading to durable suppression of leukemic growth. These results identify Ubash3b as a potential target for drug development.

18.
J Insect Sci ; 21(1)2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33620485

RESUMO

The lacewing Chrysoperla sinica (Tjeder) is a common natural enemy of many insect pests in China and is frequently employed for biological control programs. Adults make migratory flights after emergence, which reduces their effectiveness as biological control agents. Previously, we proved that 2-d-old unmated females exhibited significantly stronger flight ability than 3-d-old ones. Meanwhile, 3-d-old unmated adults flew significantly longer distances than mated ones. In this study, Illumina RNA sequencing was performed to characterize differentially expressed genes (DEGs) between virgin and mated adults of different ages in a single female strain of C. sinica. In total, 713,563,726 clean reads were obtained and de novo assembled into 109,165 unigenes with an average length of 847 bp (N50 of 1,754 bp), among which 4,382 (4.01%) unigenes matched known proteins. Based on these annotations, many putative transcripts were related to C. sinica's flight capacity and muscle structure, energy supply, growth, development, environmental adaptability, and metabolism of nutritional components and bioactive components. In addition, the differential expression of transcripts between different ages and mating status were analyzed, and DEGs participating in flight capacity and muscles were detected, including glutathione hydrolase, NAD-specific glutamate dehydrogenase, aminopeptidase, and acidic amino acid decarboxylase. The DEGs with functions associated with flight capacity and muscles exhibited higher transcript levels for younger (2 d--old) virgins. This comprehensive C. sinica transcriptomic data provide a foundation for a better understanding of the molecular mechanisms underlying the flight capacity to meet the physiological demands of flight muscles in C. sinica.


Assuntos
Voo Animal , Genes de Insetos/genética , Insetos/fisiologia , Transcriptoma/fisiologia , Animais , Insetos/genética
19.
J Immunol Res ; 2021: 6617841, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33628845

RESUMO

As the most prevalent internal eukaryotic modification, N6-methyladenosine (m6A) is installed by methyltransferases, removed by demethylases, and recognized by readers. However, there are few studies on the role of m6A in clear cell renal cell carcinoma (ccRCC). In this study, we researched the RNA-seq transcriptome data of ccRCC in the TCGA dataset and used bioinformatics analyses to detect the relationship between m6A RNA methylation regulators and ccRCC. First, we compared the expression of 18 m6A RNA methylation regulators in ccRCC patients and normal tissues. Then, data from ccRCC patients were divided into two clusters by consensus clustering. LASSO Cox regression analysis was used to build a risk signature to predict the prognosis of patients with ccRCC. An ROC curve, univariate Cox regression analysis, and multivariate Cox regression analysis were used to verify this risk signature's predictive ability. Then, we internally validated this signature by random sampling. Finally, we explored the role of the genes in the signature in some common pathways. Gene distribution between the two subgroups was different; cluster 2 was gender-related and had a worse prognosis. IGF2BP3, IGF2BP2, HNRNPA2B1, and METTL14 were chosen to build the risk signature. The overall survival of the high- and low-risk groups was significantly different (p = 7.47e - 12). The ROC curve also indicated that the risk signature had a decent predictive significance (AUC = 0.72). These results imply that the risk signature has a potential value for ccRCC treatment.

20.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(2): 143-147, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33627208

RESUMO

OBJECTIVE: To study the clinical features of children with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome, a polygenic and multifactorial autoinflammatory disease with unknown pathogenesis. METHODS: A retrospective analysis was performed on the medical data of 13 children with PFAPA syndrome. RESULTS: All 13 children had disease onset within the age of 3 years, with a mean age of onset of (14±10) months. They all had periodic fever, with 8-18 attacks each year. The mean interictal period of fever was (30±5) days. Pharyngitis, cervical adenitis, and aphthous stomatitis were the three cardinal symptoms, with incidence rates of 100% (13/13), 85% (11/13), and 38% (5/13) respectively. There were increases in white blood cells, C-reactive protein, and erythrocyte sedimentation rate during fever. Of all the 13 children, 6 underwent whole exome sequencing and 7 underwent panel gene detection for autoinflammatory disease, and the results showed single heterozygous mutations in the MEFV gene in 6 children (46%). Recurrent fever in all children gradually returned to normal without antibiotics. Ten children were treated with a single dose of glucocorticoids, and fever was relieved after treatment. Of all the children, 4 were treated with cimetidine, among whom 2 had response; 4 children were treated with colchicine, among whom 2 had response and 2 were withdrawn from the drug due to adverse reactions. Tonsillectomy was performed for 2 children, among whom 1 was followed up for 3 years without recurrence and 1 still had recurrence. CONCLUSIONS: For children with unexplained periodic fever with early onset accompanied by pharyngitis, cervical adenitis, aphthous stomatitis, elevated inflammatory indices, and good response to glucocorticoids, PFAPA syndrome should be considered. This disorder has good prognosis, and early diagnosis can avoid the long-term repeated use of antibiotics.


Assuntos
Linfadenite , Faringite , Estomatite Aftosa , Criança , Pré-Escolar , Febre/etiologia , Humanos , Lactente , Linfadenite/diagnóstico , Faringite/diagnóstico , Faringite/tratamento farmacológico , Pirina , Estudos Retrospectivos , Estomatite Aftosa/diagnóstico , Estomatite Aftosa/tratamento farmacológico , Estomatite Aftosa/genética
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