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1.
Genome Biol ; 22(1): 175, 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34108023

RESUMO

BACKGROUND: The maize inbred line A188 is an attractive model for elucidation of gene function and improvement due to its high embryogenic capacity and many contrasting traits to the first maize reference genome, B73, and other elite lines. The lack of a genome assembly of A188 limits its use as a model for functional studies. RESULTS: Here, we present a chromosome-level genome assembly of A188 using long reads and optical maps. Comparison of A188 with B73 using both whole-genome alignments and read depths from sequencing reads identify approximately 1.1 Gb of syntenic sequences as well as extensive structural variation, including a 1.8-Mb duplication containing the Gametophyte factor1 locus for unilateral cross-incompatibility, and six inversions of 0.7 Mb or greater. Increased copy number of carotenoid cleavage dioxygenase 1 (ccd1) in A188 is associated with elevated expression during seed development. High ccd1 expression in seeds together with low expression of yellow endosperm 1 (y1) reduces carotenoid accumulation, accounting for the white seed phenotype of A188. Furthermore, transcriptome and epigenome analyses reveal enhanced expression of defense pathways and altered DNA methylation patterns of the embryonic callus. CONCLUSIONS: The A188 genome assembly provides a high-resolution sequence for a complex genome species and a foundational resource for analyses of genome variation and gene function in maize. The genome, in comparison to B73, contains extensive intra-species structural variations and other genetic differences. Expression and network analyses identify discrete profiles for embryonic callus and other tissues.

2.
BMC Cancer ; 21(1): 469, 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33906632

RESUMO

BACKGROUND: As is well recognized that inflammation plays a crucial role in the genesis and progression of various cancer. Here we investigate the prognostic value of a novel index: the combination of neutrophil to lymphocyte ratio and platelet distribution width (coNLR-PDW) in post-operation patients with resectable hepatocellular carcinoma (HCC). METHODS: The receiver operating characteristic (ROC) curve was utilized to determine the optimal cutoff values of continuous variables, including the neutrophil-lymphocyte ratio (NLR) and platelet distribution width (PDW). Kaplan-Meier method and the Log-rank test were used to compare survival differences across three groups stratified by the coNLR-PDW score. Univariate and multivariate Cox proportional hazard regression analyses were adopted to identify independent factors of HCC patient's prognosis. RESULTS: 1.59 and 13.0 were perceived as the optimal cutoff value for NLR and PDW based on the ROC curve, respectively. Kaplan-Meier method revealed that a higher coNLR-PDW score predicts poorer overall survival (OS) and disease-free survival (DFS) (P < 0.001). coNLR-PDW was demonstrated as an independent factor for both OS and DFS using Cox regression analysis in training and validation cohort. CONCLUSION: coNLR-PDW is recognized as a valuable biomarker for predicting the survival of patients with HCC.

3.
Stem Cell Res Ther ; 12(1): 244, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33863383

RESUMO

BACKGROUND: ABO-incompatible liver transplantation (ABO-i LT) has become a rescue therapeutic option for patients with severe hepatic failure. Although the use of rituximab greatly reduces the morbidity of antibody-mediated rejection (AMR), severe adverse effects, such as infection and biliary complications, still seriously threaten the survival of transplant recipients. The aim of this study was to evaluate the safety and feasibility of using mesenchymal stem cells (MSCs) to replace rituximab in ABO-i LT. METHODS: Twenty-two patients with severe hepatic failure undergoing ABO-i LT were enrolled and randomly divided into two groups: the MSC group and the rituximab group. The safety of the application of MSCs and the incidence of allograft rejection, including antibody-mediated rejection (AMR) and acute cellular rejection (ACR), were evaluated in both groups at the 2-year follow-up period as primary endpoints. Recipients and graft survival and other postoperative complications were compared as secondary endpoints. RESULTS: No severe MSC-related adverse events were observed during the trial. MSC treatment yielded comparable, if not better, results than rituximab at decreasing the incidence of acute rejection (9.1% vs 27.3%). Inspiringly, compared to those in the rituximab group, the rates of biliary complications (0% vs 45.5%) and infection (9.1% vs 81.8%) were significantly decreased in the MSC group. In addition, there were no significant differences in 2-year graft and recipient survival between the two groups (81.8% vs 72.7%). CONCLUSIONS: Our data show that MSC transfusion is comparable to rituximab treatment for AMR prophylaxis following ABO-i LT. Additionally, the results indicate that MSCs are more beneficial to the prevention of infection and biliary complications and may be introduced as a novel immunosuppressive approach for ABO-i LT. TRIAL REGISTRATION: Trial registration: chictr.org.cn , ChiCTR2000037732. Registered 31 August 2020- Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=57074 .

4.
New Phytol ; 230(6): 2337-2354, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33749863

RESUMO

RUBylation plays essential roles in plant growth and development through regulating Cullin-RING ubiquitin E3 ligase (CRL) activities and the CRL-mediated protein degradations. However, the function of RUBylation in regulating kernel development remains unclear. Through genetic and molecular analyses of a small kernel 501 (smk501) mutant in maize (Zea mays), we cloned the smk501 gene, revealed its molecular function, and defined its roles in RUBylation pathway and seed development. Smk501 encodes a RUBylation activating enzyme E1 subunit ZmECR1 (E1 C-TERMINAL RELATED 1) protein. Destruction in RUBylation by smk501 mutation resulted in less embryo and endosperm cell number and smaller kernel size. The transcriptome and proteome profiling, hormone evaluation and cell proliferation observation revealed that disturbing ZmECR1 expression mainly affects pathways on hormone signal transduction, cell cycle progression and starch accumulation during kernel development. In addition, mutant in zmaxr1 (Auxin resistant 1), another RUB E1 subunit, also showed similar defects in kernel development. Double mutation of zmecr1 and zmaxr1 lead to empty pericarp kernel phenotype. RUBylation is a novel regulatory pathway affecting maize kernel development, majorly through its functions in modifying multiple cellular progresses.


Assuntos
Endosperma , Zea mays , Perfilação da Expressão Gênica , Ácidos Indolacéticos , Proteínas de Plantas/genética , Sementes , Zea mays/genética
5.
J Phys Chem A ; 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33754720

RESUMO

In the troposphere, the knowledge about nitrous acid (HONO) sources is incomplete. The missing source of sulfate and fine particles cannot be explained during haze events. Air quality models cannot predict high levels of secondary fine-particle pollution. Despite extensive studies, one challenging issue in atmospheric chemistry is identifying the source of HONO. Here, we present direct ab initio molecular dynamics simulation evidence and typical air pollution events of the formation of gaseous HONO, nitrogen dioxide/hydrogen sulfite (HOS(O)2-NO2 or NO2-HSO3) from nitrogen dioxide (NO2), sulfur dioxide (SO2), water (H2O), and ammonia (NH3) molecules in a proportion of 2:1:3:3. The reactions show a new mechanism for the formation of HONO and NO2-HSO3 in the troposphere, especially when the concentration of NO2, SO2, H2O, and NH3 is high (e.g., 2:1:3:3 or higher) in the air. Contrary to the proportion NO2, SO2, H2O, and NH3 equaling to 1:1:3:1 and 1:1:3:2, the proportion (2:1:3:3) enables barrierless reactions and weak interactions between molecules via the formation of HONO, NO2-HSO3, and NH3/H2O. In addition, field observations are carried out, and the measured data are summarized. Correlation analysis supported the conversion of NO2 to HONO during observational studies. The weak interactions promote proton transfer, resulting in the generation of HONO, NO2-HSO3, and NH3/H2O pairs.

6.
Clin Epigenetics ; 13(1): 47, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33663600

RESUMO

BACKGROUND: Maternal smoking affects more than half a million pregnancies each year in the US and is known to result in fetal growth restriction as measured by lower birthweight and its associated long-term consequences. Maternal smoking also has been linked to altered fetal DNA methylation (DNAm). However, what remains largely unexplored is whether these DNAm alterations are merely markers of smoking exposure or if they also have implications for health outcomes. This study tested the hypothesis that fetal DNAm mediates the effect of maternal smoking on newborn birthweight. METHODS: This study included mother-newborn pairs from a US predominantly urban, low-income multi-ethnic birth cohort. DNAm in cord blood were determined using the Illumina Infinium MethylationEPIC BeadChip. After standard quality control and normalization procedures, an epigenome-wide association study (EWAS) of maternal smoking was performed using linear regression models, controlling for maternal age, education, race, parity, pre-pregnancy body mass index, alcohol consumption, gestational age, maternal pregestational/gestational diabetes, child sex, cord blood cell compositions and batch effects. To quantify the degree to which cord DNAm mediates the smoking-birthweight association, the VanderWeele-Vansteelandt approach for single mediator and structural equational model for multiple mediators were used, adjusting for pertinent covariates. RESULTS: The study included 954 mother-newborn pairs. Among mothers, 165 (17.3%) ever smoked before or during pregnancy. Newborns with smoking exposure had on average 258 g lower birthweight than newborns without exposure (P < 0.001). Using a false discovery rate (FDR) < 0.05 as the significance cutoff, the EWAS identified 38 differentially methylated CpG sites associated with maternal smoking. Of those, 17 CpG sites were mapped to previously reported genes: GFI1, AHRR, CYP1A1, and CNTNAP2; 8 of those, located in the first three genes, were Bonferroni significantly associated with newborn birthweight and mediated the smoking-birthweight association. The combined mediation effect of the three genes explained 67.8% of the smoking-birthweight association. CONCLUSIONS: Our study not only lends further support that maternal smoking alters fetal DNAm in a multiethnic population, but also suggests that fetal DNAm substantially mediates the maternal smoking-birthweight association. Our findings, if further validated, indicate that DNAm modification is likely an important pathway by which maternal smoking impairs fetal growth and, perhaps, even long-term health outcomes.

7.
Bioresour Technol ; 323: 124620, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33429314

RESUMO

In this study, physio-chemical properties, 45 antibiotics, 6 heavy metals, 42 antibiotic resistance genes (ARGs), 3 mobile genetic elements, and the bacterial community structure were investigated to analyze the fate of ARGs during sheep manure aerobic heap composting. Results showed that sheep manure heap composting could produce mature compost. The degradation processes reduced the total antibiotics content by 85%. The abundance of ARGs and mobile genetic elements (MGEs) were enriched 9-fold, with the major increases to sul and tet genes (sulI, sulII, tetQ, and tetX). Tetracycline and sulfonamide resistance genes were the most abundant ARGs after composting (more than 88% of all genes). The genes tetA, tetX and sulI were related to the most diverse bacteria that were most able to proliferate during heap composting. Therefore, sulI and tetX are the major ARGs to be controlled, and Actinobacteria and Bacteroidetes may be the major host bacteria.


Assuntos
Compostagem , Animais , Antibacterianos/farmacologia , Resistência Microbiana a Medicamentos/genética , Genes Bacterianos/genética , Esterco , Ovinos
9.
J Nutr ; 151(3): 570-578, 2021 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-33438012

RESUMO

BACKGROUND: Although manganese (Mn) is an essential trace element and a common component of most multivitamins on the market, an adverse effect on blood pressure (BP) has been reported in adults. In addition, the longitudinal relation between prenatal Mn status and childhood BP is still unknown. OBJECTIVE: This study investigated the association between prenatal Mn concentrations and risk of elevated BP at ages 3-12 y. METHOD: The analyses included 1268 mother-child dyads who were enrolled at birth and followed prospectively at the Boston Medical Center. Maternal RBC Mn concentrations were measured by inductively coupled plasma mass spectrometry, using RBCs collected within 1-3 d after delivery (reflecting late-pregnancy Mn exposure). Child elevated BP was defined as systolic or diastolic BP ≥90th percentile for a given age, sex and height. Multivariate logistic regression models were conducted. Path analysis was applied to mediation estimation. RESULTS: The median (IQR) maternal RBC Mn concentration was 37.5 (29.2-48.5) µg/L. The rate of child elevated BP at ages 3-12 y was 25%. Both the lowest and highest quartiles of maternal RBC Mn concentrations were associated with higher risk of elevated BP among children aged 6-12 y (OR: 1.52; 95% CI: 1.04, 2.21 and OR: 1.65; 95% CI: 1.13, 2.40, respectively) compared with those in the second and third quartiles. Gestational age and fetal growth mediated the association between low maternal RBC Mn (first quartile) and child elevated BP, explaining 25% of the association, but not for high (fourth quartile) maternal RBC Mn concentrations. No association was found between maternal RBC Mn concentrations and BP among children aged 3-5 y. CONCLUSION: We found a nonlinear association between maternal RBC Mn concentrations and elevated BP among children aged 6-12 y from a high-risk, predominantly minority population. Our findings warrant further investigation.


Assuntos
Eritrócitos/química , Manganês/química , Efeitos Tardios da Exposição Pré-Natal , Fenômenos Fisiológicos da Nutrição Pré-Natal , Adulto , Pressão Sanguínea , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Hipertensão , Masculino , Gravidez , Estudos Prospectivos , Adulto Jovem
10.
Mol Plant ; 14(1): 77-94, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33340690

RESUMO

The functional genes underlying phenotypic variation and their interactions represent "genetic mysteries". Understanding and utilizing these genetic mysteries are key solutions for mitigating the current threats to agriculture posed by population growth and individual food preferences. Due to advances in high-throughput multi-omics technologies, we are stepping into an Interactome Big Data era that is certain to revolutionize genetic research. In this article, we provide a brief overview of current strategies to explore genetic mysteries. We then introduce the methods for constructing and analyzing the Interactome Big Data and summarize currently available interactome resources. Next, we discuss how Interactome Big Data can be used as a versatile tool to dissect genetic mysteries. We propose an integrated strategy that could revolutionize genetic research by combining Interactome Big Data with machine learning, which involves mining information hidden in Big Data to identify the genetic models or networks that control various traits, and also provide a detailed procedure for systematic dissection of genetic mysteries,. Finally, we discuss three promising future breeding strategies utilizing the Interactome Big Data to improve crop yields and quality.

11.
J Environ Sci (China) ; 99: 324-335, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33183711

RESUMO

The hydroxyl radical (•OH) has a crucial function in the oxidation and removal of many atmospheric compounds that are harmful to health. Nevertheless, high reactivity, low atmospheric abundance, determination of hydroxyl, and hydroperoxyl radical's quantity is very difficult. In the atmosphere and troposphere, hydroperoxyl radicals (HO2) are closely demanded in the chemical oxidation of the troposphere. But advances in technology have allowed researchers to improve the determination methods on the research of free radicals through some spectroscopic techniques. So far, several methods such as laser-induced fluorescence (LIF), high-performance liquid chromatography (HPLC), and chemical ionization mass spectroscopy have been identified and mostly used in determining the quantity of hydroxyl and hydroperoxyl radicals. In this systematic review, we have advised the use of scavenger as an advance for further researchers to circumvent some of these problems caused by free radicals. The primary goal of this review is to deepen our understanding of the functions of the most critical free radical (•OH, HO2) and also understand the currently used methods to quantify them in the atmosphere and troposphere.


Assuntos
Atmosfera , Radical Hidroxila , Radicais Livres , Oxirredução
12.
Am J Kidney Dis ; 77(6): 879-888.e1, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33359152

RESUMO

RATIONALE & OBJECTIVES: Preeclampsia, which disproportionately affects Black women, is a leading cause of preterm delivery and risk for future hypertension and chronic kidney disease (CKD). Apolipoprotein L1 (APOL1) kidney risk alleles, common among Black individuals, contribute substantially to CKD disparities. Given the strong link between preeclampsia and CKD, we investigated whether maternal and fetal APOL1 risk alleles can jointly influence preeclampsia risk, and explored potential modifiers of the association between APOL1 and preeclampsia. STUDY DESIGN: Nested case-control study. SETTING & PARTICIPANTS: 426 Black mother-infant pairs (275 African Americans and 151 Haitians) from the Boston Birth Cohort. EXPOSURE: Maternal and fetal APOL1 risk alleles. OUTCOMES: Preeclampsia. ANALYTICAL APPROACH: Logistic regression models with adjustment for demographic characteristics were applied to analyze associations between fetal and maternal APOL1 risk alleles and risk of preeclampsia and to investigate the effects of modification by maternal country of origin. RESULTS: Fetal APOL1 risk alleles tended to be associated with an increased risk of preeclampsia, which was not statistically significant in the total genotyped population. However, this association was modified by maternal country of origin (P<0.05 for interaction tests): fetal APOL1 risk alleles were significantly associated with an increased risk of preeclampsia among African Americans under recessive (odds ratio [OR], 3.6 [95% CI, 1.3-9.7]; P=0.01) and additive (OR, 1.7 [95% CI, 1.1-2.6]; P=0.01) genetic models but not in Haitian Americans. Also, maternal-fetal genotype discordance at the APOL1 locus was associated with a 2.6-fold higher risk of preeclampsia (P<0.001) in African Americans. LIMITATIONS: Limited sample size in stratified analyses; self-reported maternal country of origin; pre-pregnancy estimated glomerular filtration rate (eGFR) and proteinuria data in mothers were not collected; unmeasured confounding social and/or environmental factors; no replication study. CONCLUSIONS: This study supports the hypothesis that fetal APOL1 kidney risk alleles are associated with increased risk for preeclampsia in a recessive mode of inheritance in African Americans and suggests that maternal-fetal genotype discordance is also associated with this risk. These conclusions underscore the need to better understand maternal-fetal interaction and their genetic and environmental factors as contributors to ethnic disparities in preeclampsia.

13.
Plant Cell Physiol ; 62(2): 293-305, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33377894

RESUMO

Splicing of plant organellar group II introns from precursor-RNA transcripts requires the assistance of nuclear-encoded splicing factors. Maturase (nMAT) is one such factor, as its three homologs (nMAT1, 2 and 4) have been identified as being required for the splicing of various mitochondrial introns in Arabidopsis. However, the function of nMAT in maize (Zea mays L.) is unknown. In this study, we identified a seed development mutant, empty pericarp 2441 (emp2441) from maize, which showed severely arrested embryogenesis and endosperm development. Positional cloning and transgenic complementation assays revealed that Emp2441 encodes a maturase-related protein, ZmnMAT3. ZmnMAT3 is highly expressed during seed development and its protein locates to the mitochondria. The loss of function of ZmnMAT3 resulted in the reduced splicing efficiency of various mitochondrial group II introns, particularly of the trans-splicing of nad1 introns 1, 3 and 4, which consequently abolished the transcript of nad1 and severely impaired the assembly and activity of mitochondrial complex I. Moreover, the Zmnmat3 mutant showed defective mitochondrial structure and exhibited expression and activity of alternative oxidases. These results indicate that ZmnMAT3 is essential for mitochondrial complex I assembly during kernel development in maize.


Assuntos
Mitocôndrias/metabolismo , Proteínas de Plantas/fisiologia , Sementes/crescimento & desenvolvimento , Zea mays/crescimento & desenvolvimento , Clonagem Molecular , Regulação da Expressão Gênica de Plantas , Íntrons , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas Nucleares/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Processamento de RNA/genética , Fatores de Processamento de RNA/metabolismo , Fatores de Processamento de RNA/fisiologia , Sementes/metabolismo , Zea mays/genética , Zea mays/metabolismo
14.
Hum Reprod ; 36(3): 712-720, 2021 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-33367618

RESUMO

STUDY QUESTION: Is in utero exposure to mercury associated with the risk of precocious puberty? SUMMARY ANSWER: Prenatal exposure to high levels of mercury was associated with increased risk of precocious puberty, which was strengthened by concomitant maternal cardiometabolic conditions and adverse birth outcomes. WHAT IS KNOWN ALREADY: The developing fetus is sensitive to mercury, a well-known endocrine disruptor which impacts the endocrine and reproductive system. STUDY DESIGN, SIZE, DURATION: This study included 1512 mother-child pairs from the Boston Birth Cohort, a longitudinal cohort which recruited at birth and followed prospectively up to 21 years of age. PARTICIPANTS/MATERIALS, SETTING, METHODS: Mother-child pairs, from a predominantly urban minority population, were enrolled from 2002 to 2013. Prenatal exposure was assessed by maternal mercury concentration in red blood cells (RBCs) collected at 1-3 days after delivery. Precocious puberty was defined based on International Classification of Disease codes. Cox proportional hazards models were applied to the association between maternal mercury concentrations and the risk of precocious puberty. MAIN RESULTS AND THE ROLE OF CHANCE: The median (interquartile range) of maternal mercury concentrations among children with and without precocious puberty were 3.4 (1.9-4.6) µg/l and 2.0 (1.0-3.7) µg/l, respectively. Compared to those in the lowest tertile for mercury, the highest tertile was associated with increased risk of precocious puberty, with an adjusted hazard ratio (HR) of 2.41, 95% CI: 1.16-5.03. In addition, concomitant maternal cardiometabolic conditions and adverse birth outcomes strengthened the effects of mercury on the risk of precocious puberty. The highest risk of precocious puberty was observed among children who had adverse birth outcomes and whose mothers had high RBC-mercury concentrations along with cardiometabolic conditions, with an HR of 4.76 (95% CI: 1.66-13.60) compared to children with favorable profiles of all three risk factors. LIMITATIONS, REASONS FOR CAUTION: Precocious puberty was defined based on medical records, not on a direct assessment, which may have led to underdiagnosis and the inability to make a subclassification. The study included a predominately urban, low-income, minority population and as such our findings may not be widely generalizable. WIDER IMPLICATIONS OF THE FINDINGS: Prenatal Hg exposure was associated with an increased risk of precocious puberty. This risk was strengthened by concomitant maternal cardiometabolic conditions during pregnancy and adverse birth outcomes. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the NIH/National Institute of Environmental Health Sciences, NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Health Resources and Services Administration of the U.S. Department of Health and Human Services. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.


Assuntos
Mercúrio , Efeitos Tardios da Exposição Pré-Natal , Puberdade Precoce , Boston , Criança , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Mercúrio/toxicidade , Gravidez , Estudos Prospectivos , Puberdade Precoce/induzido quimicamente
15.
Artigo em Inglês | MEDLINE | ID: mdl-33252313

RESUMO

Background: Hypertensive disorders of pregnancy are a recognized risk factor of a woman's future cardiovascular risk. The potential role of micronutrients in mitigating hypertensive disorders is not fully understood. This study examined maternal postpartum plasma B vitamin profiles by hypertensive disorders of pregnancy in a high-risk multiethnic U.S. population. Materials and Methods: The analyses included 2584 mothers enrolled within 3 days postpartum at the Boston Medical Center. Hypertensive disorders of pregnancy included gestational hypertension and pre-eclampsia disorders (pre-eclampsia, eclampsia, hemolysis, elevated liver enzymes, and/or low platelets syndrome) as documented in the medical records. Plasma folate, vitamin B12, and homocysteine levels were measured in blood samples collected at enrollment. Kernel density plots and multivariable regressions were used to examine the relationship between hypertensive disorders and postpartum B vitamin profiles. Results: Of the 2584 mothers, 10% had pre-eclampsia disorders that were associated with significantly lower plasma folate (adjusted beta coefficient (aß): -0.10; 95% CI: -0.22 to -0.06) and increased homocysteine (aß: 0.08; 95% CI: 0.04-0.13), but not with vitamin B12 concentrations. These associations remained robust after adjusting for a range of pertinent covariables and were more pronounced in non-Hispanic Black women compared with other groups. However, gestational hypertension was not significantly associated with any postpartum biomarker. Conclusions: We found that pre-eclampsia disorders, but not gestational hypertension, was associated with lower folate and higher homocysteine levels postpartum, especially among Black mothers. This finding, if further confirmed, may have implications for postpartum care, including attention to maternal micronutrient status to reduce and prevent hypertensive disorders in pregnancy-associated consequences in subsequent pregnancies and lifespan. Registration date: July 25, 2017; Registry website: https://clinicaltrials.gov/ct2/show/NCT03228875.

16.
J Pediatr ; 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33253732

RESUMO

OBJECTIVE: To examine the associations between body-mass index (BMI) at 2-4 years and 5-7 years and age at peak height velocity (APHV), an objective measure of pubertal timing, among boys and girls from predominantly racial/ethnic minorities in the US that have been historically underrepresented in this research topic. STUDY DESIGN: This study included 1,296 mother-child dyads from the Boston Birth Cohort, a predominantly Black and low-income cohort enrolled at birth and followed prospectively during 1998-2018. The exposure was overweight or obesity, based on Centers for Disease Control and Prevention reference standards. The outcome was APHV, derived using a mixed effects growth curve model. Multiple regression was used to estimate overweight or obesity-APHV association and control for confounders. RESULTS: Obesity at 2-4 years was associated with earlier APHV in boys (B in years, -0.19; 95%CI, -0.35 to -0.03) and girls (B, -0.22; 95%CI, -0.37 to -0.07). Obesity at 5-7 years was associated with earlier APHV in boys (B, -0.18; 95%CI, -0.32 to -0.03), while overweight and obesity at 5-7 years were both associated with earlier APHV in girls (overweight:B,-0.24; 95%CI, -0.40 to -0.08; obesity: B, -0.27; 95%CI, -0.40 to -0.13). With BMI trajectory, boys persistently overweight or obese and girls who were overweight or obese at 5-7 years, irrespective of overweight or obesity status at 2-4 years, had earlier APHV. CONCLUSIONS: This prospective birth cohort study found that overweight or obesity during 2-7 years was associated with earlier pubertal onset in both boys and girls. The BMI trajectory analyses further suggest that removal of overweight or obesity may halt the progression towards early puberty.

17.
Food Funct ; 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33191416

RESUMO

Oxidative stress plays a central role in the common pathophysiology of neurodegenerative diseases such as Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease. Antioxidant therapy has been suggested for the prevention and treatment of neurodegenerative diseases. Compounds derived from natural sources may offer the potential for new treatment options. Semen Celosiae is a traditional Chinese edible herbal medicine with a long history in China and exhibits wide-reaching biological activities such as hepatoprotective, anti-tumor, anti-diarrheal, anti-diabetic, anti-oxidant, etc. In this study, nine saponins and two phenylacetonitrile glycosides were isolated from Semen Celosiae and their structures were identified using ESI-MS and NMR techniques. Among them, compounds 1 and 2 have not been previously reported. The total concentrations of the five triterpenoid saponins and the two phenylacetonitrile glycosides were 3.348 mg g-1 and 0.187 mg g-1, respectively, suggesting that Semen Celosiae is a novel viable source of the two kinds of compounds. These compounds were observed to significantly attenuate t-BHP-induced neuronal damage by effectively enhancing cell viability and decreasing reactive oxygen species generation and cell apoptosis rate in NSC-34 cells. Furthermore, compounds 1 and 7 reduced the ratios of cleaved caspase-3: caspase-3 and cleaved caspase-7: caspase-7 and the level of cytochrome C, while they increased the levels of SOD1 and Beclin 1. These findings suggest that compounds 1-11 are potent inhibitors of neuron injury elicited by t-BHP, possibly via inhibition of oxidative stress and apoptosis, and activation of autophagy; therefore they may be valuable leads for future therapeutic development.

18.
World J Gastrointest Oncol ; 12(10): 1209-1215, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33133387

RESUMO

BACKGROUND: Sarcomatoid hepatocellular carcinoma (SHC) is a rare subtype of hepatocellular carcinoma (HCC), with a high recurrence rate after surgery. In addition to limited effective treatment for the advanced stage of SHC, the prognosis of patients with this malignancy is worse than that of patients with conventional HCC. CASE SUMMARY: We present the case of a 54-year-old man with SHC who underwent radical segmental hepatectomy, which relapsed 4 mo after surgery due to lymphatic metastasis in the porta hepatis. Although a second surgery was performed, new metastasis developed in the mediastinal lymph nodes. Therefore, sorafenib and lenvatinib were sequentially administered as first- and second-line systemic therapies, respectively. However, progressive disease was confirmed based on a recurrent hepatic lesion and new metastatic lesion in the abdominal cavity. Percutaneous transhepatic cholangial drainage was performed to alleviate the biliary obstruction. Because the tumor was strongly positive for programmed death-ligand 1, the patient was started on nivolumab. Imaging studies revealed that after two cycles of immunotherapy, the metastatic lesions decreased to undetectable levels. CONCLUSION: The patient experienced continuous complete remission for 8 mo. Immune checkpoint inhibitors are useful for the treatment of advanced SHC.

19.
Cell Oncol (Dordr) ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33034848

RESUMO

PURPOSE: Multiple circular RNAs (circRNAs) have been reported to be dysregulated in hepatocellular carcinoma (HCC). However, their functions and modes of action are still largely unclear. Identifying key circRNAs and revealing their potential functions and molecular mechanisms is considered important for improving the diagnosis and treatment of HCC. METHODS: Dysregulated circRNAs in HCC were identified through integration of three human HCC circRNAs microarray datasets (GSE94508, GSE97332 and GSE 78520), followed by qRT-PCR validation in primary HCC tissues and cell lines. circRNA characteristics were verified through Sanger sequencing, RNase R treatment, northern blotting and intracellular localization analyses. In addition, circRNA functions in HCC development were assessed using CCK8, colony formation, EDU incorporation, flow cytometry, transwell and scratch wound healing assays in vitro and tumor xenograft assays in vivo. Next, underlying molecular mechanisms in HCC were assessed using dual-luciferase reporter, RNA pull-down, RNA immunoprecipitation and western blotting assays. RESULTS: We found that a novel circular RNA, circ-102,166, was down-regulated in HCC and that its expression level was significantly associated with multiple clinicopathologic characteristics, as well as the clinical prognosis of HCC patients. In vitro and in vivo experiments revealed that circ-102,166 overexpression significantly inhibited the proliferation, invasion, migration and tumorigenicity of HCC cells. Furthermore, we found that circ-102,166 can bind to miR-182 and miR-184 to regulate the expression of several of their downstream targets (FOXO3a, MTSS1, SOX7, p-RB and c-MYC). CONCLUSION: Our data revealed a tumor-suppressing role of circ-102,166 in HCC. Down-regulation of circ-102,166 enhanced the proliferation and invasion of HCC cells by releasing the oncomiRs miR-182 and miR-184.

20.
BMC Med ; 18(1): 277, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33046083

RESUMO

BACKGROUND: Preeclampsia and preterm delivery (PTD) are believed to affect women's long-term health including cardiovascular disease (CVD), but the biological underpinnings are largely unknown. We aimed to test whether maternal postpartum metabolomic profiles, especially CVD-related metabolites, varied according to PTD subtypes with and without preeclampsia, in a US urban, low-income multi-ethnic population. METHODS: This study, from the Boston Birth Cohort, included 980 women with term delivery, 79 with medically indicated PTD (mPTD) and preeclampsia, 52 with mPTD only, and 219 with spontaneous PTD (sPTD). Metabolomic profiling in postpartum plasma was conducted by liquid chromatography-mass spectrometry. Linear regression models were used to assess the associations of each metabolite with mPTD with preeclampsia, mPTD only, and sPTD, respectively, adjusting for pertinent covariates. Weighted gene coexpression network analysis was applied to investigate interconnected metabolites associated with the PTD/preeclampsia subgroups. Bonferroni correction was applied to account for multiple testing. RESULTS: A total of 380 known metabolites were analyzed. Compared to term controls, women with mPTD and preeclampsia showed a significant increase in 36 metabolites, mainly representing acylcarnitines and multiple classes of lipids (diacylglycerols, triacylglycerols, phosphocholines, and lysophosphocholines), as well as a decrease in 11 metabolites including nucleotides, steroids, and cholesteryl esters (CEs) (P < 1.3 × 10-4). Alterations of diacylglycerols, triacylglycerols, and CEs in women with mPTD and preeclampsia remained significant when compared to women with mPTD only. In contrast, the metabolite differences between women with mPTD only and term controls were only seen in phosphatidylethanolamine class. Women with sPTD had significantly different levels of 16 metabolites mainly in amino acid, nucleotide, and steroid classes compared to term controls, of which, anthranilic acid, bilirubin, and steroids also had shared associations in women with mPTD and preeclampsia. CONCLUSION: In this sample of US high-risk women, PTD/preeclampsia subgroups each showed some unique and shared associations with maternal postpartum plasma metabolites, including those known to be predictors of future CVD. These findings, if validated, may provide new insight into metabolomic alterations underlying clinically observed PTD/preeclampsia subgroups and implications for women's future cardiometabolic health.

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