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1.
Neurotoxicol Teratol ; : 107371, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38971339

RESUMO

We examined associations between prenatal tobacco exposure (with and without cannabis exposure) and children's performance on laboratory measures of sustained attention, attentional set shifting, and working memory in middle childhood (9-12 years of child age). Participants were recruited in the first trimester of pregnancy and oversampled for prenatal tobacco exposure; with a smaller sample (n = 133; n = 34 non-substance exposed, n = 37 exposed to tobacco only, n = 62 co-exposed) invited (oversampled for co-exposure) to participate in the middle-childhood assessment (M age = 10.6, SD = 0.77; 68% Black, 20% Hispanic). Results for sustained attention indicated lower attention (percent hits) at the first epoch for tobacco only exposed compared to non-exposed and co-exposed; a trend (p = .07) towards increases in impulsive responding across time (a total of 8 epochs) for tobacco exposed (with and without cannabis) compared to non-exposed children; and a significant association between higher number of cigarettes in the first trimester and greater increases in impulsive responding across epochs. However, children prenatally exposed to tobacco (with and without cannabis) demonstrated greater short-term memory compared to children not prenatally exposed, and this difference was driven by higher scores for children prenatally co-exposed to tobacco and cannabis compared to those who were non-exposed. Overall, results suggest that prenatal tobacco exposure, especially in the first trimester, may increase risk for impulsive responding on tasks requiring sustained attention, and that co-use of cannabis did not exacerbate these associations. The higher short-term memory scores among children who were co-exposed compared to non-exposed are perplexing and need replication, particularly in studies with larger sample sizes and samples exposed only to cannabis to examine this more closely.

2.
Eur J Med Chem ; 269: 116341, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38518523

RESUMO

Protein arginine methyltransferase 5 (PRMT5) and epidermal growth factor receptor (EGFR) are both involved in the regulation of various cancer-related processes, and their dysregulation or overexpression has been observed in many types of tumors. In this study, we designed and synthesized a series of 1-phenyl-tetrahydro-ß-carboline (THßC) derivatives as the first class of dual PRMT5/EGFR inhibitors. Among the synthesized compounds, 10p showed the most potent dual PRMT5/EGFR inhibitory activity, with IC50 values of 15.47 ± 1.31 and 19.31 ± 2.14 µM, respectively. Compound 10p also exhibited promising antiproliferative activity against A549, MCF7, HeLa, and MDA-MB-231 cell lines, with IC50 values below 10 µM. Molecular docking studies suggested that 10p could bind to PRMT5 and EGFR through hydrophobic, π-π, and cation-π interactions. Furthermore, 10p displayed favorable pharmacokinetic properties and oral bioavailability (F = 30.6%) in rats, and administrated orally 10p could significantly inhibit the growth of MCF7 orthotopic xenograft tumors. These results indicate that compound 10p is a promising hit compound for the development of novel and effective dual PRMT5/EGFR inhibitors as potential anticancer agents.


Assuntos
Antineoplásicos , Carbolinas , Humanos , Ratos , Animais , Relação Estrutura-Atividade , Simulação de Acoplamento Molecular , Linhagem Celular Tumoral , Proliferação de Células , Antineoplásicos/química , Receptores ErbB , Inibidores de Proteínas Quinases/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular , Proteína-Arginina N-Metiltransferases
3.
Infect Dis Ther ; 13(2): 361-371, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38291280

RESUMO

INTRODUCTION: Kukoamine B mesylate (KB) is a mesylate chrysamine B targeting lipopolysaccharides and CpG DNA, two potential treatment targets in sepsis. METHODS: This first-in-human, randomized, double-blind, placebo-controlled, phase I study was conducted from July 2014 to May 2015 to explore the safety, tolerability, and pharmacokinetics of KB in healthy subjects. This study consisted of a pre-phase (four participants; KB at 0.005 mg/kg) and a dose escalation phase (eight participants/dose group, randomized 6:2 to KB or placebo; KB at 0.02, 0.04, 0.08, 0.12, 0.24, and 0.48 mg/kg). The primary endpoint was safety. RESULTS: Fifty-two participants were enrolled, including four in the pre-phase and 48 in the dose escalation phase. Among the 40 participants who received KB, 12 (30.0%) experienced adverse events (AEs), while two (16.7%) experienced AEs among 12 participants who received the placebo. The most common AEs in the KB group were headache (5.0%), influenza (5.0%) and positive white blood cell in urine (5.0%). After the administration of KB, the mean plasma elimination half was around 1.61-4.24 h. The relationship between the KB plasma exposure of KB and the administered dose was not linear. The percentage of cumulative urinary excretion of KB was similar among the different dose groups (21.7-35.2%) and the urinary excretion of KB decreased significantly about 8 h after administration. CONCLUSIONS: Single-dose KB demonstrated favorable safety and tolerability in healthy subjects at the dose level of 0.005-0.48 mg/kg. KB exhibited a non-linear pharmacokinetic profile with a half-life of about 1.61-4.24 h, which mainly distributed in plasma. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02219971.

4.
Nat Chem Biol ; 20(4): 484-492, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37945893

RESUMO

GPR101 is an orphan G protein-coupled receptor actively participating in energy homeostasis. Here we report the cryo-electron microscopy structure of GPR101 constitutively coupled to Gs heterotrimer, which reveals unique features of GPR101, including the interaction of extracellular loop 2 within the 7TM bundle, a hydrophobic chain packing-mediated activation mechanism and the structural basis of disease-related mutants. Importantly, a side pocket is identified in GPR101 that facilitates in silico screening to identify four small-molecule agonists, including AA-14. The structure of AA-14-GPR101-Gs provides direct evidence of the AA-14 binding at the side pocket. Functionally, AA-14 partially restores the functions of GH/IGF-1 axis and exhibits several rejuvenating effects in wild-type mice, which are abrogated in Gpr101-deficient mice. In summary, we provide a structural basis for the constitutive activity of GPR101. The structure-facilitated identification of GPR101 agonists and functional analysis suggest that targeting this orphan receptor has rejuvenating potential.


Assuntos
Receptores Acoplados a Proteínas G , Camundongos , Animais , Microscopia Crioeletrônica , Receptores Acoplados a Proteínas G/metabolismo , Ligantes
5.
Infancy ; 29(1): 72-79, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37823562

RESUMO

Effortful control (EC), a self-regulation skill, is associated with long-term developmental outcomes. Music has been associated with infant self-regulation and may be an intervention strategy for enhancing EC during toddlerhood. This investigation included 32 parent-child dyads from a previously conducted randomized controlled trial (RCT). Participants (9-15-months old at baseline) attended either a music enrichment program or a playdate control once a week for 1 year and monthly for an additional year. At age 3, participants completed snack and gift delay effortful control tasks. Groups were compared using one-way ANOVA. We found that participants in the music group had a significantly higher score during snack delay (music mean = 3.47 ± 0.94; control mean = 2.45 ± 1.51; p = 0.03; Cohen's d = 0.84). We did not find a significant group difference for latency to peek (music mean = 39.10 ± 20.10; control mean = 30.90 ± 19.88; p = 0.25; d = 0.57) or latency to touch (music mean = 105.73 ± 417.69; control mean = 98.35 ± 28.84; p = 0.38; d = 0.29) for the gift task. This study provides initial evidence that early participation in a music enrichment program may benefit later development of EC. This study is registered at ClinicalTrials.gov (NCT02936284).


Assuntos
Música , Autocontrole , Pré-Escolar , Humanos , Lactente
6.
Child Dev ; 95(2): 481-496, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37767574

RESUMO

The early language environment, especially high-quality, contingent parent-child language interactions, is crucial for a child's language development and later academic success. In this secondary analysis study, 89 parent-child dyads were randomly assigned to either the Music Together® (music) or play date (control) classes. Children were 9- to 15-month old at baseline, primarily white (86.7%) and female (52%). Measures of conversational turns (CTs) and parental verbal quality were coded from parent-child free play episodes at baseline, mid-intervention (month 6), and post-intervention (month 12). Results show that participants in the music group had a significantly greater increase in CT measures and quality of parent verbalization post-intervention. Music enrichment programs may be a strategy to enhance parent-child language interactions during early childhood.


Assuntos
Música , Humanos , Feminino , Pré-Escolar , Criança , Lactente , Linguagem Infantil , Relações Pais-Filho , Desenvolvimento da Linguagem , Pais
7.
Cell ; 186(24): 5347-5362.e24, 2023 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-37963465

RESUMO

Trace amine-associated receptor 1 (TAAR1) senses a spectrum of endogenous amine-containing metabolites (EAMs) to mediate diverse psychological functions and is useful for schizophrenia treatment without the side effects of catalepsy. Here, we systematically profiled the signaling properties of TAAR1 activation and present nine structures of TAAR1-Gs/Gq in complex with EAMs, clinical drugs, and synthetic compounds. These structures not only revealed the primary amine recognition pocket (PARP) harboring the conserved acidic D3.32 for conserved amine recognition and "twin" toggle switch for receptor activation but also elucidated that targeting specific residues in the second binding pocket (SBP) allowed modulation of signaling preference. In addition to traditional drug-induced Gs signaling, Gq activation by EAM or synthetic compounds is beneficial to schizophrenia treatment. Our results provided a structural and signaling framework for molecular recognition by TAAR1, which afforded structural templates and signal clues for TAAR1-targeted candidate compounds design.


Assuntos
Receptores Acoplados a Proteínas G , Transdução de Sinais , Humanos , Aminas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Esquizofrenia/metabolismo
8.
Med Microbiol Immunol ; 212(5): 369-379, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37658121

RESUMO

Sepsis is a severe syndrome caused by the imbalance of the host response to infection, accompanied by multiple organ damage, especially acute lung injury. SET Domain-Containing 2 (SETD2) is a methyltransferase catalyzing H3 lysine 36 trimethylation (H3K36me3) that regulates multiple biological processes. This study focused on explicating the action of SETD2 on macrophage function in sepsis and the precise mechanism involved. Enzyme-linked immunosorbent assay, real-time quantitative polymerase chain reaction (RT-qPCR), and Western blotting were used to determine expression. Luciferase reporter assay and chromatin immunoprecipitation assay were conducted to detect the binding of SETD2 or H3K36me3 with the hypoxia-inducible factor 1, alpha subunit (Hif1a) gene. A sepsis-induced acute lung injury model was constructed via cecal ligation and puncture (CLP). SETD2 was decreased in RAW 264.7 cells stimulated by lipopolysaccharide (LPS). Besides, SETD2 suppressed M1 macrophage polarization and glycolysis caused by LPS. HIF-1α was enhanced in RAW 264.7 cells stimulated by LPS and inversely related to SETD2 expression. In addition, SETD2-catalyzed H3K36me3 bound to the Hif1a gene to modulate HIF-1α expression. Furthermore, Hif1a silencing suppressed Setd2 silencing-induced M1 macrophage polarization and glycolysis in RAW 264.7 cells. Moreover, overexpression of Setd2 inhibited CLP-induced lung injury and M1 macrophage polarization in mice. SETD2 suppressed M1 macrophage polarization and glycolysis via regulating HIF-1α through catalyzing H3K36me3 in sepsis.


Assuntos
Lesão Pulmonar Aguda , Sepse , Animais , Camundongos , Histona Metiltransferases , Subunidade alfa do Fator 1 Induzível por Hipóxia , Lipopolissacarídeos , Macrófagos , Lesão Pulmonar Aguda/etiologia , Glicólise , Sepse/complicações , Histona-Lisina N-Metiltransferase
9.
Front Nutr ; 10: 1188852, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37743928

RESUMO

Background: Research has shown that early exposure to added sugars from table food is related to increased intake of added sugars in later childhood. The earliest window of exposure to added sugars may be in infancy via infant formula. However, beyond the well-established factors of maternal lifestyle and modeling, there is a lack of research examining how exposure to added sugars from infant formula influences infant/toddler added sugar intakes from table foods and sugar sweetened beverages (SSB). Objective: While accounting factors previously associated with infant/toddler added sugar intakes and maternal SSB consumption (proximal measure of maternal modeling), this study aims to examine if there is an association between added sugars in infant formula and added sugar intakes from table foods and SSB during the complementary feeding period. Methods: This is a secondary, cross-sectional analysis using three-day caregiver-reported 24-h dietary recalls in a cohort of infant/toddlers (n = 95), ages 9- < 16 mos., enrolled in a music intervention trial. Hierarchical stepwise regression was used to estimate the association between exposure to added sugars from infant formula and (1) intake of added sugars from table food and (2) SSB consumption. Infant/toddler SSB consumption was transformed to account for distributional properties. We performed incremental F-tests to determine whether the addition of each step improved model fit (R2). Results: Early exposure to added sugars via infant formula was associated with infant/toddler SSB (ΔR2 = 0.044, Finc (1, 87) =6.009, p = 0.016) beyond sociodemographic and maternal SSB consumption, but not with infant/toddler added sugar intakes from table foods (ΔR2 = 0.02, Finc (1, 87) =3.308, p = 0.072). Conclusion: While past studies have identified circumstantial (i.e., sociodemographic), or indirect (i.e., maternal lifestyle and modeling), mechanisms contributing to higher infant/toddler added sugar intakes, this study identifies exposure to added sugars from infant formula as a possible direct mechanism explaining why some infants/toddlers consume more added sugars.

10.
Eur J Med Chem ; 258: 115625, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37429083

RESUMO

Protein arginine methyltransferase 5 (PRMT5) is an epigenetics related enzyme that has been validated as an important therapeutic target for treating various types of cancer. Upregulation of tumor suppressor hnRNP E1 has also been considered as an effective antitumor therapy. In this study, a series of tetrahydroisoquinolineindole hybrids were designed and prepared, and compounds 3m and 3s4 were found to be selective inhibitors of PRMT5 and upregulators of hnRNP E1. Molecular docking studies indicated that compounds 3m occupied the substrate site of PRMT5 and formed essential interactions with amino acid residues. Furthermore, compounds 3m and 3s4 exerted antiproliferative effects against A549 cells by inducing apoptosis and inhibiting cell migration. Importantly, silencing of hnRNP E1 eliminated the antitumor effect of 3m and 3s4 on the apoptosis and migration in A549 cells, suggesting a regulatory relationship between PRMT5 and hnRNP E1. Additionally, compound 3m exhibited high metabolic stability on human liver microsomes (T1/2 = 132.4 min). In SD rats, the bioavailability of 3m was 31.4%, and its PK profiles showed satisfactory AUC and Cmax values compared to the positive control. These results suggest that compound 3m is the first class of dual PRMT5 inhibitor and hnRNP E1 upregulator that deserves further investigation as a potential anticancer agent.


Assuntos
Antineoplásicos , Inibidores Enzimáticos , Humanos , Ratos , Animais , Simulação de Acoplamento Molecular , Ratos Sprague-Dawley , Inibidores Enzimáticos/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Ribonucleoproteínas Nucleares Heterogêneas , Linhagem Celular Tumoral , Proteína-Arginina N-Metiltransferases
11.
Nutrients ; 15(13)2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37447316

RESUMO

Substance use during pregnancy increases the risk for poor developmental outcomes of the offspring, and for substance-dependent mothers, abstaining from substance use during pregnancy is often difficult. Given the addictive nature of many substances, strategies that may mitigate the harmful effects of prenatal substance exposure are important. Prenatal nutrient supplementation is an emerging intervention that may improve developmental outcomes among substance-exposed offspring. We provide a narrative review of the literature on micronutrient and fatty acid supplementation during pregnancies exposed to substance use in relation to offspring developmental outcomes. We first discuss animal models exposed to ethanol during pregnancy with supplementation of choline, zinc, vitamin E, iron, and fatty acids. We follow with human studies of both alcohol- and nicotine-exposed pregnancies with supplementation of choline and vitamin C, respectively. We identified only 26 animal studies on ethanol and 6 human studies on alcohol and nicotine that supplemented nutrients during pregnancy and reported offspring developmental outcomes. There were no studies that examined nutrient supplementation during pregnancies exposed to cannabis, illicit substances, or polysubstance use. Implementations and future directions are discussed.


Assuntos
Efeitos Tardios da Exposição Pré-Natal , Transtornos Relacionados ao Uso de Substâncias , Gravidez , Animais , Feminino , Humanos , Mães , Nicotina/efeitos adversos , Suplementos Nutricionais , Vitaminas , Colina/farmacologia , Etanol/efeitos adversos
12.
Prev Med Rep ; 34: 102254, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37292426

RESUMO

Underrepresentation of pregnant populations in randomized controlled trials of lifestyle change interventions is concerning due to high attrition and providers' limited clinical time. The purpose of this evaluative study was to assess intervention uptake of pregnant individuals enrolled in a three-arm feasibility randomized controlled trial, electronic Monitoring Of Mom's Schedule (eMOMSTM), examining lifestyle changes and lactation support alone, and in combination. Measures included: (1) participation and completion rates, and characteristics of intervention completers versus other eligible participants; and (2) provider experiences with screening and enrolling pregnant participants. Pregnant people with a pre-pregnancy body mass index ≥ 25 and < 35 kg/m2 were enrolled into the eMOMSTM trial between September 2019 - December 2020. Of the 44 consented participants, 35 were randomized, at a participation rate of 35%, and 26 completed the intervention, resulting in a completion rate of 74%. Intervention completers were slightly older and entered the study earlier in pregnancy compared to non-completers. Completers were more likely to be first-time mothers, resided in urban areas, had higher educational attainment, and were slightly more racially and ethnically diverse. A majority of providers reported willingness to participate, believed the study aligned with their organization's mission, and were satisfied with using iPads for screening. Lessons learned to guide recruitment success include use of: (1) designated research staff in combination with physician support; and (2) user-friendly technology to help mitigate time burden on physicians and their staff. Future work should focus on successful strategies to recruit/retain pregnant populations in clinical trials.

13.
Appetite ; 187: 106590, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37148975

RESUMO

BACKGROUND: Parent-child interactions are linked to childhood obesity. Music enrichment programs enhance parent-child interactions and may be a strategy for early childhood obesity prevention. OBJECTIVE: We implemented a 2-year randomized, controlled trial to assess the effects of a music enrichment program (music, n = 45) vs. active play date control (control, n = 45) on parent-child interactional quality and infant weight status. METHODS: Typically developing infants aged 9-to 15-months were enrolled with a primary caregiver in the Music Together ® or a play date program. Participants attended once per week group meetings for 12 months and once per month group meetings for an additional 12 months. Parent-child interaction was measured using the Parent Child Early Relational Assessment (PCERA) at baseline, month 6, 12, and 24. We used a modified intent-to-treat mixed model regression to test group differences in parent-child interactions and Weight for length z-score (zWFL) growth trajectories were modeled. RESULTS: There were significant differential group changes across time for negative affect during feeding (group*month; p = 0.02) in that those parents in the music group significantly decreased their negative affect score compared with the control group from baseline to month 12 (music change = -0.279 ± 0.129; control change = +0.254 ± 0.131.; p = 0.00). Additionally, we also observed significant differential group changes across time for parent intrusiveness during feeding (group*month; p = 0.04) in that those parents in the music group significantly decreased their intrusiveness score compared with the control group from month 6 to month 12 (music change = -0.209 ± 0.121; control change = 0.326 ± 0.141; p = 0.01). We did not find a significant association between any of the changes in parental negative affect and intrusiveness with child zWFL trajectories. CONCLUSION: Participating in a music enrichment program from an early age may promote positive parent-child interactions during feeding, although this improvement in the quality of parent-child interactions during feeding was not associated with weight gain trajectories.


Assuntos
Música , Obesidade Infantil , Criança , Pré-Escolar , Humanos , Lactente , Obesidade Infantil/prevenção & controle , Pais , Relações Pais-Filho , Refeições , Poder Familiar
14.
Appetite ; 186: 106551, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37024055

RESUMO

Snacking starts early in childhood, yet little is known about child versus family influences on snacking during infancy and toddlerhood. This secondary analysis of baseline data examined associations of child characteristics (e.g., appetitive traits, temperament), caregiver feeding decisions, and sociodemographic characteristics with the mean frequency of (times/day) and mean energy from (kcal/day) child snack food intake. Caregivers and their children (ages 9-15 months) were recruited in Buffalo, NY from 2017 to 2019. Caregivers reported on sociodemographics, child appetitive traits (Baby Eating Behaviour Questionnaire), and child temperament (Infant Behavior Questionnaire-Revised). Three 24-h dietary recalls were collected, and USDA food categories were used to categorize snack foods (e.g., cookies, chips, and puffs). Hierarchical multiple linear regression models examined associations of child characteristics (Step 1: age, sex, baseline weight-for-length z-score, appetitive traits, and temperament), caregiver feeding decisions (Step 2: breastfeeding duration and age of solid food introduction), and caregiver sociodemographic characteristics (Step 3: caregiver age, prepregnancy BMI, education, and household size) with mean child snack food intake. Caregivers (n = 141) were on average 32.6 years of age, predominantly white (89.1%), and college-educated (84.2%). Age of solid food introduction (B = -0.21, p = 0.03), prepregnancy BMI (B = 0.03, p = 0.04), and household size (B = 0.23, p = 0.02) were significantly associated with the mean frequency of (times/day) snack food intake, over and above other variables of interest. Child age (B = 15.96, p = 0.002) was significantly associated with mean energy from (kcal/day) snack food intake. Household size (B = 28.51, p = 0.006) was significantly associated with mean energy from (kcal/day) snack food intake, over and above other variables of interest. There were no significant associations of other child characteristics with snack food intake. Findings show that child snack food intake is more closely associated with caregiver feeding decisions and sociodemographic characteristics than child characteristics. TRIAL REGISTRATION: National Institute on Child Health and Human Development, Grant/Award Number R01HD087082-01.


Assuntos
Cuidadores , Tomada de Decisões , Comportamento Alimentar , Lanches , Fatores Sociodemográficos , Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Adulto , Gravidez , Dieta Saudável , Características da Família , New York , Aleitamento Materno , Comportamento Infantil , Comportamento Apetitivo , Inquéritos e Questionários , Ingestão de Alimentos , Ingestão de Energia , Preferências Alimentares
15.
Lipids Health Dis ; 22(1): 37, 2023 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-36906556

RESUMO

BACKGROUND: Previous animal model studies have highlighted a role for cholesterol and its oxidized derivatives (oxysterols) in uterine contractile activity, however, a lipotoxic state associated with hypercholesterolemia may contribute to labor dystocia. Therefore, we investigated if maternal mid-pregnancy cholesterol and oxysterol concentrations were associated with labor duration in a human pregnancy cohort. METHODS: We conducted a secondary analysis of serum samples and birth outcome data from healthy pregnant women (N = 25) with mid-pregnancy fasting serum samples collected at 22-28 weeks of gestation. Serum was analyzed for total-C, HDL-C, and LDL-C by direct automated enzymatic assay and oxysterol profile including 7α-hydroxycholesterol (7αOHC), 7ß-hydroxycholesterol (7ßOHC), 24-hydroxycholesterol (24OHC), 25-hydroxycholesterol (25OHC), 27-hydroxycholesterol (27OHC), and 7-ketocholesterol (7KC) by liquid chromatography-selected ion monitoring-stable isotope dilution-atmospheric pressure chemical ionization-mass spectroscopy. Associations between maternal second trimester lipids and labor duration (minutes) were assessed using multivariable linear regression adjusting for maternal nulliparity and age. RESULTS: An increase in labor duration was observed for every 1-unit increment in serum 24OHC (0.96 min [0.36,1.56], p < 0.01), 25OHC (7.02 min [1.92,12.24], p = 0.01), 27OHC (0.54 min [0.06, 1.08], p < 0.05), 7KC (8.04 min [2.7,13.5], p < 0.01), and total oxysterols (0.42 min [0.18,0.06], p < 0.01]. No significant associations between labor duration and serum total-C, LDL-C, or HDL-C were observed. CONCLUSIONS: In this cohort, mid-pregnancy concentrations of maternal oxysterols (24OHC, 25OHC, 27OHC, and 7KC) were positively associated with labor duration. Given the small population and use of self-reported labor duration, subsequent studies are required for confirmation.


Assuntos
Hipercolesterolemia , Oxisteróis , Animais , Humanos , Feminino , Gravidez , Projetos Piloto , LDL-Colesterol , Hidroxicolesteróis , Família
16.
Appetite ; 185: 106525, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36898582

RESUMO

This study sought to identify sucking profiles among healthy, full-term infants and assess their predictive value for future weight gain and eating behaviors. Pressure waves of infant sucking were captured during a typical feeding at age 4 months and quantified via 14 metrics. Anthropometry was measured at 4 and 12 months, and eating behaviors were measured by parent report via the Children's Eating Behavior Questionnaire-Toddler (CEBQ-T) at 12 months. Sucking profiles were created using a clustering approach on the pressure wave metrics, and utility of these profiles was assessed for predicting which infants will have weight-for-age (WFA) percentile changes from ages 4-12 months that exceed thresholds of 5, 10, and 15 percentiles, and for estimating each CEBQ-T subscale score. Among 114 infants, three sucking profiles were identified: Vigorous (51%), Capable (28%), and Leisurely (21%). Sucking profiles were found to improve estimation of change in WFA from 4 to 12 months and 12-month maternal-reported eating behaviors above infant sex, race/ethnicity, birthweight, gestational age, and pre-pregnancy body mass index alone. Infants with a Vigorous sucking profile gained significantly more weight during the study period than infants with a Leisurely profile. Infant sucking characteristics may aid in predicting which infants may be at greater risk of obesity, and therefore sucking profiles deserve more investigation.


Assuntos
Ingestão de Alimentos , Comportamento Alimentar , Feminino , Gravidez , Lactente , Humanos , Aumento de Peso , Obesidade , Índice de Massa Corporal
17.
Front Microbiol ; 14: 1138830, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36922969

RESUMO

Introduction: Dimeric natural products are widespread in plants and microorganisms, which usually have complex structures and exhibit greater bioactivities than their corresponding monomers. In this study, we report five new dimeric tetrahydroxanthones, aculeaxanthones A-E (4-8), along with the homodimeric tetrahydroxanthone secalonic acid D (1), chrysoxanthones B and C (2 and 3), and 4-4'-secalonic acid D (9), from different fermentation batches of the title fungus. Methods: A part of the culture was added to a total of 60 flasks containing 300 ml each of number II fungus liquid medium and culture 4 weeks in a static state at 28˚C. The liquid phase (18 L) and mycelia was separated from the fungal culture by filtering. A crude extract was obtained from the mycelia by ultrasound using acetone. To obtain a dry extract (18 g), the liquid phase combined with the crude extract were further extracted by EtOAc and concentrated in vacuo. The MIC of anaerobic bacteria was examined by a broth microdilution assay. To obtain MICs for aerobic bacteria, the agar dilution streak method recommended in Clinical and Laboratory Standards Institute document (CLSI) M07-A10 was used. Compounds 1-9 was tested against the Bel-7402, A-549 and HCT-116 cell lines according to MTT assay. Results and Discussion: The structures of these compounds were elucidated on the base of 1D and 2D NMR and HR-ESIMS data, and the absolute configurations of the new xanthones 4-8 were determined by conformational analysis and time-dependent density functional theory-electronic circular dichroism (TDDFT-ECD) calculations. Compounds 1-9 were tested for cytotoxicity against the Bel-7402, A549, and HCT-116 cancer cell lines. Of the dimeric tetrahydroxanthone derivatives, only compound 6 provided cytotoxicity effect against Bel-7402 cell line (IC50, 1.96 µM). Additionally, antimicrobial activity was evaluated for all dimeric tetrahydroxanthones, including four Gram-positive bacteria including Enterococcus faecium ATCC 19434, Bacillus subtilis 168, Staphylococcus aureus ATCC 25923 and MRSA USA300; four Gram-negative bacteria, including Helicobacter pylori 129, G27, as well as 26,695, and multi drug-resistant strain H. pylori 159, and one Mycobacterium M. smegmatis ATCC 607. However, only compound 1 performed activities against H. pylori G27, H. pylori 26695, H. pylori 129, H. pylori 159, S. aureus USA300, and B. subtilis 168 with MIC values of 4.0, 4.0, 2.0, 2.0, 2.0 and 1.0 µg/mL, respectively.

18.
Pediatr Obes ; 18(5): e13010, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36734672

RESUMO

BACKGROUND: Although the association between prenatal tobacco exposure and child obesity risk is well-established, less is known about co-exposure to tobacco and cannabis. OBJECTIVE: Determine the relation between prenatal substance co-exposure and obesity risk. METHODS: In a diverse sample of pregnant women, we examined the association between prenatal substance exposure (tobacco-only and co-exposure) and child BMI (kg/m2 ) trajectories from birth to mid-childhood (n = 262), overweight/obese status based on BMI percentiles from toddlerhood (24 months) to mid-childhood (9-12 years), and adiposity outcomes at mid-childhood (fat mass [kg], fat mass [%] and fat free mass [kg]; n = 128). Given that the major goal of this study was to examine the associations between prenatal substance exposure and child outcomes, we oversampled pregnant women for substance use (with tobacco as the primary focus). RESULTS: Multilevel models demonstrated that children in both exposure groups had a steeper increase in BMI trajectory from birth to mid-childhood and among co-exposed children, girls had a steeper increase than boys. Odds ratio of having obesity by mid-childhood was 12 times higher among those co-exposed than non-exposed. Co-exposure led to significantly greater fat mass and fat mass % compared with no exposure, but exposure to only tobacco was no different than no exposure. CONCLUSIONS: Results highlight potentiating effects of cannabis exposure in the context of maternal tobacco use in pregnancy on obesity risk and the importance of multi-method assessments of obesity.


Assuntos
Cannabis , Obesidade Infantil , Efeitos Tardios da Exposição Pré-Natal , Criança , Masculino , Gravidez , Feminino , Humanos , Cannabis/efeitos adversos , Nicotiana/efeitos adversos , Obesidade Infantil/epidemiologia , Obesidade Infantil/etiologia , Sobrepeso , Adiposidade , Índice de Massa Corporal , Efeitos Tardios da Exposição Pré-Natal/epidemiologia
19.
Nat Prod Res ; : 1-6, 2023 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-36787196

RESUMO

Two new monoterpenoid indole alkaloids, named taberibogines E and F (1 and 2), together with three known ones (3-5) were isolated from the stems of Tabernaemontana bovina Lour (Apocynaceae). Their structures including absolute configurations were elucidated from a combination of NMR and HRESIMS data and NMR calculations as well as DP4+ probability analyses. Compounds 1 and 2 exhibited inhibitory effects on LPS-induced nitric oxide (NO) production in RAW 264.7 macrophages.

20.
Public Health Nutr ; 26(1): 182-189, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35581172

RESUMO

OBJECTIVE: To quantify the change in availability of hyper-palatable foods (HPF) in the US foods system over 30 years (1988-2018). DESIGN: Three datasets considered representative of the US food system were used in analyses to represent years 1988, 2001 and 2018. A standardised definition from Fazzino et al. (2019) that specifies combinations of nutrients was used to identify HPF. SETTING: Analysis of food-item level data was conducted. Differences in the prevalence of HPF were characterised by Cochran's Q and McNemar's tests. Generalised linear mixed models with a fixed effect for time and random intercept for food item estimated change in the likelihood that a food was classified as hyper-palatable over time. PARTICIPANTS: No participant data were used. RESULTS: The prevalence of HPF increased 20 % from 1988 to 2018 (from 49 % to 69 %; P < 0·0001). The most prominent difference was in the availability of HPF high in fat and Na, which evidenced a 17 % higher prevalence in 2018 compared with 1988 (P < 0·0001). Compared with 1988, the same food items were >2 times more likely to be hyper-palatable in 2001, and the same food items were >4 times more likely to be classified as hyper-palatable in 2018 compared with 1988 (P values < 0·0001). CONCLUSIONS: The availability of HPF in the US food system increased substantially over 30 years. Existing food products in the food system may have been reformulated over time to enhance their palatability.


Assuntos
Alimentos , Nutrientes , Humanos
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