Aldehyde Oxidase Contributes to All-Trans-Retinoic Acid Biosynthesis in Human Liver.

All-trans-retinoic acid (atRA) is a critical endogenous signaling molecule. atRA is predominantly synthesized from retinaldehyde by aldehyde dehydrogenase 1A1 (ALDH1A1), but aldehyde oxidase (AOX) may also contribute to atRA biosynthesis. The goal of this study was to test the hypothesis that AOX contributes significantly to atRA formation in human liver. Human recombinant AOX formed atRA from retinaldehyde (Km ∼1.5 ± 0.4 µM; kcat ∼3.6 ± 2.0 minute-1). In human liver S9 fractions (HLS9), atRA formation was observed in the absence of NAD+, suggesting AOX contribution to atRA formation. In the presence of NAD+, Eadie-Hofstee plots of atRA formation in HLS9 indicated that two enzymes contributed to atRA formation. The two enzymes were identified as AOX and ALDH1A1 based on inhibition of atRA formation by AOX inhibitor hydralazine (20%-50% inhibition) and ALDH1A1 inhibitor WIN18,446 (50%-80%inhibition). The expression of AOX in HLS9 was 9.4-24 pmol mg-1 S9 protein, whereas ALDH1A1 expression was 156-285 pmol mg-1 S9 protein measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) quantification of signature peptides. The formation velocity of atRA in the presence of NAD+ correlated significantly with the expression of ALDH1A1 and AOX protein. Taken together, the data show that both AOX and ALDH1A1 contribute to atRA biosynthesis in the human liver, with ALDH1A1 being the high-affinity, low-capacity enzyme and AOX being the low-affinity, high-capacity enzyme. The results suggest that in the case of ALDH1A dysfunction or excess vitamin A, AOX may play an important role in regulating hepatic vitamin A homeostasis and that inhibition of AOX may alter atRA biosynthesis and signaling. SIGNIFICANCE STATEMENT: This study provides direct evidence to show that human AOX converts retinaldehyde to atRA and contributes to hepatic atRA biosynthesis. The finding that AOX may be responsible for 20%-50% of overall hepatic atRA formation suggests that alterations in AOX activity via drug-drug interactions, genetic polymorphisms, or disease states may impact hepatic atRA concentrations and signaling and alter vitamin A homeostasis.

Evening Chronotype Is Associated with Poorer Habitual Diet in US Women, with Dietary Energy Density Mediating a Relation of Chronotype with Cardiovascular Health.

BACKGROUND: An innate preference for later timing of sleep and activity, termed evening chronotype, is linked to poorer cardiovascular health (CVH). However, associations of chronotype with specific health behaviors in US women are not well characterized. Of particular interest is habitual diet, because <1% of US adults meet recommendations for a healthful diet. OBJECTIVES: We aimed to evaluate cross-sectional and prospective associations of chronotype with diet quantity and quality in US women, and to assess whether dietary energy density (ED), a robust predictor of cardiometabolic outcomes, mediates an established chronotype-CVH relation. METHODS: Data were collected from participants in the AHA Go Red for Women Strategically Focused Research Network cohort (aged 20-76 y; 61% racial/ethnic minority) at baseline (n = 487) and 1-y follow-up (n = 432). Chronotype (evening compared with morning/intermediate) and habitual diet were ascertained from the Morningness-Eveningness Questionnaire and an FFQ, respectively. Multivariable-adjusted linear regression models evaluated cross-sectional and prospective associations of chronotype with diet. Causal mediation analyses assessed whether dietary ED mediated a relation between chronotype and CVH, quantified using AHA Life's Simple 7 score, derived from clinical measurements and validated assessments of CVH components. RESULTS: Evening compared with morning/intermediate chronotype was associated with poorer diet quality, including lower intakes of plant protein (cross-sectional: ß = -0.63 ± 0.24, P < 0.01; prospective: ß = -0.62 ± 0.26, P = 0.01), fiber (cross-sectional: ß = -2.19 ± 0.65, P < 0.001; prospective: ß = -2.39 ± 0.66, P < 0.001), and fruits and vegetables (cross-sectional: ß = -1.24 ± 0.33, P < 0.001; prospective: ß = -1.15 ± 0.36, P = 0.001). Evening chronotype was also associated with higher dietary ED at baseline (ß = 0.20 ± 0.05, P = 0.001) and 1 y (ß = 0.19 ± 0.06, P = 0.001). Dietary ED was a partial mediator of the association between evening chronotype and poorer CVH (24.6 ± 9.1%, P < 0.01). CONCLUSIONS: Evening chronotype could contribute to unhealthful dietary patterns in US women, with higher dietary ED partially mediating the relation between eveningness and poorer CVH. Behavioral interventions to reduce dietary ED might mitigate cardiovascular disease risk in women with evening chronotype.

History of Weight Cycling Is Prospectively Associated With Shorter and Poorer-Quality Sleep and Higher Sleep Apnea Risk in Diverse US Women.

BACKGROUND: Poor sleep and history of weight cycling (HWC) are associated with worse cardiovascular health, yet limited research has evaluated the association between HWC and poor sleep patterns. METHODS: The American Heart Association Go Red for Women Strategically Focused Research Network cohort at Columbia University (n = 506; mean age, 37 ± 15.7 years; 61% racial/ethnic minority) was used to evaluate the cross-sectional associations of HWC and sleep at baseline and the prospective associations of HWC from baseline with sleep at the 1-year visit. History of weight cycling, defined as losing and gaining 10 lb or more at least once (excluding pregnancy), was self-reported. Sleep duration, sleep quality, insomnia severity, and obstructive sleep apnea risk were assessed using the validated Pittsburgh Sleep Quality Index, Insomnia Severity Index, and Berlin questionnaires. Linear and logistic regression models, adjusted for age, race/ethnicity, education, health insurance status, pregnancy history, and menopausal status, were used to evaluate the relation of HWC with sleep. RESULTS: Most women reported 1 or more episodes of weight cycling (72%). In linear models of cross-sectional and prospective data, each additional weight cycling episode was related to shorter sleep duration, poorer sleep quality, longer sleep onset latency, greater insomnia severity, more sleep disturbances, lower sleep efficiency, and higher sleep medication use frequency. In the logistic models, HWC (≥1 vs 0 episodes) was associated with greater odds for short sleep, poor sleep quality, long sleep onset latency (≥26 minutes), high obstructive sleep apnea risk, and sleep efficiency lower than 85%. CONCLUSION: History of weight cycling predicted poor sleep among women, suggesting that weight maintenance may represent an important strategy to promote sleep health. The potential bidirectional relationship between HWC and sleep requires further investigation.

Therapeutic potential of Angelica sinensis in addressing organ fibrosis: A comprehensive review.

Fibrosis-related diseases (FRD) include conditions like myocardial fibrosis, pulmonary fibrosis, hepatic fibrosis, renal fibrosis, and others. The impact of fibrosis can be severe, causing organ dysfunction, reduced functionality, and even organ failure, leading to significant health issues. Currently, there is a lack of effective modern anti-fibrosis drugs in clinical practice. However, Chinese medicine has a certain beneficial effect on the treatment of such diseases. Angelica sinensis, with its considerable medicinal value, has garnered attention for its anti-fibrosis properties in recent investigations. In the past few years, there has been a growing number of experimental inquiries into the impact of angelica polysaccharide (ASP), angelica water extract, angelica injection, and angelica compound preparation on fibrosis-associated ailments, piquing the interest of researchers. This paper aims to consolidate recent advances in the study of Angelica sinensis for the treatment of fibrosis-related disorders, offering insights for prospective investigations. Literature retrieval included core electronic databases, including Baidu Literature, CNKI, Google-Scholar, PubMed, and Web of Science. The applied search utilized specified keywords to extract relevant information on the pharmacological and phytochemical attributes of plants. The investigation revealed that Angelica sinensis has the potential to impede the advancement of fibrotic diseases by modulating inflammation, oxidative stress, immune responses, and metabolism. ASP, Angelica sinensis extract, Angelica sinensis injection, and Angelica sinensis compound preparation were extensively examined and discussed. These constituents demonstrated significant anti-fibrosis activity. In essence, this review seeks to gain a profound understanding of the role of Angelica sinensis in treating fiber-related diseases. Organ fibrosis manifests in nearly all tissues and organs, posing a critical challenge to global public health due to its widespread occurrence, challenging early diagnosis, and unfavorable prognosis. Despite its prevalence, therapeutic options are limited, and their efficacy is constrained. Over the past few years, numerous studies have explored the protective effects of traditional Chinese medicine on organ fibrosis, with Angelica sinensis standing out as a multifunctional natural remedy. This paper provides a review of organ fibrosis pathogenesis and summarizes the recent two decades' progress in treating fibrosis in various organs such as the liver, lung, kidney, and heart. The review highlights the modulation of relevant signaling pathways through multiple targets and channels by the effective components of Angelica sinensis, whether used as a single medicine or in compound prescriptions.

A nationally representative study on discharge against medical advice among those living with epilepsy.

PURPOSE: Discharges against medical advice (DAMA) are associated with adverse patient outcomes among those with epilepsy. Our goal was to examine trends and factors associated with DAMA among those living with epilepsy. METHODS: A retrospective cross-sectional study was performed using the 2003-2014 National Inpatient Sample database. ICD-9-CM diagnosis codes were used to identify admissions of patients with epilepsy. Following outcomes were examined among epilepsy patients: proportion and predictors of DAMA, 12-year DAMA trends and causes of admissions. RESULTS: In 2014, of the 187,850 admissions in patients with epilepsy, 3783 (2.01 %) were DAMA. Male sex, Black race, younger age, lower household income, Medicaid/self-pay/other as primary payer, lower Elixhauser comorbidities index, weekend admission, non-elective admission, hospital in northeast region, and urban nonteaching hospital were all associated with DAMA. There was a significant increase in the proportion of DAMA in people with epilepsy from 2003 to 2014 (1.13 %-2.01 %, p < 0.0001). The top reasons of admissions for epilepsy patients who were DAMA were: epilepsy/convulsion (21.02 %), alcohol- (8.86 %) and substance-related disorders (3.75 %), and diabetes mellitus with complications (3.33 %). CONCLUSIONS: Our findings provide opportunities to understand DAMA among those living with epilepsy, which is more prevalent in socially-disadvantaged populations. This study highlight the need to develop electronic medical records-based prediction tools that could be used at the point-of-care to enable the early identification of people at risk for DAMA, since it is often likely preventable. Future mixed methods studies are recommended to identify facilitators of DAMA and strategies for prevention.

A Mediterranean Dietary Pattern Predicts Better Sleep Quality in US Women from the American Heart Association Go Red for Women Strategically Focused Research Network.

Consumption of a Mediterranean diet has been linked to better sleep health in older, European populations. However, whether this dietary pattern is predictive of sleep quality in US women, a group prone to poor sleep, is unknown. This prospective cohort study of 432 US women (20-76 y; 60% racial/ethnic minority) evaluated whether compliance with a Mediterranean diet at baseline predicted sleep quality at 1-y follow-up. Alternate Mediterranean (aMed) diet scores and habitual sleep quality were computed from the validated Block Brief Food Frequency Questionnaire and Pittsburgh Sleep Quality Index (PSQI), respectively. Linear regression models evaluated prospective associations of the aMed diet pattern and its components with measures of sleep quality, after adjustment for age, BMI, race/ethnicity, education, and health insurance status. Higher baseline aMed scores were associated with lower PSQI scores (ß = -0.30 ± 0.10, p < 0.01), indicative of better sleep quality, higher sleep efficiency (ß = 1.20 ± 0.35, p < 0.001), and fewer sleep disturbances (ß = -0.30 ± 0.12, p = 0.01) at 1-y. Fruit and vegetable consumption also predicted lower PSQI scores, higher sleep efficiency and fewer sleep disturbances (all p < 0.05). Higher legume intake predicted better sleep efficiency (ß = 1.36 ± 0.55, p = 0.01). These findings suggest that adherence to a Mediterranean diet pattern should be evaluated as a strategy to promote sleep quality in US women.