Title: Today's Kids May Be Destined for Adult Heart Disease
Category: Health News
Created: 5/4/2012 10:05:00 AM
Last Editorial Review: 5/4/2012 12:00:00 AM

Title: A Heart Disease Veteran at Just Age 12
Category: Health News
Created: 5/4/2012 10:05:00 AM
Last Editorial Review: 5/4/2012 12:00:00 AM

Title: Positive Thinking, Persistence Pay Off in Job Search: Study
Category: Health News
Created: 5/3/2012 8:05:00 PM
Last Editorial Review: 5/4/2012 12:00:00 AM

Title: Migraines More Likely for People With Celiac Disease, Study Says
Category: Health News
Created: 5/3/2012 4:05:00 PM
Last Editorial Review: 5/4/2012 12:00:00 AM

Title: Researchers Rejuvenate Blood-Forming Stem Cells in Mice
Category: Health News
Created: 5/3/2012 2:05:00 PM
Last Editorial Review: 5/4/2012 12:00:00 AM

Title: Study Debunks Lyme Disease-Autism Link
Category: Health News
Created: 4/30/2013 12:35:00 PM
Last Editorial Review: 5/1/2013 12:00:00 AM

Title: At-Home Drug Errors Common for Kids With Cancer, Research Shows
Category: Health News
Created: 5/3/2013 10:35:00 AM
Last Editorial Review: 5/3/2013 12:00:00 AM

Title: Muhammad Ali's Daughter Champions Fight Against Parkinson's Disease
Category: Health News
Created: 5/3/2013 10:35:00 AM
Last Editorial Review: 5/3/2013 12:00:00 AM

Title: Ex-Baseball Star Kirk Gibson Has Parkinson's Disease
Category: Health News
Created: 4/28/2015 12:00:00 AM
Last Editorial Review: 4/29/2015 12:00:00 AM

Title: Put Car Seat on Your Summer-Travel Checklist
Category: Health News
Created: 4/29/2015 12:00:00 AM
Last Editorial Review: 4/30/2015 12:00:00 AM

Title: Let Safety Bloom in Your Garden This Season
Category: Health News
Created: 4/22/2016 12:00:00 AM
Last Editorial Review: 4/25/2016 12:00:00 AM

Title: Brain Research Fuels New Migraine Treatments
Category: Health News
Created: 5/3/2017 12:00:00 AM
Last Editorial Review: 5/3/2017 12:00:00 AM

Title: Climate Change May Worsen Sneezin' Season
Category: Health News
Created: 5/2/2017 12:00:00 AM
Last Editorial Review: 5/3/2017 12:00:00 AM

Title: More Cases of Tick-Borne Powassan Disease Expected in U.S. This Year
Category: Health News
Created: 5/3/2017 12:00:00 AM
Last Editorial Review: 5/4/2017 12:00:00 AM

Title: Health Tip: Prevent Hand, Foot and Mouth Disease
Category: Health News
Created: 4/30/2018 12:00:00 AM
Last Editorial Review: 4/30/2018 12:00:00 AM

Title: Health Tip: Recognizing Lung Disease
Category: Health News
Created: 5/2/2018 12:00:00 AM
Last Editorial Review: 5/2/2018 12:00:00 AM

Title: Health Tip: Understanding Diabetic Eye Disease
Category: Health News
Created: 5/4/2018 12:00:00 AM
Last Editorial Review: 5/4/2018 12:00:00 AM

Title: Many Women With Heart Disease Falling Short on Exercise
Category: Health News
Created: 4/26/2019 12:00:00 AM
Last Editorial Review: 4/29/2019 12:00:00 AM

Title: Health Tip: Managing Nausea for Cancer Patients
Category: Health News
Created: 4/30/2019 12:00:00 AM
Last Editorial Review: 4/30/2019 12:00:00 AM

Title: Many Cardiologists Ill-Equipped to Treat Heart Disease in Cancer Survivors
Category: Health News
Created: 4/29/2019 12:00:00 AM
Last Editorial Review: 4/30/2019 12:00:00 AM

Title: AHA News: Predicting Heart Disease, Stroke Could Be as Easy as a Blood Test
Category: Health News
Created: 4/29/2019 12:00:00 AM
Last Editorial Review: 4/30/2019 12:00:00 AM

Title: Job Strain May Boost Odds of Serious Artery Disease
Category: Health News
Created: 4/28/2020 12:00:00 AM
Last Editorial Review: 4/28/2020 12:00:00 AM

Title: Researchers Report First U.S. Dog With Coronavirus
Category: Health News
Created: 4/29/2020 12:00:00 AM
Last Editorial Review: 4/30/2020 12:00:00 AM

Title: COVID-19 May Be Causing Kawasaki Disease Heart Condition in Kids
Category: Health News
Created: 4/29/2020 12:00:00 AM
Last Editorial Review: 4/30/2020 12:00:00 AM

Title: Pain Is a Growing Threat to the Nation's Surgeons, New Research Reveals
Category: Health News
Created: 4/1/2020 12:00:00 AM
Last Editorial Review: 4/2/2020 12:00:00 AM

Title: New Drug Could Help Stop Blindness From Thyroid Eye Disease
Category: Health News
Created: 1/22/2020 12:00:00 AM
Last Editorial Review: 1/23/2020 12:00:00 AM

Title: AHA News: Traumatic Childhood Increases Lifelong Risk for Heart Disease, Early Death
Category: Health News
Created: 4/28/2020 12:00:00 AM
Last Editorial Review: 4/29/2020 12:00:00 AM

Title: AHA News: Statins May Do Double Duty on Heart Disease and Cancer
Category: Health News
Created: 1/6/2020 12:00:00 AM
Last Editorial Review: 1/7/2020 12:00:00 AM

You can now find embargoed articles and their corresponding PMCIDs through a recently released search option in the PMC Entrez database. Using the “Limits” tab, click in the field, “Show both free and embargoed articles” and refine your search by journal, author, date, article type, and/or tag term, as needed. Once you’re on the summary page, click on the “embargoed” tab at the top to find the articles in this category. You can then find the PMCID and date of availability at the bottom of the article citation, as indicated in the example below. Note: The PMC search option only includes articles with an initial embargo of up to 12 months. Articles with an embargo greater than 12 months are not compliant with the NIH Public Access Policy and will appear in search results only when the full text is free in PMC. For more information, see the article in the September-October issue of the NLM Technical Bulletin.

You can now search for Open Access articles that have certain types of licenses, by using special filters in both PMC and PubMed. These filters are based on license information that is provided to PMC by publishers and other content providers, as encoded by machine-readable identifiers in the source XML of each article. For more information, see our updated Open Access Subset page.

As of August 2016, PMC is home to four million articles! To make this wealth of full-text content easier to navigate, PMC has rolled out a few updates:

1) Search Result Filters
On all search results pages, you will now see filters (similar to PubMed’s filters) on the left-hand side that allow you to filter your results by article attributes, publication date, research funder, and search fields. These filters replace the Limits page and allow you to more readily:

• find open access articles (PMC has more than 1.35 million open access articles that can be reused according to their license statements),
• explore PMC’s rich historical content from NLM's back issue digitization project,
• browse research supported by PMC-participating funding organizations (click "Customize" to view additional funder options),
• and much more.

You can now also quickly add articles that are under a 12-month or less embargo in PMC to your search results by selecting the “Include embargoed articles” filter option under Text Availability. See the PMC User Guide for more information on these filters.

2) Reference List Display
Using related article data available in PMC, articles that cite papers that have been either retracted or named in a Findings of Research Misconduct issued by the HHS Office of Research Integrity and not yet retracted will now include a red hyperlink to the relevant notice directly from the article’s reference list. This update will help users more easily identify post-publication updates to existing research.

Since March 2016, the NIH Manuscript Submission (NIHMS) system has added support for researchers from the following federal agencies to deposit in PMC any manuscripts that fall under the agency’s public access policy:

• Assistant Secretary for Preparedness and Response (ASPR/HHS; intramural only at this time)
• Environmental Protection Agency (EPA; intramural only at this time)
• National Aeronautics and Space Administration (NASA; intramural/civil servants and grantees)

Manuscript deposit support for all Administration for Community Living (ACL/HHS) researchers will be available in NIHMS by October 2017 and for Department of Homeland Security researchers in early 2018.

Additionally, the Bill & Melinda Gates Foundation Open Access Policy now requires their grantees to make their published research results available in PMC immediately upon publication under a Creative Commons Attribution (CC-BY) license. Manuscript deposit support is not provided in NIHMS for Gates-funded researchers; rather the final published version of any Gates-funded article is to be deposited directly to PMC by the publisher or a funder-supported data provider without author involvement. More information on this open access policy is available on the Gates Foundation website.

PMC will continue to update the list of participating funding agencies at Public Access and PMC as support is implemented.

Title: Peyronie's Disease (Curvature of the Penis)
Category: Diseases and Conditions
Created: 11/14/2002 12:00:00 AM
Last Editorial Review: 12/5/2019 12:00:00 AM

Title: Fabry Disease
Category: Diseases and Conditions
Created: 12/31/1997 12:00:00 AM
Last Editorial Review: 4/2/2020 12:00:00 AM

Title: Researchers Move Toward Once-Yearly Treatment for HIV
Category: Health News
Created: 4/30/2020 12:00:00 AM
Last Editorial Review: 5/1/2020 12:00:00 AM

Title: Research Finds Contagious Staph in Lupus-Related Skin Rashes
Category: Health News
Created: 2/28/2020 12:00:00 AM
Last Editorial Review: 3/2/2020 12:00:00 AM

Title: Some NFL Players May Be Misdiagnosed With Brain Disease: Study
Category: Health News
Created: 4/27/2020 12:00:00 AM
Last Editorial Review: 4/28/2020 12:00:00 AM

Title: Welcome to the 'Smart Toilet' That Can Spot Disease
Category: Health News
Created: 4/17/2020 12:00:00 AM
Last Editorial Review: 4/17/2020 12:00:00 AM

Title: Flu Season That's Sickened 26 Million May Be at Its Peak
Category: Health News
Created: 2/21/2020 12:00:00 AM
Last Editorial Review: 2/21/2020 12:00:00 AM

Title: Could the Weather Swings of Climate Change Make Flu Seasons Worse?
Category: Health News
Created: 2/20/2020 12:00:00 AM
Last Editorial Review: 2/21/2020 12:00:00 AM

Title: Flu Vaccine Making a Strong Showing This Season
Category: Health News
Created: 2/20/2020 12:00:00 AM
Last Editorial Review: 2/21/2020 12:00:00 AM

Membrane-bound proteins have been proposed to mediate the transport of long-chain FA (LCFA) transport through the plasma membrane (PM). These proposals are based largely on reports that PM transport of LCFAs can be blocked by a number of enzymes and purported inhibitors of LCFA transport. Here, using the ratiometric pH indicator (2',7'-bis-(2-carboxyethyl)-5-(and-6-)-carboxyfluorescein and acrylodated intestinal FA-binding protein-based dual fluorescence assays, we investigated the effects of nine inhibitors of the putative FA transporter protein CD36 on the binding and transmembrane movement of LCFAs. We particularly focused on sulfosuccinimidyl oleate (SSO), reported to be a competitive inhibitor of CD36-mediated LCFA transport. Using these assays in adipocytes and inhibitor-treated protein-free lipid vesicles, we demonstrate that rapid LCFA transport across model and biological membranes remains unchanged in the presence of these purported inhibitors. We have previously shown in live cells that CD36 does not accelerate the transport of unesterified LCFAs across the PM. Our present experiments indicated disruption of LCFA metabolism inside the cell within minutes upon treatment with many of the "inhibitors" previously assumed to inhibit LCFA transport across the PM. Furthermore, using confocal microscopy and a specific anti-SSO antibody, we found that numerous intracellular and PM-bound proteins are SSO-modified in addition to CD36. Our results support the hypothesis that LCFAs diffuse rapidly across biological membranes and do not require an active protein transporter for their transmembrane movement.

Geranylgeranoic acid (GGA) originally was identified in some animals and has been developed as an agent for preventing second primary hepatoma. We previously have also identified GGA as an acyclic diterpenoid in some medicinal herbs. Recently, we reported that in human hepatoma-derived HuH-7 cells, GGA is metabolically labeled from ¹³C-mevalonate. Several cell-free experiments have demonstrated that GGA is synthesized through geranylgeranial by oxygen-dependent oxidation of geranylgeraniol (GGOH), but the exact biochemical events giving rise to GGA in hepatoma cells remain unclear. Monoamine oxidase B (MOAB) has been suggested to be involved in GGOH oxidation. Here, using two human hepatoma cell lines, we investigated whether MAOB contributes to GGA biosynthesis. Using either HuH-7 cell lysates or recombinant human MAOB, we found that: 1) the MAO inhibitor tranylcypromine dose-dependently downregulates endogenous GGA levels in HuH-7 cells; and 2) siRNA-mediated MAOB silencing reduces intracellular GGA levels in HuH-7 and Hep3B cells. Unexpectedly, however, CRISPR/Cas9-generated MAOB-KO human hepatoma Hep3B cells had GGA levels similar to those in MAOB-WT cells. A sensitivity of GGA levels to siRNA-mediated MAOB downregulation was recovered when the MAOB-KO cells were transfected with a MAOB-expression plasmid, suggesting that MAOB is the enzyme primarily responsible for GGOH oxidation and that some other latent metabolic pathways may maintain endogenous GGA levels in the MAOB-KO hepatoma cells. Along with the previous findings, these results provide critical insights into the biological roles of human MAOB and provide evidence that hepatic MAOB is involved in endogenous GGA biosynthesis via GGOH oxidation.

Many clinical studies and epidemiological investigations have clearly demonstrated that women are twice as likely to develop cholesterol gallstones as men, and oral contraceptives and other estrogen therapies dramatically increase that risk. Further, animal studies have revealed that estrogen promotes cholesterol gallstone formation through the estrogen receptor (ER) α, but not ERβ, pathway. More importantly, some genetic and pathophysiological studies have found that G protein-coupled estrogen receptor (GPER) 1 is a new gallstone gene, Lith18, on chromosome 5 in mice and produces additional lithogenic actions, working independently of ERα, to markedly increase cholelithogenesis in female mice. Based on computational modeling of GPER, a novel series of GPER-selective antagonists were designed, synthesized, and subsequently assessed for their therapeutic effects via calcium mobilization, cAMP, and ERα and ERβ fluorescence polarization binding assays. From this series of compounds, one new compound, 2-cyclohexyl-4-isopropyl-N-(4-methoxybenzyl)aniline (CIMBA), exhibits superior antagonism and selectivity exclusively for GPER. Furthermore, CIMBA reduces the formation of 17β-estradiol-induced gallstones in a dose-dependent manner in ovariectomized mice fed a lithogenic diet for 8 weeks. At 32 μg/day/kg CIMBA, no gallstones are found, even in ovariectomized ERα (^–/–) mice treated with 6 μg/day 17β-estradiol and fed the lithogenic diet for 8 weeks. In conclusion, CIMBA treatment protects against the formation of estrogen-induced cholesterol gallstones by inhibiting the GPER signaling pathway in female mice. CIMBA may thus be a new agent for effectively treating cholesterol gallstone disease in women.­

The formation and properties of liquid-ordered (Lo) lipid domains (rafts) in the plasma membrane are still poorly understood. This limits our ability to manipulate ordered lipid domain-dependent biological functions. Giant plasma membrane vesicles (GPMVs) undergo large-scale phase separations into coexisting Lo and liquid-disordered lipid domains. However, large-scale phase separation in GPMVs detected by light microscopy is observed only at low temperatures. Comparing Förster resonance energy transfer-detected versus light microscopy-detected domain formation, we found that nanodomains, domains of nanometer size, persist at temperatures up to 20°C higher than large-scale phases, up to physiologic temperature. The persistence of nanodomains at higher temperatures is consistent with previously reported theoretical calculations. To investigate the sensitivity of nanodomains to lipid composition, GPMVs were prepared from mammalian cells in which sterol, phospholipid, or sphingolipid composition in the plasma membrane outer leaflet had been altered by cyclodextrin-catalyzed lipid exchange. Lipid substitutions that stabilize or destabilize ordered domain formation in artificial lipid vesicles had a similar effect on the thermal stability of nanodomains and large-scale phase separation in GPMVs, with nanodomains persisting at higher temperatures than large-scale phases for a wide range of lipid compositions. This indicates that it is likely that plasma membrane nanodomains can form under physiologic conditions more readily than large-scale phase separation. We also conclude that membrane lipid substitutions carried out in intact cells are able to modulate the propensity of plasma membranes to form ordered domains. This implies lipid substitutions can be used to alter biological processes dependent upon ordered domains.

The autosomal dominant disorder Schnyder corneal dystrophy (SCD) is caused by mutations in UbiA prenyltransferase domain-containing protein-1 (UBIAD1), which uses geranylgeranyl pyrophosphate (GGpp) to synthesize the vitamin K₂ subtype menaquinone-4 (MK-4). SCD is characterized by opacification of the cornea, owing to aberrant build-up of cholesterol in the tissue. We previously discovered that sterols stimulate association of UBIAD1 with ER-localized HMG-CoA reductase, which catalyzes a rate-limiting step in the synthesis of cholesterol and nonsterol isoprenoids, including GGpp. Binding to UBIAD1 inhibits sterol-accelerated ER-associated degradation (ERAD) of reductase and permits continued synthesis of GGpp in cholesterol-replete cells. GGpp disrupts UBIAD1-reductase binding and thereby allows for maximal ERAD of reductase as well as ER-to-Golgi translocation of UBIAD1. SCD-associated UBIAD1 is refractory to GGpp-mediated dissociation from reductase and remains sequestered in the ER to inhibit ERAD. Here, we report development of a biochemical assay for UBIAD1-mediated synthesis of MK-4 in isolated membranes and intact cells. Using this assay, we compared enzymatic activity of WT UBIAD1 with that of SCD-associated variants. Our studies revealed that SCD-associated UBIAD1 exhibited reduced MK-4 synthetic activity, which may result from its reduced affinity for GGpp. Sequestration in the ER protects SCD-associated UBIAD1 from autophagy and allows intracellular accumulation of the mutant protein, which amplifies the inhibitory effect on reductase ERAD. These findings have important implications not only for the understanding of SCD etiology but also for the efficacy of cholesterol-lowering statin therapy, which becomes limited, in part, because of UBIAD1-mediated inhibition of reductase ERAD.

Adipocytes take up long chain FAs through diffusion and protein-mediated transport, whereas FA efflux is considered to occur by diffusion. To identify potential membrane proteins that are involved in regulating FA flux in adipocytes, the expression levels of 55 membrane transporters without known function were screened in subcutaneous adipose samples from obese patients before and after bariatric surgery using branched DNA methodology. Among the 33 solute carrier (SLC) transporter family members screened, the expression of 14 members showed significant changes before and after bariatric surgery. One of them, Slc43a3, increased about 2.5-fold after bariatric surgery. Further investigation demonstrated that Slc43a3 is highly expressed in murine adipose tissue and induced during adipocyte differentiation in primary preadipocytes and in OP9 cells. Knockdown of Slc43a3 with siRNA in differentiated OP9 adipocytes reduced both basal and forskolin-stimulated FA efflux, while also increasing FA uptake and lipid droplet accumulation. In contrast, overexpression of Slc43a3 decreased FA uptake in differentiated OP9 cells and resulted in decreased lipid droplet accumulation. Therefore, Slc43a3 seems to regulate FA flux in adipocytes, functioning as a positive regulator of FA efflux and as a negative regulator of FA uptake.

Acne is one of the most common dermatological conditions, but the details of its pathology are unclear, and current management regimens often have adverse effects. Cutibacterium acnes is known as a major acne-associated bacterium that derives energy from lipase-mediated sebum lipid degradation. C. acnes is commensal, but lipase activity has been observed to differ among C. acnes types. For example, higher populations of the type IA strains are present in acne lesions with higher lipase activity. In the present study, we examined a conserved lipase in types IB and II that was truncated in type IA C. acnes strains. Closed, blocked, and open structures of C. acnes ATCC11828 lipases were elucidated by X-ray crystallography at 1.6–2.4 Å. The closed crystal structure, which is the most common form in aqueous solution, revealed that a hydrophobic lid domain shields the active site. By comparing closed, blocked, and open structures, we found that the lid domain-opening mechanisms of C. acnes lipases (_CAlipases) involve the lid-opening residues, Phe-179 and Phe-211. To the best of our knowledge, this is the first structure-function study of _CAlipases, which may help to shed light on the mechanisms involved in acne development and may aid in future drug design.

Fatty liver involves ectopic lipid accumulation and dysregulated hepatic oxidative metabolism, which can progress to a state of elevated inflammation and fibrosis referred to as nonalcoholic steatohepatitis (NASH). The factors that control progression from simple steatosis to NASH are not fully known. Here, we tested the hypothesis that dietary vitamin E (VitE) supplementation would prevent NASH progression and associated metabolic alterations induced by a Western diet (WD). Hyperphagic melanocortin-4 receptor-deficient (MC4R^–/–) mice were fed chow, chow+VitE, WD, or WD+VitE starting at 8 or 20 weeks of age. All groups exhibited extensive hepatic steatosis by the end of the study (28 weeks of age). WD feeding exacerbated liver disease severity without inducing proportional changes in liver triglycerides. Eight weeks of WD accelerated liver pyruvate cycling, and 20 weeks of WD extensively upregulated liver glucose and oxidative metabolism assessed by ²H/¹³C flux analysis. VitE supplementation failed to reduce the histological features of NASH. Rather, WD+VitE increased the abundance and saturation of liver ceramides and accelerated metabolic flux dysregulation compared with 8 weeks of WD alone. In summary, VitE did not limit NASH pathogenesis in genetically obese mice, but instead increased some indicators of metabolic dysfunction.

The pregnane X receptor (PXR) is a nuclear receptor that can be activated by numerous drugs and xenobiotic chemicals. PXR thereby functions as a xenobiotic sensor to coordinately regulate host responses to xenobiotics by transcriptionally regulating many genes involved in xenobiotic metabolism. We have previously reported that PXR has pro-atherogenic effects in animal models, but how PXR contributes to atherosclerosis development in different tissues or cell types remains elusive. In this study, we generated an LDL receptor-deficient mouse model with myeloid-specific PXR deficiency (PXR^MyeLDLR^–/–) to elucidate the role of macrophage PXR signaling in atherogenesis. The myeloid PXR deficiency did not affect metabolic phenotypes and plasma lipid profiles, but PXR^MyeLDLR^–/– mice had significantly decreased atherosclerosis at both aortic root and brachiocephalic arteries compared with control littermates. Interestingly, the PXR deletion did not affect macrophage adhesion and migration properties, but reduced lipid accumulation and foam cell formation in the macrophages. PXR deficiency also led to decreased expression of the scavenger receptor CD36 and impaired lipid uptake in macrophages of the PXR^MyeLDLR^–/– mice. Further, RNA-Seq analysis indicated that treatment with a prototypical PXR ligand affects the expression of many atherosclerosis-related genes in macrophages in vitro. These findings reveal a pivotal role of myeloid PXR signaling in atherosclerosis development and suggest that PXR may be a potential therapeutic target in atherosclerosis management.