- Momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis (MOMENTUM): results from an international, double-blind, randomised, controlled, phase 3 study. [Journal Article]Lancet. 2023 Jan 28; 401(10373):269-280.Lct
- CONCLUSIONS: Treatment with momelotinib, compared with danazol, resulted in clinically significant improvements in myelofibrosis-associated symptoms, anaemia measures, and spleen response, with favourable safety. These findings support the future use of momelotinib as an effective treatment in patients with myelofibrosis, especially in those with anaemia.
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- Surface LDLR is a major receptor for lipoprotein(a) clearance in male mice lacking PCSK9. [Journal Article]Biochim Biophys Acta Mol Cell Biol Lipids. 2023 Jan 25 [Online ahead of print]BB
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- Australian Atherosclerosis Society Position Statement on Lipoprotein(a): Clinical and Implementation Recommendations. [Journal Article]Heart Lung Circ. 2023 Jan 25 [Online ahead of print]HL
- This position statement provides guidance to cardiologists and related specialists on the management of adult patients with elevated lipoprotein(a) [Lp(a)]. Elevated Lp(a) is an independent and causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve disease (CAVD). While circulating Lp(a) levels are largely determined by ancestry, they are also influenced b…
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- Relationship of Apolipoprotein(a) Isoform Size with Clearance and Production of Lipoprotein(a) in a Diverse Cohort. [Journal Article]J Lipid Res. 2023 Jan 24 [Online ahead of print]JL
- Lipoprotein(a) [Lp(a)] has two main proteins, apolipoprotein B100 (apoB100) and apolipoprotein(a) [apo(a)]. High levels of Lp(a) confer an increased risk for atherosclerotic cardiovascular disease (ASCVD). Most people have two circulating isoforms of apo(a) differing in their molecular mass, determined by the number of Kringle IV Type 2 repeats. Previous studies report a strong inverse relationsh…
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- Stepwise assembly of the active site of [NiFe]-hydrogenase. [Journal Article]Nat Chem Biol. 2023 Jan 26 [Online ahead of print]NC
- [NiFe]-hydrogenases are biotechnologically relevant enzymes catalyzing the reversible splitting of H2 into 2e- and 2H+ under ambient conditions. Catalysis takes place at the heterobimetallic NiFe(CN)2(CO) center, whose multistep biosynthesis involves careful handling of two transition metals as well as potentially harmful CO and CN- molecules. Here, we investigated the sequential assembly of the …
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- Impact of Rabeprazole on APO-Dabigatran Exposure in Healthy Volunteers. [Journal Article]CJC Open. 2023 Jan; 5(1):1-7.CO
- CONCLUSIONS: When APO-dabigatran is administered with rabeprazole, the exposure to dabigatran is reduced by about 30%, which is similar to the level observed with Pradaxa when it was co-administered with a proton pump inhibitor. However, the finding that one-third of participants had a > 50% reduction in exposure is concerning, and it highlights the need for caution in patients who have, or are at risk of, reduced gastric acidity.
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- Ixodes ricinus ticks have a functional association with Midichloria mitochondrii. [Journal Article]Front Cell Infect Microbiol. 2022; 12:1081666.FC
- In addition to being vectors of pathogenic bacteria, ticks also harbor intracellular bacteria that associate with ticks over generations, aka symbionts. The biological significance of such bacterial symbiosis has been described in several tick species but its function in Ixodes ricinus is not understood. We have previously shown that I. ricinus ticks are primarily inhabited by a single species of…
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- Probing into the Flap-Dimer Dynamics of the Mycobacterium Tuberculosis Kasa Enzyme Binding Landscape provides The Underlying Inhibitory Mechanisms Of JSF-3285 And 5G. [Journal Article]Curr Top Med Chem. 2023 Jan 25 [Online ahead of print]CT
- CONCLUSIONS: These findings provide a background for a new structure-based design of novel KasA inhibitors.
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- Design of a gold clustering site in an engineered apo-ferritin cage. [Journal Article]
- Water-soluble and biocompatible protein-protected gold nanoclusters (Au NCs) hold great promise for numerous applications. However, design and precise regulation of their structure at an atomic level remain challenging. Herein, we have engineered and constructed a gold clustering site at the 4-fold symmetric axis channel of the apo-ferritin cage. Using a series of X-ray crystal structures, we eva…
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- Intramolecular charge-transfer enhances energy transfer efficiency in carotenoid-reconstituted light-harvesting 1 complex of purple photosynthetic bacteria. [Journal Article]
- In bacterial photosynthesis, the excitation energy transfer (EET) from carotenoids to bacteriochlorophyll a has a significant impact on the overall efficiency of the primary photosynthetic process. This efficiency can be enhanced when the involved carotenoid has intramolecular charge-transfer (ICT) character, as found in light-harvesting systems of marine alga and diatoms. Here, we provide insigh…
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- Structural insights into the elevator-type transport mechanism of a bacterial ZIP metal transporter. [Journal Article]
- The Zrt-/Irt-like protein (ZIP) family consists of ubiquitously expressed divalent metal transporters critically involved in maintaining systemic and cellular homeostasis of zinc, iron, and manganese. Here, we present a study on a prokaryotic ZIP from Bordetella bronchiseptica (BbZIP) by combining structural biology, evolutionary covariance, computational modeling, and a variety of biochemical as…
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- Apolipoprotein Proteomics for Residual Lipid-Related Risk in Coronary Heart Disease. [Journal Article]Circ Res. 2023 Jan 24 [Online ahead of print]CircR
- CONCLUSIONS: Apolipoproteins were associated with CHD independent of conventional risk factors and lipids, suggesting apolipoproteins could help to identify patients with residual lipid-related risk and guide personalized approaches to CHD risk reduction.
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- Lutein nanodisks protect human retinal pigment epithelial cells from UV light-induced damage. [Journal Article]
- The hydrophobic carotenoid, lutein, was conferred with aqueous solubility upon formulation into reconstituted discoidal high density lipoprotein particles, termed lutein nanodisks (ND). When formulated with phosphatidylcholine (PC), apolipoprotein (apo) A-I and lutein (formulation ratio = 5 mg PC/2 mg apoA-I/1 mg lutein), lutein solubilization efficiency in phosphate buffered saline (PBS) was ~90…
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- Effects of peroxisome proliferator activated receptor-α agonist on growth performance, blood profiles, gene expression related to liver fat metabolism in broilers fed diets containing corn naturally contaminated with mycotoxins. [Journal Article]
- This study was conducted to determine the subclinical symptom of broilers exposure to mycotxoins from corn naturally contaminated, and the preventive effect with peroxisome proliferator activated receptor-α (PPARα) agonist (Wy-14643) supplementation. A total of 360 one-day -old male Arbor Acres broilers were randomly distributed into 4 treatments with 9 replicates of 10 birds. Dietary treatments …
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- Identification of Plasma Proteomic Biomarkers in Patients with Mild Cognitive Impairment. [Journal Article]
- Plasma proteomic profiling may provide novel biomarkers for the identification of mild cognitive impairment (MCI). The early diagnosis of MCI still remains a challenging task due to its diverse origin. Currently, molecular approaches have been used to identify MCI diversified origin as its onset is governed by a variety of molecular changes. Therefore, we aimed to find out molecular alteration in…
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- Relationship of idiopathic femoral head necrosis with blood lipid metabolism and coagulation function: A propensity score-based analysis. [Journal Article]
- CONCLUSIONS: IONFH has strong associations with blood lipid metabolism and coagulation function, which provide an avenue for exploring the mechanism of IONFH.
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- Consumption of Eggs Alone or Enriched with Annatto (Bixa orellana L.) Does Not Increase Cardiovascular Risk in Healthy Adults-A Randomized Clinical Trial, the Eggant Study. [Randomized Controlled Trial]
- Most atherosclerotic cardiovascular diseases can be prevented by modifying lifestyles, including unhealthy diets. Eggs contain important carotenoids that may impact cardiovascular risk. The lipid nature of eggs can improve the bioavailability of other carotenoids, such as Annatto (Bixa orellana L.), with reported antioxidant properties. Although numerous studies have shown that there is no associ…
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- Protoporphyrin IX Binds to Iron(II)-Loaded and to Zinc-Loaded Human Frataxin. [Journal Article]
- (1) Background: Human frataxin is an iron binding protein that participates in the biogenesis of iron sulfur clusters and enhances ferrochelatase activity. While frataxin association to other proteins has been extensively characterized up to the structural level, much less is known about the putative capacity of frataxin to interact with functionally related metabolites. In turn, current knowledg…
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- Enhancement of High-Density Lipoprotein (HDL) Quantity and Quality by Regular and Habitual Exercise in Middle-Aged Women with Improvements in Lipid and Apolipoprotein Profiles: Larger Particle Size and Higher Antioxidant Ability of HDL. [Journal Article]
- Regular exercise, especially aerobic exercise, is beneficial for increasing serum high-density lipoprotein-cholesterol (HDL-C) levels in the general population. In addition to the HDL-C quantity, exercise enhances HDL functionality, antioxidants, and cholesterol efflux. On the other hand, the optimal intensity and frequency of exercise to increase HDL quantity and enhance HDL quality in middle-ag…
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- Structural Insights Uncover the Specific Phosphoinositide Recognition by the PH1 Domain of Arap3. [Journal Article]
- Arap3, a dual GTPase-activating protein (GAP) for the small GTPases Arf6 and RhoA, plays key roles in regulating a wide range of biological processes, including cancer cell invasion and metastasis. It is known that Arap3 is a PI3K effector that can bind directly to PI(3,4,5)P3, and the PI(3,4,5)P3-mediated plasma membrane recruitment is crucial for its function. However, the molecular mechanism o…
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- Biomarkers for Premature Coronary Artery Disease (PCAD): A Case Control Study. [Journal Article]
- Coronary artery disease (CAD) is often associated with the older generation. However, in recent years, there is an increasing trend in the prevalence of CAD among the younger population; this is known as premature CAD. Although biomarkers for CAD have been established, there are limited studies focusing on premature CAD especially among the Malay male population. Thus, the aim of this research wa…
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- Integrated Transcriptomics Profiling in Chahua and Digao Chickens' Breast for Assessment Molecular Mechanism of Meat Quality Traits. [Journal Article]
- Meat quality traits are an important economic trait and remain a major argument, from the producer to the consumer. However, there are a few candidate genes and pathways of chicken meat quality traits that were reported for chicken molecular breeding. The purpose of the present study is to identify the candidate genes and pathways associated with meat quality underlying variations in meat quality…
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- Gestational Hypertension and High-Density Lipoprotein Function: An Explorative Study in Overweight/Obese Women of the DALI Cohort. [Journal Article]
- Gestational hypertension (GHTN) is associated with an increased cardiovascular risk for mothers and their offspring later in life. High-density lipoproteins (HDL) are anti-atherogenic by promoting efflux of cholesterol from macrophages and suppression of endothelial cell activation. Functional impairment of HDL in GHTN-complicated pregnancies may affect long-term health of both mothers and offspr…
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- Binding to Iron Quercetin Complexes Increases the Antioxidant Capacity of the Major Birch Pollen Allergen Bet v 1 and Reduces Its Allergenicity. [Journal Article]
- Bet v 1 is the major allergen in birch pollen to which up to 95% of patients sensitized to birch respond. As a member of the pathogenesis-related PR 10 family, its natural function is implicated in plant defense, with a member of the PR10 family being reported to be upregulated under iron deficiency. As such, we assessed the function of Bet v 1 to sequester iron and its immunomodulatory propertie…
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- Biomedical consequences of elevated cholesterol-containing lipoproteins and apolipoproteins on cardiovascular and non-cardiovascular outcomes. [Journal Article]
- CONCLUSIONS: The cholesterol content of a wide range of lipoprotein and apolipoproteins associate with measures of atherosclerosis, blood pressure, CRP, and CHD, with a subset affecting HF, T2DM, AD and IBD risk. Many of the observed effects appear to act independently of LDL-C, HDL-C, and TG, supporting the targeting of lipid fractions beyond LDL-C for disease prevention.
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- Structural and functional characterization of TraI from pKM101 reveals basis for DNA processing. [Journal Article]
- Type 4 secretion systems are large and versatile protein machineries that facilitate the spread of antibiotic resistance and other virulence factors via horizontal gene transfer. Conjugative type 4 secretion systems depend on relaxases to process the DNA in preparation for transport. TraI from the well-studied conjugative plasmid pKM101 is one such relaxase. Here, we report the crystal structure …
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- Depletion Assisted Hemin Affinity (DAsHA) Proteomics Reveals an Expanded Landscape of Heme Binding Proteins in the Human Proteome. [Journal Article]Metallomics. 2023 Jan 20 [Online ahead of print]M
- Heme b (iron protoporphyrin IX) plays important roles in biology as a metallocofactor and signaling molecule. However, the targets of heme signaling and the network of proteins that mediate the exchange of heme from sites of synthesis or uptake to heme dependent or regulated proteins are poorly understood. Herein, we describe a quantitative mass spectrometry-based chemoproteomics strategy to iden…
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- Advancing the field of computational drug design using multicanonical molecular dynamics-based dynamic docking. [Review]
- Multicanonical molecular dynamics (McMD)-based dynamic docking is a powerful tool to not only predict the native binding configuration between two flexible molecules, but it can also be used to accurately simulate the binding/unbinding pathway. Furthermore, it can also predict alternative binding sites, including allosteric ones, by employing an exhaustive sampling approach. Since McMD-based dyna…
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- The framing of time-dependent machine learning models improves risk estimation among young individuals with acute coronary syndromes. [Journal Article]
- Acute coronary syndrome (ACS) is a common cause of death in individuals older than 55 years. Although younger individuals are less frequently seen with ACS, this clinical event has increasing incidence trends, shows high recurrence rates and triggers considerable economic burden. Young individuals with ACS (yACS) are usually underrepresented and show idiosyncratic epidemiologic features compared …
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