scholarly journals Alpha-Tocopherol Metabolites (The Vitamin E Metabolome) and Their Interindividual Variability during Supplementation

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 173
Author(s):  
Desirée Bartolini ◽  
Rita Marinelli ◽  
Danilo Giusepponi ◽  
Roberta Galarini ◽  
Carolina Barola ◽  
...  
Keyword(s):  
Vitamin E ◽  
Target Genes ◽  
Interindividual Variability ◽  
Pregnane X Receptor ◽  
Alpha Tocopherol ◽  
Therapeutic Interventions ◽  
Intrinsic Variability ◽  
Blood Leukocytes ◽  
Definition Of ◽  
And Function

The metabolism of α-tocopherol (α-TOH, vitamin E) shows marked interindividual variability, which may influence the response to nutritional and therapeutic interventions with this vitamin. Recently, new metabolomics protocols have fostered the possibility to explore such variability for the different metabolites of α-TOH so far identified in human blood, i.e., the “vitamin E metabolome”, some of which have been reported to promote important biological functions. Such advances prompt the definition of reference values and degree of interindividual variability for these metabolites at different levels of α-TOH intake. To this end, a one-week oral administration protocol with 800 U RRR-α-TOH/day was performed in 17 healthy volunteers, and α-TOH metabolites were measured in plasma before and at the end of the intervention utilizing a recently validated LC-MS/MS procedure; the expression of two target genes of α-TOH with possible a role in the metabolism and function of this vitamin, namely pregnane X receptor (PXR) and the isoform 4F2 of cytochrome P450 (CYP4F2) was assessed by immunoblot in peripheral blood leukocytes. The levels of enzymatic metabolites showed marked interindividual variability that characteristically increased upon supplementation. With the exception of α-CEHC (carboxy-ethyl-hydroxychroman) and the long-chain metabolites M1 and α-13′OH, such variability was found to interfere with the possibility to utilize them as sensitive indicators of α-TOH intake. On the contrary, the free radical-derived metabolite α-tocopheryl quinone significantly correlated with the post-supplementation levels of α-TOH. The supplementation stimulated PXR, but not CYP4F2, expression of leucocytes, and significant correlations were observed between the baseline levels of α-TOH and both the baseline and post-supplementation levels of PXR. These findings provide original analytical and molecular information regarding the human metabolism of α-TOH and its intrinsic variability, which is worth considering in future nutrigenomics and interventions studies.

scholarly journals TCF11 Has a Potent Tumor-Repressing Effect Than Its Prototypic Nrf1α by Definition of Both Similar Yet Different Regulatory Profiles, With a Striking Disparity From Nrf2

2021 ◽  
Vol 11 ◽  
Author(s):  
Meng Wang ◽  
Yonggang Ren ◽  
Shaofan Hu ◽  
Keli Liu ◽  
Lu Qiu ◽  
...  
Keyword(s):  
Target Genes ◽  
Transcriptomic Sequencing ◽  
Distinct Cell ◽  
Terminal Amino ◽  
Definition Of ◽  
And Function ◽  
Growth Of Tumor ◽  
Gene Regulations ◽  
Common Target ◽  
Potent Tumor

Nrf1 and Nrf2, as two principal CNC-bZIP transcription factors, regulate similar but different targets involved in a variety of biological functions for maintaining cell homeostasis and organ integrity. Of note, the unique topobiological behavior of Nrf1 makes its functions more complicated than Nrf2, because it is allowed for alternatively transcribing and selectively splicing to yield multiple isoforms (e.g., TCF11, Nrf1α). In order to gain a better understanding of their similarities and differences in distinct regulatory profiles, all four distinct cell models for stably expressing TCF11, TCF11ΔN, Nrf1α or Nrf2 have been herein established by an Flp-In™ T-REx™-293 system and then identified by transcriptomic sequencing. Further analysis revealed that Nrf1α and TCF11 have similar yet different regulatory profiles, although both contribute basically to positive regulation of their co-targets, which are disparate from those regulated by Nrf2. Such disparity in those gene regulations by Nrf1 and Nrf2 was further corroborated by scrutinizing comprehensive functional annotation of their specific and/or common target genes. Conversely, the mutant TCF11ΔN, resulting from a deletion of the N-terminal amino acids 2–156 from TCF11, resembles Nrf2 with the largely consistent structure and function. Interestingly, our further experimental evidence demonstrates that TCF11 acts as a potent tumor-repressor relative to Nrf1α, albeit both isoforms possess a congruous capability to prevent malignant growth of tumor and upregulate those genes critical for improving the survival of patients with hepatocellular carcinoma.

Kontrast und Wissen

2009 ◽  
Vol 54 (1) ◽  
pp. 69-102
Author(s):  
Robin Rehm
Keyword(s):  
19Th Century ◽  
Edmund Husserl ◽  
Specific Knowledge ◽  
Max Scheler ◽  
Black And White ◽  
Black Circle ◽  
Black Cross ◽  
Definition Of ◽  
And Function ◽  
The 19Th Century

Kasimir Malewitschs suprematistische Hauptwerke ›Schwarzes Quadrat‹, ›Schwarzer Kreis‹ und ›Schwarzes Kreuz‹ von 1915 setzen sich aus schwarzen Formen auf weißem Grund zusammen. Der Typus des Schwarzweißbildes weist überraschende Parallelen zu den bildlichen Wahrnehmungsinstrumenten auf, die vom ausgehenden 18. bis Anfang des 20. Jahrhunderts in den Experimenten der Farbenlehre, physiologischen Optik und Psychologie verwendet worden sind. Die vorliegende Studie untersucht diese Parallelen in drei Schritten: Zunächst erfolgt eine allgemeine Charakterisierung des Schwarzweißbildes mit Hilfe des Kontrastbegriffs von Edmund Husserl. Des weiteren wird die Entstehung und Funktion des schwarzweißen Kontrastbildes in den Wissenschaften des 19. Jahrhunderts typologisch herausgearbeitet. Unter Berücksichtigung des Wissensbegriffs von Max Scheler wird abschließend die Spezifik des Wissens eruiert, das die Schwarzweißbilder sowohl in der Malerei Malewitschs als auch in den genannten Wissenschaften generieren. Malevich’s main Suprematist works, such as ›Black Square‹, ›Black Circle‹, and ›Black Cross‹ from 1915, consist of black shapes on white ground. Surprisingly this series of shapes strongly resembles scientific black-and-white images used for research on colour theory, physiological optics, and psychology throughout the 19th century. This paper examines the parallels between Malevich’s paintings and the scientific drawings in three steps: It first characterizes black-and-white images in general, using Edmund Husserl’s definition of the term ›contrast‹. Secondly, the paper investigates the development and function of black-and-white images as tools of perception in the sciences. It finally discusses the specific knowledge generated through Malevich’s art and through scientific black-and-white images, following Max Scheler’s phenomenological identification of knowledge.

Effects of Maternal Obesity and Gestational Diabetes Mellitus on the Placenta: Current Knowledge and Targets for Therapeutic Interventions

2020 ◽  
Vol 19 (2) ◽  
pp. 176-192
Author(s):  
Samantha Bedell ◽  
Janine Hutson ◽  
Barbra de Vrijer ◽  
Genevieve Eastabrook
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Maternal Obesity ◽  
Environmental Changes ◽  
Current Knowledge ◽  
Therapeutic Interventions ◽  
Placental Development ◽  
Exchange Site ◽  
And Function

: Obesity and gestational diabetes mellitus (GDM) are becoming more common among pregnant women worldwide and are individually associated with a number of placenta-mediated obstetric complications, including preeclampsia, macrosomia, intrauterine growth restriction and stillbirth. The placenta serves several functions throughout pregnancy and is the main exchange site for the transfer of nutrients and gas from mother to fetus. In pregnancies complicated by maternal obesity or GDM, the placenta is exposed to environmental changes, such as increased inflammation and oxidative stress, dyslipidemia, and altered hormone levels. These changes can affect placental development and function and lead to abnormal fetal growth and development as well as metabolic and cardiovascular abnormalities in the offspring. This review aims to summarize current knowledge on the effects of obesity and GDM on placental development and function. Understanding these processes is key in developing therapeutic interventions with the goal of mitigating these effects and preventing future cardiovascular and metabolic pathology in subsequent generations.

Alpha Tocopherol Loaded in Liposome: Preparation, Optimization, Characterization and Sperm Motility Protection

2020 ◽  
Vol 10 (3) ◽  
pp. 228-236 ◽  
Author(s):  
Lamia Taouzinet ◽  
Sofiane Fatmi ◽  
Allaeddine Khellouf ◽  
Mohamed Skiba ◽  
Mokrane Iguer-ouada
Keyword(s):  
Vitamin E ◽  
Sperm Motility ◽  
High Performance ◽  
Positive Impact ◽  
Alpha Tocopherol ◽  
Ethanol Injection ◽  
Liposome Preparation ◽  
Liposome Size ◽  
Optimum Solution ◽  
The Impact

Background: Alpha-tocopherol is a potent antioxidant involved in sperm protection particularly during cryopreservation. However, its poor solubility limits the optimal protection in aqueous solutions. Objective: The aim of this study was to enhance the solubility of α-tocopherol by the use of liposomes. Methods: The experimental approach consisted to load vitamin E in liposomes prepared by ethanol injection method and the optimization carried out by an experimental design. The optimum solution was characterized by high performance liquid chromatography and scanning electron microscope. Finely, the impact on sperm motility protection was studied by the freezing technic of bovine sperm. Results: The optimum solution was obtained when using 10.9 mg/ml of phospholipids, 1.7 mg/ml of cholesterol and 2 mg/ml of vitamin E. The liposome size was 99.86 nm, providing 78.47% of loaded efficiency. The results showed also a significant positive impact on sperm motility after hours of preservation. Conclusion: In conclusion, the current results showed the interest of liposome preparation as an alternative to enhance vitamin E solubility and to protect spermatozoa during cryopreservation.

John among the Apocalypses

2020 ◽  
Author(s):  
Benjamin E. Reynolds
Keyword(s):  
Gospel Of John ◽  
Central Place ◽  
Reception History ◽  
Genre Theory ◽  
Synoptic Gospels ◽  
Book Of Revelation ◽  
Distinctive Features ◽  
History Of ◽  
Definition Of ◽  
And Function

The central place of revelation in the Gospel of John and the Gospel’s revelatory telling of the life of Jesus are distinctive features of John when compared with the Synoptic Gospels; yet, when John is compared among the apocalypses, these same features indicate John’s striking affinity with the genre of apocalypse. By paying attention to modern genre theory and making an extensive comparison with the standard definition of “apocalypse,” the Gospel of John reflects similarities with Jewish apocalypses in form, content, and function. Even though the Gospel of John reflects similarities with the genre of apocalypse, John is not an apocalypse, but in genre theory terms, John may be described as a gospel in kind and an apocalypse in mode. John’s narrative of Jesus’s life has been qualified and shaped by the genre of apocalypse, such that it may be called an “apocalyptic” gospel. Understanding the Fourth Gospel as “apocalyptic” Gospel provides an explanation for John’s appeal to Israel’s Scriptures and Mosaic authority. Possible historical reasons for the revelatory narration of Jesus’s life in the Gospel of John may be explained by the Gospel’s relationship with the book of Revelation and the history of reception concerning their writing. An examination of Byzantine iconographic traditions highlights how reception history may offer a possible explanation for reading John as “apocalyptic” Gospel.

Physicianship and the Rebirth of Medical Education

2018 ◽  
Author(s):  
J. Donald Boudreau ◽  
Eric Cassell ◽  
Abraham Fuks
Keyword(s):  
Medical Education ◽  
Educational Process ◽  
Medical Attention ◽  
Patient Centeredness ◽  
Goals Of Medicine ◽  
The Subject ◽  
Definition Of ◽  
And Function ◽  
William Osler ◽  
The Relationship

This book reimagines medical education and reconstructs its design. It originates from a reappraisal of the goals of medicine and the nature of the relationship between doctor and patient. The educational blueprint outlined is called the “Physicianship Curriculum” and rests on two linchpins. First is a new definition of sickness: Patients know themselves to be ill when they cannot pursue their purposes and goals in life because of impairments in functioning. This perspective represents a bulwark against medical attention shifting from patients to diseases. The curriculum teaches about patients as functional persons, from their anatomy to their social selves, starting in the first days of the educational program and continuing throughout. Their teaching also rests on the rock-solid grounding of medicine in the sciences and scientific understandings of disease and function. The illness definition and knowledge base together create a foundation for authentic patient-centeredness. Second, the training of physicians depends on and culminates in development of a unique professional identity. This is grounded in the historical evolution of the profession, reaching back to Hippocrates. It leads to reformulation of the educational process as clinical apprenticeships and moral mentorships. “Rebirth” in the title suggests that critical ingredients of medical education have previously been articulated. The book argues that the apprenticeship model, as experienced, enriched, taught, and exemplified by William Osler, constitutes a time-honored foundation. Osler’s “natural method of teaching the subject of medicine” is a precursor to the Physicianship Curriculum.

scholarly journals Breeder Diet Strategies for Generating Ttpa-Null and Wild-Type Mice with Low Vitamin E Status to Assess Neurological Outcomes

2020 ◽  
Vol 4 (11) ◽  
Author(s):  
Katherine M Ranard ◽  
Matthew J Kuchan ◽  
John W Erdman
Keyword(s):  
Animal Model ◽  
Vitamin E ◽  
Mouse Model ◽  
Wild Type ◽  
Future Studies ◽  
Neurological Outcomes ◽  
Transfer Protein ◽  
And Function ◽  
The Brain ◽  
Vitamin E Status

ABSTRACT Studying vitamin E [α-tocopherol (α-T)] metabolism and function in the brain and other tissues requires an animal model with low α-T status, such as the transgenic α-T transfer protein (Ttpa)–null (Ttpa−/−) mouse model. Ttpa+/− dams can be used to produce Ttpa−/− and Ttpa+/+mice for these studies. However, the α-T content in Ttpa+/− dams’ diet requires optimization; diets must provide sufficient α-T for reproduction, while minimizing the transfer of α-T to the offspring destined for future studies that require low baseline α-T status. The goal of this work was to assess the effectiveness and feasibility of 2 breeding diet strategies on reproduction outcomes and offspring brain α-T concentrations. These findings will help standardize the breeding methodology used to generate the Ttpa−/− mice for neurological studies.

The Pleiotropic Intricacies of Hedgehog Signaling: From Craniofacial Patterning to Carcinogenesis

FACE ◽  
2021 ◽  
pp. 273250162110243
Author(s):  
Mikhail Pakvasa ◽  
Andrew B. Tucker ◽  
Timothy Shen ◽  
Tong-Chuan He ◽  
Russell R. Reid
Keyword(s):  
Intracellular Signaling ◽  
Limb Development ◽  
Hedgehog Signaling ◽  
Target Genes ◽  
Craniofacial Development ◽  
Signaling Cascade ◽  
Signaling Mechanisms ◽  
Intracellular Signaling Cascade ◽  
And Function

Hedgehog signaling was discovered more than 40 years ago in experiments demonstrating that it is a fundamental mediator of limb development. Since that time, it has been shown to be important in development, homeostasis, and disease. The hedgehog pathway proceeds through a pathway highly conserved throughout animals beginning with the extracellular diffusion of hedgehog ligands, proceeding through an intracellular signaling cascade, and ending with the activation of specific target genes. A vast amount of research has been done elucidating hedgehog signaling mechanisms and regulation. This research has found a complex system of genetics and signaling that helps determine how organisms develop and function. This review provides an overview of what is known about hedgehog genetics and signaling, followed by an in-depth discussion of the role of hedgehog signaling in craniofacial development and carcinogenesis.

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