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Journal of Animal Science and... Nov 2023As an important epigenetic modification, DNA methylation is involved in many biological processes such as animal cell differentiation, embryonic development, genomic... (Review)
Review
As an important epigenetic modification, DNA methylation is involved in many biological processes such as animal cell differentiation, embryonic development, genomic imprinting and sex chromosome inactivation. As DNA methylation sequencing becomes more sophisticated, it becomes possible to use it to solve more zoological problems. This paper reviews the characteristics of DNA methylation, with emphasis on the research and application of DNA methylation in poultry.
PubMed: 37925454
DOI: 10.1186/s40104-023-00939-9 -
Cureus Aug 2023Hair loss is a problem for everyone, regardless of their age or sex. The three most prevalent types of hair loss, telogen effluvium, alopecia areata, and androgenetic... (Review)
Review
Hair loss is a problem for everyone, regardless of their age or sex. The three most prevalent types of hair loss, telogen effluvium, alopecia areata, and androgenetic alopecia, have been associated with a variety of risk factors. Strong evidence links thyroid hormones (THs) to hair loss. THs control the growth, differentiation, metabolism, and thermogenesis of body cells. The skin is a significant target organ for THs; however, the cellular and molecular causes of thyroid dysfunction-related skin diseases remain unknown. Hyperthyroidism, hypothyroidism, and drug-induced hypothyroidism can induce widespread hair shedding. Little information is available regarding the incidence and effects of thyroid dysfunction on hair problems. This study aimed to review the impact and prevalence of thyroid disorders on hair loss. The conclusions drawn from this study highlight the underestimated prevalence and impact of thyroid disorders on hair loss. The review of scientific articles, including original research, review articles, and a case report, provides a comprehensive understanding of the topic. This research adds to the existing literature by enhancing our understanding of the relationship between thyroid dysfunction and hair disorders. It contributes to the body of evidence by reviewing relevant studies and summarizing the impact of thyroid disorders on hair loss. The study also highlights the gaps in knowledge and the need for more research in this area to improve the diagnosis and management of hair disorders associated with thyroid dysfunction.
PubMed: 37692605
DOI: 10.7759/cureus.43266 -
Frontiers in Endocrinology 2024Anti-Müllerian hormone (AMH) is a Sertoli cell-secreted glycoprotein involved in male fetal sex differentiation: it provokes the regression of Müllerian ducts, which... (Review)
Review
Anti-Müllerian hormone (AMH) is a Sertoli cell-secreted glycoprotein involved in male fetal sex differentiation: it provokes the regression of Müllerian ducts, which otherwise give rise to the Fallopian tubes, the uterus and the upper part of the vagina. In the first trimester of fetal life, AMH is expressed independently of gonadotropins, whereas from the second trimester onwards AMH testicular production is stimulated by FSH and oestrogens; at puberty, AMH expression is inhibited by androgens. AMH has also been suggested to participate in testicular descent during fetal life, but its role remains unclear. Serum AMH is a well-recognized biomarker of testicular function from birth to the first stages of puberty. Especially in boys with nonpalpable gonads, serum AMH is the most useful marker of the existence of testicular tissue. In boys with cryptorchidism, serum AMH levels reflect the mass of functional Sertoli cells: they are lower in patients with bilateral than in those with unilateral cryptorchidism. Interestingly, serum AMH increases after testis relocation to the scrotum, suggesting that the ectopic position result in testicular dysfunction, which may be at least partially reversible. In boys with cryptorchidism associated with micropenis, low AMH and FSH are indicative of central hypogonadism, and serum AMH is a good marker of effective FSH treatment. In patients with cryptorchidism in the context of disorders of sex development, low serum AMH is suggestive of gonadal dysgenesis, whereas normal or high AMH is found in patients with isolated androgen synthesis defects or with androgen insensitivity. In syndromic disorders, assessment of serum AMH has shown that Sertoli cell function is preserved in boys with Klinefelter syndrome until mid-puberty, while it is affected in patients with Noonan, Prader-Willi or Down syndromes.
Topics: Female; Humans; Male; Anti-Mullerian Hormone; Cryptorchidism; Androgens; Follicle Stimulating Hormone; Peptide Hormones
PubMed: 38501100
DOI: 10.3389/fendo.2024.1361032 -
JCI Insight Aug 2023Reactive oxygen species (ROS) are natural products of mitochondrial oxidative metabolism and oxidative protein folding. ROS levels must be well controlled, since...
Reactive oxygen species (ROS) are natural products of mitochondrial oxidative metabolism and oxidative protein folding. ROS levels must be well controlled, since elevated ROS has been shown to have deleterious effects on osteoblasts. Moreover, excessive ROS is thought to underlie many of the skeletal phenotypes associated with aging and sex steroid deficiency in mice and humans. The mechanisms by which osteoblasts regulate ROS and how ROS inhibits osteoblasts are not well understood. Here, we demonstrate that de novo glutathione (GSH) biosynthesis is essential in neutralizing ROS and establish a proosteogenic reduction and oxidation reaction (REDOX) environment. Using a multifaceted approach, we demonstrate that reducing GSH biosynthesis led to acute degradation of RUNX2, impaired osteoblast differentiation, and reduced bone formation. Conversely, reducing ROS using catalase enhanced RUNX2 stability and promoted osteoblast differentiation and bone formation when GSH biosynthesis was limited. Highlighting the therapeutic implications of these findings, in utero antioxidant therapy stabilized RUNX2 and improved bone development in the Runx2+/- haplo-insufficient mouse model of human cleidocranial dysplasia. Thus, our data establish RUNX2 as a molecular sensor of the osteoblast REDOX environment and mechanistically clarify how ROS negatively impacts osteoblast differentiation and bone formation.
Topics: Mice; Humans; Animals; Osteogenesis; Reactive Oxygen Species; Core Binding Factor Alpha 1 Subunit; Oxidation-Reduction; Glutathione
PubMed: 37432749
DOI: 10.1172/jci.insight.166888 -
JCI Insight Sep 2023IgG4-related disease (IgG4-RD) is a systemic autoimmune disease with unclear pathogenesis. We performed single-cell RNA-seq and surface proteome analyses on 61,379 PBMCs...
IgG4-related disease (IgG4-RD) is a systemic autoimmune disease with unclear pathogenesis. We performed single-cell RNA-seq and surface proteome analyses on 61,379 PBMCs from 9 treatment-naive IgG4-RD patients and 7 age- and sex-matched healthy controls. Integrative analyses were performed for altered gene expression in IgG4-RD, and flow cytometry and immunofluorescence were used for validation. We observed expansion of plasmablasts with enhanced protein processing and activation, which correlated with the number of involved organs in IgG4-RD. Increased proportions of CD4+ cytotoxic T lymphocytes (CTLs), CD8+ CTLs-GNLY (granulysin), and γδT cells with enhanced chemotaxis and cytotoxicity but with suppressed inhibitory receptors characterize IgG4-RD. Prominent infiltration of lymphocytes with distinct compositions were found in different organs of IgG4-RD patients. Transcription factors (TFs), including PRDM1/XBP1 and RUNX3, were upregulated in IgG4-RD, promoting the differentiation of plasmablasts and CTLs, respectively. Monocytes in IgG4-RD have stronger expression of genes related to cell adhesion and chemotaxis, which may give rise to profibrotic macrophages in lesions. The gene activation pattern in peripheral immune cells indicated activation of multiple interaction pathways between cell types, in part through chemokines or growth factors and their receptors. Specific upregulation of TFs and expansion of plasmablasts and CTLs may be involved in the pathogenesis of IgG4-RD, and each of these populations are candidate targets for therapeutic interventions in this disease.
Topics: Humans; Immunoglobulin G4-Related Disease; Single-Cell Gene Expression Analysis; CD4-Positive T-Lymphocytes; Plasma Cells; T-Lymphocytes, Cytotoxic
PubMed: 37561593
DOI: 10.1172/jci.insight.167602 -
The Journal of Allergy and Clinical... Jul 2023Food is one of the most common elicitors of anaphylaxis, with an increasing incidence over recent years.
BACKGROUND
Food is one of the most common elicitors of anaphylaxis, with an increasing incidence over recent years.
OBJECTIVES
To characterize elicitor-specific phenotypes and identify factors enhancing the risk or severity of food-induced anaphylaxis (FIA).
METHODS
We analyzed data from the European Anaphylaxis Registry applying an age- and sex-matched analysis of associations (Cramer's V) for single food triggers and calculated odds ratios (ORs) for severe FIA.
RESULTS
We identified 3,427 cases of confirmed FIA showing an age-dependent elicitor ranking (for children: peanut, cow's milk, cashew, and hen's egg; and for adults: wheat flour, shellfish, hazelnut, and soy). The age- and sex-matched analysis revealed defined symptom patterns for wheat and cashew. Wheat-induced anaphylaxis was more frequently associated with cardiovascular symptoms (75.7%; Cramer's V = 0.28) and cashew-induced anaphylaxis with gastrointestinal symptoms (73.9%; Cramer's V = 0.20). Furthermore, concomitant atopic dermatitis was slightly associated with anaphylaxis to hen's egg (Cramer's V = 0.19) and exercise was strongly associated with anaphylaxis to wheat (Cramer's V = 0.56). Additional factors influencing the severity were alcohol intake in wheat anaphylaxis (OR = 3.23; CI, 1.31-8.83) and exercise in peanut anaphylaxis (OR = 1.78; CI, 1.09-2.95).
CONCLUSIONS
Our data show that FIA is age-dependent. In adults, the range of elicitors inducing FIA is broader. For some elicitors, the severity of FIA seems to be related to the elicitor. These data require confirmation in future studies considering a clear differentiation between augmentation and risk factors in FIA.
Topics: Cattle; Humans; Female; Animals; Anaphylaxis; Food Hypersensitivity; Chickens; Flour; Triticum; Allergens; Registries; Arachis
PubMed: 36990430
DOI: 10.1016/j.jaip.2023.03.026 -
Nutrients Sep 2023Lipid metabolism plays a major role in the regulation of the immune system. Exogenous (dietary and microbial-derived) and endogenous (non-microbial-derived) lipids play... (Review)
Review
Lipid metabolism plays a major role in the regulation of the immune system. Exogenous (dietary and microbial-derived) and endogenous (non-microbial-derived) lipids play a direct role in regulating immune cell activation, differentiation and expansion, and inflammatory phenotypes. Understanding the complexities of lipid-immune interactions may have important implications for human health, as certain lipids or immune pathways may be beneficial in circumstances of acute infection yet detrimental in chronic inflammatory diseases. Further, there are key differences in the lipid effects between specific immune cell types and location (e.g., gut mucosal vs. systemic immune cells), suggesting that the immunomodulatory properties of lipids may be tissue-compartment-specific, although the direct effect of dietary lipids on the mucosal immune system warrants further investigation. Importantly, there is recent evidence to suggest that lipid-immune interactions are dependent on sex, metabolic status, and the gut microbiome in preclinical models. While the lipid-immune relationship has not been adequately established in/translated to humans, research is warranted to evaluate the differences in lipid-immune interactions across individuals and whether the optimization of lipid-immune interactions requires precision nutrition approaches to mitigate or manage disease. In this review, we discuss the mechanisms by which lipids regulate immune responses and the influence of dietary lipids on these processes, highlighting compelling areas for future research.
PubMed: 37764683
DOI: 10.3390/nu15183899 -
Journal of Cardiovascular Development... Jun 2023Heart failure (HF) remains an important global health issue, substantially contributing to morbidity and mortality. According to epidemiological studies, men and women... (Review)
Review
Heart failure (HF) remains an important global health issue, substantially contributing to morbidity and mortality. According to epidemiological studies, men and women face nearly equivalent lifetime risks for HF. However, their experiences diverge significantly when it comes to HF subtypes: men tend to develop HF with reduced ejection fraction more frequently, whereas women are predominantly affected by HF with preserved ejection fraction. This divergence underlines the presence of numerous sex-based disparities across various facets of HF, encompassing aspects such as risk factors, clinical presentation, underlying pathophysiology, and response to therapy. Despite these apparent discrepancies, our understanding of them is far from complete, with key knowledge gaps still existing. Current guidelines from various professional societies acknowledge the existence of sex-based differences in HF management, yet they are lacking in providing explicit, actionable recommendations tailored to these differences. In this comprehensive review, we delve deeper into these sex-specific differences within the context of HF, critically examining associated definitions, risk factors, and therapeutic strategies. We provide a specific emphasis on aspects exclusive to women, such as the impact of pregnancy-induced hypertension and premature menopause, as these unique factors warrant greater attention in the broader HF discussion. Additionally, we aim to clarify ongoing controversies and knowledge gaps pertaining to the pharmacological treatment of HF and the sex-specific indications for cardiac implantable electronic devices. By shining a light on these issues, we hope to stimulate a more nuanced understanding and promote the development of more sex-responsive approaches in HF management.
PubMed: 37504533
DOI: 10.3390/jcdd10070277 -
Cells Jul 2023In this review, advances in the understanding of epigenetic reprogramming from fertilization to the development of primordial germline cells in a mouse and embryo are... (Review)
Review
In this review, advances in the understanding of epigenetic reprogramming from fertilization to the development of primordial germline cells in a mouse and embryo are discussed. To gain insights into the molecular underpinnings of various diseases, it is essential to comprehend the intricate interplay between genetic, epigenetic, and environmental factors during cellular reprogramming and embryonic differentiation. An increasing range of diseases, including cancer and developmental disorders, have been linked to alterations in DNA methylation and histone modifications. Global epigenetic reprogramming occurs in mammals at two stages: post-fertilization and during the development of primordial germ cells (PGC). Epigenetic reprogramming after fertilization involves rapid demethylation of the paternal genome mediated through active and passive DNA demethylation, and gradual demethylation in the maternal genome through passive DNA demethylation. The de novo DNA methyltransferase enzymes, and , restore DNA methylation beginning from the blastocyst stage until the formation of the gastrula, and DNA maintenance methyltransferase, , maintains methylation in the somatic cells. The PGC undergo a second round of global demethylation after allocation during the formative pluripotent stage before gastrulation, where the imprints and the methylation marks on the transposable elements known as retrotransposons, including long interspersed nuclear elements (LINE-1) and intracisternal A-particle (IAP) elements are demethylated as well. Finally, DNA methylation is restored in the PGC at the implantation stage including sex-specific imprints corresponding to the sex of the embryo. This review introduces a novel perspective by uncovering how toxicants and stress stimuli impact the critical period of allocation during formative pluripotency, potentially influencing both the quantity and quality of PGCs. Furthermore, the comprehensive comparison of epigenetic events between and breaks new ground, empowering researchers to make informed decisions regarding the suitability of mouse models for their experiments.
Topics: Male; Female; Humans; Mice; Animals; Epigenesis, Genetic; Cell Differentiation; Germ Cells; Fertilization; DNA; Mammals
PubMed: 37508536
DOI: 10.3390/cells12141874 -
Hepatology Communications Nov 2023Alpha-fetoprotein (AFP) and des-gamma carboxyprothrombin (DCP), also known as protein induced by vitamin K absence-II (PIVKA-II [DCP]) are biomarkers for HCC with...
BACKGROUND
Alpha-fetoprotein (AFP) and des-gamma carboxyprothrombin (DCP), also known as protein induced by vitamin K absence-II (PIVKA-II [DCP]) are biomarkers for HCC with limited diagnostic value when used in isolation. The novel GAAD algorithm is an in vitro diagnostic combining PIVKA-II (DCP) and AFP measurements, age, and gender (biological sex) to generate a semi-quantitative result. We conducted prospective studies to develop, implement, and clinically validate the GAAD algorithm for differentiating HCC (early and all-stage) and benign chronic liver disease (CLD), across disease stages and etiologies.
METHODS
Patients aged ≥18 years with HCC or CLD were prospectively enrolled internationally into algorithm development [n = 1084; 309 HCC cases (40.7% early-stage) and 736 controls] and clinical validation studies [n = 877; 366 HCC cases (47.6% early-stage) and 303 controls]. Serum samples were analyzed on a cobas® e 601 analyzer. Performance was assessed using receiver operating characteristic curve analyses to calculate AUC.
RESULTS
For algorithm development, AUC for differentiation between early-stage HCC and CLD was 90.7%, 84.4%, and 77.2% for GAAD, AFP, and PIVKA-II, respectively. The sensitivity of GAAD for the detection of early-stage HCC was 71.8% with 90.0% specificity. Similar results were shown in the clinical validation study; AUC for differentiation between early-stage HCC and CLD was 91.4% with 70.1% sensitivity and 93.7% specificity. GAAD also showed strong specificity, with a lower rate of false positives regardless of disease stage, etiology, or region.
CONCLUSIONS
The GAAD algorithm significantly improves early-stage HCC detection for patients with CLD undergoing HCC surveillance. Further phase III and IV studies are warranted to assess the utility of incorporating the algorithm into clinical practice.
Topics: Humans; Adolescent; Adult; Carcinoma, Hepatocellular; Liver Neoplasms; Prospective Studies; alpha-Fetoproteins; Algorithms
PubMed: 37938100
DOI: 10.1097/HC9.0000000000000317