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International Journal of Molecular... Jul 2023Sporadic inclusion body myositis (s-IBM) represents a unique disease within idiopathic inflammatory myopathies with a dual myodegenerative-autoimmune physiopathology and...
Sporadic inclusion body myositis (s-IBM) represents a unique disease within idiopathic inflammatory myopathies with a dual myodegenerative-autoimmune physiopathology and a lack of an efficacious treatment. Circulating miRNA expression could expand our knowledge of s-IBM patho-mechanisms and provide new potential disease biomarkers. To evaluate the expression of selected pre-amplified miRNAs in the serum of s-IBM patients compared to those of a sex- and age-matched healthy control group, we enrolled 14 consecutive s-IBM patients and 8 sex- and age-matched healthy controls. By using two different normalization approaches, we found one downregulated and three upregulated miRNAs. hsa-miR-192-5p was significantly downregulated, while hsa-miR-372-3p was found to be upregulated more in the s-IBM patients compared to the level of the controls. The other two miRNAs had a very low expression levels (raw Ct data > 29). hsa-miR-192-5p and hsa-miR-372-3p were found to be significantly dysregulated in the serum of s-IBM patients. These miRNAs are involved in differentiation and regeneration processes, thus possibly reflecting pathological mechanisms in s-IBM muscles and potentially representing disease biomarkers.
Topics: Humans; Circulating MicroRNA; Myositis, Inclusion Body; MicroRNAs; Myositis; Biomarkers
PubMed: 37446317
DOI: 10.3390/ijms241311139 -
Annual Review of Animal Biosciences Feb 2024Sexual reproduction is prevalent across diverse taxa. However, sex-determination mechanisms are so diverse that even closely related species often differ in... (Review)
Review
Sexual reproduction is prevalent across diverse taxa. However, sex-determination mechanisms are so diverse that even closely related species often differ in sex-determination systems. Teleost fish is a taxonomic group with frequent turnovers of sex-determining mechanisms and thus provides us with great opportunities to investigate the molecular and evolutionary mechanisms underlying the turnover of sex-determining systems. Here, we compile recent studies on the diversity of sex-determination mechanisms in fish. We demonstrate that genes in the TGF-β signaling pathway are frequently used for master sex-determining (MSD) genes. MSD genes arise via two main mechanisms, duplication-and-transposition and allelic mutations, with a few exceptions. We also demonstrate that temperature influences sex determination in many fish species, even those with sex chromosomes, with higher temperatures inducing differentiation into males in most cases. Finally, we review theoretical models for the turnover of sex-determining mechanisms and discuss what questions remain elusive.
Topics: Male; Animals; Sex Determination Processes; Fishes; Sex Chromosomes; Biological Evolution; Mutation
PubMed: 37863090
DOI: 10.1146/annurev-animal-021122-113935 -
Phenomics (Cham, Switzerland) Aug 2023Ageing is often accompanied with a decline in immune system function, resulting in immune ageing. Numerous studies have focussed on the changes in different lymphocyte...
UNLABELLED
Ageing is often accompanied with a decline in immune system function, resulting in immune ageing. Numerous studies have focussed on the changes in different lymphocyte subsets in diseases and immunosenescence. The change in immune phenotype is a key indication of the diseased or healthy status. However, the changes in lymphocyte number and phenotype brought about by ageing have not been comprehensively analysed. Here, we analysed T and natural killer (NK) cell subsets, the phenotype and cell differentiation states in 43,096 healthy individuals, aged 20-88 years, without known diseases. Thirty-six immune parameters were analysed and the reference ranges of these subsets were established in different age groups divided into 5-year intervals. The data were subjected to random forest machine learning for immune-ageing modelling and confirmed using the neural network analysis. Our initial analysis and machine modelling prediction showed that naïve T cells decreased with ageing, whereas central memory T cells (Tcm) and effector memory T cells (Tem) increased cluster of differentiation (CD) 28-associated T cells. This is the largest study to investigate the correlation between age and immune cell function in a Chinese population, and provides insightful differences, suggesting that healthy adults might be considerably influenced by age and sex. The age of a person's immune system might be different from their chronological age. Our immune-ageing modelling study is one of the largest studies to provide insights into 'immune-age' rather than 'biological-age'. Through machine learning, we identified immune factors influencing the most through ageing and built a model for immune-ageing prediction. Our research not only reveals the impact of age on immune parameter differences within the Chinese population, but also provides new insights for monitoring and preventing some diseases in clinical practice.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s43657-023-00106-0.
PubMed: 37589027
DOI: 10.1007/s43657-023-00106-0 -
Translational Psychiatry Dec 2023Peripheral blood metabolomics was used to gain chemical insight into the biology of treatment-refractory Major Depressive Disorder with suicidal ideation, and to...
Peripheral blood metabolomics was used to gain chemical insight into the biology of treatment-refractory Major Depressive Disorder with suicidal ideation, and to identify individualized differences for personalized care. The study cohort consisted of 99 patients with treatment-refractory major depressive disorder and suicidal ideation (trMDD-SI n = 52 females and 47 males) and 94 age- and sex-matched healthy controls (n = 48 females and 46 males). The median age was 29 years (IQR 22-42). Targeted, broad-spectrum metabolomics measured 448 metabolites. Fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) were measured as biomarkers of mitochondrial dysfunction. The diagnostic accuracy of plasma metabolomics was over 90% (95%CI: 0.80-1.0) by area under the receiver operator characteristic (AUROC) curve analysis. Over 55% of the metabolic impact in males and 75% in females came from abnormalities in lipids. Modified purines and pyrimidines from tRNA, rRNA, and mRNA turnover were increased in the trMDD-SI group. FGF21 was increased in both males and females. Increased lactate, glutamate, and saccharopine, and decreased cystine provided evidence of reductive stress. Seventy-five percent of the metabolomic abnormalities found were individualized. Personalized deficiencies in CoQ10, flavin adenine dinucleotide (FAD), citrulline, lutein, carnitine, or folate were found. Pathways regulated by mitochondrial function dominated the metabolic signature. Peripheral blood metabolomics identified mitochondrial dysfunction and reductive stress as common denominators in suicidal ideation associated with treatment-refractory major depressive disorder. Individualized metabolic differences were found that may help with personalized management.
Topics: Male; Female; Humans; Adult; Suicidal Ideation; Depressive Disorder, Major; Lutein; Biomarkers; Mitochondrial Diseases
PubMed: 38097555
DOI: 10.1038/s41398-023-02696-9 -
Seminars in Arthritis and Rheumatism Oct 2023To determine the prognostic factors of dermatomyositis with anti-melanoma differentiation-associated gene 5 (MDA5) antibody, a rare disease and often complicated by... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To determine the prognostic factors of dermatomyositis with anti-melanoma differentiation-associated gene 5 (MDA5) antibody, a rare disease and often complicated by life-threatening, rapidly progressive interstitial lung disease.
METHODS
Herein, we searched the Medline, Embase, and Cochrane Library databases and extracted studies published before August 23, 2022. Pooled analysis of hazard ratios (HRs) or odds ratios was used to identify prognostic factors for mortality among patients with anti-MDA5 antibody-positive dermatomyositis (MDA5+ DM).
RESULTS
Twenty-nine cohorts with 2,645 patients were included in this meta-analysis. Factors related to poor prognosis included old age (HR 1.54, 95% confidence interval (CI) 1.41-1.69, p < 0.01), male sex (HR 2.07, 95% CI 1.34-3.18, p < 0.01), rapidly progressive interstitial lung disease (RP-ILD) (HR 9.34, 95% CI 6.39-13.6, p < 0.01), high levels of ferritin (HR 1.05, 95% CI 1.01-1.08, p < 0.01), C-reactive protein (CRP) (HR 1.12, 95% CI 1.06-1.19, p < 0.01), creatine kinase (HR 1.05, 95% CI 1.03-1.07, p < 0.01), and lactate dehydrogenase (LDH) (HR 1.27, 95% CI 1.12-1.45, p < 0.01), whereas oxygen index (HR 0.990, 95% CI 0.988-0.992, p < 0.01), partial pressure of oxygen (HR 0.933, 95% CI 0.906-0.961, p < 0.01), forced vital capacity (HR 0.962, 95% CI 0.928-0.998, p = 0.038), and lymphocyte count (HR 0.421, 95% CI 0.282-0.629, p < 0.01) were associated with better outcomes.
CONCLUSIONS
Old age, male sex, hypoxemia, low forced vital capacity, lymphocytopenia, and high levels of ferritin, CRP, creatine kinase, and LDH are risk factors for mortality in patients with MDA5+ DM. However, a cautious interpretation of these results and further quality investigation are warranted.
Topics: Humans; Male; Autoantibodies; Dermatomyositis; Disease Progression; Ferritins; Interferon-Induced Helicase, IFIH1; Lung Diseases, Interstitial; Prognosis; Retrospective Studies; Risk Factors
PubMed: 37348186
DOI: 10.1016/j.semarthrit.2023.152231 -
International Journal of Molecular... Nov 2023Despite extensive research on orchid reproductive strategies, the genetic studies of sex differentiation in the orchid family are still lacking. In this study, we...
Despite extensive research on orchid reproductive strategies, the genetic studies of sex differentiation in the orchid family are still lacking. In this study, we compared three sexual phenotypes of bisexual flowers as well as female and male unisexual mutants. Through comparative transcriptomes, we analyzed the sex-biased differentially expressed genes (DEGs) and gene co-expression networks of sex organs (gynostemium and ovary) among them, identified the candidate genes of sex differentiation, and validated their expression by qRT-PCR. The unisexual mutants with degenerated phenotypes were compared to the bisexual plants with respect to both the flower organs and plant morphologies. Totally, 12,145, 10,789, and 14,447 genes were uniquely expressed in the female, male, and hermaphrodite sex organs, respectively. A total of 4291 sex-biased DEGs were detected among them, with 871, 2867, and 1937 DEGs in the comparisons of bisexual vs. female, bisexual vs. male, and male vs. female flowers, respectively. Two co-expressed network modules, with 81 and 419 genes were tightly correlated with female sexual traits, while two others with 265 and 135 genes were highly correlated with male sexual traits. Two female-biased hub genes ( and ) nested in the female modules, the homologs of maize sex determinant , may control the feminization of . At the same time, two male-biased hub genes ( and ) nested in the male modules, the homologs of grape sex determinant may control the androphany of . This study discovered the molecular regulation networks and proposed a model for orchid sex differentiation, therefore providing for the first time the genetic basis for the sex separation in the orchid family.
Topics: Female; Humans; Transcriptome; Gene Regulatory Networks; Flowers; Sexual and Gender Minorities; Orchidaceae; Gene Expression Regulation, Plant; Gene Expression Profiling
PubMed: 38068950
DOI: 10.3390/ijms242316627 -
Developmental Cell Feb 2024During human fetal development, sex differentiation occurs not only in the gonads but also in the adjacent developing reproductive tract. However, while the cellular...
During human fetal development, sex differentiation occurs not only in the gonads but also in the adjacent developing reproductive tract. However, while the cellular composition of male and female human fetal gonads is well described, that of the adjacent developing reproductive tract remains poorly characterized. Here, we performed single-cell transcriptomics on male and female human fetal gonads together with the adjacent developing reproductive tract from first and second trimesters, highlighting the morphological and molecular changes during sex differentiation. We validated different cell populations of the developing reproductive tract and gonads and compared the molecular signatures between the first and second trimesters, as well as between sexes, to identify conserved and sex-specific features. Together, our study provides insights into human fetal sex-specific gonadogenesis and development of the reproductive tract beyond the gonads.
Topics: Humans; Male; Female; Testis; Gonads; Ovary; Sex Differentiation; Gene Expression Profiling
PubMed: 38295793
DOI: 10.1016/j.devcel.2024.01.006 -
Radiologia Oct 2023Myxoid liposarcoma is classified in the group of sarcomas with adipose differentiation, which is the second most common group of sarcomas. However, myxoid liposarcoma is...
BACKGROUND AND AIMS
Myxoid liposarcoma is classified in the group of sarcomas with adipose differentiation, which is the second most common group of sarcomas. However, myxoid liposarcoma is not a homogeneous entity, because the behavior and clinical course of these tumours can vary widely. This study aimed to describe the magnetic resonance imaging (MRI) features of myxoid liposarcomas and to determine whether the MRI features are associated with the histologic grade and can differentiate between low-grade and high-grade tumours and thus help in clinical decision making.
MATERIAL AND METHODS
We studied 36 patients with myxoid liposarcomas treated at our centre between 2010 and 2018. We analysed clinical variables (age, sex, and tumour site) and MRI features (size, depth, borders, fatty component, myxoid component, non-fatty/non-myxoid component, apparent diffusion coefficient (ADC), and type of enhancement after the administration of intravenous contrast material). We correlated the MRI features with the histologic grade and the percentage of round cells.
RESULTS
In our series, patients with myxoid liposarcomas were mainly young adults (median age, 43 years). There were no differences between sexes; 97.2% were located in the lower limbs, 86.1% were deep, and 77.8% had well-defined borders. Of the 23 myxoid liposarcomas that contained no fat, 16 (69.6%) were high grade (p = 0.01). All the tumors with a myxoid component of less than 25% were high grade (p = 0.01); 83.3% of those with a non-fatty/non-myxoid component greater than 50% were high grade (p = 0.03) and 61.5% had more than 5% round cells (p = 0.01). Diffusion sequences were obtained in 14 of the 36 patients; ADC values were high (median, 2 × 10 mm/s), although there were no significant associations between low-grade and high-grade tumours. Contrast-enhanced images were available for 30 (83.3%) patients; 83.3% of the tumours with heterogeneous enhancement were high grade (p = 0.01).
CONCLUSIONS
MRI can be useful for differentiating between high- and low-grade myxoid liposarcomas and can help in clinical decision making.
Topics: Young Adult; Humans; Adult; Liposarcoma, Myxoid; Soft Tissue Neoplasms; Magnetic Resonance Imaging; Retrospective Studies
PubMed: 37858349
DOI: 10.1016/j.rxeng.2021.01.006 -
Bulletin of the World Health... Oct 2023Effectively tracking progress on initiatives focused on gender equity requires clear differentiation between the terms sex and gender. Sex usually refers to a person's...
Effectively tracking progress on initiatives focused on gender equity requires clear differentiation between the terms sex and gender. Sex usually refers to a person's biological characteristics, whereas gender refers to socially constructed roles and norms. Although both terms are often treated as binaries, gender is a spectrum and sex may include intersex individuals. While the terms are interrelated, they are sometimes conflated or used interchangeably in health data. Their fundamental distinctions, however, have implications for the conduct of research and the design of interventions targeting sex- and gender-based health disparities. We use the example of coronavirus disease 2019 to show how conflating these terms in data collection makes it difficult to ascertain whether disparities in infection rates, morbidity and mortality are determined by sex or gender. Although the exact process of collecting data on sex and gender may need to be adapted for specific contexts, there are steps that can be taken so that health data better reflect the differences between these concepts. Possible actions include using a two-step data collection process to determine both sex and gender of individuals, and encouraging recognition of intersex, third gender, transgender and gender nonbinary people. There also needs to be acceptance and commitment by data collectors and research editors; for example, by using tools such as the Sex and Gender Equity in Research checklist. With clearer distinctions between these foundational terms and how they are used in health data, we can achieve more accurate research findings, better-tailored interventions and better progress towards gender equity.
Topics: Male; Female; Humans; Gender Equity; COVID-19; Gender Identity; Transgender Persons; Data Collection; Health Equity
PubMed: 37772198
DOI: 10.2471/BLT.22.289310