-
Frontiers in Immunology 2024Polymorphisms in the KIR and HLA genes contribute to the diversity of the NK cell repertoire. Extrinsic factors also play a role in modifying this repertoire. The best...
INTRODUCTION
Polymorphisms in the KIR and HLA genes contribute to the diversity of the NK cell repertoire. Extrinsic factors also play a role in modifying this repertoire. The best example is cytomegalovirus, which promotes the expansion of memory-like NK cells. However, the mechanisms governing this phenotypic structure are poorly understood. Furthermore, the influence of age and sex has been understudied.
METHODS
In this study, we examined these parameters in a cohort of 200 healthy volunteer blood donors, focusing on the major inhibitory KIR receptors and CD94/NKG2A, as well as the differentiation marker CD57 and the memory-like population marker NKG2C. Flow cytometry and two joint analyses, unsupervised and semi-supervised, helped define the impact of various intrinsic and extrinsic markers on the phenotypic structure of the NK cell repertoire.
RESULTS
In the KIR NK cell compartment, the KIR3DL1 gene is crucial, as unexpressed alleles lead to a repertoire dominated by KIR2D interacting only with HLA-C ligands, whereas an expressed KIR3DL1 gene allows for a greater diversity of NK cell subpopulations interacting with all HLA class I ligands. KIR2DL2 subsequently favors the KIR2D NK cell repertoire specific to C1/C2 ligands, whereas its absence promotes the expression of KIR2DL1 specific to the C2 ligand. The C2C2Bw4+ environment, marked by strong -21T motifs, favors the expansion of the NK cell population expressing only CD57, whereas the absence of HLA-A3/A11 ligands favors the population expressing only NKG2A, a population highly represented within the repertoire. The AA KIR genotype favors NK cell populations without KIR and NKG2A receptors, whereas the KIR B+ genotypes favor populations expressing KIR and NKG2A. Interestingly, we showed that women have a repertoire enriched in CD57- NK cell populations, while men have more CD57+ NK cell subpopulations.
DISCUSSION
Overall, our data demonstrate that the phenotypic structure of the NK cell repertoire follows well-defined genetic rules and that immunological history, sex, and age contribute to shaping this NK cell diversity. These elements can contribute to the better selection of hematopoietic stem cell donors and the definition of allogeneic NK cells for cell engineering in NK cell-based immunotherapy approaches.cters are displayed correctly.
Topics: Humans; Killer Cells, Natural; Female; Male; Adult; Cytomegalovirus Infections; Cytomegalovirus; Genotype; Receptors, KIR; Middle Aged; Sex Factors; Age Factors; CD57 Antigens; Histocompatibility Testing; Young Adult; NK Cell Lectin-Like Receptor Subfamily C; HLA Antigens; Aged; Receptors, KIR3DL1
PubMed: 38736873
DOI: 10.3389/fimmu.2024.1389358 -
Journal of Advanced Research May 2024Understanding the sex determination mechanisms in birds has great significance for the biological sciences and production in the poultry industry. Sex determination in...
INTRODUCTION
Understanding the sex determination mechanisms in birds has great significance for the biological sciences and production in the poultry industry. Sex determination in chickens is a complex process that involves fate decisions of supporting cells such as granulosa or Sertoli cells. However, a systematic understanding of the genetic regulation and cell commitment process underlying sex determination in chickens is still lacking.
OBJECTIVES
We aimed to dissect the molecular characteristics associated with sex determination in the gonads of chicken embryos.
METHODS
Single-nucleus RNA-seq (snRNA-seq) and ATAC-seq (snATAC-seq) analysis were conducted on the gonads of female and male chickens at embryonic day 3.5 (E3.5), E4.5, and E5.5.
RESULTS
Here, we provided a time-course transcriptional and chromatin accessible profiling of gonads during chicken sex determination at single-cell resolution. We uncovered differences in cell composition and developmental trajectories between female and male gonads and found that the divergence of transcription and accessibility in gonadal cells first emerged at E5.5. Furthermore, we revealed key cell-type-specific transcription factors (TFs) and regulatory networks that drive lineage commitment. Sex determination signaling pathways, dominated by BMP signaling, are preferentially activated in males during gonadal development. Further pseudotime analysis of the supporting cells indicated that granulosa cells were regulated mainly by the TEAD gene family and that Sertoli cells were driven by the DMRT1 regulons. Cross-species analysis suggested high conservation of both cell types and cell-lineage-specific TFs across the six vertebrates.
CONCLUSIONS
Overall, our study will contribute to accelerating the development of sex manipulation technology in the poultry industry and the application of chickens as a unique model for studying cell fate decisions.
PubMed: 38734369
DOI: 10.1016/j.jare.2024.05.007 -
Genomics May 2024Temperature is one of the most important non-genetic sex differentiation factors for fish. The technique of high temperature-induced sex reversal is commonly used in... (Review)
Review
Temperature is one of the most important non-genetic sex differentiation factors for fish. The technique of high temperature-induced sex reversal is commonly used in Nile tilapia (Oreochromis niloticus) culture, although the molecular regulatory mechanisms involved in this process remain unclear. The brain is an essential organ for the regulation of neural signals involved in germ cell differentiation and gonad development. To investigate the regulatory roles of miRNAs-mRNAs in the conversion of female to male Nile tilapia gender under high-temperature stress, we compared RNA-Seq data from brain tissues between a control group (28 °C) and a high temperature-treated group (36 °C). The result showed that a total of 123,432,984 miRNA valid reads, 288,202,524 mRNA clean reads, 1128 miRNAs, and 32,918 mRNAs were obtained. Among them, there were 222 significant differentially expressed miRNAs (DE miRNAs) and 810 differentially expressed mRNAs (DE mRNAs) between the two groups. Eight DE miRNAs and eight DE mRNAs were randomly selected, and their expression patterns were validated by qRT-PCR. The miRNA-mRNA co-expression network demonstrated that 40 DE miRNAs targeted 136 protein-coding genes. Functional enrichment analysis demonstrated that these genes were involved in several gonadal differentiation pathways, including the oocyte meiosis signaling pathway, progesterone-mediated oocyte maturation signaling pathway, cell cycle signaling pathway and GnRH signaling pathway. Then, an interaction network was constructed for 8 miRNAs (mir-137-5p, let-7d, mir-1388-5p, mir-124-4-5p, mir-1306, mir-99, mir-130b and mir-21) and 10 mRNAs (smc1al, itpr2, mapk1, ints8, cpeb1b, bub1, fbxo5, mmp14b, cdk1 and hrasb) involved in the oocyte meiosis signaling pathway. These findings provide novel information about the mechanisms underlying miRNA-mediated sex reversal in female Nile tilapia.
Topics: Animals; MicroRNAs; Cichlids; Female; RNA, Messenger; Brain; Sex Differentiation; Male; Hot Temperature; Gene Regulatory Networks; Sex Determination Processes
PubMed: 38734154
DOI: 10.1016/j.ygeno.2024.110856 -
Animals : An Open Access Journal From... Apr 2024Ovarian tumors in mares are uncommon in comparison to other neoplasms and are classified into three categories: gonadal stromal tumors, coelomic epithelium surface...
Ovarian tumors in mares are uncommon in comparison to other neoplasms and are classified into three categories: gonadal stromal tumors, coelomic epithelium surface tumors, and germinal cell tumors. Some ovarian neoplasms histologically show a mixture of multiple cell types in the same tumor, such as fibrothecoma; therefore, the differentiation between fibroma and thecoma is often difficult. According to the World Health Organization, fibrothecomas are classified as sex-cord stromal tumors (pure stromal tumors). Neoplasms such as fibrothecoma present with limited morphological, clinical, ultrasonographic, and endocrine profile characteristics. To diagnose this type of tumor, a broad clinical examination is needed, but histopathology remains the most accurate. Herein, we report a case of incidentally found ovarian fibrothecoma during a diagnostic laparotomy in a 6-year-old Dutch Warmblood (KWPN) mare who presented to the clinic with colic symptoms. After a unilateral ovariectomy, the altered right ovary was diagnosed as fibrothecoma based on histopathological features.
PubMed: 38731310
DOI: 10.3390/ani14091307 -
Journal of Clinical Medicine May 2024Assessment of potential lymph node metastasis is mandatory in the appropriate treatment of early gastric cancers. This study analysed factors associated with lymph node...
Assessment of potential lymph node metastasis is mandatory in the appropriate treatment of early gastric cancers. This study analysed factors associated with lymph node metastasis to identify differences between node-negative and node-positive patients and between T1a and T1b cancers. The clinicopathological features of 129 early gastric cancer patients who had undergone radical gastrectomy were analysed to identify predictive factors for lymph node metastasis. Lymph node metastasis was detected in 76 (59.0%) patients. Node-positive patients were younger (58.1 ± 11.3 years) than those without metastasis (61.9 ± 9.6 years, = 0.02). Greater tumour sizes were observed in patients with lymph node metastasis (3.6 ± 1.0 cm) compared to node-negative patients (1.9 ± 0.5 cm, = 0.00001). Depressed form, ulceration, diffuse histological type, and undifferentiated lesions were more frequent in node-positive patients than in the node-negative group. Tumour size > 3.0 cm showed a correlation with lymph node metastasis in both T1a ( = 0.0001) and T1b ( = 0.006) cancer. The male sex ( = 0.006) had a significant correlation with lymph node metastasis in T1a cancer. Depressed appearance ( = 0.02), ulceration ( = 0.03), differentiation ( = 0.0001), diffuse type ( = 0.0002), and lower third location ( = 0.005) were associated with lymph node metastasis in T1b cancer. Tumour size > 3 cm, undifferentiated lesions, ulceration, diffuse type, lower third location, and submucosal invasion are risk factors for lymph node metastasis in early gastric cancer.
PubMed: 38731188
DOI: 10.3390/jcm13092659 -
Medicine May 2024Both Parkinson disease (PD) and Essential tremor (ET) are movement disorders causing tremors in elderly individuals. Although PD and ET are different disease, they often... (Comparative Study)
Comparative Study
Both Parkinson disease (PD) and Essential tremor (ET) are movement disorders causing tremors in elderly individuals. Although PD and ET are different disease, they often present with similar initial symptoms, making their differentiation challenging with magnetic resonance imaging (MRI) techniques. This study aimed to identify structural brain differences among PD, ET, and health controls (HCs) using 7-Tesla (T) MRI. We assessed the whole-brain parcellation in gray matter volume, thickness, subcortical volume, and small regions of basal ganglia in PD (n = 18), ET (n = 15), and HCs (n = 18), who were matched for age and sex. Brain structure analysis was performed automatic segmentation through Freesurfer software. Small regions of basal ganglia were manually segmented by ITK-SNAP. Additionally, we examined the associations between clinical indicators (symptom duration, unified Parkinson diseases rating scale (UPDRS), and clinical rating scale for tremor (CRST)) and brain structure. PD showed a significant reduction in gray matter volume in the postcentral region compared to ET. ET showed a significant reduction in cerebellum volume compared to HCs. There was a negative correlation between CRST scores (B and C) and gray matter thickness in right superior frontal in ET. This study demonstrated potential of 7T MRI in differentiating brain structure differences among PD, ET, and HCs. Specific findings, such as parietal lobe atrophy in PD compared to ET and cerebellum atrophy in ET compared to HCs, the importance of advanced imaging techniques in accurately diagnosing and distinguishing between movement disorders that present with similar initial symptoms.
Topics: Humans; Essential Tremor; Parkinson Disease; Magnetic Resonance Imaging; Female; Male; Aged; Middle Aged; Brain; Case-Control Studies; Gray Matter
PubMed: 38728497
DOI: 10.1097/MD.0000000000038139 -
Frontiers in Endocrinology 2024In mammals, the development of male or female gonads from fetal bipotential gonads depends on intricate genetic networks. Changes in dosage or temporal expression of... (Review)
Review
In mammals, the development of male or female gonads from fetal bipotential gonads depends on intricate genetic networks. Changes in dosage or temporal expression of sex-determining genes can lead to differences of gonadal development. Two rare conditions are associated with disruptions in ovarian determination, including 46,XX testicular differences in sex development (DSD), in which the 46,XX gonads differentiate into testes, and 46,XX ovotesticular DSD, characterized by the coexistence of ovarian and testicular tissue in the same individual. Several mechanisms have been identified that may contribute to the development of testicular tissue in XX gonads. This includes translocation of to the X chromosome or an autosome. In the absence of , other genes associated with testis development may be overexpressed or there may be a reduction in the activity of pro-ovarian/antitesticular factors. However, it is important to note that a significant number of patients with these DSD conditions have not yet recognized a genetic diagnosis. This finding suggests that there are additional genetic pathways or epigenetic mechanisms that have yet to be identified. The text will provide an overview of the current understanding of the genetic factors contributing to 46,XX DSD, specifically focusing on testicular and ovotesticular DSD conditions. It will summarize the existing knowledge regarding the genetic causes of these differences. Furthermore, it will explore the potential involvement of other factors, such as epigenetic mechanisms, in developing these conditions.
Topics: Humans; Male; Testis; Animals; Female; 46, XX Disorders of Sex Development; Sex Differentiation; Disorders of Sex Development
PubMed: 38721146
DOI: 10.3389/fendo.2024.1385901 -
Discover Oncology May 2024Supraglottic squamous cell carcinoma (SGSCC) is characterized by low differentiation, rapid growth, and inconspicuous initial manifestations. Early detection and prompt...
BACKGROUND
Supraglottic squamous cell carcinoma (SGSCC) is characterized by low differentiation, rapid growth, and inconspicuous initial manifestations. Early detection and prompt treatment can significantly improve survival rates. The main focus of treatment is to maintain optimal laryngeal function.
METHODS
Using the Surveillance, Epidemiology, and End Results (SEER) database, we conducted univariate and multivariate Cox regression analyses to identify independent prognostic factors for T1-T2 SGSCC. We also enrolled 109 patients with T1-T2 SGSCC from the First Affiliated Hospital of Xinjiang Medical University as an external validation set. In addition, we developed a nomogram to predict the prognosis of T1-T2 SGSCC, assessed the predictive accuracy and discriminatory ability of the nomogram using the area under the curve (AUC), C-index, receiver operating characteristic (ROC) curve and calibration curve, and confirmed the clinical validity of the nomogram using decision curve analysis (DCA).
RESULTS
Our investigation identified nine prognostic indicators for T1-T2 SGSCC: age (≥ 65 years), marital status, American Joint Committee on Cancer (AJCC) stage (II-IV), grade (III-IV), M stage (M1), radiotherapy, chemotherapy, sex (female), and surgery. These variables were used to create accurate nomograms that predict overall and specific survival rates at 1, 3, and 5 years. The nomograms demonstrated superior prognostic value and accuracy compared to AJCC staging. Laryngectomy with partial laryngectomy is the preferred treatment option for T1-T2 SGSCC cases, providing superior overall survival (OS) and cancer-specific survival (CSS). Radiotherapy also improves OS and CSS. Our results were based on a comprehensive analysis of various indicators, including the C-index, ROC curve, calibration curve, and DCA curve.
CONCLUSION
Nomograms provide significant advantages in treatment decision making and diagnosis. Laryngectomy with partial laryngectomy is the most appropriate method for T1-T2 SGSCC cases. However, radiotherapy can also be used. Thus, patients with T1-T2 SGSCC should be evaluated to determine if combination therapy is the optimal treatment approach. Nevertheless, further research is needed to understand the role of chemotherapy. Overall, this study identified nine key predictors of future outcomes, aiding healthcare professionals in assessing risks and making treatment decisions for T1-T2 SGSCC patients.
PubMed: 38717631
DOI: 10.1007/s12672-024-01015-y -
Clinical and Translational... Jun 2024The characteristics of gastric carcinoma in young individuals differ from that in older individuals. We conducted a systematic review and meta-analysis to explore the... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The characteristics of gastric carcinoma in young individuals differ from that in older individuals. We conducted a systematic review and meta-analysis to explore the clinicopathological features and risk factors associated with young-onset (younger than 50 years) gastric carcinoma.
METHODS
We searched for studies published between January 1, 1990, and September 1, 2023, on patients with young-onset gastric carcinoma in PubMed, EMBASE, Web of Science, and MEDLINE to explore clinicopathological characteristics among this specific patient group. Extracted information included the proportion of patients with symptoms or family history of gastric cancer, tumor location, and histological features such as Lauren or World Health Organization histological classification and degree of differentiation. Additional analyses were conducted on risk factors such as positive family history, Helicobacter pylori infection, or high-risk nutritional or behavioral factors. The estimates were derived using random or fixed-effect models and included subgroup analyses based on different sex and age groups. This study was registered in PROSPERO (CRD42023466131).
RESULTS
We identified 5,696 records, 1,292 were included in the quality assessment stage. Finally, 84 studies from 18 countries or regions including 89,447 patients with young-onset gastric carcinoma were included. Young-onset gastric carcinoma has slight female predominance (53.7%, 95% confidence interval [CI]: 51.6-55.7%), with most having symptoms (87.0%, 95% CI: 82.4%-91.7%). Family history was reported in 12.1% (95% CI: 9.5%-14.7%). H. pylori infection was detected in 60.0% of cases (95% CI: 47.1%-72.8%). Most of these carcinomas were in the non-cardia region (89.6%, 95% CI: 82.4%-96.8%), exhibiting Lauren diffuse-type histology (71.1%, 95% CI: 66.8%-75.3%) and poor/undifferentiated features (81.9%, 95% CI%: 79.7-84.2%). A positive family history of gastric cancer was the most important risk factor associated with the development of gastric carcinoma in young individuals (pooled odds ratios 4.0, 95% CI: 2.8-5.2), followed by H. pylori infection (odds ratio 2.3; 95% CI: 1.4-3.2) and dietary and other lifestyle risk factors.
DISCUSSION
Young-onset gastric carcinoma exhibits specific clinicopathological characteristics, with positive family history being the most important risk factor. Most of the patients were symptomatic at diagnosis. These findings could help to inform future strategies for the early detection of gastric carcinoma among young individuals.
Topics: Humans; Stomach Neoplasms; Risk Factors; Age of Onset; Helicobacter Infections; Helicobacter pylori; Adult; Middle Aged; Male; Female
PubMed: 38717039
DOI: 10.14309/ctg.0000000000000714 -
Nature Communications May 2024Mammalian sex determination is controlled by antagonistic gene cascades operating in embryonic undifferentiated gonads. The expression of the Y-linked gene SRY is...
Mammalian sex determination is controlled by antagonistic gene cascades operating in embryonic undifferentiated gonads. The expression of the Y-linked gene SRY is sufficient to trigger the testicular pathway, whereas its absence in XX embryos leads to ovarian differentiation. Yet, the potential involvement of non-coding regulation in this process remains unclear. Here we show that the deletion of a single microRNA cluster, miR-17~92, induces complete primary male-to-female sex reversal in XY mice. Sry expression is delayed in XY knockout gonads, which develop as ovaries. Sertoli cell differentiation is reduced, delayed and unable to sustain testicular development. Pre-supporting cells in mutant gonads undergo a transient state of sex ambiguity which is subsequently resolved towards the ovarian fate. The miR-17~92 predicted target genes are upregulated, affecting the fine regulation of gene networks controlling gonad development. Thus, microRNAs emerge as key components for mammalian sex determination, controlling Sry expression timing and Sertoli cell differentiation.
Topics: Animals; MicroRNAs; Female; Male; Sertoli Cells; Mice; Ovary; Testis; Sex-Determining Region Y Protein; Cell Differentiation; Sex Determination Processes; Gene Expression Regulation, Developmental; Mice, Knockout; Sex Differentiation; Disorders of Sex Development; Gonads
PubMed: 38714644
DOI: 10.1038/s41467-024-47658-x