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The Booroola fecundity mutation (FecB) in Small Tail Han sheep has been shown to enhance ovulation rates and litter sizes by affecting the hypothalamic-pituitary-gonadal (HPG) axis. Despite the pituitary's role in reproductive regulation, its involvement in FecB-induced ovulation remains understudied. Our study aimed to fill this gap by analyzing pituitary tissues from FecB homozygous (BB) and wild-type (WW) ewes during luteal and follicular phases using tandem mass tag-based protein quantification and the DIABLO framework for proteomic and transcriptomic data integration. Significant differences in 277 proteins were observed across estrus periods, with network analysis highlighting the voltage-dependent calcium channel L-type alpha-1C as a key convergence point in oxytocin signaling and GnRH secretion pathways. The DIABLO method revealed a strong correlation (0.98) between proteomic and transcriptomic datasets, indicating a coordinated response in FecB ewes. Notably, higher expression levels of Follicle Stimulating Hormone Subunit Beta (FSHB) and Luteinizing Hormone Subunit Beta (LHB) were found in BB ewes during the follicular phase, potentially due to elevated E2 concentrations. Furthermore, our analysis identified genes related to the Gamma-aminobutyric acid type A receptor family (GABRA2, GABRG1, GABRB1) in the pituitary, with GABRB1 showing higher expression in BB ewes. This suggests a role for GABA in modulating GnRH and gonadotropin feedback loops, potentially contributing to the FecB mutation's effect on ovulation. This study provides novel insights into the pituitary's role in fertility among FecB sheep, identifying GABA as a potential regulatory factor within the HPG axis. The findings also open avenues for discovering new biomarkers in pituitary endocrinology for sheep breeding purposes.
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Biomarcadores , Fertilidad , Mutación , Hipófisis , Proteoma , Transcriptoma , Animales , Femenino , Ovinos/genética , Fertilidad/genética , Hipófisis/metabolismo , Proteoma/metabolismo , Biomarcadores/metabolismo , Proteómica/métodosRESUMEN
Chemotherapy-induced premature ovarian insufficiency (CIPOI) triggers gonadotoxicity in women undergoing cancer treatment, leading to loss of ovarian reserves and subfertility, with no effective therapies available. In our study, fecal microbiota transplantation in a cisplatin-induced POI mouse model reveals that a dysbiotic gut microbiome negatively impacts ovarian health in CIPOI. Multi-omics analyses show a significant decrease in Limosilactobacillus reuteri and its catabolite, ß-resorcylic acid , in the CIPOI group in comparison to healthy controls. Supplementation with L. reuteri or ß-RA mitigates cisplatin-induced hormonal disruptions, morphological damages, and reductions in follicular reserve. Most importantly, ß-RA pre-treatment effectively preserves oocyte function, embryonic development, and fetus health, thereby protecting against chemotherapy-induced subfertility. Our results provide evidence that ß-RA suppresses the nuclear accumulation of sex-determining region Y-box 7, which in turn reduces Bcl-2-associated X activation and inhibits granulosa cell apoptosis. These findings highlight the therapeutic potential of targeting the gut-ovary axis for fertility preservation in CIPOI.
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Cisplatino , Limosilactobacillus reuteri , Ovario , Insuficiencia Ovárica Primaria , Femenino , Animales , Cisplatino/efectos adversos , Cisplatino/toxicidad , Ratones , Insuficiencia Ovárica Primaria/inducido químicamente , Insuficiencia Ovárica Primaria/patología , Ovario/efectos de los fármacos , Ovario/patología , Ovario/metabolismo , Microbioma Gastrointestinal/efectos de los fármacos , Apoptosis/efectos de los fármacos , Trasplante de Microbiota Fecal , Oocitos/efectos de los fármacos , Oocitos/metabolismo , Ratones Endogámicos C57BL , Antineoplásicos/toxicidad , Antineoplásicos/efectos adversos , Células de la Granulosa/efectos de los fármacos , Células de la Granulosa/metabolismo , Modelos Animales de Enfermedad , InfertilidadRESUMEN
Platelets are a significant component of the cell population in the tumour microenvironment (TME). Platelets influence other immune cells and perform cross-talk with tumour cells, playing an important role in tumour development. Extracellular vesicles (EVs) are small membrane vesicles released from the cells into the TME. They can transfer biological information, including proteins, nucleic acids, and metabolites, from secretory cells to target receptor cells. This process affects the progression of various human diseases, particularly cancer. In recent years, several studies have demonstrated that platelet-derived extracellular vesicles (PEVs) can help regulate the malignant biological behaviours of tumours, including malignant proliferation, resistance to cell death, invasion and metastasis, metabolic reprogramming, immunity, and angiogenesis. Consequently, PEVs have been identified as key regulators of tumour progression. Therefore, targeting PEVs is a potential strategy for tumour treatment. Furthermore, the extensive use of nanomaterials in medical research has indicated that engineered PEVs are ideal delivery systems for therapeutic drugs. Recent studies have demonstrated that PEV engineering technologies play a pivotal role in the treatment of tumours by combining photothermal therapy, immunotherapy, and chemotherapy. In addition, aberrant changes in PEVs are closely associated with the clinicopathological features of patients with tumours, which may serve as liquid biopsy markers for early diagnosis, monitoring disease progression, and the prognostic assessment of patients with tumours. A comprehensive investigation into the role and potential mechanisms of PEVs in tumourigenesis may provide novel diagnostic biomarkers and potential therapeutic strategies for treating human tumours.
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BACKGROUND: To date, clinical laboratories face challenges in quantifying retinol from DBS samples. Disputes arise throughout the whole detection process, encompassing the storage condition, the release strategy as well as the selection of internal standards. METHODS: We incubated DBS with ascorbic acid solution. Then, retinol-d4 in acetonitrile was introduced to incorporate isotopic internal standard and promote protein precipitation. Afterward, sodium carbonate solution was added to ionize cytochromes (such as bilirubin), which amplified the difference of their hydrophobicity to retinol. Subsequently, cold-induced phase separation could be facilitated to separate retinol from the impurities. In the end, the upper layer was injected for LC-MS/MS analysis. RESULTS: By comparing the detected retinol content in whole blood and DBS samples prepared from the same volume, we confirmed the established pretreatment was capable to extract most of retinol from DBS (recovery >90 %). Thereafter, we verified that within DBS, retinol possessed satisfying stability without antioxidation. Indoor-light exposure and storage duration would not cause obvious degradation (<10 %). Following systematic validation, the established method well met the criteria outlined in the relevant guidelines. After comparing with detected DBS results to the paired plasma samples, 54 out of 60 met the acceptance limit for cross-validation of ±20 %. CONCLUSIONS: We realized precise quantification of retinol from one 3.2 mm DBS disc. By circumventing conventional antioxidation, liquid-liquid/solid-phase extraction and organic solvent evaporation, the pretreatment could be completed within 15 min consuming only minimal amounts of low-toxicity chemicals (ascorbic acid, acetonitrile, and sodium carbonate). We expect this contribution holds the potential to significantly facilitate the evaluation of patients' vitamin A status by using DBS samples in the future.
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Pruebas con Sangre Seca , Cromatografía Líquida con Espectrometría de Masas , Espectrometría de Masas en Tándem , Vitamina A , Humanos , Pruebas con Sangre Seca/métodos , Cromatografía Líquida con Espectrometría de Masas/métodos , Espectrometría de Masas en Tándem/métodos , Vitamina A/sangre , Vitamina A/aislamiento & purificaciónRESUMEN
Abnormal glucose homeostasis is associated with metabolic syndromes including cardiovascular diseases, hypertension, type 2 diabetes mellitus, and obesity, highlighting the significance of maintaining a balanced glucose level for optimal biological function. This highlights the importance of maintaining normal glucose levels for proper biological functioning. Sulforaphane (SFN), the primary bioactive compound in broccoli from the Cruciferae or Brassicaceae family, has been shown to enhance glucose homeostasis effectively while exhibiting low cytotoxicity. This paper assesses the impact of SFN on glucose homeostasis in vitro, in vivo, and human trials, as well as the molecular mechanisms that drive its regulatory effects. New strategies have been proposed to enhance the bioavailability and targeted delivery of SFN in order to overcome inherent instability. The manuscript also covers the safety evaluations of SFN that have been documented for its production and utilization. Hence, a deeper understanding of the favorable influence and mechanism of SFN on glucose homeostasis, coupled with the fact that SFN is abundant in the human daily diet, may ultimately offer theoretical evidence to support its potential use in the food and pharmaceutical industries.
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Homeostasis , Isotiocianatos , Sulfóxidos , Isotiocianatos/farmacología , Isotiocianatos/administración & dosificación , Humanos , Homeostasis/efectos de los fármacos , Animales , Glucosa/metabolismo , Brassica/química , Glucemia/metabolismo , Glucemia/efectos de los fármacos , Disponibilidad BiológicaRESUMEN
Background: Hypovitaminosis K has been linked to depression and suicide, but epidemiological research is scarce. This study aimed to explore the association among vitamin K with depression and suicidal attempts. Methods: This was a retrospective cross-sectional study involving 146 cases with a history of suicidal attempts and 149 subjects without a lifetime history of suicidal attempts. The levels of thyroid hormones, lipid profile, inflammatory cytokines, and vitamins were measured. Results: Subjects who had suicidal attempts presented with a significant decrease in FT4, TC, vitamin D, and vitamin K but increased CRP levels. In these variables, vitamin K has a better diagnostic value for suicidal attempts in depressed patients, with a sensitivity of 0.842 and a specificity of 0.715. Correlation analysis suggested that vitamin K was significantly and positively related to FT4, TC, LDL, and sdLDL. Multivariate analysis showed that serum vitamin K level predicts suicidal attempts in depressive patients (OR = 0.614, P = 0.004, 95% CI 0.153-0.904). Moreover, a negative correlation between vitamin K and suicidal attempts was also noted for partial FT4, CRP, and vitamin D strata analysis. Conclusion: Our study suggests that low vitamin K levels were correlated with suicidal attempts in patients with depression, indicating that vitamin K deficiency might be a biological risk factor for depression.
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Small membranes known as exosomes surround them and are released by several cell types both in vitro and in vivo. These membranes are packed with a variety of biomolecules, including proteins, lipids, deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and non-coding RNA (ncRNA). As a source of biological nanomaterials, exosomes play a role in information and substance transmission between cells and have been identified as a general method of facilitating communication during interactions between the body, target organs, and toxins.. In order to understand the changes and mechanism of the composition and level of exosomes after biotoxin infection, this review focuses on current findings on the exosomes and highlights their novel uses in the toxicity mechanism. Exosomes are mainly used as a delivery carrier or mediated by receptors, and play an immune role after the toxin enters the body. This review expounds on the importance of exosomes in the toxicological mechanism of biotoxins and provides new insights for further diagnosis of toxic biomarkers, detoxification, and treatment development.
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Exosomas , Exosomas/metabolismo , Humanos , Animales , Toxinas Biológicas/toxicidad , Toxinas Biológicas/metabolismo , Transducción de Señal/efectos de los fármacos , Biomarcadores/metabolismoRESUMEN
Nanozyme, characterized by outstanding and inherent enzyme-mimicking properties, have emerged as highly promising alternatives to natural enzymes owning to their exceptional attributes such as regulation of oxidative stress, convenient storage, adjustable catalytic activities, remarkable stability, and effortless scalability for large-scale production. Given the potent regulatory function of nanozymes on oxidative stress and coupled with the fact that reactive oxygen species (ROS) play a vital role in the occurrence and exacerbation of metabolic diseases, nanozyme offer a unique perspective for therapy through multifunctional activities, achieving essential results in the treatment of metabolic diseases by directly scavenging excess ROS or regulating pathologically related molecules. The rational design strategies, nanozyme-enabled therapeutic mechanisms at the cellular level, and the therapies of nanozyme for several typical metabolic diseases and underlying mechanisms are discussed, mainly including obesity, diabetes, cardiovascular disease, diabetic wound healing, and others. Finally, the pharmacokinetics, safety analysis, challenges, and outlooks for the application of nanozyme are also presented. This review will provide some instructive perspectives on nanozyme and promote the development of enzyme-mimicking strategies in metabolic disease therapy.
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Enfermedades Metabólicas , Estrés Oxidativo , Especies Reactivas de Oxígeno , Humanos , Enfermedades Metabólicas/tratamiento farmacológico , Enfermedades Metabólicas/metabolismo , Animales , Especies Reactivas de Oxígeno/metabolismo , Estrés Oxidativo/efectos de los fármacos , Nanoestructuras/química , Nanoestructuras/uso terapéutico , Nanopartículas/química , Enzimas/metabolismo , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/metabolismo , Obesidad/metabolismo , Obesidad/tratamiento farmacológicoRESUMEN
Never in mitosis gene A-related kinase (NEK) is an 11-membered family of serine/threonine kinases (NEK1-NEK11), which are known to play important roles in the formation and development of cancer. However, few studies have examined the roles of these kinases in the development of stomach adenocarcinoma (STAD). In this study, we conducted a comprehensive analysis of the relationships between the NEKs family members and STAD. The differential expression of the NEK genes in STAD was validated using The Cancer Genome Atlas (TCGA) and Tumor Immune Estimation Resource (TIMER) databases, and their prognostic and diagnostic values of NEKs in STAD were assessed using the Kaplan-Meier plotter and TCGA data. The effect of NEK expression on immune cell infiltration in STAD was analysed using the TIMER and TISIDB databases. The expression levels of the majority of the NEK family members were consistently upregulated in STAD, whereas that of NEK10 was downregulated. The upregulation of NEK2/3/4/5/6/8 was closely associated with clinicopathological parameters of patients, and the overexpressed levels of these proteins had good diagnostic value for the disease. NEK1/8/9/10/11 expression correlated with poor overall survival and post-progressive survival, whereas a higher NEK1/6/9/11 level implied worse first progressive survival. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that the NEKs may be related to immunological responses. Additionally, our study confirmed that these kinases correlated with immune cell infiltration and different immune infiltration subtypes in STAD. Our results suggest that NEK9 in particular has the potential to be used as a diagnostic and prognostic biomarker of STAD development and progression and an immune target for treatment of the disease. These findings expand our understanding of the biological functions of the NEK family members in STAD.
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Transfer RNA (tRNA)-derived small RNAs (tsRNAs) are a new type of non-coding RNAs (ncRNAs) produced by the specific cleavage of precursor or mature tRNAs. tsRNAs are involved in various basic biological processes such as epigenetic, transcriptional, post-transcriptional, and translation regulation, thereby affecting the occurrence and development of various human diseases, including cancers. Recent studies have shown that tsRNAs play an important role in tumorigenesis by regulating biological behaviors such as malignant proliferation, invasion and metastasis, angiogenesis, immune response, tumor resistance, and tumor metabolism reprogramming. These may be new potential targets for tumor treatment. Furthermore, tsRNAs can exist abundantly and stably in various bodily fluids (e.g., blood, serum, and urine) in the form of free or encapsulated extracellular vesicles, thereby affecting intercellular communication in the tumor microenvironment (TME). Meanwhile, their abnormal expression is closely related to the clinicopathological features of tumor patients, such as tumor staging, lymph node metastasis, and poor prognosis of tumor patients; thus, tsRNAs can be served as a novel type of liquid biopsy biomarker. This review summarizes the discovery, production, and expression of tsRNAs and analyzes their molecular mechanisms in tumor development and potential applications in tumor therapy, which may provide new strategies for early diagnosis and targeted therapy of tumors.
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Neoplasias , ARN de Transferencia , Humanos , ARN de Transferencia/genética , ARN de Transferencia/metabolismo , Neoplasias/genética , Carcinogénesis , Biopsia Líquida , Microambiente Tumoral/genéticaRESUMEN
BACKGROUND: The pituitary directly regulates the reproductive process through follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Transcriptomic research on the pituitaries of ewes with different FecB (fecundity Booroola) genotypes has shown that some key genes and lncRNAs play an important role in pituitary function and sheep fecundity. Our previous study found that ewes with FecB + + genotypes (without FecB mutation) still had individuals with more than one offspring per birth. It is hoped to analyze this phenomenon from the perspective of the pituitary transcriptome. RESULTS: The 12 Small Tail Han Sheep were equally divided into polytocous sheep in the follicular phase (PF), polytocous sheep in the luteal phase (PL), monotocous sheep in the follicular phase (MF), and monotocous sheep in the luteal phase (ML). Pituitary tissues were collected after estrus synchronous treatment for transcriptomic analysis. A total of 384 differentially expressed genes (DEGs) (182 in PF vs. MF and 202 in PL vs. ML) and 844 differentially expressed lncRNAs (DELs) (427 in PF vs. MF and 417 in PL vs. ML) were obtained from the polytocous-monotocous comparison groups in the two phases. Functional enrichment analysis showed that the DEGs in the two phases were enriched in signaling pathways known to play an important role in sheep fecundity, such as calcium ion binding and cAMP signaling pathways. A total of 1322 target relationship pairs (551 pairs in PF vs. MF and 771 pairs in PL vs. ML) were obtained for the target genes prediction of DELs, of which 29 DEL-DEG target relationship pairs (nine pairs in PF vs. MF and twenty pairs in PL vs. ML). In addition, the competing endogenous RNA (ceRNA) networks were constructed to explore the regulatory relationships of DEGs, and some important regulatory relationship pairs were obtained. CONCLUSION: According to the analysis results, we hypothesized that the pituitary first receives steroid hormone signals from the ovary and uterus and that VAV3 (Vav Guanine Nucleotide Exchange Factor 3), GABRG1 (Gamma-Aminobutyric Acid A Receptor, Gamma 1), and FNDC1 (Fibronectin Type III Domain Containing 1) played an important role in this process. Subsequently, the reproductive process was regulated by gonadotropins, and IGFBP1 (Insulin-like Growth Factor Binding Protein 1) was directly involved in this process, ultimately affecting litter size. In addition, TGIF1 (Transforming Growth Factor-Beta-Induced Factor 1) and TMEFF2 (Transmembrane Protein With EGF Like And Two Follistatin Like Domains 2) compensated for the effect of the FecB mutation and function by acting on TGF-ß/SMAD signaling pathway, an important pathway for sheep reproduction. These results provided a reference for understanding the mechanism of multiple births in Small Tail Han Sheep without FecB mutation.
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Hipófisis , ARN Largo no Codificante , ARN Mensajero , Animales , Ovinos/genética , Hipófisis/metabolismo , Femenino , ARN Largo no Codificante/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Fertilidad/genética , Reproducción/genética , Perfilación de la Expresión Génica , TranscriptomaRESUMEN
Coreopsis tinctoria (CT) improves energy metabolism. However, the role of CT in alleviating obesity-induced hyperglycemia by targeting the liver remains unknown. Therefore, this article aims to explore the mechanism by which CT improves energy metabolism and resists hyperglycemia. The water and ethanol extracts of CT were administered to high-fat diet-induced (HFD) obese C57BL/6J mice at a dose of 4 g/kg.bw (low-dose water extract, WL; low-dose ethanol extract, EL) or 10 g/kg.bw (high-dose water extract, WH; high-dose ethanol extract, EH). Mice that consumed a maintenance diet (LFD) were included as blank controls. Network pharmacology, liquid chromatography-mass spectrometry (LC-MS), L02 cell cultivation, and liver transcriptomics were used to examine the mechanism and functional components of CT against obesity-induced hyperglycemia. The results indicated that WL significantly (p < 0.05) alleviated glucose intolerance and insulin resistance in obesity-induced hyperglycemia. Kaempferol is the main active compound of CT, which demonstrated significant (p < 0.05) anti-hyperglycemic effects in obese mice and L02 cells. Finally, kaempferol significantly (p < 0.05; fold change >1.2) shifted the genes involved in carbon metabolism, glycolysis/gluconeogenesis, and the mitogen-activated protein kinase (MAPK) pathways toward the trend of LFD, indicating that it exerts an anti-hyperglycemic effect through these molecular mechanisms. Overall, oral intake of CT lowers blood glucose and improves insulin sensitivity in mice with obesity-induced hyperglycemia. Kaempferol is the primary functional component of CT.
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Long noncoding RNAs (lncRNAs), as competitive endogenous RNAs (ceRNAs), can directly or indirectly affect the proliferation and apoptosis of granulosa cells by regulating microRNA (miRNA) pathways. A ceRNA network of the SLC19A1-AS-miR-1343-WNT11 axis was constructed via comprehensive transcriptome sequencing of ovaries from goats with various fertility levels to further elucidate the function and regulatory mechanism of SLC19A1-AS in modulating miR-1343 and WNT11 during granulosa cell proliferation and apoptosis. Subsequent validation experiments were conducted in vitro using granulosa cells. In these experiments, we performed RNA immunoprecipitation (RIP) and identified SLC19A1-AS as a ceRNA in goat granulosa cells that promoted proliferation. Through bioinformatics prediction, luciferase reporter gene assays, and RNA pulldown assays, we confirmed that SLC19A1-AS acts as a sponge for miR-1343, preventing its binding to WNT11 mRNA and thereby increasing the expression of WNT11. This interaction also influenced the proliferation and apoptosis of granulosa cells. Our study systematically validated the biological function of the lncRNA-miRNA-mRNA ceRNA network in goat ovaries and revealed the potential regulatory mechanism by which SLC19A1-AS functions as a ceRNA in granulosa cells. These findings are expected to provide an important experimental foundation for further elucidating the physiological regulatory network of the ovary and contributing to reproductive health in goats.
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MicroARNs , ARN Largo no Codificante , Animales , Femenino , ARN Endógeno Competitivo , Cabras/genética , Cabras/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Proliferación Celular/genética , ARN Mensajero/genética , ARN Largo no Codificante/genética , Redes Reguladoras de GenesRESUMEN
In previous studies, NOX4, PDE11A and GHR genes have been screened as important candidate genes for litter size in sheep by using the GWAS method; however, neither their effects on litter size nor the loci associated with litter size have been identified. In this study, three candidate loci (c.1057-4C > T in NOX4, c.1983C > T in PDE11A and c.1618C > T in GHR) were first screened based on our previous resequencing data of 10 sheep breeds. After the three loci were genotyped using Sequenom MassARRAY technology, we carried out population genetics analysis on the three loci and performed association analysis between the polymorphism of the three loci and the litter size of sheep. The results of population genetics analysis suggested that c.1057-4C > T in NOX4 and c.1983C > T in PDE11A may be subject to natural or artificial selection. The results of association analysis indicated that litter size was significantly associated with c.1057-4C > T in NOX4 and c.1983C > T in PDE11A (p < 0.05) in Small Tail Han sheep, and there was no significant interaction effect between the two loci on the litter size. In summary, c.1057-4C > T in NOX4 and c.1983 C > T in PDE11A can be considered candidate molecular markers for improving litter size in sheep.
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Colorectal cancer (CRC) intricacies, involving dysregulated cellular processes and programmed cell death (PCD), are explored in the context of N6-methyladenosine (m6A) RNA modification. Utilizing the TCGA-COADREAD/CRC cohort, 854 m6A-related PCD genes are identified, forming the basis for a robust 10-gene risk model (CDRS) established through LASSO Cox regression. qPCR experiments using CRC cell lines and fresh tissues was performed for validation. The CDRS served as an independent risk factor for CRC and showed significant associations with clinical features, molecular subtypes, and overall survival in multiple datasets. Moreover, CDRS surpasses other predictors, unveiling distinct genomic profiles, pathway activations, and associations with the tumor microenvironment. Notably, CDRS exhibits predictive potential for drug sensitivity, presenting a novel paradigm for CRC risk stratification and personalized treatment avenues.
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Head and neck squamous cell carcinoma (HNSCC) ranks as the eighth most prevalent malignancy globally and has the eighth greatest fatality rate when compared to all other forms of cancer. The inhibitor of apoptosis protein (IAP) family comprises a collection of apoptosis-negative modulators characterized by at least one single baculovirus IAP repeat (BIR) domain in its N-terminal region. While the involvement of the IAP family is associated with the initiation and progression of numerous tumours, its specific role in HNSCC remains poorly understood. Thus, this study aimed to comprehensively examine changes in gene expression, immunomodulatory effects, prognosis, and functional enrichment of HNSCC utilising bioinformatics analysis. Elevated levels of distinct IAP family members were observed to varying degrees in HNSCC, with high BIRC2 expression indicating a worse prognosis. Additionally, Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to probe the enrichment of gene expression and biological processes related to the IAP family in HNSCC. The infiltration levels of immune cells were shown to be strongly associated with the IAP gene expression, as determined by subsequent analysis. Hence, BIRC2 could be an effective immunotherapy target for HNSCC. Collectively, novel knowledge of the biological roles and prognostic implications of IAP family members in HNSCC is presented in this study.
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Neoplasias de Cabeza y Cuello , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Pronóstico , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/terapia , Biomarcadores de Tumor/genética , Proteínas Inhibidoras de la Apoptosis/genética , Regulación Neoplásica de la Expresión GénicaRESUMEN
BACKGROUND: The thyroid gland is an important endocrine gland in animals that secretes thyroid hormones and acts on various organs throughout the body. lncRNAs are long non-coding RNAs that play an important role in animal reproduction; however, there is a lack of understanding of their expression patterns and potential roles in the thyroid gland of the Small Tail Han (STH) sheep. In this study, we used RNA-Seq technology to examine the transcriptome expression pattern of the thyroid from the luteal phase (LP) and follicular phase (FP) of FecB BB (MM) STH sheep. RESULTS: We identified a total of 122 and 1287 differential expression lncRNAs (DELs) and differential expression mRNAs (DEGs), respectively, which were significantly differentially expressed. These DELs target genes and DEGs can be enriched in several signalling pathways related to the animal reproduction process. CONCLUSIONS: The expression profiles of DELs and DEGs in thyroid glands provide a more comprehensive resource for elucidating the reproductive regulatory mechanisms of STH sheep.
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ARN Largo no Codificante , Glándula Tiroides , Femenino , Ovinos/genética , Animales , ARN Largo no Codificante/genética , ARN Mensajero/genética , Cola (estructura animal) , Perfilación de la Expresión Génica/veterinaria , GenotipoRESUMEN
Colorectal cancer (CRC) is a type of gastrointestinal cancer with high morbidity and mortality rates, and is often accompanied by distant metastases. Metastasis is a major cause of shortened survival time and poor treatment outcomes for patients with CRC. However, the molecular mechanisms underlying the metastasis of CRC remain unclear. Exosomes are a class of small extracellular vesicles that originate from almost all human cells and can transmit biological information (e.g., nucleic acids, lipids, proteins, and metabolites) from secretory cells to target recipient cells. Recent studies have revealed that non-coding RNAs (ncRNAs) can be released by exosomes into the tumour microenvironment or specific tissues, and play a pivotal role in tumorigenesis by regulating a series of key molecules or signalling pathways, particularly those involved in tumour metastasis. Exosomal ncRNAs have potential as novel therapeutic targets for CRC metastasis, and can also be used as liquid biopsy biomarkers because of their specificity and sensitivity. Therefore, further investigations into the biological function and clinical value of exosomal ncRNAs will be of great value for the prevention, early diagnosis, and treatment of CRC metastasis.
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Neoplasias Colorrectales , Exosomas , Vesículas Extracelulares , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/diagnóstico , ARN no Traducido/genética , Exosomas/metabolismo , Vesículas Extracelulares/patología , Transducción de Señal , Microambiente TumoralRESUMEN
Circular RNAs (circRNAs) are a specific type of noncoding RNA, and some have defined roles in cellular and biological processes. However, little is known about the role of circRNAs in follicular development in sheep with FecB (fecundity Booroola) mutations. Here, the expression profiles of circRNAs were investigated using RNA sequencing (RNA-seq) in the follicular phase (F) and the luteal phase (L) of FecB mutant homozygous (BB) and wild-type (WW) Small Tail Han sheep. A total of 38,979 circRNAs were identified, and 314, 343, 336, and 296 of them were differentially expressed (DE) between BB_F and BB_L, WW_F and WW_L, BB_F and WW_F, and BB_L and WW_L, respectively. The length, type, and chromosome distribution of the circRNAs and the expression characteristic between the circRNAs and their host genes in the sheep hypothalamus were ascertained. Enrichment analysis showed that the host genes of DE circRNAs in the follicular and luteal phases were annotated to MAPK, gap junctions, progesterone-mediated oocyte maturation, oocyte meiosis, and other hormone-related signaling pathways, and the different FecB genotypes were annotated to the gap junctions, circadian entrainment, MAPK, and other hormone-related signaling pathways. The competing endogenous RNA network prediction revealed that the 129 target miRNAs might be bound to 336 DE circRNAs. oar_circ_0000523 and oar_circ_0028984, which were specifically expressed during the follicular phase in the BB genotype sheep, probably acted as miRNA sponges involved in the regulation of LH synthesis and secretion. This study reveals the expression profiles and characterization of circRNAs at two phases of follicular development considering different FecB genotypes, thereby providing an improved understanding of the roles of circRNAs in the sheep hypothalamus and their involvement in follicular development and ovulation.