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Immunity, Inflammation and Disease Jun 2024Tumor immunotherapy has become an important adjuvant therapy after surgery, radiotherapy, and chemotherapy. In recent years, the role of tumor-associated antigen (TAA)... (Review)
Review
BACKGROUND
Tumor immunotherapy has become an important adjuvant therapy after surgery, radiotherapy, and chemotherapy. In recent years, the role of tumor-associated antigen (TAA) in tumor immunotherapy has become increasingly prominent. Cancer-testis antigen (CTA) is a kind of TAA that is highly restricted in a variety of tumors and can induce an immune response.
AIMS
This review article aimed to evaluate the role of CTA on the progression of ovarian cancer, its diagnostic efficacy, and the potential for immunotherapy.
METHODS
We analyzed publications and outlined a comprehensive of overview the regulatory mechanism, immunogenicity, clinical expression significance, tumorigenesis, and application prospects of CTA in ovarian cancer, with a particular focus on recent progress in CTA-based immunotherapy.
RESULTS
The expression of CTA affects the occurrence, development, and prognosis of ovarian cancer and is closely related to tumor immunity.
CONCLUSION
CTA can be used as a biomarker for the diagnosis and prognosis evaluation of ovarian cancer and is an ideal target for antitumor immunotherapy. These findings provide novel insights on CTA in the improvement of diagnosis and treatment for ovarian cancer. The successes, current challenges and future prospects were also discussed to portray its significant potential.
Topics: Humans; Female; Ovarian Neoplasms; Antigens, Neoplasm; Immunotherapy; Biomarkers, Tumor; Prognosis; Animals
PubMed: 38896069
DOI: 10.1002/iid3.1284 -
EJHaem Jun 2024Primary large B-cell lymphomas of immune-privileged sites (IP-LBCLs) comprise LBCLs arising within "immune sanctuaries," including the central nervous system (CNS),...
Clonally unrelated primary large B-cell lymphomas separated by over a decade involving the central nervous system and testicle: Possible predisposition to lymphomas of immune-privileged sites?
Primary large B-cell lymphomas of immune-privileged sites (IP-LBCLs) comprise LBCLs arising within "immune sanctuaries," including the central nervous system (CNS), vitreoretina, and testes. Although patients present with localized disease, the prognosis remains poor with high relapse rates, either at the originating site or within another immune-privileged site. Generally, in the presence of an antecedent IP-LBCL, subsequent LBCLs are expected to be clonally related. However, we present a primary CNS LBCL and later primary testicular LBCL in a middle-aged man, diagnosed over a decade apart, which proved to be clonally unrelated by targeted ultra-deep next-generation sequencing of the locus.
PubMed: 38895078
DOI: 10.1002/jha2.898 -
International Journal of Molecular... Jun 2024Elasmobranchs have an ancestral reproductive system, which offers insights into vertebrate reproductive evolution. Despite their unchanged design over 400 million years,...
Elasmobranchs have an ancestral reproductive system, which offers insights into vertebrate reproductive evolution. Despite their unchanged design over 400 million years, they evolved complex mechanisms ensuring reproductive success. However, human activities induced a significant decline in elasmobranch populations worldwide. In the Mediterranean basin, the smooth-hound shark () is one of the species that are considered vulnerable to human activities. Conservation efforts necessitate a thorough understanding of its reproductive strategy. This study focused on mature male specimens of smooth-hound sharks that were captured in the Adriatic area and successively analyzed to provide, for the first time, a histologically detailed description of testicular development in the species. Seven phases of the spermatogenesis process were identified, along with the macromolecular characterization of cells obtained using Fourier-transform infrared imaging. Histological analysis showed structural and cellular features similar to those documented in the spermatocysts of other elasmobranchs. The examination of the evolution and migration of both germinative and Sertoli cells at each phase revealed their close connection. Furthermore, different expression levels of lipids, proteins, and phosphates (DNA) at each spermatogenesis stage were observed. This research provided new information on spermatogenesis in the common smooth-hound shark, which is crucial for conservation efforts against population decline and anthropogenic pressures.
Topics: Animals; Sharks; Male; Spermatogenesis; Testis; Sertoli Cells
PubMed: 38892415
DOI: 10.3390/ijms25116230 -
International Journal of Molecular... May 2024Type 2 diabetes mellitus (T2DM) is a risk factor for male infertility, but the underlying molecular mechanisms remain unclear. Advanced glycation end products (AGEs) are...
DNA Aptamer Raised against Advanced Glycation End Products Improves Sperm Concentration, Motility, and Viability by Suppressing Receptors for Advanced Glycation End Product-Induced Oxidative Stress and Inflammation in the Testes of Diabetic Mice.
Type 2 diabetes mellitus (T2DM) is a risk factor for male infertility, but the underlying molecular mechanisms remain unclear. Advanced glycation end products (AGEs) are pathogenic molecules for diabetic vascular complications. Here, we investigated the effects of the DNA aptamer raised against AGEs (AGE-Apt) on testicular and sperm abnormalities in a T2DM mouse model. KK-Ay (DM) and wild-type (non-DM) 4- and 7-week-old male mice were sacrificed to collect the testes and spermatozoa for immunofluorescence, RT-PCR, and histological analyses. DM and non-DM 7-week-old mice were subcutaneously infused with the AGE-Apt or control-aptamer for 6 weeks and were then sacrificed. Plasma glucose, testicular AGEs, and gene expression in 4-week-old DM mice and plasma glucose, testicular AGEs, oxidative stress, and pro-inflammatory gene expressions in 7-week-old DM mice were higher than those in age-matched non-DM mice, the latter of which was associated with seminiferous tubular dilation. AGE-Apt did not affect glycemic parameters, but it inhibited seminiferous tubular dilation, reduced the number of testicular macrophages and apoptotic cells, and restored the decrease in sperm concentration, motility, and viability of 13-week-old DM mice. Our findings suggest that AGEs-Apt may improve sperm abnormality by suppressing AGE-RAGE-induced oxidative stress and inflammation in the testes of DM mice.
Topics: Animals; Male; Oxidative Stress; Glycation End Products, Advanced; Mice; Aptamers, Nucleotide; Testis; Receptor for Advanced Glycation End Products; Diabetes Mellitus, Experimental; Sperm Motility; Diabetes Mellitus, Type 2; Inflammation; Spermatozoa; Sperm Count
PubMed: 38892134
DOI: 10.3390/ijms25115947 -
International Journal of Molecular... May 2024DNA methylation is an important way to regulate gene expression in eukaryotes. In order to reveal the role of DNA methylation in the regulation of germ cell-specific...
DNA methylation is an important way to regulate gene expression in eukaryotes. In order to reveal the role of DNA methylation in the regulation of germ cell-specific gene expression during spermatogenesis of Japanese flounder (), the expression profiles of () and () genes in the gonads of female, male, and sex-reversed pseudo-male were analyzed, and the dynamic of DNA methylation was investigated. As a result, and genes were highly expressed in the testis of both male and pseudo-male , with significant variation among male individuals. The DNA methylation levels in the promoter regions of both and were negatively correlated with their expression levels, which may contribute to the transcriptional regulation of genes during spermatogenesis. There was also sperm quality variation among male , and the sperm curvilinear velocity was positively correlated with the expression of both and genes. These results indicated that the DNA methylation in and promoter regions may affect the initiation of gene transcription, thereby regulating gene expression and further affecting the spermatogenesis process and gamete quality in .
Topics: Animals; Male; DNA Methylation; Argonaute Proteins; Flounder; Spermatozoa; Spermatogenesis; Female; Promoter Regions, Genetic; Testis; Gene Expression Regulation; Fish Proteins
PubMed: 38892123
DOI: 10.3390/ijms25115935 -
International Journal of Molecular... May 2024The testes serve as the primary source of androgens and the site of spermatogenesis, with their development and function governed by hormonal actions via endocrine and... (Review)
Review
The testes serve as the primary source of androgens and the site of spermatogenesis, with their development and function governed by hormonal actions via endocrine and paracrine pathways. Male fertility hinges on the availability of testosterone, a cornerstone of spermatogenesis, while follicle-stimulating hormone (FSH) signaling is indispensable for the proliferation, differentiation, and proper functioning of Sertoli and germ cells. This review covers the research on how androgens, FSH, and other hormones support processes crucial for male fertility in the testis and reproductive tract. These hormones are regulated by the hypothalamic-pituitary-gonad (HPG) axis, which is either quiescent or activated at different stages of the life course, and the regulation of the axis is crucial for the development and normal function of the male reproductive system. Hormonal imbalances, whether due to genetic predispositions or environmental influences, leading to hypogonadism or hypergonadism, can precipitate reproductive disorders. Investigating the regulatory network and molecular mechanisms involved in testicular development and spermatogenesis is instrumental in developing new therapeutic methods, drugs, and male hormonal contraceptives.
Topics: Humans; Male; Testis; Animals; Spermatogenesis; Follicle Stimulating Hormone; Hypothalamo-Hypophyseal System; Androgens; Testosterone
PubMed: 38891991
DOI: 10.3390/ijms25115805 -
International Journal of Molecular... May 2024The dynamic process of spermatogenesis involves asymmetric division, mitosis, and meiosis, which ultimately results in the production of mature spermatozoa. Disorders...
The dynamic process of spermatogenesis involves asymmetric division, mitosis, and meiosis, which ultimately results in the production of mature spermatozoa. Disorders of spermatogenesis can lead to infertility in males. ADAR (adenosine deaminase acting on RNA) mutations in cause male infertility, yet the causative factors remain unclear. In this study, immunofluorescence staining was employed to visualize endogenous ADAR proteins and assess protein levels via fluorescence-intensity analysis. In addition, the early differentiation disorders and homeostatic alterations during early spermatogenesis in the testes were examined through quantification of transit-amplifying region length, counting the number of GSCs (germline stem cells), and fertility experiments. Our findings suggest that deletion of ADAR causes testicular tip transit-amplifying cells to accumulate and become infertile in older male . By overexpressing ADAR in early germline cells, male infertility can be partially rescued. Transcriptome analysis showed that ADAR maintained early spermatogenesis homeostasis through the bone-morphogenetic-protein (BMP) signaling pathway. Taken together, these findings have the potential to help explore the role of ADAR in early spermatogenesis.
Topics: Animals; Male; Spermatogenesis; Drosophila melanogaster; Signal Transduction; Drosophila Proteins; Adenosine Deaminase; Bone Morphogenetic Proteins; Infertility, Male; RNA-Binding Proteins; Testis
PubMed: 38891830
DOI: 10.3390/ijms25115643 -
International Journal of Molecular... May 2024The testis-specific double sex and mab-3-related transcription factor 1 () has long been recognized as a crucial player in sex determination across vertebrates, and its...
The testis-specific double sex and mab-3-related transcription factor 1 () has long been recognized as a crucial player in sex determination across vertebrates, and its essential role in gonadal development and the regulation of spermatogenesis is well established. Here, we report the cloning of the key spermatogenesis-related cDNA, named , from the gonads of (), with a molecular weight of 41.93 kDa and an isoelectric point of 7.83 (pI). Our hypothesis is that machinery governs spermatogenesis and regulates gonadogenesis. RNAi-mediated knockdown revealed its critical role in hindering spermatogenesis and reducing expression levels in boring giant clams. A histological analysis showed structural changes, with normal sperm cell counts in the control group (ds-EGFP) but significantly lower concentrations of sperm cells in the experimental group (). transcripts during embryogenesis exhibited a significantly high expression pattern ( < 0.05) during the early zygote stage, and whole-embryo in-situ hybridization confirmed its expression pattern throughout embryogenesis. A qRT-PCR analysis of various reproductive stages revealed an abundant expression of in the gonads during the male reproductive stage. In-situ hybridization showed tissue-specific expression of , with a positive signal detected in male-stage gonadal tissues comprising sperm cells, while no signal was detected in other stages. Our study findings provide an initial understanding of the molecular machinery controlling spermatogenesis and its specificity in male-stage gonads of the key bivalve species, , and suggest that predominantly functions as a key regulator of spermatogenesis in giant clams.
Topics: Animals; Spermatogenesis; Transcription Factors; Male; Testis; Bivalvia; Gene Expression Regulation, Developmental; Gonads; Hermaphroditic Organisms; Cloning, Molecular; Phylogeny; Amino Acid Sequence
PubMed: 38891762
DOI: 10.3390/ijms25115574 -
Animals : An Open Access Journal From... May 2024The transcriptome complexity and splicing patterns in male and female cattle are ambiguous, presenting a substantial obstacle to genomic selection programs that seek to...
The transcriptome complexity and splicing patterns in male and female cattle are ambiguous, presenting a substantial obstacle to genomic selection programs that seek to improve productivity, disease resistance, and reproduction in cattle. A comparative transcriptomic analysis using Oxford Nanopore Technologies (ONT) was conducted in bovine testes (TESTs), ovaries (OVAs), muscles (MUSCs), and livers (LIVs). An average of 5,144,769 full-length reads were obtained from each sample. The TESTs were found to have the greatest number of alternative polyadenylation (APA) events involved in processes such as sperm flagellum development and fertilization in male reproduction. In total, 438 differentially expressed transcripts (DETs) were identified in the LIVs in a comparison of females vs. males, and 214 DETs were identified in the MUSCs between females and males. Additionally, 14,735, 36,347, and 33,885 DETs were detected in MUSC vs. LIV, MUSC vs. TEST, and OVA vs. TEST comparisons, respectively, revealing the complexity of the TEST. Gene Set Enrichment Analysis (GSEA) showed that these DETs were mainly involved in the "spermatogenesis", "flagellated sperm motility", "spermatid development", "reproduction", "reproductive process", and "microtubule-based movement" KEGG pathways. Additional studies are necessary to further characterize the transcriptome in different cell types, developmental stages, and physiological conditions in bovines and ascertain the functions of the novel transcripts.
PubMed: 38891695
DOI: 10.3390/ani14111646 -
Animals : An Open Access Journal From... May 2024Upon encountering a virus, fish initiate an innate immune response, guided by IFNs. Foxo3 plays a part in the body's immune response; however, its specific role in the...
Upon encountering a virus, fish initiate an innate immune response, guided by IFNs. Foxo3 plays a part in the body's immune response; however, its specific role in the IFN-guided immune response in fish is yet to be clarified. In this study, we characterized in Japanese medaka () and examined its role in the IFN-dependent immune response upon infection with the RGNNV. The results show that the coding region of the medaka gene is 2007 base pairs long, encoding 668 amino acids, and possesses a typical forkhead protein family structural domain. The product of this gene shares high homology with foxo3 in other fish species and is widely expressed, especially in the brain, eyes, testes, and heart. Upon RGNNV infection, mutant larvae showed a lower mortality rate, and adults exhibited a significant reduction in virus replication. Moreover, the absence of expression led to an increase in the expression of , and a decrease in the expression of other IFN-related genes such as and , implying that may function as a negative regulator in the antiviral signaling pathway. These findings provide crucial insights for disease-resistant breeding in the aquaculture industry.
PubMed: 38891634
DOI: 10.3390/ani14111587