bims-simsho 2025-08-31 papers

bims-simsho

Biomed News

on Systems immunology and sex hormones

Issue of 2025–08–31
25 papers selected by
Chun-Chi Chang, Lunds universitet

Deciphering polycystic ovary syndrome: A brief overview from metabolic drivers to genetic and fetal origins.
PCOS and the Genome: Is the Genetic Puzzle Still Worth Solving?
Sex Differences in Genital Area Hyperpigmentation Induced by 5-Fluorouracil Administration in Mice.
Coregulators determine androgen receptor activity in prostate cancer.
High-dimensional immune profiling of follicular fluid and systemic circulation reveals distinct immune signatures in women with polycystic ovary syndrome.
Immune and Vascular Function in Cardiometabolic Disorders: Interplay With Sex Differences and Impact on Incretin Therapy.
Seasonal Changes of Circulating Sex Steroid Hormones Associated With Vomeronasal Function of the Male Muskrats (Ondatra zibethicus).
Increased Serum AMH in a Subgroup of Women with Idiopathic Hyperandrogenism: Do These Women Have PCOS?
Optimizing Ovarian Stimulation for IVF in PCOS Patients: A Novel Day 1 GnRH Antagonist Protocol.
NLRP3 inflammasome activation in PCOS: A novel target for managing insulin resistance and metabolic dysregulation.
Sex-biased transcriptome in in vitro produced bovine early embryos.
Exogenous estrogen enhances T cell activation in male primates.
Advancing Prostate Cancer Treatment: Innovations and Challenges in Immunotherapy.
Clinical utility of FAI and SHBG in differentiating PCOS from anovulatory cycles in adolescent girls.
The impact of exercise on prostate-specific antigen and testosterone in prostate cancer: a systematic review and meta-analysis.
The Sweet Side of IVF: Biological Role and Diagnostic Potential of Galectin-9 in Female Infertility.
Long-Term Durability and Variant-Specific Modulation of SARS-CoV-2 Humoral and Cellular Immunity over Two Years.
Oligometastatic prostate cancer: new horizons for local treatment with the androgen receptor target therapy.
Effects of Naringenin (NG) as an Anti- Proliferative and Anti-Apoptotic Factor on ER Alpha and ER Beta in PCOS.
Oxidative Stress, Antioxidants, Gut Microbiota and Male Fertility.
Testosterone Enhances Wound Healing and Stress Resistance in A549 Lung Adenocarcinoma Cells via Actin Remodeling and AQP3 Upregulation.
From Petri Dish to Primitive Heart: How IVF Alters Early Cardiac Gene Networks and Epigenetic Landscapes.
Prenatal androgen exposure delays puberty onset in female offspring rats: possible roles of leptin and α-MSH.
Interferons in health and disease.
CD56 on immune and tumor cells: what is the known and beyond?

Rev Invest Clin. 2025 May-Jun;77(3):pii: S0034-8376(25)00018-X. [Epub ahead of print]77(3): 100008

Deciphering polycystic ovary syndrome: A brief overview from metabolic drivers to genetic and fetal origins.

Mario Morales-Esponda, Ramón de Los Santos-Aguilar, Raúl Villanueva-Rodríguez, Luis David Sol-Oliva, Carlos Alberto Aguilar-Salinas, Mayel Chirinos, Fernando Larrea.

  Polycystic ovary syndrome (PCOS) is a multifactorial endocrine and metabolic disorder in women of reproductive age characterized by hormonal imbalances, menstrual irregularities, and changes in ovarian morphology. Excess body fat plays a significant role in the clinical development of PCOS. The complex relationship between adiposity and PCOS involves disruptions in hormonal balance and inflammatory processes, which both contribute to the clinical and phenotypic manifestations of the syndrome. Insulin resistance is a significant factor linking adiposity and PCOS. Moreover, reduced fertility is associated with adiposity in PCOS, with obesity exacerbating anovulation. Recent studies have raised questions about the role of androgen exposure during fetal life, including genetic factors related to PCOS identified in genome-wide association studies and Mendelian randomization studies. Managing PCOS should concentrate on addressing adiposity as a crucial target, positively impacting the syndrome, particularly regarding reproductive and fertility outcomes. This review aims to understand how metabolic conditions such as obesity and insulin resistance are linked to PCOS and how early prenatal androgen exposure is involved in its etiology. Particular attention is given to its role in developmental programming, fat distribution, and fat type, as well as how these factors contribute to the onset of metabolic disturbances in adulthood.

Keywords:  Adiposity; Hyperandrogenism; Infertility; Insulin resistance; Obesity; PCOS

DOI:  https://doi.org/10.1016/j.ric.2025.100008
Biomedicines. 2025 Aug 05. pii: 1912. [Epub ahead of print]13(8):

PCOS and the Genome: Is the Genetic Puzzle Still Worth Solving?

Mario Palumbo, Luigi Della Corte, Dario Colacurci, Mario Ascione, Giuseppe D'Angelo, Giorgio Maria Baldini, Pierluigi Giampaolino, Giuseppe Bifulco.

  Background: Polycystic ovary syndrome (PCOS) is a complex and multifactorial disorder affecting reproductive, endocrine, and metabolic functions in women of reproductive age. While environmental and lifestyle factors play a role, increasing evidence highlights the contribution of genetic and epigenetic mechanisms to its pathogenesis. Objective: This narrative review aims to provide an updated overview of the current evidence regarding the role of genetic variants, gene expression patterns, and epigenetic modifications in the etiopathogenesis of PCOS, with a focus on their impact on ovarian function, fertility, and systemic alterations. Methods: A comprehensive search was conducted across MEDLINE, EMBASE, PubMed, Web of Science, and the Cochrane Library using MeSH terms including "PCOS", "Genes involved in PCOS", and "Etiopathogenesis of PCOS" from January 2015 to June 2025. The selection process followed the SANRA quality criteria for narrative reviews. Seventeen studies published in English were included, focusing on original data regarding gene expression, polymorphisms, and epigenetic changes associated with PCOS. Results: The studies analyzed revealed a wide array of molecular alterations in PCOS, including the dysregulation of SIRT and estrogen receptor genes, altered transcriptome profiles in cumulus cells, and the involvement of long non-coding RNAs and circular RNAs in granulosa cell function and endometrial receptivity. Epigenetic mechanisms such as the DNA methylation of TGF-β1 and inflammation-related signaling pathways (e.g., TLR4/NF-κB/NLRP3) were also implicated. Some genetic variants-particularly in DENND1A, THADA, and MTNR1B-exhibit signs of positive evolutionary selection, suggesting possible ancestral adaptive roles. Conclusions: PCOS is increasingly recognized as a syndrome with a strong genetic and epigenetic background. The identification of specific molecular signatures holds promise for the development of personalized diagnostic markers and therapeutic targets. Future research should focus on large-scale genomic studies and functional validation to better understand gene-environment interactions and their influence on phenotypic variability in PCOS.

Keywords:  DNA methylation; endocrine disorders; epigenetics; genetics; gene–environment interaction; insulin resistance; non-coding RNAs; ovarian dysfunction; polycystic ovary syndrome; reproductive health

DOI:  https://doi.org/10.3390/biomedicines13081912
Biol Pharm Bull. 2025 ;48(8): 1260-1264

Sex Differences in Genital Area Hyperpigmentation Induced by 5-Fluorouracil Administration in Mice.

Masashi Imai, Keiichi Hiramoto, Kazuya Ooi.

  Pigmentation is one of the most prominent side effects caused by anticancer drugs, especially in female patients, as these changes in appearance can decrease QOL. A typical drug causing such pigmentation is 5-fluorouracil (5-FU); we have previously shown that 5-FU-induced pigmentation is associated with increased adrenocorticotropic hormone (ACTH) and reactive oxygen species (ROS) levels. In male Hos:HRM-2 mice, 5-FU administration resulted in pigmentation appearing in the genital area, accompanied by elevations in neutrophils, ACTH, and ROS. By contrast, female mice showed increases in neutrophils and noradrenaline, but not in ACTH or ROS levels; furthermore, they did not develop pigmentation. In addition, estradiol levels were markedly decreased in female mice, which may have enhanced neutrophil apoptosis and suppressed ROS production. In addition, noradrenaline reflects the stress response and may contribute to the decrease in estradiol, suggesting the hypothalamus-pituitary-adrenal axis and sex hormones may interact in the formation of sex differences. These results suggest that sex differences exist in the development of 5-FU-induced hyperpigmentation and that fluctuations in estradiol and associated changes in neutrophils, ROS, and ACTH may underlie this phenomenon.

Keywords:  5-fluorouracil; neutrophil; pigmentation; reactive oxygen species; sex difference

DOI:  https://doi.org/10.1248/bpb.b25-00340
Biosci Rep. 2025 Aug 20. pii: BSR20253197. [Epub ahead of print]45(8):

Coregulators determine androgen receptor activity in prostate cancer.

Kerim Yavuz, Nathan A Lack.

  The androgen receptor (AR) is the main driver of nearly all prostate cancer (PCa). It alters gene expression by binding to specific cis-regulatory elements on the DNA. Where the AR binds in the genome determines what genes are expressed. However, the AR cistrome is not static and dramatically changes during PCa initiation and progression to activate distinct transcriptional programs that fuel disease growth and therapeutic resistance. Emerging evidence suggests that these changes in DNA binding are not caused by chromatin accessibility but rather from interactions with AR coregulators. These proteins influence AR at every step of its activity and play a critical role in DNA binding and gene activation. These context-specific coregulator interactions can stabilize AR binding with DNA that has low- to moderate-affinity and also affect locus-specific epigenetic modifications to promote transcription. Given their critical role in this process, alterations to coregulator proteins define the normal and oncogenic cistrome and profoundly affect AR-mediated gene transcription. In this review, we aim to provide a new perspective on the role of AR coregulators in transcriptional activity, how these interactions evolve through different stages of PCa and their potential as therapeutic targets in advanced disease.

Keywords:  androgen receptor; coregulator proteins; epigenetics; gene expression and regulation; prostate cancer

DOI:  https://doi.org/10.1042/BSR20253197
Front Immunol. 2025 ;16 1628031

High-dimensional immune profiling of follicular fluid and systemic circulation reveals distinct immune signatures in women with polycystic ovary syndrome.

Soma Banerjee, Fernanda L Jaimes, Mona A Mohamed, Abigail Zettel, Nesya G Graupe, Laura G Cooney, Aleksandar K Stanic.

   Background: Persistent low-grade inflammation has been hypothesized as a possible key contributor to polycystic ovary syndrome pathophysiology through associative studies. Since immune cells within the ovarian follicle-the central site of PCOS dysfunction-play pivotal roles in immune defense and regulation of ovulation, establishing a definitive cellular map of normal and PCOS-affected follicular immune composition is essential.
Method: This is a prospective cohort study of women with PCOS (Rotterdam criteria) and controls undergoing in vitro fertilization (IVF). Peripheral blood was collected before treatment (visit 1) and again at transvaginal oocyte retrieval (TVOR, visit 2). Follicular fluid (FF) was obtained from the first two dominant follicles during TVOR. We measured the cytokines and angiogenic factors in both plasma and FF using multiplexed cytometric bead assays. The cellular immune composition was evaluated by using high-dimensional multispectral flow cytometry, followed by dimensionality reduction and graph-based clustering analyses.
Results: We found that the TVOR plasma contained significantly higher concentrations of IL-2, IL-4, IL-9, IL-17A, TNF-α, and MCP-1 compared to the follicular fluid, whereas the follicular fluid was enriched with angiogenic factors such as VEGF and EGF. Notably, pre-treatment plasma samples from PCOS patients showed elevated Il-4, IL-6, IL-9, and IL-10, which were partially resolved by TVOR. Moreover, the PCOS follicular fluid exhibited higher numbers of classical monocytes and a trend toward increased CTLA4-positive T regulatory cells relative to the controls.
Conclusion: Our findings highlight a compartment-specific immunome in PCOS, marked by distinct cytokine and angiogenic factor distributions in circulation versus follicular fluid. PCOS was characterized by elevated systemic inflammatory markers before treatment, which were partially normalized by TVOR, yet key immune differences persisted at the follicular level. These results underscore the utility of comprehensive multiparametric analyses-including high-dimensional flow cytometry-to uncover immune dysregulation and identify potential therapeutic targets in PCOS.

Keywords:  cytokines; high-dimensional flowcytometry; immune cells; in-vitro fertilization; in-vitro fertilization polycystic ovary syndrome; polycystic ovary syndrome

DOI:  https://doi.org/10.3389/fimmu.2025.1628031
Acta Physiol (Oxf). 2025 Sep;241(9): e70091

Immune and Vascular Function in Cardiometabolic Disorders: Interplay With Sex Differences and Impact on Incretin Therapy.

Anirudh Subramanian Muralikrishnan, Valentina Biasin, Diana Zabini, Elena Osto.

   BACKGROUND AND AIMS: Vascular dysfunction, driven by endothelial impairment, arterial stiffness, inflammation, and immune activation, contributes to cardiometabolic disorders such as hypertension and atherosclerosis. Sex differences and sex hormones influence the progression of vascular and immune dysfunction. Incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), regulate glucose homeostasis and also impact vascular and immuno-metabolic health. This review examines their roles in these processes, with emphasis on sex-specific effects.
METHODS: A narrative review of preclinical and clinical studies assessing GLP-1 and GIP actions on vascular function, immune regulation, and metabolism, and their modulation by sex and sex hormones.
RESULTS: Incretins improve endothelial function, reduce vascular inflammation, and modulate immune-metabolic crosstalk, processes often impaired in cardiometabolic disease. Sex differences affect incretin secretion, signalling, and therapeutic responses, though underlying mechanisms remain unclear.
CONCLUSIONS: Incretin hormones are promising targets for improving vascular and immune-metabolic health in cardiometabolic disorders. Understanding sex-specific mechanisms will be essential for optimizing incretin-based therapies.

Keywords:  GIP; GLP‐1; endothelial cells; immune cells; incretins; sex differences

DOI:  https://doi.org/10.1111/apha.70091
J Exp Zool A Ecol Integr Physiol. 2025 Aug 22.

Seasonal Changes of Circulating Sex Steroid Hormones Associated With Vomeronasal Function of the Male Muskrats (Ondatra zibethicus).

Bowen Zhu, Qingjing Gao, Meiqi Chen, Yuning Liu, Haolin Zhang, Qiang Weng.

  The vomeronasal organ (VNO) is a key receptor for pheromones involved in regulating reproductive and social behaviors in animals, such as mating between males and females and male-male competition. The aim of this study was to explore variations in circulating androgen and estrogen concentrations in male muskrats in relation to seasonal changes in vomeronasal function. Phylogenetic analysis revealed a total of 212 vomeronasal receptor (VR) genes in muskrats. Previous experimental results demonstrated that among these genes, VN1R41 and VN2R1 act as potential VNO receptors to mediate chemical communication behaviors in muskrats. Therefore, we selected VN1R41 and VN2R1 as representatives of VRs for subsequent experiments. Molecular docking simulations showed that VRs can bind to sex steroid hormones and their sulfated derivatives. Circulating concentrations of testosterone (T), dihydrotestosterone (DHT), and 17β-estradiol (E2) increased significantly during the breeding season. Type 1 vomeronasal receptors (V1Rs), type 2 vomeronasal receptors (V2Rs), P450arom, androgen receptor (AR), estrogen receptor α (ERα), and estrogen receptor β (ERβ) were detected in both sensory and non-sensory epithelial cells of the VNO in male muskrats. Immunofluorescence assays of VNO also revealed AR and ERα signals in sustentacular cells and sensory cells of the sensory epithelium. The messenger RNA (mRNA) expression levels of VN1R41, AR, ERα, and P450arom in the VNO were significantly higher during the breeding season compared with the nonbreeding season, whereas the mRNA expression levels of VN2R1 and ERβ were lower. Additionally, transcriptomic analysis revealed that differentially expressed genes might be associated with estrogen signaling pathways. These results suggest that androgens and estrogens may regulate vomeronasal function through the expression of AR, ERs, and VRs in the VNO of male muskrats.

Keywords:  AR; ERα; ERβ; VN1R41; VN2R1; VNO; muskrat

DOI:  https://doi.org/10.1002/jez.70026
Biomedicines. 2025 Aug 08. pii: 1942. [Epub ahead of print]13(8):

Increased Serum AMH in a Subgroup of Women with Idiopathic Hyperandrogenism: Do These Women Have PCOS?

Enrico Carmina, Rogerio A Lobo.

  Background: Idiopathic Hyperandrogenism (IH) is often encountered in the general population and particularly in women presenting with androgen excess. It is diagnosed in women who have normal ovulatory cycles, elevated androgen levels, and normal appearing ovaries on ultrasound. Using serum anti-mullerian hormone (AMH), which has been suggested to be a surrogate marker of polycystic ovarian morphology, we wished to determine if some women with IH may have the ovulatory phenotype of PCOS, where metabolic abnormalities may be more prevalent. Methods: This was a retrospective study of 84 women diagnosed with IH and 50 age- and BMI-matched ovulatory controls who were evaluated between 2021 and 2024. Androgen levels, ovarian ultrasound, and serum AMH were assessed. In addition, glucose, insulin, HOMA-IR, and lipid levels were measured. Results: Twenty-four women (29%) with IH had elevated AMH levels (>4.7 ng/mL). None of the control women had elevated values. These 24 women with IH had values ranging from 5.5-11.9 ng/mL, compared to the other 60 women whose AMH levels were 0.8-4.3 ng/mL. Age and weight were similar in these two subgroups of women with IH. Glucose, insulin, and HOMA-IR were similar in the two groups, but cholesterol and LDL-cholesterol were elevated in the 24 women with elevated AMH. Elevations in LDL-cholesterol were observed in 3.5% of the women with normal AMH and in 21% of those with elevated AMH. Conclusions: Despite normal ovarian morphology on ultrasound, approximately 30% of women with IH were found to have elevated AMH and may be considered to have the ovulatory phenotype of PCOS. These women also have some metabolic dysfunction, which is more characteristic of women with PCOS. These data reinforce the notion that AMH findings are not always concordant with ovarian morphological findings and suggest wider implication of elevated AMH levels in the pathophysiology of PCOS.

Keywords:  AMH; PCOS; PCOS phenotypes; idiopathic hyperandrogenism

DOI:  https://doi.org/10.3390/biomedicines13081942
J Clin Med. 2025 Aug 21. pii: 5901. [Epub ahead of print]14(16):

Optimizing Ovarian Stimulation for IVF in PCOS Patients: A Novel Day 1 GnRH Antagonist Protocol.

Sudarsan Ghosh Dastidar, Biswanath Ghosh Dastidar, Ratna Chattopadhyay, Chandan Chakraborty.

  Objectives: Gonadotropin-releasing hormone (GnRH) antagonist protocols are preferred in polycystic ovary syndrome (PCOS) patients undergoing in vitro fertilization (IVF) as they provide the best combination of flexibility, acceptable outcomes, and safety. Numerous studies have compared outcomes between GnRH agonist long protocol and standard flexible antagonist protocol. However, there are scant studies investigating the effectiveness of antagonist administration from day 1 of ovarian stimulation in PCOS patients. Methods: We performed a retrospective cohort study to compare laboratory and clinical outcomes in IVF between standard flexible day 5/day 6 versus day 1 GnRH antagonist protocol in PCOS patients. Results: Our data indicates significantly superior oocyte yield and top-quality embryo proportion in patients with antagonists from day 1. Cumulative clinical pregnancy rates also tended to be superior in this group. Conclusions: Our findings indicate that administration of GnRH antagonists from day 1 of stimulation in PCOS patients undergoing IVF may lead to superior results.

Keywords:  GnRH antagonist; in vitro fertilization (IVF) outcome; luteinizing hormone (LH); ovarian stimulation (OS); pituitary suppression; polycystic ovarian syndrome (PCOS)

DOI:  https://doi.org/10.3390/jcm14165901
Tissue Cell. 2025 Aug 22. pii: S0040-8166(25)00379-9. [Epub ahead of print]97 103097

NLRP3 inflammasome activation in PCOS: A novel target for managing insulin resistance and metabolic dysregulation.

Fatemeh Samadi Nasab, Hanie Babei, Mehrnaz Nayebzadeh, Elahe Sadati, Ziba Zahiri, Tayebeh Esfidani, Shabnam Forouzin, Atoosa Etezadi.

  In this comprehensive narrative review, we systematically examine the role of the NLRP3 inflammasome in the pathogenesis of polycystic ovary syndrome (PCOS) and evaluate its potential as a therapeutic target for managing insulin resistance. We performed literature searches in PubMed, Scopus, and Web of Science up to April 2025, using keywords including "PCOS," "NLRP3 inflammasome," "insulin resistance," and "reproductive dysfunction." Only peer-reviewed studies directly addressing inflammasome activation in PCOS were included, while articles lacking mechanistic or clinical relevance were excluded. PCOS is a highly prevalent and complex endocrine-metabolic disorder characterized by chronic low-grade inflammation, insulin resistance, and reproductive dysfunction, affecting millions of women globally. Despite its widespread impact, current treatments mainly address symptoms rather than underlying disease mechanisms, highlighting the urgent need for novel, targeted therapeutic approaches. Emerging evidence implicates the NLRP3 inflammasome as a central mediator linking immune activation, metabolic dysregulation, and ovarian pathology in PCOS. Activation of NLRP3 triggers release of IL-1β and IL-18, which impair insulin signaling, disrupt glucose homeostasis, and sustain systemic inflammation. Beyond metabolic effects, NLRP3-driven inflammation contributes to anovulation, follicular atresia, and hormonal imbalance. Interactions with mitochondrial dysfunction and endoplasmic reticulum stress further amplify cellular stress responses, accelerating disease progression. This review synthesizes current mechanistic insights into how NLRP3 activation drives both metabolic and reproductive impairments in PCOS, and highlights emerging therapeutic strategies-including pharmacological inhibitors, anti-inflammatory agents, and precision medicine approaches-aimed at disrupting the inflammatory-insulin resistance cycle. By elucidating these immunometabolic mechanisms, our findings support a shift from symptom-based management toward targeted, disease-modifying interventions, advancing precision medicine in women's health.

Keywords:  Chronic Inflammation; Metabolic Syndrome; Mitochondrial Dysfunction; NLRP3; Polycystic Ovary Syndrome

DOI:  https://doi.org/10.1016/j.tice.2025.103097
Cell Biosci. 2025 Aug 27. 15(1): 123

Sex-biased transcriptome in in vitro produced bovine early embryos.

IISAGE Consortium

   BACKGROUND: Morphologic sex differences between males and females typically emerge after the primordial germ cell migration and gonad formation, although sex is determined at fertilization based on chromosome composition. A key debated sexual difference is the embryonic developmental rate, with in vitro produced male embryos often developing faster. However, the molecular mechanisms driving early embryonic sex differences remain unclear.
RESULTS: To investigate the transcriptional sex difference during early development, in vitro produced bovine blastocysts were collected and sexed by PCR. A significant male-biased development is consistently observed in expanded blastocysts. Ultra-low input RNA-seq analysis identified 837 DEGs, 1555 significantly sex-biased differential alternative splicing (AS), and 1151 differentially expressed isoforms (DEIs). Among all of the DEGs, there were 231 upregulated and 606 downregulated in males. Functional enrichment analysis revealed male-biased DEGs were associated with metabolic regulation, whereas female-biased DEGs were related to female gonad development, sex differentiation, inflammatory pathways, and TGF-beta signaling. Comparing X chromosome and autosome expression ratio, we found that female-biased DEGs contributed to the higher X-linked gene dosage, a phenomenon not observed in male embryos. Moreover, we identified the sex-biased transcription factors and RNA-bind proteins, including pluripotent factors such as SOX21 and PRDM14, and splicing factors FMR1 and HNRNPH2. Additionally, we revealed that the significantly sex-biased differential AS were predominantly skipped exons, and they could be mapped to 906 genes, with 59 overlapping with DEGs enriched in metabolic and autophagy pathways. By incorporating novel isoforms from long reads sequencing, the sex-biased DEIs were associated with 1017 genes. Functional analysis showed that female-biased DEIs were involved in the negative regulation of transcriptional activity, while male-biased DEIs were related to energy metabolism. Furthermore, we identified sex-biased differential exon usage in DENND1B, DIS3L2, DOCK11, IL1RAPL2, and ZRSR2Y, indicating their sex-specific regulation in early embryo development.
CONCLUSION: This study provided a comprehensive analysis of transcriptome differences between male and female bovine blastocysts, integrating sex-biased gene expression, alternative splicing, and isoform dynamics. Our findings indicate that enriched metabolism processes in male embryos may contribute to the faster developmental pace, providing insights into sex-specific regulatory mechanisms during early embryogenesis.

Keywords:  Bovine blastocyst; Differential gene expression; Isoform expression; Sex difference; Sex-biased alternative splicing

DOI:  https://doi.org/10.1186/s13578-025-01459-x
Cell Rep. 2025 Aug 22. pii: S2211-1247(25)00941-6. [Epub ahead of print]44(9): 116170

Exogenous estrogen enhances T cell activation in male primates.

Patricia A Hahn, Joan Escrivà-Font, Eric S Alexander, Kimberly Weisgrau, Tianling Ou, Wenhui He, Daniel O'Hagan, Laura C F Da Silva, Noah J Gurley, Li Lin, Michael D Cameron, Eva Rakasz, Michael Farzan, Joe R Kurian, Saverio Capuano, Camila R Consiglio, Mauricio A Martins.

  Estrogen influences T cell development and enhances infection resistance in females, but its immunological effects during gender-affirming hormone therapy (GAHT) remain poorly understood. Here, we characterize immune adaptations in male rhesus macaques (RMs) treated with 17β-estradiol (E2) or placebo over 7 months. E2 therapy suppressed endogenous testosterone production, induced female physical traits, and altered blood cell counts and chemistry profiles. Additionally, E2 treatment attenuated innate immune responses while increasing T cell activation. Following mRNA vaccination, E2-treated RMs exhibited significantly higher frequencies of CCR5+ CD4+ T cells, the primary targets for HIV-1 replication, compared to placebo-treated RMs. Overall, our findings reveal the immunological consequences of estrogen in male primates, emphasizing the need to investigate how supraphysiological E2 levels may affect HIV susceptibility and pathogenesis. This work highlights the potential of RMs as a model for studying immune interventions in the context of GAHT.

Keywords:  CP: Immunology; CP: Metabolism; estradiol; gender-affirming hormone therapy; human immunodeficiency virus; mRNA vaccine; nonhuman primates; transgender women

DOI:  https://doi.org/10.1016/j.celrep.2025.116170
Cancer Treat Res. 2025 ;129 267-291

Advancing Prostate Cancer Treatment: Innovations and Challenges in Immunotherapy.

Gargi Singhal, Pankaj Garg, Atish Mohanty, Sudarsan Vishnu Kollimuttathuillam, Deric Wheeler, Bamidele A Adesunloye, Sharad S Singhal.

  Prostate cancer (PCa), a leading cause of cancer mortality in men, has experienced a paradigm shift with the rise of immunotherapy. This chapter examines the immunological landscape of PCa and highlights key immunotherapeutic approaches, including cancer vaccines, immune checkpoint inhibitors (ICIs), adoptive cell therapies, and cytokine-based treatments. Emerging innovations, such as oncolytic viruses, neoantigen-based therapies, and bispecific antibodies, are also examined. Challenges like the immunosuppressive tumor microenvironment (TME), limited predictive biomarkers, and immune-related adverse events (irAEs) are addressed, alongside promising combination strategies with androgen deprivation therapy (ADT), radiotherapy, and targeted therapies. Advances in biomarker discovery and artificial intelligence (AI) are emphasized for their role in optimizing personalized immunotherapy. This chapter underscores the need for equitable access to these advancements and concludes with a vision for integrating immunotherapy into standard care, offering durable and transformative outcomes for PCa patients.

Keywords:  Androgen deprivation therapy; Cancer vaccine; Chemotherapy; Immune checkpoint inhibitors; Immunotherapy; Prostate cancer; Targeted therapy; Tumor microenvironment

DOI:  https://doi.org/10.1007/978-3-031-97242-3_12
Front Pediatr. 2025 ;13 1581060

Clinical utility of FAI and SHBG in differentiating PCOS from anovulatory cycles in adolescent girls.

Emre Özer, Demet Taş, Seçil Çakır Gündoğan, Mehmet Boyraz, Fatih Gürbüz.

   Introduction: Menstrual irregularities are common in adolescents, often linked to anovulatory cycles. This study aims to establish diagnostic cut-off values for Polycystic Ovary Syndrome (PCOS) and differentiate it from anovulatory dysfunction in adolescents, while evaluating the diagnostic sensitivity of the Free Androgen Index (FAI) and Sex Hormone Binding Globulin (SHBG).
Methods: The study included 305 adolescents with oligomenorrhea at a tertiary center. Statistical analyses were performed, and Receiver Operating Characteristic (ROC) curves were used to assess diagnostic performance.
Results: Of the 305 patients, 229 (75%) had anovulatory cycles, and 36 (11.8%) were diagnosed with PCOS. Mean FAI values were 3.5 ± 2 in anovulatory cycles, 8.0 ± 5 in PCOS, and 8.3 ± 4 in hyperinsulinism (p < 0.001). FAI showed significant positive correlations with HOMA-IR (r = 0.389, p < 0.001) and BMI z-score (r = 0.499, p < 0.001). ROC analysis identified an LH threshold of 9.7 U/L and an LH/FSH ratio of 2.62 as predictive markers for PCOS.
Discussion: Anovulatory cycles are the leading cause of menstrual irregularities in adolescents. While hyperandrogenism is crucial for PCOS diagnosis, elevated FAI levels in PCOS are also observed in hyperinsulinemia and obesity. PCOS is more prevalent in obese adolescents, which limits the diagnostic reliability of FAI. Lower SHBG levels in hyperinsulinemic obese adolescents further complicate FAI interpretation, underscoring the significant impact of glucose and insulin metabolism on these markers. Therefore, a comprehensive diagnostic approach, including androgen levels, LH/FSH ratio, SHBG, FAI, and ovarian ultrasound, is essential for accurate PCOS diagnosis in adolescent girls.

Keywords:  LH-FSH; free androgen index; menstrual irregularity; oligomenorrhea; polycystic ovary syndrome; sex hormone binding globuline

DOI:  https://doi.org/10.3389/fped.2025.1581060
Aging Male. 2025 Dec;28(1): 2549292

The impact of exercise on prostate-specific antigen and testosterone in prostate cancer: a systematic review and meta-analysis.

Fuxun Zhang, Zhirong Luo, Qi Xue, Xuyan Guo, Wei Zhang, Yang Xiong, Yong Jiao, Uzoamaka Adaobi Okoli, Geng Zhang.

   BACKGROUND: Exercise prescription can promote the rehabilitation of patients with prostate cancer (PCa). However, the effect of exercise intervention onserum levels of prostate-specific antigen (PSA) and testosterone remains unclear.
METHODS: The primary outcome was the effect of exercise prescription on PSA level. The secondary outcome was the effect of exercise training on testosterone level. The pooled standardized mean difference (SMD) with 95% confidence interval (CI) was selected as the indicator. Meta-regression was conducted to assess the relationship between covariates and outcomes. Publication bias was evaluated using funnel plots and Egger's test.
RESULTS: The data of 594 patients from 8 randomized controlled trials (RCTs) were included and analyzed. Pooled effect of exercise intervention on PSA was 0.13 (95% CI: -0.04 to 0.29, I2 = 0.0%, p = 0.984), while the pooled effect on testosterone was 0.19 (95% CI: -0.00 to 0.39, I2 = 0.0%, p = 0.435). The meta-regression showed there was no significant association of age, body mass index, and the exercise duration with PSA or testosterone. No significant publication bias was detected in meta-analysis.
CONCLUSIONS: Although many benefits were documented, exercise intervention have no significant effect on PSA and testosterone levels in PCa patients.

Keywords:  Prostate cancer; exercise; prostate-specific antigen; testosterone; treatment

DOI:  https://doi.org/10.1080/13685538.2025.2549292
Int J Mol Sci. 2025 Aug 08. pii: 7672. [Epub ahead of print]26(16):

The Sweet Side of IVF: Biological Role and Diagnostic Potential of Galectin-9 in Female Infertility.

Beata Polgar, Matyas Meggyes, Krisztina Godony, Akos Varnagy, Kalman Kovacs, Peter Mauchart, Peter Matrai, Krisztina Kovacs, David Semjen, Tamas Tornoczki, Laszlo Szereday.

  Infertility rates are indeed increasing globally, which emphasizes a pressing need to identify novel biomarkers exhibiting superior potential for laboratory diagnosis and personalized clinical management. This study aimed to explore the biological role of Galectin-9 (Gal-9) in female fertility and evaluate its diagnostic potential in the In Vitro Fertilization (IVF) program. A prospective cohort study was performed on 83 follicular fluids (FF) and 19 serum-FF pairs from IVF patients, 16 serum samples from fertile women, and 12 tissue sections. Gal-9 expression was characterized by immunostaining and ELISA. The ROC analysis was employed to evaluate the overall diagnostic performance. Cell-specific ovarian Gal-9 expression and significant differences in soluble Gal-9 levels were identified in the serum and FF of fertile and infertile women. Elevated intrafollicular Gal-9 levels were linked to poor ovarian reserve, served as a predictive marker for ovarian hyperstimulation, and marked unfavorable IVF outcomes. Follicular Gal-9 levels positively correlated with peak estradiol and total daily FSH dosage. ROC analysis revealed an excellent diagnostic value of Gal-9 for predicting fertilization success and a moderate ability to predict IVF outcomes. Our findings suggest a potential role for Gal-9 in oogenesis and its promise as a diagnostic marker for predicting fertilization success in IVF. However, further studies are needed to confirm its clinical utility in assisted reproduction.

Keywords:  Galectin-9; biomarker; follicular fluid; in vitro fertilization; infertility

DOI:  https://doi.org/10.3390/ijms26167672
Int J Mol Sci. 2025 Aug 21. pii: 8106. [Epub ahead of print]26(16):

Long-Term Durability and Variant-Specific Modulation of SARS-CoV-2 Humoral and Cellular Immunity over Two Years.

Lilia Matei, Mihaela Chivu-Economescu, Laura Denisa Dragu, Camelia Grancea, Coralia Bleotu, Raluca Hrișcă, Corneliu Petru Popescu, Carmen C Diaconu, Simona Maria Ruţă.

  There is an increasing need to understand the long-term dynamics and quality of SARS-CoV-2 immune memory-both humoral and cellular-particularly with emerging variants. This study aimed to evaluate immune durability and variant-specific modulation through a longitudinal analysis of individuals with diverse SARS-CoV-2 exposure histories, over two years after infection and/or vaccination. The study involved assessing anti-spike IgG and IgA levels over time and analyzing their relationship with neutralizing activity against both ancestral and Omicron SARS-CoV-2 variants. Persistence of T cell responses was evaluated using intracellular cytokine staining (ICS) and activation-induced marker (AIM) assays. Anti-S IgG levels remained stable over time and increased after each immune stimulation, suggesting cumulative immune memory. Neutralizing capacity correlated strongly with IgG levels, showing long-term stability for pre-Omicron variants, but a moderate decline for Omicron. CD4+ and CD8+ T cell responses persisted across all groups, largely unaffected by Omicron mutations. However, cytokine profiles revealed subtle, variant-dependent changes. These findings underscore the durability of cellular immunity and the comparatively reduced robustness of Omicron-specific humoral responses. Such insights are crucial for understanding long-term protection against evolving SARS-CoV-2 variants and guiding public health strategies.

Keywords:  SARS-CoV-2; T-cell immunity; anti-SARS-CoV-2-specific antibodies; cytokine profile; long-term immunity; longitudinal analysis; neutralization capacity; viral variants

DOI:  https://doi.org/10.3390/ijms26168106
Chin Clin Oncol. 2025 Aug 12. pii: cco-25-44. [Epub ahead of print]

Oligometastatic prostate cancer: new horizons for local treatment with the androgen receptor target therapy.

Giulio Francesco Reale, Riccardo Scarlatti, Diana Aresu.

DOI: https://doi.org/10.21037/cco-25-44
Adv Biomed Res. 2025 ;14 63

Effects of Naringenin (NG) as an Anti- Proliferative and Anti-Apoptotic Factor on ER Alpha and ER Beta in PCOS.

Fardad Saremi, Fatemeh Parvin Sabet, Kimia Nabiee, Fatemeh Tolouei, Kooshyar Kouchaki, Mahya Yasami, Shaghayegh Soltani, Reza Zandi, Mona Gorji.

   Background: Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder among women of reproductive age, characterized by elevated androgen levels, chronic inflammation, and oxidative stress. This research investigated the therapeutic impact of Naringine (NAR) on antioxidant and anti-inflammatory factor levels in the ovarian tissues of rats diagnosed with PCOS.
Materials and Methods: Forty two mature (6-8 weeks old) female wistar rats were assigned into six groups (seven rats in each group), including control, PCOS-induced (PCOS like condition was induced based on the previous study, control with a dose of 20 mg/kg, control with a dose of 40 mg/kg, PCOS-induced with a dose of 20 mg/kg, PCOS-induced with a dose of 40 mg/kg groups. After 21 days of intervention, the animals were euthanized. The serum levels of sex hormones (estrogen, progesterone) and androstendion were measured. Ovary samples were also collected for RNA extraction, which was done to compare the expression levels of the Erα and Erβ among groups.
Results: Treatment with Naringine significantly increased the total antioxidant capacity (TAC), superoxide dismutase (SOD), glotathion peroxidase (GPX) and while decreasing malondialdeyide (MDA) level. Additionally, it increased estrogen and progestone concentration and decreased androstendion concentration. Moreover, the level of gene expression and production of ER-a and ER-b proteins significantly increased in the groups treated with Naringine.
Conclusion: Naringine can be considered a potent antioxidative and antiapoptotic agent for therapeutic strategies in reproductive and regenerative medicine. These findings suggest that Naringine could be a potential candidate for the treatment of PCOS disorders.

Keywords:  Anti-apoptotic factor; anti-proliferative; folliculogenesis; naringenin; ovulation; polycystic ovary syndrome

DOI:  https://doi.org/10.4103/abr.abr_457_24
Cell Physiol Biochem. 2025 08 25. 59(S2): 82-123

Oxidative Stress, Antioxidants, Gut Microbiota and Male Fertility.

Natalia Kurhaluk, Piotr Kamiński, Halina Tkaczenko.

  It is imperative to comprehend the multifactorial causes of male infertility and to identify effective treatment methods, to enhance male reproductive health, and to develop more personalised and effective therapeutic interventions. This review discusses the multifactorial aspects contributing to male infertility, focusing on oxidative stress (OS), sperm quality, gut microbiota, and the potential role of adaptogens. A comprehensive literature search was conducted across several major databases, including the Cochrane Library, Medline, Embase, SciSearch, PubMed, Web of Science, Scopus, and Google Scholar. The findings from the studies included in the databases highlight the significant role of oxidative stress in male infertility, with reactive oxygen species (ROS) contributing to sperm DNA fragmentation and impairment of spermatogenesis. The review further elucidates the influence of both endogenous and exogenous sources of ROS, including lifestyle factors and environmental exposures, on male reproductive health. Emerging research also highlights the involvement of key molecular pathways, such as Nrf2, AMPK/PGC-1α, and NF-κB, in regulating OS within the male reproductive system. Additionally, the review outlines the relationship between endothelial dysfunction, cardiovascular health, and male infertility, identifying OS as a common underlying factor. In addition to the OS, the gut microbiota has been identified as a pivotal factor in male fertility, influencing inflammation and hormonal regulation. This review underscores the potential merits of a synergistic strategy that integrates dietary interventions, antioxidants, gut microbiota modulation, and adaptogens to enhance fertility outcomes. Adaptogens, recognised for their capacity to assist the body in coping with stress and re-establishing equilibrium, may confer protective effects against OS and improve reproductive health. The review under discussion emphasises the importance of a holistic approach to male infertility, integrating molecular, clinical, and lifestyle factors to optimise reproductive health.

Keywords:  Reproductive health in men ; Oxidative stress ; Sperm DNA fragmentation ; Endothelial dysfunction ; Nrf2 pathway ; Cardiovascular diseases ; Stress management

DOI:  https://doi.org/10.33594/000000802
Cell Biol Int. 2025 Aug 24.

Testosterone Enhances Wound Healing and Stress Resistance in A549 Lung Adenocarcinoma Cells via Actin Remodeling and AQP3 Upregulation.

Mi Nam Lee, Seong-Eung Cha, Hyunwoo Lim, Eung-Sam Kim.

  The role of androgens in lung function is contentious, yet their effects on type II alveolar epithelial cells (AECII)-derived lung cancer models remain underexplored. This study reveals that androgens provide survival advantages to A549 cells, a male lung adenocarcinoma AECII cell line, by promoting wound healing and enhancing stress resilience. We demonstrated that testosterone and dihydrotestosterone (DHT) significantly upregulate aquaporin 3 (AQP3) through androgen receptor (AR) accumulation and ERK pathway activation, thereby mitigating cell death under oxidative stress induced by hydrogen peroxide and cyclic cell-stretching. Testosterone facilitated cellular wound healing by promoting actin cytoskeleton remodeling and focal adhesion complex formation, reliant on AR rather than AQP3. Under air-liquid interface culture conditions, testosterone consistently induced AQP3 upregulation, enhanced actin remodeling, and facilitated cellular wound healing responses. Validation of these findings was achieved through gene expression analyses, protein level assessments, cell imaging, and in vitro wound healing assays. The underlying molecular mechanisms of androgen action were elucidated using AQP3- and AR-specific siRNAs and pharmacological inhibitors. These findings underscore the urgent need to investigate the role of sex hormones in lung cancer and other androgen-responsive epithelial models, focusing on their influence on cancer cell survival and motility.

Keywords:  A549; alveolar epithelial cells type II; aquaporin 3; cyclic stretches; testosterone; wound healing

DOI:  https://doi.org/10.1002/cbin.70075
Biomedicines. 2025 Aug 21. pii: 2044. [Epub ahead of print]13(8):

From Petri Dish to Primitive Heart: How IVF Alters Early Cardiac Gene Networks and Epigenetic Landscapes.

Charalampos Voros, Georgios Papadimas, Marianna Theodora, Despoina Mavrogianni, Diamantis Athanasiou, Ioakeim Sapantzoglou, Kyriakos Bananis, Antonia Athanasiou, Aikaterini Athanasiou, Charalampos Tsimpoukelis, Ioannis Papapanagiotou, Dimitrios Vaitsis, Aristotelis-Marios Koulakmanidis, Maria Anastasia Daskalaki, Vasileios Topalis, Nikolaos Thomakos, Panagiotis Antsaklis, Fotios Chatzinikolaou, Dimitrios Loutradis, Georgios Daskalakis.

  Numerous infants have been conceived by in vitro fertilization (IVF) and other assisted reproductive technologies (ART). Increasing evidence indicates that these approaches induce minor alterations in molecules during the initial phases of embryogenesis. This narrative review examines the molecular pathophysiology of embryonic cardiogenesis in the context of assisted reproductive technology, emphasizing transcriptional and epigenetic regulation. Essential transcription factors for cardiac development, including NKX2-5, GATA4, TBX5, ISL1, MEF2C, and HAND1/2, play a crucial role in mesodermal specification, heart tube formation, and chamber morphogenesis. Animal models and human preimplantation embryos have demonstrated that ART-related procedures, including gamete micromanipulation, supraphysiological hormone exposure, and extended in vitro culture, can alter the expression or epigenetic programming of these genes. Subsequent to ART, researchers have identified anomalous patterns of DNA methylation, alterations in histones, and modifications in chromatin accessibility in cardiogenic loci. These alterations indicate that errors occurred during the initial reprogramming process, potentially resulting in structural congenital heart abnormalities (CHDs) or modifications in cardiac function later in life. Analysis of the placental epigenome in babies conceived using assisted reproductive technology reveals that imprinted and developmental genes critical for cardiac development remain dysfunctional. This review proposes a mechanistic theory about the potential subtle alterations in the cardiogenic gene network induced by ART, synthesizing findings from molecular embryology, transcriptomics, and epigenomics. Understanding these molecular issues is crucial not only for enhancing ART protocols but also for evaluating the cardiovascular risk of children conceived by ART postnatally and for early intervention.

Keywords:  cardiac transcription factors; cardiogenesis; congenital heart defects; epigenetic regulation; in vitro fertilization

DOI:  https://doi.org/10.3390/biomedicines13082044
Endocrine. 2025 Aug 26.

Prenatal androgen exposure delays puberty onset in female offspring rats: possible roles of leptin and α-MSH.

Runfei Ge, Yongting Yuan, Jingqi Liu, Ya Zhang, Yun Zhang, Songhui Liu, Mei Han, Hui Han, Rongying Yao, Lianguo Fu.

   OBJECTIVE: To clarify the possible mechanism of leptin and α-MSH on the onset of puberty in female offspring rats after prenatal androgen exposure.
METHODS: Sixteen 8-week-old specific pathogen free (SPF) healthy Sprague Dawley (SD) pregnant rats were randomly divided into the testosterone-treated group (TG, female offspring termed PNA group) or the olive oil control group (OOG, female offspring termed VEH group). The female offspring rats of two groups were raised to 21 days (PND21) and weaned. Six female offspring rats at PND21 (VEH:PNA = 3:3) were randomly selected for transcriptome sequencing. Twenty-seven offspring female rats were randomly divided into three groups (VEHI:VEHII:PNA = 9:9:9). VEHI group was observed until the onset of puberty, VEHII and PNA groups were observed until the 8th week.
RESULTS: Compared with VEH group, onset of puberty was not observed in PNA group, and hypothalamic Pomc gene expression at PND21 was lower. Compared with the VEHI group, the body weight, abdominal fat, serum testosterone (T), dehydroepiandrosterone (DHEA) and leptin (LEP) levels were upregulated in the PNA group, while serum gonadotropin-releasing hormone (GnRH), mRNA of hypothalamic estrogen receptor α (ERα), α-melanocyte stimulating hormone (α-MSH), melanocortin receptor-4 (MC4R), GnRH and adipose AR, and the protein of androgen receptor (AR) and leptin receptor (LEPR) in the hypothalamic arcuate nucleus (ARC) were decreased. In the PNA group, there were positive correlations between serum DHEA and mRNA of hypothalamic ERα, MC4R and AR, negative correlations between mRNA of adipose AR and serum T and free testosterone (FT).
CONCLUSION: Prenatal androgen exposure delayed the onset of puberty in female offspring, the possible mechanism of which is that prenatal androgen exposure may increase the levels of androgen and LEP, decreases their sensitivity and the expression of AR, LEPR, and MC4R, reducing GnRH secretion.

Keywords:  GnRH; Leptin; Prenatal androgen; Puberty onset; α-MSH

DOI:  https://doi.org/10.1007/s12020-025-04388-4
Cell. 2025 Aug 21. pii: S0092-8674(25)00746-9. [Epub ahead of print]188(17): 4480-4504

Interferons in health and disease.

Daniel Boehmer, Ivan Zanoni.

Interferons (IFNs) are signaling proteins that play fundamental roles during health and disease. Although types I, II, and III IFNs are structurally and functionally different, all IFNs signal via an intricate network of Janus kinases, named after the Roman god of time and duality. IFNs are characterized by activities that vary over time and can lead to opposing outcomes. IFNs have protective roles during bacterial, viral, and fungal infections but can also drive numerous inflammatory and autoimmune diseases. In this review, we provide an overview of the cellular and molecular mechanisms governing IFN induction and responses, emphasizing their roles in infections, tumorigenesis, and inflammatory, autoimmune, and genetic diseases, with particular attention to mucosal tissues. Overall, we spotlight how the balanced production of distinct members of the IFN families over time is necessary to exert their protective functions and the detrimental consequences for the host when this balance is lost.

DOI: https://doi.org/10.1016/j.cell.2025.06.044
Clin Exp Immunol. 2025 Aug 16. pii: uxaf056. [Epub ahead of print]

CD56 on immune and tumor cells: what is the known and beyond?

Yuan Meng, Feng Zhang, Yiying Jin, Zhihao Wen, Fengyu Chen, Nenggang Jiang, Hongyan Liao.

  Recent studies on cancer cells and the immune microenvironment have offered valuable insights into personalized diagnostics, targeted therapies, and individualized prognosis evaluation. A comprehensive understanding of new and existing biomarkers in both healthy and diseased conditions is essential for advancing these goals. CD56, also known as the neural cell adhesion molecule (NCAM), is a well-established phenotypic marker of natural killer (NK) cells. It is also expressed by various immune cells under healthy conditions, such as T cells, dendritic cells, and monocytes. Despite its widespread expression, the functions of CD56 are still poorly understood. In patients with infectious, autoimmune, or malignant diseases, changes in the proportion, phenotype, and function of CD56+ immune cells have been observed. In patients with hematolymphoid disorders, malignant cells may exhibit aberrant CD56 expression, making it a valuable diagnostic and prognostic marker. CD56 also holds potential as a therapeutic target. In this review, we summarize the current understanding of CD56 expression and function across various immune cells in infectious, immune-related, and cancerous conditions. We also explore its diagnostic, prognostic, and therapeutic significance in hematological malignancies. This review aims to present a comprehensive overview of CD56 in hematolymphoid disorders, offering insights into how CD56 and its associated immune cells could inform future immunotherapeutic strategies.

Keywords:  CD56; diagnosis; hematological neoplasm; immune cell; prognosis; therapeutics

DOI:  https://doi.org/10.1093/cei/uxaf056