Follicular Cells Research Articles

Clinicopathologic features and outcomes of follicular dendritic cell sarcoma with or without Castleman disease: A large retrospective cohort analysis.

11549 Background: Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm with a subset associated with unicentric Castleman disease (UCD). However, the impact of CD association on clinicopathologic features and survival outcomes remains unclear. This study aims to elucidate differences in disease characteristics and outcomes in FDCS with and without CD to guide future research and clinical practice. Methods: We retrospectively analyzed 41 FDCS patients seen at Mayo Clinic between January 2000 and December 2024. Patients were categorized into CD-related (n = 9) and FDCS-only (n = 32) groups. Demographic, clinical, pathological, and survival data were compared. Kaplan-Meier survival analyses were used to evaluate overall survival (OS) and progression-free survival (PFS). Epstein-Barr virus-associated inflammatory FDCS were excluded. Results: The CD-related group was younger at diagnosis (46.0 vs. 58.0 years, p = 0.041). Among those with CD-related FDCS, FDCS was diagnosed concurrently as CD in 6/9 (66.7%) and after the diagnosis of CD in 3/9 (33.3%). The FDCS-only patients were more likely to have extranodal disease (71.9% vs. 22.2%) and to have metastasis (62.5% vs 22.2%). One CD-related FDCS patient had paraneoplastic pemphigus. Among 11 patients with next-generation sequencing (NGS) results, 9 had pathogenic mutations. The most common pathogenic mutations included CDKN2A, CDKN2B, and TRAF3 copy number losses. Surgery was the preferred first-line intervention in FDCS-only and CD-related FDCS groups (19/32, 59.4% vs. 6/9, 66.7%). Eight out of 32 (25.0%) of the FDCS-only group received chemotherapy at first-line, most commonly Gemcitabine/Docetaxel or Adriamycin/Ifosphamide. While Gemcitabine/Docetaxel was the most preferred in the second line, different regimens were pursued in the third and later lines of therapy, including Pembrolizumab, Pazopanib, and stem cell transplant. Five out of 6 patients in the CD-related FDCS group received either adjuvant radiation or chemotherapy, which led to complete remission during the follow-up periods. The median follow-up was 22.4 months for the whole population. There was a trend for better OS and PFS among CD-related FDCS patients. The respective 2-year OS rates were 100% and 66.7%, and 2-year PFS rates were 57.1% and 43.1% for CD-related FDCS and FDCS-only patients, respectively. Conclusions: This study provides novel insights into clinicopathologic differences and survival trends for FDCS. Our data would suggest a less aggressive disease course among CD-related FDCS, which implies the need for different treatment strategies for CD and non-CD-related FDCS. Further research is warranted to elucidate these mechanisms, such as multi-omic analysis on benign FDC proliferation in the microdissected UCD areas and the adjacent FDCS cells to determine factors associated with progression to sarcoma.

Perfluorooctanoic acid disrupts thyroid hormone biosynthesis by altering glycosylation of Na+/I- symporter in larval zebrafish.

Perfluorooctanoic acid disrupts thyroid hormone biosynthesis by altering glycosylation of Na+/I- symporter in larval zebrafish.

Regulation of T peripheral helper and T follicular helper cells in lupus.

Regulation of T peripheral helper and T follicular helper cells in lupus.

Immunological characteristics of the recombinant pseudorabies virus with chimeric PCV Cap protein in pigs.

Immunological characteristics of the recombinant pseudorabies virus with chimeric PCV Cap protein in pigs.

Morphological characteristics, extracellular vesicle structure and stem-like specificity of human follicular fluid cell subpopulation during osteodifferentiation.

Morphological characteristics, extracellular vesicle structure and stem-like specificity of human follicular fluid cell subpopulation during osteodifferentiation.

Leucine enhances the cGAS-STING-NLRP3 pathway in autoimmune thyroiditis.

Leucine enhances the cGAS-STING-NLRP3 pathway in autoimmune thyroiditis.

Regulated cell death in thyroid follicular cells: Molecular insights into pyroptosis, apoptosis, and necrosis

Regulated cell death in thyroid follicular cells: Molecular insights into pyroptosis, apoptosis, and necrosis

Delineation of the Human Germinal Centre Immune Landscape Using Multiplex Imaging Analysis.

Given the role of follicular immune dynamics, especially the germinal centre, for the development of pathogen-specific antibodies, their insitu characterisation is of great importance. We have developed a multiplex immunofluorescence imaging pipeline that allows the analysis of human follicular adaptive and innate immune cell subsets. Our data revealed the insitu phenotypic heterogeneity and differential localisation of follicular helper CD4 T (TFH) cell subsets across follicular areas in tonsils and reactive lymph nodes (LNs). Cell clustering analysis identified specific TFH subsets with differential prevalence between tonsils and LNs. Further, a multiplex RNAscope/protein imaging assay revealed the functional heterogeneity of TFH cells. No significant differences in follicular innate immune cell densities were found between tonsils and LNs. In conclusion, we present a combinatory experimental approach that provides a comprehensive analysis of human follicular and/or germinal centre immune dynamics and could be used to further understand the pathogenesis of diseases such as HIV and lymphomas.

Unraveling the Transcriptomic Profiles of Large and Small Donkey Follicles.

The diameter of mature follicles in donkeys is several times larger than in cattle and sheep, but the key genes responsible for maintaining follicular development and preventing apoptosis remain unclear. This study observed the process of donkey follicular development using ultrasound and analyzed the changes in common reproductive hormones in serum. Granulosa cells (GCs) were collected from large (mature follicles, diameter ≥ 37 mm) and small (atretic follicles, diameter 10-25 mm) follicles for sequencing to screen differentially expressed genes (DEGs) and signaling pathways influencing the development of mature follicles. The roles of selected genes were further validated in in vitro cultured GCs. Donkey follicles exhibited rapid growth 5-7 days before ovulation, reaching maturity at a diameter of 37 mm. The maximum diameter of ovulatory follicles was approximately 40.7 mm, while non-ovulatory follicles began to undergo atresia when reaching about 25 mm. Serum reproductive hormone levels aligned with follicular developmental status. RNA sequencing identified 3291 DEGs between large and small follicles, with KEGG analysis highlighting enrichment in the PI3K-Akt signaling pathway, focal adhesion, amoebiasis, and cancer pathways. Lentiviral overexpression and interference assays targeting the DEGs EMCN and SYT12 revealed that EMCN positively regulates FOXO3, a key gene in the PI3K-Akt pathway. The EMCN gene in mature donkey follicles regulates FOXO3 in the PI3K-Akt signaling pathway, potentially inhibiting apoptosis in follicular granulosa cells and sustaining follicular development until ovulation. This study provides insights into the mechanisms underlying follicular development in donkeys.

Heterogeneity of T follicular regulatory cells: exploring their expanding ontogeny and differentiation pathways.

T follicular regulatory (Tfr) cells have emerged as key mediators in controlling germinal center (GC) responses, preventing excessive immune activation and preserving self-tolerance. Initially thought to originate solely from thymic T regulatory cells (tTregs), recent findings reveal a more complex picture involving multiple differentiation pathways contributing to their heterogeneity. The natural route of differentiation comprises the most abundant subset, which originates from tTregs and retains the expression of CD25 (CD25+ nTfr), before transitioning into a more mature CD25-negative state within the GC (CD25- nTfr). Conversely, the induced route (iTfr) includes Tfr cells that arise alongside nTfr cells but originate from peripheral Tregs or CD25-expressing Tfh cells, in addition to a late-GC subset (late Tfr) that emerges through the expression of FoxP3 by Tfh cells. The identification of circulating Tfr cells (cTfr) in peripheral blood, especially useful for studying immune dysregulation in humans, provides insights into their systemic roles and potential as biomarkers for immune dysfunction in different clinical scenarios. While it becomes evident that Tfr cells exhibit a heterogeneous nature, a deeper understanding of their distinct subsets could pave the way for targeted immunomodulatory strategies in the development of novel vaccines and therapeutics. This review provides a comprehensive overview of Tfr cell diversity, exploring their ontogeny, functional roles, and impact on immune homeostasis and disease.

Study of the Effect of Nanosilica (SiO2 NPs) on the Gene Expression of Reproductive Hormones and Fertility in Female Rats

The present research was carried out in the animal facility of the Department of Biology, College of Science, University of Al-Qadisiyah, from January 20, 2023, until June 27, 2023. This study sought to observe the effect of varying dosages of nano-silica (SiO2 NPs) on the gene expression of the genes encoding follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in female rats. The findings indicated marked reduction (P<0.05) in the gene expression of both FSH and LH within the treatment groups (T1: 100 mg/kg, T2: 150 mg/kg, and T3: 200 mg/kg) relative to the control group. The most marked reduction was noted within the T3 group, suggesting a dose-dependent response. Histopathological exam of the ovaries, oviducts, and uterus established various structural changes within the dose groups. The ovaries of the T2 and T3 experimental groups had granulosa cell degeneration, massive congestion, and follicular cell deterioration. The oviducts of the T1 experimental group had epithelial lining destruction and considerable congestion, but the uterine sections of the T2 and T3 experimental groups were considered histologically unremarkable. The results imply that the administration of nano-silica may cause widespread alterations in the gene expression of reproductive hormones, potentially resulting in compromised reproductive function and fertility in female rats. Further research is needed to clarify the fundamental mechanism and long -time effects of nano-silica exposure on the female reproductive system.

MiR-370-3p Inhibited the Proliferation of Sheep Dermal Papilla Cells by Inhibiting the Expression of SMAD4.

The proliferation and maturation of hair follicles in follicular papilla cells are predominantly governed by miRNAs, which significantly influence the cell cycle, apoptosis, and proliferation. miR-370-3p has been associated with several biological processes and targets SMAD4, a crucial component in hair follicle development. Tissue expression profiling revealed significant differences in miR-370-3p levels between skin tissues of the two sheep breeds in January and October, as well as between tissues of the Xinji fine-wool sheep and Small-tail Han sheep. SMAD4 exhibited significant differences in tissue-specific expression in the heart, spleen, skin, lungs, and muscles from Xinji fine-wool sheep and Small-tail Han sheep. Bioinformatics analysis and dual-luciferase reporter assays validated the regulatory interaction between miR-370-3p and SMAD4. CCK-8 experiments demonstrated that miR-370-3p's targeting of SMAD4 suppressed cell growth. Cell cycle analysis demonstrated that miR-370-3p's targeting of SMAD4 influenced the cell cycle. Annexin V-FITC/PI dual labeling demonstrated that miR-370-3p's targeting of SMAD4 promoted cell apoptosis. RT-qPCR data demonstrated that miR-370-3p's targeting of SMAD4 elevated the expression of JUN, c-MYC, and TCF7L2 while suppressing β-catenin expression. Western blot (WB) analysis demonstrated that miR-370-3p targeting of SMAD4 significantly promoted c-MYC expression while inhibiting CCND1, CCND2, and β-catenin expression. miR-370-3p and SMAD4 exhibit spatiotemporal expression differences in sheep skin tissues, with widespread expression across various tissues. Furthermore, it confirmed that miR-370-3p targets SMAD4 to inhibit follicular papilla cell proliferation, promote apoptosis, and influence the cell cycle.

Oncostatin-M: a novel leukocyte-derived factor facilitating the ovulatory process in the human ovary.

Does leukocyte-derived Oncostatin-M (OSM) regulate the ovulatory process in human dominant follicles? Leukocyte-derived OSM activates key signaling pathways in human preovulatory granulosa cells and modulates steroidogenesis, prostaglandin synthesis, and tissue remodeling in human ovulatory follicles. Leukocytes are essential regulators of ovulation. Our recent single-cell RNA sequencing (scRNA-seq) has identified diverse leukocyte subpopulations in follicular aspirates obtained from IVF patients and revealed the expression of OSM in leukocytes and its receptors (OSMR, LIFR, IL6ST) in follicular cells. However, the function of leukocyte-derived OSM in human ovulatory follicle remains unclear. This study analyzed dominant follicles from naturally cycling women (n = 19) across the periovulatory period and follicular aspirates from IVF patients (n = 12). Primary human granulosa/lutein cells (hGLCs) treated with hCG and/or recombinant human OSM (rhOSM) were used to assess its functional effects. Our recent scRNA-seq dataset was used to identify cell types expressing OSM and its receptors in human follicular aspirates. The expression of OSM and its receptors was assessed in dominant follicles by quantitative PCR (qPCR) and immunohistochemistry. hGLCs were treated with hCG and/or rhOSM, and functional analyses included qPCR, western blotting, RNA sequencing, and hormone assays for progesterone (P4), estradiol (E2), and prostaglandin E2 (PGE2) production. Bioinformatics analysis of scRNA-seq revealed that OSM is exclusively expressed in leukocytes, whereas its receptors are predominantly expressed in granulosa cells. Immunohistochemistry and qPCR analyses exhibited increased OSM expression in leukocytes and receptor expression in granulosa cells, respectively, after ovulatory hCG administration (P < 0.05). Western blotting demonstrated that rhOSM treatment activated STAT3, ERK1/2, AKT, and p38MAPK pathways in hGLCs. RNA sequencing and following qPCR revealed rhOSM-induced significant transcriptional changes in genes involved in steroidogenesis, prostaglandin synthesis/transport, inflammation, and tissue remodeling (FDR < 0.05). Functionally, rhOSM increased P4 and PGE2 secretion (P < 0.05) while decreasing E2 production (P < 0.05), suggesting a role in ovulation and luteinization. RNA sequencing datasets are available in the Gene Expression Omnibus under accession number GSE277343. This study was conducted using in vitro hGLC cultures, which may not fully recapitulate in vivo ovulatory dynamics. Additionally, the findings are specific to human samples and require validation in other mammalian species. These results suggest that leukocyte-derived OSM is a key cytokine regulating ovulatory events, providing novel insights into the immunoendocrine crosstalk within the human follicle. This study enhances our understanding of cytokine-mediated follicular maturation and may have implications for improving ovulation-related fertility treatments. This study was supported by grants P01HD71875 (to M.J. and T.E.C.), R01HD096077 (to M.J.), R03HD095098 (to Y.C.), and R01HD115554 (to Y.C.). The authors declare no competing interests.

Mechanism of the N6-methyladenosine reader heterogeneous nuclear ribonucleoprotein C facilitating immune escape in thyroid cancer by stabilizing programmed death ligand 1.

Thyroid cancer (TC) is a leading malignancy of the endocrine system. We investigated mechanism of the N6-methyladenosine (m6A) reader heterogeneous nuclear ribonucleoprotein C (HNRNPC) facilitating immune escape in TC by stabilizing programmed death ligand 1 (PD-L1). HNRNPC expression in TC tissues was analyzed using databases. Human TC cells (BHT-101, B-CPAP, SW579) and human thyroid follicular epithelial cells (Nthy-ori3-1) were cultured in vitro. SW579 cells were treated with pcDNA3.1-HNRNPC (oe-HNRNPC) and small interfering (si)-PD-L1, and B-CPAP cells were transfected with si-HNRNPC. HNRNPC and PD-L1 expression levels were assessed by RT-qPCR and Western blot. Cell proliferation, migration and invasion were evaluated by CCK-8, colony formation, and Transwell assays. Carboxyfluorescein diacetate succinimidyl ester-labelled CD8+ T cell proliferation and effector cytokine (interferon-γ, tumor necrosis factor-α) levels were measured by flow cytometry and ELISA. The correlation between HNRNPC and PD-L1 expression in TC tissues, m6A modification sites on PD-L1 messenger RNA (mRNA), and HNRNPC-PD-L1 interaction were analyzed by databases and RIP assay. PD-L1 m6A modification was determined by Me-RIP assay. PD-L1 mRNA stability was detected by treating cells with actinomycin D. HNRNPC was notably highly expressed in TC cells. HNRNPC promoted TC cell proliferation, migration and invasion, facilitating immune escape. Mechanistically, HNRNPC mediated m6A modification to strengthen PD-L1 mRNA stability and up-regulate PD-L1 expression. Moreover, knockdown of PD-L1 partially reversed the promotional effect of HNRNPC on immune escape in TC cells. HNRNPC bolstered PD-L1 stability and up-regulated PD-L1 expression through m6A modification, thus promoting immune escape in TC.

Glutathione Peroxidase 3 in Mouse Oocytes, Preimplantation Embryos and Female Genital Organs During The Preimplantation Period Of Pregnancy

Abstract Objectives This study describes the presence of glutathione peroxidase 3 (GPx3) in mice oocytes, preimplantation embryos (O/PEs), and female genital organs during the preimplantation period of pregnancy. Background Glutathione peroxidase 3, the antioxidant enzyme, is important in protecting cells against the oxidative stress. Methods O/PEs were isolated from genital organs of superovulated females for the immunofluorescence analysis and these organs were used for the immunohistochemistry to detect GPx3. Results GPx3 was present in all O/PEs, where it formed clusters diffusely in the cytoplasm, or under the cytoplasmic membrane. Moreover, GPx3 was likely indicated in nucleoli. GPx3 was found in the cytoplasm of granulosa-lutein cells as well as in follicular cells. The oocyte cytoplasm inside the ovary was negative. Oviductal epithelial cells before and after fertilization had different positivity patterns. Uterine luminal epithelial cells were negative before fertilization. After fertilization, a few positive luminal epithelial cells and a few cells of uterine glands had positive cytoplasm. Conclusion The differences of the GPx3 signal intensity in nucleoli of the zygote and the 2-cell embryo, and the different localization of GPx3 in the cytoplasm of 2-cell and 4-cell embryos may be the signs of the maternal-zygotic genome transition. Moreover, GPx3 may be significant during the preimplantation period of pregnancy in O/PEs and female genital organs, where it could protect cells from oxidative stress during the hormone and protein synthesis, and during the cell metabolism. The presence of cytoplasmic granules in epithelial cells of fallopian tube may indicate their secretion into the lumen of the organ to protect gametes and preimplantation embryos passing through. To our knowledge, this is the first study investigating GPx3 occurrence in mammalian preimplantation embryos.

TP53 and CDKN2A alterations define a poor prognostic subgroup in patients with nodal T follicular helper cell lymphoma.

Nodal T follicular helper cell lymphoma (nTFHL) exhibits unique immunophenotypes and somatic alterations, while the prognostic value of these alterations remains unclear. By analyzing 173 nTFHL cases, we identified 36 driver genes, including 4 novel ones (TET3, HLA-C, NRAS, and KLF2). Then, we classified nTFHL cases into four molecular subgroups by major driver alterations. TR-I (+) and TR-I (-) were characterized by TET2 and/or RHOA mutations with and without IDH2 mutations; AC53 by TP53 and/or CDKN2A alterations and aneuploidy; and NSD with no subgroup-defining alterations (namely without any of the above alterations). AC53 exhibited the worst survival, while NSD, particularly those lacking driver alterations, showed the best prognosis. nTFHL had a better prognosis than peripheral T-cell lymphoma, not otherwise specified, when TP53 and/or CDKN2A alterations were absent. Multivariable analyses showed that AC53, the presence of driver alterations, and international prognostic index high-risk were independently associated with worse survival. Finally, we developed a simple prognostic index (mTFHL-PI), which classified patients into three risk categories with a median OS of 181, 67, and 20 months, respectively. Our study identifies novel prognostic factors, namely TP53 and/or CDKN2A alterations and the presence of driver alterations, demonstrating the clinical relevance of molecular classification in nTFHL.

Sarcoma of the thyroid co-occurrence with Carcinoma (Carcinosarcoma)

Thyroid carcinosarcoma (TC) is an aggressive biphasic malignancy. It has a high mortality rate even after the application of a Multi-disciplinary therapeutic approach. We studied a 63-year-old lady with neck swelling for 4 years with a rapid increase in size in 2 months. Fine Needle Aspiration Cytology (FNAC) of the thyroid nodule was reported as papillary thyroid carcinoma. Positron Emission Tomography and Computed Tomography (PETCT) showed a hypermetabolic lesion in the thyroid with a hypermetabolic lytic lesion in the 4th rib, suggestive of metastasis. Subsequently, patients underwent total thyroidectomy with central compartment clearance and left selective neck dissection. Histopathological evaluation and immunohistochemistry showed that spindle cells were positive for smooth muscle actin (SMA) and negative for Pan Cytokeratin (Pan CK), Carcinoembryonic Antigen (CEA), Paired-box-gene (PAX8), SRY-related HMG-box 10 (SOX10) and Desmin. Thyroid transcription factor 1 (TTF-1) was positive in follicular cells and Cytokeratin 19 (CK19) was focal positive. Hence, a diagnosis of Sarcoma with myoid differentiation and Follicular Carcinoma (carcinosarcoma) was made. Treatment of this disease remains not very clear. The method of management in is still Surgical removal of primary tumor.

Comparative analysis of follicular cell- derived thyroid carcinoma: assessing the impact of high-grade features in an advanced disease cohort.

The 5th edition of the WHO Classification of Tumors of Endocrine Organs introduced the term Differentiated High-Grade Thyroid Carcinoma (DHGTC) to identify cases of differentiated follicular cell-derived thyroid carcinomas (DFCDTC) with a worse prognosis. This study aimed to determine the frequency and clinicopathological features of DHGTC within a cohort of advanced follicular cell-derived thyroid carcinomas (AdvTC) and compare them to non-high-grade DFCDTC (non-HGDTC) and poorly differentiated thyroid carcinoma (PDTC).A retrospective analysis was conducted on 138 patients with AdvTC who underwent total thyroidectomy followed by radioactive iodine therapy (131I).DHGTC was identified in 15.9% of the cases (22/138), showing a higher prevalence in this selected cohort of AdvTC compared to other studies. Compared to non-HGDTC, DHGTC was significantly associated with adverse clinicopathological features, including age ranges ≤ 18 and ≥ 55years, presence of distant and synchronous metastasis, larger tumor size (> 2cm), tall-cell subtype of papillary thyroid carcinoma, higher mitotic index (≥ 5/2 mm2), tumor necrosis, angioinvasion, higher AJCC 8th edition pT stage (pT3/T4), and more frequent administration of additional therapies, such as tyrosine kinase inhibitors. In comparison to PDTC, DHGTC displayed lower median tumor size, less frequent tumor necrosis, and a higher mitotic count. Independent prognostic factors for worse DSS in the entire cohort were age ≥ 55years (HR = 19.625, p = 0.005) and male sex (HR = 7.441, p = 0.029). DHGTC cases consistently demonstrated worse clinical outcomes compared to non-HGDTC, including lower survival rates and higher persistence of disease at the end of follow-up.Our results validate the inclusion of DHGTC as a distinct high-grade subgroup within follicular cell-derived thyroid carcinomas, as proposed by the 5th WHO classification. DHGTC exhibits aggressive clinicopathological features and poor outcomes, supporting its relevance in clinical risk stratification and therapeutic decision-making.

COL1A1 promotes cell proliferation, cell cycle progression, and anoikis resistance in granulosa cells of chicken pre-ovulatory follicles.

COL1A1 promotes cell proliferation, cell cycle progression, and anoikis resistance in granulosa cells of chicken pre-ovulatory follicles.

AMPKα alleviates the inhibitory effect of NEFA on the function of bovine follicular granulosa cells cultured in vitro.

AMPKα alleviates the inhibitory effect of NEFA on the function of bovine follicular granulosa cells cultured in vitro.