Expression Of Sox2 Research Articles

Correlation of hsa-mirna-342-3p and SOX 6 Expression with Diabetic Nephropathy Classification, Prognostic Histomorphological Parameters and Laboratory Findings in Diabetic Nephropathy.

Correlation of hsa-mirna-342-3p and SOX 6 Expression with Diabetic Nephropathy Classification, Prognostic Histomorphological Parameters and Laboratory Findings in Diabetic Nephropathy.

Selective effects of collagen-derived peptides Pro-Hyp and Hyp-Gly on the proliferation and differentiation of SSEA3-positive human dental pulp stem cells.

Selective effects of collagen-derived peptides Pro-Hyp and Hyp-Gly on the proliferation and differentiation of SSEA3-positive human dental pulp stem cells.

Respiratory Syncytial Virus-Infected Human Mesenchymal Stem Cells Overexpress Toll-like Receptors and Change the Pattern of Distribution of Their Cytoskeleton

Acute respiratory tract infections (ARIs) are one of the major causes of morbimortality in children and adulthood. Furthermore, the respiratory syncytial virus (RSV) is the main pathogen in severe lower respiratory tract infections. In Mexico, RSV is the second cause of ARI, affecting mainly children and seniors. RSV infects the airway epithelium, including mesenchymal stem cells (MSCs). These cells express a variety of surface molecules which may function as viral receptors, i.e., Toll-like receptors (TLRs), but the consequences that viral infection has on their biological activities are poorly understood. The aim of this study is to determinate if RSV infection of MSC modifies the expression of stemness biomarkers, TLRs, and the organization of the cytoskeleton. To study the viral infection of MSCs, we determined the mRNA expression using qRT-PCR of SOX2, NANOG, and POU5F1; vimentin and actin; and TLRs 2, 4, and 6. In addition, we determined the cell surface expression of TLR 2 and 4 using flow cytometry. Our results showed that the infection did not change the mRNA expression of SOX2, NANOG, and POU5F1, but increased the mRNA expression of TLR4 and the cell surface expression. Meanwhile, the mRNA in the actin was unchanged, vimentin decreased, and the infection generated a redistribution of the cytoskeleton.

Intraspinal ASPSCR1::TFE3 rearranged tumor with nerve differentiation.

The ASPSCR1::TFE3 rearrangement has been described in alveolar soft part sarcoma, MiT family translocation renal cell carcinomas as well as perivascular epithelioid cell tumors (PEComas). However, this rearrangement has not been reported in the primary spinal canal. Here, we report a case of an 18-year-old male who had pain in his left lower limb for 2months. Neuroimaging revealed a lesion in the spinal canal from thoracic 12 to lumbar 1. Histopathological examination showed the tumor consisting of nested architectural pattern with abundant psammomatous calcification. Tumor cells exhibited strong and diffuse positivity for TFE3 and SOX10, patchy positivity for HMB-45 and S100, while other immunomarkers were negatively stained. RNA sequencing confirmed the ASPSCR1::TFE3 gene rearrangement. The Heidelberg DNA methylation classifier classified this case as "Cranial and Paraspinal Nerve Tumor". This case may represent a novel intraspinal neoplasm entity that expands the spectrum of ASPSCR1::TFE3-rearranged neoplasms by unique histopathological features and potential neural differentiation. We named this case as intraspinal ASPSCR1::TFE3 rearranged tumor with SOX10 expression.

SOX4 reprograms fatty acid metabolism through the CHREBP to inhibit ferroptosis in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality, characterized by aggressive progression and poor prognosis. Pathological angiogenesis in HCC is closely linked to metabolic reprogramming, particularly concerning fatty acid metabolism. The interplay between fatty acid metabolism and ferroptosis, a type of cell death driven by lipid peroxidation, is emerging as a crucial area of study. The transcription factor SOX4 is known to be overexpressed in various cancers, including HCC, and may play a key role in these processes. We assessed SOX4 expression in HCC using clinical samples and data from online databases. Next-generation RNA sequencing was employed to explore the effects of SOX4 on fatty acid metabolism, focusing on the CHREBP pathway. Functional assays, including lipid peroxidation and angiogenesis studies, were conducted to investigate the role of SOX4 in regulating ferroptosis and angiogenesis in HCC. SOX4 was found to be significantly upregulated in HCC and associated with enhanced angiogenesis. Mechanistically, SOX4 activated the CHREBP/SCD1 pathway, leading to increased production of monounsaturated fatty acids, which in turn inhibited ferroptosis. This suppression of ferroptosis contributed to the promotion of angiogenesis and tumor progression in HCC. In conclusion, SOX4 reprograms fatty acid metabolism via the CHREBP/SCD1 pathway, thereby inhibiting ferroptosis and promoting angiogenesis in HCC. These findings suggest that targeting the SOX4-CHREBP axis could represent a novel therapeutic strategy for HCC.

Deep Reinforcement Learning for CT-Based Non-Invasive Prediction of SOX9 Expression in Hepatocellular Carcinoma.

Background: The transcription factor SOX9 plays a critical role in various diseases, including hepatocellular carcinoma (HCC), and has been implicated in resistance to sorafenib treatment. Accurate assessment of SOX9 expression is important for guiding personalized therapy in HCC patients; however, a reliable non-invasive method for evaluating SOX9 status remains lacking. This study aims to develop a deep learning (DL) model capable of preoperatively and non-invasively predicting SOX9 expression from CT images in HCC patients. Methods: We retrospectively analyzed a dataset comprising 4011 CT images from 101 HCC patients who underwent surgical resection followed by sorafenib therapy at West China Hospital, Sichuan University. A deep reinforcement learning (DRL) approach was proposed to enhance prediction accuracy by identifying and focusing on image regions highly correlated with SOX9 expression, thereby reducing the impact of background noise. Results: Our DRL-based model achieved an area under the curve (AUC) of 91.00% (95% confidence interval: 88.64-93.15%), outperforming conventional DL methods by over 10%. Furthermore, survival analysis revealed that patients with SOX9-positive tumors had significantly shorter recurrence-free survival (RFS) and overall survival (OS) compared to SOX9-negative patients, highlighting the prognostic value of SOX9 status. Conclusions: This study demonstrates that a DRL-enhanced DL model can accurately and non-invasively predict SOX9 expression in HCC patients using preoperative CT images. These findings support the clinical utility of imaging-based SOX9 assessment in informing treatment strategies and prognostic evaluation for patients with advanced HCC.

Lomibuvir sensitizes radioiodine-resistant thyroid cancer cell lines to radioiodine treatment by targeting hTERT RNA-dependent polymerase activity.

Radioactive iodine (RAI) is selectively used in the treatment of residual or recurrent differentiated thyroid cancer for over fifty years. However, radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) is difficult to treat with radioactive iodine because of the decreased sodium iodide symporter (NIS) activity. Patients with RAIR-DTC derive limited benefit from RAI therapy, necessitating the exploration of new treatment options. In the current study, we aimed to explore the mechanism underlying thyroid cancer dedifferentiation and to provide new targets for RAIR therapy. We established a RAIR thyroid cancer cell line which was verified by the colony formation ability under radioiodine-131 treatment at doses up to 100 µCi. As expected, higher expressions of cancer stem cell genes, SOX2, CD133, and OCT4 A were found in RAIR cells compared to non-RAIR cells. Correspondingly, the expression of iodine-handling genes such as NIS, TPO, and Pendrin were downregulated. Interestingly, we discovered that the RNA-dependent RNA polymerase (RdRP) activity of TERT was also upregulated in RAIR cells, evidenced by the upregulation of phosphorylated telomerase reverse transcriptase (TERT), BRG1 and CDK1. Moreover, miR-146b-5p, transcribed by TERT gene, was likewise upregulated. RdRP inhibitor lomibuvir treatment downregulated miR-146b-5p level in RAIR cells, resulting in the upregulation of NIS gene expression. Lomibuvir not only restored the expressions of TPO and NIS but also downregulated the elevated ALDH1A1 and CD133 in RAIR cells. Consequently, the uptake of radioiodine-131 was significantly enhanced in these RAIR cells. Taken together, our research identifies novel therapeutic targets and provides new insights into the management of RAIR-DTC.

New Insights into Ameloblastic Fibromas, Fibrodentinomas, and Fibro-Odontomas: Findings from an International Multicenter Study.

Ameloblastic fibroma (AF), ameloblastic fibrodentinoma (AFD), and ameloblastic fibro-odontoma (AFO) are rare mixed odontogenic tumors. While some authors propose that some cases may evolve into odontomas, other tumors with aggressive clinical features suggest a neoplastic origin. A subset of AF and AFD/AFO harbor the pathogenic BRAF p.V600E mutation. SOX9, known for its role in the differentiation of various cell types, particularly in chondrogenesis, has not been previously studied in odontogenic tumors. In this study, we report the clinicopathologic features of a large international cohort of AF and AFD/AFO cases and analyze the immunohistochemical expression of BRAF p.V600E and SOX9. Clinical and radiographic data were collected from four Oral and Maxillofacial Pathology service archives spanning from 1991 to 2024. Deidentified slides were reviewed by two independent oral pathologists. Immunohistochemical staining for BRAF p.V600E and SOX9 was performed on non-decalcified tissue samples from cases with available specimens. A total of 62 tumors were identified, including 30 AF cases and 32 AFD/AFO cases. The cohort consisted of 33 male and 29 female patients, with average ages of 15.3 years for AF and 12.3 years for AFD/AFO. Tumors predominantly affected the posterior mandible and appeared as unilocular or multilocular radiolucent or mixed lesions, often causing tooth impaction and cortical expansion, with an average size of 3.7 cm for AF and 2.5cm for AFD/AFO. Two cases were classified as peripheral AF/AFD. Microscopically, all cases exhibited cellular mesenchymal components resembling dental papilla, with branching strands and islands of odontogenic epithelium. AFD/AFO cases also displayed dental hard tissue, and occasional chondromyxoid differentiation was observed within the stroma. Rare hybrid tumors were identified, including associations with calcifying odontogenic cysts, cemento-ossifying fibroma and central giant cell granuloma. BRAF p.V600E showed cytoplasmic positivity in the mesenchymal component of AF (81%) and AFD/AFO (54%). SOX9 exhibited diffuse nuclear immunoreactivity in both epithelial and mesenchymal components (92%). This study represents one of the largest well-documented series of AF and AFO/AFD, providing valuable clinicopathologic and immunohistochemical insights. Additionally, the diffuse expression of SOX9 in both epithelial and mesenchymal components suggests a potential role in odontogenic differentiation, a novel finding that may have implications for understanding the histogenesis of these lesions. The aggressive behavior of some AFs and AFD/AFOs in our study supports their classification as odontogenic neoplasms rather than hamartomas.

(-)-Epicatechin regulates the resistance of lung adenocarcinoma cells to radiotherapy through the downregulation of FOXM1.

Radioresistance, particularly as manifested by cancer stem cells (CSCs), is the most common reason for the failure of cancer radiotherapy. It is essential for effective radiotherapy to inhibit cancer cell stemness. Research indicates that (-)-epicatechin (EC) enhances the radiosensitivity of non-small cell lung cancer (NSCLC); however, its influence on cell stemness in lung adenocarcinoma (LUAD) resistant to radiotherapy is still not well understood. In this study, radioresistant cell lines A549R and H1299R were constructed by repeatedly irradiating A549 and H1299 cells with gradient doses of X-rays. CCK-8, cell cloning, flow cytometry, RT-qPCR, Western blot, sphere formation detection, and other methods were used for experimental exploration. This study revealed that the radioresistance of LUAD cells was related to their stemness. By inhibiting KLF4, SOX2, CD133, and ALDH1A1 expression, EC treatment increased radiosensitivity and reduced cell sphere formation. Also, FOXM1 expression was upregulated in LUAD and in radioresistant LUAD cells. Knocking down FOXM1 inhibited the stemness of radioresistant LUAD cells. Mechanistically, EC inhibited radiotherapy-resistant LUAD cell stemness by downregulating FOXM1 expression, thereby increasing radiosensitivity. In summary, our study revealed that EC inhibited radiotherapy resistance in LUAD cells through downregulating FOXM1, and it provides a theoretical framework for treating LUAD clinically.

Mechanism of SMYD2 promoting stemness maintenance of bladder cancer stem cells by regulating PYCR1 expression and PINK1/Parkin mitophagy pathway.

SET and MYND domain‑containing protein 2 (SMYD2), an identified protein‑lysine methyltransferase, is key for bladder cancer (BC) progression. The tumor‑formation capacity and metastatic potential of bladder cancer stem cells (BCSCs) are due to their stemness characteristics. The present study explores the mechanism of SMYD2 in promoting BCSC stemness maintenance by pyrroline‑5‑carboxylate reductase 1 (PYCR1). BC cells were treated with PYCR1, SMYD2 and putative kinase 1 (PINK1) small interfering (si)RNA, pcDNA3.1‑PYCR1 and pcDNA3.1‑SMYD2. Mito‑Tracker Green and light chain‑3B (LC3B) expression, in vitro colony formation ability and tumor stemness were assessed, as well as histone H3 lysine 4 trimethylation (H3K4me3) enrichment and PYCR1, SMYD2, H3K4me3, LC3B II/I, p62, PINK1, Parkin, Nanog and SRY‑box transcription factor 2 (Sox2) expression. A nude mouse xenograft model was used for in vivo verification. PYCR1 mRNA and protein expression were elevated in BCSCs. Following PYCR1 or SMYD2 siRNA treatment, PYCR1, SMYD2 and CD44+CD33+ expression, cancer cell colony formation, number of tumor spheres and Nanog and Sox2 expression were decreased, but pcDNA3.1‑PYCR1 or pcDNA3.1‑SMYD2 transfection enhanced BCSC stemness maintenance. SMYD2 was associated with PYCR1 expression. SMYD2 upregulated PYCR1 expression through H3K4me3, subsequently activating the PINK1/Parkin mitophagy pathway, which supports maintenance of BCSC stemness.

Exploration of Dentition Development and Replacement in Two Forms of Mexican Tetra (Astyanax mexicanus).

There are two main subforms of the teleost fish Mexican tetra (Astyanax mexicanus): the river-dwelling surface fish and the cave-dwelling blind cavefish. Recently, this species has become a popular animal model in developmental biology research. It was reported that cavefish bore more teeth than surface fish; however, a detailed description of oral dentition development and replacement in the Mexican tetra remains unavailable. In this study, we investigated the differences in tooth count between surface fish and cavefish by characterising the features of mandibular dentition in adult Mexican tetras and explored the process of first-generation dentition development in larval fish. Regarding early dentition development, larval surface fish and Pachón cavefish at 12-, 18-, 21-, 24-, and 30-days post-fertilisation were euthanised. Haematoxylin and eosin staining was performed for histological analysis, and immunohistochemistry was employed to detect the expression of the odontogenic marker Sox2. The results show that Mexican tetras replaced functional teeth via the successional dental lamina marked by Sox2 expression. Adult Pachón cavefish possessed more intraosseous replacement teeth. Mandibular tooth development in larval fish was also marked by Sox2 expression, and no evidence supported tooth development in a continual dental lamina. Our findings describe the appearance of a successional dental lamina in tooth replacement in the Mexican tetra but provide no evidence regarding a continual dental lamina. In the Mexican tetra, teeth of the first-generation dentition may develop independently. The results of this project will offer valuable histological information for future research into tooth development in the Mexican tetra.

Shear stress preconditioning enhances periodontal ligament stem cell survival.

Shear stress preconditioning enhances periodontal ligament stem cell survival.

IRF4 contributes to chemoresistance in IGH::BCL2-positive diffuse large B-cell lymphomas by mediating BCL2-induced SOX9 expression.

Diffuse large B-cell lymphoma (DLBCL), an aggressive type of non-Hodgkin's lymphoma, has a high relapse/refractory rate. We previously identified sex-determining region Y (SRY)-box transcription factor (SOX9) as a transcription factor that serves as a prognostic biomarker, particularly in BCL2-overexpressing DLBCL, and plays a vital role in lymphomagenesis. However, the molecular mechanisms that modulate the aberrant expression of SOX9 in this DLBCL subset remain unknown. Cell viability, apoptosis and cell cycle assays were performed to determine whether SOX9 contributes to DLBCL chemoresistance and rescues silencing IRF4-induced phenotypes. Protein‒protein interactions and protein ubiquitination were elucidated using immunoprecipitation, immunohistochemistry, immunofluorescence and immunoblotting. Chromatin immunoprecipitation sequencing (ChIP-seq), ChIP and dual-luciferase reporter assays were used to investigate IRF4 binding to the SOX9 promoter. The therapeutic potential of IRF4 inhibition was evaluated in vitro and in a mouse model of DLBCL xenografts. SOX9 enhanced the resistance of the BCL2-overexpressing DLBCL subset to chemotherapy or a BCL2 inhibitor. Moreover, BCL2 inhibition downregulated SOX9 in an immunoglobulin heavy chain/BCL2-positive DLBCL subset. We further identified IRF4 as a key regulator of BCL2-induced SOX9 expression, and ChIP-seq confirmed that IRF4 is a key transcription factor for SOX9 in DLBCL. In addition, BCL2 promotes IRF4 entry into the nucleus by enhancing protein stability and downregulating proteasomal ubiquitination, thereby enforcing SOX9-mediated phenotypes. Finally, in a DLBCL cell line and xenografted mouse model, in vivo inhibition of IRF4 with an hIRF4 antisense oligonucleotide repressed lymphomagenesis and DLBCL chemoresistance. Our data support the conclusion that IRF4 plays an essential role in BCL2-induced upregulation of SOX9 expression, and targeting IRF4 may represent a promising therapeutic strategy to cure relapsed and refractory DLBCL. BCL2 activated IRF4 by enhancing its nuclear activity to induce sex-determining region Y (SRY)-box 9 protein (SOX9) aberrant expression, which is a critical pathway for drug resistance in BCL2-overexpressing diffuse large B-cell lymphoma (DLBCL). Targeting IRF4 may be worth investigating further regarding its potential to overcome the chemoresistance of BCL2-overexpressing DLBCL to standard therapies.

The Severity of Sepsis-induced Acute Lung Injury Is Determined by SOX18 Expression

The Severity of Sepsis-induced Acute Lung Injury Is Determined by SOX18 Expression

Innovative injectable, self-healing, exosome cross-linked biomimetic hydrogel for cartilage regeneration.

Innovative injectable, self-healing, exosome cross-linked biomimetic hydrogel for cartilage regeneration.

Proanthocyanidin polymers (condensed tannins) from lychee seeds exhibit antioxidant, anticancer, anti-α-amylase, and anti-tyrosinase activities.

Proanthocyanidin polymers (condensed tannins) from lychee seeds exhibit antioxidant, anticancer, anti-α-amylase, and anti-tyrosinase activities.

Curdlan/chitosan NIR-responsive in situ forming gel: An injectable scaffold for the treatment of epiphyseal plate injury.

Curdlan/chitosan NIR-responsive in situ forming gel: An injectable scaffold for the treatment of epiphyseal plate injury.

Meningeal-derived retinoic acid regulates neurogenesis via suppression of Notch and Sox2.

Meningeal-derived retinoic acid regulates neurogenesis via suppression of Notch and Sox2.

ADH1B regulates tumor stemness by activating the cAMP/PKA/CREB1 signaling axis to inhibit recurrence and metastasis of lung adenocarcinoma.

ADH1B regulates tumor stemness by activating the cAMP/PKA/CREB1 signaling axis to inhibit recurrence and metastasis of lung adenocarcinoma.

Role of KLF5 in enhancing ovarian cancer stemness and PARPi resistance: mechanisms and therapeutic targeting

BackgroundOvarian cancer (OC) often presents at advanced stages with poor prognosis. Although poly(ADP-ribose) polymerase inhibitors (PARPi) offer clinical benefits, resistance remains a major challenge. This study investigates the role of KLF5 in regulating OC cell stemness and contributing to PARPi resistance.MethodsGene expression analysis was conducted on OC cell lines and their PARPi-resistant counterparts. qRT-PCR and Western blotting assessed the expression levels of stemness markers and KLF5. IHC evaluated KLF5 expression in ovarian cancer tissue samples. Sphere formation and ALDH activity assays were used to evaluate stemness. Chromatin immunoprecipitation (ChIP) investigated KLF5’s binding to the Vimentin promoter. The effects of the KLF5 inhibitor ML264 were tested in vitro using cell viability and apoptosis assays, and in vivo using a xenograft mouse model to evaluate tumor growth and response to PARPi treatment.ResultsPARPi-resistant OC cells showed elevated stemness, indicated by increased SOX2, KLF4, Nanog, and OCT4 expression. KLF5 was significantly upregulated in these cells and linked to poor clinical outcomes. PARPi-resistant cells formed larger and more numerous spheres and had higher ALDH activity. KLF5 bound to the Vimentin promoter, upregulating its expression. Inhibition of KLF5 with ML264 reduced stemness features, decreased Vimentin expression, and resensitized resistant cells to PARPi. In vivo, ML264-treated mice with PARPi-resistant tumors exhibited reduced tumor growth and increased sensitivity to PARPi.ConclusionKLF5 enhances stemness and contributes to PARPi resistance in ovarian cancer through Vimentin regulation. Targeting KLF5 offers a promising therapeutic strategy to overcome resistance and improve patient outcomes.