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BACKGROUND: Medulloblastoma (MB), the predominant pediatric malignant brain tumor, remains poorly characterized in terms of its molecular drivers. The lack of reliable early diagnostic biomarkers and effective therapeutic targets continues to pose significant clinical challenges. Recent studies have implicated circular RNAs (circRNAs) as key regulators of diverse oncogenic pathways across multiple solid malignancies. However, the precise processes that underlie circRNAs' function in Sonic Hedgehog (SHH)-driven MB remain unclear. METHODS: RNA-sequencing of three SHH-MB tumors paired with adjacent non-malignant cerebellum was first employed to profile circRNA landscapes, after which hsa_circ_PCNT abundance was precisely quantified by quantitative real-time PCR in an extended cohort of clinical specimens and in established cell lines. The oncogenic and metastatic consequences of altering this transcript were subsequently interrogated through a comprehensive battery of in vitro functional assays and orthotopic xenograft models. To decipher the mechanism, we integrated dual-luciferase reporters, fluorescence in situ hybridization, RNA immunoprecipitation and biotinylated RNA pull-down, thereby demonstrating that hsa_circ_PCNT serves as a cytoplasmic sponge for hsa-miR-133b and consequently alleviates the micRNA-imposed repression of the downstream effector TAGLN2. RESULTS: Our investigations identified hsa_circ_PCNT as a significantly upregulated circRNA in SHH-MB, with its circular conformation being experimentally validated. Genetic knockdown of this circRNA exerted profound tumor-suppressive effects, including enhanced apoptosis coupled with impaired proliferative capacity, migratory potential, and invasive behavior in vitro. These anti-tumorigenic properties were further corroborated in vivo through xenograft models, where hsa_circ_PCNT depletion markedly attenuated tumor formation. Mechanistically, we established that hsa_circ_PCNT operates as a competitive endogenous RNA by sequestering hsa-miR-133b. Rescue experiments demonstrated phenotypic reversal when hsa-miR-133b levels were experimentally modulated, while subsequent investigations confirmed that TAGLN2 serves as the critical downstream effector mediating these oncogenic processes. CONCLUSIONS: The results show that hsa_circ_PCNT promotes SHH-MB aggression through the hsa-miR-133b /TAGLN2 pathway. In summary, our research demonstrates that hsa_circ_PCNT occupies a crucial position in SHH-MB and emerges as a potential therapeutic target.
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There is compelling evidence that TNF preferentially activates and expands CD4+Foxp3+ regulatory T cells (Tregs) through TNFR2. However, the precise mechanisms underlying TNF-TNFR2 pathway-mediated Treg proliferation remain to be fully elucidated. In this study, using RNA-seq profiling of TNFR2+ and TNFR2-deficient Treg cells, we identified that Trip13 is required for promoting TNF-TNFR2 pathway-mediated Treg expansion. Mechanistically, TRIP13 inhibited UBE4A-mediated ubiquitination degradation of HAT1 by directly binding to HAT1, thereby competing with UBE4A and promoting Treg expansion. In addition, TRIP13's ATPase activity was essential for its binding to HAT1, which promoted Treg expansion by increasing Foxp3 expression. In a mouse colitis model, TRIP13 overexpression markedly alleviated colon inflammation by enhancing Treg expansion, an effect that was reversed by HAT1 knockdown. Conversely, genetic ablation of TRIP13 substantially reversed the effects induced by HAT1 overexpression, including enhanced Treg expansion and attenuation of colitis. These findings illustrate the TRIP13/HAT1 axis-mediated mechanism for TNF-TNFR2-induced Treg expansion and indicate that targeting TRIP13 may offer therapeutic potential for autoimmune and inflammatory diseases.
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ATPasas Asociadas con Actividades Celulares Diversas , Factores de Transcripción Forkhead , Linfocitos T Reguladores , Animales , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Ratones , Factores de Transcripción Forkhead/metabolismo , Colitis/patología , Colitis/inmunología , Colitis/genética , ATPasas Asociadas con Actividades Celulares Diversas/metabolismo , ATPasas Asociadas con Actividades Celulares Diversas/genética , Ratones Endogámicos C57BL , Proliferación Celular , Ubiquitinación , Receptores Tipo II del Factor de Necrosis Tumoral/metabolismo , Humanos , Transducción de Señal , Factor de Necrosis Tumoral alfa , Modelos Animales de Enfermedad , Estabilidad Proteica , Proteínas PortadorasRESUMEN
Emerging evidence reveals that intratumoral microbial (ITM) communities within the tumor immune microenvironment (TIME) critically influence tumor progression and immunotherapy response. Studies have shown that resident bacteria within tumors, such as Sphingobacterium multivorum, regulate the secretion of chemokines like CCL20 and CXCL8, promoting the infiltration of regulatory T cells (Tregs) and inhibiting the function of cytotoxic T cells (CD8+ T cells)-thereby weakening the efficacy of immune checkpoint inhibitors. Additionally, microbial metabolites may serve as potential biomarkers for predicting sensitivity to immunotherapy. Concurrently, engineered bacteria (e.g., oncolytic mineralizing bacteria) demonstrate significant antitumor effects by activating innate immunity and enhancing antitumor-specific immune responses, providing new strategies to overcome immunotherapy resistance. These findings highlight the dual role of ITM in tumor immune evasion and immunotherapy sensitivity, laying an important theoretical foundation for developing novel immunotherapy strategies targeting tumoral microbiota metabolism.
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INTRODUCTION: Perineural invasion (PNI) is a significant factor associated with tumor recurrence and metastasis in intrahepatic cholangiocarcinoma (ICC). This study aims to develop predictive model for PNI in ICC using preoperative MRI features and explore its molecular basis. MATERIALS AND METHODS: We analyzed 165 ICC patients from two centers, dividing them into training (n = 120), internal validation (n = 24), and external validation (n = 21) cohorts. Clinical and MRI features associated with PNI were used to construct predictive models. The molecular mechanisms underlying PNI were analyzed using data from The Cancer Genome Atlas (TCGA) and were further validated with a subset of the training cohort. RESULTS: The study identified high CEA level, tumor morphology, location, intrahepatic bile duct dilatation, and tumor invasion into the portal vein as independent predictors of PNI. The clinical-radiological model showed an AUC of 0.839 in the training set, with AUCs of 0.754 and 0.872 in the internal and external validation cohorts, respectively. The COL1A1 gene was found to exhibit up-regulation in the PNI-positive group and was closely linked to poorer overall survival (OS). The arterial-phase enhancement pattern, tumor location, and tumor invasion into portal vein were significantly correlated with COL1A1 expression. CONCLUSIONS: This preoperative clinical-radiological model effectively predicts PNI in ICC, thereby aiding in the clinical management and prognosis stratification for patients. COL1A1 may serve as a significant biomarker for the development of PNI in ICC, which was significantly correlated with MRI features.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Colágeno Tipo I , Imagen por Resonancia Magnética , Nervios Periféricos , Humanos , Colangiocarcinoma/patología , Colangiocarcinoma/genética , Colangiocarcinoma/diagnóstico por imagen , Colangiocarcinoma/cirugía , Masculino , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/diagnóstico por imagen , Neoplasias de los Conductos Biliares/cirugía , Femenino , Persona de Mediana Edad , Invasividad Neoplásica , Anciano , Biología Computacional , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Cadena alfa 1 del Colágeno Tipo I , Vena Porta/patología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Nervios Periféricos/patología , AdultoRESUMEN
Prenatal caffeine exposure (PCE), stemming from widespread maternal intake of caffeine-containing substances, has emerged as a major pharmacological stressor affecting fetal neurodevelopment. Although epidemiological studies have consistently linked PCE to cognitive impairments and emotional deficits in offspring, the underlying mechanisms have long been confined to direct adenosine receptor antagonism, failing to explain the persistent neurodevelopmental consequences. Here, using cross-species models (rat PCE, astrocyte-specific Abcg1 knockout mice, and glucocorticoid-treated zebrafish) and multi-scale analyses, we demonstrate that PCE activates the maternal-fetal glucocorticoid axis, leading to dysregulation of the GR-miR-130b/301b-PPARγ signaling cascade in hippocampal astrocytes. This disrupts expression of the cholesterol transporter- ATP binding cassette subfamily G member 1 (ABCG1), impairing astrocytic cholesterol efflux and depriving neurons of cholesterol-rich microenvironments essential for synaptic development. Abcg1 knockout mice recapitulate PCE-induced synaptic defects, while astrocyte-specific ABCG1 overexpression or miR-130b/301b inhibition rescues neuronal cholesterol supply and synaptic structure. Luciferase assays confirm that miR-130b/301b directly suppress Pparγ-mediated Abcg1 transcription. Our findings identify the GR-miR-130b/301b-PPARγ-ABCG1 axis as a core mechanism of PCE-induced neurotoxicity, establishing astrocytic cholesterol transport as a potential intervention target and providing a shared molecular framework for evaluating central nervous system risks of glucocorticoid-disruptive agents.
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Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 1 , Astrocitos , Cafeína , Colesterol , Epigénesis Genética , Glucocorticoides , Efectos Tardíos de la Exposición Prenatal , Animales , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 1/genética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 1/metabolismo , Colesterol/metabolismo , Astrocitos/metabolismo , Astrocitos/efectos de los fármacos , Embarazo , Ratones , Femenino , Ratones Noqueados , Glucocorticoides/farmacología , Glucocorticoides/metabolismo , Cafeína/efectos adversos , Cafeína/farmacología , Efectos Tardíos de la Exposición Prenatal/metabolismo , Efectos Tardíos de la Exposición Prenatal/genética , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Epigénesis Genética/efectos de los fármacos , Ratas , Pez Cebra , MicroARNs , Masculino , Transporte Biológico/efectos de los fármacos , PPAR gamma/metabolismoRESUMEN
Ulcerative colitis (UC) is a chronic inflammatory bowel disease marked by intestinal barrier dysfunction, immune dysregulation, and gut microbiota dysbiosis. This study examined the therapeutic potential of lacto-N-triose II (LNT II), a core component of human milk oligosaccharides, in colitis. Results showed LNT II significantly alleviated disease pathology, restored epithelial barrier integrity, and modulated inflammatory responses. It reversed colitis-induced microbial dysbiosis and altered key metabolites such as D-xylulosonic acid, Sakacin P, and taurocholic acid. Transcriptomic analysis revealed LNT II suppresses inflammation via the PI3K-Akt signaling pathway. Integrated multiomics analysis established a complete mechanistic cascade: LNT II remodels gut microbiota, regulates specific metabolites, and inhibits the PI3K-Akt pathway to alleviate colitis. These findings provide comprehensive experimental evidence supporting LNT II as a novel prebiotic therapy for UC, demonstrating its efficacy through systematic regulation of the microbiota-metabolite-immune network.
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Colitis Ulcerosa , Colitis , Microbioma Gastrointestinal , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Trisacáridos , Microbioma Gastrointestinal/efectos de los fármacos , Animales , Ratones , Humanos , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Sulfato de Dextran/efectos adversos , Ratones Endogámicos C57BL , Colitis/microbiología , Colitis/tratamiento farmacológico , Colitis/inducido químicamente , Colitis/metabolismo , Colitis/genética , Masculino , Transducción de Señal/efectos de los fármacos , Colitis Ulcerosa/microbiología , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/metabolismo , Colitis Ulcerosa/genética , Prebióticos/administración & dosificación , Prebióticos/análisis , Trisacáridos/administración & dosificaciónRESUMEN
The regulation of bone mass relies on a dynamic interplay between boneforming osteoblasts and boneresorbing osteoclasts. Imbalances in this regulatory system favor bone resorption and are implicated in the development of osteolytic disorders such as osteoporosis. Although current treatments targeting osteoclast activity are effective, safety concerns remain a notable limitation. As a multifunctional adipokine, apelin (APLN) serves a role in angiogenesis and metabolic regulation. However, to the best of our knowledge, its involvement in osteoclast differentiation has not yet been characterized. The present study thus examined the effects of APLN on osteoclastogenesis using a murinemacrophage model stimulated with receptor activator of NFκB ligand (RANKL). The results revealed that APLN augmented RANKLinduced osteoclast differentiation, promoting the formation of tartrateresistant acid phosphatasepositive multinucleated cells and the development of organized Factin rings. Transcriptome analyses of a public dataset confirmed the temporal upregulation of osteoclastrelated genes under RANKL stimulation. It was further discovered that cotreatment with APLN and RANKL significantly enhanced the expression of these osteoclastspecific markers. APLN cotreatment with RANKL upregulated the ERK, JNK, p38 and NFκB signaling pathways, and this activation was effectively attenuated by specific pathway inhibitors. In conclusion, these findings identified APLN as an enhancer of RANKLdependent osteoclast differentiation and signaling, suggesting that the modulation of APLN activity may provide a promising strategy for controlling excessive bone resorption in skeletal diseases.
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Apelina , Sistema de Señalización de MAP Quinasas , FN-kappa B , Osteoclastos , Osteogénesis , Ligando RANK , Animales , Ligando RANK/metabolismo , Ligando RANK/farmacología , Osteogénesis/efectos de los fármacos , Ratones , Apelina/farmacología , Apelina/metabolismo , FN-kappa B/metabolismo , Osteoclastos/metabolismo , Osteoclastos/citología , Osteoclastos/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Células RAW 264.7 , Sistema de Señalización de MAP Quinasas/efectos de los fármacosRESUMEN
Extramedullary breast relapse of leukemia is uncommon and primarily occurs in cases of acute myeloid leukemia(AML), and secondary acute lymphoblastic leukemia (ALL) affecting the breast may also occur occasionally. The mechanism of extramedullary involvement remains unclear; patients' risk of hematological recurrence is high. TCF3::PBX1 (also known as E2A:: PBX1) is an oncogenic transcription factor arising from the T (1; 19) (q23; P13) translocation, observed in 5 % to 6 % of childhood acute lymphoblastic leukemia (ALL) cases and approximately 3 % of adult ALL cases. Here, we report a case of B-ALL with TCF3::PBX1 fusion gene, where extramedullary breast infiltration was the earliest clinical indication of recurrence. Adult ALL with the TCF3::PBX1 fusion gene is relatively uncommon compared to other ALL. Despite the satisfactory effect of chemotherapy, the patient ultimately decided to discontinue treatment following breast infiltration by ALL.
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Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal-derived neoplasm that most commonly arises in the lung. It can also occur in other parts of the body. Primary IMT of the gallbladder is exceptionally uncommon. Due to the absence of large-sample studies, the current understanding of gallbladder IMT remains largely limited to case reports. This article reports the diagnosis and treatment course of a 13-year-old male with inflammatory myofibroblastoma of the gallbladder. It specifically focuses on delineating its distinct imaging characteristics across ultrasonography, computed tomography, and magnetic resonance imaging, aiming to enhance the accuracy of pre-operative diagnosis and provide valuable insights into the literature for this rare condition.
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Nonmelanoma skin cancers are rising in incidence and are largely driven by solar ultraviolet B radiation (UVB) exposure. A growing body of evidence suggests that m6A RNA methylation plays a critical role in regulating the DNA damage response to UVB. Here, we identify a novel function for the m6A demethylase FTO in modulating the UVB damage response and skin carcinogenesis. We show that FTO loss enhances the repair of cyclobutane pyrimidine dimers (CPD), the major DNA lesions induced by UV radiation, in a METTL14-dependent manner, at least in part by promoting protein translation of the global genome repair (GGR) factor DDB2 through increased m6A methylation of DDB2 mRNA. These effects were recapitulated using two small-molecule FTO inhibitors, CS1 and FB23-2. Furthermore, loss of FTO reduced tumor growth in mice and FTO expression was upregulated in cutaneous squamous cell carcinoma (cSCC) compared with normal skin. Together, these findings uncover a critical role for FTO in regulating post-transcriptional gene expression in the UVB damage response and suggest that FTO may be a therapeutic target in skin cancer.
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Aqueous zinc ion batteries (AZIBs) have received increasing attention due to their intrinsic safety, low cost, and environmental friendliness, and the design of advanced cathode materials is crucial for their practical application. Herein, the V2O3/Zn3V3O8@C heterostructured materials derived from polyoxovanadates are developed as advanced cathodes for AZIBs. The formation of a carbon protective layer originated from the coated polypyrrole leads to the abundant oxygen vacancies during the pyrolysis process. Density functional theory calculation reveals that the construction of the heterostructure effectively regulates the electronic properties of the V2O3. The collaborative effect of heterostructures with oxygen vacancies significantly facilitates the electron/ion transport and mechanical stability of V2O3/Zn3V3O8@C. As expected, the V2O3/Zn3V3O8@C cathode delivers a high specific capacity of 419.0 mAh g-1 at 0.1 A g-1 and excellent cycling stability with 80.6% capacity retention after 1000 cycles at 2 A g-1.
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OBJECTIVE: The purpose of this study is to validate the efficacy of the Deep Convolutional Neural Network (DCNN) model to automatically detect Leukocyte Esterase (LE) strips in the diagnosis of Periprosthesis Joint Infection (PJI). METHODS: This study is a prospective diagnostic trial. We constructed an automatic detection system for LE strips based on the AlexNet deep convolutional model to diagnose PJI.LE strip images and white blood cell counts from 46 patients were used to train the DCNN model.96 patients were prospectively enrolled in this single-center study and underwent joint aspiratio. Based on inclusion and exclusion criteria, 18 patients were excluded; 78 patients were included for analysis, and they all agreed to participate. The ICM2018 standard was used as the gold standard to classify the included patients. One drop of synovial fluid (100 µL) from patients was applied to LE strips before and after centrifugation. The DCNN Model automatically captures the images of the strips and outputs the results. The framework of the DCNN Model includes LE strip image acquisition, preprocessing, and intelligent detection. Three observers performed LE strip colorimetric test, and the majority result was considered the final result. The clinical laboratory provided results for WBC count, PMN%, serological tests, histopathology, and microbial cultures. The diagnostic performance of the DCNN Model was analyzed using sensitivity, specificity, PPV, NPV, ROC curve, and AUC. The reliability of the DCNN Model in diagnosing PJI was assessed through a consistency test (Kappa value) with traditional PJI diagnostic methods. RESULTS: The AUC of the DCNN Model was 0.92 before centrifugation and 0.91 after centrifugation. Before centrifugation, the sensitivity, specificity, PPV, and NPV of the model were 0.83, 0.97, 0.98 and 0.79, respectively. After centrifugation, they were 0.79, 1.00,1.00 and 0.76, respectively. The Kappa value for diagnosing PJI using the model before and after centrifugation was 0.82 (P<0.05). The Kappa values of the model results for PJI diagnosis compared to WBC count, PMN%, LE strip colorimetric test, ESR, CRP, and microbial culture before centrifugation were 0.82, 0.72, 0.59, 0.69, 0.64 and 0.4. After centrifugation, the Kappa values were 0.90, 0.75, 0.69, 0.67, 0.62 and 0.48. CONCLUSION: The DCNN Model demonstrates excellent performance and high reliability in diagnosing PJI. Utilizing this model improves the objectivity of LE strip test for diagnosing PJI and mitigates the influence of external factors on the test results. Large-scale, multicenter clinical studies are necessary to further enhance the diagnostic performance of the model.
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BACKGROUND: Single-incision laparoscopic cholecystectomy (SILC) offers excellent cosmetic results but is technically challenging. Robotic systems can overcome these limitations, and although the da Vinci Xi is designed for multiport surgery, it can be adapted for single-port procedures. This study reports our experience performing single-port robotic cholecystectomy (SPRC) with straight instruments, emphasizing technical optimization and perioperative outcomes. METHODS: SPRC was performed using an optimized umbilical port configuration and docking technique. Surgical steps were standardized to ensure stable traction and precise dissection, with a crossover method applied in difficult cases to improve exposure (see Supplemental Videos 1, Supplemental Digital Content 1, http://links.lww.com/SLE/A507 , and 2, Supplemental Digital Content 2, http://links.lww.com/SLE/A508 ). Eleven patients underwent SPRC, and demographic, operative, and perioperative data were analyzed. RESULTS: All procedures were completed without conversion to open or multiport surgery. The mean operative time was 116.7 ± 22.2 minutes, with minimal blood loss (13.8 ± 7.5 mL). No intraoperative complications or gallbladder perforations occurred, and only one patient required temporary drainage for minor oozing. Postoperative VAS scores averaged 3.1 ± 1.0 on day 0 and 1.6 ± 0.5 on day 1, with a mean hospital stay of 2.2 ± 1.1 days. No readmissions or port-site complications were observed. CONCLUSIONS: SPRC with the da Vinci Xi system using straight instruments is feasible and safe. Optimized port placement and instrument coordination yield outcomes comparable to those reported for the SP system or single-site platform, providing an accessible alternative for centers without these platforms.
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Five previously undescribed spatane-type diterpenoids 1-5, one pair of previously unreported enantiomers 6 and 7, along with two known related compounds 8 and 9, have been isolated and characterized from the Hainan soft coral Sinularia nanolobata collected off Ximao Island in the South China Sea. Their structures were determined by extensive spectroscopic analysis, QM-NMR, TDDFT-ECD calculations, chemical conversion and comparison with those of related known compounds reported in literature. In bioassays, compounds 5 and 9 inhibited MDA-MB-231 cells proliferation with IC50 values of 5.26 ± 0.68 and 22.2 ± 2.9 µM, respectively, while compounds 5-7 and 9 showed inhibitory effects against HT-29 cells with IC50 values of 2.87 ± 1.48, 17.68 ± 0.39, 13.27 ± 3.56, and 29.19 ± 1.78 µM, respectively. Further investigation revealed that compound 5 induced S-phase arrest in HT-29 cells, promoted apoptosis through elevation of intracellular reactive oxygen species (ROS) and reduction of mitochondrial membrane potential. Combining a human RTK array kit with cellular protein and transcriptional analyses, demonstrated that the anticancer activity of 5 is closely related to the regulation of c-MET signaling pathways.
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BACKGROUND: Pulmonary interstitial macrophages can be divided into 2 distinct subsets with different origins: resident macrophages (resMФs) and recruited macrophages (recMФs). However, their specific roles in pulmonary arterial hypertension remain unclear. METHODS: Bone marrow transplantation, the DT (diphtheria toxin) receptor system, and genetically modified murine models were utilized to explore how key TFs (transcription factors) regulate phenotype alterations in pulmonary resMФs and recMФs in an SU5416/hypoxia murine model of pulmonary hypertension (PH). Therapeutic approaches included DNA aptamer-based proteolysis-targeting chimera and small interfering RNA-loaded lipid nanoparticle for treating SU5416/hypoxia-exposed rats. RESULTS: Depletion of either resMФs or recMФs using DT treatment significantly reduced SU5416/hypoxia-induced PH in mice. Pulmonary recMФs exhibited a proinflammatory phenotype during PH, driven by the TF Hic1 (hypermethylated in cancer 1). Bone marrow transplantation with Hic1-/- recMФs ameliorated PH in mice. Hic1 enhanced proinflammatory gene transcription by inhibiting Sirt1-mediated H3K9ac deacetylation in the promoter regions. In contrast, pulmonary resMФs demonstrated a profibrotic transcriptome characterized by upregulation of MMP genes that are, in turn, regulated by Prrx2 (paired-related homeobox 2). Prrx2 deletion in resMФs protected against PH in mice by reducing perivascular fibrosis. Simultaneously targeting Prrx2 and Hic1 in macrophages significantly alleviated SU5416/hypoxia-induced PH in rats. CONCLUSIONS: The differential roles of pulmonary resMФs and recMФs in pulmonary vascular remodeling highlight novel therapeutic targets for pulmonary arterial hypertension treatment, specifically through inhibition of Hic1 and Prrx2 in macrophages.
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Extranodal NK/T-cell lymphoma (ENKTL), an aggressive non-Hodgkin lymphoma subtype, exhibits understudied links between lipid metabolism and clinical outcomes. We analyzed 1,017 patients newly diagnosed with ENKTL and matched controls, with longitudinal LC-MS-based metabolomic profiling (n = 29) and pretreatment tumor transcriptomic analysis (n = 65). Multivariable Cox models evaluated lipid biomarkers. Patients with ENKTL showed significantly elevated triglycerides (TG) and reduced apolipoprotein A1 (ApoA1) vs. controls (both p < 0.001). Elevated TG (progression-free survival [PFS] HR = 1.33, 95% CI 1.04-1.69; overall survival [OS] HR = 1.37, 95% CI 1.04-1.80) and reduced ApoA1 (PFS HR = 1.47, 95% CI 1.07-2.03; OS HR = 1.65, 95% CI 1.15-2.38) independently predicted inferior survival (all p < 0.05). Patients with an objective response demonstrated metabolic profile normalization: patients with high-TG levels (≥ median) experienced TG reduction and patients with low-ApoA1 levels (< median) experienced ApoA1 elevation (both p < 0.001), whereas patients with stable or progressive disease retained baseline profiles. These metabolic shifts predicted survival benefit (all p < 0.001). In the prospective cohort, patients with complete response (CR) had significantly higher baseline levels of 22 serum TG species compared with non-CR patients (fold change > 2.0, p < 0.05). Longitudinal analyses revealed divergent TG trajectories: patients without CR exhibited sustained high-level fluctuations, whereas patients with CR demonstrated stabilization at low levels. Transcriptome analysis suggested tumor-intrinsic lipid dysregulation in patients with high-TG/low-ApoA1 levels. Serum TG and ApoA1 serve as dynamic biomarkers in ENKTL.
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Apolipoproteína A-I , Biomarcadores de Tumor , Linfoma Extranodal de Células NK-T , Triglicéridos , Humanos , Apolipoproteína A-I/sangre , Masculino , Femenino , Persona de Mediana Edad , Linfoma Extranodal de Células NK-T/sangre , Linfoma Extranodal de Células NK-T/mortalidad , Linfoma Extranodal de Células NK-T/diagnóstico , Triglicéridos/sangre , Adulto , Anciano , Estudios Retrospectivos , Biomarcadores de Tumor/sangre , Estudios ProspectivosRESUMEN
BACKGROUND: Resection of lower extremity malignant tumors may create soft tissue defects that may benefit from flap reconstruction. Owing to the requirement for multidisciplinary surgical services, the utilization of this procedure may be affected by systemic barriers. This study incorporated a large national inpatient database to identify the drivers of such socioeconomic disparities. METHODS: Lower extremity resection cases for malignant tumors were identified in the 2016-2022 National Inpatient Sample. A multivariable logistic regression model was used to evaluate independent predictors of flap reconstruction during admission. Nearest-neighbor propensity score matching was used to quantify the impact of flap reconstruction on the odds of wound-related complications (p<0.05). RESULTS: The final cohort included 11,635 cases. The overall rate of flap reconstruction was 25.4%. Preoperative radiation (OR: 1.55, 95% CI: 1.41-1.72, p<0.001), private insurance (OR: 1.20, 95% CI: 1.06-1.36, p=0.0030), and higher annual institutional plastic surgery volume (OR: 1.18, 95% CI: 1.14-1.23, p<0.001 per 100 cases) predicted higher odds of flap reconstruction. After propensity score matching, flap reconstruction was associated with lower odds of total wound-related complications during admission (OR: 0.82, 95% CI: 0.68-0.98, p=0.032). CONCLUSION: Socioeconomic factors drive disparities in receiving flap reconstruction after oncologic lower extremity resection. Flap reconstruction is associated with lower odds of short-term wound-related complications, emphasizing the importance of access to reconstructive services.