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Clear cell renal cell carcinoma (ccRCC) is a common malignant tumor of the urinary system characterized by poor prognosis and difficult treatment. It has been reported that iron metabolism dysregulation is a common phenomenon in ccRCC and is closely related to the process of ccRCC. But still now, the exact function and underlying mechanisms of iron metabolism dysregulation in ccRCC have not been fully elucidated. In this study, we comprehensively investigated the prognostic value and potential role of STEAP3 (an iron metabolism-related gene) in ccRCC. STEAP3 is significantly up-regulated in ccRCC. High STEAP3 expression is associated with gender, hemoglobin level, pathological grade, tumor stage and significantly predicts an unfavorable prognosis of ccRCC patients. Functional enrichment analysis and evaluation of the tumor microenvironment indicated that STEAP3 was involved in the remodeling of tumor extracellular matrix and the shaping of an immune-suppressive tumor microenvironment to promote tumor metastasis and evade immune killing. Besides, the expression of STEAP3 is also associated with the expression of various immune checkpoint molecules and the IC50 of targeted drugs. Finally, we verified STEAP3 by RT-qPCR and IHC staining. In conclusion, we found that STEAP3 can serve as a candidate prognostic biomarker for ccRCC, and targeting STEAP3 and its biological processes may provide new references for the individualized treatment of ccRCC.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/patología , Neoplasias Renales/patología , Microambiente Tumoral/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Pronóstico , HierroRESUMEN
Kidney transplantation is the best therapy for end-stage renal disease. Demand for kidney transplantation rises year-on-year, and the gap between kidney supply and demand remains large. To meet this clinical need, a gradual expansion in the supply of donors is required. However, clinics lack appropriate tools capable of quickly and accurately predicting post-transplant renal allograft function, and thus assess donor-kidney quality before transplantation. Mitochondrial DNA (mtDNA) is a key component of damage-associated molecular patterns (DAMPs) and plays an important part in ischemia-reperfusion injury (IRI), accelerating the progression of IRI by inducing inflammation and type I interferon responses. mtDNA is known to be closely involved in delayed graft function (DGF) and acute kidney injury (AKI) after transplantation. Thus, mtDNA is a potential biomarker able to predict post-transplant renal allograft function. This review summarizes mtDNA biology, the role mtDNA plays in renal transplantation, outlines advances in detecting mtDNA, and details mtDNA's able to predict post-transplant renal allograft function. We aim to elucidate the potential value of mtDNA as a biomarker in the prediction of IRI, and eventually provide help for predicting donor-kidney quality.
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Trasplante de Riñón , Daño por Reperfusión , Biomarcadores , ADN Mitocondrial/genética , Funcionamiento Retardado del Injerto , Humanos , Riñón , Donantes de TejidosRESUMEN
Transferrin (TrF) is a very important human body glycoprotein and a clinical biomarker which controls the body's iron ion channels and iron ion balance. Any change in TrF concentration and isoform also reflects the emergence of some diseases. In this work, we prepared magnetic molecularly imprinted nanoparticles (deep eutectic solvent-molecular imprinting polymers [DES-MIPs]) with a deep eutectic solvent (DES) as a functional monomer to separate TrF in human serum. The DES dosage for MIP, pH value, and time for adsorption have been optimized, and these materials show special adsorption properties for TrF. The maximum adsorption capacity (Qmax) and dissociation constant KL of the MIP by the Langmuir adsorption curve (R2 = 0.9949) were 37.5 mg/g and 0.015 g/L, respectively. The imprinting factor of the MIP is 3.50 with relative standard deviation (5.63%). In summary, the use of DES as a functional monomer in molecular imprinting technology provides a novel, efficient, and biocompatible method for the isolation and purification of proteins. Graphical abstract á .
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Nanopartículas de Magnetita/química , Impresión Molecular/métodos , Polímeros/química , Extracción en Fase Sólida/métodos , Transferrina/aislamiento & purificación , Adsorción , Humanos , Solventes/química , Transferrina/análisisRESUMEN
The objective of the study was to evaluate the contribution of insulin resistance and ß cell dysfunction to gestational diabetes mellitus (GDM) in Chinese women stratified by pre-pregnant body mass index (BMI). A total of 847 pregnant women were enrolled. They were divided into low BMI and high BMI groups according to the median of pre-pregnancy BMI. The homeostasis model assessment of insulin resistance (HOMA-IR) and ß cell function (HOMA-ß), Matsuda index, and 60-min insulinogenic index (IGI60) were used to evaluate insulin resistance and ß cell function. In all the participants, 150 (17.71%) were diagnosed with GDM. ROC analyses showed that in the low BMI group, the association of ß cell dysfunction (IGI60 or HOMA-ß) with GDM was stronger than that of insulin resistance (Matsuda index or HOMA-IR), while in the high BMI group, the association of ß cell dysfunction with GDM was weaker than that of insulin resistance (all P < 0.05). Among all GDM patients, 47.33% demonstrated predominant insulin resistance (Matsuda index < 25th percentile), and 46% had predominant ß cell defect (IGI60 < 25th percentile). In the low BMI group, 15.09% of GDM patients demonstrated predominant insulin resistance, and 62.26% of GDM patients had predominant ß cell defect, whereas in the high BMI group, 64.95% of GDM patients demonstrated mainly insulin resistance and 36.08% of GDM patients had mainly ß cell defect. In women with low BMI, ß cell dysfunction is the major etiologic factor, whereas, in women with high BMI, insulin resistance is the predominant etiologic factor in the development of GDM.
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Diabetes Gestacional , Resistencia a la Insulina , Femenino , Humanos , Embarazo , Diabetes Gestacional/diagnóstico , Índice de Masa Corporal , Insulina , Glucemia/análisisRESUMEN
ABSTRACT: With the rapid aging of the global population posing a serious problem, frailty, a non-specific state that reflects physiological senescence rather than aging in time, has become more widely addressed by researchers in various medical fields. A high prevalence of frailty is found among kidney transplant (KT) candidates and recipients. Therefore, their frailty has become a research hotspot in the field of transplantation. However, current studies mainly focus on the cross-sectional survey of the incidence of frailty among KT candidates and recipients and the relationship between frailty and transplantation. Research on the pathogenesis and intervention is scattered, and relevant review literature is scarce. Exploring the pathogenesis of frailty in KT candidates and recipients and determining effective intervention measures may reduce waiting list mortality and improve the long-term quality of life of KT recipients. Therefore, this review explains the pathogenesis and intervention measures for frailty in KT candidates and recipients to provide a reference for the formulation of effective intervention strategies.
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Fragilidad , Fallo Renal Crónico , Trasplante de Riñón , Humanos , Fragilidad/epidemiología , Factores de Riesgo , Calidad de Vida , Trasplante de Riñón/efectos adversos , Estudios Transversales , Receptores de TrasplantesRESUMEN
Background: Clear cell renal cell carcinoma (CCRCC) is a common urological neoplasm, and even though surgical resection is effective for localized CCRCC, the prognosis of metastatic CCRCC is poor. Currently, there is a paucity of recognized effective therapeutic protocols for metastatic CCRCC. Case presentation: A 76-year-old Asian man underwent radical left nephrectomy for CCRCC 26 years ago; this patient visited our hospital with abdominal pain due to multiple abdominal metastases 24 years after the nephrectomy. After metastasectomy, he underwent targeted therapy combined with a programmed death receptor-1 (PD-1) inhibitor, and the current imaging results indicate remarkable tumor remission. Conclusions: Metachronous pancreatic metastasis from CCRCC after nephrectomy is rare, but clinicians and patients should not ignore this possibility. The combination of targeted therapy and immunotherapy can result in satisfactory outcomes in cases where metastatic CCRCC continues to progress despite metastasectomy and targeted therapy. The combination of local and systemic therapy can be an effective therapeutic protocol for metastatic CCRCC, but there is no consensus on suitable therapeutics.
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Monolayer group-IV tellurides with phosphorene-derived structures are attracting increasing research interest because of their unique properties. Here, we systematically studied the quasiparticle electronic and optical properties of two-dimensional group-IV tellurides (SiTe, GeTe, SnTe, PbTe) using the GW and Bethe-Salpeter equation method. The calculations revealed that all group-IV tellurides are indirect bandgap semiconductors except for monolayer PbTe with a direct gap of 1.742 eV, while all of them are predicted to have prominent carrier transport ability. We further found that the excitonic effect has a significant impact on the optical properties for monolayer group-IV tellurides, and the predicted exciton binding energy is up to 0.598 eV for SiTe. Interestingly, the physical properties of monolayer group-IV tellurides were subject to an increasingly isotropic trend: from SiTe to PbTe, the differences of the calculated quasiparticle band gap, optical gap, and further exciton binding energy along different directions tended to decrease. We demonstrated that these anisotropic electronic and optical properties originate from the structural anisotropy, which in turn is the result of Coulomb repulsion between non-bonding electron pairs. Our theoretical results provide a deeper understanding of the anisotropic properties of group-IV telluride monolayers.
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Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent renal malignant cancer, whose survival rate and quality of life of patients are still not satisfactory. Nevertheless, the TNM staging system currently used in clinical cannot make accurate survival predictions and precise treatment decisions for ccRCC patients. Therefore, there is an urgent need for more reliable biomarkers to identify high-risk subgroups of ccRCC patients to guide timely intervention and treatment. Recently, MiRNAs have been shown to be closely related to the procession of a variety of tumors, and they have high stability in various tissues, which makes them suggested to have the potential as a prognostic biomarker of ccRCC. In this study, by analyzing and processing the miRNAs expression profile of ccRCC patients from the TCGA database, we finally constructed an excellent miRNAs signature and verified it through a variety of methods. In order to build a more accurate and reliable clinical predictive model, we integrated the miRNAs signature with other prognostic-related clinical parameters to construct a nomogram. Functional enrichment analysis showed that miRNAs in the signature may regulate the genes involved in the Hippo signaling pathway, Tight junction, and Wnt signaling pathway to cause different prognoses of ccRCC patients, which may provide a reference for subsequent basic research and targeted therapy. To conclude, our study constructed a useful miRNAs signature, which allows the prognosis stratification for ccRCC patients and thereby guides the timely and effective interventions on high-risk patients. At the same time, this study also found the potential biological pathways involved in the procession of ccRCC.
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Carcinoma de Células Renales/genética , Neoplasias Renales/genética , MicroARNs/genética , Modelos Biológicos , Nomogramas , Anciano , Biomarcadores de Tumor/genética , Bases de Datos Genéticas , Femenino , Vía de Señalización Hippo/genética , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Ajuste de Riesgo , Tasa de Supervivencia , Uniones Estrechas/genética , Vía de Señalización Wnt/genéticaRESUMEN
Bladder cancer (BC) is a commonly occurring malignant tumor affecting the urinary tract. Zinc finger proteins (ZNFs) constitute the largest transcription factor family in the human genome and are therefore attractive biomarker candidates for BC prognosis. In this study, we profiled the expression of ZNFs in The Cancer Genome Atlas (TCGA) BC cohort and developed a novel prognostic signature based on 7 ZNF-coding genes. After external validation of the model in the GSE48276 dataset, we integrated the 7-ZNF-gene signature with patient clinicopathological data to construct a nomogram that forecasted 1-, 2-, and 3-year OS with good predictive accuracy. We then accessed The Genomics of Drug Sensitivity in Cancer database to predict the therapeutic drug responses of signature-defined high- and low-risk BC patients in the TCGA cohort. Greater sensitivity to chemotherapy was revealed in the low-risk group. Finally, we conducted gene set enrichment analysis of the signature genes and established, by applying the ESTIMATE algorithm, distinct correlations between the two risk groups and the presence of stromal and immune cell types in the tumor microenvironment. By allowing effective risk stratification of BC patients, our novel ZNF gene signature may enable tailoring more intensive treatment for high-risk patients.