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Influenza A virus (IAV) infection while primarily affects the lungs, it is often associated with cardiovascular complications. However, the mechanisms underlying this association are not fully understood. Here, we investigated the potential role of FBXL19, a member of the Skp1-Cullin-F-box family of E3 ubiquitin ligase, in IAV-induced cardiac inflammation. We demonstrated that FBXL19 overexpression in endothelial cells (ECs) reduced viral titers and IAV matrix protein 1 (M1) levels, while increasing antiviral genes expression, including interferon (IFN)-α, ß, γ and RANTES in the cardiac tissue of IAV-infected mice. Moreover, EC-specific overexpression of FBXL19 attenuated the IAV infection-reduced interferon regulatory factor 3 (IRF3) level without altering its mRNA level, and suppressed cardiac inflammation. Furthermore, IAV infection triggered cellular senescence programs in the heart as indicated by the upregulation of p16 and p21 mRNA levels, and the downregulation of lamin B1 levels, which were partially reversed by FBXL19 overexpression in ECs. Our findings indicate that EC-specific overexpression of FBXL19 protects against IAV-induced cardiac damage by enhancing interferon-mediated antiviral signaling, reducing cardiac inflammation, and suppressing cellular senescence programs.
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Polylactic acid (PLA) fiber is a degradable material with good environmental friendliness for textile applications. However, the main problems of difficult dyeing of PLA fibers were: high crystallinity to the adsorption of dyes, more ester and methyl groups producing non-hydrophilic problems, long chains making dyes difficult to penetrate, and producing a low dyeing rate. Here, we attempted to change the crystallinity of the PLA fiber to a lower degree from hydrophobic to hydrophilicity property variation, destroy the long chain structure to grant more staining sites, and improve the PLA fiber staining depth and the resilience dyeing effect with deep eutectic solvent (DES) treatment and natural dyes. We discovered that a controlled DES treatment process could make PLA fibers less crystallized, help amorphous areas form, and break up long chains, which lead to more dye sites. After DES treatment, the crystallinity decreased from 56.12 to 29.86%, and the instantaneous water contact angle decreased from 108.79 to 64.39°. The DES-treated PLA fabric exhibited a higher K/S value of 15.14 for natural dyes under specific conditions. The fabric, which had remarkable fastness characteristics and wash resistance, could endure frequent laundering and fulfill the demands of everyday use. Moreover, the fabric had good antimicrobial activity against Escherichia coli, Staphylococcus aureus, and Candida albicans and possessed a certain level of biocompatibility with fibroblasts. This DES treatment and natural dye combination method offered a new strategy for improving PLA fabric staining depth and color fastness, making it a promising option for low-carbon environmental protection in the textile industry.
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BACKGROUND: TUBA1C is an α-tubulin isoform involved in mitosis, and its dysregulation has been implicated in tumor progression. There is still no clear understanding of its role in bladder urothelial carcinoma (BLCA). METHODS: This study examined the differential expression of TUBA1C and its prognostic significance in bladder cancer based on data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) and also assessed the correlation of TUBA1C expression level with immune cell infiltration and immune checkpoint gene expression levels and the half-inhibitory concentration (IC50) of different chemotherapeutic agents. Immunotherapy response was estimated using the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm. We detected TUBA1C expression in BLCA cells using PCR and Western blotting. Functional assays, including CCK-8, colony formation, transwell, apoptosis and cell cycle assays, were also performed to assess the oncogenic role of TUBA1C in BLCA. RESULT: In three independent public cohorts, TUBA1C was significantly upregulated in bladder tumor tissues, and high TUBA1C expression in bladder cancer was associated with a poorer outcome than low expression. TUBA1C was an independent prognostic risk factor for bladder cancer, and numerous immune checkpoint genes and infiltrating immune cells were associated with TUBA1C. TIDE analysis revealed that TUBA1C showed great potential for predicting the immunotherapy response in bladder cancer patients. In addition, drug sensitivity analysis revealed that high TUBA1C expression indicated sensitivity to multiple chemotherapeutic agents. Functional assays revealed that silencing TUBA1C significantly inhibited the proliferation, migration and invasion of BLCA cells and induced apoptosis and cell cycle arrest. CONCLUSION: The overexpression of TUBA1C in bladder cancer predicts a poor prognosis and may also be a potential immunotherapeutic target. As a prognostic marker, TUBA1C influences tumor progression by regulating the cell cycle.
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Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Humanos , Carcinoma de Células Transicionales/genética , Neoplasias de la Vejiga Urinaria/genética , Pronóstico , Vejiga Urinaria , Ciclo Celular/genética , Mitosis , BiomarcadoresRESUMEN
This study was designed to detecting the influences of lncRNA MEG3 in prostate cancer. Aberrant lncRNAs expression profiles of prostate cancer were screened by microarray analysis. The qRT-PCR and Western blot were employed to investigating the expression levels of lncRNA MEG3, miR-9-5p and QKI-5. The luciferase reporter assay was utilized to testifying the interactions relationship among these molecules. Applying CCK-8 assay, wound healing assay, transwell assay and flow cytometry in turn, the cell proliferation, migration and invasion abilities as well as apoptosis were measured respectively. LncRNA MEG3 was a down-regulated lncRNA in prostate cancer tissues and cells and could inhibit the expression of miR-9-5p, whereas miR-9-5p down-regulated QKI-5 expression. Overexpressed MEG3 and QKI-5 could decrease the abilities of proliferation, migration and invasion in prostate cancer cells effectively and increased the apoptosis rate. On the contrary, miR-9-5p mimics presented an opposite tendency in prostate cancer cells. Furthermore, MEG3 inhibited tumour growth and up-regulated expression of QKI-5 in vivo. LncRNA MEG3 was a down-regulated lncRNA in prostate cancer and impacted the abilities of cell proliferation, migration and invasion, and cell apoptosis rate, this regulation relied on regulating miR-9-5p and its targeting gene QKI-5.
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Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Neoplasias de la Próstata/genética , ARN Largo no Codificante/genética , Proteínas de Unión al ARN/genética , Animales , Apoptosis/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Progresión de la Enfermedad , Perfilación de la Expresión Génica/métodos , Humanos , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Células PC-3 , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/terapia , Proteínas de Unión al ARN/metabolismo , Carga Tumoral/genética , Ensayos Antitumor por Modelo de Xenoinjerto/métodosRESUMEN
With growing concern over world environmental problems and increasing legislative restriction on using lead and lead-containing materials, a feasible replacement for lead-based piezoceramics is desperately needed. Herein, we report a large piezoelectric strain (d33*) of 470 pm/V and a high Curie temperature (Tc) of 243 °C in (Na0.5K0.5)NbO3-(Bi0.5Li0.5)TiO3-BaZrO3 lead-free ceramics by doping MnO2. Moreover, excellent temperature stability is also observed from room temperature to 170 °C (430 pm/V at 100 °C and 370 pm/V at 170 °C). Thermally stimulated depolarization currents (TSDC) analysis reveals the reduced defects and improved ferroelectricity in MnO2-doped piezoceramics from a macroscopic view. Local poling experiments and local switching spectroscopy piezoresponse force microscopy (SS-PFM) demonstrates the enhanced ferroelectricity and domain mobility from a microscopic view. Distinct grain growth and improvement in phase angle may also account for the enhancement of piezoelectric properties.
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(Pb,La)(Zr,Sn,Ti)O3 (PLZST) single crystals with their chemical composition located at the tetragonal antiferroelectric region are grown via the flux method in a PbO-PbF2-B2O3 mixture. Segregation of the Ti4+ component in the as-grown crystals is observed due to the strong affinity between the oxygen anion and Ti4+ ions. The critical electric field of the antiferroelectric to ferroelectric phase transition is determined to be about 0.5 kV mm-1. The electric field induced ferroelectric phase transforms back into the antiferroelectric phase at a depolarization temperature of 125 °C. Anisotropy of the harvested energy density and electrocaloric behaviors are achieved for the [100], [110] and [111]-oriented PLZST crystals. Based on the thermodynamic theory approach, all the abovementioned behaviors originate from the anisotropic total entropy change. Enhanced electrocaloric strength (0.3 K mm kV-1) and the harvested energy density of 0.62 J cm-3 are obtained in the [111]-oriented PLZST crystals. Our results demonstrate the competence of PLZST single crystals for cooling devices and pyroelectric energy harvesting and provide new opportunities to improve energy harvesting density and electrocaloric properties via the anisotropic structural layout, which make the PLZST crystals attractive for solid state cooling devices and energy conversion technologies.
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Rho-associated coiled-coil forming protein kinase 2 (Rock2), as a key effector of the small GTPase RhoA, is involved in tumor development. Scavenger receptor class A member 5 (SCARA5) is an important regulator of biological processes in cancer cells. However, the roles and relationship of Rock2 and SCARA5 in renal cell carcinoma (RCC) remain unclear. In this study, we found that Rock2 expression was markedly increased in clinical RCC tissues compared with that in adjacent non-cancerous tissues. High expression of Rock2 was inversely correlated with patient survival in RCC, which indicated that Rock2 may be a prognostic marker in human RCC. In addition, Rock2 knockdown increased SCARA5 expression and suppressed RCC cell proliferation both in vitro and in vivo. Furthermore, we found that the ß-catenin/TCF4 pathway contributed to the effect of Rock2 on SCARA5-mediated RCC proliferation. Taken together, these results suggest that this newly identified Rock2-ß-catenin/TCF4-SCARA5 axis will provide novel insight into the understanding of the regulatory mechanisms of proliferation in human RCC.
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Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Carcinoma de Células Renales/metabolismo , Proliferación Celular , Receptores Depuradores de Clase A/metabolismo , Factores de Transcripción/metabolismo , beta Catenina/metabolismo , Quinasas Asociadas a rho/metabolismo , Carcinoma de Células Renales/patología , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Humanos , Transducción de Señal , Factor de Transcripción 4 , Células Tumorales CultivadasRESUMEN
Both continuous and discontinuous spin reorientation transitions in the HoFeO3 orthoferrite have been further investigated in this paper. Here, we use terahertz spectroscopy through the terahertz ferromagnetic and antiferromagnetic resonances to study the thermodynamics of the spin reorientation transitions in HoFeO3 ceramics. The spin reorientations are driven by changes in the anisotropy energy, and the spin moments in and out of the (a, c) plane correspond to the continuous transitions and discontinuous transitions. We fitted the antiferromagnetic resonant frequencies, and we achieved quantitative insight on the changes in anisotropy energy. Measuring M-H (moment-magnetic field) curves, we found changes in macroscopic magnetization and verified the thermodynamics.
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BACKGROUND: MicroRNAs (miR) have come into focus as powerful regulators of gene expression and potential diagnostic tools during renal ischemia reperfusion injury (IRI). The aim of this study was to investigate the molecular regulation and function of miR-21, and to analyze the relationship between caspases and miR-21 expression levels in an experimental model of renal IRI. METHODS: IRI was induced by bilateral renal ischemia for 45 min followed by reperfusion. The male BALB/c mice were randomly assigned to the following groups: pre-miR-21 + IRI group, antagomiR-21 + IRI group, PBS + IRI group, pre-miR-21 + sham operation group, antagomiR-21 + sham operation group, PBS + sham operation group. The pre-miR-21 or antagomiR-21 was administered intraperitoneally (200 ng/kg weight) 24 and 6 h before induction of ischemia. Renal function, histological damage, renal cell apoptosis proteins were evaluated at 24 h after reperfusion. RESULTS: Mice upregulated miR-21 had lower plasma levels of blood urea nitrogen (BUN) and creatinine, lower histopathological scores and a decrease in programmed cell death 4 (PDCD4) mRNA and active caspase-3, caspase-8 proteins expressions. CONCLUSIONS: miR-21 is endowed with anti-apoptotic properties by suppressing the expression of PDCD4 gene and active caspase 3/8 fragments in the condition of renal IRI. miR-21 exerts significant functional protection in our renal murine model of IRI.
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Caspasas/metabolismo , Isquemia/metabolismo , Riñón/patología , MicroARNs/genética , MicroARNs/metabolismo , Daño por Reperfusión/patología , Animales , Apoptosis , Proteínas Reguladoras de la Apoptosis/metabolismo , Nitrógeno de la Urea Sanguínea , Caspasa 3/metabolismo , Caspasa 8/metabolismo , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , Interleucina-18/sangre , Riñón/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Proteínas de Unión al ARN/metabolismo , Distribución Aleatoria , Transducción de Señal , Regulación hacia ArribaRESUMEN
The rotational and vibrational dynamics of molecules in copper sulfate pentahydrate crystal are investigated with terahertz dielectric spectra. It is shown that the relaxation-like dielectric dispersion in the low frequency region is related to the reorientation of water molecules under the driving of terahertz electric field, whereas the resonant dispersion can be ascribed to lattice vibration. It is also found that, due to the hydrogen-bond effect, the vibrational mode at about 1.83 THz along [-111] direction softens with decreasing temperature, that is, the crystal expands in this direction when cooled. On the contrary, the mode hardens in the direction perpendicular to [-111] during the cooling process. This contributes to the further understanding of the molecular structure and bonding features of hydrate crystals.
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BACKGROUND: Previous studies have established a positive correlation between serum uric acid to creatinine (SUA/Cr) ratio and cardiovascular disease, but the relationship between SUA/Cr ratio and the prognosis of heart failure (HF) remains unknown. This study investigated the potential of SUA/Cr ratio as a prognostic predictor for patients with HF. METHODS: This single-center prospective cohort study enrolled 2,122 patients with HF between March 2013 and June 2017. All patients were divided into 3 groups according to SUA/Cr ratio tertiles and were followed up with until December 31, 2022. The association between SUA/Cr ratio and the prognosis of HF was assessed using the Cox proportional hazards model. RESULTS: The mean (SD) age and mean (SD) SUA/Cr ratio of the study cohort (66% male) were 59.3 (14.7) years and 4.71 (2.09), respectively. During a median follow-up period of 15 months (range, 11-26 months), 390 end-point events were observed. Prognosis analysis revealed that a high SUA/Cr ratio was associated with an increased mortality risk of HF (hazard ratio, 1.62 [95% CI, 1.26-2.09]; P < .001) compared with the SUA/Cr ratio in the lowest tertile. After adjusting for covariates, the hazard ratio for mortality risk of HF was 1.71 (95% CI, 1.23-2.37; P = .001). Subgroup analysis showed that mortality risk increased in direct proportion with the SUA/Cr ratio in female patients, patients with a history of hypertension and ß-blocker use, and patients with UA levels below 428 µmol/L and creatinine levels less than 97 mg/dL. Stratification by age; by history of diabetes, hyperlipidemia, and smoking; and by level of fasting plasma glucose, however, had no obvious effect on the association between SUA/Cr ratio and HF prognosis. Patients with higher SUA/Cr ratios had reduced left ventricular ejection fraction and increased left ventricular end-diastolic diameter. CONCLUSION: A high SUA/Cr ratio was an independent risk factor for the mortality risk of HF.
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Biomarcadores , Creatinina , Insuficiencia Cardíaca , Ácido Úrico , Humanos , Ácido Úrico/sangre , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Creatinina/sangre , Biomarcadores/sangre , Pronóstico , Medición de Riesgo/métodos , Factores de Riesgo , Estudios de Seguimiento , Valor Predictivo de las Pruebas , Tasa de Supervivencia/tendencias , AncianoRESUMEN
Acute kidney injury (AKI) induced by renal ischemia/reperfusion injury (IRI) is a severe clinical condition. ROS accumulation, antioxidant pathways deficiency, and inflammation are involved in IRI. Pioglitazone (Pio) exerts anti-inflammatory and antioxidant effects. The aim of this study was to explore the protective effects of pioglitazone against IRI-induced AKI. Pathogen-free Sprague-Dawley (SD) rats were arbitrarily divided into four groups: Sham operation group Control (CON) group, CON + Pio group, I/R + Saline group, and I/R + Pio group. In addition, HK-2 cells were subjected to hypoxia and reoxygenation to develop an H/R model for investigation of the protective mechanism of Pio. Pretreatment with pioglitazone in the model rats reduced urea nitrogen and creatinine levels, histopathological scores, and cytotoxicity after IRI. Pioglitazone treatment significantly attenuated renal cell apoptosis, decreased cytotoxicity, increased Bcl-2 expression, and downregulated Bax expression. Besides, the levels of ROS and inflammatory factors, including NLRP3, ASC, pro-IL-1ß, pro-caspase-1, cleaved-caspase-1, TNF-α, IL-6, and IL-1ß, in I/R rats and H/R cells were normalized by the pioglitazone treatment. Pioglitazone improved IRI-induced AKI by attenuating oxidative stress and NLRP3 inflammasome activation. Therefore, pioglitazone has the potential to serve as a novel agent for renal IRI treatment and prevention.
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Lesión Renal Aguda , Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Estrés Oxidativo , Pioglitazona , Ratas Sprague-Dawley , Daño por Reperfusión , Pioglitazona/farmacología , Daño por Reperfusión/prevención & control , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Lesión Renal Aguda/etiología , Lesión Renal Aguda/prevención & control , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/metabolismo , Estrés Oxidativo/efectos de los fármacos , Inflamasomas/metabolismo , Animales , Humanos , Masculino , Modelos Animales de Enfermedad , Ratas , Apoptosis/efectos de los fármacos , Antioxidantes/farmacología , Línea CelularRESUMEN
BACKGROUND: In our previous study, we showed that pioglitazone exerts protective effects on renal ischemia-reperfusion injury (IRI) in mice by abrogating renal cell apoptosis. Oxidative stress due to excessive production of reactive oxygen species and subsequent lipid peroxidation plays a critical role in renal IRI. The purpose of the current study is to demonstrate the effect of pioglitazone on renal IRI by modulation of oxidative stress. MATERIALS AND METHODS: IRI was induced by bilateral renal ischemia for 45 min followed by reperfusion. Thirty healthy male Balb/c mice were randomly assigned to one of the following groups: phosphate buffer solution (PBS) + IRI, pioglitazone + IRI, PBS + sham IRI, pioglitazone + sham IRI. Kidney function tests and kidney antioxidant activities were determined 24 h after reperfusion. RESULTS: Pretreatment with pioglitazone produced reduction in serum levels of blood urea nitrogen and creatinine caused by IRI. Pretreatment with pioglitazone before IRI resulted in a higher level of kidney enzymatic activities of superoxide dismutase, glutathione, catalase, and total antioxidant capacity than in the PBS-pretreated IRI group. CONCLUSIONS: Our results indicate that pioglitazone can provide protection for kidneys against IRI by enhancing antioxidant capacity. Therefore, pioglitazone could be a potential therapeutic approach to prevent renal IRI relevant to various clinical conditions.
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Antioxidantes/uso terapéutico , Riñón/irrigación sanguínea , Riñón/patología , Daño por Reperfusión/prevención & control , Tiazolidinedionas/uso terapéutico , Animales , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Riñón/fisiopatología , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos BALB C , Modelos Animales , Estrés Oxidativo/efectos de los fármacos , Pioglitazona , Especies Reactivas de Oxígeno/metabolismo , Daño por Reperfusión/metabolismo , Daño por Reperfusión/fisiopatología , Tiazolidinedionas/farmacologíaRESUMEN
Circular RNAs (circRNAs) are linked to cancer, but it's still not clear what role they play in prostatic cancer. Through high-throughput sequencing, the goal of this study was to compare how circRNAs are expressed at different stages of prostate cancer. 12 patients attending the Department of Urology at the Second Affiliated Hospital of Nanchang University between June 2020 and October 2021 were used for RNA sequencing, and 14 patients were used for real-time fluorescent quantitative PCR (qRT-PCR). The expression profiles of prostate cancer circRNAs were constructed by sequencing with the help of next-generation high-throughput sequencing technology, and the differentially expressed circRNAs were analyzed by targeting microRNA (miRNA) loci and Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the genes from which circRNAs originated. Finally, the expression of target circRNAs in two prostate tissues was verified by qRT-PCR. Following high-throughput sequencing, 13,047 circRNAs were identified, and 605 circRNAs with significant differential expression were identified, of which 361 circRNAs were up-regulated, and 244 circRNAs were down-regulated. Analysis of circRNA-originated genes using GO and the KEGG enrichment analysis showed that circRNA host genes can regulate and influence multiple signaling pathways in prostate cancer with important biological functions. And the circRNA-miRNA network was constructed. The highest number of differentially expressed circRNA-binding miRNAs were: hsa_circ_000 7582 (52), hsa_circ_000 6198 (37), hsa_circ_000 6759 (28), hsa_circ_000 5675 (25), and hsa_circ_000 2172 (22). Moreover, we further screened out the circRNA (hsa_circ_0005692) that was significantly differentially expressed and common to all groups and verified by qRT-PCR that the expression of the target circRNA (hsa_circ_0005692) was significantly downregulated in prostate cancer compared with benign prostatic hyperplasia (BPH) tissues.
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MicroARNs , Neoplasias de la Próstata , Masculino , Humanos , ARN Circular/genética , MicroARNs/genética , Secuencia de Bases , Neoplasias de la Próstata/genética , Análisis de Secuencia de ARNRESUMEN
Conventional therapy for kidney renal clear cell carcinoma (KIRC) is unpromising. The tumor microenvironment (TME) is intimately linked to the invasiveness of a variety of tumor forms, including KIRC. The purpose of this research is to establish the prognostic and immune-related significance of dihydrolipoamide branched chain transacylase E2 (DBT) in individuals with KIRC. In this investigation, we discovered that DBT expression was down-regulated in a range of human malignancies, and low DBT expression in KIRC was linked to higher-level clinicopathological characteristics as well as a poor prognosis for KIRC patients. Based on the findings of univariate and multivariate Cox regression analyses, DBT might be employed as an independent prognostic factor in KIRC patients. Furthermore, we developed a nomogram to better investigate DBT's predictive usefulness. To confirm DBT expression, we examined KIRC cell lines using RT-qPCR and Western blotting. We also examined the role of DBT in KIRC using colony formation, CCK-8, EdU, transwell, and wound healing assays. We discovered that plasmid-mediated overexpression of DBT in KIRC cells slowed cell proliferation and decreased migration and invasion. Multiple enrichment analyses revealed that DBT may be involved in processes and pathways related to immunotherapy and drug metabolism. We computed the immune infiltration score and discovered that the immunological score and the ESTIMATE score were both greater in the DBT low expression group. According to the CIBERSORT algorithm, DBT seems to promote anti-cancer immune responses in KIRC by activating M1 macrophages, mast cells, and dendritic cells while inhibiting regulatory T cells. Finally, in KIRC, DBT expression was found to be highly linked to immunological checkpoints, targeted medicines, and immunotherapeutic agents. Our findings suggest that DBT is a distinct predictive biomarker for KIRC patients, playing a significant role in the TME of KIRC and serving as a reference for the selection of targeted treatment and immunotherapy.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Algoritmos , Bioensayo , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/terapia , Inmunoterapia , Neoplasias Renales/genética , Microambiente TumoralRESUMEN
BACKGROUND: Renal ischemia-reperfusion injury (IRI) is a complex pathophysiologic process involving cell apoptosis and oxidant damages that leads to acute renal failure in both native kidneys and renal allografts. Pioglitazone is a novel class of oral antidiabetic agents currently used to treat type 2 diabetes mellitus. Pioglitazone exerts protective effects on acute myocardial ischemia and acute cerebral ischemia. The aim of this study was to investigate the possible beneficial effects of pioglitazone on renal IRI in mice. METHODS: IRI was induced by bilateral renal ischemia for 45 min followed by reperfusion. Fifty-five healthy male Balb/c mice were randomly assigned to one of the following groups: PBS + IRI, pioglitazone + IRI, PBS + sham IRI, pioglitazone + sham IRI. Kidney function tests, histopathologic examination, renal cell Bcl-2, and Bax expression were determined 24 h after reperfusion. Animals' survival was examined 7 days after operation. RESULTS: Animals pretreated with pioglitazone had lower plasma levels of blood urea nitrogen and creatinine caused by IRI, lower histopathologic scores, and improved survival rates following IRI. Renal cell apoptosis induced by IRI was abrogated in kidneys of mice pretreated by pioglitazone, with an increase in Bcl-2 expression and a decrease in Bax expression. Furthermore, pioglitazone pretreatment protected against lethal renal IRI. CONCLUSIONS: Peroxisome proliferator-activated receptor activation by pioglitazone exerts protective effects on renal IRI in mice by abrogating renal cell apoptosis. Thus, pioglitazone could be a novel therapeutic tool in renal IRI.
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Lesión Renal Aguda/tratamiento farmacológico , Daño por Reperfusión/tratamiento farmacológico , Tiazolidinedionas/farmacología , Lesión Renal Aguda/patología , Animales , Apoptosis/efectos de los fármacos , Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Modelos Animales de Enfermedad , Hipoglucemiantes/farmacología , Túbulos Renales/efectos de los fármacos , Túbulos Renales/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Pioglitazona , Distribución Aleatoria , Daño por Reperfusión/patologíaRESUMEN
Background: Immunotherapy has emerged as an important technique for treating a variety of cancers. The dynamic interplay between tumor cells and invading lymphocytes in the tumor microenvironment is responsible for the good response to immunotherapy (TME). Pyroptosis, or inflammation-induced cell death, is closely linked to a number of cancers. However, in papillary renal cell carcinoma (KIRP), the association between pyroptosis and clinical prognosis, immune cell infiltration, and immunotherapy impact remains unknown. Methods: We carefully investigated the link between pyroptosis and tumor growth, prognosis, and immune cell infiltration by evaluating 52 pyroptosis-related genes. The PRG score was utilized to measure a single tumor patient's pyroptosis pattern. After that, we looked at how well these values predicted prognoses and therapy responses in KIRP. Results: We discovered that PRG differences between subgroups were linked to clinical and pathological aspects, prognosis, and TME in two separate genetic subtypes. After that, a PRG score for estimating overall survival (OS) was developed, and its predictive potential in KIRP patients was confirmed. As a result, we developed a very precise nomogram to improve the PRG score's clinical usefulness. A low PRG score, which is determined by mutation load and immune activation, suggests a good chance of survival. Furthermore, the PRG score was linked to chemotherapeutic drug sensitivity in a substantial way. Conclusions: The possible functions of PRGs in the TME, clinical and pathological characteristics, and prognosis were established in our thorough investigation of PRGs in KIRP. These results might help us better understand PRGs in KIRP and offer a new avenue for prognostic evaluation and the development of more effective immunotherapy treatments.
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Cuproptosis is a novel kind of programmed cell death that has been linked to tumor development, prognosis, and responsiveness to therapy. Nevertheless, the precise function of cuproptosis-related genes (CRGs) in the tumor microenvironment (TME) remains unknown. We characterized the genetic and transcriptional changes of CRGs in papillary renal cell carcinoma (PRCC) samples and analyzed the expression patterns in two separate cohorts. We observed that two unique cuproptosis-related subgroups and three separate gene subgroups were connected with clinicopathological, prognostic, and TME features of patients. Then, a risk score for predicting overall survival (OS) was created and validated in patients with PRCC. To make the risk score more clinically useful, we created a nomogram that was very accurate. A lower risk score, which was associated with higher tumor mutation burden, and immune activity, suggested a better prognosis for OS. Additionally, the risk score was shown to be substantially linked with the drug's susceptibility to chemotherapeutic agents. Our extensive research of CRGs in PRCC identified possible roles for them in the TME, clinicopathological features, and overall survival. These findings may help advance our knowledge of CRGs in PRCC and pave the way for improved prognosis and the creation of more effective immunotherapy therapies.
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Objective: Long-chain acyl-coenzyme A synthases (ACSLs) catalyze the activation of fatty acid and are often dysregulated in malignancies. The purpose of this research was to figure out the ACSL3's prognostic value and mechanism in clear cell renal cell carcinoma (ccRCC). Methods: The expression of ACSL3 in ccRCC was investigated in this work using data from the GEO, TCGA, Oncomine and HPA databases. The expression differences of ACSL3 in the cell lines were further detected by qPCR and Western blot. GEPIA, MethSurv, cBioPortal, and the TIMER were used to perform survival and correlation analysis on ACSL3. GO and KEGG analyses were carried out in R using clusterProfiler and GOplot. Protein-protein interactions (PPI) are constructed from Strings website, and the results were visualized in Cytoscape software. Results: The expression level of ACSL3 was significantly reduced in ccRCC tissues, and its mRNA and protein expression were also significantly lower in both renal cancer cell lines. ACSL3 is significantly related to clinical stage, OS, DFS, DNA methylation, and immune-cell infiltration. Conclusion: Our findings demonstrated that data mining was capable of eliciting information on ACSL3 levels and its role in genetic regulatory pathways in ccRCC.
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Objective: The aim of this study was to investigate gender differences after renal ischemia-reperfusion injury in mice and the effects of androgen receptor (AR) and microRNA-21 (miR-21) on apoptosis in renal ischemia-reperfusion injury. Methods: Renal ischemia-reperfusion injury model was induced by 45 min of bilateral renal artery ischemia and reperfusion. BALB/c mice were randomly divided into groups according to different experimental protocols. The levels of renal function were evaluated by serum creatinine and blood urea nitrogen. TUNEL staining was used to analyze the pathological changes and apoptosis levels of renal tissue, and western blotting and qPCR were used to detect the expressions of miR-21, AR, PDCD4 and caspase3. Results: After renal ischemia-reperfusion injury in mice with different genders, the levels of plasma urea nitrogen and creatinine in female and male mice increased, the histopathological score increased, and TUNEL staining in renal tissue indicated increased apoptosis. The expressions of miR-21, PDCD4, and active caspase-3 protein were up-regulated. The above trend was more pronounced in male mice, and a significant decrease in AR mRNA expression was detected. Silencing the expression of AR aggravated the decline of renal function and renal tubular injury after renal ischemia in mice. The expression of PDCD4 and active caspase-3 increased, while the level of miR-21 was correspondingly decreased. Up-regulation of miR-21 expression by pre-miR-21 could negatively regulate PDCD4, reduce the expression level of active caspase3, and yet induce AR expression accordingly. MiR-21 alleviated renal ischemia-reperfusion injury by inhibiting renal tubular epithelial cell apoptosis. The effect of antagomiR-21 was the opposite, which aggravated renal ischemia-reperfusion injury. Conclusion: There are gender differences in renal ischemia-reperfusion injury. Male mice are more susceptible to renal ischemia-reperfusion injury than female. Silencing AR expression or down-regulating the level of miR-21 can promote the expression of PDCD4 and apoptosis protein caspase3, thereby aggravating ischemia-reperfusion injury in mice. The protective effect of AR and miR-21 in renal ischemia-reperfusion injury has a certain synergy.