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1.
Sci Rep ; 14(1): 2859, 2024 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-38310106

RESUMO

As the malignancy with the highest global incidence, breast cancer represents a significant threat to women's health. Recent advances have shed light on the importance of mitochondrial function in cancer, particularly in metabolic reprogramming within tumors. Recognizing this, we developed a novel risk signature based on mitochondrial-related genes to improve prognosis prediction and risk stratification in breast cancer patients. In this study, transcriptome data and clinical features of breast cancer samples were extracted from two sources: the TCGA, serving as the training set, and the METABRIC, used as the independent validation set. We developed the signature using LASSO-Cox regression and assessed its prognostic efficacy via ROC curves. Furthermore, the signature was integrated with clinical features to create a Nomogram model, whose accuracy was validated through clinical calibration curves and decision curve analysis. To further elucidate prognostic variations between high and low-risk groups, we conducted functional enrichment and immune infiltration analyses. Additionally, the study encompassed a comparison of mutation landscapes and drug sensitivity, providing a comprehensive understanding of the differing characteristics in these groups. Conclusively, we established a risk signature comprising 8 mitochondrial-related genes-ACSL1, ALDH2, MTHFD2, MRPL13, TP53AIP1, SLC1A1, ME3, and BCL2A1. This signature was identified as an independent risk predictor for breast cancer patient survival, exhibiting a significant high hazard ratio (HR = 3.028, 95%CI 2.038-4.499, P < 0.001). Patients in the low-risk group showed a more favorable prognosis, with enhanced immune infiltration, distinct mutation landscapes, and greater sensitivity to anti-tumor drugs. In contrast, the high-risk group exhibited an adverse trend in these aspects. This risk signature represents a novel and effective prognostic indicator, suggesting valuable insights for patient stratification in breast cancer.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Prognóstico , Genes Mitocondriais , Mitocôndrias/genética , Medição de Risco , Aldeído-Desidrogenase Mitocondrial
2.
Front Oncol ; 13: 1142976, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37901326

RESUMO

Objective: Using the latest cohort study of prostate cancer patients, explore the epidemiological trend and prognostic factors, and develop a new nomogram to predict the specific survival rate of prostate cancer patients. Methods: Patients with prostate cancer diagnosed from January 1, 1975 to December 31, 2019 in the Surveillance, Epidemiology, and End Results Program (SEER) database were extracted by SEER stat software for epidemiological trend analysis. General clinical information and follow-up data were also collected from 105 135 patients with pathologically diagnosed prostate cancer from January 1, 2010 to December 1, 2019. The factors affecting patient-specific survival were analyzed by Cox regression, and the factors with the greatest influence on specific survival were selected by stepwise regression method, and nomogram was constructed. The model was evaluated by calibration plots, ROC curves, Decision Curve Analysis and C-index. Results: There was no significant change in the age-adjusted incidence of prostate cancer from 1975 to 2019, with an average annual percentage change (AAPC) of 0.45 (95% CI:-0.87~1.80). Among the tumor grade, the most significant increase in the incidence of G2 prostate cancer was observed, with an AAPC of 2.99 (95% CI:1.47~4.54); the most significant decrease in the incidence of G4 prostate cancer was observed, with an AAPC of -10.39 (95% CI:-13.86~-6.77). Among the different tumor stages, the most significant reduction in the incidence of localized prostate cancer was observed with an AAPC of -1.83 (95% CI:-2.76~-0.90). Among different races, the incidence of prostate cancer was significantly reduced in American Indian or Alaska Native and Asian or Pacific Islander, with an AAPC of -3.40 (95% CI:-3.97~-2.82) and -2.74 (95% CI:-4.14~-1.32), respectively. Among the different age groups, the incidence rate was significantly increased in 15-54 and 55-64 age groups with AAPC of 4.03 (95% CI:2.73~5.34) and 2.50 (95% CI:0.96~4.05), respectively, and significantly decreased in ≥85 age group with AAPC of -2.50 (95% CI:-3.43~-1.57). In addition, age, tumor stage, race, PSA and gleason score were found to be independent risk factors affecting prostate cancer patient-specific survival. Age, tumor stage, PSA and gleason score were most strongly associated with prostate cancer patient-specific survival by stepwise regression screening, and nomogram prediction model was constructed using these factors. The Concordance indexes are 0.845 (95% CI:0.818~0.872) and 0.835 (95% CI:0.798~0.872) for the training and validation sets, respectively, and the area under the ROC curves (AUC) at 3, 6, and 9 years was 0.7 or more for both the training and validation set samples. The calibration plots indicated a good agreement between the predicted and actual values of the model. Conclusions: Although there was no significant change in the overall incidence of prostate cancer in this study, significant changes occurred in the incidence of prostate cancer with different characteristics. In addition, the nomogram prediction model of prostate cancer-specific survival rate constructed based on four factors has a high reference value, which helps physicians to correctly assess the patient-specific survival rate and provides a reference basis for patient diagnosis and prognosis evaluation.

3.
PeerJ ; 11: e16158, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37818332

RESUMO

Background: Different prostate cancer patients take different amounts of time to progress to castration-resistant prostate cancer (CRPC), and this difference in time determines the patient's ultimate survival time. If the time to progression to CRPC can be estimated for each patient, the treatment can be better individualized. Objective: Castration-resistant prostate cancer is a challenge in attacking prostate cancer, the aim of the paper is to analyze the correlation between lactate dehydrogenase (LDH) and CRPC occurrence based on the restricted cubic spline model, and to provide a theoretical basis for LDH as a prognostic biomarker for prostate cancer patients. Methods: We retrospectively analyzed clinical and follow-up data of patients diagnosed with prostate cancer and treated with Androgen Deprivation Therapy (ADT) in our hospital from October 2019 to August 2022. Investigate the correlation between LDH and CRPC by COX regression, restricted cubic spline model and survival analysis. Results: The initial tPSA concentration, prostate volume, LDH and alkaline phosphatase levels in patients with prostate cancer with rapid progression are higher than those in patients with prostate cancer with slow progression. Multivariate COX regression showed that initial tPSA level and LDH level are independent risk factors for prostate cancer. Restricted cubic spline model further showed that LDH level is linearly correlated with the risk of CRPC in prostate cancer patients (total P < 0.05, nonlinear P > 0.05). Conclusion: LDH was associated with the prognosis of prostate cancer and had a dose-response relationship with the risk of CRPC in prostate caner patients.


Assuntos
Biomarcadores Tumorais , L-Lactato Desidrogenase , Neoplasias de Próstata Resistentes à Castração , Humanos , Masculino , Antagonistas de Androgênios/uso terapêutico , L-Lactato Desidrogenase/análise , Prognóstico , Neoplasias de Próstata Resistentes à Castração/diagnóstico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Estudos Retrospectivos , Biomarcadores Tumorais/análise , Resistencia a Medicamentos Antineoplásicos , Modelos Biológicos
4.
World J Surg Oncol ; 21(1): 270, 2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37641123

RESUMO

OBJECTIVE: To screen for miRNAs differentially expressed in prostate cancer and prostate hyperplasia tissues and to validate their association with prostate cancer. METHODS: Patients diagnosed by pathology in the Department of Urology of the First Affiliated Hospital of Xinjiang Medical University from October 2021 to June 2022 were selected, and their general clinical information, blood samples, and prostate tissue samples were collected. miRNA microarray technology was performed to obtain differentially expressed miRNAs in prostate cancer and hyperplasia tissues, and miRNAs to be studied were screened by microarray results and review of relevant literature. The detection of miRNA expression in the patients' blood and prostate tissue samples was measured. The miRNA-222-mimics were transfected into PC3 cells, and cell biology experiments such as CCK8, scratch, Transwell, and flow cytometry were performed to detect the effects of overexpressed miRNA-222 on the growth and proliferation, invasive ability, apoptotic ability, and metastatic ability of prostate cancer cells. RESULTS: The results of the miRNA microarray showed that there were many differentially expressed miRNAs in prostate cancer and hyperplasia tissues, and four miRNAs, miRNA-144, miRNA-222, miRNA-1248, and miRNA-3651 were finally selected as the subjects by reviewing relevant literature. The results showed that the expression of miRNA-222 in prostate cancer tissues was lower than that in prostate hyperplasia tissues (P < 0.05). The expression of miRNA-222, miRNA-1248, and miRNA-3651 in blood samples of prostate cancer patients was lower than that in prostate hyperplasia patients (P < 0.05). The analysis results indicated that the f/t ratio and the relative expression of miRNA-222 and miRNA-1248 were independent influences of prostate cancer (P < 0.05), in which overexpression of miRNA-222 decreased the proliferative, invasive, and metastatic abilities of PC3 cells and enhanced the level of apoptosis of cancer cells. CONCLUSIONS: Although there was no significant change in the overall incidence of prostate cancer in this study, significant changes occurred in the incidence of prostate cancer with different characteristics. In addition, the nomogram prediction model of prostate cancer-specific survival rate constructed based on four factors has a high reference value, which helps physicians to correctly assess the patient-specific survival rate and provides a reference basis for patient diagnosis and prognosis evaluation.


Assuntos
MicroRNAs , Neoplasias da Próstata , Masculino , Humanos , MicroRNAs/genética , Hiperplasia , Neoplasias da Próstata/genética , Próstata , Apoptose
5.
Nat Commun ; 14(1): 4205, 2023 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-37452017

RESUMO

Metallic zinc anodes of aqueous zinc ion batteries suffer from severe dendrite and side reaction issues, resulting in poor cycling stability, especially at high rates and capacities. Herein, we develop two three-dimensional hierarchical graphene matrices consisting of nitrogen-doped graphene nanofibers clusters anchored on vertical graphene arrays of modified multichannel carbon. The graphene matrix with radial direction carbon channels possesses high surface area and porosity, which effectively minimizes the surface local current density, manipulates the Zn2+ ions concentration gradient, and homogenizes the electric field distribution to regulate Zn deposition. As a result, the engineered matrices achieve a superior coulombic efficiency of 99.67% over 3000 cycles at 120 mA cm-2, the symmetric cells with the composite zinc anode demonstrates 2600 h dendrite-free cycles at 80 mA cm-2 and 80 mAh cm-2. The as-designed full cell exhibits an inspiring capacity of 16.91 mAh cm-2. The Zn capacitor matched with activated carbon shows a superior long-term cycle performance of 20000 cycles at 40 mA cm-2. This strategy of constructing a 3D hierarchical structure for Zn anodes may open up a new avenue for metal anodes operating under high rates and capacities.


Assuntos
Grafite , Carvão Vegetal , Fontes de Energia Elétrica , Eletrodos , Zinco
6.
Front Endocrinol (Lausanne) ; 13: 1090763, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36561563

RESUMO

Objective: The aim of this study was to investigate the relevance of metabolic syndrome (MetS) and metabolic scores to the occurrence, progression and prognosis of metastatic prostate cancer (mPCA), assessing the definition of the variables of metabolic syndrome, and the potential mechanisms of MetS and mPCA. Methods: Data were obtained from the database of prostate cancer follow-up at the Urology Centre of the First Affiliated Hospital of Xinjiang Medical University (N=1303). After screening by inclusion and exclusion criteria, clinical data of 190 patients diagnosed with mPCA by pathology and imaging from January 2010 to August 2021 were finally included, including 111 cases in the MetS group and 79 cases in the Non-MetS group. Results: The MetS group was higher than the Non-MetS group: T stage, Gleasson score, initial PSA, tumor load, PSA after 7 months of ADT (P<0.05),with a shorter time to progression to CRPC stage(P<0.05)[where the time to progression to CRPC was relatively shorter in the high metabolic score subgroup of the MetS group than in the low subgroup (P<0.05)].Median survival time was significantly shorter in the MetS group than in the Non-MetS group (P<0.05),and there was a correlation with metabolic score, with the higher metabolic score subgroup having a lower survival time than the lower metabolic score subgroup (P<0.05). Conclusion: Those with mPCA combined with MetS had lower PSA remission rates, more aggressive tumors, shorter time to progression to CRPC and shorter median survival times than those with mPCA without MetS.Tumour progression and metabolic score showed a positive correlation, predicting that MetS may promote the progression of mPCA, suggesting that MetS may be a risk factor affecting the prognosis of mPCA.


Assuntos
Síndrome Metabólica , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Antígeno Prostático Específico , Neoplasias de Próstata Resistentes à Castração/patologia , Síndrome Metabólica/complicações , Correlação de Dados , Prognóstico
7.
Dalton Trans ; 50(9): 3240-3246, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33585853

RESUMO

A new three-dimensional (3-D) inorganic metal-oxygen network vanadoborate Na3H10[Ni(H2O)2(VO)6(B10O22)2]·NH4·19H2O (1) constructed from lantern-type {(VO)6(B10O22)2} clusters, NaO6 polyhedra and NiO6 octahedra, was successfully synthesized by a hydrothermal method. In the structure, the {V6B20} clusters are linked together through NiO6 octahedral bridges, resulting in 1-D chains along the c-axis. The 1-D chains are further connected by NaO6 polyhedra to give rise to a 3-D open-framework structure. Furthermore, lots of NH4+ and H2O molecules are accommodated in the void of the structure, and may interact with the [V6B20] system via N-HO, O-HO hydrogen bonds, constructing a complex hydrogen-bonding network system. Strikingly, compound 1 exhibited a high proton conductivity of 3.22 × 10-3 S cm-1 at 50 °C under 100% RH with an activation energy of 1.66 eV.

8.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 21(1): 23-8, 2004 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-14767903

RESUMO

OBJECTIVE: To investigate whether the variants A(-6)G and A(-20)C of angiotensinogen (AGT) gene are involved in the pathogenesis of essential hypertension in Kazakans. METHODS: T his case control study recruited 125 subjects with hypertension and 74 normotensive subjects from Kazakans of Xinjiang. Genomic DNA from leukocytes was analyzed for genetic variants A(-6)G and A(-20)C in 5' upstream core promoter of AGT gene by polymerase chain reaction (PCR), single strand conformation polymorphism (SSCP), restriction fragment length polymorphism (RFLP) and automatic sequencing. RESULTS: (1)There were only A(-6)G and A(-20)C variants in the -164 to +73 region of Kazakans' AGT gene. (2) The distributions of genotypes AA, AG, GG at locus -6 of AGT gene showed significant difference between the hypertensive group (0.39, 0.45, 0.16) and the normotensive group (0.49, 0.49, 0.02; Chi2=8.56, P=0.014). There were evident differences in the frequencies of the -6A and the -6G allele of the two groups (0.62, 0.38 and 0.73, 0.27; Chi2=5.35, P=0.021). (3) No significant difference was observed in the distribution of genotypes AA, AC, CC at locus -20 of AGT gene between the hypertensive group (0.69, 0.26, 0.05) and the normotensive group (0.65, 0.32, 0.03; Chi2=2.42, P=0.30). There was no distinct difference in the frequencies of the -20A allele and the -20C allele of the two groups (0.82, 0.18 and 0.82, 0.18; Chi2=0, P=0.99). (4) No significant difference was found at the levels of systolic and diastolic blood pressure between the groups corresponding to genotypes at the loci -6 and -20 of AGT gene. CONCLUSION: The results suggest that the polymorphism of A(-6)G in 5' upstream core promoter of the AGT gene may be involved in the pathogenesis of essential hypertension in Kazakans, while the A(-20)C variant may not play an important role in the etiology of essential hypertension in Kazakans.


Assuntos
Região 5'-Flanqueadora/genética , Angiotensinogênio/genética , Hipertensão/genética , Regiões Promotoras Genéticas/genética , Adulto , Alelos , Sequência de Bases , Pressão Sanguínea/fisiologia , Estudos de Casos e Controles , China , DNA/química , DNA/genética , Análise Mutacional de DNA , Feminino , Frequência do Gene , Genótipo , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Polimorfismo Genético , Polimorfismo Conformacional de Fita Simples
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