Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Nomogramas , Qualidade de Vida , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/secundário , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Prognóstico , Autorrelato , Inibidores de Proteínas Quinases/uso terapêuticoAssuntos
Carcinoma de Células Renais , Neoplasias Renais , Nefrectomia , Humanos , Neoplasias Renais/cirurgia , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/secundário , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/radioterapia , Nefrectomia/métodos , Estadiamento de NeoplasiasRESUMO
BACKGROUND: We explored the potential novel anticancer mechanisms of 25-hydroxyvitamin D (25(OH)D), a vitamin D metabolite with antitumour effects in breast cancer. It is stable in serum and is used to assess vitamin D levels in clinical practice. Transfer RNA-derived small RNAs are small noncoding RNAs that generate various distinct biological functions, but more research is needed on their role in breast cancer. METHODS: Small RNA microarrays were used to explore the novel regulatory mechanism of 25(OH)D. High-throughput RNA-sequencing technology was used to detect transcriptome changes after 25(OH)D treatment and tRF-1-Ser knockdown. RNA pull-down and high-performance liquid chromatography-mass spectrometry/mass spectrometry were used to explore the proteins bound to tRF-1-Ser. In vitro and in vivo functional experiments were conducted to assess the influence of 25(OH)D and tRF-1-Ser on breast cancer. Semi-quantitative PCR was performed to detect alternative splicing events. Western blot assay and qPCR were used to assess protein and mRNA expression. RESULTS: The expression of tRF-1-Ser is negatively regulated by 25(OH)D. In our breast cancer (BRCA) clinical samples, we found that the expression of tRF-1-Ser was higher in cancer tissues than in paired normal tissues, and was significantly associated with tumour invasion. Moreover, tRF-1-Ser inhibits the function of MBNL1 by hindering its nuclear translocation. Functional experiments and transcriptome data revealed that the downregulation of tRF-1-Ser plays a vital role in the anticancer effect of 25(OH)D. CONCLUSIONS: In brief, our research revealed a novel anticancer mechanism of 25(OH)D, unveiled the vital function of tRF-1-Ser in BRCA progression, and suggested that tRF-1-Ser could emerge as a new therapeutic target for BRCA.
Assuntos
Neoplasias da Mama , Proliferação de Células , Proteínas de Ligação a RNA , Vitamina D , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Feminino , Vitamina D/metabolismo , Vitamina D/análogos & derivados , Vitamina D/farmacologia , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Proliferação de Células/genética , Camundongos , AnimaisRESUMO
Myocardial ischemia/reperfusion (I/R) injury is a classic type of cardiovascular disease characterized by injury to cardiomyocytes leading to different types of cell death. The degree of irreversible myocardial damage is closely related to age, and ferroptosis is involved in cardiomyocyte damage. However, the mechanisms underlying ferroptosis regulation in aging myocardial I/R injury are still unclear. The present study aims to explore the underlying mechanism of piRNA regulation in ferroptosis. Using left anterior descending coronary artery ligation in an aging rat model and a D-galactose-induced rat cardiomyocyte line (H9C2) to construct an aging cardiomyocyte model, we investigate whether ferroptosis occurs after reperfusion injury in vitro and in vivo. This study focuses on the upregulation of piR-000699 after hypoxia/reoxygenation treatment in aging cardiomyocytes by observing hypoxia/reoxygenation (H/R) injury indicators and ferroptosis-related indicators and clarifying the role of piR-000699 in H/R injury caused by ferroptosis in aging cardiomyocytes. Bioinformatics analysis reveals that SLC39A14 is a gene that binds to piR-000699. Our data show that ferroptosis plays an important role in I/R injury both in vivo and in vitro. Furthermore, the results show the potential role of piR-000699 in regulating SLC39A14 in ferroptosis in aging cardiomyocytes under hypoxia/reoxygenation conditions. Together, our results reveal that the mechanism by which piR-000699 binds to SLC39A14 regulates ferroptosis in aging myocardial I/R injury.
RESUMO
BACKGROUND: Atherosclerosis, characterized by abnormal arterial lipid deposition, is an age-dependent inflammatory disease and contributes to elevated morbidity and mortality. Senescent foamy macrophages are considered to be deleterious at all stages of atherosclerosis, while the underlying mechanisms remain largely unknown. In this study, we aimed to explore the senescence-related genes in macrophages diagnosis for atherosclerotic plaque progression. METHODS: The atherosclerosis-related datasets were retrieved from the Gene Expression Omnibus (GEO) database, and cellular senescence-associated genes were acquired from the CellAge database. R package Limma was used to screen out the differentially expressed senescence-related genes (DE-SRGs), and then three machine learning algorithms were applied to determine the hub DE-SRGs. Next, we established a nomogram model to further confirm the clinical significance of hub DE-SRGs. Finally, we validated the expression of hub SRG ABI3 by Sc-RNA seq analysis and explored the underlying mechanism of ABI3 in THP-1-derived macrophages and mouse atherosclerotic lesions. RESULTS: A total of 15 DE-SRGs were identified in macrophage-rich plaques, with five hub DE-SRGs (ABI3, CAV1, NINJ1, Nox4 and YAP1) were further screened using three machine learning algorithms. Subsequently, a nomogram predictive model confirmed the high validity of the five hub DE-SRGs for evaluating atherosclerotic plaque progression. Further, the ABI3 expression was upregulated in macrophages of advanced plaques and senescent THP-1-derived macrophages, which was consistent with the bioinformatics analysis. ABI3 knockdown abolished macrophage senescence, and the NF-κB signaling pathway contributed to ABI3-mediated macrophage senescence. CONCLUSION: We identified five cellular senescence-associated genes for atherogenesis progression and unveiled that ABI3 might promote macrophage senescence via activation of the NF-κB pathway in atherogenesis progression, which proposes new preventive and therapeutic strategies of senolytic agents for atherosclerosis.
Assuntos
Aterosclerose , Placa Aterosclerótica , Animais , Camundongos , Aterosclerose/genética , Aterosclerose/metabolismo , Macrófagos/metabolismo , NF-kappa B/metabolismo , Placa Aterosclerótica/genética , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia , Transdução de SinaisRESUMO
Maize, the most widely planted and highest yielding of the three major crops in the world, requires the development and breeding of new varieties to accommodate the shift towards mechanized harvesting. However, the moisture content of kernels during harvest poses a significant challenge to mechanized harvesting, leading to seed breakage and increased storage costs. Previous studies highlighted the importance of LEA (Late Embryogenesis Abundant) members in regulating kernel dehydration. In this study, we aimed to gain a better understanding of the relationship between the LEA family and grain dehydration in maize. Through expression pattern analysis of maize, we identified 52 LEA genes (ZmLEAs) distributed across 10 chromosomes, organized into seven subgroups based on phylogenetic analysis, gene structure, and conserved motifs. Evolutionary and selective pressure analysis revealed that the amplification of ZmLEA genes primarily resulted from whole-genome or fragment replication events, with strong purifying selection effects during evolution. Furthermore, the transcriptome data of kernels of two maize inbred lines with varying dehydration rates at different developmental stages showed that 14 ZmLEA genes were expressed differentially in the two inbreds. This suggested that the ZmLEA genes might participate in regulating the kernel dehydration rate (KDR) in maize. Overall, this study enhances our understanding of the ZmLEA family and provides a foundation for further research into its role in regulating genes associated with grain dehydration in maize.
RESUMO
This study aimed to compare the efficacy of neoadjuvant systemic therapy (NST) with solvent-based paclitaxel (Sb-P), liposomal paclitaxel (Lps-P), nanoparticle albumin-bound paclitaxel (Nab-P), and docetaxel in human epidermal growth factor receptor 2 (HER2)-low-positive and HER2-zero breast cancers. A total of 430 patients receiving 2-weekly dose-dense epirubicin and cyclophosphamide (EC) followed by 2-weekly paclitaxel (Sb-P, Lps-P, or Nab-P), or 3-weekly EC followed by 3-weekly docetaxel for NST were enrolled in the study. In HER2-low-positive patients, the pathological complete response (pCR) rate in Nab-P group was significantly higher than that in the other three paclitaxel groups (2.8 % in Sb-P group, 4.7 % in Lps-P group, 23.2 % in Nab-P group and 3.2 % in docetaxel group, p < 0.001). In HER2-zero patients, the pCR rate did not differ significantly among the four paclitaxel groups (p = 0.278). The NST regimen containing Nab-P could be considered a promising treatment option in HER2-low-positive breast cancer.
Assuntos
Neoplasias da Mama , Nanopartículas , Humanos , Feminino , Neoplasias da Mama/patologia , Paclitaxel Ligado a Albumina/uso terapêutico , Terapia Neoadjuvante , Docetaxel/uso terapêutico , Lipopolissacarídeos , Ciclofosfamida/uso terapêutico , Epirubicina/uso terapêutico , Paclitaxel/uso terapêutico , Albuminas , Receptor ErbB-2/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resultado do TratamentoRESUMO
The production of biodiesel using microbial lipids derived from renewable lignocellulosic biomass is considered a promising strategy to reduce environmental pressure and promote the green energy transition. The hydrolysates of lignocellulosic biomass are rich in glucose and xylose, which makes it crucial to efficiently utilize both sugars. Here, we combined metabolic engineering and adaptive laboratory evolution (ALE) to construct an engineered Yarrowia lipolytica strain that can efficiently produce lipids from glucose and xylose. First, the "Push-Pull-Block" strategy was adopted to increase lipid content to 73.42% of the dry cell weight (DCW). Then, a heterologous xylose-utilization pathway was integrated into the engineered strain, which was subjected to ALE. The final evolved strain could accumulate 53.64% DCW of lipids from xylose, and the lipid titer reached 16.25 g/L. This work sheds light on the potential of microbial lipid overproduction from lignocellulose using engineered Y. lipolytica.
Assuntos
Xilose , Yarrowia , Xilose/metabolismo , Yarrowia/genética , Yarrowia/metabolismo , Glucose/metabolismo , Engenharia Metabólica , LipídeosRESUMO
BACKGROUND AND AIM: Over the past decades, glycosylated haemoglobin (HbA1c) has been a gold standard for monitoring diabetes control over a long period, relative to blood glucose level (BGL) which measures short-term results. It is speculated that anaemia and factors that induce haemolysis may cause falsely elevated HbA1c leading to 'false positive' interpretations. This study aimed to investigate how anaemia impacts HbA1c. METHODS: This was a pathology-based observational pilot study using archived data of diabetic subjects monitored with both BGL and HbA1c in regional New South Wales (NSW), Australia. A total of 28,487 cases of blood glucose results were pooled and those with HbA1c and anaemia results were evaluated for correlation with the BGL results. Data collection was limited to de-identified information from the laboratory information system, hence details on the ethnicity and medical history were unavailable. Descriptive frequencies and Pearson correlations were performed. RESULTS: In the pooled data, 53.36% of individuals were females, and 50.54% had BGL ≥5.6 mmol/L. In the pilot dataset, the majority (64.86%) were males, 18.92% with BGL ≤5.6 mmol/L and 67.57% had HbA1c (≥6.5%). In the entire dataset, BGL was moderately and positively correlated with HbA1c (r = 0.6), whereas in the subset of individuals with normo-BGL and anaemia, the correlation was negative (r = -0.2). DISCUSSION: This pilot investigation observed a pertinent issue, which is a negative correlation between glycaemia and HbA1c in patients with anaemia. HbA1c was falsely increased despite normal blood glucose levels in individuals with anaemia. This advances the speculation that anaemia falsely increases HbA1c. Therefore, caution is necessary while interpreting HbA1c results for patients with anaemia, and new methods for interpretation are required.