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Septic cardiomyopathy, a life-threatening complication of sepsis, can cause acute heart failure and carry a high mortality risk. Current treatments have limitations. Fortunately, engineered exosomes, created through bioengineering technology, may represent a potential new treatment method. These exosomes can both diagnose and treat septic cardiomyopathy, playing a crucial role in its development and progression. This article examines the strategies for using engineered exosomes to protect cardiac function and treat septic cardiomyopathy. It covers three innovative aspects: exosome surface modification technology, the use of exosomes as a multifunctional drug delivery platform, and plant exosome-like nanoparticle carriers. The article highlights the ability of exosomes to deliver small molecules, proteins, and drugs, summarizing several RNA molecules, proteins, and drugs beneficial for treating septic cardiomyopathy. Although engineered exosomes are a promising biotherapeutic carrier, they face challenges in clinical application, such as understanding the interaction mechanism with host cells, distribution within the body, metabolism, and long-term safety. Further research is essential, but engineered exosomes hold promise as an effective treatment for septic cardiomyopathy.
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SLC7A11 is a cystine transporter and ferroptosis inhibitor. How the stability of SLC7A11 is coordinately regulated in response to environmental cystine by which E3 ligase and deubiquitylase (DUB) remains elusive. Here, we report that neddylation inhibitor MLN4924 increases cystine uptake by causing SLC7A11 accumulation, via inactivating Cullin-RING ligase-3 (CRL-3). We identified KCTD10 as the substrate-recognizing subunit of CRL-3 for SLC7A11 ubiquitylation, and USP18 as SLC7A11 deubiquitylase. Upon cystine deprivation, the protein levels of KCTD10 or USP18 are decreased or increased, respectively, contributing to SLC7A11 accumulation. By destabilizing or stabilizing SLC7A11, KCTD10, or USP18 inversely regulates the cystine uptake and ferroptosis. Biologically, MLN4924 combination with SLC7A11 inhibitor Imidazole Ketone Erastin (IKE) enhanced suppression of tumor growth. In human breast tumor tissues, SLC7A11 levels were negatively or positively correlated with KCTD10 or USP18, respectively. Collectively, our study defines how SLC7A11 and ferroptosis is coordinately regulated by the CRL3KCTD10/E3-USP18/DUB axis, and provides a sound rationale of drug combination to enhance anticancer efficacy.
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Cistina , Ferroptose , Pirimidinas , Ubiquitina Tiolesterase , Animais , Feminino , Humanos , Camundongos , Sistema y+ de Transporte de Aminoácidos/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Ciclopentanos/metabolismo , Ciclopentanos/farmacologia , Cistina/metabolismo , Células HEK293 , Piperazinas/farmacologia , Pirimidinas/farmacologia , Ubiquitina Tiolesterase/metabolismo , Ubiquitina Tiolesterase/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , UbiquitinaçãoRESUMO
Flooding stress is an increasingly serious problem in wetlands, often affecting large areas of crops and timber production areas. The current study aimed to explore the species differences in responses to flooding stress between Q. nuttallii and Q. palustris in an outdoor environment. All the tested plants survived after a 60-day flooding treatment that left 5 cm of water above the soil surface. This suggests that the two species are flood-tolerant, so they can be applied in the construction of riparian protection forests and wetland restoration. Compared with control conditions, flooding treatment significantly decreased seedling height and diameter and the Pn, Gs, Tr, Fv/Fm, ABS/CSm, TR0/CSm, ET0/CSm, RE0/CSm, IAA, and GA3 content and significantly increased the content of MDA, H2O2, soluble sugars, SOD, POD, ADH, ABA, and JA. Under control conditions, Q. nuttallii showed significantly greater growth and photosynthetic capability than Q. palustris. In contrast, Q. palustris exhibited less inhibition of growth and photosynthesis, oxidative stress levels, and antioxidant enzyme activities than Q. nuttallii under flooding conditions. The findings indicate that Q. palustris has better defense mechanisms against the damage caused by flooding stress than Q. nuttallii. Q. nuttallii was more sensitive and responsive to flooding than Q. palustris.
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Background: Cancer-associated fibroblasts (CAFs) constitute the primary constituents of the tumor microenvironment (TME) and exert significant influences on cancer progression. However, adequate comprehension of CAF profiles in breast cancer, as well as the precise mechanisms underlying their promotion of cancer, remains lacking. Objectives: To discerns the biological differences between normal fibroblasts (NFs) and CAFs in breast cancer and explore the underlying mechanism. Methods: Three pairs of CAFs and NFs were isolated from breast cancer patients of diverse subtypes who had not undergone prior radiotherapy or chemotherapy. Morphological characteristics of CAFs and NFs were assessed through optical and electron microscopy, their biological attributes were examined using cell counting kits and transwell assays, and their impact on breast cancer cells was simulated using a coculture system. Furthermore, the miRNA profiles of CAFs and NFs were sequenced via an Illumina HiSeq 2500 platform. Results: CAFs exhibited higher growth rate and motility than NFs and a stronger potential to promote the malignancy of breast cancer cells. RNA sequencing of both NFs and CAFs revealed differentially expressed miRNAs with notable variability among distinct patients within their NFs and CAFs, while the enrichment of the target genes of differentially expressed miRNAs within both GO terms and KEGG pathways demonstrated significant similarity across patients with different profiles. Conclusion: CAFs have greater malignancy and higher potential to influence the growth, migration, invasion and chemoresistance of cocultured breast cancer cells than NFs. In addition, the miRNAs that are differentially expressed in CAFs when compared to NFs display substantial variability across patients with distinct breast cancer subtypes, while the enrichment of target genes regulated by these miRNAs, within GO terms and KEGG pathways, remains remarkably consistent among patients with varying profiles.
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Accurate pathologic diagnosis and molecular classification of breast mass biopsy tissue is important for determining individualized therapy for (neo)adjuvant systemic therapies for invasive breast cancer. The CassiII rotational core biopsy system is a novel biopsy technique with a guide needle and a "stick-freeze" technology. The comprehensive assessments including the concordance rates of diagnosis and biomarker status between CassiII and core needle biopsy were evaluated in this study. Estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), and Ki67 were analyzed through immunohistochemistry. In total, 655 patients with breast cancer who underwent surgery after biopsy at Sir Run Run Shaw Hospital between January 2019 to December 2021 were evaluated. The concordance rates (CRs) of malignant surgical specimens with CassiII needle biopsy was significantly high compared with core needle biopsy. Moreover, CassiII needle biopsy had about 20% improvement in sensitivity and about 5% improvement in positive predictive value compared to Core needle biopsy. The characteristics including age and tumor size were identified the risk factors for pathological inconsistencies with core needle biopsies. However, CassiII needle biopsy was associated with tumor diameter only. The CRs of ER, PgR, HER2, and Ki67 using Cassi needle were 98.08% (kappa, 0.941; p<.001), 90.77% (kappa, 0.812; p<.001), 69.62% (kappa, 0.482; p<.001), and 86.92% (kappa, 0.552; p<.001), respectively. Post-biopsy complications with CassiII needle biopsy were also collected. The complications of CassiII needle biopsy including chest stuffiness, pain and subcutaneous ecchymosis are not rare. The underlying mechanism of subcutaneous congestion or hematoma after CassiII needle biopsy might be the larger needle diameter and the effect of temperature on coagulation function. In summary, CassiII needle biopsy is age-independent and has a better accuracy than CNB for distinguishing carcinoma in situ and invasive carcinoma.
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The process of lymphatic metastasis was proved to be associated with podoplanin-expressing macrophages in breast cancer (BC). This study aimed to investigate the role of the M2 phenotype of tumor-associated macrophages and mine the key M2 macrophages-related genes for lymph node metastasis in BC. We downloaded the GSE158399 dataset from the Gene Expression Omnibus (GEO) database, which includes transcriptomic profiles of individual cells from primary tumors, negative lymph nodes (NLNs), and positive lymph nodes (PLNs) of breast cancer patients. The cell subsets were identified by clustering analysis after quality control of the scRNA-seq using Seurat. The activation and migration capability of M2 macrophages were evaluated with R package "GSVA". The key M2 macrophages-related genes were screened from the differential expressed genes (DEGs) and M2 macrophages activation and migration gene sets collected from MSigDB database. Our analysis identified three main cell types in primary tumors, NLNs, and PLNs: basal cells, luminal cells, and immune cell subsets. The further cell type classification of immune cell subsets indicated M2 macrophages accumulation in NLs and PLs. The GSVA enrichment scores for activation and migration capability were increased significantly in M2 macrophages from primary tumors than NLNs and PLNs (p-value < 0.001). Seven M2 macrophages activation-related and 15 M2 macrophages migration-related genes were significantly up-regulated in primary tumors than NLNs and PLNs. The proportion and GSVA enrichment scores for activation and migration of M2 macrophages may be potential markers for lymph node metastasis in breast cancer. Our study demonstrated that twenty-two up-regulated mRNA may be possible therapeutic targets for lymph node metastasis in breast cancer.
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Neoplasias da Mama , Macrófagos Associados a Tumor , Humanos , Feminino , Neoplasias da Mama/genética , Metástase Linfática , Análise da Expressão Gênica de Célula Única , FenótipoRESUMO
Neocaridina denticulata sinensis is a crustacean of major economic significance in the Baiyangdian drainage area. In this study, the first assessment of N. denticulata sinensis genetic diversity and population structure was performed based on sequence analysis of nine polymorphic microsatellite loci and the mitochondrial cytochrome oxidase subunit I (cox1) gene. Samples (n = 192) were collected from four different regions in the Baiyangdian drainage area i.e., Baiyangdian Lake, Jumahe River, Xidayang Reservoir, and Fuhe River. Microsatellite loci analysis identified high levels of genetic diversity represented by observed heterozygosity (Ho) of 0.6865 â¼ 0.9583, expected heterozygosity (He) of 0.7151 â¼ 0.8723, and polymorphism information content (PIC) of 0.6676 â¼ 0.8585. Based on the analysis of cox1 sequences, haplotype diversity (Hd) ranged from 0.568 to 0.853 while nucleotide diversity (π) ranged from 0.0029 to 0.2236. Furthermore, there was no evidence of expansion events in the N. denticulata sinensis populations. Pairwise FST revealed pronounced genetic differentiation, and clustering analyses showed defined genetic structures within the N. denticulata sinensis population. Three groups were identified from four sampled stocks, with Xidayang Reservoir, and Fuhe River populations clustered in the same group. This work identified novel molecular markers and provided an important reference to guide management strategies to assist conservation of N. denticulata sinensis resources.
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Decápodes , Polimorfismo Genético , Animais , Decápodes/genética , Genes Mitocondriais , Haplótipos , Repetições de Microssatélites/genética , China , Variação GenéticaRESUMO
Sepsis often causes cell death via pyroptosis and hence results in septic cardiomyopathy. Triggering receptors expressed in myeloid cells-1 (TREM-1) may initiate cellular cascade pathways and, in turn, induce cell death and vital organ dysfunction in sepsis, but the evidence is limited. We set to investigate the role of TREM-1 on nucleotide-binding oligomerization domain-like receptors with pyrin domain-3 (NLRP3) inflammasome activation and cardiomyocyte pyroptosis in sepsis models using cardiac cell line (HL-1) and mice. In this study, TREM-1 was found to be significantly increased in HL-1 cells challenged with lipopolysaccharide (LPS). Pyroptosis was also significantly increased in the HL-1 cells challenged with lipopolysaccharide and an NLRP3 inflammasome activator, nigericin. The close interaction between TREM-1 and structural maintenance of chromosome 4 (SMC4) was also identified. Furthermore, inhibition of TREM-1 or SMC4 prevented the upregulation of NLRP3 and decreased Gasdermin-D, IL-1ß and caspase-1 cleavage. In mice subjected to caecal ligation and puncture, the TREM-1 inhibitor LR12 decreased the expression of NLRP3 and attenuated cardiomyocyte pyroptosis, leading to improved cardiac function and prolonged survival of septic mice. Our work demonstrates that, under septic conditions, TREM-1 plays a critical role in cardiomyocyte pyroptosis. Targeting TREM-1 and its associated molecules may therefore lead to novel therapeutic treatments for septic cardiomyopathy.
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Inflamassomos , Miócitos Cardíacos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Piroptose , Sepse , Receptor Gatilho 1 Expresso em Células Mieloides , Animais , Humanos , Camundongos , Adenosina Trifosfatases/imunologia , Cardiomiopatias/etiologia , Cardiomiopatias/genética , Cardiomiopatias/imunologia , Caspase 1/genética , Proteínas Cromossômicas não Histona/genética , Proteínas Cromossômicas não Histona/imunologia , Cromossomos Humanos Par 4/imunologia , Inflamassomos/agonistas , Inflamassomos/genética , Inflamassomos/imunologia , Lipopolissacarídeos/efeitos adversos , Lipopolissacarídeos/farmacologia , Células Mieloides/imunologia , Miócitos Cardíacos/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/agonistas , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Piroptose/genética , Piroptose/imunologia , Sepse/complicações , Sepse/genética , Sepse/imunologia , Receptor Gatilho 1 Expresso em Células Mieloides/antagonistas & inibidores , Receptor Gatilho 1 Expresso em Células Mieloides/genética , Receptor Gatilho 1 Expresso em Células Mieloides/imunologiaRESUMO
Introduction: Small cell lung cancer (SCLC) transformation serves as a significant mechanism of resistance to tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. To address this clinical challenge, we conducted a retrospective analysis at Zhejiang University School of Medicine, the First Affiliated Hospital, focusing on patients with EGFR sensitizing mutations. Methods: A total of 1012 cases were included in this retrospective analysis. The cohort primarily consisted of patients with EGFR sensitizing mutations. Biopsy-confirmed small cell transformation was observed in seven patients, accounting for 0.7% of the cases. All patients in this subset were initially diagnosed with stage IV adenocarcinoma (ADC), with four cases classified as poorly differentiated and three as moderately to poorly differentiated ADC. EGFR exon 19 deletions were identified in five of these cases. Next-generation sequencing (NGS) was performed on seven cases, revealing mutations in the tumor protein p53 (TP53) gene in four cases and loss of the retinoblastoma1 (RB1) gene in three cases. Results: The median duration from the initial diagnosis to small cell transformation was 35.9 months (interquartile range: 12.1-84 months). Following small cell transformation during EGFR inhibition, all patients received etoposide/platinum-based treatment, leading to a median progression-free survival (PFS) of 4.7 months (interquartile range: 2.7-10.1 months). Notably, most patients in this series had poorly differentiated adenocarcinomas at the outset. TP53 mutations and RB1 loss were common genetic alterations observed in patients with small cell transformation in this cohort. Discussion: The findings underscore the clinical significance of SCLC transformation as a resistance mechanism to EGFR TKIs in NSCLC with EGFR mutations. The observed genetic alterations, including TP53 mutations and RB1 loss, suggest potential associations with the transformation process and warrant further investigation. Understanding the genetic landscape and clinical outcomes in patients experiencing small cell transformation can contribute to improved strategies for managing resistance in EGFR-mutant NSCLC.
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BACKGROUND: Triple-negative breast cancer is characterized by a poor prognosis and lack of targeted treatments, and thus, new targeting markers and therapeutic strategies are urgently needed. We previously indicated that PLAC8 promotes tumorigenesis and exerts multidrug resistance in breast cancer. Therefore, we aimed to characterize the PLAC8-regulated network in triple-negative breast cancer. METHODS: We measured the levels of PLAC8 in breast cancer cell lines and found that PLAC8 is post-translationally modified by ubiquitin-fold modifier 1 (UFM1). Then, we revealed a new regulatory system of PD-L1 by PLAC8 in triple-negative breast cancer. We also tested the molecular functions of PLAC8 in triple-negative breast cancer cell lines and measured the expression of PLAC8 and PD-L1 in breast cancer tissues. RESULTS: PLAC8 was generally highly expressed in triple-negative breast cancer and could be modified by UFM1, which maintains PLAC8 protein stability. Moreover, PLAC8 could promote cancer cell proliferation and affect the immune response by regulating the level of PD-L1 ubiquitination. Additionally, among patients with breast cancer, the expression of PLAC8 was higher in triple-negative breast cancer than in non-triple-negative breast cancer and positively correlated with the level of PD-L1. CONCLUSIONS: Our current study discoveries a new PLAC8-regulated network in triple-negative breast cancer and provides corresponding guidance for the clinical diagnosis and immunotherapy of triple-negative breast cancer.
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Antígeno B7-H1 , Neoplasias de Mama Triplo Negativas , Humanos , Antígeno B7-H1/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Imunoterapia , Imunidade , Proliferação de Células , Proteínas/uso terapêuticoRESUMO
AIM: We aim to explore the status of nurses' ethical behaviours in clinical practice and what contributes to nurses' unethical behaviours. BACKGROUND: Nurses' ethical behaviours strongly impact the nurse-patient relationship and the quality of nursing services. Therefore, we must understand the status of clinical nurses' ethical behaviours and the causes of nurses' unethical behaviours. METHODS: Focus group and in-depth semistructured interviews were conducted with 21 head nurses and nine nurses, respectively. The data were analysed by content analysis. RESULTS: The analysis revealed seven themes: lack of awareness of the protection of patients' privacy; violation of patients' autonomy; improper communication; failure to protect the patient's best interests; lack of moral emotion; lack of psychological care for special patients; and causes of unethical behaviour. CONCLUSIONS: The present situation of ethical nursing behaviour is not optimistic, and there are still many unethical nursing behaviours in clinical work. There are many reasons for unethical behaviours. Efforts should be made related to nurses, patients, workload, the ethical climate and rules and regulations to improve the situation. IMPLICATIONS FOR NURSING MANAGEMENT: Nursing managers can improve ethical behaviour by strengthening nurses' ethics studies, enhancing nurses' professional identity and social status, optimizing the allocation of nursing human resources, creating a good ethical climate and improving relevant rules and regulations.
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Atitude do Pessoal de Saúde , Ética em Enfermagem , Humanos , Princípios Morais , Pesquisa Qualitativa , Hospitais , ChinaRESUMO
Circulating tumor cells (CTCs) are cells that shed from a primary tumor and travel through the bloodstream. Studying the functional and molecular characteristics of CTCs may provide in-depth knowledge regarding highly lethal tumor diseases. Researchers are working to design devices and develop analytical methods that can capture and detect CTCs in whole blood from cancer patients with improved sensitivity and specificity. Techniques using whole blood samples utilize physical prosperity, immunoaffinity or a combination of the above methods and positive and negative enrichment during separation. Further analysis of CTCs is helpful in cancer monitoring, efficacy evaluation and designing of targeted cancer treatment methods. Although many advances have been achieved in the detection and molecular characterization of CTCs, several challenges still exist that limit the current use of this burgeoning diagnostic approach. In this review, a brief summary of the biological characterization of CTCs is presented. We focus on the current existing CTC detection methods and the potential clinical implications and challenges of CTCs. We also put forward our own views regarding the future development direction of CTCs.
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Abnormal neddylation activation is frequently observed in human cancers and neddylation inhibition has been proposed as a therapy for cancer. Here, we report that MLN4924, a small-molecule inhibitor of neddylation activating enzyme, increases glutamine uptake in breast cancer cells by causing accumulation of glutamine transporter ASCT2/SLC1A5, via inactivation of CRL3-SPOP E3 ligase. We show the E3 ligase SPOP promotes ASCT2 ubiquitylation, whereas SPOP itself is auto-ubiquitylated upon glutamine deprivation. Thus, SPOP and ASCT2 inversely regulate glutamine uptake and metabolism. SPOP knockdown increases ASCT2 levels to promote growth which is rescued by ASCT2 knockdown. Adding ASCT2 inhibitor V-9302 enhances MLN4924 suppression of tumor growth. In human breast cancer specimens, SPOP and ASCT2 levels are inversely correlated, whereas lower SPOP with higher ASCT2 predicts a worse patient survival. Collectively, our study links neddylation to glutamine metabolism via the SPOP-ASCT2 axis and provides a rational drug combination for enhanced cancer therapy.
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Neoplasias da Mama , Proteínas Nucleares , Proteínas Repressoras , Ubiquitina-Proteína Ligases , Sistema ASC de Transporte de Aminoácidos/genética , Sistema ASC de Transporte de Aminoácidos/metabolismo , Linhagem Celular Tumoral , Feminino , Glutamina/metabolismo , Humanos , Antígenos de Histocompatibilidade Menor/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Triple-negative breast cancer is still a difficult point in clinical treatment at present, and a deep study of its pathogenesis has great clinical value. Therefore, our research mainly focuses on exploring the progression of triple-negative breast cancer and determines the important role of the HJURP/YAP1/NDRG1 transcriptional regulation axis in triple-negative breast cancer. We observed significantly increased HJURP expression levels in triple-negative breast cancer compared to other subtypes. HJURP could affect the level of ubiquitination modification of YAP1 protein and then regulate its downstream transcriptional activity. Mechanistically, we found that YAP1 positively regulates NDRG1 transcription by binding the promoter region of the NDRG1 gene. And HJURP/YAP1/NDRG1 axis could affect cell proliferation and chemotherapy sensitivity in triple-negative breast cancer. Taken together, these findings provide insights into the transcriptional regulation axis of HJURP/YAP1/NDRG1 in triple-negative breast cancer progression and therapeutic response.
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Proteínas de Ligação a DNA/metabolismo , Neoplasias de Mama Triplo Negativas , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Transcrição Gênica , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Proteínas de Sinalização YAPRESUMO
[This corrects the article DOI: 10.3389/fonc.2021.697950.].
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Ferroptosis, which is characterized by intracellular iron accumulation and lipid peroxidation, is a newly described form of regulated cell death that may play a key role in tumour suppression. In the present study, we investigated the expression profiles and biological effects of fascin actin-bundling protein 1 (Fascin, gene name FSCN1) in breast cancer. In addition, bioinformatics analysis of the TCGA cancer database and gain- and loss-of-function studies showed that Fascin enhances sensitivity to erastin-induced ferroptosis. Mechanistically, Fascin directly interacts with cysteine/glutamate transporter (xCT, gene name SLC7A11) and decreases its stability via the ubiquitin-mediated proteasome degradation pathway. Furthermore, we observed that Fascin is substantially upregulated in tamoxifen-resistant breast cancer cell lines, and drug-resistant cells were also more vulnerable to erastin-induced ferroptosis. Taken together, our findings reveal a previously unidentified role of Fascin in ferroptosis by regulating xCT. Thus, ferroptosis activation in breast cancer with high Fascin level may serve as a potential treatment.
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Neoplasias da Mama , Proteínas de Transporte , Ferroptose , Proteínas dos Microfilamentos , Piperazinas , Neoplasias da Mama/genética , Proteínas de Transporte/genética , Linhagem Celular Tumoral , Feminino , Ferroptose/genética , Humanos , Proteínas dos Microfilamentos/genética , Piperazinas/farmacologiaRESUMO
Multiple myeloma is an incurable malignancy with marked clinical and genetic heterogeneity. The cytogenetic abnormality t(4;14) (p16.3;q32.3) confers aggressive behavior in multiple myeloma. Recently, essential oncogenic drivers in a wide range of cancers have been shown to be controlled by super-enhancers (SE). We used chromatin immunoprecipitation sequencing of the active enhancer marker histone H3 lysine 27 acetylation (H3K27ac) to profile unique SEs in t(4;14)-translocated multiple myeloma. The histone chaperone HJURP was aberrantly overexpressed in t(4;14)-positive multiple myeloma due to transcriptional activation by a distal SE induced by the histone lysine methyltransferase NSD2. Silencing of HJURP with short hairpin RNA or CRISPR interference of SE function impaired cell viability and led to apoptosis. Conversely, HJURP overexpression promoted cell proliferation and abrogated apoptosis. Mechanistically, the NSD2/BRD4 complex positively coregulated HJURP transcription by binding the promoter and active elements of its SE. In summary, this study introduces SE profiling as an efficient approach to identify new targets and understand molecular pathogenesis in specific subtypes of cancer. Moreover, HJURP could be a valuable therapeutic target in patients with t(4;14)-positive myeloma. SIGNIFICANCE: A super-enhancer screen in t(4;14) multiple myeloma serves to identify genes that promote growth and survival of myeloma cells, which may be evaluated in future studies as therapeutic targets.
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Proteínas de Ligação a DNA/metabolismo , Mieloma Múltiplo/genética , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Regulação para CimaRESUMO
AIM: To explore the experiences of nurses' work stress related to COVID-19 regular epidemic prevention and control in China. BACKGROUND: The global COVID-19 epidemic is still severe, and China's ongoing regular epidemic prevention and control still cannot be relaxed, which places demands on nurses. METHODS: Thirty nurses and eight nurse managers were interviewed using semistructured in-depth interviews, and the data were analysed by the Colaizzi seven-step analysis method. RESULTS: Four themes were extracted as follows: environmental factors, organizational factors, personal factors and positive factors in coping with stress. CONCLUSIONS: Nursing managers should pay attention to construction of the first-line departments of regular epidemic prevention and control. The shortage of nurses' human resources and the increase of nurse-patient conflicts are problems that need to be solved urgently. In addition, this research also emphasizes the importance of promoting nurses' stress-related growth and thinking about the possibility of reform. IMPLICATIONS FOR NURSING MANAGEMENT: The construction of the hospital environment and increasing the resilience of nursing teams require attention. We should attach importance to the training of nurses' communication skills and provide sufficient organizational support and economic guarantees for nurses. Finally, perhaps we should also consider whether it is necessary to reform the relevant hospital systems and how to reform them.
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COVID-19 , Enfermeiros Administradores , Enfermeiras e Enfermeiros , Recursos Humanos de Enfermagem Hospitalar , COVID-19/epidemiologia , COVID-19/prevenção & controle , China/epidemiologia , Humanos , Pesquisa Qualitativa , SARS-CoV-2RESUMO
Autophagy and ferroptosis have been major foci of biomedical research in recent years. Elucidation of their intrinsic molecular relationships is important for cancer prevention and treatment. Metformin can directly inhibit tumorigenesis, although the mechanism responsible for this is not fully understood. Here, we demonstrate that metformin and lncRNA-H19 can regulate both autophagy and ferroptosis. Autophagy inducers and H19 can reverse the production of lipid reactive oxygen species and the inhibition of autophagy induced by metformin. The present study suggests that metformin may induce ferroptosis by inhibiting autophagy via H19, and this discovery may facilitate the development of novel therapies for the treatment of breast cancer.