Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 43
Filtrar
1.
Front Microbiol ; 15: 1453162, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39228385

RESUMO

The surge in global energy demand mandates a significant expansion of electric power substations. Nevertheless, the ecological consequences of electric power substation operation, particularly concerning the electromagnetic field, on soil microbial communities and nitrogen enrichment remain unexplored. In this study, we collected soil samples from six distinct sites at varying distances from an electric power substation in Xintang village, southeastern China, and investigated the impacts of electromagnetic field on the microbial diversity and community structures employing metagenomic sequencing technique. Our results showed discernible dissimilarities in the fungal community across the six distinct sites, each characterized by unique magnetic and electric intensities, whereas comparable variations were not evident within bacterial communities. Correlation analysis revealed a diminished nitrogen fixation capacity at the site nearest to the substation, characterized by low moisture content, elevated pH, and robust magnetic induction intensity and electric field intensity. Conversely, heightened nitrification processes were observed at this location compared to others. These findings were substantiated by the relative abundance of key genes associated with ammonium nitrogen and nitrate nitrogen production. This study provides insights into the relationships between soil microbial communities and the enduring operation of electric power substations, thereby contributing fundamental information essential for the rigorous environmental impact assessments of these facilities.

2.
JAMA Intern Med ; 184(5): 573-574, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38558109

RESUMO

This case report describes a patient in their 70s presenting to the hospital with dyspnea and fatigue.


Assuntos
Eletrocardiografia , Humanos
3.
J Med Chem ; 67(7): 5945-5956, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38504504

RESUMO

Multivalent glycosidase inhibitors based on 1-deoxynojirimycin derivatives against α-glucosidases have been rapidly developed. Nonetheless, the mechanism based on self-assembled multivalent glucosidase inhibitors in living systems needs to be further studied. It remains to be determined whether the self-assembly possesses sufficient stability to endure transit through the small intestine and subsequently bind to the glycosidases located therein. In this paper, two amphiphilic compounds, 1-deoxynojirimycin and α-peptoid conjugates (LP-4DNJ-3C and LP-4DNJ-6C), were designed. Their self-assembling behaviors, multivalent α-glucosidase inhibition effect, and fluorescence imaging on living organs were studied. LP-4DNJ-6C exhibited better multivalent α-glucosidase inhibition activities in vitro. Moreover, the self-assembly of LP-4DNJ-6C could effectively form a complex with Nile red. The complex showed fluorescence quenching effect upon binding with α-glucosidases and exhibited potent fluorescence imaging in the small intestine. This result suggests that a multivalent hypoglycemic effect achieved through self-assembly in the intestine is a viable approach, enabling the rational design of multivalent hypoglycemic drugs.


Assuntos
1-Desoxinojirimicina , Hipoglicemiantes , Hipoglicemiantes/farmacologia , Hipoglicemiantes/metabolismo , 1-Desoxinojirimicina/farmacologia , alfa-Glucosidases/metabolismo , Inibidores Enzimáticos/farmacologia , Glicosídeo Hidrolases , Inibidores de Glicosídeo Hidrolases/farmacologia
4.
Complement Ther Clin Pract ; 55: 101828, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38241803

RESUMO

BACKGROUND AND PURPOSE: Post-stroke depression (PSD) has major implications for rehabilitation, motor recovery, activities of daily living, social and interpersonal functioning, and mortality. In view of the side effects of antidepressants, aromatherapy, a widely used non-pharmacological therapy, has received growing attention in recent years for its benefits of reduced complications, accessibility, and effectiveness. This study was designed to assess the effects of inhalation aromatherapy with lavender essential oil on depression and sleep quality in patients with PSD. MATERIALS AND METHODS: Forty patients with PSD were enrolled and randomized into experimental and placebo groups. Experimental-group patients inhaled microencapsulated lavender essential oil every night at bedtime over a period of 4 weeks. A nonwoven bag containing 2.3 g of microcapsules with about 1.5 g of lavender essential oil was placed on or under the patient's pillow, depending on the patient's scent sensitivity. Placebo-group patients used the empty nonwoven bags for the same period as the experimental group. The 17-item Hamilton Rating Scale for Depression (HAMD-17), the Zung Self-Rating Depression Scale (SDS), and the Pittsburgh Sleep Quality Index (PSQI) were used to measure outcomes. RESULTS: The HAMD-17 score, SDS score, and PSQI score showed statistically significant differences between both groups before and after intervention (P ≤ 0.01). The improvement in the experimental group was more marked than in the placebo group (P < 0.05). CONCLUSION: Lavender essential oil inhalation aromatherapy may help reduce depression and improve sleep quality in patients with PSD.


Assuntos
Aromaterapia , Lavandula , Óleos Voláteis , Humanos , Qualidade do Sono , Atividades Cotidianas , Método Simples-Cego , Depressão/tratamento farmacológico , Depressão/etiologia , Óleos Voláteis/uso terapêutico , Óleos de Plantas/uso terapêutico
5.
ACS Omega ; 8(18): 16251-16262, 2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37179598

RESUMO

To eliminate internal defects of grains developed during melt-cast charging, the formation mechanism and the trend of crystal morphology of internal defects of 2,4,6-trinitrotoluene and 2,4-dinitroanisole-based melt-cast explosives under different process conditions were simulated. The effects of solidification treatment on melt-cast explosive molding quality were investigated by combining pressurized feeding, head insulation, and water bath cooling. The single pressurized treatment technology results showed that grains were exposed to layer-by-layer solidification from outside to inside, resulting in V-shaped shrink areas of the contract cavity in the core. The defect area was proportional to the treatment temperature. However, the combination of treatment technologies, such as head insulation and water bath cooling, promoted longitudinal gradient solidification of the explosive and controllable migration of its internal defects. Moreover, the combined treatment technologies effectively improved the heat transfer efficiency of the explosive with the help of a water bath to reduce the solidification time, thus achieving highly efficient equal-material manufacturing of microdefect or zero-defect grains.

6.
Cell Death Dis ; 13(10): 843, 2022 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-36192394

RESUMO

Abnormality of enhancer regulation has emerged as one of the critical features for cancer cells. KDM5C is a histone H3K4 demethylase and frequently mutated in several types of cancer. It is critical for H3K4me3 and activity of enhancers, but its regulatory mechanisms remain elusive. Here, we identify TRIM11 as one ubiquitin E3 ligase for KDM5C. TRIM11 interacts with KDM5C, catalyzes K48-linked ubiquitin chain on KDM5C, and promotes KDM5C degradation through proteasome. TRIM11 deficiency in an animal model represses the growth of breast tumor and stabilizes KDM5C. In breast cancer patient tissues, TRIM11 is highly expressed and KDM5C is lower expressed, and their expression is negatively correlated. Mechanistically, TRIM11 regulates the enhancer activity of genes involved in cell migration and immune response by targeting KDM5C. TRIM11 and KDM5C regulate MCAM expression and cell migration through targeting H3K4me3 on MCAM enhancer. Taken together, our study reveals novel mechanisms for enhancer regulation during breast cancer tumorigenesis and development.


Assuntos
Histonas , Neoplasias , Animais , Carcinogênese/genética , Linhagem Celular Tumoral , Histona Desmetilases/genética , Histona Desmetilases/metabolismo , Histonas/genética , Histonas/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinas/metabolismo
7.
Affect Sci ; 3(2): 498-504, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36046000

RESUMO

Recent evidence has shown that Western parents are five times more vulnerable to developing parental burnout than parents in other parts of the world. It has also been found that this augmented susceptibility is explained by the group tendency of individualism cultural value that prevails in Western societies. Still, whether this relation observed at the group mean level across countries can be generalized to the association of personal value with parental burnout across individuals has not yet been explored. In order to address this question, the current study collected a sample of 643 Polish parents and assessed their report of value priorities and parental burnout. The results demonstrated that individual-level values indeed predict susceptibility to parental burnout. Specifically, parents are more susceptible to parental burnout when prioritizing values that emphasize power and achievement, whereas prioritizing benevolence protects parents from parental burnout. Associations between parents' gender, personal values, and parental burnout were also examined. Consistent with previous studies, fathers reported fewer parental burnout symptoms compared to mothers. However, gender differences in parental burnout were not mediated by personal values, nor did parents' gender moderate the effect of personal values on burnout. In sum, together with previous results obtained at the society level, our finding points out the role of values in predicting parental burnout. A possible future direction of research was discussed: examining the affective mechanism (e.g. parental regulation of emotions) underlying the relationship between personal values and parental burnout. Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-022-00103-y.

8.
Disaster Med Public Health Prep ; 17: e256, 2022 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-36017705

RESUMO

BACKGROUND: The outbreak has had a devastating impact, and efforts are underway to speed up vaccination. The study's objective was to describe the clinical characteristics of the coronavirus disease 2019 (COVID-19) vaccination clinic in the Second People's Hospital of Fujian Province, China. Meanwhile, we monitored all the vaccine recipients to evaluate adverse reactions. METHODS: A cross-sectional study was done at the COVID-19 Vaccination Clinic, the Second People's Hospital of Fujian Province, China. We systematically collected Clinical data from the COVID-19 vaccination clinic between March 11 and November 11, 2021, including the type of vaccine, number of doses, gender, age, educational level, occupational category, adverse reactions, etc. Investigators will contact vaccine recipients by means of phone call or WeChat message to record the negative responses. Last, this report covers data through 8 mo, so it will be better to Evaluate the Safety of 2 inactivated COVID-19 vaccines from China (BBIBP-CorV [Beijing Institute of Biological Products, Beijing, China] and CoronaVac [Sinovac Life Sciences, Beijing, China]). RESULTS: The results indicated that the Second People's Hospital of Fujian Province received a total of 64,602 COVID-19 vaccines from March 11 to November 11, 2021, including 34,331 (53.14%) first doses, 29,245 (45.27%) second doses, and 1026 (1.59%) third doses. This study found the highest proportion in other personnel (38.69% at the first dose, 38.75% at the second dose, and 2.44% at the third dose), who were mainly retirees. People with higher levels of education are more likely to be vaccinated against COVID-19 during the early stages of vaccine rollout. In terms of age stratification, the highest proportion was found among people aged 18-49 (BBIBP-CorV: first dose 61%, second dose 62.6%, and third dose 76.8%; CoronaVac: first dose 66.1%, double dose 63.6%, and third dose 75.5%), followed by those over 60. The common adverse reactions were mainly local and systemic, and there were some differences between the 2 inactivated vaccines (P < 0.05). CONCLUSIONS: This is the first study to analyze the actual status of hospitals as COVID-19 vaccination clinics in China. The hospital has focused on vaccinating citizens and the initial rollout of vaccines to ensure any safety issues are identified. More citizens are willing to vaccinate in hospitals because of the uncertain safety of the available vaccines and adverse reactions. The good news is that vaccine-related severe adverse events have not been found in the hospital vaccination clinic. The Safety of BBIBP-CorV and CoronaVac is relatively high.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , Vacinas contra COVID-19/efeitos adversos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos Transversais , China/epidemiologia , Hospitais , Vacinas de Produtos Inativados , Vacinação/efeitos adversos
9.
Br J Clin Psychol ; 61(4): 1089-1102, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35852015

RESUMO

OBJECTIVES: Parental burnout is a prevalent condition that affects parents' functioning and health. While various protective factors have been examined, little is known about their interplay. In the current study, we examined the joint effect of two protective factors against parental burnout (one external-social support and one internal-cognitive reappraisal). We were specifically interested in whether the presence of one factor could compensate for the lack of the other. METHODS: To address this question, 1835 participants were drawn from five countries: United States, Poland, Peru, Turkey and Belgium. RESULTS: Results suggested that both social support and cognitive reappraisal were associated with lower parental burnout. An interaction was also found between the resource factors, such that the presence of cognitive reappraisal compensated for the absence of social support. CONCLUSIONS: These findings point to ways in which parental burnout could be reduced, especially in situations where social support is not easily available.


Assuntos
Esgotamento Psicológico , Pais , Esgotamento Psicológico/psicologia , Humanos , Pais/psicologia , Apoio Social
10.
Zhongguo Yi Liao Qi Xie Za Zhi ; 46(3): 302-306, 2022 May 30.
Artigo em Chinês | MEDLINE | ID: mdl-35678441

RESUMO

Hyperbaric oxygen therapy is a method of breathing pure oxygen or high-concentration oxygen in a highpressure environment to treat hypoxic diseases and related diseases. According to clinical verification, this therapy has an irreplaceable effect on certain diseases and has gradually become a comprehensive clinical treatment. One of the main methods of certain diseases is widely recognized by the medical field at home and abroad. The development history, treatment principles, key technologies, and future development trends of hyperbaric oxygen are discussed in detail, provide a research direction for the development of hyperbaric oxygen therapy in the future, and at the same time, it has also improved physicians' awareness of hyperbaric oxygen therapy, so as to improving Industry influence.


Assuntos
Oxigenoterapia Hiperbárica , Oxigênio/uso terapêutico , Projetos de Pesquisa
11.
Complement Ther Clin Pract ; 48: 101596, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35483297

RESUMO

BACKGROUND AND PURPOSE: Post-stroke depression (PSD) has an important impact on rehabilitation, motor recovery, daily activities, social and interpersonal life, and mortality. This study aimed to evaluate the effects of auricular acupressure (AurPrs) on depression in PSD patients. MATERIALS AND METHODS: Fifty-six PSD patients were recruited and randomly assigned to the AurPrs group (receiving AurPrs treatment) or the sham group (receiving sham AurPrs treatment). The outcome was measured by the 17-item Hamilton Rating Scale for Depression (HAMD-17), Zung Self-Rating Depression Scale (SDS), and World Health Organization Quality of Life Brief Version (WHOQOL-BREF). RESULTS: There was a statistically significant difference in HAMD-17 score, SDS score and WHOQOL-BREF score between both groups before and after treatment (P < 0.01). The improvement of the AurPrs group was more obvious than that of the sham group (P < 0.05). CONCLUSION: AurPrs could help to reduce depression levels and improve the quality of life in patients with PSD.


Assuntos
Acupressão , Acidente Vascular Cerebral , Depressão/etiologia , Depressão/terapia , Humanos , Qualidade de Vida , Método Simples-Cego , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Resultado do Tratamento
12.
Sci Rep ; 12(1): 4156, 2022 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-35264680

RESUMO

The transition from the geometry to the mesh can be rather difficult, manual and time-consuming, especially for the large scale complex structures. The procedure of mesh generation needs massive human intervention making the automatic engineering analyses of structures from CAD geometry models hardly possible. This paper focuses on implementing a polyhedron element with arbitrary convex topology based on the Scaled Boundary Finite Element Method (SBFEM) in ABAQUS on the strength of the interface of UEL (the subroutine to define a general user-defined element) for automatic dynamic analyses of three-dimensional structures. This implementation empowers ABAQUS to analyze any model with arbitrary polyhedron elements. When the geometry of a structure is obtained from CAD, the dynamic analyses can be launched seamlessly and automatically. Cases of a cantilever subjected to a dynamic harmonic excitation with the traditional hexahedron element and this polyhedron element are compared to verify the accuracy of the UEL. Taking a practical example of the Soil-Structure Interaction analysis of a Nuclear Power Plant, the applicability and performance of this implementation are tested. The results of the two examples confirm that this polyhedron element based on SBFEM can be more accurate using much less degrees of freedom and its implementation in ABAQUS is robust and compatible.


Assuntos
Análise de Elementos Finitos , Simulação por Computador , Humanos , Matemática
13.
Cell Biol Toxicol ; 38(6): 1079-1096, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-34755307

RESUMO

The modern categories of endogenous non-coding RNAs, namely circular RNAs (circRNAs), involved within the carcinogenesis and progression of various human cancers. The fundamental aim of the current investigation was the evaluation of the hsa_circ_0014130 expressions, their biological functions, and potential regulatory network in bladder cancer. The level of expression for hsa_circ_0014130 was evaluated by qRT-PCR, and its relationships to clinicopathological features and survival outcomes of cases experiencing cancer of the bladder were scrutinized. The impact of hsa_circ_0014130 expressions on biological attitudes of bladder cancer cells in vitro was investigated. The interactions between hsa_circ_0014130 and microRNA (miRNA) sponge, miRNA, and its direct targets were determined by RNA pull-down as well as luciferase reporter gene assay. The correlations of their expression were determined by Pearson's correlation analysis. Rescue experiments were carried out to identify the biological roles of the regulation network. The expressions of hsa_circ_0014130 were markedly ameliorated in bladder cancer samples and linked with aggressive characteristics and unfavorable survival. Ectopic expression of hsa_circ_0014130 clearly enhanced the differentiation, proliferative, migratory, invasive potential of the cell in bladder cancer, and the development of tumor xenograft in vivo, while malignant biological behaviors were inhibited by hsa_circ_0014130 knockdown. The expression of hsa_circ_0014130 was tied to miR-132-3p in a negative manner with the cells and tissues of bladder cancer. hsa_circ_0014130 function as a competitive endogenous RNA for miR-132-3p to play oncogenic roles in bladder cancer cells. On the other hand, KCNJ12 was a straightforward target of miR-132-3p at the downstream, and the expressions of KCNJ12 were inversely related to that of miR-132-3p. Furthermore, a significantly positive correlation was found between hsa_circ_0014130 and KCNJ12 mRNA expression. More importantly, the oncogenic impact of hsa_circ_0014130 on bladder cancer cells was partly suppressed by ectopic expression of miR-132-3p or KCNJ12 knockdown. The underlined data revealed that hsa_circ_0014130 exerted its biological roles by regulating miR-132-3p/KCNJ12 expression. Further research revealed hsa_circ_0014130/miR-132-3p/KCNJ12 axis has participated in the Epithelial-mesenchymal transition (EMT) progress and GSK3ß/AKT signaling pathway. hsa_circ_0014130 works as a sponge of miR-132-3p to advance the oncogenesis and metastasis of bladder cancer by regulation of the KCNJ12 expression. These achievements might ameliorate the comprehension of tumor pathogenesis and provide novel therapeutic targets for cancer of the bladder.


Assuntos
MicroRNAs , Canais de Potássio Corretores do Fluxo de Internalização , RNA Circular , Neoplasias da Bexiga Urinária , Humanos , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/genética , MicroRNAs/genética , RNA Circular/genética , Neoplasias da Bexiga Urinária/genética , Canais de Potássio Corretores do Fluxo de Internalização/genética
14.
PLoS One ; 16(12): e0261566, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34919581

RESUMO

An air-fluid level within a gastrointestinal stromal tumor (GIST) is unusual and indicates the presence of a fistula within the lumen of the GI tract. Until recently, the optimal management of such patients was not clear-cut. This retrospective study investigated the clinicopathological characteristics, surgical procedures, pre-and post-operative management, and prognosis of patients with GIST containing an air-fluid level. Data of GIST patients, spanning 5 years, including 17 GIST patients with air-fluid levels in the experimental group and 34 GIST patients without air-fluid levels in the control group, were retrieved from two hospitals in China. The clinicopathological characteristics, types of surgery, management, and clinical outcomes of GIST patients were compared between the two groups. GISTs containing air-fluid levels were significantly different from GISTs without air-fluid levels regarding tumor morphology, NIH risk category, invasion of adjacent organs, and necrosis or ulceration. Most GIST patients with air-fluid levels (14/17, 82.4%) received open surgery, significantly higher than the 20.6% in the control group. Targeted therapy with Imatinib mesylate (IM) was implemented in all GIST patients in the experimental group (17/17, 100%); markedly higher than those (3/34, 8.8%) in the control group. During follow-up, recurrence and death rates (5.9% and 5.9%) in the experimental group were higher than those (2.9% and 0%) in the control group. Open surgery is commonly performed in GIST patients with air-fluid levels who also require targeted therapy with IM. The Torricelli-Bernoulli sign could be a risk factor, adversely affecting the patient's prognosis.


Assuntos
Fístula do Sistema Digestório/cirurgia , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/patologia , Trato Gastrointestinal/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Fístula do Sistema Digestório/patologia , Feminino , Neoplasias Gastrointestinais/cirurgia , Tumores do Estroma Gastrointestinal/cirurgia , Trato Gastrointestinal/cirurgia , Humanos , Mesilato de Imatinib/uso terapêutico , Mucosa Intestinal/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
16.
PLoS Pathog ; 17(9): e1009918, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34529741

RESUMO

Under RNA virus infection, retinoic acid-inducible gene I (RIG-I) in host cells recognizes viral RNA and activates the expression of type I IFN. To investigate the roles of protein methyltransferases and demethylases in RIG-I antiviral signaling pathway, we screened all the known related enzymes with a siRNA library and identified LSD1 as a positive regulator for RIG-I signaling. Exogenous expression of LSD1 enhances RIG-I signaling activated by virus stimulation, whereas its deficiency restricts it. LSD1 interacts with RIG-I, promotes its K63-linked polyubiquitination and interaction with VISA/MAVS. Interestingly, LSD1 exerts its function in antiviral response not dependent on its demethylase activity but through enhancing the interaction between RIG-I with E3 ligases, especially TRIM25. Furthermore, we provide in vivo evidence that LSD1 increases antiviral gene expression and inhibits viral replication. Taken together, our findings demonstrate that LSD1 is a positive regulator of signaling pathway triggered by RNA-virus through mediating RIG-I polyubiquitination.


Assuntos
Regulação da Expressão Gênica/fisiologia , Histona Desmetilases/metabolismo , Infecções por Vírus de RNA/metabolismo , Receptores de Superfície Celular/metabolismo , Animais , Chlorocebus aethiops , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Ubiquitinação , Células Vero
17.
Affect Sci ; 2(1): 58-79, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33758826

RESUMO

High levels of stress in the parenting domain can lead to parental burnout, a condition that has severe consequences for both parents and children. It is not yet clear, however, whether parental burnout varies by culture, and if so, why it might do so. In this study, we examined the prevalence of parental burnout in 42 countries (17,409 parents; 71% mothers; Mage = 39.20) and showed that the prevalence of parental burnout varies dramatically across countries. Analyses of cultural values revealed that individualistic cultures, in particular, displayed a noticeably higher prevalence and mean level of parental burnout. Indeed, individualism plays a larger role in parental burnout than either economic inequalities across countries, or any other individual and family characteristic examined so far, including the number and age of children and the number of hours spent with them. These results suggest that cultural values in Western countries may put parents under heightened levels of stress. Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-020-00028-4.

18.
Hepatology ; 73(5): 1797-1815, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33058300

RESUMO

BACKGROUND AND AIMS: Trimethylation of Lys36 on histone 3 (H3K36me3) catalyzed by histone methyltransferase SET domain-containing 2 (SETD2) is one of the most conserved epigenetic marks from yeast to mammals. SETD2 is frequently mutated in multiple cancers and acts as a tumor suppressor. APPROACH AND RESULTS: Here, using a liver-specific Setd2 depletion model, we found that Setd2 deficiency is sufficient to trigger spontaneous HCC. Meanwhile, Setd2 depletion significantly increased tumor and tumor size of a diethylnitrosamine-induced HCC model. The mechanistic study showed that Setd2 suppresses HCC not only through modulating DNA damage response, but also by regulating lipid metabolism in the liver. Setd2 deficiency down-regulated H3K36me3 enrichment and expression of cholesterol efflux genes and caused lipid accumulation. High-fat diet enhanced lipid accumulation and promoted the development of HCC in Setd2-deficient mice. Chromatin immunoprecipitation sequencing analysis further revealed that Setd2 depletion induced c-Jun/activator protein 1 (AP-1) activation in the liver, which was trigged by accumulated lipid. c-Jun acts as an oncogene in HCC and functions through inhibiting p53 in Setd2-deficient cells. CONCLUSIONS: We revealed the roles of Setd2 in HCC and the underlying mechanisms in regulating cholesterol homeostasis and c-Jun/AP-1 signaling.


Assuntos
Carcinoma Hepatocelular/etiologia , Histona-Lisina N-Metiltransferase/deficiência , Metabolismo dos Lipídeos , Neoplasias Hepáticas/etiologia , Fígado/metabolismo , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Proteína 9 Associada à CRISPR , Sistemas CRISPR-Cas , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Colesterol/sangue , Imunoprecipitação da Cromatina , Edição de Genes , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Células Hep G2 , Histona-Lisina N-Metiltransferase/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Triglicerídeos/sangue
19.
Clin Epigenetics ; 11(1): 48, 2019 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-30867030

RESUMO

BACKGROUND: Activation of transcription enhancers, especially super-enhancers, is one of the critical epigenetic features of tumorigenesis. However, very few studies have systematically identified the enhancers specific in cancer tissues. METHODS: Here, we studied the change of histone modifications in MMTV-PyVT breast cancer model, combining mass spectrometry-based proteomics and ChIP-seq-based epigenomics approaches. Some of the proteomic results were confirmed with western blotting and IHC staining. An inhibitor of H3K27ac was applied to study its effect on cancer development. RESULTS: H3K27ac and H4K8ac are elevated in cancer, which was confirmed in patient tissue chips. ChIP-seq revealed that H4K8ac is co-localized with H3K27ac on chromatin, especially on distal enhancers. Epigenomic studies further identified a subgroup of super-enhancers marked by H3K4me3 peaks in the intergenic regions. The H3K4me3-enriched regions enhancers are associated with higher level of H3K27ac and H4K8ac compared with the average level of conventional super-enhancers and are associated with higher transcription level of their adjacent genes. We identified 148 H3K4me3-enriched super-enhancers with higher gene expression in tumor, which may be critical for breast cancer. One inhibitor for p300 and H3K27ac, C646, repressed tumor formation probably through inhibiting Vegfa and other genes. CONCLUSIONS: Taken together, our work identifies novel regulators and provides important resource to the genome-wide enhancer studies in breast cancer and raises the possibility of cancer treatment through modulating enhancer activity.


Assuntos
Neoplasias da Mama/patologia , Elementos Facilitadores Genéticos , Histonas/genética , Histonas/metabolismo , Neoplasias Mamárias Experimentais/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Sequenciamento de Cromatina por Imunoprecipitação , Epigênese Genética , Epigenômica , Feminino , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Código das Histonas , Humanos , Neoplasias Mamárias Experimentais/genética , Neoplasias Mamárias Experimentais/metabolismo , Proteômica , Ativação Transcricional , Regulação para Cima
20.
Cell Death Differ ; 26(6): 1156-1168, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30237511

RESUMO

SPOP is one of the important subunits for CUL3/SPOP/RBX1 complex tightly connected with tumorigenesis. However, its exact roles in different cancers remain debatable. Here, we identify CYCLIN E1, as a novel substrate for SPOP. SPOP directly interacts with CYCLIN E1 and specific regulates its stability in prostate cancer cell lines. SPOP/CUL3/RBX1 complex regulates CYCLIN E1 stability through poly-ubiquitination. CDK2 competes with SPOP for CYCLIN E1 interaction, suggesting that SPOP probably regulates the stability of CDK2-free CYCLIN E1. CYCLIN E1 expression rescued proliferation, migration, and tumor formation of prostate cancer cell suppressed by SPOP. Furthermore, we found SPOP selectively regulates the substrates' stability and signaling pathways in prostate cancer and CCRC cell lines, suggesting that complicated mechanisms exist for SPOP to regulate substrate specificity. Altogether, we have revealed a novel mechanism for SPOP in suppressing prostate cancer and provided evidence to show SPOP has dual functions in prostate cancer and CCRC.


Assuntos
Ciclina E/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Oncogênicas/metabolismo , Neoplasias da Próstata/metabolismo , Proteínas Repressoras/metabolismo , Linhagem Celular , Movimento Celular , Proliferação de Células , Ciclina E/genética , Humanos , Masculino , Proteínas Oncogênicas/genética , Neoplasias da Próstata/patologia , Estabilidade Proteica , Transdução de Sinais
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...