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1.
PLoS Genet ; 20(2): e1011176, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38408082

RESUMEN

Colorectal cancer (CRC) is a major cause of cancer mortality and a serious health problem worldwide. Mononuclear phagocytes are the main immune cells in the tumor microenvironment of CRC with remarkable plasticity, and current studies show that macrophages are closely related to tumor progression, invasion and dissemination. To understand the immunological function of mononuclear phagocytes comprehensively and deeply, we use single-cell RNA sequencing and classify mononuclear phagocytes in CRC into 6 different subsets, and characterize the heterogeneity of each subset. We find that tissue inhibitor of metalloproteinases (TIMPs) involved in the differentiation of proinflammatory and anti-inflammatory mononuclear phagocytes. Trajectory of circulating monocytes differentiation into tumor-associated macrophages (TAMs) and the dynamic changes at levels of transcription factor (TF) regulons during differentiation were revealed. We also find that C5 subset, characterized by activation of lipid metabolism, is in the terminal state of differentiation, and that the abundance of C5 subset is negatively correlated with CRC patients' prognosis. Our findings advance the understanding of circulating monocytes' differentiation into macrophages, identify a new subset associated with CRC prognosis, and reveal a set of TF regulons regulating mononuclear phagocytes differentiation, which are expected to be potential therapeutic targets for reversing immunosuppressive tumor microenvironment.


Asunto(s)
Neoplasias Colorrectales , Monocitos , Humanos , ARN/metabolismo , Macrófagos/metabolismo , Diferenciación Celular/genética , Neoplasias Colorrectales/patología , Fagocitos/metabolismo , Microambiente Tumoral/genética
2.
Heart Lung Circ ; 31(7): 934-943, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35361533

RESUMEN

Pulmonary arterial hypertension (PAH) is a complex and serious cardiopulmonary disease; it is characterised by increased pulmonary arterial pressure and pulmonary vascular remodelling accompanied by disordered endothelial and smooth muscle cell proliferation within pulmonary arterioles and arteries. Although recent reports have suggested that dysregulated immunity and inflammation are key players in PAH pathogenesis, their roles in PAH progression remain unclear. Intriguingly, altered host immune cell distribution, number, and polarisation within the lung arterial vasculature have been linked to disease development. This review mainly focusses on the roles of different immune cells in PAH and discusses the underlying mechanisms.


Asunto(s)
Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Proliferación Celular , Hipertensión Pulmonar Primaria Familiar , Humanos , Hipertensión Pulmonar/patología , Miocitos del Músculo Liso , Arteria Pulmonar/patología , Remodelación Vascular
3.
J Nurs Manag ; 30(6): 1931-1939, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35475528

RESUMEN

AIM: The aim of this study was to examine the mediating role of work-family conflict and the moderating role of job autonomy on the association between risk perception of COVID-19 and job withdrawal among Chinese nurses during the initial disease outbreak. BACKGROUND: Nurses' job withdrawal can not only reduce the quality and efficiency of care but also give rise to turnover during the COVID-19 pandemic. Thus, it is essential to clarify how and when the risk perception of COVID-19 influences the job withdrawal behaviours of nurses and to provide guidelines for reducing nurses' job withdrawal. METHODS: A two-wave study was conducted among 287 Chinese nurses from 11 COVID-19-designated hospitals during the initial outbreak of the disease from March through April 2020. Data on the risk perception of COVID-19, job autonomy and work-family conflict were collected at time 1, and 1 month later, job withdrawal data were collected at time 2. Model 4 and Model 14 from SPSS macro PROCESS were used to test the mediating effect of work-family conflict and the moderating effect of job autonomy, respectively. RESULTS: Work-family conflict mediated 60.54% of the relationship between risk perception of COVID-19 and job withdrawal. Job autonomy positively moderated the relation between work-family conflict and job withdrawal (ß = 0.12, P < 0.01). CONCLUSION: Risk perception of COVID-19 influenced nurses' job withdrawal through work-family conflict. Job autonomy exaggerated the association between work-family conflict and job withdrawal. IMPLICATIONS FOR NURSING MANAGEMENT: Managers should provide more supportive resources to help nurses cope with the risk of COVID-19 to decrease work-family conflict and job withdrawal, and they should strengthen supervision over the work processes of nurses.


Asunto(s)
COVID-19 , Enfermeras y Enfermeros , COVID-19/epidemiología , China/epidemiología , Conflicto Familiar , Humanos , Satisfacción en el Trabajo , Pandemias , Percepción , Encuestas y Cuestionarios
4.
Int J Mol Sci ; 22(23)2021 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-34884813

RESUMEN

Cytokine storm is a phenomenon characterized by strong elevated circulating cytokines that most often occur after an overreactive immune system is activated by an acute systemic infection. A variety of cells participate in cytokine storm induction and progression, with profiles of cytokines released during cytokine storm varying from disease to disease. This review focuses on pathophysiological mechanisms underlying cytokine storm induction and progression induced by pathogenic invasive infectious diseases. Strategies for targeted treatment of various types of infection-induced cytokine storms are described from both host and pathogen perspectives. In summary, current studies indicate that cytokine storm-targeted therapies can effectively alleviate tissue damage while promoting the clearance of invading pathogens. Based on this premise, "multi-omics" immune system profiling should facilitate the development of more effective therapeutic strategies to alleviate cytokine storms caused by various diseases.


Asunto(s)
COVID-19/patología , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/patología , Citocinas/sangre , Sepsis/patología , Antiinflamatorios/uso terapéutico , Bacterias/inmunología , Infecciones Bacterianas/patología , Citocinas/metabolismo , Humanos , Inflamación/patología , Macrófagos/inmunología , SARS-CoV-2/inmunología , Sepsis/microbiología
5.
Reprod Fertil Dev ; 32(7): 657-666, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32317091

RESUMEN

Autophagy plays an important role in embryo development; however, only limited information is available on how autophagy specifically regulates embryo development, especially under low oxygen culture conditions. In this study we used parthenogenetic activation (PA) of porcine embryos to test the hypothesis that a low oxygen concentration (5%) could promote porcine embryo development by activating autophagy. Immunofluorescence staining revealed that low oxygen tension activated autophagy and alleviated oxidative stress in porcine PA embryos. Development was significantly affected when autophagy was blocked by 3-methyladenine, even under low oxygen culture conditions, with increased reactive oxygen species levels and malondialdehyde content. Furthermore, the decreased expression of pluripotency-associated genes induced by autophagy inhibition could be recovered by treatment with the antioxidant vitamin C. Together, these results demonstrate that low oxygen-induced autophagy regulates embryo development through antioxidant mechanisms in the pig.


Asunto(s)
Autofagia/fisiología , Técnicas de Cultivo de Embriones/veterinaria , Desarrollo Embrionario/fisiología , Oxígeno/administración & dosificación , Partenogénesis/fisiología , Porcinos/embriología , Adenina/análogos & derivados , Adenina/farmacología , Animales , Antioxidantes/farmacología , Ácido Ascórbico/farmacología , Autofagia/efectos de los fármacos , Técnicas de Cultivo de Embriones/métodos , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología
6.
Fungal Genet Biol ; 107: 24-30, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28778753

RESUMEN

Histone H3 lysine 36 methylation (H3K36me) is generally associated with activation of gene expression in most eukaryotic cells. However, the function of H3K36me in filamentous fungi is largely unknown. Set2 is the sole lysine histone methyltransferase (KHMTase) enzyme responsible for the methylation of H3K36 in Saccharomyces cerevisiae. In the current study, we identified a single ortholog of S. cerevisiae Set2 in Fusarium verticillioides. We report that FvSet2 is responsible for the trimethylation of H3K36 (H3K36me3). The FvSET2 deletion mutant (ΔFvSet2) showed significant defects in vegetative growth, FB1 biosynthesis, pigmentation, and fungal virulence. Furthermore, trimethylation of H3K36 was found to be important for active transcription of genes involved in FB1 and bikaverin biosyntheses. These data indicate that FvSet2 plays an important role in the regulation of secondary metabolism, vegetative growth and fungal virulence in F. verticillioides.


Asunto(s)
Proteínas Fúngicas/metabolismo , Fusarium/fisiología , Regulación Fúngica de la Expresión Génica , N-Metiltransferasa de Histona-Lisina/metabolismo , Histonas/metabolismo , Metabolismo Secundario , Proteínas Fúngicas/genética , Fusarium/genética , Fusarium/crecimiento & desarrollo , Fusarium/patogenicidad , Histona Metiltransferasas , N-Metiltransferasa de Histona-Lisina/genética , Metilación , Metiltransferasas/genética , Metiltransferasas/metabolismo , Mutación , Pigmentos Biológicos/biosíntesis , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Virulencia/genética
7.
Sci Rep ; 14(1): 6379, 2024 03 16.
Artículo en Inglés | MEDLINE | ID: mdl-38493244

RESUMEN

The regulatory mechanism of long non-coding RNAs (lncRNAs) in autophagy is as yet not well established. In this research, we show that the long non-coding RNA MLLT4 antisense RNA 1 (lncRNA MLLT4-AS1) is induced by the MTORC inhibitor PP242 and rapamycin in cervical cells. Overexpression of MLLT4-AS1 promotes autophagy and inhibits tumorigenesis and the migration of cervical cancer cells, whereas knockdown of MLLT4-AS1 attenuates PP242-induced autophagy. Mass spectrometry, RNA fluorescence in situ hybridization (RNA-FISH), and immunoprecipitation assays were performed to identify the direct interactions between MLLT4-AS1 and other associated targets, such as myosin-9 and autophagy-related 14(ATG14). MLLT4-AS1 was upregulated by H3K27ac modification with PP242 treatment, and knockdown of MLLT4-AS1 reversed autophagy by modulating ATG14 expression. Mechanically, MLLT4-AS1 was associated with the myosin-9 protein, which further promoted the transcription activity of the ATG14 gene. In conclusion, we demonstrated that MLLT4-AS1 acts as a potential tumor suppressor in cervical cancer by inducing autophagy, and H3K27ac modification-induced upregulation of MLLT4-AS1 could cause autophagy by associating with myosin-9 and promoting ATG14 transcription.


Asunto(s)
Proteínas Adaptadoras del Transporte Vesicular , MicroARNs , ARN Largo no Codificante , Neoplasias del Cuello Uterino , Femenino , Humanos , ARN sin Sentido/genética , ARN sin Sentido/metabolismo , ARN Largo no Codificante/metabolismo , Neoplasias del Cuello Uterino/genética , Hibridación Fluorescente in Situ , Línea Celular Tumoral , Proliferación Celular/genética , Carcinogénesis/genética , Transformación Celular Neoplásica/genética , Proteínas del Citoesqueleto/metabolismo , Miosinas/genética , Miosinas/metabolismo , Autofagia/genética , MicroARNs/genética , Regulación Neoplásica de la Expresión Génica , Proteínas Relacionadas con la Autofagia/genética
8.
Gastroenterol Rep (Oxf) ; 12: goae055, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38818308

RESUMEN

Background: Metastasis is the main cause of death in colorectal cancer (CRC). Metastasis is a sequential and dynamic process, but the development of tumor cells during this process is unclear. In this study, we aimed to reveal characteristics of tumor cell subset during CRC metastasis. Methods: Single-cell RNA sequence CRC data of normal epithelium, non-metastatic primary tumor, metastatic primary tumor, and liver metastases from gene expression omnibus (GEO) dataset were analyzed to reveal characteristics of CRC metastasis. Primary tumor tissues of three non-metastatic CRC and three metastatic CRC patients from Union Hospital of Tongji Medical College (Wuhan, China) were used to verify the characteristics of CRC metastasis. Results: We identified a metastasis-related cancer cell subset EP1, which was characterized with a high expression of KRT17, LAMC2, EMP1, and PLAC8. EP1 had an enhanced cell-cell interaction, which interacted with SPP+ macrophages and drove them toward anti-inflammatory and immunosuppressive phenotype. Dynamic changes in genes and TF regulons during the metastasis were also revealed. Conclusions: This study advanced our understanding of the development of tumor cells during CRC metastasis and further identified metastasis-related subset and potential therapeutic targets for the treatment and prevention of CRC metastasis.

9.
Cell Prolif ; 56(5): e13471, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37199039

RESUMEN

Robust allogeneic immune reactions after transplantation impede the translational pace of human embryonic stem cells (hESCs)-based therapies. Selective genetic editing of human leucocyte antigen (HLA) molecules has been proposed to generate hESCs with immunocompatibility, which, however, has not been specifically designed for the Chinese population yet. Herein, we explored the possibility of customizing immunocompatible hESCs based on Chinese HLA typing characteristics. We generated an immunocompatible hESC line by disrupting HLA-B, HLA-C, and CIITA genes while retaining HLA-A*11:01 (HLA-A*11:01-retained, HLA-A11R ), which covers ~21% of the Chinese population. The immunocompatibility of HLA-A11R hESCs was verified by in vitro co-culture and confirmed in humanized mice with established human immunity. Moreover, we precisely knocked an inducible caspase-9 suicide cassette into HLA-A11R hESCs (iC9-HLA-A11R ) to promote safety. Compared with wide-type hESCs, HLA-A11R hESC-derived endothelial cells elicited much weaker immune responses to human HLA-A11+ T cells, while maintaining HLA-I molecule-mediated inhibitory signals to natural killer (NK) cells. Additionally, iC9-HLA-A11R hESCs could be induced to undergo apoptosis efficiently by AP1903. Both cell lines displayed genomic integrity and low risks of off-target effects. In conclusion, we customized a pilot immunocompatible hESC cell line based on Chinese HLA typing characteristics with safety insurance. This approach provides a basis for establishment of a universal HLA-AR bank of hESCs covering broad populations worldwide and may speed up the clinical application of hESC-based therapies.


Asunto(s)
Células Madre Embrionarias Humanas , Humanos , Animales , Ratones , Células Madre Embrionarias , Alelos , Antígeno HLA-A11/genética , Antígeno HLA-A11/metabolismo , Pueblos del Este de Asia , Células Endoteliales , Edición Génica , Antígenos HLA/genética , Histocompatibilidad , Diferenciación Celular
10.
Int Immunopharmacol ; 109: 108814, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35533555

RESUMEN

The dramatically increasing incidence and prevalence of inflammatory bowel disease (IBD) are reportedly related to a Western diet, which is characterized by high sugar consumption. Dietary simple sugars aggravate IBD in animal models. However, the mechanisms underlying this effect remain unclear. Given that high-fructose corn syrup (HFCS) is a major added sugar in food and beverages, we focus on HFCS and investigated the effects of HFCS on a dextran sulfate sodium (DSS)-induced murine colitis model and in RAW264.7 macrophages. Our data demonstrate that short-term consumption of HFCS aggravates colitis and upregulates the proportion of macrophages in IBD mice but not in healthy mice. We find that HFCS promotes proinflammatory cytokine production through reactive oxygen species (ROS)-mediated nuclear factor-κB (NF-κB) signaling in RAW264.7 macrophages. Furthermore, N-acetylcysteine (NAC), an ROS scavenger, alleviates HFCS-aggravated colitis in mice and inhibits the ROS-mediated NF-κB signaling pathway in RAW264.7 macrophages. Our work unveils the important role of macrophages in HFCS-induced exacerbation of colitis and reveals the mechanism of how HFCS immunologically aggravates IBD.


Asunto(s)
Colitis , Jarabe de Maíz Alto en Fructosa , Enfermedades Inflamatorias del Intestino , Animales , Colitis/inducido químicamente , Sulfato de Dextran/farmacología , Modelos Animales de Enfermedad , Fructosa , Jarabe de Maíz Alto en Fructosa/efectos adversos , Activación de Macrófagos , Ratones , FN-kappa B/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Zea mays
11.
Sci Data ; 9(1): 502, 2022 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-35977969

RESUMEN

Material utilisation has been playing a fundamental role in economic development, but meanwhile, it may have environmental and social consequences. Given China's rapid economic growth, understanding China's material utilisation patterns would inform decisions for researchers and policymakers. However, fragmented data from multiple statistical sources hinder us from comprehensively portraying China's material utilisation dynamics. This study harmonised China-specific official statistics and constructed a China economy-wide material flow accounts database. This database covers hundreds of materials and more than 30 years (1990-2020) from thousands of data sources, which is comprehensive, long-term, up-to-date, and publicly accessed. This database would provide insights into the historical metabolic dynamics of China's economy with elaboration on the production, consumption, and end-of-life disposal of materials. This database also allows for international analyses since it is developed based on an internationally standardised analytical framework. Furthermore, this study would benefit studies on policy impact evaluation, environmental pressure assessment, and sustainable development strategies.

12.
Science ; 377(6609): 967-975, 2022 08 26.
Artículo en Inglés | MEDLINE | ID: mdl-36007034

RESUMEN

Chromosome engineering has been attempted successfully in yeast but remains challenging in higher eukaryotes, including mammals. Here, we report programmed chromosome ligation in mice that resulted in the creation of new karyotypes in the lab. Using haploid embryonic stem cells and gene editing, we fused the two largest mouse chromosomes, chromosomes 1 and 2, and two medium-size chromosomes, chromosomes 4 and 5. Chromatin conformation and stem cell differentiation were minimally affected. However, karyotypes carrying fused chromosomes 1 and 2 resulted in arrested mitosis, polyploidization, and embryonic lethality, whereas a smaller fused chromosome composed of chromosomes 4 and 5 was able to be passed on to homozygous offspring. Our results suggest the feasibility of chromosome-level engineering in mammals.


Asunto(s)
Fusión Artificial Génica , Edición Génica , Cariotipo , Translocación Genética , Animales , Fusión Artificial Génica/métodos , Cromatina/química , Células Madre Embrionarias , Edición Génica/métodos , Haploidia , Ratones , Mitosis
13.
Cancer Lett ; 518: 180-195, 2021 10 10.
Artículo en Inglés | MEDLINE | ID: mdl-34216690

RESUMEN

Human anterior gradient homolog 2 (AGR2) reportedly acts as an oncogene in multiple types of cancers. As a secreted protein, the oncogenic roles of extracellular AGR2 have been the focus of the increasing number of studies. In contrast, the oncological functions of intracellular AGR2 (iAGR2) remain elusive. Here, we report that intracellular AGR2 (iAGR2) is sufficient to promote CRC metastasis. iAGR2 binds to KDEL receptors (KDELRs) via its KTEL motif to activate downstream Gs-PKA signaling. Activated PKA upregulates the expression of NF-κB subunit c-Rel (REL) and acetylates histone H3 at lysine 9 (H3K9ac) to promote the transcription of SNAIL and SLUG. AGR2 can be upregulated by prostaglandin E2 (PGE2) via EP4-PI3K-AKT pathway and is indispensable for PGE2-induced CRC metastasis. AGR2 knockdown enhances therapeutic effects of a COX-2 inhibitor, celecoxib, in CRC metastasis. Collectively, our study reveals a promoting role and molecular mechanisms of iAGR2 in CRC metastasis and uncovers a new tumor microenvironment signal regulating AGR2 expression, which may provide new targets for treating metastatic CRC.


Asunto(s)
Neoplasias Colorrectales/genética , Dinoprostona/genética , Transición Epitelial-Mesenquimal/genética , Mucoproteínas/genética , Proteínas Oncogénicas/genética , Animales , Celecoxib/farmacología , Línea Celular , Línea Celular Tumoral , Neoplasias Colorrectales/patología , Células HCT116 , Células HEK293 , Células HT29 , Histonas/genética , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Oncogenes/genética , Fosfatidilinositol 3-Quinasas/genética , Receptores de Péptidos/genética , Transducción de Señal/genética , Microambiente Tumoral/genética
14.
Biomaterials ; 223: 119475, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31520888

RESUMEN

Multidrug resistance (MDR) is a key issue accounting for ineffectiveness of cancer chemotherapy. Numerous multifunctional nanocarriers have been developed to increase drug delivery efficacy and inhibit drug efflux for overcoming cancer drug resistance. However, limited success has been achieved in clinic because of nanocarriers' complicated multi-step fabrication procedures and their undesired side toxicity as well as potential immunogenicity. Here, hyaluronic acid (HA) functionalized extracellular vesicles (EVs) are generated as natural vehicles to efficiently deliver doxorubicin (DOX) and reverse MDR. The EVs isolated from noncancerous HEK293T cells (hEVs) reduce P-glycoprotein (P-gp) expression in drug resistant MCF7/ADR cells. To acquire tumor-targeting capability, hEVs are modified with lipidomimetic chains-grafted HA (lipHA) by a simple incubation. Owing to CD44-mediated cancer-specific targeting and P-gp suppressive capability, the HA-functionalized hEVs (lipHA-hEVs) remarkably promote the intracellular DOX accumulation in drug resistant breast cancer cells. In preclinical MDR tumor models, lipHA-hEVs deeply penetrate into tumor tissue and effectively transport DOX into tumor local, while eliminating DOX's systemic toxicity. Importantly, DOX@lipHA-hEVs inhibited MDR tumor growth by 89% and extend animal survival time by approximately 50%. Thus, our engineered tumor-targeting hEVs are promising natural carriers for overcoming cancer MDR.


Asunto(s)
Resistencia a Antineoplásicos/efectos de los fármacos , Vesículas Extracelulares/química , Ácido Hialurónico/química , Lípidos/química , Neoplasias/tratamiento farmacológico , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Animales , Apoptosis , Línea Celular Tumoral , Doxorrubicina/administración & dosificación , Portadores de Fármacos , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Femenino , Células HEK293 , Células Endoteliales de la Vena Umbilical Humana , Humanos , Membrana Dobles de Lípidos , Células MCF-7 , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Nanomedicina/métodos , Ingeniería de Proteínas , Células RAW 264.7
15.
Dis Model Mech ; 12(8)2019 08 29.
Artículo en Inglés | MEDLINE | ID: mdl-31371383

RESUMEN

Human tumors exhibit plasticity and evolving capacity over time. It is difficult to study the mechanisms of how tumors change over time in human patients, in particular during the early stages when a few oncogenic cells are barely detectable. Here, we used a Drosophila tumor model caused by loss of scribble (scrib), a highly conserved apicobasal cell polarity gene, to investigate the spatial-temporal dynamics of early tumorigenesis events. The fly scrib mutant tumors have been successfully used to model many aspects of tumorigenesis processes. However, it is still unknown whether Drosophila scrib mutant tumors exhibit plasticity and evolvability along the temporal axis. We found that scrib mutant tumors displayed different growth rates and cell cycle profiles over time, indicative of a growth arrest-to-proliferation transition as the scrib mutant tumors progress. Longitudinal bulk and single-cell transcriptomic analysis of scrib mutant tumors revealed that the MAPK pathway, including JNK and ERK signaling activities, showed quantitative changes over time. We found that high JNK signaling activity caused G2/M cell cycle arrest in early scrib mutant tumors. In addition, JNK signaling activity displayed a radial polarity with the JNKhigh cells located at the periphery of scrib mutant tumors, providing an inherent mechanism that leads to an overall decrease in JNK signaling activity over time. We also found that ERK signaling activity, in contrast to JNK activity, increased over time and promoted growth in late-stage scrib mutant tumors. Furthermore, high JNK signaling activity repressed ERK signaling activity in early scrib mutant tumors. Together, these data demonstrate that dynamic MAPK signaling activity, fueled by intratumor heterogeneity derived from tissue topological differences, drives a growth arrest-to-proliferation transition in scrib mutant tumors.This article has an associated First Person interview with the joint first authors of the paper.


Asunto(s)
Puntos de Control del Ciclo Celular/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/citología , Drosophila melanogaster/genética , Sistema de Señalización de MAP Quinasas , Proteínas de la Membrana/genética , Mutación/genética , Neoplasias/enzimología , Neoplasias/patología , Animales , Proliferación Celular , Factores de Tiempo , Transcriptoma/genética
16.
J Gerontol A Biol Sci Med Sci ; 74(8): 1322-1330, 2019 07 12.
Artículo en Inglés | MEDLINE | ID: mdl-30252020

RESUMEN

BACKGROUND: Although it is accepted that the etiology of cerebral small vessel disease (CSVD) is associated with cardiovascular risk factors, the association between CSVD and the circadian rhythm of blood pressure (BP) is unclear. We aimed to determine if such an association existed in the elderly population. METHOD: White matter hyperintensities (WMHs), lacunes, microbleeds, nocturnal dipping pattern (NDP), and morning surge in systolic blood pressure (SBP) were assessed in 2,091 participants ≥60 years of age. RESULTS: During an average of 63 months of follow-up, WMH and the WMH-to-intracranial volume ratio were significantly increased in extreme dippers, nondippers, and reverse dippers than those in dippers (p < .001). For new-incident Fazekas scale ≥2, the hazard ratios were 1.77 (95% confidence interval [CI], 1.09-2.86) for extreme dippers, 2.20 (95% CI, 1.48-3.28) for nondippers, and 2.43 (95% CI, 1.59-3.70) for reverse dippers compared with dippers, and 1.04 (95% CI, 0.81-1.35) for higher morning surge compared with lower morning surge. Nondippers and reverse dippers were associated with higher risks of new-incident lacunes and microbleeds than dippers (p < .05). Higher morning surge was associated with a higher risk of new-incident microbleeds than lower morning surge (p < .05). CONCLUSION: NDPs in SBP played an important role in CSVD, and the morning surge in SBP was associated with cerebral microbleeds in community-based elderly population beyond the average SBP level.


Asunto(s)
Presión Sanguínea/fisiología , Enfermedades de los Pequeños Vasos Cerebrales/fisiopatología , Ritmo Circadiano/fisiología , Anciano , Angiografía Cerebral , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , China , Progresión de la Enfermedad , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Angiografía por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Prospectivos
17.
Hypertens Res ; 42(5): 717-729, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30552406

RESUMEN

Cerebral white matter hyperintensities (WMHs) and cognitive impairment are common in elderly hypertensive patients, and more needs to be learned about their prevention and treatment. Our aim was to investigate the effect of low-dose statins on WMH and cognitive function in elderly patients undergoing antihypertensive treatment. A total of 732 elderly hypertensive patients taking hydrochlorothiazide as their baseline medication were randomized using a 2 × 2 factorial design with antihypertensive (telmisartan vs. placebo) and lipid-modulating (low-dose rosuvastatin vs. placebo) arms. Brain magnetic resonance imaging (MRI) and cognitive function data were obtained. After a mean follow-up time of 59.8 (range 12-65) months, there were no differences in WMH progression and cognitive function decline over time between the groups in the antihypertensive arm. The risks of new-incident WMH Fazekas scale scores ≥ 2 and the incidence of cognitive impairment did not differ between the telmisartan and placebo groups. Rosuvastatin use was associated with lower risks of new-incident Fazekas scale scores ≥2 (hazard ratio = 0.500; 95% confidence interval: 0.34-0.74) and cognitive impairment (hazard ratio = 0.54; 95% confidence interval: 0.36-0.80). Telmisartan interacted with rosuvastatin on reducing WMH progression and cognitive function decline. Findings suggest that low-dose rosuvastatin could reduce WMH progression and cognitive function decline in antihypertensive patients, as demonstrated by the interaction between telmisartan and low-dose rosuvastatin to this effect.


Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Disfunción Cognitiva/prevención & control , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Leucoencefalopatías/prevención & control , Rosuvastatina Cálcica/uso terapéutico , Telmisartán/uso terapéutico , Anciano , Disfunción Cognitiva/complicaciones , Progresión de la Enfermedad , Método Doble Ciego , Hipertensión Esencial/complicaciones , Hipertensión Esencial/tratamiento farmacológico , Femenino , Humanos , Leucoencefalopatías/complicaciones , Masculino , Persona de Mediana Edad
18.
Lab Chip ; 19(3): 422-431, 2019 01 29.
Artículo en Inglés | MEDLINE | ID: mdl-30575843

RESUMEN

Non-adherent cells play key roles in various biological processes. Studies on this type of cell, especially at single-cell resolution, help reveal molecular mechanisms underlying many biological and pathological processes. The emerging microfluidics technology has developed effective methods for analyzing cells. However, it remains challenging to treat and monitor single live non-adherent cells in an in situ, long-term, and real-time manner. Herein, a microfluidic platform was set up to generate and anchor cell-laden water-in-oil-in-water (W/O/W) double emulsions (DEs) to investigate these cells. Within the device, W/O/W DEs encapsulating non-adherent cells were generated through two adjacent flow-focusing structures and subsequently anchored in an array of microchambers. These droplets maintained the W/O/W structure and the anchorage status in the continuous perfusion fluid for at least one week. The mass transfer of different molecules with suitable molecular weights and partition coefficients between the interior and exterior of W/O/W DEs could be regulated by perfusion fluid flow rates. These features endow this platform with potential to continuously supply encapsulated non-adherent cells with nutrients or small-molecule stimuli/drugs through fluid perfusion. Meanwhile, the confinement of cells in the anchored DEs favored long-term monitoring of cellular dynamic behaviors and responses. As a proof of concept, fluorescein diacetate (FDA) was employed to visualize the cellular uptake and biochemical metabolism of TF-1 human erythroleukemia cells. We believe that this W/O/W DE anchorage and perfusion platform would benefit single-cell-level studies as well as small-molecule drug discovery requiring live non-adherent cells.


Asunto(s)
Dispositivos Laboratorio en un Chip , Aceites/química , Análisis de la Célula Individual/instrumentación , Agua/química , Adhesión Celular , Línea Celular Tumoral , Emulsiones , Humanos , Fenómenos Mecánicos , Propiedades de Superficie
19.
J Am Med Dir Assoc ; 19(11): 995-1002.e4, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30006015

RESUMEN

OBJECTIVES: To investigate the effect of low-dose statins and apolipoprotein E (APOE) genotypes on cerebral small vessel disease (CSVD) to prevent CSVD in older hypertensive patients. DESIGN: A subgroup analysis of a randomized clinical trial. SETTING: Shandong area, China. PARTICIPANTS: Hypertensive patients aged ≥60 years were recruited from April 2008 to November 2010. MEASUREMENTS: Patients were randomly assigned to rosuvastatin (10 mg/day) or placebo groups. APOE genotypes were categorized as ε4 carriers and non-ε4 carriers. White matter hyperintensities (WMH), Fazekas scale, lacunes, and microbleeds were assessed. RESULTS: After an average of intervention period of 61.8 months, WMH volume increased 1.45 ± 0.52 mL. There were 107 new-incident Fazekas scale ≥2, 65 new-incident lacunes, and 63 new-incident microbleeds. The increase in WMH volume was significantly lower in the rosuvastatin group than in the placebo group and was higher in APOE ε4 carriers than in non-ε4 carriers (all adjusted P < .001). The risk of new-incident Fazekas scale ≥2 was higher in the placebo group than in the rosuvastatin group (hazard ratio 2.150, 95% confidence interval 1.443-3.203; P < .001). APOE ε4 carriers were associated with an increased risk of new-incident Fazekas scale ≥2 compared with non-ε4 carriers (hazard ratio 1.973, 95% confidence interval 1.334-2.920; P = .001). There were no statistically significant differences in the risk of new-incident cerebral microbleeds between the rosuvastatin and placebo groups or between APOE ε4 carriers and non-ε4 carriers. There were no significant interactions between rosuvastatin use and APOE ε4 status regarding increased WMH volume (F = 1.020, P = .313) or for new-incident Fazekas scale ≥2 (P = .377), lacunes (P = .232), and microbleeds (P = .362). CONCLUSIONS/IMPLICATIONS: Low-dose rosuvastatin is an effective and safe therapy for CSVD. The presence of APOE ε4 allele may not be able to predict rosuvastatin treatment outcomes for preventing and/or treating CSVD in older hypertensive patients.


Asunto(s)
Apolipoproteínas E/genética , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Enfermedades de los Pequeños Vasos Cerebrales/prevención & control , Genotipo , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Hipertensión/tratamiento farmacológico , Encéfalo/diagnóstico por imagen , Heterocigoto , Humanos , Hipertensión/complicaciones , Imagen por Resonancia Magnética , Rosuvastatina Cálcica/administración & dosificación , Sustancia Blanca/diagnóstico por imagen
20.
RSC Adv ; 8(18): 9963-9969, 2018 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-35540848

RESUMEN

Traditional artificial opals are assembled from silica or polystylene colloidals which have poor swellability and a lower response to stimuli. A novel three-dimensional photonic crystal array sensor which has a high stability and desired structural colour was fabricated from the self assembly of nano hydrogel colloids. The nano hydrogel colloids were prepared by co-polymerisation of N-isopropylacrylamide, functional monomer acrylic acid and N-tert-butylacrylamide. The relative humidity from 20% to 100% could be detected rapidly via the reflection spectrum of the nano hydrogel colloidal array with a maximum amount of red shift of 24 nm. The response kinetics for humidity of the nano hydrogel colloidal array were investigated, and correspondingly, a rational response mechanism of the compactness of the close-packed structure caused by the swelling of the nano hydrogel colloidal array was discussed. The nano hydrogel colloidal array sensor presented good reversibility and can be reused for at least five rounds.

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