RESUMEN
IGF2BP2 binds to a number of RNA transcripts and has been suggested to function as a tumor promoter, although little is known regarding the mechanisms that regulate its roles in RNA metabolism. Here we demonstrate that IGF2BP2 binds to the 3' untranslated region of the transcript encoding ATP6V1A, a catalytic subunit of the vacuolar ATPase (v-ATPase), and serves as a substrate for the NAD+-dependent deacetylase SIRT1, which regulates how IGF2BP2 affects the stability of the ATP6V1A transcript. When sufficient levels of SIRT1 are expressed, it catalyzes the deacetylation of IGF2BP2, which can bind to the ATP6V1A transcript but does not mediate its degradation. However, when SIRT1 expression is low, the acetylated form of IGF2BP2 accumulates, and upon binding to the ATP6V1A transcript recruits the XRN2 nuclease, which catalyzes transcript degradation. Thus, the stability of the ATP6V1A transcript is significantly compromised in breast cancer cells when SIRT1 expression is low or knocked-down. This leads to a reduction in the expression of functional v-ATPase complexes in cancer cells and to an impairment in their lysosomal activity, resulting in the production of a cellular secretome consisting of increased numbers of exosomes enriched in ubiquitinated protein cargo and soluble hydrolases, including cathepsins, that together combine to promote tumor cell survival and invasiveness. These findings describe a previously unrecognized role for IGF2BP2 in mediating the degradation of a messenger RNA transcript essential for lysosomal function and highlight how its sirtuin-regulated acetylation state can have significant biological and disease consequences.
Asunto(s)
Neoplasias , ATPasas de Translocación de Protón Vacuolares , Humanos , ATPasas de Translocación de Protón Vacuolares/genética , ATPasas de Translocación de Protón Vacuolares/metabolismo , Sirtuina 1/metabolismo , ARN/metabolismo , Procesos Neoplásicos , Lisosomas/genética , Lisosomas/metabolismo , Neoplasias/metabolismo , Línea Celular Tumoral , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismoRESUMEN
BACKGROUND: The aim of this study was to verify the analytical performance of the UD90DT electrochemiluminescence immunoassay system (the UD90DT system) for measuring high-sensitivity cardiac troponin T (hs-cTnT). METHODS: According to the Clinical and Laboratory Standards Institute guidelines, the imprecision, linearity, reference interval, limit of blank (LoB), limit of detection (LoD), and functional sensitivity (FS) of hs-cTnT using the UD90DT system were verified. The trueness was validated using the Proficiency Testing (PT) materials. RESULTS: The within-run and between-run coefficients of variations (CVs) of two hs-cTnT levels were 7.2% and 1.5%, and 7.1% and 2.6%, respectively. The biases of the PT samples (n = 6) all fell within the allowable total error. The linearity satisfied the requirements, with a slope of 0.9963 and an R12 value of 0.9998. The hs-cTnT levels of the healthy volunteers (n = 20) ranged from 3.0 ng/L to 7.7 ng/L. All blank calibrator measurements (n = 20) fell within the LoD claim, and none of the samples (n = 25) had a LoB value ≤ 3.0 ng/L. The FS was 5.3 ng/L. Furthermore, a good correlation between the UD90DT system and the Cobas e 601 module was observed for hs-cTnT. CONCLUSIONS: The analytical performance of hs-cTnT using the UD90DT system is acceptable and satisfies clinical needs.
Asunto(s)
Pruebas Inmunológicas , Troponina T , Humanos , Límite de Detección , Inmunoensayo , BiomarcadoresRESUMEN
BACKGROUND: Cervical mullerian adenosarcoma is a rare uterine sarcoma, especially in young women. Its pathological features are low-grade malignant tumors with bidirectional differentiation, and the degree of malignancy is similar to that of low-grade endometrial stromal sarcoma. This paper reports the case of a young asexual patient who has been closely followed up after tumor resection and has not had any recurrences. CASE PRESENTATION: A 20-year-old, young asexual woman was diagnosed with cervical mullerian adenosarcoma with sarcomatous overgrowth (MASO). Cervical tumor resection was performed after admission, and the resection margin was negative. After the operation, she refused to undergo secondary surgery due to fertility requirements and did not receive adjuvant treatment. The patient was closely followed up after the operation and has not yet relapsed. CONCLUSION: A young woman with cervical MASO did not receive adjuvant treatment after cervical tumor resection. For women with fertility requirements, close follow-ups should be conducted after the operation to guard against tumor recurrence and radical tumor resection should be performed as early as possible after the patient no longer requires their fertility.
Asunto(s)
Adenosarcoma , Neoplasias del Cuello Uterino , Neoplasias Uterinas , Humanos , Femenino , Adenosarcoma/cirugía , Adenosarcoma/patología , Adenosarcoma/diagnóstico , Adulto Joven , Neoplasias del Cuello Uterino/cirugía , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias Uterinas/cirugía , Neoplasias Uterinas/patología , Neoplasias Uterinas/complicaciones , Neoplasias Uterinas/diagnóstico , Conducta SexualRESUMEN
A sedentary lifestyle affects the diversity and composition of the gut microbiota, but previous studies have mainly focused on bacteria instead of fungi. Here, we compared both the fecal bacterial and fungal microbiota compositions and functions in sedentary persons and controls. Subjects from the China Railway Corporation, including 99 inspectors and 88 officials, were enrolled in our study. Fecal microbiota communities were analyzed using 16S rRNA gene sequencing for bacteria and ITS sequencing for fungi. We found that the diversity of the gut microbiota of the sedentary group was significantly lower than that of the control group (P < 0.05). The sedentary group had a higher abundance of Firmicutes, a lower abundance of Actinobacteria and Proteobacteria and a higher abundance of Ascomycota, and a lower abundance of Basidiomycota. Furthermore, functional prediction analysis of the fungal microbiota revealed more L-tryptophan degradation to 2-amino-3-carboxymuconate semialdehyde, more phospholipid remodeling (phosphatidylethanolamine, yeast), and more L-tyrosine degradation I, as well as less pentose phosphate pathway (non-oxidative branch), less adenosine nucleotide biosynthesis and less L-valine biosynthesis in the sedentary group (P < 0.05). Thus, a sedentary lifestyle changes the composition and function of the gut microbiota. It may change the pentose phosphate pathway (non-oxidative branch), nucleic acid and amino acid biosynthesis and phospholipid metabolism in fungi.
Asunto(s)
Microbioma Gastrointestinal , Micobioma , Humanos , Microbioma Gastrointestinal/genética , ARN Ribosómico 16S/genética , ARN Ribosómico 16S/metabolismo , Conducta Sedentaria , Bacterias , Hongos/genética , Fosfolípidos/metabolismoRESUMEN
Altered microarchitecture of collagen type I is a hallmark of wound healing and cancer that is commonly attributed to myofibroblasts. However, it remains unknown which effect collagen microarchitecture has on myofibroblast differentiation. Here, we combined experimental and computational approaches to investigate the hypothesis that the microarchitecture of fibrillar collagen networks mechanically regulates myofibroblast differentiation of adipose stromal cells (ASCs) independent of bulk stiffness. Collagen gels with controlled fiber thickness and pore size were microfabricated by adjusting the gelation temperature while keeping their concentration constant. Rheological characterization and simulation data indicated that networks with thicker fibers and larger pores exhibited increased strain-stiffening relative to networks with thinner fibers and smaller pores. Accordingly, ASCs cultured in scaffolds with thicker fibers were more contractile, expressed myofibroblast markers, and deposited more extended fibronectin fibers. Consistent with elevated myofibroblast differentiation, ASCs in scaffolds with thicker fibers exhibited a more proangiogenic phenotype that promoted endothelial sprouting in a contractility-dependent manner. Our findings suggest that changes of collagen microarchitecture regulate myofibroblast differentiation and fibrosis independent of collagen quantity and bulk stiffness by locally modulating cellular mechanosignaling. These findings have implications for regenerative medicine and anticancer treatments.
Asunto(s)
Colágeno/ultraestructura , Miofibroblastos/citología , Células del Estroma/citología , Tejido Adiposo/citología , Fenómenos Biomecánicos , Diferenciación Celular , Células Cultivadas , Colágeno/metabolismo , Matriz Extracelular/ultraestructura , Fibronectinas/metabolismo , Humanos , Mecanotransducción Celular , Miofibroblastos/metabolismo , Miofibroblastos/ultraestructura , Células del Estroma/metabolismo , Células del Estroma/ultraestructuraRESUMEN
BACKGROUND: Understanding non-epidemiological factors is essential for the surveillance and prevention of infectious diseases, and the factors are likely to vary spatially and temporally as the disease progresses. However, the impacts of these influencing factors were primarily assumed to be stationary over time and space in the existing literature. The spatiotemporal impacts of mobility-related and social-demographic factors on disease dynamics remain to be explored. METHODS: Taking daily cases data during the coronavirus disease 2019 (COVID-19) outbreak in the US as a case study, we develop a mobility-augmented geographically and temporally weighted regression (M-GTWR) model to quantify the spatiotemporal impacts of social-demographic factors and human activities on the COVID-19 dynamics. Different from the base GTWR model, the proposed M-GTWR model incorporates a mobility-adjusted distance weight matrix where travel mobility is used in addition to the spatial adjacency to capture the correlations among local observations. RESULTS: The results reveal that the impacts of social-demographic and human activity variables present significant spatiotemporal heterogeneity. In particular, a 1% increase in population density may lead to 0.63% more daily cases, and a 1% increase in the mean commuting time may result in 0.22% increases in daily cases. Although increased human activities will, in general, intensify the disease outbreak, we report that the effects of grocery and pharmacy-related activities are insignificant in areas with high population density. And activities at the workplace and public transit are found to either increase or decrease the number of cases, depending on particular locations. CONCLUSIONS: Through a mobility-augmented spatiotemporal modeling approach, we could quantify the time and space varying impacts of non-epidemiological factors on COVID-19 cases. The results suggest that the effects of population density, socio-demographic attributes, and travel-related attributes will differ significantly depending on the time of the pandemic and the underlying location. Moreover, policy restrictions on human contact are not universally effective in preventing the spread of diseases.
Asunto(s)
COVID-19 , COVID-19/epidemiología , Demografía , Brotes de Enfermedades/prevención & control , Humanos , Viaje , Enfermedad Relacionada con los ViajesRESUMEN
OBJECTIVE: To explore the expression of the Spag6L gene during spermatogenesis and the effects of Spag6L silencing on the proliferation and apoptosis of mouse GC-2 spd cells. METHODS: Using reverse-transcription PCR and real-time qPCR, we detected the expression of the Spag6L gene in the testis tissue collected from the mice at 8, 16, 20, 28 and 42 postnatal days. We prepared lentiviral particles inhibiting the expression of Spag6L and transfected them into the GC-2 spd cells. Then we screened the stably transfected cell lines with the Spag6L expression effectively down-regulated by real-time qPCR, analyzed the effects of Spag6L silencing on the proliferation, activity, cell cycle and apoptosis of the GC-2 spd cells by cell counting and flow cytometry, and on the expression levels of pro-apoptotic Bax and anti-apoptotic Bcl-2 by Western blot. RESULTS: The Spag6L gene was slightly expressed in the testis tissue of the mice at 8 postnatal days and gradually up-regulated with the development of the testis. Inhibition of the Spag6Lexpression significantly decreased the activity of the GC-2 spd cells (P < 0.01), leading to cell arrest in the G1 phase. The expression of the Bax protein was dramatically up-regulated (P < 0.01) while that of Bcl-2 remarkably down-regulated (P < 0.01) in the Spag6L shRNA- transfected cells, inducing the apoptosis of the cells. CONCLUSIONS: The Spag6L gene is involved in the spermatogenesis of mice by regulating the cell cycle, proliferation and apoptosis of spermatocytes.
Asunto(s)
Apoptosis , Espermatocitos , Animales , Proliferación Celular , Masculino , RatonesRESUMEN
Obesity increases the risk and worsens the prognosis for breast cancer due, in part, to altered adipose stromal cell (ASC) behavior. Whether ASCs from obese individuals increase migration of breast cancer cells relative to their lean counterparts, however, remains unclear. To test this connection, multicellular spheroids composed of MCF10A-derived tumor cell lines of varying malignant potential and lean or obese ASCs were embedded into collagen scaffolds mimicking the elastic moduli of interstitial breast adipose tissue. Confocal image analysis suggests that tumor cells alone migrate insignificantly under these conditions. However, direct cell-cell contact with either lean or obese ASCs enables them to migrate collectively, whereby obese ASCs activate tumor cell migration more effectively than their lean counterparts. Time-resolved optical coherence tomography (OCT) imaging suggests that obese ASCs facilitate tumor cell migration by mediating contraction of local collagen fibers. Matrix metalloproteinase (MMP)-dependent proteolytic activity significantly contributes to ASC-mediated tumor cell invasion and collagen deformation. However, ASC contractility is also important, as co-inhibition of both MMPs and contractility is necessary to completely abrogate ASC-mediated tumor cell migration. These findings imply that obesity-mediated changes of ASC phenotype may impact tumor cell migration and invasion with potential implications for breast cancer malignancy in obese patients.
RESUMEN
Ginsenoside Rg1 (Rg1) has been widely used in a broad range of cardiovascular and cerebral-vascular diseases because of its unique therapeutic properties. However, the underlying mechanisms of Rg1 in the treatment of atherosclerosis have not been fully explored. This study sought to determine the precise molecular mechanisms on how Rg1 might be involved in regulating apoptosis in serum deprivation-induced Raw264.7 macrophages and primary bone marrow-derived macrophages. Results demonstrated that Rg1 treatment effectively suppressed apoptosis and the expression of phosphorylation level of mTOR induced by serum deprivation in Raw264.7 macrophages; the expressions of autophagic flux-related proteins including Atg5, Beclin1, microtubule-associated protein 1 light chain 3 (LC3), p62/SQSMT1, and the phosphorylation level of AMPK were concomitantly up-regulated. 3-Methyl-adennine (3-MA), the most widely used autophagy inhibitor, strongly up-regulated the expression of cleaved caspase-3, and blocked the anti-apoptosis function of Rg1 in macrophages. Importantly, autophagic flux was activated by Rg1, while Beclin1 knockdown partially abolished the anti-apoptosis of Rg1. Moreover, compound C, an AMPK inhibitor, partially decreased the expressions of phosphorylation of mTOR, Atg5, Beclin1, LC3, and p62/SQSMT1, which were increased by Rg1. AICAR, an AMPK inducer, promoted the protein expressions of phosphorylation of mTOR, Atg5, Beclin1, LC3, and p62/SQSMT1. In conclusion, Rg1 significantly suppressed apoptosis induced by serum deprivation in macrophages. Furthermore, Rg1 could effectively induce the autophagic flux by attenuating serum deprivation-induced apoptosis in Raw264.7 macrophages through activating the AMPK/mTOR signaling pathway.
Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Ginsenósidos/farmacología , Macrófagos/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Animales , Western Blotting , Medio de Cultivo Libre de Suero/farmacología , Ginsenósidos/química , Macrófagos/metabolismo , Ratones , Estructura Molecular , Fosforilación/efectos de los fármacos , Células RAW 264.7 , Transducción de Señal/efectos de los fármacosRESUMEN
With the rapid growth of the Chinese zebrafish community, there is an increasing demand for various types of zebrafish-related resources and technologies. The China Zebrafish Resource Center (CZRC, web: http://zfish.cn) was established at the Institute of Hydrobiology (IHB), Chinese Academy of Sciences (CAS) in 2012. Till now, CZRC has built the largest zebrafish aquaculture unit in China, organized a resource bank containing more than 1200 zebrafish lines and more than 10 000 frozen sperm samples, among which over 200 mutant and transgenic lines were generated by CZRC. CZRC has established several technical supporting platforms, such as the zebrafish husbandry and health control program of international standard, a high-efficient gene manipulation technology platform, and a stable and efficient sperm cryopreservation technology platform. The main task of CZRC is to provide different types of services to zebrafish investigators in China and worldwide, such as resource services (e.g. zebrafish lines), technical services (e.g. gene knockout) and transgenic services, consultancy services (e.g. zebrafish husbandry and health consultation), and conference services [e.g. holding regular technical training courses and biennale Chinese Zebrafish Principal Investigator Meeting (CZPM)]. After five years' development, CZRC is now recognized as one of the three major resource centers in the global zebrafish community.
Asunto(s)
Animales Modificados Genéticamente/genética , Pez Cebra/genética , Animales , Animales Modificados Genéticamente/fisiología , Acuicultura/organización & administración , China , Criopreservación , Humanos , Pez Cebra/fisiología , Zoología/organización & administraciónRESUMEN
This study explores the vaccine prioritization strategy to reduce the overall burden of the pandemic when the supply is limited. Existing vaccine distribution methods focus on macro-level or simplified micro-level assuming homogeneous behavior within populations without considering mobility patterns. Directly applying these models for micro-level vaccine allocation leads to sub-optimal solutions. To address the issue, we first proposed a Trans-vaccine-SEIR model to incorporate mobility heterogeneity in disease propagation. Then we develop a novel deep reinforcement learning to seek the optimal vaccine allocation strategy for the disease evolution system. The graph neural network is used to effectively capture the structural properties of the mobility network and extract disease features. In our evaluation, the proposed framework reduces 7%-10% of infections and deaths compared to the baseline strategies. Extensive evaluation shows that the proposed framework is robust to seek the optimal vaccine allocation with diverse mobility patterns. In particular, we find transit usage restriction is significantly more effective than restricting cross-zone mobility for the top 10% age-based and income-based zones under optimal vaccine allocation strategy. These results provide valuable insights for areas with limited vaccines and low logistic efficacy.
Asunto(s)
Aprendizaje Profundo , Redes Neurales de la Computación , Humanos , COVID-19/prevención & control , COVID-19/epidemiología , SARS-CoV-2/inmunología , Vacunas contra la COVID-19RESUMEN
BACKGROUND/AIMS: The purpose of this study is to screen the feature genes related to gut microflora and explore the role of the genes in predicting the prognosis of patients with gastric cancer. MATERIALS AND METHODS: We downloaded the gene profile of gastric cancer from the University of California Santa Cruz, the gut microflora related to gastric cancer from The Cancer Microbiome Atlas. The GSE62254 dataset was downloaded from National Center for Biotechnology Information Gene Expression Omnibus as a validation dataset. A correlation network between differentially expressed genes and gut microflora was constructed using Cytoscape. The optimized prognostic differentially expressed genes were identified through least absolute shrinkage and selection operator (LASSO) algorithm and univariate Cox regression analysis. The risk score model was established and then measured via Kaplan-Meier and area under the curve. Finally, the nomogram model was constructed according to the independent clinical factors, which was evaluated using C-index. RESULTS: A total of 754 differentially expressed genes and 8 gut microflora were screened, based on which we successfully constructed the correlation network. We obtained 9 optimized prognostic differentially expressed genes, including HSD17B3, GNG7, CHAD, ARHGAP8, NOX1, YY2, GOLGA8A, DNASE1L3, and ABCA8. Moreover, Kaplan-Meier curves indicated the risk score model correctly predicted the prognosis of gastric cancer in both University of California Santa Cruz and GSE62254 dataset (area under the curve >0.8; area under the curve >0.7). Finally, we constructed the nomogram, in which the C index of 1, 3, and 5 years was 0.824, 0.772, and 0.735 representing that the nomogram was consistent with the actual situation. CONCLUSIONS: These results indicate the 9 differentially expressed genes related to gut microflora might predict the survival time of patients with gastric cancer. Both risk signature and nomogram could effectively predict the prognosis for patients with gastric cancer.
Asunto(s)
Microbioma Gastrointestinal , Neoplasias Gástricas , Humanos , Pronóstico , Microbioma Gastrointestinal/genética , Neoplasias Gástricas/genética , Nomogramas , Algoritmos , Factores de Transcripción , Proteínas Activadoras de GTPasaRESUMEN
The causal impact of COVID-19 vaccine coverage on effective reproduction number R(t) under the disease control measures in the real-world scenario is understudied, making the optimal reopening strategy (e.g., when and which control measures are supposed to be conducted) during the recovery phase difficult to design. In this study, we examine the demographic heterogeneity and time variation of the vaccine effect on disease propagation based on the Bayesian structural time series analysis. Furthermore, we explore the role of non-pharmaceutical interventions (NPIs) and the entrance of the Delta variant of COVID-19 in the vaccine effect for U.S. counties. The analysis highlights several important findings: First, vaccine effects vary among the age-specific population and population densities. The vaccine effect for areas with high population density or core airport hubs is 2 times higher than for areas with low population density. Besides, areas with more older people need a high vaccine coverage to help them against the more contagious variants (e.g., the Delta variant). Second, the business restriction policy and mask requirement are more effective in preventing COVID-19 infections than other NPI measures (e.g., bar closure, gather ban, and restaurant restrictions) for areas with high population density and core airport hubs. Furthermore, the mask requirement consistently amplifies the vaccine effects against disease propagation after the presence of contagious variants. Third, areas with a high percentage of older people are suggested to postpone relaxing the restaurant restriction or gather ban since they amplify the vaccine effect against disease infections. Such empirical insights assist recovery phases of the pandemic in designing more efficient reopening strategies, vaccine prioritization, and allocation policies.
Asunto(s)
COVID-19 , Vacunas , Humanos , Anciano , Vacunas contra la COVID-19 , COVID-19/epidemiología , COVID-19/prevención & control , Teorema de Bayes , SARS-CoV-2RESUMEN
INTRODUCTION: Right-turn lane (RTL) crashes are among the key contributors to intersection crashes in the US. Unfortunately, the lack of deep insights into understanding the effects of RTL geometric design factors on crash frequency impedes improving RTL safety performance. METHOD: Taking the crash data in ten counties in Indiana state from 2013 to 2016 as a case study, this study investigates the safety performance of RTL geometric configuration based on multi-sources. We introduce the geographically and temporally weighted negative binomial model (GTWNBR) to capture the space and time instability in crashes. RESULTS: The results show that the impacts of RTL geometric design factors on crash frequency vary significantly among space and time. Several key insights can be obtained from the state-wide and multi-years crash analysis by associating the estimated parameters with road classes, localities, and counties. CONCLUSIONS: First, the RTL's length, width, turning radius, and the installments of traffic roundabouts present higher spatiotemporal heterogeneity than other factors in modeling the crash frequency. Second, the effects of RTL's geometric factors vary significantly across space and time. The presence of bicycle and pedestrian lanes is more likely to increase crashes in urban areas than in rural ones, especially at nighttime. Third, while exclusive RTLs decrease the crash frequency compared to the shared RTLs, the exclusive RTLs are more likely to increase the crashes for RTLs on the county road than on other road classes. Increasing RTL's turning radius and decreasing RTL's length is more likely to promote crashes for RTLs on county roads than on other road classes. PRACTICAL APPLICATIONS: The insights provide vital guidance to improve the safety performance of geometric configuration for RTLs and intersections.
Asunto(s)
Modelos Estadísticos , Peatones , Humanos , IndianaRESUMEN
Increased fibrotic extracellular matrix (ECM) deposition promotes tumor invasion, which is the first step of the metastatic cascade. Yet, the underlying mechanisms are poorly understood as conventional studies of tumor cell migration are often performed in 2D cultures lacking the compositional and structural complexity of native ECM. Moreover, these studies frequently focus on select candidate pathways potentially overlooking other relevant changes in cell signaling. Here, we combine a cell-derived matrix (CDM) model with phosphotyrosine phosphoproteomic analysis to investigate tumor cell migration on fibrotic ECM relative to standard tissue culture plastic (TCP). Our results suggest that tumor cells cultured on CDMs migrate faster and in a more directional manner than their counterparts on TCP. These changes in migration correlate with decreased cell spreading and increased cell elongation. While the formation of phosphorylated focal adhesion kinase (pFAK)+ adhesion complexes did not vary between TCP and CDMs, time-dependent phosphoproteomic analysis identified that the SRC family kinase LYN may be differentially regulated. Pharmacological inhibition of LYN decreased tumor cell migration and cytoskeletal rearrangement on CDMs and also on TCP, suggesting that LYN regulates tumor cell migration on CDMs in combination with other mechanisms. These data highlight how the combination of physicochemically complex in vitro systems with phosphoproteomics can help identify signaling mechanisms by which the fibrotic ECM regulates tumor cell migration.
Asunto(s)
Citoesqueleto , Matriz Extracelular , Movimiento Celular/fisiología , Matriz Extracelular/metabolismo , Citoesqueleto/metabolismo , Transducción de SeñalRESUMEN
C1q/TNF-related protein 4 (CTRP4) is generally thought to be released extracellularly and plays a critical role in energy metabolism and protecting against sepsis. However, its physiological functions in autoimmune diseases have not been thoroughly explored. In this study, we demonstrate that Th17 cell-associated experimental autoimmune encephalomyelitis was greatly exacerbated in Ctrp4-/- mice compared with WT mice due to increased Th17 cell infiltration. The absence of Ctrp4 promoted the differentiation of naive CD4+ T cells into Th17 cells in vitro. Mechanistically, CTRP4 interfered with the interaction between IL-6 and the IL-6 receptor (IL-6R) by directly competing to bind with IL-6R, leading to suppression of IL-6-induced activation of the STAT3 pathway. Furthermore, the administration of recombinant CTRP4 protein ameliorated disease symptoms. In conclusion, our results indicate that CTRP4, as an endogenous regulator of the IL-6 receptor-signaling pathway, may be a potential therapeutic intervention for Th17-driven autoimmune diseases.
Asunto(s)
Encefalomielitis Autoinmune Experimental , Encefalomielitis , Ratones , Animales , Interleucina-6/genética , Interleucina-6/metabolismo , Células Th17 , Complemento C1q , Diferenciación Celular , Factores Inmunológicos , Receptores de Interleucina-6/genética , Receptores de Interleucina-6/metabolismo , Ratones Endogámicos C57BL , Adipoquinas/metabolismoRESUMEN
The current discourse addresses fiscal issues, financial decentralization, and environmental quality and significantly affects economic development and sustainability. This investigation aims to address the research gap in fiscal decentralization and haze pollution for innovation and sustainable growth. This study uses the annual data of 270 Chinese cities from 2007 to 2016 for comprehensive analysis and employs spatial regression methods. The key findings imply that haze pollution in neighbouring cities causes further ecological issues. While the environmental regulations of China tend to have negative impacts on pollution, fiscal decentralization was found to be a key contributor to environmental pollution in Chinese cities. Overall, the study supports the validity of the pollution refuge hypothesis in China. Lastly, the conclusions allow us to conclude that China might need micro-level reforms regarding fiscal decentralization, environmental tax laws, and encouragement of cleaner production technologies.
Asunto(s)
Contaminación del Aire , Desarrollo Económico , Contaminación del Aire/análisis , China , Ciudades , Contaminación Ambiental/análisis , PolíticaRESUMEN
Emerging evidence from observational studies proves the association between preterm birth (PTB) and phthalate metabolites; however, such findings are inconsistent and inconclusive. This meta-analysis aimed to clarify this association by accessing the connection between 11 phthalate metabolites and PTB, and 6 phthalate metabolites and spontaneous PTB. The PubMed, Embase, and WOS (Web of Science) databases were searched up to July 2020. Seven prospective studies met the inclusion criteria. Pooled odds ratios (OR) with 95 % confidence intervals (CIs) were calculated for risk estimation. Our results indicated that mono-n-butyl phthalate (MBP), sum of di-2-ethylhexyl phthalate (ΣDEHP), and mono 3-carboxypropyl phthalate (MCPP) significantly correlated with the risk of PTB (MBP: OR = 1.23, 95 % CI = 1.05-1.45; ΣDEHP: OR = 1.21, 95 % CI =1.01-1.44; MCPP: OR = 1.09, 95 % CI = 1.00-1.19). Pooled results showed that spontaneous PTB was associated with higher urinary levels of mono-ethyl phthalate (MEP), MCPP, mono-isobutyl phthalate (MIBP), and MBP (MBP: OR = 1.27, 95 % CI = 1.02-1.58; MEP: OR = 1.19, 95 % CI = 1.01-1.40; MCPP: OR = 1.15, 95 % CI = 1.02-1.30; MIBP: OR = 1.38, 95 % CI = 1.12-1.71). Overall, we conclude that during pregnancy, MBP, ΣDEHP, and MCPP levels are associated positively with PTB. MBP, MEP, MCPP, and MIBP levels had increased odds of spontaneous PTB. No significant associations were observed between other phthalate metabolites and PTB or spontaneous PTB. Further research is needed to verify these findings and elucidate the association of phthalate levels and PTB.
Asunto(s)
Contaminantes Ambientales , Ácidos Ftálicos , Nacimiento Prematuro , Exposición a Riesgos Ambientales/análisis , Contaminantes Ambientales/orina , Femenino , Humanos , Recién Nacido , Ácidos Ftálicos/orina , Embarazo , Nacimiento Prematuro/epidemiología , Estudios ProspectivosRESUMEN
This study aims to evaluate the effects of cold atmospheric plasma (CAP) treatment on the bonding of resin cement to high-translucency zirconia. Zirconia specimens were subjected to different treatments: no treatment (ZrT), 10-methacryloyloxydecyl dihydrogen phosphate (MDP)-containing primer (ZrT-M), alumina particle air-abrasion with/without MDP-containing primer (ZrT-AM/ZrT-A), CAP with/without MDP-containing primer (ZrT-PM/ZrT-P). The surface topography, wettability, and chemical composition were evaluated. The shear bond strength (SBS) was tested before and after thermocycling. CAP did not alter the morphology, increased the wettability, and decreased the carbon/oxygen ratio of zirconia surface. The SBSs of ZrT-PM and ZrT-P were significantly higher than the other groups. After thermocycling, ZrT-A, ZrT-M, ZrT-AM, and ZrT-P showed comparable SBSs, all of which were lower than ZrT-PM. It was concluded that CAP improved the bonding performance of high-translucency zirconia without damaging its surface. The combination of CAP with MDP further enhanced the bond strength and may enable durable bonding.
Asunto(s)
Recubrimiento Dental Adhesivo , Gases em Plasma , Ensayo de Materiales , Propiedades de Superficie , Circonio/química , Cementos de Resina/química , Cerámica , Resistencia al Corte , Metacrilatos/químicaRESUMEN
Despite decades of research and advancements in diagnostic and treatment modalities, cancer remains a major global healthcare challenge. This is due in part to a lack of model systems that allow investigating the mechanisms underlying tumor development, progression, and therapy resistance under relevant conditions in vitro. Tumor cell interactions with their surroundings influence all stages of tumorigenesis and are shaped by both biological and biophysical cues including cell-cell and cell-extracellular matrix (ECM) interactions, tissue architecture and mechanics, and mass transport. Engineered tumor models provide promising platforms to elucidate the individual and combined contributions of these cues to tumor malignancy under controlled and physiologically relevant conditions. This review will summarize current knowledge of the biological and biophysical microenvironmental cues that influence tumor development and progression, present examples of in vitro model systems that are presently used to study these interactions and highlight advancements in tumor engineering approaches to further improve these technologies.