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1.
Emerg Microbes Infect ; 13(1): 2322671, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38390796

RESUMEN

The increasing incidence of diseases caused by Coxsackievirus A6 (CV-A6) and the presence of various mutants in the population present significant public health challenges. Given the concurrent development of multiple vaccines in China, it is challenging to objectively and accurately evaluate the level of neutralizing antibody response to different vaccines. The choice of the detection strain is a crucial factor that influences the detection of neutralizing antibodies. In this study, the National Institutes for Food and Drug Control collected a prototype strain (Gdula), one subgenotype D1, as well as 13 CV-A6 candidate vaccine strains and candidate detection strains (subgenotype D3) from various institutions and manufacturers involved in research and development. We evaluated cross-neutralization activity using plasma from naturally infected adults (n = 30) and serum from rats immunized with the aforementioned CV-A6 strains. Although there were differences between the geometric mean titer (GMT) ranges of human plasma and murine sera, the overall trends were similar. A significant effect of each strain on the neutralizing antibody test (MAX/MIN 48.0 ∼16410.3) was observed. Among all strains, neutralization of the S112 strain by 15 different sera resulted in higher neutralizing antibody titers (GMTS112 = 132.0) and more consistent responses across different genotypic immune sera (MAX/MIN = 48.0). Therefore, S112 may serve as a detection strain for NtAb testing in various vaccines, minimizing bias and making it suitable for evaluating the immunogenicity of the CV-A6 vaccine.


Asunto(s)
Anticuerpos Neutralizantes , Vacunas , Adulto , Humanos , Animales , Ratones , Ratas , Anticuerpos Antivirales , Investigación , China
2.
Mol Cancer Ther ; 23(3): 316-329, 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-37816504

RESUMEN

Expression of the serine/threonine kinase never in mitosis gene A (NIMA)-related kinase 2 (NEK2) is essential for entry into mitosis via its role in facilitating centrosome separation. Its overactivity can lead to tumorigenesis and drug resistance through the activation of several oncogenic pathways, including AKT. Although the cancer-enabling activities of NEK2 are documented in many malignancies, including correlations with poor survival in myeloma, breast, and non-small cell lung cancer, little is known about the role of NEK2 in lymphoma. Here, in tumors from patients with diffuse large B-cell lymphoma (DLBCL), the most common, aggressive non-Hodgkin lymphoma, we found a high abundance of NEK2 mRNA and protein associated with an inferior overall survival. Using our recently developed NEK2 inhibitor, NBI-961, we discovered that DLBCL cell lines and patient-derived cells exhibit a dependency on NEK2 for their viability. This compromised cell fitness was directly attributable to efficient NEK2 inhibition and proteasomal degradation by NBI-961. In a subset of particularly sensitive DLBCL cells, NBI-961 induced G2/mitosis arrest and apoptosis. In contrast, an existing indirect NEK2 inhibitor, INH154, did not prevent NEK2 autophosphorylation, induce NEK2 proteasomal degradation, or affect cell viability. Global proteomics and phospho-proteomics revealed that NEK2 orchestrates cell-cycle and apoptotic pathways through regulation of both known and new signaling molecules. We show the loss of NEK2-sensitized DLBCL to the chemotherapy agents, doxorubicin and vincristine, and effectively suppressed tumor growth in mice. These studies establish the oncogenic activity of NEK2 in DLBCL and set the foundation for development of anti-NEK2 therapeutic strategies in this frequently refractory and relapse-prone cancer.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Linfoma de Células B Grandes Difuso , Linfoma , Humanos , Animales , Ratones , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Quinasas Relacionadas con NIMA/genética , Línea Celular Tumoral , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/genética
3.
Environ Sci Pollut Res Int ; 31(4): 6106-6124, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38146026

RESUMEN

The opening of high-speed railway (HSR) has accelerated the reorganization and reallocation of regional production elements, and constantly promoted the adjustment and upgrading of industrial structure. The cleaner production effect produced by industrial structure upgrading is of great significance to industrial pollution reduction. As a bridge connecting resources within the city and elements outside the city, the location of HSR stations has become an important factor affecting the structural emission reduction effect. Based on the data of 285 prefecture level and above cities in China from 2004 to 2018, this paper investigates the structural emission reduction effects of HSR opening and the impact of HSR station location on it by employing difference-in-differences (DID) model combined with mediation effect method. The results demonstrate that the opening of HSR has significant structural emission reduction effect, and the upgrading of inter-industry structure and the intra-industry structure are important mechanisms for HSR to achieve industrial emission reduction. The structural emission reduction effect of HSR opening is closely related to the location of HSR stations. With the increase of the distance between HSR station and city center, the industrial structure upgrading effect will continue to weaken, thus inhibiting the exertion of structural emission reduction effect, of which 10 km away from the city center is the optimal site strategy for the HSR service to give full play to the structural emission reduction effect, and exceeding 50 km will be significantly detrimental to its role in promoting industrial structure upgrading.


Asunto(s)
Contaminación Ambiental , Industrias , China , Ciudades , Desarrollo Económico
4.
Environ Sci Pollut Res Int ; 30(51): 110395-110416, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37783999

RESUMEN

The digital economy has become a new driving force for China's economic development in recent years, and it may contribute to solving the corresponding problems of resource and environmental pressure. Therefore, this study strives to explore whether the digital economy contributes to the green development of foreign trade. First, this study measures the digital economy development in China. Second, this study presents a list of environmental and polluting products and examines the impact of digital economy development on exports of representative products based on an extended gravity model. The main findings are as follows. First, the digital economy significantly promotes the green development of foreign trade. Second, the signing of Free Trade Agreements (FTAs) and the income level of importing countries and regions strengthen the role of the digital economy in promoting the green development of foreign trade. Third, the digital economy promotes the green development of foreign trade through green technological innovation. Finally, some policy implications are proposed based on the findings of this study.


Asunto(s)
Desarrollo Económico , Desarrollo Sostenible , China , Gravitación , Políticas
5.
Heliyon ; 9(9): e19163, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37809901

RESUMEN

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide and become a major global public health concern. Although novel investigational COVID-19 antiviral candidates such as the Pfizer agent PAXLOVID™, molnupiravir, baricitinib, remdesivir, and favipiravir are currently used to treat patients with COVID-19, there is still a critical need for the development of additional treatments, as the recommended therapeutic options are frequently ineffective against SARS-CoV-2. The efficacy and safety of vaccines remain uncertain, particularly with the emergence of several variants. All 10 versions of the National Health Commission's diagnosis and treatment guidelines for COVID-19 recommend using traditional Chinese medicine. Xuanfei Baidu Decoction (XFBD) is one of the "three Chinese medicines and three Chinese prescriptions" recommended for COVID-19. This review summarizes the clinical evidence and potential mechanisms of action of XFBD for COVID-19 treatment. With XFBD, patients with COVID-19 experience improved clinical symptoms, shorter hospital stay, prevention of the progression of their symptoms from mild to moderate and severe symptoms, and reduced mortality in critically ill patients. The mechanisms of action may be associated with its direct antiviral, anti-inflammatory, immunomodulatory, antioxidative, and antimicrobial properties. High-quality clinical and experimental studies are needed to further explore the clinical efficacy and underlying mechanisms of XFBD in COVID-19 treatment.

8.
Artículo en Inglés | MEDLINE | ID: mdl-36538228

RESUMEN

Collaborative reduction of carbon and air pollutants can more efficiently achieve green technological change, industrial low-carbon transition, and high-quality economic and social development. As a typical environmental policy in China, the pilot carbon Emission Trading Scheme (ETS) has obvious advantages in achieving the collaborative reduction of carbon and air pollutants. Therefore, an evaluation of China's pilot carbon ETS from the perspective of collaborative reduction of carbon and air pollutants is performed in this paper. Compared with previous studies, first, this study innovatively uses the coupled coordination degree (CCD) model to measure the collaborative reduction level of carbon and air pollutants under different scenarios based on the panel data of China's 30 provincial-level regions during 2004-2018. Second, this study uses the DID method to evaluate the impact of China's pilot carbon ETS on the collaborative reduction of carbon and air pollutants and conducts some robustness checks and regional heterogeneity regressions. Third, this study uses the synthetic control method (SCM) further to examine the policy outcomes of the pilot carbon ETS. Scenario analysis shows that attaching importance to reducing air pollution will improve the collaborative reduction effect of carbon and air pollutants. Furthermore, the implementation of China's pilot carbon ETS exerts an effect of roughly 24.7% on reducing carbon, roughly 10.1% on reducing air pollutants, and roughly 22.0% on the collaborative reduction of carbon and air pollutants, ceteris paribus. Regional heterogeneity analysis shows that the impacts of the pilot carbon ETS are significant in all regions, except that the impact on reducing air pollutants in the central region is not significant. In addition, results from SCM indicate that the impacts of the pilot carbon ETS on the collaborative reduction of carbon and air pollutants are significantly efficient in Beijing, Tianjin, Shanghai, Hubei, and Chongqing, while not much efficient in Guangdong and Fujian. The main policy implications include strengthening the top-level design of the ETS in the collaborative reduction of carbon and air pollutants, attaching importance to the governance of air pollution, making the regional governance more targeted, and improving energy efficiency.

9.
Phytomedicine ; 107: 154459, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36183476

RESUMEN

BACKGROUND: Hypertension is one of the most significant public health challenges worldwide. An increasing number of patients prefer to incorporate traditional Chinese medicine into their hypertensive care. The Songling Xuemaikang capsule (SXC), a Chinese herbal formula, is widely used in China for essential hypertension. PURPOSE: To assess the efficacy and safety of SXC for essential hypertension. STUDY DESIGN: Systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: We conducted a systematic literature search of seven databases to identify randomized controlled trials of SXC for hypertension. The outcome measures included blood pressure parameters and patient-reported outcomes. Potential heterogeneity between the studies was resolved by subgroup and sensitivity analyses. The quality of the results was evaluated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. RESULTS: A total of 34 trials with 4306 patients were included. The results showed that SXC plus antihypertensive drugs produced a greater effect on reducing systolic blood pressure (SBP) (MD: -7.54 mmHg; 95% CI: -8.92, -6.17; p < 0.00001), diastolic blood pressure (DBP) (MD: -6.42 mmHg; 95% CI: -7.54, -5.29; p < 0.00001), 24-hour SBP (MD: -6.88 mmHg; 95% CI: -8.36, -5.39; p < 0.00001), and 24-hour DBP (MD: -4.31 mmHg; 95% CI: -6.55, -2.07; p = 0.0002) and improving hypertensive symptoms (SMD: -1.09; 95% CI: -1.34, -0.84; p < 0.00001) than antihypertensive drugs alone. SXC monotherapy was less effective than antihypertensive drugs for 24-hour SBP reduction (MD: 2.07 mmHg; 95% CI: 0.19, 3.96; p = 0.03). No significant difference was observed in the incidence of adverse events between the SXC and control groups. CONCLUSION: SXC is beneficial for essential hypertension; it can lower BP, improve hypertensive symptoms and is well tolerated.


Asunto(s)
Antihipertensivos , Hipertensión , Antihipertensivos/efectos adversos , Presión Sanguínea , Medicamentos Herbarios Chinos , Hipertensión Esencial/tratamiento farmacológico , Humanos , Hipertensión/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto
10.
Genes (Basel) ; 13(7)2022 06 25.
Artículo en Inglés | MEDLINE | ID: mdl-35885931

RESUMEN

The aggressive nature of the activated B cell such as (ABC) subtype of diffuse large B cell (DLBCL) is frequently associated with altered B cell Receptor (BCR) signaling through the activation of key components including the scaffolding protein, CARD11. Most inhibitors, such as ibrutinib, target downstream BCR kinases with often modest and temporary responses for DLBCL patients. Here, we pursue an alternative strategy to target the BCR pathway by leveraging a novel DNA secondary structure to repress transcription. We discovered that a highly guanine (G)-rich element within the CARD11 promoter forms a stable G-quadruplex (G4) using circular dichroism and polymerase stop biophysical techniques. We then identified a small molecule, naptho(2,1-b)furan-1-ethanol,2-nitro- (NSC373981), from a fluorescence-resonance energy transfer-based screen that stabilized CARD11 G4 and inhibited CARD11 transcription in DLBCL cells. In generating and testing analogs of NSC373981, we determined that the nitro group is likely essential for the downregulation of CARD11 and interaction with CARD11 G4, and the removal of the ethanol side chain enhanced this activity. Of note, the expression of BCL2 and MYC, two other key oncogenes in DLBCL pathology with known promoter G4 structures, were often concurrently repressed with NSC373981 and the highly potent R158 analog. Our findings highlight a novel approach to treat aggressive DLBCL by silencing CARD11 gene expression that warrants further investigation.


Asunto(s)
Proteínas Adaptadoras de Señalización CARD , Linfoma de Células B Grandes Difuso , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Adaptadoras de Señalización CARD/genética , Etanol , Furanos , Guanilato Ciclasa/genética , Guanilato Ciclasa/metabolismo , Humanos , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/patología , Oncogenes/genética
11.
Environ Sci Pollut Res Int ; 29(46): 70340-70359, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35588036

RESUMEN

The new Agenda 2030 for sustainable development call for initiatives to bridge the gap between environmental protection and socio-economic development. To provide insight on the relationship between socio-economics, and ecology, the current study examines the effectiveness of environmental stringency and green energy to mitigate the effects of fossil energy and greenhouse gas emissions on human well-being and income for 12 emerging economies. The outcomes from dynamic heterogeneous panel estimators of cross-sectional-based auto regressive distributed lag and cross-sectional-augmented distributed lag indicate that: (i) green energy consumption and electricity consumption have a substantial positive effect on well-being and per capita income. (ii) The stringent environmental policy is found to decrease per capita income, but it increases well-being, while the square of environmental stringency is found to increase per capita income. (iii) Fossil energy consumption and greenhouse gas emissions have a negative effect on well-being but a positive impact on income. The outcome of U-test confirmed the presence of a U-shaped curve with a turning point (0.433) between per capita income and environmental policy stringency. This study yielded consistent results from the panel Granger causality test. Based on our findings, we may argue that it is necessary to prioritize human well-being over economic growth, and suggest several policy implications to achieve sustainable development goals.


Asunto(s)
Gases de Efecto Invernadero , Dióxido de Carbono/análisis , Estudios Transversales , Desarrollo Económico , Fósiles , Humanos , Energía Renovable
12.
Environ Sci Pollut Res Int ; 29(24): 36626-36639, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35064495

RESUMEN

The construction of new-type urbanization with the theme of innovation, green, and smart development is becoming the endogenous driving force of China's economic transformation and upgrading, and green technological innovation is a key factor in cracking the problems of development motivation and environmental constraints in urbanization construction. This paper investigates the impact of green technology innovation on urbanization based on a panel dataset covering 30 provinces in China from 2005 to 2019. First, we use the entropy method and the super-efficiency DEA method to measure the level of urbanization and green technology innovation, respectively. Moreover, on this basis, we use panel regression model and FGLS model to estimate the direct impact of green technological innovation on urbanization and its three dimensions-population urbanization, industrial urbanization, and ecological urbanization. Then, the mediating effect model is used to further study the indirect impact of green technological innovation on urbanization. The results indicate that green technological innovation is the most effective way to promote the development of new urbanization currently. In addition, green technology innovation can indirectly affect urbanization through the effects of foreign capital, energy consumption and information development, while the effect of industrial structure optimization effects is not significant. Finally, some policy suggestions are discussed to better promote the development of urbanization in China.


Asunto(s)
Invenciones , Urbanización , China , Desarrollo Económico , Industrias
13.
Environ Sci Pollut Res Int ; 29(16): 23249-23263, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34800274

RESUMEN

In 2013, the Chinese government officially announced the Belt and Road Initiative (BRI). Since then, environmentalists have raised concerns regarding the environmental impact of trade between China and BRI countries. Therefore, the current study aims to analyze the environmental impact of the two aspects of BRI countries' trade: First, it examines the environmental impact of trade openness between China and BRI countries. Second, it examines the environmental impact of trade openness among BRI countries. For this purpose, the current study employs the two-step system GMM model with a panel dataset for the period 2001-2018. The results obtained for the whole sample of 88 selected BRI countries suggest that the trade openness between China and BRI countries significantly reduces CO2 emissions. However, the trade openness among BRI countries has no significant effect on CO2 emissions. In addition, BRI countries' exports to China do not have a significant effect on CO2 emissions. However, BRI countries' imports from China significantly reduce CO2 emissions in these countries. The results obtained for the subsamples of BRI countries suggest that the trade openness between China and BRI countries, BRI countries' exports to China, and BRI countries' imports from China have no significant effect on CO2 emissions in both low-income and high-income BRI countries. Moreover, the trade openness among BRI countries significantly increases CO2 emissions in low-income BRI countries only.


Asunto(s)
Dióxido de Carbono , Análisis de Datos , Dióxido de Carbono/análisis , China , Desarrollo Económico , Ambiente , Renta
14.
Viruses ; 13(5)2021 04 21.
Artículo en Inglés | MEDLINE | ID: mdl-33919184

RESUMEN

Enterovirus A-71 (EV71) is a global, highly contagkkious pathogen responsible for severe cases of hand-food-mouth-disease (HFMD). The use of vaccines eliciting cross neutralizing antibodies (NTAbs) against the different circulating EV71 sub-genotypes is important for preventing HFMD outbreaks. Here, we tested the cross-neutralizing activities induced by EV71 genotype/sub-genotype A, B0-B4, C1, C2, C4, and C5 viruses using rats. Differences were noted in the cross-neutralization of the 10 sub-genotypes tested but there were generally good levels of cross-neutralization except against genotype A virus, against which neutralization antibody titres (NTAb) where the lowest with NTAbs being the highest against sub-genotype B4. Moreover, NTAb responses induced by C4, B4, C1, and C2 viruses were homogenous, with values of maximum/minimum NTAb ratios (MAX/MIN) against all B and C viruses ranging between 4.0 and 6.0, whereas MAX/MIN values against B3 and A viruses were highly variable, 48.0 and 256.0, respectively. We then dissected the cross-neutralizing ability of sera from infants and children and rats immunized with C4 EV71 vaccines. Cross-neutralizing titers against the 10 sub-genotypes were good in both vaccinated infants and children and rats with the MAX/MIN ranging from 1.8-3.4 and 5.1-7.1, respectively, which were similar to those found in naturally infected patients (2.8). Therefore, we conclude that C4 EV71 vaccines can provide global protection to infants and children against HFMD caused by different sub-genotypes.


Asunto(s)
Antígenos Virales/inmunología , Reacciones Cruzadas/inmunología , Enterovirus Humano A/genética , Enterovirus Humano A/inmunología , Infecciones por Enterovirus/inmunología , Infecciones por Enterovirus/virología , Genotipo , Animales , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Infecciones por Enterovirus/prevención & control , Humanos , Inmunogenicidad Vacunal , Pruebas de Neutralización , Ratas , Vacunas de Productos Inactivados/inmunología , Vacunas Virales/inmunología
15.
Front Neurol ; 12: 747380, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35173663

RESUMEN

The morbidity and mortality rates of ischemic stroke (IS) are very high, and IS constitutes one of the main causes of disability and death worldwide. The pathogenesis of ischemic stroke includes excitotoxicity, calcium overload, oxygen radical injury, inflammatory reactions, necrosis/apoptosis, destruction of the blood-brain barrier (BBB), and other pathologic processes. Recent studies have shown that exosomes are critical to the pathogenesis, diagnosis, and treatment of cerebral infarctions resulting from ischemic stroke; and there is growing interest in the role of exosomes and exosomal miRNAs in the diagnosis and treatment of IS. Exosomes from central nervous system cells can be found in cerebrospinal fluid and peripheral bodily fluids, and exosomal contents have been reported to change with disease occurrence. Exosomes are small membranous extracellular vesicles (EVs), 30-150 nm in diameter, that are released from the cell membrane into the depressions that arise from the membranes of multivesicular bodies. Exosomes carry lipids, proteins, mRNAs, and microRNAs (miRNAs) and transport information to target cells. This exosomal transfer of functional mRNAs/miRNAs and proteins ultimately affects transcription and translation within recipient cells. Exosomes are EVs with a double-membrane structure that protects them from ribonucleases in the blood, allowing exosomal miRNAs to be more stable and to avoid degradation. New evidence shows that exosomes derived from neural cells, endothelial cells, and various stem cells create a fertile environment that supports the proliferation and growth of neural cells and endothelial cells, inhibits apoptosis and inflammatory responses, and promotes angiogenesis. In the present review, we discuss how circulating exosomes-and exosomal miRNAs in particular-may provide novel strategies for the early diagnosis and treatment of ischemic stroke via their potential as non-invasive biomarkers and drug carriers.

16.
Artículo en Inglés | MEDLINE | ID: mdl-33178313

RESUMEN

AIM: Stroke is the second significant cause for death, with ischemic stroke (IS) being the main type threatening human being's health. Acorus tatarinowii (AT) is widely used in the treatment of Alzheimer disease, epilepsy, depression, and stroke, which leads to disorders of consciousness disease. However, the systemic mechanism of AT treating IS is unexplicit. This article is supposed to explain why AT has an effect on the treatment of IS in a comprehensive and systematic way by network pharmacology. METHODS AND MATERIALS: ADME (absorbed, distributed, metabolized, and excreted) is an important property for screening-related compounds in AT, which were screening out of TCMSP, TCMID, Chemistry Database, and literature from CNKI. Then, these targets related to screened compounds were predicted via Swiss Targets, when AT-related targets database was established. The gene targets related to IS were collected from DisGeNET and GeneCards. IS-AT is a common protein interactive network established by STRING Database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were analysed by IS-AT common target genes. Cytoscape software was used to establish a visualized network for active compounds-core targets and core target proteins-proteins interactive network. Furthermore, we drew a signal pathway picture about its effect to reveal the basic mechanism of AT against IS systematically. RESULTS: There were 53 active compounds screened from AT, inferring the main therapeutic substances as follows: bisasaricin, 3-cyclohexene-1-methanol-α,α,4-trimethyl,acetate, cis,cis,cis-7,10,13-hexadecatrienal, hydroxyacoronene, nerolidol, galgravin, veraguensin, 2'-o-methyl isoliquiritigenin, gamma-asarone, and alpha-asarone. We obtained 398 related targets, 63 of which were the same as the IS-related genes from targets prediction. Except for GRM2, remaining 62 target genes have an interactive relation, respectively. The top 10 degree core target genes were IL6, TNF, IL1B, TLR4, NOS3, MAPK1, PTGS2, VEGFA, JUN, and MMP9. There were more than 20 terms of biological process, 7 terms of cellular components, and 14 terms of molecular function through GO enrichment analysis and 13 terms of signal pathway from KEGG enrichment analysis based on P < 0.05. CONCLUSION: AT had a therapeutic effect for ischemic via multicomponent, multitarget, and multisignal pathway, which provided a novel research aspect for AT against IS.

17.
NAR Cancer ; 2(4): zcaa029, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33094287

RESUMEN

Diffuse large B-cell lymphoma (DLBCL) is a molecularly heterogeneous group of malignancies with frequent genetic abnormalities. G-quadruplex (G4) DNA structures may facilitate this genomic instability through association with activation-induced cytidine deaminase (AID), an antibody diversification enzyme implicated in mutation of oncogenes in B-cell lymphomas. Chromatin immunoprecipitation sequencing analyses in this study revealed that AID hotspots in both activated B cells and lymphoma cells in vitro were highly enriched for G4 elements. A representative set of these targeted sequences was validated for characteristic, stable G4 structure formation including previously unknown G4s in lymphoma-associated genes, CBFA2T3, SPIB, BCL6, HLA-DRB5 and MEF2C, along with the established BCL2 and MYC structures. Frequent genome-wide G4 formation was also detected for the first time in DLBCL patient-derived tissues using BG4, a structure-specific G4 antibody. Tumors with greater staining were more likely to have concurrent BCL2 and MYC oncogene amplification and BCL2 mutations. Ninety-seven percent of the BCL2 mutations occurred within G4 sites that overlapped with AID binding. G4 localization at sites of mutation, and within aggressive DLBCL tumors harboring amplified BCL2 and MYC, supports a role for G4 structures in events that lead to a loss of genomic integrity, a critical step in B-cell lymphomagenesis.

18.
Biochimie ; 179: 190-204, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33010339

RESUMEN

Stroke is one of the most common causes of disability and death, and currently, ideal clinical treatment is lacking. Stem cell transplantation is a widely-used treatment approach for stroke. When compared with other types of stem cells, bone marrow mesenchymal stem cells (BMSCs) have been widely studied because of their many advantages. The paracrine effect is the primary mechanism for stem cells to play their role, and exosomes play an essential role in the paracrine effect. When compared with cell therapy, cell-free exosome therapy can prevent many risks and difficulties, and therefore, represents a promising and novel approach for treatment. In this study, we reviewed the research progress in the application of BMSCs-derived exosomes (BMSCs-exos) and BMSCs in the treatment of stroke. In addition, the advantages and disadvantages of cell therapy and cell-free exosome therapy were described, and the possible factors that hinder the introduction of these two treatments into the clinic were analyzed. Furthermore, we reviewed the current optimization methods of cell therapy and cell-free exosome therapy. Taken together, we hypothesize that cell-free exosome therapy will have excellent research prospects in the future, and therefore, it is worth further exploring. There are still some issues that need to be further addressed. For example, differences between the in vivo microenvironment and in vitro culture conditions will affect the paracrine effect of stem cells. Most importantly, we believe that more preclinical and clinical design studies are required to compare the efficacy of stem cells and exosomes.


Asunto(s)
Exosomas , Células Madre , Accidente Cerebrovascular/terapia , Animales , Células de la Médula Ósea/química , Humanos , Trasplante de Células Madre , Células Madre/química
19.
Environ Sci Pollut Res Int ; 27(35): 43829-43844, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32740847

RESUMEN

Over the past 40 years since China's reform and opening up, the industrial structure has undergone tremendous changes. The rapid development of the economy has been accompanied by a surge in carbon emissions. How to achieve a win-win situation for economic growth and carbon emissions reduction has aroused widespread concern from all sectors of society. Here, this paper discusses the dynamic relationship of industrial structure upgrading, economic growth, and carbon emission reduction. Results show that there is a long-term equilibrium relationship among industrial structure upgrading, economic growth, and carbon emissions. In the short term, when the three variables deviate from the long-term equilibrium state, the non-equilibrium state will be pulled back to equilibrium with the adjustment strength of - 0.0633, - 0.0097, and 0.0013. Carbon emission reduction promotes industrial structure upgrading. Industrial structure upgrading has a greater positive impact on economic growth. Industrial structure upgrading and economic growth have a negative impact on carbon emissions, thereby promoting emission reduction. And at the 10% significance level, there is a one-way Granger causality from carbon emissions to industrial structure upgrading, economic growth can cause one-way changes in carbon emissions, and industrial structure upgrading is a one-way Granger cause of economic growth. Finally, several carbon emission reduction policies are proposed promote industrial restructuring and sustainable economic development.


Asunto(s)
Carbono , Desarrollo Económico , Carbono/análisis , Dióxido de Carbono/análisis , China , Industrias
20.
Environ Sci Pollut Res Int ; 26(25): 25500-25512, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31264153

RESUMEN

Energy strategy has been an essential strand in the view of economists in achieving rapid development process of any country. The recent wave of globalization exerts pressure on energy consumption via financial development which ultimately vindicates economic growth. This paper has covered a period of 1976-2016 using annual data for the empirical analysis and constructed a growth equation as the main equation and the energy consumption equation as a channel equation. The empirical study has been undertaken by performing ARDL and nonlinear autoregressive distributed lag models (NARDL). The bound test result declares a long-run association in both equations. Consequently, energy consumption and economic globalization have significantly enhanced economic growth in the long run. Whereas, financial development index has no influence on the economic growth of Pakistan. The results of channel equation suggested that due to growing the price of crude oil, the energy consumption is reduced in the long run. The increasing imports of energy products and increasing urbanization are conducive for energy consumption in Pakistan. By NARDL model, our empirical findings provide robust support for the existence of asymmetric co-integration linking among underlying variables of the study.


Asunto(s)
Desarrollo Económico , Internacionalidad , Pakistán , Urbanización
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