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1.
Health Commun ; : 1-19, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38742648

RESUMO

This systematic review evaluates health messaging strategies for the prevention and cessation of e-cigarette use among youth and young adults. Health messaging strategies were defined as the strategic process of developing messages with the intent to shape, reinforce, or change recipients' health attitudes and behaviors. McGuire's Communication/Persuasion Model guided the analysis of the messaging strategies, focusing on the model's five communication inputs (i.e. source, message, channel, audience, destination) and 14 persuasive outcomes. Nine databases were searched from January 2007 to September 2023. The inclusion criteria encompassed studies in English that presented quantitative data on messaging strategies aimed at discouraging vaping among youth and young adults. Each study was also coded for study characteristics and the utilization of theory. Out of 6,045 studies, 25 met the inclusion criteria. The reviewed studies exhibit a diverse array of research methods and a consistent integration of theories. The review emphasizes the nuanced main and interaction effects of various communication inputs, such as message features and audience characteristics, while also pointing out a research gap in message sources. In addition, the utilization of social media for effective messaging to engage the audience requires further research. Only one study specifically evaluated messaging strategies for vaping cessation. More research is imperative to develop targeted and tailored messages that effectively prevent and reduce vaping, especially among populations at higher risk of vaping-related harms, while also leveraging effective channels and innovative communication technologies to engage the audience.

2.
Addict Behav ; 154: 108000, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38461745

RESUMO

OBJECTIVE: To evaluate whether frequent social media use and liking/following tobacco brand accounts was associated with increased risk of tobacco and polytobacco initiation over approximately 1-year follow-up among youth with no prior tobacco use. METHODS: Associations between measures of social media engagement (daily social media use and liking/following tobacco brands) and tobacco initiation risk were examined using data from Waves 2 and 3 (2014-2015) of the US Population Assessment for Tobacco and Health study. Separate log-binomial models, accounting for missing data via multiple imputation and using propensity score adjustment to address confounding, estimated the adjusted relative risk (aRR) of any tobacco initiation and poly-use (2 + products) initiation at 1-year follow-up. RESULTS: Among the 8,672 youth with no prior tobacco use (49.3% female, mean [SD] age 14.1 [1.7]), 63.5% used social media at least daily, and 3.3% reported liking/following ≥ 1 tobacco brands on social media. Those reporting daily or more frequent social media use (compared to less) were at increased risk for tobacco (aRR 1.67; 95% CI 1.38-2.02) and polytobacco initiation (aRR 1.32; 95% CI 0.98-1.78). Although results were imprecise, liking/following ≥ 1 tobacco brands on social media (versus none) was associated with tobacco (aRR 1.34; 95% CI 0.95-1.89) or polytobacco initiation (aRR 1.60; 95% CI 0.99-2.60). In sensitivity analyses, liking/following cigarette or cigarillo brands was associated with polytobacco initiation. CONCLUSIONS: This study adds to a growing evidence-base describing the exposure of youth to tobacco-related social media content. Such content-often generated by tobacco companies-may contribute to youth tobacco initiation.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Mídias Sociais , Produtos do Tabaco , Humanos , Adolescente , Feminino , Masculino , Estudos Prospectivos , Marketing/métodos , Uso de Tabaco/epidemiologia , Nicotiana
3.
Small ; : e2311729, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38415811

RESUMO

Rare earth-doped upconversion nanoparticles (UCNPs) have achieved a wide range of applications in the sensing field due to their unique anti-Stokes luminescence property, minimized background interference, excellent biocompatibility, and stable physicochemical properties. However, UCNPs-based sensing platforms still face several challenges, including inherent limitations from UCNPs such as low quantum yields and narrow absorption cross-sections, as well as constraints related to energy transfer efficiencies in sensing systems. Therefore, the construction of high-performance UCNPs-based sensing platforms is an important cornerstone for conducting relevant research. This work begins by providing a brief overview of the upconversion luminescence mechanism in UCNPs. Subsequently, it offers a comprehensive summary of the sensors' types, design principles, and optimized design strategies for UCNPs sensing platforms. More cost-effective and promising point-of-care testing applications implemented based on UCNPs sensing systems are also summarized. Finally, this work addresses the future challenges and prospects for UCNPs-based sensing platforms.

4.
Insects ; 15(2)2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38392535

RESUMO

The Camellia weevil, Curculio chinensis (Chevrolat, 1978), is a dominant oligophagous pest that bores into the fruit of oil-tea Camellia. Genetic differentiation among populations in various hosts can easily occur, which hinders research on pest management. In this study, the genetic structure, genetic diversity, and phylogenetic structure of local C. chinensis populations were examined using 147 individuals (from 6 localities in Jiangxi), based on 2 mitochondrial COI markers. Results indicated that the C. chinensis population in Jiangxi exhibits a high haplotype diversity, especially for the populations from Cam. meiocarpa plantations. Structural differentiation was observed between Haplogroup 1 (73 individuals from Ganzhou, Jian, and Pingxiang) in the monoculture plantations of Cam. meiocarpa and Haplogroup 2 (75 individuals from Pingxiang and Jiujiang) in Cam. oleifera. Two haplogroups have recently undergone a demographic expansion, and Haplogroup 1 has shown a higher number of effective migrants than Haplogroup 2. This suggests that C. chinensis has been spreading from Cam. meiocarpa plantations to other oil-tea Camellia, such as Cam. oleifera. The increased cultivation of oil-tea Camellia in Jiangxi has contributed to a unique genetic structure within the C. chinensis population. This has, in turn, expanded the distribution of C. chinensis and increased migration between populations.

5.
Sci Total Environ ; 916: 170257, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38253098

RESUMO

The mineralization of dissolved organic matter (DOM) in sediments is an important factor leading to the eutrophication of macrophyte-dominated lakes. However, the changes in the molecular characteristics of sediment-derived DOM during microbial degradation in macrophyte-dominated lakes are not well understood. In this study, the microbial degradation process of sediment-derived DOM in Lake Caohai under aerobic and hypoxic conditions was investigated using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) and metagenomics. The results revealed that the microbial degradation of sediment-derived DOM in macrophyte-dominated lakes was more intense under aerobic conditions. The microorganisms mainly metabolized the protein-like substances in the macrophyte-dominated lakes, and the carbohydrate-active enzyme genes and protein/lipid-like degradation genes played key roles in sediment-derived DOM degradation. Organic compounds with high H/C ratios such as lipids, carbohydrates, and protein/lipid-like compounds were preferentially removed by microorganisms during microbial degradation. Meanwhile, there was an increase in the abundance of organic molecular formula with a high aromaticity such as tannins and unsaturated hydrocarbons with low molecular weight and low double bond equivalent. In addition, aerobic/hypoxic environments can alter microbial metabolic pathways of sediment-derived DOM by affecting the relative abundance of microbial communities (e.g., Gemmatimonadetes and Acidobacteria) and functional genes (e.g., ABC.PE.P1 and ABC.PE.P) in macrophyte-dominated lakes. The abundances of lipids, unsaturated hydrocarbons, and protein compounds in aerobic environments decreased by 58 %, 50 %, and 44 %, respectively, compared to in hypoxic environments under microbial degradation. The results of this study deepen our understanding of DOM biodegradation in macrophyte-dominated lakes under different redox environments and provide new insights into nutrients releases from sediment and continuing eutrophication in macrophyte-dominated lakes.


Assuntos
Matéria Orgânica Dissolvida , Poluentes Químicos da Água , Lagos/química , Poluentes Químicos da Água/análise , Hidrocarbonetos/análise , Lipídeos , China
6.
Heliyon ; 9(10): e20891, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37876453

RESUMO

Residential photovoltaics (PV) presents an effective means of achieving low-carbon development, owing to its installation flexibility and resource-saving properties. To explore the residents' behavioral intentions to purchase and install residential PV systems, this study collected 1424 samples and analyze the impact of different policies on residents' adoption of residential PV using the theory of TPB and the Partial Least Squares Structural Equation Model (PLS-SEM). The main conclusions are summarized as follows: (1) Bungalow residents exhibit a stronger inclination to install residential PV than building residents. (2) Perceived reward (PR) affects installation intention (II) more than perceived guide (PG) among bungalow residents. (3) Both PR and PG indirectly affect II through Perceived behavioral control (PBC) among bungalow residents. Economic policies, represented by PR, are likely to have more substantial indirect effects than propaganda and guidance policies. The findings suggest that China's recent residential PV installation policies should increase users' trust and guide the future decline of subsidy policy.

7.
Signal Transduct Target Ther ; 8(1): 327, 2023 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-37661226

RESUMO

Severe combined immunodeficiency (SCID) encompasses a range of inherited disorders that lead to a profound deterioration of the immune system. Among the pivotal genes associated with SCID, RAG1 and IL2RG play crucial roles. IL2RG is essential for the development, differentiation, and functioning of T, B, and NK cells, while RAG1 critically contributes to adaptive immunity by facilitating V(D)J recombination during the maturation of lymphocytes. Animal models carrying mutations in these genes exhibit notable deficiencies in their immune systems. Non-human primates (NHPs) are exceptionally well-suited models for biomedical research due to their genetic and physiological similarities to humans. Cytosine base editors (CBEs) serve as powerful tools for precisely and effectively modifying single-base mutations in the genome. Their successful implementation has been demonstrated in human cells, mice, and crop species. This study outlines the creation of an immunodeficient monkey model by deactivating both the IL2RG and RAG1 genes using the CBE4max system. The base-edited monkeys exhibited a severely compromised immune system characterized by lymphopenia, atrophy of lymphoid organs, and a deficiency of mature T cells. Furthermore, these base-edited monkeys were capable of hosting and supporting the growth of human breast cancer cells, leading to tumor formation. In summary, we have successfully developed an immunodeficient monkey model with the ability to foster tumor growth using the CBE4max system. These immunodeficiency monkeys show tremendous potential as valuable tools for advancing biomedical and translational research.


Assuntos
Linfopenia , Imunodeficiência Combinada Severa , Animais , Camundongos , Imunodeficiência Combinada Severa/genética , Haplorrinos , Edição de Genes , Proteínas de Homeodomínio/genética
8.
Adv Sci (Weinh) ; 10(31): e2301120, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37688357

RESUMO

Accumulation of misfolded proteins leads to many neurodegenerative diseases that can be treated by lowering or removing mutant proteins. Huntington's disease (HD) is characterized by the intracellular accumulation of mutant huntingtin (mHTT) that can be soluble and aggregated in the central nervous system and causes neuronal damage and death. Here, an intracellular antibody (intrabody) fragment is generated that can specifically bind mHTT and link to the lysosome for degradation. It is found that delivery of this peptide by either brain injection or intravenous administration can efficiently clear the soluble and aggregated mHTT by activating the lysosomal degradation pathway, resulting in amelioration of gliosis and dyskinesia in HD knock-in (KI-140Q) mice. These findings suggest that the small intrabody peptide linked to lysosomes can effectively lower mutant proteins and provide a new approach for treating neurodegenerative diseases that are caused by the accumulation of mutant proteins.


Assuntos
Doença de Huntington , Doenças Neurodegenerativas , Animais , Camundongos , Proteína Huntingtina/genética , Proteína Huntingtina/metabolismo , Doença de Huntington/metabolismo , Lisossomos/metabolismo , Proteínas Mutantes , Proteínas do Tecido Nervoso , Peptídeos
9.
Behav Sci (Basel) ; 13(7)2023 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-37504061

RESUMO

In order to achieve the "dual carbon goal", the Chinese government is actively encouraging the adoption of household photovoltaic (PV) systems. While there has been considerable research on residents' inclination to install PV, limited attention has been given to understanding how the installation and utilization of PV systems influence pro-environmental behaviors. Therefore, this paper aims to investigate the potential impact of pro-environmental behavior resulting from household PV installation on users' green purchasing behavior. Based on the "learning by doing" theory, a survey was conducted with 1249 participants, and the generalized structural equation model was employed as our analytical approach. The findings of this research indicate that the adoption and utilization of household photovoltaic (PV) systems have a positive impact on green consumption. The test results demonstrate that the overall effect coefficient is 0.03, indicating that current PV promotion policies have an indirect impact on green consumption. Moreover, economic incentive policies have a more substantial influence than environmental publicity policies, with total indirect effect coefficients of 0.005 and 0.002, respectively. Based on the findings above, the following recommendations are proposed: (1) It is recommended to maintain stable economic incentives to promote the adoption of household PV systems. (2) Emphasizing the dissemination of knowledge and skills for promoting environmental protection should be prioritized. (3) Efforts should be made to align personal interests and societal interests with low-carbon policies.

10.
JMIR Infodemiology ; 3: e41969, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37113379

RESUMO

Background: Health warnings in tobacco advertisements provide health information while also increasing the perceived risks of tobacco use. However, existing federal laws requiring warnings on advertisements for tobacco products do not specify whether the rules apply to social media promotions. Objective: This study aims to examine the current state of influencer promotions of little cigars and cigarillos (LCCs) on Instagram and the use of health warnings in influencer promotions. Methods: Instagram influencers were identified as those who were tagged by any of the 3 leading LCC brand Instagram pages between 2018 and 2021. Posts from identified influencers, which mentioned one of the three brands were considered LCC influencer promotions. A novel Warning Label Multi-Layer Image Identification computer vision algorithm was developed to measure the presence and properties of health warnings in a sample of 889 influencer posts. Negative binomial regressions were performed to examine the associations of health warning properties with post engagement (number of likes and comments). Results: The Warning Label Multi-Layer Image Identification algorithm was 99.3% accurate in detecting the presence of health warnings. Only 8.2% (n=73) of LCC influencer posts included a health warning. Influencer posts that contained health warnings received fewer likes (incidence rate ratio 0.59, P<.001, 95% CI 0.48-0.71) and fewer comments (incidence rate ratio 0.46, P<.001, 95% CI 0.31-0.67). Conclusions: Health warnings are rarely used by influencers tagged by LCC brands' Instagram accounts. Very few influencer posts met the US Food and Drug Administration's health warning requirement of size and placement for tobacco advertising. The presence of a health warning was associated with lower social media engagement. Our study provides support for the implementation of comparable health warning requirements to social media tobacco promotions. Using an innovative computer vision approach to detect health warning labels in influencer promotions on social media is a novel strategy for monitoring health warning compliance in social media tobacco promotions.

11.
Acc Chem Res ; 56(10): 1143-1155, 2023 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-36897248

RESUMO

Phototherapy including optogenetics, photodynamic therapy (PDT), photothermal therapy (PTT), and photoimmunotherapy (PIT) has been proven to be effective against different diseases. However, as the name suggests, phototherapy requires light irradiation, thus its therapeutic efficiency is often restricted by limited depth of light penetration within biological tissue. This light penetration limitation is significantly adverse to PDT and optogenetics because both therapies are usually activated with UV and visible light of very poor tissue penetration efficiency. Current light delivery methods usually involve cumbersome setups and require optical fiber or catheter insertion, which not only restrict the movement of patients but also impose incompatibility issues with chronic implantation. To address the existing challenges, wireless phototherapy was developed through various approaches over recent years, which usually relies on implantable wireless electronic devices. However, the application of wireless electronic devices is limited by invasion during implantation, unwanted heat generation, and adverse immunogenicity of these devices.Over the recent years, applying light conversion nanomaterials as light transducers for wireless phototherapy has garnered much interest. Compared with implantable electronic devices and optical fiber, nanomaterials can be easily injected into the body with minimal invasiveness and can also be surface functionalized to increase their biocompatibility and cell accumulation efficiency. Commonly applied light conversion nanomaterials include upconversion nanoparticles (UCNPs), X-ray nanoscintillators, and persistent luminescence nanoparticles (PLNPs). UCNPs and X-ray nanoscintillators can respectively convert near-infrared (NIR) light and X-ray, which have good tissue penetration efficiency, to UV or visible light, which is suitable for activating phototherapy. PLNPs can be excited by external light such as X-rays and NIR light and retain long afterglow luminescence after the removal of the excitation light source. As a result, applying PLNPs in phototherapy can potentially reduce irradiation time from external light sources, thus minimizing tissue photodamage. This Account aims to briefly discuss (i) the mechanisms of different phototherapies, (ii) the development and mechanisms of light conversion nanomaterials, (iii) the application of light conversion nanomaterials in wireless phototherapy, highlighting how they relieve current challenges in phototherapy, and (iv) perspectives for future development of light conversion nanomaterials for wireless phototherapy.


Assuntos
Nanopartículas , Fotoquimioterapia , Humanos , Fototerapia , Nanopartículas/uso terapêutico , Luminescência
12.
Sci Adv ; 9(11): eade4395, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36930708

RESUMO

The interleukin-6 (IL-6) family cytokines signal through gp130 receptor homodimerization or heterodimerization with a second signaling receptor and play crucial roles in various cellular processes. We determined cryo-electron microscopy structures of five signaling complexes of this family, containing full receptor ectodomains bound to their respective ligands ciliary neurotrophic factor, cardiotrophin-like cytokine factor 1 (CLCF1), leukemia inhibitory factor, IL-27, and IL-6. Our structures collectively reveal similarities and differences in the assembly of these complexes. The acute bends at both signaling receptors in all complexes bring the membrane-proximal domains to a ~30 angstrom range but with distinct distances and orientations. We also reveal how CLCF1 engages its secretion chaperone cytokine receptor-like factor 1. Our data provide valuable insights for therapeutically targeting gp130-mediated signaling.


Assuntos
Antígenos CD , Interleucina-6 , Receptor gp130 de Citocina/metabolismo , Interleucina-6/metabolismo , Subunidade alfa de Receptor de Fator Inibidor de Leucemia/metabolismo , Microscopia Crioeletrônica , Antígenos CD/metabolismo , Glicoproteínas de Membrana/metabolismo , Citocinas/metabolismo
13.
Nucleic Acids Res ; 51(D1): D1242-D1248, 2023 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-36259664

RESUMO

Extensive in vitro cancer drug screening datasets have enabled scientists to identify biomarkers and develop machine learning models for predicting drug sensitivity. While most advancements have focused on omics profiles, cancer drug sensitivity scores precalculated by the original sources are often used as-is, without consideration for variabilities between studies. It is well-known that significant inconsistencies exist between the drug sensitivity scores across datasets due to differences in experimental setups and preprocessing methods used to obtain the sensitivity scores. As a result, many studies opt to focus only on a single dataset, leading to underutilization of available data and a limited interpretation of cancer pharmacogenomics analysis. To overcome these caveats, we have developed CREAMMIST (https://creammist.mtms.dev), an integrative database that enables users to obtain an integrative dose-response curve, to capture uncertainty (or high certainty when multiple datasets well align) across five widely used cancer cell-line drug-response datasets. We utilized the Bayesian framework to systematically integrate all available dose-response values across datasets (>14 millions dose-response data points). CREAMMIST provides easy-to-use statistics derived from the integrative dose-response curves for various downstream analyses such as identifying biomarkers, selecting drug concentrations for experiments, and training robust machine learning models.


Assuntos
Antineoplásicos , Bases de Dados Factuais , Neoplasias , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Teorema de Bayes , Biomarcadores , Aprendizado de Máquina , Neoplasias/tratamento farmacológico , Neoplasias/genética
14.
Health Commun ; 38(8): 1666-1676, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-35057690

RESUMO

E-cigarette use, or vaping, is undergoing a process of moralization in which issues about vaping evolve from being morally neutral to having discernible moral implications. Using Moral Foundations Theory, this study compared the moral narratives underlying polarized views about e-cigarette use and regulation. We integrated computational and human strategies by conducting the Chow test on the time series data and classification, topic modeling, and Chi-square tests on posts (N = 2,669) from 26 pro-vaping and 19 anti-vaping Facebook Pages. The observation period (August 1, 2019 to March 5, 2020) encompassed the outbreak of "e-cigarette or vaping product use associated lung injury" (EVALI), deaths and subsequent legislation. Results revealed that pro-vaping posts were more likely than anti-vaping posts to mention Fairness/cheating and Authority/subversion, involving a conspiracy belief in an "e-cigarettes vs. Big Tobacco" rivalry, while anti-vaping posts were more likely to mention Sanctity/degradation. There were no significant differences between pro-vaping and anti-vaping posts in the likelihood of mentioning Care/harm or Loyalty/betrayal. Nevertheless, according to the topic modeling results, the use of moral foundations varied between pro-vaping and anti-vaping narratives, with the meanings of Care/harm and Loyalty/betrayal dependent on the post author's group affiliation. Health interventions can tailor persuasive messages to different moral values and debunk misinformation about public health policies to mitigate the vaping epidemic. Theoretical implications are also discussed.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Epidemias , Lesão Pulmonar , Vaping , Humanos , Lesão Pulmonar/epidemiologia , Surtos de Doenças
15.
Patient Educ Couns ; 105(12): 3446-3452, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36064518

RESUMO

OBJECTIVE: Motivating older adults to follow up with an outpatient clinician after discharge from emergency departments (ED) is beneficial yet challenging. We aimed to answer whether psychological needs for motivation and discrete emotions observed by care transition coaches would predict this behavioral outcome. METHODS: Community-dwelling older adults following ED discharge were recruited from three EDs in two U.S. states. We examined home visit notes documented by coaches (N = 725). Retrospective chart reviews of medical records tracked participants' health care utilization for 30 days. RESULTS: Observed knowledge-based competence predicted higher likelihood of outpatient follow-up within 30 days, while observed sadness predicted a lower likelihood of follow-up within seven days following discharge. Moreover, participants who demonstrated happiness were marginally more likely to have an in-person follow-up within seven days, and those who demonstrated knowledge-based competence were more likely to have an electronic follow-up within 30 days. CONCLUSIONS: Knowledge-based competence and emotions, as observed and documented in coach notes, can predict older adults' subsequent outpatient follow-up following their ED-discharge. PRACTICE IMPLICATIONS: Intervention programs might encourage coaches to check knowledge-based competence and to observe emotions in addition to delivering the content. Coaches could also customize strategies for patients with different recommended timeframes of follow-up.


Assuntos
Tutoria , Alta do Paciente , Idoso , Humanos , Serviço Hospitalar de Emergência , Emoções , Pacientes Ambulatoriais , Estudos Retrospectivos , Estados Unidos
16.
Artigo em Inglês | MEDLINE | ID: mdl-35742315

RESUMO

Little is known about the content, promotions, and individuals in cigar-related videos on TikTok. TikTok videos with large cigar and Swisher Sweets-related hashtags between July 2016 and September 2020 were analyzed. Follower count was used to identify influencers. We compared content characteristics and demographics of featured individuals between cigar types, and by influencer status. We also examined the association between content characteristics and video engagement. Compared to large cigar videos, Swisher Sweets videos were more likely to feature arts and crafts with cigar packages, cannabis use, and flavored products. In addition, Swisher Sweets videos were also more likely to feature females, Black individuals, and younger individuals. Both Swisher Sweets and large cigar influencers posted more videos of cigar purchasing behaviors than non-influencers, which was associated with more video views. None of the videos disclosed sponsorship with #ad or #sponsored. Videos containing the use of cigar packages for arts and crafts, and flavored products highlight the importance of colorful packaging and flavors in the appeal of Swisher Sweets cigars, lending support for plain packaging requirements and the prohibition of flavors in cigar products to decrease the appeal of cigars. The presence and broad reach of cigar promotions on TikTok requires stricter enforcement of anti-tobacco promotion policies.


Assuntos
Cannabis , Mídias Sociais , Produtos do Tabaco , Comportamento do Consumidor , Feminino , Humanos , Embalagem de Produtos
17.
Acta Pharmacol Sin ; 43(5): 1251-1263, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34417577

RESUMO

Transcriptional factor EB (TFEB), a master regulator of autophagy and lysosomal biogenesis, is generally regarded as a pro-survival factor. Here, we identify that besides its effect on autophagy induction, TFEB exerts a pro-apoptotic effect in response to the cyclopentenone prostaglandin 15-deoxy-∆-12,14-prostaglandin J2 (15d-PGJ2). Specifically, 15d-PGJ2 promotes TFEB translocation from the cytoplasm into the nucleus to induce autophagy and lysosome biogenesis via reactive oxygen species (ROS) production rather than mTORC1 inactivation. Surprisingly, TFEB promotes rather than inhibits apoptosis in response to 15d-PGJ2. Mechanistically, ROS-mediated TFEB translocation into the nucleus transcriptionally upregulates the expression of ATF4, which is required for apoptosis elicited by 15d-PGJ2. Additionally, inhibition of TFEB activation by ROS scavenger N-acetyl cysteine or inhibition of protein synthesis by cycloheximide effectively compromises ATF4 upregulation and apoptosis in response to 15d-PGJ2. Collectively, these results indicate that ROS-induced TFEB activation exerts a novel role in promoting apoptosis besides its role in regulating autophagy in response to 15d-PGJ2. This work not only evidences how TFEB is activated by 15d-PGJ2, but also unveils a previously unexplored role of ROS-dependent activation of TFEB in modulating cell apoptosis in response to 15d-PGJ2.


Assuntos
Prostaglandina D2 , Prostaglandinas , Apoptose , Autofagia , Ciclopentanos , Prostaglandina D2/análogos & derivados , Prostaglandina D2/farmacologia , Prostaglandinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo
18.
Front Cell Dev Biol ; 10: 1115348, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36762127

RESUMO

Animal models are important for understanding the pathogenesis of human diseases and for developing and testing new drugs. Pigs have been widely used in the research on the cardiovascular, skin barrier, gastrointestinal, and central nervous systems as well as organ transplantation. Recently, pigs also become an attractive large animal model for the study of neurodegenerative diseases because their brains are very similar to human brains in terms of mass, gully pattern, vascularization, and the proportions of the gray and white matters. Although adeno-associated virus type 9 (AAV9) has been widely used to deliver transgenes in the brain, its utilization in large animal models remains to be fully characterized. Here, we report that intravenous injection of AAV9-GFP can lead to widespread expression of transgene in various organs in the pig. Importantly, GFP was highly expressed in various brain regions, especially the striatum, cortex, cerebellum, hippocampus, without detectable inflammatory responses. These results suggest that intravenous AAV9 administration can be used to establish large animal models of neurodegenerative diseases caused by gene mutations and to treat these animal models as well.

19.
Tob Induc Dis ; 19: 01, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33437228

RESUMO

INTRODUCTION: The public most frequently associates tobacco use solely with pulmonary health risks, despite heart disease being the leading cause of death in smokers. The health perceptions of e-cigarettes, especially cardiovascular health, have not been well studied. We aimed to evaluate the prevalence and health perceptions of tweets related to cardiovascular, pulmonary, and brain health - three organ systems for which tobacco use is a major disease risk factor. METHODS: We examined the cardiovascular, pulmonary, and brain health perceptions of vaping and JUUL on Twitter, followed by a content analysis of tweets pertaining to the cardiovascular risks. A Twitter firehose API scraped about 6.2 million publicly available tweets from 2015-2019 that contained vaping-related terms, and a separate dataset of about 1.9 million tweets that contained the term JUUL. A quantitative content analysis (n=2145) of tweets was subsequently conducted to assess the health perceptions of vaping and JUUL. Two trained coders independently assessed the posts and Twitter profiles to determine age (<18 or ≥18 years), sex, race, sentiment towards JUUL, and vaping-related topics. RESULTS: The majority of tweets containing vaping or JUUL-related terms did not also contain cardiovascular, pulmonary, or brain health terms (97.99% and 96.67%, respectively). Multiple linear regression analysis showed that youth (<18 years), females, non-White individuals, mention of a flavor, and mention of cardiovascular health harm words were associated with more positive sentiments towards JUUL. Pearson's chi-squared analyses indicated that youth were more likely to mention a JUUL flavor. Females and youth were more likely to reference cardiovascular terms with humor. CONCLUSIONS: The cardiovascular health risks of vaping are not fully recognized by the public. Vulnerable populations such as youth and females reference JUUL with cardiovascular-related words that downplay the severity of tobacco as a major risk factor for cardiovascular disease.

20.
J Exp Med ; 217(11)2020 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-32808016

RESUMO

The marginal zone (MZ) of the spleen contains multiple cell types that are involved in mounting rapid immune responses against blood-borne pathogens, including conventional dendritic cells (cDCs) and MZ B cells. MZ B cells develop later than other B cell types and are sparse in neonatal mice. Here, we show that cDC2s are abundant in the MZ of neonatal compared with adult mice. We find that conditions associated with reduced MZ B cell numbers in adult mice cause increased cDC2 occupancy of the MZ. Treatment with the S1PR1-modulating drug, FTY720, causes cDC2 movement into the MZ through the indirect mechanism of displacing MZ B cells into follicles. Splenic cDC2s express high amounts of α4ß1 and αLß2 integrins and depend on these integrins and the adaptor Talin for their retention in blood-exposed regions of the spleen. Splenic CD4 T cell activation by particulate antigens is increased in mice with higher cDC2 density in the MZ, including in neonatal mice. Our work establishes requirements for homeostatic cDC2 positioning in the spleen and provides evidence that localization in blood-exposed regions around the white pulp augments cDC2 capture of particulate antigens. We suggest that MZ positioning of cDC2s partially compensates for the lack of MZ B cells during the neonatal period.


Assuntos
Células Dendríticas/imunologia , Baço/citologia , Baço/imunologia , Animais , Animais Recém-Nascidos , Antígenos/imunologia , Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Células Dendríticas/metabolismo , Cloridrato de Fingolimode/farmacologia , Integrina alfa4beta1/metabolismo , Ativação Linfocitária , Antígeno-1 Associado à Função Linfocitária/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
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