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1.
Nature ; 606(7915): 769-775, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35676476

RESUMO

Adaptive immune components are thought to exert non-overlapping roles in antimicrobial host defence, with antibodies targeting pathogens in the extracellular environment and T cells eliminating infection inside cells1,2. Reliance on antibodies for vertically transferred immunity from mothers to babies may explain neonatal susceptibility to intracellular infections3,4. Here we show that pregnancy-induced post-translational antibody modification enables protection against the prototypical intracellular pathogen Listeria monocytogenes. Infection susceptibility was reversed in neonatal mice born to preconceptually primed mothers possessing L. monocytogenes-specific IgG or after passive transfer of antibodies from primed pregnant, but not virgin, mice. Although maternal B cells were essential for producing IgGs that mediate vertically transferred protection, they were dispensable for antibody acquisition of protective function, which instead required sialic acid acetyl esterase5 to deacetylate terminal sialic acid residues on IgG variable-region N-linked glycans. Deacetylated L. monocytogenes-specific IgG protected neonates through the sialic acid receptor CD226,7, which suppressed IL-10 production by B cells leading to antibody-mediated protection. Consideration of the maternal-fetal dyad as a joined immunological unit reveals protective roles for antibodies against intracellular infection and fine-tuned adaptations to enhance host defence during pregnancy and early life.


Assuntos
Imunidade Materno-Adquirida , Imunoglobulina G , Espaço Intracelular , Listeria monocytogenes , Mães , Gravidez , Acetilesterase , Animais , Animais Recém-Nascidos , Linfócitos B , Feminino , Imunidade Materno-Adquirida/imunologia , Imunoglobulina G/imunologia , Interleucina-10/biossíntese , Espaço Intracelular/imunologia , Espaço Intracelular/microbiologia , Listeria monocytogenes/imunologia , Listeriose/imunologia , Listeriose/prevenção & controle , Camundongos , Ácido N-Acetilneuramínico/metabolismo , Gravidez/imunologia , Lectina 2 Semelhante a Ig de Ligação ao Ácido Siálico , Linfócitos T
2.
PLoS Genet ; 19(10): e1010776, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37871041

RESUMO

Sinorhizobium meliloti is a model alpha-proteobacterium for investigating microbe-host interactions, in particular nitrogen-fixing rhizobium-legume symbioses. Successful infection requires complex coordination between compatible host and endosymbiont, including bacterial production of succinoglycan, also known as exopolysaccharide-I (EPS-I). In S. meliloti EPS-I production is controlled by the conserved ExoS-ChvI two-component system. Periplasmic ExoR associates with the ExoS histidine kinase and negatively regulates ChvI-dependent expression of exo genes, necessary for EPS-I synthesis. We show that two extracytoplasmic proteins, LppA (a lipoprotein) and JspA (a lipoprotein and a metalloprotease), jointly influence EPS-I synthesis by modulating the ExoR-ExoS-ChvI pathway and expression of genes in the ChvI regulon. Deletions of jspA and lppA led to lower EPS-I production and competitive disadvantage during host colonization, for both S. meliloti with Medicago sativa and S. medicae with M. truncatula. Overexpression of jspA reduced steady-state levels of ExoR, suggesting that the JspA protease participates in ExoR degradation. This reduction in ExoR levels is dependent on LppA and can be replicated with ExoR, JspA, and LppA expressed exogenously in Caulobacter crescentus and Escherichia coli. Akin to signaling pathways that sense extracytoplasmic stress in other bacteria, JspA and LppA may monitor periplasmic conditions during interaction with the plant host to adjust accordingly expression of genes that contribute to efficient symbiosis. The molecular mechanisms underlying host colonization in our model system may have parallels in related alpha-proteobacteria.


Assuntos
Fabaceae , Sinorhizobium meliloti , Peptídeo Hidrolases/genética , Peptídeo Hidrolases/metabolismo , Proteínas de Bactérias/metabolismo , Fabaceae/metabolismo , Sinorhizobium meliloti/genética , Sinorhizobium meliloti/metabolismo , Simbiose/genética , Endopeptidases/genética , Transdução de Sinais/genética , Lipoproteínas/genética , Lipoproteínas/metabolismo , Regulação Bacteriana da Expressão Gênica , Polissacarídeos Bacterianos
3.
Immunology ; 172(4): 517-532, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38503445

RESUMO

Sialic acid is a unique sugar moiety that resides in the distal and most accessible position of the glycans on mammalian cell surface and extracellular glycoproteins and glycolipids. The potential for sialic acid to obscure underlying structures has long been postulated, but the means by which such structural changes directly affect biological processes continues to be elucidated. Here, we appraise the growing body of literature detailing the importance of sialic acid for the generation, differentiation, function and death of haematopoietic cells. We conclude that sialylation is a critical post-translational modification utilized in haematopoiesis to meet the dynamic needs of the organism by enforcing rapid changes in availability of lineage-specific cell types. Though long thought to be generated only cell-autonomously within the intracellular ER-Golgi secretory apparatus, emerging data also demonstrate previously unexpected diversity in the mechanisms of sialylation. Emphasis is afforded to the mechanism of extrinsic sialylation, whereby extracellular enzymes remodel cell surface and extracellular glycans, supported by charged sugar donor molecules from activated platelets.


Assuntos
Diferenciação Celular , Ácido N-Acetilneuramínico , Humanos , Animais , Ácido N-Acetilneuramínico/metabolismo , Hematopoese , Processamento de Proteína Pós-Traducional , Polissacarídeos/metabolismo
4.
Health Commun ; : 1-16, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38655579

RESUMO

The role of experts in news coverage has become increasingly prominent, but the evidence regarding the effectiveness of expert opinions in affecting public behavior remains mixed. This study seeks to examine the influence of expert opinions covered in the news on the public's response to public health crises. By adopting a macro-level framing perspective, we investigated how framing consistency, a macro-level concept indicating the agreement between expert opinions in news coverage and government policies or among peer experts, evolves over time and its temporal causal relationship with public behavior. Specifically, this study collected all press news coverage in Hong Kong over four months during the fifth outbreak, including 1,416 articles with 650 expert opinions, as well as the vaccination data that paralleled with this period. We constructed time series of expert opinions and vaccination behavior, and then conducted Vector Autoregressive (VAR) models with Granger causality analysis to examine how framing consistency of expert opinions in news coverage influenced vaccination. The results indicate that the consistent framing between expert opinions and government policies increased COVID-19 vaccination during the fifth outbreak in Hong Kong, while conflicting opinions responding to government policies had no significant effect on vaccination. Opinions among medical experts on COVID-19 issues also did not significantly impact vaccination. The implications for designing communication strategies and enhancing public behavioral support during public health crises are discussed.

5.
J Youth Adolesc ; 53(6): 1428-1440, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38555341

RESUMO

Despite extensive research on the psychological impacts of digital technology, the nuanced dynamics between adolescent loneliness and problematic smartphone use, particularly across different educational levels and genders, remain underexplored. This study aims to fill this gap by employing a Random Intercept Cross-Lagged Panel Model to dissect the bidirectional relationship between loneliness and problematic smartphone use among adolescents, with a focus on the moderating roles of educational levels and gender. Engaging 3132 students from various educational institutions in China, the research conducted a three-wave longitudinal analysis across 2022-2023. The final number of participants included 1120 adolescents (53.5% female; age in 2022: M = 14.57 years, SD = 1.57). Results reveal that loneliness significantly predicts problematic smartphone use, but not vice versa, highlighting a unidirectional influence. The study uncovers crucial differences across educational levels and gender, emphasizing the stronger effect of loneliness on problematic smartphone use among junior high students and female adolescents. These findings underscore the complexity of adolescent loneliness and its relationship with digital behavior, suggesting a need for tailored interventions considering both gender and developmental stages.


Assuntos
Comportamento do Adolescente , Solidão , Smartphone , Humanos , Solidão/psicologia , Adolescente , Feminino , Masculino , Comportamento do Adolescente/psicologia , Estudos Longitudinais , China , Estudantes/psicologia , Estudantes/estatística & dados numéricos , Transtorno de Adição à Internet/psicologia , Fatores Sexuais , Escolaridade
6.
Glycobiology ; 33(7): 579-590, 2023 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-37171590

RESUMO

Despite decades of research, glycosaminoglycans (GAGs) have not been known to interact with sialyl transferases (STs). Using our in-house combinatorial virtual library screening (CVLS) technology, we studied seven human isoforms, including ST6GAL1, ST6GAL2, ST3GAL1, ST3GAL3, ST3GAL4, ST3GAL5, and ST3GAL6, and predicted that GAGs, especially heparan sulfate (HS), are likely to differentially bind to STs. Exhaustive CVLS and molecular dynamics studies suggested that the common hexasaccharide sequence of HS preferentially recognized ST6GAL1 in a site overlapping the binding site of the donor substrate CMP-Sia. Interestingly, CVLS did not ascribe any special role for the rare 3-O-sulfate modification of HS in ST6GAL1 recognition. The computational predictions were tested using spectrofluorimetric studies, which confirmed preferential recognition of HS over other GAGs. A classic chain length-dependent binding of GAGs to ST6GAL1 was observed with polymeric HS displaying a tight affinity of ~65 nM. Biophysical studies also confirmed a direct competition between CMP-Sia and an HS oligosaccharide and CS polysaccharide for binding to ST6GAL1. Overall, our novel observation that GAGs bind to ST6GAL1 with high affinity and compete with the donor substrate is likely to be important because modulation of sialylation of glycan substrates on cells has considerable physiological/pathological consequences. Our work also brings forth the possibility of developing GAG-based chemical probes of ST6GAL1.


Assuntos
Glicosaminoglicanos , Transferases , Humanos , Glicosaminoglicanos/química , Transferases/metabolismo , Heparitina Sulfato/metabolismo , Sítios de Ligação , Simulação de Dinâmica Molecular
7.
Int J Gynecol Pathol ; 42(4): 421-425, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-36044308

RESUMO

We report an unusual case of a pelvic extraovarian moderately differentiated Sertoli-Leydig cell tumor arising in a 4-yr-old female. The tumor contained a DICER1 pathogenic variant which was absent in the germline ruling out DICER1 syndrome. In reporting this case, we discuss the differential diagnosis and possible histogenesis and review reported cases of extraovarian Sertoli-Leydig cell tumor.


Assuntos
Síndromes Neoplásicas Hereditárias , Neoplasias Ovarianas , Tumor de Células de Sertoli-Leydig , Tumores do Estroma Gonadal e dos Cordões Sexuais , Masculino , Humanos , Feminino , Tumor de Células de Sertoli-Leydig/diagnóstico , Tumor de Células de Sertoli-Leydig/genética , Tumor de Células de Sertoli-Leydig/patologia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Tumores do Estroma Gonadal e dos Cordões Sexuais/diagnóstico , Tumores do Estroma Gonadal e dos Cordões Sexuais/genética , Tumores do Estroma Gonadal e dos Cordões Sexuais/patologia , Ribonuclease III/genética , Diagnóstico Diferencial , Síndromes Neoplásicas Hereditárias/diagnóstico , RNA Helicases DEAD-box/genética
8.
AIDS Care ; 35(8): 1243-1250, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-33565316

RESUMO

Traditional surveys only provide local observations about the topological structure of isolated individuals. This study aims to develop a novel data-driven approach to reconstructing the social network of men who have sex with men (MSM) communities from locally observed information by surveys. A large social network consisting of 1075 users and their public relationships was obtained manually from BlueD.com. We followed the same survey-taking procedure to sample locally observed information and adapted an Exponential Random Graph Model (ERGM) to model the full structure of the BlueD social network (number of local nodes N = 1075, observed average degree k = 6.46). The parameters were learned and then used to reconstruct the MSM social networks by two real-world survey datasets in Hong Kong (N = 600, k = 5.61) and Guangzhou (N = 757, k = 5). Our method performed well on reconstructing the BlueD social network, with a high accuracy (90.3%). In conclusion, this study demonstrates the feasibility of using parameters learning methods to reconstruct the social networks of HIV key populations. The method has the potential to inform data-driven intervention programs that need global social network structures.


Assuntos
Infecções por HIV , Minorias Sexuais e de Gênero , Masculino , Humanos , Homossexualidade Masculina , Comportamento Sexual , Rede Social
9.
Sleep Breath ; 27(1): 337-344, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35377089

RESUMO

PURPOSE: The prevalence of under-diagnosis among individuals with obstructive sleep apnea (OSA) is alarming, and may be associated with perceptions regarding OSA. To facilitate future studies on OSA, this study validated the revised version of the Illness Perception Questionnaire (IPQ-R) for OSA in a general population. METHODS: A random anonymous population-based telephone survey interviewed 580 adults aged ≥ 50 years in Hong Kong, who self-reported not having been told by doctors as having OSA, from February 5 to March 19, 2021. RESULTS: The confirmatory factor analysis identified a modified 7-factor model (i.e., timeline chronic, consequence, personal control, treatment control, illness coherence, timeline cyclical, and emotional representation) that showed satisfactory model fit index and internal consistency. Nine items were removed from the original version because of low factor loadings. No floor and ceiling effects were observed. Convergent validity was supported by the positive associations between the consequence subscale with perceived negative outcomes of OSA and between the illness coherence subscale and perceived understanding of OSA symptoms. The participants tended to endorse the items of timeline chronic, treatment control, and illness coherence but not with those of emotional representations. The mean scores of the IPQ-R subscales differed by age and education level. CONCLUSION: The modified IPQ-R of OSA showed acceptable psychometric properties. It is applicable to assessing illness perceptions of OSA in the Chinese general population aged ≥ 50 years not having received OSA diagnosis. The validated tool would support future studies and health practices related to OSA.


Assuntos
População do Leste Asiático , Apneia Obstrutiva do Sono , Adulto , Idoso , Humanos , Cognição , Emoções , Percepção , Inquéritos e Questionários , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/psicologia
10.
Int J Behav Med ; 30(4): 555-565, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36104550

RESUMO

BACKGROUND: Free antiretroviral therapy (ART) has been expanded to all people living with HIV (PLWH) in China since 2016, and adherence to ART has been shown to be the primary determinant of viral suppression. This study aimed to investigate the ART adherence and its associated factors among PLWH in China in the context of a scaling-up of treatment policy. METHOD: A prospective cohort study was conducted from June 2016 to May 2018 in Guangzhou, China. A total of 400 eligible participants were recruited from the Guangzhou Eighth People's hospital in Guangzhou, China. The Theory of Planned Behavior and the Behavioral Maintenance Theory were applied to guide the questionnaire design. Participants were invited to completed self-administered questionnaire at baseline and months 3 and 6 post-baseline. Logistic regression models were fitted to explore factors associated with ART adherence. RESULTS: Of the 400 participants, the prevalence of optimal ART adherence was 83.6% at month 3 and 83.3% at month 6. The baseline attitude (ORa = 1.11, P < 0.05), behavioral intention (ORa = 1.90, P < 0.05), and outcome expectations (ORa = 1.09, P < 0.001) predicted ART adherence at month 3 in adjusted analyses, but only outcome expectations (ORa = 1.09, P < 0.01) remained significant in the final multivariate model. At month 3, negative experiences (ORa = 0.62, P < 0.05) were the only predictor of adherence at month 6. CONCLUSION: Approximately 15% of participants reported suboptimal ART adherence. The developments of tailored interventions that target factors such as outcome expectations at baseline and negative experiences during treatment are warranted.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Humanos , Estudos Prospectivos , Infecções por HIV/tratamento farmacológico , Adesão à Medicação , China/epidemiologia , Inquéritos e Questionários , Fármacos Anti-HIV/uso terapêutico
11.
J Med Internet Res ; 25: e43532, 2023 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-36649059

RESUMO

BACKGROUND: The minority stress model postulates that men who have sex with men (MSM) often encounter multiple stressors because of their sexual minority status, which may lead to psychological problems and maladaptive coping such as addictive behaviors (eg, internet gaming disorder [IGD]). It was hypothesized that hopelessness and loneliness would be associated with IGD via self-control among MSM. OBJECTIVE: This study investigated the prevalence of IGD and its associations with variables related to minority stress (loneliness and hopelessness) among MSM who were university students. Mediation involving such associations via self-control was also explored. METHODS: With informed consent, 305 MSM attending universities in Sichuan, China participated in the study. The validated Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) checklist was used to assess IGD. Multivariable logistic regression adjusted for background factors and structural equation modeling were conducted. RESULTS: The prevalence of IGD was 12.8% (n=39). Logistic regression found that IGD was positively associated with hopelessness and loneliness, and negatively associated with self-control. The structural equation modeling identified three significant paths between hopelessness/loneliness and IGD: (1) hopelessness → lower self-control → higher IGD (full mediation), (2) loneliness → lower self-control → higher IGD (partial mediation: effect size of 28%), and (3) a direct effect from loneliness to IGD. CONCLUSIONS: IGD was prevalent among young MSM and warrants interventions that may try to reduce the level of psychosocial problems such as loneliness and hopelessness and improve self-control. According to the socioecological model, the promotion of social acceptance and reduction in stigma toward MSM are important in reducing loneliness and hopefulness among MSM. Self-control links up the relationships between psychosocial problems and IGD and should be given special attention. Longitudinal studies are warranted to confirm the findings and test new mediations between loneliness/hopelessness and MSM with IGD.


Assuntos
Comportamento Aditivo , Minorias Sexuais e de Gênero , Jogos de Vídeo , Masculino , Humanos , Feminino , Homossexualidade Masculina/psicologia , Universidades , Solidão/psicologia , Estudos Transversais , Transtorno de Adição à Internet/epidemiologia , Estudantes/psicologia , Internet , Jogos de Vídeo/psicologia , Comportamento Aditivo/psicologia
12.
J Med Internet Res ; 25: e40176, 2023 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-37099367

RESUMO

BACKGROUND: Men who have sex with men (MSM) in China are disproportionately affected by the HIV epidemic, and medication adherence to antiretroviral treatment in this vulnerable population is suboptimal. To address this issue, we developed an app-based case management service with multiple components, informed by the Information Motivation Behavioral skills model. OBJECTIVE: We aimed to conduct a process evaluation for the implementation of an innovative app-based intervention guided by the Linnan and Steckler framework. METHODS: Process evaluation was performed alongside a randomized controlled trial in the largest HIV clinic in Guangzhou, China. Eligible participants were HIV-positive MSM aged ≥18 years planning to initiate treatment on the day of recruitment. The app-based intervention had 4 components: web-based communication with case managers, educational articles, supportive service information (eg, information on mental health care and rehabilitation service), and hospital visit reminders. Process evaluation indicators of the intervention include dose delivered, dose received, fidelity, and satisfaction. The behavioral outcome was adherence to antiretroviral treatment at month 1, and Information Motivation Behavioral skills model scores were the intermediate outcome. Logistic and linear regression was used to investigate the association between intervention uptake and outcomes, controlling for potential confounders. RESULTS: A total of 344 MSM were recruited from March 19, 2019, to January 13, 2020, and 172 were randomized to the intervention group. At month 1 follow-up, there was no significant difference in the proportion of adherent participants between the intervention and control groups (66/144, 45.8% vs 57/134, 42.5%; P=.28). In the intervention group, 120 participants engaged in web-based communication with case managers and 158 accessed at least 1 of the delivered articles. The primary concern captured in the web-based conversation was the side effects of the medication (114/374, 30.5%), which was also one of the most popular educational articles topics. The majority (124/144, 86.1%) of participants that completed the month 1 survey rated the intervention as "very helpful" or "helpful." The number of educational articles accessed was associated with adequate adherence in the intervention group (odds ratio 1.08, 95% CI 1.02-1.15; P=.009). The intervention also improved the motivation score after adjusting for baseline values (ß=2.34, 95% CI 0.77-3.91; P=.004). However, the number of web-based conversations, regardless of conversation features, was associated with lower motivation scores in the intervention group. CONCLUSIONS: The intervention was well-received. Delivering educational resources of interest may enhance medication adherence. The uptake of the web-based communication component could serve as an indicator of real-life difficulties and could be used by case managers to identify potential inadequate adherence. TRIAL REGISTRATION: Clinicaltrial.gov NCT03860116; https://clinicaltrials.gov/ct2/show/NCT03860116. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12889-020-8171-5.


Assuntos
Infecções por HIV , Aplicativos Móveis , Minorias Sexuais e de Gênero , Masculino , Humanos , Adolescente , Adulto , Homossexualidade Masculina , Administração de Caso , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , China , Antirretrovirais/uso terapêutico
13.
Child Psychiatry Hum Dev ; 54(1): 26-33, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34338962

RESUMO

This study aims to develop and validate a checklist for IGD symptoms of Chinese adolescents based on the fifth edition of the diagnostic and statistical manual of mental disorders (DISCA). We recruited 2144 secondary school students who reported that they had played Internet games in the past 12 months in two large cities of China. The 9 item of DISCA were all significantly and positively correlated and the scale reliability was satisfactory. The unidimensional structure of the scale was confirmed by Confirmatory Factor Analysis (CFA), χ2/df = 246.18/27, CFI = .95, RMSEA = .06. Measurement invariance across gender and city groups was confirmed by Multiple-group CFA. Criterion validity was demonstrated by the significant positive associations between DISCA score and self-identified IGD, loss of control regarding time spent on Internet gaming, time spent on playing Internet games, depression, and suicidal ideation. DISCA is a brief, reliable, and validated assessment to measure adolescent IGD.


Assuntos
Comportamento Aditivo , Jogos de Vídeo , Humanos , Adolescente , Lista de Checagem , Manual Diagnóstico e Estatístico de Transtornos Mentais , Reprodutibilidade dos Testes , População do Leste Asiático , Transtorno de Adição à Internet , Comportamento Aditivo/diagnóstico , Psicometria , Internet
14.
Curr Psychol ; 42(8): 6447-6456, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-34155427

RESUMO

Globally, the coronavirus disease 2019 (COVID-19) pandemic has caused severe and multi-dimensional resource losses among individuals. The Conservation of Resource (COR) theory postulates that resource loss generates related stress responses. It can suitably be applied to understand the pandemic's encompassing adverse consequences. Yet, no assessment tool exists. This study hence developed and validated the COR Scale for COVID-19 (CORS-COVID-19) to facilitate relevant research. The five hypothesized domains included losses in financial resource, family resource, future control, fun, and social resource. A population-based random telephone survey interviewed 300 Chinese adults in the general population in Hong Kong, China during April 3-10, 2020. The levels of different types of resource losses were high (especially for loss in fun). The 5-factor structure identified by factor analysis matches with the five hypothesized dimensions. Its psychometric properties are acceptable, including good internal consistency, content validity (the correlations between the items and their respective subscales were stronger than that between the items and the other four subscales), concurrent validity (significant correlations between the scale/subscale scores and both emotional distress due to COVID-19 and satisfaction with living in Hong Kong), and convergent validity (significant correlations between specific subscales and corresponding external variables). Relatively high floor effects were detected in some subscales. The scale, which is the first of the types to assess resource losses during a pandemic, can provide theory-based understandings/assessment about the negative impacts of COVID-19. It also facilitates warranted comparisons across countries and time periods in future studies. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-021-01933-y.

15.
Glycobiology ; 32(5): 414-428, 2022 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-35157771

RESUMO

Interactions between the neonate host and its gut microbiome are central to the development of a healthy immune system. However, the mechanisms by which animals alter early colonization of microbiota for their benefit remain unclear. Here, we investigated the role of early-life expression of the α2,6-sialyltransferase ST6GAL1 in microbiome phylogeny and mucosal immunity. Fecal, upper respiratory, and oral microbiomes of pups expressing or lacking St6gal1 were analyzed by 16S rRNA sequencing. At weaning, the fecal microbiome of St6gal1-KO mice had reduced Clostridiodes, Coprobacillus, and Adlercreutzia, but increased Helicobacter and Bilophila. Pooled fecal microbiomes from syngeneic donors were transferred to antibiotic-treated wild-type mice, before analysis of recipient mucosal immune responses by flow cytometry, RT-qPCR, microscopy, and ELISA. Transfer of St6gal1-KO microbiome induced a mucosal Th17 response, with expression of T-bet and IL-17, and IL-22-dependent gut lengthening. Early life intestinal sialylation was characterized by RT-qPCR, immunoblot, microscopy, and sialyltransferase enzyme assays in genetic mouse models at rest or with glucocorticoid receptor modulators. St6gal1 expression was greatest in the duodenum, where it was mediated by the P1 promoter and efficiently inhibited by dexamethasone. Our data show that the inability to produce α2,6-sialyl ligands contributes to microbiome-dependent Th17 inflammation, highlighting a pathway by which the intestinal glycosylation regulates mucosal immunity.


Assuntos
Microbioma Gastrointestinal , Sialiltransferases , Animais , Animais Recém-Nascidos , Camundongos , RNA Ribossômico 16S/genética , Sialiltransferases/genética , Sialiltransferases/metabolismo , Células Th17/metabolismo
16.
Glycobiology ; 32(8): 701-711, 2022 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-35661210

RESUMO

Interaction of immune cells with the systemic environment is necessary for the coordinated development and execution of immune responses. Monocyte-macrophage lineage cells reside at the junction of innate and adaptive immunity. Previously we reported that the sialyltransferase ST6GAL1 in the extracellular milieu modulates B cell development and IgG production, granulocyte production, and attenuates acute airway inflammation to bacterial challenge in mouse models. Here, we report that extracellular ST6GAL1 also elicits profound responses in monocyte-macrophage lineage cells. We show that recombinant ST6GAL1 adheres to subsets of thioglycolate-elicited inflammatory cells in the mouse peritoneum and to cultured human monocyte THP-1 cells. Exposure of the inflammatory cells to recombinant ST6GAL1 elicited wholesale changes in the gene expression profile of primary mouse myeloid cells; most notable was the striking up-regulation of monocyte-macrophage and monocyte-derived dendritic cell development pathway signature genes and transcription factors PU.1, NFκB and their target genes, driving increased monocyte-macrophage population and survival ex vivo. In the cultured human monocyte cells, the essential cell surface receptor of the monocyte-macrophage lineage, the M-CSF receptor (M-CSF-R, Csfr1) was a target of extracellular ST6GAL1 catalytic activity. Extracellular ST6GAL1 activated the M-CSF-R and initiated intracellular signaling events, namely, the nuclear translocation of NFκB subunit p65, and phosphorylation of ERK 1/2 and AKT. The findings implicate extracellular ST6GAL1 in monocyte development by a mechanism initiated at the cell surface and support an emerging paradigm of an extracellular glycan-modifying enzyme as a central regulator coordinating immune hematopoietic cell development and function.


Assuntos
Fator Estimulador de Colônias de Macrófagos , Monócitos , Animais , Antígenos CD/metabolismo , Diferenciação Celular , Humanos , Fator Estimulador de Colônias de Macrófagos/metabolismo , Macrófagos/metabolismo , Camundongos , Monócitos/metabolismo , Fosforilação , Sialiltransferases/genética , Sialiltransferases/metabolismo , Transdução de Sinais , Células THP-1
17.
AIDS Behav ; 26(7): 2435-2445, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35084614

RESUMO

The study compared the level of physical activity (PA) between older people living with HIV (PLWH) and their HIV-negative counterparts in China and tested the mediational roles of self-compassion, attitudes toward aging, and perceived stress in the between-group difference in PA. From December 2017 to August 2018, face-to-face interviews were conducted among 337 and 363 HIV-positive and -negative people aged ≥ 50 in Yongzhou City, Hunan, China. Path analysis was performed. The proportions of low, moderate, and high levels of PA in the HIV-positive and -negative groups were 18.9% versus 6.7%, 43.1% versus 32.0%, and 38.0% versus 61.3%, respectively, yielding a statistically significant difference. The path analysis showed that older PLWH reported less self-compassion and positive attitudes toward aging, which was in turn associated with more perceived stress and ultimately associated with less PA. Chinese older PLWH were more sedentary than their HIV-negative counterparts. Future PA interventions may modify the mediators.


Assuntos
Infecções por HIV , Análise de Mediação , Idoso , Envelhecimento , China/epidemiologia , Estudos Transversais , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Humanos
18.
AIDS Behav ; 26(4): 1126-1137, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34698955

RESUMO

We explored the predictors and predictive models of loss to follow-up (LTFU) during the first year of anti-retroviral therapy (ART). LTFU was defined as the failure to visit the clinic for antiretroviral drugs for ≥ 90 days after the last missed scheduled visit. Based on the electronic medical records of 5953 patients who were HIV positive and began ART between 2016 and 2019 in China, the LTFU rate was 7.24 (95% confidence interval 6.49-7.97) per 100 person-years during the first year of ART. ART baseline factors were associated with LTFU, but were non-optimal predictors. A model including ART process-related factors such as follow-up behaviors and physical health status had an area under the receiver operating characteristic curve of 73.4% for predicting LTFU. Therefore, the medical records of follow-up visits can be used to identify patients with a high risk of LTFU and allow interventions to be implemented proactively.


Assuntos
Infecções por HIV , China/epidemiologia , Registros Eletrônicos de Saúde , Seguimentos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Perda de Seguimento , Estudos Retrospectivos
19.
AIDS Care ; 34(1): 95-104, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33563048

RESUMO

The present study examined the association between outcome expectations, self-efficacy, and intention to disclose HIV status to children among HIV-positive women in China, and the moderating and mediating role of self-efficacy on the association between outcome expectations and intention to disclose. A cross-sectional survey was conducted among 179 HIV-positive mothers who had at least one living child aged >5 years and had not yet disclosed their HIV status to her oldest child. Results from hierarchical regressions revealed that after adjusting for socio-demographic and medical variables, negative outcome expectations had a negative association (ß = -0.22), while disclosure self-efficacy had a positive association (ß = 0.43) with an intention to disclose HIV. The moderation effect of self-efficacy on the association between outcome expectations and intention to disclose HIV was not significant. Results from structural equation modeling showed that self-efficacy mediated the association between negative/positive outcome expectations and intention to disclose HIV. Findings support the importance of outcome expectations and self-efficacy and also the mediating role of self-efficacy in HIV disclosure among HIV-positive mothers in the Chinese context.


Assuntos
Infecções por HIV , Mães , Criança , Estudos Transversais , Feminino , Humanos , Intenção , Motivação , Autoeficácia , Revelação da Verdade
20.
Soc Psychiatry Psychiatr Epidemiol ; 57(6): 1235-1246, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34727203

RESUMO

PURPOSE: This study investigated the associations between some factors related to working from home status (WFHS) and positive/negative experiences due to social distancing and their interactions effects on depressive symptoms during the COVID-19 pandemic. METHODS: A random population-based telephone survey interviewed income-earning adults in the Hong Kong general population during April 21-28, 2020 (n = 200). RESULTS: Mild to severe depression (according to PHQ-9) was reported by 12% of the participants. The prevalence of WFHS categories was 14% for 3-7 days and 13% for ≥ 8 days (past 2 weeks). The multivariable regression analysis showed that, social isolation (ß = 0.36; p < 0.001), relaxation feeling in daily life (ß = - 0.22; p = 0.002), and WFHS ≥ 8 days (ß = 0.15; p = 0.027), but not perceived huge inconvenience and improved family relationship, were associated with depressive symptoms. Statistically significant interaction effects were found. Some positive experiences buffered the potential harms of some negative experiences of social distancing on depressive symptoms; WFHS ≥ 8 days significantly moderated the risk/protective effects of social isolation, improved family relationship, and relaxation feeling on depressive symptoms. CONCLUSIONS: Social distancing is double-edged. Positive experiences should be maximized while negative experiences be minimized, as both were directly and interactively associated with depression. Intensive but not mild to moderate (< 80%) WFHS may impact depressive symptoms negatively via its direct association with depression; it also moderated the associations between positive/negative experiences due to social distancing and depression. Further research is required to discern the inter-relationships among WFHS, positive/negative experiences of social distancing, and depression to better cope with the stressful pandemic.


Assuntos
COVID-19 , Distanciamento Físico , Adulto , COVID-19/epidemiologia , Depressão/epidemiologia , Hong Kong/epidemiologia , Humanos , Pandemias
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