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Coal dust is the main occupational hazard factor during coal mining operations. This study aimed to investigate the role of macrophage polarization and its molecular regulatory network in lung inflammation and fibrosis in Sprague-Dawley rats caused by coal dust exposure. Based on the key exposure parameters (exposure route, dose and duration) of the real working environment of coal miners, the dynamic inhalation exposure method was employed, and a control group and three coal dust groups (4, 10 and 25 mg/m3) were set up. Lung function was measured after 30, 60 and 90 days of coal dust exposure. Meanwhile, the serum, lung tissue and bronchoalveolar lavage fluid were collected after anesthesia for downstream experiments (histopathological analysis, RT-qPCR, ELISA, etc.). The results showed that coal dust exposure caused stunted growth, increased lung organ coefficient and decreased lung function in rats. The expression level of the M1 macrophage marker iNOS was significantly upregulated in the early stage of exposure and was accompanied by higher expression of the inflammatory cytokines TNF-α, IL-1ß, IL-6 and the chemokines IL-8, CCL2 and CCL5, with the most significant trend of CCL5 mRNA in lung tissues. Expression of the M2 macrophage marker Arg1 was significantly upregulated in the mid to late stages of coal dust exposure and was accompanied by higher expression of the anti-inflammatory cytokines IL-10 and TGF-ß. In conclusion, macrophage polarization and its molecular regulatory network (especially CCL5) play an important role in lung inflammation and fibrosis in SD rats exposed to coal dust by dynamic inhalation.
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Exposição por Inalação , Pneumonia , Ratos , Animais , Ratos Sprague-Dawley , Exposição por Inalação/efeitos adversos , Pneumonia/induzido quimicamente , Fibrose , Poeira , Citocinas/metabolismo , Macrófagos/metabolismo , Carvão MineralRESUMO
BACKGROUND: To explore the relationship between occupational stress, burnout and depressive symptoms among railroad workers in Fuzhou, and to analyze the interaction of burnout and occupational stress on depressive symptoms. METHODS: In this study, 861 railway employees of Fuzhou railway bureau were randomly selected from January to April, 2022. Occupational stress inventory revised edition (OSI-R), China job burnout inventory (CMBI) and Symptom Checklist-90 (SCL-90) were used to investigate the occupational stress, job burnout and depressive symptoms of railway workers. Interactions associated with depressive symptoms were assessed by linear hierarchical regression analysis and SPSS macros (PROCESS). RESULTS: Occupational stress, job burnout and depressive symptoms accounted for 50.58%, 93.47%, and 11.19% of the study population, respectively. There were intergroup differences between age, marriage status, and length of service (P < 0.05). Occupational stress and job burnout are the main risk factors for depressive symptoms (OR: 2.01, 95% CI: 1.17-3.45; 1.94, 1.69-2.23, respectively). More importantly, further analysis of the interaction between occupational stress and job burnout showed that those with high levels of job burnout had a high-risk effect on depressive symptoms at high levels of occupational stress. CONCLUSION: Occupational stress and job burnout are risk factors for depressive symptoms among railroad workers in Fuzhou City. The interaction of job burnout and occupational stress increases the risk of depressive symptoms.
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Esgotamento Profissional , Depressão , Estresse Ocupacional , Ferrovias , Humanos , China/epidemiologia , Masculino , Esgotamento Profissional/epidemiologia , Esgotamento Profissional/psicologia , Depressão/epidemiologia , Depressão/psicologia , Adulto , Feminino , Estresse Ocupacional/psicologia , Estresse Ocupacional/epidemiologia , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Anemia seriously affects the health and quality of life of the older adult population and may be influenced by various types of environmental metal exposure. Current studies on metals and anemia are mainly limited to single metals, and the association between polymetals and their mixtures and anemia remains unclear. METHODS: We determined 11 urinary metal concentrations and hemoglobin levels in 3781 participants. Binary logistic regression and restricted cubic spline (RCS) model were used to estimate the association of individual metals with anemia. We used Bayesian kernel machine regression (BKMR) and Quantile g-computation (Q-g) regression to assess the overall association between metal mixtures and anemia and identify the major contributing elements. Stratified analyses were used to explore the association of different metals with anemia in different populations. RESULTS: In a single-metal model, nine urinary metals significantly associated with anemia. RCS analysis further showed that the association of arsenic (As) and copper (Cu) with anemia was linear, while cobalt, molybdenum, thallium, and zinc were non-linear. The BKMR model revealed a significant positive association between the concentration of metal mixtures and anemia. Combined Q-g regression analysis suggested that metals such as Cu, As, and tellurium (Te) were positively associated with anemia, with Te as the most significant contributor. Stratified analyses showed that the association of different metals with anemia varied among people of different sexes, obesity levels, lifestyle habits, and blood pressure levels. CONCLUSIONS: Multiple metals are associated with anemia in the older adult population. A significant positive association was observed between metal mixture concentrations and anemia, with Te being the most important factor. The association between urinary metal concentrations and anemia is more sensitive in the non-hypertensive populations.
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Anemia , Arsênio , Humanos , Idoso , Estudos Transversais , Teorema de Bayes , Vida Independente , Qualidade de Vida , Metais/urina , Arsênio/urina , Anemia/epidemiologia , China/epidemiologiaRESUMO
BACKGROUND: Environmental metal exposure is associated with elevated triglycerides (TG) and the development of chronic kidney disease (CKD). However, the relationship between metal exposure and glomerular filtration rate (GFR) remains uncertain, and the mediating effect of TG between the two is unclear. METHODS: This study measured the concentrations of 14 metals in urine samples from 3752 elderly people in the community. The most relevant metals were screened by least absolute shrinkage and selection operator (LASSO) regression. The relationship between combined exposure to multiple metals and abnormal estimated glomerular filtration rate (eGFR) was explored using multivariate logistic regression analysis and Bayesian kernel machine regression (BKMR) analysis. Generalized linear regression models and the Karlson-Holm-Breen (KHB) method were used to assess the mediating effects of TG. RESULTS: In the single-metal model, calcium (Ca), iron (Fe), selenium (Se), strontium (Sr), and thallium (Tl) showed significant negative correlations with the prevalence of abnormal eGFR (all P < 0.05). In the multi-metals model, Ca, Se, and Tl continued to show significant negative correlations, while vanadium (V) and zinc (Zn) showed significant positive correlations with abnormal eGFR (all P < 0.05). The BKMR model showed a negative joint effect of the mixture of Ca, V, Zn, Se, and Tl on the prevalence of abnormal eGFR. The generalized linear regression model showed a significant positive correlation between the concentrations of Ca (ß = 0.07), Zn (ß = 0.07), Se (ß = 0.09), and TG levels (all P < 0.05). In the mediation analysis, TG masked a 4.30% and 5.21% correlation between Ca and Se and the prevalence of eGFR abnormalities, respectively. CONCLUSIONS: Urinary concentration of multiple metals is significantly associated with eGFR abnormalities, and Ca, and Se may be among the potential protective factors. TG masked some of the protective effects of Ca and Se.
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Taxa de Filtração Glomerular , Metais , Triglicerídeos , Idoso , Humanos , Teorema de Bayes , Cálcio , População do Leste Asiático , Vida Independente , Selênio , Zinco , Metais/urinaRESUMO
BACKGROUND: The cognitive function of people with diabetes has gained an increasing interest in recent years, and this study focuses on exploring the relationship between undiagnosed diabetes and cognitive function among the middle-aged and elderly people in China. METHODS: The data came from the China Health and Retirement Longitudinal Study (CHARLS) which was conducted between July and October 2015. 9855 subjects were enrolled in the study. Executive function and episodic memory were used to assess cognitive function. The subjects were divided into three groups: no diabetes, diagnosed diabetes, and undiagnosed diabetes, and weighted multiple linear regression models were established to evaluate the association of undiagnosed diabetes with cognitive function. RESULTS: After controlling for covariates, undiagnosed diabetes was statistically associated with executive function (ß = -0.215, P < 0.01). In the age group of ≥65 years, undiagnosed diabetes was statistically associated with executive function (ß = -0.358, P < 0.01) and episodic memory (ß = -0.356, P < 0.01). When adjusting for confounders, no statistically significant associations were found between diagnosed diabetes and cognitive function except in 45-54 age group (ß = 0.374, P < 0.05). CONCLUSIONS: The cross-sectional study suggested that undiagnosed diabetes was linked to poor cognitive function, especially in the elderly population. Timely diagnosis and active treatment of diabetes are important to reduce the occurrence of cognitive impairment. Further prospective cohort studies are required to articulate the association between undiagnosed diabetes and cognitive function.
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Disfunção Cognitiva , Diabetes Mellitus , Idoso , China/epidemiologia , Cognição , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Estudos Transversais , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , AposentadoriaRESUMO
AIMS: The present study investigated the association between resilience, stigma, life satisfaction and the intention to receive a COVID-19 vaccination among Chinese HCWs. It also explored the mediating role of stigma and life satisfaction on the association between resilience and intention to receive a COVID-19 vaccination. DESIGN: An anonymous cross-sectional survey. METHODS: 1733 HCWs from five hospitals in four provinces of mainland China completed a cross-sectional online survey in October and November 2020. RESULTS: Among the HCWs, the rate of intention to receive a COVID-19 vaccination was 73.1%. Results from structural equation modelling showed that resilience was associated both directly, and indirectly with greater intent to receive a COVID-19 vaccination through two pathways: first by increasing life satisfaction, and second by reducing stigma and increasing life satisfaction. CONCLUSION: Promoting the resilience of HCWs has the potential to increase the COVID-19 vaccination uptake rate among HCWs in China. IMPACT: This study tested the relationship between several psychological factors and the COVID-19 vaccination intention of HCWs in China, finding that resilience played a significant role in improving COVID-19 vaccination intention rates by reducing stigma and increasing life satisfaction.
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COVID-19 , Intenção , COVID-19/prevenção & controle , Vacinas contra COVID-19 , China , Estudos Transversais , Pessoal de Saúde/psicologia , Humanos , Satisfação Pessoal , Inquéritos e Questionários , Vacinação/psicologiaRESUMO
BACKGROUND: Prenatal stress can cause neurobiological and behavioral defects in offspring; environmental factors play a crucial role in regulating the development of brain and behavioral; this study was designed to test and verify whether an enriched environment can repair learning and memory impairment in offspring rats induced by prenatal stress and to explore its mechanism involving the expression of insulin-like growth factor-2 (IGF-2) and activity-regulated cytoskeletal-associated protein (Arc) in the hippocampus of the offspring. METHODS: Rats were selected to establish a chronic unpredictable mild stress (CUMS) model during pregnancy. Offspring were weaned on 21st day and housed under either standard or an enriched environment. The learning and memory ability were tested using Morris water maze and Y-maze. The expression of IGF-2 and Arc mRNA and protein were respectively measured by using RT-PCR and Western blotting. RESULTS: There was an elevation in the plasma corticosterone level of rat model of maternal chronic stress during pregnancy. Maternal stress's offspring exposed to an enriched environment could decrease their plasma corticosterone level and improve their weight. The offspring of maternal stress during pregnancy exhibited abnormalities in Morris water maze and Y-maze, which were improved in an enriched environment. The expression of IGF-2, Arc mRNA, and protein in offspring of maternal stress during pregnancy was boosted and some relationships existed between these parameters after being exposed enriched environment. CONCLUSIONS: The learning and memory impairment in offspring of prenatal stress can be rectified by the enriched environment, the mechanism of which is related to the decreasing plasma corticosterone and increasing hippocampal IGF-2 and Arc of offspring rats following maternal chronic stress during pregnancy.
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Proteínas do Citoesqueleto/genética , Regulação da Expressão Gênica , Fator de Crescimento Insulin-Like II/genética , Deficiências da Aprendizagem/genética , Transtornos da Memória/genética , Proteínas do Tecido Nervoso/genética , Efeitos Tardios da Exposição Pré-Natal/genética , Meio Social , Estresse Psicológico/genética , Animais , Proteínas do Citoesqueleto/metabolismo , Feminino , Hipocampo/metabolismo , Fator de Crescimento Insulin-Like II/metabolismo , Aprendizagem , Deficiências da Aprendizagem/psicologia , Masculino , Transtornos da Memória/psicologia , Proteínas do Tecido Nervoso/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/psicologia , Distribuição Aleatória , Ratos , Ratos WistarRESUMO
This article reviews mushrooms with anti-breast cancer activity. The mushrooms covered which are better known include the following: button mushroom Agaricus bisporus, Brazilian mushroom Agaricus blazei, Amauroderma rugosum, stout camphor fungus Antrodia camphorata, Jew's ear (black) fungus or black wood ear fungus Auricularia auricula-judae, reishi mushroom or Lingzhi Ganoderma lucidum, Ganoderma sinense, maitake mushroom or sheep's head mushroom Grifola frondosa, lion's mane mushroom or monkey head mushroom Hericium erinaceum, brown beech mushroom Hypsizigus marmoreus, sulfur polypore mushroom Laetiporus sulphureus, Lentinula edodes (shiitake mushroom), Phellinus linteus (Japanese "meshimakobu," Chinese "song gen," Korean "sanghwang," American "black hoof mushroom"), abalone mushroom Pleurotus abalonus, king oyster mushroom Pleurotus eryngii, oyster mushroom Pleurotus ostreatus, tuckahoe or Fu Ling Poria cocos, and split gill mushroom Schizophyllum commune. Antineoplastic effectiveness in human clinical trials and mechanism of anticancer action have been reported for Antrodia camphorata, Cordyceps sinensis, Coriolus versicolor, Ganoderma lucidum, Grifola frondosa, and Lentinula edodes.
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Agaricales/química , Agaricales/classificação , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Ensaios Clínicos como Assunto , Misturas Complexas/química , Misturas Complexas/farmacologia , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , RatosRESUMO
Ribosome-inactivating proteins (RIPs) consist of three varieties. Type 1 RIPs are single-chained and approximately 30-kDa in molecular weight. Type 2 RIPs are double-chained and composed of a type 1 RIP chain and a lectin chain. Type III RIPs, such as maize b-32 barley and JIP60 which are produced as single-domain proenzymes, possess an N-terminal domain corresponding to the A domain of RIPs and fused to a C-terminal domain. In addition to the aforementioned three types of RIPs originating from flowering plants, there are recently discovered proteins and peptides with ribosome-inactivating and protein synthesis inhibitory activities but which are endowed with characteristics such as molecular weights distinctive from those of the regular RIPs. These new/unusual RIPs discussed in the present review encompass metazoan RIPs from Anopheles and Culex mosquitos, antimicrobial peptides derived from RIP of the pokeweed Phytolacca dioica, maize RIP (a type III RIP derived from a precursor form), RIPs from the garden pea and the kelp. In addition, RIPs with a molecular weight smaller than those of regular type 1 RIPs are produced by plants in the Cucurbitaceae family including the bitter gourd, bottle gourd, sponge gourd, ridge gourd, wax gourd, hairy gourd, pumpkin, and Chinese cucumber. A small type II RIP from camphor tree (Cinnamomum camphora) seeds and a snake gourd type II RIP with its catalytic chain cleaved into two have been reported. RIPs produced from mushrooms including the golden needle mushroom, king tuber mushroom, straw mushroom, and puffball mushroom are also discussed in addition to a type II RIP from the mushroom Polyporus umbellatus. Bacterial (Spiroplasma) RIPs associated with the fruitfly, Shiga toxin, and Streptomyces coelicolor RIP are also dealt with. The aforementioned proteins display a diversity of molecular weights, amino acid sequences, and mechanisms of action. Some of them are endowed with exploitable antipathogenic activities.
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Biossíntese de Proteínas/efeitos dos fármacos , Proteínas Inativadoras de Ribossomos/metabolismo , Sequência de Aminoácidos , Animais , Culicidae/química , Proteínas de Insetos/metabolismo , Proteínas de Plantas/metabolismo , Proteínas Inativadoras de Ribossomos/classificação , Proteínas Inativadoras de Ribossomos/farmacologia , Sementes/químicaRESUMO
Fungi comprise organisms like molds, yeasts and mushrooms. They have been used as food or medicine for a long time. A large number of fungal proteins or peptides with diverse biological activities are considered as antibacterial, antifungal, antiviral and anticancer agents. They encompass proteases, ribosome inactivating proteins, defensins, hemolysins, lectins, laccases, ribonucleases, immunomodulatory proteins, and polysaccharopeptides. The target of the present review is to update the status of the various bioactivities of these fungal proteins and peptides and discuss their therapeutic potential.
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Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/farmacologia , Fungos/metabolismo , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antineoplásicos/farmacologia , Antivirais/farmacologia , Proliferação de Células/efeitos dos fármacos , Defensinas/farmacologia , Fatores Imunológicos/farmacologia , Proteínas Inativadoras de Ribossomos/farmacologiaRESUMO
OBJECTIVES: The aim of this study was to assess the risk of cataract following protracted low doses of radiation exposure among industry radiographers and comparison groups of unexposed workers. METHODS: A cohort of 1401 industry radiographers and 1878 unexposed workers in China was followed up for 12â years. The lens doses were based on individual monitoring. Presence of cataract was assessed clinically based on lens photographs using the Lens Opacities Classification System III. Radiation dose-response analyses were performed for cataract incidence by using Poisson regression, adjusting for confounding factors. RESULTS: Industry radiographers were significantly more likely than unexposed workers to develop cortical (HR=2.58, 95% CI 1.36 to 3.82), posterior subcapsular (PSC) cataract (HR=3.57, 95% CI 1.27 to 4.79) and mixed cataract (HR=3.25, 95% CI 1.20 to 6.78), but not nuclear cataract (HR=0.93, 95% CI 0.78 to 1.11). Hypertension, diabetes mellitus, old age at exposure, and high body mass index (>27â km/m(2)) were significantly associated with increased risk of cortical, PSC and mixed cataracts. However, the risk decreased for regular users of shielded enclosures, lead eyeglasses and lead aprons. No dose-effect relationship was observed for cortical (excess relative risk (ERR)/Sv=0.16; 95% CI -0.04 to 0.36) and PSC cataract (ERR/Sv=0.14; 95% CI -0.90 to 0.76). CONCLUSIONS: The results indicated a radiation effect for cortical and PSC cataract at doses less than the annual limit of the International Commission on Radiological Protection (ICRP) guidelines. Regarding current eye risk guidelines, the results challenged the ICRP assumption that cataract is a dose-limiting ocular pathology. Regular use of radiation-protective equipment is therefore strongly recommended for eye safety.
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Catarata/etiologia , Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Ocupações , Lesões por Radiação/etiologia , Radiografia , Adolescente , Adulto , Catarata/prevenção & controle , Feminino , Humanos , Cristalino/patologia , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/prevenção & controle , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: It is debatable whether or not glucocorticoid receptor (GR) polymorphisms moderate susceptibility to PTSD. Our objective was to examine the effects of stressful life events, social support, GR genotypes, and gene-environment interactions on the etiology of PTSD. METHODS: Three tag single nucleotide polymorphisms, trauma events, stressful life events, and social support were assessed in 460 patients with PTSD and 1158 control subjects from a Chinese Han population. Gene-environment interactions were analyzed by generalized multifactor dimensionality reduction (GMDR). RESULTS: Variation in GR at rs41423247 and rs258747, stressful life events, social support, and the number of traumatic events were each separately associated with the risk for PTSD. A gene-environment interaction among the polymorphisms, rs41423247 and rs258747, the number of traumatic events, stressful life events, and social support resulted in an increased risk for PTSD. High-risk individuals (a large number of traumatic events, G allele of rs258747 and rs41423247, high level stressful life events, and low social support) had a 3.26-fold increased risk of developing PTSD compared to low-risk individuals. The association was statistically significant in the sub-groups with and without childhood trauma. CONCLUSIONS: Our data support the notion that stressful life events, the number of trauma events, and social support may play a contributing role in the risk for PTSD by interacting with GR gene polymorphisms.
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Acontecimentos que Mudam a Vida , Receptores de Glucocorticoides/genética , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Adulto , Alelos , Feminino , Interação Gene-Ambiente , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Apoio Social , Transtornos de Estresse Pós-Traumáticos/genéticaRESUMO
Maternal immune activation (MIA), defined as elevated levels of inflammatory markers beyond the normal range, can occur due to psychological stress, infection, and other disruptions during pregnancy. MIA affects the immune system development in offspring and increases the risk of immune-related disorders. Limited studies have investigated the effects of prenatal stress on offspring's immune system. In this study, pregnant rats were exposed to chronic unpredictable mild stress (CUMS) during pregnancy, involving seven different stressors. We examined the impact of prenatal stress stimuli on the offspring's immune system and observed activation of the PI3K/Akt/NF-κB signaling pathway, resulting in an imbalance of Th17/Treg cells in the offspring's spleen. Our findings revealed increased plasma levels of corticosterone, IL-1ß, and IL-6 in female rats exposed to prenatal stress, as well as elevated serum levels of IL-6 and TNF-α in the offspring. Furthermore, we identified a correlation between cytokine levels in female rats and their offspring. Transcriptome sequencing and qPCR experiments indicated differentially expressed mRNAs in offspring exposed to prenatal stress, which may contribute to the imbalance of Th17/Treg cells through the activation of the Gng3-related PI3K/Akt/NF-κB pathway.
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NF-kappa B , Proteínas Proto-Oncogênicas c-akt , Gravidez , Ratos , Feminino , Animais , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Interleucina-6 , Linfócitos T Reguladores/metabolismo , Transdução de SinaisRESUMO
Objective: To examine the relationship between pregnancy-related anxiety, family functions, and sleep quality, and to determine whether family functions mediate the relationship between pregnancy-related anxiety and sleep quality. Methods: A cross-sectional survey was conducted on pregnant women between April to August in 2022 in the obstetrics outpatient clinic of a tertiary care hospital in the Ningxia Hui Autonomous Region of China. A total of 1014 pregnant women aged 18 years and older were surveyed. They completed questionnaires, including: general demographic characteristics, the Pregnancy-related anxiety scale (PAQ), the Family Adaptation, Partnership, Growth, Affection, and Resolve (APGAR), and the Pittsburgh Sleep Quality Index Questionnaire (PSQI). Model 4 in PROCESS was used to analyze the relationships among pregnancy-related anxiety, family functions, and sleep quality, with family functions as a mediator. Results: Among the 1014 pregnant women, the pregnancy-related anxiety scale score was (21.84 ± 5.64). The total score of the family functions scale was (8.10±2.26), and the overall sleep quality scale score was (7.89±2.99). When participants were grouped according to different socio-demographic characteristics, the study showed that all variables differed from anxiety, family functions or sleep quality, except for age, pre-pregnancy BMI and whether or not they had a first birth, which was not associated with anxiety, family functions, or sleep quality (P<0.05). The pregnancy-related anxiety was positively associated with sleep quality (P<0.01), while family functions were negatively associated with sleep quality (P<0.01). In addition, family functions mediate the relationship between pregnancy-related anxiety and sleep quality during pregnancy, on the first and second trimesters, intermediation rate is 9.31% (P<0.05), and on the third trimesters, intermediation rate is 21.38% (P<0.05). Conclusion: Pregnancy- related anxiety is a risk factor for sleep quality, however, family functions are protective factors for sleep quality. Family functions play an intermediary role in sleep quality caused by pregnancy-related anxiety, especially on the third trimesters. This finding may provide a scientific basis for developing intervention strategies to improve the sleep quality of pregnant women.
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The effects and underlying mechanisms of adolescent exposure to combined environmental hazards on cognitive function remain unclear. Here, using a combined exposure model, we found significant cognitive decline, hippocampal neuronal damage, and neuronal senescence in mice exposed to cadmium (Cd) and high-fat diet (HFD) during adolescence. Furthermore, we observed a significant downregulation of Sirtuin 6 (SIRT6) expression in the hippocampi of co-exposed mice. UBCS039, a specific SIRT6 activator, markedly reversed the above adverse effects. Further investigation revealed that co-exposure obviously reduced the levels of La ribonucleoprotein 7 (LARP7), disrupted the interaction between LARP7 and SIRT6, ultimately decreasing SIRT6 expression in mouse hippocampal neuronal cells. Overexpression of Larp7 reversed the combined exposure-induced SIRT6 decrease and senescence in mouse hippocampal neuronal cells. Additionally, the results showed notably elevated levels of Larp7 m6A and YTH domain family protein 2 (YTHDF2) in mouse hippocampal neuronal cells treated with the combined hazards. Ythdf2 short interfering RNA, RNA immunoprecipitation, and RNA stability assays further demonstrated that YTHDF2 mediated the degradation of Larp7 mRNA under combined exposure. Collectively, adolescent co-exposure to Cd and HFD causes hippocampal senescence and cognitive decline in mice by inhibiting LARP7-mediated SIRT6 expression in an m6A-dependent manner.
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Cádmio , Disfunção Cognitiva , Dieta Hiperlipídica , Hipocampo , Ribonucleoproteínas , Sirtuínas , Animais , Masculino , Camundongos , Adenosina/análogos & derivados , Cádmio/toxicidade , Disfunção Cognitiva/induzido quimicamente , Dieta Hiperlipídica/efeitos adversos , Poluentes Ambientais/toxicidade , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ribonucleoproteínas/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Sirtuínas/metabolismo , Sirtuínas/genética , Antígeno SS-BRESUMO
Background: Inflammation is a risk factor for cardiovascular disease (CVD), and particular inflammatory parameters can be used to predict the incidence of CVD. The aim of this study was to assess the association between fibrinogen (FIB), interleukin-6 (IL-6), C-reactive protein (CRP) and galectin-3 (Gal-3) and the risk of cardiovascular disease using meta-analysis. Methods: PubMed, Embase, Scopus, and Web of Science databases were searched with the appropriate strategies to identify observational studies relevant to this meta-analysis. A random-effects model was used to combine inflammation factor-associated outcomes and cardiovascular disease outcomes, except in the case of galectin-3, where a fixed-effects model was used because of less heterogeneity. Location, age, type of cardiovascular disease, and sample size factors were used to explore heterogeneity in stratification and metaregression for subgroup analysis. A case-by-case literature exclusion approach was used for sensitivity analysis. The funnel plot and Begg's test were combined to assess publication bias. Results: Thirty-three papers out of 11,456 were screened for inclusion in the analysis. Four inflammation biomarkers were significantly associated with the development of CVD: FIB (OR: 1.21, 95% CI: 1.15-1.27, P < 0.001; HR: 1.04, 95% CI: 1.00-1.07, P < 0.05), IL-6 (HR: 1.16, 95% CI: 1.10-1.22, P < 0.001), CRP (OR: 1.25, 95% CI: 1.15-1.35, P < 0.001; HR: 1.20, 95% CI: 1.14-1.25, P < 0.001) and Gal-3 (HR: 1.09, 95% CI: 1.05-1.14, P < 0.001). Location factors help explain the source of heterogeneity, and there is publication bias in the Gal-3 related literature. Conclusion: Taken together, the current research evidence suggests that high levels of fibrinogen, interleukin-6, C-reactive protein and galectin-3 are risk factors for cardiovascular disease and can be used as biomarkers to predict the development of cardiovascular disease to some extent. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier: CRD42023391844.
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Background: Chronic long-term stress is associated with a range of disorders, including depression and a variety of other chronic illnesses. It is well known that maternal exposure to psychosocial stress during pregnancy significantly increases the likelihood of adverse pregnancy outcomes. The gut microbiota has been a popular topic, it is a key mediator of the gut-brain axis and plays an important role in human health; changes in the gut microbiota have been related to chronic stress-induced health impairment, however, the relationship between maternal negative emotions and abnormal gut microbiota and its metabolites during maternal exposure to chronic stress during pregnancy remains unclear. Methods: Pregnant rats were subjected to chronic unpredicted mild stress (CUMS) to establish the rat model of chronic stress during pregnancy. The behavioral changes were recorded using sucrose preference test (SPT) and open-field test (OFT), plasma corticosterone levels were determined by radioimmunoassay, and a comprehensive method combining 16S rRNA gene sequencing and gas chromatography-mass spectrometry (GC-MS) metabolomics was used to study the effects of stress during pregnancy on the function of intestinal microbiota and its metabolites. Results: Chronic stress during pregnancy not only increased maternal plasma corticosterone (P < 0.05), but also caused maternal depression-like behaviors (P < 0.05). Chronic stress during pregnancy changed the species composition at the family level of maternal gut microbiota, the species abundance of Ruminococcaceae in the stress group (23.45%) was lower than the control group (32.67%) and the species abundance of Prevotellaceae in the stress group (10.45%) was higher than the control group (0.03%) (P < 0.05). Vertical locomotion and 1% sucrose preference percentage in pregnant rats were negatively correlated with Prevotellaceae (r = - 0.90, P < 0.05). Principal component analysis with partial least squares discriminant analysis showed that the integration points of metabolic components in the stress and control groups were completely separated, indicating that there were significant differences in the metabolic patterns of the two groups, and there were seven endogenous metabolites that differed (P < 0.05). Conclusions: The negative emotional behaviors that occur in pregnant rats as a result of prenatal chronic stress may be associated with alterations in the gut microbiota and its metabolites. These findings provide a basis for future targeted metabolomics and gut flora studies on the effects of chronic stress during pregnancy on gut flora.
Assuntos
Microbioma Gastrointestinal , Humanos , Gravidez , Feminino , Ratos , Animais , RNA Ribossômico 16S/genética , Corticosterona , Metabolômica , EmoçõesRESUMO
BACKGROUND: Early life experiences may have a persistent influence throughout life. However, little is known about the effect of parental absence during infancy and early childhood on offspring's cognition and risk of depression. METHODS: Data were obtained from the China Family Panel Studies (CFPS). We examined the effect of parental absence during infancy and early childhood on cognitive development and depression in later life using weighted linear regression models. A series of sensitivity analyses and subgroup analyses were also conducted. RESULTS: Parental absence during infancy and early childhood was associated with poor mathematics performance and high depression scores measured 8 years later. The coefficients of association between parental absence and math test performance and depression were -0.012 (95%CI: -0.024, -0.001, P = 0.031) and 0.009 (95%CI: 0.001, 0.017, P = 0.028) in adjusted models, respectively. Moreover, a similar association was observed among children who were females, urban dwellers, and had more years of education. LIMITATIONS: Recall bias may exist for the exposure measure, and the current study cannot control residual confounders. CONCLUSION: Long parental absence during infancy and early childhood may attenuate the cognitive process and increase risk of depression in later life, indicating the necessity of parental care as an intervention initiative.
Assuntos
Depressão , Pais , Criança , Feminino , Pré-Escolar , Humanos , Masculino , Estudos Longitudinais , Depressão/epidemiologia , Depressão/psicologia , Pais/psicologia , Cognição , China/epidemiologiaRESUMO
Background: Numerous studies have shown that exposure to prenatal maternal stress (PMS) is associated with various psychopathological outcomes of offspring. The accumulating evidence linking bacteria in the gut and neurons in the brain (the microbiota-gut-brain axis) has been aconsensus; however, there is a lack of research on the involvement mechanism of gut microbiota in the regulation of the BDNF/CREB signaling pathway in the hippocampus of prenatally stressed offspring. Methods: Pregnant rats were subjected to chronic unpredictable mild stress (CUMS) to establish the prenatal maternal stress model. The body weight was measured and the behavioral changes were recorded. Offspring were tested to determine emotional state using sucrose preference test (SPT), open-field test (OFT) and suspended tail test (STT). Gut microbiota was evaluated by sequencing the microbial 16S rRNA V3-V4 region, and the interactive analysis of bacterial community structure and diversity was carried out. The expression of hippocampal BDNF, TrkB and CREB mRNA and proteins were respectively measured using RT-PCR and Western blotting. Results: Prenatal maternal stress increased maternal plasma corticosterone levels, slowed maternal weight gain and caused depression-like behaviors (all P < 0.05). In offspring, prenatal maternal stress increased plasma corticosterone levels (P < 0.05) and emotional behavior changes (depression-like state) were observed (P < 0.05). The species abundance, diversity and composition of the offspring's gut microbiota changed after the maternal stress during pregnancy (P < 0.05). Compared with the control group's offspring, the species abundance of Lactobacillaceae was dropped, while the abundance of the Muribaculaceae species abundance was risen. Concurrent, changes in the hippocampal structure of the offspring and decreases in expression of BDNF/CREB signaling were noted (P < 0.05). Conclusions: Prenatal maternal stress leads to high corticosterone status and abnormal emotion behavior of offspring, which may be associated with the abnormal BDNF/CREB signaling in hippocampus of offspring caused by the change of gut microbiota composition.
Assuntos
Fator Neurotrófico Derivado do Encéfalo , Microbioma Gastrointestinal , Animais , Feminino , Gravidez , Ratos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Corticosterona , Emoções , Hipocampo/metabolismo , RNA Ribossômico 16S/metabolismo , Transdução de SinaisRESUMO
Numerous clinical and animal studies have found that antenatal chronic stress can lead to pathological changes the hippocampal development from embryos to adult, but the mechanisms are not well understood. Proteomic analyses provide a new insight to explore the potential mechanisms of this impairment. In this study, gestating rats were subjected to chronic unpredictable mild stress (CUMS) during pregnant days using nine different stimulations, and the changes of the learning and memory performance and the expression of proteins in the hippocampus of offspring were measured. It was found that prenatal chronic stress led to growth retardation, impaired spatial learning and memory ability in the offspring. Furthermore, prenatal stress caused various degrees of damage to neurons, Nissl body, mitochondria and synaptic structures in hippocampal CA3 region of offspring. In addition, 26 significantly different expressed proteins (DEPs) were found between the two groups by using isoquantitative tag-based relative and absolute quantification (iTRAQ) proteomics analysis. Further analyses of these DEPs showed that involved with different molecular functions and several biological processes, such as biological regulation and metabolic processes. Among these, the KEGG pathway enrichment showed that learning and memory impairment was mainly associated with the cyclic guanosine monophosphate protein kinase G (cGMP-PKG) pathway. At the same time, compared with OPC group, the NO, nNOS and cGMP level were significantly decreased, and the expression of PKG protein was also dropped. All of these results suggested that pregnant rats exposed to chronic psychological stress might impair spatial learning and memory ability of offspring, by disturbing the NO/cGMP/PKG signaling pathway.