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With economic development and overnutrition, including high-fat diets (HFD) and high-glucose diets (HGD), the incidence of obesity in children is increasing, and thus, the incidence of precocious puberty is increasing. Therefore, it is of great importance to construct a suitable animal model of overnutrition-induced precocious puberty for further in-depth study. Here, we fed a HFD, HGD, or HFD combined with a HGD to pups after P-21 weaning, while weaned pups fed a normal diet served as the control group. The results showed that HFD combined with a HGD increased the body weight (BW) of weaned rat pups. In addition, a HFD, HGD, and HFD combined with a HGD lowered the age at which vaginal opening occurred and accelerated the vaginal cell cycle. Furthermore, a HFD combined with a HGD increased the weight of the uterus and ovaries of weaned rat pups. Additionally, a HFD combined with a HGD promoted the development of reproductive organs in weaned female rat pups. Ultimately, a HFD combined with a HGD was found to elevate the serum levels of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), follicle stimulating hormone (FSH), leptin, adiponectin, and oestradiol (E2) and increase hypothalamic GnRH, Kiss-1, and GPR54 expression levels in weaned female rat pups. The current study found that overnutrition, such as that through a HFD combined with HGD, could induce precocious puberty in weaned female rat pups. In addition, a rat model of overnutrition-induced precocious puberty was established.
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Obesidade Infantil , Puberdade Precoce , Humanos , Criança , Animais , Ratos , Feminino , Ratos Sprague-Dawley , Puberdade Precoce/induzido quimicamente , Obesidade Infantil/complicações , Hormônio Liberador de Gonadotropina , Dieta Hiperlipídica/efeitos adversos , GlucoseRESUMO
OBJECTIVES: To investigate the levels of serum folate and vitamin B12 (VB12) and their association with the level of neurodevelopment in preschool children with autism spectrum disorder (ASD). METHODS: A total of 324 ASD children aged 2-6 years and 318 healthy children aged 2-6 years were recruited. Serum levels of folate and VB12 were measured using chemiluminescent immunoassay. The Social Responsiveness Scale and the Childhood Autism Rating Scale were used to assess the core symptoms of ASD children, and the Gesell Developmental Schedule was employed to evaluate the level of neurodevelopment. RESULTS: The levels of serum folate and VB12 in ASD children were significantly lower than those in healthy children (P<0.05). Serum folate levels in ASD children were positively correlated with gross and fine motor developmental quotients (P<0.05), and serum VB12 levels were positively correlated with adaptive behavior, fine motor, and language developmental quotients (P<0.05). In ASD children aged 2 to <4 years, serum folate levels were positively correlated with developmental quotients in all domains (P<0.05), and serum VB12 levels were positively correlated with language developmental quotient (P<0.05). In male ASD children, serum VB12 levels were positively correlated with language and personal-social developmental quotients (P<0.05). CONCLUSIONS: Serum folate and VB12 levels in preschool ASD children are lower than those in healthy children and are associated with neurodevelopmental levels, especially in ASD children under 4 years of age. Therefore, maintaining normal serum folate and VB12 levels may be beneficial for the neurodevelopment of ASD children, especially in ASD children under 4 years of age.
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Transtorno do Espectro Autista , Ácido Fólico , Vitamina B 12 , Humanos , Transtorno do Espectro Autista/sangue , Transtorno do Espectro Autista/etiologia , Pré-Escolar , Masculino , Feminino , Ácido Fólico/sangue , Vitamina B 12/sangue , Criança , Desenvolvimento InfantilRESUMO
Semi-quantum key distribution (SQKD) protocols are used to distribute secret keys between a quantum party and a classical party. However, existing SQKD protocols rely on two-way communication, and may still be vulnerable to Trojan horse side-channel attacks where Eve sends her own photon into a receiver's apparatus and measures the reflected photon to estimate the key. In this paper, we propose a practical SQKD with one-way key. This requires that the single photons travelling through the one-way channel are used to encode bit information, and the returned photons are used to quantify Eve's information, thus reducing the security analysis of the Trojan horse attack in SQKD. Meanwhile, our protocol with one basis enjoys security advantage in practical SQKD systems when source flaws are taken into account. In particular, the present protocol is secure under practical conditions when weak coherent pulses (WCP) are used. Our simulation results show that the protocol using WCP can distribute secret keys over a distance of 110 km without decoy states.
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OBJECTIVES: To study the mechanism of retinoic acid receptor α (RARα) signal change to regulate neurexin 1 (NRXN1) in the visual cortex and participate in the autistic-like behavior in rats with vitamin A deficiency (VAD). METHODS: The models of vitamin A normal (VAN) and VAD pregnant rats were established, and some VAD maternal and offspring rats were given vitamin A supplement (VAS) in the early postnatal period. Behavioral tests were performed on 20 offspring rats in each group at the age of 6 weeks. The three-chamber test and the open-field test were used to observe social behavior and repetitive stereotyped behavior. High-performance liquid chromatography was used to measure the serum level of retinol in the offspring rats in each group. Electrophysiological experiments were used to measure the long-term potentiation (LTP) level of the visual cortex in the offspring rats. Quantitative real-time PCR and Western blot were used to measure the expression levels of RARα, NRXN1, and N-methyl-D-aspartate receptor 1 (NMDAR1). Chromatin co-immunoprecipitation was used to measure the enrichment of RARα transcription factor in the promoter region of the NRXN1 gene. RESULTS: The offspring rats in the VAD group had autistic-like behaviors such as impaired social interactions and repetitive stereotypical behaviors, and VAS started immediately after birth improved most of the behavioral deficits in offspring rats. The offspring rats in the VAD group had a significantly lower serum level of retinol than those in the VAN and VAS groups (P<0.05). Compared with the offspring rats in the VAN and VAS groups, the offspring rats in the VAD group had significant reductions in the mRNA and protein expression levels of NMDAR1, RARα, and NRXN1 and the LTP level of the visual cortex (P<0.05). The offspring rats in the VAD group had a significant reduction in the enrichment of RARα transcription factor in the promoter region of the NRXN1 gene in the visual cortex compared with those in the VAN and VAS groups (P<0.05). CONCLUSIONS: RARα affects the synaptic plasticity of the visual cortex in VAD rats by regulating NRXN1, thereby participating in the formation of autistic-like behaviors in VAD rats.
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Transtorno Autístico , Córtex Visual , Deficiência de Vitamina A , Animais , Feminino , Gravidez , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato , Receptor alfa de Ácido Retinoico , Vitamina ARESUMO
OBJECTIVE: To study the association of serum levels of trace elements with core symptoms in children with autism spectrum disorder (ASD). METHODS: From September 2018 to September 2019, an investigation was performed for 1 020 children with ASD and 1 038 healthy children matched for age and sex in the outpatient service of grade A tertiary hospitals and special education institutions in 13 cities of China. Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and Childhood Autism Rating Scale (CARS) were used to assess the core symptoms of the children with ASD. The inductively coupled plasma mass spectrometry was used to measure serum levels of trace elements magnesium, iron, copper, and zinc. RESULTS: The children with ASD had significantly lower serum levels of magnesium, copper, and zinc than the healthy children (P < 0.05). The children with severe ASD had significantly lower serum levels of magnesium and zinc than those with mild-to-moderate ASD (P < 0.05). The results of partial correlation analysis showed that serum magnesium level was negatively correlated with the total score of ABC and the score of communication (r=-0.318 and -0.282 respectively; P 0.001), and serum zinc level was negatively correlated with the total score of ABC and the scores of communication and somatic movement (r=-0.221, -0.270, and -0.207 respectively; P < 0.001). CONCLUSIONS: The serum levels of magnesium and zinc may be associated with core symptoms in children with ASD, which requires further studies. The nutritional status of trace elements should be monitored for children with ASD in clinical practice.
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Transtorno do Espectro Autista , Oligoelementos , Criança , China , Cobre/análise , Humanos , Oligoelementos/análise , ZincoRESUMO
The production and usage of non-polybrominated diphenyl ether (PBDE) halogenated flame retardants (HFRs) have substantially increased after the ban of several PBDEs. This has resulted in widespread environmental occurrence of non-PBDE HFRs, further amplified by emissions from primitive recycling of obsolete electronics (e-waste). The present study conducted chamber experiments to characterize 15 HFRs (∑15HFR) from thermal treatment and open burning of typical e-waste. Emission factors of ∑15HFR from thermal treatment were 2.6 × 104-3.9 × 105 ng g-1, slightly higher than those from open burning (8.8 × 103-1.0 × 105 ng g-1). Greater output over input mass ratios of ∑15HFR were obtained in thermal treatment than in open burning. Particulate and gaseous HFRs dominated the emissions in thermal treatment and open burning, respectively, largely because of the different temperatures used in the two processes. Particulate HFRs were primarily affiliated with fine particles (Dp < 1.8 µm) peaking at 0.56-1.0 or 0.32-0.56 µm in both thermal treatment and open burning. Occupational exposure to most FRs was relatively low, but several PBDEs may pose potential health risk to workers in e-waste home-workshops. Potentially accruing emissions and health risks of non-PBDE HFRs from primitive recycling of e-waste remain a great concern.
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Resíduo Eletrônico , Retardadores de Chama , Exposição Ocupacional , China , Monitoramento Ambiental , Éteres Difenil Halogenados , Humanos , ReciclagemRESUMO
Primitive processing of e-waste potentially releases abundant organic contaminants to the environment, but the magnitudes and mechanisms remain to be adequately addressed. We conducted thermal treatment and open burning of typical e-wastes, that is, plastics and printed circuit boards. Emission factors of the sum of 39 polybrominated diphenyl ethers (∑39PBDE) were 817-1.60 × 105 ng g-1 in thermal treatment and nondetected-9.14 × 104 ng g-1, in open burning. Airborne particles (87%) were the main carriers of PBDEs, followed by residual ashes (13%) and gaseous constituents (0.3%), in thermal treatment, while they were 30%, 43% and 27% in open burning. The output-input mass ratios of ∑39PBDE were 0.12-3.76 in thermal treatment and 0-0.16 in open burning. All PBDEs were largely affiliated with fine particles, with geometric mean diameters at 0.61-0.83 µm in thermal degradation and 0.57-1.16 µm in open burning from plastic casings, and 0.44-0.56 and nondetected- 0.55 µm, from printed circuit boards. Evaporation and reabsorption may be the main emission mechanisms for lightly brominated BDEs, but heavily brominated BDEs tend to affiliate with particles from heating or combustion. The different size distributions of particulate PBDEs in emission sources and adjacent air implicated a noteworthy redisposition process during atmospheric dispersal.
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Resíduo Eletrônico , Éteres Difenil Halogenados , China , Poeira , Monitoramento Ambiental , PlásticosRESUMO
The biological function of interleukin-10 (IL-10) and the relationship between IL-10 secretion and the Toll-like receptor 2 (TLR2) expression levels in the central nervous system following hypoxic-ischemic brain damage (HIBD) are poorly understood. Here, we intend to elucidate the biological function and mechanism of IL-10 secretion following HIBD. In this study, we used a neonatal rat model of HIBD and found that rats injected with adeno-associated virus-IL-10-shRNA (short hairpin RNA) exhibited partially impaired learning and memory function compared to rats administered adeno-associated virus-control-shRNA. In vitro oxygen-glucose deprivation (OGD) induced IL-10 release from astrocytes but not from neurons. Pretreatment with exogenous recombinant IL-10 alleviated OGD-mediated apoptosis of neurons but not astrocytes. In addition, we also observed that hypoxic injury induced a marked increase in IL-10 expression in astrocytes as a result of activation of the TLR2/phosphorylated nuclear factor kappa B (p-NFκB) p65 signaling cascade; furthermore, this effect disappeared upon small interfering RNA targeting rat TLR2 gene (siTLR2) treatment. Pyrrolidinedithiocarbamate, an inhibitor of NFκB activation, reduced the IL-10 expression levels in both OGD-injured astrocytes in vitro and the hippocampi of HIBD rats in vivo but did not significantly affect TLR2 expression. Furthermore, a luciferase assay revealed that p-NFκB p65 could bind the -1700/-1000 bp proximal region of the IL-10 gene promoter to regulate IL-10 secretion from astrocytes and that this interaction could be controlled by OGD treatment. These data suggest that HIBD induces IL-10 secretion from astrocytes to exert a paracrine-induced anti-apoptotic effect on injured neurons via the TLR2/NFκB signaling pathway, which may improve learning and memory dysfunction after ischemic injury.
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BACKGROUND: Dysbiosis of gut microbiota are commonly reported in autism spectrum disorder (ASD) and may contribute to behavioral impairment. Vitamin A (VA) plays a role in regulation of gut microbiota. This study was performed to investigate the role of VA in the changes of gut microbiota and changes of autism functions in children with ASD. RESULTS: Sixty four, aged 1 to 8 years old children with ASD completed a 6-month follow-up study with VA intervention. High-performance liquid chromatography was used to assess plasma retinol levels. The Autism Behaviour Checklist (ABC), Childhood Autism Rating Scale (CARS) and Social Responsiveness Scale (SRS) were used to assess autism symptoms. CD38 and acid-related orphan receptor alpha (RORA) mRNA levels were used to assess autism-related biochemical indicators' changes. Evaluations of plasma retinol, ABC, CARS, SRS, CD38 and RORA mRNA levels were performed before and after 6 months of intervention in the 64 children. Illumina MiSeq for 16S rRNA genes was used to compare the differences in gut microbiota before and after 6 months of treatment in the subset 20 of the 64 children. After 6 months of intervention, plasma retinol, CD38 and RORA mRNA levels significantly increased (all P < 0.05); the scores of ABC, CARS and SRS scales showed no significant differences (all P > 0.05) in the 64 children. Meanwhile, the proportion of Bacteroidetes/Bacteroidales significantly increased and the proportion of Bifidobacterium significantly decreased in the subgroup of 20 (all false discovery rate (FDR) q < 0.05). CONCLUSIONS: Bacteroidetes/Bacteroidales were the key taxa related to VA. Moreover, VA played a role in the changes in autism biomarkers. It remains unclear whether the VA concentration is associated with autism symptoms. TRIAL REGISTRATION: The study protocol was peer reviewed and approved by the institutional review board of Children's Hospital, Chongqing Medical University in 2013 and retrospectively registered in Chinese Clinical Trial Registry (ChiCTR) on November 6, 2014 (TRN: ChiCTR-ROC-14005442 ).
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Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/tratamento farmacológico , Suplementos Nutricionais , Microbioma Gastrointestinal/efeitos dos fármacos , Vitamina A/farmacologia , ADP-Ribosil Ciclase 1/sangue , Transtorno do Espectro Autista/sangue , Transtorno do Espectro Autista/psicologia , Biomarcadores/sangue , Criança , Comportamento Infantil/efeitos dos fármacos , Pré-Escolar , DNA Bacteriano/análise , Fezes/microbiologia , Feminino , Seguimentos , Microbioma Gastrointestinal/genética , Humanos , Lactente , Masculino , Ensaios Clínicos Controlados não Aleatórios como Assunto , Projetos Piloto , RNA Mensageiro/sangue , RNA Ribossômico 16S/genética , Método Simples-Cego , Vitamina A/sangueRESUMO
OBJECTIVE: To study the relationship between dietary vitamin A intake and plasma vitamin A concentration, and establish the theoretical basis for dietary intake predicting vitamin A nutritional status. METHODS: By using cluster sampling, 492 children aged 2-7 years in kindergartens in Banan district of Chongqing were selected. A cross-sectional nutrition and health survey was conducted, including the clinical examination, anthropometry, laboratory test and dietary survey. RESULTS: Among the children surveyed, 229 were boys, and 263 girls, the mean age was (4.54 ± 0.87) years, height (107.50 ± 7.20) cm, and weight (18.42 ± 3.41) kg, the mean value of plasma vitamin A was (1.04 ± 0.30) µmol/L. The prevalence of marginal vitamin A deficiency (MVAD) was 43.5%. No cases of severe clinical vitamin A deficiency were found (plasma vitamin A ≤ 0.35 µmol/L). Clinical examination found no conjunctiva, corneaor skin abnormalities, and no Bitot's spots. Prevalence of the last two weeks colds were 27.4% (135/492), no diarrhea and other gastrointestinal or digestive diseases were found. The proportion of insufficient dietary vitamin A intake (<600 µg RE/d) was as high as 50.0%. By using correlation analysis, plasma retinol concentrations were related to dietary vitamin A intake (r=0.162, P<0.001), and to dietary energy intake (r=0.107, P=0.017). After adjustment for the effects of other non-dietary factors on vitamin A deficiency, the multivariate logistic regression showed that vitamin A-rich foods of liver intake=0 g/d (OR=1.95, 95% CI: 1.05-3.61, P=0.034), vitamin A-rich fruits intake=0 g/d (OR=1.55, 95% CI: 1.03-2.33, P=0.034), vitamin A-rich vegetables intake<200 g/d (OR=3.47, 95% CI: 1.37-8.75, P=0.009) were important risk factors of vitamin A deficiency. But we had not found the correlation between the intake of meat, eggs and milk and vitamin A deficiency. CONCLUSION: Dietary factors may be the major risk factor of vitamin A deficiency in the three kindergartens. The dietary vitamin A intakes are significantly related to plasma retinol concentrations, and the vitamin A-rich foods intakes can predict the body's vitamin A nutritional status.
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Dieta , Vitamina A/administração & dosagem , Vitamina A/sangue , Animais , Antropometria , Peso Corporal , Criança , Pré-Escolar , China , Estudos Transversais , Feminino , Frutas , Inquéritos Epidemiológicos , Humanos , Masculino , Leite , Inquéritos Nutricionais , Estado Nutricional , Prevalência , Verduras , Deficiência de Vitamina A/epidemiologiaRESUMO
Alzheimer's disease (AD) is the most common cause of dementia worldwide. Due to its uncertain pathogenesis, there is currently no treatment available for AD. Increasing evidences have linked cellular senescence to AD, although the mechanism triggering cellular senescence in AD requires further exploration. To investigate the involvement of cellular senescence in AD, we explored the effects of cadmium chloride (CdCl2) exposure, one of the potential environmental risk factors for AD, on neuron senescence in vivo and in vitro. ß-amyloid (Aß) and tubulin-associated protein (tau) pathologies were found to be enhanced by CdCl2 exposure in the in vitro models, while p53/p21/Rb cascade-related neuronal senescence pathways were activated. Conversely, the use of melatonin, a cellular senescence inhibitor, or a cadmium ion chelator suppressed CdCl2-induced neuron senescence, along with the Aß and tau pathologies. Mechanistically, CdCl2 exposure activated the suppressor enhancer Lin-12/Notch 1-like (SEL1L)/HMG-CoA reductase degradation 1 (HRD1)-regulated endoplasmic reticulum-associated degradation (ERAD), which enhanced the ubiquitin degradation of sigma-1 receptor (SigmaR1) by specifically recognizing its K142 site, resulting in the activation of the p53/p21/Rb pathway via the induction of Ca2+ dyshomeostasis and mitochondrial dysfunction. In the in vivo models, the administration of the SigmaR1 agonist ANAVEX2-73 rescues neurobehavioral inhibition and alleviates cellular senescence and AD-like pathology in the brain tissue of CdCl2-exposed mice. Consequently, the present study revealed a novel senescence-associated regulatory route for the SEL1L/HRD1/SigmaR1 axis that affects the pathological progression of CdCl2 exposure-associated AD. CdCl2 exposure activated SEL1L/HRD1-mediated ERAD and promoted the ubiquitinated degradation of SigmaR1, activating p53/p21/Rb pathway-regulated neuronal senescence. The results of the present study suggest that SigmaR1 may function as a neuroprotective biomarker of neuronal senescence, and pharmacological activation of SigmaR1 could be a promising intervention strategy for AD therapy.
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Cloreto de Cádmio , Senescência Celular , Degradação Associada com o Retículo Endoplasmático , Neurônios , Receptores sigma , Animais , Senescência Celular/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Cloreto de Cádmio/toxicidade , Receptores sigma/metabolismo , Degradação Associada com o Retículo Endoplasmático/efeitos dos fármacos , Peptídeos beta-Amiloides/metabolismo , Camundongos , Proteínas tau/metabolismo , Masculino , Doença de Alzheimer/metabolismo , Humanos , Melatonina/farmacologia , Camundongos Endogâmicos C57BLRESUMO
Background: Vitamins A and D are essential for the health of pregnant women and infants. Nevertheless, the relationship between umbilical cord blood vitamins A and D levels and the physical growth of exclusively breastfed infants remains uncertain. Objective: This cohort study aims to examine the relationship between cord blood vitamins A and D levels and the physical growth of exclusively breastfed infants aged 0-6 months. Methods: 140 singleton mother-infant pairs were recruited in total. Questionnaires were used to collect maternal and infant information, and liquid chromatography was utilized to quantify the levels of vitamins A and D in the umbilical cord blood. Anthropometric measurements were conducted at birth, at 3 and 6 months of age, and the weight-for-age z-score (WAZ), length-for-age z-score (LAZ), head circumference-for-age z-score (HAZ), and BMI-for-age z-score (BMIZ) were calculated. Univariate and multivariate linear regression models were used for the analysis. Results: The average concentration of vitamins A and D in cord blood was 0.58 ± 0.20 µmol/L and 34.07 ± 13.35 nmol/L, both below the normal range for children. After adjusting for confounding factors, vitamin A levels in cord blood positively correlated with HAZ growth in infants aged 3-6 months (ß= 0.75, P < 0.01) while vitamin D levels negatively correlated with LAZ growth (ß= -0.01, P = 0.01) and positively correlated with BMIZ growth (ß= 0.02, P < 0.01). Conclusion: Higher Vitamin A levels at birth promote HAZ growth in infants aged 3-6 months while higher vitamin D levels at birth promote BMIZ growth in infants aged 3-6 months. Clinical trial registration: https://register.clinicaltrials.gov, identifier NCT04017286.
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Aleitamento Materno , Desenvolvimento Infantil , Sangue Fetal , Vitamina A , Vitamina D , Humanos , Vitamina D/sangue , Lactente , Feminino , Sangue Fetal/química , Sangue Fetal/metabolismo , Recém-Nascido , Masculino , Vitamina A/sangue , Desenvolvimento Infantil/fisiologia , Adulto , Estudos de CoortesRESUMO
BACKGROUND: Autism spectrum disorder (ASD) is a complex group of neurodevelopmental disorders. Research has highlighted a close association between the retinoic acid (RA) signaling pathway and ASD. This study investigates alterations in the vitamin A (VA, retinol) to RA metabolic pathway in children with ASD and speculates on the underlying reasons for these changes. We propose a subtype characterized by downregulated RA signaling in ASD, laying the groundwork for precise diagnosis and treatment research. METHODS: We included 489 children with ASD and 280 typically developing (TD) children. Those with ASD underwent evaluations of core symptoms and neuro-developmental levels, which were conducted by professional developmental behavior physicians using assessment scales. Serum VA and all-trans RA (atRA) levels were determined by high-performance liquid chromatography and ultra-high-performance liquid chromatography-tandem mass spectrometry. The expression levels and concentrations of enzyme molecules such as retinol dehydrogenase 10 were assessed using quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: Children with ASD exhibited reduced serum atRA, accompanied by a downregulation of atRA synthesis enzymes. The reduction in serum atRA levels was linked not only to VA levels but also to the aberrant expression of metabolic enzymes responsible for atRA. Furthermore, the serum atRA levels in children with ASD were more strongly correlated with core symptoms and neurodevelopmental levels than VA levels. CONCLUSION: Children with ASD exhibited a dual regulation of reduced serum atRA levels, influenced by both VA levels and abnormal expression of atRA metabolic enzymes.
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MSCs have been shown to improve functional and pathological outcome in lung fibrosis. However, low in vivo cell engraftment of the transplanted cells limits their overall effectiveness. KGF (also known as FGF-7) is a critical mediator of pulmonary epithelial repair through stimulation of epithelial cell proliferation. However, the role of KGF in MSCs and its therapeutic effects have not been identified. In this study, we investigated the effect of KGF on MSCs and its preventive role in hyperoxia-induced fibrosis in neonatal rats. Neonatal rats exposed to normoxia or hyperoxia were randomly assigned to receive intraperitoneal injections of normal saline (PL), MSCs, or KGF pretreated MSCs on the fourth day of exposure. Our results showed that as compared to PL, while MSCs attenuated lung fibrosis, KGF pretreated MSCs exhibited enhanced preventive effect against lung fibrosis. This effect was partly attributed to enhanced mobilization of MSCs to the fibrotic lungs. In addition, the SHH signaling pathway, which is associated with the differentiation of stem cells was activated by KGF. Our data suggest that MSCs, especially KGF preconditioned MSCs, can attenuate lung fibrosis and KGF may regulate the MSCs behavior by activating SHH pathway.
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Transplante de Células/métodos , Fator 7 de Crescimento de Fibroblastos/metabolismo , Hiperóxia/patologia , Células-Tronco Mesenquimais/citologia , Animais , Diferenciação Celular , Proliferação de Células , Feminino , Fibrose , Citometria de Fluxo , Regulação da Expressão Gênica , Proteínas Hedgehog/metabolismo , Hidroxiprolina/química , Hiperóxia/metabolismo , Pulmão/patologia , Lesão Pulmonar/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais , Células-Tronco/citologia , Regulação para CimaRESUMO
The species of Saussurea sagittifolia Y. S. Chen & S. R. Yi belongs to the family Asteraceae (Cardueae). The complete chloroplast genome of S. sagittifolia was assembled and annotated for the first time in this study. The complete chloroplast genome of S. sagittifolia was 152,535 bp, including a large single-copy (LSC) region of 83,511 bp, a small single-copy (SSC) region of 18,632 bp, and a pair of inverted repeats (IRs) of 25,196 bp. The overall GC content of the chloroplast genome was 37.7%. The chloroplast genome encoded 131 genes, including 87 protein-coding genes, 36 tRNA genes, and eight rRNA genes. Phylogenetic analysis based on complete chloroplast sequences revealed that it related closely to Saussurea medusa.
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Aflatoxin B1 (AFB1) is a common contaminant in many foodstuffs and is considered a public health concern worldwide due to its hepatotoxicity caused by lipid metabolism disorders. However, the molecular mechanism underlying AFB1-induced lipotoxicity-dependent liver injury via regulating cholesterol metabolism remains unclear. We established a cholesterol trafficking disorder-mediated hepatic lipotoxicity model with AFB1 mixture exposure in vitro (HepaRG and HepG2 cells, 1.6 µM for 36 h) and in vivo (C57BL/6 mice, 3 mg kg-1, i.g., every other day for 6 weeks). In vitro, the interaction between lysosomal Niemann-Pick type C1 (NPC1) protein and mitochondrial translocator protein (TSPO) regulated lipotoxicity induced by AFB1 mixture exposure, including lysosomal membrane permeabilization and mitochondria-dependent necroptosis. Moreover, the downregulation of lysosomal Ras-associated protein 7a (Rab7a) enhanced the mammalian target of rapamycin complex 1 (mTORC1)-mediated disorders of cholesterol trafficking from the lysosome to mitochondria. Furthermore, cholesterol trafficking disorder-mediated hepatic lipotoxicity induced by the low-dose level of AFB1 exposure was relieved by genetic or pharmaceutic activation of Rab7a to inhibit mTORC1 in vitro and ex vivo. In vivo, mTORC1 inhibitor (Torin1, 4 mg kg-1, i.p., every other day for 3 weeks) alleviated the cholesterol trafficking disorder-mediated hepatic lipotoxicity via upregulating the molecular machinery of lysosomes and mitochondria contact mediated by NPC1 and TSPO interaction in the low dose of AFB1 exposure. Altogether, our data suggested a novel mechanism that lysosomal Rab7a-mTORC1 signaling determined the cholesterol trafficking regulated by NPC1-TSPO from the lysosome to mitochondria, which promoted hepatic lipotoxicity via lysosomal quality control and mitochondria-dependent necroptosis signaling pathways in chemical mixture exposure.
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Aflatoxina B1 , Fígado , Animais , Camundongos , Aflatoxina B1/metabolismo , Colesterol/metabolismo , Fígado/metabolismo , Lisossomos/metabolismo , Mamíferos/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , proteínas de unión al GTP Rab7/metabolismoRESUMO
BACKGROUND: Autism spectrum disorder (ASD) is a multifactorial, pervasive, neurodevelopmental disorder, of which intestinal symptoms collectively represent one of the most common comorbidities. METHODS: In this study, 1,222 children with ASD and 1,206 typically developing (TD) children aged 2-7 years were enrolled from 13 cities in China. Physical measurement and basic information questionnaires were conducted in ASD and TD children. The Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), and Autism Behavior Checklist (ABC) were used to evaluate the clinical symptoms of children with ASD. The six-item Gastrointestinal Severity Index (6-GSI) was used to evaluate the prevalence of intestinal symptoms in two groups. RESULTS: The detection rates of constipation, stool odor, and total intestinal symptoms in ASD children were significantly higher than those in TD children (40.098% vs. 25.622%, 17.021% vs. 9.287%, and 53.601% vs. 41.294%, respectively). Autistic children presenting with intestinal comorbidity had significantly higher scores on the ABC, SRS, CARS, and multiple subscales than autistic children without intestinal symptoms, suggesting that intestinal comorbidity may exacerbates the core symptoms of ASD children. CONCLUSION: Intestinal dysfunction was significantly more common in autistic than in TD children. This dysfunction may aggravate the core symptoms of children with ASD.
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Vitamin A (VA) is important for postnatal brain development, and VA deficiency (VAD) can cause learning and spatial memory deficits in rats. Most of the biological functions of VA are mediated by retinoic acid (RA). To investigate the mechanisms underlying VA deficits, mother rats were fed elemental diets to achieve blood VA levels classified as normal, deficient or severely deficient. Shuttle box and Morris water maze tests revealed impairments in learning ability and spatial memory, respectively, in adolescent VAD rats (p 30-35). Electrophysiology showed weaker long-term potentiation in VAD rats compared to VA normal rats. Examination of NMDA-induced calcium (Ca(2+) ) excitability revealed decreased excitability in hippocampal slices from VAD rats during postnatal development. Relative to VA normal rats, VAD rats also had decreased NMDA receptor NR1 mRNA and protein expression in later stages of postnatal development (p 10-30), as well as differences in retinoic acid receptor (RARα) mRNA and protein expression. Furthermore, primary hippocampal neurons in culture showed increased neuronal Ca(2+) excitability in response to all-trans-RA or 9-cis-RA, coupled with increases in RARα and NR1 expression similar to those observed in vivo. We also found weaker calcium excitability and lower expression of NR1 mRNA and protein after specific silencing of RARα. Finally, we found that RA signals affected the expression of NR1 do not directly through transcriptional regulation. These data support the new idea that continuous postnatal VAD inhibits RARα expression, which decreases NR1 expression via no direct transcriptional regulation and then inhibits hippocampal neuronal Ca(2+) excitability which affects long-term potentiation, finally producing deficits in active learning and spatial memory in adolescence.
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Cálcio/metabolismo , Cognição/fisiologia , Hipocampo/metabolismo , Neurônios/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Deficiência de Vitamina A/metabolismo , Animais , Feminino , Hipocampo/fisiopatologia , Potenciação de Longa Duração/fisiologia , Aprendizagem em Labirinto/fisiologia , Transtornos da Memória/etiologia , Transtornos da Memória/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Interferência de RNA , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Receptores de N-Metil-D-Aspartato/biossíntese , Receptores do Ácido Retinoico/biossíntese , Receptor alfa de Ácido Retinoico , Comportamento Espacial/fisiologia , Deficiência de Vitamina A/complicações , Deficiência de Vitamina A/fisiopatologiaRESUMO
OBJECTIVE: To explore the associations between sugar-sweetened beverage (SSB) consumption and obesity as well as obesity-related cardiometabolic disorders among children in China. METHODS: A total of 6974 (boys 3558, girls 3412) children aged 6-13 years participated in the study. Each participant's height, weight, waist circumference, fasting glucose, triglycerides, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were measured. The type of beverage consumption was determined using a self-administered questionnaire. RESULTS: SSBs were consumed regularly by 46.1% of the children. The prevalence [adjusted odds ratio (95% confidence internal (CI)] of obesity was 7.6% [as the reference group (ref.)], 10.1% [1.36(1.07, 1.74)], and 11.6% [1.46(1.21, 1.75)], among children who regularly drank milk, other beverages and SSBs, respectively. Regularly drinking SSBs elevated the likelihood of abdominal obesity [adjusted odds ratio (95% CI): 1.36 (1.17, 1.59)]. The prevalence [adjusted odds ratio (95% CI)] of obesity among children who regularly drank sports/caloric beverages, carbonated beverages, sweet tea, and plant protein beverages was 16.8% [2.00(1.31, 3.07)], 12.7% [1.52(1.23, 1.88)], 11.5% [1.52(1.18, 1.95)], and 10.4% [1.41(1.03, 1.94)], respectively, which was higher than that of regular milk drinkers [7.6 % (ref.)]. The prevalence [adjusted odds ratio (95% CI)] of abdominal obesity among children who regularly drank sweet tea, fruit/vegetable juices, and carbonated beverages was 17.7% [1.55(1.26, 1.90)], 16.2% [1.36(1.09, 1.70)], and 15.3% [1.24(1.03, 1.50)], respectively, which was much higher than that of regular milk drinkers [12.8% (ref.)]. CONCLUSIONS: Regular SSB consumption was positively related to obesity and abdominal obesity. This relationship should be investigated further using a longitudinal study design.
Assuntos
Bebidas , Obesidade/epidemiologia , Edulcorantes , Adolescente , Antropometria , Pressão Sanguínea , Criança , China/epidemiologia , Feminino , Humanos , MasculinoRESUMO
Increasing attentions have been paid on widespread contaminations of perfluoroalkyl substances (PFAS). Particularly, simultaneous occurrence of multiple PFAS in the aquatic environments globally has been recognized as a crucial emerging issue. The present study aimed to perform simultaneous removal of multiple PFAS contaminations from groundwater around a fluorochemical facility based upon the technique of periodically reversing electrocoagulation (PREC). Accordingly, the experiments were implemented on the best conditions, actual application, and removal mechanism in the process of PREC with Al-Zn electrodes. Consequently, 1 mg/L synthetic solution of ten PFAS could be eliminated ideally during the initial 10 min, under the optimal conditions involving voltage at 12 V, pH at 7.0, and electrolyte with NaCl. The maximum removal rates of perfluorobutanoic acid (PFBA), perfluorobutane sulfonate (PFBS), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonate (PFOS) were 90.9%, 91.0%, 99.7%, and 100%, respectively. The PREC performed a significant improvement for the wide scope of PFAS removal with the levels ranging from 10 µg/L to 100 mg/L. In addition, the optimized PREC technique was further applied to remove various PFAS contaminations from the natural groundwater samples underneath the fluorochemical facility, subsequently generating the removal efficiencies in the range between 31.3% and 99.9%, showing the observable advantages compared with other removal techniques for the actual application. Finally, the mechanism of PFAS removal was mainly related to enmeshment and synergistic bridging adsorption, together with oxidation degradation that determined by potential formation of short-chain PFAS in the PREC process. As a result, the PREC technique would be a promising technique for the efficient removal of multiple PFAS contaminations simultaneously from natural water bodies.