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1.
Nutrients ; 14(9)2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35565956

RESUMO

In this study, changes of carotenoids in breast milk were observed longitudinally for up to one year. Our study aimed to analyze the profile of carotenoids in breast milk and maternal/cord plasma and its correlation with dietary intake in Guangzhou. Plasma and breast milk samples of five stages during lactation (i.e., colostrum; transitional milk; and early, medium, and late mature milk) were collected from lactating mothers. The food frequency questionnaire (FFQ) was used for collecting data on dietary intake in the corresponding stages. Levels of lutein, zeaxanthin, ß-cryptoxanthin, ß-carotene, and lycopene were analyzed by high-performance liquid chromatography. We found that the total carotenoid level decreased gradually with the extension of lactation and eventually stabilized. Among them, the content of lutein increased from colostrum to transitional milk and decreased thereafter until it plateaued in the mature milk. Furthermore, lutein was reported as the dominant nutrient in maternal plasma, cord plasma, transitional milk, and mature milk at up to 400 days postpartum, while beta-carotene was predominant in colostrum. The content of ß-carotenoid in middle and late mature breast milk was related to dietary intake (r = 1.690, p < 0.05). Carotenoid level in cord blood was lower than that in the mother's plasma and was related to the carotenoid intake in the mother's diet. Correlation of carotenoids between maternal and umbilical cord blood, breast milk, and maternal blood could well reflect the transport of carotenoids. These findings may help to guide mothers' diets during breastfeeding.

2.
BMJ Open ; 12(4): e052457, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35365515

RESUMO

OBJECTIVES: This study explored the prevalence of and individual influencing factors for metabolic syndrome (MS) as well as associated socioeconomic factors and regional aggregation. DESIGN: Four cross-sectional surveys were analysed for trends in MS and associations with socioeconomic and individual factors through multilevel logistic regression analyses. The risk associated with nutrient intake was also assessed through a dietary survey in 2015. SETTING: From 2010 to 2018, 8-15 counties/districts of West China were included. PARTICIPANTS: A total of 28 274 adults were included in the prevalence analysis. A total of 23 708 adults were used to analyse the related factors. RESULTS: The overall prevalence of MS ranged from 21.4% to 27.8% over the 8 years, remaining basically stable within the 95% CI. Our study found that the urbanisation rate and hospital beds per 1000 people were positively associated with MS, and the number of doctors in healthcare institutions per 1000 persons was negatively associated with MS. The ORs for females, people with college education and higher and unmarried or single people were 1.49, 0.67 and 0.51, respectively (p<0.05). The ORs of people who smoked at least 20 cigarettes/day, ate more than 100 g of red meat/day, consumed fruit or vegetable juice and drank carbonated soft drinks less than weekly were 1.10, 1.16, 1.19-1.27 and 0.81-0.84, respectively. The ORs rose with increasing sedentary time and decreased with higher physical activity. CONCLUSION: The high burden of MS, unreasonable proportions of energy and micronutrient intake and low percentage of high levels of physical activity were the major challenges to public health in western China. Improving the human resources component of medical services, such as the number of doctors, increasing the availability of public sports facilities and E-health tools and improving individual dietary quality and education might help prevent MS.


Assuntos
Síndrome Metabólica , Adulto , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Síndrome Metabólica/epidemiologia , Prevalência , Fatores Socioeconômicos
3.
J Pharm Biomed Anal ; 214: 114734, 2022 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-35378366

RESUMO

Atherosclerosis (AS) is a progressive disease with a complex pathogenesis which is characterized by dyslipidemia and changes in the vascular wall composition. According to the degree of lesions, atherosclerosis can be divided into four stages: hyperlipidemia, lipid stria, fiber plaque, and atherosclerotic plaque. The present study aimed to establish a prediction model for the different pathological stages of AS based on lipidomics. ApoE-/- mice and C57BL/6 mice fed a normal diet were divided into seven groups according to the feeding time (8, 12, 16, 20, 24, 28, and 32 weeks). The changes in the lipid composition and serum content were detected using ultra-performance liquid chromatography coupled with quadrupole time-of-flight high-definition mass spectrometry (UPLC-Q-TOF/MS). Through the results of serum total cholesterol, triglyceridelow density lipoprotein at each time and HE staining of the head and arm artery, the seven time points of the model group were corresponding to the four courses of atherosclerosis. In accordance with the lipid data of each course of AS and mathematical modeling, this study established a multi-index prediction model of the different processes of AS. Notably, while establishing the model, several indicators were combined with one of four dimension reduction methods, such as principal component logistics regression method, cumulative logistics regression method, Partial least squares-discriminant analysis(PLS-DA), and canonical discriminant analysis (CDA). The error rate of the four methods were 28.5%, 16.22%, 18.24%, and 14.86%, respectively. CDA had the lowest error rate and the best prediction accuracy of the AS different courses for the training and verification sets after 5-fold cross-validation of this model. This study showed that lipidomics combined with mathematical methods could establish a non-invasive and accurate model for the prediction of AS.


Assuntos
Aterosclerose , Lipidômica , Animais , Apolipoproteínas E , Progressão da Doença , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos C57BL
4.
Ecotoxicol Environ Saf ; 237: 113523, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35429799

RESUMO

Bisphenol A (BPA) is of great concern in public health, of which female reproductive toxicity is one major adverse health effect with the unclear mode of action (MOA) yet. Based on the principle of Toxicity Testing in the 21st Century, the purpose of this study is to explore the MOA for female reproductive toxicity using human normal ovarian epithelial cells IOSE80 at 28-day human-relevant-level exposure. A physiological based pharmacokinetic model was used to select the administration concentrations according to the BPA levels in female gonads at human actual exposure scenario. Enrichment KEGG pathways interrupted by BPA consisted of RNA transport, ribosome biogenesis in eukaryotes, cell cycle, cellular senescence, progesterone-mediated oocyte maturation, and oocyte meiosis. Increased relative mRNA and protein expressions of ERK and CDKN3, and proportion of S phase, as well as decreased proportion of G0/G1 phase were observed with increasing BPA concentrations, which could be partially inhibited by ERK inhibitor U0126. Among all the benchmark concentration lower confidence limits, mRNA expression of MAPK3 served as the lowest. In conclusion, the MOA of BPA induced female reproductive toxicity at human-relevant levels may include: key event (KE)1-ERK activation, KE2-increased expression of CDKN3, and KE3-cell cycle arrest. However, more in vivo studies may be needed to complete the MOA.


Assuntos
Benchmarking , Transcriptoma , Compostos Benzidrílicos/toxicidade , Feminino , Humanos , Técnicas In Vitro , Fenóis , RNA Mensageiro/genética
5.
Ecotoxicol Environ Saf ; 237: 113560, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35468439

RESUMO

The aim of our study was to explore the developmental immunotoxicity (DIT) and its potential gender differences of perinatal exposure to 4-nonylphenol (4-NP), which was significant for the risk assessment of 4-NP exposure to fetuses and infants. Wistar pregnant rats were given the National Institution of Health (NIH)- 31 modified feed containing 0, 10, 100 and 500 mg/kg 4-NP from the gestation day (GD) 6 to the postnatal day (PND) 21. At PND21, the offspring rats were randomly selected to detect developmental immunotoxicity related indicators. Results suggested that high-dose 4-NP perinatal exposure caused growth retardation in infancy of male offspring rats, which was not obvious in female offspring rats. Also, 4-NP perinatal exposure induced DIT (mainly manifested as immunosuppression) with potential gender differences, including decreased weight of immune organs, suppressed immune function, decreased ratio of transforming growth factor (TGF)-ß/interleukin (IL)- 17A, increased ratio of T helper (Th) 17/regulatory T (Treg) cells et al. In addition, exploration of the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway showed that JAK-STAT pathway mediated the leftward of Th17/Treg cells balance. Furthermore, the DIT to female offspring rats was more sensitive than to the males, which may be related to the differences of biological processes involved and needed to be further explored.


Assuntos
Fenômenos Biológicos , Janus Quinases , Animais , Feminino , Humanos , Janus Quinases/metabolismo , Masculino , Fenóis , Gravidez , Ratos , Ratos Wistar , Fatores de Transcrição STAT/metabolismo , Fatores Sexuais , Transdução de Sinais
6.
J Diabetes Investig ; 2022 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-35340117

RESUMO

AIMS/INTRODUCTION: Metals play an important role in diabetes mellitus. This cross-sectional study aimed to evaluate the overall, individual and interactive effects of multi-metal exposure on the prevalence of diabetes mellitus, impaired fasting glucose (IFG) rate and fasting blood glucose (FBG) levels. MATERIALS AND METHODS: The FBG levels of a study population from a cadmium (Cd)-polluted area (n = 250) and an unpolluted area (n = 204), and the metal levels, including magnesium, calcium (Ca), iron (Fe), zinc (Zn), arsenic (As), Cd, copper and lead (Pb) in blood and urine were detected. The study population was divided into a normal fasting glucose group, an IFG group and a diabetes mellitus group on the basis of FBG levels. RESULTS: The IFG rate and diabetes mellitus prevalence were negatively associated with blood Cd and urine Zn levels (IFG rate: odds ratio [OR] 0.780, 95% confidence interval [CI] 0.655-0.928; OR 0.622, 95% CI 0.465-0.831. Diabetes mellitus prevalence: OR 0.506, 95% CI 0.288-0.888; OR 0.609, 95% CI 0.395-0.939), the IFG rate was positively associated with urine Fe levels (OR 1.876, 95% CI 1.290-2.778), and diabetes mellitus prevalence was positively associated with urine Pb and blood Fe levels (OR 1.185, 95% CI 1.022-1.376; OR 1.008, 95% CI 1.001-1.014). A linear negative correlation was observed between FBG levels and blood Cd, and non-linear inverted U-shaped associations were found between FBG levels and Zn, Pb and copper in urine. CONCLUSIONS: This research suggests that multi-metal exposure, especially Cd, Fe, Zn, copper and Pb, is linked to diabetes mellitus, and the interactive effects of multiple metals require further exploration.

7.
Neurology ; 98(13): e1374-e1383, 2022 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-35131904

RESUMO

BACKGROUND AND OBJECTIVES: To evaluate the therapeutic potential of targeting highly differentiated T cells in patients with inclusion body myositis (IBM) by establishing high-resolution mapping of killer cell lectin-like receptor subfamily G member 1 (KLRG1+) within the T and natural killer (NK) cell compartments. METHODS: Blood was collected from 51 patients with IBM and 19 healthy age-matched donors. Peripheral blood mononuclear cells were interrogated by flow cytometry using a 12-marker antibody panel. The panel allowed the delineation of naive T cells (Tn), central memory T cells (Tcm), 4 stages of effector memory differentiation T cells (Tem 1-4), and effector memory re-expressing CD45RA T cells (TemRA), as well as total and subpopulations of NK cells based on the differential expression of CD16 and C56. RESULTS: We found that a population of KLRG1+ Tem and TemRA were expanded in both the CD4+ and CD8+ T-cell subpopulations in patients with IBM. KLRG1 expression in CD8+ T cells increased with T-cell differentiation with the lowest levels of expression in Tn and highest in highly differentiated TemRA and CD56+CD8+ T cells. The frequency of KLRG1+ total NK cells and subpopulations did not differ between patients with IBM and healthy donors. IBM disease duration correlated with increased CD8+ T-cell differentiation. DISCUSSION: Our findings reveal that the selective expansion of blood KLRG1+ T cells in patients with IBM is confined to the TemRA and Tem cellular compartments.


Assuntos
Linfócitos T CD8-Positivos , Miosite de Corpos de Inclusão , Humanos , Memória Imunológica , Imunofenotipagem , Células Matadoras Naturais/metabolismo , Leucócitos Mononucleares
8.
J Appl Toxicol ; 2022 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-35128692

RESUMO

The mycotoxin altertoxin I (ATX-I) is one of secondary metabolites produced by Alternaria fungi and is frequently detected as food and feed contaminants. Little is known about the genotoxicity of the ATX-I. In order to evaluate potential genotoxicity and general toxicity of ATX-I, the novel 28-day multiendpoint (Pig-a assay + micronucleus [MN] test + comet assay) genotoxicity platform was applied. Male Sprague-Dawley (SD) rats were randomized to five groups (six rats per group), that is, a positive control group (N-ethyl-N-nitrosourea [ENU], 40 mg/kg.bw/d), two solvent control groups (PBS and corn oil), and two ATX-I-treated groups (low-dose group [1.10 µg/kg.bw/d] and high-dose group [5.51 µg/kg.bw/d]). Treatments were administered by oral gavage to male SD rats for 28 consecutive days. Histopathological damages in the liver, kidney, and spleen were observed, but without significant changes in hematological and serum biochemical parameters. Genotoxic endpoints indicated that ATX-I could cause DNA damage. To summarize, in a relatively low-dose range, ATX-I may not have direct genotoxicity in vivo but could induce liver, kidney, and spleen damage.

9.
Artigo em Inglês | MEDLINE | ID: mdl-35094809

RESUMO

Alternariol monomethyl ether (AME), a typical Alternaria toxin, has often been detected in grains. We have measured the general toxicity and genotoxicity of AME with a 28-day multi-endpoint (Pig-a assay + in vivo micronucleus [MN] test + comet assay) platform. Male Sprague-Dawley rats were administered AME (1.84, 3.67, or 7.35 µg/kg body weight/day), N-Ethyl-N-nitrosourea (40 mg/kg body weight/day), or corn oil by gavage for 28 consecutive days. Another group (AME-high-dose + recovery) was maintained for a further 14 days after the end of the AME administration. Hematology and serum biochemistry results suggested that AME might compromise the immune system. The histopathology results indicated that AME can cause liver (inflammatory cell infiltration, steatosis, and edema), kidney (renal glomerular atrophy), and spleen (white pulp atrophy) damage. The genotoxicity results showed that AME can induce gene mutations, chromosome breakage, and DNA damage, but the effects were diminished after the recovery period. According to point-of-departure analysis (BMDL10), the risk to the population of exposure to AME cannot be ignored and further assessment is needed.


Assuntos
Alternaria , Dano ao DNA , Lactonas/toxicidade , Micotoxinas/toxicidade , Animais , Masculino , Ratos , Ratos Sprague-Dawley
10.
Gastric Cancer ; 25(1): 96-106, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34370147

RESUMO

The tumor suppressor gene phosphatase and tensin homolog (PTEN) in PI3K/Akt/mTOR pathway is essential in inhibiting tumor growth and metastasis. However, whether the mutation of PTEN gene could induce tumorigenesis and impact the treatment of gastric cancer is still unclear. The purpose of the study was to investigate the combined treatment of gastric tumorigenesis using Rapamycin and Fluorouracil (5-Fu) through interfering with the Akt/mTOR pathway in a mouse model with PTEN conditional deletion. Three groups of mice were exposed for 5 days to Rapamycin and 5-Fu separately and together. The gene expression of the Akt/mTOR pathway, the protein expression of caspase-3 and p-Akt, p-S6K and p-4EBP1, and the pathological changes in stomachs were analyzed. Our study demonstrates that the conditional PTEN deletion in the cells of glandular stomach induces hyperplastic gastric tumors in mice. The combined Rapamycin administration with 5-Fu resulted in better outcomes than their separate administration for the treatment of gastric cancer by inhibiting the mTOR signal pathway. Our study indicates that Rapamycin has a synergistic interaction with chemotherapeutic 5-Fu, and demonstrates a potential therapeutic combination treatment on glandular stomach tumor with PTEN functional absence or aberrantly activated Akt/mTOR pathway. It provides important insights into the inhibition of the Akt/mTOR pathway in gastric cancer clinical therapy.


Assuntos
Neoplasias Gástricas , Animais , Linhagem Celular Tumoral , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Humanos , Camundongos , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
11.
J Appl Toxicol ; 42(6): 1044-1056, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34927272

RESUMO

Heavy metals exposure has been associated with liver dysfunction in recent reports, while the hepatoxicity of lead (Pb) and cadmium (Cd) has been well established. However, the combined effects of multi-metal in real-world scenario on liver dysfunction are still unclear. This cross-sectional study examined associations between 10 biomarkers of early liver injury and multiple heavy metals levels. The levels of heavy metals/metalloid (magnesium [Mg], calcium [Ca], iron [Fe], zinc [Zn], arsenic [As], Cd, copper [Cu], and Pb) were measured in blood and urinary sample collected from 725 participants in a Cd-polluted area and an unpolluted area in southwest China. The early liver dysfunction biomarkers included the liver enzymes (ALT, ALP, AST, and GGT), proteins (TP, ALB, and GLO), and bilirubin (TBIL, DBIL, and IBIL). Confounder-adjusted beta coefficients were determined using multiple linear regression model analysis for the group-classified and gender-classified samples. Our results showed that blood Fe, Cd, and Cu levels were found to be positively related to elevated ALT levels and blood Cu was positively associated with AST levels in the Cd-polluted area, while the highest blood Zn quartile in the polluted area and blood Mg quartile in the unpolluted area were associated with lower ALT levels. Our finding implies that industrial pollution results in heavy metals of Cd and Pb exposure and effects of Fe, Cd, Cu, and Pb in the Cd-polluted area may be the main contributors to increase the risk of liver dysfunction while Zn in the Cd-polluted area and Mg in the unpolluted area may be the protective factors.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34299918

RESUMO

Chenopodium ambrosioides L. (C. ambrosioides) has been used as dietary condiments and as traditional medicine in South America. The oil of Chenopodium ambrosioides L. (C. ambrosioides) can be used as a natural antioxidant in food processing. It also has analgesic, sedating, and deworming effects, and can be used along with the whole plant for its medical effects: decongestion, as an insecticide, and to offer menstruation pain relief. This study was conducted to investigate the cytotoxicity and apoptosis effects of an essential oil from C. ambrosioides in vitro. The cytotoxicity evaluation of the essential oil from C. ambrosioides on human normal liver cell line L02 was assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. AO/EB dual fluorescent staining assay and Annexin V-FITC were used for apoptosis analysis. The changes in mitochondrial membrane potential (MMP) were analyzed with 5,5,6,6'-tetrachloro-1,1,3,3,-tetraethyl-imidacarbocyanine iodide (JC-1) dye under a fluorescence microscope. The level of apoptosis related protein expression was quantified by Western blot. The L02 cells were treated with the essential oil from C. ambrosioides at 24, 48, and 72 h, and the IC50 values were 65.45, 58.03, and 35.47 µg/mL, respectively. The AO/EB staining showed that viable apoptotic cells, non-viable apoptotic cells, and non-viable non-apoptotic cells appeared among the L02 cells under the fluorescence microscope. Cell cycle arrest at the S phase and cell apoptosis increased through flow cytometry in the L02 cells treated with the essential oil. MMP decreased in a concentration-dependent manner, as seen through JC-1 staining under the fluorescence microscope. In the L02 cells as shown by Western blot and qPCR, the amount of the apoptosis-related proteins and the mRNA expression levels of cytochrome C, Bax, Caspase-9, and Caspase-3 increased, Bcl-2 decreased, and Caspase-12, which is expressed in the endoplasmic reticulum, showed no obvious changes in protein amount or mRNA expression level. The essential oil form C. ambrosioides had a cytotoxic effect on L02 cells. It could inhibit L02 cell proliferation, arrest the cell cycle at the S phase, and induce L02 cell apoptosis through the endogenous mitochondrial pathway.


Assuntos
Chenopodium ambrosioides , Óleos Voláteis , Apoptose , Linhagem Celular , Estresse do Retículo Endoplasmático , Feminino , Humanos , Fígado , Óleos Voláteis/toxicidade
13.
Obes Facts ; 14(4): 346-356, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34247171

RESUMO

INTRODUCTION: Little attention has been paid to the interacting effect of specific intensities of physical activities (PAs) and sedentary lifestyle, like television watching, and genetic predisposition on body composition indices among Chinese adults. Herein, we aimed to examine whether specific types of PAs and sedentary behaviors (SBs) were associated with body composition indices among Chinese adults and to further explore whether these associations interacted with the genetic predisposition to high BMI. METHODS: Cross-sectional data regarding PAs and time spent on SBs and dietary intake of 3,976 Chinese adults (54.9% women) aged 25-65 years in Southwest China were obtained via questionnaires in 2013-2015. Weight, height, and waist circumference (WC) were measured, and BMI, percentage of body fat (%BF), fat mass index (FMI), and fat-free mass index (FFMI) of the participants were calculated. Genetic risk score (GRS) was calculated on 9 established BMI-associated SNPs among Chinese adults. RESULTS: When the participants were stratified by GRS for BMI, significant associations were only found for adults with high GRS for BMI: moderate-to-vigorous physical activity (MVPA) was negatively associated with WC and %BF and positively related to FFMI. The adjusted positive relationship of time spent watching television with BMI, WC, %BF, and FMI were also just found between adults with high weighted GRS for high BMI: for every 1 h increment in television watching, the BMI, WC, %BF, and FMI of the participants increased by 0.2 kg/m2, 0.9 cm, 0.3%, and 0.1 kg/m2, respectively (p < 0.02). CONCLUSION: MVPA may be a protective factor against obesity, and prolonged television watching may accentuate adiposity. These putative effects may be more pronounced among individuals with a high genetic risk of a high BMI.


Assuntos
Predisposição Genética para Doença , Comportamento Sedentário , Tecido Adiposo , Adulto , Índice de Massa Corporal , China , Estudos Transversais , Exercício Físico , Feminino , Humanos , Masculino
14.
Artigo em Inglês | MEDLINE | ID: mdl-34266625

RESUMO

Deoxynivalenol (DON), zearalenone (ZEN), and fumonisin B1 (FB1), as the main mycotoxins contaminating rice, often coexist in food. Thus, we have measured the genotoxicity of the three rice fungal contaminants, singly and in different combinations, with a 28-day multi-endpoint (Pig-a assay + in vivo micronucleus [MN] test + comet assay) genotoxicity platform. Male Sprague-Dawley rats received the agents orally via gavage for 28 consecutive days, before performing the abovementioned tests. Results indicated that low dose of a single mycotoxin did not show significant genotoxicity. However, some of these mycotoxins in combination induced significant genotoxicity in the peripheral blood and tissues, at sacrifice. In the peripheral blood, the binary combination of DON and FB1 significantly induced MN. In the liver, ZEN might aggravate the DNA-damaging effects of DON and FB1. Therefore, the genotoxicity of sub-chronic exposure to mycotoxins in combination cannot be ignored.


Assuntos
Micotoxinas/toxicidade , Oryza/toxicidade , Animais , Ensaio Cometa/métodos , Dano ao DNA/efeitos dos fármacos , Fumonisinas/toxicidade , Masculino , Ratos , Ratos Sprague-Dawley , Tricotecenos/toxicidade , Zearalenona/toxicidade
15.
J Appl Toxicol ; 41(12): 2042-2054, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34081793

RESUMO

PM2.5 is a well-known air pollutant threatening public health. Studies confirmed that exposure to the particles could impair pulmonary function, cause chronic obstructive pulmonary disease, and increase the incidence of lung cancer. The characteristic of PM2.5 varies across regions. The toxic function of PM2.5 in southwest China remains to be elucidated. This study aimed to investigate lung injury and its mechanisms induced by PM2.5 collected in Chengdu. Rats were administered with PM2.5 by intratracheal instillation for 4 weeks. Biochemical, cell count, and inflammation-related parameters were measured. Lung tissues were obtained for hematoxylin and eosin and Masson's trichrome staining. The expression levels of vascular endothelial growth factor (VEGF), Janus tyrosine protein kinase-2 (JAK-2), and signal transducer and activator of transcription-3 (STAT-3) were detected by immunohistochemistry assays. Meanwhile, A549 cells were treated with the PM2.5. The cell cycle, and apoptosis were measured by flow cytometry. mRNA and protein expressions of JAK-2, STAT-3, p-STAT-3, and VEGFA were detected using qPCR and Western blot analysis respectively. Results of in vivo study showed that PM2.5 induced lung pathological injury, aggravated the accumulation of inflammatory cells, and increased the serum levels of inflammatory factors. In vitro experiments showed that PM2.5 disrupted the cell growth cycle and increased cell apoptosis through the activation of the JAK-2/STAT-3 signaling pathway. Taken together, this study provided convincing experimental evidence that PM2.5 collected in southwest China could induce pulmonary injury as manifested by inflammatory response and lung fibrosis, possibly through the modulation of the JAK-2/STAT-3 signaling pathway.


Assuntos
Poluentes Atmosféricos/toxicidade , Janus Quinase 2/genética , Material Particulado/toxicidade , Fator de Transcrição STAT3/genética , Transdução de Sinais/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/genética , Células A549 , Animais , China , Humanos , Janus Quinase 2/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Fator de Transcrição STAT3/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
16.
Front Immunol ; 12: 618501, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34149684

RESUMO

Macrophage polarization is mainly steered by metabolic reprogramming in the tissue microenvironment, thus leading to distinct outcomes of various diseases. However, the role of lipid metabolism in the regulation of macrophage alternative activation is incompletely understood. Using human THP-1 and mouse bone marrow derived macrophage polarization models, we revealed a pivotal role for arachidonic acid metabolism in determining the phenotype of M2 macrophages. We demonstrated that macrophage M2 polarization was inhibited by arachidonic acid, but inversely facilitated by its derived metabolite prostaglandin E2 (PGE2). Furthermore, PPARγ bridges these two seemingly unrelated processes via modulating oxidative phosphorylation (OXPHOS). Through inhibiting PPARγ, PGE2 enhanced OXPHOS, resulting in the alternative activation of macrophages, which was counterweighted by the activation of PPARγ. This connection between PGE2 biosynthesis and macrophage M2 polarization also existed in human and mouse esophageal squamous cell carcinoma. Our results highlight the critical role of arachidonic acid and metabolic PGE2 as immune regulators in modulating tissue homeostasis and pathological process.


Assuntos
Ácido Araquidônico/metabolismo , Carcinoma de Células Escamosas/imunologia , Dinoprostona/metabolismo , Neoplasias Esofágicas/imunologia , Inflamação/metabolismo , Macrófagos/fisiologia , PPAR gama/metabolismo , Animais , Diferenciação Celular , Homeostase , Humanos , Metabolismo dos Lipídeos , Ativação de Macrófagos , Camundongos , Fosforilação Oxidativa , Transdução de Sinais , Células THP-1 , Células Th2/imunologia
17.
BMC Complement Med Ther ; 21(1): 137, 2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-33964908

RESUMO

BACKGROUND: Natural products, especially those with high contents of phytochemicals, are promising alternative medicines owing to their antitumor properties and few side effects. In this study, the effects of a plant-based medicinal food (PBMF) composed of six medicinal and edible plants, namely, Coix seed, Lentinula edodes, Asparagus officinalis L., Houttuynia cordata, Dandelion, and Grifola frondosa, on gastric cancer and the underlying molecular mechanisms were investigated in vivo. METHODS: A subcutaneous xenograft model of gastric cancer was successfully established in nude mice inoculated with SGC-7901 cells. The tumor-bearing mice were separately underwent with particular diets supplemented with three doses of PBMF (43.22, 86.44, and 172.88 g/kg diet) for 30 days. Tumor volumes were recorded. Histopathological changes in and apoptosis of the xenografts were evaluated by hematoxylin and eosin staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining, respectively. Serum levels of TNF-α, MMP-2, and MMP-9 were detected by enzyme-linked immunosorbent assay. The mRNA expression levels of ß-catenin, GSK-3ß, E-cadherin, N-cadherin, MMP-2/9, Snail, Bax, Bcl-2, Caspase-3/9, and Cyclin D1 were evaluated via real-time quantitative polymerase chain reaction. The protein expression levels of GSK-3ß, E-cadherin, N-cadherin, and Ki-67 were determined by immunohistochemistry staining. RESULTS: PBMF treatment efficiently suppressed neoplastic growth, induced apoptosis, and aggravated necrosis in the xenografts of SGC-7901 cells. PBMF treatment significantly decreased the serum levels of MMP-2 and MMP-9 and significantly increased that of TNF-α. Furthermore, PBMF treatment notably upregulated the mRNA expression levels of GSK-3ß, E-cadherin, Bax, Caspase-3, and Caspase-9 but substantially downregulated those of ß-catenin, N-cadherin, MMP-2, MMP-9, Snail, and Cyclin D1 in tumor tissues. The Bax/Bcl-2 ratio was upregulated at the mRNA level. Moreover, PBMF treatment remarkably increased the protein expression levels of GSK-3ß and E-cadherin but notably reduced those of Ki-67 and N-cadherin in tumor tissues. CONCLUSIONS: The PBMF concocted herein exerts anti-gastric cancer activities via epithelial-mesenchymal transition reversal, apoptosis induction, and proliferation inhibition. The underlying molecular mechanisms likely rely on suppressing the Wnt/ß-catenin signaling pathway.


Assuntos
Transição Epitelial-Mesenquimal/efeitos dos fármacos , Preparações de Plantas/farmacologia , Plantas Medicinais , Neoplasias Gástricas/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Humanos , Masculino , Camundongos , Camundongos Nus
18.
Eur J Med Chem ; 219: 113433, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-33878564

RESUMO

Due to the threat of escalating multi-drug resistant gram-negative bacteria to human health and life, novel antimicrobial agents against gram-negative pathogens are urgently needed. As antimicrobial peptides are not prone to induce bacteria resistance, they are believed to be one kind of promising class of potential antimicrobial agent candidates to combat multi-drug resistant bacteria for long-term use. Jelleine-1, first isolated from the royal jelly of honeybees, is a typical amphiphilic antimicrobial peptide and shows broad antimicrobial spectrum and negligible toxicity. To promote its antimicrobial activity and extend its potential of clinical use against multi-drug resistant gram-negative bacteria, novel analogs of jelleine-1 were designed, synthesized and their antimicrobial functions and toxicity were examined in this study. Our results showed that fine tuning of the cationic charge, polarity, and basicity of the sequence through amino acids substitution at position 3, 5, 7 and maintaining position 1, 4, 6, 8 unchanged could improve the bioactivity of jelleine-1 significantly. Meanwhile, we also found that the substitution of phenylalanine by tryptophan also could improve the antimicrobial activity of jelleine-1. Among all the analogs, analog 15, which is enriched in arginine and leucine, showed the most potent antimicrobial activity against both gram-negative and gram-positive bacteria, especially to multi-drug resistant Pseudomonas aeruginosa in vivo and in vitro. In addition, analog 15 also showed potent inhibition of the formation of multi-drug resistant P. aeruginosa biofilm and negligible toxicity, which was certified by MTT, hemolysis, blood assay, and biochemical analysis.


Assuntos
Peptídeos Catiônicos Antimicrobianos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Oligopeptídeos/química , Sequência de Aminoácidos , Animais , Peptídeos Catiônicos Antimicrobianos/química , Abelhas/metabolismo , Biofilmes/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Ácidos Graxos/metabolismo , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Humanos , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Oligopeptídeos/farmacologia , Oligopeptídeos/uso terapêutico , Permeabilidade/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Sepse/tratamento farmacológico
19.
Ann Nutr Metab ; 77(1): 29-37, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33730729

RESUMO

INTRODUCTION: Although lipid is the major energy source and exerts beneficial effects on infant growth, research on the composition of fatty acid (FA) at the sn-2 position of human milk (HM) in China and abroad is limited. OBJECTIVES: This study aimed to investigate the FA positional distribution in colostrum and mature HM of women living in the inland and coastal areas of China and explore the potential influences of geographical region and lactation stage on the FA profile of Chinese women. METHODS: Colostrum milk (n = 61) and mature milk (n = 56) samples were obtained longitudinally from healthy lactating women in Guangzhou and Chengdu, China. Gas chromatography was used to determine the total and sn-2 FA composition. RESULTS: Significant differences were observed in the FA profile of HM between different regions and lactation stages, with differences in polyunsaturated FA levels being the most pronounced. Nearly 70% of sn-2 FAs were saturated FAs, of which C16:0 accounted for approximately 75%. C8:0, C10:0, C18:0, C20:0, C22:0, and all of the unsaturated FAs were mainly located at the sn-1 and sn-3 positions, while C14:0, C15:0, and C16:0 were mainly at the sn-2 position. The proportion of C12:0 and C17:0 at sn-2 was approximately equivalent to that at the sn-1, 3 positions. CONCLUSIONS: The results indicate the variability in the FA profile of HM between regions and lactation stages. The contents of polyunsaturated FAs and sn-2 FAs, especially palmitic acid, should be paid more attention when optimizing infant formula.


Assuntos
/estatística & dados numéricos , Colostro/química , Ácidos Graxos Insaturados/análise , Ácidos Graxos/análise , Leite Humano/química , China , Feminino , Geografia , Humanos , Lactação , Oceanos e Mares , Gravidez , Adulto Jovem
20.
Br J Nutr ; 126(9): 1281-1287, 2021 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-33413728

RESUMO

Carotenoids are increasingly being implicated to have an important role in brain and eye development. This study aimed to quantify the content and profile of carotenoids in human breast milk, maternal plasma and neonatal umbilical cord plasma in Chengdu, an urban area in Southwest China. In this study, fifty-four healthy mothers were enrolled. Maternal blood, umbilical cord blood, colostrum, transitional milk and mature milk were collected. Concentrations of carotenoids (lutein, zeaxanthin, ß-cryptoxanthin, ß-carotene and lycopene) were analysed by HPLC. We found that carotenoid concentrations decreased from colostrum to mature milk. Hydrocarbon carotenoids with weaker polarity decreased more than the polar carotenoids. Lycopene concentrations dropped by 99 %, ß-carotene by 92 %, ß-cryptoxanthin by 83 %, lutein by 32 % and zeaxanthin by 22 %. Lycopene and ß-carotene accounted for 70 % of the total carotenoids in colostrum, and lutein predominated amongst carotenoids in transitional milk and mature milk (51-55 %). Carotenoid concentrations in maternal plasma were much higher than that in cord plasma. Lutein predominated in cord plasma. The concentrations of all carotenoids in maternal plasma were correlated with those of cord plasma and human milk. These results are consistent with selective transport mechanisms in the mammary gland related to the polarity of carotenoids, and each carotenoid has its own implications, which may have different priorities in the early life development of infants. These findings may help guide dietary recommendations for carotenoid inclusion in infant formulas.


Assuntos
Carotenoides , Sangue Fetal/química , Leite Humano , beta-Criptoxantina , Carotenoides/análise , China , Feminino , Humanos , Recém-Nascido , Estudos Longitudinais , Luteína , Licopeno , Leite Humano/química , Gravidez , Zeaxantinas , beta Caroteno
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