Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 397
Filtrar
1.
Food Chem ; 409: 135342, 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-36586262

RESUMO

As a common food processing technology, microbial fermentation is becoming increasingly popular to promote the bioactivity of materials. This study aims to enhance rape bee pollen bioactivity through fermentation and trace the potential components associated with its bioactivity. The antioxidant and anti-inflammatory activities of unfermented bee pollen and fermented bee pollen were evaluated, and their correlation with differential metabolites was analyzed. The results indicated that fermentation significantly (p < 0.05) improved the antioxidant (>2.3-fold) and anti-inflammatory (>1.36-fold) activities of bee pollen, and increased the contents of total phenolics and flavonoids by 1.99 and 1.53 folds. Moreover, the correlation analysis results indicated that 15 components, including three phenolamides, one flavonoid aglycone, seven fatty acids, three amino acids and one ketone compound, were positively correlated with bee pollen antioxidant and anti-inflammatory activities. These results suggest that fermentation is a promising approach to increase the bioactivity of bee pollen.


Assuntos
Antioxidantes , Flavonoides , Animais , Abelhas , Antioxidantes/química , Fermentação , Flavonoides/análise , Espectrometria de Massas , Cromatografia Líquida , Cromatografia Líquida de Alta Pressão/métodos , Pólen/química , Anti-Inflamatórios/análise , Metabolômica
2.
ISA Trans ; 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36503618

RESUMO

The analysis of convergence of extended state observers (ESOs) requires the total disturbance to be differentiable. However, this requirement is not satisfied in many control engineering practices. In this paper, we attempt to analyze the convergence of ESOs for nonlinear systems with non-differentiable uncertainties. A decomposition method is first presented to divide the non-differentiable total disturbance into a differentiable signal and a bounded but non-differentiable signal. Based on this decomposition, we give out the convergence of both nonlinear and linear ESOs (NLESO/LESO), low- and high-power ESOs (LPESO/HPESO), and fixed-time ESO (FxESO). We also derive the explicit formulas for the estimation errors of these ESOs. Simulations and experiments demonstrate the correctness of the analysis results.

3.
Acta Pharmacol Sin ; 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36347997

RESUMO

Previous studies have shown mitochondrial dysfunction in various acute kidney injuries and chronic kidney diseases. Lipoic acid exerts potent effects on oxidant stress and modulation of mitochondrial function in damaged organ. In this study we investigated whether alpha lipoamide (ALM), a derivative of lipoic acid, exerted a renal protective effect in a type 2 diabetes mellitus mouse model. 9-week-old db/db mice were treated with ALM (50 mg·kg-1·d-1, i.g) for 8 weeks. We showed that ALM administration did not affect blood glucose levels in db/db mice, but restored renal function and significantly improved fibrosis of kidneys. We demonstrated that ALM administration significantly ameliorated mitochondrial dysfunction and tubulointerstitial fibrotic lesions, along with increased expression of CDX2 and CFTR and decreased expression of ß-catenin and Snail in kidneys of db/db mice. Similar protective effects were observed in rat renal tubular epithelial cell line NRK-52E cultured in high-glucose medium following treatment with ALM (200 µM). The protective mechanisms of ALM in diabetic kidney disease (DKD) were further explored: Autodock Vina software predicted that ALM could activate RXRα protein by forming stable hydrogen bonds. PROMO Database predicted that RXRα could bind the promoter sequences of CDX2 gene. Knockdown of RXRα expression in NRK-52E cells under normal glucose condition suppressed CDX2 expression and promoted phenotypic changes in renal tubular epithelial cells. However, RXRα overexpression increased CDX2 expression which in turn inhibited high glucose-mediated renal tubular epithelial cell injury. Therefore, we reveal the protective effect of ALM on DKD and its possible potential targets: ALM ameliorates mitochondrial dysfunction and regulates the CDX2/CFTR/ß-catenin signaling axis through upregulation and activation of RXRα. Schematic figure illustrating that ALM alleviates diabetic kidney disease by improving mitochondrial function and upregulation and activation of RXRα, which in turn upregulated CDX2 to exert an inhibitory effect on ß-catenin activation and nuclear translocation. RTEC renal tubular epithelial cell. ROS Reactive oxygen species. RXRα Retinoid X receptor-α. Mfn1 Mitofusin 1. Drp1 dynamic-related protein 1. MDA malondialdehyde. 4-HNE 4-hydroxynonenal. T-SOD Total-superoxide dismutase. CDX2 Caudal-type homeobox transcription factor 2. CFTR Cystic fibrosis transmembrane conductance regulator. EMT epithelial mesenchymal transition. α-SMA Alpha-smooth muscle actin. ECM extracellular matrix. DKD diabetic kidney disease. Schematic figure was drawn by Figdraw ( www.figdraw.com ).

4.
Ecotoxicol Environ Saf ; 248: 114271, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36370670

RESUMO

Mercury ion (Hg2+) is a toxic heavy metal ion and Hg2+ is convertible to methylmercury (MeHg) by many aquatic microorganisms, leading to bioaccumulation and biomagnification in aquatic organisms, which can interfere with brain development and function in humans. This study employs a newly developed AIEgen (Aggregation-induced emission fluorogen) to quantify and visualise the process of MeHg bioaccumulation in vivo on the species of water flea Daphnia carinata. Two approaches to MeHg absorption were taken, either by direct incubation in a MeHg solution or by indirect consumption of algae contaminated with MeHg. We analysed the relationship between the ratio of photoluminescence (PL) intensities (I585/I480) and MeHg concentration (CMeHg) and generated a master curve for determining MeHg concentration based on the measurement of PL intensities. Fluorescent image analysis showed the occurrence of MeHg in D. carinata to be mainly in the compound eyes, optic nerve and carapace. This study indicates that MeHg absorption can be quantified and visualised in the body of zooplankton, and the MeHg transfer to zooplankton is more likely through direct exposure than via indirect food intake. The accumulation of MeHg in the eye and the nervous system could be the cause of the high mortality of D. carinata exposed to MeHg in water.


Assuntos
Cladóceros , Mercúrio , Compostos de Metilmercúrio , Poluentes Químicos da Água , Animais , Humanos , Compostos de Metilmercúrio/análise , Daphnia , Bioacumulação , Poluentes Químicos da Água/análise , Mercúrio/análise , Cadeia Alimentar , Monitoramento Ambiental
5.
J Vis Exp ; (188)2022 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-36314830

RESUMO

The intestinal epithelium regenerates every 5-7 days, and is controlled by the intestinal epithelial stem cell (IESC) population located at the bottom of the crypt region. IESCs include active stem cells, which self-renew and differentiate into various epithelial cell types, and quiescent stem cells, which serve as the reserve stem cells in the case of injury. Regeneration of the intestinal epithelium is controlled by the self-renewing and differentiating capabilities of these active IESCs. In addition, the balance of the crypt stem cell population and maintenance of the stem cell niche are essential for intestinal regeneration. Organoid culture is an important and attractive approach to studying proteins, signaling molecules, and environmental cues that regulate stem cell survival and functions. This model is less expensive, less time-consuming, and more manipulatable than animal models. Organoids also mimic the tissue microenvironment, providing in vivo relevance. The present protocol describes the isolation of colonic crypts, embedding these isolated crypt cells into a three-dimensional gel matrix system and culturing crypt cells to form colonic organoids capable of self-organization, proliferation, self-renewal, and differentiation. This model allows one to manipulate the environment-knocking out specific proteins such as claudin-7, activating/deactivating signaling pathways, etc.-to study how these effects influence the functioning of colonic stem cells. Specifically, the role of tight junction protein claudin-7 in colonic stem cell function was examined. Claudin-7 is vital for maintaining intestinal homeostasis and barrier function and integrity. Knockout of claudin-7 in mice induces an inflammatory bowel disease-like phenotype exhibiting intestinal inflammation, epithelial hyperplasia, weight loss, mucosal ulcerations, epithelial cell sloughing, and adenomas. Previously, it was reported that claudin-7 is required for intestinal epithelial stem cell functions in the small intestine. In this protocol, a colonic organoid culture system is established to study the role of claudin-7 in the large intestine.


Assuntos
Colo , Células-Tronco , Camundongos , Animais , Camundongos Knockout , Intestinos , Mucosa Intestinal/metabolismo , Diferenciação Celular/fisiologia , Organoides , Claudinas/metabolismo
6.
Tissue Barriers ; : 2133880, 2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36220768

RESUMO

Tight junctions (TJs) are the most apical components of junctional complexes in epithelial and endothelial cells. Barrier function is one of the major functions of TJ, which restricts the ions and small water-soluble molecules from passing through the paracellular pathway. Adherens junctions (AJs) play an important role in cell-cell adhesion and cell signaling. Gap junctions (GJs) are intercellular channels regulating electrical and metabolic signals between cells. It is well known that TJ integral membrane proteins, such as claudins and occludins, are the molecular building blocks responsible for TJ barrier function. However, recent studies demonstrate that proteins of other junctional complexes can influence and regulate TJ barrier function. Therefore, the crosstalk between different cell junctions represents a common means to modulate cellular activities. In this review, we will discuss the interactions among TJ, AJ, and GJ by focusing on how AJ and GJ proteins regulate TJ barrier function in different biological systems.

7.
BMC Med Genomics ; 15(1): 214, 2022 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-36221081

RESUMO

Left ventricular non-compaction cardiomyopathy (LVNC) is one of the most common inherited cardiovascular diseases. The genetic backgrounds of most LVNC patients are not fully understood. We collected clinical data, family histories, and blood samples and performed genetic analysis using next-generation sequencing (NGS) from a Chinese family of 15 subjects. Clinically LVNC affected subjects showed marked cardiac phenotype heterogeneity. We found that these subjects with LVNC carried a missense heterozygous genetic mutation c.905G>A (p.R302Q) in γ2 subunit of AMP-activated protein kinase (PRKAG2) gene through NGS. Individuals without this mutation showed no symptoms or cardiac structural abnormalities related to LVNC. One subject was the victim of sudden cardiac death. To sum up, PRKAG2 mutation c.905G>A (p.R302Q) caused familial LVNC. Our results described a potentially pathogenic mutation associated with LVNC, which may further extend the spectrum of LVNC phenotypes related to PRKAG2 gene mutations.


Assuntos
Proteínas Quinases Ativadas por AMP , Cardiomiopatias , Proteínas Quinases Ativadas por AMP/genética , Cardiomiopatias/genética , Morte Súbita Cardíaca/etiologia , Humanos , Mutação , Fenótipo
8.
Front Nutr ; 9: 985665, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36185689

RESUMO

Dietary pattern is excellent in reflecting an individual's eating conditions. Longitudinal data on fetal growth can reflect the process of intrauterine growth. We aimed to evaluate the associations between maternal dietary patterns and intrauterine parameters in middle and late pregnancy. The present study was conducted within Jiangsu Birth Cohort (JBC) study. Dietary information was assessed with a food frequency questionnaire (FFQ) in the second and third trimester of gestation. B-ultrasound scans were performed to obtain fetal intrauterine parameters, including head circumference (HC), femur length (FL), abdominal circumference (AC), and estimated fetal weight (EFW). Exploratory factor analysis was used to extract dietary patterns. Multiple linear regression and linear mixed-effects model (LMM) were used to investigate the association between maternal dietary patterns and fetal growth. A total of 1,936 pregnant women were eligible for the study. We observed inverse associations of maternal "Vegetables and fish" and "Snack and less eggs" patterns during mid-pregnancy with fetal HC Z-score, respectively ("Vegetables and fish": ß = -0.09, 95% CI -0.12, -0.06; "Snack and less eggs": ß = -0.05, 95% CI -0.08, -0.02). On the contrary, "Animal internal organs, thallophyte and shellfish" pattern in the second trimester was associated with increased HC Z-scores (ß = 0.04, 95% CI 0.02, 0.06). Consistently, score increase in "Vegetables and fish" pattern in the third trimester was inversely associated with the Z-scores of HC (ß = -0.05, 95% CI -0.09, -0.02), while "Meat and less nuts" pattern was positively correlated with the Z-scores of HC (ß = 0.04, 95% CI 0.02, 0.07). As compared to the fetus whose mothers at the lowest tertile of "Snack and less eggs" pattern in both trimesters, those whose mothers at the highest tertile demonstrated 1.08 fold (RR = 2.10, 95% CI 1.34-3.28) increased risk of small HC for gestational age (GA). No correlation was observed between maternal dietary patterns and other intrauterine parameters. Our results suggested the effects of maternal dietary patterns on fetal growth, particularly HC. These findings highlighted the adverse impact of unhealthy dietary pattern on fetal growth, might provide evidence for strategies to prevent intrauterine dysplasia and dietary guidelines during pregnancy.

9.
Front Pharmacol ; 13: 1015035, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36188580

RESUMO

Sinomenine is a natural compound extracted from the medicinal plant Sinomenium acutum. Its supplementation has been shown to present benefits in a variety of animal models of central nervous system (CNS) disorders, such as cerebral ischemia, intracerebral hemorrhage, traumatic brain injury (TBI), Alzheimer's disease (AD), Parkinson's disease (PD), epilepsy, depression, multiple sclerosis, morphine tolerance, and glioma. Therefore, sinomenine is now considered a potential agent for the prevention and/or treatment of CNS disorders. Mechanistic studies have shown that inhibition of oxidative stress, microglia- or astrocyte-mediated neuroinflammation, and neuronal apoptosis are common mechanisms for the neuroprotective effects of sinomenine. Other mechanisms, including activation of nuclear factor E2-related factor 2 (Nrf2), induction of autophagy in response to inhibition of protein kinase B (Akt)-mammalian target of rapamycin (mTOR), and activation of cyclic adenosine monophosphate-response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF), may also mediate the anti-glioma and neuroprotective effects of sinomenine. Sinomenine treatment has also been shown to enhance dopamine receptor D2 (DRD2)-mediated nuclear translocation of αB-crystallin (CRYAB) in astrocytes, thereby suppressing neuroinflammation via inhibition of Signal Transducer and Activator of Transcription 3 (STAT3). In addition, sinomenine supplementation can suppress N-methyl-D-aspartate (NMDA) receptor-mediated Ca2+ influx and induce γ-aminobutyric acid type A (GABAA) receptor-mediated Cl- influx, each of which contributes to the improvement of morphine dependence and sleep disturbance. In this review, we outline the pharmacological effects and possible mechanisms of sinomenine in CNS disorders to advance the development of sinomenine as a new drug for the treatment of CNS disorders.

10.
Am J Transl Res ; 14(8): 5420-5440, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105024

RESUMO

OBJECTIVES: To analyze the serum and urine metabolites present in type 2 diabetes mellitus (T2DM) patients and T2DM patients with diabetic peripheral neuropathy (DPN) and to select differentially expressed biomarkers for early diagnosis of DPN. METHODS: Serum and urine metabolites from 74 T2DM patients with peripheral neuropathy and 41 without peripheral neuropathy were analyzed using gas chromatograph system with time-of-flight mass spectrometer metabolomics to detect biomarkers of peripheral neuropathy in T2DM. RESULTS: There were increased serum triglycerides, alanine aminotransferase, and decreased C-peptide, and total cholesterol levels in T2DM patients with DPN compared to those without peripheral neuropathy. Metabolomic analysis revealed visible differences in metabolic characteristics between two groups, and overall 53 serum differential metabolites and 56 urine differential metabolites were identified with variable influence on projection (VIP) >1 and P<0.05. To further analyze the correlation between the identified metabolites and DPN, four serum metabolites and six urine metabolites were selected with VIP>2, and fold change (FC) >1, including serum ß-alanine, caproic acid, ß-alanine/L-aspartic acid, and L-arabinose/L-arabitol, and urine gluconic acid, erythritol, galactonic acid, guanidoacetic acid, cytidine, and aminoadipic acid. Furthermore, five serum biomarkers and six urine biomarkers were found to show significant changes (P<0.05, VIP>1, and FC>1) respectively in patients with mild, moderate, and severe DPN. In addition, we found that glyoxylate and dicarboxylate metabolism was a differential metabolic pathway not only between T2DM and DPN, but also among different degrees of DPN. The differential metabolites such as ß-alanine and caproic acid are expected to be biomarkers for DPN patients, and the significant changes in glyoxylate and dicarboxylate metabolism may be related to the pathogenesis of DPN. CONCLUSION: There were serum and urine spectrum metabolomic differences in patients with DPN, which could serve as biomarkers for T2DM and DPN patients.

11.
Environ Res ; 215(Pt 2): 114305, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36096164

RESUMO

Previous epidemiological studies have reported that prenatal exposure to metals might have influence on fetal growth. Most studies assessed the effect of individual metals, while the investigation on the relationship between multiple metal exposure and fetal growth is sparse. The objective of the present study is to assess the joint impact of metal mixtures on fetal growth during pregnancy. A total of 1275 maternal-infant pairs from the Jiangsu Birth Cohort (JBC) Study were included to investigate the effect of maternal metal exposure on fetal biometry measures at 22-24, 30-32, and 34-36 weeks of gestation. Lead (Pb), arsenic (As), cadmium (Cd), mercury (Hg), chromium (Cr), vanadium(V), thallium (Tl) and barium (Ba) were measured by inductively coupled plasma mass spectrometry (ICP-MS) in maternal urine samples collected in the first trimester. We used general linear models and restricted cubic splines to test dose-response relationships between single metals and fetal growth. The weighted quantile sum (WQS) models were then applied to evaluate the overall effect of all these metals. We observed inverse associations of exposure to Pb, V and Cr with estimated fetal weight (EFW) at 34-36 weeks of gestation. Notably, maternal exposure to metal mixtures was significantly associated with reduced EFW at 34-36 weeks of gestation after adjusting for some covariates and confounders (aß -0.05 [95% CI: 0.09, -0.01], P = 0.023), and this association was mainly driven by Cr (30.41%), Pb (23.92%), and Tl (15.60%). These findings indicated that prenatal exposure to metal mixtures might impose adverse effects on fetal growth.


Assuntos
Arsênio , Mercúrio , Efeitos Tardios da Exposição Pré-Natal , Bário/farmacologia , Coorte de Nascimento , Cádmio , China , Cromo , Feminino , Desenvolvimento Fetal , Peso Fetal , Humanos , Chumbo , Exposição Materna , Gravidez , Tálio/farmacologia , Vanádio
13.
Front Pharmacol ; 13: 918177, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910388

RESUMO

Recently, innate immune system stimulants, such as lipopolysaccharide (LPS) and macrophage-colony stimulating factor (M-CSF), were reported to prevent and reverse chronic stress-induced behavioral abnormalities, suggesting that innate immune stimulation could be a potential strategy for the treatment and prevention of mental disorders. Amphotericin B liposome is a clinically available antifungal medication that can stimulate macrophages and microglia. We hypothesize that amphotericin B liposome may be used to prevent and reverse behavioral abnormalities triggered by chronic stress. As expected, our results showed that a single injection of amphotericin B liposome (1 mg/kg) immediately after stress cessation reversed the decrease in time spent in the interaction zone in the social interaction test (SIT) and the increase in immobility time in the tail suspension test (TST) and forced swimming test (FST) in mice caused by chronic social defeat stress (CSDS). In addition, a single injection of amphotericin B liposomes (1 mg/kg) 1 day before stress exposure was found to prevent the CSDS-induced decrease in time spent in the interaction zone in the SIT and the increase in immobility time in the TST and FST in mice. Pretreatment with minocycline to inhibit the innate immune response was able to abolish the reversal effect of post-stress injection of amphotericin B liposomes on CSDS-induced behavioral abnormalities and the prophylactic effect of pre-stress injection of amphotericin B liposomes on CSDS-induced behavioral abnormalities. These results demonstrate that amphotericin B liposomes have both therapeutic and prophylactic effects on chronic stress-induced behavioral abnormalities in mice by mobilizing the innate immune response.

14.
Brain Behav Immun ; 106: 147-160, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35995236

RESUMO

Depressed mice have lower numbers of microglia in the dentate gyrus (DG). Reversal of this decline by a single low dose of lipopolysaccharide (LPS) may have antidepressant effects, but there is little information on the molecular mechanisms underlying this effect. It is known that impairment of brain-derived neurotrophic factor (BDNF) signaling is involved in the development of depression. Here, we used a combination of neutralizing antibodies, mutant mice, and pharmacological approaches to test the role of BDNF-tyrosine kinase receptor B (TrkB) signaling in the DG in the effect of microglial stimulation. Our results suggest that inhibition of BDNF signaling by infusion of an anti-BDNF antibody, the BDNF receptor antagonist K252a, or knock-in of the mutant BDNF Val68Met allele abolished the antidepressant effect of LPS in chronically stressed mice. Increased BDNF synthesis in DG, mediated by extracellular signal-regulated kinase1/2 (ERK1/2) signaling but not protein kinase B (Akt)-mammalian target of rapamycin (mTOR) signaling, was essential for the antidepressant effect of microglial stimulation. These results suggest that increased BDNF synthesis through activation of ERK1/2 caused by a single LPS injection and subsequent TrkB signaling are required for the antidepressant effect of hippocampal microglial stimulation.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Receptor trkB , Animais , Anticorpos Neutralizantes/farmacologia , Antidepressivos/metabolismo , Antidepressivos/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipocampo/metabolismo , Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/farmacologia , Sistema de Sinalização das MAP Quinases , Mamíferos/metabolismo , Camundongos , Microglia/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor trkB/metabolismo , Receptor trkB/farmacologia , Serina-Treonina Quinases TOR/metabolismo
15.
Sci Total Environ ; 849: 157872, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-35940265

RESUMO

Spontaneous preterm birth (SPB) has drawn public attention due to its increasing incidence and adverse effects on fetal growth. Effect of copper (Cu) imbalance in maternal bodies on the risk of SPB remains a subject of debate, and the related mechanisms are still unraveled. Here we applied natural stable copper isotopes to explore the underlying association and mechanism of copper imbalance with SPB using a nested case-control study. We collected maternal sera at the early pregnancy stage and then measured their copper isotopic ratio (65Cu/63Cu, expressed as δ65Cu) as well as physiological and biochemical indexes from women with and without delivering SPB. We found that SPB cases had no significant difference in serum copper level from their controls, but their serum copper was significantly isotopically heavier than the controls (δ65Cu value = 0.15 ± 0.34 ‰ versus -0.15 ± 0.17 ‰, P = 0.0149). Compared with the controls with lower δ65Cu values, the crude odds ratio (OR) associated with SPB risk increased to 4.00 (95 % confidence interval (CI): 1.37-11.70) and the adjusted OR reached up to 11.35 (95 % CI: 1.35-95.60). Furthermore, via the copper isotopic fractionation, we revealed that dietary intake and blood ceruloplasmin may play more important roles than blood lipids and mother-to-child transmission in the copper imbalance associated with SPB. Further studies will be needed to understand the mechanisms of isotope fractionation related to reproductive health.


Assuntos
Nascimento Prematuro , Estudos de Casos e Controles , Ceruloplasmina , Cobre , Feminino , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Isótopos , Gravidez , Nascimento Prematuro/epidemiologia
16.
J Glob Health ; 12: 04041, 2022 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-35861492

RESUMO

Background: Alcoholic cardiomyopathy (ACM) remains a significant public health issue with a growing global burden. The burden of ACM in China and different regions remains poorly understood. Methods: Data on ACM deaths, disability-adjusted life years (DALYs), the corresponding global age-standardized death rate (ASDR), age-standardized DALY rate and estimated annual percentage change (EAPC) were analysed based on age, sex, socio-demographic index (SDI) quintiles, different regions and in China from the Global Burden of Disease (GBD) study 2019. Results: Globally, the death rate and DALYs due to ACM were 71 723 and 2 441 108 in 2019, 33.06% and 38.79% increase from 1990, respectively. The corresponding ASDR and age-standardized DALY rate decreased with EAPC of -1.52 (95% uncertainty interval (UI) = -2.39, -0.65) and -1.12 (95% UI = -2.14, -0.10). The high-middle SDI regions, especially Eastern Europe, showed the highest number of ACM-related deaths and DALYs. The ACM-related deaths and DALYs were 2545 and 87823 in China in 2019, 171.03% and 147.17% increase from 1990, respectively. Unlike the world level, ASDR and age-standardized DALY rate also increased in China. The ACM burden is higher in men, and people with 50 to 69 years old accounted for the most. Conclusions: ACM burden in China and across the world increased substantially from 1990 to 2019. The greatest burden was borne by the high-middle SDI regions, especially by men aged 50-69 years old. Geographically and gender-age tailored strategies were needed to prevent ACM.


Assuntos
Cardiomiopatia Alcoólica , Idoso , Cardiomiopatia Alcoólica/epidemiologia , China/epidemiologia , Carga Global da Doença , Saúde Global , Humanos , Masculino , Pessoa de Meia-Idade , Anos de Vida Ajustados por Qualidade de Vida
17.
Front Endocrinol (Lausanne) ; 13: 884851, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35846339

RESUMO

Objectives: Adequate maternal thyroid hormone availability is crucial for fetal neurodevelopment, but the role of maternal mild hypothyroidism is not clear. We aim to investigate the association of maternal mild hypothyroidism with neurodevelopment in infants at 1 year of age among TPOAb-negative women. Methods: The present study was conducted within the Jiangsu Birth Cohort. A total of 793 mother-infant pairs were eligible for the present study. Maternal thyroid function was assessed by measuring serum thyroid-stimulating hormone, free thyroxine, and thyroid peroxidase antibodies. Neurodevelopment of infants was assessed by using the Bayley Scales of Infant and Toddler Development third edition screening test (Bayley-III screening test). Results: In the multivariate adjusted linear regression analyses, infants of women with subclinical hypothyroidism and isolated hypothyroxinemia were associated with decreased receptive communication scores (ß = -0.68, p = 0.034) and decreased gross motor scores (ß = -0.83, p = 0.008), respectively. Moreover, infants of women with high-normal TSH concentrations (3.0-4.0 mIU/L) and low FT4 concentrations were significantly associated with lower gross motor scores (ß = -1.19, p = 0.032), while no differences were observed in infants when the mothers had a high-normal TSH concentration and normal FT4 levels. Conclusions: Maternal subclinical hypothyroidism is associated with decreased receptive communication scores in infants at 1 year of age. In addition, maternal TSH concentration greater than 4.0 mIU/L and maternal isolated hypothyroxinemia are associated with impaired gross motor ability of infants, especially in infants of women with high-normal TSH concentrations (3.0-4.0 mIU/L).


Assuntos
Hipotireoidismo , Tiroxina , Feminino , Humanos , Hipotireoidismo/complicações , Lactente , Estudos Prospectivos , Testes de Função Tireóidea , Hormônios Tireóideos , Tireotropina
18.
Life Sci ; 305: 120742, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35777584

RESUMO

AIMS: This study aims to investigate whether 3,4-dihydroxyphenylacetic acid (DHAA) can improve gut barrier function by inhibiting the mitogen-activated protein kinase (MAPK) - myosin light-chain kinase (MLCK) signaling pathway in type 2 diabetes (T2D) mice. MAIN METHODS: T2D mice were induced by a high-fat diet combined with streptozotocin. T2D mice were intragastrically administered with DHAA at 75 and 150 mg kg/body weight per day for 4 weeks. Blood glucose, insulin level, oxidative stress and inflammatory cytokines were measured. TJ (tight junction) protein and MAPK-MLCK pathway-related proteins were analyzed by western blot. KEY FINDINGS: DHAA alleviated hyperglycemia and decreased insulin resistance of T2D mice. It also decreased oxidative stress via increased glutathione (GSH) and total superoxide dismutase (T-SOD) activities and reduced containing malondialdehyde (MDA). DHAA exhibited a significant anti-inflammatory effect by decreasing the level of pro-inflammatory cytokines lipopolysaccharide (LPS) and interleukin (IL)-6 and increasing that of anti-inflammatory cytokine IL-10. More importantly, DHAA improved gut barrier function by enhancing tight junction protein expression and inhibiting the MAPK-MLCK signaling pathway. SIGNIFICANCE: DHAA could reduce oxidative stress, decrease inflammatory response, and improve intestinal function in T2D mice, which may help to relieve the symptoms of T2D.


Assuntos
Diabetes Mellitus Tipo 2 , Cadeias Leves de Miosina , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Animais , Anti-Inflamatórios/metabolismo , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Mucosa Intestinal/metabolismo , Camundongos , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Cadeias Leves de Miosina/metabolismo , Quinase de Cadeia Leve de Miosina/metabolismo , Proteínas de Junções Íntimas/metabolismo
19.
Brain Behav Immun ; 105: 44-66, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35781008

RESUMO

Our previous studies had reported that microglia activation one day before stress exposure prevented the behavioral abnormalities induced by chronic stress in adult mice, and a 10-day interval between microglia stimulation and stress exposure can abolish the prophylactic effect of LPS preinjection on the behavioral abnormalities induced by chronic stress, which, however, could be rescued by repeated LPS injection. This suggests that increased stimulation of microglia results in animals developing a strong ability to prevent deleterious stress stimuli. Because microglia in the adolescent brain exhibit flexible immunological plasticity, we hypothesize that a single low-dose LPS injection during adolescence may provide long-lasting protection against behavioral abnormalities induced by chronic stress in adult mice. As expected, our results showed that a single injection of LPS (100 µg/kg) at post-natal day 28 (PND 28) prevented the development of abnormal behaviors and shifted neuroinflammatory responses toward an anti-inflammatory phenotype in adult mice treated with CSDS at their different stages of the age (PND 56, 140, and 252). Moreover, pretreatment with minocycline or PLX3397 to inhibit microglial activation abolished the prophylactic effect of LPS preinjection after PND 28 on behavioral abnormalities and neuroinflammatory responses induced by CSDS in adult mice at their different stages of the age, PND 56, 140, and 252. These results indicate that stimulation of microglia in adolescence may confer long-lasting protection against neuroinflammatory responses and behavioral abnormalities induced by chronic stress in adult mice. This may offer the potential for the development of a "vaccine-like strategy" to prevent mental disorders.


Assuntos
Lipopolissacarídeos , Microglia , Animais , Anti-Inflamatórios/farmacologia , Encéfalo , Humanos , Inflamação/tratamento farmacológico , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Minociclina/farmacologia
20.
Biomark Res ; 10(1): 48, 2022 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-35831872

RESUMO

BACKGROUND: Docetaxel (DTX) is the most widely prescribed first-line chemotherapy for advanced prostate cancer (PCa). Unfortunately, DTX resistance invariably emerges, leading to worse prognosis of PCa. Growing evidence has shown that circRNAs had complex spatiotemporal specificity during the tumor development and oncogenesis. This study was designed to investigate the biological functions and possible molecular mechanisms of circRNAs in DTX resistance of PCa. METHODS: circRNAs in established DTX-resistant DU145 cell line were identified by RNA sequencing. Biological function of circCYP24A1 was verified in vitro and in vivo. The potential role of circCYP24A1 in the development of DTX-resistant PCa was investigated via dual-luciferase reporter assays, RIP assays and RNA pull-down assays. Univariate and multivariate logistic regression analyses was used to predict DTX-chemotherapy response based on patients' clinical and biological information. RESULTS: CircCYP24A1 was identified to be upregulated in DTX-resistant DU145 cells. Upregulated circCYP24A1 was found to suppress the DTX chemosensitivity in vitro and in vivo. Furthermore, we found that circCYP24A1 promoted DTX resistance in PCa via regulating ALDH1A3 expression by sponging miR-1301-3p and activating PI3K/AKT/mTOR signaling pathway. Statistical analyses elucidated that circCYP24A1 was an independent risk factor to predict DTX response (OR = 0.165; 95% CI: 0.038-0.723; P = 0.017). CONCLUSIONS: This study demonstrated that circCYP24A played an essential role in DTX resistance in PCa, suggesting that circCYP24A1 could be a promising biomarker to predict DTX response and a potential therapeutic target in PCa patients resistant to DTX chemotherapy.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...