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1.
J Med Virol ; 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35441419

RESUMO

Viral diarrhea is one of the leading causes of morbidity and mortality in children. This study was conducted to disclose the etiological cause and epidemiological features of viral diarrhea among children in China. From 2009 to 2021, active surveillance was performed on pediatric patients with acute diarrhea and tested for five enteric viruses. Positive detection was determined in 65.56% (3325/5072) patients and an age-specific infection pattern was observed. A significantly higher positive rate was observed in 12-23-month-old children for rotavirus (47.46%) and adenovirus (7.06%), while a significantly higher positive rate was observed for norovirus (37.62%) in 6-11-month-old patients, and for astrovirus (11.60%) and sapovirus (10.79%) in 24-47-month-old patients. A higher positive rate of rotavirus in girls and norovirus in boys was observed only among 6-11 months of patients. We also observed more norovirus among patients from rural areas in the 0-5- and 36-47-month groups and more rotavirus among those from rural areas in the 12-23-month group. Diarrhea severity was greater for rotavirus in the 6-23-month group and norovirus in the 6-11-month group. Coinfections were observed in 29.26% (973/3325) of positive patients, and were most frequently observed between rotavirus and others (89.31%). Our findings could help the prediction, prevention, and potential therapeutic approaches to viral diarrhea in children.

2.
J Agric Food Chem ; 70(11): 3529-3540, 2022 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35212227

RESUMO

The lipid alternation in mitochondria and endoplasmic reticulum (ER) might be indicative of their abnormal morphology and function, which contribute to development of nonalcoholic fatty liver disease (NAFLD). However, the influence of dietary phospholipids (PLs) on the PL composition of the organellar membrane is largely unknown. High-fat/high-fructose (HFHF)-diet-induced NAFLD mice were administrated with different PLs (2%, w/w) with specific fatty acids and headgroups, including eicosapentaenoic acid (EPA)-phosphatidylcholine (PC)/phosphatidylethanolamine (PE)/phosphatidylserine (PS), docosahexaenoic acid (DHA)-PC/PE/PS, egg-PC/PE/PS, and soy-PC/PE/PS. After 8 weeks of feeding, PLs dramatically decreased hepatic lipid accumulation, in which EPA/DHA-PS had the best efficiency. Furthermore, lipidomic analysis revealed that the HFHF diet narrowed the difference in PL composition between mitochondria and ER, significantly reduced the PC/PE ratio, and changed the unsaturation of cardiolipin in mitochondria. Dietary PLs reversed these alterations. Heatmap analysis indicated that dietary PL groups containing the same fatty acids clustered together. Moreover, dietary PLs significantly increased the ratio of PC/PE in both hepatic mitochondria and ER, especially EPA-PE. This study showed that fatty acid composition of PLs might represent greater impact on the PL composition of the organellar membrane than headgroups.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Fosfolipídeos , Animais , Dieta Hiperlipídica/efeitos adversos , Retículo Endoplasmático , Ácidos Graxos , Frutose/efeitos adversos , Lipidômica , Camundongos , Mitocôndrias , Hepatopatia Gordurosa não Alcoólica/etiologia
3.
Mar Drugs ; 20(2)2022 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-35200681

RESUMO

Hypertensive nephropathy is a chronic kidney disease caused by hypertension. Eicosapentaenoic acid (EPA) has been reported to possess an antihypertensive effect, and our previous study suggested that EPA-enriched phospholipid (EPA-PL) had more significant bioactivities compared with traditional EPA. However, the effect of dietary EPA-PL on hypertensive nephropathy has not been studied. The current study was designed to examine the protection of EPA-PL against kidney damage in spontaneously hypertensive rats (SHRs). Treatment with EPA-PL for three weeks significantly reduced blood pressure through regulating the renin-angiotensin system in SHRs. Moreover, dietary EPA-PL distinctly alleviated kidney dysfunction in SHRs, evidenced by reduced plasma creatinine, blood urea nitrogen, and 24 h proteinuria. Histology results revealed that treatment of SHRs with EPA-PL alleviated renal injury and reduced tubulointerstitial fibrosis. Further mechanistic studies indicated that dietary EPA-PL remarkably inhibited the activation of TGF-ß and Smad 3, elevated the phosphorylation level of PI3K/AKT, suppressed the activation of NF-κB, reduced the expression of pro-inflammatory cytokines, including IL-1ß and IL-6, and repressed the oxidative stress and the mitochondria-mediated apoptotic signaling pathway in the kidney. These results indicate that EPA-PL has potential value in the prevention and alleviation of hypertensive nephropathy.


Assuntos
Anti-Hipertensivos/farmacologia , Ácido Eicosapentaenoico/farmacologia , Hipertensão Renal/tratamento farmacológico , Nefrite/tratamento farmacológico , Fosfolipídeos/farmacologia , Animais , Anti-Hipertensivos/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Ácido Eicosapentaenoico/administração & dosagem , Fibrose , Hipertensão Renal/fisiopatologia , Masculino , NF-kappa B/metabolismo , Nefrite/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinase/metabolismo , Fosfolipídeos/administração & dosagem , Ratos , Ratos Endogâmicos SHR , Ratos Sprague-Dawley , Sistema Renina-Angiotensina/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo
4.
Sci Rep ; 12(1): 819, 2022 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-35039555

RESUMO

Fe-based amorphous coatings with outstanding corrosion resistance are promise for marine applications. However, these coatings encounter a great challenge of biofouling in marine environments. Inspired by the unique micro-nano hierarchical structure of shark skin with excellent antifouling properties, in this paper, we construct a bioinspired Fe-based amorphous coating with killing-resisting dual-effect via proper surface modifications, i.e., the modification with micro-patterned nanostructured Cu2O fibers (killing effect), followed by the modification with superhydrophobic surface (resisting effect). As a result, the modified amorphous coating exhibits impressive antifouling properties, achieving 98.6% resistance to Nitzschia closterium f. minutissima, 87% resistance to Bovine serum albumin protein and 99.8% resistance to Pseudomonas aeruginosa, respectively. The remarkable antifouling performance is attributed to a synergistic antifouling mechanism from both resisting effect and killing effect, wherein the superhydrophobic surface provides a barrier to resist protein adsorption, while the patterned nanostructured Cu2O fibers supply Cu+ ions to kill bacterial cells. In addition, the modified amorphous coating also exhibits excellent mechanical robustness, which ensures the durability of the Fe-based amorphous coating in practical services. This work may promote the development of new durable metal-based coatings integrated with anti-fouling and anti-corrosion properties.

6.
Neural Regen Res ; 17(4): 875-880, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34472488

RESUMO

The neutrophil-to-lymphocyte ratio (NLR) is considered a robust prognostic biomarker for predicting patient survival outcomes in many diseases. However, it remains unclear whether it can be used as a biomarker for amyotrophic lateral sclerosis (ALS). To correlate NLR with disease progression and survival in sporadic ALS, 1030 patients with ALS between January 2012 and December 2018 were included in this study. These patients were assigned into three groups according to their NLR values: Group 1 (NLR < 2, n = 544 [52.8%]), Group 2 (NLR = 2-3, n = 314 [30.5%]), and Group 3 (NLR > 3, n = 172 [16.7%]). All patients were followed up until April 2020. Patients in Group 3 had a significantly older onset age, a lower score on the Revised ALS Functional Rating Scale, and rapidly progressing disease conditions. Furthermore, faster disease progression rates were associated with higher NLR values (odds ratio = 1.211, 95% confidence interval [CI]: 1.090-1.346, P < 0.001) after adjusting for other risk factors. Compared with Groups 1 and 2, the survival time in Group 3 was significantly shorter (log-rank P = 0.002). The NLR value was considered an independent parameter for the prediction of survival in ALS patients after normalizing for all other potential parameters (hazard ratio [HR] = 1.079, 95% CI: 1.016-1.146, P = 0.014). The effects on ALS survival remained significant when adjusted for treatment (HR = 1.074, 95% CI: 1.012-1.141, Ptrend = 0.019) or when considering the stratified NLR value (HR = 1.115, 95% CI: 1.009-1.232, Ptrend = 0.033). Thus, the NLR may help to predict the rate of disease progression and survival in patients with sporadic ALS. The study was approved by the Institutional Ethics Committee of West China Hospital of Sichuan University, China (approval No. 2015 (236)) on December 23, 2015.

7.
J Nutr Biochem ; 99: 108843, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34407449

RESUMO

Epigallocatechin-3-gallate (EGCG), the main active ingredient of green tea, exhibits low toxic side effect and versatile bioactivities, and its anti-cancer effect has been extensively studied. Most of the studies used cancer cell lines and xenograft models. However, whether EGCG can prevent tumor onset after cancer-associated mutations occur is still controversial. In the present study, Krt14-cre/ERT-Kras transgenic mice were developed and the expression of K-RasG12D was induced by tamoxifen. Two weeks after induction, the K-Ras mutant mice developed exophytic tumoral lesions on the lips and tongues, with significant activation of Notch signaling pathway. Administration of EGCG effectively delayed the time of appearance, decreased the size and weight of tumoral lesions, relieved heterotypic hyperplasia of tumoral lesions, and prolonged the life of the mice. The Notch signaling pathway was significantly inhibited by EGCG in the tumoral lesions. Furthermore, EGCG significantly induced cell apoptosis and inhibited the proliferation of tongue cancer cells by blocking the activation of Notch signaling pathway. Taken together, these results indicate EGCG as an effective chemotherapeutic agent for tongue cancer by targeting Notch pathway.


Assuntos
Antineoplásicos/administração & dosagem , Catequina/análogos & derivados , Neoplasias Labiais/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Receptores Notch/metabolismo , Neoplasias da Língua/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Camellia sinensis/química , Catequina/administração & dosagem , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Neoplasias Labiais/genética , Neoplasias Labiais/metabolismo , Camundongos , Camundongos Transgênicos , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Receptores Notch/genética , Transdução de Sinais/efeitos dos fármacos , Neoplasias da Língua/genética , Neoplasias da Língua/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Front Genet ; 12: 765833, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34868249

RESUMO

Background: The association between inflammation and neurodegeneration has long been observed in parkinson's disease (PD) and multiple system atrophy (MSA). Previous genome-wide association studies (GWAS) and meta-analyses have identified several risk loci in inflammation-associated genes associated with PD. Objective: To investigate whether polymorphisms in some inflammation-associated genes could modulate the risk of developing PD and MSA in a Southwest Chinese population. Methods: A total of 2,706 Chinese subjects comprising 1340 PD, 483 MSA and 883 healthy controls were recruited in the study. Three polymorphisms (rs2074404 GG/GT/TT, rs17425622 CC/CT/TT, rs34043159 CC/CT/TT) in genes linked to inflammation in all the subjects were genotyped by using the Sequenom iPLEX Assay. Results: The allele G of WNT3 rs2074404 can increase risk on PD (OR: 1.048, 95% CI: 1.182-1.333, p = 0.006), exclusively in the LOPD subgroup (OR: 1.166, 95% CI:1.025-1.327, p = 0.019), but not in EOPD or MSA. And the recessive model analysis also demonstrated an increased PD risk in GG genotype of this locus (OR = 1.331, p = 0.007). However, no significant differences were observed in the genotype distributions and alleles of HLA-DRB5 rs17425622 and IL1R2 rs34043159 between the PD patients and controls, between the MSA patients and controls, or between subgroups of PD or MSA and controls. Conclusion: Our results suggested the allele G of WNT3 rs2074404 have an adverse effect on PD and particularly, on the LOPD subgroup among a Chinese population.

9.
Front Physiol ; 12: 724470, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34483973

RESUMO

Cardiac fibrosis is evident even in the situation without a significant cardiomyocyte loss in diabetic cardiomyopathy and a high glucose (HG) level independently activates the cardiac fibroblasts (CFs) and promotes cell proliferation. Mitochondrial respiration and glycolysis, which are key for cell proliferation and the mitochondria-associated membranes (MAMs), are critically involved in this process. However, the roles and the underlying mechanism of MAMs in the proliferation of HG-induced CFs are largely unknown. The proliferation and apoptosis of CFs responding to HG treatment were evaluated. The MAMs were quantified, and the mitochondrial respiration and cellular glycolytic levels were determined using the Seahorse XF analyzer. The changes of signal transducer and activator of transcription 3 (STAT3) and mitofusin-2 (MFN2) in responding to HG were also determined, the effects of which on cell proliferation, MAMs, and mitochondrial respiration were assessed. The effects of STAT3 on MFN2 transcription was determined by the dual-luciferase reporter assay (DLRA) and chromatin immunoprecipitation (CHIP). HG-induced CFs proliferation increased the glycolytic levels and adenosine triphosphate (ATP) production, while mitochondrial respiration was inhibited. The MAMs and MFN2 expressions were significantly reduced on the HG treatment, and the restoration of MFN2 expression counteracted the effects of HG on cell proliferation, mitochondrial respiration of the MAMs, glycolytic levels, and ATP production. The mitochondrial STAT3 contents were not changed by HG, but the levels of phosphorylated STAT3 and nuclear STAT3 were increased. The inhibition of STAT3 reversed the reduction of MFN2 levels induced by HG. The DLRA and CHIP directly demonstrated the negative regulation of MFN2 by STAT3 at the transcription levels via interacting with the sequences in the MFN2 promoter region locating at about -400 bp counting from the start site of transcription. The present study demonstrated that the HG independently induced CFs proliferation via promoting STAT3 translocation to the nucleus, which switched the mitochondrial respiration to glycolysis to produce ATP by inhibiting MAMs in an MFN2-depression manner.

10.
J Med Genet ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34544842

RESUMO

BACKGROUND: A large number of new causative and risk genes for amyotrophic lateral sclerosis (ALS) have been identified mostly in patients of European ancestry. In contrast, we know relatively little regarding the genetics of ALS in other ethnic populations. This study aims to provide a comprehensive analysis of the genetics of ALS in an unprecedented large cohort of Chinese mainland population and correlate with the clinical features of rare variants carriers. METHODS: A total of 1587 patients, including 64 familial ALS (FALS) and 1523 sporadic ALS (SALS), and 1866 in-house controls were analysed by whole-exome sequencing and/or testing for G4C2 repeats in C9orf72. Forty-one ALS-associated genes were analysed. FINDINGS: 155 patients, including 26 (40.6%) FALS and 129 (8.5%) SALS, carrying rare pathogenic/likely pathogenic (P/LP) variants of ALS causative genes were identified. SOD1 was the most common mutated gene, followed by C9orf72, FUS, NEK1, TARDBP and TBK1. By burden analysis, rare variants in SOD1, FUS and TARDBP contributed to the collective risk for ALS (p<2.5e-6) at the gene level, but at the allelic level TARDBP p.Gly294Val and FUS p.Arg521Cys and p.Arg521His were the most important single variants causing ALS. Clinically, P/LP variants in TARDBP and C9orf72 were associated with poor prognosis, in FUS linked with younger age of onset, and C9orf72 repeats tended to affect cognition. CONCLUSIONS: Our data provide essential information for understanding the genetic and clinical features of ALS in China and for optimal design of genetic testing and evaluation of disease prognosis.

11.
J Parkinsons Dis ; 11(4): 1845-1855, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34250953

RESUMO

BACKGROUND: Genetic studies have indicated that variants in several lysosomal genes are risk factors for idiopathic Parkinson's disease (PD). However, the role of lysosomal genes in PD in Asian populations is largely unknown. OBJECTIVE: This study aimed to analyze rare variants in lysosomal related genes in Chinese population with early-onset and familial PD. METHODS: In total, 1,136 participants, including 536 and 600 patients with sporadic early-onset PD (SEOPD) and familial PD, respectively, underwent whole-exome sequencing to assess the genetic etiology. Rare variants in PD were investigated in 67 candidate lysosomal related genes (LRGs), including 15 lysosomal function-related genes and 52 lysosomal storage disorder genes. RESULTS: Compared with the autosomal dominant PD (ADPD) or SEOPD cohorts, a much higher proportion of patients with multiple rare damaging variants of LRGs were found in the autosomal recessive PD (ARPD) cohort. At a gene level, rare damaging variants in GBA and MAN2B1 were enriched in PD, but in SCARB2, MCOLN1, LYST, VPS16, and VPS13C were much less in patients. At an allele level, GBA p. Leu483Pro was found to increase the risk of PD. Genotype-phenotype correlation showed no significance in the clinical features among patients carrying a discrepant number of rare variants in LRGs. CONCLUSION: Our study suggests rare variants in LRGs might be more important in the pathogenicity of ARPD cases compared with ADPD or SEOPD. We further confirm rare variants in GBA are involve in PD pathogenecity and other genes associated with PD identified in this study should be supported with more evidence.


Assuntos
Lisossomos , Doença de Parkinson , China , Estudos de Coortes , Estudos de Associação Genética , Humanos , Lisossomos/genética , Doença de Parkinson/genética
13.
Huan Jing Ke Xue ; 42(6): 3074-3083, 2021 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-34032108

RESUMO

Roxithromycin (ROX) is widespread in the water environment and has been reported to have ecotoxicological effects on aquatic organisms. To improve our understanding of these effects, we selected Daphnia magna as a test organism to study acute and chronic ROX toxicity on reproduction, growth, and antioxidant systems. The acute ROX toxicity was low, with 48 h-LC50 and 96h-LC50ROX values of 60.26 mg·L-1 and 39.81 mg·L-1, respectively. Furthermore, ROX concentrations of 0.5 µg·L-1 and 50 µg·L-1 significantly increased the frequency of egg laying, total number of eggs, and number of eggs per fetus. In the early exposure stages, ROX altered the sexual maturation time of Daphnia magna, affecting the frequency of egg laying and the number of eggs per fetus to cope with environmental stress. The intrinsic growth rate was also significantly increased by 50 µg·L-1 ROX. In both treatment groups, Daphnia magna had a shorter body length, abnormal heart rate, and inhibited swimming activity. Moreover, 50 µg·L-1 ROX inhibited the activities of POD, CAT, and GSH-Px by approximately 50% and induced MDA by more than 100%, resulting in the accumulation of reactive oxygen species in the body, which could potentially damage the cell membrane. In the 50 µg·L-1 ROX treatment, per 06 was up-regulated, enhancing the immune response of Daphnia magna. In contrast. gst and gst-theta were down-regulated, suggesting that ROX could weaken the detoxification effect of Daphnia magna. jhe, ecra, ecrb, rxr, vg1, vg2, and vit-2 were also down-regulated. ROX affected the secretion of juvenile and thyroid hormones, inhibiting the synthesis of vitellogenin. Finally, ROX also affected the growth and disturbed the population stability of Daphnia magna. This study provides a reference for the effects of ROX on the reproduction and growth of aquatic organisms and their responses at protein and gene levels.


Assuntos
Roxitromicina , Poluentes Químicos da Água , Animais , Daphnia , Oxirredução , Reprodução , Poluentes Químicos da Água/toxicidade
14.
BMC Neurol ; 21(1): 181, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33910524

RESUMO

BACKGROUND: Camptocormia is common in patients with multiple system atrophy (MSA). The current study was aimed at assessing the frequency of camptocormia and its related factors in MSA patients with different disease durations. Also, the impact of camptocormia on disability was evaluated. METHODS: A total of 716 patients were enrolled in the study. They were classified into three groups based on disease duration (≤ 3, 3-5, ≥ 5 years). Specific scales were used to evaluate the motor and non-motor symptoms. Disease severity was assessed using the Unified Multiple System Atrophy Rating Scale (UMSARS). The binary logistic regression model was used to explore the factors related to camptocormia. To analyze the impact of camptocormia on disability in patients with disease duration less than 5 years, propensity score matching (PSM) and stratified Cox regression analysis were used. RESULTS: In the current study, we found that the frequency of camptocormia was 8.9, 19.7 and 19.2% when the disease duration was ≤3, 3-5, ≥ 5 years, respectively. In the disease duration ≤3 years group, we found that MSA-parkinsonian subtype (MSA-P) (OR = 2.043, P = 0.043), higher total UMSARS score (OR = 1.063, P < 0.001), older age of onset (OR = 1.047, P = 0.042), and lower score on the frontal assessment battery (FAB) (OR = 0.899, P = 0.046) were associated with camptocormia. Only greater disease severity was associated with camptocormia in the group of patients with disease duration 3-5 years (OR = 1.494, P = 0.025) and in the group of patients with disease duration ≥5 years (OR = 1.076, P = 0.005). There was no significant impact of camptocormia on disability in patients with a disease duration of < 5 years (HR = 0.687, P = 0.463). CONCLUSION: The frequency of camptocormia increased with prolonged disease duration. Disease severity was related to camptocormia at different stages of the disease. The MSA-P subtype, older age of onset, and lower FAB score were associated with camptocormia in the early stage of the disease.


Assuntos
Atrofia de Múltiplos Sistemas/complicações , Atrofia Muscular Espinal/etiologia , Curvaturas da Coluna Vertebral/etiologia , Idade de Início , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atrofia Muscular Espinal/epidemiologia , Fatores de Risco , Índice de Gravidade de Doença , Curvaturas da Coluna Vertebral/epidemiologia
15.
Mol Neurobiol ; 58(7): 3435-3442, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33723766

RESUMO

Functional and genetic studies have identified association between several Zinc finger (ZNF) proteins and Parkinson's disease (PD). However, most of them were still awaiting further replications, especially in the Asian population. Here, we systematically selected PD-relevant ZNF genes and analyzed the genetic associations between these ZNFs and PD in a large Chinese PD cohort. We identified rare variants (minor allele frequency < 0.01) in 743 unrelated patients with early-onset PD (EOPD, age at onset < 50 years) using whole exome sequencing and evaluated the association between rare variants and EOPD at both allele and gene levels. Totally 91 rare variants were identified in ZNF746, ZNF646, ZNF184, ZNF165, ZND219, and GLIS1. One variant p.R373H in ZNF219 and two variants p.G161D and p.R158H in ZNF746 were significantly associated with EOPD, and gene-based burden analysis showed enrichment of rare variants of ZNF746 in EOPD. Our findings build up the connection between ZNF746 and PD from a genetic perspective for the first time, supplement current understanding for the genetic role of ZNFs in EOPD, and broaden the mutation spectrum in PD.


Assuntos
/genética , Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença/genética , Testes Genéticos/métodos , Doença de Parkinson/genética , Proteínas Repressoras/genética , Adulto , Idade de Início , China/epidemiologia , Estudos de Coortes , Feminino , Predisposição Genética para Doença/epidemiologia , Variação Genética/genética , Humanos , Masculino , Doença de Parkinson/diagnóstico , Doença de Parkinson/epidemiologia
16.
J Nutr Biochem ; 89: 108578, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33388352

RESUMO

The maternal nutritional status during pregnancy and lactation was closely related to the growth and development of the fetus and infants, which had a profound impact on the health of the offspring. N-3 polyunsaturated fatty acid (PUFA) had been proved to have beneficial effects on glucolipid metabolism. However, the effects of dietary different n-3 PUFA levels for mother during pregnancy and lactation on susceptibility to high-fat-diet-induced metabolic syndrome for offspring in adulthood are still unclear. The maternal mice were fed with control, n-3 PUFA-deficient or fish oil-contained n-3 PUFA-rich diets during pregnancy and lactation, and the weaned offspring were fed with high-fat or low-fat diet for 13 weeks, then were subjected to oral glucose tolerance tests. The results showed that dietary n-3 PUFA-deficiency in early life could aggravate the high-fat-diet-induced glucolipid metabolism disorders, including glucose intolerance, insulin resistance, obesity, and dyslipidemia, thus increased the susceptibility to metabolic syndrome of adult mice. Notably, nutritional supplementation with n-3 PUFA in early life could significantly alleviate the glucose metabolism disorders by increasing insulin sensitivity, inhibiting gluconeogenesis and promoting glycogenesis. In addition, administration with n-3 PUFA in early life remarkably reduced serum and hepatic lipid profiles by mediating the expression of genes related to lipogenesis and ß-oxidation of fatty acids. Dietary n-3 PUFA-deficiency in early life increases the susceptibility to metabolic syndrome of adult offspring, and nutritional supplementation with n-3 PUFA enhances the tolerance to a high-fat diet of adult offspring.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Ácidos Graxos Ômega-3/farmacologia , Fenômenos Fisiológicos da Nutrição Materna , Síndrome Metabólica/prevenção & controle , Animais , Dieta com Restrição de Gorduras , Suplementos Nutricionais , Dislipidemias/etiologia , Dislipidemias/prevenção & controle , Feminino , Óleos de Peixe/farmacologia , Intolerância à Glucose/metabolismo , Teste de Tolerância a Glucose , Resistência à Insulina , Lactação/metabolismo , Metabolismo dos Lipídeos , Lipídeos/sangue , Lipogênese , Fígado/metabolismo , Masculino , Síndrome Metabólica/etiologia , Síndrome Metabólica/patologia , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/prevenção & controle , Gravidez
17.
Neural Regen Res ; 16(8): 1660-1670, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33433498

RESUMO

Patients with Parkinson's disease (PD) have impaired insulin signaling in the brain. Incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), can re-sensitize insulin signaling. In a recent phase II clinical trial, the first GLP-1 mimic, exendin-4, has shown reliable curative effect in patients with PD. DA-CH5 is a novel GLP-1/GIP receptor unimolecular co-agonist with a novel peptide sequence added to cross the blood-brain barrier. Here we showed that both exendin-4 and DA-CH5 protected against 6-hydroxydopamine (6-OHDA) cytotoxicity, inhibited apoptosis, improved mitogenesis and induced autophagy flux in SH-SY5Y cells via activation of the insulin receptor substrate-1 (IRS-1)/alpha serine/threonine-protein kinase (Akt)/cAMP response element-binding protein (CREB) pathway. We also found that DA-CH5 (10 nmol/kg) daily intraperitoneal administration for 30 days post-lesion alleviated motor dysfunction in rats and prevented stereotactic unilateral administration of 6-OHDA induced dopaminergic neurons loss in the substantia nigra pars compacta. However, DA-CH5 showed curative effects in reducing the levels of α-synuclein and the levels of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-1ß). It was also more effective than exendin-4 in inhibiting apoptotic process and protecting mitochondrial functions. In addition, insulin resistance was largely alleviated and the expression of autophagy-related proteins was up-regulated in PD model rats after DA-CH5 treatment. These results in this study indicate DA-CH5 plays a therapeutic role in the 6-OHDA-unilaterally lesioned PD rat model and is superior to GLP-1 analogue exendin-4. The study was approved by the Animal Ethics Committee of Shanxi Medical University of China.

18.
Neural Regen Res ; 16(3): 591-595, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32985493

RESUMO

Creatine kinase is a muscle enzyme that has been reported at various levels in different studies involving patients with amyotrophic lateral sclerosis. In the present retrospective case-control study, we included 582 patients with amyotrophic lateral sclerosis and 582 age- and sex-matched healthy controls. All amyotrophic lateral sclerosis participants received treatment in the Department of Neurology, West China Hospital, China, between May 2008 and December 2018. Serum creatine kinase levels in patients with amyotrophic lateral sclerosis were significantly higher than those in healthy controls. Subgroup analysis revealed that serum creatine kinase levels in men were higher than those in women in both amyotrophic lateral sclerosis patients and healthy controls. Compared with patients with bulbar-onset amyotrophic lateral sclerosis, patients with limb-onset amyotrophic lateral sclerosis had higher creatine kinase levels. Spearman's correlation analysis revealed that serum creatine kinase levels were not correlated with body mass index, Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised score, or progression rate. After adjusting for prognostic covariates, higher log creatine kinase values were correlated with higher overall survival in the amyotrophic lateral sclerosis patients. We also investigated the longitudinal changes in serum creatine kinase levels in 81 amyotrophic lateral sclerosis patients; serum creatine kinase levels were decreased at the second blood test, which was sampled at least 6 months after the first blood test. Together, our results suggest that serum creatine kinase levels can be used as an independent factor for predicting the prognosis of amyotrophic lateral sclerosis patients. This study received ethical approval from the Ethics Committee of West China Hospital, China (approval No. 2015(236)) on December 23, 2015.

19.
Mol Neurobiol ; 58(4): 1583-1592, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33219486

RESUMO

Recent genetic studies clearly indicate that variants in several lysosomal genes act as risk factors for idiopathic Parkinson's disease (PD). Variants in the co-activator of glucocerebrosidase gene (GBA) and the four active saposins (Sap A-D) which are encoded by the prosaposin gene (PSAP) are of particular interest; however, their genetic roles in PD are unknown. Whole-exome sequencing and Sanger sequencing were used to assess the genetic etiology of 400 autosomal dominant inherited PD (ADPD) and 300 sporadic PD (SPD) patients. Variants from public databases, including Genome Aggregation Database-East Asian (GnomAD_EAS) and Chinese Millionome Database (CMDB), were used as control groups. Burden analysis based on gene and domains level were performed to investigate the role of rare PSAP variants in PD. Six rare and likely pathogenic variants, located in the Sap A-D domains, were identified and accounted for 0.75% (3/400) of ADPD and 1.33% (4/300) of SPD in the Chinese population. Based on the gene or domain, burden analysis showed that damaging missense variants in SapC had statistical significance on the risk of developing PD. Interestingly, rs4747203, an intronic variant potentially linked to PSAP expression, was associated with reduced risk for PD (p = 8.6e-7 in GnomAD EAS and p = 0.002 in Chinese). Clinically, patients carrying the likely pathogenic variants presented typical PD motor symptoms and responded well to levodopa treatment. Six out of seven patients carrying the likely pathogenic variants of PSAP presented slow disease progression, and none of the patients developed cognitive impairment. Our study expands the spectrum of mutations associated with the risk of developing PD and enhances the understanding of the relationship of the clinical phenotype of PD with PSAP variants.


Assuntos
Predisposição Genética para Doença , Doenças por Armazenamento dos Lisossomos/genética , Doença de Parkinson/genética , Saposinas/genética , Idade de Início , Sequência de Aminoácidos , Sequência de Bases , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Frequência do Gene/genética , Estudos de Associação Genética , Humanos , Masculino , Mutação/genética , Linhagem , Fatores de Risco , Saposinas/química
20.
Front Aging Neurosci ; 13: 767211, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34987378

RESUMO

Background: Few studies have focused on the cold hand sign (CHS), a red flag symptom, in multiple system atrophy (MSA). Objective: This study aimed to investigate the frequency and correlative factors of CHS in patients with MSA and the impact of its early occurrence on the survival of these patients. Methods: A total of 483 patients with MSA were enrolled in this study, and the motor and non-motor symptoms between patients with MSA with and without CHS were compared. Moreover, patients with disease duration ≤ 3 years at baseline were followed, and the association between CHS and survival of patients with MSA was examined. Results: The frequencies of CHS in patients with MSA were 20, 15.4, and 25.3% in MSA, MSA-parkinsonian subtype (MSA-P), and MSA-cerebellar subtype (MSA-C), respectively. Higher Unified Multiple System Atrophy Rating Scale (UMSARS) scores and higher Non-Motor Symptom Scale (NMSS) scores at baseline were associated with CHS in MSA. CHS was associated with shorter survival after adjusting for baseline diagnosis subtype, age at onset, sex, orthostatic hypotension, disease duration, autonomic onset, UMSARS total score, and NMSS score (p = 0.001; HR = 3.701; 95% CI = 1.765-7.760). Conclusion: CHS is not rare in patients with MSA. Greater disease severity and more severe non-motor symptoms were associated with CHS in patients with MSA. Patients with early occurrence of CHS had a poor prognosis.

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