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1.
Am J Reprod Immunol ; 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34599631

RESUMO

Although a number of theories have been suggested, including roles for oxidative stress, an abnormal maternal-fetal interface, and genetic and environmental factors, the etiopathology of PE remains unclear. Maternal immune tolerance is important for maintaining pregnancy, and researchers have increasingly focused on the critical roles of cytokines in the pathogenesis of PE in recent years. The assessment of candidate genetic polymorphisms in PE could partially elucidate the mechanisms of susceptibility to disease, and contribute to seeking for new diagnosis and treatment methods of PE. PE can lead to severe complications, and even the death of both mother and fetus. Although the complex pathology is not yet clear, some evidence suggested that the occurrence of PE is related to inflammatory factors. We reviewed the current understandings of roles of cytokines in pre-eclampsia (PE), and provided an extensive overview of the role of single nucleotide chain polymorphisms (SNPs) in the genes potentially underlying the pathophysiology of PE. This article is protected by copyright. All rights reserved.

2.
J Anim Sci ; 99(10)2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34487146

RESUMO

Constipation in gestating and lactating sows is common and the inclusion of dietary fiber may help to alleviate this problem. We investigated the effects of inulin (INU) and isomalto-oligosaccharide (IMO), two sources of soluble dietary fiber, on gastrointestinal motility-related hormones, short-chain fatty acids (SCFA), fecal microflora, and reproductive performance in pregnant sows. On day 64 of gestation, 30 sows were randomly divided into three groups and fed as follows: a basal diet, a basal diet with 0.5% INU, and a basal diet with 0.5% IMO. We found that INU and IMO significantly modulated the levels of gastrointestinal motility-related hormones, as evidenced by an increase in substance P (P < 0.05), and a decrease in the vasoactive intestinal peptide concentrations (P < 0.05), indicating the capacity of INU and IMO to alleviate constipation. Furthermore, IMO enhanced the concentrations of acetic, propionic, isobutyric, butyric, isovaleric, and valeric acids in the feces (P < 0.05). High-throughput sequencing showed that IMO and INU increased the fecal microflora α- and ß-diversity (P < 0.05). Methanobrevibacter was more abundant (P < 0.05), whereas the richness of Turicibacter was lower in the INU and IMO groups than in the control group (P < 0.05). In addition, IMO significantly increased litter size (P < 0.05). Overall, our findings indicate that INU and IMO can relieve constipation, optimize intestinal flora, and promote reproductive performance in pregnant sows.


Assuntos
Microbioma Gastrointestinal , Inulina , Animais , Constipação Intestinal/tratamento farmacológico , Constipação Intestinal/veterinária , Ácidos Graxos Voláteis , Fezes , Feminino , Hormônios , Inulina/farmacologia , Lactação , Oligossacarídeos/farmacologia , Gravidez , Suínos
3.
Poult Sci ; 100(9): 101358, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34358955

RESUMO

This study investigated the effects of dietary supplementation with Bacillus subtilis (B. subtilis) or Bacillus licheniformis (B. licheniformis) on growth performance, immunity, antioxidant capacity, short chain fatty acid (SCFA) production, and the cecal microflora in broiler chickens. In total, 360 male, 1-day-old Cobb 500 birds were randomly divided into 3 groups: the control group was fed a basal diet; the B. subtilis group was fed a basal diet supplemented with 1.5 × 109 CFU/kg B. subtilis; the B. licheniformis group was fed a basal diet supplemented with 1.5 × 109 CFU/kg B. licheniformis. Results showed that chickens supplemented with either B. subtilis or B. licheniformis had comparatively higher (P < 0.05) body weight and average daily gain, whereas no difference (P > 0.05) was observed in feed efficiency. Concentrations of serum IgA, IgY, and IgM, as well as anti-inflammatory IL-10 were significantly increased (P < 0.05), and proinflammatory IL-1ß and IL-6 were significantly decreased (P < 0.05) by B. subtilis or B. licheniformis supplementation. Moreover, chickens fed with diets supplemented by either B. subtilis or B. licheniformis had greater antioxidant capacity, indicated by the notable increases (P < 0.05) in glutathione peroxidase, superoxide dismutase, and catalase, along with decrease (P < 0.05) in malondialdehyde. Compared to the control group, levels of SCFA, excluding acetic and propionic acid, in cecal content had improved (P < 0.05) by adding B. licheniformis, and significant increase (P < 0.05) in acetic and butyric acid was observed with B. subtilis supplementation. Microbial analysis showed that both B. subtilis or B. licheniformis supplementation could increase butyrate-producing bacteria such as Alistipes and Butyricicoccus, and decrease pathogenic bacteria such as the Synergistetes and Gammaproteobacteria. In summary, dietary supplemented with B. subtilis or B. licheniformis improved growth performance, immune status, and antioxidant capacity, increased SCFA production, and modulated cecal microbiota in chickens. Moreover, B. licheniformis was more effective than B. subtilis with the same supplemental amount.


Assuntos
Bacillus licheniformis , Microbioma Gastrointestinal , Probióticos , Ração Animal/análise , Animais , Antioxidantes , Bacillus subtilis , Galinhas , Dieta/veterinária , Suplementos Nutricionais , Ácidos Graxos Voláteis , Masculino
4.
BMC Pregnancy Childbirth ; 20(1): 759, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33287755

RESUMO

BACKGROUND: Gestational diabetes mellitus (GDM) is a pregnancy-specific carbohydrate intolerance Which can cause a large number of perinatal and postpartum complications. The members of Transforming growth factor-ß (TGF-ß) superfamily play key roles in the homeostasis of pancreatic ß-cell and may involve in the development of GDM. This study aimed to explore the association between the polymorphisms of TGF-ß1, TGF-ß3 and the risk to GDM in Chinese women. METHODS: This study included 919 GDM patients (464 with preeclampsia and 455 without preeclampsia) and 1177 healthy pregnant women. TaqMan allelic discrimination real-Time PCR was used to genotype the TGF-ß1 (rs4803455) and TGF-ß3 (rs2284792 and rs3917201), The Hardy-Weinberg equilibrium (HWE) was evaluated by chi-square test. RESULTS: An increased frequency of TGF-ß3 rs2284792 AA and AG genotype carriers was founded in GDM patients (AA vs. AG + GG: χ2 = 6.314, P = 0.012, OR = 1.270, 95%CI 1.054-1.530; AG vs. GG + AA: χ2 = 8.545, P = 0.003, OR = 0.773, 95%CI 0.650-0.919). But there were no significant differences in the distribution of TGF-ß1 rs4803455 and TGF-ß3 rs3917201 between GDM and healthy women. In addition, no significant differences were found in allele and genotype frequencies among GDM patients with preeclampsia (PE). CONCLUSIONS: The AA and AG genotype of TGF-ß3 rs2284792 polymorphism may be significantly associated with increased risk of GDM in Chinese population.


Assuntos
Diabetes Gestacional/genética , Fator de Crescimento Transformador beta3/genética , Adulto , Estudos de Casos e Controles , China , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Pré-Eclâmpsia/genética , Gravidez , Fator de Crescimento Transformador beta1/genética
5.
J Gene Med ; 22(11): e3272, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32889728

RESUMO

BACKGROUND: The dysferlin gene or the DYSF gene encodes the Ca2+ -dependent phospholipid-binding protein dysferlin, which belongs to the ferlin family and is associated with muscle membrane regeneration and repair. Variants in the DYSF gene are responsible for limb-girdle muscular dystrophy type 2B (LGMD2B), also called limb-girdle muscular dystrophy recessive 2 (LGMDR2), a rare subtype of muscular dystrophy involving progressive muscle weakness and atrophy. The present study aimed to identify the variants responsible for the clinical symptoms of a Chinese patient with limb girdle muscular dystrophies (LGMDs) and to explore the genotype-phenotype associations of LGMD2B. METHODS: A series of clinical examinations, including blood tests, magnetic resonance imaging scans for the lower legs, electromyography and muscle biopsy, was performed on the proband diagnosed with muscular dystrophies. Whole exome sequencing was conducted to detect the causative variants, followed by Sanger sequencing to validate these variants. RESULTS: We identified two compound heterozygous variants in the DYSF gene, c.1058 T>C, p.(Leu353Pro) in exon 12 and c.1461C>A/p.Cys487* in exon 16 in this proband, which were inherited from the father and mother, respectively. In silico analysis for these variants revealed deleterious results by PolyPhen-2 (Polymorphism Phenotyping v2; http://genetics.bwh.harvard.edu/pph2), SIFT (Sorting Intolerant From Tolerant; https://sift.bii.a-star.edu.sg), PROVEAN (Protein Variation Effect Analyzer; http://provean.jcvi.org/seq_submit.php) and MutationTaster (http://www.mutationtaster.org). In addition, the two compound heterozygous variants in the proband were absent in 100 control individuals who had an identical ethnic origin and were from the same region, suggesting that these variants may be the pathogenic variants responsible for the LGMD2B phenotypes for this proband. CONCLUSIONS: The present study broadens our understanding of the mutational spectrum of the DYSF gene, which provides a deep insight into the pathogenesis of LGMDs and accelerates the development of a prenatal diagnosis.

6.
J Biochem Mol Toxicol ; 34(12): e22591, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32711407

RESUMO

The aim of this study was to investigate the protective effect of rosmarinic acid (RA) in a premature ovarian failure (POF) mouse model and the potential mechanisms. The POF model was induced by a single intraperitoneal injection of 120 mg/kg cyclophosphamide (CP). Additionally, 40 mg/kg RA was administered for 7 days before CP injection. The concentration of sex hormones was determined by fluorescence immunohistochemistry. Histological analysis was performed after ovarian tissue sections were stained with hematoxylin and eosin. The expression of the NLRP3 inflammasome was examined by western blot analysis and polymerase chain reaction. The expression of apoptosis markers of cytochrome c and caspase-3 was also detected by western blot analysis and immunohistochemistry. The results showed that RA not only decreased the ovarian index in POF mice but also improved the abnormal secretion of reproductive hormones associated with POF. Treatment with RA suppressed the ovarian expression of the NLRP3 inflammasome and regulated the ovarian expression of apoptosis-related proteins. The results suggested that RA exhibited a protective effect against CP-induced POF potentially by suppressing apoptosis and the NLRP3 inflammasome.

7.
J Virol Methods ; 283: 113917, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32579894

RESUMO

Proteins and nucleic acids from ultrasonically ruptured white spot syndrome virus (WSSV) can infect crayfish and cause death as effectively as intact WSSV virions. In this study, ultrasound was used to rupture the virus and the resulting suspension was filtered through a 50 nm membrane. Analysis by PCR and SDS-PAGE showed that both viral genes (VP19, VP26, VP28 and DNA polymerase) and proteins (VP15, VP19, VP26 and VP28) were present in the filtered solution. Electron microscopy showed that there were no intact virions in the filtered solution. When crayfish were injected with the filtered solution or with intact WSSV, the mortality in each group was 100 %. The same result was seen when crayfish were challenged orally with the filtered solution and intact WSSV. The filtered solution of ultrasonically ruptured virus, which contains viral proteins and residual DNA genome, can thus infect the host as effectively as intact virions. When the solution of viral proteins and residual DNA genome was digested with DNase I and then injected into crayfish, the survival rate was 100 %. We also found that, although viral proteins (except VP15) in the solution of ruptured virus were destroyed by treatment with DNase I, DNase I did not destroy the structural proteins of intact virions. A remaining viral protein in the DNase I-treated solution protects the DNA genome from degradation and we concluded that this protein is VP15, which is a DNA-binding protein. Our study highlights the extreme danger in producing vaccines from proteins obtained by ultrasonic rupture of viruses sincethe viral DNA genome is difficult to degrade and, if present, will lead to viral infection.

8.
Eur J Obstet Gynecol Reprod Biol ; 248: 211-221, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32240894

RESUMO

OBJECTIVE: Pre-eclampsia (PE) is a common multi-systemic disease, and the effect of cytokines on PE is not clear. The purpose of this meta-analysis was to evaluate the circulating levels of interferon gamma (IFN-γ), interleukin (IL)-1, IL-17 and IL-22 in patients with PE. STUDY DESIGN: Relevant studies were identified after a preliminary investigation of studies published up to May 2019 using PubMed and Embase. In this study, all 27 included articles underwent quality rating, with a total of 495 patients with PE and 557 controls. Among them, eight papers and 932 subjects contributed to the meta-analysis of IFN-γ, and six papers and 343 subjects contributed to the meta-analysis of IL-17. Based on the inclusion and exclusion criteria, the retrieved papers were screened and evaluated independently. Relevant data for IFN-γ and IL-17 were extracted for meta-analysis and subgroup analysis, and the stability of the results was evaluated by sensitivity analysis. At the same time, a systematic evaluation was carried out for IL-1 and IL-22 with a small number of included papers. RESULTS: Several papers included in the systematic review showed that the circulating levels of IL-22 were higher in patients with severe PE than in controls, while IL-1 levels did not differ significantly between the two groups. The meta-analysis showed that patients with PE had higher circulating levels of IFN-γ than controls [standardized mean difference (SMD) 1.45, 95 % confidence interval (CI) 0.56-2.34]. There was no evidence of a difference in the circulating levels of IL-17 between patients with PE and controls (SMD 0.53, 95 %CI -0.43 to 1.48). CONCLUSION: This meta-analysis suggested that changes in circulating levels of IFN-γ might be associated with PE.


Assuntos
Interferon gama/sangue , Pré-Eclâmpsia/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Interleucina-1/sangue , Interleucina-17/sangue , Interleucinas/sangue , Pré-Eclâmpsia/diagnóstico , Gravidez , Índice de Gravidade de Doença
9.
Placenta ; 93: 26-33, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32250736

RESUMO

INTRODUCTION: Accumulating evidences have suggested a crucial role of epigenetics in the initiation and progression of pre-eclampsia (PE). Here, we studied the expression of the metalloproteinase ADAMTS7 and the methylation level of its promoter in PE placentas and investigated ADAMTS7 role in the pathogenesis of PE. METHODS: We first explored ADAMTS7 expression in PE and normal placentas by reverse transcription quantitative PCR (RT-qPCR), western blot, and immunohistochemistry. Methylation specific PCR (MSP) and bisulfite sequencing PCR (BSP) were performed to evaluate the methylation status of ADAMTS7 promoter. Treatment with 5'-Aza was used to induce demethylation and thereby to explore the direct relationship between promoter methylation and ADAMTS7 expression. CCK8 assay, colony formation assay, and trans-well assay were conducted to assess the viability, migration, and invasion of HTR-8/SVneo and JEG-3 cells. RESULTS: Our results showed that ADAMTS7 expression was upregulated in PE placentas. Methylation analysis revealed a hypomethylated status of ADAMTS7 promoter regions in PE placenta tissues. Besides, demethylation induced by 5'-Aza directly restored ADAMTS7 expression in trophoblast cells. Finally, overexpression of ADAMTS7 inhibited viability, migration, and invasion of HTR-8/SVneo and JEG-3 cells, while silence of ADAMTS7 by RNA interference reciprocally facilitated cell viability, migration and invasion in vitro. DISCUSSION: Upregulation of ADAMTS7 by promoter hypomethylation in placenta might contribute to the etiology of PE via suppressing cell functions of trophoblasts.


Assuntos
Metilação de DNA , Pré-Eclâmpsia/genética , Regiões Promotoras Genéticas/genética , Trofoblastos/metabolismo , Proteína ADAMTS7/genética , Proteína ADAMTS7/metabolismo , Adulto , Estudos de Casos e Controles , Linhagem Celular , Movimento Celular/genética , Sobrevivência Celular/genética , Células Cultivadas , Metilação de DNA/genética , Epigênese Genética , Feminino , Regulação Enzimológica da Expressão Gênica , Humanos , Placenta/metabolismo , Placenta/patologia , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/patologia , Gravidez , Trofoblastos/patologia , Regulação para Cima/genética
10.
J Anim Physiol Anim Nutr (Berl) ; 104(2): 597-605, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31891214

RESUMO

In this study, we aimed to determine the effects of dietary supplementation with chitosan nanoparticles (CNP) on growth performance, immune status, gut microbiota and immune responses after lipopolysaccharide challenge in weaned pigs. A total of 144 piglets were assigned to four groups receiving different dietary treatments, including basal diets supplemented with 0, 100, 200 and 400 mg/kg CNP fed for 28 days. Each treatment group included six pens (six piglets per pen). The increase in supplemental CNP concentration improved the average daily gain (ADG) and decreased the feed and gain (F/G) and diarrhoea rate (p < .05). However, significant differences in the average daily feed intake (ADFI) among different CNP concentrations were not observed. CNP also increased plasma immunoglobulin (Ig)A and IgG, and C3 and C4 concentrations in piglets in a dose-dependent manner on day 28, whereas IgM concentration was not affected by CNP. A total of 24 piglets in the control diet and control diet with 400 mg/kg CNP supplementation groups were randomly selected for the experiment of immunological stress. Half of the pigs in each group (n = 6) were injected i.p. with Escherichia coli lipopolysaccharide (LPS) at a concentration of 100 µg/kg. The other pigs in each group were injected with sterile saline solution at the same volume. Plasma concentrations of cortisol, prostaglandin E2 (PEG2), interleukin (IL)-6, tumour necrosis factor (TNF)-α and IL-1ß dramatically increased after LPS challenge. However, CNP inhibited the increase in cortisol, PEG2, IL-6 and IL-1ß levels in plasma, whereas TNF-α level slightly increased. Moreover, the effects of CNP on the gut microbiota were also evaluated. Our results showed that dietary supplementation with CNP modified the composition of colonic microbiota, where it increased the amounts of some presumably beneficial intestinal bacteria and suppressed the growth of potential bacterial pathogens. These findings suggested CNP supplementation improved the growth performance and immune status, alleviated immunological stress and regulated intestinal ecology in weaned piglets. Based on these beneficial effects, CNP could be applied as a functional feed additives supplemented in piglets diet.


Assuntos
Quitosana/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Nanopartículas/química , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Quitosana/química , Dieta/veterinária , Suplementos Nutricionais , Hidrocortisona/sangue , Imunidade Humoral , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/veterinária , Suínos
11.
Immunol Invest ; 49(3): 307-316, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31401902

RESUMO

Background: Mutations in CD40 ligand gene (CD40L) affecting immunoglobulin class-switch recombination and somatic hypermutation can result in X-Linked Hyper IgM Syndrome (HIGM1, XHIGM), a kind of rare serious primary immunodeficiency disease (PID) characterized by the deficiency of IgG, IgA and IgE and normal or increased serum concentrations of IgM. The objective of this study is to explain genotype-phenotype correlation and highlight the mutation responsible for a Chinese male patient with XHIGM.Methods: Whole exome sequencing (WES) and Sanger sequencing validation were performed to identify and validate the likely pathogenic mutation in the XHIGM family.Results: The results of the sequencing revealed that a new causative mutation in CD40L (c.714delT in exon 5, p.F238Lfs*4) which leads to the change in amino acids (translation terminates at the third position after the frameshift mutation) appeared in the proband. As his mother in the family was carrier with this heterozygous mutation, the hemizygous mutation in this patient came from his mother indicating that genetic mode of XHIGM is X-linked recessive inheritance.Conclusion: This study broadens our knowledge of the mutation in CD40L and lays a solid foundation for prenatal diagnosis and genetic counseling for the XHIGM family.


Assuntos
Ligante de CD40/genética , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/genética , Grupo com Ancestrais do Continente Asiático , Transplante de Células-Tronco Hematopoéticas , Hemizigoto , Humanos , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/diagnóstico , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/patologia , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/terapia , Imunoglobulinas/sangue , Lactente , Masculino , Mutação , Linhagem , Albumina Sérica Humana/uso terapêutico
12.
Mol Genet Genomic Med ; 8(2): e1076, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31833240

RESUMO

BACKGROUND: Autosomal recessive congenital ichthyosis (ARCI) is a rare genetically heterogeneous cutaneous disease predominantly characterized by erythroderma, generalized abnormal scaling of the whole body and a collodion membrane at birth. Numerous causative genes have been demonstrated to be responsible for ARCI including PNPLA1 which can cause ARCI type 10. The objectives of this study are to describe clinical features of three ARCI patients from two Chinese unrelated families and to identify the underlying causative mutations. METHODS: Genomic DNA was extracted from peripheral venous blood obtained from the two Chinese ARCI families in Shandong province. Subsequently, targeted regions sequencing (TRS) followed by Sanger sequencing was conducted to identify and validate the likely pathogenic mutations of the ARCI families. RESULTS: Genetic analyses revealed four novel PNPLA1 variants that are predicted to be probably to lead to ARCI in three patients of two families. Patient 1 in one family was in compound heterozygous status for c.604delC/p.Arg202Glyfs*27 and c.820dupC/p.Arg274Profs*15, whereas c.738_742delinsCCCACAGATCCTGC/ p.Gly247_Tyr248delinsProGlnIleLeuHis, and c.816dupC/p.Arg274Profs*15 were found in patient 2 and 3 of the other family. In addition, these variants cosegregate in the two pedigrees and are all within highly conserved regions of the PNPLA1 protein, which indicate that the four mutations are likely pathogenic. CONCLUSION: Our findings not only broaden the mutational spectrum of PNPLA1, but also contribute to establishing genotype-phenotype correlations for different forms of ARCI.


Assuntos
Genes Recessivos , Ictiose/genética , Lipase/genética , Mutação , Criança , Sequência Conservada , Feminino , Testes Genéticos/métodos , Humanos , Ictiose/patologia , Lipase/química , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Análise de Sequência de DNA/métodos
13.
Mol Psychiatry ; 25(2): 476-490, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31673123

RESUMO

Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder characterized by repetitive motor movements and vocal tics. The clinical manifestations of TS are complex and often overlap with other neuropsychiatric disorders. TS is highly heritable; however, the underlying genetic basis and molecular and neuronal mechanisms of TS remain largely unknown. We performed whole-exome sequencing of a hundred trios (probands and their parents) with detailed records of their clinical presentations and identified a risk gene, ASH1L, that was both de novo mutated and associated with TS based on a transmission disequilibrium test. As a replication, we performed follow-up targeted sequencing of ASH1L in additional 524 unrelated TS samples and replicated the association (P value = 0.001). The point mutations in ASH1L cause defects in its enzymatic activity. Therefore, we established a transgenic mouse line and performed an array of anatomical, behavioral, and functional assays to investigate ASH1L function. The Ash1l+/- mice manifested tic-like behaviors and compulsive behaviors that could be rescued by the tic-relieving drug haloperidol. We also found that Ash1l disruption leads to hyper-activation and elevated dopamine-releasing events in the dorsal striatum, all of which could explain the neural mechanisms for the behavioral abnormalities in mice. Taken together, our results provide compelling evidence that ASH1L is a TS risk gene.


Assuntos
Proteínas de Ligação a DNA/genética , Histona-Lisina N-Metiltransferase/genética , Síndrome de Tourette/genética , Adolescente , Adulto , Animais , Criança , Pré-Escolar , China , Proteínas de Ligação a DNA/metabolismo , Família , Feminino , Predisposição Genética para Doença/genética , Histona-Lisina N-Metiltransferase/metabolismo , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Mutação/genética , Pais , Transtornos de Tique/genética , Síndrome de Tourette/complicações , Fatores de Transcrição/genética , Sequenciamento Completo do Exoma/métodos
15.
J Anim Sci ; 97(10): 4140-4151, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31310662

RESUMO

This study was conducted to investigate the effects of Clostridium butyricum and Enterococcus faecalis on growth performance, immune function, inflammation-related pathways, and microflora community in weaned piglets challenged with lipopolysaccharide (LPS). One hundred and eighty 28-d-old weaned piglets were randomly divided into 3 treatments groups: piglets fed with a basal diet (Con), piglets fed with a basal diet containing 6 × 109 CFU C. butyricum·kg-1 (CB), and piglets fed with a basal diet containing 2 × 1010 CFU E. faecali·kg-1 (EF). At the end of trial, 1 pig was randomly selected from for each pen (6 pigs per treatment group) and these 18 piglets were orally challenged with LPS 25 µg·kg-1 body weight. The result showed that piglets fed C. butyricum and E. faecalis had greater final BW compared with the control piglets (P < 0.05). The C. butyricum and E. faecalis fed piglets had lower levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), IL-1ß, tumor inflammatory factor-α (TNF-α), and had greater level of serum interferon-γ (IFN-γ) than control piglets at 1.5 and 3 h after injection with LPS (P < 0.05). Furthermore, piglets in the C. butyricum or E. faecalis treatment groups had a greater ratio of jejunal villus height to crypt depth (V/C) compared with control piglets after challenge with LPS for 3 h (P < 0.05). Compared with the control treatment, the CB and EF treatments significantly decreased the expression of inflammation-related pathway factors (TLR4, MyD88, and NF-κB) after challenge with LPS for 3 h (P < 0.05). High-throughput sequencing revealed that C. butyricum and E. faecalis modulated bacterial diversity in the colon. The species richness and alpha diversity (Shannon) of bacterial samples in CB or EF piglets challenged with LPS were higher than those in LPS-challenged control piglets. Furthermore, the relative abundance of Bacteroidales-Rikenellanceae in the CB group was higher than that in the control group (P < 0.05), whereas EF piglets had a higher relative abundance of Lactobacillus amylovorus and Lactobacillus gasseri (P < 0.05). In conclusion, dietary supplementation with C. butyricum or E. faecalis promoted growth performance, improved immunity, relieved intestinal villus damage and inflammation, and optimized the intestinal flora in LPS-challenged weaned piglets.


Assuntos
Ração Animal/análise , Clostridium butyricum/fisiologia , Enterococcus faecalis/fisiologia , Microbioma Gastrointestinal , Probióticos/análise , Suínos/fisiologia , Animais , Dieta/veterinária , Inflamação/veterinária , Mucosa Intestinal/microbiologia , Intestinos/microbiologia , Lactobacillus/crescimento & desenvolvimento , Lipopolissacarídeos/administração & dosagem , Distribuição Aleatória , Suínos/crescimento & desenvolvimento , Suínos/imunologia , Suínos/microbiologia
16.
J Anim Sci ; 97(1): 133-143, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30388227

RESUMO

The present study was conducted to assess the effects of a mixture of essential oils and organic acids on the growth performance, immune system, major fecal volatile fatty acids (VFAs), and microflora community in the weaned piglets. We also evaluated the antibacterial activity of the essential oil mixture on Escherichia coli and Staphylococcus aureus. Three hundred weaned piglets (Duroc × Landrace × Yorkshire) were randomly divided into the following 3 treatment groups: basal diet (C), basal diet supplemented with the mixture of essential oils and organic acids (T1), and basal diet supplemented with antibiotics (T2). The mixture of essential oils and organic acids comprised of cinnamaldehyde (15%), thymol (5%), citric acid (10%), sorbic acid (10%), malic acid (6.5%), and fumaric acid (13.5%). In vitro studies showed that the mixture of essential oils extremely damaged the cell structure of pathogenic bacteria by deforming the membranes and disorganizing the intracellular components. In vivo studies revealed that diet supplementation with a mixture of essential oils and organic acids improved the final body weight and ADG of piglets (P < 0.05), increased the concentration of serum complement 4 (P < 0.05), and enhanced the fecal level of isovaleric acid (P < 0.05) compared with controls on day 28. Result of high-throughput sequencing revealed that: 1) a total of 1,177 and 1,162 observed taxonomic units (OTUs) were shared between all treatment groups on day 14 and 28, respectively; 2) the T1 exhibited higher (P < 0.05) beta diversity (unweighted UniFrac distance) than control and antibiotics treatment on day 28; 3) the samples in principle component analysis plot and tree of relative abundance were separated from each other based on dietary treatments and age; 4) Firmicutes and Bacteroidetes were the most 2 dominate phyla; Lactobacillus and Streptococcus were the 2 top species among the recognized microbiota; 5) T1 had higher (P < 0.05) relative abundance of Lactobacillus mucosae than control and antibiotics treatment on day 28. To conclude, the mixture of cinnamaldehyde and citric acids damaged the structure of pathogens in vitro; the mixture of essential oils and organic acids improved the growth performance, increased the fecal concentration of isovaleric acid, and modulated the microflora community in weaned piglets.


Assuntos
Ácidos Carboxílicos/farmacologia , Suplementos Nutricionais/análise , Ácidos Graxos Voláteis/análise , Microbioma Gastrointestinal/efeitos dos fármacos , Óleos Voláteis/farmacologia , Suínos/fisiologia , Ração Animal/análise , Animais , Bacteroidetes/isolamento & purificação , Dieta/veterinária , Fezes/química , Firmicutes/isolamento & purificação , Imunidade/efeitos dos fármacos , Lactobacillus/isolamento & purificação , Distribuição Aleatória , Streptococcus/isolamento & purificação , Suínos/crescimento & desenvolvimento , Suínos/imunologia , Desmame
17.
World J Biol Psychiatry ; 19(7): 521-526, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-28090804

RESUMO

OBJECTIVES: Twin and family analyses have revealed a genetic contribution to Tourette syndrome (TS) and post-mortem studies have raised the intriguing possibility of a reduction in cholinergic interneuronsin TS patients. METHODS: We selected five tag SNPs (rs100824791, rs12264845, rs1880676, rs3793790 and rs3793798) of choline acetyltransferase (CHAT) from the Han Chinese population Hapmap database. Genotyping was conducted on 401 TS nuclear family trios and 405 control subjects. Transmission disequilibrium test (TDT) and haplotype relative risk (HRR) analyses were used to analyse the family-based study and a case-control study was also used to assess the genetic susceptibility to TS. RESULTS: The results revealed a significant over-transmission of rs3793790 (TDT, χ2 = 9.121, P = 0.003; HRR, χ2 = 6.579, P = 0.01), while case-control analysis found no differences between the two groups (genotype, χ2 = 0.436, P = 0.804; allele, χ2 = 0.149, P = 0.700). Also, rs3793798 also indicated a positive association associated with TS (TDT, χ2 = 5.025, P = 0.028; HRR, χ2 = 0.250, P = 0.617). However, the other three SNPs investigated were found not to be associated with TS in both in the family-based and case-control studies. CONCLUSIONS: Our association analysis demonstrates that CHAT may contribute to TS susceptibility in the Han Chinese population. This gives strong support to the involvement of cholinergic interneurons in the aetiology of TS and reveals a potential therapeutic target.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Colina O-Acetiltransferase/genética , Síndrome de Tourette/genética , Adolescente , Adulto , Alelos , Estudos de Casos e Controles , Criança , Pré-Escolar , China , Família , Feminino , Predisposição Genética para Doença , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Polimorfismo de Nucleotídeo Único , Medição de Risco , Adulto Jovem
18.
Front Microbiol ; 9: 3260, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30671050

RESUMO

Several Bacillus strains exert beneficial effects on the maintenance of intestinal homeostasis and host health. However, whether Bacillus amyloliquefaciens (BA) can improve gut microbial dysbiosis and ameliorate colitis is unknown. Therefore, we conducted the present study to investigate the effects of BA administration on intestinal morphology, inflammatory response, and colonic microbial composition in a mouse model of dextran sulfate sodium (DSS)-induced colitis. Results showed that BA administration significantly ameliorated body weight loss, decreased disease activity index, and improved colonic tissue morphology in DSS-treated mice. In addition, levels of immunoglobulins, as well as pro-inflammatory cytokines, were decreased after BA administration. Importantly, colonic microbiota profiling indicated a significant (p < 0.05) difference in beta-diversity between BA-administrated and DSS-treated mice, according to weighted principal coordinate analysis (PCoA) results. The relative abundance of the Firmicutes genus was increased, whereas that of Bacteroidetes was decreased by BA administration. Furthermore, phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) analysis showed that the most significantly changed pathways between the four groups of mice were carbohydrate, lipid, and amino acid metabolism. In conclusion, our results showed that BA administration has beneficial effects on DSS-induced colitis, suggesting that this strategy might be useful for the treatment of dysbiosis during ulcerative colitis. Further, the changes in metabolism, especially amino acid metabolism, might contribute to the beneficial effects of BA on the amelioration of DSS-induced colitis.

19.
Clin Chim Acta ; 470: 36-41, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28455095

RESUMO

BACKGROUND: The abnormal expression of certain transcription factors (NKX2.1, FOXE1, NKX2.5, and PAX8) and thyroid stimulating hormone receptor (TSHR) genes has been associated with athyreosis, which is a form of thyroid dysgenesis (TD). We aimed to identify candidate gene mutations in CH patients with athyreosis and to establish the genotype-phenotype correlations in a Chinese population. METHODS: The exons and flanking sequences of NKX2.1, FOXE1, NKX2.5, PAX8, and TSHR were screened by next-generation sequencing and further confirmed by direct Sanger sequencing. The mutation frequencies were calculated and compared against databases. The relationship between genotype and phenotype was also determined. RESULTS: Seven variants were detected in TSHR-p.P52T, p.G132R, p.M164K, p.R450H, p.C700E, p.A522V, and p.R528S. The p. G132R, p. M164K and p. R528S variants were first identified in public databases. Five variants (p.G44D, p.G360V, p.R401Q, p.L418I, and p.E453Q) were found in NKX2.1 and one variant (p.P243T) was detected in FOXE1. In addition, one variant (p.N291I) was found in NKX2.5 and two variants (p.A355V and c.-26G>A) were detected in PAX8. CONCLUSIONS: Our study indicated that TSHR mutations have phenotypic variability and has further expanded the mutation spectrum of TSHR. We also revealed that the rate of NKX2.1, FOXE1, NKX2.5, and PAX8 mutations were low in patients with CH and athyreosis, in contrast to the higher rate of TSHR mutations.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Hipotireoidismo Congênito/genética , Análise Mutacional de DNA , Sequenciamento de Nucleotídeos em Larga Escala , Receptores da Tireotropina/genética , Disgenesia da Tireoide/genética , Fatores de Transcrição/genética , Sequência de Bases , Criança , Pré-Escolar , Feminino , Fatores de Transcrição Forkhead/genética , Genótipo , Proteína Homeobox Nkx-2.5/genética , Humanos , Masculino , Fator de Transcrição PAX8/genética , Fenótipo , Glândula Tireoide/metabolismo , Fator Nuclear 1 de Tireoide/genética
20.
Int J Biol Macromol ; 86: 848-56, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26854884

RESUMO

Chitosan nanoparticles (CNP), an extensively oral-administered drug carrier, was investigated for the anti-inflammatory effects on LPS-inflamed Caco-2 cells and the relate mechanisms. CNP could alleviate the decrease of transepithelial electrical resistance (TEER) induced by LPS in Caco-2 monolayer, and significantly inhibit LPS-induced production of TNF-α, MIF, IL-8 and MCP-1 in a dose-dependent manner. PCR array assay revealed that CNP down-regulated the mRNA expression levels of TLR4 in LPS-inflamed Caco-2 cells. CNP was further showed to reduce cytoplasmic IκB-α degradation and nuclear NF-κB p65 levels in LPS-inflamed Caco-2 cells. These results suggested that CNP suppressed LPS-induced inflammatory response by decreasing permeability of intestinal epithelial monolayer and secretion of pro-inflammatory cytokine in Caco-2 cells, which were partially mediated by NF-κB signaling pathway.


Assuntos
Quitosana/química , Quitosana/farmacologia , Lipopolissacarídeos/farmacologia , Nanopartículas , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Células CACO-2 , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Citocinas/biossíntese , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Inibidor de NF-kappaB alfa/metabolismo , Proteólise/efeitos dos fármacos , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
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