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1.
Acta Biomater ; 179: 300-312, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38518865

RESUMO

Deep tissue bacterial infections, especially methicillin-resistant Staphylococcus aureus (MRSA) infections, pose challenges to clinical therapy due to their low debridement efficiency and relapsing. Molybdenum disulfide (MoS2) is used in the antibacterial field as a classic photothermal agent (NIR-I) with good biocompatibility. However, due to its limited NIR-I tissue penetration ability and single treatment mode, MoS2 has poor therapeutic effects on deep tissue infection. Herein, we prepared a defect-type hybrid 2H-MoS2 nanozyme (MoWS2) using hydrothermal method fabricate the MoWS2 composite, which is a new antibacterial strategy involving photothermal and enzyme catalysis, and further enhances the activity of the nanozyme through overheating. The regulation of 2H-MoS2 defects through tungsten ion doping endows MoWS2 with better near-infrared two-region absorption (NIR-II) and enzyme catalytic performance. Antibacterial activity experiments in vitro have shown that MoWS2 can achieve efficient bactericidal activity and biofilm clearance through hyperthermia and reactive oxygen species (ROS). Deep MRSA infection experiments have shown that MoWS2 rapidly removes bacteria from subcutaneous infected tissues through photothermal therapy (PTT) and chemodynamic therapy (CDT), accelerates the dissipation of abscesses, and promotes the healing of infected wounds. Additionally, the versatile treatment mode of MoWS2 was further confirmed through tissue sectioning and immunofluorescence staining analysis. Overall, these results provide a feasible approach for achieving efficient treatment of deep tissue infections through tungsten ion doping to regulate defective 2H-MoS2. STATEMENT OF SIGNIFICANCE: The photothermal effect of MoS2 nanosheets in the NIR-I (650-900 nm) window in anti-MRSA therapy is considered to be highly reliable and efficient in PTA. However, most of the developed PPT therapies or antimicrobial systems based on PTT therapies developed with 1T-MoS2 have in vivo sterilization temperatures of more than 55°C, which have the risk of damaging the normal tissues of the skin. In this study, we prepared W@MoS2 with a good photothermal effect (36.9%) in the NIR-II window and good peroxidase-like activity. The combined effect of PTT and CDT has a stronger bactericidal effect while avoiding high-temperature damage, which makes the W@MoS2 material more advantageous in terms of antimicrobial effect.


Assuntos
Antibacterianos , Staphylococcus aureus Resistente à Meticilina , Molibdênio , Infecções Estafilocócicas , Cicatrização , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Molibdênio/química , Molibdênio/farmacologia , Animais , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/patologia , Antibacterianos/farmacologia , Antibacterianos/química , Camundongos , Dissulfetos/química , Dissulfetos/farmacologia , Raios Infravermelhos , Biofilmes/efeitos dos fármacos , Terapia Fototérmica
2.
Nat Microbiol ; 9(2): 434-450, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38233647

RESUMO

A strong correlation between gut microbes and host health has been observed in numerous gut metagenomic cohort studies. However, the underlying mechanisms governing host-microbe interactions in the gut remain largely unknown. Here we report that the gut commensal Christensenella minuta modulates host metabolism by generating a previously undescribed class of secondary bile acids with 3-O-acylation substitution that inhibit the intestinal farnesoid X receptor. Administration of C. minuta alleviated features of metabolic disease in high fat diet-induced obese mice associated with a significant increase in these acylated bile acids, which we refer to as 3-O-acyl-cholic acids. Specific knockout of intestinal farnesoid X receptor in mice counteracted the beneficial effects observed in their wild-type counterparts. Finally, we showed that 3-O-acyl-CAs were prevalent in healthy humans but significantly depleted in patients with type 2 diabetes. Our findings indicate a role for C. minuta and acylated bile acids in metabolic diseases.


Assuntos
Ácidos e Sais Biliares , Diabetes Mellitus Tipo 2 , Humanos , Animais , Camundongos , Clostridiales , Dieta Hiperlipídica
3.
BMC Pregnancy Childbirth ; 23(1): 377, 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37226082

RESUMO

BACKGROUND: Patients with polycystic ovary syndrome (PCOS) exhibit a chronic inflammatory state, which is often accompanied by immune, endocrine, and metabolic disorders. Clarification of the pathogenesis of PCOS and exploration of specific biomarkers from the perspective of immunology by evaluating the local infiltration of immune cells in the follicular microenvironment may provide critical insights into disease pathogenesis. METHODS: In this study, we evaluated immune cell subsets and gene expression in patients with PCOS using data from the Gene Expression Omnibus database and single-sample gene set enrichment analysis. RESULTS: In total, 325 differentially expressed genes were identified, among which TMEM54 and PLCG2 (area under the curve = 0.922) were identified as PCOS biomarkers. Immune cell infiltration analysis showed that central memory CD4+ T cells, central memory CD8+ T cells, effector memory CD4+ T cells, γδ T cells, and type 17 T helper cells may affect the occurrence of PCOS. In addition, PLCG2 was highly correlated with γδ T cells and central memory CD4+ T cells. CONCLUSIONS: Overall, TMEM54 and PLCG2 were identified as potential PCOS biomarkers by bioinformatics analysis. These findings established a basis for further exploration of the immunological mechanisms of PCOS and the identification of therapeutic targets.


Assuntos
Síndrome do Ovário Policístico , Feminino , Humanos , Síndrome do Ovário Policístico/genética , Linfócitos T CD8-Positivos , Biomarcadores , Biologia Computacional , Bases de Dados Factuais , Microambiente Tumoral
4.
Technol Health Care ; 31(S1): 97-109, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37038785

RESUMO

BACKGROUND: Unexplained recurrent spontaneous abortion (URSA) is difficult to diagnose and treat clinically due to its unknown causeOBJECTIVE: Changes in natural killer (NK) cells, T lymphocytes, and Th1(IFNγ)/Th2(IL-4) cytokines were investigated in the peripheral blood of patients with URSA to examine the pathogenesis, clinical diagnosis, and inform potential treatment strategies for this condition. METHODS: For this study, we selected patients with URSA as the case group and included normal women in the control group. Flow cytometry was performed to detect lymphocytes and cytokines in the peripheral blood of all subjects. RESULTS: The proportion of NK cells, Th1 cells, and the Th1/Th2 ratio were significantly higher in the URSA group compared to the control group; whereas the proportion of CD3+T cells was lower. Pairwise correlation analysis revealed a positive correlation between the percentage of NK cells and CD3+T cells, as well as CD3+CD4+T cells. Canonical correlation analysis indicated a significant correlation between NK cells and T cells, including their subgroups. CONCLUSION: Patients with URSA have immune balance disorders, characterised by an increased proportion of peripheral blood NK cells, Th1, and Th1/Th2 ratio along with a decreased proportion of CD3+T cells. The proportion of NK cells and CD3+T may serve as predictive factors for URSA, while NK cells are closely related to the regulation of CD3+T cells and their subsets. By regulating the level of IFN-γ, NK cells can influence the proportion of CD3+T cells and induce a Th1 (IFNγ)/Th2 (IL-4) imbalance.


Assuntos
Aborto Habitual , Interleucina-4 , Gravidez , Humanos , Feminino , Aborto Habitual/terapia , Células Matadoras Naturais , Células Th1 , Citocinas
5.
Artigo em Inglês | MEDLINE | ID: mdl-36735588

RESUMO

The human gastrointestinal tract is inhabited by various microorganisms, including thousands of bacterial taxa that have yet to be cultured and characterized. In this report, we describe the isolation, cultivation, genotypic and phenotypic characterization and taxonomy of five novel anaerobic bacterial strains that were recovered during the massive cultivation and isolation of gut microbes from human faecal samples. On the basis of the polyphasic taxonomic results, we propose two novel genera and five novel species. They are Acidaminococcus hominis sp. nov. (type strain NSJ-142T=CGMCC 1.17903T=KCTC 25346T), Amedibacillus hominis sp. nov. (type strain NSJ-176T=CGMCC 1.17933T=KCTC 25355T), Lientehia hominis gen. nov. sp. nov. (type strain NSJ-141T=CGMCC 1.17902T=KCTC 25345T), Merdimmobilis hominis gen. nov. sp. nov. (type strain NSJ-153T=CGMCC 1.17915T=KCTC 25350T) and Paraeggerthella hominis sp. nov. (type strain NSJ-152T=CGMCC 1.17914T=KCTC 25349T).


Assuntos
Actinobacteria , Tenericutes , Humanos , Ácidos Graxos/química , Acidaminococcus , Filogenia , DNA Bacteriano/genética , RNA Ribossômico 16S/genética , Composição de Bases , Técnicas de Tipagem Bacteriana , Análise de Sequência de DNA , Firmicutes , Fezes/microbiologia , Fosfolipídeos
6.
Am J Reprod Immunol ; 89(6): e13691, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36793182

RESUMO

PROBLEM: Unexplained recurrent spontaneous abortion (URSA) is one of the most frustrating and confounding conditions in reproductive medicine, and its exact pathogenesis has not been clearly established. METHOD OF STUDY: In this study, we used RNA sequencing to characterize the mRNA and lncRNA expression profiles in peripheral blood. Thereafter, enrichment analysis was performed to determine the functions of the differentially expressed genes, and Cytoscape was used to construct lncRNA-mRNA interaction networks. RESULTS: Our results showed that the peripheral blood of patients with URSA has distinct mRNA and lncRNA expression profiles, with a total of 359 mRNAs and 683 lncRNAs being differentially expressed. Moreover, the top hub genes, including IGF1, PPARG, CCL3, RETN, SERPINE1, HESX1, and PRL, were identified and further validated using real-time quantitative PCR. Furthermore, we demonstrated a lncRNA-mRNA interaction network that achieved 12 key lncRNAs and their targeted mRNAs are involved in systemic lupus erythematosus, allograft rejection, and complement and coagulation cascades. Finally, the correlation between immune cell subtypes and IGF1 expression was evaluated; a negative correlation was observed with the proportion of natural killer cells, which increased significantly in URSA. CONCLUSION: We identified seven top hub genes, constructed a lncRNA-related network and suggested that IGF1 plays a key role in regulating maternal immune response by affecting NK and T cells' function, which helps to identify the pathogenesis of URSA.


Assuntos
Aborto Habitual , MicroRNAs , RNA Longo não Codificante , Feminino , Gravidez , Humanos , RNA Longo não Codificante/genética , Redes Reguladoras de Genes , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Células Matadoras Naturais/metabolismo , MicroRNAs/genética
7.
Open Life Sci ; 17(1): 1443-1450, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36448060

RESUMO

Unexplained recurrent spontaneous abortion (URSA) is a major concern in reproductive medicine. Neutrophil cytosolic factor 1 (NCF1) polymorphisms leading to low production of reactive oxygen species (ROS) are strongly associated with autoimmune diseases. We investigated the association of the missense single nucleotide polymorphism (SNP) rs201802880 (NCF1-339) in NCF1 with URSA and explored its function. We performed NCF1-339 SNP genotyping of samples from 152 Chinese patients with URSA and 72 healthy controls using nested PCR and TaqMan assays. ROS production and RELA (NF-κB subunit) expression in the blood of participants with different NCF1-339 genotypes were determined. The frequencies of the wild-type (GG) and mutant (GA) genotypes remarkably differed between the URSA and control groups. The mutant genotype was associated with an increased risk of recurrent abortion. Furthermore, ROS levels in the URSA group with the GG genotype were significantly higher than those in the group with the GA genotype (p < 0.05). RELA expression in URSA patients with the GA genotype was considerably higher than that in control individuals with the GG genotype. These findings indicate that mutations in NCF1 may increase the risk of URSA via the NADP/ROS/NF-κB signaling pathway, which has implications for the diagnosis and treatment of URSA.

9.
Artigo em Inglês | MEDLINE | ID: mdl-35559790

RESUMO

A strictly anaerobic, motile bacterium, designated as strain NSJ-9T, was isolated from human faeces. Cells were Gram-negative, non-spore-forming, non-pigmented, and spiral-shaped or slightly curved rods with flagella. Optimal growth in M2GSC medium was observed at 37 °C (growth range 30-45 °C) and pH 6.5-7.0 (growth range 6.5-7.5) under anaerobic conditions. Phylogenetic analysis of the 16S rRNA gene revealed that strain NSJ-9T formed a distinct phylogenetic lineage that reflects a new genus in the family Lachnospiraceae, with high levels of similarity to Roseburia hominis A2-183T (95.2 %), Roseburia cecicola ATCC 33874T (95.2 %), Pseudobutyrivibrio ruminis DSM 9787T (95.2 %), Pseudobutyrivibrio xylanivorans MZ 5T (94.8%) and Roseburia faecis M72/1T (94.4 %). Genomic similarity (average nucleotide identity and digital DNA-DNA hybridization) values between strain NSJ-9T and its phylogenetic neighbours were below 71 and 31 %, respectively, indicating that strain NSJ-9T represented a novel species. The average amino acid identity and the percentage of conserved proteins between strain NSJ-9T and other related members of the family Lachnospiraceae were below 63 and 50 %, respectively, supporting that strain NSJ-9T was a member of a new genus. The predominant cellular fatty acids of strain NSJ-9T were C16 : 0 and C17 : 0 2-OH, and major polar lipids were glycolipids. The end products of glucose fermentation were acetate, propionate, iso-butyrate, butyrate and valerate. Phylogenetic and phylogenomic lineage, pairwise determined genome identity analysis suggested that strain NSJ-9T represents a novel genus in the family Lachnospiraceae. The genome size of strain NSJ-9T is 2.56 Mbp with 44.9 mol% G+C content. Collectively, the genotypic and phenotypic differences between phylogenetic relatives suggested strain NSJ-9T represented a novel species of a new genus, for which the name Pararoseburia lenta gen. nov., sp. nov. is proposed. The type strain of Pararoseburia lenta is NSJ-9T (=CGMCC 1.32469T=KCTC 15957T).


Assuntos
Bactérias Anaeróbias , Ácidos Graxos , Técnicas de Tipagem Bacteriana , Composição de Bases , Butiratos , DNA Bacteriano/genética , Ácidos Graxos/química , Fezes/microbiologia , Humanos , Fosfolipídeos/química , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
10.
Artigo em Inglês | MEDLINE | ID: mdl-35258450

RESUMO

Non-human primates harbour diverse microbiomes in their guts. As a part of the China Microbiome Initiatives, we cultivated and characterized the gut microbiome of cynomolgus monkeys (Macaca fascicularis). In this report, we communicate the characterization and taxonomy of eight bacterial strains that were obtained from faecal samples of captive cynomolgus monkeys. The results revealed that they represented eight novel bacterial species. The proposed names of the eight novel species are Alkaliphilus flagellatus (type strain MSJ-5T=CGMCC 1.45007T=KCTC 15974T), Butyricicoccus intestinisimiae MSJd-7T (MSJd-7T=CGMCC 1.45013T=KCTC 25112T), Clostridium mobile (MSJ-11T=CGMCC 1.45009T=KCTC 25065T), Clostridium simiarum (MSJ-4T=CGMCC 1.45006T=KCTC 15975T), Dysosmobacter acutus (MSJ-2T=CGMCC 1.32896T=KCTC 15976T), Paenibacillus brevis MSJ-6T (MSJ-6T=CGMCC 1.45008T=KCTC 15973T), Peptoniphilus ovalis (MSJ-1T=CGMCC 1.31770T=KCTC 15977T) and Tissierella simiarum (MSJ-40T=CGMCC 1.45012T=KCTC 25071T).


Assuntos
Paenibacillus , Animais , Técnicas de Tipagem Bacteriana , Composição de Bases , Clostridium , DNA Bacteriano/genética , Ácidos Graxos/química , Fezes , Haplorrinos , Fosfolipídeos , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
11.
mLife ; 1(2): 210-217, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38817672

RESUMO

Nonhuman primates (NHPs) such as monkeys are the closest living relatives to humans and are the best available models for causative studies of human health and diseases. Gut microbiomes are intensively involved in host health. In this study, by large-scale cultivation of microbes from fecal samples of monkeys, we obtained previously uncultured bacterial species and constructed a Macaca fascicularis Gut Microbial Biobank (MfGMB). The MfGMB consisted of 250 strains that represent 97 species of 63 genera, 25 families, and 4 phyla. The information of the 250 strains and the genomes of 97 cultured species are publicly accessible. The MfGMB represented nearly 50% of core gut microbial compositions at the genus level and covered over 80% of the KO-based known gut microbiome functions of M. fascicularis. Data mining showed that the bacterial species in the MfGMB were prevalent not only in NHPs gut microbiomes but also in human gut microbiomes. This study will help the understanding and future investigations on how gut microbiomes interact with their mammalian hosts.

12.
Front Immunol ; 12: 717832, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34421922

RESUMO

Identifying the mechanisms underlying unexplained recurrent spontaneous abortion (URSA) can help develop effective treatments. This study provides novel insights into the biological characteristics and related pathways of differentially expressed genes (DEGs) in URSA. Nineteen patients with URSA and three healthy fertile women with regular menstruation (control group) were recruited. RNA was extracted from the two groups to determine the differential expression of immunoregulatory gene sequences. Gene ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analyses were used to identify the biological functions and pathways of the identified DEGs. A protein-protein interaction (PPI) network was constructed using the STRING database. Furthermore, qRT-PCR and ELISA were performed to validate the differential expression of the hub genes. We also explored the regulatory mechanism of Th1/Th2 imbalance. A total of 99 DEGs were identified, comprising 94 upregulated and five downregulated genes. Through GO analysis, nine immune cell function-related clusters were selected, and genes with significant differential expression were primarily enriched in eight immune regulatory functions related to the KEGG signalling pathway. Subsequently, five hub genes (TLR2, CXCL8, IFNG, IL2RA, and ITGAX) were identified using Cytoscape software; qRT-PCR confirmed the differential expression among the hub genes, whereas ELISA revealed a significant difference in extracellular IFN-γ and IL-8 levels. The levels of Th1 (IFN-γ) and the Th1/Th2 ratio were higher in the peripheral blood of URSA patients than in control group patients. These findings suggest that the occurrence of URSA may be associated with the abnormal expression of some specific immunoregulatory genes involved in T-cell activation and differentiation. Among the identified DEGs, IFNG may play a key role in regulating maternal immune response. Although further validation is required, our data provide an important theoretical basis for elucidating the pathogenesis of recurrent spontaneous abortion.


Assuntos
Aborto Habitual/etiologia , Aborto Habitual/metabolismo , Biomarcadores , Suscetibilidade a Doenças , Regulação da Expressão Gênica , Transdução de Sinais , Aborto Habitual/diagnóstico , Adulto , Biologia Computacional/métodos , Citocinas , Feminino , Perfilação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Gravidez , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas
13.
Microbiome ; 9(1): 119, 2021 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-34020714

RESUMO

BACKGROUND: In gut microbiome studies, the cultured gut microbial resource plays essential roles, such as helping to unravel gut microbial functions and host-microbe interactions. Although several major studies have been performed to elucidate the cultured human gut microbiota, up to 70% of the Unified Human Gastrointestinal Genome species have not been cultured to date. Large-scale gut microbial isolation and identification as well as availability to the public are imperative for gut microbial studies and further characterizing human gut microbial functions. RESULTS: In this study, we constructed a human Gut Microbial Biobank (hGMB; homepage: hgmb.nmdc.cn ) through the cultivation of 10,558 isolates from 31 sample mixtures of 239 fresh fecal samples from healthy Chinese volunteers, and deposited 1170 strains representing 400 different species in culture collections of the International Depository Authority for long-term preservation and public access worldwide. Following the rules of the International Code of Nomenclature of Prokaryotes, 102 new species were characterized and denominated, while 28 new genera and 3 new families were proposed. hGMB represented over 80% of the common and dominant human gut microbial genera and species characterized from global human gut 16S rRNA gene amplicon data (n = 11,647) and cultured 24 "most-wanted" and "medium priority" taxa proposed by the Human Microbiome Project. We in total sequenced 115 genomes representing 102 novel taxa and 13 previously known species. Further in silico analysis revealed that the newly sequenced hGMB genomes represented 22 previously uncultured species in the Unified Human Gastrointestinal Genome (UHGG) and contributed 24 representatives of potentially "dark taxa" that had not been discovered by UHGG. The nonredundant gene catalogs generated from the hGMB genomes covered over 50% of the functionally known genes (KEGG orthologs) in the largest global human gut gene catalogs and approximately 10% of the "most wanted" functionally unknown proteins in the FUnkFams database. CONCLUSIONS: A publicly accessible human Gut Microbial Biobank (hGMB) was established that contained 1170 strains and represents 400 human gut microbial species. hGMB expands the gut microbial resources and genomic repository by adding 102 novel species, 28 new genera, 3 new families, and 115 new genomes of human gut microbes. Video abstract.


Assuntos
Microbioma Gastrointestinal , Microbiota , Bactérias/genética , Bancos de Espécimes Biológicos , Escuridão , Microbioma Gastrointestinal/genética , Humanos , Microbiota/genética , RNA Ribossômico 16S/genética
14.
Front Immunol ; 12: 669819, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33936113

RESUMO

Purpose: This study aimed to investigate the profiles of messenger RNAs (mRNAs) and long noncoding RNAs (lncRNAs) in peripheral blood samples collected from polycystic ovary syndrome (PCOS) patients. In addition, an in-depth bioinformatics analysis regarding the lncRNA-mRNA co-expression network was performed. Methods: High-throughput sequencing was used to measure the profiles of mRNAs and lncRNAs expressed in the peripheral blood samples isolated from six patients (three patients with PCOS and three normal women). In addition, five differentially expressed lncRNAs were chosen to validate the results of high-throughput sequencing by quantitative RT-PCR (qRT-PCR). Furthermore, a lncRNA-mRNA co-expression network was constructed using the Cytoscape software. Results: A total of 14,276 differentially expressed mRNAs and 4,048 differentially expressed lncRNAs were obtained from the RNA-seq analysis of PCOS patients and healthy controls (adjusted q-value < 0.05, Fold change >2.0).The qRT-PCR results were consistent with the data obtained through high-throughput sequencing. Gene ontology (GO) and KEGG pathway analyses showed that the differentially expressed mRNAs were enriched in the chemokine signaling pathway. In addition, the analysis of the lncRNA-mRNA co-expression network of the chemokine signaling pathway showed the involvement of 6 mRNAs and 42 lncRNAs. Conclusion: Clusters of mRNAs and lncRNAs were aberrantly expressed in the peripheral blood of PCOS patients compared with the controls. In addition, several pairs of lncRNA-mRNAs in the chemokine signaling pathway may be related to PCOS genetically.


Assuntos
Ácidos Nucleicos Livres/genética , Perfilação da Expressão Gênica , Síndrome do Ovário Policístico/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Transcriptoma , Adulto , Ácidos Nucleicos Livres/sangue , Biologia Computacional , Feminino , Redes Reguladoras de Genes , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Projetos Piloto , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/diagnóstico , RNA Longo não Codificante/sangue , RNA Mensageiro/sangue , Reação em Cadeia da Polimerase em Tempo Real , Adulto Jovem
15.
Technol Health Care ; 29(S1): 11-25, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33682741

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common gynecologic endocrinopathy, characterized by menstrual disorders, ovulation disorders, polycystic ovary, hyperandrogen syndrome and insulin resistance. At present, the etiology and exact pathogenesis of PCOS are still unclear. Anti-Müllerian hormone is a local regulator secreted by ovarian granulosa cells, and participates in regulating the occurrence and development of PCOS. Insulin resistance is another important pathophysiological feature of PCOS. Although the expression of anti-müllerian hormone receptor (AMHR) and insulin receptor (INSR) in PCOS have been previously reported, the DNA methylation of the genes have not been well characterized. OBJECTIVE: To study AMHR II/INSR and its role in gene methylation in Ovarian and endometrial pathology of PCOS subjects. METHODS: We recruited seventy-five women with PCOS as cases and twenty healthy women as controls, using immunohistochemical method, study localization, distribution and expression of MHRII/INSR in ovary and endometrium and then discover the correlation of AMHRII/INSR gene methylation. RESULTS: Different clinical features in PCOS group AMHRII gene methylation level and insulin resistance relations have significant differences (r= 0.532, P= 0.000); INSR gene methylation level and insulin resistance relations have significant differences (r= 0.281, P= 0.03). CONCLUSIONS: The analysis of DNA methylation suggested that methylation of AMHRII and INSR genes was associated with basic clinical characteristics and insulin resistance of PCOS. These results provide evidence for AMHRII and INSR genes, and their methylation levels are intimately associated with the pathogenesis of PCOS.


Assuntos
Antígenos CD/genética , Metilação de DNA , Resistência à Insulina , Síndrome do Ovário Policístico , Receptor de Insulina/genética , Receptores de Peptídeos/genética , Receptores de Fatores de Crescimento Transformadores beta/genética , Adulto , Hormônio Antimülleriano/genética , Hormônio Antimülleriano/metabolismo , Antígenos CD/metabolismo , Metilação de DNA/genética , Feminino , Células da Granulosa/metabolismo , Humanos , Resistência à Insulina/genética , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/metabolismo , Receptor de Insulina/metabolismo , Adulto Jovem
16.
Nat Commun ; 11(1): 79, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31911589

RESUMO

Mice are widely used as experimental models for gut microbiome (GM) studies, yet the majority of mouse GM members remain uncharacterized. Here, we report the construction of a mouse gut microbial biobank (mGMB) that contains 126 species, represented by 244 strains that have been deposited in the China General Microorganism Culture Collection. We sequence and phenotypically characterize 77 potential new species and propose their nomenclatures. The mGMB includes 22 and 17 species that are significantly enriched in ob/ob and wild-type C57BL/6J mouse cecal samples, respectively. The genomes of the 126 species in the mGMB cover 52% of the metagenomic nonredundant gene catalog (sequence identity ≥ 60%) and represent 93-95% of the KEGG-Orthology-annotated functions of the sampled mouse GMs. The microbial and genome data assembled in the mGMB enlarges the taxonomic characterization of mouse GMs and represents a useful resource for studies of host-microbe interactions and of GM functions associated with host health and diseases.


Assuntos
Bactérias/isolamento & purificação , Microbioma Gastrointestinal , Camundongos/microbiologia , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/crescimento & desenvolvimento , Ceco/microbiologia , China , Bases de Dados Factuais , Genoma Bacteriano , Masculino , Camundongos Endogâmicos C57BL , Filogenia
17.
J Ethnopharmacol ; 187: 28-41, 2016 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-27085942

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Acupuncture is a key part of traditional Chinese medicine, shown to induce favorable neuroplasticity for injuries in the central and peripheral nervous systems. Recent studies report elongated needle therapy (ENT) with BL54 and ST28 may restore acute spinal cord injury (ASCI). However, the precise mechanism for this has not been elucidated. AIM OF THE STUDY: In our current study, we investigated the effects of ENT on inflammation and neuronal apoptosis induced by ASCI, and whether PI3K/Akt and MAPK/ERK signaling pathways are involved in the ENT restoration effect. MATERIALS AND METHODS: Rat models of moderate SCI were established in accordance with the modified Allen's method and were treated with ENT continuously for 7 days. Spontaneous activities were evaluated by the Basso Beattie and Bresnahan locomotor scale. Levels of inflammatory cytokines, such as tumor necrosis factor alpha, interleukin-6, IL-1ß, and nuclear factor kappa-ß, were determined by enzyme-linked immunosorbent assay. Cell apoptosis was examined by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The proportions of cells with positive Bcl-2 and Bax expression were determined by immunohistochemical assays, whilst the expression profiles of p-AKT and p-ERK in spinal cord tissues were evaluated by western blotting. Furthermore, the expression profiles of Cytochrome-C (Cyt-C) and caspase-3 in vivo were analyzed by reverse transcription polymerase chain reaction. The potential inhibitory effects downstream of the Akt and ERK signaling pathways were examined by administration of specific inhibitors LY294002 and PD98059 in vivo. RESULTS: As indicated by this study, inflammation as well as PI3K/Akt- and MAPK/ERK signaling pathway-mediated neuronal apoptosis were involved in the course of SCI in rats. The neuro-protective effect of ENT was associated with reduced Bax protein-positive neurons and increased Bcl-2 protein-positive neurons. ENT enhanced recovery of rat activities. Activation of p-Akt and p-ERK in the PI3K/Akt and MAPK/ERK signaling pathways, inhibited expression of the critical component Cyt-C. Cyt-C is required for the mitochondrial apoptosis pathway and cascade of caspase-3, which is involved in activation of neuronal apoptosis through down-regulation of Bax protein and up-regulation of Bcl-2, as determined by TUNEL. The administration of PI3K/Akt and MAPK/ERK signaling pathway specific inhibitors, LY294002 and PD98059, suppressed expression of both p-Akt and p-ERK. CONCLUSION: ENT with BL54 and ST28 points can promote the recovery of ASCI. And the neuro-protective effect of ENT during the restoration of SCI may be associated with the suppression of both inflammation and activation of PI3K/Akt and MAPK/ERK signaling pathways, resulting from down-regulation of Bax protein, up-regulation of Bcl-2, and inhibition of the mitochondrial apoptosis pathway.


Assuntos
Terapia por Acupuntura , Medicina Tradicional Chinesa , Agulhas , Traumatismos da Medula Espinal/terapia , Animais , Caspase 3/genética , Cromonas/farmacologia , Citocromos c/genética , Citocinas/metabolismo , Flavonoides/farmacologia , Masculino , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Morfolinas/farmacologia , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos Sprague-Dawley , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/metabolismo , Proteína X Associada a bcl-2/metabolismo
18.
Artigo em Inglês | MEDLINE | ID: mdl-24348723

RESUMO

Acute spinal cord injury is one of the most common and complicated diseases among human spinal injury. We aimed to explore the effect of point-through-point acupuncture therapy with elongated needles on acute spinal cord injury in rabbits and its possible mechanism. Adult rabbits were randomly divided into a model group, elongated needle therapy group, and blank group. Immunohistochemical staining showed that the protein levels of Fas and caspase-3 in the model group were significantly higher than those in the blank group at each time point (P < 0.05) and significantly lower than those in the elongated needle therapy group on the 3rd and 5th days after operation (P < 0.05). RT-PCR showed that Fas and caspase-3 mRNA levels in the model group and elongated needle therapy group were significantly higher than those in the blank group (P < 0.05, 0.01). The mRNA levels of Fas and caspase-3 in the elongated needle therapy group were significantly lower than those in model group on the 3rd day (P < 0.05, 0.01). Therefore, we confirmed that elongated needle therapy has an obvious effect on acute spinal cord injury in rabbits. Its mechanism is made possible by inhibiting the expression of the Fas→caspase-3 cascade, thereby inhibiting cell apoptosis after spinal cord injury.

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