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1.
Brain ; 147(9): 3131-3143, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-38538210

RESUMO

Biallelic SORD mutations cause one of the most frequent forms of recessive hereditary neuropathy, estimated to affect ∼10 000 patients in North America and Europe alone. Pathogenic SORD loss-of-function changes in the encoded enzyme sorbitol dehydrogenase result in abnormally high sorbitol levels in cells and serum. How sorbitol accumulation leads to peripheral neuropathy remains to be elucidated. A reproducible animal model for SORD neuropathy is essential to illuminate the pathogenesis of SORD deficiency and for preclinical studies of potential therapies. Therefore, we have generated a Sord knockout (KO), Sord-/-, Sprague Dawley rat, to model the human disease and to investigate the pathophysiology underlying SORD deficiency. We have characterized the phenotype in these rats with a battery of behavioural tests as well as biochemical, physiological and comprehensive histological examinations. Sord-/- rats had remarkably increased levels of sorbitol in serum, CSF and peripheral nerve. Moreover, serum from Sord-/- rats contained significantly increased levels of neurofilament light chain, an established biomarker for axonal degeneration. Motor performance significantly declined in Sord-/- animals starting at ∼7 months of age. Gait analysis evaluated with video motion-tracking confirmed abnormal gait patterns in the hindlimbs. Motor nerve conduction velocities of the tibial nerves were slowed. Light and electron microscopy of the peripheral nervous system revealed degenerating myelinated axons, de- and remyelinated axons, and a likely pathognomonic finding-enlarged 'ballooned' myelin sheaths. These findings mainly affected myelinated motor axons; myelinated sensory axons were largely spared. In summary, Sord-/- rats develop a motor-predominant neuropathy that closely resembles the human phenotype. Our studies revealed novel significant aspects of SORD deficiency, and this model will lead to an improved understanding of the pathophysiology and the therapeutic options for SORD neuropathy.


Assuntos
Modelos Animais de Doenças , Animais , Feminino , Masculino , Ratos , L-Iditol 2-Desidrogenase/deficiência , L-Iditol 2-Desidrogenase/metabolismo , Condução Nervosa , Doenças do Sistema Nervoso Periférico/fisiopatologia , Doenças do Sistema Nervoso Periférico/patologia , Doenças do Sistema Nervoso Periférico/genética , Ratos Sprague-Dawley , Sorbitol/metabolismo
2.
J Transl Med ; 22(1): 364, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632610

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is an endocrinological and metabolic disorder that can lead to female infertility. Lipid metabolomics and proteomics are the new disciplines in systems biology aimed to discover metabolic pathway changes in diseases and diagnosis of biomarkers. This study aims to reveal the features of PCOS to explore its pathogenesis at the protein and metabolic level. METHODS: We collected follicular fluid samples and granulosa cells of women with PCOS and normal women who underwent in vitro fertilization(IVF) and embryo transfer were recruited. The samples were for the lipidomic study and the proteomic study based on the latest metabolomics and proteomics research platform. RESULTS: Lipid metabolomic analysis revealed abnormal metabolism of glycerides, glycerophospholipids, and sphingomyelin in the FF of PCOS. Differential lipids were strongly linked with the rate of high-quality embryos. In total, 144 differentially expressed proteins were screened in ovarian granulosa cells in women with PCOS compared to controls. Go functional enrichment analysis showed that differential proteins were associated with blood coagulation and lead to follicular development disorders. CONCLUSION: The results showed that the differential lipid metabolites and proteins in PCOS were closely related to follicle quality,which can be potential biomarkers for oocyte maturation and ART outcomes.


Assuntos
Síndrome do Ovário Policístico , Feminino , Humanos , Líquido Folicular/química , Líquido Folicular/metabolismo , Proteômica , Biomarcadores/metabolismo , Lipídeos
3.
Inflamm Res ; 73(4): 581-595, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38363325

RESUMO

OBJECTIVE: The treatment of eosinophilic chronic rhinosinusitis with nasal polyps (E-CRSwNP) remains a challenge due to its complex pathogenesis. Inositol polyphosphate-4-phosphatase type IA (INPP4A), a lipid phosphatase, has been implicated in allergic asthma. However, the expression and function of INPP4A in E-CRSwNP remain unclear. This study aims to investigate the role of INPP4A in macrophages in E-CRSwNP. METHODS: We assessed the expression of INPP4A in human and mouse nasal mucosal tissues via immunofluorescence staining. THP-1 cells were cultured and exposed to various cytokines to investigate the regulation of INPP4A expression and its functional role. Additionally, we established a murine nasal polyp (NP) model and administrated an INPP4A-overexpressing lentivirus evaluate its impact on NP. RESULTS: The percentage of INPP4A + CD68 + macrophages among total macrophages decreased in the E-CRSwNP group compared to the control and the non-eosinophilic CRSwNP (NE-CRSwNP) groups, exhibiting an inverse correlation with an increased percentage of CD206 + CD68 + M2 macrophages among total macrophages. Overexpression of INPP4A led to a reduced percentage of THP-1 cells polarizing towards the M2 phenotype, accompanied by decreased levels of associated chemotactic factors including CCL18, CCL22, CCL24, and CCL26. We also validated the involvement of the PI3K-AKT pathway in the function of INPP4A in vitro. Furthermore, INPP4A overexpression in the murine NP model resulted in the attenuation of eosinophilic inflammation in the nasal mucosa. CONCLUSIONS: INPP4A deficiency promotes macrophage polarization towards the M2 phenotype, leading to the secretion of chemokines that recruit eosinophils and Th2 cells, thereby amplifying eosinophilic inflammation in E-CRSwNP. INPP4A may exert a suppressive role in eosinophilic inflammation and could potentially serve as a novel therapeutic strategy.


Assuntos
Pólipos Nasais , Rinite , Rinossinusite , Sinusite , Humanos , Animais , Camundongos , Fosfatidilinositol 3-Quinases , Macrófagos , Eosinófilos , Inflamação/complicações , Monoéster Fosfórico Hidrolases/genética , Doença Crônica
4.
J Assist Reprod Genet ; 41(4): 1087-1096, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38321265

RESUMO

PURPOSE: Decreased ovarian reserve function is mainly characterized by female endocrine disorders and fertility decline. Follicular fluid (FF) exosomal microRNAs (miRNAs) have been shown to regulate the function of granulosa cells (GCs). The present study explored differentially expressed miRNAs (DEmiRNAs) in patients with diminished ovarian reserve (DOR). METHODS: FF was collected from 12 DOR patients and 12 healthy controls. DEmiRNAs between the two groups were identified and analyzed using high-throughput sequencing technology and validated by real-time quantitative PCR (RT-qPCR). RESULTS: A total of 592 DEmiRNAs were identified using high-throughput miRNA sequencing, of which 213 were significantly upregulated and 379 were significantly downregulated. The sequencing results were further validated by RT-qPCR. These DEmiRNA target genes were mainly involved in the cancer pathway, phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, regulation of actin cytoskeleton signaling pathway, and biological processes related to protein binding, nucleoplasm, cytoplasm, and cell membrane. CONCLUSION: FF exosomal miRNAs are significantly differentially expressed in DOR patients versus non-DOR patients, underscoring their crucial role in regulating the pathogenesis of DOR.


Assuntos
Exossomos , Líquido Folicular , MicroRNAs , Reserva Ovariana , Humanos , Feminino , Líquido Folicular/metabolismo , MicroRNAs/genética , Exossomos/genética , Exossomos/metabolismo , Reserva Ovariana/genética , Adulto , Células da Granulosa/metabolismo , Células da Granulosa/patologia , Infertilidade Feminina/genética , Infertilidade Feminina/metabolismo , Infertilidade Feminina/patologia , Transdução de Sinais/genética , Sequenciamento de Nucleotídeos em Larga Escala , Regulação da Expressão Gênica/genética , Perfilação da Expressão Gênica
5.
Alzheimers Dement ; 20(6): 4032-4042, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38700095

RESUMO

INTRODUCTION: Delirium is associated with mortality and new onset dementia, yet the underlying pathophysiology remains poorly understood. Development of imaging biomarkers has been difficult given the challenging nature of imaging delirious patients. Diffuse optical tomography (DOT) offers a promising approach for investigating delirium given its portability and three-dimensional capabilities. METHODS: Twenty-five delirious and matched non-delirious patients (n = 50) were examined using DOT, comparing cerebral oxygenation and functional connectivity in the prefrontal cortex during and after an episode of delirium. RESULTS: Total hemoglobin values were significantly decreased in the delirium group, even after delirium resolution. Functional connectivity between the dorsolateral prefrontal cortex and dorsomedial prefrontal cortex was strengthened post-resolution compared to during an episode; however, this relationship was still significantly weaker compared to controls. DISCUSSION: These findings highlight DOT's potential as an imaging biomarker to measure impaired cerebral oxygenation and functional dysconnectivity during and after delirium. Future studies should focus on the role of cerebral oxygenation in delirium pathogenesis and exploring the etiological link between delirium and dementias. HIGHLIGHTS: We developed a portable diffuse optical tomography (DOT) system for bedside three-dimensional functional neuroimaging to study delirium in the hospital. We implemented a novel DOT task-focused seed-based correlation analysis. DOT revealed decreased cerebral oxygenation and functional connectivity strength in the delirium group, even after resolution of delirium.


Assuntos
Delírio , Tomografia Óptica , Humanos , Tomografia Óptica/métodos , Delírio/diagnóstico por imagem , Delírio/fisiopatologia , Masculino , Feminino , Idoso , Córtex Pré-Frontal/diagnóstico por imagem , Hemodinâmica/fisiologia , Circulação Cerebrovascular/fisiologia , Mapeamento Encefálico , Pessoa de Meia-Idade
6.
Public Health Nurs ; 2024 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-39445623

RESUMO

OBJECTIVES: Compliance is crucial for patients to control and manage their high blood pressure. This study assesses the compliance levels of hypertensive patients in China and explores the factors influencing compliance. DESIGN: A descriptive, cross-sectional design was conducted. SAMPLE: A total of 371 hypertensive patients were recruited from six County hospitals and 12 township health centers in Zhejiang Province, China. MEASURE: Patient compliance was measured using the Hypertensive Patient Scale (CHPS). Independent-sample T-test or variance analysis was applied to analyze CHPS scores by sociodemographic factors, and linear regression was used to explore the significant correlates of the total CHPS score. RESULTS: The total score of CHPS was 50.18 ± 6.12. Among the seven domains, drug treatment and lifestyle had the highest and lowest average scores, 3.59 ± 0.87 and 2.74 ± 0.73, respectively. The total score of CHPS positively associated with age (ß = 0.075, p = 0.028), > 7 years of hypertension (ß = 1.896, p = 0.022; Ref: < 3 years), and negatively associated with males (ß = -2.224, p = 0.001; Ref: female) and rural area (ß = -2.008, p = 0.007; Ref: urban area). CONCLUSION: These findings highlight the importance of related measurements of the local "health-oriented" healthcare system. Primary health professionals should strengthen their health behavior intervention capacity and improve hypertension management among their patients.

7.
Angew Chem Int Ed Engl ; : e202410378, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39143026

RESUMO

Various isomers have been developed to regulate the morphology and reduce defects in state-of-the-art perovskite solar cells (PSCs). To insight the structure-function-effect correlations for the isomerization of thiourea derivatives on the performance of the PSCs, we developed two thiourea derivatives [(3,5-dichlorophenyl)amino]thiourea (AT) and N-(3,5-dichlorophenyl)hydrazinecarbothioamide (HB). Supported by experimental and calculated results, it was found that AT can bind with undercoordinated Pb2+ defect through synergistic interaction between N1 and C=S group with a defect formation energy of 1.818 eV, which is much higher than that from the synergistic interaction between two -NH- groups in HB and perovskite (1.015 eV). Moreover, the stronger interaction between AT and Pb2+ regulates the crystallization process of perovskite film to obtain a high-quality perovskite film with high crystallinity, large grain size, and low defect density. Consequently, the AT-treated FACsPbI3 device engenders an efficiency of 25.71 % (certified as 24.66 %), which is greatly higher than control (23.74 %) and HB-treated FACsPbI3 devices (25.05 %). The resultant device exhibits a remarkable stability for maintaining 91.0 % and 95.2 % of its initial efficiency after aging 2000 h in air condition or tracking at maximum power point for 1000 h, respectively.

8.
Dev Neurosci ; 45(1): 8-18, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36323241

RESUMO

Cerebral palsy (CP) is a motor and postural disorder syndrome caused by the nonprogressive dysfunction of the developing brain. Previous studies strongly indicated that the Nogo-A gene might be related to the pathogenesis of CP. The objective of this research was to explore the relationship between Nogo-A polymorphisms (rs1012603, rs12464595, and rs2864052) and CP in Southern China. The Hardy-Weinberg equilibrium (HWE) testing, allele and genotype frequencies analysis, and haplotype association analysis were applied to the genotyping of 592 CP children and 600 controls. The results showed that the allele and genotype frequencies of rs1012603 of CP group were significantly different from the control group. The haplotype "TTGGG" was significantly associated with an increased risk of CP. The allele frequencies of rs1012603 were significant differences between CP with spastic diplegia, female CP cases, and controls. Furthermore, significant differences in allele and genotype frequencies were also noticed between GMFCS I of CP and controls for rs1012603, and significant differences in allele and genotype frequencies were observed between the ADL (>9) of CP and controls for rs1012603 and rs12464595. This study showed that the SNPs rs1012603 of Nogo-A were significantly correlated with CP, and the correlations were also found in spastic diplegia, GMFCS I of CP, ADL (>9) of CP, and female subgroups, indicating that Nogo-A might mainly affect mild types of CP and there might be sex-related differences.


Assuntos
Paralisia Cerebral , Criança , Feminino , Humanos , Estudos de Casos e Controles , Paralisia Cerebral/genética , China , Proteínas Nogo/genética , Polimorfismo de Nucleotídeo Único/genética , Masculino
9.
Microb Ecol ; 86(3): 1829-1846, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36702929

RESUMO

The riparian zone ecosystems have greater energy flow and elemental cycling than adjacent terrestrial and aquatic ecosystems. Mineralization and nitrification are important initiating processes in the nitrogen cycle, but their distribution and activity under different environmental conditions in the riparian zone and the driving mechanisms are still not clear. We investigated the effects of environmental and microbial factors on mineralization and nitrification activities by analyzing the community of alkaline (apr) and neutral (npr) metallopeptidase, ammonia-oxidizing archaea (AOA), and bacteria (AOB) in soils and sediments under different land-use types in the riparian zone of Miyun Reservoir, as well as measuring potential nitrogen mineralization and ammonia oxidation rates (AOR). The results showed that the mineralization and nitrification activities of soils were greater than those of sediments. AOA and AOB dominate the ammonia oxidation activity of soil and sediment, respectively. NH4+ content was a key factor influencing the ecological niche differentiation between AOA and AOB. The high carbon and nitrogen content of the woodland significantly increased mineralization and nitrification activity. Microbial communities were significantly clustered in the woodland. The land-use type, not the flooding condition, determined the distribution of microbial community structure. The diversity of npr was significantly correlated with potential N mineralization rates, while the transcript abundance of AOA was significantly correlated with ammonia oxidation rates. Our study suggests that environmental changes regulate the distribution and activity of mineralization and nitrification processes in the reservoir riparian zone by affecting the transcript abundance, diversity and community structure of the microbial functional genes.


Assuntos
Microbiota , Nitrificação , Amônia , Oxirredução , Microbiologia do Solo , Archaea/genética , Nitrogênio , Solo/química , Filogenia
10.
Brain ; 145(1): 119-141, 2022 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-34077496

RESUMO

Cerebral palsy is the most prevalent physical disability in children; however, its inherent molecular mechanisms remain unclear. In the present study, we performed in-depth clinical and molecular analysis on 120 idiopathic cerebral palsy families, and identified underlying detrimental genetic variants in 45% of these patients. In addition to germline variants, we found disease-related postzygotic mutations in ∼6.7% of cerebral palsy patients. We found that patients with more severe motor impairments or a comorbidity of intellectual disability had a significantly higher chance of harbouring disease-related variants. By a compilation of 114 known cerebral-palsy-related genes, we identified characteristic features in terms of inheritance and function, from which we proposed a dichotomous classification system according to the expression patterns of these genes and associated cognitive impairments. In two patients with both cerebral palsy and intellectual disability, we revealed that the defective TYW1, a tRNA hypermodification enzyme, caused primary microcephaly and problems in motion and cognition by hindering neuronal proliferation and migration. Furthermore, we developed an algorithm and demonstrated in mouse brains that this malfunctioning hypermodification specifically perturbed the translation of a subset of proteins involved in cell cycling. This finding provided a novel and interesting mechanism for congenital microcephaly. In another cerebral palsy patient with normal intelligence, we identified a mitochondrial enzyme GPAM, the hypomorphic form of which led to hypomyelination of the corticospinal tract in both human and mouse models. In addition, we confirmed that the aberrant Gpam in mice perturbed the lipid metabolism in astrocytes, resulting in suppressed astrocytic proliferation and a shortage of lipid contents supplied for oligodendrocytic myelination. Taken together, our findings elucidate novel aspects of the aetiology of cerebral palsy and provide insights for future therapeutic strategies.


Assuntos
Paralisia Cerebral , Deficiência Intelectual , Animais , Paralisia Cerebral/genética , Cognição , Estudos de Coortes , Comorbidade , Humanos , Deficiência Intelectual/complicações , Deficiência Intelectual/genética , Camundongos
11.
Foodborne Pathog Dis ; 20(8): 351-357, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37471209

RESUMO

To conduct a study that examined the molecular epidemiology and pathogenesis of Salmonella Senftenberg isolates associated with an outbreak of foodborne disease in Guizhou Province and to provide a reference basis for the traceability of foodborne salmonellosis outbreaks and clinical diagnosis and treatment in the province. Fourteen strains of suspected Salmonella isolated from patient stool and food samples were used for pathogenic identification and serotyping by biochemical and mass spectrometry methods. Fourteen types of antibiotics were tested for drug sensitivity by the microbroth dilution method, and molecular typing was performed by pulsed-field gel electrophoresis (PFGE) and whole genome sequencing (WGS). After the sequencing data were spliced by SPAdes, the gene protein sequences were compared with the Comprehensive Antibiotic Research Database and Virulence Factor Database, drug resistance and virulence genes were predicted, and whole genome multilocus sequence typing (wgMLST) was performed. The results were compared with those for Salmonella strains of the same serotype from the past 5 years in China detailed on the TraNet website. All 14 strains were identified as Salmonella Senftenberg (with the antigenic formula 1,3,19:g,s,t:-), and in the PFGE cluster tree, the strains were divided into two band types, with a similarity of 88.9%. The 14 strains were sensitive to the 14 antibiotics. WGS analysis showed that the 14 strains carried the same drug resistance and virulence genes and that all strains carried 3 aminoglycoside and lipopeptide drug resistance genes, including 114 virulence genes. The wgMLST results showed that the strains were distributed on the same small branch as those obtained from previous outbreaks of infection in Tianjin and Jilin. Salmonella Senftenberg, which caused the outbreak, carries a variety of virulence genes, which suggests that the strain is highly pathogenic. These pathogenic bacteria may be associated with the Salmonella strain in Tianjin, Jilin, and other places and have caused foodborne disease outbreaks as a result of imported contamination.


Assuntos
Doenças Transmitidas por Alimentos , Infecções por Salmonella , Humanos , Doenças Transmitidas por Alimentos/epidemiologia , Doenças Transmitidas por Alimentos/microbiologia , Infecções por Salmonella/microbiologia , Surtos de Doenças , Salmonella/genética , Antibacterianos/farmacologia , Eletroforese em Gel de Campo Pulsado
12.
Int J Mol Sci ; 24(9)2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37176151

RESUMO

Chronic rhinosinusitis with nasal polyps (CRSwNP) has long been considered a benign, chronic inflammatory, and hyperplastic disease. Recent studies have shown that autoimmune-related mechanisms are involved in the pathology of nasal polyps. Activated plasma cells, eosinophils, basophils, innate type 2 lymphocytes, mast cells, and proinflammatory cytokine in polyp tissue indicate the mobilization of innate and adaptive immune pathways during polyp formation. The discovery of a series of autoantibodies further supports the autoimmune nature of nasal polyps. Local homeostasis dysregulation, infection, and chronic inflammation may trigger autoimmunity through several mechanisms, including autoantigens overproduction, microbial translocation, molecular mimicry, superantigens, activation or inhibition of receptors, bystander activation, dysregulation of Toll-Like Receptors (TLRs), epitope spreading, autoantigens complementarity. In this paper, we elaborated on the microbiome-mediated mechanism, abnormal host immunity, and genetic changes to update the role of autoimmunity in the pathogenesis of chronic rhinosinusitis with nasal polyps.


Assuntos
Pólipos Nasais , Rinite , Sinusite , Humanos , Pólipos Nasais/patologia , Autoimunidade , Inflamação/patologia , Sinusite/metabolismo , Doença Crônica , Plasmócitos/metabolismo , Autoantígenos , Rinite/patologia
13.
Int J Mol Sci ; 24(16)2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37628813

RESUMO

Liver cancer is one of the most lethal malignant cancers worldwide. However, the therapeutic options for advanced liver cancers are limited and reveal scant efficacy. The current study investigated the effects of nivolumab (Niv) and escitalopram oxalate (Esc) in combination on proliferation of liver cancer cells both in vitro and in vivo. Significantly decreased viability of HepG2 cells that were treated with Esc or Niv was observed in a dose-dependent manner at 24 h, 48 h, and 72 h. Administration of Esc (50 µM) + Niv (20 µM), Esc (75 µM) + Niv (5 µM), and Esc (75 µM) + Niv (20 µM) over 24 h exhibited synergistic effects, inhibiting the survival of HepG2 cells. Additionally, treatment with Esc (50 µM) + Niv (1 µM), Esc (50 µM) + Niv (20 µM), and Esc (75 µM) + Niv (20 µM) over 48 h exhibited synergistic effects, inhibiting the survival of HepG2 cells. Finally, treatment with Esc (50 µM) + Niv (1 µM), Esc (50 µM) + Niv (20 µM), and Esc (75 µM) + Niv (20 µM) for 72 h exhibited synergistic effects, inhibiting HepG2 survival. Com-pared with controls, HepG2 cells treated with Esc (50 µM) + Niv (20 µM) exhibited significantly increased sub-G1 portion and annexin-V signals. In a xenograft animal study, Niv (6.66 mg/kg) + Esc (2.5 mg/kg) significantly suppressed the growth of xenograft HepG2 tumors in nude mice. This study reports for the first time the synergistic effects of combined administration of Niv and Esc for inhibiting HepG2 cell proliferation, which may provide an alternative option for liver cancer treatment.


Assuntos
Escitalopram , Neoplasias Hepáticas , Humanos , Animais , Camundongos , Nivolumabe/farmacologia , Camundongos Nus , Apoptose , Neoplasias Hepáticas/tratamento farmacológico
14.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 52(1): 33-45, 2023 Feb 25.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-37283116

RESUMO

OBJECTIVES: To explore the effect and mechanism of Chinese medicine Bushen Huatan formula in treatment of polycystic ovary syndrome (PCOS). METHODS: Twenty-four SPF female C57BL/6J mice were randomly divided into 3 groups with 8 animals in each group. Control group was given drinking water ad libitum; PCOS was induced by giving letrozole gavage and high-fat diet in model group and treatment group; treatment group received Bushen Huatan formula suspension for 35 d. The sex hormone levels of mice were detected by enzyme-linked immunosorbent assay. Ovary morphology was observed under light microscope after hematoxylin and eosin staining. The feces in the colon of mice were collected, and the gut microbiota was detected by 16S rRNA sequencing. The short chain fatty acids were detected by gas chromatography-mas spectrometry. The expression of peroxisome proliferator activated receptor (PPARγ) was detected by immunohistochemistry. The mRNA expression of mucin-2, occludin-1, tight junction protein zonula occludens 1 (ZO-1) and PPARγ in intestinal epithelium were detected by realtime RT-PCR. The expression of inducible nitric oxide synthase (iNOS) and PPARγ was detected by Western blotting. RESULTS: Compared with the control group, the body weight, serum levels of follicle stimulating hormone, luteinizing hormone and testosterone in the model group were increased, and serum levels of estradiol were decreased (all P<0.01); the ovarian structure under light microscope was consistent with the characteristics of PCOS. Compared with the model group, the serum levels of sex hormone and ovarian structure in treatment group were improved. The overall structure of gut microbiota in PCOS model mice changed. Compared with control group, there were significantly reduced abundance of Firmicutes, and increased abundance of Verrucomicrobia, Proteobacteria and Actinobacteria inthe model group at phylum level (all P<0.05); there were significantly reduced abundance of Lactobacillus, and increased abundance of Akkermansia, Lachnoclostridium, Lactococcus and Eubacterium_coprostanoligenes at genus level (all P<0.05). The disordered condition of gut microbiota was significantly improved in treatment group. Compared with control group, the contents of acetic acid, propionic acid and butyric acid in feces of model group were significantly decreased (all P<0.05); while the contents of propionic acid and butyric acid in treatment group were significantly increased compared with model control group (both P<0.05). Compared with control group, the mRNA expression of ZO-1 and protein expression of iNOS in model group were significantly increased, and the protein expression of PPARγ and the mRNA expressions of mucin-2 and occludin-1 were significantly decreased (all P<0.05). Compared with model group, the mRNA expression of ZO-1 and protein expression of iNOS in treatment group were decreased, and the protein expression of PPARγ and the mRNA expressions of mucin-2 and occludin-1 were increased. CONCLUSIONS: PCOS induced by letrozole high-fat diet induces microflora imbalance in mice. Chinese medicine Bushen Huatan formula may increase the level of short chain fatty acid by regulating gut microbiota, thereby activating the intestinal PPARγ pathway and improving intestinal barrier function to act as a cure for PCOS.


Assuntos
Microbioma Gastrointestinal , Síndrome do Ovário Policístico , Humanos , Camundongos , Feminino , Animais , Síndrome do Ovário Policístico/tratamento farmacológico , PPAR gama/farmacologia , Propionatos/farmacologia , Mucina-2 , Letrozol , RNA Ribossômico 16S , Medicina Tradicional Chinesa , Ocludina/farmacologia , Camundongos Endogâmicos C57BL , Hormônios Esteroides Gonadais/farmacologia , Butiratos/farmacologia , RNA Mensageiro
15.
Arch Microbiol ; 204(8): 475, 2022 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-35829834

RESUMO

A Gram-negative, aerobic, chemoheterotrophic, rod-shaped, and motile bacterium, designated as LST-1T, was isolated from wild Stevia rebaudiana Bertoni and subjected to a polyphasic taxonomic analysis. The LST-1 strain grew optimally at 37 °C and pH 6.0-7.0 in the presence of 0.5% (w/v) NaCl. Phylogenetic analysis based on the 16S rDNA sequence indicated that LST-1 is closely related to Lelliottia jeotgali PFL01T (99.85%), Lelliottia nimipressuralis LMG10245T (98.82%), and Lelliottia amnigena LMG2784T (98.54%). Multi-locus sequence typing of concatenated partial atpD, infB, gyrB, and rpoB genes was performed to improve the resolution, and clear distinctions between the closest related type strains were observed. The results of average nucleotide identify analyses and DNA-DNA hybridization with four species (16S rDNA similarity > 98.65%) were less than 90 and 40%, respectively, verifying the distinct characteristics from other species of Lelliottia. The cellular fatty acid profile of the strain consisted of C16:0, Summed Feature3, and Summed Feature8 (possibly 16:1 w6c/16:1 w7c and 18:1 w6c) as major components. The major polar lipids included phosphatidylethanolamine, phosphatidylglycerol, an aminophospholipid, three non-characteristic phospholipids, and a non-characteristic lipid. The genome of LST-1T was 4,611,055 bp in size, with a G + C content of 55.02%. The unique combination of several phenotypic, chemotaxonomic, and genomic characteristics proved that strain LST-1T belongs to a novel species, for which the name Lelliottia steviae sp. nov. is proposed. The type strain is LST-1T (= CGMCC 1.19175T = JCM 34938T).Repositories: The genbank accession numbers for the 16S rRNA gene and genome sequences of strain LST-1T are MZ497264 and CP063663, respectively.


Assuntos
Stevia , Técnicas de Tipagem Bacteriana , DNA Bacteriano/genética , DNA Ribossômico , Ácidos Graxos/análise , Tipagem de Sequências Multilocus , Hibridização de Ácido Nucleico , Fosfolipídeos/química , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Stevia/genética
16.
J Appl Microbiol ; 132(3): 1887-1899, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34606155

RESUMO

AIMS: The present study aimed to specifically transform stevioside (ST) into rubusoside (RS) through bioconversion with high efficiency, seeking to endow steviol glycosides (SGs) with subtle flavours for commercial acceptability. METHODS AND RESULTS: An endophytic bacterium named Lelliottia LST-1 was screened and confirmed to specifically convert ST into RS, reaching a conversion rate of 75.4% after response surface optimization. Phylogenetic analysis combined with complete genome sequencing demonstrated that LST-1 was also presumed to be a new species. To further explore the principle and process of biological transformation, the potential beta-glucosidases GH3-1, GH3-2, GH3-3 and GH3-4 were expressed, purified and reacted with SGs. High-performance liquid chromatography revealed that all enzymes hydrolysed ST and generated RS, but substrate specificity analysis indicated that GH3-2 had the highest substrate specificity towards STs and the highest enzyme activity. CONCLUSION: The potential ß-glucosidase GH3-2 in Lelliottia sp. LST-1 was found to specifically and efficiently convert ST to RS. SIGNIFICANCE AND IMPACT OF STUDY: The efficient biotransformation of ST into RS will be beneficial to its large-scale production and extensive application in the food and pharmaceutical industries.


Assuntos
Diterpenos do Tipo Caurano , Diterpenos do Tipo Caurano/metabolismo , Glucosídeos/metabolismo , Filogenia
17.
Appl Opt ; 61(5): 1254-1260, 2022 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-35201178

RESUMO

We propose an all-media photonic crystal (PC) composed of isosceles triangle dielectric cylinders that realizes the topological phase transition by simply rotating the isosceles triangular dielectric cylinders. Additionally, the topological phase transition is closely linked with the size parameters and rotation angle of the isosceles triangle. The topological boundary states with lossless transmission are constructed on the interface of two different topological structures, and the optical quantum spin Hall effect is simulated. Further, we verified that the boundary state is unidirectional and immune to disorder, cavity, and sharp bend defects. By rotating the angle of the triangle to control the transmission path of the pseudo-spin state, we realize diverse transport pathways of light, such as the "straight line" shape, "Z" shape, "U" shape, and "Y" shape. This topological system shows a higher degree of freedom, which can promote the research on topological boundary states and the development of topological insulators in practical applications.

18.
J Basic Microbiol ; 62(10): 1179-1192, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35730619

RESUMO

As a transitional boundary between terrestrial and aquatic ecosystems, the riparian zone is considered a hotspot for N2 O production because of the active nitrogen processes. Ammoxidation is an important microbial pathway for N2 O production, but the distribution of ammonia oxidizers under different land-use types in the reservoir riparian zone and what role they played in N2 O emissions are still not clear. We investigated spatiotemporal distributions of ammonia-oxidizing archaea (AOA) and bacteria (AOB) and their role in N2 O emissions in different land-use types along the riparian zone of Miyun Reservoir: grassland, sparse woods, and woodland. We found significant differences in both AOA abundance and AOB diversity indices among land-use types. AOA and AOB communities were significantly separated by different land-use types. The main drivers to determine the distribution of ammonia-oxidizing microbial community were soil water content, NH4 + , NO3 - , and total organic carbon (TOC). In situ N2 O flux was highest in woodland with a mean value of 12.28 µg/m2 ·h, and it was substantially decreased by 121% and 123% in sparse woods and grassland. TOC content was decreased by 20% and 40% in sparse woods and grassland compared with woodland, and it was significantly positively correlated with in situ N2 O flux. Meanwhile, AOB diversity indices were significantly correlated with in situ N2 O flux. These results showed that the heterogeneity of physicochemical properties among different land-use types affected the community of AOA and AOB in riparian zones. AOB not AOA, and community diversity rather than abundance, played a role in N2 O emissions.


Assuntos
Amônia , Microbiota , Amônia/metabolismo , Archaea/metabolismo , Carbono/metabolismo , Nitrificação , Nitrogênio/metabolismo , Oxirredução , Filogenia , Solo/química , Microbiologia do Solo , Água
19.
Sensors (Basel) ; 22(22)2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36433319

RESUMO

In comparison with traditional space infrared spectroscopy technology, the interference signals of a large focal plane array (FPA) can be used to obtain spectra over a larger area range and rapidly achieve large-scale coverage of hyperspectral remote sensing. However, the low signal-to-noise ratio of the interference signals limits the application of spectral data, especially when atmospheric detection occurs in the long-wavelength infrared (LWIR) band. In this paper, we construct an LWIR hyperspectral system of a Fourier transform spectrometer composed of a HgCdTe photovoltaic IR FPA and a Michelson interferometer. The LWIR interference signals are obtained by a high-frequency oversampling technique. We use the Kalman filter (KF) and its improved weighted adaptive Kalman filter (WAKF) to reduce the noise of multiple measured data of each pixel. The effect of overshoot and ringing artifacts on the objective signals is reduced by the WAKF. The applicability is studied by the interference signals from the different sampling frequencies and different pixels. The effectiveness is also verified by comparing the spectra of denoised interferograms with the reference spectrum. The experimental results show that the WAKF algorithm has excellent noise suppression, and the standard deviation of the interferogram can be reduced by 39.50% compared with that of KF. The WAKF is more advantageous in improving the signal-to-noise ratio of the interferogram and spectra. The results indicate that our system can be applied to atmospheric vertical detection and hyperspectral remote sensing over large area ranges because our denoised technique is suitable for large LWIR FPA.

20.
Int J Mol Sci ; 23(24)2022 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36555820

RESUMO

Owing to its high recurrence rate, gastric cancer (GC) is the leading cause of tumor-related deaths worldwide. Besides surgical treatment, chemotherapy is the most commonly used treatment against GC. However, the adverse events associated with chemotherapy use limit its effectiveness in GC treatment. In this study, we investigated the effects of using combinations of low-dose 5-fluorouracil (5-FU; 0.001 and 0.01 mM) with different concentrations of escitalopram oxalate (0.01, 0.02, 0.06, and 0.2 mM) to evaluate whether the assessed combination would have synergistic effects on SNU-1 cell survival. 5-FU (0.01 mM) + escitalopram oxalate (0.02 mM) and 5-FU (0.01 mM) + escitalopram oxalate (0.06 mM) administered over 24 h showed synergistic effects on the inhibition of SNU-1 cell proliferation. Moreover, 5-FU (0.001 mM) + escitalopram oxalate (0.02 or 0.06 mM) and 5-FU (0.01 mM) + escitalopram oxalate (0.02, 0.06, or 0.2 mM) administered over 48 h showed synergistic effects on the inhibition of SNU-1 cell proliferation. Compared with controls, SNU-1 cells treated with 5-FU (0.01 mM) + escitalopram oxalate (0.02 mM) exhibited significantly increased levels of annexin V staining, reactive oxygen species, cleaved poly (ADP-ribose) polymerase, and caspase-3 proteins. Furthermore, 5-FU (12 mg/kg) + escitalopram oxalate (12.5 mg/kg) significantly attenuated xenograft SNU-1 cell proliferation in nude mice. Our study is the first to report the synergistic effects of the combinational use of low-dose 5-FU and escitalopram oxalate on inhibiting SNU-1 cell proliferation. These findings may be indicative of an alternative option for GC treatment.


Assuntos
Fluoruracila , Neoplasias Gástricas , Animais , Camundongos , Humanos , Fluoruracila/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Escitalopram , Camundongos Nus , Apoptose , Proliferação de Células , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
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