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1.
J Periodontal Res ; 59(3): 421-430, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38282328

RESUMO

BACKGROUND AND OBJECTIVES: Vitamin D binding protein (DBP) is biosynthesised in the liver and is predominantly expressed in serum. Its primary role centres on facilitating the systemic transportation of vitamin D and its metabolites, notably 25-hydroxyvitamin D, to specific target tissues where vitamin D exerts its biological functions. Due to the paucity of studies, it is unclear whether there is an association between DBP and periodontal status and thus its potential use as a diagnostic biomarker. Therefore, the aim of the systematic review is to investigate the association between DBP in periodontal disease. METHODS: Two independent reviewers (YD and RG) performed a systematic literature search of English publications using several databases including MEDLINE (OVID interface, 1946 onwards), EMBASE (OVID interface, 1974 onwards), and Global Health (OVID interface, 1973 onwards). This search strategy enabled the identification of relevant publications and the development of a comprehensive library of studies. Studies were included based on previously agreed eligibility criteria. Of the eight studies included as part of this systematic review, seven were case-control studies and one was a cross-sectional study. The quality assessment was based on the Newcastle-Ottawa Scale (NOS) for case-control studies and the modified NOS for the cross-sectional study. RESULTS: The NOS quality assessment was 'favorable' for 6 included case control studies; and 'fair' for one study. The modified NOS quality assessment for the single cross-sectional study demonstrated a medium risk of bias. The results of the majority of the included studies indicated a statistically significant higher concentration of DBP levels in individuals with periodontitis in comparison to those who were periodontally healthy. This trend held true irrespective of the sampling method employed for the assessment of DBP concentration. CONCLUSION: The results summarised in this systematic review indicate a positive association between DBP and periodontitis. Nonetheless, there is a need for longitudinal, prospective trials, to confirm the use of DBP as a potential biomarker for the diagnosis of periodontitis.


Assuntos
Proteína de Ligação a Vitamina D , Humanos , Proteína de Ligação a Vitamina D/sangue , Proteína de Ligação a Vitamina D/metabolismo , Biomarcadores/sangue , Doenças Periodontais/metabolismo , Vitamina D/sangue , Vitamina D/metabolismo
2.
Arterioscler Thromb Vasc Biol ; 41(3): 1032-1046, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33380171

RESUMO

Innate immune cells can develop exacerbated immunologic response and long-term inflammatory phenotype following brief exposure to endogenous or exogenous insults, which leads to an altered response towards a second challenge after the return to a nonactivated state. This phenomenon is known as trained immunity (TI). TI is not only important for host defense and vaccine response but also for chronic inflammations such as cardiovascular and metabolic diseases such as atherosclerosis. TI can occur in innate immune cells such as monocytes/macrophages, natural killer cells, endothelial cells (ECs), and nonimmune cells, such as fibroblast. In this brief review, we analyze the significance of TI in ECs, which are also considered as innate immune cells in addition to macrophages. TI can be induced by a variety of stimuli, including lipopolysaccharides, BCG (bacillus Calmette-Guerin), and oxLDL (oxidized low-density lipoprotein), which are defined as risk factors for cardiovascular and metabolic diseases. Furthermore, TI in ECs is functional for inflammation effectiveness and transition to chronic inflammation. Rewiring of cellular metabolism of the trained cells takes place during induction of TI, including increased glycolysis, glutaminolysis, increased accumulation of tricarboxylic acid cycle metabolites and acetyl-coenzyme A production, as well as increased mevalonate synthesis. Subsequently, this leads to epigenetic remodeling, resulting in important changes in chromatin architecture that enables increased gene transcription and enhanced proinflammatory immune response. However, TI pathways and inflammatory pathways are separated to ensure memory stays when inflammation undergoes resolution. Additionally, reactive oxygen species play context-dependent roles in TI. Therefore, TI plays significant roles in EC and macrophage pathology and chronic inflammation. However, further characterization of TI in ECs and macrophages would provide novel insights into cardiovascular disease pathogenesis and new therapeutic targets. Graphic Abstract: A graphic abstract is available for this article.


Assuntos
Células Endoteliais/imunologia , Macrófagos/imunologia , Animais , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/imunologia , Citocinas/biossíntese , Metabolismo Energético , Epigênese Genética , Humanos , Imunidade Inata , Memória Imunológica , Infecções/etiologia , Infecções/imunologia , Inflamação/etiologia , Inflamação/imunologia , Doenças Metabólicas/etiologia , Doenças Metabólicas/imunologia , Redes e Vias Metabólicas/imunologia , Modelos Imunológicos , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/imunologia , Fatores de Risco
3.
Cereb Cortex ; 28(3): 974-987, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28108498

RESUMO

The newly evolved circuits in layer III of primate dorsolateral prefrontal cortex (dlPFC) generate the neural representations that subserve working memory. These circuits are weakened by increased cAMP-K+ channel signaling, and are a focus of pathology in schizophrenia, aging, and Alzheimer's disease. Cognitive deficits in these disorders are increasingly associated with insults to mGluR3 metabotropic glutamate receptors, while reductions in mGluR2 appear protective. This has been perplexing, as mGluR3 has been considered glial receptors, and mGluR2 and mGluR3 have been thought to have similar functions, reducing glutamate transmission. We have discovered that, in addition to their astrocytic expression, mGluR3 is concentrated postsynaptically in spine synapses of layer III dlPFC, positioned to strengthen connectivity by inhibiting postsynaptic cAMP-K+ channel actions. In contrast, mGluR2 is principally presynaptic as expected, with only a minor postsynaptic component. Functionally, increase in the endogenous mGluR3 agonist, N-acetylaspartylglutamate, markedly enhanced dlPFC Delay cell firing during a working memory task via inhibition of cAMP signaling, while the mGluR2 positive allosteric modulator, BINA, produced an inverted-U dose-response on dlPFC Delay cell firing and working memory performance. These data illuminate why insults to mGluR3 would erode cognitive abilities, and support mGluR3 as a novel therapeutic target for higher cognitive disorders.


Assuntos
Memória de Curto Prazo/fisiologia , Neurônios/citologia , Densidade Pós-Sináptica/metabolismo , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/fisiologia , Receptores de Glutamato Metabotrópico/metabolismo , Potenciais de Ação/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Fármacos Atuantes sobre Aminoácidos Excitatórios/farmacologia , Movimentos Oculares/efeitos dos fármacos , Movimentos Oculares/fisiologia , Feminino , Processamento de Imagem Assistida por Computador , Macaca mulatta , Imageamento por Ressonância Magnética , Masculino , Memória de Curto Prazo/efeitos dos fármacos , Neurônios/metabolismo , Densidade Pós-Sináptica/ultraestrutura , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/ultraestrutura , Ratos , Receptores de Glutamato Metabotrópico/ultraestrutura , Aprendizagem Espacial/efeitos dos fármacos , Frações Subcelulares/efeitos dos fármacos
4.
Nature ; 476(7359): 210-3, 2011 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-21796118

RESUMO

Many of the cognitive deficits of normal ageing (forgetfulness, distractibility, inflexibility and impaired executive functions) involve prefrontal cortex (PFC) dysfunction. The PFC guides behaviour and thought using working memory, which are essential functions in the information age. Many PFC neurons hold information in working memory through excitatory networks that can maintain persistent neuronal firing in the absence of external stimulation. This fragile process is highly dependent on the neurochemical environment. For example, elevated cyclic-AMP signalling reduces persistent firing by opening HCN and KCNQ potassium channels. It is not known if molecular changes associated with normal ageing alter the physiological properties of PFC neurons during working memory, as there have been no in vivo recordings, to our knowledge, from PFC neurons of aged monkeys. Here we characterize the first recordings of this kind, revealing a marked loss of PFC persistent firing with advancing age that can be rescued by restoring an optimal neurochemical environment. Recordings showed an age-related decline in the firing rate of DELAY neurons, whereas the firing of CUE neurons remained unchanged with age. The memory-related firing of aged DELAY neurons was partially restored to more youthful levels by inhibiting cAMP signalling, or by blocking HCN or KCNQ channels. These findings reveal the cellular basis of age-related cognitive decline in dorsolateral PFC, and demonstrate that physiological integrity can be rescued by addressing the molecular needs of PFC circuits.


Assuntos
Envelhecimento/fisiologia , Macaca mulatta/fisiologia , Memória de Curto Prazo/fisiologia , Modelos Neurológicos , Córtex Pré-Frontal/citologia , Córtex Pré-Frontal/fisiologia , Potenciais de Ação/efeitos dos fármacos , Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Envelhecimento/efeitos dos fármacos , Envelhecimento/patologia , Animais , Melhoramento Biomédico , Sinais (Psicologia) , AMP Cíclico/antagonistas & inibidores , AMP Cíclico/metabolismo , Canais de Cátion Regulados por Nucleotídeos Cíclicos/antagonistas & inibidores , Canais de Cátion Regulados por Nucleotídeos Cíclicos/metabolismo , Guanfacina/farmacologia , Humanos , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização , Canais de Potássio KCNQ/antagonistas & inibidores , Canais de Potássio KCNQ/metabolismo , Masculino , Memória de Curto Prazo/efeitos dos fármacos , Vias Neurais/efeitos dos fármacos , Bloqueadores dos Canais de Potássio/farmacologia , Canais de Potássio/metabolismo , Córtex Pré-Frontal/patologia , Córtex Pré-Frontal/fisiopatologia , Receptores Adrenérgicos alfa 2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo
5.
Proc Natl Acad Sci U S A ; 111(13): 5036-41, 2014 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-24707050

RESUMO

The pattern of neurodegeneration in Alzheimer's disease (AD) is very distinctive: neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau selectively affect pyramidal neurons of the aging association cortex that interconnect extensively through glutamate synapses on dendritic spines. In contrast, primary sensory cortices have few NFTs, even in late-stage disease. Understanding this selective vulnerability, and why advancing age is such a high risk factor for the degenerative process, may help to reveal disease etiology and provide targets for intervention. Our study has revealed age-related increase in cAMP-dependent protein kinase (PKA) phosphorylation of tau at serine 214 (pS214-tau) in monkey dorsolateral prefrontal association cortex (dlPFC), which specifically targets spine synapses and the Ca(2+)-storing spine apparatus. This increase is mirrored by loss of phosphodiesterase 4A from the spine apparatus, consistent with increase in cAMP-Ca(2+) signaling in aging spines. Phosphorylated tau was not detected in primary visual cortex, similar to the pattern observed in AD. We also report electron microscopic evidence of previously unidentified vesicular trafficking of phosphorylated tau in normal association cortex--in axons in young dlPFC vs. in spines in aged dlPFC--consistent with the transneuronal lesion spread reported in genetic rodent models. pS214-Tau was not observed in normal aged mice, suggesting that it arises with the evolutionary expansion of corticocortical connections in primates, crossing the threshold into NFTs and degeneration in humans. Thus, the cAMP-Ca(2+) signaling mechanisms, needed for flexibly modulating network strength in young association cortex, confer vulnerability to degeneration when dysregulated with advancing age.


Assuntos
Envelhecimento/patologia , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Degeneração Neural/enzimologia , Degeneração Neural/patologia , Córtex Pré-Frontal/enzimologia , Córtex Pré-Frontal/patologia , Proteínas tau/metabolismo , Animais , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Espinhas Dendríticas/metabolismo , Espinhas Dendríticas/ultraestrutura , Macaca mulatta , Camundongos , Modelos Biológicos , Fosforilação , Transporte Proteico , Vesículas Transportadoras/metabolismo
6.
Proc Natl Acad Sci U S A ; 110(29): 12078-83, 2013 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-23818597

RESUMO

The cognitive function of the highly evolved dorsolateral prefrontal cortex (dlPFC) is greatly influenced by arousal state, and is gravely afflicted in disorders such as schizophrenia, where there are genetic insults in α7 nicotinic acetylcholine receptors (α7-nAChRs). A recent behavioral study indicates that ACh depletion from dlPFC markedly impairs working memory [Croxson PL, Kyriazis DA, Baxter MG (2011) Nat Neurosci 14(12):1510-1512]; however, little is known about how α7-nAChRs influence dlPFC cognitive circuits. Goldman-Rakic [Goldman-Rakic (1995) Neuron 14(3):477-485] discovered the circuit basis for working memory, whereby dlPFC pyramidal cells excite each other through glutamatergic NMDA receptor synapses to generate persistent network firing in the absence of sensory stimulation. Here we explore α7-nAChR localization and actions in primate dlPFC and find that they are enriched in glutamate network synapses, where they are essential for dlPFC persistent firing, with permissive effects on NMDA receptor actions. Blockade of α7-nAChRs markedly reduced, whereas low-dose stimulation selectively enhanced, neuronal representations of visual space. These findings in dlPFC contrast with the primary visual cortex, where nAChR blockade had no effect on neuronal firing [Herrero JL, et al. (2008) Nature 454(7208):1110-1114]. We additionally show that α7-nAChR stimulation is needed for NMDA actions, suggesting that it is key for the engagement of dlPFC circuits. As ACh is released in cortex during waking but not during deep sleep, these findings may explain how ACh shapes differing mental states during wakefulness vs. sleep. The results also explain why genetic insults to α7-nAChR would profoundly disrupt cognitive experience in patients with schizophrenia.


Assuntos
Cognição/fisiologia , N-Metilaspartato/metabolismo , Córtex Pré-Frontal/fisiologia , Receptores Nicotínicos/metabolismo , Sinapses/fisiologia , Percepção Visual/fisiologia , Acetilcolina/metabolismo , Aconitina/análogos & derivados , Análise de Variância , Animais , Compostos Bicíclicos Heterocíclicos com Pontes , Agonistas Colinérgicos/administração & dosagem , Agonistas Colinérgicos/farmacologia , Antagonistas Colinérgicos/administração & dosagem , Antagonistas Colinérgicos/farmacologia , Feminino , Iontoforese , Macaca mulatta , Masculino , Mecamilamina , Microscopia Imunoeletrônica , Fenóis , Piperidinas , Córtex Pré-Frontal/metabolismo , Quinuclidinas , Comportamento Espacial/efeitos dos fármacos , Receptor Nicotínico de Acetilcolina alfa7
7.
Molecules ; 21(1): 86, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26784154

RESUMO

A new abeo-abietane diterpenoid, 12-methoxy-6,11,14,16-tetrahydroxy-17(15→16)-abeo-5,8,11,13-abietatetraen-3,7-dione (8), was isolated from the hydroalcoholic extract of the herb of Clerodendrum kiangsiense along with seven known diterpenoids (1-7). Their structures were identified on the basis of spectroscopic analyses including two-dimensional NMR and comparison with literature data. All of these compounds were evaluated for their cytotoxic activities against the growth of human cancer cells lines HL-60, SMMC-7721, A-549 and MCF-7 by the MTT assay. The results showed that cryptojaponol (4), fortunin E (6) and 8 exhibited significant cytotoxicity against four human cancer cell lines.


Assuntos
Abietanos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Clerodendrum/química , Diterpenos/farmacologia , Abietanos/química , Abietanos/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Diterpenos/química , Diterpenos/isolamento & purificação , Células HL-60 , Humanos , Concentração Inibidora 50 , Células MCF-7 , Caules de Planta/química , Relação Estrutura-Atividade
8.
Pak J Med Sci ; 32(6): 1547-1552, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28083062

RESUMO

OBJECTIVE: To identify the association between radiation dose volume and acute hematological toxicity (HT) in postoperative gynecological cancer patients receiving whole pelvic radiotherapy (RT) or intensity-modulated RT (IMRT), a principal component regression model was used to calculate HT. METHODS: Women (n=100) receiving with or without chemotherapy RT were retrospectively analyzed, 52 of whom received chemotherapy (paclitaxel and nedaplatin). The pelvis and lumbar vertebrae, defined as the prolong-pelvic bone marrow, were divided into the (1) combined ilium, ischium and pubis and the (2) lumbar vertebrae and the sacrum. The V5-V40 of subsides was calculated. The complete blood counts were recorded weekly. The principal component analysis was performed on volumes which generated the principal components (PCs), followed by using a logistic regression model. RESULTS: Forty-seven patients presented with grade 2-3 HT during RT. Chemotherapy increased the incidence of HT compared with RT alone (70.21% vs. 29.79%; p=0.001). Fifty-three patients with persistent HT developed more serious HT at an earlier stage of RT. The chemotherapy cycles and three PCs associated with grade 2-3 HT was identified to form the resulting principal logistic regression model. CONCLUSION: A new method to calculate the NTCP was achieved by PCs logistic regression.

9.
BMC Biotechnol ; 15: 30, 2015 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-25962418

RESUMO

BACKGROUND: The objective of this paper was to study antimicrobial activity and safety of Enterococcus faecium KQ 2.6 (E. faecium KQ 2.6) isolated from peacock feces. METHODS: Agar well diffusion method was adopted in antimicrobial activity assay. Disk diffusion test was used to determine the antibiotic resistance. The identification and virulence potential of E. faecium KQ 2.6 were investigated using PCR amplification. RESULTS: The results indicated that cell free supernatant (CFS) of the strain had the good antimicrobial activity against selected gram-positive and gram-negative bacteria. The biochemical characteristics of antimicrobial substances were investigated. The results indicated that the antimicrobial substances were still active after treatment with catalase and proteinase, respectively. Moreover, the stability of antimicrobial substances did not change after heat treatment at 40, 50, 60, 70 and 80°C for 30 min, respectively. The activity of antimicrobial substances remained stable at 4 and -20°C after long time storage. The antimicrobial activity of CFS was compared with that of the buffer with similar strength and pH. The inhibitory zone of the buffer was apparently smaller than that of CFS, which meant that the acid in CFS was not the only factor that was contributed to antibacterial activity of CFS. The antibiotic resistance and virulence potential were evaluated using disk diffusion test and PCR amplification. The results showed that E. faecium KQ 2.6 did not harbor any tested virulence genes such as gelE, esp, asa1, cylA, efaA and hyl. It was susceptible to most of tested antibiotics except for vancomycin and polymyxin B. CONCLUSION: E. faecium KQ 2.6 may be used as bio-preservative cultures for the production of fermented foods.


Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Produtos Biológicos/farmacologia , Enterococcus faecium/química , Enterococcus faecium/fisiologia , Galliformes/microbiologia , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Técnicas Bacteriológicas , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Enterococcus faecium/efeitos dos fármacos , Enterococcus faecium/genética , Enterococcus faecium/isolamento & purificação , Fezes/microbiologia , Testes de Sensibilidade Microbiana
10.
Mult Scler ; 20(9): 1260-4, 2014 08.
Artigo em Inglês | MEDLINE | ID: mdl-24500603

RESUMO

We linked several population-based clinical and health administrative databases in British Columbia, Canada. We identified and compared birth outcomes of pregnancies fathered by men with multiple sclerosis (MS) (n=202) and men from a frequency-matched general population cohort (n=981) between 1996 and 2010. Using multivariate models, we analyzed the association of paternal MS, disease duration at conception and disability (as measured by the Expanded Disability Status Scale) with birth weight and gestational age. Paternal MS and MS-related clinical factors were not significantly associated with birth outcomes (p>0.05). This study provides assurance to expecting fathers with MS and their families.


Assuntos
Pai , Esclerose Múltipla/epidemiologia , Resultado da Gravidez , Peso ao Nascer , Colúmbia Britânica/epidemiologia , Bases de Dados Factuais , Avaliação da Deficiência , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Modelos Lineares , Masculino , Esclerose Múltipla/diagnóstico , Análise Multivariada , Gravidez , Sistema de Registros , Medição de Risco , Fatores de Risco , Fatores de Tempo
11.
Biotechnol Biotechnol Equip ; 28(3): 559-566, 2014 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-26019543

RESUMO

A new non-specific nuclease from Yersinia enterocolitica subsp. palearctica (Y. NSN) was expressed in Escherichia coli (E. coli) BL 21 StarTM (DE3)plysS. Induction conditions, including isopropyl-ß-D-thiogalactoside (IPTG) concentration, cell density (OD600), induction time and induction temperature, were optimized using response surface methodology. Statistical analysis of the results revealed that induction temperature and all the quadratic terms of variables had significant effects on enzyme activity of Y. NSN. The optimal induction conditions were as follows: 1.5 mmol/L IPTG, OD600 of 0.80, induction time of 20.5 h, and induction temperature of 32 °C. Under the optimized conditions, the highest enzyme activity could be obtained.

12.
Int J Biol Macromol ; 261(Pt 1): 129663, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38278396

RESUMO

Paenibacillus polymyxa (P. polymyxa) is a member of the genus Paenibacillus, which is a rod-shaped, spore-forming gram-positive bacterium. P. polymyxa is a source of many metabolically active substances, including polypeptides, volatile organic compounds, phytohormone, hydrolytic enzymes, exopolysaccharide (EPS), etc. Due to the wide range of compounds that it produces, P. polymyxa has been extensively studied as a plant growth promoting bacterium which provides a direct benefit to plants through the improvement of N fixation from the atmosphere and enhancement of the solubilization of phosphorus and the uptake of iron in the soil, and phytohormones production. Among the metabolites from P. polymyxa, EPS exhibits many activities, for example, antioxidant, immunomodulating, anti-tumor and many others. EPS has various applications in food, agriculture, environmental protection. Particularly, in the field of sustainable agriculture, P. polymyxa EPS can be served as a biofilm to colonize microbes, and also can act as a nutrient sink on the roots of plants in the rhizosphere. Therefore, this paper would provide a comprehensive review of the advancements of diverse aspects of EPS from P. polymyxa, including the production, extraction, structure, biosynthesis, bioactivity and applications, etc. It would provide a direction for future research on P. polymyxa EPS.


Assuntos
Paenibacillus polymyxa , Paenibacillus , Paenibacillus polymyxa/metabolismo , Paenibacillus/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Desenvolvimento Vegetal , Plantas/metabolismo
13.
Genes Immun ; 14(3): 179-86, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23392275

RESUMO

Genome-wide association studies (GWAS) have successfully identified several loci associated with primary biliary cirrhosis (PBC) risk. Pathway analysis complements conventional GWAS analysis. We applied the recently developed linear combination test for pathways to datasets drawn from independent PBC GWAS in Italian and Canadian subjects. Of the Kyoto Encyclopedia of Genes and Genomes and BioCarta pathways tested, 25 pathways in the Italian dataset (449 cases, 940 controls) and 26 pathways in the Canadian dataset (530 cases, 398 controls) were associated with PBC susceptibility (P<0.05). After correcting for multiple comparisons, only the eight most significant pathways in the Italian dataset had FDR <0.25 with tumor necrosis factor/stress-related signaling emerging as the top pathway (P=7.38 × 10⁻4, FDR=0.18). Two pathways, phosphatidylinositol signaling and hedgehog signaling, were replicated in both datasets (P<0.05), and subjected to two additional complementary pathway tests. Both pathway signals remained significant in the Italian dataset on modified gene set enrichment analysis (P<0.05). In both GWAS, variants nominally associated with PBC were significantly overrepresented in the phosphatidylinositol pathway (Fisher exact P<0.05). These results point to established and novel pathway-level associations with inherited predisposition to PBC that, on further independent replication and functional validation, may provide fresh insights into PBC etiology.


Assuntos
Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Cirrose Hepática Biliar/genética , Transdução de Sinais/genética , Algoritmos , Canadá , Estudos de Coortes , Bases de Dados Genéticas , Feminino , Frequência do Gene , Genótipo , Humanos , Itália , Desequilíbrio de Ligação , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
14.
Mult Scler ; 19(9): 1182-9, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23386429

RESUMO

BACKGROUND: Fatigue and pelvic organ dysfunction are common among women with multiple sclerosis (MS), which may prolong labor and increase the risk of labor induction and/or augmentation. OBJECTIVE: We set out to investigate the association between MS and related clinical factors (disease duration and the Expanded Disability Status Scale, EDSS) with labor induction/augmentation. METHODS: Data from the British Columbia (BC) MS database were linked with the BC Perinatal Database Registry. Multivariable models were used to compare the likelihood of labor induction and augmentation between attempted vaginal deliveries (1998-2009) in women with MS (n=381) and the general population (n=2615). RESULTS: In the MS cohort, 94/381 deliveries (25%) required labor induction and 147/381 deliveries (39%) required labor augmentation. Having MS was not associated with labor induction (adjusted odds ratio (OR)=0.91; 95% confidence interval (CI)=0.68-1.22, p=0.54) or augmentation (adjusted OR=0.91; 95% CI=0.72-1.15, p=0.43), but was associated with multiple methods of labor induction (OR=1.94; 95% CI=1.23-3.06, p=0.004). A higher EDSS score was associated with an increased risk of labor induction (adjusted p=0.04), but not labor augmentation (adjusted p > 0.5). Disease duration was not associated with either outcome (adjusted p > 0.2). CONCLUSIONS: Greater intervention may be required to initiate labor for women with a higher degree of disability due to MS.


Assuntos
Trabalho de Parto Induzido/estatística & dados numéricos , Esclerose Múltipla/complicações , Complicações na Gravidez , Adulto , Feminino , Humanos , Gravidez , Adulto Jovem
15.
Int J Food Sci Nutr ; 64(3): 380-4, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23216386

RESUMO

Lactobacillus delbrueckii subsp. bulgaricus (L. bulgaricus) was encapsulated in alginate-skim milk microspheres. Characteristics of encapsulated L. bulgaricus, such as pH stability, bile stability, storage stability and release property, were studied in this paper. The viability of free L. bulgaricus was not observed after 1 min in simulated gastric fluids (SGF) at pH 2.5 or 2.0. Compared with that of free L. bulgaricus, the viability of encapsulated L. bulgaricus only decreased 0.7 log CFU/g and 2 log CFU/g after 2.0 h incubation in SGF at pH 2.5 and pH 2.0, respectively. L. bulgaricus was also sensitive to bile solution. The viability of free L. bulgaricus was fully lost after 1 h incubation in 1 and 2% bile solution, while the viability of encapsulated L. bulgaricus was only lost 2 log CFU/g and 2.6 log CFU/g in 1 and 2% bile solution at the same time, respectively. Encapsulated L. bulgaricus could be completely released from microspheres in simulated intestinal fluid (pH 6.8) within 2 h. The viability of encapsulated L. bulgaricus retained around 8 log CFU/g when stored at 4°C for 30 days. The current encapsulation technique enables a large proportion of L. bulgaricus to remain good bioactive in a simulated gastrointestinal tract environment.


Assuntos
Alginatos , Suco Gástrico/química , Trato Gastrointestinal/química , Lactobacillus , Microesferas , Leite , Probióticos/administração & dosagem , Animais , Ácido Glucurônico , Ácidos Hexurônicos , Concentração de Íons de Hidrogênio
16.
J Sci Food Agric ; 93(10): 2351-61, 2013 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-23553505

RESUMO

Date fruit has served as a staple food in the Arab world for centuries. Worldwide production of date fruit has increased almost threefold over the last 40 years, reaching 7.68 million tons in 2010. Date fruit can provide many essential nutrients and potential health benefits to the consumer. Date fruit goes through four ripening stages named kimri, khalal, rutab and tamer. The main chemical components of date fruit include carbohydrates, dietary fibre, enzymes, protein, fat, minerals, vitamins, phenolic acids and carotenoids. The chemical composition of date fruit varies according to ripening stage, cultivar, growing environment, postharvest conditions, etc. The nutritional and medicinal activities of date fruit are related to its chemical composition. Many studies have shown that date fruit has antioxidant, antimutagenic, anti-inflammatory, gastroprotective, hepatoprotective, nephroprotective, anticancer and immunostimulant activities. Various date fruit-based products such as date syrup, date paste, date juice and their derived products are available. Date by-products can be used as raw materials for the production of value-added products such as organic acids, exopolysaccharides, antibiotics, date-flavoured probiotic-fermented dairy produce, bakery yeasts, etc. In this paper the chemical composition and nutritional and medicinal values of date fruit as well as date fruit-based products are reviewed.


Assuntos
Arecaceae/química , Dieta , Alimentos , Frutas/química , Valor Nutritivo , Fitoterapia , Preparações de Plantas/farmacologia , Humanos , Preparações de Plantas/uso terapêutico
17.
Pulmonology ; 29(3): 188-193, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-32753319

RESUMO

INTRODUCTION: GOLD 2017 report proposed that the combined COPD assessment should be done according only to symptom burden and exacerbation history in the previous year. OBJECTIVE: This study aims to investigate the change in the COPD groups after the GOLD 2017 revision and also to discuss the evaluation of group C and D as a single group after the GOLD 2019 report. METHOD: The study was designed as a cross-sectional. 251 stable COPD patients admitted to our out-patient clinic; aged ...40 years, at least one-year diagnosis of COPD and ...10 pack-year smoking history were consecutively recruited for the study. RESULTS: In GOLD 2017, a significant difference was found between the distribution of all groups compared to GOLD 2011 (P...=...0,001). 31 patients included in group C were reclassified into group A and 37 patients in group D were reclassified into group B. The FEV1 values of group A and B patients were significantly low and group C and D patients had had exacerbations in more frequently the previous year in GOLD 2017 compared to GOLD 2011. CONCLUSION: After the GOLD 2017 revision, the rate of group C patients decreased even more compared to GOLD 2011 and the group C and D may be considered as a single group in terms of the treatment recommendations with the GOLD 2019 revision. We think that future prospective studies are needed to support this suggestion.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Humanos , Idoso , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/terapia , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Estudos Transversais , Progressão da Doença , Estudos Prospectivos , Hospitalização
18.
J Dent Res ; 102(1): 61-71, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36112902

RESUMO

Periodontitis comprises a series of inflammatory responses resulting in alveolar bone loss. The suppression of osteogenesis of periodontal ligament stem cells (PDLSCs) by inflammation is responsible for impaired alveolar bone regeneration, which remains an ongoing challenge for periodontitis therapy. Ubiquitin C-terminal hydrolase L1 (UCHL1) belongs to the family of deubiquitinating enzymes, which was found to play roles in inflammation previously. In this study, the upregulation of UCHL1 was identified in inflamed PDLSCs isolated from periodontitis patients and in healthy PDLSCs treated with tumor necrosis factor-α or interleukin-1ß, and the higher expression level of UCHL1 was accompanied with the impaired osteogenesis of PDLSCs. Then UCHL1 was inhibited in PDLSCs using the lentivirus or inhibitor, and the osteogenesis of PDLSCs suppressed by inflammation was rescued by UCHL1 inhibition. Mechanistically, the negative effect of UCHL1 on the osteogenesis of PDLSCs was attributable to its negative regulation of mitophagy-dependent bone morphogenetic protein 2/Smad signaling pathway in periodontitis-associated inflammation. Furthermore, a ligature-induced murine periodontitis model was established, and the specific inhibitor of UCHL1 was administrated to periodontitis mice. The histological results showed increased active osteoblasts on alveolar bone surface and enhanced alveolar bone regeneration when UCHL1 was inhibited in periodontitis mice. Besides, the therapeutic effects of UCHL1 inhibition on ameliorating periodontitis were verified, as indicated by less bone loss and reduced inflammation. Altogether, our study proved UCHL1 to be a key negative regulator of the osteogenesis of PDLSCs in periodontitis and suggested that UCHL1 inhibition holds promise for alveolar bone regeneration in periodontitis treatment.


Assuntos
Células-Tronco Mesenquimais , Periodontite , Camundongos , Animais , Osteogênese , Ligamento Periodontal , Diferenciação Celular , Periodontite/metabolismo , Células-Tronco , Inflamação/metabolismo , Células Cultivadas , Ubiquitina Tiolesterase/metabolismo , Ubiquitina Tiolesterase/farmacologia
19.
J Fungi (Basel) ; 9(3)2023 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-36983506

RESUMO

Calcium is one of the essential minerals that enhances various biological activities, including the regulation of blood pressure, the prevention of osteoporosis and colorectal adenomas. Calcium-enriched edible mushrooms can be considered as one of the important daily sources of calcium in foods. Calcium accumulation in edible mushrooms is an effective way to enhance its activities because the organic state of calcium metabolites in edible mushrooms can be formed from the original inorganic calcium. The main calcium sources for calcium-enriched edible mushrooms' cultivation are CaCO3, CaCl2 or Ca(NO3)2. The growth and metabolic process of edible mushrooms are significantly influenced by calcium enrichment. Generally, Ca at low levels is good for the production of edible mushrooms, whereas the reverse phenomenon for the growth of edible mushrooms at high Ca contents is observed. In addition, metabolites, for example, phenolics, flavonoids, polysaccharides, enzymes, minerals, etc., are improved when edible mushrooms are enriched at a moderate level of calcium. This review summarized the literature regarding the influence of calcium enrichment on edible mushrooms' growth and major metabolites. Furthermore, the mechanisms of calcium enrichment in edible mushrooms were highlighted. Understanding calcium-enriched mechanisms in edible mushrooms would not only be beneficial to manipulate the cultivation of edible mushrooms having excellent biological activities and high levels of active Ca, but it would also contribute to the applications of calcium enrichment products in food industries.

20.
J Fungi (Basel) ; 9(2)2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36836375

RESUMO

Polyketides are an important class of structurally diverse natural products derived from a precursor molecule consisting of a chain of alternating ketone and methylene groups. These compounds have attracted the worldwide attention of pharmaceutical researchers since they are endowed with a wide array of biological properties. As one of the most common filamentous fungi in nature, Aspergillus spp. is well known as an excellent producer of polyketide compounds with therapeutic potential. By extensive literature search and data analysis, this review comprehensively summarizes Aspergillus-derived polyketides for the first time, regarding their occurrences, chemical structures and bioactivities as well as biosynthetic logics.

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