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Enterovirus 71 (EV71) is a neurotropic enterovirus associated with hand, foot, and mouth disease (HFMD) fatalities. In this study, we investigated the impact of EV71 on plasmacytoid dendritic cells (pDCs) and CD4+ T cells. The results showed that pDCs were promptly activated, secreting interferon (IFN)-α and inducing CD4+ T cell proliferation and differentiation during early EV71 infection. This initiated adaptive immune responses and promoted proinflammatory cytokine production by CD4+ T cells. Over time, viral nucleic acids and proteins were synthesized in pDCs and CD4+ T cells. Concurrently, the cholinergic anti-inflammatory pathway (CAP) was activated, exhibiting an anti-inflammatory role. With constant viral stimulation, pDCs and CD4+ T cells showed reduced differentiation and cytokine secretion. Defects in pDCs were identified as a key factor in CD4+ T cell tolerance. CAP had a more significant regulatory effect on CD4+ T cells than on pDCs and was capable of inhibiting inflammation in these cells.
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Enterovirus Humano A , Infecções por Enterovirus , Humanos , Neuroimunomodulação , Regulação para Cima , Interferon-alfa/metabolismo , Diferenciação Celular , Infecções por Enterovirus/metabolismo , Linfócitos T CD4-Positivos , Células DendríticasRESUMO
Further evidence is needed to explore the impact of high-altitude environments on the neurologic function of neonates. Non-invasive techniques such as cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography can provide data on cerebral oxygenation and brain electrical activity. This study will conduct multiple cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography monitoring sessions at various time points within the first 3 days postpartum for healthy full-term neonates at different altitudes. The obtained data on cerebral oxygenation and brain electrical activity will be compared between different altitudes, and corresponding reference ranges will be established. The study involves 6 participating centers in the Chinese High Altitude Neonatal Medicine Alliance, with altitude gradients divided into 4 categories: 800 m, 1 900 m, 2 400 m, and 3 500 m, with an anticipated sample size of 170 neonates per altitude gradient. This multicenter prospective cohort study aims to provide evidence supporting the impact of high-altitude environments on early brain function and metabolism in neonates.
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Altitude , Encéfalo , Eletroencefalografia , Oxigênio , Humanos , Recém-Nascido , Encéfalo/metabolismo , Oxigênio/metabolismo , Espectroscopia de Luz Próxima ao Infravermelho , Estudos ProspectivosRESUMO
Alcoholism is a worldwide health problem, and diseases caused by alcoholism are killing people every year. Amomum kravanh is a traditional Chinese medicine used to relieve hangovers. However, whether its bioactive components improve alcohol metabolism is not clear. In this study, ten new (amomumols A-J, 1-10) and thirty-five known (11-45) compounds were isolated from the fruits of Amomum kravanh by an activity-guided separation. Ten novel compounds were identified as four sesquiterpenoids (1-4), three monoterpene derivatives (5-7), two neolignans (8, 9), and a novel norsesquiterpenoid (10) with a new C14 nor-bisabolane skeleton. Their structures were determined by the comprehensive analysis of high-resolution electrospray ionization mass spectrometry (HRESIMS), nuclear magnetic resonance (NMR), and electronic circular dichroism (ECD) calculation. The effects of all isolated compounds on the activity of alcohol dehydrogenase were evaluated in vitro, and it was found that eight compounds (11, 12, 15, 18, 26, and 36-38) exhibited significant activation effects on the alcohol dehydrogenase at 50 µM.
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Alcoolismo , Amomum , Humanos , Frutas/química , Amomum/química , Álcool Desidrogenase , Monoterpenos/químicaRESUMO
Activated B cells contribute to heart diseases, and inhibition of B-cell activating factor (BAFF) expression is an effective therapeutic target for heart diseases. Whether activated B cells participate in the development and progression of hyperthyroid heart disease, and what induces B cells activation in hyperthyroidism are unknown. The present study aimed to determine the roles of BAFF overexpression induced by high concentrations of triiodothyronine (T3) in the pathogenesis of hyperthyroid heart disease. Female C57BL/6J mice were subcutaneously injected with T3 for 6 weeks, and BAFF expression was inhibited using shRNA. Protein and mRNA expression of BAFF in mouse heart tissues evaluated via immunohistochemistry, western blotting and polymerase chain reaction (PCR). Proportions of B cells in mouse cardiac tissue lymphocytes were quantified via flow cytometry. Morphology and left ventricle function were assessed using pathological sections and echocardiography, respectively. Here, we demonstrate that compared with the control group, the proportion of myocardial B cells was larger in the T3 group; immunohistochemistry, western blotting and PCR analyses revealed increased protein and mRNA expression levels of TNF-α and BAFF in heart tissues of the T3 group. Compared with the normal controls group, in the T3 group, the diameter of myocardial cells and some echocardiographic values significantly increased and hypertrophy and structural disorder were noticeable. Our results revealed that elevated levels of circulating T3 can promote the expression of BAFF in myocardial cells and can lead to B-cell activation, an elevated inflammatory response and ventricular remodelling.
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Fator Ativador de Células B , Hipertireoidismo , Animais , Fator Ativador de Células B/genética , Fator Ativador de Células B/metabolismo , Cardiomegalia/genética , Feminino , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética , Tri-IodotironinaRESUMO
Two Ni-substituted polyoxometalates (NiSPs), [Ni6(Py)6(H2O)5(µ3-OH)3(PW9O34)]2·10H2O (1), [Ni7(Py)6(Im)(H2O)5O(WO4)(µ3-OH)3(H2PW9O34)]·3H2O (2) (Py = pyridine, Im = imidazole), were successfully hydrothermally synthesized. Compounds 1 and 2 have significantly different configurations by introducing different amounts of imidazole ligands. For compound 1, two malposed {Ni6(Py)6PW9} units that are face to face are bridged by two Ni-O-W bonds to constitute an isolated dimeric structure. Differently, the {Ni7(Py)6(Im)PW9}2 dimer in compound 2 connects with four adjacent dimers by four {WO4} groups in an interesting two-dimensional (2-D) arrangement. The magnetism of compounds 1 and 2 was studied, and magnetic test results demonstrated that both compounds have ferromagnetic interactions between the nickel centers. Meanwhile, the third-order nonlinear optical (NLO) measurements indicated that compound 1 can serve as potential nonlinear optical materials.
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Objective Graves' disease is the most common autoimmune thyroid disease and its prevalence and clinical manifestations are disparate between females and males. Costimulatory molecules play an essential role in regulating autoimmune responses. The objective of this study was to determine if expression of inhibitory molecules was correlated with treatment by dihydrotestosterone (DHT) in an in vivo BALB/c mouse model of experimental autoimmune Graves' disease.Methods Female BALB/c mice were immunized three times with thyroid stimulating hormone receptor A-subunit encoded by adenovirus to establish a Graves' disease model. Three different doses of DHT or a matching placebo were administered by implantation of slow-release pellets a week before the first immunization. Four weeks after the third immunization, the mice were euthanatized, and then the spleen and thymus were removed. Total thyroxine and free thyroxine levels in serum of mice were detected using a radioimmunoassay kit. Real-time polymerase chain reaction was performed to estimate the expression of costimulatory molecules in lymphocytes from the spleen and thymus. Flow cytometry was used to analyze the percentage of CD4+ T cells in splenic lymphocytes. Quantitative data were compared with unpaired t-tests. Correlation between two variables was analyzed using Analysis of Variance.Results Treatment with DHT can dramatically reduce total thyroxine and free thyroxine levels. Higher expression of programmed death-1 was found in the spleen of Graves' disease mice receiving 5 mg of DHT treatment (0.635±0.296 vs. 0.327±0.212; t=2.714, P=0.014), similarly, T-cell immunoglobulin domain and mucin domain 3 (TIM-3) in both the spleen (1.004±0.338 vs. 0.646±0.314; t=2.205, P=0.022) and the thymus (0.263±0.127 vs. 0.120±0.076; t=3.221, P=0.004) also increased after 5 mg of DHT treatment compared with the parallel placebo model mice. Moreover, the percentage of CD4+ T cells declined in the splenic lymphocytes of Graves' disease mice treated with 5 mg of DHT (19.90%±3.985% vs. 24.05%±2.587%; t=2.804, P=0.012). A significant negative association was observed between expression of TIM-3 in the spleen and serum levels of total thyroxine (r=-0.7106, P=0.014) as well as free thyroxine (r=-0.6542, P=0.029).Conclusion This study demonstrates that DHT can ameliorate experimental autoimmune Graves' disease, which may occur by up-regulating expression of programmed death-1 and TIM-3 and inhibiting development of CD4+ T cells.
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Di-Hidrotestosterona/uso terapêutico , Doença de Graves/tratamento farmacológico , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Animais , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Di-Hidrotestosterona/farmacologia , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Doença de Graves/sangue , Doença de Graves/patologia , Doença de Graves/fisiopatologia , Peptídeos e Proteínas de Sinalização Intercelular/genética , Modelos Lineares , Camundongos Endogâmicos BALB C , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Baço/efeitos dos fármacos , Baço/metabolismo , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/patologia , Glândula Tireoide/fisiopatologia , Tireotropina/metabolismo , Tiroxina/sangueRESUMO
AIM: The purpose of this study was to analyse the diagnostic value of gated myocardial perfusion imaging (G-MPI) in the evaluation of myocardial injury in sarcoglycanopathy. MATERIALS AND METHODS: Twenty-eight patients diagnosed with sarcoglycanopathy were evaluated using 99m- -methoxyisobutylisonitrile(99Tcm-MIBI) G-MPI. The data was processed into tomographic images, and the left ventricular function was analysed using quantitative gated SPECT (QGS) to assess the degree of impairment in myocardial and cardiac function. RESULTS: The images of 23 of the patients (82.1%) were positive. Two hundred and twenty-nine sub-segments with abnormal lesions were detected out of 391 cardiac sub-segments of these 23 positive cases. According to the segmental abnormalities, the cases were divided into two cases (8.7%) with single abnormal wall segment, six cases (26.1%) with two abnormal wall segments, and 15 cases (65.2%) with three or more abnormal wall segments or scattered lesions. CONCLUSIONS: 99Tcm-MIBI G-MPI can objectively show impaired myocardium in patients with sarcoglycanopathy. Therefore, this method is helpful for early diagnosis and follow-up of myocardial damage.
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Imagem de Perfusão do Miocárdio , Sarcoglicanopatias , Humanos , Compostos Radiofarmacêuticos , Sarcoglicanopatias/diagnóstico , Tecnécio Tc 99m Sestamibi , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
At present,Western medicine is widely used in the treatment of epilepsy.However,about 30%-40% of epileptic patients are resistant to them and are affected by the side effects of these drugs.Traditional Chinese medicine is effective in treating epileptic seizures and relieving complications caused by Western medicine.However,the active ingredients and mechanisms of traditional Chinese medicine remain unclear.This article reviews and summarizes the advances and mechanisms in treating epilepsy,such as Chinese medicine monomer,the extracts of single Chinese medicine and Chinese medicine compound.Chinese medicine monomers,including gastrodin,asarone,rhynchophylline,ligustrazine,tanshinone ⠡A,curcumin,etc.,have antiepileptic effects via regulating excitatory neurotransmitters and receptors,the expression of inflammatory factors,sodium/potassium ion channels and the expression of apoptotic protein,therefore protecting neurons.The extracts of single Chinese herbal including the extracts of Gastrodiae Rhizoma,Acori Tatarinowii Rhizoma,Ginseng Radix et Rhizoma,Ganoderma,Scutellariae Radix and Ginkgo Folium,etc.,have antiepileptic effects related to the inhibition of γ-aminobutyric acid receptor,upregulation of phosphatidylinositol 3-kinase signaling pathway and reduction of glutamate-induced excitotoxicity and oxidative stress response.Furthermore,these extracts can regulate ion channels and reduce oxidative damage of neurons.Chinese medicine compounds including Dianxian Qing Granules,Danxing Ningxian Granules,Huoxue Dingxian formulae,etc.,can improve the therapeutic effect on epilepsy through simultaneously regulating excitatory transmitters,apoptosis factors and cytokines.
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Medicamentos de Ervas Chinesas/uso terapêutico , Epilepsia/tratamento farmacológico , Fitoterapia , Humanos , Medicina Tradicional ChinesaRESUMO
OBJECTIVE: To study the clinical value of lymphocyte subsets, immunoglobulins, and complement C3 and C4 in the evaluation of immune status in children with hand-foot-mouth disease (HFMD). METHODS: A total of 282 children with HFMD were enrolled as the HFMD group, and 130 healthy children were enrolled as the healthy control group. The percentages of peripheral CD3+, CD4+, and CD8+ T lymphocytes, CD19+ B lymphocytes, and CD56+ natural killer cells were measured. The CD4+/CD8+ ratio was calculated. The levels of immunoglobulin A (IgA), immunoglobulin M (IgM), immunoglobulin G (IgG), and complement C3 and C4 were measured. RESULTS: The multivariate analysis showed that compared with the healthy control group, the HFMD group had significantly lower percentages of CD3+, CD4+, and CD8+ T lymphocytes and levels of complement C3 and C4 (P<0.05), as well as significantly higher percentage of CD56+ natural killer cells and level of IgG (P<0.05). The individual effect analysis showed that the children aged 0-3 years in the HFMD group had a significantly higher CD4+/CD8+ ratio than the healthy control group (P<0.05); boys aged 0-3 and ≥3 years in the HFMD group had a significantly higher level of IgM than the healthy control group (P<0.05); boys aged ≥3 years and girls aged 0-3 years in the HFMD group had a significantly lower level of IgA than the healthy control group (P<0.05). CONCLUSIONS: Cellular and humoral immunity disorders are observed in children with HFMD. The monitoring of lymphocyte subsets and immunoglobulin levels can provide a laboratory basis for immune status assessment in children with HFMD.
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Doença de Mão, Pé e Boca , Pré-Escolar , Complemento C3 , Complemento C4 , Feminino , Humanos , Imunoglobulinas , Lactente , Recém-Nascido , Células Matadoras Naturais , Contagem de Linfócitos , Subpopulações de Linfócitos , MasculinoRESUMO
Cyathula capitate is the main adulterant of C.offinalis. According to the literature reported, there are obvious differences in properties, taste and pharmacological activity between C. capitate and C.offinalis. Therefore, C. capitate can only be used as a local conventional medicine and can't be a substitute for C. offinalis. Since the appearance of C.capitata is very similar to the C.offinalis and the content of cyasterone also can reach the limit of the current pharmacopoeia standard, the C.capitata is mostly sold in the form of impersonation oradmixture, which seriously affected the safety of the clinical medication and the development of the genuine crude drugs. In view of this, HPLC characteristic fingerprint was used to reveal the difference of multi-ingredients of C. offinalis, C. capitata and their admixture. According to the HPLC chromatogram of C.offinalis, C. capitata. and their admixture, 65 different components were obtained to set up a peak area data matrix of 26×65, which was applied to perform the characteristic peak difference analysis, similarity analysis, hierarchical clustering analysis HCA and principal component analysis (PCA). Characteristic peak difference analysis showed that the characteristic peaks of C. capitata and their admixture are more and higher respond than those of C. offinalis. The 9 characteristic peaks were used to distinguish C. capitata, 2 of which were used to distinguish C. offinalis mixed with 5% C. capitata. UV spectra of 9 characteristic peaks are mostly similar to the end absorption spectra of saponins, indicating that C. capitata may contain a large amount of saponins. By the reference fingerprint of C.offinalis established, the similarity analysis showed that the similarity degree of C. offinalis are higher than 0.942, while the similarity degree of C. capitata, C.offinalis mixed with 5% C. capitata are less than 0.383 and 0.399. C.offinalis, C. capitata, C.offinalis mixed with 5% C. capitata could be obviously divided into 3 classes by HCA and PCA. These results showed that there are obvious difference in the chemical composition of C. offinalis, C. capitata and their admixture, which could provide evidence for their identification.
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Amaranthaceae/química , Medicamentos de Ervas Chinesas/química , Compostos Fitoquímicos/análise , Amaranthaceae/classificação , Cromatografia Líquida de Alta Pressão , Contaminação de Medicamentos , Controle de Qualidade , Saponinas/análiseRESUMO
Gene doping can be easily concealed since its product is similar to endogenous protein, making its effective detection very challenging. In this study, we selected insulin-like growth factor I (IGF-I) exogenous gene for gene doping detection. First, the synthetic IGF-I gene was subcloned to recombinant adeno-associated virus (rAAV) plasmid to produce recombinant rAAV2/IGF-I-GFP vectors. Second, in an animal model, rAAV2/IGF-I-GFP vectors were injected into the thigh muscle tissue of mice, and then muscle and blood specimens were sampled at different time points for total DNA isolation. Finally, real-time quantitative PCR was employed to detect the exogenous gene doping of IGF-I. In view of the characteristics of endogenous IGF-I gene sequences, a TaqMan probe was designed at the junction of exons 2 and 3 of IGF-I gene to distinguish it from the exogenous IGF-I gene. In addition, an internal reference control plasmid and its probe were used in PCR to rule out false-positive results through comparison of their threshold cycle (Ct) values. Thus, an accurate exogenous IGF-I gene detection approach was developed in this study.
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Fator de Crescimento Insulin-Like I/genética , Reação em Cadeia da Polimerase em Tempo Real , Animais , Ensaio de Imunoadsorção Enzimática , Vetores Genéticos/genética , Humanos , Camundongos , Camundongos Endogâmicos ICRRESUMO
Exosomes, a population of extracellular membrane vesicles of 30-100 nm in diameter, play important roles in cell biological functions, intercellular signal transduction and especially in cancer diagnosis and therapy. To better apply exosomes in mechanistic study of breast cancer signal transduction, we constructed recombinant eukaryotic expression vector expressing the near-infrared fluorescence protein and CD63 fusion protein through cloning iRFP682 gene and exosomal marker protein CD63 gene into plasmid containing the ITR of AAV. The constructed plasmids were co-transfected with helper plasmid in AAV-293 cell lines and were packaged into rAAV. After titer measurement, the recombinant plasmids were transfected into breast cancer cell lines. The cell lines that stably expressing near-infrared fluorescence protein were selected by fluorescence. Through isolation, purification and identification, we finally obtained a new biomarker: iRFP682 labeled exosomes secreted by breast cancer cell lines, which could be used in further studies of the distribution and signal transduction of exosomes in breast cancer microenvironment.
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Neoplasias da Mama/ultraestrutura , Exossomos , Linhagem Celular Tumoral , Dependovirus/genética , Feminino , Corantes Fluorescentes , Humanos , Plasmídeos , Proteínas Recombinantes de Fusão/genética , Tetraspanina 30/genéticaRESUMO
OBJECTIVE: To study the effect of osthole (Ost) on adrenocortical function in Y1 mouse adrenocortical tumor cells. METHODS: Y1 mouse adrenocortical tumor cells were taken as subjects in this experiment. In 10.0%, 1.0%, and 0.1% serum DMEM-F12 medium, Y1 cells were treated with 1, 10, 25, 50, 100, and 200 micromol/L Ost for 24 and 48 h. 0.1% Dimethyl Sulfoxide (DMSO) was taken as negative control group and 1 mmol/L (Bu) 2cAMP as positive control group. Cell growth morphology was observed under inverted microscope. Contents of corticosterone were tested by ELISA. Expression levels of steroids synthase such as Star, Cyp11a1, Cyp21a1, Hsd3b2, Cyp11b1, Cyp11b2, Cyp17a1, and Hsd17b3 mRNA were detected by Real time quantitative PCR (RT-qPCR). RESULTS: Y1 cell proliferation was obviously inhibited by 100 and 200 micromol/L Ost, and its inhibitory effect was more significant in 0.1% serum medium. Compared with the negative control group, gene expressions of Star, Cyp11a1 , Cyp21a1, Hsd3b2, Cyp11b1, Cyp17a1, and Hsd17b3 were significantly enhanced in the posi- tive control group (P < 0.05). Y1 cell corticosterone levels significantly increased in 50 micromol/L Ost treatment group after 24-and 48-h intervention (P < 0.05). Contents of corticosterone increased more obviously in 25 and 50 +/- mol/L Ost treatment groups after 48-h intervention, as compared with 24-h intervention (P < 0.01). After 24-h intervention, expression levels of Star, Cyp21a1, and Hsd3b2 genes were significantly up-regulated in 25 and 50 lLmol/L Ost groups (P < 0.05). Star gene expression was further enhanced after 48-h intervention (P < 0.05). However, Ost showed no effect on Cyp11a1 (P > 0.05). Additionally, gene expressions of Cyp11b1 and Cyp17a1 were significantly enhanced by 10, 25, and 50 pLmolIL Ost after treatment for 24 and 48 h (P < 0.05). Ost showed no obvious effect on Cyp11b2 and Hsd17b3 expressions. CONCLUSION: Ost could regulate adrenal cortex function and promote corticosterone synthesis and secretion through strengthening gene expressions of steroidogenic enzymes.
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Neoplasias do Córtex Suprarrenal/patologia , Córtex Suprarrenal/efeitos dos fármacos , Corticosterona/biossíntese , Cumarínicos/farmacologia , Animais , Expressão Gênica , Camundongos , RNA Mensageiro/metabolismo , Células Tumorais CultivadasRESUMO
Tri-ortho-cresyl phosphate (TOCP) has been widely used as plasticizers, plastic softeners, and flame retardants in industry and reported to have a deleterious effect on the male reproductive system in animals besides delayed neurotoxicity. Our preliminary results found that TOCP could disrupt the seminiferous epithelium in the testis and inhibit spermatogenesis, but the precise mechanism is yet to be elucidated. This study shows that TOCP inhibited viability of rat spermatogonial stem cells in a dose-dependent manner. TOCP could not lead to cell cycle arrest in the cells; the mRNA levels of p21, p27, p53, and cyclin D1 in the cells were also not affected by TOCP. Meanwhile, TOCP did not induce apoptosis of rat spermatogonial stem cells. After treatment with TOCP, however, both LC3-II and the ratio of LC3-II/LC3-I were markedly increased; autophagy proteins ATG5 and beclin 1 were also increased after treatment with TOCP, indicating that TOCP could induce autophagy in the cells. Ultrastructural observation under the transmission electron microscopy indicated that autophagic vesicles in the cytoplasm containing extensively degraded organelles such as mitochondria and endoplasmic reticulum increased significantly after the cells were treated with TOCP. In summary, we have shown that TOCP can inhibit viability of rat spermatogonial stem cells and induce autophagy of the cells, without affecting cell cycle and apoptosis.
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Autofagia/efeitos dos fármacos , Espermatogônias/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Tritolil Fosfatos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/análise , Proteína 5 Relacionada à Autofagia , Proteína Beclina-1 , Ciclo Celular/efeitos dos fármacos , Células Cultivadas , Masculino , Microscopia Eletrônica de Transmissão , Proteínas/análise , Ratos , Espermatogônias/química , Espermatogônias/ultraestrutura , Células-Tronco/química , Células-Tronco/ultraestruturaRESUMO
BACKGROUND: Latent tuberculosis infection (LTBI) relies on a homeostasis of macrophages and Mycobacterium tuberculosis (Mtb). The small heat shock protein, Mtb Hsp16.3 (also known as latency-associated antigen), plays an important role in Mtb persistence within macrophages. However, the mechanism of LTBI remains elusive. The aim of this study was to delineate LTBI-related miRNA expression in U937 macrophages expressing Mtb Hsp16.3 protein. U937 macrophages were infected with an integrase-deficient Lentivirus vector to transiently express Mtb Hsp16.3, and green fluorescent protein (GFP) as a control. We used a microRNA (miRNA) microarray chip containing more than 1000 probes to identify the significant differentially expressed miRNAs in the infected U937 cells, and employed real-time quantitative polymerase chain reaction (qRT-PCR) for validation. Furthermore, we confirmed these candidate LTBI-related miRNAs in peripheral blood mononuclear cells from subjects with LTBI and in healthy control individuals. Functional annotation prediction of miRNA target genes and pathway enrichment analyses were used to explore the putative links between these miRNAs and LTBI. RESULTS: Analysis of the miRNA expression profile identified 149 miRNAs that were differentially expressed in U937 macrophages expressing Mtb Hsp16.3 compared with the control expressing GFP. The expression level of seven miRNAs (miR-424-5p, miR-493-5p, miR-296-5p, miR-27b-3p, miR-377-5p, miR-3680-5p, miR-191-5p) were validated by qRT-PCR. The expression level of four miRNAs (miR-424-5p, miR-27b-3p, miR-377-5p, miR-3680-5p) in the peripheral blood mononuclear cells samples from LTBI and healthy participants reflected the altered patterns observed in the microarray profile. The bioinformatic analyses suggest that the miRNAs may regulate Mtb latent infection by affecting the development of macrophage cells. CONCLUSIONS: The results suggest that miRNA expression may play a considerable role in the pathogenesis of LTBI, and this would increase our understanding of the molecular basis of Hsp16.3-facilitated Mtb survival in macrophages.
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Proteínas de Bactérias/biossíntese , Chaperoninas/biossíntese , Interações Hospedeiro-Patógeno , Tuberculose Latente/imunologia , Tuberculose Latente/microbiologia , Macrófagos/microbiologia , MicroRNAs/biossíntese , Mycobacterium tuberculosis/imunologia , Proteínas de Bactérias/genética , Sangue/imunologia , Células Cultivadas , Chaperoninas/genética , Perfilação da Expressão Gênica , Humanos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/microbiologia , MicroRNAs/genéticaRESUMO
An aerobic, Gram-stain negative, pale, rod-shaped, nitrogen-fixing bacterial strain, DDT-3(T), was isolated from dichlorodiphenyltrichloroethane-contaminated soil in Liyang, PR China. Strain DDT-3(T) grew at temperatures ranging from 20 to 40 °C (optimum 30-37 °C) and a pH of between 5.0 and 10.0 (optimum pH 7.0-8.0). The G+C content of the total DNA was 70.1 mol%. The 16S rRNA gene sequence of strain DDT-3(T) showed the highest similarity to that of Pseudoxanthobacter soli CC4(T) (99.6%), followed by Kaistia dalseonensis B6-8(T) (93.3%), Kaistia soli 5YN9-8(T) (93.0%) and Amorphus orientalis YIM D10(T) (93.0%). Strain DDT-3(T) showed less than 92.6â% similarity with other species of the family Xanthobacteraceae. The major cellular fatty acids of strain DDT-3(T) were C19:0 cyclo ω8c (42.6%), C16:0 (33.2%) and C18:1ω7c (10.0%). The only respiratory quinone was ubiquinone Q-10. The characteristic diamino acid of the peptidoglycan was meso-diaminopimelic acid. The major polar lipids were glycolipid, lipid, phosphatidylcholine, aminolipid, phosphatidylmethylethanolamine, diphosphatidylglycerol and phosphatidylglycerol. The polyamine profile consisted of major amounts of putrescine (92.9%) and minor amounts of spermidine (5.0%) and spermine (2.1%). These chemotaxonomic data support the affiliation of strain DDT-3(T) with the genus Pseudoxanthobacter. The DNA-DNA hybridization value between strain DDT-3(T) and strain CC4(T) was 47.8% (reciprocal 44.3%). DNA-DNA hybridization data as well as the biochemical and physiological characteristics strongly supported the genotypic and phenotypic differentiation of strain DDT-3(T) and strain CC4(T). Strain DDT-3(T), therefore, represents a novel species of the genus Pseudoxanthobacter, for which the name Pseudoxanthobacter liyangensis sp. nov. is proposed. The type strain is DDT-3(T) ( = KACC 16601(T) = CCTCC AB 2013167(T)).
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Alphaproteobacteria/classificação , DDT/química , Filogenia , Microbiologia do Solo , Alphaproteobacteria/genética , Alphaproteobacteria/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Peptidoglicano/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Poluentes do Solo/química , Ubiquinona/químicaRESUMO
The design of efficient catalysts for photocatalytic CO2 conversion is of great importance for the sustainable development of society. Herein, three polyoxometalate (POM)-based crystalline materials were formulated prepared by substituting transition metals and adjusting solvent acidity with 2-(2-pyridyl) benzimidazole (pyim) as the light-trapping ligand, namely {[SiW12O40][Co(pyim)2]2}·2C2H5OH (SiW12Co2), {[SiW12O40][Ni(pyim)2]2}·2C2H5OH (SiW12Ni2), and {[SiW12O40][Mn(pyim)2]2}·2C2H5OH (SiW12Mn2). X-ray crystallography diffraction analysis indicates that the three complexes exhibit isostructural properties, and form a stable one-dimensional chain structure stabilized by two [M(pyim)2]22+ (M = Co, Ni, and Mn) fragments serving as dual-nodes to the adjacent SiW12 units. A comprehensive analysis of the structural characterization and photocatalytic CO2 reduction properties is presented. Under light irradiation, SiW12Co2 exhibited a remarkable CO generation rate of 10 733 µmol g-1 h-1 with a turnover number of 328, outperforming most of the reported heterogeneous POM-based photocatalysts. Besides, cycling tests revealed that SiW12Co2 is an efficient and stable photocatalyst with great recyclability for at least four successive runs. This study proves that the successful incorporation of diverse transition metals into the POM anion could facilitate the development of highly efficient photocatalysts for the CO2RR.
RESUMO
Huangqi Guizhi Wuwu Decoction (HQGZWWD) has shown promising potential in treating various cardiovascular diseases. This study aimed to elucidate the molecular basis and therapeutic role of HQGZWWD in the treatment of doxorubicin (DOX)-induced myocardial injury. The HPLC fingerprint of HQGZWWD was used to analyze the active components. A DOX-induced myocardial damage rat model was developed, and the therapeutic effects of HQGZWWD were evaluated using echocardiography, myocardial enzyme levels, and hematoxylin and eosin staining. Network pharmacology was used to screen treatment targets, and western blotting and immunohistochemistry were performed to assess cellular pyroptosis levels. Oxidative stress levels were measured using assay kits, and mitochondrial damage was examined using transmission electron microscopy. An in vitro model of DOX-induced cell damage was established, and treatment was administered using serum containing HQGZWWD and N-acetylcysteine (NAC). Oxidative stress levels were detected using assay kits and DCFH-DA, whereas cellular pyroptosis levels were assessed through WB, immunofluorescence, and ELISA assays. HQGZWWD ameliorated DOX-induced myocardial injury. Network pharmacology identified IL-1ß and IL-18 as crucial targets. HQGZWWD downregulated the protein levels of the inflammatory factors IL-1ß and IL-18, inhibited the expression of GSDMD-NT, and simultaneously suppressed the synthesis of Caspase-1, ASC, NLRP3, and Caspase-11. Additionally, HQGZWWD inhibited oxidative stress, and the use of NAC as an oxidative stress inhibitor resulted in significant inhibition of the GSDMD-NT protein in H9C2 cells. These findings highlight the myocardial protective effects of HQGZWWD by inhibiting oxidative stress and suppressing both canonical and non-canonical pyroptotic pathways.
Assuntos
Cardiotoxicidade , Doxorrubicina , Medicamentos de Ervas Chinesas , Estresse Oxidativo , Piroptose , Ratos Sprague-Dawley , Animais , Doxorrubicina/toxicidade , Piroptose/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Cardiotoxicidade/tratamento farmacológico , Cardiotoxicidade/metabolismo , Cardiotoxicidade/prevenção & controle , Ratos , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Linhagem Celular , Farmacologia em RedeRESUMO
BACKGROUND: This study aims to evaluate the effect of telephone and short-message follow-ups on compliance and efficacy in asthmatic children treated with inhaled corticosteroids. METHODS: A total of 120 children with moderate bronchial asthma who visited the Asthma Outpatient Department of the Affiliated Hospital of Qingdao University were enrolled in the study. They were divided randomly into 3 groups based on the type of follow-up given: a combined telephone and short-message service (Telâ +â SMS) group, a SMS group, and a control group. After being followed up for 12 weeks, each child's asthma control level was assessed and their lung function was measured. RESULTS: The compliance rates of children in the Telâ +â SMS group and SMS group were 86.49% and 56.25%, respectively. The total effective rates of these 2 groups (94.59% and 75.0%, respectively) were significantly higher than the rate of the control group (Pâ <â .01). The lung function indicators of the children in all 3 groups were better than those before treatment, although only the Telâ +â SMS group and SMS group improved significantly (P < .05). The lung function indicators of the large and small airways in the Telâ +â SMS group and the SMS group were also significantly better than those of the control group (P < .01). The results of the study suggest that 1 of the causes of poor compliance in asthmatic children is fear of an adverse reaction to inhaled corticosteroids. CONCLUSION: Telephone and short-message follow-ups can increase compliance with inhaled corticosteroid treatment and improve the asthma control levels and lung function of asthmatic children.
Assuntos
Corticosteroides , Asma , Telefone , Humanos , Asma/tratamento farmacológico , Criança , Masculino , Feminino , Administração por Inalação , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Envio de Mensagens de Texto , Adesão à Medicação/estatística & dados numéricos , Resultado do Tratamento , Testes de Função Respiratória , Antiasmáticos/administração & dosagem , Antiasmáticos/uso terapêutico , Antiasmáticos/efeitos adversos , Adolescente , Pré-EscolarRESUMO
A high-performance anion-exchange chromatography coupled with diode array detection method was developed for the determination of dencichine in Panax notoginseng and related species. The analysis was performed on an Eprogen Synchropak WAX column (4.6 × 250 mm, 6 µm) with 50 mM NaH2 PO4 aqueous solution isocratic elution. The method was validated in terms of linearity, sensitivity, precision, stability, and accuracy. It was found that the calibration curve for dencichine showed good linearity (R(2) = 0.9999) within the test range. The LOD and LOQ were 0.77 and 3.06 ng, respectively. The RSD for intra- and interday repeatability was 0.2 and 0.5%, respectively. The test solution of dencichine is stable at least for three days at room temperature and for seven days at 4 °C. The mean recovery of dencichine was 102.0%. The established method was successfully applied to determine dencichine in the raw root of P. nogoginseng, P. ginseng, and P. quinquefolium as well as the steamed root of P. notoginseng. Compared with previous reports, this method is sensitive, selective, and accurate, which is helpful to evaluate the quality of P. notoginseng and related species.