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Astragaloside IV (AST) has been confirmed to have antiasthmatic effects. However, the underline mechanism is unclear. The study aimed to explore the treatment mechanism of AST based on autophagy of memory T cells. AST treatment significantly decreased the number of T effector cells in asthma mice blood and the nude mice that received AST-treated TCMs had relieved inflammation compared with the untreated group; meanwhile, we found that AST significantly decreased the autophagy level and inhibited OX40/OX40L signal pathway of lymphocytes. The results highlighted that AST regulated autophagy to inhibit differentiation of effector T-cell phenotype.
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Asma , Autofagia , Inflamação , Saponinas , Linfócitos T , Triterpenos , Animais , Saponinas/farmacologia , Asma/tratamento farmacológico , Triterpenos/farmacologia , Triterpenos/química , Camundongos , Autofagia/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Inflamação/tratamento farmacológico , Camundongos Nus , Estrutura Molecular , Transdução de Sinais/efeitos dos fármacos , Camundongos Endogâmicos BALB CRESUMO
PURPOSE: There are limited studies on the use of bronchodilators for the treatment of bronchiectasis. This study investigated the efficacy of tiotropium in patients with bronchiectasis and airflow limitation. METHODS: This study was a prospective cohort study, including 169 patients with bronchiectasis and airflow limitation from 2015 to 2019. The clinical outcomes observed in our study were the effect of tiotropium on the frequency of moderate exacerbations, the time to the first severe exacerbation, and the annual decline in FEV1. RESULTS: After 12 months, the annual decline in the FEV1 after bronchodilator use was 27.08 ml or 42.9 ml per year in the group with or without tiotropium, respectively. Treatment with tiotropium was associated with a decreased risk of moderate exacerbation of bronchiectasis (Adjusted RR 0.618 95% CI 0.493-0.774; P < 0.005). The time to the first severe acute exacerbation of bronchiectasis in the tiotropium group was longer than the non-tiotropium group (Adjusted HR 0.333 95% CI 0.219-0.506; P < 0.001). CONCLUSION: In conclusion, prospective cohort study showed that tiotropium effectively ameliorated the annual decline in the FEV1, with a lower-risk rate of moderate exacerbations and prolonging the time to the first-time severe exacerbation in patients with bronchiectasis and airflow limitation.
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Bronquiectasia , Doença Pulmonar Obstrutiva Crônica , Humanos , Brometo de Tiotrópio/uso terapêutico , Estudos Prospectivos , Derivados da Escopolamina/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Broncodilatadores/uso terapêutico , Resultado do TratamentoRESUMO
The transcription factor Woolly (Wo) and its downstream gene CycB2 have been shown to regulate trichome development in tomato (Solanum lycopersicum). It has been demonstrated that only the gain-of-function allele of Slwo (SlWoV, the Slwo woolly motif mutant allele) can increase the trichome density; however, it remains unclear why the two alleles function differently in trichome development. In this study, we used Nicotiana benthamiana as a model and cloned the homologues of Slwo and SlCycB2 (named Nbwo and NbCycB2). We also constructed a Nbwo gain-of-function allele with the same mutation site as SlWoV (named NbWoV). We found that both Nbwo and NbWoV directly regulate NbCycB2 and their own expression by binding to the promoter of NbCycB2 and their own genomic sequences. As form of a feedback regulation, NbCycB2 negatively regulates trichome formation by repressing Nbwo activity at the protein level. We also found that mutations in the Nbwo woolly motif can prevent repression of NbWoV by NbCycB2, which results in a significant increase in the amount of active Nbwo proteins and in increases in trichome density and the number of branches. Our results reveal a novel reciprocal regulation mechanism between NbCycB2 and Nbwo during trichome formation in N. benthamiana.
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Proteínas de Arabidopsis , Solanum lycopersicum , Proteínas de Arabidopsis/metabolismo , Retroalimentação , Regulação da Expressão Gênica de Plantas , Solanum lycopersicum/genética , Solanum lycopersicum/metabolismo , Nicotiana/genética , Nicotiana/metabolismo , Tricomas/metabolismoRESUMO
AIM: Physcion is a major bioactive ingredient in the traditional Chinese medicine Radix et Rhizoma Rhei, which has an anthraquinone chemical structure and exhibits a variety of pharmacological activities including laxative, hepatoprotective, anti-inflammatory, anti-microbial and anti-proliferative effects. In this study we investigated the effect of physcion on human nasopharyngeal carcinoma in vitro and in vivo, as well as the mechanisms underlying the anti-tumor action. METHODS: The nasopharyngeal carcinoma cell line CNE2 was treated with physcion, and cell viability was detected using MTT and colony formation assays. Flow cytometry was used to assess the cell cycle arrest, mitochondrial membrane potential loss, apoptosis, autophagy and intracellular ROS generation. Apoptotic cell death was also confirmed by a TUNEL assay. The expression of target or marker molecules was determined using Western blotting. The activity of caspase-3, 8, and 9 was detected with an ELISA kit. A xenograft murine model was used to evaluate the in vivo anti-tumor action of physcion, the mice were administered physcion (10, 20 mg·kg-1·d-1, ip) for 30 d. RESULTS: Treatment with physcion (5, 10, and 20 µmol/L) dose-dependently suppressed the cell viability and colony formation in CNE2 cells. Physcion (10 and 20 µmol/L) dose-dependently blocked cell cycle progression at G1 phase and induced both caspase-dependent apoptosis and autophagy in CNE2 cells. Furthermore, physcion treatment induced excessive ROS generation in CNE2 cells, and subsequently disrupted the miR-27a/ZBTB10 axis, resulting in repression of the transcription factor Sp1 that was involved in physcion-induced apoptosis and autophagy. Moreover, physcion-induced autophagy acted as a pro-apoptotic factor, and possibly contributed to physcion-induced apoptosis. In the xenograft murine model, administration of physcion dose-dependently suppressed the tumor growth without affecting the body weight. Furthermore, the anti-tumor effects of physcion were correlated with downregulation of Sp1 and suppression of miR-27a in the tumor tissues. CONCLUSION: Physcion induces apoptosis and autophagy in human nasopharyngeal carcinoma by targeting Sp1, which was mediated by ROS/miR-27a/ZBTB10 signaling. The results suggest that physcion is a promising candidate for the treatment of human nasopharyngeal carcinoma.
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Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Emodina/análogos & derivados , Neoplasias Nasofaríngeas/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/uso terapêutico , Linhagem Celular Tumoral , Emodina/farmacologia , Emodina/uso terapêutico , Xenoenxertos , Humanos , Camundongos , Neoplasias Nasofaríngeas/metabolismo , Transplante de Neoplasias , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição Sp1/genética , Fator de Transcrição Sp1/metabolismoRESUMO
OBJECTIVE: To investigate the relationship between single nucleotide polymorphisms (SNPs) of cytochrome P450 (CYP450) 3A4 rs2242480 and inter-individual differences of sufentanil consumption in accouchement sans douleur. METHODS: A total of 131 parturient women were collected. According to the distribution of genotypes and allele frequencies of rs2242480, the doses of sufentanil were individually designed. CC homozygotes were given the standard analgesia dose, CT heterozygotes and TT homozygotes were given 87.6% of standard sufentanil dose. RESULTS: Visual analogue score (VAS) between CC group and CT/TT group were 3.67±1.2 and 3.44±1.5, consistent with the expected analgesic standards. The difference was not statistically significant. CONCLUSION: The parturient women carrying CT heterozygotes and TT homozygotes of CYP3A4 rs2242480 required less sufentanil in accouchement sans douleur.
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Analgésicos Opioides/uso terapêutico , Citocromo P-450 CYP3A/genética , Trabalho de Parto/efeitos dos fármacos , Polimorfismo Genético , Sufentanil/uso terapêutico , Analgesia , Feminino , Frequência do Gene , Genótipo , Humanos , Dor/tratamento farmacológico , Medição da Dor , Polimorfismo de Nucleotídeo Único , GravidezRESUMO
BACKGROUND: Infected acute necrotic collection (ANC) is a fatal complication of acute pancreatitis with substantial morbidity and mortality. Drainage plays an exceedingly important role as the first step in invasive intervention for infected necrosis; however, there is great controversy about the optimal drainage time, and better treatment should be explored. CASE SUMMARY: We report the case of a 43-year-old man who was admitted to the hospital with severe intake reduction due to early satiety 2 wk after treatment for acute pancreatitis; conservative treatment was ineffective, and a pancreatic pseudocyst was suspected on contrast-enhanced computed tomography (CT). Endoscopic ultrasonography (EUS) suggested hyperechoic necrotic tissue within the cyst cavity. The wall was not completely mature, and the culture of the puncture fluid was positive for A-haemolytic Streptococcus. Thus, the final diagnosis of ANC infection was made. The necrotic collection was not walled off and contained many solid components; therefore, the patient underwent EUS-guided aspiration and lavage. Two weeks after the collection was completely encapsulated, pancreatic duct stent drainage via endoscopic retrograde cholangiopancreatography (ERCP) was performed, and the patient was subsequently successfully discharged. On repeat CT, the pancreatic cysts had almost disappeared during the 6-month follow-up period after surgery. CONCLUSION: Early EUS-guided aspiration and lavage combined with late ERCP catheter drainage may be effective methods for intervention in infected ANCs.
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BACKGROUND: Interventional endoscopic ultrasound is clinically used for the treatment of isolated gastric varices (IGVs) owing to its precise visualization. CASE SUMMARY: A 39-year-old man was diagnosed with a large IGV during a routine physical examination. Endoscopic ultrasonography showed gastric varices entwined with an artery, which greatly increased the difficulty of treatment. We successfully treated the patient with endoscopic ultrasonography-guided coil embolization combined with cyanoacrylate injection. CONCLUSION: Endoscopic ultrasonography-guided coil embolization combined with cyanoacrylate injection was safe and effective for the treatment of an IGV entwined with an artery.
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PURPOSE: To investigate whether resting-state brain functional connectivity (FC) differed among cirrhotic patients without overt hepatic encephalopathy (HE) (OHE), those who currently had minimal HE (MHE), or those who had recovered from previous OHE and to investigate whether previous bouts of OHE rather than current MHE predominantly contributed to brain dysfunction in patients without current OHE. MATERIALS AND METHODS: This study was approved by the institutional ethics committee, and informed consent was obtained. Resting-state functional magnetic resonance (MR) data were compared between healthy controls and the following groups of cirrhotic patients: (a) patients without MHE and without previous OHE, (b) patients with current MHE and without previous OHE, and (c) patients with previous OHE. Independent component analysis was applied to identify the best-fit component for the default-mode network (DMN). One-way analysis of variance was performed to detect different FC among groups. Pearson correlation analyses were conducted to determine the relationships between FC and neurocognitive performance. RESULTS: Two important regions within the DMN, including the precuneus and posterior cingulate cortex and left medial frontal gyrus, showed significantly different FC among the four groups. A trend of gradually reduced FC in two regions was observed from controls, to patients without HE, and to patients with current MHE, while patients with previous OHE showed remarkably reduced FC in these two regions. Significant correlations were found between FC and neurocognitive performance in cirrhotic patients. CONCLUSION: The reduced resting-state FC within DMN was associated with neurocognitive impairments in MHE and after clinical resolution of OHE. Previous OHE rather than current MHE might be primarily related to brain dysfunction in patients with latent OHE. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120026/-/DC1.
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Mapeamento Encefálico/métodos , Encéfalo/fisiopatologia , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/fisiopatologia , Encefalopatia Hepática/complicações , Encefalopatia Hepática/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Encéfalo/patologia , Transtornos Cognitivos/diagnóstico , Feminino , Encefalopatia Hepática/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Índice de Gravidade de DoençaRESUMO
Invasive pulmonary aspergillosis (IPA) is difficult to diagnose in chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate whether detection of galactomannan (GM) in bronchoalveolar lavage fluid (BALF) might be a useful means of making the diagnosis. Patients with COPD and new pulmonary infiltrates were enrolled. BALF was collected for culture and detection of GM. Venous blood was also sampled for GM detection. Biopsy samples were obtained whenever possible. Eleven cases of IPA were diagnosed (three proven and eight probable); 80 controls without IPA diagnosed were recruited. At a GM cut-off of 0.5, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for diagnosing IPA were 90.9, 66.3, 27.0 and 98.1% in serum, and 90.9, 62.5, 25.0 and 98.0% in BALF, respectively. At a cut-off of 1.0, the specificity, PPV and NPV in BALF increased to 95.0, 71.4 and 98.7%; the sensitivity remained 90.9%. The sensitivity in serum was substantially lower than BALF (45.5% versus 90.9%). Receiver operating characteristic curve analysis identified an optimal BALF GM cut-off value of 1.25, with a sensitivity of 90.9% and a specificity of 96.3% for diagnosing IPA. At a relatively high cut-off value, BALF GM detection is a useful tool for the diagnosis of IPA in COPD. Besides piperacillin-tazobactam and amoxicillin-clavulanate, many other factors may also cause false-positive of GM detection in patients without IPA. Further work is needed to identify factors that might lead to false-positive or false-negative results.
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Líquido da Lavagem Broncoalveolar/química , Técnicas de Laboratório Clínico/métodos , Aspergilose Pulmonar Invasiva/diagnóstico , Mananas/análise , Micologia/métodos , Doença Pulmonar Obstrutiva Crônica/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Análise Química do Sangue , Estudos de Coortes , Feminino , Galactose/análogos & derivados , Humanos , Pulmão/microbiologia , Masculino , Mananas/sangue , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Sensibilidade e EspecificidadeRESUMO
This study aims to detect S100A12 in serum and synovial fluid (SF) of knee osteoarthritis (OA) patients and to investigate their correlation with clinical severity of the disease. This study enrolled 198 OA patients and 84 healthy controls. The radiological/symptomatic severity of the disease was assessed by the Kellgren-Lawrence (KL) grading system/Western Ontario McMaster University Osteoarthritis (WOMAC) scores. We demonstrated that S100A12 levels in SF but not serum were independently associated with KL grades and WOMAC scores. These results suggested that the S100A12 in SF might be a potential biomarker for predicting the development and progression of knee OA.
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Articulação do Joelho/metabolismo , Osteoartrite do Joelho/metabolismo , Proteínas S100/metabolismo , Índice de Gravidade de Doença , Líquido Sinovial/química , Idoso , Biomarcadores/metabolismo , Estudos de Casos e Controles , Progressão da Doença , Feminino , Humanos , Articulação do Joelho/patologia , Articulação do Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico , Osteoartrite do Joelho/patologia , Osteoartrite do Joelho/cirurgia , Proteína S100A12RESUMO
We previously demonstrated that the effects of diethylhexyl phthalate (DEHP) alter reproduction function on male mice. Immature male mice were treated daily with DEHP from postnatal day 7-21, 7-35, 7-49, in a dose-dependent manner. As results, both the quality and quantity of spermatozoa were decreased in 60-day-old mice. The results by RT-PCR analysis indicated that DDx3Y, Usp9Y, RBM, E1F1AY, EGF, FSHR and EGFR genes were down-regulated, and LHR, Cyp17a1 and Cyp19a1 were down-regulated in response to DEHP. These genes were selected based on their markedly increased or decreased expression levels. However, DEHP had no effect on the meiotic process and recombination levels in male mouse germ cells. Treatment with DEHP induced histopathological changes in the testes. Taken together, these results provide a new insight into the molecular mechanisms underlying the detrimental impacts of DEHP in humans and wildlife.
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Dietilexilftalato/farmacologia , Espermatogênese/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Aberrações Cromossômicas , Dietilexilftalato/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Meiose/efeitos dos fármacos , Camundongos , Análise do Sêmen , Espermatogênese/genética , Testículo/efeitos dos fármacos , Testículo/metabolismo , Testículo/patologia , Fatores de TempoRESUMO
OBJECTIVE: To investigate the features of airway inflammation and hypothalamic-pituitary-adrenal axis (HPAA) activity in patients with asthma accompanied by depression. METHODS: Adult asthmatics were recruited and enrolled into one of the two groups based on scores on the Hamilton Depression Rating Scale (HAMD): asthmatics with depression (HAMD score ≥8, n = 23), and asthmatics without depression (HAMD score <8, n = 41). In addition, 27 healthy individuals and 21 adults with depression only were enrolled as controls. Induced sputum and blood samples were collected for measurement of cytokines and other inflammatory factors. The diurnal rhythm profiles of salivary cortisol and other hormones were obtained for assessment of the HPAA activity. RESULTS: For the group of asthmatics with depression, the mean HAMD score was 19.0, and for the group of asthmatics without depression, the HAMD score averaged 4.9(p < .001). Serum and sputum tumor necrosis factor alpha (TNF-α) were significantly higher in asthmatics with depression than those in the other groups (p < .05) while serum interferon-gamma (IFN-γ) was lower in asthmatics with depression than that in the other groups (p < .05). Twenty-four-hour urinary cortisol, salivary cortisol at 8 a.m. and 4 p.m. were lower in asthmatics with depression compared to other groups (p < .05). CONCLUSIONS: As compared to healthy individuals and those with asthma or depression alone, individuals with comorbid depression and asthma showed the highest level of pro-inflammatory cytokines and the lowest level of anti-inflammatory cytokines and cortisol. These observations may serve as a valuable reference for diagnosis and clinic therapies of depression in asthmatics.
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Asma/patologia , Depressão/patologia , Sistema Hipotálamo-Hipofisário/fisiologia , Sistema Hipófise-Suprarrenal/fisiologia , Adolescente , Adulto , Idoso , Asma/imunologia , Asma/metabolismo , Asma/psicologia , Ritmo Circadiano/fisiologia , Citocinas/sangue , Depressão/imunologia , Depressão/metabolismo , Depressão/psicologia , Feminino , Humanos , Hidrocortisona/metabolismo , Masculino , Pessoa de Meia-Idade , Hipersensibilidade Respiratória/imunologia , Hipersensibilidade Respiratória/metabolismo , Hipersensibilidade Respiratória/patologia , Hipersensibilidade Respiratória/psicologia , Saliva/química , Saliva/imunologia , Saliva/metabolismo , Adulto JovemRESUMO
OBJECTIVE: To detect the functional networks of the red nucleus and substantia nigra during the resting state in normal subjects with functional magnetic resonance imaging (fMRI). METHODS: Sixteen normal subjects were performed resting state fMRI scanning and susceptibility weighted imaging. The function connectivity networks base on seed regions of the red nucleus and substantia nigra were extracted from low frequency fluctuation signal in fMRI data by using a temporal correlation method. Individual functional maps were entered two-tailed one-sample t test to determine brain regions with significant positive correlation to the seeds. The statistic threshold was set at P < 0.001, cluster size>42 (336 mm(3)), cluster connectivity criterion 5 min with Alphasim correction. RESULTS: Brain regions involved in the functional connectivity network of the red nucleus include: dorsal anterior cingutate, supramarginal gyrus, the ventrolateral and the ventromedial nucleus of the thalamus, globus pallidus, dorsal thalamus, hippocampus, substantia nigra, red nucleus, pons, dentate nucleus, vermis; Brain regions involved in the functional connectivity network of the substantia nigra include: anterior cingutate, supramarginal gyrus, globus pallidus, dorsal thalamus, hippocampus, lobus insularis, substantia nigra, red nucleus, pons, dentate nucleus. The distribution of the networks of the red nucleus and substantia nigra presented symmetrical. Although the functional networks of the red nucleus and substantia nigra over lapped largely with each other, the rubral network was slightly different with the nigral network, witch showed strong correlations with more wide-spread striatum and thalamus areas. CONCLUSION: The functional networks of the red nucleus and substantia nigra reflected strong interplay within the extrapyramidal subcortical system, as well as correlations between some limited cerebral cortices; Functional magnetic resonance imaging is a potential powerful tool to explore the extrapyramidal system.
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Mesencéfalo/fisiologia , Núcleo Rubro/fisiologia , Substância Negra/fisiologia , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Vias Neurais , Adulto JovemRESUMO
Bronchial asthma and chronic obstructive pulmonary disease (COPD), as chronic airway inflammatory diseases, seriously threaten the health of human beings. Chinese medicine has obvious advantages in prevention and treatment of them. "Preventive treatment theory" is a sort summarization of preventive medicine in Chinese medicine. The theory is not only reflected at the disease prevention levels, also embodied in the active treatment and the rehabilitation process. It was especially deep and colorfully embodied in the prevention and treatment of chronic airway inflammatory diseases such as asthma and COPD. In this paper,clarified were the prevention and treatment targets, ways of thinking and methods in different stages of asthma and COPD from various viewpoints including prevention before disease occurrence, treating disease at disease onset, preventing the aggravation once disease occurs, and consolidation after disease occurs. We hope to improve ways of thinking and prevention and treatment levels of bronchial asthma and COPD by Chinese medicine.
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Asma/prevenção & controle , Medicina Tradicional Chinesa/métodos , Doença Pulmonar Obstrutiva Crônica/prevenção & controle , Doença Crônica , HumanosRESUMO
Treating different diseases by the same method is one of the most important characteristics in Chinese medicine, and as the main principle of treatment it has been widely applied in Chinese clinics. Its clinical effect is clear. The integration of 'differentiation of diseases' and 'differentiation of syndrome' should be the prerequisite and basis of 'treating different diseases by the same method'. Only if different diseases have the same syndrome, the same treatment can be used on them. Replenishing qi and strengthening Shen is a widely used method that carries out 'treating different diseases by the same method'. It is indicated that the method of 'replenishing qi and strengthening Shen' has preferable effects on many diseases. Part of its mechanism is associated with the improvement of function of neuro-endocrine-immune network, and therefore, it has the clinical effect of 'adjustment of the whole and improvement of the part' on partial disorders. Asthma, chronic obstructive pulmonary disease (COPD), uterine bleeding in puberty, anovulatory infertility, Kidney syndrome and aging, although they are attributed to different diseases and states, only if they have the syndrome of Shen deficiency, the principle of 'treating different diseases by the same method' and the method of 'replenishing qi 'and strengthening Shen' can be used effectively.
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Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa/métodos , Fitoterapia/métodos , HumanosRESUMO
The strength of phylogeographic breaks can vary among species in the same area despite being subject to the same geological and climate history due to differences in biological traits. Several important phylogeographic breaks exist around the Sichuan Basin in Southwest China but few studies have focused on wind-dispersed plants. Here, we investigated the phylogeographic patterns and the evolutionary history of Populus lasiocarpa, a wind-pollinated and wind-dispersed tree species with a circum-Sichuan Basin distribution in southwest China. We sequenced and analyzed three plastid DNA fragments (ptDNA) and eight nuclear microsatellites (nSSRs) of 265 individuals of P. lasiocarpa from 21 populations spanning the entire distribution range. Distribution patterns based on nSSR data revealed that there are three genetic groups in P. lasiocarpa. This is consistent with the three phylogeographic breaks (Sichuan Basin, the Kaiyong Line and the 105°E line), where the Sichuan basin acts as the main barrier to gene flow between western and eastern groups. However, the distribution pattern based on ptDNA haplotypes poorly matched the phylogeographic breaks, and wind-dispersed seeds may be one of the main contributing factors. Species distribution modelling suggested a larger potential distribution in the last glacial maximum with a severe bottleneck during the last interglacial. A DIYABC model also suggested a population contraction and expansion for both western and eastern lineages. These results indicate that biological traits are likely to affect the evolutionary history of plants, and that nuclear molecular markers, which experience higher levels of gene flow, might be better indicators of phylogeographic breaks.
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The lack of M-Fe-S (M = Mo or W) clusters incorporating a second period (2p) atom in the core has resulted in limited investigations and poor understanding of the physical and chemical properties of the M-Fe-S clusters closely related to the FeMo cofactor. In this work, systematic studies have been carried out to explore the chemical reactivities at the terminal ligand sites and the redox properties of a series of clusters comprising a [WFe3S3N] cubane core, based on the previously developed cluster [(Tp*)WFe3S3(µ3-NSiMe3)Cl3]1-. Substitutions of the terminal chlorides with ethanethiolate, methanethiolate, thiophenolate, p-thiocresolate and azide occurred smoothly, while the replacement of the chlorides with carbene ligands required the reduction of the precursor into [(Tp*)WFe3S3(µ3-NSiMe3)Cl3]2- first. The reduced cluster core could also be supported by thiophenolates as terminal ligands, but not thiolates or azides. It is remarkable that the thiophenolate ligated reduced cluster can be synthesized from the precursor [(Tp*)WFe3S3(µ3-NSiMe3)Cl3]1-via different synthetic routes, either reduction followed by substitution or substitution followed by reduction, either in situ or stepwise. This work indicates that terminal ligands contribute significantly to determine the chemical and physical properties of the clusters, even though they might affect the cluster core to a limited extent from a structural point of view, which raises the possibility of delicate control in regulating the physical/chemical properties of M-Fe-S clusters with a heteroleptic core incorporating 2p atom(s).
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The objective of this study was to explore the expression and clinical significance of Notch signaling genes in colorectal cancer. Colorectal cancer samples were prospectively collected from patients post-surgery at the 3rd Affiliated Hospital, Nanjing University of Traditional Chinese Medicine. Immunohistochemistry of tissue arrays was used to analyze the samples and genes involved in the Notch signaling pathway. Microsatellite instability (MSI) was detected by fluorescence multiplex polymerase chain reaction. A total of 146 colorectal cancer samples were collected, including 84 men (57.7%) and 62 women (42.5%). The average age of the study population was 60.8 ± 10.5 years. Notch1 and Notch2 gene expression correlated with tumor pathology type and degree of differentiation. In addition, Jagged 1 (JAG1) and hairy enhancer of split 1 gene expression correlated with the degree of tumor differentiation. Delta-like 1 gene expression varied significantly with tumor location. There was a significant difference between gene expression and MSI. Of the 138 patients, 134 (91.8%) participated in on-site visits, and the average follow-up time was 42.3 ± 13.3 months. During this period, 86 patients (71.6%) were tumor-free. At 1 year post-surgery, 93% of patients were alive, 74% of patients lived for 3 years, and 67% of patients lived for 5 years. The log-rank test was used to perform univariate analysis, and the COX proportional hazards model was used for the multivariate analysis. Based on these analyses, tumor prognosis correlated with the TNM stage, pathological type, microsatellite status as well as Notch2 and JAG1 gene expression. Patients expressing high levels of Notch2 and JAG1 presented with a significantly better prognosis compared to patients expressing negative or weak levels of Notch2 and JAG1. The expression levels of genes associated with the Notch signaling pathway correlated with tumor pathology and the degree of differentiation. In addition, Notch2 and JAG1 expression levels correlated with survival; however, the underlying mechanism for these correlations remains unclear.
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Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Perfilação da Expressão Gênica , Receptores Notch/genética , Transdução de Sinais , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/mortalidade , Feminino , Humanos , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida , Adulto JovemRESUMO
OBJECTIVE: To investigate the frequencies of chemokine (C-C motif) receptor 5 gene (CCR5)Δ32 deletional mutation of in Han and Dai populations from Yunnan province. Immortalized cell lines were derived from a family carrying the CCR5Δ32 mutation. METHODS: Blood samples of 346 Han and 355 Dai individuals were collected for genotyping. The coding regions of CCR5 gene were amplified with PCR followed by agarose gel electrophoresis. Suspected mutations were verified with DNA sequencing. Immortalized cell lines were constructed by using Epstain Barr virus and cyclosporine A. The difference between the cell lines and original blood samples was verified with PCR. RESULTS: One ethnic Han individual was confirmed to be heterozygous for a deletional mutation by sequencing, which has led to discovery of a family with CCR5Δ32. Nine immortalized cell lines were established from this family, and no difference between the cell lines and original blood samples was detected by PCR. CONCLUSION: Together with previous reports, this study has indicated a significant difference in CCR5Δ32 among different ethnic groups in China. Established immortalized cell lines can also provide material for future research.
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Receptores CCR5/genética , Deleção de Sequência , Sequência de Bases , China , Etnicidade , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Dados de Sequência Molecular , LinhagemRESUMO
Leukoaraiosis (LA) is commonly found in aging healthy people but its pathophysiological mechanism is not entirely known. Furthermore, there is still a lack of effective pathological biomarkers that can be used to identify the early stage of LA. Our aim was to investigate the white matter structural network in asymptomatic patients with the early stage of LA. Tractography data of 35 asymptomatic patients and 20 matched healthy controls (HCs) based on diffusion kurtosis imaging (DKI) were analysed by using graph theory approaches and tract-based spatial statistics (TBSS). Diffusion parameters measured within the ALAs and HCs were compared. Decreased clustering coefficient and local efficiency values of the overall topological white matter network were observed in the ALAs compared with those of the HCs. Participants in the asymptomatic group also had lower nodal efficiency in the left triangular part of the inferior frontal gyrus, left parahippocampal gyrus, right calcarine fissure and surrounding cortex, right temporal pole of the superior temporal gyrus and left middle temporal gyrus compared to the ALAs. Moreover, similar hub distributions were found within participants in the two groups. In this study, our data demonstrated a topologic efficiency abnormalities of the structural network in asymptomatic patients with leukoaraiosis. The structural connectome provides potential connectome-based measures that may be helpful for detecting leukoaraiosis before clinical symptoms evolve.