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1.
Front Immunol ; 14: 1263988, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38090564

RESUMO

Background: Autophagy plays a critical role in the progression of osteoarthritis (OA), mainly by regulating inflammatory and immune responses. However, the underlying mechanisms remain unclear. This study aimed to investigate the potential relevance of autophagy-related genes (ARGs) associated with infiltrating immune cells in OA. Methods: GSE114007, GSE169077, and ARGs were obtained from the Gene Expression Omnibus (GEO) database and the Human Autophagy database. R software was used to identify the differentially expressed autophagy-related genes (DEARGs) in OA. Functional enrichment and protein-protein interaction (PPI) analyses were performed to explore the role of DEARGs in OA cartilage, and then Cytoscape was utilized to screen hub ARGs. Single-sample gene set enrichment analysis (ssGSEA) was used to conduct immune infiltration analysis and evaluate the potential correlation of key ARGs and immune cell infiltration. Then, the expression levels of hub ARGs in OA were further verified by the GSE169077 and qRT-PCR. Finally, Western blotting and immunohistochemistry were used to validate the final hub ARGs. Results: A total of 24 downregulated genes and five upregulated genes were identified, and these genes were enriched in autophagy, mitophagy, and inflammation-related pathways. The intersection results identified nine hub genes, namely, CDKN1A, DDIT3, FOS, VEGFA, RELA, MAP1LC3B, MYC, HSPA5, and HSPA8. GSE169077 and qRT-PCR validation results showed that only four genes, CDKN1A, DDT3, MAP1LC3B, and MYC, were consistent with the bioinformatics analysis results. Western blotting and immunohistochemical (IHC) showed that the expression of these four genes was significantly downregulated in the OA group, which is consistent with the qPCR results. Immune infiltration correlation analysis indicated that DDIT3 was negatively correlated with immature dendritic cells in OA, and FOS was positively correlated with eosinophils. Conclusion: CDKN1A, DDIT3, MAP1LC3B, and MYC were identified as ARGs that were closely associated with immune infiltration in OA cartilage. Among them, DDIT3 showed a strong negative correlation with immature dendritic cells. This study found that the interaction between ARGs and immune cell infiltration may play a crucial role in the pathogenesis of OA; however, the specific interaction mechanism needs further research to be clarified. This study provides new insights to further understand the molecular mechanisms of immunity involved in the process of OA by autophagy.


Assuntos
Cartilagem Articular , Osteoartrite , Humanos , Genes Reguladores , Genes cdc , Osteoartrite/genética , Autofagia/genética
2.
J Vis Exp ; (197)2023 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-37578257

RESUMO

Helicobacter pylori is a major human pathogen that infects approximately half of the global population and is becoming a serious health threat due to its increasing antibiotic resistance. It is the causative agent of chronic active gastritis, peptic ulcer disease, and gastric cancer and has been classified as a Group I Carcinogen by the International Agency for Research on Cancer. Therefore, the rapid and accurate diagnosis of H. pylori and the determination of its antibiotic resistance are important for the efficient eradication of this bacterial pathogen. Currently, H. pylori diagnosis methods mainly include the urea breath test (UBT), the antigen test, the serum antibody test, gastroscopy, the rapid urease test (RUT), and bacterial culture. Among them, the first three detection methods are noninvasive, meaning they are easy tests to conduct. However, bacteria cannot be retrieved through these techniques; thus, drug resistance testing cannot be performed. The last three are invasive examinations, but they are costly, require high skills, and have the potential to cause damage to patients. Therefore, a noninvasive, rapid, and simultaneous method for H. pylori detection and drug resistance testing is very important for efficiently eradicating H. pylori in clinical practice. This protocol aims to present a specific procedure involving the string test in combination with quantitative polymerase chain reaction (qPCR) for the rapid detection of H. pylori infection and antibiotic resistance. Unlike bacterial cultures, this method allows for easy, rapid, noninvasive diagnosis of H. pylori infection status and drug resistance. Specifically, we used qPCR to detect rea for H. pylori infection and mutations in the 23S rRNA and gyrA genes, which encode resistance against clarithromycin and levofloxacin, respectively. Compared to routinely used culturing techniques, this protocol provides a noninvasive, low-cost, and time-saving technique to detect H. pylori infection and determine its antibiotic resistance using qPCR.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Humanos , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Claritromicina/farmacologia , Resistência Microbiana a Medicamentos , Reação em Cadeia da Polimerase , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética
3.
J Orthop Surg Res ; 18(1): 289, 2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-37038162

RESUMO

BACKGROUND: Mesenchymal stem cells (MSCs)-based therapy offers an effective strategy for bone regeneration to solve the clinical orthopedic problems. However, the transcriptional regulation of multiple transitional stages of continuous osteogenesis from MSCs has not been fully characterized. METHODS: Bone marrow mesenchymal stem cells (BMSCs) stimulated with osteogenic induction media were utilized to construct the in vitro osteogenic differentiation model. BMSCs were harvested after induction for 0, 7, 14 and 21 days, respectively, to perform the mRNA-sequencing (mRNA-Seq). The transcription factor networks and common molecules during the osteogenesis were revealed by using the temporal transcriptome. Further verification was performed by the quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence and Western blotting. RESULTS: It showed that BMSCs could differentiate into osteogenic, and crucial regulator in the MAPK signaling pathway, the PPAR signaling pathway, the Toll-like receptor signaling and the Cytokine/JAK/STAT signaling pathway. PPI protein interaction analysis also suggested that three cytokines are involved in osteogenic differentiation as core genes, including leukemia inhibitory factor (LIF), interleukin-6 (IL6) and colony-stimulating factor 3 (CSF3). The osteogenic process was negatively affected by the inhibition of JAK/STAT3 signaling pathway. CONCLUSIONS: This work might provide new insights in the crucial features of the transcriptional regulation during the osteogenesis, as well as offer important clues about the activity and regulation of the relatively long-activated Cytokine/JAK/STAT3 signaling pathway in osteoinduction of BMSCs.


Assuntos
Células-Tronco Mesenquimais , Osteogênese , Transcriptoma , Citocinas/metabolismo , Transdução de Sinais/fisiologia , Diferenciação Celular , Células-Tronco Mesenquimais/metabolismo , RNA Mensageiro/metabolismo , Células da Medula Óssea/metabolismo , Células Cultivadas
4.
Front Oncol ; 12: 828849, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35463319

RESUMO

Background: Osteosarcoma (OS) is a malignant bone tumor common in children and adolescents. The 5-year survival rate is only 67-69% and there is an urgent need to explore novel drugs effective for the OS. G protein-coupled receptors (GPCRs) are the common drug targets and have been found to be associated with the OS, but have been seldom used in OS. Methods: The GPCRs were obtained from GPCRdb, and the GPCRs expression profile of the OS was downloaded from the UCSC Xena platform including clinical data. 10-GPCRs model signatures related to OS risk were identified by risk model analysis with R software. The predictive ability and pathological association of the signatures in OS were explored by bio-informatics analysis. The therapeutic effect of the target was investigated, followed by the investigation of the targeting drug by the colony formation experiment were. Results: We screened out 10 representative GPCRs from 50 GPCRs related to OS risk and established a 10-GPCRs prognostic model (with CCR4, HCRTR2, DRD2, HTR1A, GPR158, and GPR3 as protective factors, and HTR1E, OPN3, GRM4, and GPR144 as risk factors). We found that the low-risk group of the model was significantly associated with the higher survival probability, with the area under the curve (AUC) of the ROC greater than 0.9, conforming with the model. Moreover, both risk-score and metastasis were the independent risk factor of the OS, and the risk score was positively associated with the metastatic. Importantly, the CD8 T-cells were more aggregated in the low-risk group, in line with the predict survival rate of the model. Finally, we found that DRD2 was a novel target with approved drugs (cabergoline and bromocriptine), and preliminarily proved the therapeutic effects of the drugs on OS. These novel findings might facilitate the development of OS drugs. Conclusion: This study offers a satisfactory 10-GPCRs model signature to predict the OS prognostic, and based on the model signature, candidate targets with approved drugs were provided.

5.
Food Funct ; 12(8): 3562-3571, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33900303

RESUMO

Luteolin attenuates myocardial ischemia/reperfusion (I/R) injury in diabetes through activating the nuclear factor erythroid 2-related factor 2 (Nrf2)-related antioxidative response. Though sestrin2, a highly conserved stress-inducible protein, is regarded as a modulator of Nrf2 and reduces I/R injury, the effect of sestrin2 on luteolin-induced prevention of the diabetic heart from I/R injury remains unclear. We hypothesized that luteolin could relieve myocardial I/R injury in diabetes by activating the sestrin2-modulated Nrf2 antioxidative response. Diabetes was induced in rats using a single dose of streptozotocin (65 mg kg-1, i.p.) for 6 weeks, and then luteolin (100 mg kg-1 d-1, i.g.), Nrf2 inhibitor brusatol, or sestrin2 blocker leucine was administered for 2 consecutive weeks. After that, the hearts were isolated and exposed to global I/R (30 min/120 min). Luteolin markedly improved cardiac function, myocardial viability and expressions of Nrf2-regulated antioxidative genes, and reduced lactate dehydrogenase release, malondialdehyde, and 8-hydroxydeoxyguanosine in the diabetic I/R hearts. Ca2+-induced mitochondrial permeability transition and membrane potential disruption were markedly inhibited in luteolin-treated diabetic ventricular myocytes. All these effects of luteolin were significantly reversed by Nrf2 inhibitor brusatol or sestrin2 inhibitor leucine. Luteolin-induced diminished Keap1 and augmented nuclear translocation and ARE binding activity of Nrf2 were hampered by leucine in the diabetic I/R heart. In addition, luteolin-induced augmented transcription of sestrin2 was markedly blocked by brusatol in the diabetic I/R heart. These data suggest that sestrin2 and Nrf2 positively interact to promote antioxidative actions and attenuate mitochondrial damage, by which luteolin relieves diabetic myocardial I/R injury.


Assuntos
Cardiotônicos/farmacologia , Luteolina/farmacologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Animais , Diabetes Mellitus Experimental , Modelos Animais de Doenças , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Ratos , Ratos Sprague-Dawley , Sestrinas/metabolismo , Estreptozocina
6.
J Phys Chem B ; 125(15): 3824-3829, 2021 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-33830761

RESUMO

The computational determination of peptide conformations is a challenging task of finding minima in a high dimensional space. By combining the sampling efficiency of the genetic algorithm (GA) and the dimensionality reduction resulted from the backbone dihedral angle correlations, named as the path matrix (PM) method, a new searching algorithm, parallel microgenetic algorithm (PMGA), is proposed. Meanwhile, PMGA employs the density functional theory based energy as the fitness function and performs local geometry optimizations to enhance the reliability of its GA encoding strategy. Tests on peptides with up to eight amino-acid residues show PMGA is quite efficient for providing high-quality conformational coverages. The computational cost of the PMGA search increases slowly with the number of amino-acid residues in a peptide, with no sign of deterioration on the searching results for the increased length of the peptide. The PMGA method should therefore be useful for determining the conformations of oligopeptide, studying the protein-ligand interactions, and designing the peptide-based drugs.


Assuntos
Algoritmos , Peptídeos , Modelos Moleculares , Conformação Proteica , Reprodutibilidade dos Testes
7.
Artigo em Inglês | MEDLINE | ID: mdl-32889045

RESUMO

Growth hormone (GH) is the most important endocrine factor to regulate somatic growth. Spotted scat (Scatophagus argus) is a famous marine aquaculture species in China with a typical sexual growth dimorphism in which females grow faster and larger than males. In this study, gh messenger RNA (gh mRNA) and GH protein expression were examined in the pituitary glands of female and male spotted scat. Based on qPCR analysis, gh mRNA was mainly expressed in the pituitary gland, and weakly in the gonads and hypothalamus. Furthermore, gh mRNA expression in the pituitary gland was significantly higher in females at stages II-IV than in males at stages III-V. In addition, gh mRNA was highly expressed in the ovary and testis during mature development stages. In this study, spotted scat GH polyclonal antibody was produced. Western blot analysis showed that the molecular weight of spotted scat GH was about 21 KDa. Immunohistochemistry (IHC) in pituitary glands showed that GH was mainly expressed in the proximal pars distal (PPD) and a few cells were distributed in the rostral pairs distal (RPD). After injecting 17ß-Estradiol (E2) in vivo, gh mRNA expression was significantly up-regulated in the pituitary gland, whereas igf1 and ghr1 mRNA levels were down-regulated in the liver, which might regulate gh mRNA expression in the pituitary gland. These results provide valuable insight into the molecular mechanisms of E2 regulating gh expression in spotted scat.


Assuntos
Estradiol/farmacologia , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Perciformes/crescimento & desenvolvimento , Perciformes/genética , Animais , Feminino , Masculino , Ovário/efeitos dos fármacos , Ovário/crescimento & desenvolvimento , Ovário/metabolismo , Testículo/efeitos dos fármacos , Testículo/crescimento & desenvolvimento , Testículo/metabolismo
8.
Neurosci Bull ; 36(4): 346-358, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31939095

RESUMO

Patients with diabetes mellitus have a higher risk of developing Parkinson's disease (PD). However, the molecular links between PD and diabetes remain unclear. In this study, we investigated the roles of thioredoxin-interacting protein (TXNIP) in Parkin/PINK1-mediated mitophagy in dopaminergic (DA) cells under high-glucose (HG) conditions. In streptozotocin-induced diabetic mice, TXNIP was upregulated and autophagy was inhibited in the midbrain, while the loss of DA neurons was accelerated by hyperglycemia. In cultured PC12 cells under HG, TXNIP expression was upregulated and the intracellular reactive oxygen species (ROS) levels increased, leading to cell death. Autophagic flux was further blocked and PINK1 expression was decreased under HG conditions. Parkin expression in the mitochondrial fraction and carbonyl cyanide 3-chlorophenylhydrazone (CCCP)-induced co-localization of COX IV (marker for mitochondria) and LAMP1 (marker for lysosomes) were also significantly decreased by HG. Overexpression of TXNIP was sufficient to decrease the expression of both PINK1 and Parkin in PC12 cells, while knockdown of the expression of TXNIP by siRNA decreased intracellular ROS and attenuated cellular injury under HG. Moreover, inhibition of TXNIP improved the CCCP-induced co-localization of COX IV and LAMP1 in PC12 cells under HG. Together, these results suggest that TXNIP regulates Parkin/PINK1-mediated mitophagy under HG conditions, and targeting TXNIP may be a promising therapeutic strategy for reducing the risk of PD under hyperglycemic conditions.


Assuntos
Proteínas de Transporte/metabolismo , Neurônios Dopaminérgicos/metabolismo , Mitofagia , Proteínas Quinases/metabolismo , Tiorredoxinas/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Animais , Diabetes Mellitus Experimental , Glucose , Masculino , Camundongos , Células PC12 , Doença de Parkinson , Ratos
9.
Appl Microbiol Biotechnol ; 103(2): 893-902, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30421106

RESUMO

It is generally considered that bile salt hydrolase (BSH) activity is hardly detected in nonintestinal lactic acid bacteria (LAB). The aim of this study was to investigate the distribution and intensity of BSH activity in LAB isolated from naturally fermented vegetables and milk. A total of 624 lactic acid bacterial strains classified into 6 genera and 50 species were isolated from 144 naturally fermented vegetable samples and 103 naturally fermented milk samples, and their BSH activity was screened by gas chromatography with electron capture detection. The BSH-positive strains were further analyzed quantitatively for their deconjugation ability against six human-conjugated bile salts by HPLC based on the disappearance of the conjugated bile salts from the reaction mixture. The results showed that 39% of the strains possessed BSH activity distributed in 24 lactic acid bacterial species. The strains of the fermented vegetable origin showed a 0.5-fold higher incidence of BSH-positive strains than those of the fermented milk origin, and the lactic acid bacilli exhibited 2.5-fold higher incidence of BSH-positive strains than the lactic acid cocci in general. The strains of the fermented vegetable origin generally had greater bile salt deconjugation ability than those of the fermented milk origin. More than 97% and 93% of the BSH-positive strains exhibited a greater substrate preference for glycoconjugated bile salts than tauroconjugated bile salts and for dihydroxy bile salts than trihydroxy bile salts, respectively. This study demonstrated that BSH activity was also present in nonintestinal LAB.


Assuntos
Amidoidrolases/análise , Lactobacillales/enzimologia , Ácidos e Sais Biliares/metabolismo , Laticínios/microbiologia , Hidrólise , Lactobacillales/classificação , Lactobacillales/isolamento & purificação , Verduras/microbiologia
10.
J Am Soc Nephrol ; 29(9): 2287-2297, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29976586

RESUMO

BACKGROUND: After injury, mesenchymal progenitors in the kidney interstitium differentiate into myofibroblasts, cells that have a critical role in kidney fibrogenesis. The ability to deliver genetic material to myofibroblast progenitors could allow new therapeutic approaches to treat kidney fibrosis. Preclinical and clinical studies show that adeno-associated viruses (AAVs) efficiently and safely transduce various tissue targets in vivo; however, protocols for transduction of kidney mesenchymal cells have not been established. METHODS: We evaluated the transduction profiles of various pseudotyped AAV vectors expressing either GFP or Cre recombinase reporters in mouse kidney and human kidney organoids. RESULTS: Of the six AAVs tested, a synthetic AAV called Anc80 showed specific and high-efficiency transduction of kidney stroma and mesangial cells. We characterized the cell specificity, dose dependence, and expression kinetics and showed the efficacy of this approach by knocking out Gli2 from kidney mesenchymal cells by injection of Anc80-Cre virus into either homozygous or heterozygous Gli2-floxed mice. After unilateral ureteral obstruction, the homozygous Gli2-floxed mice had less fibrosis than the Gli2 heterozygotes had. We observed the same antifibrotic effect in ß-catenin-floxed mice injected with Anc80-Cre virus before obstructive injury, strongly supporting a central role for canonical Wnt signaling in kidney myofibroblast activation. Finally, we showed that the Anc80 synthetic virus can transduce the mesenchymal lineage in human kidney organoids. CONCLUSIONS: These studies establish a novel method for inducible knockout of floxed genes in mouse mesangium, pericytes, and perivascular fibroblasts and are the foundation for future gene therapy approaches to treat kidney fibrosis.


Assuntos
Dependovirus/genética , Terapia Genética/métodos , Integrases/genética , Nefropatias/terapia , Animais , Biópsia por Agulha , Modelos Animais de Doenças , Fibrose/patologia , Fibrose/terapia , Humanos , Imuno-Histoquímica , Nefropatias/patologia , Masculino , Camundongos , Camundongos Endogâmicos , Miofibroblastos/metabolismo , Pericitos/patologia , Distribuição Aleatória , Sensibilidade e Especificidade , Transdução Genética , beta Catenina/genética
11.
Environ Sci Pollut Res Int ; 25(16): 15357-15367, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29564701

RESUMO

A hydroponic experiment was performed to investigate the Cd absorption and subcellular distribution in tea plant, Camellia sinensis. Increased Cd accumulation potential was observed in the tea plant in a Cd-enriched environment, but most of the Cd was absorbed by the roots of C. sinensis. The Cd in all the root fractions was mostly distributed in the soluble fraction, followed by the cell wall fraction. By contrast, the Cd was least distributed in the organelle fraction. The adsorption of Cd onto the C. sinensis roots was described well by the Langmuir isotherm model than the Freundlich isotherm. Most of the Cd (38.6 to 59.4%) was integrated with pectates and proteins in the roots and leaves. Fourier transform infrared spectroscopy (FTIR) analysis showed that small molecular organic substances, such as amino acids, organic acids, and carbohydrates with N-H, C=O, C-N, and O-H functional groups in the roots, bonded with Cd(II). The Cd accumulation in the C. sinensis leaves occurred in the cell wall and organelle fractions. C. sinensis has great capability to transport Cd, thereby indicating pollution risk. The metal homeostasis of Fe, Mn, Ca, and Mg in C. sinensis was affected when the Cd concentration was 1.0-15.0 mg/L.


Assuntos
Cádmio/análise , Camellia sinensis/química , Folhas de Planta/metabolismo , Raízes de Plantas/metabolismo , Adsorção , Hidroponia , Chá
12.
J Phys Chem B ; 121(12): 2525-2533, 2017 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-28267338

RESUMO

Predictions of structures of biomolecules are challenging due to the high dimensionalities of the potential energy surfaces (PESs) involved. Reducing the necessary PES dimensionality is helpful for improving the computational efficiency of all relevant structure prediction methods. For that purpose, a systematic analysis of the backbone dihedral angles (DAs) in the low energy conformations of amino acids, di-, tri-, and tetrapeptides is performed. The analysis reveals that the DAs can be represented by a set of discretized values. Moreover, there are rules limiting the combinations of neighboring DA states. The DA combination rules are used to formulate a path matrix scheme for locating the low energy conformations of peptides. Comparing with the full DA combinations, the PES dimensionality in the path matrix method is reduced by a factor of 2.5n, where n is the number of amino acid residues in a peptide. The path matrix method is validated by applications to find the conformations of representative tri-, tetra-, and pentapeptides and comparison with the best literature results. All the tests show that the path matrix method is very efficient and highly reliable by producing the best search results for the low energy peptide conformations.


Assuntos
Oligopeptídeos/química , Algoritmos , Sequência de Aminoácidos , Aminoácidos/química , Simulação por Computador , Modelos Moleculares , Conformação Proteica , Termodinâmica
13.
World Neurosurg ; 91: 409-18, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27132181

RESUMO

OBJECTIVE: To propose and further validate a basic progression scoring system for patients with skull base chordoma. METHODS: All patients (n = 170) undergoing operation for skull base chordoma were classified randomly into a training (n = 113) or validation set (n = 57). In the training set, adverse factors for progression were analyzed by univariate and multivariate analyses. Significant independent factors were included into the scoring system. Scores for each risk category were allocated 1 point and each protection category 0 point. Three prognostic groups were formed on the basis of total score. The same scoring and grouping dispositions were made in the validation set. Analyses of the differences among the 3 groups in individual sets with regard to recurrence and the comparisons between the corresponding prognostic groups of both sets were all carried out by the Kaplan-Meier method. RESULTS: In the training set, age, treatment history, preoperative Karnofsky performance scale, pathology, and features on magnetic resonance imaging were all significant independent factors and were included into the scoring system. According to the total score, 3 prognostic groups were formed, group A (0-1 points), group B (2-3 points), and group C (3-4 points), respectively. The pairwise comparisons between every 2 of 3 groups in the training set showed significance with P < 0.001, whereas in validation set, a log-rank test showed significance, P ≤ 0.001 (log-rank test). The comparisons between the corresponding prognostic groups of both sets did not show significance. CONCLUSIONS: The basic progression scoring system for patients with skull base chordoma is valid and reproducible.


Assuntos
Cordoma/diagnóstico , Neoplasias da Base do Crânio/diagnóstico , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Cordoma/patologia , Cordoma/radioterapia , Craniotomia/métodos , Progressão da Doença , Feminino , Humanos , Avaliação de Estado de Karnofsky , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Radiocirurgia/métodos , Neoplasias da Base do Crânio/patologia , Neoplasias da Base do Crânio/radioterapia , Resultado do Tratamento , Carga Tumoral , Adulto Jovem
14.
J Comput Chem ; 37(13): 1214-22, 2016 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-26833761

RESUMO

The genetic algorithm (GA) is an intelligent approach for finding minima in a highly dimensional parametric space. However, the success of GA searches for low energy conformations of biomolecules is rather limited so far. Herein an improved GA scheme is proposed for the conformational search of oligopeptides. A systematic analysis of the backbone dihedral angles of conformations of amino acids (AAs) and dipeptides is performed. The structural information is used to design a new encoding scheme to improve the efficiency of GA search. Local geometry optimizations based on the energy calculations by the density functional theory are employed to safeguard the quality and reliability of the GA structures. The GA scheme is applied to the conformational searches of Lys, Arg, Met-Gly, Lys-Gly, and Phe-Gly-Gly representative of AAs, dipeptides, and tripeptides with complicated side chains. Comparison with the best literature results shows that the new GA method is both highly efficient and reliable by providing the most complete set of the low energy conformations. Moreover, the computational cost of the GA method increases only moderately with the complexity of the molecule. The GA scheme is valuable for the study of the conformations and properties of oligopeptides. © 2016 Wiley Periodicals, Inc.


Assuntos
Algoritmos , Aminoácidos/química , Dipeptídeos/química , Modelos Genéticos , Oligopeptídeos/química , Conformação Proteica
15.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 23(5): 1509-12, 2015 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-26524067

RESUMO

Myelodysplastic syndromes (MDS) are a group of clonal hematopioetic disorders characterized by myelodysplasia, decreased peripheral blood cells and high-risk of transformation into acute leukemia. MDS are often accompanied by a variety of chromosomal aberrations which play a role in disease pathogenesis, and are crucial in diagnosis and prognostic evaluation of this disease. About half of the patients with MDS have chromosomal abnormalities, mainly unbalanced chromosomal aberration. Different chromosomal aberration types are associated with different clinical outcome of this disease. Though balanced chromosomal translocations are not common in MDS, it seems that the patients with them have a higher leukemia transformation rate than those with other type of chromosomal aberrations. In this review, the chromosomal aberrations in MDS and their clinical significance for diagnosis and prognosis are briefly summarized.


Assuntos
Aberrações Cromossômicas , Síndromes Mielodisplásicas/genética , Doença Aguda , Transformação Celular Neoplásica , Transtornos Cromossômicos , Humanos , Leucemia , Prognóstico
16.
Artigo em Chinês | MEDLINE | ID: mdl-26510370

RESUMO

Medical parasitology education has been facing some difficulties, because it is a course of wide range, lacking clinical cases and concerned specimens of parasites currently. In addition, its relationship with life is not closely enough. All these reasons may impact the effect of class education negatively. Therefore, it is important to increase the vitality of parasitology education and diversify the instructional mode by using the resources from Internet. In recent years, the Discovery Channel has uploaded a documentary Monsters Inside Me online. This documentary is high professional and closely linked with parasitology. It maintains numbers of clinical cases about parasitic diseases. Each episode is about 3 minutes and shortly enough to be introduced into class teaching. However, this resource has not been fully used in domestic temporally. We found that direct introduction of the documentary into class teaching can enrich teaching forms to attract learning interest of students, and finally improve the teaching effect of class. Above that, another popular documentary A Bite of China involves many related knowledge points of parasitology. The appropriate usage of the knowledge can build up close linkage between book and life, which is extremely helpful to give students a deep impression of parasitology. In brief, it is our strong recommendation to introduce the documentary Monsters Inside Me into class.


Assuntos
Documentação , Parasitologia/educação , Ensino
17.
Ecotoxicol Environ Saf ; 122: 392-8, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26363148

RESUMO

This study investigated the effects of various Cd concentrations on the bioaccumulation, antioxidative defense, and stress responses of rice (Oryza sativa L.). The distribution characteristics of Cd in rice were in the following order: roots>stems>grains. The bioconcentration factor values of Cd increased at concentrations lower than 3.00 mg Cd/kg and approximately decreased to a constant value at concentrations higher than 3.00 mg Cd/kg. Rice showed a higher Cd accumulation potential at low Cd concentrations than at high Cd concentrations. The Freundlich isotherm model described well the adsorption isotherms of Cd in rice roots. The biosorption mechanism of rice roots was determined to be cooperative adsorption. The malondialdehyde (MDA) content increased at a concentration range of 0.00-5.00 mg/L, indicating the enhancement of lipid peroxidation. By contrast, the MDA content slightly decreased at concentrations higher than 5.00 mg/L. Peroxidase (POD) activity exhibited active response to oxidative stress at concentrations lower than 5.00 mg/L but was inhibited at concentrations higher than 5.00 mg/L. The response to Cd stress of the N-H, O-H and C-O functional groups in rice shoots was observed via Fourier transform infrared spectroscopy.


Assuntos
Cádmio/toxicidade , Oryza/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Poluentes do Solo/toxicidade , Adsorção , Cádmio/análise , Catalase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Malondialdeído/metabolismo , Oryza/química , Oryza/enzimologia , Peroxidase/metabolismo , Raízes de Plantas/química , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/enzimologia , Poluentes do Solo/análise , Espectroscopia de Infravermelho com Transformada de Fourier , Superóxido Dismutase/metabolismo
18.
Environ Sci Pollut Res Int ; 22(21): 16535-41, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26077320

RESUMO

Effects of various concentrations of Cu(2+) and Zn(2+) (0.0, 0.1, 0.25, 0.5, or 1.0 mg/L) on the growth, malondialdehyde (MDA), the intracellular calcium, and physiological characteristics of green algae, Cladophora, were investigated. Low Zn(2+) concentrations accelerated the growth of Cladophora, whereas Zn(2+) concentration increases to 0.25 mg/L inhibited its growth. Cu(2+) greatly influences Cladophora growth. The photosynthesis of Cladophora decreased under Zn(2+) and Cu(2+) stress. Cu(2+) and Zn(2+) treatment affected the content of total soluble sugar in Cladophora and has small increases in its protein content. Zn(2+) induced the intracellular calcium release, and copper induced the intracellular calcium increases in Cladophora. Exposure to Cu(2+) and Zn(2+) induces MDA in Cladophora. The stress concent of Cu(2+) was strictly correlated with the total soluble sugar content, Chla+Chlb, and MDA in Cladophora, and the stress concent of Zn(2+) was strictly correlated with the relative growth rate (RGR) and MDA of Cladophora.


Assuntos
Clorófitas/efeitos dos fármacos , Cobre/toxicidade , Fotossíntese/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Zinco/toxicidade , Sinalização do Cálcio/efeitos dos fármacos , Clorófitas/crescimento & desenvolvimento , Clorófitas/metabolismo , Relação Dose-Resposta a Droga , Malondialdeído/metabolismo
19.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 21(1): 116-20, 2013 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-23484703

RESUMO

This study was aimed to investigate the value of interval fluorescence in situ hybridization (FISH) in detection of abnormal karyotypes of patients with myelodysplastic syndromes (MDS). Conventional cytogenetics (CC) and interval FISH methods were carried out to analyze the bone marrow cells in 80 cases of MDS and 20 normal people. The results showed that using FISH, 53.8% cases of MDS (43/80) were found with abnormal karyotypes which was higher than 21.3% detected by CC method. There was significant difference between the 2 methods in detecting abnormal karyotypes in MDS (P < 0.05). Among all World Health Organization (WHO) subtypes, more chromosome abnormal were detected by FISH than by CC, especially for refractory anemia (RA) and refractory cytopenia with multilineage dysplasia (RCMD) groups. The detecting rate in patients with intermediate risk of International Prognostic Scoring System (IPSS) also had a statistical difference between FISH and CC methods. It is concluded that the FISH is more sensitive than CC in detection of abnormal karyotypes in MDS and is informative for the cases with karyotype failure or normal karyotype tested by CC. It is mainly embodied in the intermediate risk cases of IPSS. In addition, patients with RA and RCMD may benefit more from FISH for diagnosis compared with other WHO subtypes.


Assuntos
Aberrações Cromossômicas , Hibridização in Situ Fluorescente/métodos , Síndromes Mielodisplásicas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Cariotipagem , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/diagnóstico , Adulto Jovem
20.
Singapore Med J ; 53(7): e156-8, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22815035

RESUMO

Primary idiopathic chylopericardium is a rare clinical entity characterised by the collection of chyle within the pericardial cavity without a definitive cause. This case report describes the history, physical examination, evaluation, diagnosis and treatment of a 19-year-old boy with primary idiopathic chylopericardium. Radiological findings and biochemical analysis of the pericardial fluid following pericardiocentesis sustained this diagnosis. Initial conservative management failed, and the patient was surgically treated subsequently. He recovered well postoperatively and remained asymptomatic thereafter. Primary idiopathic chylopericardium is a rare pathology with very few cases reported till date, and the symptoms are commonly due to cardiac compression. Computed tomography of the chest and bipedal lymphoscintigraphy are considered the standard methods for accurate diagnosis, and in cases of failed medical treatment, open and thoracoscopic thoracic duct ligation with pericardiectomy have been described as the best surgical options.


Assuntos
Derrame Pericárdico/diagnóstico , Derrame Pericárdico/etiologia , Adulto , Humanos , Linfocintigrafia/métodos , Masculino , Pericardiectomia/métodos , Pericardiocentese/métodos , Procedimentos Cirúrgicos Operatórios/métodos , Ducto Torácico/cirurgia , Toracoscopia/métodos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
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