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1.
J Cell Mol Med ; 28(8): e18292, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38652116

RESUMO

Foodborne illnesses, particularly those caused by Salmonella enterica with its extensive array of over 2600 serovars, present a significant public health challenge. Therefore, prompt and precise identification of S. enterica serovars is essential for clinical relevance, which facilitates the understanding of S. enterica transmission routes and the determination of outbreak sources. Classical serotyping methods via molecular subtyping and genomic markers currently suffer from various limitations, such as labour intensiveness, time consumption, etc. Therefore, there is a pressing need to develop new diagnostic techniques. Surface-enhanced Raman spectroscopy (SERS) is a non-invasive diagnostic technique that can generate Raman spectra, based on which rapid and accurate discrimination of bacterial pathogens could be achieved. To generate SERS spectra, a Raman spectrometer is needed to detect and collect signals, which are divided into two types: the expensive benchtop spectrometer and the inexpensive handheld spectrometer. In this study, we compared the performance of two Raman spectrometers to discriminate four closely associated S. enterica serovars, that is, S. enterica subsp. enterica serovar dublin, enteritidis, typhi and typhimurium. Six machine learning algorithms were applied to analyse these SERS spectra. The support vector machine (SVM) model showed the highest accuracy for both handheld (99.97%) and benchtop (99.38%) Raman spectrometers. This study demonstrated that handheld Raman spectrometers achieved similar prediction accuracy as benchtop spectrometers when combined with machine learning models, providing an effective solution for rapid, accurate and cost-effective identification of closely associated S. enterica serovars.


Assuntos
Salmonella enterica , Sorogrupo , Análise Espectral Raman , Máquina de Vetores de Suporte , Análise Espectral Raman/métodos , Salmonella enterica/isolamento & purificação , Humanos , Algoritmos
2.
J Clin Lab Anal ; 34(5): e23197, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31912542

RESUMO

BACKGROUND: To calculate the reference intervals for thyroid-stimulating hormone (TSH) and thyroid hormones using the Access TSH 3rd IS method and evaluate the differences between age and genders in Chinese populations. METHODS: This study collected 349 serum samples of healthy subjects were from Shengli Oilfield Central Hospital in China. Subjects who tested positive for thyroid peroxidase antibody or thyroglobulin antibody were excluded. Accordingly, 313 subjects were included for establishing reference intervals for the thyroid hormones. The serum concentrations of TSH, total and free thyroxine (TT4 and FT4), and total and free triiodothyronine (TT3 and FT3) were measured using the Access TSH 3rd IS method. The 2.5th and 97.5th percentiles or mean with standard deviation were calculated as the reference interval as appropriate. RESULTS: The reference intervals for TSH, FT4, FT3, TT4, and TT3 calculated in present study were 0.61-4.16 mIU/L, 0.67-1.11 ng/dL, 2.63-4.33 pg/mL, 5.56-11.33 µg/dL, and 0.72-1.32 ng/mL, respectively. The FT3, TT4, and TT3 levels in males were significantly higher than in females (P < .05), while TSH levels in males were significantly lower than in females (P < .05). The levels of FT3 in subjects with the age of less than 30 years were significantly higher than other groups (P < .05). CONCLUSION: The present study provided a valid basis for the reference intervals for TSH, FT4, FT3, TT4, and TT3 in Chinese populations. In addition, this present study indicated that age and gender should be considered in diagnostic evaluation of thyroid diseases.


Assuntos
Hormônios Tireóideos/sangue , Tireotropina/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , China , Feminino , Humanos , Imunoensaio/métodos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Tiroxina/sangue , Tri-Iodotironina/sangue , Adulto Jovem
3.
Digestion ; 91(3): 187-96, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25790748

RESUMO

AIM: This study aimed to determine the effects of small-conductance Ca(2+)-activated K(+) (SK) channels in colonic relaxation and the regulation of SK channels by estrogen. METHODS: The contractile activity of muscle strips from male rats was estimated, and drugs including vehicle (DMSO), 17ß-estradiol (E2), or apamin (SK blocker) were added, respectively. In a further experiment, muscle strips were preincubated with apamin before exposure to E2. The levels of the SK2 and SK3 protein expression in the colonic smooth muscle cells (SMCs) were detected. SMCs were treated with ICI 182780 (estrogen receptor [ER] antagonist) plus E2, BSA-E2, PPT (ERα agonist), or DPN (ERß agonist). SK3 mRNA and protein expression levels were detected. RESULTS: The muscle strips responded to E2 with a decrease and to apamin with a transient increase in tension. Preincubation with apamin partially prevented E2-induced relaxation. Two SK channel subtypes, SK2 and SK3, were coexpressed with α-actin in colonic SMCs. The quantitative ratio of the SK transcriptional expression in colonic SMCs was SK3 > SK2. The SK3 expression was upregulated by E2, and was downregulated by ICI 182780, but was not influenced by BSA-E2. Furthermore, the effect of PPT on the expression of SK3 was almost the same as that of E2, while DPN did not influence the protein expression of SK3. CONCLUSION: These findings indicate that SK3 is involved in the E2-induced relaxing effect on rat colonic smooth muscle. Furthermore, E2 upregulates the expression of SK3 in rat SMCs, and that this effect is mediated via the ERα receptor.


Assuntos
Apamina/farmacologia , Colo/efeitos dos fármacos , Estradiol/farmacologia , Estrogênios/farmacologia , Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Canais de Potássio Ativados por Cálcio de Condutância Baixa/metabolismo , Actinas/efeitos dos fármacos , Actinas/genética , Animais , Carbacol/farmacologia , Colo/citologia , Colo/fisiologia , Dimetil Sulfóxido/farmacologia , Estradiol/análogos & derivados , Antagonistas do Receptor de Estrogênio/farmacologia , Estrogênios/agonistas , Fulvestranto , Masculino , Contração Muscular/efeitos dos fármacos , Músculo Liso/fisiologia , Miócitos de Músculo Liso/metabolismo , Veículos Farmacêuticos/farmacologia , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Soroalbumina Bovina/farmacologia , Canais de Potássio Ativados por Cálcio de Condutância Baixa/genética , Transcrição Gênica , Regulação para Cima
4.
J Vis Exp ; (205)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38619279

RESUMO

Respiratory tract infections (RTIs) are among the most common problems in clinical settings. Rapid and accurate identification of bacterial pathogens will provide practical guidelines for managing and treating RTIs. This study describes a method for rapidly detecting bacterial pathogens that cause respiratory tract infections via multi-channel loop-mediated isothermal amplification (LAMP). LAMP is a sensitive and specific diagnostic tool that rapidly detects bacterial nucleic acids with high accuracy and reliability. The proposed method offers a significant advantage over traditional bacterial culturing methods, which are time-consuming and often require greater sensitivity for detecting low levels of bacterial nucleic acids. This article presents representative results of K. pneumoniae infection and its multiple co-infections using LAMP to detect samples (sputum, bronchial lavage fluid, and alveolar lavage fluid) from the lower respiratory tract. In summary, the multi-channel LAMP method provides a rapid and efficient means of identifying single and multiple bacterial pathogens in clinical samples, which can help prevent the spread of bacterial pathogens and aid in the appropriate treatment of RTIs.


Assuntos
Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , Ácidos Nucleicos , Infecções Respiratórias , Humanos , Microfluídica , Reprodutibilidade dos Testes , Infecções Respiratórias/diagnóstico , Klebsiella pneumoniae
5.
J Dig Dis ; 25(3): 176-190, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38697922

RESUMO

OBJECTIVES: Functional constipation (FC), a common functional gastrointestinal disorder, is usually overlapping with upper gastrointestinal symptoms (UGS). We aimed to explore the clinical characteristics of patients with FC overlapping UGS along with the related risk factors. METHODS: The differences in the severity of constipation symptoms, psychological state, quality of life (QoL), anorectal motility and perception function, autonomic function, and the effect of biofeedback therapy (BFT) among patients with FC in different groups were analyzed, along with the risk factors of overlapping UGS. RESULTS: Compared with patients with FC alone, those with FC overlapping UGS had higher scores in the Patient Assessment of Constipation Symptoms and Self-Rating Anxiety Scale and lower scores in the Short Form-36 health survey (P < 0.05). Patients with FC overlapping UGS also had lower rectal propulsion, more negative autonomic nervous function, and worse BFT efficacy (P < 0.05). Overlapping UGS, especially overlapping functional dyspepsia, considerably affected the severity of FC. Logistic regression model showed that age, body mass index (BMI), anxiety, exercise, and sleep quality were independent factors influencing overlapping UGS in patients with FC. CONCLUSIONS: Overlapping UGS reduces the physical and mental health and the QoL of patients with FC. It also increases the difficulty in the treatment of FC. Patient's age, BMI, anxiety, physical exercise, and sleep quality might be predictors for FC overlapping UGS.


Assuntos
Constipação Intestinal , Qualidade de Vida , Humanos , Constipação Intestinal/fisiopatologia , Constipação Intestinal/psicologia , Constipação Intestinal/etiologia , Feminino , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto , Índice de Gravidade de Doença , Biorretroalimentação Psicológica , Ansiedade , Gastroenteropatias/psicologia , Gastroenteropatias/fisiopatologia , Gastroenteropatias/etiologia , Idoso , Motilidade Gastrointestinal/fisiologia
6.
Zhonghua Yi Xue Za Zhi ; 93(30): 2367-71, 2013 Aug 13.
Artigo em Zh | MEDLINE | ID: mdl-24300204

RESUMO

OBJECTIVE: To explore the effects and possible mechanism of 17ß-estradiol on the expression of small conductance Ca(2+) activated K(+) channel 3 (SK3) in rat colonic smooth muscle cells (SMC). METHODS: The SMC isolated from male SD rats by enzymolysis were cultured. And double immunofluorescence staining was used to detect the co-expression of SK3 and α-actin. Colonic SMC were cultured with different concentrations of 17ß-estradiol for 24 h or with 50 nmol/L 17ß-estradiol at different time points respectively. The expressions of SK3 in colonic SMC were measured by real-time quantitative reverse transcription (qRT)-PCR and Western blotting. The effects of estrogen receptor (ER) inhibitor ICI 182780, albumin bovine serum-17ß-estradiol (BSA-E2), ERα selective agonist propyl pyrazole triol (PPT) and ERß selective agonist diarylpropionitrile (DPN) on SK3 expression were observed. RESULTS: Double immunofluorescence staining showed that SK3 and α-actin co-expressed in cultured colonic SMC. The expression of SK3 of 17ß-estradiol at different concentration (10, 50 nmol/L) significantly higher than the control group (protein: 0.217 ± 0.030 and 0.321 ± 0.077 vs 0.103 ± 0.063, mRNA: 1.872 ± 0.606 and 2.967 ± 0.659 vs 0.813 ± 0.202, all P < 0.05). And 50 nmol/L was the most effective in vitro concentration. The peak expression of SK3 appeared at 12 and 24 hour (2.91 and 3.30-fold in protein vs 3.46 and 3.37-fold in mRNA respectively, all P < 0.05). The protein levels of SK3 in ICI 182780 plus 17ß-estradiol group was less than 17ß-estradiol group (0.111 ± 0.050 vs 0.351 ± 0.084, P < 0.05). But it was not influenced by BSA-E2. The expressions of SK3 in PPT and E2 groups were both higher than control group (0.270 ± 0.071, 0.309 ± 0.052 vs 0.087 ± 0.018, both P < 0.05) . However DPN had no effect on SK3 protein levels. CONCLUSIONS: SK3 is localized in rat colonic SMC. And 17ß-estradiol increases its expression in an ERα-dependent manner.


Assuntos
Estradiol/análogos & derivados , Receptor alfa de Estrogênio/metabolismo , Miócitos de Músculo Liso/metabolismo , Canais de Potássio Ativados por Cálcio de Condutância Baixa/metabolismo , Animais , Células Cultivadas , Colo/citologia , Estradiol/farmacologia , Receptor alfa de Estrogênio/antagonistas & inibidores , Fulvestranto , Masculino , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
7.
Front Cell Infect Microbiol ; 13: 1159891, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37197207

RESUMO

Background: Extra-urogenital infections due to Mycoplasma hominis (M. hominis) are rare, particularly co-infection with Pseudomonas aeruginosa (P. aeruginosa). Herein, we report on a patient who was co-infected and successfully treated despite delayed treatment. Case presentation: We reported the case of a 43-year-old man with M. hominis and P. aeruginosa co-infection after a traffic accident. The patient developed a fever and severe infection despite postoperative antimicrobial therapies. The blood culture of wound tissues was positive for P. aeruginosa. Meanwhile, culturing of blood and wound samples showed pinpoint-sized colonies on blood agar plates and fried-egg-type colonies on mycoplasma medium, which were identified as M. hominis by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and 16S rRNA sequencing. Based on antibiotic susceptibility and symptoms, ceftazidime-avibactam and moxifloxacin were administered for P. aeruginosa infection. Meanwhile, after the failure of a series of anti-infective agents, M. hominis and P. aeruginosa co-infection was successfully treated with a minocycline-based regimen and polymyxin B. Conclusion: The co-infection with M. hominis and P. aeruginosa was successfully treated with anti-infective agents despite delayed treatment, providing information for the management of double infection.


Assuntos
Anti-Infecciosos , Coinfecção , Infecções por Mycoplasma , Infecções por Pseudomonas , Masculino , Humanos , Adulto , Pseudomonas aeruginosa/genética , Mycoplasma hominis/genética , Infecções por Mycoplasma/diagnóstico , Infecções por Mycoplasma/tratamento farmacológico , RNA Ribossômico 16S , Coinfecção/tratamento farmacológico , Infecções por Pseudomonas/diagnóstico , Infecções por Pseudomonas/tratamento farmacológico , Antibacterianos/uso terapêutico
8.
Infect Drug Resist ; 16: 5085-5090, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37576520

RESUMO

Scedosporium apiospermum (S. apiospermum) is typically reported to be involved in superficial and subcutaneous fungal infections but overlooked in invasive infections, which is associated with a high mortality rate. It poses a diagnostic challenge due to its confusable characteristics to other hyaline hyphomycetes. Here, we reported a psoriasis patient with an invasive S. apiospermum infection. The patient presents an abscess at the intermuscular space of the left hip and an increased C-reactive protein level. Pus culture showed white-greyish, cottonlike colonies with aerial mycelium and terminal oval conidia, suggesting S. apiospermum. This rare fungus was rapidly confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and RNA sequencing. The patient was successfully treated with voriconazole with no recurrence of the abscesses despite delayed treatment. This is the first such case infection report from China that described an unusual case of intermuscular space abscesses due to S. apiospermum. This report highlights the possibility of fungal infections in deeper tissue, as well as the necessity of thorough evaluation and microbiological diagnosis for invasive infections, particularly in immunocompromised patients.

9.
World J Clin Cases ; 10(15): 5082-5087, 2022 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-35801055

RESUMO

BACKGROUND: Mycobacterium abscessus (M. abscessus) is a rapidly growing mycobacterium and ubiquitous in the environment, which infrequently causes disease in humans. However, it can cause cutaneous or respiratory infections among immunocompromised hosts. Due to the resistance to most antibiotics, the pathogen is formidable and difficult-to-treat. CASE SUMMARY: Here, we present a case of catheter-related M. abscessus infections in a patient with motor neurone disease. Catheter and peripheral blood cultures of the patient showed positive results during Gram staining and acid-fast staining. The alarm time of catheter blood culture was 10.6 h earlier than that of peripheral blood. After removal of the peripherally inserted central catheter, secretion and catheter blood culture were positive. M. abscessus was identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry and 16S rDNA sequencing. CONCLUSION: For catheter-related M. abscessus infection, rapid diagnosis and timely and adequate antimicrobial therapy are crucial.

10.
Am J Physiol Gastrointest Liver Physiol ; 298(2): G241-7, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19875700

RESUMO

The aim of this study was to investigate the effects of stem cell factor (SCF) on interstitial cell of Cajal (ICC) depletion in the colon of diabetic mice. Male C57/BL6 mice were treated by a single intraperitoneally injected dose of streptozotocin, and those displaying sustained high blood glucose were selected as diabetes mellitus models. Six groups of mice were used: three groups of normal nondiabetic mice (untreated and treated with IgG or SCF antibody), and three groups of diabetic mice (untreated and treated with vehicle or SCF). Changes of the ICC quantities were analyzed by immunohistochemistry. ICC morphologies were observed with transmission electron microscopy. The SCF levels in sera and colon tissues were detected by ELISA and Western blot, respectively. The nondiabetic mice treated with SCF antibody and the untreated diabetic mice showed decreased SCF levels in the sera and colonic tissues, reduced numbers of ICC, and pathological changes of the ICC ultrastructures, whereas the nondiabetic mice treated with mouse IgG showed no significant changes compared with the nondiabetic mice. The diabetic mice treated with exogenous SCF showed restored SCF levels in both sera and colon tissues and improvement in the numbers of ICC and the damages of ICC ultrastructures, whereas the vehicle control of diabetic mice showed no significant changes compared with the diabetic mice. The blood glucose remained high and unchanged with the treatment of SCF or vehicle in the diabetic mice. These results indicate that diabetic mice show a decline in the number of ICC and impairment in the ultrastructures of ICC, and these abnormalities are attributed to a deficiency in the endogenous SCF but are not related to hyperglycemia. Exogenous SCF partially reverses the pathological changes of ICC in diabetic mice.


Assuntos
Colo/inervação , Colo/patologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Células Intersticiais de Cajal/patologia , Fator de Células-Tronco/metabolismo , Animais , Anticorpos/farmacologia , Glicemia , Western Blotting , Peso Corporal , Colo/metabolismo , Ensaio de Imunoadsorção Enzimática , Motilidade Gastrointestinal/fisiologia , Imuno-Histoquímica , Células Intersticiais de Cajal/efeitos dos fármacos , Células Intersticiais de Cajal/ultraestrutura , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Eletrônica de Transmissão , Proteínas Proto-Oncogênicas c-kit/metabolismo , Fator de Células-Tronco/imunologia , Fator de Células-Tronco/farmacologia
11.
J Dig Dis ; 21(9): 490-497, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32687660

RESUMO

OBJECTIVE: We aimed to identify the differences in symptoms, high-resolution manometry (HRM) characteristics, and the efficacy of peroral endoscopic myotomy (POEM) regarding patients' sex in achalasia. METHODS: All patients diagnosed with achalasia by HRM who underwent POEM and were followed up for more than 6 months were included. The individual characteristics, symptoms and signs, POEM findings, HRM results and potentially related complications in male and female patients were reviewed. RESULTS: Prior to POEM, dysphagia was more severe in female than male patients (P = 0.044), while regurgitation was more severe (P = 0.013) and heartburn was more common in male patients (P = 0.003). Regarding HRM characteristics, the lower esophageal sphincter pressure (LESP) was higher (P = 0.01) and length of esophagus was shorter in female patients than in male patients. Eckardt scores, LESP and integrated relaxation pressure were significantly improved after the POEM procedure (P < 0.001). No significant difference was observed between the sexes regarding the efficacy of POEM, reflux symptoms, HRM data and complications after POEM. CONCLUSIONS: Before they seek treatment, female patients with achalasia may experience severe dysphagia and male patients are more likely to experience heartburn and more severe regurgitation. POEM is a safe and effective option for treating both male and female patients with achalasia.


Assuntos
Acalasia Esofágica , Miotomia , Cirurgia Endoscópica por Orifício Natural , China , Esfíncter Esofágico Inferior , Esofagoscopia , Feminino , Humanos , Masculino , Manometria , Caracteres Sexuais , Resultado do Tratamento
12.
BMC Bioinformatics ; 9: 101, 2008 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-18282281

RESUMO

BACKGROUND: As one of the most common protein post-translational modifications, glycosylation is involved in a variety of important biological processes. Computational identification of glycosylation sites in protein sequences becomes increasingly important in the post-genomic era. A new encoding scheme was employed to improve the prediction of mucin-type O-glycosylation sites in mammalian proteins. RESULTS: A new protein bioinformatics tool, CKSAAP_OGlySite, was developed to predict mucin-type O-glycosylation serine/threonine (S/T) sites in mammalian proteins. Using the composition of k-spaced amino acid pairs (CKSAAP) based encoding scheme, the proposed method was trained and tested in a new and stringent O-glycosylation dataset with the assistance of Support Vector Machine (SVM). When the ratio of O-glycosylation to non-glycosylation sites in training datasets was set as 1:1, 10-fold cross-validation tests showed that the proposed method yielded a high accuracy of 83.1% and 81.4% in predicting O-glycosylated S and T sites, respectively. Based on the same datasets, CKSAAP_OGlySite resulted in a higher accuracy than the conventional binary encoding based method (about +5.0%). When trained and tested in 1:5 datasets, the CKSAAP encoding showed a more significant improvement than the binary encoding. We also merged the training datasets of S and T sites and integrated the prediction of S and T sites into one single predictor (i.e. S+T predictor). Either in 1:1 or 1:5 datasets, the performance of this S+T predictor was always slightly better than those predictors where S and T sites were independently predicted, suggesting that the molecular recognition of O-glycosylated S/T sites seems to be similar and the increase of the S+T predictor's accuracy may be a result of expanded training datasets. Moreover, CKSAAP_OGlySite was also shown to have better performance when benchmarked against two existing predictors. CONCLUSION: Because of CKSAAP encoding's ability of reflecting characteristics of the sequences surrounding mucin-type O-glycosylation sites, CKSAAP_ OGlySite has been proved more powerful than the conventional binary encoding based method. This suggests that it can be used as a competitive mucin-type O-glycosylation site predictor to the biological community. CKSAAP_OGlySite is now available at http://bioinformatics.cau.edu.cn/zzd_lab/CKSAAP_OGlySite/.


Assuntos
Glicosilação , Mucinas/química , Mapeamento de Interação de Proteínas/métodos , Proteínas/química , Análise de Sequência de Proteína/métodos , Motivos de Aminoácidos , Sequência de Aminoácidos , Animais , Inteligência Artificial , Sítios de Ligação , Humanos , Mamíferos , Dados de Sequência Molecular , Reconhecimento Automatizado de Padrão , Ligação Proteica
13.
Protein Eng Des Sel ; 21(5): 295-302, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18287176

RESUMO

The protein databases contain a huge number of function unknown proteins, including many proteins with newly determined 3D structures resulted from the Structural Genomics Projects. To accelerate experiment-based assignment of function, de novo prediction of protein functional sites, like active sites in enzymes, becomes increasingly important. Here, we attempted to improve the prediction of catalytic residues in enzyme structures by seeking and refining different encodings (i.e. residue properties) as well as employing new machine learning algorithms. In particular, considering that catalytic residues can often reveal specific network centrality when representing enzyme structure as a residue contact network, the corresponding measurement (i.e. closeness centrality) was used as one of the most important encodings in our new predictor. Meanwhile, a genetic algorithm integrated neural network (GANN) was also employed. Thanks to the above strategies, our GANN predictor demonstrated a high accuracy of 91.2% in the prediction of catalytic residues based on balanced datasets (i.e. the 1:1 ratio of catalytic to non-catalytic residues). When the GANN method was optimally applied to real enzyme structures, 73.9% of the tested structures had the active site correctly located. Compared with two existing methods, the proposed GANN method also demonstrated a better performance.


Assuntos
Enzimas/química , Algoritmos , Sítios de Ligação , Catálise , Biologia Computacional/métodos , Bases de Dados de Proteínas , Humanos , Ligação de Hidrogênio , Modelos Genéticos , Modelos Moleculares , Modelos Estatísticos , Conformação Molecular , Redes Neurais de Computação , Conformação Proteica , Análise de Sequência de Proteína
14.
Eur J Med Chem ; 43(1): 8-18, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17498849

RESUMO

Developing novel anti-inflammatory drugs is increasingly important in modern pharmaceutical industry. In this work, the reactions of both amino acids and their methylesters with 3-(5,5-dimethyl-1,3-dioxane-2-yl)propanal (2) were performed to either directly provide the goal products N-[2-(5,5-dimethyl-1,3-dioxane-2-yl)ethyl]amino acids (4a-s) in 9-65% yields or provide the intermediates N-[2-(5,5-dimethyl-1,3-dioxane-2-yl)ethyl]amino acid methylesters (3a-s) in 78-87% yields. The saponification of 3a-s provided 4a-s in 80-89% yields. Using a xylene-induced ear edema model, the anti-inflammatory activities of these newly synthesized anti-inflammatory agents were evaluated. The results indicated that comparing to the vehicle control 17 out of 4a-s significantly inhibited the development of inflammation in mice (p<0.01). In particular, eight out of 4a-s exhibited an even higher anti-inflammatory activity than the standard reference drug aspirin (p<0.05-0.01). A QSAR analysis was performed by use of the molecular descriptors generated from e-dragon software. The predictive accuracy of the established QSAR model implies that it may be promising for screening the new derivatives of 2-position amino acid substituted 1,3-dioxanes as potential anti-inflammatory agents.


Assuntos
Aminoácidos/síntese química , Aminoácidos/farmacologia , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/farmacologia , Dioxanos/química , Relação Quantitativa Estrutura-Atividade , Aminoácidos/química , Aminoácidos/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/uso terapêutico , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Orelha/patologia , Edema/induzido quimicamente , Edema/tratamento farmacológico , Inflamação/tratamento farmacológico , Inflamação/patologia , Camundongos , Camundongos Endogâmicos ICR , Xilenos/toxicidade
15.
Eur J Med Chem ; 43(5): 1048-58, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-17804120

RESUMO

By studying the structural similarity of analgesic imidazolines and 2-phenylnitronyl nitroxides, 20 1-hydroxyl-2-substituted phenyl-4,4,5,5-tetramethylimidazolines (2a-t) were newly synthesized as selective antagonists of prostacyclin receptor (IP receptor). In the in vivo tail-flick assay, 2a-t (dose, 0.13 mmol/kg) receiving mice showed increased pain thresholds ranging from 20.52+/-7.25% to 90.94+/-11.97%, which were significantly higher than that ranged from 12.27+/-9.56% to 17.71+/-7.00% shown by normal saline (NS) receiving mice. In the in vivo tail bleeding assay, 2a-t (dose, 1.30 mmol/kg) receiving mice gave a bleeding time ranging from 116.3+/-8.0 s to 119.6+/-7.1 s, and NS receiving mice gave a bleeding time ranging from 116.7+/-7.5s to 119.1+/-8.7s, which were at a substantially equal level. These observations imply that no bleeding risk occurred even when 10-fold dose of analgesic assay was used. In the in vitro vasorelaxation assay, it was found that when the aortic strip contracted by noradrenaline (NE, final concentration, 10(-7) M) was treated with the solution of 2a-t in NS (final concentration, 5 x 10(-3) M) only lower percentage inhibitions ranged from 6.63+/-2.72% to 46.28+/-2.63% were recorded. Relatively higher concentration of 2a-t (5 x 10(-3) M) and relatively lower percentage inhibitions (13 of 20 less than 23.27+/-3.47%) suggest that 2a-t exhibit few vasodilation activity. To shed some light on the potential analgesic mechanisms of 2a-t, moreover, a QSAR analysis was carried out by using the multiple linear regression method. Taken altogether, the current study confirms that as selective antagonist of IP receptor 1-hydroxyl-2-substituted phenyl-4,4,5,5-tetramethylimidazoline may be a promising lead compound of analgesic agent without cardiovascular and bleeding side effects.


Assuntos
Analgésicos/síntese química , Imidazolinas/síntese química , Relação Quantitativa Estrutura-Atividade , Receptores de Epoprostenol/antagonistas & inibidores , Analgésicos/efeitos adversos , Analgésicos/farmacologia , Animais , Aorta/efeitos dos fármacos , Aorta/fisiologia , Hemorragia/induzido quimicamente , Imidazolinas/efeitos adversos , Imidazolinas/farmacologia , Técnicas In Vitro , Modelos Lineares , Camundongos , Camundongos Endogâmicos ICR , Medição da Dor , Limiar da Dor , Cauda/irrigação sanguínea , Vasodilatação/efeitos dos fármacos
16.
Int J Ophthalmol ; 11(8): 1322-1329, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30140636

RESUMO

AIM: To investigate the incidence rate and risk factors for grade III flat anterior chamber (FAC) after glaucoma filtration surgery based on 5-year data. METHODS: Patients who underwent glaucoma filtration surgery in Daping hospital from January 2009 to December 2013 were enrolled in this retrospective study. The incidence of grade III FAC following glaucoma filtration surgery was determined. Regression analysis was performed to investigate the influence of glaucoma type, surgical approach, age, and preoperative intraocular pressure (IOP) on the risk of postoperative FAC. RESULTS: A total of 2179 eyes receiving anti-glaucoma surgery were included. Ninety-one eyes suffered from postoperative FAC, with an overall incidence rate of 4.18%. Of 471 eyes with primary open angle glaucoma (POAG), grade III FAC occurred in only 3 eyes (0.64%). Primary angle-closure glaucoma (PACG) was diagnosed in 1076 eyes, 39 (3.62%) of which developed grade III FAC, including 12 eyes (12/300, 4%) with acute PACG (aPACG) and 27 eyes (27/776, 3.48%) with chronic PACG (cPACG). Six of 259 eyes (2.32%) with secondary glaucoma, 28 of 186 eyes (15.05%) with neovasular glaucoma, 1 of 66 eyes (1.52%) with congenital glaucoma, and 14 of 115 eyes (12.17%) with remnant glaucoma suffered from grade III FAC. Of 6 eyes with mixed glaucoma, none developed grade III FAC after surgery. When stratified by surgical approach, 24 of 766 eyes (3.13%) undergoing trabeculectomy, 21 of 924 eyes (2.27%) treated by trabeculectomy plus mitomycin C (MMC), 18 of 109 eyes (16.51%) undergoing Ahmed glaucoma valve implantation, 23 of 201 eyes (11.44%) managed by Ahmed implantation plus MMC, and 5 of 133 eyes (3.76%) treated by Ahmed implantation plus lens extraction or vitrectomy developed grade III FAC. Logistic regression analysis revealed that factors including neovasular glaucoma, remnant glaucoma, glaucoma valve implantation, glaucoma valve implantation+MMC, glaucoma valve implantation+vitrectomy, age>60y, and IOP at admission >50 mm Hg were significantly associated with an increased risk for grade III FAC. CONCLUSION: The overall incidence of grade III FAC after glaucoma filtration surgery is 4.18%. Patients with neovasular glaucoma and remnant glaucoma are at a higher risk of developing FAC. Ahmed glaucoma valve implantation is associated with a higher risk for grade III FAC compared with trabeculectomy. No significant correlation was observed between the use of MMC in glaucoma filtration surgery and the risk of postoperative FAC. Higher IOP at admission (>50 mm Hg) and old age (>60y) are risk factors for grade III FAC.

17.
Int J Ophthalmol ; 11(1): 135-142, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29376002

RESUMO

Technological advances in glaucoma have challenged the traditional treatment paradigm. Historically incisional surgery has been used in cases of advanced disease and/or uncontrolled intraocular pressures resistant to medical or laser interventions. More recently, perhaps due to advancements in imaging, surgery has been suggested to be beneficial earlier in the treatment paradigm. Despite these trends, surgical manipulation of the tissues and unpredictability of wound healing continue to result in surgical failure. Magnesium is an essential element for human body and plays a critically important role in maintaining the functional and structural integrity of several tissues, including the eye. Due to several of its advantageous properties such as non-toxicity, biodegradability, and high biological compatibility, magnesium alloy has attracted great attention as a novel biomaterial. Biodegradable cardiovascular stents made of magnesium alloy have already been introduced into clinical practice. The purpose of this review is to determine if bioabsorbable magnesium alloys can be utilized as a promising candidate for the development of a new generation of glaucoma surgical assistive devices.

18.
J Anal Methods Chem ; 2018: 2402676, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29686928

RESUMO

To evaluate the effect of 60Co-γ irradiation sterilization technology on the chemical composition of saffron, we collected 10 batches of saffron samples and treated them with different irradiation doses. UPLC characteristic chromatogram showed that there was no significant effect of irradiation on 13 common peak areas. The results of cluster analysis and principal component analysis showed that there were no differences in the chemical composition in nonirradiated and irradiated samples. UPLC/Q-TOF-MS identified 40 characteristic components of saffron, and the results showed that all of these were detected in the saffron samples both with and without irradiation. Irradiation doses at or below 10 kGy had no significant effect on the chemical components of saffron. This provides a sound basis for the use of 60Co-γ ray irradiation sterilization technology during the preparation of original powder saffron as a medicinal herb, for the effective destruction of mycotoxin contamination.

19.
Protein Eng Des Sel ; 20(8): 405-12, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17652129

RESUMO

With the advance of modern molecular biology it has become increasingly clear that few cellular processes are unaffected by protein phosphorylation. Therefore, computational identification of phosphorylation sites is very helpful to accelerate the functional understanding of huge available protein sequences obtained from genomic and proteomic studies. Using a genetic algorithm integrated neural network (GANN), a new bioinformatics method named GANNPhos has been developed to predict phosphorylation sites in proteins. Aided by a genetic algorithm to optimize the weight values within the network, GANNPhos has demonstrated a high accuracy of 81.1, 76.7 and 73.3% in predicting phosphorylated S, T and Y sites, respectively. When benchmarked against Back-Propagation neural network and Support Vector Machine algorithms, GANNPhos gives better performance, suggesting the GANN program can be used for other prediction tasks in the field of protein bioinformatics.


Assuntos
Algoritmos , Biologia Computacional/métodos , Redes Neurais de Computação , Sequência de Aminoácidos , Benchmarking , Sítios de Ligação , Bases de Dados de Proteínas , Dados de Sequência Molecular , Fosforilação , Valor Preditivo dos Testes , Ligação Proteica , Proteínas/química
20.
Protein Pept Lett ; 14(3): 291-7, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17346235

RESUMO

To investigate diverse enzyme structure-function combination (SFC) types in different species, 34 different genome sequences were annotated using the protein catalytic domain database SCOPEC (http://www.enzome.com/enzome/), in which both the structure and function for each entry are known. Annotated enzymes with catalytic domains from the same SCOP superfamily are considered to have an identical structure. Annotated enzymes sharing the identical three-digit EC number are considered to have the same enzymatic function. Results reveal that the different SFC types for enzymes identified in archaea, bacteria and eukaryota are 137, 300 and 313, respectively. About 80% of the SFCs identified in archaea can be consistently found in bacteria and eukaryota species, whereas 28% and 35% combination types in bacteria and eukaryota respectively are unique to their corresponding groups. The number of functions per structure and the number of structures per function for the annotated sequences were measured in different species. Furthermore, a new concept was proposed to represent enzymatic structures as a functional similarity network. Thus, the current study will be helpful to enhance the global view on the evolution of enzymatic structure and function.


Assuntos
Archaea/enzimologia , Bactérias/enzimologia , Mapeamento Cromossômico , Enzimas/química , Enzimas/genética , Enzimas/fisiologia , Células Eucarióticas/enzimologia , Relação Estrutura-Atividade , Animais , Archaea/genética , Bactérias/genética , Bases de Dados Genéticas , Evolução Molecular , Genoma , Humanos , Camundongos , Análise de Sequência de DNA
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