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1.
Oral Dis ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38654678

RESUMO

AIMS: To evaluate long COVID of gustatory dysfunction and the associated risk factors regarding onset and recovery in Chinese patients. METHODS: We conducted a cross-sectional study of patients with SARS-CoV-2 Omicron infection at Changxing Mobile Cabin Hospital in Shanghai, China, from March to May 2022. A prospective follow-up of patients with gustatory dysfunction was conducted at 6 months after discharge. RESULTS: In total, 18.48% (241/1304) reported gustatory dysfunction. The 6-month follow-up response rate was 89.63% (216/241) and 74.02% recovered their taste sense within 1-3 weeks. A total of 20.37% of patients (44/216) presented with long COVID. Symptoms persisted for 12 patients (5.56%) after 6 months. Having multiple taste impairments (OR, 2.364; 95% CI, 1.286-4.348; p = 0.006) was associated with a higher risk of gustatory dysfunction with long COVID. Having received a COVID-19 vaccine booster was positively associated with taste sensation recovery (HR, 1.344; 95% CI, 1.012-1.785; p = 0.041). CONCLUSIONS: About 20.37% of patients with COVID-19 might develop long COVID of gustatory dysfunction and 5.56% with persisting changes in their sense of taste. Most patients recovered taste sensations within 1-3 weeks after COVID-19 symptom onset and receiving a booster shot of the COVID-19 vaccine presented a protective effect on the taste sensation recovery.

2.
Artigo em Inglês | MEDLINE | ID: mdl-37917895

RESUMO

Objective: Our aim was to evauate the application value of esesketamine and dexmedetomidine in preventing postoperative hyperalgesia in elderly patients who received thoracic anesthesia. Methods: A total of 94 elderly patients who underwent thoracic anesthesia in Sanmen People's Hospital from January 2021 to October 2022 were selected and divided into a dexmedetomidine group (n = 47) and an esketamine group (n = 47) by the random number table method. All patients were continuously received intravenous (IV) remifentanil. In the dexmedetomidine group, dexmedetomidine 0.7 µg/kg was administered IV, followed by 0.2 to 0.5 µg/kg/h to maintain anesthesia, while in the esketamine group, esketamine 0.5 mg/kg was given IV 20 min after induction of anesthesia was completed. Results: Visual analogue scale (VAS) scores in the esketamine group were lower than in the dexmedetomidine group at 1, 6, 12 and 24 h postoperatively (P < .05), and Ramsay sedation scores were not statistically different from those in the dexmedetomidine group (P > .05). At 3 d postoperatively, the Mini-Mental State Examination (MMSE) scores in the dexmedetomidine group were lower than 1 d preoperatively; at 5 d postoperatively, the negative mood and Pittsburgh Sleep Quality Index (PSQI) scores were significantly higher in both groups than 1 d preoperatively; at 14 d postoperatively, the PSQI scores were higher in both groups than 1 d preoperatively, and there was no statistical difference between the negative mood scores at 1 d before surgery (P > .05). At 5 d postoperatively in the esketamine group, the negative mood scores were lower than in the dexmedetomidine group at 5 d postoperatively and the PSQI scores at 5 and 14 d postoperatively were lower than in the dexmedetomidine group (P < .05). Conclusion: Both esketamine and dexmedetomidine can be used to prevent postoperative delirium and nociceptive hypersensitivity after anesthesia in elderly patients with thoracic surgery. However, esketamine is superior to dexmedetomidine in analgesic effect, improvement of negative mood and sleep and stabilization of intraoperative hemodynamics, leading to better effect in preventing delirium and hyperalgesia after anesthesia.

3.
Altern Ther Health Med ; 29(7): 424-428, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37573591

RESUMO

Objective: This retrospective study aimed to evaluate the effectiveness and safety of esketamine as an analgesic during cesarean section procedures. Methods: 102 puerperae undergoing cesarean section were divided into a control group and an esketamine (SK) group. Various parameters, including HR, MAP, and postoperative pain, were analyzed. Blood gas analysis and Apgar scores were assessed in neonates. Postoperative depression and satisfaction were evaluated in puerperae. Drug concentrations were measured using liquid-phase tandem mass spectrometry. Results: No significant differences in dimension levels were observed between the two groups (P > .05). However, the SK group showed better HR and MAP indicators at various time points, less postoperative pain, and better mental well-being on postpartum days 1, 3, and 7 (P < .05). Adverse reaction rates were similar between groups (P > .05), but postoperative satisfaction was significantly different (P = .027). Neonatal outcomes did not differ significantly (P > .05). In the SK group, SK2 and SK3 groups had better results compared to SK1 (P < .05). Conclusion: Esketamine during cesarean section stabilized vital signs, reduced pain, and improved well-being in puerperae without affecting newborns. Optimal dosage: 30 µg/kg/h esketamine, 15 ng/kg/h sufentanil.


Assuntos
Analgesia , Cesárea , Gravidez , Recém-Nascido , Humanos , Feminino , Cesárea/efeitos adversos , Estudos Retrospectivos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Analgésicos/uso terapêutico , Emoções
4.
Sci Rep ; 13(1): 11870, 2023 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-37481622

RESUMO

Cuproptosis is a recently discovered type of programmed cell death that shows significant potential in the diagnosis and treatment of cancer. It has important significance in the prognosis of HSNC. This study aims to construct a cuproptosis-related prognostic model and risk score through new data analysis methods such as machine learning algorithms for the prognosis analysis of HSNC. Protein-protein interaction network and machine learning methods were employed to identify hub genes that were used to construct a TreeGradientBoosting model for predicting overall survival. The relationship between the risk scores obtained from the model and features such as tumor microenvironment (TME) and tumor immunity was explored. The C-indexes of the TreeGradientBoosting model in the training and validation cohorts were 0.776 and 0.848, respectively. The nomogram based on risk scores and clinical features showed good performance, and distinguished the TME and immunity between high-risk and low-risk groups. The cuproptosis-associated risk score can be used to predict prognoses, TME, and tumor immunity of HNSC patients.


Assuntos
Apoptose , Neoplasias de Cabeça e Pescoço , Microambiente Tumoral , Humanos , Algoritmos , Aprendizado de Máquina , Prognóstico , Fatores de Risco , Carcinoma de Células Escamosas de Cabeça e Pescoço , Cobre
5.
J Gen Intern Med ; 38(11): 2486-2493, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37127751

RESUMO

BACKGROUND: It is important to identify older adults at high risk of functional disability and to take preventive measures for them at an early stage. To our knowledge, there are no studies that predict functional disability among community-dwelling older adults using machine learning algorithms. OBJECTIVE: To construct a model that can predict functional disability over 5 years using basic machine learning algorithms. DESIGN: A cohort study with a mean follow-up of 5.4 years. PARTICIPANTS: We used data from the Japan Gerontological Evaluation Study, which involved 73,262 people aged ≥ 65 years who were not certified as requiring long-term care. The baseline survey was conducted in 2013 in 19 municipalities. MAIN MEASURES: We defined the onset of functional disability as the new certification of needing long-term care that was ascertained by linking participants to public registries of long-term care insurance. All 183 candidate predictors were measured by self-report questionnaires. KEY RESULTS: During the study period, 16,361 (22.3%) participants experienced the onset of functional disability. Among machine learning-based models, ridge regression (C statistic = 0.818) and gradient boosting (0.817) effectively predicted functional disability. In both models, we identified age, self-rated health, variables related to falls and posture stabilization, and diagnoses of Parkinson's disease and dementia as important features. Additionally, the ridge regression model identified the household characteristics such as the number of members, income, and receiving public assistance as important predictors, while the gradient boosting model selected moderate physical activity and driving. Based on the ridge regression model, we developed a simplified risk score for functional disability, and it also indicated good performance at the cut-off of 6/7 points. CONCLUSIONS: Machine learning-based models showed effective performance prediction over 5 years. Our findings suggest that measuring and adding the variables identified as important features can improve the prediction of functional disability.


Assuntos
Avaliação da Deficiência , Vida Independente , Desempenho Físico Funcional , Idoso , Humanos , Estudos de Coortes , População do Leste Asiático , Aprendizado de Máquina , Inquéritos e Questionários
6.
Rev Sci Instrum ; 92(4): 044705, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-34243433

RESUMO

A new micro-ocean-bottom electromagnetic (EM) receiver is presented for marine magnetotelluric (MT) and controlled-source EM (CSEM) data acquisition, avoiding the bulkiness, high cost, high power consumption, and narrow bandwidth of the existing ocean-bottom EM receivers. The efficient, compact, and easy-to-use data logger employs a single 17-in. spherical glass as a float and uses an acoustic telemetry modem unit to control the burn-wire release of the seafloor instrument via a smartphone. The receiver design involves two induction coils for the magnetometer and four 8-m-span electric-field sensors for MT and CSEM data acquisition. The new ocean-bottom EM receiver was tested in sea. Compared with other miniaturized seabed EM receivers, the proposed receiver achieves better comprehensive performance for MT and CSEM data acquisition and meets the requirements of deep-mantle-structure research and seabed resource exploration.

7.
Am J Transl Res ; 13(2): 781-791, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33594326

RESUMO

The forkhead box O1 (FOXO1) transcription factor plays a key role in wound healing process. Recently it has been reported that lineage-specific genetic ablation of FOXO1 significantly improves diabetic wound healing in a mouse model. To investigate the clinical usefulness of these findings, translational preclinical studies with a large animal model are needed. We report for the first time that the local application of a FOXO1 inhibitor (AS1842856) significantly improves connective tissue healing in a preclinical T2DM minipig model, reflected by increased collagen matrix formation, increased myofibroblast numbers, improved angiogenesis, and a shift in cell populations from pro-inflammatory (IL-1ß+, TNF-α+ and iNOS+) to pro-healing (CD163+). Our results set up the basis for the clinical application of a FOXO1 antagonist in early diabetic wounds where there is impaired connective tissue healing.

8.
JSES Int ; 4(1): 25-29, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32544930

RESUMO

BACKGROUND: The Kocher approach is often adopted for surgical treatment of partial radial head fractures. However, anterior exposure of the radial head is limited by the Kocher approach. Radial head fractures are predisposed to be located at the anterior radius. The deviation of susceptible fracture locations against the regular operative approach imposes certain challenges on surgical procedures. This study explored whether there are any clinically significant differences in the exposure between the Henry and Kocher approaches. MATERIALS AND METHODS: Ten fresh-frozen cadaveric upper limbs were obtained as specimens. The radial head was exposed by both the Henry and Kocher approaches, followed by a long-axis parallel incision at the joint capsule until the capsular attachment was reached; the extracapsular ligaments and surrounding soft tissues were avoided. The 2 approaches were compared in the blind zone and in the visualized area. RESULTS: The blind-zone arc of radial head exposure with the Henry and Kocher approaches averaged 132° ± 16° and 112° ± 21°, respectively. The supinated angle between the borderline of the blind-zone arc and the biceps tuberosity-radial medullary cavity centerline averaged 268° ± 20° and 75° ± 16°, respectively. CONCLUSIONS: The Henry approach offered optimal exposure of the anterior and lateral radial head but had a blind zone at the posteromedial radial head, whereas the Kocher approach offered optimal exposure of the posterolateral radial head but had a blind zone at the anterolateral radial head. The Henry approach could be a better option for specific management of radial head fractures based on the fracture location.

9.
Bone ; 123: 159-167, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30904630

RESUMO

Diabetes increases the risk of fracture, impairs fracture healing and causes rapid loss of the fracture callus cartilage, which was linked to increased FOXO1 expression in chondrocytes. We recently demonstrated that deletion of FOXO1 in chondrocytes blocked the premature removal of cartilage associated with endochondral bone formation during fracture healing. However, the ultimate impact of this deletion on mechanical strength was not investigated and remains unknown. Closed fractures were induced in Col2α1Cre+.FOXO1L/L mice with lineage specific deletion of FOXO1 in chondrocytes compared to littermate controls. Type 1 diabetes was induced by multiple low dose streptozotocin treatment. Thirty-five days after fracture micro CT analysis showed that diabetes significantly reduced callus volume and bone volume (P < 0.05), both which were reversed by FOXO1 deletion in chondrocytes. Diabetes significantly reduced mechanical strength measured by maximum torque, stiffness, modulus of rigidity and toughness and FOXO1 deletion in diabetic mice rescued each parameter (P < 0.05). Diabetes also reduced both bone volume and mechanical strength in non-fractured femurs. However, FOXO1 deletion did not affect bone volume or strength in non-fractured bone. These results point to the important effect that diabetes has on chondrocytes and show for the first time that the premature removal of cartilage induced by FOXO1 in chondrocytes has a significant impact on the mechanical strength of the healing bone.


Assuntos
Condrócitos/metabolismo , Diabetes Mellitus Experimental/metabolismo , Fraturas do Colo Femoral/metabolismo , Proteína Forkhead Box O1/deficiência , Consolidação da Fratura/fisiologia , Deleção de Genes , Animais , Fenômenos Biomecânicos/fisiologia , Condrócitos/patologia , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Fraturas do Colo Femoral/genética , Fraturas do Colo Femoral/patologia , Proteína Forkhead Box O1/genética , Camundongos , Camundongos Transgênicos
10.
J Pathol ; 245(3): 258-264, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29574902

RESUMO

Angiogenesis is a critical aspect of wound healing. We investigated the role of keratinocytes in promoting angiogenesis in mice with lineage-specific deletion of the transcription factor FOXO1. The results indicate that keratinocyte-specific deletion of Foxo1 reduces VEGFA expression in mucosal and skin wounds and leads to reduced endothelial cell proliferation, reduced angiogenesis, and impaired re-epithelialization and granulation tissue formation. In vitro FOXO1 was needed for VEGFA transcription and expression. In a porcine dermal wound-healing model that closely resembles healing in humans, local application of a FOXO1 inhibitor reduced angiogenesis. This is the first report that FOXO1 directly regulates VEGFA expression and that FOXO1 is needed for normal angiogenesis during wound healing. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Proteína Forkhead Box O1/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Gengiva/metabolismo , Mucosa Bucal/metabolismo , Neovascularização Fisiológica , Pele/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Cicatrização , Ferimentos e Lesões/metabolismo , Animais , Linhagem Celular , Modelos Animais de Doenças , Feminino , Proteína Forkhead Box O1/deficiência , Proteína Forkhead Box O1/genética , Fatores de Transcrição Forkhead/genética , Gengiva/lesões , Gengiva/patologia , Humanos , Queratinócitos/metabolismo , Queratinócitos/patologia , Masculino , Camundongos Knockout , Mucosa Bucal/lesões , Mucosa Bucal/patologia , Transdução de Sinais , Pele/lesões , Pele/patologia , Suínos , Porco Miniatura , Fator A de Crescimento do Endotélio Vascular/genética , Ferimentos e Lesões/genética , Ferimentos e Lesões/patologia
11.
Acta Crystallogr F Struct Biol Commun ; 73(Pt 4): 196-201, 2017 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-28368277

RESUMO

The serine/threonine protein kinase liver kinase B1 (LKB1) is a tumour suppressor and plays important roles in development and metabolism. It phosphorylates AMPK and AMPK-related kinases to regulate multiple physiological processes. Mutations in LKB1 often occur in multiple cancers. LKB1 can be suppressed by 14-3-3 proteins in a phosphorylation-dependent manner. Previously, the structure of a 14-3-3ζ-LKB1 fusion protein has been reported, revealing a phosphorylation-independent binding mode of LKB1 to 14-3-3 proteins. Here, the crystal structure of phosphorylated LKB1 peptide in complex with 14-3-3ζ was solved, which provides a structural basis for the phosphorylation-dependent recognition of LKB1 by 14-3-3 proteins.


Assuntos
Proteínas 14-3-3/química , Fígado/química , Proteínas Serina-Treonina Quinases/química , Proteínas 14-3-3/genética , Proteínas 14-3-3/metabolismo , Quinases Proteína-Quinases Ativadas por AMP , Motivos de Aminoácidos , Sítios de Ligação , Clonagem Molecular , Cristalografia por Raios X , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Humanos , Fígado/enzimologia , Modelos Moleculares , Fosforilação , Ligação Proteica , Conformação Proteica em alfa-Hélice , Domínios e Motivos de Interação entre Proteínas , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
12.
Oncotarget ; 7(6): 6727-47, 2016 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-26734995

RESUMO

Activator protein 1 (AP-1) is a transcriptional factor composed of the dimeric members of bZIP proteins, which are frequently deregulated in human cancer cells. In this study, we aimed to identify an oncogenic AP-1 dimer critical for the proliferation of neuroblastoma cells and to investigate whether histone deacetylase inhibitors (HDACIs), a new generation of anticancer agents, could target the AP-1 dimer. We report here that HDACIs including trichostatin A, suberoylanilidehydroxamic acid, valproic acid and M344 can transcriptionally suppress both c-Jun and Fra-1, preceding their inhibition of cell growth. c-Jun preferentially interacting with Fra-1 as a heterodimer is responsible for AP-1 activity and critical for cell growth. Mechanistically, HDACIs suppress Fra-1 expression through transcriptionally downregulating Raf1 and subsequently decreasing MEK1/2-ERK1/2 activity. Unexpectedly, HDACI treatment caused MKK7 downregulation at both the protein and mRNA levels. Deletion analysis of the 5'-flanking sequence of the MKK7 gene revealed that a major element responsible for the downregulation by HDACI is located at -149 to -3 relative to the transcriptional start site. Knockdown of MKK7 but not MKK4 remarkably decreased JNK/c-Jun activity and proliferation, whereas ectopic MKK7-JNK1 reversed HDACI-induced c-Jun suppression. Furthermore, suppression of both MKK-7/c-Jun and Raf-1/Fra-1 activities was involved in the tumor growth inhibitory effects induced by SAHA in SH-SY5Y xenograft mice. Collectively, these findings demonstrated that c-Jun/Fra-1 dimer is critical for neuroblastoma cell growth and that HDACIs act as effective suppressors of the two oncogenes through transcriptionally downregulating MKK7 and Raf1.


Assuntos
Inibidores de Histona Desacetilases/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/genética , MAP Quinase Quinase 7/genética , Neuroblastoma/genética , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-raf/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Regulação para Baixo/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Xenoenxertos , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , MAP Quinase Quinase 7/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Multimerização Proteica , Proteínas Proto-Oncogênicas c-fos/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteínas Proto-Oncogênicas c-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-raf/metabolismo , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Fator de Transcrição AP-1/metabolismo , Transfecção
13.
Lipids Health Dis ; 12: 85, 2013 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-23758630

RESUMO

BACKGROUND: Hyperlipidaemia is a major risk factor for coronary artery disease (CAD) and cholesteryl ester transfer protein (CETP) gene polymorphisms are known to be associated with lipid profiles. METHODS: In this study, we investigated the association of two polymorphisms in the CETP, Taq1B (rs708272) and -629C > A (rs1800775), with CAD and lipid levels HDL-C in 662 CAD + cases and 927 controls from the Singapore population comprising Chinese, Malays and Indians. RESULTS: TaqB2 frequency was significantly lowest in the Malays (0.43) followed by Chinese (0.47) and highest in the Indians (0.56) in the controls. The B2 allele frequency was significantly lower in the Chinese CAD + cases compared to the controls (p = 0.002). The absence of the B2 allele was associated with CAD with an OR 2.0 (95% CI 1.2 to 3.4) after adjustment for the confounding effects of age, smoking, BMI, gender, hypertension, dyslipidemia and diabetes mellitus. The B2 allele was significantly associated with higher plasma HDL-C levels in the Chinese men after adjusting for confounders. Associations with plasma apoA1 levels were significant only in the Chinese men for Taq1B and -629C > A. In addition, the Taq1B polymorphism was only associated with plasma Apo B and Lp(a) in the Malay men. Significant associations were only found in non-smoking subjects with BMI <50th percentile. In this study, the LD coefficients between the Taq1B and -629C > A polymorphisms seemed to be weak. CONCLUSION: The absence the Taq1B2 allele was associated with CAD in the Chinese population only and the minor allele of the Taq1B polymorphism of the CETP gene was significantly associated with higher plasma HDL-C levels in Chinese men.


Assuntos
Proteínas de Transferência de Ésteres de Colesterol/genética , HDL-Colesterol/genética , Doença da Artéria Coronariana/genética , Hiperlipidemias/genética , Adulto , Estudos de Casos e Controles , HDL-Colesterol/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/patologia , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Hiperlipidemias/patologia , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Fatores de Risco , Caracteres Sexuais , Singapura
14.
Structure ; 21(6): 1042-50, 2013 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-23685212

RESUMO

Human APOBEC3F is an antiretroviral single-strand DNA cytosine deaminase, susceptible to degradation by the HIV-1 protein Vif. In this study the crystal structure of the HIV Vif binding, catalytically active, C-terminal domain of APOBEC3F (A3F-CTD) was determined. The A3F-CTD shares structural motifs with portions of APOBEC3G-CTD, APOBEC3C, and APOBEC2. Residues identified to be critical for Vif-dependent degradation of APOBEC3F all fit within a predominantly negatively charged contiguous region on the surface of A3F-CTD. Specific sequence motifs, previously shown to play a role in Vif susceptibility and virion encapsidation, are conserved across APOBEC3s and between APOBEC3s and HIV-1 Vif. In this structure these motifs pack against each other at intermolecular interfaces, providing potential insights both into APOBEC3 oligomerization and Vif interactions.


Assuntos
Citosina Desaminase/metabolismo , HIV-1/metabolismo , Produtos do Gene vif do Vírus da Imunodeficiência Humana/metabolismo , Catálise , Cristalografia por Raios X , Citosina Desaminase/química , Modelos Moleculares , Conformação Proteica
15.
Biology (Basel) ; 1(2): 260-76, 2012 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-24832226

RESUMO

APOBEC3G is the best known of several DNA cytosine deaminases that function to inhibit the replication of parasitic genetic elements including the lentivirus HIV. Several high-resolution structures of the APOBEC3G catalytic domain have been generated, but none reveal how this enzyme binds to substrate single-stranded DNA. Here, we constructed a panel of APOBEC3G amino acid substitution mutants and performed a series of biochemical, genetic, and structural assays to distinguish between "Brim" and "Kink" models for single-strand DNA binding. Each model predicts distinct sets of interactions between surface arginines and negatively charged phosphates in the DNA backbone. Concordant with both models, changing the conserved arginine at position 313 to glutamate abolished both catalytic and restriction activities. In support of the Brim model, arginine to glutamate substitutions at positions 213, 215, and 320 also compromised these APOBEC3G activities. Arginine to glutamate substitutions at Kink model residues 374 and 376 had smaller effects. These observations were supported by A3G catalytic domain-ssDNA chemical shift perturbation experiments. The overall data set is most consistent with the Brim model for single-stranded DNA binding by APOBEC3G.

16.
Ying Yong Sheng Tai Xue Bao ; 22(9): 2316-24, 2011 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-22126042

RESUMO

Arbuscular mycorrhiza (AM) can not only improve host plants nutrient absorption, but also enhance their disease resistance. Taking the tomato (Lycopersicon esculentum) seedlings preinoculated with axbuscular mycorrhizal fungus (AMF) Glomus versiforme as test materials, this paper studied their protective enzyme activities and defense-related genes expression, and their resistance against a fungal pathogen Alternaria solani Sorauer which causes early blight. The seedlings pre-inoculated with AMF and later inoculated with A. solani showed significantly higher activities of superoxide dismutase (SOD) and peroxidase (POD) in leaves. The leaf SOD activity of the dually inoculated plants reached the maximum 18 h after pathogen inoculation, being 28.6%, 79.2% and 82.8% higher than that of the plants with G. versiforme inoculation alone, pathogen inoculation alone, and non-inoculation, and the Leaf POD activity reached the maximum 65 h after pathogen inoculation, being 762%, 18.3%, and 1710% higher, respectively. Real time RT-PCR analysis showed that dual inoculation with C. versiforme and A. solani strongly induced the expression of three defense-related genes. The transcript levels of pathogen-related protein (PR1), basic type beta-1,3-glucanase (PR-2), and chitinase (PR-3) in leaves were 9.67-, 8.54-, and 13.4-fold higher, as compared with the non-inoculation control, respectively. Bioassay showed that the disease incidence and disease index of the seedlings pre-inoculated with C. versiforme were reduced by 36.3% and 61.4%, respectively, as compared with the non-mycorrhizal control plants. These findings indicated that mycorrhizal colonization could induce stronger and quicker defense responses of host tomato plants, and priming could be an important mechanism of the enhanced disease resistance of mycorrhizal tomato plants.


Assuntos
Resistência à Doença , Micorrizas/fisiologia , Doenças das Plantas/prevenção & controle , Solanum lycopersicum/microbiologia , Alternaria/patogenicidade , Glomeromycota/fisiologia , Solanum lycopersicum/crescimento & desenvolvimento , Doenças das Plantas/microbiologia , Plântula/crescimento & desenvolvimento , Plântula/microbiologia , Simbiose
17.
Neurosci Lett ; 499(3): 164-9, 2011 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-21641965

RESUMO

The transcription factor E2F1 is upregulated when cerebellar granular neurons (CGNs) undergo apoptosis under potassium deprivation. In this study, we examined the effects of E2F1 upregulation on the survival and death of CGNs isolated from C57 mice and Sprague-Dawley (SD) rats. Plasmid- and adenovirus-mediated expression of E2F1 dose-dependently induced apoptosis in mouse CGNs but unexpectedly failed to induce apoptosis in rat CGNs. Caspase 3, a marker for neuronal apoptosis, was significantly activated by ectopic E2F1 expression in mouse CGNs but not in rat CGNs. Furthermore, overexpression of E2F1 significantly promoted apoptotic progression in mouse CGNs following potassium deprivation but attenuated apoptosis in rat CGNs, whereas E2F1 lacking DNA binding ability (E2F1-M132) lost its pro-apoptotic role in mouse CGNs and anti-apoptotic role in rat CGNs. Together, our results demonstrated that upregulation of E2F1 by potassium deprivation promotes apoptosis in C57 mouse CGNs but antagonizes apoptosis in SD rat CGNs, suggesting opposing roles for E2F1 in regulating CGN fate.


Assuntos
Apoptose/fisiologia , Sobrevivência Celular/fisiologia , Cerebelo/fisiologia , Fator de Transcrição E2F1/fisiologia , Neurônios/fisiologia , Animais , Caspase 3/metabolismo , Linhagem Celular Transformada , Cerebelo/metabolismo , Proteínas de Ligação a DNA/metabolismo , Fator de Transcrição E2F1/genética , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Potássio/efeitos adversos , Ratos , Ratos Sprague-Dawley
18.
Nan Fang Yi Ke Da Xue Xue Bao ; 30(8): 1860-3, 2010 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-20813686

RESUMO

OBJECTIVE: To study the relationship between muscle motor evoked potentials (MEP) and hindlimbs motor function in rabbits with spinal cord injury. METHODS: Forty-five rabbits were randomly divided into 9 groups, including one control group and 8 injured groups (receiving Allen's injury of 0, 50, 75, 100, 125, 150, 175, 200, or 250 gcf). Hindlimb strength and muscle MEP were recorded at the 1st day and 4th week postoperatively. At 4 weeks after spinal section, the spinal cord tissue was sampled for histological examination with HE staining and immunohistochemistry with anti-NF antibody of the corticospinal tract fibers. RESULTS: During the operation, MEP showed an all-or-none pattern with significant correlations to postoperative optical density of NF and postoperative hindlimb motor function. The latency prolongation of the muscle MEP at the 4th week showed a linear correlation to the hindlimb Tarlov's score, whereas the MEP amplitude was not correlated to postoperative hindlimb motor function. CONCLUSIONS: The all-or-none pattern of muscle MEP can be used to evaluate the severity of spinal cord injury.


Assuntos
Potencial Evocado Motor , Membro Posterior/fisiopatologia , Tratos Piramidais/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologia , Animais , Coelhos
19.
J Mol Biol ; 389(5): 819-32, 2009 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-19389408

RESUMO

Human APOBEC3G (A3G) belongs to a family of polynucleotide cytidine deaminases. This family includes APOBEC1 and AID, which edit APOB mRNA and antibody gene DNA, respectively. A3G deaminates cytidines to uridines in single-strand DNA and inhibits the replication of human immunodeficiency virus-1, other retroviruses, and retrotransposons. Although the mechanism of A3G-catalyzed DNA deamination has been investigated genetically and biochemically, atomic details are just starting to emerge. Here, we compare the DNA cytidine deaminase activities and NMR structures of two A3G catalytic domain constructs. The longer A3G191-384 protein is considerably more active than the shorter A3G198-384 variant. The longer structure has an alpha1-helix (residues 201-206) that was not apparent in the shorter protein, and it contributes to catalytic activity through interactions with hydrophobic core structures (beta1, beta3, alpha5, and alpha6). Both A3G catalytic domain solution structures have a discontinuous beta2 region that is clearly different from the continuous beta2 strand of another family member, APOBEC2. In addition, the longer A3G191-384 structure revealed part of the N-terminal pseudo-catalytic domain, including the interdomain linker and some of the last alpha-helix. These structured residues (residues 191-196) enabled a novel full-length A3G model by providing physical overlap between the N-terminal pseudo-catalytic domain and the new C-terminal catalytic domain structure. Contrary to predictions, this structurally constrained model suggested that the two domains are tethered by structured residues and that the N- and C-terminal beta2 regions are too distant from each other to participate in this interaction.


Assuntos
Domínio Catalítico , Citidina Desaminase/química , Citidina Desaminase/metabolismo , Desaminase APOBEC-3G , Sequência de Aminoácidos , Citidina Desaminase/genética , Holoenzimas/química , Holoenzimas/genética , Holoenzimas/metabolismo , Humanos , Modelos Moleculares , Dados de Sequência Molecular , Ressonância Magnética Nuclear Biomolecular , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Alinhamento de Sequência
20.
Zhen Ci Yan Jiu ; 34(6): 398-402, 2009 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-20209976

RESUMO

OBJECTIVE: To observe the effect of ginger-partitioned moxibustion in the treatment of patients with primary dysmenorrhea (PD) of cold-damp stagnation type. METHODS: A total of 209 PD patients were randomized into moxibustion group (n=105) and control group (medication group, n=104). Patients of the former group were treated with ginger-partitioned moxibustion at Shenque (CV 8) and Guanyuan (CV 4), once daily for 3 days in the first menstrual cycle, and 3 days before menstruation and once daily for 6 days in the 2nd and 3rd menstrual cycles, and those of control group were asked to take Yueyueshu Granules (a Chinese herbal patent drug for relieving PD). Clinical symptom scores were assessed before and after the treatment. RESULTS: After the treatment, of the 105 and 104 cases in the moxibustion and control groups, the cured, markedly effective, effective and failed cases were 58 (55.24%) and 32 (30.77%), 37 (35.24%) and 33 (31.73%), 5 (4.76%) and 24 (23.08%), and 5 (4.76%) and 15 (14.42%), respectively. The total therapeutic effect of moxibustion group wassignificantly better than that of control group (P<0.01). The effects of moxibustion for relieving mild, moderate and severe dysmenorrhea were evidently superior to those of medication (P<0.01). The symptom scores after the treatment and 3 months of post-treatment in moxibustion group were significantly lower than those of control group (P<0.01). CONCLUSION: Ginger-partitioned moxibustion therapy was effective for PD of cold-damp stagnation type.


Assuntos
Dismenorreia/terapia , Moxibustão , Pontos de Acupuntura , Adolescente , Adulto , Feminino , Humanos , Resultado do Tratamento , Adulto Jovem
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