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1.
Artigo em Inglês | MEDLINE | ID: mdl-39012652

RESUMO

BACKGROUND: Colorectal cancer (CRC) continues to be a major global health concern. Recent advances in molecular biology have highlighted the gut microbiota's role in CRC. This study investigates long-term (≥5 years) gut microbiota changes in patients postcholecystectomy, comparing them with CRC patients and healthy controls to assess their impact on CRC development. METHODS: Sixty participants were divided into three groups: 20 healthy controls, 20 postcholecystectomy (PCE) patients, and 20 CRC patients. Demographic data and stool samples were collected. Gut microbiota composition, abundance, and diversity were analyzed using high-throughput 16S rDNA sequencing. RESULTS: Significant differences in microbial community, α-diversity (P < 0.05) and ß-diversity (P = 0.006), were observed among the three groups. At the phylum level, Firmicutes abundance was significantly reduced in PCE and CRC groups compared with the control group (P = 0.002), while changes in other phyla were not significant (P>0.05). At the genus level, Bacteroides, Dialister, and Parabacteroides increased progressively from control to PCE to CRC groups (P = 0.004, 0.001, and 0.002). Prevotella decreased across these groups (P = 0.041). Faecalibacterium and Roseburia abundances were reduced in PCE and CRC groups compared with controls (P = 0.001 and 0.003). The Random Forest algorithm identified Parabacteroides, Bacteroides, Roseburia, and Dialister as key distinguishing genera. CONCLUSION: The gut microbiota of long-term (≥5 years) PCE patients significantly differs from that of controls and resembles that of CRC patients, suggesting a potential link between cholecystectomy and CRC development through key microbial changes.

2.
Heliyon ; 9(12): e22905, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38125492

RESUMO

CD47 is a 50 kDa five-spanning membrane receptor that plays a crucial role in multiple cellular processes, including myeloid cell activation, neutrophils transmigration, vascular remodeling, leukocyte adhesion and trans-endothelial migration. Recent studies have revealed that CD47 is a highly expressed anti-phagocytic signal in several types of cancer, and therefore, blocking of CD47 has shown an effective therapeutic potential in cancer immunotherapy. In addition, CD47 has been found to be involved in a complex interplay with microglia and other types of cells, and increasing evidence indicates that CD47 can be targeted as part of immune modulatory strategies for non-neoplastic diseases as well. In this review, we focus on CD47 and its role in non-neoplastic diseases, including neurological disorders, atherosclerosis and autoimmune diseases. In addition, we discuss the major challenges and potential remedies associated with CD47-SIRPα-based immunotherapies.

3.
Environ Sci Technol ; 57(19): 7599-7611, 2023 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-37140343

RESUMO

Spent lithium-ion batteries (LIBs) and benzene-containing polymers (BCPs) are two major pollutants that cause serious environmental burdens. Herein, spent LIBs and BCPs are copyrolyzed in a sealed reactor to generate Li2CO3, metals, and/or metal oxides without emitting toxic benzene-based gases. The use of a closed reactor allows the sufficient reduction reaction between the BCP-derived polycyclic aromatic hydrocarbon (PAH) gases and lithium transition metal oxides, achieving the Li recovery efficiencies of 98.3, 99.9, and 97.5% for LiCoO2, LiMn2O4, and LiNi0.6Co0.2Mn0.2O2, respectively. More importantly, the thermal decomposition of PAHs (e.g., phenol and benzene) is further catalyzed by the in situ generated Co, Ni, and MnO2 particles, which forms metal/carbon composites and thus prevent the emissions of toxic gases. Overall, the copyrolysis in a closed system paves a green way to synergistically recycle spent LIBs and handle waste BCPs.


Assuntos
Benzeno , Lítio , Plásticos , Compostos de Manganês , Óxidos , Metais , Fontes de Energia Elétrica , Reciclagem , Polímeros
4.
Front Immunol ; 14: 1334922, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38313430

RESUMO

CD24 has emerged as a molecule of significant interest beyond the oncological arena. Recent studies have unveiled its surprising and diverse roles in various biological processes and diseases. This review encapsulates the expanding spectrum of CD24 functions, delving into its involvement in immune regulation, cancer immune microenvironment, and its potential as a therapeutic target in autoimmune diseases and beyond. The 'magic' of CD24, once solely attributed to cancer, now inspires a new paradigm in understanding its multifunctionality in human health and disease, offering exciting prospects for medical advancements.


Assuntos
Doenças Autoimunes , Neoplasias , Humanos , Antígeno CD24 , Neoplasias/terapia , Doenças Autoimunes/terapia , Microambiente Tumoral
5.
J Card Surg ; 37(12): 5090-5094, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36378854

RESUMO

OBJECTIVE: The lack of chest tube maintenance and management knowledge in nurses can lead to serious adverse consequences. The purpose of this study was to develop a chest tube maintenance and management knowledge questionnaire for clinical nurses, and to verify its reliability and validity. METHODS: Based on literature review and expert consultation, a questionnaire on chest tube maintenance and management knowledge of clinical nurses was designed, and the reliability and validity of the questionnaire were tested in 60 clinical nurses. RESULTS: The initial questionnaire of chest tube maintenance and management knowledge for clinical nurses included 20 items, and three dimensions were finally determined by expert consultation method, including 15 items. The Cronbach's α coefficient of the questionnaire was 0.850, and the Cronbach's α coefficient of each dimension ranged from 0.704 to 0.743. Spearman-brown's split reliability was 0.756. The content validity (content validity index [CVI]) of each item of the questionnaire ranged from 0.833 to 1.000, and the total CVI was 0.978. CONCLUSIONS: The clinical nurses' knowledge questionnaire developed in this study has good reliability and validity, which can effectively and objectively evaluate clinical nurses' mastery of chest tube maintenance and management knowledge.


Assuntos
Tubos Torácicos , Competência Clínica , Humanos , Reprodutibilidade dos Testes , Inquéritos e Questionários
6.
Front Immunol ; 13: 757480, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36081498

RESUMO

CD47 is ubiquitously expressed on the surface of cells and plays a critical role in self-recognition. By interacting with SIRPα, TSP-1 and integrins, CD47 modulates cellular phagocytosis by macrophages, determines life span of individual erythrocytes, regulates activation of immune cells, and manipulates synaptic pruning during neuronal development. As such, CD47 has recently be regarded as one of novel innate checkpoint receptor targets for cancer immunotherapy. In this review, we will discuss increasing awareness about the diverse functions of CD47 and its role in immune system homeostasis. Then, we will discuss its potential therapeutic roles against cancer and outlines, the possible future research directions of CD47- based therapeutics against cancer.


Assuntos
Antígeno CD47 , Imunoterapia , Neoplasias , Humanos , Imunoterapia/métodos , Macrófagos , Neoplasias/imunologia , Neoplasias/terapia , Fagocitose
7.
Orthop Surg ; 14(9): 2219-2229, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35979946

RESUMO

OBJECTIVES: The objective of this study was to introduce a retractor that can be temporarily installed on unilateral pedicle screws to achieve distraction-reduction and nerve root protection, and to analyze the efficacy and safety of retractor-assisted transforaminal lumbar interbody fusion (TLIF) in the treatment of lumbar spondylolisthesis. METHODS: This was a retrospective study of 125 patients who underwent retractor-assisted TLIF for single-segment spondylolisthesis from November 2017 to February 2021. Based on morphology, patients were divided into degenerative (N = 66) and isthmic groups (N = 59). Differences in demographics and preoperative characteristics between the groups were analyzed using the independent samples t-test and χ2 test. Changes in radiographic parameters (disc height, foramen height, spondylolisthesis degree, slippage length, and segmental lordosis) before and after surgery were compared using the paired samples t-test. Logistic regression analysis was performed to analyze the relationship between facet joint angle (FJA) and degenerative lumbar spondylolisthesis (DLS). RESULTS: Unilateral screw retractor-assisted TLIF significantly corrected spondylolisthesis and improved disc height and segmental lordosis (p < 0.05). There was no significant difference in foramen height between the two sides before and after operation (pre: 15.81 ± 3.58 mm vs 15.69 ± 3.68 mm, p = 0.599; post: 18.65 ± 2.31 mm vs 18.74 ± 2.26 mm, p = 0.516). The degree of spondylolisthesis in the DLS group before surgery was significantly lower than that in the isthmic spondylolisthesis group (17.70 ± 5.62% vs 25.18 ± 9.73%, p < 0.001), whereas a similar degree of correction could be achieved after surgery (5.91 ± 3.12% vs 7.16 ± 5.69%, p = 0.135). FJAs from L3/4 to L5/S1 were significantly smaller in patients with DLS than those in with isthmic spondylolisthesis (p < 0.05). Patients with facet sagittalization were more likely to have DLS (ß: -0.101, odds ratio [OR]:0.904, 95% confidence interval [CI]: 0.874-0.934, p < 0.001), while the cut-off FJA of L4/5 for predicting L4 spondylolisthesis was 53.19. CONCLUSIONS: Pedicle screw retractor-assisted TLIF is effective and safe in treating both degenerative and isthmic lumbar spondylolisthesis. The unilateral retractor has the capacity to maintain the disc height achieved by paddle distractors, which optimizes the nerve protection and distractor placement. Patients with an FJA on L4/5 <53.19 were more likely to have DLS.


Assuntos
Lordose , Parafusos Pediculares , Fusão Vertebral , Espondilolistese , Adulto , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Estudos Retrospectivos , Espondilolistese/diagnóstico por imagem , Espondilolistese/cirurgia , Resultado do Tratamento
8.
Front Psychol ; 13: 870312, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35496243

RESUMO

Objective: There is little literature on the validity of kurtosis-adjusted noise energy metrics in human studies. Therefore, this study aimed to validate the application of cumulative noise exposure (CNE) adjusted by kurtosis in evaluating occupational hearing loss associated with non-Gaussian noise among manufacturing workers. Methods: A cross-sectional survey was conducted on 1,558 manufacturing workers exposed to noise from five industries to collect noise exposure and hearing loss data. Both CNE and kurtosis-adjusted CNE (CNE') were collapsed into 2-dB(A)∙year bins, and the mean noise-induced permanent threshold shifts at 3, 4, and 6 kHz (NIPTS346) in each bin were calculated. The contributions of CNE and CNE' to noise-induced hearing loss (NIHL) were compared using the multiple linear regression. The degree of overlap of two linear regression equations (i.e., between CNE' and NIPTS346 for non-Gaussian noise and between CNE and NIPTS346 for Gaussian noise) was used to evaluate the validity of the CNE' using a stratified analysis based on age and sex. Results: Multiple linear regression models showed that after kurtosis adjustment, the standardized regression coefficient of CNE increased from 0.230 to 0.255, and R 2 increased from 0.147 to 0.153. The linear relationship between NIPTS346 and CNE' or CNE showed that the regression line of non-Gaussian noise was closer to that of Gaussian noise when using CNE' than using CNE. The mean difference in NIPTS346 between the equations of non-Gaussian noise and Gaussian noise was significantly reduced from 4.32 to 1.63 dB HL after kurtosis adjustment (t = 12.00, p < 0.001). Through a stratified analysis, these significant decreases were observed in male and female workers, and workers aged ≥30 years old. Conclusion: As a noise exposure metric combining noise energy and temporal characteristics, the kurtosis-adjusted-CNE metric was more effective than CNE alone in assessing occupational hearing loss among manufacturing workers in non-Gaussian noise environment. However, more studies are needed to verify the validity of the kurtosis-adjusted-CNE metric.

9.
Front Surg ; 9: 1050308, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36684349

RESUMO

Study Design: Retrospective. Objectives: To investigate the efficacy of cervical single open-door laminoplasty with and without local lateral mass screw fixation and fusion as treatments for cervical spinal cord injuries accompanied by multisegmental spinal canal stenosis. Setting: The Second Affiliated Hospital, School of Medicine, Zhejiang University. Methods: Of all enrolled patients, 42 formed a stable group who underwent cervical single open-door laminoplasty alone and 14 formed an unstable group who underwent the procedure combined with lateral mass screw fixation and fusion. Neurological function was evaluated before surgery, at discharge, and at final follow-up using the American Spinal Cord Injury Association (ASIA) impairment scale and the Japanese Orthopedic Association (JOA) score. Results: ASIA scores reflected improved neurological function in 52.5% of the stable group (15 with grade-D and 4 with grade-A injuries did not improve) and 45.5% of the unstable group (3 with grade-D and 3 with grade-A injuries did not improve). Postoperative JOA scores reflected 19.1% ± 21.6% improvement in the stable group and 18.6% ± 18.4% improvement in the unstable group (P > 0.05). Final follow-up JOA scores reflected 49.2% ± 31.7% improvement in the stable group and 47.1% ± 39.2% improvement in the unstable group (P > 0.05). Conclusions: Laminoplasty combined with local fusion aided the treatment of unstable cervical spinal cord injuries and spinal stenosis. Such stenosis is the main pathological factor causing multiple spinal cord compressions in patients with cervical spinal cord injuries.

10.
Ear Hear ; 42(6): 1782-1796, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34369415

RESUMO

OBJECTIVE: The association of occupational noise-induced hearing loss (NIHL) with noise energy was well documented, but the relationship between occupational noise and noise temporal structure is rarely reported. The objective of this study was to investigate the principal characteristics of the relationship between occupational NIHL and the temporal structure of noise. METHODS: Audiometric and shift-long noise exposure data were collected from 3102 Chinese manufacturing workers from six typical industries through a cross-sectional survey. In data analysis, A-weighted 8-h equivalent SPL (LAeq.8h), peak SPL, and cumulative noise exposure (CNE) were used as noise energy indicators, while kurtosis (ß) was used as the indicator of noise temporal structure. Two NIHL were defined: (1) high-frequency noise-induced hearing loss (HFNIHL) and (2) noise-induced permanent threshold shift at test frequencies of 3, 4, and 6 kHz (noise-induced permanent threshold shift [NIPTS346]). The noise characteristics of different types of work and the relationship between these characteristics and the prevalence of NIHL were analyzed. RESULTS: The noise waveform shape, with a specific noise kurtosis, was unique to each type of work. Approximately 27.92% of manufacturing workers suffered from HFNIHL, with a mean NIPTS346 of 24.16 ± 14.13 dB HL. The Spearman correlation analysis showed that the kurtosis value was significantly correlated with the difference of peak SPL minus its LAeq.8h across different types of work (p < 0.01). For a kurtosis-adjusted CNE, the linear regression equation between HFNIHL% and CNE for complex noise almost overlapped with Gaussian noise. Binary logistic regression analysis showed that LAeq.8h, kurtosis, and exposure duration were the key factors influencing HFNIHL% (p < 0.01). The notching extent in NIPTS at 4 kHz became deeper with the increase in LAeq.8h and kurtosis. HFNIHL% increased most rapidly during the first 10 years of exposure. HFNIHL% with ß ≥ 10 was significantly higher than that with ß < 10 (p < 0.05), and it increased with increasing kurtosis across different CNE or LAeq.8h levels. When LAeq.8h was 80 to 85 dB(A), the HFNIHL% at ß ≥ 100 was significantly higher than that at 10 ≤ ß < 100 or ß < 10 (p < 0.05 and p < 0.01, respectively). CONCLUSIONS: In the evaluation of hearing loss caused by complex noise, not only noise energy but also the temporal structure of noise must be considered. Kurtosis of noise is an indirect metric that is sensitive to the presence of impulsive components in complex noise exposure, and thus, it could be useful for quantifying the risk for NIHL. It is necessary to re-evaluate the safety of permissible exposure limit of 85 dB(A) as noise with a high kurtosis value can aggravate or accelerate early NIHL.


Assuntos
Surdez , Perda Auditiva Provocada por Ruído , Ruído Ocupacional , Exposição Ocupacional , Audiometria , Estudos Transversais , Surdez/complicações , Perda Auditiva Provocada por Ruído/epidemiologia , Perda Auditiva Provocada por Ruído/etiologia , Humanos , Ruído Ocupacional/efeitos adversos , Exposição Ocupacional/efeitos adversos
11.
Ann Transl Med ; 9(10): 886, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34164520

RESUMO

BACKGROUND: Colorectal cancer (CRC), one of the most common malignancies worldwide, is associated with poor survival and has a high mortality rate. Taxol is a chemotherapeutic agent that has been clinically applied as a first-line drug against diverse cancers. Yet, development of drug resistance has become the major challenge for anti-cancer treatments. F-box and WD40 domain protein 7 (Fbxw7) is a known tumor suppressor which is frequently downregulated in cancers. However, the biological roles and mechanisms of Fbxw7 in Taxol resistance are still under investigation. METHODS: We report that Fbxw7 is significantly inactivated in CRC tumors and cell lines compared with normal tissues and colon cells. Expressions of Fbxw7 and Nox1 were detected from human colon tumors and cells by qRT-PCR and Western blot. Glycolysis rate was assessed by glucose uptake and lactate product assay. Interactions between Fbxw7 and Nox1 were determined by co-immunoprecipitation (Co-IP). Chemosensitivity and resistance of colon cancer cells were determined by MTT assay and Annexin V-FITC assay. RESULTS: Overexpression of Fbxw7 sensitized colon cancer cells to Taxol. Moreover, we observed a negative correlation between Fbxw7 and glucose metabolism. From the established Taxol-resistant (TR) cell line from HCT-116, Fbxw7 was found to be markedly downregulated in HCT-116 TR cells. We detected that NADPH oxidase 1 (Nox1), a superoxide-generating NADPH oxidase, is negatively regulated by Fbxw7. The Co-IP assay showed that Fbxw7 interacted with Nox1, which was observed to be significantly upregulated in CRC tissues. Nox1 therefore promotes the Taxol resistance and glucose metabolism of colon cancer cells. Finally, rescue experiments demonstrated that the Fbxw7-promoted Taxol sensitivity was partially through the Nox1-glycolysis axis. Restoration of Nox1 in Fbxw7-overexpressed TR colon cancer cells significantly recovered the Taxol resistance, which could be further overridden by glycolysis inhibition. CONCLUSIONS: Collectively, this study uncovered that targeting the Fbxw7-Nox1-glucose metabolism axis could be an effective strategy against chemoresistant colon cancer.

12.
J Gastrointest Oncol ; 12(2): 630-638, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34012655

RESUMO

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer, according to recently published literature. While the incidence and the mortality of CRC has decreased due to effective cancer screening measures, there has been an increase in the number of young patients diagnosed with colon cancer due to unclear reasons. As a target molecule of the Wnt signaling pathway, Ascl2 is an important marker of CRC stem cells and plays an important role in maintaining the nature of colon cancer stem/precursor cells. However, the role of Ascl2 in autophagy in CRC cells is rarely elucidated. METHODS: In this study, we found that Ascl2 was increased in CRC compared with adjacent tissue. Downregulation of Ascl2 in CRC cells could suppress proliferation and invasion, and induce apoptosis, of CRC cells. Moreover, we found that autophagy-relative protein LC3 increased after Ascl2 knockdown. Furthermore, we treated CRC cells with autophagy inhibitors 3-MA (3-Methyladenine) and CQ (Chloroquine). RESULTS: The results showed that autophagy inhibitors could prevent apoptosis, which was induced by Ascl2 knockdown. Finally, we confirmed that the downregulation of Ascl2 in CRC cells could alleviate the pathological process in vivo by xenograft experiment. CONCLUSIONS: Our findings indicated that si-Ascl2 (small/short interfering) exerted a tumor suppression function in CRC by inducing autophagic cell death, and suggest that Ascl2 targeted therapy represents a novel strategy for CRC treatment.

13.
ACS Chem Neurosci ; 12(7): 1252-1261, 2021 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-33720698

RESUMO

A key transcriptional activator, activating transcription factor 5 (ATF5), is aberrantly overexpressed in glioma and supports both poor prognosis and antiapototic potential. Unfortunately, data on ATF5 is largely based on its regulatory mechanism. Further investigation of the upstream regulatory factor for ATF5 transcription in glioma is required. Clinical data for patients with diagnosed glioma were obtained from The Cancer Genome Atlas (TCGA). Additionally, transcription factors potentially regulating the ATF5 promoter in glioma were screened with bioinformatics. A further experimental study was performed to investigate both the role of E74-like factor 1 (ELF1) and the binding of ELF1 and the ATF5 promoter in glioma. We show that ATF5 expression is upregulated in glioma tissues and associated with tumor malignancy and worse prognosis. As a putative upstream regulator, silencing ELF1 inhibits glioma cell growth and migration with ATF5 involvement. Moreover, ELF1 upregulation is also associated with poor prognosis in glioma. Importantly, the luciferase assay and chromatin immunoprecipitation (ChIP) reveal that the ATF5 gene promoter is essential for ELF1-dependent activation of ATF5 gene transcription. These results indicate that a high expression of ELF1 may be related to the malignant behavior of human glioma and ELF1 promotes glioma development mediated by transactivation of the ATF5 gene.


Assuntos
Fatores Ativadores da Transcrição , Glioma , Fatores Ativadores da Transcrição/genética , Fatores Ativadores da Transcrição/metabolismo , Linhagem Celular Tumoral , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Glioma/genética , Humanos , Proteínas Nucleares , Regiões Promotoras Genéticas , Fatores de Transcrição/genética , Regulação para Cima
14.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(11): 1368-1371, 2020 Nov 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-35753753

RESUMO

OBJECTIVES: To observe the clinical effect and recurrence rate of mitomycin C combined with operation in the treatment of hyperplastic scar of auricle with different diameters. METHODS: A total of 53 patients (67 ears) collected from January 2011 to June 2019 were randomly divided into a combined treatment group (31 ears) and a control group (36 ears). The recurrence rate was observed from one year to three years after operation. RESULTS: The recurrence rate was 52.8% in the control group and 16.1% in the combined treatment group, respectively. For the hyperplastic scar of auricle with diameter from >1.0 cm to 3.0 cm, the recurrence rate was significantly lower in the combined treatment group than that in the control group (χ2=10.804, P<0.05). But there was no significant difference for the hyperplastic scar of auricle with diameter less than 1.0 cm or more than 3.0 cm (both P>0.05). CONCLUSIONS: Mitomycin C combined with surgery can significantly reduce or delay the recurrence rate of middle diameter of hyperplastic scar of auricle, but it does not affect the hyperplastic scar of auricle with too large or too small diameter.

15.
J Neurosurg ; 127(3): 670-678, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27982773

RESUMO

OBJECTIVE Therapeutic neovascularization is a promising strategy for treating patients after an ischemic stroke; however, single-factor therapy has limitations. Stromal cell-derived factor 1 (SDF-1) and vascular endothelial growth factor (VEGF) proteins synergistically promote angiogenesis. In this study, the authors assessed the effect of combined gene therapy with VEGF165 and SDF-1 in a rat model of cerebral infarction. METHODS An adenoviral vector expressing VEGF165 and SDF-1 connected via an internal ribosome entry site was constructed (Ad- VEGF165-SDF-1). A rat model of middle cerebral artery occlusion (MCAO) was established; either Ad- VEGF165-SDF-1 or control adenovirus Ad- LacZ was stereotactically microinjected into the lateral ventricle of 80 rats 24 hours after MCAO. Coexpression and distribution of VEGF165 and SDF-1 were examined by reverse-transcription polymerase chain reaction, Western blotting, and immunofluorescence. The neurological severity score of each rat was measured on Days 3, 7, 14, 21, and 28 after MCAO. Angiogenesis and vascular remodeling were evaluated via bromodeoxyuridine and CD34 immunofluorescence labeling. Relative cerebral infarction volumes were determined by T2-weighted MRI and triphenyltetrazolium chloride staining. Cerebral blood flow, relative cerebral blood volume, and relative mean transmit time were assessed using perfusion-weighted MRI. RESULTS The Ad- VEGF165-SDF-1 vector mediated coexpression of VEGF165 and SDF-1 in multiple sites around the ischemic core, including the cortex, corpus striatum, and hippocampal granular layer. Coexpression of VEGF165 and SDF-1 improved neural function, reduced cerebral infarction volume, increased microvascular density and promoted angiogenesis in the ischemic penumbra, and improved cerebral blood flow and perfusion. CONCLUSIONS Combined VEGF165 and SDF-1 gene therapy represents a potential strategy for improving vascular remodeling and recovery of neural function after cerebral infarction.


Assuntos
Isquemia Encefálica/genética , Isquemia Encefálica/fisiopatologia , Circulação Cerebrovascular , Quimiocina CXCL12/genética , Terapia Genética/métodos , Fator A de Crescimento do Endotélio Vascular/genética , Remodelação Vascular/genética , Animais , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-Dawley
16.
Anal Chem ; 88(13): 6844-51, 2016 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-27266261

RESUMO

Accuracy is an important metric when mass spectrometry (MS) is used in large-scale quantitative proteomics research. For MS-based quantification by extracting ion chromatogram (XIC), both the mass and intensity dimensions must be accurate. Although much research has focused on mass accuracy in recent years, less attention has been paid to intensity errors. Here, we investigated signal intensity measurement errors systematically and quantitatively using the natural properties of isotopic distributions. First, we defined a normalized isotopic abundance error model and presented its merits and demerits. Second, a comprehensive survey of the isotopic abundance errors using data sets with increasing sample complexities and concentrations was performed. We examined parameters such as error distribution, relationships between signal intensities within one isotopic cluster, and correlations between different peak errors in isotopic profiles. Our data demonstrated that the high resolution MS platforms might also generate large isotopic intensity measurement errors (approximately 20%). Meanwhile, this error can be reduced to less than 5% using a novel correction algorithm, which is based on the theoretical isotopic abundance distribution. Finally, a nonlinear relationship was observed as the abundance error decreased in isotopic profiles with higher intensity. Our findings are expected to provide insight into isotopic abundance recalibration in quantitative proteomics.


Assuntos
Peptídeos/análise , Proteômica/métodos , Algoritmos , Animais , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas/métodos , Camundongos , Proteínas Mitocondriais/química , Peso Molecular , Células RAW 264.7 , Saccharomyces cerevisiae/metabolismo , Razão Sinal-Ruído
17.
J Biomed Inform ; 61: 10-8, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27012904

RESUMO

OBJECTIVES: With the announcement of human proteome and interaction data, it becomes possible to comprehensively investigate the tissue-expression and network properties of inherited disease proteins. In this study, our goal was to develop methods to map the disease and expression data and analyze the disorder-tissue associations. METHODS: In this paper, we manually classified the human disease proteins into 22 disorder classes and systematically analyzed the properties of disease proteins in different disorder classes. Then, we investigated the similarity of different disorder classes by computing the overlap of different disorder proteins and networks. We proposed two novel measures, Enrichment Ratio and P-value for comparative analysis of disease proteins across tissues and revealed the associations between disorder classes and tissues/cells. RESULTS: Compared with non-disease proteins, disease proteins tend to express in more tissues, have higher expression levels and interact with more other proteins in the network. The overlap percentages of networks are much higher than those of proteins, implying that different disorder classes usually influence each other by means of their interacting neighbors. The metabolic, muscular and hematologic proteins are related with most tissues/cells, and cancer proteins are closely associated with the disorders in immune cells. CONCLUSION: This paper provided novel methods to investigate proteome-wide disease proteins and their interacting networks in order to understand different disease's associations.


Assuntos
Expressão Gênica , Proteínas/metabolismo , Proteoma , Algoritmos , Predisposição Genética para Doença , Humanos
18.
J Proteome Res ; 14(6): 2385-97, 2015 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-25869096

RESUMO

SUMOylation has emerged as a new regulatory mechanism for proteins involved in multiple physiological and pathological processes. However, the detailed function of SUMOylation in liver cancer is still elusive. This study reveals that the SUMOylation-activating enzyme UBA2 is highly expressed in liver cancer cells and clinical samples. Silencing of UBA2 expression could to some extent suppress cell proliferation. To elucidate the function of UBA2, we used a large scale proteomics strategy to identify SUMOylation targets in HepG2 cells. We characterized 827 potential SUMO1-modified proteins that were not present in the control samples. These proteins were enriched in gene expression processes. Twelve candidates were validated as SUMO1-modified proteins by immunoprecipitation-Western blotting. We further characterized SUMOylated protein TFII-I that was identified in this study and determined that TFII-I was modified by SUMO1 at K221 and K240. PIAS4 was an E3 ligase for TFII-I SUMOylation, and SENP2 was responsible for deSUMOylating TFII-I in HepG2 cells. SUMOylation reduced TFII-I binding to its repressor HDAC3 and thus promoted its transcriptional activity. We further show that SUMOylation is critical for TFII-I to promote cell proliferation and colony formation. Our findings contribute to understanding the role of SUMOylation in liver cancer development.


Assuntos
Proliferação de Células , Neoplasias Hepáticas/patologia , Proteômica , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Sumoilação , Fatores de Transcrição TFII/metabolismo , Enzimas Ativadoras de Ubiquitina/metabolismo , Inativação Gênica , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Transcrição Gênica , Enzimas Ativadoras de Ubiquitina/genética
19.
J Craniofac Surg ; 25(5): 1773-5, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24999673

RESUMO

BACKGROUND: The objective of this article was to investigate the operation outcome, complications, and the patient's quality of life after surgical therapy for central gyrus region meningioma with epilepsy as the primary symptom. METHODS: All patients get at least 6 months of follow-up (range, 6-34 mo) after surgery. They underwent preoperative magnetic resonance imaging and video electroencephalography, and their clinical manifestations, imaging characteristics, microsurgical methods, and prognosis were retrospectively analyzed. RESULTS: The meningioma was located in the front and back of the central sulcus vein in 3 and 2 patients, respectively; in the compressed precentral gyrus and central sulcus vein in 3 patients; and in the precentral gyrus and postcentral gyrus each in 1 patient; beside the right sagittal sinus and invaded a thick draining vein on the brain surface in 1 patient and beside the right sagittal sinus and close to the precentral gyrus in 2 patients; invaded the superior sagittal sinus in 8 patients; crossed the cerebral falx and compressed cortex gyrus veins in 1 patient; invaded duramater and irritated skull hyperplasia in 3 patients; invaded duramater and its midline infiltrated into the superior sagittal sinus, was located behind the precentral gyrus, and enveloped the central sulcus vein. They were resected and classified by Simpson standards: 17 of the 26 patients had grade I, 6 patients had in grade II, and 3 patients had in grade III. CONCLUSIONS: Resection of central gyrus region meningioma by microsurgical technique avoids injury to the cerebral cortex, central sulcus vein, and other draining veins. Microsurgery improves the total resection rate, reduces recurrence rate, and lowers disability or death rate.


Assuntos
Neoplasias Encefálicas/cirurgia , Epilepsia/cirurgia , Lobo Frontal/cirurgia , Meningioma/cirurgia , Microcirurgia/métodos , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/patologia , Eletroencefalografia , Epilepsia/etiologia , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Meningioma/complicações , Meningioma/patologia , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Retrospectivos , Seio Sagital Superior/patologia
20.
Proteomics ; 14(13-14): 1593-603, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24827140

RESUMO

Precise protein quantification is essential in comparative proteomics. Currently, quantification bias is inevitable when using proteotypic peptide-based quantitative proteomics strategy for the differences in peptides measurability. To improve quantification accuracy, we proposed an "empirical rule for linearly correlated peptide selection (ERLPS)" in quantitative proteomics in our previous work. However, a systematic evaluation on general application of ERLPS in quantitative proteomics under diverse experimental conditions needs to be conducted. In this study, the practice workflow of ERLPS was explicitly illustrated; different experimental variables, such as, different MS systems, sample complexities, sample preparations, elution gradients, matrix effects, loading amounts, and other factors were comprehensively investigated to evaluate the applicability, reproducibility, and transferability of ERPLS. The results demonstrated that ERLPS was highly reproducible and transferable within appropriate loading amounts and linearly correlated response peptides should be selected for each specific experiment. ERLPS was used to proteome samples from yeast to mouse and human, and in quantitative methods from label-free to O18/O16-labeled and SILAC analysis, and enabled accurate measurements for all proteotypic peptide-based quantitative proteomics over a large dynamic range.


Assuntos
Espectrometria de Massas/métodos , Peptídeos/análise , Proteínas/química , Proteômica/métodos , Animais , Cromatografia Líquida/métodos , Células HEK293 , Humanos , Marcação por Isótopo/métodos , Fígado/química , Camundongos , Camundongos Endogâmicos C57BL , Peptídeos/metabolismo , Proteínas/metabolismo , Proteólise , Reprodutibilidade dos Testes , Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/metabolismo , Fluxo de Trabalho
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