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1.
Int J Cancer ; 154(3): 530-537, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37815300

RESUMO

Several observational studies have reported an association between obesity and primary liver cancer (PLC), while the causality behind this association and the comparison of the risk effects of different obesity indicators on PLC remain unclear. In this study, we performed two-sample Mendelian randomization (MR) analyses to assess the associations of genetically determined liver fat, visceral adipose tissue (VAT), and body mass index (BMI) with the risk of PLC. The summary statistics of exposures were obtained from two genome-wide association studies (GWASs) based on the UK Biobank (UKB) imaging cohort and the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. GWAS summary statistics for PLC were obtained from FinnGen consortium R7 release data, including 304 PLC cases and 218 488 controls. Inverse-variance weighted (IVW) was used as the primary analysis, and a series of sensitivity analyses were performed to further verify the robustness of these findings. IVW analysis highlighted a significant association of genetically determined liver fat (OR per SD increase: 7.14; 95% CI: 5.10-9.99; P = 2.35E-30) and VAT (OR per SD increase: 5.70; 95% CI: 1.32-24.72; P = .020) with PLC but not of BMI with PLC. The findings were further confirmed by a series of MR methods. No evidence of horizontal pleiotropy between these associations existed. Our study suggested that genetically determined liver fat and VAT rather than BMI were associated with an increased risk of PLC, which suggested that visceral fat distribution is more predictive of the clinical risk of PLC than common in vitro measures.


Assuntos
Estudo de Associação Genômica Ampla , Neoplasias Hepáticas , Adulto , Humanos , Análise da Randomização Mendeliana , Obesidade/complicações , Obesidade/genética , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/genética , Polimorfismo de Nucleotídeo Único
2.
BMC Cancer ; 24(1): 1241, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39379833

RESUMO

BACKGROUND & AIMS: The benefit of postoperative adjuvant transcatheter arterial chemoembolization (pTACE) for patients with hepatocellular carcinoma (HCC), especially those with Child-Pugh (CP) B, remains controversial. This study aimed to assess the survival benefit of pTACE for HCC patients with CP B. METHODS: Data from 297 HCC patients with CP B7 or B8 were analyzed, dividing them into groups with and without pTACE (70, 23.6% vs. 227, 76.4%). Propensity score matching (PSM) was used to control for confounding bias, and competing-risk regression was applied to address bias from non-cancer-specific death (NCSD). RESULTS: Preliminary findings suggest that pTACE did not increase the incidence of severe complications in HCC patients with CP B7 or B8. Survival analysis indicated that the group receiving pTACE had better overall survival and recurrence-free survival than the group without pTACE after PSM. Furthermore, competitive risk analysis revealed that pTACE was an independent prognostic factor associated with reduced cancer-specific death incidence (subdistribution hazard ratio [SHR] 0.644, 95%CI: 0.378-0.784, P = 0.011) and recurrence (SHR 0.635, 95% CI: 0.379-0.855, P = 0.001). Importantly, pTACE did not increase NCSD. Subgroup analysis corroborated these results. CONCLUSION: Adjuvant TACE demonstrates the potential to significantly enhance the long-term prognosis of HCC patients with CP B7 or B8 following hepatectomy, particularly those with multiple tumors, large tumor size, macrovascular or microvascular invasion, and narrow resection margin. Hence, pTACE should be considered for patients at high risk of recurrence following thorough evaluation.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Hepatectomia , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Masculino , Quimioembolização Terapêutica/métodos , Feminino , Pessoa de Meia-Idade , Idoso , Pontuação de Propensão , Recidiva Local de Neoplasia/epidemiologia , Prognóstico , Estudos Retrospectivos , Adulto , Resultado do Tratamento , Quimioterapia Adjuvante/métodos
3.
BMC Cancer ; 24(1): 727, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877445

RESUMO

BACKGROUND: The Naples Prognostic Score (NPS), integrating inflammatory and nutritional biomarkers, has been reported to be associated with the prognosis of various malignancies, but there is no report on intrahepatic cholangiocarcinoma (ICC). This study aimed to explore the prognostic value of NPS in patients with ICC. METHODS: Patients with ICC after hepatectomy were collected, and divided into three groups. The prognosis factors were determined by Cox regression analysis. Predictive efficacy was evaluated by the time-dependent receiver operating characteristic (ROC) curves. RESULTS: A total of 174 patients were included (Group 1: 33 (19.0%) patients; Group 2: 83 (47.7%) patients; and Group 3: 58 (33.3%) patients). The baseline characteristics showed the higher the NPS, the higher the proportion of patients with cirrhosis and Child-Pugh B, and more advanced tumors. The Kaplan-Meier curves reflect higher NPS were associated with poor survival. Multivariable analysis showed NPS was an independent risk factor of overall survival (NPS group 2 vs. 1: HR = 1.671, 95% CI: 1.022-3.027, p = 0.009; NPS group 3 vs. 1: HR = 2.208, 95% CI: 1.259-4.780, p = 0.007) and recurrence-free survival (NPS group 2 vs. 1: HR = 1.506, 95% CI: 1.184-3.498, p = 0.010; NPS group 3 vs. 1: HR = 2.141, 95% CI: 2.519-4.087, P = 0.001). The time ROC indicated NPS was superior to other models in predicting prognosis. CONCLUSIONS: NPS is a simple and effective tool for predicting the long-term survival of patients with ICC after hepatectomy. Patients with high NPS require close follow-up, and improving NPS may prolong the survival time.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Hepatectomia , Humanos , Colangiocarcinoma/cirurgia , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Idoso , Curva ROC , Estudos Retrospectivos , Estimativa de Kaplan-Meier , Adulto , Fatores de Risco
4.
BMC Surg ; 24(1): 148, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734630

RESUMO

BACKGROUND & AIMS: Complications after laparoscopic liver resection (LLR) are important factors affecting the prognosis of patients, especially for complex hepatobiliary diseases. The present study aimed to evaluate the value of a three-dimensional (3D) printed dry-laboratory model in the precise planning of LLR for complex hepatobiliary diseases. METHODS: Patients with complex hepatobiliary diseases who underwent LLR were preoperatively enrolled, and divided into two groups according to whether using a 3D-printed dry-laboratory model (3D vs. control group). Clinical variables were assessed and complications were graded by the Clavien-Dindo classification. The Comprehensive Complication Index (CCI) scores were calculated and compared for each patient. Multivariable analysis was performed to determine the risk factors of postoperative complications. RESULTS: Sixty-two patients with complex hepatobiliary diseases underwent the precise planning of LLR. Among them, thirty-one patients acquired the guidance of a 3D-printed dry-laboratory model, and others were only guided by traditional enhanced CT or MRI. The results showed no significant differences between the two groups in baseline characters. However, compared to the control group, the 3D group had a lower incidence of intraoperative blood loss, as well as postoperative 30-day and major complications, especially bile leakage (all P < 0.05). The median score on the CCI was 20.9 (range 8.7-51.8) in the control group and 8.7 (range 8.7-43.4) in the 3D group (mean difference, -12.2, P = 0.004). Multivariable analysis showed the 3D model was an independent protective factor in decreasing postoperative complications. Subgroup analysis also showed that a 3D model could decrease postoperative complications, especially for bile leakage in patients with intrahepatic cholelithiasis. CONCLUSION: The 3D-printed models can help reduce postoperative complications. The 3D-printed models should be recommended for patients with complex hepatobiliary diseases undergoing precise planning LLR.


Assuntos
Laparoscopia , Hepatopatias , Complicações Pós-Operatórias , Impressão Tridimensional , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Laparoscopia/métodos , Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Hepatopatias/cirurgia , Idoso , Doenças Biliares/prevenção & controle , Doenças Biliares/cirurgia , Doenças Biliares/etiologia , Hepatectomia/métodos , Hepatectomia/efeitos adversos , Adulto , Estudos Retrospectivos , Estudos de Coortes
5.
HPB (Oxford) ; 26(8): 1062-1071, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38830783

RESUMO

BACKGROUND: Postoperative complications are vital factors affecting the prognosis of patients with hepatocellular carcinoma (HCC), especially for complex hepatectomy. The present study aimed to compare perioperative complications between laparoscopic and robotic complex hepatectomy (LCH vs. RCH). METHODS: Patients with solitary HCC after complex hepatectomy were collected from a multicenter database. Propensity score-matched (PSM) analysis was adopted to control confounding bias. Multivariable analysis was performed to determine the prognostic factors. RESULTS: 436 patients were included. After PSM, 43 patients were included in both the LCH and RCH groups. The results showed that compared to LCH, RCH had lower rates of blood loss and transfusion, and lower postoperative 30-day and major morbidity, and post-hepatectomy liver failure (PHLF) (all P < 0.05). Additionally, the length of hospital stay was shorter in the RCH group (P = 0.026). Multivariable analysis showed RCH is an independent protective factor for reducing the 30-day morbidity, major morbidity and PHLF. CONCLUSION: RCH has advantages over LCH in the minimally invasive treatment of complex HCC, as it can reduce the incidence of postoperative morbidity. Therefore, RCH should be considered for patients with HCC who require complex hepatectomy.


Assuntos
Carcinoma Hepatocelular , Hepatectomia , Laparoscopia , Neoplasias Hepáticas , Complicações Pós-Operatórias , Pontuação de Propensão , Procedimentos Cirúrgicos Robóticos , Humanos , Carcinoma Hepatocelular/cirurgia , Hepatectomia/efeitos adversos , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Masculino , Laparoscopia/efeitos adversos , Feminino , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento , Idoso , Bases de Dados Factuais , Tempo de Internação , Fatores de Risco , Fatores de Tempo , Medição de Risco , Adulto
6.
J Integr Plant Biol ; 62(3): 314-329, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30791211

RESUMO

Rice is a major source of cadmium (Cd) intake for Asian people. Indica rice usually accumulates more Cd in shoots and grains than Japonica rice. However, underlying genetic bases for differential Cd accumulation between Indica and Japonica rice are still unknown. In this study, we cloned a quantitative trait locus (QTL) grain Cd concentration on chromosome 7 (GCC7) responsible for differential grain Cd accumulation between two rice varieties by performing QTL analysis and map-based cloning. We found that the two GCC7 alleles, GCC7PA64s and GCC793-11 , had different promoter activity of OsHMA3, leading to different OsHMA3 expression and different shoot and grain Cd concentrations. By analyzing the distribution of different haplotypes of GCC7 among diverse rice accessions, we discovered that the high and low Cd accumulation alleles, namely GCC793-11 and GCC7PA64s , were preferentially distributed in Indica and Japonica rice, respectively. We further showed that the GCC7PA64s allele can be used to replace the GCC793-11 allele in the super cultivar 93-11 to reduce grain Cd concentration without adverse effect on agronomic traits. Our results thus reveal that the QTL GCC7 with sequence variation in the OsHMA3 promoter is an important determinant controlling differential grain Cd accumulation between Indica and Japonica rice.


Assuntos
Cádmio/metabolismo , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Alelos , Oryza/genética , Proteínas de Plantas/genética , Regiões Promotoras Genéticas/genética , Locos de Características Quantitativas/genética
7.
Proc Natl Acad Sci U S A ; 110(35): 14492-7, 2013 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-23940322

RESUMO

The growing world population and shrinkage of arable land demand yield improvement of rice, one of the most important staple crops. To elucidate the genetic basis of yield and uncover its associated loci in rice, we resequenced the core recombinant inbred lines of Liang-You-Pei-Jiu, the widely cultivated super hybrid rice, and constructed a high-resolution linkage map. We detected 43 yield-associated quantitative trait loci, of which 20 are unique. Based on the high-density physical map, the genome sequences of paternal variety 93-11 and maternal cultivar PA64s of Liang-You-Pei-Jiu were significantly improved. The large recombinant inbred line population combined with plentiful high-quality single nucleotide polymorphisms and insertions/deletions between parental genomes allowed us to fine-map two quantitative trait loci, qSN8 and qSPB1, and to identify days to heading8 and lax panicle1 as candidate genes, respectively. The quantitative trait locus qSN8 was further confirmed to be days to heading8 by a complementation test. Our study provided an ideal platform for molecular breeding by targeting and dissecting yield-associated loci in rice.


Assuntos
Genoma de Planta , Hibridização Genética , Oryza/genética , Recombinação Genética , Ligação Genética , Locos de Características Quantitativas
8.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(6): 1930-5, 2016 Jun.
Artigo em Zh | MEDLINE | ID: mdl-30053356

RESUMO

In order to calibrate the corresponding center wavelength and bandwidth to the prism's rotating angle of a scanning prism-dispersive solar spectrometer, a prism-rotating method to measure the spectral response function (SRF) of the solar spectrometer is suggested. The measuring process is as follows. With the wavelength of monochromatic light invariant, the prism is rotated for scanning the monochromatic image at the location of detector. Then the spectral response function is obtained by mapping the coordinate in position to the coordinate in wavelength. At first in this paper, by analyzing the definition of SRF, the conclusion is deduced that the prism-rotating method is equivalent to the wavelength-scanning method in practice. Then the 532 nm solid-state laser and 632.8 nm He-Ne laser are used as light source. The measurement of SRF of the solar spectrometer based on prism-rotating method is performed. A measurement of SRF with wavelength-scanning method is also performed to be used as a comparison. Experimental results indicate that the center wavelength of the scanning prism-dispersive solar spectrometer measured with prism-rotating method is 531.86 and 632.67 nm respectively. On the other hand, the result is 53139 and 631.97 nm with wavelength-scanning method, which is less precise than the result of prism-rotating method. The values of bandwidth measured with prism-rotating method are also more precise than the latter owing to avoiding the performance deficiency of monochromator. At last, using mercury vapor lamp as light source, an experiment for spectral calibration of the solar spectrometer with prism-rotating method is performed. The values of center wavelength and bandwidth are both achieved with the method combining the prism-rotating method and chracteristic spectrum. This method can also be used to calibrate the monochromator and the grating-dispersive spectrometer whose grating is rotatable.

9.
Zhonghua Nan Ke Xue ; 20(3): 218-24, 2014 Mar.
Artigo em Zh | MEDLINE | ID: mdl-24738457

RESUMO

OBJECTIVE: To investigate whether bortezomib can enhance the sensitivity of human prostate cancer (PCa) cells to natural killer (NK) cell-mediated cytotoxicity, and whether it produces the same effect on different PCa cell lines. METHODS: We treated androgen-dependent PCa LNCaP cells and androgen-independent PCa DU145 cells with bortezomib at the concentrations of 0, 5, 10, 15, 20 and 25 nmol/L for 24, 48 and 72 hours, and then detected the proliferation and apoptosis of the tumor cells by CCK-8 and Annexin V/PI, respectively. RESULTS: The proliferation rates of the DU145 cells treated with 15, 20 and 25 nmol/L bortezomib were (82.79 +/-2.04)%, (73.59+/- 2.95)% and (74.16+/- 6. 16)% at 48 hours and (71.24+/- 5.30)%, (51.20+/- 2.91)% and (38.02+/- 2.67)% at 72 hours, and those of the LNCaP cells were (77.04+/- 7.74)% , (42.61 +/- 6.62)% and (23.85 +/-6.04)% at 48 hours and (36.45 +/-7.02)%, (14.94 +/-5.76)% and (11.65 +/-5. 87)% at 72 hours, both significantly inhibited as compared with the control group (P <0.05). At 24 hours, the apoptosis rates of the DU145 cells treated with 15, 20 and 25 nmol/L bortezomib were (14.41 +/- 1.32)% , (16.13 +/- 1.55)% and (14.48 +/- 1.42)% , and those of the LNCaP cells treated with 20 and 25 nmol/L bortezomib were (12.77 +/- 1.28)% and (14. 84 +/- 1.65)% , significantly higher than those of the control group (P <0.05) , and the DU145 cells showed an even higher sensitivity to bortezomib than the LNCaP cells. Bortezomib failed to sensitize these two cell lines to NK cell-mediated cytotoxicity in short-term assay, while long-term assay manifested that the apoptosis rates of DU145 and LNCaP cells after treated with 20 nmol/L bortezomib + NK cells were (41.83 +/- 5.06)% and (30.31 +/- 3.62)% , respectively, significantly higher CONCLUSION: Bortezomib enhances the sensitivity of than those after treated with either bortezomib or NK cells alone (P <0.05). PCa cells to NK cell-mediated cytotoxicity and adds to the effect of current cancer therapies, and it is more efficacious for androgen-independent prostate cancer.


Assuntos
Ácidos Borônicos/farmacologia , Citotoxicidade Imunológica/efeitos dos fármacos , Células Matadoras Naturais/efeitos dos fármacos , Neoplasias da Próstata/patologia , Pirazinas/farmacologia , Apoptose/efeitos dos fármacos , Bortezomib , Linhagem Celular Tumoral , Humanos , Masculino
10.
Obes Surg ; 34(4): 1333-1342, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38427150

RESUMO

BACKGROUND: Liver fibrosis is a predisposing factor for liver cancer. This study will investigate the predictive role of the Triglyceride-glucose and Gamma-glutamyl transferase index (TyG-GGT) as a non-invasive indicator of advanced liver fibrosis in individuals with obesity or overweight. METHOD: We enrolled patients who underwent metabolic and bariatric surgery as well as intraoperative liver biopsies at Zhejiang provincial people's hospital from August 2020 to March 2023. Clinical characteristics, comorbidities, laboratory data, and pathological variables of patients were collected and analysed. Then, we conducted logistics regression model to compare the performance of the TyG-GGT index with other 4 non-invasive models. RESULTS: A total of 65 patients were included in this study. 43(66.2%) of them were female, with the mean body mass index (BMI) of 39.0 ± 7.3 kg/m2. Meanwhile, 24(36.9%) patients were diagnosed with diabetes. Advanced liver fibrosis were observed in 16.9% of patients, while liver cirrhosis was found in 4.6% of patients. The multivariable logistics regression showed that TyG-GGT was an independent risk factor of advanced liver fibrosis (OR = 6.989, P = 0.049). Additionally, compared to another 4 non-invasive liver fibrosis models (NFS = 0.66, FIB4 = 0.65, METS-IR = 0.68, APRI = 0.65), TyG-GGT exhibits the highest AUC value of 0.75. CONCLUSIONS: More than one-third of patients undergoing metabolic and bariatric surgery are afflicted with nonalcoholic steatohepatitis (NASH), and a significant proportion exhibit advanced fibrosis. TyG-GGT was a potentially reliable predictor for screening individuals with overweight or obesity at high risk of advanced liver fibrosis, thus providing clinical guidance for early intervention in this targeted group.


Assuntos
Glicemia , Cirrose Hepática , Triglicerídeos , gama-Glutamiltransferase , Feminino , Humanos , Masculino , Fibrose , Cirrose Hepática/diagnóstico , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade/sangue , Obesidade/complicações , Sobrepeso/sangue , Sobrepeso/complicações , Triglicerídeos/análise , Triglicerídeos/sangue , gama-Glutamiltransferase/análise , gama-Glutamiltransferase/sangue , Glicemia/análise , Glicemia/metabolismo
11.
Asian J Surg ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38724372

RESUMO

BACKGROUND AND AIMS: The prognosis of patients with hepatocellular carcinoma (HCC) undergoing hepatectomy is unsatisfactory, especially for those with microvascular invasion (MVI). This study aimed to determine the impact of adjuvant transcatheter arterial chemoembolization (TACE) and Lenvatinib on the prognosis of patients with HCC and MVI after hepatectomy. METHODS: Patients diagnosed with HCC and MVI were reviewed, and stratified into four groups according to adjuvant TACE and/or Lenvatinib. Multivariate Cox regression analyses are used to determine independent risk factors. RESULTS: 346 patients were included, and divided into four groups (Group I, TACE+ Lenvatinib; Group II, Lenvatinib; Group III, TACE; Group IV, without adjuvant therapy). Multivariable analysis showed that compared to Group IV, Group I had the best effect on improving the overall survival (OS, HR 0.321, 95%CI 0.099-0.406, P = 0.001) and recurrence-free survival (RFS, HR 0.319, 95%CI 0.129-0.372, P = 0.001). Additionally, compared with Group II or Group III, Group I also can significantly improve the OS and RFS. There is no significant difference between Group II and Group III in OS and RFS. CONCLUSION: The combination of TACE and Lenvatinib should be considered for anti-recurrence therapy for patients with HCC and MVI after hepatectomy.

12.
Sci Rep ; 14(1): 25427, 2024 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-39455669

RESUMO

Background Gastroesophageal reflux disease (GERD) is among the most common complications of bariatric surgery. This study aimed to analyse the risk factors affecting the worsening of GERD symptoms after laparoscopic sleeve gastrectomy (LSG), and to establish and validate a related nomogram model. Methods The study recruited 236 participants and randomly divided them into training and validation sets in a ratio of 7:3. LASSO regression technique was used to select the optimal predictive features, and multivariate logistic regression was used to construct the column line graphs. The performance of the nomogram was evaluated and validated by analyzing the area under the receiver operating characteristic (ROC) curve, calibration curve, and decision curve. Results In this study, Lasso-logistic regression was applied to select 5 predictors from the relevant variables, which were body mass index (BMI), diabetes, hiatal hernia, GERD, and triglyceride levels. These 5 predictor variables constructed a model with moderate predictive power, with an area under the ROC curve of 0.779 for the training set and 0.796 for the validation set. Decision curve analysis showed that in external validation, if the risk thresholds were between 4 and 98% and 14-95%, then the nomogram can be applied to the clinic. Conclusions We have developed and validated a nomogram that effectively predicts the risk of worsening gastroesophageal reflux symptoms following LSG.


Assuntos
Gastrectomia , Refluxo Gastroesofágico , Laparoscopia , Nomogramas , Humanos , Refluxo Gastroesofágico/etiologia , Refluxo Gastroesofágico/diagnóstico , Feminino , Masculino , Gastrectomia/efeitos adversos , Laparoscopia/efeitos adversos , Adulto , Pessoa de Meia-Idade , Modelos Logísticos , Fatores de Risco , Curva ROC , Cirurgia Bariátrica/efeitos adversos , Índice de Massa Corporal , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/diagnóstico
13.
Clin Rheumatol ; 41(2): 437-452, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34553293

RESUMO

BACKGROUND: Lupus erythematosus is an autoimmune disease that causes damage to multiple organs ranging from skin lesions to systemic manifestations. Cutaneous lupus erythematosus (CLE) is a common type of lupus erythematosus (LE), but its molecular mechanisms are currently unknown. The study aimed to explore changes in the gene expression profiles and identify key genes involved in CLE, hoping to uncover its molecular mechanism and identify new targets for CLE. METHOD: We analyzed the microarray dataset (GSE109248) derived from the Gene Expression Omnibus (GEO) database, which was a transcriptome profiling of CLE cutaneous lesions. The differentially expressed genes (DEGs) were identified, and the functional annotation of DEGs was performed with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Protein-protein interaction (PPI) network was also constructed to identify hub genes involved in CLE. RESULT: A total of 755 up-regulated DEGs and 405 down-regulated DEGs were identified. GO enrichment analysis showed that defense response to virus, immune response, and type I interferon signaling pathway were the most significant enrichment items in DEGs. The KEGG pathway analysis identified 51 significant enrichment pathways, which mainly included systemic lupus erythematosus, osteoclast differentiation, cytokine-cytokine receptor interaction, and primary immunodeficiency. Based on the PPI network, the study identified the top 10 hub genes involved in CLE, which were CXCL10, CCR7, FPR3, PPARGC1A, MMP9, IRF7, IL2RG, SOCS1, ISG15, and GSTM3. By comparison between subtypes, the results showed that ACLE had the least DEGs, while CCLE showed the most gene and functional changes. CONCLUSION: The identified hub genes and functional pathways found in this study may expand our understanding on the underlying pathogenesis of CLE and provide new insights into potential biomarkers or targets for the diagnosis and treatment of CLE. Key Points • The bioinformatics analysis based on CLE patients and healthy controls was performed and 1160 DEGs were identified • The 1160 DEGs were mainly enriched in biological processes related to immune responses, including innate immune response, type I interferon signaling pathway, interferon-γ-mediated signaling pathway, positive regulation of T cell proliferation, regulation of immune response, antigen processing, and presentation via MHC class Ib and so on • KEGG pathway enrichment analysis indicated that DEGs were mainly enriched in several immune-related diseases and virus infection, including systemic lupus erythematosus, primary immunodeficiency, herpes simplex infection, measles, influenza A, and so on • The hub genes such as CXCL10, IRF7, MMP9, CCR7, and SOCS1 may become new markers or targets for the diagnosis and treatment of CLE.


Assuntos
Biologia Computacional , Lúpus Eritematoso Cutâneo , Perfilação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Mapas de Interação de Proteínas , Transcriptoma
14.
J Pharmacol Exp Ther ; 336(1): 282-93, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20952482

RESUMO

We have found that mutation of D-amino acid oxidase (DAO) diminished formalin-induced tonic pain. The present research further studied the analgesic effects of a series of DAO inhibitors in this model. 5-Chlorobenzo[d]isoxazol-3-ol (CBIO), 4H-thieno[3,2-b]pyrrole-5-carboxylic acid (compound 8), 5-methylpyrazole-3-carboxylic acid (AS057278), sodium benzoate, and 4-nitro-3-pyrazole carboxylic acid (NPCA) inhibited rat spinal cord-derived DAO activity in a concentration-dependent manner, with maximal inhibition of 100% and potency rank of CBIO > compound 8 > AS057278 > sodium benzoate > NPCA. In rats, intrathecal injections of CBIO, compound 8, AS057278, and sodium benzoate but not NPCA specifically prevented formalin-induced tonic pain but not acute nociception, with the same potency order as in the DAO activity assay. The highly potent analgesia of DAO inhibitors was evidenced by CBIO, which prevented 50% pain at 0.06 µg, approximately 5-fold the potency of morphine. CBIO given after formalin challenge also reversed the established pain state to the same degree as prevention. The antihyperalgesic potencies of these DAO inhibitors were highly correlated to their inhibitions of spinal DAO activity. Maximum inhibition of pain by these compounds was approximately 60%, comparable with that of the N-methyl-D-aspartic acid receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801), suggesting that a larger portion of formalin-induced tonic pain is "DAO-sensitive," whereas the remaining 40% of tonic pain and acute nociception is "DAO-insensitive." These findings, combined with our previous DAO gene mutation and induction results, indicate spinal DAO mediates both induction and maintenance of formalin-induced tonic pain and further validate spinal DAO as a novel and efficacious target molecule for the treatment of chronic pain.


Assuntos
D-Aminoácido Oxidase/antagonistas & inibidores , D-Aminoácido Oxidase/metabolismo , Formaldeído/toxicidade , Medição da Dor/efeitos dos fármacos , Dor/enzimologia , Dor/prevenção & controle , Animais , Ácido Benzoico/química , Ácido Benzoico/farmacologia , Ácido Benzoico/uso terapêutico , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Isoxazóis/química , Isoxazóis/farmacologia , Isoxazóis/uso terapêutico , Masculino , Medição da Dor/métodos , Ratos , Ratos Wistar
15.
J Pharmacol Exp Ther ; 332(1): 248-54, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19828879

RESUMO

D-amino acid oxidase (DAO) is an enzyme catalyzing oxidative deamination of neutral and polar d-amino acids and is expressed in the kidneys, liver, and central nervous system (CNS) including the spinal cord. We have previously demonstrated that DAO gene deletion/mutation by using mutant ddY/DAO(-/-) mice and systemic administration of the DAO inhibitor sodium benzoate blocked formalin-induced hyperalgesia in mice. In this study, we further investigated the potential role of DAO in neuropathic pain in a rat model of tight L(5)/L(6) spinal nerve ligation. After L(5)/L(6) spinal nerve ligation, the mRNA expression (measured by real-time quantitative polymerase chain reaction) and enzyme activity (measured by a colorimetric method) of DAO in the lumbar spinal cord were markedly increased, in agreement with the development of neuropathic pain (mechanical allodynia). Intraperitoneal injection of sodium benzoate (400 mg/kg) specifically blocked mechanical allodynia in neuropathic rats and formalin-induced hyperalgesia but did not suppress acute pain responses in the tail-flick test or formalin test. Systemic injection of sodium benzoate also inhibited DAO activity in the lumbar spinal cord of rats. Furthermore, direct intrathecal (spinal cord) injection of benzoate (30 mug/rat) specifically blocked spinal nerve ligation-induced mechanical allodynia in neuropathic rats and formalin-induced hyperalgesia (but not acute pain) in the formalin test. Based on the above results, we conclude that spinal DAO plays a pronociceptive (rather than an antinociceptive) role and might be a target molecule for the treatment of chronic pain of neuropathic origin.


Assuntos
D-Aminoácido Oxidase/metabolismo , Dor Lombar/enzimologia , Neuralgia/enzimologia , Medula Espinal/enzimologia , Doença Aguda , Animais , D-Aminoácido Oxidase/antagonistas & inibidores , D-Aminoácido Oxidase/biossíntese , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Hiperalgesia/tratamento farmacológico , Hiperalgesia/enzimologia , Dor Lombar/tratamento farmacológico , Masculino , Neuralgia/tratamento farmacológico , Medição da Dor , Limiar da Dor , Ratos , Ratos Wistar , Benzoato de Sódio/administração & dosagem , Benzoato de Sódio/farmacologia , Benzoato de Sódio/uso terapêutico
16.
Exp Biol Med (Maywood) ; 233(9): 1142-8, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18535164

RESUMO

Impaired glucose metabolism is implicated in cardiac failure during ischemia-reperfusion. This study examined cardiac glucose uptake and expression of glucose transport-4 (GLUT-4) in dogs undergoing ischemia-reperfusion. Cardiac ischemia was induced by cardiopulmonary bypass for 30 min or 120 min in dogs. Plasma insulin and glucose concentrations were measured at pre-bypass (control), and aortic cross-clamp off (ischemia-reperfusion) at 15, 45, and 75 min. At the same time, the left ventricle biopsies were taken for GLUT-4 immunohistochemistry and glycogen content analysis. In dogs receiving 120-min ischemia, coronary arterial and venous glucose concentrations were increased, but the net glucose uptake in ischemia-reperfusion heart were significantly decreased from 25% (control) to zero at 15 and 45 min of reperfusion, and recovered to only 7% after 75 min reperfusion. Myocardium glycogen contents were decreased by 65%. Plasma insulin levels and Insulin Resistant Index were markedly increased in dogs undergoing 120-min ischemia and reperfusion. These changes were relatively mild and reversible in dogs receiving only 30-min ischemia followed by reperfusion. Expression of total GLUT-4 in myocardium was decreased 40% and translocation of GLUT-4 from cytoplasm to surface membrane was decreased 90% in dogs receiving 120-min ischemia followed by 15-min reperfusion. Suppressed translocation of GLUT-4 was also evident in dogs receiving 30-min ischemia, but to a lesser extent. Reduced myocardium glucose uptake, utilization, and glycogen content are clearly associated with ischemia-reperfusion heart injury. This appears to be due, at least in part, to suppressed expression and translocation of myocardium GLUT-4.


Assuntos
Transportador de Glucose Tipo 4/metabolismo , Glucose/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Animais , Biópsia , Cães , Imuno-Histoquímica , Insulina/sangue , Resistência à Insulina , Transporte Proteico
17.
Zhong Xi Yi Jie He Xue Bao ; 4(2): 185-8, 2006 Mar.
Artigo em Zh | MEDLINE | ID: mdl-16529697

RESUMO

OBJECTIVE: To investigate the effects of compound preparation of Cordyceps sinensis and Tripterygium hypoglaucum (CSTHC) on survival time of grafted pigskin after allogeneic transplantation and its mechanism. METHODS: The pigskin was treated with CSTHC solution before allogeneic transplantation, and CSTHC ointment was applied for external use on the grafted pigskin after skin transplantation. Cyclosporine A (CsA) and normal saline were served as control. The survival time, the appearance and the histomorphological changes of the grafted pigskin were observed. The histomorphological changes of testicles in pigs were also examined. The CD4 and CD8 expressions in the grafted pigskins were measured by immunohistochemical method. The white blood cell count in peripheral blood and the liver and renal functions were also examined. RESULTS: The survival time of the grafted pigskin in the CSTHC-treated group was (28.50+/-3.26)d, which was much longer as compared with (10.60+/-1.52)d in the untreated group (P<0.01). The survival time of the grafted pigskin in the CsA-treated group was (28.33+/-3.50)d, and there was no remarkable difference in the survival time of the grafted pigskin between the CsA-treated group and the CSTHC-treated group. The expressions of CD4 and CD8 were lower in the CSTHC-treated group than those in the untreated group on the 7th and 14th day after skin graft (P<0.05), while there was no significant difference in the indices between the CSTHC-treated group and the CsA-treated group. The WBC count was higher in the untreated group than that in the CSTHC-treated group or CsA-treated group on the 7th day after skin graft (P<0.05). CONCLUSION: CSTHC can prolong the survival time of allogeneic grafted pigskin. Its mechanism of inhibiting the immunological rejection may relate to decreasing the expressions of CD4(+) and CD8(+) in the grafted pigskin and reducing the local inflammatory reaction.


Assuntos
Cordyceps , Medicamentos de Ervas Chinesas/farmacologia , Sobrevivência de Enxerto/efeitos dos fármacos , Transplante de Pele , Tripterygium , Animais , Antígenos CD4/metabolismo , Antígenos CD8/metabolismo , Sinergismo Farmacológico , Masculino , Suínos , Porco Miniatura , Transplante Homólogo
18.
Artigo em Zh | MEDLINE | ID: mdl-15627701

RESUMO

Amylopectin, accounting for 70%-80% of storage starch, is one of the key components for quality of fruits and seeds in plant. Research on biosynthetic pathway of plant amylopectin holds great promise for modifying the structural composition of amylopectin and being used in food industry. The structure of plant amylopectin is summarized in this review and three types of amylopectin synthetase: starch branching enzyme (SBE), soluble starch synthase (SSS) and starch debranching enzyme (SDBE), which have become hotspots for research now, are expatiated in terms of genetics, enzymology and function. A model for the synthesis of amylopectin, "two-step branching and improper branch clearing model" is discussed. Problems in plant amylopectin biosynthesis and prospects for its application are also presented.


Assuntos
Amilopectina/biossíntese , Plantas/metabolismo , Enzima Ramificadora de 1,4-alfa-Glucana/análise , Enzima Ramificadora de 1,4-alfa-Glucana/genética , Enzima Ramificadora de 1,4-alfa-Glucana/fisiologia , Amilopectina/química , Amido/metabolismo , Sintase do Amido/análise , Sintase do Amido/genética , Sintase do Amido/fisiologia
19.
Mol Plant ; 7(8): 1350-1364, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24795339

RESUMO

The basic premise of high yield in rice is to improve leaf photosynthetic efficiency and coordinate the source-sink relationship in rice plants. Quantitative trait loci (QTLs) related to morphological traits and chlorophyll content of rice leaves were detected at the stages of heading to maturity, and a major QTL (qLSCHL4) related to flag leaf shape and chlorophyll content was detected at both stages in recombinant inbred lines constructed using the indica rice cultivar 93-11 and the japonica rice cultivar Nipponbare. Map-based cloning and expression analysis showed that LSCHL4 is allelic to NAL1, a gene previously reported in narrow leaf mutant of rice. Overexpression lines transformed with vector carrying LSCHL4 from Nipponbare and a near-isogenic line of 93-11 (NIL-9311) had significantly increased leaf chlorophyll content, enlarged flag leaf size, and improved panicle type. The average yield of NIL-9311 was 18.70% higher than that of 93-11. These results indicate that LSCHL4 had a pleiotropic function. Exploring and pyramiding more high-yield alleles resembling LSCHL4 for super rice breeding provides an effective way to achieve new breakthroughs in raising rice yield and generate new ideas for solving the problem of global food safety.


Assuntos
Alelos , Genes de Plantas/genética , Oryza/crescimento & desenvolvimento , Oryza/genética , Clorofila/metabolismo , Mapeamento Cromossômico , Oryza/metabolismo , Folhas de Planta/metabolismo , Locos de Características Quantitativas , Solo , Especificidade da Espécie , Transformação Genética
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