ABSTRACT
To effectively develop and utilize high-quality Tianfu broilers, this study evaluated the morphological and structural characteristics of the immune organs of such broilers with different strains (HS1 and HS2) at different developmental stages and analyzed the distribution of mast cells by toluidine blue staining. Moreover, the localization and expression of immunoglobulin, complement C3, C4 and CD3 in immune organs were also detected. The results showed that although there was no significant difference in the development of immune organs in the HS1 and HS2, the number of lymphatic follicles and capsule thickness in the spleen and bursa of Fabricius in HS1 were greater than those in HS2. Additionally, the number of mast cells in the spleen of HS1 was greater at Day 1 and Day 21 and was significantly higher than that of HS2 (p<0.05); the number of mast cells in the bursa of Fabricius reached 9.17 on Day 7, which was significantly higher than that of HS2 (p<0.05). Moreover, the serum IgA and IgM levels in HS1 were higher than those in HS2 on Day 14 and 21 (p<0.05). In addition, the complement C3 content in HS1 was significantly or extremely significantly higher than that in HS2 on Days 1, 14 and 21 (p<0.01, p<0.05), respectively, but significantly lower than in HS2 on Day 7 (p<0.05). These results indicated that the disease resistance of the HS1 line was stronger than that of the HS2 line, which lays a foundation for future disease- resistance breeding of Tianfu broilers.(AU)
Subject(s)
Chickens/immunology , Immune System , Mast Cells/immunology , Immunoglobulins/analysisABSTRACT
PURPOSE: Glioblastoma multiforme (GBM) is one of the most common malignant brain tumors in adults and has high mortality and relapse rates. Over the past few years, great advances have been made in the diagnosis and treatment of GBM, but unfortunately, the five-year overall survival rate of GBM patients is approximately 5.1%. Inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKBKE) is a major oncogenic protein in tumors and can promote evil development of GBM. Snail1, a key inducer of the epithelial-mesenchymal transition (EMT) transcription factor, is subjected to ubiquitination and degradation, but the mechanism by which Snail1 is stabilized in tumors remains unclear. Our study aimed to investigate the mechanism of IKBKE regulating Snail1 in GBM. METHODS: First, we analyzed the correlation between the expression of IKBKE and the tumor grade and prognosis through public databases and laboratory specimen libraries. Second, immunohistochemistry (IHC) and western blot were used to detect the correlation between IKBKE and Snail expression in glioma samples and cell lines. Western blot and immunofluorescence (IF) experiments were used to detect the quality and distribution of IKBKE and Snail1 proteins. Third, In situ animal model of intracranial glioma to detect the regulatory effect of IKBKE on intracranial tumors. RESULTS: In this study, Our study reveals a new connection between IKBKE and Snail1, where IKBKE can directly bind to Snail1, translocate Snail1 into the nucleus from the cytoplasm. Downregulation of IKBKE results in Snail1 destabilization and impairs the tumor cell migration and invasion capabilities. CONCLUSION: Our studies suggest that the IKBKE-Snail1 axis may serve as a potential therapeutic target for GBM treatment.
Subject(s)
Brain Neoplasms , Glioblastoma , Glioma , Animals , Brain Neoplasms/pathology , Cell Line, Tumor , Cell Movement , Epithelial-Mesenchymal Transition/physiology , Gene Expression Regulation, Neoplastic , Glioblastoma/pathology , Glioma/metabolism , Humans , I-kappa B Kinase/genetics , I-kappa B Kinase/metabolism , Neoplasm Recurrence, Local , Snail Family Transcription Factors/genetics , Snail Family Transcription Factors/metabolismABSTRACT
Chemotherapy is one of the most commonly used clinical treatments among the currently available cancer therapies. However, the phenomenon of Multidrug resistance (MDR) has become a challenge in the treatment process, weakening the impact of chemotherapy. Extensive research on elucidating the development of cancer MDR has identified the following mechanisms that play a critical role in the development of several MDR reversal agents: abnormal expression of cell membrane transporters, adaptation of cancer cells to the microenvironment, regulation of hypoxia, repair of DNA damage and reduction of apoptosis, the enhancement of the EMT process, the existence of cancer stem cells (CSCs), and the abnormal activation of key signaling pathways. However, they failed to demonstrate significant efficacy due to severe side effects during their clinical trials. Traditional Chinese medicines (TCMs) are known to play an important anti-cancer role since they have low toxicity, high efficacy, and safety and can reverse MDR. TCMs reversal agents can be divided into Chinese medicine monomers, synthetic monomers, analogs, or derivatives. Several studies have shown that TCMs can effectively overcome cancer MDR and can be effectively used for treating cancer patients.
Subject(s)
Drug Resistance, Neoplasm , Medicine, Chinese Traditional , Neoplasms/drug therapy , HumansABSTRACT
PURPOSE: The activation of stimulator of interferon genes (STING) pathway triggers the antitumor immunity by CD8 + T cells. However, the differentiated antitumor effects of STING activation in different cell types is still unclear. We aimed to investigate the expression and potential prognostic value of cancer cell-intrinsic STING in hepatocellular carcinoma (HCC), and whether STING could be a potential immunotherapeutic target of HCC was then evaluated. METHODS: We separately assessed the expression of STING in cancer cells and infiltrating immune cells in HCC tissues. The independent clinicopathological factors associated with survival outcomes were evaluated by the multivariable analysis. The HCC orthotopic mice model were used to confirm the immunotherapeutic effects of STING agonists, and CD8 + T-cell infiltration level was analyzed through immunofluorescence and flow cytometry. RESULTS: The expression of cancer cell-intrinsic STING was significantly reduced in HCC compared with adjacent tissues. Patients with low levels of cancer cell-intrinsic STING expression was associated with increased tumor volume (P = 0.009), higher serum AFP levels (P = 0.028), and decreased CD8 + T-cell infiltration (P = 0.002). Low levels of cancer cell-intrinsic STING expression indicated a poor overall survival (OS) and disease-free survival (DFS). Multivariate analysis demonstrated that low levels of cancer cell-intrinsic STING expression was an independent prognostic factor. Additionally, cancer cell-intrinsic STING expression was positively related with CD8 + T-cell infiltration levels in HCC patients (r = 0.308; P = 0.001). When mice with orthotopic HCC tumors treated with STING agonists, tumor growth was significantly reduced with enhanced levels of CD8 + T-cell infiltration. CONCLUSION: Cancer cell-intrinsic STING might affect HCC tumor progression through enhancing CD8 + T-cell infiltration and can be an immunotherapeutic target for HCC.
Subject(s)
CD8-Positive T-Lymphocytes , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/therapy , Immunotherapy , Liver Neoplasms/pathology , Liver Neoplasms/therapy , Lymphocytes, Tumor-Infiltrating , Membrane Proteins/physiology , Animals , Carcinoma, Hepatocellular/immunology , Liver Neoplasms/immunology , Male , Mice , Mice, Inbred C57BLABSTRACT
BACKGROUND: Acute myeloid leukemia (AML) is the most common type of acute leukemia and biologically heterogeneous diseases with poor prognosis. Thus, we aimed to identify prognostic markers to effectively predict the prognosis of AML patients and eventually guide treatment. METHODS: Prognosis-associated genes were determined by Kaplan-Meier and multivariate analyses using the expression and clinical data of 173 AML patients from The Cancer Genome Atlas database and validated in an independent Oregon Health and Science University dataset. A prognostic risk score was computed based on a linear combination of 5-gene expression levels using the regression coefficients derived from the multivariate logistic regression model. The classification of AML was established by unsupervised hierarchical clustering of CALCRL, DOCK1, PLA2G4A, FCHO2 and LRCH4 expression levels. RESULTS: High FCHO2 and LRCH4 expression was related to decreased mortality. While high CALCRL, DOCK1, PLA2G4A expression was associated with increased mortality. The risk score was predictive of increased mortality rate in AML patients. Hierarchical clustering analysis of the five genes discovered three clusters of AML patients. The cluster1 AML patients were associated with lower cytogenetics risk than cluster2 or 3 patients, and better prognosis than cluster3 patients (P values < 0.05 for all cases, fisher exact test or log-rank test). CONCLUSION: The gene panel comprising CALCRL, DOCK1, PLA2G4A, FCHO2 and LRCH4 as well as the risk score may offer novel prognostic biomarkers and classification of AML patients to significantly improve outcome prediction.
Subject(s)
Calcitonin Receptor-Like Protein/genetics , Fatty Acid-Binding Proteins/genetics , Gene Expression , Group IV Phospholipases A2/genetics , Leukemia, Myeloid, Acute/genetics , Membrane Proteins/genetics , Nerve Tissue Proteins/genetics , rac GTP-Binding Proteins/genetics , Databases, Genetic , Gene Expression Profiling , Humans , Kaplan-Meier Estimate , Leukemia, Myeloid, Acute/mortality , Multivariate Analysis , Prognosis , Risk Factors , Treatment OutcomeABSTRACT
This study was conducted to evaluate the influence of supplementing tea polyphenols (TP) in diet of laying hens on yolk cholesterol content and production performance. A total of 1800 Lohmann laying hens aged 48 weeks were randomly allocated to 6 groups. Each group consisted of 6 replicates with 50 layers. The feeding experiment was 4 weeks including one-week acclimatization. Layers fed basal diet supplemented with 0, 150, 200, 250, 300 and 350 mg TP/kg diet, respectively. The results showed that average daily feed intake (ADFI), feed conversion ratio (FCR), average egg weight (AEW), laying rate and the indicators of egg quality were not significantly affected by the diet supplemented with 300 mg/kg TP (p>0.05). However, yolk cholesterol content decreased by increasing TP concentration (p 0.01), with 18.06% reduction in layers fed diet supplemented with 300 mg TP/kg. Also, the diet supplemented with 300 mg/kg TP significantly decreased plasma triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) level (p 0.05). The activity of serum glutathione peroxidase (GSH-Px) was enhanced by increasing TP concentration, while the content of serum methane dicarboxylic aldehyde (MDA) was decreased by increasing TP concentration. The highest activity of GSH-Px and the lowest serum MDA content were both determined in 300 mg/kg TP group (p 0.01). In conclusion, this study suggests that the addition of 300 mg TP/kg basal diet had no negative effect on the production performance laying hens, yet decreased the egg yolk cholesterol content and enhanced the antioxidant capacity of laying hens at the same time.
Subject(s)
Animals , Cholesterol , Chickens/growth & development , Chickens/physiology , Polyphenols/analysis , Polyphenols/chemistry , AntioxidantsABSTRACT
This study was conducted to evaluate the influence of supplementing tea polyphenols (TP) in diet of laying hens on yolk cholesterol content and production performance. A total of 1800 Lohmann laying hens aged 48 weeks were randomly allocated to 6 groups. Each group consisted of 6 replicates with 50 layers. The feeding experiment was 4 weeks including one-week acclimatization. Layers fed basal diet supplemented with 0, 150, 200, 250, 300 and 350 mg TP/kg diet, respectively. The results showed that average daily feed intake (ADFI), feed conversion ratio (FCR), average egg weight (AEW), laying rate and the indicators of egg quality were not significantly affected by the diet supplemented with 300 mg/kg TP (p>0.05). However, yolk cholesterol content decreased by increasing TP concentration (p 0.01), with 18.06% reduction in layers fed diet supplemented with 300 mg TP/kg. Also, the diet supplemented with 300 mg/kg TP significantly decreased plasma triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) level (p 0.05). The activity of serum glutathione peroxidase (GSH-Px) was enhanced by increasing TP concentration, while the content of serum methane dicarboxylic aldehyde (MDA) was decreased by increasing TP concentration. The highest activity of GSH-Px and the lowest serum MDA content were both determined in 300 mg/kg TP group (p 0.01). In conclusion, this study suggests that the addition of 300 mg TP/kg basal diet had no negative effect on the production performance laying hens, yet decreased the egg yolk cholesterol content and enhanced the antioxidant capacity of laying hens at the same time.(AU)
Subject(s)
Animals , Chickens/growth & development , Chickens/physiology , Polyphenols/analysis , Polyphenols/chemistry , Cholesterol , AntioxidantsABSTRACT
INTRODUCTION: Urothelial carcinoma (UC) is an aggressive malignancy and has a poor prognosis in the metastatic state. Treatment of UC remains a challenge, and as a first-line regimen for advanced UC, standard platinum-based chemotherapy is unfit for many patients due to numerous comorbidities and poor performance status. Recently, five immune checkpoint inhibitors have been approved for the treatment of patients with advanced UC who were ineligible for platinum-based regimens or suffered tumor progression in post-platinum setting. However, not long ago, the U.S. Food and Drug Administration restricted the use of two common immune checkpoint blockades, atezolizumab and pembrolizumab, due to uncertain survival benefit as mono-therapy. In this scenario, we reviewed rapidly surfacing clinical trials to assess the efficacy and safety of immunotherapy targeting the PD-1 pathway for advanced UC. METHODS: A comprehensive search was conducted in PubMed, EMBASE and Cochrane Library for all clinical trials where the efficacy and safety were reported. Our primary outcome was efficacy evaluated by objective response rate (ORR), 1-year overall survival (OS) rate and 1-year progression-free survival (PFS) rate, and second outcome was safety assessed by any grade and grade 3-4 treatment-related adverse events (TRAEs). We chose percentages with 95% confidence intervals (CI) as the evaluation indexes and used a random-effects model to account for heterogeneity. RESULTS: We included 14 clinical trials with 2674 total patients in this meta-analysis. After removing unqualified studies on the basis of sensitivity analyses, 13 studies were pooled to evaluate the overall ORR, 8 studies for the 1-year OS rate and 6 studies for the 1-year PFS rate. The pooled data of ORR, 1-year OS rate, and 1-year PFS rate were 0.20 (95% CI 0.18-0.22, I2 = 38.4%, P = 0.078), 0.50 (95% CI 0.46-0.53, I2 = 30.3%, P = 0.186), and 0.17 (95% CI 0.14-0.20, I2 = 0.0%, P = 0.668), respectively. Similarly, 13 trials were utilized to compute the pooled rate of any-grade TRAEs. The pooled estimation of any-grade was 0.65 (95% CI 0.63-0.67, I2 = 1.7%, P = 0.429). The pooled rate of grade 3-4 TRAEs subgroups with Atezolizumab, Pembrolizumab, Durvalumab, Nivolumab and Avelumab were 0.11 (95% CI 0.06-0.15, I2 = 83.5%, P = 0.000), 0.15 (95% CI 0.13-0.18, I2 = 0.0%, P = 0.971), 0.06 (95% CI 0.03-0.09, I2 = 0.0%, P = 0.566), 0.19 (95% CI 0.15-0.23, I2 = 0.0%, P = 0.480) and 0.08 (95% CI 0.05-0.11, I2 = 0.0%, P = 0.702), respectively. CONCLUSION: This study showed that the immunotherapy targeting the PD-1 pathway had durable efficacy and acceptable safety in patients with advanced UC. The comprehensive role of immune checkpoint inhibitors in comparison to other treatments needs further confirmation basing on RCTs.
Subject(s)
Immune Checkpoint Inhibitors/therapeutic use , Urologic Neoplasms/drug therapy , Urothelium/pathology , Clinical Trials as Topic , Humans , Immune Checkpoint Inhibitors/adverse effects , Publication Bias , Urologic Neoplasms/mortalityABSTRACT
PURPOSE: Glioblastoma multiforme (GBM) is the most common and aggressive malignant type of brain tumor. Despite advances in diagnosis and therapy, the prognosis of patients with GBM has remained dismal. Multidrug resistance and high recurrence are two of the major challenges in successfully treating brain tumors. IKBKE (inhibitor of nuclear factor kappa-B kinase subunit epsilon) is a major oncogenic protein in tumors and can inhibit glioblastoma cell proliferation, migration, and tumorigenesis. Our study aimed to investigate the mechanism of IKBKE enhancing the resistance of glioma cells to temozolomide. METHODS: For the in vitro experiments, LN18 and U118 glioblastoma cells were treated with a combination of sh/oe-IKBKE lentivirus and TMZ. Cell proliferation was determined by the EdU assay and colony formation assays. Apoptosis was analyzed by the TUNEL assay. In vivo, LN18 NC and LN18 sh-IKBKE cells were implanted into the cerebrums of nude mice to detect the effect of combination therapy. The protein and mRNA levels were assayed by western blot, immunohistochemistry, and qRT-PCR. RESULTS: In this study, we demonstrated that IKBKE enhances the resistance of glioblastoma cells to temozolomide (TMZ) by activating the AKT/NF-κB signaling pathway to upregulate the expression of the DNA repair enzyme o6-methylguanine-dna methyltransferase (MGMT). In glioblastoma cells, IKBKE knockdown enhances apoptosis and suppresses cell proliferation, clone formation, and tumor development in vivo induced by TMZ. However, overexpression of IKBKE reduces the effects of TMZ. CONCLUSION: Our studies suggest that inhibition of IKBKE can enhance the therapeutic effect of TMZ on GBM in vitro and in vivo, providing new research directions and therapeutic targets for the treatment of GBM.
Subject(s)
Antineoplastic Agents, Alkylating/pharmacology , Brain Neoplasms/drug therapy , DNA Modification Methylases/metabolism , DNA Repair Enzymes/metabolism , Drug Resistance, Neoplasm/physiology , Glioblastoma/drug therapy , I-kappa B Kinase/metabolism , Temozolomide/pharmacology , Tumor Suppressor Proteins/metabolism , Animals , Apoptosis/physiology , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Cell Line, Tumor , Cell Movement , Cell Proliferation , Drug Resistance, Multiple/physiology , Female , Gene Knockdown Techniques , Glioblastoma/metabolism , Glioblastoma/pathology , Humans , I-kappa B Kinase/antagonists & inhibitors , I-kappa B Kinase/genetics , I-kappa B Kinase/pharmacology , Lentivirus , Mice , Mice, Inbred BALB C , Mice, Nude , NF-kappa B/metabolism , Neoplasm Proteins/antagonists & inhibitors , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Neoplasm Proteins/pharmacology , Neoplasm Transplantation , Proto-Oncogene Proteins c-akt/metabolism , RNA, Messenger/analysis , Transduction, Genetic/methods , Up-Regulation , Xenograft Model Antitumor AssaysABSTRACT
Heparan sulfate proteoglycans (HSPGs) are present on the cell surface and in the extracellular matrix in all metazoans. HSPGs interact with growth factors and receptors through heparan sulfate (HS) chains. The sulfation pattern of heparan sulfate chains influences signaling events mediated by heparan sulfate proteoglycans located on the cell surface. SULF1 and SULF2 are two endo-sulfatases that can cleave specific 6-O-sulfate groups within the heparan chains. To determine their possible roles in tissues and satellite cells in vitro, their expression pattern was examined in tissues from 40-day-old chickens and in satellite cells from the breast muscles of 1-week-old and 2-week-old chickens using RT-PCR and immunocytochemistry analyses. The SULF1 and SULF2 transcripts were widely distributed in various tissues. Upon increasing culture times in chicken´s primary skeletal muscle satellite cells, SULF1 and SULF2 expression in 1-week-old chickens was significantly higher than in 2-week-old chickens, suggesting that sulfatases play a key role in satellite cell development. Therefore, our findings increase our knowledge of sulfatase expression diversity and provide a solid basis for further research concerning this molecular mechanism.
Subject(s)
Animals , Satellite Cells, Skeletal Muscle , Chickens/genetics , Chickens/immunology , Sulfatases/analysis , Sulfatases/immunologyABSTRACT
Heparan sulfate proteoglycans (HSPGs) are present on the cell surface and in the extracellular matrix in all metazoans. HSPGs interact with growth factors and receptors through heparan sulfate (HS) chains. The sulfation pattern of heparan sulfate chains influences signaling events mediated by heparan sulfate proteoglycans located on the cell surface. SULF1 and SULF2 are two endo-sulfatases that can cleave specific 6-O-sulfate groups within the heparan chains. To determine their possible roles in tissues and satellite cells in vitro, their expression pattern was examined in tissues from 40-day-old chickens and in satellite cells from the breast muscles of 1-week-old and 2-week-old chickens using RT-PCR and immunocytochemistry analyses. The SULF1 and SULF2 transcripts were widely distributed in various tissues. Upon increasing culture times in chicken´s primary skeletal muscle satellite cells, SULF1 and SULF2 expression in 1-week-old chickens was significantly higher than in 2-week-old chickens, suggesting that sulfatases play a key role in satellite cell development. Therefore, our findings increase our knowledge of sulfatase expression diversity and provide a solid basis for further research concerning this molecular mechanism.(AU)
Subject(s)
Animals , Sulfatases/analysis , Sulfatases/immunology , Chickens/genetics , Chickens/immunology , Satellite Cells, Skeletal MuscleABSTRACT
This study aimed to investigate the antidepressant effect and the mechanism of action of Kai-Xin-San (KXS) in fluoxetine-resistant depressive (FRD) rats. Two hundred male Wistar rats weighing 200±10 g were exposed to chronic and unpredictable mild stresses (CUMS) for 4 weeks and given fluoxetine treatment simultaneously. The rats that did not show significant improvement in behavioral indexes were chosen as the FRD model rats. These rats were randomly divided into four groups: FRD model control; oral fluoxetine and aspirin; oral KXS at a dose of 338 mg·kg-1·day-1; and oral KXS at a dose of 676 mg·kg-1·day-1. Rats continued to be exposed to CUMS and underwent treatment once a day for 3 weeks, then cytokine (COX-2, IFN-γ, IL-1ß, IL-2, IL-4, IL-6, IL-10, TGF-ß, and TNF-α) levels in the hippocampus and serum, and organ coefficients were measured. Both doses of KXS improved the crossing and rearing frequencies, sucrose-preference index, and body weight in FRD rats. KXS at a dose of 338 mg·kg-1·day-1reduced COX-2, IL-2, IL-6, TNF-α levels, increased IL-10 level in the hippocampus, and reduced IL-2 and TNF-α levels in serum. KXS at a dose of 676 mg·kg-1·day-1reduced TNF-α level in the hippocampus, reduced IL-2 and TNF-α levels in serum, and increased IFN-γ and IL-10 levels in the hippocampus and serum. There were no significant differences in organ-coefficients of the spleen among and between groups. The results suggested that oral administration of KXS in FRD rats was effective in improving behavior disorders by influencing various inflammatory pathways.
Subject(s)
Antidepressive Agents/therapeutic use , Cytokines/metabolism , Depression/drug therapy , Drugs, Chinese Herbal/therapeutic use , Hippocampus/metabolism , Animals , Cytokines/drug effects , Depression/metabolism , Disease Models, Animal , Drug Resistance , Fluoxetine/adverse effects , Hippocampus/drug effects , Male , Random Allocation , Rats , Rats, Wistar , Stress, Psychological/psychologyABSTRACT
This meta-analysis compared the efficacy and safety of the contact force (CF)-sensing catheter and second-generation cryoballoon (CB) ablation for treating atrial fibrillation (AF). Six controlled clinical trials comparing ablation for AF using a CF-sensing catheter or second-generation CB were identified from PubMed, EMBASE, Cochrane Library, Wanfang Data, and China National Knowledge Infrastructure. The procedure duration was significantly lower in the CB group compared with that in the CF group [mean difference (MD)=29.4; 95%CI=17.84-40.96; P=0.01], whereas there was no difference between the groups for fluoroscopy duration (MD=0.59; 95%CI=-4.48-5.66; P=0.82). Moreover, there was no difference in the incidence of non-lethal complications (embolic event, tamponade, femoral/subclavian hematoma, arteriovenous fistula, pulmonary vein stenosis, phrenic nerve palsy, and esophageal injury) between the CB and the CF groups (8.38 vs 5.35%; RR=0.66; 95%CI=0.37-1.17; P=0.15). Transient phrenic nerve palsy occurred in 17 of 326 patients (5.2%) of the CB group vs none in the CF group (RR=0.12; 95%CI=0.03-0.43; P=0.001). A comparable proportion of patients in CF and CB groups suffered from AF recurrence during the 12-month follow-up after a single ablation procedure [risk ratio (RR)=1.03; 95%CI=0.78-1.35; P=0.84]. AF ablation using CF-sensing catheters and second-generation CB showed comparable fluoroscopy duration and efficacy (during a 12-month follow-up), with shorter procedure duration and different complications in the CB group.
Subject(s)
Atrial Fibrillation/surgery , Catheter Ablation/methods , Cryosurgery/methods , Catheter Ablation/adverse effects , Catheters , Controlled Clinical Trials as Topic , Cryosurgery/adverse effects , HumansABSTRACT
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects motor neurons and lacks an effective treatment. The disease pathogenesis has not been clarified at present. Pathological transactive response DNA-binding protein 43 (TDP-43) plays an important role in the pathogenesis of ALS. Nuclear translocation of nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) is found in a mutant TDP-43 transgenic cell model, but its downstream antioxidant enzyme expression is decreased. To elucidate the specific mechanism of Nrf2/ARE (antioxidant responsive element) signaling dysfunction, we constructed an ALS cell model with human mutant TDP-43 using the NSC-34 cell line to evaluate the impact of the TDP-43 mutation on the Nrf2/ARE pathway. We found the nuclear translocation of Nrf2, but the expression of total Nrf2, cytoplasmic Nrf2, and downstream phase II detoxifying enzyme (NQO1) was decreased in NSC-34 cells transfected with the TDP-43-M337V plasmid. Besides, TDP-43-M337V plasmid-transfected NSC-34 cells were rounded with reduced neurites, shortened axons, increased levels of intracellular lipid peroxidation products, and decreased viability, which suggests that the TDP-43-M337V plasmid weakened the antioxidant capacity of NSC-34 cells and increased their susceptibility to oxidative damage. We further showed that expression of the MafK protein and the Jun dimerization protein 2 (JDP2) was reduced in TDP-43-M337V plasmid-transfected NSC-34 cells, which might cause accumulation of Nrf2 in nuclei but a decrease in NQO1 expression. Taken together, our results confirmed that TDP-43-M337V impaired the Nrf2/ARE pathway by reducing the expression of MafK and JDP2 proteins, and provided information for further research on the molecular mechanisms of TDP-43-M337V in ALS.
Subject(s)
Amyotrophic Lateral Sclerosis/metabolism , DNA-Binding Proteins/metabolism , MafK Transcription Factor/metabolism , Mutation, Missense , NF-E2-Related Factor 2/metabolism , Repressor Proteins/metabolism , Response Elements , Animals , Cell Line , DNA-Binding Proteins/genetics , MafK Transcription Factor/genetics , Mice , NAD(P)H Dehydrogenase (Quinone)/metabolism , Neurons/metabolism , Oxidative Stress , Repressor Proteins/geneticsABSTRACT
This meta-analysis compared the efficacy and safety of the contact force (CF)-sensing catheter and second-generation cryoballoon (CB) ablation for treating atrial fibrillation (AF). Six controlled clinical trials comparing ablation for AF using a CF-sensing catheter or second-generation CB were identified from PubMed, EMBASE, Cochrane Library, Wanfang Data, and China National Knowledge Infrastructure. The procedure duration was significantly lower in the CB group compared with that in the CF group [mean difference (MD)=29.4; 95%CI=17.84-40.96; P=0.01], whereas there was no difference between the groups for fluoroscopy duration (MD=0.59; 95%CI=-4.48-5.66; P=0.82). Moreover, there was no difference in the incidence of non-lethal complications (embolic event, tamponade, femoral/subclavian hematoma, arteriovenous fistula, pulmonary vein stenosis, phrenic nerve palsy, and esophageal injury) between the CB and the CF groups (8.38 vs 5.35%; RR=0.66; 95%CI=0.37-1.17; P=0.15). Transient phrenic nerve palsy occurred in 17 of 326 patients (5.2%) of the CB group vs none in the CF group (RR=0.12; 95%CI=0.03-0.43; P=0.001). A comparable proportion of patients in CF and CB groups suffered from AF recurrence during the 12-month follow-up after a single ablation procedure [risk ratio (RR)=1.03; 95%CI=0.78-1.35; P=0.84]. AF ablation using CF-sensing catheters and second-generation CB showed comparable fluoroscopy duration and efficacy (during a 12-month follow-up), with shorter procedure duration and different complications in the CB group.
Subject(s)
Humans , Atrial Fibrillation/surgery , Catheter Ablation/methods , Cryosurgery/methods , Catheter Ablation/adverse effects , Controlled Clinical Trials as Topic , Cryosurgery/adverse effects , CathetersABSTRACT
Fibroblast growth factors (FGFs) play important roles in angiogenesis, wound healing, embryonic development, and endocrine signaling pathways. Increasingly, recent studies have reported aberrant FGF expression in various malignancies. However, the involvement of FGFs in cervical carcinoma pathogenesis remains unclear. We aimed to investigate expression of acidic (aFGF) and basic FGF (bFGF) in patients with this disease, and assess their effects on cervical cancer cell proliferation. Twenty cervical cancer patients and 10 cervical intraepithelial neoplasia (CIN) patients were recruited, and 10 cancer-free individuals were included as controls. Reverse transcription-polymerase chain reaction and western blotting were employed to detect FGF mRNA and protein levels, respectively. Furthermore, HeLa cells were treated with FGFs and subjected to thiazolyl blue tetrazolium bromide assays to quantify proliferation. Compared with CIN and normal cervical tissues, aFGF and bFGF mRNA and protein levels were significantly elevated in cervical carcinomas (P < 0.05). CIN tissues exhibited higher expression of these FGFs than normal tissues (P < 0.05). Moreover, their mRNA levels were increased in advanced cancer stages (P < 0.05), although no significant difference was detected between tumors of different differentiation grades in this regard (P > 0.05). HeLa cell proliferation increased in an aFGF- and bFGF-dose-dependent manner (P < 0.05), the latter exerting a more potent proliferative influence, with its effect peaking at 75 ng/mL. aFGF and bFGF were highly expressed in cervical cancer tissues and their levels positively correlated with clinical stage. Both facilitate proliferation of cervical carcinoma cells and are implicated in cancer pathogenesis and progression.
Subject(s)
Adenocarcinoma/pathology , Carcinoma, Squamous Cell/pathology , Fibroblast Growth Factor 1/metabolism , Fibroblast Growth Factor 2/metabolism , Uterine Cervical Neoplasms/pathology , Adenocarcinoma/genetics , Adenocarcinoma/metabolism , Adult , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/metabolism , Cell Proliferation , Female , Fibroblast Growth Factor 1/genetics , Fibroblast Growth Factor 2/genetics , Gene Expression Regulation, Neoplastic , HeLa Cells , Humans , Middle Aged , Neoplasm Staging , Prognosis , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/metabolism , Young AdultABSTRACT
Tobacco is an economically important crop, and its potassium content can greatly affect the quality of tobacco leaves. However, the molecular mechanism involved in potassium starvation in tobacco has not been elucidated to date. In this study, Illumina (Solexa) sequencing technology was used to analyze the transcriptome of tobacco seedlings under low-potassium stress for 6, 12, and 24 h. After analysis, 107,824 assembled unigenes were categorized into 57 GO functional groups, and 31,379 unigenes (29.08%) were clustered into 25 COG categories. A total of 9945 genes were classified into 233 KEGG pathways, and 15,209 SSRs were found among the 107,824 unigenes. Between the two samples, 1034 genes were differentially expressed. Twelve randomly selected gene expression levels were analyzed by quantitative RT-PCR, and the results were highly consistent with those obtained by Solexa sequencing. Our results provide a comprehensive analysis of the gene-regulatory network of tobacco seedlings under low-potassium stress.
Subject(s)
Nicotiana/genetics , Potassium/metabolism , Seedlings/genetics , Stress, Physiological , Transcriptome , Gene Expression Profiling , Gene Expression Regulation, Plant , Gene Ontology , Gene Regulatory Networks , Genes, Plant , Microsatellite Repeats , Molecular Sequence Annotation , Plant Proteins/genetics , Plant Proteins/metabolism , Seedlings/metabolism , Nicotiana/metabolismABSTRACT
The peel of mango (Mangifera indica L.) is a special plant tissue that contains many compounds that interfere with protein extraction. A successful separation with Two-dimensional electrophoresis (2-DE) is the key step for proteomic analysis. To evaluate the efficiencies of mango peel protein extraction for 2-DE, four extraction methods were tested: 1) 2-D clean-up kit, 2) trichloroacetic acid/acetone precipitation, 3) phenol extraction, 4) phenol with methanol/ammonium acetate precipitation. The results showed that the phenol with methanol/ammonium acetate precipitation produced the best quality protein extraction and separation. Proteins were separated in 30-70 and >70 kDa ranges better than with the other methods. Acidic proteins had better resolution with fewer horizontal and vertical streaks. Sixteen proteins were identified by maxtrix-assisted laser desorption/ ionisation time-of-flight tandem mass spectrometry (MALDI-TOF/ TOF-MS/MS). The result demonstrated that each of these four methods can be used to prepare mango peel proteins. The phenol with methanol/ ammonium acetate precipitation was the best choice for proteomic analysis of mango peel.
Subject(s)
Fruit/chemistry , Mangifera/chemistry , Plant Proteins/isolation & purification , Proteome/isolation & purification , Acetates/chemistry , Chemical Precipitation , Methanol/chemistry , Phenol/chemistry , Plant Proteins/chemistry , Proteome/chemistry , Proteomics , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Tandem Mass SpectrometryABSTRACT
The aim of this study was to determine the association between two SNPs (rs2235371 and rs2013162) in the interferon regulatory factor 6 (IRF6) gene and non-syndromic cleft palate (NSCP) in northeast China. We genotyped these two SNPs in 104 NSCP cases, as well as in 178 parents and 300 controls. Case-control and case-parent analyses were performed using χ2 tests and family-based association tests (FBAT). Results indicated that there were significant differences in both genotypic and allelic distributions between patients and controls at rs2235371 and rs2013162 in the IRF6 gene. Case-parent analysis revealed over-transmission of the C allele in rs2235371 and the A allele in rs2013162. Lastly, FBAT showed over-transmission of the CA haplotype. This study demonstrated that the two SNPs, rs2235371 and rs2013162, are strongly associated with NSCP in the northeast Chinese population.
Subject(s)
Cleft Palate/genetics , Genetic Predisposition to Disease , Interferon Regulatory Factors/genetics , Polymorphism, Single Nucleotide , Adult , Alleles , Asian People , Asymptomatic Diseases , Case-Control Studies , Child , Cleft Palate/diagnosis , Cleft Palate/ethnology , Female , Gene Expression , Gene Frequency , Genetic Association Studies , Haplotypes , Humans , Male , PhenotypeABSTRACT
The Chinese hawthorn (Crataegus pinnatifida Bge. var. major N.E.Br.) is uniquely originated in northern China. The ecological and horticultural importance of Chinese hawthorn is considerable and some varieties are valued for their fruit or medicine extracts. Its taxonomy and phylogeny remain poorly understood. Apart from general plant morphological traits, pollen is an important trait for the classification of plants and their evolutionary origin. However, few studies have investigated the pollen of Chinese hawthorn. Here, an analysis of plant and pollen morphological characteristics was conducted in 57 cultivars from the Shenyang region. Thirty plant morphological characters and nine pollen grain characters were investigated. The plant morphological analysis revealed that the coefficient of variation for 13 traits was >20%, which indicates a high degree of variability. We also found that the pollen grains varied greatly in size, shape (from prolate to perprolate), and exine pattern (striate-perforate predominantly). The number of apertures was typically three. Based on these findings, we suggest that pollen morphology associated with plant morphological traits can be used for classification and phylogenetic analysis of Chinese hawthorn cultivars. In sum, our results provide new insights and constitute a scientific basis for future studies on the classification and evolution of Chinese hawthorn.