ABSTRACT
Cardiovascular diseases(CVD) with high morbidity and mortality pose severe threats to human life. Allicin, a main active ingredient of garlic, possesses multiple pharmaceutical activities. It not only exerts cardioprotective effects but also prevents the risk factors for CVD. Allicin exerts cardioprotective effects via a variety of mechanisms, including inhibiting oxidative stress, apoptosis, autophagy, and inflammatory responses, regulating lipid metabolism and gut microbiota, inducing hydrogen sulfide production, and dilating vessels. Despite the valuable cardioprotective effects, the instability of allicin has hindered the basic research and clinical application. This paper reviews the progress in the cardioprotective effects and mechanisms of allicin in the last decade and summarizes the methods to improve the stability of allicin. In addition, this review provides a reference for further research and development of allicin in cardiovascular protection.
Subject(s)
Cardiovascular Diseases , Disulfides , Humans , Heart , Sulfinic Acids/pharmacology , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/prevention & control , Pharmaceutical PreparationsABSTRACT
Under alkaline conditions, Fluorescein mercury has strong fluorescence, however, when it met S(2-), its fluorescence would quench, in view of the above, a fluorescence method for determination of H2S in biological samples was established. In the 0.1 mol · L(-1) NaOH dilution, when the concentration of fluorescein Mercury and Na2S was 5.0 × 10(-5) and 1.0 × 10(-5) mol · L(-1) respectively, the fluorescence intensity of system was determined at 522 nm. The results showed that, at the range of 4.0 × 10(-7)~2.0 × 10(-6) mol · L(-1), the concentration decreasing of H2S and fluorescence intensity had good linear relationship, r=0.9980, the RSD of precision test was 4.59% (n=7), the detection limit was 3.5 × 10(-8) mol · L(-1), the content of H2S in the sample were 1.01 × 10(-6) and 1.15 × 10(-6) mol · L(-1), and the recovery rate was 95.8%~101.0%, the method has the advantages of simple operation, high sensitivity, good selectivity, can accurately determine of H2S in intestinal perfused solution, and provides the basis for the determination of endogenous H2S.
Subject(s)
Hydrogen Sulfide/analysis , Pharmaceutical Solutions/chemistry , Animals , Fluorescein , Fluorescence , Intestines , Limit of Detection , Mercury , Perfusion , Rats , Spectrometry, Fluorescence , SulfidesABSTRACT
With the application of monoclonal antibody technology more and more widely, its production technology is becoming more and more perfect. Small molecule monoclonal antibody technology is becoming a hot research topic for people. The application of traditional Chinese medicine small molecule monoclonal antibody technology has been more and more widely, the technology for effective Chinese medicine component knockout provide strong technical support. The preparation of monoclonal antibodies and small molecule knockout technology are reviewed in this paper. The preparation of several steps, such as: in the process of preparation of antigen, hapten carrier coupling, coupling ratio determination and identification of artificial antigen and establishment of animal immunization and hybridoma cell lines of monoclonal antibody, the large-scale preparation; small molecule monoclonal antibody on Immune in affinity chromatography column method is discussed in detail. The author believes that this technology will make the traditional Chinese medicine research on a higher level, and improve the level of internationalization of Chinese medicine research.
Subject(s)
Antibodies, Monoclonal/immunology , Immunologic Techniques/methods , Animals , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/genetics , Humans , Hybridomas/metabolism , Immunologic Techniques/trendsABSTRACT
The apparatus for intrinsic dissolution test recorded in United States Pharmacopeia (USP) integrating with fiber-optic drug dissolution test system (FODT) were used to real-time monitor intrinsic dissolution processes of alliin in four media which were water, solution of HCl with pH 1.2, buffer solution of acetate with pH 4.5, and buffer solution of phosphate with pH 6.8. The intrinsic dissolution rate (IDR) and the similarity factor (f2) of two intrinsic dissolution curves with two apparatuses were calculated. The IDR values of alliin with rotating disk system were 28.1.3, 33.55, 28.38 and 30.95 mg x cm(-2) x min(-1) in four media, respectively. And the IDR values of alliin with stationary disk system were 44.16, 47.07, 45.11 and 51.34 mg x cm(-2) x min(-1), respectively. The similarity factors were 56.42, 50.75, 40.30 and 40.64, respectively. The results showed that the intrinsic alliin dissolution rates were much greater than 1 mg x cm(-2) x min(-1). It inferred that alliin dissolution would not be the rate limiting step to absorption.
Subject(s)
Cysteine/analogs & derivatives , Cysteine/chemistry , Fiber Optic Technology , SolubilityABSTRACT
The drug dissolution test is an important examination of drug testing, which plays a very important role in the drug quality assessment. Automation and proceduring monitoring of drug dissolution can be implemented by the optical fiber sensing technology. Two modes of detection of UV-Vis absorption and fluorescence quenching were established by software implementation, with xenon lamp, deuterium lamp or halogen tungsten lamp as fluorescence, UV and visible light source, branch Y type optical fiber as light path transmission medium, UV-Vis probe and fluorescence molecular probe as light response devices, and CCD as detector. Optical fiber sensing drug dissolution monitor not only solves the current problems of time-consuming, and sampling of off-line analysis, but also provides real-time information of drug dissolution process. Thus, our study may provide a better evaluation method for the drug quality control.
Subject(s)
Drug Liberation , Fiber Optic Technology , Optical Fibers , Quality Control , Software , SolutionsABSTRACT
A method for on-line monitoring the dissolution of Valsartan and hydrochlorothiazide tablets assisted by mathematical separation model of linear equations was established. UV spectrums of valsartan and hydrochlorothiazide were overlapping completely at the maximum absorption wavelength respectively. According to the Beer-Lambert principle of absorbance additivity, the absorptivity of Valsartan and hydrochlorothiazide was determined at the maximum absorption wavelength, and the dissolubility of Valsartan and hydrochlorothiazide tablets was detected by fiber-optic dissolution test (FODT) assisted by the mathematical separation model of linear equations and compared with the HPLC method. Results show that two ingredients were real-time determined simultaneously in given medium. There was no significant difference for FODT compared with HPLC (p > 0.05). Due to the dissolution behavior consistency, the preparation process of different batches was stable and with good uniformity. The dissolution curves of valsartan were faster and higher than hydrochlorothiazide. The dissolutions at 30 min of Valsartan and hydrochlorothiazide were concordant with US Pharmacopoeia. It was concluded that fiber-optic dissolution test system assisted by the mathematical separation model of linear equations that can detect the dissolubility of Valsartan and hydrochlorothiazide simultaneously, and get dissolution profiles and overall data, which can directly reflect the dissolution speed at each time. It can provide the basis for establishing standards of the drug. Compared to HPLC method with one-point data, there are obvious advantages to evaluate and analyze quality of sampling drug by FODT.
Subject(s)
Hydrochlorothiazide/analysis , Tetrazoles/analysis , Valine/analogs & derivatives , Chromatography, High Pressure Liquid , Models, Theoretical , Solubility , Tablets , Valine/analysis , ValsartanABSTRACT
OBJECTIVE: To compare the antioxidant active components from two species of chamomile-matricaria and Roman chamomile produced in Xinjiang. METHOD: The TLC-bioautography was used, with 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical as the experimental model. The peak areas of various antioxidant components were obtained by TLC-scanning for analyzing antioxidant active components contained in volatile oil extracts and flavone extracts from the two species of chamomiles. The total peak area was taken as the indicator for comparing the antioxidant capacities of the two types of extracts, and comparing them with the total antioxidant activity of flavone extracts of the two species of chamomiles. RESULTS: According to the result of TLC-bioautography in volatile oil extracts from the two species of chamomiles, volatile oil extracts from chamomile showed four white antioxidant spots, including en-yne-dicycloether, and volatile oil extracts from Roman chamomile showed only one white antioxidant spot. The TLC-scanning result showed that the peak area of antioxidant spots of volatile oil extracts from chamomile was significantly larger than that of volatile oil extracts from Roman chamomile. According to the test on the antioxidant activity of the two species of chamomiles with ultraviolet-visible spectrophotometry, the concentration of chamomile after scavenging 50% of DPPH radicals was 0.66 g x L(-1), whereas the figure for Roman chamomile was 0.33 g x L(-1). According to the result of TLC-bioautography in flavone extracts from the two species of chamomiles, flavone extracts from chamomile showed seven yellowish antioxidant spots, including apigenin and apigenin-7-glucoside, and flavone extracts of Roman chamomile showed eight yellowish antioxidant spots, including apigenin and apigenin-7-glucoside. The TLC-scanning results showed that the peak area of antioxidant spots of flavone extracts from Roman chamomile was significantly larger than that of flavone extracts from chamomile. CONCLUSION: Volatile oil extracts from the two species of chamomiles have significant difference in the antioxidant activity in TLC-bioautography. Specifically, the antioxidant activity of volatile oil extracts from chamomile is stronger than volatile oil extracts from Roman chamomile; the known antioxidant active components in volatile oil extracts from chamomile is en-yne-dicycloether, while all of the other three antioxidant active components as well as antioxidant active components in volatile oil extracts from Roman chamomile are unknown components and remain to be further determined. Considering the significant difference in the number of antioxidant active spots in volatile oil extracts from the two species of chamomiles, the result can be applied to distinguish the two species of chamomiles. The antioxidant activity determination result for flavone extracts from two species of chamomiles was consistent with the result of TLC-bioautography, showing that flavone extracts from chamomile and Roman chamomile are more antioxidant active, while that of Roman chamomile is stronger than chamomile. Flavone extracts from both of the two species of chamomiles contain apigenin and pigenin-7-glucoside, which are known, while all of the other five antioxidant active components contained in flavone extracts from chamomile and the other six antioxidant active components contained in flavone extracts from Roman chamomile are unknown and remain to be further identified. The method lays a foundation for further identification of antioxidant active components contained in chamomile.
Subject(s)
Antioxidants/chemistry , Chamaemelum/chemistry , Chromatography, Thin Layer/methods , Flavones/chemistry , Matricaria/chemistry , Oils, Volatile/chemistry , Antioxidants/isolation & purification , Apigenin/chemistry , Apigenin/isolation & purification , Biphenyl Compounds/metabolism , Flavones/isolation & purification , Free Radical Scavengers/chemistry , Free Radical Scavengers/isolation & purification , Glucosides/chemistry , Glucosides/isolation & purification , Oils, Volatile/isolation & purification , Picrates/metabolism , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Oils/chemistry , Plant Oils/isolation & purificationABSTRACT
OBJECTIVE: To study the correlation between loss of heterozygosity (LOH) on chromosome 10q and pathologic features, pathogenesis, prognosis of astrocytic tumors. METHODS: LOH on 10q was studied by interphase fluorescence in-situ hybridization (FISH) in 85 cases of astrocytic tumor, including 35 cases of WHO grade II tumors and 50 cases of WHO grade IV tumors. RESULTS: LOH on 10q was detected in 6 cases (17.1%) of diffuse astrocytoma (WHO grade II) and 34 cases (68.0%) of glioblastoma (WHO grade IV). 10q polysomy was detected in 7 cases (20.0%) of diffuse astrocytoma and 11 cases (22.0%) of glioblastoma. The rates of LOH on 10q in young age group and elderly group were 36.4% (12/33) and 82.4% (28/34), respectively. The difference was of statistical significance (P < 0.05). The rates of LOH on 10q in the diffuse astrocytoma and glioblastoma were 21.4% (6/28) and 87.2% (34/39), respectively. The difference was also statistically significant (P < 0.05). Univariate survival analysis showed that patient age, pathologic grade and 10q on LOH correlated with duration of survival (P < 0.05). CONCLUSIONS: There are correlation between 10q LOH, patient age and pathologic grade of astrocytic tumors. LOH on 10q is also related to the pathogenesis of astrocytic tumors and is helpful in predicting prognosis.
Subject(s)
Astrocytoma/genetics , Brain Neoplasms/genetics , Chromosomes, Human, Pair 10/genetics , Glioblastoma/genetics , Loss of Heterozygosity , Adolescent , Adult , Age Factors , Astrocytoma/pathology , Astrocytoma/surgery , Brain Neoplasms/pathology , Brain Neoplasms/surgery , Child , Female , Follow-Up Studies , Glioblastoma/pathology , Glioblastoma/surgery , Humans , Male , Middle Aged , Neoplasm Grading , Survival Rate , Young AdultABSTRACT
OBJECTIVE: To study the clinicopathologic features and differential diagnosis of blastic plasmacytoid dendritic cell neoplasm. METHODS: The clinical, morphology and immunophenotypic features were analyzed in 3 cases of blastic plasmacytoid dendritic cell neoplasm, with review of literature. RESULTS: The pathologic changes of these tumors accorded with that of blastic plasmacytoid dendritic cell neoplasm, and they also had new characteristics, including lineage other than T, B, myeloid and NK cells, and immunophenotypes of CD56(+) CD4(-) CD123(+) TdT(+) CD43(+) CD68(+) , CD56(+) CD4(+) CD123(-) TdT(+) CD43(+) CD68(-) and CD56(+) CD4(+) CD123(-/+) TdT(-) CD43(+) CD68(+) in the 3 cases, respectively. Bone marrow involvement was found 5 years later in case 1, and was then stable after chemotherapy; case 2 and case 3 were died 5 and 2 months after diagnosis, respectively. CONCLUSION: Blastic plasmacytoid dendritic cell neoplasm is a heterogeneous group of lymphoproliferative disorders, with different clinical, morphologic and immunophenotypic features.
Subject(s)
Dendritic Cells/pathology , Hematologic Neoplasms/pathology , Skin Neoplasms/pathology , Adolescent , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bleomycin/therapeutic use , CD56 Antigen/metabolism , Cyclophosphamide/therapeutic use , Dendritic Cells/metabolism , Diagnosis, Differential , Doxorubicin/therapeutic use , Female , Follow-Up Studies , Hematologic Neoplasms/drug therapy , Hematologic Neoplasms/metabolism , Humans , Interleukin-3 Receptor alpha Subunit/metabolism , Leukemia, Myeloid/metabolism , Leukemia, Myeloid/pathology , Lymphoma, Extranodal NK-T-Cell/metabolism , Lymphoma, Extranodal NK-T-Cell/pathology , Lymphoma, T-Cell, Peripheral/metabolism , Lymphoma, T-Cell, Peripheral/pathology , Male , Middle Aged , Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Prednisone/therapeutic use , Skin Neoplasms/drug therapy , Skin Neoplasms/metabolism , Treatment Outcome , Vincristine/therapeutic useABSTRACT
This study aimed to investigate the expression and prognostic significance of the signal transducer and activator of transcription protein 6 (STAT6YE361) and EB virus encoding a small molecule RNA (EBER) in Hodgkin lymphoma (HL), as well as their correlation with clinical parameters. The expression of STAT6YE361 and EBER was investigated in HL via immunohistochemistry and in situ hybridization. Patient clinical data were retrospectively collected from archival libraries, and statistical analysis was performed. Overall, the nuclear positive expression rate of STAT6YE361 was 46%, and the EBER positive expression rate was 57%. STAT6YE361 was specifically expressed on the nucleus in cHL tissues. EBER was overexpressed in HL and had correlations with several clinical data, including age, gender, ethnicity, and primary cancer site. Interestingly, nuclear STAT6YE361 expression was correlated with EBER expression. Based on survival analysis, the nuclear expression of STAT6YE361 and female patients were associated with poor prognosis and were independent prognostic factors for five-year OS. These findings suggest that STAT6YE361 is a potential valuable index in the differential diagnosis and prognosis of HL. The mechanism of STAT6YE361 is related to Epstein-Barr virus infection.
Subject(s)
Gene Expression/genetics , Hodgkin Disease/diagnosis , STAT6 Transcription Factor/analysis , Adolescent , Adult , Aged , Aged, 80 and over , Chi-Square Distribution , Child , Child, Preschool , Female , Gene Expression/physiology , Hodgkin Disease/genetics , Humans , Immunohistochemistry/methods , Immunohistochemistry/statistics & numerical data , Male , Middle Aged , Prognosis , Proportional Hazards Models , STAT6 Transcription Factor/geneticsABSTRACT
Garlic has been considered as a source of highly promising functional food and traditional herbal medicine for thousands of years. Garlic polysaccharides is one of the important effective components of garlic, which has various bioactivities, including immune-enhancing, hepatoprotective, and antioxidant. Garlic polysaccharides is mainly composed of monosaccharides, such as Fru, Glc, and Gal, having a (2 â 1)-linked ß-D-Fruf backbone with (2 â 6)-linked ß-D-Fruf side chains. With great marketing potential and development prospects, garlic polysaccharides has drawn much attention from researchers worldwide. Therefore, this review aimed at providing systematic and current information on the extraction, isolation, structural characteristics, and bioactivities of garlic polysaccharides to support their further application as therapeutic agents and functional foods.
Subject(s)
Garlic , Antioxidants/chemistry , Antioxidants/pharmacology , Garlic/chemistry , Monosaccharides , Plant Extracts/chemistry , Polysaccharides/chemistryABSTRACT
The paper is to report the development of an optic-fiber sensing technology method to analyze metronidazole tablets rapidly. In this fiber-optic sensing system, the light from source delivering to probe can be dipped into simple-handling sample solution, absorbed by the solution and reflected to the fiber-optic and detected in the detection system at last. Then the drug content can be shown in the screen from the ultraviolet absorption spectra and the consistency between that obtained by this method and that in China Pharmacopoeia can be compared. With regard to data processing, a new method is explored to identify the authenticity of drugs using the similarity between the sample map and the standard pattern by full ultraviolet spectrum. The results indicate that ultraviolet spectra of tablets can be obtained from this technology and the determination results showed no significant difference as compared with the method in China Pharmacopoeia (P > 0.05), and the similarity can be a parameter to identify the authenticity of drugs.
Subject(s)
Drug Contamination , Fiber Optic Technology/methods , Metronidazole/analysis , Spectrophotometry, Ultraviolet/methods , Chemistry, Pharmaceutical , Metronidazole/administration & dosage , Optical Fibers , Solubility , TabletsABSTRACT
Diffuse large B-cell lymphoma (DLBCL) is the most common type of B-cell non-Hodgkin lymphoma in adults and the pathogenesis of DLBCL is multifactorial and complex. Understanding the molecular mechanisms involved in DLBCL is important to identify new therapeutic targets. The present study aimed to screen and identify differentially expressed microRNAs (miRNAs/miRs) between diffuse large B-cell lymphoma (DLBCL) and control [lymph node reactive hyperplasia (LRH)] groups, and to investigate whether miRNAs associated with DLBCL could serve as potential therapeutic targets. In total, 5 DLBCL experimental samples and 5 control samples were obtained from fresh patient tissues. Firstly, the fresh samples were analyzed using miRNA microarray to identify differentially expressed miRNAs. Next, three databases (TargetScan, microRNA.org and PITA) were used to predict by intersection the potential target genes of the 204 differential miRNAs identified, and a Venn diagram of the results was performed. Subsequently, the target genes of differential miRNAs were analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Finally, to validate the miRNA microarray data, reverse transcription-quantitative PCR (RT-qPCR) was performed for 8 differentially expressed miRNAs (miR-193a-3p, miR-19a-3p, miR-19b-3p, miR-370-3p, miR-1275, miR-490-5p, miR-630 and miR-665) using DLBCL and LRH fresh samples. In total, 204 miRNAs exhibited differential expression, including 105 downregulated and 54 upregulated miRNAs. The cut-off criteria were set as P≤0.05 and fold-change ≥2. A total of 7,522 potential target genes for the 204 miRNAs were predicted. Potential target genes were enriched in the following pathways: 'Cancer', 'MAPK signaling pathway', 'regulation of actin cytoskeleton', 'focal adhesion', 'endocytosis', 'Wnt signaling pathway', 'axon guidance', 'calcium signaling pathway' and 'PI3K/AKT signaling pathway'. A total of 8 miRNAs were validated by RT-qPCR, and 4 miRNAs (miR-19b-3p, miR-193a-3p, miR-370-3p and miR-490-5p) exhibited low expression levels in DLBCL (P<0.05), while miR-630 was highly expressed in DLBCL (P<0.05). Overall, the present study screened 204 differentially expressed miRNAs and analyzed the expression levels of 8 differentially expressed miRNAs in DLBCL. These differentially expressed miRNAs may serve as therapeutic targets for improvement of therapeutic efficacy in DLBCL in the future.
ABSTRACT
OBJECTIVE: To explore the effect of continuous nursing care based on the Information, Knowledge, Attitude, and Practice (IKAP) theory on the quality of life of patients with chronic obstructive pulmonary disease (COPD). METHODS: This study is a randomized control trial. COPD patients attending the Affiliated Hospital of Inner Mongolia Medical University, China between July 1 and October 31, 2017 were eligible. Following random assignment of participants to either the intervention group or control group, 70 patients (35 in each group) were included in the final sample. The intervention group received nursing care based on the Information, Knowledge, Attitude, and Practice theory, while the control group received standard nursing care. Data were collected before the intervention, 1 month after the intervention, and three months after the intervention. The St. George's Respiratory Questionnaire (SGRQ) was used to measure quality of life. RESULTS: Three months after the intervention, there were significant differences in the total SGRQ score (20.29â±â10.03 vs 30.14â±â12.52) and in the three SGRQ dimensions between the intervention group and the control group (Pâ<â.05). A repeated-measures analysis of variance showed that the total SGRQ score and the scores for impact and symptoms had a significant time effect (Pâ<â.001), that the total SGRQ score and the score for symptoms had a significant interaction effect (Pâ<â.05), and that the impact dimension had a significant group effect (Pâ=â.042). Pairwise comparisons of the data for the intervention group showed that there were significant differences between the pre-intervention and 1 month after intervention scores as well as between pre-intervention and three months after intervention, for the total SGRQ scores and the scores for impact and symptoms(Pâ<â.001). In terms of the impact dimension, there was a significant difference in the intervention group between 1 month after intervention and 3 months after intervention (Pâ=â.016). CONCLUSION: Continuous nursing care based on Information, Knowledge, Attitude, and Practice theory improved quality of scores at 3 months after intervention among COPD patients. Given limitations of the study, future large-scale studies are needed to validate our results.
Subject(s)
Models, Nursing , Practice Patterns, Nurses' , Pulmonary Disease, Chronic Obstructive/psychology , Quality of Life , Aged , Female , Humans , Male , Pulmonary Disease, Chronic Obstructive/nursing , Treatment OutcomeABSTRACT
Peripheral T-cell lymphoma (PTCL) is a very aggressive and heterogeneous hematological malignancy and has no effective targeted therapy. The molecular pathogenesis of PTCL remains unknown. In this study, we chose the gene expression profile of GSE6338 from the Gene Expression Omnibus (GEO) database to identify hub genes and key pathways and explore possible molecular pathogenesis of PTCL by bioinformatic analysis. Differentially expressed genes (DEGs) between PTCL and normal T cells were selected using GEO2R tool. Gene ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis were performed using Database for Annotation, Visualization and Integrated Discovery (DAVID). Moreover, the Search Tool for the Retrieval of Interacting Genes (STRING) and Molecular Complex Detection (MCODE) were utilized to construct protein-protein interaction (PPI) network and perform module analysis of these DEGs. A total of 518 DEGs were identified, including 413 down-regulated and 105 up-regulated genes. The down-regulated genes were enriched in osteoclast differentiation, Chagas disease and mitogen-activated protein kinase (MAPK) signaling pathway. The up-regulated genes were mainly associated with extracellular matrix (ECM)-receptor interaction, focal adhesion and pertussis. Four important modules were detected from the PPI network by using MCODE software. Fifteen hub genes with a high degree of connectivity were selected. Our study identified DEGs, hub genes and pathways associated with PTCL by bioinformatic analysis. Results provide a basis for further study on the pathogenesis of PTCL.
Subject(s)
Biomarkers, Tumor/genetics , Lymphoma, T-Cell, Peripheral/genetics , Protein Interaction Maps/genetics , Cell Differentiation/genetics , Chagas Disease/genetics , Chagas Disease/pathology , Computational Biology , Gene Expression Regulation, Neoplastic/genetics , Gene Ontology , Humans , Lymphoma, T-Cell, Peripheral/pathology , Osteoclasts/metabolism , Signal Transduction/genetics , Transcriptome/geneticsABSTRACT
This study aimed to investigate the hub protein related to the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway in diffuse large B-cell lymphoma (DLBCL). We used proteomics methods (iTRAQ) to explore the differentially expressed proteins in the non-germinal center B-cell -like (non-GCB) DLBCL in our previous study. In this study, a total of 137 formalin-fixed paraffin-embedded DLBCL tissue samples were analyzed via immunohistochemistry to verify the expression of TCL1, AKT1 + 2+3, IKKß and to determine the differentially expressed proteins associated with the PI3K/AKT signaling pathway. Spearman correlation was used to analyze the relationship between these proteins, and survival analysis was used to investigate their effects on prognosis. Immunohistochemistry analysis indicated that TCL1, AKT1 + 2+3, and IKKß were highly positively expressed in DLBCL. Results showed that the expression of TCL1 was related to ethnicity (p = 0.022), primary site (p = 0.045), Ann Arbor stage (p = 0.037), the International Prognostic Index (p = 0.005), ß2-microglobulin (p = 0.030), BCL2 expression (p < 0.001), and Ki-67 expression (p = 0.008). A positive correlation was found between TCL1 and AKT1 + 2+3 (p < 0.001; r = 0.475). A positive correlation was also found between AKT1 + 2+3 and IKKß (p < 0.001; r = 0.342). In survival analysis, anemia, non-treatment with RCHOP, positive TCL1 expression, and Ki-67 expression≥50% independently predicted short progression-free survival and overall survival in the total cohort (p < 0.05). Thus, TCL1 as a hub protein is associated with the PI3K/AKT signaling pathway in DLBCL. TCL1 expression indicated a poor prognosis in patients with DLBCL. With further studies, TCL1 may be established as a reliable prognostic biomarker and potential immunotherapeutic target for improving therapeutic efficacy for DLBCL in the future.
Subject(s)
Lymphoma, Large B-Cell, Diffuse/metabolism , Phosphatidylinositol 3-Kinases , Proteomics , Proto-Oncogene Proteins c-akt , Signal Transduction , B-Lymphocytes/metabolism , B-Lymphocytes/pathology , Biomarkers, Tumor/metabolism , Cohort Studies , Female , Humans , Immunohistochemistry , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Middle Aged , Phosphatidylinositol 3-Kinases/metabolism , Prognosis , Proto-Oncogene Proteins c-akt/metabolismABSTRACT
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with unclear pathogenesis. DLBCL accounts for 30%-35% of all non-Hodgkin lymphomas (NHLs) and is an aggressive subtype of mature B-cell neoplasm. At present, half of DLBCL cases can be cured, although one-third of patients experience recurrence after treatment and enter advanced tumor stage. This study aimed to investigate the differentially expressed proteins in activated B-cell-like-DLBCL (ABC-DLBCL) through quantitative proteomics (iTRAQ). Seven ABC-DLBCL experimental samples and eight control samples (reactive hyperplasia of the lymph node) were obtained from fresh tissues. The exclusion criteria were expressed as follows: (1) patients with other lymphoid diseases; and (2) patients undergoing chemical treatment. A total of 5974 proteins were identified. P value < 0.05 and multiple expressions were more than 1.2-fold. A total of 131 upregulated and 204 downregulated differentially expressed proteins were identified. Gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis were performed. Protein-protein interaction (PPI) network analysis was conducted. The expression levels of HSP90AB1, GNA13, LAMB2, LAMA5, YWHAZ, and IKBKB were evaluated through PRM and TCGA to validate the accuracy of iTRAQ and liquid chromatography-tandem mass spectrometry results. Results of differential multiple and t-test showed differences in the expression levels of six target proteins between the control and experimental groups. To the best of our knowledge, the present study is the first to identify proteins associated with ABC-DLBCL using iTRAQ technology. Our results provide new insights into the pathogenesis of ABC-DLBCL. The combination of ABC-DLBCL-associated signaling pathway proteins and targeted therapy to reverse drug resistance is of great significance in improving the comprehensive treatment of lymphoma and reducing mortality of affected individuals. The feasibility of the present study is limited due to the number of samples, and future studies are required to determine the function of proteins in ABC-DLBCL development.
Subject(s)
Lymphoma, Large B-Cell, Diffuse/pathology , Transcriptome , Gene Expression Profiling/methods , Humans , Proteomics/methodsSubject(s)
Ear Canal , Ear Neoplasms/pathology , Seminoma/pathology , Adenoma/metabolism , Adenoma/pathology , Adult , Alkaline Phosphatase/metabolism , Antibodies, Monoclonal, Murine-Derived/metabolism , Diagnosis, Differential , Ear Neoplasms/metabolism , Ear Neoplasms/radiotherapy , Ear Neoplasms/surgery , GPI-Linked Proteins/metabolism , Humans , Isoenzymes/metabolism , Lymphoma, Large-Cell, Anaplastic/metabolism , Lymphoma, Large-Cell, Anaplastic/pathology , Male , Mast-Cell Sarcoma/metabolism , Mast-Cell Sarcoma/pathology , Proto-Oncogene Proteins c-kit/metabolism , Seminoma/metabolism , Seminoma/radiotherapy , Seminoma/surgery , Vimentin/metabolism , Young AdultSubject(s)
Ki-1 Antigen/metabolism , Lymphoma, Large-Cell, Anaplastic/pathology , Receptor Protein-Tyrosine Kinases/metabolism , Adolescent , Adult , Aged , Anaplastic Lymphoma Kinase , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Child , Cyclophosphamide/therapeutic use , Diagnosis, Differential , Doxorubicin/therapeutic use , Female , Follow-Up Studies , Humans , Leukocyte Common Antigens/metabolism , Lymphoma, Extranodal NK-T-Cell/metabolism , Lymphoma, Extranodal NK-T-Cell/pathology , Lymphoma, Large B-Cell, Diffuse/metabolism , Lymphoma, Large B-Cell, Diffuse/pathology , Lymphoma, Large-Cell, Anaplastic/drug therapy , Lymphoma, Large-Cell, Anaplastic/metabolism , Male , Melanoma/pathology , Middle Aged , Mucin-1/metabolism , Neoplasms, Muscle Tissue/metabolism , Neoplasms, Muscle Tissue/pathology , Prednisone/therapeutic use , Retrospective Studies , Vincristine/therapeutic use , Young AdultABSTRACT
The KRAS gene mutation is involved in several types of tumors. However, the potential role of the KRAS mutation in human primary and paired metastatic colorectal cancer (CRC) among different nationalities is poorly understood. In the present study, we assessed the relationship between KRAS mutation status and overall survival (OS) and disease-free survival (DFS) in 230 patients with primary and paired metastatic CRC. The KRAS mutation rate in primary CRC tissue was 43.0% (99/230), which was higher than in paired metastatic CRC, which was 31.9% (23/72; P<0.001). Clinicopathologically, the KRAS gene mutation rate was higher in tumors that had infiltrated more deeply (T3, T4) and in lymph node (LN) metastases (N1/N2) (P=0.029 and P=0.010, respectively). The KRAS gene status did not differ between the Han and Uyghur nationalities in both primary and metastatic CRC. In 72 paired cases, the KRAS mutation rate in primary CRC was significantly higher than in metastatic CRC (P<0.001) and in metastatic CRC that had infiltrated more deeply (T3, T4) (P=0.034). In the metastatic cases, the KRAS gene mutation rate was higher in patients aged over 65 years (P=0.035). Specifically, KRAS mutation was correlated with a poorer OS and DFS (P=0.004 and P=0.029, respectively). In our study, 35 patients with wild-type KRAS who received cetuximab targeted therapy had a better DFS than patients with mutant KRAS (P=0.029). The results of the current study demonstrate that the KRAS status is significantly associated with infiltrating LN metastases and the TNM stage in primary CRC. In addition, the results show that the KRAS mutation is significantly more common in primary tumors than in paired metastatic CRC, and the KRAS mutation is correlated with a shorter OS and DFS, as patients with wild-type KRAS who received cetuximab experienced a longer DFS.