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1.
Article in Chinese | WPRIM | ID: wpr-1008805

ABSTRACT

This study comprehensively analyzed the active components of Sanhan Huashi Formula using qualitative and quantitative mass spectrometry techniques, laying the foundation for understanding its pharmacological substance basis. UHPLC-LTQ-Orbitrap-MS and GC-MS technologies were used to analyze and identify the volatile and non-volatile components in Sanhan Huashi Formula. UHPLC-QQQ-MS/MS technology was used to simultaneously determine the content of 27 major active components in the formula. The results showed that 308 major chemical components were identified in Sanhan Huashi Formula, among which 60 compounds were identified by comparing with reference standards, mainly including alkaloids, flavonoids, coumarins, triterpenoid saponins, amino acids, and nucleosides. GC-MS technology preliminarily identified 52 volatile compounds, with γ-eudesmol and β-eudesmol as the main components. The quantitative results demonstrated good linearity(r>0.99) for the 27 active components, indicating the stability, simplicity, and reliability of the established method. Among them, amygdalin, nodakenin, arecoline, ephedrine, and pseudoephedrine had relatively high content and were presumably the main pharmacologically active substances. In conclusion, this study systematically and comprehensively characterized the major chemical components and patterns in Sanhan Huashi Formula, providing a basis for understanding its pharmacological mechanisms and clinical applications.


Subject(s)
Tandem Mass Spectrometry , Chromatography, High Pressure Liquid , Gas Chromatography-Mass Spectrometry , Reproducibility of Results , Drugs, Chinese Herbal/chemistry
2.
Article in Chinese | WPRIM | ID: wpr-1008788

ABSTRACT

This study aims to reveal the endogenous metabolic characteristics of acteoside in the young rat model of purinomycin aminonucleoside nephropathy(PAN) by non-targeted urine metabolomics and decipher the potential mechanism of action. Biochemical indicators in the urine of rats from each group were determined by an automatic biochemical analyzer. The potential biomarkers and related core metabolic pathways were identified by ultra-high performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS) combined with principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA). MetaboAnalyst 5.0 was used to establish the receiver operating characteristic(ROC) curve for evaluating the clinical diagnostic performance of core metabolites. The results showed that acteoside significantly decreased urinary protein-to-creatinine ratio in PAN young rats. A total of 17 differential metabolites were screened out by non-targeted urine metabolomics in PAN young rats and they were involved in phenylalanine metabolism and phenylalanine, tyrosine and tryptophan biosynthesis. Thirtten differential metabolites were screened by acteoside intervention in PAN young rats, and they were involved in phenylalanine metabolism and arginine and proline metabolism. Among them, leucylproline and acetophenone were the differential metabolites that were significantly recovered after acteoside treatment. These pathways suggest that acteoside treats PAN in young rats by regulating amino acid metabolism. The area under the curve of two core biomarkers, leucylproline and acetophenone, were both greater than 0.9. In summary, acteoside may restore amino acid metabolism by regulating endogenous differential metabolites in PAN young rats, which will help to clarify the mechanism of acteoside in treating chronic glomerulonephritis in children. The characteristic biomarkers screened out have a high diagnostic value for evaluating the treatment of chronic glomerulonephritis in children with acteoside.


Subject(s)
Humans , Child , Rats , Animals , Puromycin Aminonucleoside , Metabolomics/methods , Biomarkers/urine , Chromatography, High Pressure Liquid/methods , Acetophenones , Glomerulonephritis , Phenylalanine , Amino Acids
3.
Article in English | LILACS-Express | LILACS | ID: biblio-1507402

ABSTRACT

ABSTRACT PreS/S gene mutations could impact virus secretion, infection and immune evasion. However, the relationship between PreS/S mutations and intrauterine transmission has not yet been clarified. Thus, we aimed to explore the associations between PreS/S gene mutations of HBV isolated from mothers and intrauterine transmission. We analyzed the mutations of PreS/S regions of the HBV genome in mothers with HBV DNA levels ≥ 106 IU/mL whose neonates experienced HBV intrauterine transmission (transmission group, GT) and those whose neonates did not experience intrauterine transmission (control group, GC) analyzed using clone-based sequencing. In total, 206 sequences were successfully amplified, including 98 sequences (from 21 mothers) from GT and 108 sequences (from 20 mothers) from GC of genotype C for mutational analysis. Among the 1203 nucleotides of PreS/S regions, there were 219 (18.20%) base substitutions, of which 103 (47.03%) base mutations caused amino acid changes. F80S, A90V and I68T were mutation hotspots. Mothers in GT had a higher mutation rate of A90V in the PreS1 gene than mothers in GC. The A90V mutation increased the risk of HBV intrauterine transmission after adjusting the maternal age and the mode of delivery (OR = 6.23, 95% CI: 1.18-32.97). Moreover, the area under the ROC curve (AUC) for intrauterine transmission due to A90V and a combination of A90V with the mode of delivery were 0.723 (95% CI: 0.575 to 0.891, P = 0.011) and 0.848 (95% CI: 0.723 to 0.972, P < 0.001), respectively. Mothers with the A90V mutation in the PreS1 gene may be a potential risk factor for HBV intrauterine transmission.

4.
Article in Chinese | WPRIM | ID: wpr-940561

ABSTRACT

ObjectiveIn order to establish a systematic quality evaluation system for Fritillariae Cirrhosae Bulbus adulteration, portable near-infrared (NIR) spectroscopy was used to identify Fritillariae Cirrhosae Bulbus and its adulterants and detect their adulteration quantity. MethodA total of 72 batches of Fritillariae Cirrhosae Bulbus samples were collected and 570 batches of adulterated products (dry bulbs of Fritillaria thunbergii, F. ussuriensis, F. pallidiflora and F. hupehensis, Bulbus Tulipae, flour) were prepared, NIR spectral data of samples were collected by the portable NIR spectrometer. Linear discriminant analysis (LDA) was used to establish the qualitative correction models of Fritillariae Cirrhosae Bulbus-adulterants and adulterants of different categories, partial least squares (PLS) was used to establish the quantitative correction models of adulteration quantity of different kinds of adulterants. ResultThe recognition rates of qualitative analysis model of Fritillariae Cirrhosae Bulbus and its adulterants were 99.49% (calibration set) and 100.00% (validation set), respectively. In different adulterant models, the recognition rates of calibration set and validation set were 70.47% and 73.68%, respectively. Moreover, the correlation coefficients of validation set (R2P) of the six quantitative models of adulteration ratio were 0.840 2 (Fritillariae Cirrhosae Bulbus adulterated with F. thunbergii dry bulbs), 0.960 2 (Fritillariae Cirrhosae Bulbus adulterated with F. ussuriensis dry bulbs), 0.765 7 (Fritillariae Cirrhosae Bulbus adulterated with F. pallidiflora dry bulbs), 0.902 5 (Fritillariae Cirrhosae Bulbus adulterated with F. hupehensis dry bulbs), 0.957 4 (Fritillariae Cirrhosae Bulbus adulterated with Bulbus Tulipae), 0.976 1 (Fritillariae Cirrhosae Bulbus adulterated with flour), the root mean square error of prediction (RMSEP) were 10.948 5, 5.463 9, 13.256 4, 8.549 2, 5.655 3, 4.235 6, respectively. The two qualitative models and six quantitative models showed good prediction performance. ConclusionThe portable NIR spectroscopy can be used to identify Fritillariae Cirrhosae Bulbus and its adulterants in real time, the method is rapid and accurate, which can meet the requirements of nondestructive identification of Fritillariae Cirrhosae Bulbus on site.

5.
Article in Chinese | WPRIM | ID: wpr-886845

ABSTRACT

Objective To investigate status of helicobacter pylori (Hp) infection in Nantong Area and its related factors. Methods A cluster of 1 680 people who underwent a physical examination at a hospital in the Nantong area from June 2020 to February 2021 were selected as the subjects of this survey. All subjects were tested for Hp infection through the 14C-urea breath test and the Hp infection status analyzed. At the same time, the self-filled and interrogative questionnaires made by our hospital were used to collect general data of the research subjects, and then single-factor and multi-factor logistic regression was used to analyze the related factors affecting Hp infection in the physical examination population in Nantong area. Results Among the 1 680 medical examiners investigated in this study, 980 were positive for Hp infection, and the overall positive rate of infection was 58.33%. The results of univariate analysis found that Hp infection was related to the age, drinking, hotness, frequent eating of pickled food, family history of gastric cancer, and chronic gastritis in the physical examination population in Nantong area (P60 years old (OR=3.46, 95%CI: 1.35-8.84), drinking (OR=5.22, 95%CI: 2.79-9.77), addiction to spicy food (OR=5.47, 95%CI: 2.45-9.30), regular consumption of pickled foods (OR=5.28, 95%CI: 3.48-7.92), family history of gastric cancer (OR=4.29, 95%CI: 2.86-76.45), chronic gastritis (OR=5.07, 95%CI: 2.79-9.22) were all related factors affecting Hp infection(P<0.05). Conclusion Positive rate of HP infection in physical examination population in Nantong area is high, and it is related to age, drinking alcohol, spicy food, eating pickled food frequently, family history of gastric cancer, chronic gastritis and other factors. To strengthen the publicity and education of HP infection, establish good eating habits and reduce the risk factors to prevent HP infection in physical examination population in Nantong area.

6.
Article in Chinese | WPRIM | ID: wpr-911570

ABSTRACT

Objective:To investigate the expression of estrogen receptor alpha (ERα) protein and BRAF V600E protein in thyroid papillary carcinoma (PTC) and their relationship with clinical factors of PTC. Methods:The expression of ERα and BRAF V600E protein in 1 105 PTC patients was detected by immunohistochemistry. The relationship among ERα, BRAF V600E protein and clinical factors were analyzed. Results:Positive ERα protein was correlated with maleness (χ 2= 6.087, P=0.001), age< 45 years old (χ 2=5.197, P=0.023) and multifocal tumors (χ 2=4.446, P=0.035). Positive BRAF V600E protein was correlated with positive ERα protein (χ 2=6.209, P=0.013), Hashimoto thyroiditis (χ 2=29.388, P<0.001), no lateral lymph node metastasis (χ 2=6.849, P=0.009) and multifocal tumors (χ 2=9.596, P=0.035). Conclusions:ERα expression is more common in male patients, patients younger than 45 years of age, those with multifocal tumors and positive BRAF V600E protein. BRAF V600E protein may inhibit Hashimoto's thyroiditis, tumor growth and the occurrence of lateral lymph node metastasis, and promote the occurrence of multiple focal tumors.

7.
Article in Chinese | WPRIM | ID: wpr-885980

ABSTRACT

Objective: To observe the efficacy of long-retaining scalp acupuncture plus interactive training in improving upper- extremity dysfunction in cerebral stroke patients. Methods: Ninety-five patients with upper-extremity dysfunction after cerebral stroke were randomized into two groups, with 48 cases in the treatment group and 47 cases in the control group. Conventional internal medicine treatment was offered to both groups. In both groups, Anterior Oblique Line of Vertex-temporal (MS 6, the middle 2/5) and Posterior Oblique Line of Vertex-temporal (MS 7, the middle 2/5) were selected from the same side of the brain lesion (the side apposing to the hemiplegic limb) for scalp acupuncture treatment. In the treatment group, the scalp acupuncture needles were retained for 7 h, in combination with interactive training, while the needles were also retained for 7 h in the control group but without interactive training. Prior to treatment and at 2-week and 4-week treatment, the two groups were scored using the functional test for the hemiplegic upper extremity-Hong Kong (FTHUE-HK) and simplified Fugl-Meyer assessment-upper extremity (FMA-UE). Results: The total effective rate was 97.9% in the treatment group, higher than 74.5% in the control group (P<0.01). The FTHUE-HK score was higher at 2-week and 4-week treatment than before treatment in both groups, presenting statistically significant intra-group differences (all P<0.001); the FTHUE-HK score was higher at 4-week treatment than at 2-week treatment in both groups, presenting statistically significant intra-group differences (both P<0.001). At 2-week and 4-week treatment, the FTHUE-HK score was higher in the treatment group than in the control group, showing significant between-group differences (both P<0.05). During the whole treatment process, the treatment group had higher FTHUE-HK scores compared with the control group, but there was no statistical significance comparing the change of the score between the two groups at 2-week treatment (P>0.05), while the between-group difference in the change of the score was statistically significant at 4-week treatment (P<0.05). The FMA-UE score was higher at 2-week and 4-weeks treatment than before treatment in both groups, presenting statistically significant intra-group differences (all P<0.001); the FMA-UE score was higher at 4-week treatment than at 2-week treatment in both groups, presenting statistically significant intra-group differences (both P<0.001). At 2-week and 4-week treatment, the FMA-UE was higher in the treatment group than in the control group, and the between-group differences were statistically significant (both P<0.01). The FMA-UE score rose gradually with the increase of treatment session, and there was statistical significance comparing the change of the score between the two groups at 2-week and 4-week treatment, respectively (both P<0.05). Conclusion: Long-retaining scalp acupuncture plus interactive training results in more significant efficacy than long-retaining scalp acupuncture alone in improving the upper-limb dysfunction after cerebral stroke and the advantage becomes more notable after 2-week consecutive treatment.

8.
Acta Pharmaceutica Sinica ; (12): 1727-1738, 2021.
Article in Chinese | WPRIM | ID: wpr-881568

ABSTRACT

In the research and development of new drugs, it is very important to investigate the in vitro metabolism of candidate drugs. Traditional models such as liver microsomes have many limitations, while the in vitro model of recombinant human drug metabolizing enzymes is considered as an important and useful approach because of its convenient access, stable activity and low cost. In this study, six major human UDP-glucuronosyltransferases (UGTs) genes (UGT1A1, 1A3, 1A4, 1A6, 1A9 and 2B7) were cloned from human liver cDNA and heterologously expressed in Saccharomyces cerevisiae and baculovirus-infected insect cell. UGT1A1, 1A3, 1A6 and 1A9 were successfully expressed in yeast and showed glucuronidation activity against a variety of different structural types of substrates, but their activities were low. All six UGTs were successfully expressed and exhibited significantly improved glucuronidation activity when Trichopolusia ni cells BTI-TN5B1-4 (High Five) were used as the host. The recombinant human UGTs expressed in insect cells can catalyze the glucuronidation of their specific substrates, and the glucuronidation products were synthesized at milligram-scale with yields of 13%-66% for the first time, of which the structures were identified via MS, 1H NMR, and 13C NMR spectroscopic analysis. Above all, the recombinant human UGTs yeast and insect cell expression systems constructed in this study can be used for in vitro metabolism evaluation in the early stage of new drugs research and development, and also provide a new tool for the synthesis of glucuronide metabolites.

9.
Chinese Journal of Pathophysiology ; (12): 1723-1728, 2017.
Article in Chinese | WPRIM | ID: wpr-662732

ABSTRACT

AIM:To establish a method for obtaining specific cells in solid tumor tissue by sorting of CD11b + myeloid cells in hepatic metastases from colorectal cancer.METHODS:Tumor tissues were prepared into single cell suspension by mechanical method combined with enzyme digestion,and then the CD11 b + myeloid cells were isolated by flow cytometry.The sorted cells were identified by immunocytochemistry.The viability and morphologiy of the sorted cells were evaluated by Giemsa and Typan blue staining.The cell purity was evaluated by flow cytometry.RESULTS:Sufficient numbers of CD11b+cells with high purity were isolated by sorting with flow cytometry from the single cell suspension prepared by mechanical and enzyme digestion.The purity of the cells was confirmed by statistical analysis (P < 0.05).The positive rates of the cells before and after sorting were significantly different (P <0.01).The positive cells were verified by immunocytochemical method.Meanwhile,the sorted cells had complete morphology and good activity.CONCLUSION:The CD11b + myeloid cells in solid tumor tissue can be isolated by flow cytometry from the machine-enzyme digestion suspension with high purity,good activity and complete morphology.

10.
Chinese Journal of Pathophysiology ; (12): 1723-1728, 2017.
Article in Chinese | WPRIM | ID: wpr-660626

ABSTRACT

AIM:To establish a method for obtaining specific cells in solid tumor tissue by sorting of CD11b + myeloid cells in hepatic metastases from colorectal cancer.METHODS:Tumor tissues were prepared into single cell suspension by mechanical method combined with enzyme digestion,and then the CD11 b + myeloid cells were isolated by flow cytometry.The sorted cells were identified by immunocytochemistry.The viability and morphologiy of the sorted cells were evaluated by Giemsa and Typan blue staining.The cell purity was evaluated by flow cytometry.RESULTS:Sufficient numbers of CD11b+cells with high purity were isolated by sorting with flow cytometry from the single cell suspension prepared by mechanical and enzyme digestion.The purity of the cells was confirmed by statistical analysis (P < 0.05).The positive rates of the cells before and after sorting were significantly different (P <0.01).The positive cells were verified by immunocytochemical method.Meanwhile,the sorted cells had complete morphology and good activity.CONCLUSION:The CD11b + myeloid cells in solid tumor tissue can be isolated by flow cytometry from the machine-enzyme digestion suspension with high purity,good activity and complete morphology.

11.
Tianjin Medical Journal ; (12): 1181-1184, 2016.
Article in Chinese | WPRIM | ID: wpr-498751

ABSTRACT

Combined hepatocellular and cholangiocarcinoma (HCC-CC) is a rare primary hepatic neoplasm (PHN) with features of both hepatocellular and biliary differentiation. Hepatitis B and hepatitis C are the major causes of HCC-CC. Surgical treatment is the main therapeutic method for HCC-CC. For patients with unresectable lesions, curative or palliative locoregional therapy is applied, including radiofrequency ablation (RFA), transarterial chemoembolization (TACE) and supportive treatment. Because of the rare occurrence and ambiguous clinical features of HCC-CC, it is most often misdiagnosed with the other two types of primary liver cancer. Thus, the realization of the current progress of combined hepatocellular and cholangiocarcinoma is particularly important for us. This article aims to summarize the epidemiology and clinical futures, the treatment and prognosis, the progress of genetics and molecular analysis of HCC-CC.

12.
Article in Chinese | WPRIM | ID: wpr-473916

ABSTRACT

Objective To explore the antibacterial activity of garlic solution against Campylobacter jejuni,and to provide theoriti-cal basis for further utilization of garlic.Methods Mashed garlic and extracted garlic solution.Antimicrobial susceptibility was de-termined by usig K-B disk diffusion test and broth dilution method.Results The minimal inhibitory concentration(MIC)of garlic solution against campylobacter jejuni was 40%.It showed positive correlation between bacteriostatic effect and concentration of gar-lic solution.Conclusion Garlic solution has strong bacteriostasis function to campylobacter jejuni.

13.
Tianjin Medical Journal ; (12): 946-949,950, 2015.
Article in Chinese | WPRIM | ID: wpr-602450

ABSTRACT

As a new model of pre-cancer, organoid is essential for the basic understanding of tumor characteristic and effective tumor treatment. Organoids derived from prostate play an especially important role in the research of fundamental oncology and anticancer drug screen against prostate cancer. Prostate cancer cell lines and xenografts derived directly from primary human tumors are widely used now as models to study prostate cancer and have proven very valuable. But there are some caveats and shortcomes of these two models that have to be accounted for. Here we outline organoid as a third preclini?cal cancer model which may potentially overcome the shortcomes of cancer cell lines and PDTX. This article aims to summa?rizee recent progress of the role of organoid in prostate cancer research.

14.
Chinese Journal of Epidemiology ; (12): 634-638, 2015.
Article in Chinese | WPRIM | ID: wpr-240034

ABSTRACT

Objective To determine the association between U2-dependent spliceosome related 8 key genes and hepatocellular cancer (HCC).Methods A two-stage case-control study was conducted.Twenty-two candidate tag single nucleotide polymorphisms (taggNPs) were genotyped by TaqMan Openarray assay in a screened population that living in Central China (378 HCC incident cases and 461 controls).Frequencies of 4 SNPs (rs2074733,rs9608886,rs7288947 and rs5994293) showed significant difference between cases and controls in the screened population and then genotyped by TaqMan real-time polymerase chain reaction in the validation Chinese Han population from Beijing (428 cases and 647 controls).Results The rs5994293 in SF3A1 gene showed a significant association with HCC in both screened population and combined population.Subjects with G allele had a lower risk of HCC,compared to those with the TT genotype.OR appeared to be 0.70 (95% CI:0.58-0.84,false discovery rate adjusted P=0.000 5) for the combined population.An additive interaction between smoking,drinking alcohol and rs5994293 TT was observed in HBsAg negative subjects of the combined populations.Conclusion Our results showed an association existing between SF3A1 rs5994293 and HCC.These findings should be confirmed by further independently large-scale population studies and functional analysis.

15.
Chinese Journal of Epidemiology ; (12): 710-713, 2014.
Article in Chinese | WPRIM | ID: wpr-737401

ABSTRACT

Objective To determine the association between U2 small nuclear ribonucleoprotein auxiliary factor 35/65(U2AF35 and U2AF65)and pancreatic cancer(PC). Methods A two-stage analysis case-control study was conducted. Four candidate tag single nucleotide polymorphisms (tagSNPs)were genotyped by Taqman Openarray assay in a screening population living in Central China(298 PC cases and 525 controls). Thereafter,rs310445 in U2AF65 was genotyped by TaqMan real-time polymerase chain reaction(RT-PCR)in a validation Chinese Han population from Beijing (413 cases and 557 controls). Results rs310445 in U2AF65 gene was significantly associated with PC in both screened population and combined population. Subjects with C allele had a higher risk of PC compared to those with the TT genotype,with OR of 1.31(95%CI:1.07-1.60,P=0.010)for the combined population. A synergic effect of smoking and C allele of rs310445 was also observed in the combined population,with Synergic Index of 2.08(95%CI:1.37-2.78) in the combined population. Conclusion Our findings suggested the interaction between smoking and U2AF65 might play a role in PC. These findings should be confirmed by further independently large-scale population studies.

16.
Chinese Journal of Epidemiology ; (12): 710-713, 2014.
Article in Chinese | WPRIM | ID: wpr-735933

ABSTRACT

Objective To determine the association between U2 small nuclear ribonucleoprotein auxiliary factor 35/65(U2AF35 and U2AF65)and pancreatic cancer(PC). Methods A two-stage analysis case-control study was conducted. Four candidate tag single nucleotide polymorphisms (tagSNPs)were genotyped by Taqman Openarray assay in a screening population living in Central China(298 PC cases and 525 controls). Thereafter,rs310445 in U2AF65 was genotyped by TaqMan real-time polymerase chain reaction(RT-PCR)in a validation Chinese Han population from Beijing (413 cases and 557 controls). Results rs310445 in U2AF65 gene was significantly associated with PC in both screened population and combined population. Subjects with C allele had a higher risk of PC compared to those with the TT genotype,with OR of 1.31(95%CI:1.07-1.60,P=0.010)for the combined population. A synergic effect of smoking and C allele of rs310445 was also observed in the combined population,with Synergic Index of 2.08(95%CI:1.37-2.78) in the combined population. Conclusion Our findings suggested the interaction between smoking and U2AF65 might play a role in PC. These findings should be confirmed by further independently large-scale population studies.

17.
Tianjin Medical Journal ; (12): 840-842, 2014.
Article in Chinese | WPRIM | ID: wpr-473808

ABSTRACT

Runx2 is a transcription factor belongs to RUNXX family, and it is one of the important factors involved in expression and participation in regulation of mammary specific genes in the mammary gland. The overexpression is also as-sociated with certain characteristics of breast cancer. This article aims to summarize the recent progress of the role that Runx2 plays in breast cancer.

18.
Tianjin Medical Journal ; (12): 953-955,956, 2014.
Article in Chinese | WPRIM | ID: wpr-601925

ABSTRACT

Metabolic syndrome (MS) and breast cancer are common diseases of women. Triple negative breast cancer (TNBCs) is one type of breast cancer, which is of much attention in recent years. Important components of MS include central obesity, high blood sugar, high triglycerides and low level of high-density lipoprotein (HDL-C), which increased the inci-dence risk of TNBCs. Common biomarkers of MS including insulin, adiponectin and leptin play an important role in the oc-currence and development of breast cancer, especially TNBCs. Insulin-like growth factor-IImRNA binding protein 3 (IMP3, an oncofetal protein) may be TNBCs’new invasive cancer biomarkers. In this paper, the research progress on the relation-ship between MS and TNBCs is reviewed.

19.
Chinese Journal of Epidemiology ; (12): 710-713, 2014.
Article in Chinese | WPRIM | ID: wpr-348588

ABSTRACT

<p><b>OBJECTIVE</b>To determine the association between U2 small nuclear ribonucleoprotein auxiliary factor 35/65 (U2AF35 and U2AF65) and pancreatic cancer (PC).</p><p><b>METHODS</b>A two-stage analysis case-control study was conducted. Four candidate tag single nucleotide polymorphisms (tagSNPs) were genotyped by Taqman Openarray assay in a screening population living in Central China (298 PC cases and 525 controls). Thereafter, rs310445 in U2AF65 was genotyped by TaqMan real-time polymerase chain reaction (RT-PCR) in a validation Chinese Han population from Beijing (413 cases and 557 controls).</p><p><b>RESULTS</b>rs310445 in U2AF65 gene was significantly associated with PC in both screened population and combined population. Subjects with C allele had a higher risk of PC compared to those with the TT genotype, with OR of 1.31 (95%CI:1.07-1.60, P = 0.010) for the combined population. A synergic effect of smoking and C allele of rs310445 was also observed in the combined population, with Synergic Index of 2.08 (95% CI:1.37-2.78) in the combined population.</p><p><b>CONCLUSION</b>Our findings suggested the interaction between smoking and U2AF65 might play a role in PC. These findings should be confirmed by further independently large-scale population studies.</p>


Subject(s)
Aged , Female , Humans , Male , Middle Aged , Case-Control Studies , Genotype , Nuclear Proteins , Genetics , Pancreatic Neoplasms , Genetics , Polymorphism, Single Nucleotide , Ribonucleoproteins , Genetics , Risk Factors , Smoking , Splicing Factor U2AF
20.
Chinese Medical Journal ; (24): 1576-1580, 2012.
Article in English | WPRIM | ID: wpr-324933

ABSTRACT

<p><b>BACKGROUND</b>While the incidence of paroxysmal nocturnal hemoglobinuria (PNH) is relatively high in Northern China, the exact mechanism of the disease remains unknown. Immunoregulatory cytokine polymorphisms can directly regulate the expression levels of cytokines, which play a crucial role in many diseases. The purpose of this study was to study cytokine gene single nucleotide polymorphisms (SNPs) and the correlated cytokine expression levels in relationship to the PNH pathogenesis.</p><p><b>METHODS</b>Peripheral blood samples were collected from 30 PNH patients and 40 healthy donors; all of the samples were collected from the Han people of Northern China. Eight SNP loci in five cytokine genes, including tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), transforming growth factor-beta (TGF-β), interleukin-6 (IL-6), and IL-10, and aplastic anemia (AA) were assessed. TNF-a, TGF-b, IFN-g, IL-6, and IL-10 were analyzed by sequence-specific primer polymerase chain reaction (PCR-SSP). The plasma protein levels of TNF-a, TGF-b, and IFN-g were assessed by an ELISA.</p><p><b>RESULTS</b>The PNH patients had a lower frequency of the TC/GG genotype of the TGF-b gene (P < 0.01) and a higher frequency of the C allele in the TGF-b gene (+10) compared to the controls (P < 0.05). The predominant genotype of the +874 locus of the IFN-g gene was TA in the PNH patients, while that in the predominant genotype was AA in the control group and was statistically significant (P < 0.001). The frequency of the T allele in the IFN-g gene was dramatically higher in the PNH patients than in the controls (P < 0.05). The PNH patients had a reduced frequency of the GC and CC genotypes, as well as the C allele at locus -174 of the IL-6 gene compared to the controls (P < 0.01). In addition, the plasma concentrations of TNF-a, TGF-b, and IFN-g were significantly higher in the PNH group compared to the control group (P < 0.01).</p><p><b>CONCLUSIONS</b>Expression levels of the TNF-a, TGF-b, and IFN-g cytokines play an important role in PNH. The GC and CC genotypes, as well as the C allele of the IL-6 gene may protect the Han people of Northern China against PNH. Additionally, the TC/GG genotype of the TGF-b gene may be the protective allele. In contrast, the TA genotype and the T allele for the IFN-g gene, as well as the C allele of TGF-b may be susceptible to PNH. However, SNPs in the TNF-a and IL-10 genes did not correlate with PNH development. Alternatively, the increased plasma concentrations of TNF-a, TGF-b, and IFN-g in PNH patients may also be related to PNH development.</p>


Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Alleles , Anemia, Aplastic , Genetics , Asian People , China , Cytokines , Blood , Genetics , Enzyme-Linked Immunosorbent Assay , Genotype , Hemoglobinuria, Paroxysmal , Blood , Genetics , Interferon-gamma , Blood , Genetics , Interleukin-10 , Blood , Genetics , Interleukin-6 , Blood , Genetics , Polymorphism, Genetic , Genetics , Polymorphism, Single Nucleotide , Genetics , Transforming Growth Factor beta , Genetics , Tumor Necrosis Factor-alpha , Blood , Genetics
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