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1.
Acta Pharmaceutica Sinica ; (12): 2218-2225, 2023.
Article in Chinese | WPRIM | ID: wpr-999132

ABSTRACT

The most toxic DNA damage is DNA double strand breaks (DSBs), which are mainly repaired by non-homologous end joining (NHEJ). DNA-dependent protein kinase (DNA-PK) belongs to phosphatidylinositol-3-kinase-related protein kinase family (PIKK) and plays a key role in NHEJ. DNA-PK is overexpressed in a variety of cancer cells and is related to the occurrence, development and drug resistance of malignant tumors. In this article, the representative DNA-PK inhibitors with anticancer effects are reviewed, in order to provide a reference to discovery novel DNA-PK inhibitors.

2.
Article in Chinese | WPRIM | ID: wpr-1015647

ABSTRACT

β-Thalassemia caused by abnormal coding of the β-globin gene is the most common hemoglobinopathy in many Asian countries. The in-depth study of the molecular basis and epigenetic mechanism of globin gene expression is the key to explore a new treatment for thalassemia. In this study, FAIRE (formaldehyde-assisted isolation of regulatory elements), 3C (chromosome conformation capture) and ChIP (Chromatin Immunoprecipitation) were used to investigate the three-dimensional interaction network of β-globin family gene loci and the molecular mechanism of functional regulation of gene expression during rapamycin-induced chromatin remodeling in CD4+ T cells. The results showed that the opening degree of globin gene chromatin, the interaction frequency between the gene promoter region and the regulatory element LCR (Locus control regions), and the enrichment efficiency of CTCF (CCCTC-binding factor) in the gene promoter region changed differently during the change of rapamycin treatment concentration from low to high, which led to the same change trend of the gene expression pattern. At the 10 nmol/ L concentration, chromatin accessibility and gene expression decreased (P < 0. 05). At 20 nmol/ L and 50 nmol/ L concentrations, chromatin accessibility increased and gene expression was up-regulated (P < 0. 05). In this study, the molecular mechanism of gene expression regulation of the β-globin family was expounded through this dynamic change process. Our work provides a theoretical and clinical practice basis for clinical precision treatment.

3.
Article in Chinese | WPRIM | ID: wpr-1015974

ABSTRACT

Krüppel-like factor 7 (KLF7) is a negative regulator of adipogenesis, whereas hypoxia-inducible factor 1 (HIF1) promotes anoxic-induced adipose tissue development in mammals. Our previous ChIP-seq analysis showed that one of the KLF7 binding peaks was present upstream of hypoxia-inducible factor 1 alpha (HIF1α), indicating that KLF7 may regulate HIF1α transcription. For this purpose, ChIP-PCR was used to verify ChIP-seq results, which showed that KLF7 directly bound to the HIF1α upstream region. Dual luciferase reporter and qRT-PCR results showed that KLF7 overexpression significantly decreased the luciferase reporter activity of HIF1α (- 4 432/- 4 182) (P < 0. 01) and inhibited HIF1α expression. After the deletion of KLF7 binding motif “TGCGCAGCAA” (- 4 300/-4 290) predicted by bioinformatics, the luciferase reporter activity of HIF1α (-4 432/-4 182) was significantly enhanced compared with wild-type plasmid (P<0. 01). Furthermore, Northeast Agricultural University broiler lines divergently selected for abdominal fat content (NEAUHLF) at the age of 1-7 weeks from the 19

4.
Chinese Herbal Medicines ; (4): 351-358, 2021.
Article in Chinese | WPRIM | ID: wpr-953644

ABSTRACT

Objective: To study the therapeutic effect of Huoxue Tongluo Decoction (HXTLD) on erectile dysfunction caused by ischemic stroke and identify the mechanisms involved. Methods: Network pharmacology was used to predict the key active ingredients and targets of HXTLD. Surgical methods were used to create a rat model of ischemic stroke. The rats were then given a suspension of HXTLD by ig administration. Erectile function was evaluated by Apomorphine (APO) induction. Real-time fluorescence quantitative reverse transcription-polymerase chain reaction (Real-time PCR) and Western blotting were used to detect the expression of related mRNAs and proteins in rat penile corpus cavernous tissue and brain tissue. Hematoxylin & Eosin (HE) staining was used to investigate structural changes in the penile cavernous tissue. Results: Network pharmacology showed that tumor necrosis factor (TNF), nitric oxide synthase 3 (eNOS), and vascular endothelial growth factor (VEGF) were the key targets of HXTLD in the treatment of erectile dysfunction caused by ischemic stroke. Experimental studies showed that HXTLD improved erectile dysfunction caused by ischemic stroke. HE results showed that HXTLD improved the structure of the corpus cavernosa. HXTLD also inhibited the expression of TNF and VEGF proteins in penile tissue (P < 0.05) and enhanced the expression of eNOS protein in penile tissue (P < 0.05). Conclusion: HXTLD improved the erectile function of rats with erectile dysfunction caused by ischemic stroke by regulating the mRNA and protein levels of TNF, eNOS and VEGF.

5.
Article in English | WPRIM | ID: wpr-1010491

ABSTRACT

We investigated the value of autoantibodies as biomarkers of chronic graft-versus-host disease (cGVHD) by analyzing the autoantibody profiles of 65 patients (34 cGVHD and 31 non-cGVHD) surviving longer than three months after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Autoantibodies to at least one antigen were detected in 45 patients (70.8%), with multiple autoantibodies detected in 30 patients (46.2%). Antinuclear antibodies (ANAs) were the most frequently detected autoantibodies, with a significantly higher prevalence in non-cGVHD patients and cGVHD patients than that in healthy controls (HCs). ANA-nucleolar (ANA-N) was the main immunofluorescence pattern of ANA-positivity in both the non-cGVHD and cGVHD groups. There was a higher prevalence of anti-Ro52-positivity in non-cGVHD and cGVHD patients than in HC. Liver cGVHD was significantly associated with anti-Ro52-positivity. However, cGVHD activity and severity were not associated with the presence of autoantibodies. Similarly, there were no significant differences in overall survival or relapse among the four groups of patients expressing autoantibodies. Our results suggest that autoantibodies have limited value in predicting cGVHD.


Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Antibodies, Antinuclear/blood , Autoantibodies/blood , Biomarkers/blood , Chronic Disease , Graft vs Host Disease/diagnosis , Hematopoietic Stem Cell Transplantation/mortality , Recurrence , Transplantation, Homologous
6.
Article in English | WPRIM | ID: wpr-847007

ABSTRACT

We investigated the value of autoantibodies as biomarkers of chronic graft-versus-host disease (cGVHD) by analyzing the autoantibody profiles of 65 patients (34 cGVHD and 31 non-cGVHD) surviving longer than three months after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Autoantibodies to at least one antigen were detected in 45 patients (70.8%), with multiple autoantibodies detected in 30 patients (46.2%). Antinuclear antibodies (ANAs) were the most frequently detected autoantibodies, with a significantly higher prevalence in non-cGVHD patients and cGVHD patients than that in healthy controls (HCs). ANA-nucleolar (ANA-N) was the main immunofluorescence pattern of ANA-positivity in both the non-cGVHD and cGVHD groups. There was a higher prevalence of anti-Ro52-positivity in non-cGVHD and cGVHD patients than in HC. Liver cGVHD was significantly associated with anti-Ro52-positivity. However, cGVHD activity and severity were not associated with the presence of autoantibodies. Similarly, there were no significant differences in overall survival or relapse among the four groups of patients expressing autoantibodies. Our results suggest that autoantibodies have limited value in predicting cGVHD.

7.
Article in Chinese | WPRIM | ID: wpr-496606

ABSTRACT

Objective To investigate the value of 18F-FDG PET/CT in the phasing and grading of renal cell carcinoma (RCC) complicated with vena cava tumor thrombus (VCTT).Methods From December 2011 to September 2015,a total of 72 patients (52 males,20 females,age:36-74 years) were enrolled in this retrospectively study.All patients underwent 18F-FDG PET/CT and contrast-enhanced CT studies,and were diagnosed as RCC.The RCC patients combined with VCTT were classified by Mayo-level.Wilcoxon rank sum test was used to compare the grading of VCTT by PET/CT and contrast-enhanced CT.NM staging on abdominal area level was performed and the results were compared with x2 test.Results VCTT was identified in 18 RCC patients and the grading results by PET/CT were as follows:9 cases in Level 0,4 cases in Level Ⅰ,2 cases in Level Ⅱ,1 case in Level Ⅲ,and 2 cases in Level Ⅳ.When evaluated by PET/CT,20 cases were in N0M0,21 were in N1M0,9 were in N0M1,and 22 were in N1M1.NM staging results by contrast-enhanced CT were as follows:50 cases in N0M0,10 in N1M0,10 in N0M1,and 2 in N1M1.In addition,2 N1 and 2 M1 were found by the whole body PET/CT.The classification results of VCTT and staging of abdominal level by PET/CT were significantly better than those by contrast-enhanced CT (z=-2.462,P<0.05;x2=32.806,P<0.01).Conclusion 18F-FDG PET/CT is not only valuable for detecting primary RCC and local metastasis,but also useful for finding where the VCTT extends,which is conducive to therapeutic planning and further clinical treatment.

8.
Acta Pharmaceutica Sinica ; (12): 392-398, 2014.
Article in Chinese | WPRIM | ID: wpr-245071

ABSTRACT

Paracetamol was used as a model drug in this study to investigate the synergetic effects of lipid coating and beta-cyclodextrin (beta-CD) inclusion for masking the bitter taste of poorly soluble drugs. To control the concentration as low as possible of the free drug which produced a bitter taste, a kinetic model was established to calculate the drug distribution theoretically among the free drug in medium, lipid coated particles and molecular inclusion on the basis of the preparation and characterization of the lipid microspheres, so as to select the proper amount of beta-CD. Finally, the synergetic drug delivery systems were prepared and characterized by 1H nuclear magnetic resonance (1H NMR), molecular simulation and the electronic tongue. As a result, the drug release rate constant (k) of the lipid microspheres coated with octadecanol was determined as 0.001 270 s(-1). Then, the synergetic drug delivery systems were prepared with the ratio of 6.74 : 1 (w/w) for beta-CD and paracetamol. The chemical shift values for the fingerprint peaks of paracetamol all increased and hydrogen bonds were formed between the oxygen on the phenolic hydroxyl group, the nitrogen on the imino in paracetamol and the hydrogens on the hydroxyl groups in beta-CD. The results tested by the electronic tongue indicated that the paracetamol, lipid microspheres, beta-CD inclusion and their mixture showed different taste characteristics, with the bitterness order of the synergetic drug delivery systems approximately lipid microspheres < beta-CD inclusion < paracetamol, which confirmed the synergetic taste masking effects of lipid coating and beta-CD molecular inclusion. In summary, the synergetic taste masking was jointly achieved through the retard of the drug release by the lipid coating and the inclusion of the free paracetamol by beta-CD through hydrogen bonds.


Subject(s)
Acetaminophen , Chemistry , Administration, Oral , Drug Delivery Systems , Electrical Equipment and Supplies , Electrochemical Techniques , Methods , Hydrogen Bonding , Kinetics , Lipids , Chemistry , Microspheres , Solubility , Taste , beta-Cyclodextrins , Chemistry
9.
Article in Chinese | WPRIM | ID: wpr-589138

ABSTRACT

Objective To study the inhibitory effects of Probucol on the expressions of serum promatrix metalloproteinase-2(pro-MMP-2) and matrix metalloproteinase-2(MMP-2) in patients with coronary heart disease(CHD).Methods The levels of serum Pro-MMP-2 and MMP-2 were detected by zymograph and total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C)were measured by enzyme method in 30 CHD patients before and after treatment with Probucol.Results After treatment of Probucol,the expression levels of pro-MMP-2,MMP-2,TC and LDL-C in serum were decreased than those before treatment,respectively;there were obvious differences of various indexes mentioned above between before and after treatment(P0.05).Conclusion Probucol can inhibit the expressions of pro-MMP-2 and MMP-2 in serum as same as TC and LDL-C.Probucol,as one of TIMPs,may be applied to stabilize plaque..

10.
Chinese Journal of Epidemiology ; (12): 359-361, 2006.
Article in Chinese | WPRIM | ID: wpr-233951

ABSTRACT

<p><b>OBJECTIVE</b>Since males are at higher risk of cardiovascular diseases than females, the aim of the study was to examine whether there is an association between BP and a polymorphic Hind III biallelic marker in nonrecombining region of Y chromosome in essential hypertension in Tangshan district in China.</p><p><b>METHODS</b>In the study, 225 patients with essential hypertension and 187 healthy people were enrolled into this study as control group. DNA was extracted from white blood cell. Segments of polymorphic Hind III restriction site of the Y chromosome were amplified from DNA by polymerase chain reaction (PCR). PCR products were restricted with 10 U of Hind III for a night at 37 degrees C. The digested products were subjected to electrophoresis in 3% agarose gels, and stained with ethidium bromide.</p><p><b>RESULTS</b>We amplified 178 controls (95.2%) and 216 essential hypertensive patients (96.0%) successfully. Hind III(-) genotype was found in 45.8% of the men in essential hypertension and in 32.0% of the men in the controlled group. The Hind III(-) genotype was significantly higher than that in the controls (chi2 = 7.782, P = 0.007). However, the Hind III(+) genotype was lower in SBP (133.16 mm Hg +/- 21.60 mm Hg vs. 143.58 mm Hg +/- 24.16 mm Hg, P < 0.001), DBP (82.82 mm Hg +/- 11.72 mm Hg vs. 86.82 mm Hg +/- 12.65 mm Hg, P = 0.001), pulse pressure (50.34 mm Hg +/- 14.31 mm Hg vs. 56.76 mm Hg +/- 14.20 mm Hg, P < 0.001) and mean arterial pressure (99.59 mm Hg +/- 14.19 mm Hg vs. 105.74 mm Hg +/- 15.31 mm Hg, P < 0.001) than the Hind III(-) genotype.</p><p><b>CONCLUSION</b>Polymorphic Hind III restriction site of the Y chromosome seemed to be associated with essential hypertension in Tangshan district in China.</p>


Subject(s)
Humans , Male , Case-Control Studies , China , Chromosomes, Human, Y , Genetics , Genetic Predisposition to Disease , Hypertension , Genetics , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Site-Specific DNA-Methyltransferase (Adenine-Specific) , Metabolism
11.
Article in Chinese | WPRIM | ID: wpr-589972

ABSTRACT

Objective To investigate the alteration and significance of inflammatory factors in hypertension patients complicated with acute myocardial infarction(AMI).Methods Eighty seven AMI patients were grouped as normotensive group(n=43) or hypertensive group(n=44),25 healthy subjects served as control.Plasma level of IL-1?,IL-6,IL-8,TNF-? and IFN-? were determined at admission of hospitalization,24 h,48 h,5 d,7 d and 14 d after myocardial infarction using ELISA method.Results 1)Compared with the control group,the level of all inflammatory markers were elevated significantly in 2 weeks after myocardial infarction and showed a pattern of dynamic changes.2)Compared with normotensive group,IL-6 in hypertensive group was increased more significantly on 5th day(P=0.019) to 7th day(P=0.005)after AMI.Conclusion Inflammation was involved in the course of AMI since the early stage.Hypertension seems to exaggerated the inflammatory reaction after myocardial infarction.

12.
Article in Chinese | WPRIM | ID: wpr-545654

ABSTRACT

Objective:To establish a human monocyte cell line U937 stably expressing CD200.Methods:The eukaryotic expression vector pcDNA3-CD200 containing human CD200 cDNA and vector pcDNA3 were transferred into human monocyte U937 cell line by electrotransfer.These two cell lines were selected by G418, and the selected cell lines were subcultured. U937 cell line was enclosed as control group.The expression of CD200 mRNA and protein was detected by RT-PCR and flow cytometry.Results:After G418 selection,U937 cell line in control group was died, and the cell lines transferring pcDNA3 and recombined pcDNA3-CD200 were subcultured over 30 generations.The CD200 mRNA expression in pcDNA3-CD200 group was confirmed with RT-PCR.The CD200 expression in U937-pcDNA3-CD200,U937-pcDNA3 and U937 were 77.20%,3.20% and 2.10%,compared with other two groups (F=133 996.40,P0.05).Conclusion:Our study provides foundation for mechanism of action for CD200 in future.The human monocyte series U937 cell line that expresses CD200 protein stably is established successfully by gene transfection method.

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