Publications by authors named "Yan-Ping Ma"

73 Publications

Leonurine-Repressed miR-18a-5p/SOCS5/JAK2/STAT3 Axis Activity Disrupts CML malignancy.

Front Pharmacol 2021 16;12:657724. Epub 2021 Apr 16.

Department of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, China.

Leonurine, an active natural alkaloid compound isolated from Herba leonuri, has been reported to exhibit promising anticancer activity in solid tumors. The aim of this study was to explore whether leonurine is able to inhibit chronic myeloid leukemia (CML) malignancy. Here, we found that leonurine dose dependently inhibited the proliferation, migration, colony formation and promoted apoptosis of CML cells. Furthermore, leonurine markedly reduced CML xenograft growth . Mechanically, leonurine upregulated SOCS5 expression, thus leading JAK2/STAT3 signaling suppression. Silencing of SOCS5 by its siRNA abrogated the effect of leonurine on CML cells, demonstrating that SOCS5 mediates the anti-leukemia effect of leonurine. Notably, we observed that miR-18a-5p was remarkably increased in CML cells. Treating CML cells with leonurine significantly decreased miR-18a-5p expression. Moreover, we found miR-18a-5p repressed SOCS5 by directly targeting its 3'-UTR. miR-18a-5p downregulation induced by leonurine reduced the biological activity of CML cells by relieving miR-18a-5p repression of SOCS5 expression. Taken together, leonurine exerts significant anti-leukemia efficacy in CML by regulating miR-18a-5p/SOCS5/JAK2/STAT3 axis.
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http://dx.doi.org/10.3389/fphar.2021.657724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087248PMC
April 2021

[Responses of soil nitrogen to the transition from desert grassland to shrubland in eastern Ningxia, China].

Ying Yong Sheng Tai Xue Bao 2021 Apr;32(4):1230-1240

School of Agriculture, Ningxia University, Yinchuan 750021, China.

In this study, desert grassland, grassland edge, shrubland edge, shrubland were selec-ted as four transition sites in a nearly 30 years typical desert grassland-shrubland mosaic formed by anthropogenic shrub introduction. Soil properties and soil microbial characteristics under vegetation patches and bare interspace in each site were investigated to examine the responses of soil nitrogen to the desert grassland-shrubland state transition. It was shown that the aboveground biomass increased with transition from desert grassland to shrubland. Annual herbs increased largely with the introduction of shrubs. Soil moisture, microbial biomass and total nitrogen and carbon decreased with the transition. The abundance of microogranisms was lower in grassland edge and shrubland edge, and then increased in shrubland, which was slightly higher than that of desert grassland. With respect to nitrogen, nitrate content reached the highest level of 28.45 mg N·kg and ammonium reached the lowest level of 4.81 mg N·kg in shrubland, which were significantly increased by 52.3% and decreased by 10.4% compared with desert grassland. In addition, soil moisture and microbial biomass nitrogen was positively correlated across all sites. The relationship between mine-ralized nitrogen and soil moisture was non-linear, as they were positively correlated in desert grassland and grassland edge, but negatively correlated in shrubland edge and shrubland. During the 30-year transition from desert grassland to shrubland, our results showed that soil total nitrogen and microbial biomass nitrogen were significantly decreased, but mineralized nitrogen, especially for nitrate, significantly increased over time, indicating that soil nitrification was inhibited in desert grassland but accelerated in shrubland.
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http://dx.doi.org/10.13287/j.1001-9332.202104.008DOI Listing
April 2021

[Clinical Characteristics and Survival Analysis of Patients with IgD Multiple Myeloma].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Apr;29(2):547-552

Department of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China.

Objective: To explore the clinical features, prognosis and survival of patients with IgD multiple myeloma (MM).

Methods: The clinical data of 20 patients with IgD MM was analyzed retrospectively. The prognostic factors and survival analysis was carried out. We summarized their clinical characteristics. The survival analysis was carried out by Kaplan-Meier method, and the prognostic factor were analyzed by using log-rank test for single factor analysis of observation index. Variables of P<0.15 in single factor analysis were enrolled in multifactor cox regression analysis.

Results: IgD MM patients accounted for 4.3% of all MM patients in the same period, among which 80% were male, the median age of patients was 57.5(35-77) years old, 90% of the patients belongs to λ light chain type. At the time of diagnosis, 18 patients (90%) were in DS-Ⅲ stages, while 10 patients were in ISS-Ⅲ stage. The first clinical manifestations were fatigue, bone pain, kidney function impairment, anemia (Hb<100 g/L) in 14 cases (70%), 12 cases (60%) with osteolytic bone destruction≥3, combined with renal impairment in 8 cases (40%), and elevated blood calcium in 11 cases (51.4%). In only 5 patients the ratio of albumin to globntin was inverted, hypoalbuminemia accounted for 40%, and globulin increase accounted for only 15%. FISH results showed that the positive rate of 1q21 amplification (50%) was the highest, and it was easy to occur at the same time as other cytogenetic abnormalities. Extramedullary infiltration occurred in 4 cases (20%). The analysis of prognostic factors showed that only the increase of lactate dehydrogenase (LDH) level was an independent poor prognostic factor for IgD MM patients. Extramedullary infiltration and various cytogenetic abnormalities were found in 2 IgD MM patients with primary drug resistance, suggesting that extramedullary infiltration and various cytogenetic abnormalities may be prognostic factors, but the difference was not statistically significant, Which maybe related to the small sample size. All 20 patients were treated with bortezomib-containing regimen, of which 19 patients were evaluated, 17 patients (89.4%) showed effective, including CR+VGPR (52.6%), PR (31.5%), MR (5.3%), 2 patients primary drug resistance. The median PFS and OS was 9.5 and 10.5 months, respectively.

Conclusion: IgD MM is a rare and invasive disease. Increased LDH is an independent prognostic factor. Bortizomib-containing regimen can improve the prognosis of IgD MM patients.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2021.02.038DOI Listing
April 2021

[Clinical Characteristic, Prognosis and Treatment Outcome of Elderly Multiple Myeloma Patients with Impaired Renal Function].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Feb;29(1):145-151

Department of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China.

Objective: To explore the risk factors, prognosis and curative effect of elderly patients with MM renal damage.

Methods: 118 patients with primary elderly MM treated in our hospital from January 2011 to December 2018, were enrolled analyzed retrospectively. The clinical characteristics and prognosis of renal function impairment group (RI group) and normal renal function group (non-RI group) were compared. The difference of renal efficacy and survival benefit between the patients treated with bortezomib, thalidomide (combination group) and chemotherapy regimen containing only one of them (single drug group) in RI group was compared.

Results: Univariate analysis showed that DS stage, pulmonary infection, uric acid, β microglobulin and leukocyte in RI group were higher than those in non-RI group, but hemoglobin was lower than that in non-RI group (P<0.05). Multivariate logistic regression analysis showed that β microglobulin was the independent risk factor for renal damage in elderly patients with MM. Kaplan-Meier method showed that the OS and PFS in RI group were significantly lower than those in non-RI group (P<0.05). The renal efficacy in the combined treatment group was significantly better than that of the single drug group (P<0.05), and it could bring benefit to the PFS of the elderly patients with MM renal damage (P<0.05).

Conclusion: The prognosis of elderly MM patients with impaired renal function is poor. The prognosis of these patients can be improved by selecting chemotherapy regimen containing bortezomib and thalidomide at the same time, and monitoring, controlling all kinds of risk factors actively.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2021.01.023DOI Listing
February 2021

[Clinical Analysis of 46 Cases of Multiple Myeloma with Extramedullary Disease].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Feb;29(1):115-121

Department of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China,E-mail:

Objective: To investigate the effect of clinical baseline data on prognosis in patients with multiple myeloma (MM) complicated by extramedullary disease (EMD).

Methods: The clinical data of 46 MM patients with EMD were retrospectively analyzed. The clinical data and survival prognosis of MM patients in primary EMD group and recurrent EMD group were analyzed. The classified baseline data were expressed by the number of cases (percentage), the χ test was used to compare the two classification data groups. The OS and PFS curves were drawn by multiplication positive limit method (Kaplan-Meier). Log-rank test was used for the univariate analysis of prognosis, and COX proportional risk regression model was used for the multiple factors of prognosis.

Results: β microglobulin≥2.7 g/L, lactic dehydrogenase≥250 U/L, serum calcium≥2.75 mmol/L, plasma cells in bone marrow≥60% were the poor prognostic factors for PFS. Serum calcium≥2.75 mmol/L and the plasma cells in bone marrow≥60% were the poor prognostic factors for OS. Multivariate regression analysis enroling the statistically significant factors in univariate analysis baseline date in factors in showed that plasma cell level≥60% in bone marrow was independent poor prognostic factors for PFS, and serum calcium≥2.75 mmol/L was an independent poor prognostic factor for OS. The IgG type is the most common type of MM complicated by EMD. The remission depth of primary EMD group≥VGPR was lower than that of recurrent EMD group, and there was significant difference between the two groups (P<0.05), and the median OS time of patients with primary EMD group was shorter than that of patients with recurrent EMD group, the difference was statistically significant (P<0.05). The 3-year survival rates of primary EMD group and recurrent EMD group were 10.0% and 34%, respectively, there was no significant difference between the two groups (P>0.05). The 5-year survival rate was 0 and 20%, respectively, there was significant difference between the two groups (P<0.05).

Conclusion: The remission depth of primary EMD group≥VGPR is lower than that of recurrent EMD group,and the OS time of patients in primary EMD group is shorter than that in recurrent EMD group. Bortezomib-based chemotherapy could not improve the prognosis of patients with primary EMD and recurrent EMD, and the prognosis of patients with primary EMD is even worse.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2021.01.019DOI Listing
February 2021

[Effect of eIF4E on Autophagy of CD138 Cells in Multiple Myeloma].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2019 Oct;27(5):1556-1560

Shanxi Medical University;Taiyuan 030000, Shanxi Province,China,Department of Hematology,The Second Affiliated Hospital of Shanxi Medical University,Taiyuan 030000, Shanxi

Objective: To investigate the effect of eukaryotic translation initiation factor 4E(eIF4E) on the autophagy of CD138 plasma cells in multiple myeloma(MM).

Methods: Multiple myeloma CD138 plasma cells were treated with eIF4E inhibitor 4EGI, the changes of autophagy-related factors LC3-II and Beclin1 were detected by fluorescent quantitative PCR and Western blot, the changes of cell proliferation inhibition were detected by MTT assay, and cell apoptosis was detected by flow cytometry.

Results: Quantitative fluorescence PCR showed that after treatment of myeloma cells with 4EGI, the expression levels of LC3-II and Beclin1 mRNA gradually increased with the enhancomer of 4EGI concentration and the prolongation of action time, and the differences were statistically significant (48 h: LC3-Ⅱ,r=0.942, Beclin1,r=0.952; 80 μg/ml: LC3-Ⅱ,r=0.966, Beclin1,r=0.998); Western blot showed that with the enhancement of 4EGI concentration, the expression of LC3-II and Beclin1 protein gradually increased(LC3-Ⅱ,r=0.923, Beclin1,r=0.977); CCK-8 showed that the inhibition rate of cells gradually increased (r=0.996); the apoptotic rate of 4EGI-treated groups (23.23±4.47, 7.59±1.67, 2.03±0.19) was significantly different from that of control group (0.03±0.04) (P<0.05).

Conclusion: The inhibition of eIF4E can activate the autophagy of CD138 plasma cells in multiple myeloma and induce the death of myeloma cells.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2019.05.029DOI Listing
October 2019

[Expression Analysis and Epigenetics of MicroRNA-28-5p in Multiple Myeloma].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2019 Oct;27(5):1540-1547

Department of Hematology,The Second Hospital of Shanxi Medical University,Taiyuan 030001,Shanxi Province,China,E-mail:

Objective: To investigate the expression, mechanism and methylation level of miR-28-5p in multiple myeloma (MM), so as to provide the expirement basis for searching new targeted therapy.

Methods: RT-PCR was used to detect the expression levels of miR-28-5p and potential target CCND1 in CD138 cells of the patients with MM and bone marrow mononuclear cells of patients with iron defficiency anemia(IDA) as control, Methylation-specific PCR(MSP) was used to detect methylation levels of CpG island in LPP/miR-28-5p promoter region and the correlation with other clinical indicators was analyzed. The 5-aza-2'-deoxycytidine (5-Aza-dC,DAC) was used to treat MM cell line U266; after drug treatment,MSP was used to analyze the methylation status of the CpG islands in LPP/miR-28-5p promoter; the qPCR was used to detect the expression levels of miR-28-5p,and the regulatory mechanism of miR-28-5p expression was explored furtherly.

Results: The methylation level of CpG island in LPP/miR-28-5p promoter region of MM patients was significantly higher than that of IDA patients. The relative expression level of miR-28-5p in MM patients was significantly lower than that of IDA patients. The relative expression level of miR-28-5p in newly diagnosed MM patients was higher than that in relapsed/progressive patients. The miR-28-5p target CCND1 was expressed at high levels in MM patients with LPP / miR-28-5p methylation, the expression level of miR-28-5p in MM patients correlated with β-MG concentration. 5-aza-dc could significantly inhibit the growth of U266 cell line, arrest the cell cycle in G phase, inhibit the biosynthesis of cellular RNA and protein and promote cell apoptosis. At the same time, up-regulation of miR-28-5p expression was found.

Conclusion: The expression of miR-28-5p in MM patients is regulated by methylation of CpG islands in the promoter region of the genome.miR-28-5p may act as a tumor suppressor gene, and its low expression may be involved in the occurrence and development of MM, suggesting that miR-28-5p may become a new target for the treatment of MM.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2019.05.027DOI Listing
October 2019

High Expression Levels of Long Noncoding RNA Small Nucleolar RNA Host Gene 18 and Semaphorin 5A Indicate Poor Prognosis in Multiple Myeloma.

Acta Haematol 2020 9;143(3):279-288. Epub 2019 Oct 9.

Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China,

Background: The aim of this study was to detect the expression of long noncoding RNA small nucleolar RNA host gene 18 (SNHG18) andsemaphorin 5A (SEMA5A) genes in multiple myeloma (MM) patients and to explore the correlation of the expression of these genes with the clinical characteristics and prognosis of MM patients.

Methods: Forty-seven newly diagnosed MM, 18 complete remission MM, 13 refractory/relapse MM, and 22 iron deficiency anemia (serving as control) samples were extracted at the Department of Hematology, Second Affiliated Hospital of Xian Jiaotong University between January 2015 and December 2016. The clinical features of the MM patients are summarized. Real-time quantitative PCR was performed to analyze the relative expression levels of the SNHG18 and SEMA5Agenes. The clinical characteristics and overall survival (OS) of the MM patients were statistically analyzed while measuring different levels of SNHG18 and SEMA5Agene expression. At the same time, the correlation between the expression of SNHG18 and SEMA5A was also analyzed.

Results: The analysis confirmed that SNHG18 and its possible target gene SEMA5A were both highly expressed in newly diagnosed MM patients. After analyzing the clinical significance of SNHG18 and SEMA5A in MM patients, we found that the expression of SNHG18 and SEMA5A was related to the Durie-Salmon (DS), International Staging System (ISS), and Revised International Staging System (R-ISS) classification systems, and the Mayo Clinic Risk Stratification for Multiple Myeloma (mSMART; p < 0.05). Moreover, we observed a significant difference in OS between the SNHG18/SEMA5A high expression group and the low expression group. We found a positive correlation between SNHG18 and SEMA5A expression (r = 0.709, p < 0.01). Surprisingly, the expected median OS times of both the SNHG18 and SEMA5Ahigh expression groups were significantly decreased, which was in contrast to those of both the SNHG18 and SEMA5Alow expression groups and the single-gene high expression group (p < 0.05).

Conclusion: High expression of both SNHG18 and SEMA5A is associated with poor prognosis in patients with MM.
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http://dx.doi.org/10.1159/000502404DOI Listing
August 2020

[Soil organic carbon dynamics and the prediction of their spatial changes in response to anthropogenically introduced shrub encroachment in desert steppe of the Eastern Ningxia, China.]

Ying Yong Sheng Tai Xue Bao 2019 Jun;30(6):1927-1935

School of Agriculture, Ningxia University, Yinchuan 750021, China.

With the 14-year enclosed grassland and the grazed grassland as control, the impacts of anthropogenic shrublands (Caragana korshinskii) with the different planting years (3, 12, 22 a) and planting spaces (2, 8, 40 m) on soil organic carbon (SOC) contents were examined in the desert steppe of Eastern Ningxia, China. We further analyzed the spatial pattern and heterogeneity of SOC in 0-40 cm soil layer of the grassland area with introduced shrubs. The results showed that SOC in C. korshinskii shrublands had an increase trend with increased planting years and decreased spaces. The mean SOC with different planting years and spaces was 42.7% and 32.8% more than that in grazing land, respectively. There was no significant difference of SOC between shrublands and the 14-year enclosed grassland. The increase trend of SOC decreased by 27.0% in 22-year planting shrubland. The SOC content of 0-40 cm soil layer varied from 0.21 g·kg to 26.04 g·kg (with a mean of 3.75 g·kg), and the coefficient of SOC variation ranged from 90.9% to 114.7%. The SOC in 0-5 cm and 15-40 cm soil layers fitted the optimal theory formulation of Gaussian model, while that in 5-15 cm soil layer fitted a spherical model. The ranges (A) of spatial autocorrelation in the 0-5 and 5-15 cm soil layers were smaller (3.11, 3.00 km) than that in 15-40 cm soil layer (10.10 km). The nugget/sill C/(C+C) of SOC in 0-5, 5-15 cm soil layer was 0.2% and 16.3%, indicating a strong spatial correlation, while that in 15-40 cm soil layer was 36.9%, with a moderate correlation. The shrub introdution could significantly accelerate the accumulation and fixation of SOC in top 40 cm soil layer in degraded desert steppe, but also intensified the spatial heterogeneity and SOC fragmentation. The SOC content in the anthropogenic shrublands had no significant difference from that in the enclosed desert steppe (14 years). The SOC spatial heterogeneity and the degree of fragmentation were weakened and decreased with the increasing soil layer depth.
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http://dx.doi.org/10.13287/j.1001-9332.201906.001DOI Listing
June 2019

Identification and characterization of a novel group of natural anti-sense transcripts from RNA1.2 gene locus of human cytomegalovirus.

Chin Med J (Engl) 2019 Jul;132(13):1591-1598

Virus Laboratory, Affiliated Shengjing Hospital, China Medical University, Shenyang, Liaoning 110004, China.

Background: Natural anti-sense transcripts (NATs), which are transcribed from the complementary DNA strand of annotated genes, exert regulatory function of gene expression. Increasing studies recognized anti-sense transcription widespread throughout human cytomegalovirus (HCMV) genome, whereas the anti-sense transcription of RNA1.2 gene locus has never been investigated. In this study, the transcription of the RNA1.2 anti-sense strand was investigated in clinically isolated HCMV strain.

Methods: Strand-specific high-through RNA-sequencing (RNA-seq) was performed to find possible anti-sense transcripts (ASTs). For analyzing and visualization of RNA-seq data sets, Integrative Genomics Viewer software was applied. To confirm these possibilities, Northern blotting and rapid amplification of cDNA ends (RACE) were used.

Results: Transcription of the opposite strand of RNA1.2 gene locus was detected by RNA-sequencing using RNAs extracted from human embryonic lung fibroblasts infected with HCMV clinical isolate HAN. At least three HCMV NATs, named RNA1.2 AST 1, RNA1.2 AST2, and RNA1.2 AST3, were characterized by Northern blotting and RACE analyses. These RNA1.2 ASTs orientated from the complementary strand of RNA1.2 locus during the late phase of HCMV infection. The 5'- and 3'-termini of these transcripts were located within the opposite sequence of the predicted RNA1.2 gene.

Conclusion: A cluster of novel NATs was transcribed from the opposite sequence of the HCMV RNA1.2 gene region.
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http://dx.doi.org/10.1097/CM9.0000000000000299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6616230PMC
July 2019

Secretory status of monoclonal immunoglobulin is related to the outcome of patients with myeloma: a retrospective study.

Blood Adv 2019 03;3(5):751-760

State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China; and.

The treatment of multiple myeloma (MM) with proteasome inhibitor (PI) bortezomib has significantly improved the survival of patients with MM. The 26S proteasome inhibitor targets the unfolded protein response (UPR) by inhibiting proteasome degradation of ubiquitinated paraprotein, subsequently leading to the lethal accumulation of paraprotein within the endoplasmic reticulum. According to secretory status of monoclonal immunoglobulin, newly diagnosed MM (NDMM) is divided into measurable and unmeasurable disease, which includes oligosecretory, nonsecretory, and nonproducer myeloma. The present study analyzed the clinical characteristics of 822 patients with NDMM who had either measurable or unmeasurable diseases and received bortezomib- or thalidomide-based therapies. Our results showed that the median progression-free survival (PFS) and overall survival (OS) of patients with MM was significantly longer in patients with measurable disease than those in oligosecretory, nonsecretory, and nonproducer MM (PFS: 27, 18, 19, and 2.0 months, respectively [ < .001]; OS: 51, 30, 22, and 2.0 months, respectively [ < .001]). Within the unmeasurable group, patients with nonproducer myeloma showed the shortest PFS and OS. Importantly, compared with thalidomide treatment, bortezomib significantly improved the PFS and OS of patients with MM with measurable disease (PFS: 25 and 33 months [ = .022], respectively; OS: 41 and 58 months [ < .001], respectively), but not those with unmeasurable disease (PFS: 18 and 16 months [ = .617], respectively; OS: 22 and 27 months [ = .743], respectively). Our results indicate that bortezomib-based therapy performed no better than thalidomide-based treatment in patients with unmeasurable MM. The results need to be confirmed in other patient cohorts, preferably in the context of a prospective trial.
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http://dx.doi.org/10.1182/bloodadvances.2018019851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418498PMC
March 2019

Genetic and Antibiotic Resistance Characteristics of Campylobacter jejuni Isolated from Diarrheal Patients, Poultry and Cattle in Shenzhen.

Biomed Environ Sci 2018 Aug;31(8):579-585

Nanshan Center for Disease Control and Prevention, Shenzhen 518054, Guangdong, China.

Objective: To investigate genetic and antibiotic resistance characteristics of Campylobacter jejuni (C. jejuni) isolated from Shenzhen.

Methods: Multilocs sequence typing and agar dilution methods were used to define the genotype and antibiotic resistance of C. jejuni, respectively.

Results: In total, 126 C. jejuni strains were isolated. The prevalence of C. jejuni was 5.3% in diarrheal patients. The prevalence in poultry meat (36.5%) was higher than that in cattle meat (1.1%). However, the prevalence in poultry cloacal swabs (27.0%) was lower than that in cattle stool (57.3%). Sixty-two sequence types were obtained, among which 27 of the STs and 10 alleles were previously unreported. The most frequently observed clonal complexes were ST 21 (11.9%), ST-22 (10.3%), and ST-403 (7.1%). ST-21, ST-45, ST-354, ST-403, and ST-443 complexes overlapped between isolates from patients and cattle, whereas ST-45 and ST-574 complexes overlapped between isolates from patients and poultry. All C. jejuni were resistant to at least one antibiotic. The highest resistance rate was toward ciprofloxacin (89.7%), followed by tetracycline (74.6%), and nalidixic acid (69.0%).

Conclusion: This is the first report of the genotypes and antibiotic resistance of C. jejuni in Shenzhen. Overlapping clonal complexes were found between isolates from patients and cattle, and between patients and poultry.
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http://dx.doi.org/10.3967/bes2018.079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766747PMC
August 2018

[Apoptosis Effects of GM3 Ganglioside on U266 Cells and Its Possible Mechanism].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2018 Aug;26(4):1022-1026

Department of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan 030001, Shansi Province, China.E-mail:

Objective: To investigate the proliferation- inhibitory and apoptosis inducing effect of ganglioside GM3 on human multiple myeloma cell line U266 cells and its possible mechanisms.

Methods: MTT assay and flow cytometry were used to observe the effects of GM3 ganglioside on proliferation and apoptosis of human myeloma cell line U266. Effects of different concentration of ganglioside GM3 on the mRNA expression level of BCL-2 and BAX were detected by Real-time PCR.

Results: MTT assay and Flow Cytometry showed that ganglioside GM3 could induce the apoptosis and inhibit the proliferation of multiple myeloma U266 cell line, and both the effects were enhanced with the increase of GM3 ganglioside concentration. Compared with the control group, the relative expression of BAX mRNA with the increase of GM3 concentration in experimental group was enhanced gradually(r=0.968), while the relative mRNA expression of anti-apoptotic gene BCL-2 was decreased gradually(r=-0.727).

Conclusion: GM3 ganglioside can induce apoptosis and inhibit the proliferation of U266 cell line in a concentration dependent manner. The mechanism may be related with up- regulation of BAX expression and down-regulation of BCL-2.
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http://dx.doi.org/10.7534/j.issn.1009-2137.2018.04.013DOI Listing
August 2018

Serologic and viral genome prevalence of HSV, EBV, and HCMV among healthy adults in Wuhan, China.

J Med Virol 2018 03 14;90(3):571-581. Epub 2017 Nov 14.

State Key Laboratory of Virology, CAS Center for Excellence in Brain Science and Intelligence Technology (CEBSIT), Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.

The worldwide infection rate of herpesvirus is high, but the detailed prevalence in China, especially the central area, remains unclear. In the present study, the prevalence of herpes simplex virus (HSV), Epstein-Barr virus (EBV), and human cytomegalovirus (HCMV) was investigated in 303 healthy adults in Wuhan, a representative city in Central China. Viral-specific IgG and IgM titers were examined in the serum by chemiluminescent immunoassay, and the existence of viral genomic DNA in blood cells was determined by nested PCR. The overall IgG seroprevalences were 81.5%, 95.4%, and 93.7% for HSV, EBV, and HCMV, while the corresponding IgM seroprevalences were only 6.3%, 2.3%, and 0. The viral genomic DNA of HSV, EBV, and HCMV was identified in the blood samples of 5.9%, 14.2%, and 22.8% of the tested donors, respectively. Significantly, less HSV IgM-positive samples were found in the population over 20 years old than below 20 group; female displayed higher chances for HSV IgG and genome positivity; and occupations such as waiters and medical staffs were shown to be with higher risk for HCMV genome positivity. This study provided useful reference data for the HSV, EBV, and HCMV prevalence in central China, and suggested the potential importance of detecting viral genome to complement serum test data.
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http://dx.doi.org/10.1002/jmv.24989DOI Listing
March 2018

[Expression of Insulin-Like Growth Factor Binding Protein 7 Gene in Multiple Myeloma Cell Line and Methylation Regulation].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2017 Jun;25(3):813-817

Department of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China.

Objective: To investigate the expression of insulin-like growth factor binding protein 7 (IGFBP7 ) gene in multiple myeloma cell line U266, and study the effect of 5-aza-2'-deoxycytidine (5-aza-dc) on proliferation of U266 cells.

Methods: multiple myeloma cell line U266 was cultured in vitro. The bone marrow mononuclear cells from healthy persons(N-BMMNC) were collected and used as normal controls. The IGFBP7 mRNA expression of U266 cells and N-BMMNC were detected by real-time fluorescence quantitative PCR, the DNA methylation status of the IGFBP7 CpG island was measured by using methylation-specific PCR(MSP). The different concentrations of 5-aza-dc (5 µmol/L, 10 µmol/L, 20 µmol/L) were used to treat U266 cells for 48 hours, the RT-PCR and Western blot were used to detect the effect of IGFBP7 mRNA and protein expressions, the cell growth curve and Annexin V/PI were analyzed by flow cytometry.

Results: As compared with normal BMMNC, the lower expression of IGFBP7 gene was found in U266 cells, the obvious hypermethylation of the CpG island in the IGFBP7 promoter was observed. After treatment of U266 treating with different concentrations of 5-aza-dc, the IGFBP7 mRNA expression was up-regulated dose-dependently(P<0.05), the U266 cells grew slowly and apoptosis rates were enhanced dose-dependently.

Conclusion: As the hypermethylalion of CpG island in IGFBP7 promoter is a frequent event in lower expression of IGFBP7 gene in U226 cells, the 5-aza-dc can up-regulate the expression of IGFBP7 , and can inhibit cell proliferation through induction of cell apoptosis and arrest of cell cycle.
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http://dx.doi.org/10.7534/j.issn.1009-2137.2017.03.032DOI Listing
June 2017

Protective efficacy of cationic-PLGA microspheres loaded with DNA vaccine encoding the sip gene of Streptococcus agalactiae in tilapia.

Fish Shellfish Immunol 2017 Jul 2;66:345-353. Epub 2017 May 2.

Guangdong Provincial Key Laboratory of Livestock Disease Prevention; Guangdong Open Laboratory of Veterinary Public Health; Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China. Electronic address:

Streptococcus agalactiae (S. agalactiae) is an important fish pathogen, which has received more attention in the past decade due to the increasing economic losses in the tilapia industry worldwide. As existing effective vaccines of S. agalactiae in fish have obvious disadvantage, to select immunoprotective antigens and package materials would undoubtedly contribute to the development of novel oral vaccines. In the present study, surface immunogenic protein (sip) was selected from the S. agalactiae serovar I a genomes as immunogenic protein in DNA vaccine form with cationic chitosan and biodegradable and biocompatible PLGA. The pcSip plasmid in cationic-PLGA was successfully expressed in tissues of immunized tilapia and the immunogenicity was assessed in tilapia challenge model. A significant increase was observed in the cytokine levels of IL-1β, TNF-α, CC1, CC2 in spleen and kidney tissues. Furthermore, immunized tilapia conferred different levels of protection against challenge with a lethal dose of highly virulent serovar I a S. agalactiae. Our results indicated that the pcSip plasmid in cationic-PLGA induced high level of antibodies and protection against S. agalactiae infection, could be effective oral DNA vaccine candidates.
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http://dx.doi.org/10.1016/j.fsi.2017.05.003DOI Listing
July 2017

Multiple Evolutionary Selections Involved in Synonymous Codon Usages in the Streptococcus agalactiae Genome.

Int J Mol Sci 2016 Feb 24;17(3):277. Epub 2016 Feb 24.

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.

Streptococcus agalactiae is an important human and animal pathogen. To better understand the genetic features and evolution of S. agalactiae, multiple factors influencing synonymous codon usage patterns in S. agalactiae were analyzed in this study. A- and U-ending rich codons were used in S. agalactiae function genes through the overall codon usage analysis, indicating that Adenine (A)/Thymine (T) compositional constraints might contribute an important role to the synonymous codon usage pattern. The GC3% against the effective number of codon (ENC) value suggested that translational selection was the important factor for codon bias in the microorganism. Principal component analysis (PCA) showed that (i) mutational pressure was the most important factor in shaping codon usage of all open reading frames (ORFs) in the S. agalactiae genome; (ii) strand specific mutational bias was not capable of influencing the codon usage bias in the leading and lagging strands; and (iii) gene length was not the important factor in synonymous codon usage pattern in this organism. Additionally, the high correlation between tRNA adaptation index (tAI) value and codon adaptation index (CAI), frequency of optimal codons (Fop) value, reinforced the role of natural selection for efficient translation in S. agalactiae. Comparison of synonymous codon usage pattern between S. agalactiae and susceptible hosts (human and tilapia) showed that synonymous codon usage of S. agalactiae was independent of the synonymous codon usage of susceptible hosts. The study of codon usage in S. agalactiae may provide evidence about the molecular evolution of the bacterium and a greater understanding of evolutionary relationships between S. agalactiae and its hosts.
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http://dx.doi.org/10.3390/ijms17030277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4813141PMC
February 2016

Identification and BAC construction of Han, the first characterized HCMV clinical strain in China.

J Med Virol 2016 May 12;88(5):859-70. Epub 2015 Oct 12.

State Key Laboratory of Virology, CAS Center for Excellence in Brain Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.

Human cytomegalovirus (HCMV) is the leading infectious cause of birth defects, and may lead to severe or lethal diseases in immunocompromised individuals. Several HCMV strains have been identified and widely applied in research, but no isolate from China has been characterized. In the present study, we isolated, characterized and sequenced the first Chinese HCMV clinical strain Han, and constructed the novel and functional HCMV infectious clone Han-BAC-2311. HCMV Han was isolated from the urine sample of a Chinese infant with multiple developmental disorders. It expresses HCMV specific proteins and contains a representative HCMV genome with minor differences compared to other strains. By homologous recombination using mini-F derived BAC vector pUS-F6, the infectious clone Han-BAC-2311 was constructed containing representative viral genes across the HCMV genome. The insertion site and orientation of BAC sequence were confirmed by restriction enzyme digestion and Southern blotting. The reconstituted recombinant virus HanBAC-2311 expresses typical viral proteins with the same pattern as that of wild-type Han, and also displayed a similar growth kinetics to wild-type Han. The identification of the first clinical HCMV strain in China and the construction of its infectious clone will greatly facilitate the pathogenesis studies and vaccine development in China.
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http://dx.doi.org/10.1002/jmv.24396DOI Listing
May 2016

Contribution of mitochondrial function to exercise-induced attenuation of renal dysfunction in spontaneously hypertensive rats.

Mol Cell Biochem 2015 Aug 12;406(1-2):217-25. Epub 2015 May 12.

School of Physical Education, Xi'an Technological University, 4 Jinhua Road, Xi'an, 710032, Shaanxi Province, China,

It is well known that exercise training exhibits renal protective effects in animal models of hypertension and chronic renal failure. However, the mechanisms regulating these effects of exercise training remain unclear. This study aimed to investigate the role of mitochondrial function in exercise-induced attenuation of renal injury in spontaneously hypertensive rats (SHR). The adult male SHR and age-matched normotensive Wistar-Kyoto rats (WKY) were given moderate-intensity exercise for 12 weeks or treated with MitoQ10 for 8 weeks. In this work, exercise training in SHR reduced blood pressure, and effectively attenuated renal dysfunction, marked by reduced creatinine excretion, albuminuria, blood urea nitrogen, and glomerular sclerosis. Exercise training in SHR reduced MDA levels in plasma and kidneys and suppressed formation of 3-nitrotyrosine in kidneys. Exercise training suppressed mitochondrial ROS and [Formula: see text] formation, enhanced ATP formation, reduced mitochondrial swelling, and restored electron transport chain enzyme activity in kidneys of SHR. Furthermore, exercise training upregulated protein expression of uncoupling protein 2 and manganese superoxide dismutase in kidneys of SHR. In addition, treatment with mitochondria-targeted antioxidant MitoQ10 exhibited similar renal protective effects in SHR. In conclusion, chronic aerobic exercise training preserved mitochondrial function and abated oxidative stress in the kidneys of SHR, which may in part explain the protective effect of exercise on renal function and structure in hypertensive individuals.
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http://dx.doi.org/10.1007/s11010-015-2439-6DOI Listing
August 2015

Contribution of receptor for advanced glycation end products to vasculature-protecting effects of exercise training in aged rats.

Eur J Pharmacol 2014 Oct 24;741:186-94. Epub 2014 Aug 24.

Department of General Urgery, Yuquan Hospital of Tsinghua University, Beijing, China.

The aim of present work was to investigate the underlying mechanism of vasculature-protecting effects of exercise training in aged rats. Experiment 1: aged rats were given moderate-intensity exercise for 12 weeks. Exercise training suppressed advanced glycation evidenced by reduced activity of aldose reductase, increased activity of glyoxalase 1, reduced levels of methylglyoxal and N(ε)-(carboxymethyl) lysine, and decreased expression of receptor for advanced glycation end products (RAGE) in aged aortas. Experiment 2: aged rats were given moderate-intensity exercise for 12 weeks or treated with FPS-ZM1, an inhibitor of RAGE. Exercise training attenuated aortic stiffening with age marked by reduced collagen levels, increased elastin levels and reduced pulse wave velocity (PWV), and prevented aging-related endothelial dysfunction marked by restored endothelium-mediated vascular relaxation of aortas in response to acetylcholine. Exercise training in aging aortas reduced formation of malondialdehyde, 3-nitrotyrosin and reactive oxygen species, increased GSH/GSSG ratio, suppressed activation of NFκB, and reduced levels of IL-6 and chemokine (C-C motif) ligand 2. Similar effects were demonstrated in aged rats treated with FPS-ZM1. Collectively, exercise suppressed advanced glycation in the aortas of aged rats, which, at least in part, explained the vasculature-protecting effects of exercise training in aged population.
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http://dx.doi.org/10.1016/j.ejphar.2014.08.017DOI Listing
October 2014

Contribution of renin-angiotensin system to exercise-induced attenuation of aortic remodeling and improvement of endothelial function in spontaneously hypertensive rats.

Cardiovasc Pathol 2014 Sep-Oct;23(5):298-305. Epub 2014 Jun 17.

Department of General Urgery, Yuquan Hospital of Tsinghua University, Beijing, China.

Introduction: It is well known that exercise alleviates aortic remodeling and preserves endothelial function in spontaneously hypertensive rats (SHRs). However, the underlying molecular mechanism remains unclear. This study aimed to investigate the role of renin-angiotensin system (RAS) components in exercise-induced attenuation of aortic remodeling and improvement of endothelial function in an animal model of human essential hypertension.

Methods: The 10-week-old male SHR and age-matched normotensive Wistar-Kyoto rats were given moderate-intensity exercise for 12weeks (four groups, n=80-86 in each group).

Results: In this work, exercise training reduced blood pressure and effectively attenuated aortic remodeling, marked by a reduction in aortic weight/length, wall thickness, and aortic levels of elastin and hydroxyproline, and improved endothelium-mediated vascular relaxations of aortas in response to acetylcholine. Exercise training in SHR reduced angiotensin II (AngII) levels and enhanced Ang-(1-7) levels in aortas. Exercise training in SHR suppressed aortic angiotensin-converting enzyme (ACE) and AngII type 1 receptor (AT1R) messenger RNA (mRNA) levels and protein expression and up-regulated ACE2, AngII type 2 receptor, and Mas mRNA levels and protein expression. In addition, exercise training in SHR increased levels of microRNA-27a (targeting ACE) and microRNA-155 (targeting AT1R) and decreased levels of microRNA-143 (targeting ACE2) in the aortas.

Conclusion: Chronic aerobic exercise training improved RAS balance in the aortas, which may in part explain the protective effect of exercise on aortic function and structure.

Summary: Chronic aerobic exercise training improved RAS balance in the aortas, which may explain the protective effect of exercise on aortic function and structure, at least in part.
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http://dx.doi.org/10.1016/j.carpath.2014.05.006DOI Listing
May 2015

Chronic aerobic exercise training attenuates aortic stiffening and endothelial dysfunction through preserving aortic mitochondrial function in aged rats.

Exp Gerontol 2014 Aug 5;56:37-44. Epub 2014 Mar 5.

Department of General Urgery, Yuquan Hospital of Tsinghua University, Beijing, China.

Aging leads to large vessel arterial stiffening and endothelial dysfunction, which are important determinants of cardiovascular risk. The aim of present work was to assess the effects of chronic aerobic exercise training on aortic stiffening and endothelial dysfunction in aged rats and investigate the underlying mechanism about mitochondrial function. Chronic aerobic exercise training attenuated aortic stiffening with age marked by reduced collagen concentration, increased elastin concentration and reduced pulse wave velocity (PWV), and prevented aging-related endothelial dysfunction marked by improved endothelium-mediated vascular relaxation of aortas in response to acetylcholine. Chronic aerobic exercise training abated oxidative stress and nitrosative stress in aortas of aged rats. More importantly, we found that chronic aerobic exercise training in old rats preserved aortic mitochondrial function marked by reduced reactive oxygen species (ROS) formation and mitochondrial swelling, increased ATP formation and mitochondrial DNA content, and restored activities of complexes I and III and electron-coupling capacity between complexes I and III and between complexes II and III. In addition, it was found that chronic aerobic exercise training in old rats enhanced protein expression of uncoupling protein 2 (UCP-2), peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α), manganese superoxide dismutase (Mn-SOD), aldehyde dehydrogenase 2 (ALDH-2), prohibitin (PHB) and AMP-activated kinase (AMPK) phosphorylation in aortas. In conclusion, chronic aerobic exercise training preserved mitochondrial function in aortas, which, at least in part, explained the aorta-protecting effects of exercise training in aging.
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http://dx.doi.org/10.1016/j.exger.2014.02.014DOI Listing
August 2014

Codon usage bias of the phosphoprotein gene of spring viraemia of carp virus and high codon adaptation to the host.

Arch Virol 2014 Jul 12;159(7):1841-7. Epub 2014 Feb 12.

Guangdong Public Lab. of Veterinary Public Health, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou, 510640, China,

In this study, we calculated the relative synonymous codon usage (RSCU) value and the effective number of codons (ENC) value to carry out principal component analysis (PCA) and correlation analysis of the codon usage pattern of the phosphoprotein gene (P gene) of spring viraemia of carp virus (SVCV). The synonymous codon usage pattern in P genes is geography-specific, based on PCA analysis. The high correlation between (G + C)1,2 % and (G + C)3 % suggests that mutational pressure rather than natural selection is the main factor that determines the codon usage and base components in P genes. At least 40 out of 59 synonymous codons are similarly selected in all functional genes within five complete SVCV genomes, and the hosts based on the RSCU data. These results not only provide insight into variations in the codon usage pattern of SVCV but also may help in understanding the processes governing the evolution of SVCV.
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http://dx.doi.org/10.1007/s00705-014-2000-zDOI Listing
July 2014

Accelerated partial breast irradiation for breast cancer: a meta-analysis.

Transl Oncol 2013 Dec 1;6(6):619-27. Epub 2013 Dec 1.

Ningxia People's Hospital, Yinchuan, China.

To evaluate the long-term effect of breast conservation with accelerated partial breast irradiation (APBI) for early-stage breast cancer, PubMed, EMBASE, Cochrane Library, Web of Science, Chinese Biomedical Literature Database, Chinese Scientific Journals Full-text Database, and China Journal Full-text Database were searched to identify relevant original published trials. Randomized controlled trials in any language comparing APBI with whole-breast radiotherapy in patients with early-stage breast cancer were included. RevMan 5 software was used for statistical analysis. Four trials involving 919 patients were included. The rate of 5- and 7-year excellent/good cosmetic results was significant {odds ratio (OR) = 2.09 [95% confidence interval (CI) = 1.21-3.62]} between two groups. The 5- and 8-year overall survival had no significant difference [OR = 1.76 (95% CI = 0.67-4.62) and OR = 0.86 (95% CI = 0.44-1.66)]. The 10-year overall survival had significant differences [OR = 0.56 (95% CI = 0.35-0.91)]. There were no differences in the 5-year local recurrence (LR)-free survival [OR = 0.65 (95% CI = 0.18-2.34)], cancer-specific survival [OR = 1.67 (95% CI = 0.39-7.12)], disease-free survival [OR = 0.84 (95% CI = 0.38-1.84)], LR [OR = 1.36 (95% CI = 0.46-3.99)], the rate of contralateral breast cancer [OR = 2.82 (95% CI = 0.73-10.89)], and distant metastasis [OR = 0.71 (95% CI = 0.22-2.31)]. APBI significantly improved the rate of excellent/good cosmetic results anywhere in the breast, shortened the treatment time, alleviated the pain, and improved the quality of life. Future large-scale, high-quality, and double-blind trials are needed.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3890696PMC
http://dx.doi.org/10.1593/tlo.13580DOI Listing
December 2013

[Effect of flumatinib mesylate on C-MYC, HIF-1α and VEGF in U226 line].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2013 Dec;21(6):1496-500

Department of Hematology, Shanxi Medical University Second Hospital, Taiyuan 030001, Shanxi Province, China. E-mail:

The objective of this study was to investigate the effect of the new generation of tyrosine kinase inhibitor flumatinib mesylate on C-MYC, HIF-1α and VEGF in multiple myeloma (MM) cell line U266. Different concentrations (1, 5, 10 µmol/L) of flumatinib mesylate were used to act on U266 cell line for 8, 16 and 24 h, and the expression of C-MYC, and HIF-1α genes was detected by real-time fluorescence-quantitative PCR, the expression of C-MYC, HIF-1α and VEGF was measured by Western blot. The results showed that the gene expression of C-MYC and HIF-1 genes decreased gradually with the increasing of flumatinib mesylate concentration (P < 0.05). At the same concentration of flumatinib mesylate, the expression of C-MYC and HIF-1α gene decreased gradually with prolonging of treatment time with the flumatinib mesylate (P < 0.05). When the flumatinib mesylate acted the U266 cell line for 16 h, the expression of C-MYC, HIF-1α and VEGF decreased gradually with the increasing of flumatinib mesylate concentration (P < 0.05). It is concluded that the flumatinib mesylate can reduce the expression of C-MYC, HIF-1 α and VEGF in U266 cell line in a time- and dose-dependent manners, so flumatinib mesylate may become a new drug for MM therapy.
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http://dx.doi.org/10.7534/j.issn.1009-2137.2013.06.024DOI Listing
December 2013

[Research on rules of distribution and development of traditional Chinese medicine syndromes of 2,237 HIV/AIDS cases].

Zhongguo Zhong Yao Za Zhi 2013 Aug;38(15):2472-5

AIDS Research Center, Clinical Evaluation Center, China Academy of Traditional Chinese Medicine, Beijing 100700, China.

HIV/AIDS patients in high prevalence areas with different routes of infection (sexually transmitted 878 cases, 527 cases of intravenous drug user, paid blood donor 652 cases) were choosen for traditional Chinese medicine (TCM) syndrome investigation for one-year clinical follow-up. This paper primarily concluded the nature, location and pathogenesis of AIDS diseases. Deficiency of Yang and Yin, combining deficiency of Qi are the basic deficiency syndromes, while stagnation of dampness, toxic fire are the excess syndromes; the disease location of HIV infector is spleen, main syndrome is deficiency of spleen Qi; the disease location of AIDS patient is kidney, main syndrome is deficiency of spleen and kidney Yang. The pathogenic development tendency is from deficiency of Qi to combining stagnation of dampness and toxic fire, finally to deficiency of Qi and Yin, deficiency of Yang.
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August 2013

[mRNA expression of telomere protection protein TIN2 and POT1 in bone marrow of patients with myelodysplastic syndrome].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2013 Feb;21(1):110-5

Department of Hematology, The Second Hospital of Shanxi Medical University, Shanxi Province,

This study was purposed to explore the relationship between the mRNA expression of telomere protection protein TIN2 and POT1 and the pathogenesis of myelodysplastic syndrome (MDS). The expression of TIN2 and POT1 genes at the mRNA levels were detected by real-time fluorescence quantitative PCR in 51 patients with MDS and 10 normal controls. The results showed that the mRNA expressions of TIN2 in RA/RARS/RCMD/MDS-U, RAEB-1 and RAEB-2 groups according to the World Health Organization criteria were significantly higher than that in the controls (P < 0.05); the mRNA expressions of POT1 in RA/RARS/RCMD/MDS-U, RAEB-1 and RAEB-2 groups were significantly lower than that in the controls (P < 0.05). The mRNA expressions of TIN2 in high-risk group, inter risk-2 group and inter risk-1 group according to the international prognostic scoring system criteria were significantly higher than that in controls (P < 0.05). There was no significant difference between low risk group and the control group. The mRNA expressions of POT1 in high risk group, inter-risk-2 group and inter-risk-1 group were significantly lower than the controls (P < 0.05). There was no significant difference between low risk group and the control group. The mRNA expression of TIN2 in normal chromosome group was significantly lower than that in abnormal chromosome group (P < 0.05). There was no significant difference between normal chromosome group and the control group. The mRNA expression of POT1 in normal chromosome group was significantly higher than that in abnormal chromosome group (P < 0.05). There was no significant difference between normal chromosome group and the control group. It is concluded that the abnormal mRNA expression of TIN2 and POT1 may be involved in the regulation of telomere dynamics of MDS patients, the regulatory mechanism may be related to the telomere length and the pathogenesis of MDS.
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http://dx.doi.org/10.7534/j.issn.1009-2137.2013.01.023DOI Listing
February 2013

Identification of immediate early gene X-1 as a cellular target gene of hcmv-mir-UL148D.

Int J Mol Med 2013 Apr 6;31(4):959-66. Epub 2013 Feb 6.

Virus Laboratory, The Affiliated Shengjing Hospital, China Medical University, Shenyang, Liaoning 110004, PR China.

Human cytomegalovirus (HCMV) is a herpesvirus that causes congenital diseases and opportunistic infections in immunocompromised individuals. Its functional proteins and microRNAs (miRNAs) facilitate efficient viral propagation by altering host cell behavior. The identification of functional target genes of miRNAs is an important step in the study of HCMV pathogenesis. HCMV encodes at least 14 miRNAs, including hcmv-mir-UL148D, which resides in the HCMV UL/b' region. hcmv-mir-UL148D is the only miRNA encoded by the HCMV UL/b' region; however, its targets and functional effects have not yet been eludidated. In this study, hybrid-PCR screening was used to identify target genes and dual luciferase reporter assay was used to evaluate the binding effect of hcmv-miR-UL148D to the 3' untranslated region (3'UTR) of IEX-1. In addition, western blot analysis was used to detect the expression kinetics of IEX-1 protein and apoptosis assay was used to identify the effects of hcmv-miR-UL148D on cell apoptosis. The hybrid-PCR results showed that only one binding site in the 3'UTR of the cellular gene, human immediate early gene X-1 (IEX-1), was completely complementary to an 11 nucleotide (nt) sequence in the 5' terminus of hcmv-mir-UL148D, including the entire seed region. The binding site was demonstrated to be functional by dual luciferase reporter assay with a 47% repression of the relative luciferase activity. In an in vitro system of human embryonic kidney 293 (HEK293) cells, the ectopically expressed hcmv-mir-UL148D exhibited a downregulatory effect on IEX-1 expression, and decreased the cell apoptosis induced by transfected IEX-1. Our data demonstrate that hcmv-mir-UL148D targets the cellular gene, IEX-1, downregulating its expression and thus results in anti-apoptotic effects.
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http://dx.doi.org/10.3892/ijmm.2013.1271DOI Listing
April 2013

[Study on histone deacetylase inhibitor LBH589 induces apoptosis of multiple myeloma cells and its reversal of drug resistance mechanism].

Zhonghua Xue Ye Xue Za Zhi 2012 Nov;33(11):926-31

Department of Hematology, Second Hospital of Shanxi Medical University, Taiyuan, China.

Objective: To explore the impact of a new generation of histone deacetylase inhibitor LBH589 alone or in combination with proteasome inhibitor bortezomib on multiple myeloma (MM) cells proliferation and its mechanism.

Methods: MM cell line U266 and dexamethasone resistant cell line MM1R cells were treated with different concentrations of LBH589 alone or in combination with bortezomib, the inhibition of cells proliferation was detected by MTT, the cell cycle and apoptosis by flow cytometry. The expression level of histone H4 acetylation and PARP, Bcl-X protein was analyzed by western blot, expression level of caspase-3, APAF-1 and TOSO gene by real-time fluorescence quantitative PCR.

Results: U266 and MM1R cell proliferation were inhibited by different concentrations of LBH589 (0, 10, 20, 50 nmol/L) alone or 50 nmol/L of LBH589 in combination with bortezomib (10, 20 nmol/L) in a dose- and time-dependent manner. Inhibition effect was significantly higher in all combinative groups than in single agent groups (all P < 0.05). The percentage of G(0)/G(1) phase in MM1R cells were 36.60%, 46.50%, 51.40%, 57.10%, 75.48%, 79.73%, respectively, and the apoptosis rate were 5.27%, 31.41%, 39.78%, 44.07%, 73.60%, 83.27%, respectively. The effects appeared to occur in a dose-dependent manner, and being significantly higher in all combinative groups than in single agent groups (all P < 0.05). The expression of the caspase-3 and APAF-1 gene up-regulated gradually, while TOSO gene expression in MM1R cells down-regulated gradually in a dose- and time-dependent manner (all P < 0.05).

Conclusions: LBH589 can inhibit the growth of MM cells, block the cell cycle and induce cell apoptosis, which has anti-resistant effect on multidrug resistant cell. At the same time LBH589 in combination with bortezomib on myeloma cell has a synergistic effect, its mechanism and reversal of drug resistance mechanism involves in multiple changes in gene expression.
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November 2012

Contribution of hydrogen sulfide and nitric oxide to exercise-induced attenuation of aortic remodeling and improvement of endothelial function in spontaneously hypertensive rats.

Mol Cell Biochem 2013 Mar 15;375(1-2):199-206. Epub 2012 Dec 15.

School of Physical Education, Xi'an Technological University, Xi'an, 4 Jinhua Road, Xi'an 710032, Shaanxi Province, China.

It is well known that exercise training attenuates aortic remodeling and improves endothelial function in spontaneously hypertensive rats (SHR). However, the underlying molecular mechanism remains unclear. Hydrogen sulfide (H(2)S) and nitric oxide (NO), as two established physiologic messenger molecules, have important roles in the development of aortic remodeling and endothelial dysfunction in hypertensive animals and patients. In this work, it was found that exercise training had no significant effect on blood pressure, but effectively attenuated baroreflex dysfunction in SHR. Exercise training in SHR attenuated aortic remodeling and improved endothelium-mediated vascular relaxations of aortas in response to acetylcholine. Interestingly, exercise training in SHR restored plasma H(2)S levels and aortic H(2)S formation and enhanced levels of mRNA for cystathionine γ-lyase in aortas. Furthermore, exercise training in SHR resulted in augmentation of nitrite and nitrate (NOx) contents and reduction of asymmetric dimethylarginine contents of aortas, upregulation of dimethylarginine dimethylaminohydrolase 2, and phosphorylation of nitric oxide synthase 3, but had no significant effect on protein levels of NOS3. In addition, exercise training could effectively reduce malondialdehyde production and suppressed formation of O(2) (-), and OONO(-) in aortas of SHR through enhancing activities of superoxide dismutase and catalase, and suppressing NADPH oxidase activity. In conclusion, exercise training ameliorates aortic hypertrophy and endothelial dysfunction, possibly via restoring bioavailabilities of hydrogen sulfide and nitric oxide in SHR.
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http://dx.doi.org/10.1007/s11010-012-1542-1DOI Listing
March 2013