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Biomedical subjects

Song Zhao

Publications and source records attributed to Song Zhao.

12 recordsLinked to original sources

Genome-wide Association Studies of the Pathogenic Sphingosine-1-Phosphate Gene in Ulcerative Colitis.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease that can lead to malignancies over time. Sphingosine-1-phosphate (S1P) receptor signaling affects lymphocyte trafficking and vascular integrity, influencing intestinal inflammation. This study aimed to identify S1P-related key genes in UC. METHODS: Differentially expressed genes (DEGs) between the UC and control groups were analyzed in the GSE87473 (training) dataset. Genes overlapping between the DEGs and S1P-related genes were considered candidate genes. These genes were incorporated into machine learning algorithms and subjected to expression analysis to identify key genes. Gene functions were determined through a gene–gene interaction network, enrichment analysis, and immune cell infiltration analysis. In addition, transcription factor–mRNA and mRNA–miRNA–lncRNA networks were constructed. Finally, reverse transcription–quantitative polymerase chain reaction (RT-qPCR) was performed to evaluate the expression of key candidate genes in UC and control tissues. RESULTS: This study identified two key genes (SPHK2 and SPNS2) associated with UC. Notably, SPHK2 expression was lower and SPNS2 expression was higher in the UC group in both training and validation datasets and in clinical UC tissues (RT-qPCR). The area under the curve values of SPHK2 and SPNS2 exceeded 0.7 in both datasets, indicating that the genes had good diagnostic efficacy for UC. Consistently, the nomogram showed that the two genes had promising diagnostic value in UC. SPHK2 and SPNS2 were found to be localized to the plasma membrane. The correlations of the two genes with different immune cells showed significantly opposite trends. In particular, SPHK2 had the strongest positive correlation with M2 macrophages (r = 0.6) and the strongest negative correlation with neutrophils. Moreover, mRNA–miRNA–lncRNA and transcription factor– mRNA networks of the key genes were constructed. CONCLUSION: This study suggests that SPHK2 and SPNS2 are key genes associated with UC, highlighting their potential as effective diagnostic biomarkers.

Humans↗

[Cloning of A73 gene and its coding sequence analysis].

OBJECTIVE: To clone A73 gene of Epstein-Barr virus (EBV) and examine the variation of its coding sequence. METHODS: A73 coding sequence (CDS) amplified from 7 patients in nasophryngeal carcinoma (NPC) biopsies by RT-PCR was cloned into pGEM-T-Easy vector to construct the recombinant plasmid, which was subjected to sequence analysis in Gen Bank database using Blast software. RESULTS: A73 gene from nasophryngeal carcinoma was successfully cloned into pGEM-T Easy vector. A locus with conversion of A-->C in A73 was found at CDS 45 nt, located in the exonVB157154 nt, which did not result in an amino acid replacement, and the variation frequency was 7/7. CONCLUSION: There is a point mutation in A73 CDS of EBV isolated from NPC tissue, which might produce NPC-associated polymorphism with possible involvement in the composition of some subtype of EB virus.

Cloning, Molecular↗

[Investigation of simple Wiener spectrum measurement in medical imaging systems].

This paper is to approach a simple method for Wiener spectrum measurement in different medial imaging systems. The program written in VC++6.0 can be used to obtain the density datum as discrete signals by scanning films on AGFA DUOSCAN T2000XL scanner, then WS values can be calculated by using fast Fourier transform. The method is applied to different x-ray photographs and the WS values are consistent with the known datum from MD-100 micro-densimeter. The method can make automatic data collection and procedural calculation, showing the characteristics of its simplicity and high speed.

Algorithms↗

[Identification of stage Ib specific related genes in lung squamous cell cancer by oligonucleotide array].

OBJECTIVE: To establish gene expression profile of stage Ib and IIIa primary lung squamous cell cancer (SCC) within whole genome and identify genes specifically expressed in stage Ib of SCC. METHODS: Total RNA was extracted from the normal, stage Ib and IIIa lung SCC tissue. cRNA probes prepared from total RNA were hybridized with pretreatment oligonucleotide chip containing 22215 genes. The resultant data were treated with MSV 5.0 software and looked up on the affymetrix website. RT-PCR examination were used to validated the results from chip analysis. RESULTS: Comparing with the normal lung, difference genes expressed in Ib SCC are totally 1764, among which 571 were upregulated and 1193 were downregulated, and in stage IIIa, they are 554, 128 and 426 genes respectively. Genes specifically expressed in stage Ib were totally 1329, including 482 upregulation genes and 847 downregulation genes, which were classified into different category which included 480 metabolism related genes, 227 signal transduction genes, 136 cell proliferation genes, 136 immune related genes, 94 cell adhere genes, 88 transcription regulation genes, 86 cell cycle genes, 73 cytoskeleton genes, 45 differentiation genes, 42 apoptosis and 31 extracellular matrix genes. RT-PCR examination of FOXM1 and TNXB genes was consistent with the analysis of gene chip. CONCLUSION: Stage Ib and IIIa Gene expression profile of primary SCC within the whole genome were set up and genes specifically expressed in stage Ib of SCC were identified, which lay a foundation for further research on carcinogenesis mechanism and identifying new markers of early diagnosis.

Carcinoma, Squamous Cell↗

[Enhancing effects of celecoxib on the growth inhibition of pancreatic carcinoma by gemcitabine treatment].

OBJECTIVE: To investigate the effect and the mechanisms of selective cyclooxygenase-2 (COX-2) inhibitor celecoxib in the growth inhibition of pancreatic cancer by gemcitabine. METHODS: Effects of gemcitabine combined with celecoxib on the proliferation in xenograft pancreatic carcinoma induced by SW1990 were investigated by immunohistochemistry of proliferating cell nuclear antigen (PCNA) and cyclin D1. Gemcitabine was administered intraperitoneally twice a week, and celecoxib was given via water daily. Effects of celecoxib and/or gemcitabine in pancreatic carcinoma cell SW1990 with different dose and time were investigated by MTT assay and soft agar assay. Effects on apoptosis and cell cycle were studied by flow cytometry. Effects on the protein expression of cyclin A, B(1) and D(1) were assessed by Western Blot. RESULTS: The mean volume of xenograft tumor was significantly reduced in gemcitabine group, celecoxib group and combination group (0.41 cm(3) +/- 0.12 cm(3), 1.56 cm(3) +/- 0.17 cm(3), 0.05 cm(3) +/- 0.04 cm(3) vs 2.31 cm(3) +/- 0.41 cm(3), P < 0.05). The expression of PCNA and cyclin D(1) was significantly reduced in gemcitabine group and can hardly be detected in combination group, but without significant change in celecoxib group. Celecoxib and gemcitabine inhibited pancreatic carcinoma cell growth dose-dependently, and the combination of celecoxib with gemcitabine inhibited cell growth to a greater degree than either compound alone. Apoptosis were induced in SW1990 by celecoxib alone or in combined with gemcitabine. Treatment with celecoxib only or combined with gemcitabine altered the cell cycle phase distribution in SW1990, cells were mainly arrested in G(0)/G(1) phase, S phase and G(2)/M phase development were greatly inhibited. Expression of Cyclin A, B(1) and D(1) were closely related with the cell cycle distribution induced by different drug. CONCLUSIONS: Selective COX-2 inhibitor celecoxib enhances the growth inhibition of pancreatic cancer induced by gemcitabine, which may be realized partly through the arrest of cell cycle and induction of cell apoptosis.

Animals↗

[Enhancement of the protective effect of SjC23 DNA vaccine against Schistosoma japonicum infection by immunostimulatory sequence].

OBJECTIVE: To investigate the effect of immunostimulatory sequence on SjC23 DNA vaccine against Schistosoma japonicum infection. METHODS: SjC23 gene fragment was inserted into pcDNA3. 1-CpG to construct pcDNA3.1-SjC23/CpG. BALB/c mice in 4 groups were immunized intramuscularly 3 times at 2 week intervals, with 100 microg plasmid DNA per injection. Four weeks after the 3rd immunization, all mice were challenged with 45 +/- 1 cercariae of S. japonicum by abdominal skin penetration. After 45 days post-challenge, mice were perfused and the number of recovered worms and of eggs in liver was counted. Blood samples were collected from the tail vein of all mice 2 days before the 1st immunization and before challenge respectively. IgG, IgG1 and IgG2a in sera were detected. Three weeks after the 3rd inoculation, the spleen cells of 2 mice from each group were cultured and stimulated with ConA and recombinant peptide. The supernatant was collected to detect IL-2, IL-4 and IFN-gamma. Simultaneously, the cytotoxic activity was detected with 51Cr release assay in vitro. RESULTS: The worm reduction rate in SjC23 group and SjC23/CpG group was 28.1% and 35.1%, the hepatic egg reduction rate was 21.6% and 26.5%, respectively, compared with the control group. The level of protection in SjC23/CpG group was higher than that in SjC23 group (P<0.05). ELISA results indicated that mice immunized with pcDNA3.1-SjC23 and SjC23/CpG produced specific IgG to rSjC23, while mice immunized with pcDNA3.1 and pcDNA3.1-CpG did not. Mice in SjC23 group and SjC23/CpG group also produced IgG1 and IgG2a antibody isotypes, with the ratio of IgG2a/IgG1 10.1 and 12.2, respectively. In comparison with the control, the level of IL-2 and IFN-gamma in mice immunized with pcDNA3.1-SjC23 and pcDNA3.1-SjC23/CpG was augmented. The cytotoxic activity of spleen cells from mice in SjC23/CpG group was augmented from 9.7% to 40.0% compared with that in SjC23 group. CONCLUSION: The study indicates that immunostimulatory sequence appears to increase the level of protection induced by immunization with pcDNA3.1-SjC23 vaccine.

Adjuvants, Immunologic↗

Diagnosis and surgical treatment of ruptured aneurysm in sinus of Valsalva.

OBJECTIVE: To evaluate the methods used to diagnose and surgically treat ruptured aneurysm in sinus of Valsalva (RASV). METHODS: Thirty-seven hospitalized patients with ruptured aneurysms in the sinus of Valsalva from September 1981 to April 2001, including 21 cases (56.7%) of RASV associated with ventricular septal defects (VSD) and 11 (29.7%) with aortic valvular prolapse were given surgical interventions. Under hypothermia and extracorporeal circulation, we successfully performed the surgical correction of RASV for all 37 patients VSD repair in 21 patients, aortic valvuloplasty in 6 and aortic valvular replacement in 2. RESULTS: There was no hospital deaths among these patients, although residual shunting occurred in two patients and acute renal failure was found one. Follow-up study of one month to 20 years in the patients undergoing repair of RASV revealed that the mostly individuals treated with operation obtained satisfactory cardiac function. CONCLUSION: Correct diagnosis of ruptured aneurysm in sinus of Valsalva should be confirmed immediately and surgical correction should be carried out as soon as possible.

Adolescent↗

Functional analysis of FHA and BRCT domains of NBS1 in chromatin association and DNA damage responses.

Rad50/Mre11/NBS1 (R/M/N) is a multi-functional protein complex involved in DNA repair, cell cycle checkpoint activation, DNA replication and replication block-induced responses. Ionizing radiation (IR) induces the phosphorylation of NBS1 and nuclear foci formation of the complex. Although it has been suggested that the R/M/N complex is associated with DNA damage sites, we present here biochemical evidence for chromatin association of the complex. We show that the chromatin association of R/M/N is independent of IR and ataxia telangiectasia mutated (ATM). We also demonstrate that optimal chromatin association of the Rad50/Mre11/NBS1 proteins requires both the conserved forkhead-associated (FHA) and breast cancer C-terminus (BRCT) domains of NBS1. Moreover, both these domains of NBS1 are required for its phosphorylation on Ser343 but not on Ser278. Importantly, both the FHA and BRCT domains are essential for IR-induced foci (IRIF) formation of R/M/N and S phase checkpoint activation, but only the BRCT domain is needed for cell survival after IR. These data demonstrate that the FHA and BRCT domains of NBS1 are crucial for the functions of the R/M/N complex.

Acid Anhydride Hydrolases↗

SMC1 is a downstream effector in the ATM/NBS1 branch of the human S-phase checkpoint.

Structural maintenance of chromosomes (SMC) proteins (SMC1, SMC3) are evolutionarily conserved chromosomal proteins that are components of the cohesin complex, necessary for sister chromatid cohesion. These proteins may also function in DNA repair. Here we report that SMC1 is a component of the DNA damage response network that functions as an effector in the ATM/NBS1-dependent S-phase checkpoint pathway. SMC1 associates with BRCA1 and is phosphorylated in response to IR in an ATM- and NBS1-dependent manner. Using mass spectrometry, we established that ATM phosphorylates S957 and S966 of SMC1 in vivo. Phosphorylation of S957 and/or S966 of SMC1 is required for activation of the S-phase checkpoint in response to IR. We also discovered that the phosphorylation of NBS1 by ATM is required for the phosphorylation of SMC1, establishing the role of NBS1 as an adaptor in the ATM/NBS1/SMC1 pathway. The ATM/CHK2/CDC25A pathway is also involved in the S-phase checkpoint activation, but this pathway is intact in NBS cells. Our results indicate that the ATM/NBS1/SMC1 pathway is a separate branch of the S-phase checkpoint pathway, distinct from the ATM/CHK2/CDC25A branch. Therefore, this work establishes the ATM/NBS1/SMC1 branch, and provides a molecular basis for the S-phase checkpoint defect in NBS cells.

Amino Acid Sequence↗

Arsenic-induced Mre11 phosphorylation is cell cycle-dependent and defective in NBS cells.

Cancer-prone diseases ataxia-telangiectasia (AT), Nijmegen breakage syndrome (NBS) and ataxia-telangiectasia-like disorder (ATLD) are defective in the repair of DNA double-stranded break (DSB). On the other hand, arsenic (As) has been reported to cause DSB and to be involved in the occurrence of skin, lung and bladder cancers. To dissect the repair mechanism of As-induced DSB, wild type, AT and NBS cells were treated with sodium arsenite to study the complex formation and post-translational modification of Rad50/NBS1/Mre11 repair proteins. Our results showed that Mre11 went through cell cycle-dependent phosphorylation upon sodium arsenite treatment and this post-translational modification required NBS1 but not ATM. Defective As-induced Mre11 phosphorylation was rescued by reconstitution with full length NBS1 in NBS cells. Although As-induced Mre11 phosphorylation was not required for Rad50/NBS1/Mre11 complex formation, it might be required for the formation of Rad50/NBS1/Mre11 nuclear foci upon DNA damage.

Arsenites↗

[Studies on the chemical constituents of Lycianthes biflora].

AIM: To study the chemical constituents of Lycianthes biflora. METHODS: Column chromatography was used to separate the chemical constituents. IR, MS, 1HNMR, 13CNMR and 2D-NMR technique were used to determine the structures of the isolated constituents. RESULTS: Five compounds were isolated from this plant. Their structures were identified to be bifloride A (1), N-trans-cinnamoyltyramine (2), liquiritigenin (3), N-trans-p-coumaroyloctopamine (4), 1-O-beta-D-glucopyranosyl-2-N-2'-hydroxypalmitoyl-sphinga-4- trans-8-trans-dienine (5). CONCLUSION: Compounds 1 and 2 are new compounds, the others were isolated from this plant for the first time. Compound 2 showed inhibitory effects on P-388.

4-Butyrolactone↗