• Asian Pacific Journal of Cancer Prevention
• /
• 제16권5호
• /
• pp.1987-1992
• /
• 2015

The aim of this research was to investigate the possible association between gastric carcinoma (GC) and polymorphisms of the IL-$1{\beta}$ gene in the Kashmiri population using peripheral blood DNA from 150 gastric carcinoma cases and 250 population controls with detailed data for clinicopathological characteristics of the disease. Two SNPs in the IL-$1{\beta}$ gene were selected for this study. Expression of IL-$1{\beta}$ was studied in 50 gastric carcinoma cases using immunohistochemistry and RT-PCR and then correlated with genotype. The frequency of the IL-$1{\beta}$-511 C allele was significantly higher in the GC case group (53.3%) than in controls (45.4%) with an odds ratio (OR) of 0.73 and a P value of 0.03. Multivariate regression analysis showed associations of gastric carcinoma with mutant form of IL-$1{\beta}$-511 TT (OR 0.309; P value <0.001) and the CC genotype of IL-$1{\beta}$-31 (OR 0.313; P value of 0.002). Haplotype analysis of IL-$1{\beta}$-31 and IL-$1{\beta}$-511 showed decreased association of IL-$1{\beta}$-31 T with IL-$1{\beta}$-511 C with gastric carcinoma (OR 0.728; P value 0.03). Expression study of 50 samples by immunohistochemistry (IHC) and RT-PCR showed association with grade III and stage III+IV. After correlating the expression with polymorphism no association was found.

• 대한한방내과학회지
• /
• 제39권4호
• /
• pp.751-763
• /
• 2018

Objective: This study was undertaken to investigate how magnolia bark extract affects ob/ob mouse in terms of metabolic inflammation and insulin resistance. Methods: Leptin-deficient ob/ob mice were divided into 2 groups (n=5): a normal saline treatment (=control) and magnolia bark treatment. Wild type mice were the lean group (n=5). After 5 weeks, we measured fasting blood sugar (FBS) and conducted oral glucose tolerance tests (OGTTs) in each group. After 6 weeks, we measured body weight, epididymal fat pad weight, liver weight, serum glucose, serum insulin, and gene expression of tumor necrosis factor-${\alpha}$, interferon-${\gamma}$, and interleukin-6. We characterized the phenotype of adipose tissue macrophages (ATMs) and analyzed fractions of the phenotype in each group by flow cytometry. Results: In the magnolia bark group, fasting blood sugar, oral glucose tolerance levels, and insulin resistance (HOMA-IR) were significantly decreased. The population and proportion of ATMs among leukocytes in adipose tissue were significantly decreased in the magnolia bark group. The population and proportion of M1 type ATMs among ATMs were significantly decreased in the magnolia bark group. Gene expression of tumor necrosis factor-${\alpha}$ was significantly decreased in the magnolia bark group. Conclusions: These results support a positive effect of magnolia bark on metabolic diseases such as insulin resistance and metabolic inflammation in leptin-deficient ob/ob mice.

• The Korean Journal of Physiology and Pharmacology
• /
• 제21권5호
• /
• pp.457-464
• /
• 2017

Etoricoxib features antioxidant and anti-inflammatory properties concomitantly, suggesting that it may be beneficial in testicular ischemia reperfusion (I/R) damage. Our aim is to investigate the effects of etoricoxib on testicular I/R damage induced with torsion-detorsion (TD). The etoricoxib + torsion-detorsion (ETD) groups of animals were given etoricoxib in 50 and 100 mg/kg of body weight (ETD-50 and ETD-100), while the testes torsion-detorsion (TTD) and sham operation rat group (SOG) animals were given single oral doses of distilled water as a solvent. TTD, ETD-50 and ETD-100 groups were subjected to $720^{\circ}$ degrees torsion for four hours, and detorsion for four hours. The SOG group was not subjected to this procedure. Biochemical, gene expression and histopathological analyses were carried out on the testicular tissues. The levels of malondialdehyde (MDA), myeloperoxidase (MPO), interleukin-1 beta ($IL-1{\beta}$) and tumor necrosis factor alpha ($TNF-{\alpha}$) were significantly higher, and the levels of total glutathione (tGSH) and glutathione reductase (GSHRd) were significantly lower in the TTD group, compared to the ETD-50, ETD-100 and SOG groups. Etoricoxib at a dose of 100 mg/kg better prevented I/R damage than the 50 mg/kg dose. Etoricoxib may be useful in clinical practice in the reduction of I/R damage on testes caused by torsion-detorsion.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권3호
• /
• pp.1819-1823
• /
• 2013

Objective: Microarray data were analyzed to explore key genes and their functions in progression of colorectal cancer (CRC). Methods: Two microarray data sets were downloaded from Gene Expression Omnibus (GEO) database and differentially expressed genes (DEGs) were identified using corresponding packages of R. Functional enrichment analysis was performed with DAVID tools to uncover their biological functions. Results: 631 and 590 DEGs were obtained from the two data sets, respectively. A total of 32 common DEGs were then screened out with the rank product method. The significantly enriched GO terms included inflammatory response, response to wounding and response to drugs. Two interleukin-related domains were revealed in the domain analysis. KEGG pathway enrichment analysis showed that the PPAR signaling pathway and the renin-angiotensin system were enriched in the DEGs. Conclusions: Our study to systemically characterize gene expression changes in CRC with microarray technology revealed changes in a range of key genes, pathways and function modules. Their utility in diagnosis and treatment now require exploration.

• Biomolecules & Therapeutics
• /
• 제22권5호
• /
• pp.426-430
• /
• 2014

Prostate cancer is the most frequently diagnosed cancer. Although prostate tumors respond to androgen ablation therapy at an early stage, they often acquire the potential of androgen-independent growth. Elevated transcriptional activity of androgen receptor (AR) and/or signal transducer and activator of transcription-3 (STAT3) contributes to the proliferation of prostate cancer cells. In the present study, we examined the effect of resveratrol, a phytoalexin present in grapes, on the reporter gene activity of AR and STAT3 in human prostate cancer (LNCaP-FGC) cells stimulated with interleukin-6 (IL-6) and/or dihydrotestosterone (DHT). Our study revealed that resveratrol suppressed the growth of LNCaP-FGC cells in a time- and concentration-dependent manner. Whereas the AR transcriptional activity was induced by treatment with either IL-6 or DHT, the STAT3 transcriptional activity was induced only by treatment with IL-6 but not with DHT. Resveratrol significantly attenuated IL-6-induced STAT3 transcriptional activity, and DHT- or IL-6-induced AR transcriptional activity. Treatment of cells with DHT plus IL-6 significantly increased the AR transcriptional activity as compared to DHT or IL-6 treatment alone and resveratrol markedly diminished DHT plus IL-6-induced AR transcriptional activity. Furthermore, the production of prostate-specific antigen (PSA) was decreased by resveratrol in the DHT-, IL-6- or DHT plus IL-6-treated LNCaP-FGC cells. Taken together, the inhibitory effects of resveratrol on IL-6- and/or DHT-induced AR transcriptional activity in LNCaP prostate cancer cells are partly mediated through the suppression of STAT3 reporter gene activity, suggesting that resveratrol may be a promising therapeutic choice for the treatment of prostate cancer.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권24호
• /
• pp.10797-10801
• /
• 2015

Background: To explore the molecular mechanisms of metastatic osteosarcoma (OS) by using the microarray expression profiles of metastatic and non-metastatic OS samples. Materials and Methods: The gene expression profile GSE37552 was downloaded from Gene Expression Omnibus database, including 2 human metastatic OS cell line models and 2 two non-metastatic OS cell line models. The differentially expressed genes (DEGs) were identified by Multtest package in R language. In addition, functional enrichment analysis of the DEGs was performed by WebGestalt, and the protein-protein interaction (PPI) networks were constructed by Hitpredict, then the signal pathways of the genes involved in the networks were performed by Kyoto Encyclopaedia of Genes and Genomes (KEGG) automatic annotation server (KAAS). Results: A total of 237 genes were classified as DEGs in metastatic OS. The most significant up- and down-regulated genes were A2M (alpha-2-macroglobulin) and BCAN (brevican). The DEGs were significantly related to the response to hormone stimulus, and the PPI network of A2M contained IL1B (interleukin), LRP1 (low-density lipoprotein receptor-related protein 1) and PDGF (platelet-derived growth factor). Furthermore, the MAPK signaling pathway and focal adhesion were significantly enriched. Conclusions: A2M and its interactive proteins, such as IL1B, LRP1 and PDGF may be candidate target molecules to monitor, diagnose and treat metastatic OS. The response to hormone stimulus, MAPK signaling pathway and focal adhesion may play important roles in metastatic OS.

• Archives of Pharmacal Research
• /
• 제29권10호
• /
• pp.890-897
• /
• 2006

In inflammatory responses, induction of cytokines and other immune regulator genes in macrophages by pathogen-associated signal such as lipopolysaccharide (LPS) plays a crucial role. In this study, the gene expression profile changes by LPS treatment in the macrophage/monocyte lineage cell line RAW264.7 was investigated. A 60-mer oligonucleotide microarray of which probes target 32381 mouse genes was used. A reverse transcription-in vitro translation labeling protocol and a chemileuminescence detection system were employed. The mRNA expression levels in RAW264.7 cells treated for 6 h with LPS and the control vehicle were compared. 747 genes were up-regulated and 523 genes were down-regulated by more than 2 folds. 320 genes showing more than 4-fold change by LPS treatment were further classified for the biological process, molecular function, and signaling pathway. The biological process categories that showed high number of increased genes include the immunity and defense, the nucleic acid metabolism, the protein metabolism and modification, and the signal transduction process. The chemokine-cytokine signaling, interleukin signaling, Toll receptor signaling, and apoptosis signaling pathways involved high number of genes differentially expressed in response to LPS. These expression profile data provide more comprehensive information on LPS-target genes in RAW264.7 cells, which will be useful in comparing gene expression changes induced by extracts and compounds from anti-inflammatory medicinal herbs.

• Macromolecular Research
• /
• 제13권4호
• /
• pp.293-296
• /
• 2005

Transferrin ($T_{f}$) has been used as a targeting ligand for delivering liposome/interleukin-12 (IL-12) pDNA complexes to cancer cells mostly due to the greater number of transferrin receptors ($T_{f}R$) found on tumor cells than on normal cells. $T_{f}$ was conjugated to liposomes via the reaction of MPB-PE with thiol groups of $T_{f}$ introduced by a heterobifunctional cross-linking agent, N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP). Four days after C26 inoculation when the tumor volume reached ${\sim}100mm^{3}$, tumor-bearing Balb/c mice were injected intravenously with $T_{f}-liposome/IL-12 pDNA$complexes twice a week for 3 weeks. Significant suppression of tumor growth was achieved in the group treated with the $T_{f}-liposome/IL-12 pDNA$ complexes, with a dose of $10{\mu}g$ of IL-12 pDNA showing the highest suppression effect among the tested doses. Similar results were obtained when the therapy was initiated one day after tumor inoculation, although in this case $30{\mu}g$ IL-12 pDNA/$T_{f}-liposome$ complexes showed a significant suppression of tumor growth between 19 and 23 days after tumor inoculation. This result indicates that the transferrin receptor-targeted liposomal system is an efficient delivery agent of therapeutic genes, such as IL-12, in mice and that its potential clinical use warrants further research investigation.

• Nutrition Research and Practice
• /
• 제11권4호
• /
• pp.290-299
• /
• 2017

BACKGROUND/OBJECTIVES: Spirulina is a known a functional food related to lipid profiles, immune functions, and antioxidant capacity. Circulating monocyte chemoattractant protein-1 (MCP-1) level is associated with inflammation markers. Single nucleotide polymorphism in the MCP-1 promoter region -2518 have been identified and shown to affect gene transcription. Gene variation may also impact functional food supplementary effects. The current study investigated the interaction of MCP-1 -2518 polymorphism with spirulina supplements on anti-inflammatory capacity in Korean elderly. SUBJECTS/METHODS: After genotyping, healthy elderly subjects (n = 78) were included in a randomized, double blind, and placebo controlled study. Baseline characteristic, body composition, and dietary intake were measured twice (baseline vs. week 16). For 16 weeks, subjects consumed 8 g either spirulina or placebo daily. Plasma MCP-1, interleukin (IL) -2, IL-6, tumor necrosis factor (TNF)-${\alpha}$, complement (C) 3, immunoglobulin (Ig) G, and Ig A concentrations and lymphocyte proliferation rate (LPR) were analyzed as inflammatory markers. RESULTS: In the placebo group with A/A genotype, MCP-1 level was significantly increased, but the spirulina group with A/A genotype was unchanged. IL-2 was significantly increased only in subjects with spirulina supplementation. TNF-${\alpha}$ was significantly reduced in subjects with the G carrier. C3 was significantly increased in the placebo group, particularly when A/A increased more than G, but not when spirulina was ingested. LPR was significantly different only in subjects with A/A genotype; there was a significant increase in phytohemagglutinin and lipopolysaccharide induced LPR in the spirulina group. CONCLUSION: In healthy Korean elderly, spirulina supplementation may influence different inflammatory markers by the MCP-1 genotype. These results may be useful for customized dietary guidelines to improve immune function in Koreans.

• Journal of Veterinary Science
• /
• 제22권1호
• /
• pp.8.1-8.11
• /
• 2021

Background: Porcine circovirus type 2 (PCV2) is an important infectious pathogen implicated in porcine circovirus-associated diseases (PCVAD), which has caused significant economic losses in the pig industry worldwide. Objectives: A suitable viral vector-mediated gene transfer platform for the expression of the capsid protein (Cap) is an attractive strategy. Methods: In the present study, a recombinant adeno-associated virus 8 (rAAV8) vector was constructed to encode Cap (Cap-rAAV) in vitro and in vivo after gene transfer. Results: The obtained results showed that Cap could be expressed in HEK293T cells and BABL/c mice. The results of lymphocytes proliferative, as well as immunoglobulin G (IgG) 2a and interferon-γ showed strong cellular immune responses induced by Cap-rAAV. The enzyme-linked immunosorbent assay titers obtained and the IgG1 and interleukin-4 levels showed that humoral immune responses were also induced by Cap-rAAV. Altogether, these results demonstrated that the rAAV8 vaccine Cap-rAAV can induce strong cellular and humoral immune responses, indicating a potential rAAV8 vaccine against PCV2. Conclusions: The injection of rAAV8 encoding PCV2 Cap genes into muscle tissue can ensure long-term, continuous, and systemic expression.