• Title/Summary/Keyword: p-STAT3

Search Result 158, Processing Time 0.025 seconds

Identification of Gene-based Potential Biomarkers for Cephalexin-induced Nephrotoxicity in Mice

  • Park, Han-Jin;Oh, Jung-Hwa;Hwang, Ji-Yoon;Lim, Jung-Sun;Jeong, Sun-Young;Kim, Yong-Bum;Yoon, Seok-Joo
    • Molecular & Cellular Toxicology
    • /
    • v.2 no.3
    • /
    • pp.193-201
    • /
    • 2006
  • Cephalexin, one of most widely prescribed cephalosporin, has been reported to cause acute renal failure as a side effect in human and experimental animals. Although numerous animal studies have been reported for the cephalosporin nephrotoxicity, the molecular and cellular nephrotoxic mechanisms of cephalexin are still unknown. This investigation evaluated the time-dependent gene expression profile of kidney in mouse during cephalexin induced nephrotoxicity. C57BL/6 female mice were administered either saline or 1,000 mg/kg cephalexin intraperitoneally. Mice were sacrificed at 3, 6, and 24 hr after administration. Blood biochemical and histopathological results indicated cephalexin induced nephrotoxicity. Microarray experiment carried out using Affymetrix $GeneChip^{(R)}$. There were 198 informative genes that were significantly expressed >5-fold versus control at 3, 6, and 24 hr (p<0.01), of which 156 and 42 were up-and down-regulated, respectively. Major classes of up-regulated genes at 3, 6 hr included those involved in MAPK/Jak-STAT signaling pathway and immune response such as cytokine-cytokine receptor interaction and complement and coagulation cascades. At 24 hr, up-regulated genes were mainly involved in regeneration/repair and immune response; down-regulated genes were generally associated with transporters and intermediary metabolism. Among the up-regulated genes at 24 hr, several potential biomarkers on nephrotoxicity such as Kim-1, Fga, Timp1, and Slc34a2 were clustered in a same category. In addition, Tnfrsf12a and Lcn2 which were consistently up-regulated (>5 fold) were also included as potential biomarkers. These results may provide clues for elucidating the mechanism of cephalexin induced nephrotoxicity and evaluating potential biomarkers to assess nephrotoxicity.

Optimization of Growth Medium and Poly-$\beta$-hydroxybutyric Acid Production from Methanol in Methylobacterium organophilum (메탄올로부터 Methylobacterium organophilum에 의한 Poly-$\beta$-hydroxybutyric Acid의 생산과 배지성분의 최적화)

  • Choi, Joon-H;Kim, Jung H.;M. Daniel;J.M. Lebeault
    • Microbiology and Biotechnology Letters
    • /
    • v.17 no.4
    • /
    • pp.392-396
    • /
    • 1989
  • Methylobacterium organophilum, a facultative methylotroph was cultivated on a methanol as a sole carbon and energy source. The cell growth was affected by the various components of minimal synthetic medium and the medium composition was optimized with 0.5% (v/v) methanol at pH 6.8 and at 3$0^{\circ}C$. The maximum specific growth rate of M. organophilum was achieved to 0.26 hr$^{-1}$ in the optimized medium which has following composition: Methanol, 0.5% (v/v):(NH$_4$)$_2$SO$_4$, 1.0g/l:KH$_2$PO$_4$, 2.13g/l:KH$_2$PO$_4$, 1.305g/ι:MgSO$_4$.7$H_2O$. 45g/l and trace elements (CaCl$_2$.2$H_2O$, 3.3mg:FeSO$_4$.7$H_2O$, 1.3mg:MnSO$_4$.4$H_2O$, 130$\mu\textrm{g}$:ZnSO$_4$.5$H_2O$, 40$\mu\textrm{g}$:Na$_2$MoO$_4$.2$H_2O$, 40$\mu\textrm{g}$:CoCl$_2$.6$H_2O$, 40$\mu\textrm{g}$:H$_3$BO$_3$, 30$\mu\textrm{g}$ per liter). By the limitation of nitrogen and deficiency of Mn$^{+2}$ or Fe$^{+2}$, the cell growth was significantly repressed. Methanol greatly repressed the cell growth and the complete inhibition was observed at concentration above 4% (v/v). In order to overcome the methanol inhibition and to prevent the methanol limitation, intermittent feeding of methanol was conducted by a D.O.-stat technique. PHB production by M. organophilum was stimulated by deficiency of nutrients such as NH$_{4}^{+}$, SO$_{4}^{-2}$, $Mg^{+2}$, $K^{+}$, or PO$_{4}^{-3}$ in the medium. The maximum PHB content was obtained as 58% of dry cell weight under deficiency of potassium ion in the optimized synthetic medium.

  • PDF

Association of Candidate Genes with Production Traits in Korean Dairy Proven and Young Bulls

  • Jang, G.W.;Cho, K.H.;Kim, T.H.;Oh, S.J.;Cheong, I.C.;Lee, K.J.
    • Asian-Australasian Journal of Animal Sciences
    • /
    • v.18 no.2
    • /
    • pp.165-169
    • /
    • 2005
  • This study was performed to offer effective basic data for selection and improvement of Korean dairy cattle through identifying distributional properties among candidate genes (bovine butyrophilin, signal transducers and activators of transcription 5a, and prolactin hormone). In this study, polymorphisms of candidate genes were identified and the relationships between loci and production traits of each gene were analyzed using frozen semen of Holstein bulls (19 proven and 77 candidates). In butyrophilin (BTN) locus, polymorphisms information contents (PIC) value of BTN2 (0.372) was higher than those of others (BTN1; 0.155, BTN3; 0.254, BTN4; 0.169). As a result of analysis of genotyping STAT5a, using single stranded conformational polymorphism (SSCP) method and microsatellite locus, PIC values were 0.189 and 0.457, respectively. And PIC value of prolactin hormone gene was 0.176. In the relationships between genotypes and production traits, BTN3 was associated with 305-day production traits (p<0.05). PTAs for B allele were such as 110.43, 88.28 and 75.25 in BTN1, 3, 4 and these values were higher than those of A allele, but in the case of BTN2, A allele with 154.19 was higher than that of B allele. The results obtained from using candidate genes may be used as an useful index for the genetic improvement of dairy cattle population in Korea, and further studies are needed.

Loss of Heterozygosity at the Calcium Regulation Gene Locus on Chromosome 10q in Human Pancreatic Cancer

  • Long, Jin;Zhang, Zhong-Bo;Liu, Zhe;Xu, Yuan-Hong;Ge, Chun-Lin
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.16 no.6
    • /
    • pp.2489-2493
    • /
    • 2015
  • Background: Loss of heterozygosity (LOH) on chromosomal regions is crucial in tumor progression and this study aimed to identify genome-wide LOH in pancreatic cancer. Materials and Methods: Single-nucleotide polymorphism (SNP) profiling data GSE32682 of human pancreatic samples snap-frozen during surgery were downloaded from Gene Expression Omnibus database. Genotype console software was used to perform data processing. Candidate genes with LOH were screened based on the genotype calls, SNP loci of LOH and dbSNP database. Gene annotation was performed to identify the functions of candidate genes using NCBI (the National Center for Biotechnology Information) database, followed by Gene Ontology, INTERPRO, PFAM and SMART annotation and UCSC Genome Browser track to the unannotated genes using DAVID (the Database for Annotation, Visualization and Integration Discovery). Results: The candidate genes with LOH identified in this study were MCU, MICU1 and OIT3 on chromosome 10. MCU was found to encode a calcium transporter and MICU1 could encode an essential regulator of mitochondrial $Ca^{2+}$ uptake. OIT3 possibly correlated with calcium binding revealed by the annotation analyses and was regulated by a large number of transcription factors including STAT, SOX9, CREB, NF-kB, PPARG and p53. Conclusions: Global genomic analysis of SNPs identified MICU1, MCU and OIT3 with LOH on chromosome 10, implying involvement of these genes in progression of pancreatic cancer.

Bioinformatic Prediction of SNPs within miRNA Binding Sites of Inflammatory Genes Associated with Gastric Cancer

  • Song, Chuan-Qing;Zhang, Jun-Hui;Shi, Jia-Chen;Cao, Xiao-Qin;Song, Chun-Hua;Hassan, Adil;Wang, Peng;Dai, Li-Ping;Zhang, Jian-Ying;Wang, Kai-Juan
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.15 no.2
    • /
    • pp.937-943
    • /
    • 2014
  • Polymorphisms in miRNA binding sites have been shown to affect miRNA binding to target genes, resulting in differential mRNA and protein expression and susceptibility to common diseases. Our purpose was to predict SNPs (single nucleotide polymorphisms) within miRNA binding sites of inflammatory genes in relation to gastric cancer. A complete list of SNPs in the 3'UTR regions of all inflammatory genes associated with gastric cancer was obtained from Pubmed. miRNA target prediction databases (MirSNP, Targetscan Human 6.2, PolymiRTS 3.0, miRNASNP 2.0, and Patrocles) were used to predict miRNA target sites. There were 99 SNPs with MAF>0.05 within the miRNA binding sites of 41 genes among 72 inflammation-related genes associated with gastric cancer. NF-${\kappa}B$ and JAK-STAT are the two most important signaling pathways. 47 SNPs of 25 genes with 95 miRNAs were predicted. CCL2 and IL1F5 were found to be the shared target genes of hsa-miRNA-624-3p. Bioinformatic methods could identify a set of SNPs within miRNA binding sites of inflammatory genes, and provide data and direction for subsequent functional verification research.

Combined Treatment with Stattic and Docetaxel Alters the Bax/Bcl-2 Gene Expression Ratio in Human Prostate Cancer Cells

  • Mohammadian, Jamal;Sabzichi, Mehdi;Molavi, Ommoleila;Shanehbandi, Dariush;Samadi, Nasser
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.17 no.11
    • /
    • pp.5031-5035
    • /
    • 2016
  • Docetaxel, recognized as a stabilizing microtubule agent, is frequently administrated as a first line treatment for prostate cancers. Due to high side effects of monotherapy, however, combinations with novel adjuvants have emerged as an alternative strategy in cancer therapy protocols. Here, we investigated the combined effects of stattic and docetaxel on the DU145 prostate cancer cell line. Cytotoxicity was evaluated by MTT assay. To understand molecular mechanisms of stattic action, apoptotic related genes including Bcl-2, Mcl-1, Survivin and Bax were evaluated by real-time RT-PCR. Alteration in the expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 genes and Bax/Bcl-2 ratio were investigated via the $2^{{\Delta}{\Delta}CT}$ method. The $IC_{50}$ values for docetaxel and stattic were $3.7{\pm}0.9nM$ and $4.6{\pm}0.8{\mu}M$, respectively. Evaluation of key gene expression levels revealed a noticeable decrease in antiapoptotic Bcl-2 and Mcl-1 along with an increase in pro-apoptotic Bax mRNA levels (p<0.05). Our results suggest that combination of a STAT3 inhibitor with doctaxel can be considered as a potent strategy for induction of apoptosis via increasing Bax mRNA expression.

Attenuation of Experimental Autoimmune Hepatitis in Mice with Bone Mesenchymal Stem Cell-Derived Exosomes Carrying MicroRNA-223-3p

  • Lu, Feng-Bin;Chen, Da-Zhi;Chen, Lu;Hu, En-De;Wu, Jin-Lu;Li, Hui;Gong, Yue-Wen;Lin, Zhuo;Wang, Xiao-Dong;Li, Ji;Jin, Xiao-Ya;Xu, Lan-Man;Chen, Yong-Ping
    • Molecules and Cells
    • /
    • v.42 no.12
    • /
    • pp.906-918
    • /
    • 2019
  • MicroRNA-223-3p (miR-223-3p) is one of the potential microRNAs that have been shown to alleviate inflammatory responses in pre-clinical investigations and is highly encased in exosomes derived from bone mesenchymal stem cells (MSC-exosomes). MSC-exosomes are able to function as carriers to deliver microRNAs into cells. Autoimmune hepatitis is one of the challenging liver diseases with no effective treatment other than steroid hormones. Here, we examined whether MSC-exosomes can transfer miR-223-3p to treat autoimmune hepatitis in an experimental model. We found that MSC-exosomes were successfully incorporated with miR-223-3p and delivered miR-223-3p into macrophages. Moreover, there was no toxic effect of exosomes on the macrophages. Furthermore, treatments of either exosomes or exosomes with miR-223-3p successfully attenuated inflammatory responses in the liver of autoimmune hepatitis and inflammatory cytokine release in both the liver and macrophages. The mechanism may be related to the regulation of miR-223-3p level and STAT3 expression in the liver and macrophages. These results suggest that MSC-exosomes can be used to deliver miR-223-3p for the treatment of autoimmune hepatitis.

Comparative study on production, reproduction and functional traits between Fleckvieh and Braunvieh cattle

  • Cziszter, Ludovic-Toma;Ilie, Daniela-Elena;Neamt, Radu-Ionel;Neciu, Florin-Cristian;Saplacan, Silviu-Ilie;Gavojdian, Dinu
    • Asian-Australasian Journal of Animal Sciences
    • /
    • v.30 no.5
    • /
    • pp.666-671
    • /
    • 2017
  • Objective: Aim of the current comparative study was to evaluate production outputs, reproduction efficiency and functional traits in dual-purpose Fleckvieh and Braunvieh cows, reared under temperate European conditions. Methods: A data-set from 414 Fleckvieh and 42 Braunvieh cows and 799 lactations was analysed. ID tag number, milk yield per milking session, number of steps/interval and milk conductivity were recorded and collected daily using AfiMilk 3.076 A-DU software (Afimilk Ltd., Kibbutz, Israel). Production and milk quality data were taken from the results of the official performance recordings and the reproductive outputs of cows were recorded by the research stations veterinarians. Comparisons between the two genotypes were carried out using the one way analysis of variance protocol, with categorical factor being considered the breed of cows. All the statistical inferences were carried out using Statistica software (StatSoft Inc., Tulsa, OK, USA). Results: Fleckvieh cows significantly outperformed ($p{\leq}0.05$) the Braunvieh herd, with average milk yields of $5,252.1{\pm}35.79kg$ and $4,897.6{\pm}128.94kg$, respectively. Age at first calving was significantly ($p{\leq}0.01$) influenced by the breed, with Fleckvieh heifers being more precocious ($32.8{\pm}0.29mo$) compared to those of Braunvieh breed ($35.7{\pm}0.84mo$). Reproduction efficiency as defined by the number of inseminations per gestation, calving interval, dystocia, days dry and days open, was not influenced by genotype (p>0.05). Incidences of sub-clinical mastitis, clinical mastitis, lameness and abortions were not influenced by the breed factor (p>0.05). Stay-ability of cows was significantly ($p{\leq}0.001$) influenced by genotype, with Braunvieh cows having an average age at culling of $117.88{\pm}11.78$ months compared to $90.88{\pm}2.89$ months in Fleckvieh. Conclusion: Overall, results have shown that genotype significantly influenced milk yield, age at first calving and longevity.

Production of High Concentration Cellulose by Acetobacter xylinum BRC5 in Fed-Batch Culture (Acetobacter xylinum BRC5의 fed-batch 배양에 의한 셀룰로오스의 고농도 생산)

  • 황정숙;이창승;박상훈;양영국;변유량
    • KSBB Journal
    • /
    • v.14 no.3
    • /
    • pp.284-290
    • /
    • 1999
  • Glucose fed-batch culture was studied to improve cellulose productivity by Acetobacter xylinum BRC5. When initial glucose concentrations in batch cultures were less than 20 g/L, yield coefficients of cellulose (Yp/s) remained a constant value of 0.21 g cellulose/g glucose. But a low yield coefficient, Yp/s=0.13 was obtained from an initial glucose concentration of 40 g/L. Since initial high glucose concentrations in batch culture resulted in low yields of cellulose, constant fed-batch cultures were carried out. The optimal feed rate for fed-batch culture was 2.22 g glucose/L.h. In constant fed-batch culture without DO control, 10 g/L of cellulose was obtained from 40 g/L of glucose with this feed rate, which was approximately two fold higher than that of the batch culture with the same initial glucose concentration. In DO stat plus fed-batch culture, the highest cellulose productivity could be obtained when dissolved oxygen level was controlled at 10% of air saturation, and cellulose productivity increased about 1.5 times compared with that of the culture without DO control.

  • PDF

A Study of the Chewing Patterns in Patients with Temporomandibular Disorders by Electrognathography (Electrognathography를 이용한 측두하악장애환자의 저작양태에 관한 연구)

  • Moon-Gyu Kim;Kyung-Soo Han
    • Journal of Oral Medicine and Pain
    • /
    • v.20 no.2
    • /
    • pp.291-306
    • /
    • 1995
  • Mandibular movement is composed of border movement and functional movement. Border movement such as maximal mouth opening, hinge opening ad lateral eccentric movement has good reproducibility, but functional movement such as chewing, swallowing and speech has also reproducibility. Especially for chewing movement, individual reproducibility has been confirmed by many studies. Study of chewing pattern is still in controversy. In new approach for raising the diagnostic value, numeric parameters and morphologic characteristics could be used for evaluation of chewing pattern. This study was performed to investigate the differences between chewing pattern in controls and in patients with temporomandibular disorders. Sixty-three patients with temporomandibular disorders participated in this study, and they were divided into unilaterally affected subjects or bilaterally affected subjects. Then unilaterally affected subjects were classified into closed lock group, disk displacement with reduction group, and degenerative joint disease group. For recording of chewing pattern, subjects were asked to chew one piece of presoftened chewing gum on both sides, and the chewing movement was recorded with the Electrognatho- Graphy(Bio-Research Associates Inc., U.S.A.). Tooth contact pattern for occlusal stability (Total left-right statistics )was also recorded with T-Scan(Tekscan Co., U.S.A.). The dta related to chewing pattern and total left-right statistics were statistically analyzed by SAS/stat program. The obtained results were as follows : 1. In patient group, mean value of A-P distance and the ratio of A-P distance to vertical distance were larger than control group, but the value of lateral distance in affected side and the closing velocity in unaffected side were smaller than that of control group, respectively. 2. In case of unilateral affected patients, chewing pattern of other side had tendency to restricted movement and slow velocity in closed lock group or degenerative joint disease group than control group or disk displacement with reduction group. 3. In bilateral degenerative joint disease patients, contralateral side had tendency to large range of motion and slow chewing velocity than preferred chewing side. 4. The patients with restricted mouth opening below than 35mm had higher value of total left-right statistics than patient group mouth opening above 35mm. Also closed lock group had higher total left-right statistics than disk displacement with reduction group, degenerative joint disease group and control group. 5. There was some difference in morphologic characteristics of chewing pattern between in control group and in affected side of unilateral patient group, but no difference between control group and unaffected side of unilateral patient group. 6. There were positive correlations between vertical distance and A-P distance, between vertical distance and chewing velocity, between A-P distance and chewing velocity, and between opening velocity and closing velocity in unilateral affected patients.

  • PDF