Little is known about biological significance of ELK1, a transcriptional factor that activates downstream targets including c-fos proto-oncogene, in bladder cancer. Recent preclinical evidence also suggests the involvement of androgen receptor (AR) signaling in bladder cancer progression. In this study, we aim to investigate the functions of ELK1 in bladder cancer growth and their regulation by AR signals. Immunohistochemistry in bladder tumor specimens showed that the levels of phospho-ELK1 (p-ELK1) expression were significantly elevated in urothelial neoplasms, compared with non-neoplastic urothelium tissues, and were also correlated with AR positivity. Patients with p-ELK1-positive non-muscle-invasive and muscle-invasive tumors had significantly higher risks for tumor recurrence and progression, respectively. In AR-positive bladder cancer cell lines, dihydrotestosterone treatment increased ELK1 expression (mRNA, protein) and its nuclear translocation, ELK1 transcriptional activity, and c-fos expression, which was restored by an anti-androgen hydroxyflutamide. ELK1 silencing via short hairpin RNA (shRNA) resulted in decreases in cell viability/colony formation, and cell migration/invasion as well as an increase in apoptosis. Importantly, ELK1 appears to require activated AR to regulate bladder cancer cell proliferation, but not cell migration. Androgen also failed to significantly induce AR transactivation in ELK1-knockdown cells. In accordance with our in vitro findings, ELK1-shRNA expression considerably retarded tumor formation as well as its growth in xenograft-bearing male mice. Our results suggest that ELK1 plays an important role in bladder tumorigenesis and cancer progression, which is further induced by AR activation. Accordingly, ELK1 inhibition, together with AR inactivation, has the potential of being a therapeutic approach for bladder cancer.
The objectives of this research was to determine the chemical composition of roscoe extract from methanol and evaluation of antibacterial activity. The phytochemical compound screened by GC-MS method. Forty eight bioactive phytochemical compounds were identified in the methanolic extract of Zingiber officinale. The identification of phytochemical compounds is based on the peak area, retention time molecular weight, molecular formula, MS Fragment-ions and pharmacological actions. GC-MS analysis of Zingiber officinale revealed the existence of the Octanal, 2-Naphthale namine, 1,2,4a,5,6,7,8, EndoBorneol, Decanal,1,[2][3][4][5][6][7][8][9][10][11][12][13][14][15] Propanal, Benzeneacetic acid ,2,3, 3´,15,16,21,22,(3ß,15á,16á,21ß,4,6a,7,8,9,10,10a,8,1, Naphthalene, decahydro-1-pentadecyl-, 13-Docosenamide,(Z)-, 9,10-Secocholesta-5,7,10(19)-triene-3,24,25-triol, (3ß,5Z,7E)-, n-(2,4-Dinitrophenyl)-N´-13-(2,6,6-trimethyl-cyclohex-1-enyl)propylider, n-(2,4-Dinitrophenyl)-N´-13-(2,6,6-trimethyl-cyclohex-1-enyl)propylider, Ingol 12-acetate, 2,2,8,12,7,11, Piperine,8,12,4,
ELK1 is likely to be activated in prostate cancer cells and promote tumor progression. Furthermore, silodosin that inactivates ELK1 in prostate cancer cells not only inhibits their growth but also enhances the cytotoxic activity of gemcitabine. Thus, ELK1 inhibition has the potential of being a therapeutic approach for prostate cancer.
Wound infections regards one of the most common infections encountered in hospital records. Pseudomonas aeruginosa regard the 3rd common pathogen among healthcare-related infections. Their ability to adapt to different conditions and presence of pool of virulence factors may render their infections delay in healing. During a period of six months 114 wound swabs were collected and inoculated on Pseudomonas chromogenic agar and then Pseudomonas aeruginosa isolated confirmed by PCR using specific primer for 16S rDNA gene of Pseudomonas aeruginosa. Molecular investigation of some virulence factor like ExoA, OprL, OprI, LasI and LasB were performed using a sets of specific primer pairs. The results revealed that only 26 (22.8%) isolates were Pseudomonas aeruginosa and the coexistence of more than one virulence factors within the same isolates was also recorder. OprI and LasB were most common followed by LasI, ExoA and OprL. Occurrence of virulence factor genes were 12(46.15%) for exoA, oprL was 11(42.3%), oprI was 22(84.61%), lasI was 14(53.84%) and lasB was 18(69.23%). Results of this study can lead us to conclude that P. aeruginosa have an arrays of virulence traits via which can adapt to different conditions and so cause a wide-ranging of hard to cured infections and the delay in healing and worseness degree may be attributed to owning multivirulence factors.
The prevalence of Diabetic mellitus in Iraq is high for both males and females, according to the World Health Organization (WHO). The major histocompatibility complex (MHC)/HLA region on chromosome 6p21 has been shown to contain the major genetic component of Type1Diabetic mellitus. A 14-base pair polymorphism inserts and/or removal in exon-8 has a potential role in HLA. This research explores the role of 14-bp HLA-G insertion / deletion polymorphism in Type 1 Diabetes mellitus (T1DM) patients. The polymorphism allele frequency was calculated in patients with T1DM and control. Insertion allele (70.8%) and homozygous deletion genotype are associated with T1D susceptibility (51.6%), while control group (38.3%) and heterozygous genotype of the 14-bp indel are correlated with T1D defense (38.3%) and control group (50%). also a significant differences in the allele frequencies of the HLA-G 14-bp polymorphism were observed. This research shows a sturdy relation among polymorphism HLA-G 14-bp and type1D.M. (P = 0.009). Our findings describe the combination of the 14-base pair insertion allele and the homozygous genotype deletion to the progress of T1D.
Pseudomonas aeruginosa consider one of the opportunistic pathogens is able to infection almost all body tissue as a result of having it a variety of virulence factors that contribute greatly to pathogenic events in the host this bacterium has been responsible for 30% of pneumonia, 19% of urinary tract infections and 10% of bloodstream infections. And leads to nosocomial pathogens causing infections that usually develop late during hospital stay. Consequently the aim of this research was to classify and characterize P. aeruginosa isolated from various clinical samples from Iraqi patients by sequencing the 16S rRNA gene.
gemcitabine or mitomycin, significantly increased number of SP cells was found in LGUCC (9.78%), HGUCC (13.56%), MIUCC (20.45%) and bladder cancer cell lines at 24 hours. In NUC only 1.7% SP cells were found and there was no increase in SP cells (Fig1C). Treatment with gemcitabine or mitomycin caused increased expression of stemness marker in SP (p<0.001) of HGUCC, LGUCC and MIUCC as compared to SP of NUC cells (Fig1D, E). SP of UCC cells treated with gemcitabine or mitomycin for 24 hours showed lower cell death as compared to NSP cells. Higher autophagic response was observed in SP of UCC in the presence of chemo-therapeutic agents as compared to NUC (Fig1F,G). Pharmacological inhibition or siRNA-mediated inhibition of autophagy led to decreased number of SP cells (Fig1H) and tumor sphere forming ability (Fig1I) with concomitant increase in caspase-mediated cell death (Fig1 J,K) in SP of UCC.CONCLUSIONS: The present study is the first to show that urothelial cancer cells exposed to chemotherapeutic agents increases the stemness properties in UCC and could be the underlying cause of resistance and relapse of the tumor.
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