A Bee Colony Optimization Approach for Mixed Blocking Constraints Flow Shop Scheduling Problems

The flow shop scheduling problems with mixed blocking constraints with minimization of makespan are investigated. The Taguchi orthogonal arrays and path relinking along with some efficient local search methods are used to develop a metaheuristic algorithm based on bee colony optimization. In order to compare the performance of the proposed algorithm, two well-known test problems are considered. Computational results show that the presented algorithm has comparative performance with well-known algorithms of the literature, especially for the large sized problems

Mycoplasma Infection in Pyospermic Infertile and Healthy Fertile Men

Background: Infections are one of the correctable causes of infertility with low cost and cost effective treatment. The 50% of infertile cases is related to men in some way, and 30% of them are absolutely related to them. Mycoplasmas are the smallest microorganisms with capability of DNA replication. Present study is planned to compare the mycoplasma infection in infertile men and men with established fertility.Materials and Methods: 45 Semen samples were collected from case and control persons who reffered to Royan Infertility and Fertility Institute between 2004 and 2005 and stored in -20°C until time of test. DNA was extracted from semen using phenol chloroform. PCR reaction was done by mycoplasma specific primers.Results: Mycoplasma genitalium gene was amplified in 6 (40%) cases from 15 infertile semen samples and 11 (36.6%) from 30 control semen samples.Conclusion: Probability of genital infection, at least, in these studies group, is very lower than other communities' reports

Adenosine pretreatment attenuates angiotensin II-mediated p38 MAPK activation in a protein kinase A dependent manner

Background: Adenosine is known as a protective and anti-inflammatory nucleoside. Angiotensin II is the main hormone of the renin-angiotensin system. It is associated with endothelial permeability, recruitment, and activation of the immune cells through induction of inflammatory mediators. Matrix metalloproteinase-9 (MMP-9) plays an important role in inflammatory processes mediated by macrophages. Objectives: Investigate whether adenosine pretreatment modulates angiotensin II-induced MMP-9 expression and activation of signaling molecules. Methods: Human monocytic U-937 cells were treated with either adenosine or angiotensin II alone or angiotensin II following a pretreatment with adenosine. Supernatants were analyzed for MMP-9 activity by zymography method. MMP-9 gene expression was analyzed using real-time PCR. Activation of inflammatory mediators IκB-α, NF-κB, JNK, p38 MAPK, and STAT3 were analyzed by a multi-target ELISA kit. Association of Protein kinase A (PKA) in adenosine effects was studied by pre-incubation with H89, a selective PKA inhibitor. Results: Treatment of the cells with angiotensin II significantly increased MMP-9 production (p <0.05). Adenosine pretreatment did not attenuate this angiotensin II effect. Angiotensin II treatment induced NF-κB, JNK and p38 activation. Pretreatment with adenosine prior to angiotensin II stimulation showed a 40 inhibitory effect on p38 induction (p <0.05). This effect was reversed by PKA inhibition. Conclusion: The present data confirmed that monocytic MMP-9 was a target gene for angiotensin II. Adenosine pretreatment did not inhibit MMP-9 increase in response to angiotensin II. However, it showed a potential inhibitory effect on angiotensin II inflammatory signaling

Angiotensin II differentially induces matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 production and disturbs MMP/TIMP balance

Angiotensin II, the main component of the renin-angiotensin system, is associated with cardiovascular diseases such as hypertension, vascular remodeling and inflammation. Remodeling process results from dysregulation of Matrix Metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). MMPs are considered as important target genes for angiotensin II. The aim of this study was to determine the effects of angiotensin II on MMP-9 and TIMP-1 production and MMP/TIMP balance in a monocytic cell type. Human monocytic U-937 cells were cultured and treated with 100 nM angiotensin II. Supernatants were analyzed for MMP-9 and TIMP-1 using ELISA and zymography methods. Real-time PCR was utilized to evaluate relative MMP-9 and TIMP-1 genes expression following treatments. Cytotoxicity potentials of treatments were determined by assaying lactate dehydrogenase leakage from the cells. Stimulation of the monocytic cells with angiotensin II significantly increased MMP-9 and TIMP-1 secretion as measured by ELISA (p<0.05). It also augmented gelatinolytic activity of MMP-9 in the conditioned media as much as 49 (p<0.05). Incubation of the cells with angiotensin II for 12 hr increased MMP-9 and TIMP-1 gene expression 2.7 and 1.8 folds, respectively (p<0.05). Angiotensin II treatments did not establish significant cytotoxic effects. In summary, our data provide further evidences that monocytic MMP-9 is a major effector of angiotensin II. It is induced more efficiently than TIMP-1 by angiotensin II that leads to MMP/TIMP imbalance. Our data also reveal the pivotal participation of these cells in pathological cardiovascular remodeling mediated by angiotensin II. Copyright © 2010, Avicenna Journal of Medical Biotechnology. All rights reserved

Angiotensin II induces NF-κB, JNK and p38 MAPK activation in monocytic cells and increases matrix metalloproteinase-9 expression in a PKC- and Rho kinase-dependent manner

Angiotensin II (ANG II), the main effector of the renin-angiotensin system, is implicated in endothelial permeability, recruitment and activation of immune cells, and also vascular remodeling through induction of inflammatory genes. Matrix metalloproteinases (MMPs) are considered to be important inflammatory factors. Elucidation of ANG II signaling pathways and of possible cross-talks between their components is essential for the development of efficient inhibitory medications. The current study investigates the inflammatory signaling pathways activated by ANG II in cultures of human monocytic U-937 cells, and the effects of specific pharmacological inhibitors of signaling intermediates on MMP-9 gene (MMP-9) expression and activity. MMP-9 expression was determined by real-time PCR and supernatants were analyzed for MMP-9 activity by ELISA and zymography methods. A multi-target ELISA kit was employed to evaluate IκB, NF-κB, JNK, p38, and STAT3 activation following treatments. Stimulation with ANG II (100 nM) significantly increased MMP-9 expression and activity, and also activated NF-κB, JNK, and p38 by 3.8-, 2.8- and 2.2-fold, respectively (P < 0.01). ANG II-induced MMP-9 expression was significantly reduced by 75 and 67, respectively, by co-incubation of the cells with a selective inhibitor of protein kinase C (GF109203X, 5 μM) or of Rho kinase (Y-27632, 15 μM), but not with inhibitors of phosphoinositide 3-kinase (wortmannin, 200 nM), tyrosine kinases (genistein, 100 μM) or of reactive oxygen species (α-tocopherol, 100 μM). Thus, protein kinase C and Rho kinase are important components of the inflammatory signaling pathways activated by ANG II to increase MMP-9 expression in monocytic cells. Both signaling molecules may constitute potential targets for effective management of inflammation

Use of biotin targeted methotrexate–human serum albumin conjugated nanoparticles to enhance methotrexate antitumor efficacy

Biotin molecules could be used as suitable targeting moieties in targeted drug delivery systems against tumors. To develop a biotin targeted drug delivery system, we employed human serum albumin (HSA) as a carrier. Methotrexate (MTX) molecules were conjugated to HSA. MTX-HSA nanoparticles (MTX-HSA NPs) were prepared from these conjugates by cross-linking the HSA molecules. Biotin molecules were then conjugated on the surface of MTX-HSA NPs. The anticancer efficacy of biotin targeted MTX-HSA NPs was evaluated in mice bearing 4T1 breast carcinoma. A single dose of biotin targeted MTX-HSA NPs showed stronger in vivo antitumor activity than non-targeted MTX-HSA NPs and free MTX. By 7 days after treatment, average tumor volume in the biotin targeted MTX-HSA NPs-treated group decreased to 17.6% of the initial tumor volume when the number of attached biotin molecules on MTX-HSA-NPs was the highest. Average tumor volume in non-targeted MTX-HSA NPs-treated mice grew rapidly and reached 250.7% of the initial tumor volume. Biotin targeted MTX-HSA NPs increased the survival of tumor-bearing mice to 47.5 ± 0.71 days and increased their life span up to 216.7%. Mice treated with biotin targeted MTX-HSA NPs showed slight body weight loss (8%) 21 days after treatment, whereas non-targeted MTX-HSA NPs treatment at the same dose caused a body weight loss of 27.05% ± 3.1%

Biosynthesis and recovery of selenium nanoparticles and the effects on matrix metalloproteinase-2 expression

Today, green synthesis of nanoparticles is attracting increasing attention. In the present study, the Bacillus sp. MSh-1 was isolated from the Caspian Sea (located in the northern part of Iran) and identified by various identification tests and 16S ribosomal DNA analysis. The reduction time course study of selenium ion (Se4+) reduction by using this test strain was performed in a liquid culture broth. Then, the intracellular NPs (nanoparticles) were released by the liquid nitrogen disruption method and thoroughly purified using an n-octyl alcohol water extraction system. Characterization of the separated NPs on features such as particle shape, size and purity was carried out with different devices. The energy dispersive X-ray and X-ray diffraction patterns showed that the purified NPs consisted of only selenium and are amorphous respectively. In addition, the transmission electron micrograph showed that the separated NPs were spherical and 80–220 nm in size. Furthermore, the cytotoxicity effect of these extracted biogenic selenium (Se) NPs on the fibrosarcoma cell line (HT-1080) proliferation and the inhibitory effect of the Se NPs on MMP-2 (matrix metalloproteinase-2) expression were studied using the MTT [3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyl-2H-tetrazolium bromide] assay and gelatin zymography. Biogenic Se NPs showed a moderately inhibitory effect on MMP-2 expression

Molecular detection of prostate specific antigen in patients with prostate cancer or benign prostate hyperplasia the first investigation from Iran

Prostate cancer is the second common form of cancer in men. Detection of circulating Prostate Specific Antigen (PSA) transcripts has effectively been used for early diagnosis of prostate cancer cells. This investigation employed a reverse transcriptase polymerase chain reaction (RT-PCR) technique to distinguish the patients with either localized or metastatic prostate cancer (CaP) vs. Benign Prostate Hyperplasia (BPH) and control subjects, as compared with clinical and pathological records. With reservation of ethical issues, blood samples were collected from 60 cases. Based on pathological and clinical findings, 25 patients (20 with localized cancer, 5 with metastatic), 22 with BPH, and 13 healthy (including 3 females) subjects as negative controls, were selected from Shariati, Mehrad, Sina,, Khatam and Atie Hospitals in Tehran, Iran. RT-PCR for a 260 bp PSA transcript was then performed. Clinical and pathological records were used for the assessment and comparison of PSA RT-PCR results. None of the control subjects and BPH (with 7 exceptions) were found positive by RT-PCR (Relative specificity= 72.7). In patients with prostate cancer, 21 out of 25 were found PSA positive (Relative sensitivity= 83.4) and the remaining 3 have been shown to be PSA negative (Positive predictive value= 83.4). All of 5 metastatic patients (100) revealed PSA positive results. Our data reflects the clinical relevance and significance of RT-PCR results as assessed with clinical and pathological examinations. PSA RT-PCR might be used as a powerful means for diagnosis, even when either pathological or clinical findings are negative, and could be employed for further molecular epidemiology surveys