Isolation of a 60 kDa protein with in vitro anticancer activity against human cancer cell lines from the purple fluid of the Persian Gulf sea hare, Aplysia dactylomela

Sea hares have greatly attracted the interest of all those investigating chemical defense substances. Most of these substances are low molecular weight compounds derived from algal diets. In vitroanticancer effect of a 60 kDa protein isolated from the purple fluid of Aplysia dactylomela on four human cancer cell lines was investigated in this study. A 60 kDa protein was purified from secreted purple fluid of A. dactylomela, a sea hare from Persian Gulf. The protein purification procedure consisted basically of ammonium sulfate precipitation, ion exchange chromatography using DEAE– Sepharose and ultra-filtration method. In vitro antiproliferative and cytotoxic activity of the protein ofinterest were evaluated on L929, K562, HL60 and NB4 human cancer cell lines. The antiproliferative and cytotxic effects of 60 kDa protein on human cancer cell lines were measured by MTT assay. Resultsshowed that the 60 kDa protein of the purple fluid of A. dactylomela exhibited the antiproliferative effect on human cancer cell lines, especially on NB4 cell line. It was maximally active at 0.5 – 1.5 ìg/ml on NB4 cell line. Interestingly, the protein did not show significant cytotoxic effects

Stress induced polarization of immune-neuroendocrine phenotypes in Gallus gallus

Immune-neuroendocrine phenotypes (INPs) stand for population subgroups differing in immune-neuroendocrine interactions. While mammalian INPs have been characterized thoroughly in rats and humans, avian INPs were only recently described in Coturnix coturnix (quail). To assess the scope of this biological phenomenon, herein we characterized INPs in Gallus gallus (a domestic hen strain submitted to a very long history of strong selective breeding pressure) and evaluated whether a social chronic stress challenge modulates the individuals’ interplay affecting the INP subsets and distribution. Evaluating plasmatic basal corticosterone, interferon-γ and interleukin-4 concentrations, innate/acquired leukocyte ratio, PHA-P skin-swelling and induced antibody responses, two opposite INP profiles were found: LEWIS-like (15% of the population) and FISCHER-like (16%) hens. After chronic stress, an increment of about 12% in each polarized INP frequency was found at expenses of a reduction in the number of birds with intermediate responses. Results show that polarized INPs are also a phenomenon occurring in hens. The observed inter-individual variation suggest that, even after a considerable selection process, the population is still well prepared to deal with a variety of immune-neuroendocrine challenges. Stress promoted disruptive effects, leading to a more balanced INPs distribution, which represents a new substrate for challenging situations.Fil: Nazar, Franco Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Estevez, Inma. Centro de Investigación. Neiker - Tecnalia; EspañaFil: Correa, Silvia Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Marin, Raul Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentin

MicroRNA-145 Regulates Chondrogenic Differentiation of Mesenchymal Stem Cells by Targeting Sox9

Chondrogenic differentiation of mesenchymal stem cells (MSCs) is accurately regulated by essential transcription factors and signaling cascades. However, the precise mechanisms involved in this process still remain to be defined. MicroRNAs (miRNAs) regulate various biological processes by binding target mRNA to attenuate protein synthesis. To investigate the mechanisms for miRNAs-mediated regulation of chondrogenic differentiation, we identified that miR-145 was decreased during transforming growth factor beta 3 (TGF-β3)-induced chondrogenic differentiation of murine MSCs. Subsequently, dual-luciferase reporter gene assay data demonstrated that miR-145 targets a putative binding site in the 3′-UTR of SRY-related high mobility group-Box gene 9 (Sox9) gene, the key transcription factor for chondrogenesis. In addition, over-expression of miR-145 decreased expression of Sox9 only at protein levels and miR-145 inhibition significantly elevated Sox9 protein levels. Furthermore, over-expression of miR-145 decreased mRNA levels for three chondrogenic marker genes, type II collagen (Col2a1), aggrecan (Agc1), cartilage oligomeric matrix protein (COMP), type IX collagen (Col9a2) and type XI collagen (Col11a1) in C3H10T1/2 cells induced by TGF-β3, whereas anti-miR-145 inhibitor increased the expression of these chondrogenic marker genes. Thus, our studies demonstrated that miR-145 is a key negative regulator of chondrogenic differentiation by directly targeting Sox9 at early stage of chondrogenic differentiation

Bone Marrow Stromal Cells Modulate Mouse ENT1 Activity and Protect Leukemia Cells from Cytarabine Induced Apoptosis

BACKGROUND: Despite a high response rate to chemotherapy, the majority of patients with acute myeloid leukemia (AML) are destined to relapse due to residual disease in the bone marrow (BM). The tumor microenvironment is increasingly being recognized as a critical factor in mediating cancer cell survival and drug resistance. In this study, we propose to identify mechanisms involved in the chemoprotection conferred by the BM stroma to leukemia cells. METHODS: Using a leukemia mouse model and a human leukemia cell line, we studied the interaction of leukemia cells with the BM microenvironment. We evaluated in vivo and in vitro leukemia cell chemoprotection to different cytotoxic agents mediated by the BM stroma. Leukemia cell apoptosis was assessed by flow cytometry and western blotting. The activity of the equilibrative nucleoside transporter 1 (ENT1), responsible for cytarabine cell incorporation, was investigated by measuring transport and intracellular accumulation of (3)H-adenosine. RESULTS: Leukemia cell mobilization from the bone marrow into peripheral blood in vivo using a CXCR4 inhibitor induced chemo-sensitization of leukemia cells to cytarabine, which translated into a prolonged survival advantage in our mouse leukemia model. In vitro, the BM stromal cells secreted a soluble factor that mediated significant chemoprotection to leukemia cells from cytarabine induced apoptosis. Furthermore, the BM stromal cell supernatant induced a 50% reduction of the ENT1 activity in leukemia cells, reducing the incorporation of cytarabine. No protection was observed when radiation or other cytotoxic agents such as etoposide, cisplatin and 5-fluorouracil were used. CONCLUSION: The BM stroma secretes a soluble factor that significantly protects leukemia cells from cytarabine-induced apoptosis and blocks ENT1 activity. Strategies that modify the chemo-protective effects mediated by the BM microenvironment may enhance the benefit of conventional chemotherapy for patients with AML

Musculoskeletal disorders among video display terminal (VDT) workers comparing with other office workers

Background and aimsScientific and industrial development has led to increased production,which has been associated with different complications, including occupational stress, and increased incidence of work-related musculoskeletal disorders. Musculoskeletal disorders arefrequent causes of absenteeism in developed countries. We designed this study to assess musculoskeletal disorders and occupational stress among video display terminal (VDT) workers in comparison with other office workers.MethodsThis was a cross-sectional study on 72 VDT workers (case) and 145 office workers (control). In this study we used Nordic and Osipow questionnaires in order to evaluate musculoskeletal disorders and job stress, respectively. The questionnaires were filled by direct interview. T test, chi square, Fisher test and logistic regression were used for data analysis.ResultsThe frequency of musculoskeletal disorders among VDT users in the last 12 months was 46.5%, 20.3%, 5.1%, 12.4% and 57.6% in neck, shoulder, elbow, wrist and low back areas, respectively. The frequency of musculoskeletal complaints in neck, shoulder and wrist and mean score of occupational stress was significantly higher in the case group comparing with controlgroup, and both results were statistically significant.ConclusionVDT working is a high-risk job for musculoskeletal disorders. In this study the frequency of musculoskeletal disorders, especially in high-risk regions for this job, was higher in VDTworkers than other office workers. We recommend to perform other studies in order to find non-ergonomic points and postures in these persons

BCc1, the novel antineoplastic nanocomplex, showed potent anticancer effects in vitro and in vivo

Somayeh Kalanaky,1,2 Maryam Hafizi,1–3 Saideh Fakharzadeh,1 Mohammad Vasei,4 Ladan Langroudi,5 Ehsan Janzamin,6 Seyed Mahmoud Hashemi,7 Maryam Khayamzadeh,2 Masoud Soleimani,6 Mohammad Esmaeil Akbari,2 Mohammad Hassan Nazaran1 1Department of Research and Development, Sodour Ahrar Shargh Company, Tehran, Iran; 2Cancer Research Centre, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 3Stem Cell Technology Research Center, Tehran, Iran; 4Department of Pathology, Tehran University of Medical Sciences, Tehran, Iran; 5Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; 6Department of Haematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; 7Department of Immunology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Purpose: In spite of all the efforts and researches on anticancer therapeutics, an absolute treatment is still a myth. Therefore, it is necessary to utilize novel technologies in order to synthesize smart multifunctional structures. In this study, for the first time, we have evaluated the anticancer effects of BCc1 nanocomplex by vitro and in vivo studies, which is designed based on the novel nanochelating technology.Methods: Human breast adenocarcinoma cell line (MCF-7) and mouse embryonic fibroblasts were used for the in vitro study. Antioxidant potential, cell toxicity, apoptosis induction, and CD44 and CD24 protein expression were evaluated after treatment of cells with different concentrations of BCc1 nanocomplex. For the in vivo study, mammary tumor-bearing female Balb/c mice were treated with different doses of BCc1 and their effects on tumor growth rate and survival were evaluated.Results: BCc1 decreased CD44 protein expression and increased CD24 protein expression. It induced MCF-7 cell apoptosis but at the same concentrations did not have negative effects on mouse embryonic fibroblasts viability and protected them against oxidative stress. Treatment with nanocomplex increased survival and reduced the tumor size growth in breast cancer-bearing balb/c mice.Conclusion: These results demonstrate that BCc1 has the capacity to be assessed as a new anticancer agent in complementary studies. Keywords: BCc1, cancer, nanotechnology, nanochelating technology, nanocomple

Emergence of Cutaneous Leishmaniasis due to Leishmania major in a New Focus of Southern Iran

Reports from the health center of Kerman Province, southern Iran showed an increasing of cutaneous leishmaniasis cases in Orzuieh Rural District, southwest of the province in 2003. The report encouraged the team to carry out an epidemi¬ological survey in the district during 2003-2004. The objectives were to determine the ecology of sand flies, potential reser¬voir hosts and human infection. A total of 1075 sand flies were collected by sticky traps and 7 species of sand flies were identified. They comprised 3 species of the genus Phlebotomus (P. papatasi, P. mongolensis and P. bergeroti) and 4 species of the genus Sergentomyia (S. sintoni, S. clydei, S. tiberiadis and S. baghdadis). P. papatasi was the predominant species of the genus Phlebotomus in indoors (90.3%) and outdoors (50.2%). Susceptibility tests on P. papatasi with DDT 4%. Showed that the species was susceptible to this insecticide. A total of 13 rodents consist of Tatera indica (76.9%) and Nesokia indica (23.1%) were collected. A study of prevalence among 2441 inhabitants in four villages showed a rate of 1.1% for active lesions and 10.4% for scars during November- December 2003. In a separate study examination of 1662 school children aged 6-12 years old showed 1.14% for ulcers and 14.7% for scars at the same time. The Leishmania parasites were isolated from man and characterized as Leishmania major using RAPD-PCR method. It seems that cutaneous leishmaniasis due to L. major (CLM) has been prevailed in the district