Circulating matrix modulators (MMP-9 and TIMP-1) and their association with severity of diabetic retinopathy

Aims

Diabetic Retinopathy (DR) is the leading cause of vision loss in the working age population. Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1), are molecules involved in extracellular tissue matrix remodelling. They are implicated in the loss of retinal tissue integrity, a major cause of DR, that leads to retinal tissue degradation and apoptosis. This study is therefore, conducted to compare the serum levels of MMP-9 and TIMP-1 in T2DM patients without and with retinopathy, and to evaluate their association with the severity of DR.

Investigation of measles and rubella outbreaks in Tamil Nadu, India-2003

The aims of the present study were to confirm measles outbreaks by detection of measles-specific IgM antibodies, isolation of measles virus, and genetic characterization to document the circulating genotypes in Tamil Nadu. Eight outbreaks were reported from six districts of Tamil Nadu, India during the period Jan-Dec 2003. Blood samples were collected for serology, urine, and throat swabs for virus isolation. Genotypic characterization of measles isolates was based on the sequence of the N gene. All the clinically suspected outbreaks (n = 8) were confirmed by serology; six out of the eight as measles and two as combination of measles and rubella highlighting the need to carry out rubella serology on measles-negative samples. Genetic characterization of three isolates obtained revealed one as genotype D4 and two as D8. Measles genotypes D4 and D8 were found to circulate in three districts of Tamil Nadu. It is necessary to be aware of the circulating genotypes within the geographical area. The information would be valuable to evaluate control measures and identify viral transmission and importation.     

Histone deacetylase inhibitor-mediated sensitization to TRAIL-induced apoptosis in childhood malignancies is not associated with upregulation of TRAIL receptor expression, but with potentiated caspase-8 activation

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has great potential for the treatment of cancer because it targets tumor cells while sparing normal cells. Several cancers, however, fail to respond to TRAIL's antineoplastic effects. These resistant tumors require cotreatment with sensitizing agents in order for TRAIL to exert anticancer activity. Histone deacetylase inhibitors (HDACi) have been recognized as potent TRAIL sensitizers. In searching for the determinants of TRAIL responsiveness, HDACi-mediated TRAIL sensitization has been predominantly attributed to TRAIL receptor upregulation. This explanation, however, has been challenged by a few studies. The aim of the present study was to explore the relevance of TRAIL receptor expression for HDACi-mediated TRAIL sensitization in childhood tumors, i.e., in medulloblastoma, Ewing's sarcoma and osteosarcoma. In previous studies, we had shown that TRAIL and HDACi were synergistic in inducing apoptosis in medulloblastoma and Ewing's sarcoma. In the present study, we demonstrate that HDACi cooperated with TRAIL in eliciting cell death in osteosarcoma. However, HDACi treatment did not alter or even reduced cell surface expression of TRAIL receptors in the three childhood tumors. In gaining insight into the apoptotic pathway involved in TRAIL sensitization, HDACi were found to potentiate TRAIL-induced caspase-8 activation. Taken together, our findings suggest that HDACi-mediated TRAIL sensitization is not the result of TRAIL receptor upregulation, but the result of a receptor-proximal event in childhood tumor cells.     

γ-Sitosterol from Acacia nilotica L. induces G2/M cell cycle arrest and apoptosis through c-Myc suppression in MCF-7 and A549 cells

Ethnopharmacological relevance

Acacia nilotica is widely distributed in Asia. In India, it occupies an important place in the indigenous system of medicine against anti-inflammatory, antioxidant, cancers, and/or tumors.

Aim of the study

The purpose of this study is to investigate the inhibitory effect of Acacia nilotica leaves extract and γ-Sitosterol on cell proliferation, the apoptotic effect and cell cycle arrest in breast and lung cancer cells.

Materials and methods

GC–MS and HPLC were used to determine the chemical constituents of this extract and γ-Sitosterol respectively. Human MCF-7 and A549 cell lines were treated with Acacia nilotica extract and γ-Sitosterol. Cell viability was determined by MTT assay. Cell proliferation was determined by BrdU incorporation assay. Apoptosis was detected by cell morphologic observation through AO/EtBr staining, cell cycle analysis, and immunoblot analysis on the expression of protein associated with cell cycle arrest.

Results

Experimental results of bioactive compound analysis indicate that γ-Sitosterol, bioactive ingredients of Acacia nilotica extract. The IC₅₀ value of extract on MCF-7 and A549 cancer cells was 493.3 ± 15.2 and 696.6 ± 11.5 μg/ml, respectively. Acacia nilotica extract and γ-Sitosterol were inhibited the cell proliferation by 54.34 ± 1.8 and 42.18 ± 3.9% for MCF-7 and 58.26 ± 1.5 and 44.36 ± 3.05% for A549 cells. The percentage of apoptotic cells observed in the MCF-7 and A549 cell lines were increased to 42.46 and 36.8% of extract; 46.68 and 43.24% for γ-Sitosterol respectively. Flow cytometric analysis results demonstrate that cells were arrested at the G2/M phase and decrease the c-Myc expression.

Conclusions

This study demonstrates in vitro results, which support the ethnomedical use of γ-Sitosterol against cancer. Experimental results of this study suggest that γ-Sitosterol exerts potential anticancer activity through the growth inhibition, cell cycle arrest and the apoptosis on cancer cells.     

The Discovery of Pyridone and Pyridazone Heterocycles as γ-Secretase Modulators

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Transport of oxygen and carbon dioxide by hemoglobin-saline solution in the red cell-free primate.

This study was undertaken to investigate the respiratory properties of hemoglobin-saline solution. Eighteen baboons were exchange transfused with either 6 per cent dextran or 6 per cent hemoglobin-saline solution. All of the hemoglobin-saline solution treated baboons survived three hours at a zero hematocrit reading. All the dextran treated animals died when the hematocrit level fell below 6 per cent. Oxygen consumption and carbon dioxide production remained unchanged from base line during the zero hematocrit interval. It is concluded that the respiratory capability of hemoglobin-saline solution is sufficient to maintain life in the absence of erythrocytes.