Radiation Induced Changes in Haematocrit Values of Mouse

The HCT is a measurement of the volume of red blood cells as a percentage of whole blood. For automated procedures, the haematocrit is the product of the RBC and the mean cell volume (see below). For manual determinations, the haematocrit is measured after centrifugation of a microcapillary tube filled with whole blood. The percentage of blood composed of red blood cells is the haematocrit (sometimes called packed cell volume). Manual or ‘spun’ haematocrits tend to be a few percentage points higher than calculated haematocrits, because trapped plasma is included in the apparent red blood cell volume. Haematocrit is expressed as a number without units between 0.00 and 1.00. Haematocrit values for mice are generally between 0.40 and 0.50, but may range up to 0.60 depending on sampling site and fasting status or radiation induction

Depletion of mitochondrial protease OMA1 alters proliferative properties and promotes metastatic growth of breast cancer cells

Metastatic competence of cancer cells is influenced by many factors including metabolic alterations and changes in mitochondrial biogenesis and protein homeostasis. While it is generally accepted that mitochondria play important roles in tumorigenesis, the respective molecular events that regulate aberrant cancer cell proliferation remain to be clarified. Therefore, understanding the mechanisms underlying the role of mitochondria in cancer progression has potential implications in the development of new therapeutic strategies. We show that low expression of mitochondrial quality control protease OMA1 correlates with poor overall survival in breast cancer patients. Silencing OMA1 in vitro in patientderived metastatic breast cancer cells isolated from the metastatic pleural effusion and atypical ductal hyperplasia mammary tumor specimens (21MT-1 and 21PT) enhances the formation of filopodia, increases cell proliferation (Ki67 expression), and induces epithelial-mesenchymal transition (EMT). Mechanistically, loss of OMA1 results in alterations in the mitochondrial protein homeostasis, as reflected by enhanced expression of canonic mitochondrial unfolded protein response genes. These changes significantly increase migratory properties in metastatic breast cancer cells, indicating that OMA1 plays a critical role in suppressing metastatic competence of breast tumors. Interestingly, these results were not observed in OMA1-depleted non-tumorigenic MCF10A mammary epithelial cells. This newly identified reduced activity/levels of OMA1 provides insights into the mechanisms leading to breast cancer development, promoting malignant progression of cancer cells and unfavorable clinical outcomes, which may represent possible prognostic markers and therapeutic targets for breast cancer treatment

THE PHARMACEUTICO- ANALYTICAL STUDY OF OLEAGINOUS FORMULATION: ARJUNA GHRITA

Ayurvedic literature have a lot of unexplored or least tested medicines, Arjuna Ghrita is such one indicated for all types of cardiac disorder. As the incidences of cardiac disorder are increasing, need of a drug like Arjuna ghrita which could be used in many diseases should be formulated. Till date no work has been done at pharmaceuticoanalytical study of Arjuna ghrita. It is an oleaginous formulation needed to be explored in scientific light. Preparation of oleaginous dosage form is described as Sneha kalpana done by subjecting Ghrita or oil to a particular a pattern of heat treated with different Kalka (paste) and liquid media like Kwath (decoction). Murchhana is a pre-procedure to Sneha kalpana in which Ghrita is treated with few drugs. Three samples of Arjuna ghrita were prepared from three different brand cows ghee following the classical texts. Obtained samples were unctuous, viscous soft mass of yellow color with slightly bitter taste and characteristic bitter odour and its analytical study was done. In analytical study calculated mean value for refractive index is 1.456, specific gravity is 0.9181, iodine value is 31.026, saponification value is 131.13, peroxide value is 1.5 and acid value is 1.02. Assay of heavy metals and microbial contamination were under prescribed limit for samples of Arjuna ghrita. Therefore the values obtained can be considered as standard for Arjuna ghrita.

Depletion of mitochondrial protease OMA1 alters proliferative properties and promotes metastatic growth of breast cancer cells

Metastatic competence of cancer cells is influenced by many factors including metabolic alterations and changes in mitochondrial biogenesis and protein homeostasis. While it is generally accepted that mitochondria play important roles in tumorigenesis, the respective molecular events that regulate aberrant cancer cell proliferation remain to be clarified. Therefore, understanding the mechanisms underlying the role of mitochondria in cancer progression has potential implications in the development of new therapeutic strategies. We show that low expression of mitochondrial quality control protease OMA1 correlates with poor overall survival in breast cancer patients. Silencing OMA1 in vitro in patientderived metastatic breast cancer cells isolated from the metastatic pleural effusion and atypical ductal hyperplasia mammary tumor specimens (21MT-1 and 21PT) enhances the formation of filopodia, increases cell proliferation (Ki67 expression), and induces epithelial-mesenchymal transition (EMT). Mechanistically, loss of OMA1 results in alterations in the mitochondrial protein homeostasis, as reflected by enhanced expression of canonic mitochondrial unfolded protein response genes. These changes significantly increase migratory properties in metastatic breast cancer cells, indicating that OMA1 plays a critical role in suppressing metastatic competence of breast tumors. Interestingly, these results were not observed in OMA1-depleted non-tumorigenic MCF10A mammary epithelial cells. This newly identified reduced activity/levels of OMA1 provides insights into the mechanisms leading to breast cancer development, promoting malignant progression of cancer cells and unfavorable clinical outcomes, which may represent possible prognostic markers and therapeutic targets for breast cancer treatment

Cost effective technologies and renewable substrates for biosurfactants’ production

Diverse types of microbial surface-active amphiphilic molecules are produced by a range of microbial communities. The extraordinary properties of biosurfactant / bioemulsifier (BS/BE) as surface active products allows them to have key roles in various field of applications such as bioremediation, biodegradation, enhanced oil recovery, pharmaceutics, food processing among many others. This leads to a vast number of potential applications of these BS/BE in different industrial sectors. Despite the huge number of reports and patents describing BS and BE applications and advantages, commercialization of these compounds remain difficult, costly and to a large extent irregular. This is mainly due to the usage of chemically synthesized media for growing producing microorganism and in turn the production of preferred quality products. It is important to note that although a number of developments have taken place in the field of biosurfactant industries, large scale production remains economically challenging for many types of these products. This is mainly due to the huge monetary difference between the investment and achievable productivity from the commercial point of view. This review discusses low cost, renewable raw substrates and fermentation technology in BS/BE production processes and their role in reducing the production cost

Breast Cancer/Stromal Cells Coculture on Polyelectrolyte Films Emulates Tumor Stages and miRNA Profiles of Clinical Samples

In this study, we demonstrate a method for controlling breast cancer cells adhesion on polyelectrolyte multilayer (PEM) films without the aid of adhesive proteins/ ligands to study the role of tumor and stromal cell interaction on cancer biology. Numerous studies have explored engineering coculture of tumor and stromal cells predominantly using transwell coculture of stromal cells cultured onto coverslips that were subsequently added to tumor cell cultures. However, these systems imposed an artificial boundary that precluded cell−cell interactions. To our knowledge, this is the first demonstration of patterned coculture of tumor cells and stromal cells that captures the temporal changes in the miRNA signature as the breast tumor develops through various stages. In our study we used synthetic polymers, namely poly(diallyldimethylammonium chloride) (PDAC) and sulfonated poly(styrene) (SPS), as the polycation and polyanion, respectively, to build PEMs. Breast cancer cells attached and spread preferentially on SPS surfaces while stromal cells attached to both SPS and PDAC surfaces. SPS patterns were formed on PEM surfaces, by either capillary force lithography (CFL) of SPS onto PDAC surfaces or vice versa, to obtain patterns of breast cancer cells and patterned cocultures of breast cancer and stromal cells. In this study, we utilized cancer cells derived from two different tumor stages and two different stromal cells to effectively model a heterogeneous tumor microenvironment and emulate various tumor stages. The coculture model mimics the proliferative index (Ki67 expression) and tumor aggressiveness (HER-2 expression) akin to those observed in clinical tumor samples. We also demonstrated that our patterned coculture model captures the temporal changes in the miRNA-21 and miRNA-34 signature as the breast tumor develops through various stages. The engineered coculture platform lays groundwork toward precision medicine wherein patient-derived tumor cells can be incorporated within our in vitro models to identify potential pathways and drug treatment regimens for individual patients

Physical Intimacy of Breast Cancer Cells with Mesenchymal Stem Cells Elicits Trastuzumab Resistance through Src Activation

The development of resistance to trastuzumab is a major obstacle for lasting effective treatment of patients with ErbB2-overexpressing tumors. Here, we demonstrate that the physical contact of breast cancer cells with mesenchymal stem cells (MSCs) is a potential modulator of trastuzumab response by activation of nonreceptor tyrosine kinase c-Src and down regulation of phosphatase and tensin homolog (PTEN). Using an in vitro patterned breast cancer/MSC co-culture model, we find that the presence of MSCs results in Src activation that is missing in cancer cells monoculture, transwell co-culture, and cells treated with MSCs conditioned media. Interestingly, the co-culture model also results in PTEN loss and activation of PI3K/AKT pathway that has been demonstrated as fundamental proliferative and survival pathways in clinical settings. To our knowledge, this is the first report that showed PTEN loss without the use of chemical inhibitors, matrix stiffness, or silencing RNAs. In addition, breast cancer cells in co-culture with MSCs conferred trastuzumab resistance in vitro as observed in the lack of inhibition of proliferative and migrative properties of the cancer cells. Our findings show that MSCs are potent mediators of resistance to trastuzumab and might reveal targets to enhance trastuzumab efficacy in patients

\u3ci\u3eIn vitro\u3c/i\u3e evaluation of PEGylated mesoporous MgFe2O4 magnetic nanoassemblies (MMNs) for chemo-thermal therapy

A size tunable synthesis of mesoporous MgFe2O4 magnetic nanoassemblies (MMNs) through a PEG-diacid mediated polyol method is reported. The PEG-diacid coated MMNs exhibit a significant specific surface area of 92 m2 g‒1 and saturation magnetization of 57 emu g g‒1. These MMNs exhibit a very good colloidal stability in PBS (pH 7.4) with nonappreciable cytotoxicity in mouse fibroblast (L929) and cervical cancer (HeLa) cells. We demonstrate the potential of MMNs as an integrated nanosystem for drug delivery and magnetic hyperthermia (MHT) through in vitro studies. 80% loading efficiency of doxorubicin (DOX) has been achieved due to the highly negative surface charge and mesoporous nature of MMNs. It is observed that 65–70% of HeLa cells undergo apoptosis through DNA fragmentation after 24 h of incubation with DOX loaded MMNs. MHT alone induces the death of 40– 45% of cells, whereas the synergistic effect of a combination of DOX and MHT leads to the death of about 90% of cells. Our results show that MHT significantly increases the therapeutic efficacy of DOX to induce more apoptosis in cancer cells. Hence, a combination of MHT with chemotherapy makes MMNs a powerful multimodal system for synergistic chemo-thermal cancer therapy