Mesenchymal stem cells (MSCs), adherent fibroblastoid cells, present in bone marrow and many other tissues can be easily isolated and expanded in vitro. They are capable of differentiating into different cell types such as osteoblasts, chondrocytes, adipocytes, cardiomyocytes, hepatocytes, endothelial cells and neuronal cells. Such immense plasticity coupled with their ability to modulate the activity of immune cells makes them attractive for stem cell-based therapy aimed at treating previously incurable disorders. Preclinical studies have reported successful use of MSCs for delivering therapeutic proteins and repairing defects in a variety of disease models. These studies highlighted the in vivo potential of MSCs and their ability to home to injury sites and modify the microenvironment by secreting paracrine factors to augment tissue repair. Their therapeutic applicability has been widened by genetic modification to enhance differentiation and tissue targeting, and use in tissue engineering. Clinical trials for diseases such as osteogenesis imperfecta, graft-versus-host disease and myocardial infarction have shown some promise, demonstrating the safe use of both allogeneic and autologous cells. However, lack of knowledge of MSC behaviour and responses in vitro and in vivo force the need for basic and animal studies before heading to the clinic. Contrasting reports on immunomodulatory functions and tumorigenicity along with issues such as mode of cell delivery, lack of specific marker, low survival and engraftment require urgent attention to harness the potential of MSC-based therapy in the near future.

Homing and engraftment of hematopoietic stem/progenitor cells (HSPCs) in bone marrow is the major determining factor in success of hematopoietic stem cell transplantation. This is a complex, multistep process orchestrated by the coordinated interplay between adhesion molecules, cytokines, growth factors, and regulatory cofactors, many of which remain to be defined. Recent studies have highlighted the pivotal role of unique stromal-derived factor-1 (SDF-1)/CXCR4 signaling in the regulation of HSPC homing and subsequent engraftment. In addition, studies suggest that SDF-1/CXCR4 signaling acts as an essential survival-promoting factor of transplanted HSPCs as well as maintenance of quiescent HSCs in bone marrow niche. These pleiotropic effects exerted by SDF-1/CXCR4 axis make this unique signaling initiator very promising, not only for optimal hematopoietic reconstitution but also for the development of innovative approaches to achieve restoration, regeneration, or repair of other damaged tissues potentially amendable to reversal by stem cell transplantation. This goal can only be achieved when the role of SDF-1/CXCR4 axis in hematopoietic transplantation is clearly defined. Hence, this review presents current knowledge of the mechanisms through which SDF-1/CXCR4 signaling promotes restoration of hematopoiesis by regulating the homing and engraftment of HSPCs.

Abstract-Mössbauer absorption areas corresponding to 57 Fe in olivine, pyroxene, troilite, and the metallic phase in ordinary chondrites are shown to exhibit certain systematic behaviors. H chondrites occupy 2 distinct regions on the plot of metallic phase absorption area versus silicate absorption area, while L/LL chondrites fall in a separate region. Similar separation is also observed when pyroxene absorption area is plotted against olivine absorption area. The one-dimensional plot for the ratio of olivine area to pyroxene area separates L and LL chondrites. Based on these systematics, a newly fallen meteorite at Jodhpur, India is suggested to be an LL chondrite.

The RAS protein controls signaling pathway are major player in cell growth, its regulation and malignant transformation. Any activation in RAS brings alteration in upstream or downstream signaling component. Activating mutation in RAS is found in approximately 30% of human cancer. RAS plays essential role in tumor maintenance and is therefore an appropriate target for anticancer therapy. Among the anti-RAS strategies that are under evaluation in the clinic are pharmacologic inhibitors designed to prevent: (1) association with the plasma membrane (prenylation and post prenylation inhibitors). (2) Downstream signaling (kinase inhibitor), (3) upstream pathway (kinase inhibitor and monoclonal antibody), (4) Expression of RAS or other component of pathway (siRNA and antisense oligonucleotide). Several of these new therapeutic agents are showing promising result in the clinic and many more are on the way. Here, we review the current status and new hopes for targeting RAS as an anticancer drug.

During normal haematopoiesis, cell development and differentiation programs are accomplished by switching ‘on’ and ‘off’ specific set of genes. Specificity of gene expression is primarily achieved by combinatorial control, i.e. through physical and functional interactions among several transcription factors that form sequence-specific multiprotein complexes on regulatory regions (gene promoters and enhancers). Such combinatorial gene switches permit flexibility of regulation and allow numerous developmental decisions to be taken with a limited number of regulators. The haematopoietic-specific Ets family transcription factor PU.1 regulates many lymphoid- and myeloid-specific gene promoters and enhancers by interacting with multiple proteins during haematopoietic development. Such protein–protein interactions regulate DNA binding, subcellular localization, target gene selection and transcriptional activity of PU.1 itself in response to diverse signals including cytokines, growth factors, antigen and cellular stresses. Specific domains of PU.1 interact with many protein motifs such as bHLH, bZipper, zinc fingers and paired domain for regulating its activity. This review focuses on important protein–protein interactions of PU.1 that play a crucial role in regulation of normal as well as malignant haematopoiesis. Precise delineation of PU.1 protein-partner interacting interface may provide an improved insight of the molecular mechanisms underlying haematopoietic stem cell fate regulation. Its interactions with some proteins could be targeted to modulate the aberrant signalling pathways for reversing the malignant phenotype and to control the generation of specific haematopoietic progeny for treatment of haematopoietic disorders.