Rama Shanker Verma

Bio: Rama Shanker Verma is an academic researcher from Indian Institute of Technology Madras. The author has contributed to research in topics: Mesenchymal stem cell & Stem cell. The author has an hindex of 30, co-authored 159 publications receiving 3160 citations. Previous affiliations of Rama Shanker Verma include University of Pennsylvania & Thapar University.

Antibacterial activity of plants used in Indian herbal medicine

Abstract: Delonix elata, Enicostemma axillare, Merremia tridentata, Mollugo cerviana and Solanum incanum are medicinal plants used in traditional Indian medicine for the treatment of various ailments. These plants were selected to evaluate their potential antibacterial activity. To determine antibacterial activity and phytochemicals in the crude extracts of five medicinal plants used in traditional Indian medicine for the treatment of various ailments like rheumatism, piles fever, skin diseases and snake bite. The antibacterial activity of organic solvent extracts of these plants were determined by disc diffusion and broth dilution techniques against grampositive bacterial strains (Bacillus subtilis, Staphylococcus aureus) and gram-negative bacterial strains (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa). Results revealed that the chloroform and methanol extracts of D. elata and methanol extracts of M. cerviana exhibited significant antibacterial activity against gram-positive and gram-negative strains with minimum bactericidal concentration (MBC) ranging from 1.5 to 100 mg/ml. Methanol extracts of M. tridentata exhibited activity only against gram-positive bacterial strains with MBC ranging from 12.5 to 100 mg/ml. Extracts of E. axillare and S. incanum showed activity only against B. subtilis and were not bactericidal at 100 mg/ml. The most susceptible organism to the organic extracts from all the studied plants was B. subtilis and the most resistant organism was P. aeruginosa. The presence of phytochemicals such as alkaloids, tannins, triterpenoids, steroids and glycosides in the extracts of these plants supports their traditional uses as medicinal plants for the treatment of various ailments. The present study reveals potential use of these plants for developing new antibacterial compounds against pathogenic microorganisms. Key words: Antibacterial, Enicostemma axillare, Merremia tridentata, Mollugo cerviana, Solanum incanum

Hepatocyte growth factor is secreted by osteoblasts and cooperatively permits the survival of haematopoietic progenitors

Abstract: Human osteoblasts (HOBs) support the growth of human haematopoietic progenitor cells, and support the survival and limited expansion of long-term culture-initiating cells. Using human CD34+ cells and the murine myelomonocytic cell line NFS-60 as targets, we previously found that one component of HOB-derived haematopoietic activity is cell-associated granulocyte colony-stimulating factor (G-CSF). However, antibody failed to neutralize all the activity, suggesting that more than one factor supports haematopoietic cells. In the present investigations, we asked whether the HOB-derived, non-G-CSF secreted activity was as a result of other known growth factors. We found that, among the cytokines expressed by HOBs, only hepatocyte growth factor (HGF) and G-CSF stimulated NFS-60 cell proliferation. HOB cells and osteosarcoma cells secreted biologically active HGF, although the levels varied considerably. Moreover, addition of neutralizing HGF antibody to CD34+ cell/HOB co-cultures resulted in a significant reduction (≈50%) in the ability of the HOBs to support haematopoietic progenitor cells. These results suggest that a major component of osteoblast-derived haematopoietic activity is HGF. Secretion of HGF, in concert with cell-associated cytokines such as G-CSF, may account for the stem cell-stimulating activities of osteogenic cells and, thereby, the unique stem cell-supporting role of the osteoblasts within the bone marrow microenvironment.

Osteoblastic cells regulate the haematopoietic stem cell niche

Abstract: Stem cell fate is influenced by specialized microenvironments that remain poorly defined in mammals. To explore the possibility that haematopoietic stem cells derive regulatory information from bone, accounting for the localization of haematopoiesis in bone marrow, we assessed mice that were genetically altered to produce osteoblast-specific, activated PTH/PTHrP receptors (PPRs). Here we show that PPR-stimulated osteoblastic cells that are increased in number produce high levels of the Notch ligand jagged 1 and support an increase in the number of haematopoietic stem cells with evidence of Notch1 activation in vivo. Furthermore, ligand-dependent activation of PPR with parathyroid hormone (PTH) increased the number of osteoblasts in stromal cultures, and augmented ex vivo primitive haematopoietic cell growth that was abrogated by gamma-secretase inhibition of Notch activation. An increase in the number of stem cells was observed in wild-type animals after PTH injection, and survival after bone marrow transplantation was markedly improved. Therefore, osteoblastic cells are a regulatory component of the haematopoietic stem cell niche in vivo that influences stem cell function through Notch activation. Niche constituent cells or signalling pathways provide pharmacological targets with therapeutic potential for stem-cell-based therapies.

Reactive oxygen species in cell signaling

Abstract: Reactive oxygen species (ROS) are generated as by-products of cellular metabolism, primarily in the mitochondria. When cellular production of ROS overwhelms its antioxidant capacity, damage to cellular macromolecules such as lipids, protein, and DNA may ensue. Such a state of “oxidative stress” is thought to contribute to the pathogenesis of a number of human diseases including those of the lung. Recent studies have also implicated ROS that are generated by specialized plasma membrane oxidases in normal physiological signaling by growth factors and cytokines. In this review, we examine the evidence for ligand-induced generation of ROS, its cellular sources, and the signaling pathways that are activated. Emerging concepts on the mechanisms of signal transduction by ROS that involve alterations in cellular redox state and oxidative modifications of proteins are also discussed.

G1 events and regulation of cell proliferation.

Abstract: Cells prepare for S phase during the G1 phase of the cell cycle. Cell biological methods have provided knowledge of cycle kinetics and of substages of G1 that are determined by extracellular signals. Through the use of biochemical and molecular biological techniques to study effects of growth factors, oncogenes, and inhibitors, intracellular events during G1 that lead to DNA synthesis are rapidly being discovered. Many cells in vivo are in a quiescent state (G0), with unduplicated DNA. Cells can be activated to reenter the cycle during G1. Similarly, cells in culture can be shifted between G0 and G1. These switches in and out of G1 are the main determinants of post-embryonic cell proliferation rate and are defectively controlled in cancer cells.

Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours

Abstract: Activation of the Hedgehog (Hh) signalling pathway by sporadic mutations or in familial conditions such as Gorlin's syndrome is associated with tumorigenesis in skin, the cerebellum and skeletal muscle. Here we show that a wide range of digestive tract tumours, including most of those originating in the oesophagus, stomach, biliary tract and pancreas, but not in the colon, display increased Hh pathway activity, which is suppressible by cyclopamine, a Hh pathway antagonist. Cyclopamine also suppresses cell growth in vitro and causes durable regression of xenograft tumours in vivo. Unlike in Gorlin's syndrome tumours, pathway activity and cell growth in these digestive tract tumours are driven by endogenous expression of Hh ligands, as indicated by the presence of Sonic hedgehog and Indian hedgehog transcripts, by the pathway- and growth-inhibitory activity of a Hh-neutralizing antibody, and by the dramatic growth-stimulatory activity of exogenously added Hh ligand. Our results identify a group of common lethal malignancies in which Hh pathway activity, essential for tumour growth, is activated not by mutation but by ligand expression.