Shyamasree Ghosh

C-reactive protein and the biology of disease

The C-reactive protein (CRP) is a plasma protein of hepatic origin, belonging to pentraxin family and forms a major component of any inflammatory reaction. A key component of the innate immunity pathway, the concentration of CRP may rapidly increase to levels more than 1,000-folds above normal values as a consequence to tissue injury or infection. Although functioning as a classical mediator of innate immunity, it functions via interaction of components of both humoral and cellular effector systems of inflammation. Initially considered as an acute-phase marker in tissue injury, infection and inflammation, it now has a distinct status of a disease marker in cardiovascular diseases and is well known of its clinical and pathological significance. The present torrent of studies in a large number of diseases and associated conditions has highly elucidated the role of CRP as a therapeutic and research reagent. In this review, we focus our attention to role of CRP in health and disease. The future prospect of this review lies in the applicability of CRP as a molecule in understanding and monitoring of the biology of disease.

Effect of heavy metals on germination of seeds

With the expansion of the world population, the environmental pollution and toxicity by chemicals raises concern. Rapid industrialization and urbanization processes has led to the incorporation of pollutants such as pesticides, petroleum products, acids and heavy metals in the natural resources like soil, water and air thus degrading not only the quality of the environment, but also affecting both plants and animals. Heavy metals including lead, nickel, cadmium, copper, cobalt, chromium and mercury are important environmental pollutants that cause toxic effects to plants; thus, lessening productivity and posing dangerous threats to the agro-ecosystems. They act as stress to plants and affect the plant physiology. In this review, we have summarized the effects of heavy metals on seeds of different plants affecting the germination process. Although reports exist on mechanisms by which the heavy metals act as stress and how plants have learnt to overcome, the future scope of this review remains in excavating the signaling mechanisms in germinating seeds in response to heavy metal stress.

Tinospora cordifolia: One plant, many roles

Natural products with medicinal value are gradually gaining importance in clinical research due to their well-known property of no side effects as compared to drugs. Tinospora cordifolia commonly named as “Guduchi” is known for its immense application in the treatment of various diseases in the traditional ayurvedic literature. Recently the discovery of active components from the plant and their biological function in disease control has led to active interest in the plant across the globe. Our present study in this review encompasses (i) the genetic diversity of the plant and (ii) active components isolated from the plant and their biological role in disease targeting. The future scope of the review remains in exploiting the biochemical and signaling pathways affected by the compounds isolated from Tinospora so as to enable new and effective formulation in disease eradication.

O-acetylation of sialic acids is required for the survival of lymphoblasts in childhood acute lymphoblastic leukemia (ALL)

Exploiting the selective affinity of Achatinin-H towards 9-O-acetylneuraminic acid(α2-6)GalNAc, we have demonstrated the presence of 9-O-acetylated sialoglycoproteins (Neu5,9Ac2-GPs) on hematopoietic cells of children suffering from acute lymphoblastic leukemia (ALL), indicative of defective sialylation associated with this disease. The carbohydrate epitope of Neu5,9Ac2-GPsALL was confirmed by using several synthetic sialic acid analogues. They are functionally active signaling molecules as demonstrated by their role in mediating lymphoproliferative responses and consequential increased production of IFN-γ due to specific stimulation of Neu5,9Ac2-GPs on PBMCALL with Achatinin-H. Cells devoid of 9-O-acetylations (9-O-AcSA−) revealed decreased nitric oxide production as compared to 9-O-AcSA+ cells on exposure to IFN-γ. Under this condition, a decrease in viability of 9-O-AcSA− cells as compared to 9-O-AcSA+ cells was also observed which was reflected from increased caspase 3 activity and apoptosis suggesting the protective role of this glycotope. These Neu5,9Ac2-GPs are also capable of inducing disease-specific anti-Neu5,9Ac2-GPs antibodies in ALL children. Additionally, we have observed that disease-specific anti-Neu5,9Ac2-GPs have altered glycosylation profile, and they are incapable of exerting a few Fc-glycosylation-sensitive effector functions. These observations hint toward a disbalanced homeostasis, thereby enabling the cancer cells to escape host defense. Taken together, it may be hypothesized that Neu5,9Ac2-GPs and their antibodies play a prominent role in promoting the survival of lymphoblasts in ALL.

Interferon gamma promotes survival of lymphoblasts overexpressing 9‐O‐acetylated sialoglycoconjugates in childhood acute lymphoblastic leukaemia (ALL)

An enhanced linkage‐specific 9‐O‐acetylated sialic acid (9‐O‐AcSA) on peripheral blood mononuclear cells (PBMC) of children with acute lymphoblastic leukaemia, ALL (PBMCALL, 9‐O‐AcSA+ cells) was demonstrated by using a lectin, Achatinin‐H, whose lectinogenic epitope was 9‐O‐AcSAα2‐6GalNAc. Our aim was to evaluate the in vitro contributory role of this glycotope (9‐O‐AcSAα2‐6GalNAc) towards the survival of these 9‐O‐AcSA+ cells in ALL patients. For direct comparison, 9‐O‐AcSA− cells were generated by removing O‐acetyl group of 9‐O‐AcSA present on PBMCALL using O‐acetyl esterase. An elevated level of serum interferon gamma (IFN‐γ) in affected children led us to think that PBMCALL are continuously exposed specifically to this cytokine. Accordingly, 9‐O‐AcSA+ and 9‐O‐AcSA− cells were exposed in vitro to IFN‐γ. A twofold increased NO release along with inducible NO synthase (iNOS) mRNA expression by the 9‐O‐AcSA+ cells was observed as compared to the 9‐O‐AcSA− cells. The decreased viability of IFN‐γ exposed 9‐O‐AcSA− cells as compared to 9‐O‐AcSA+ cells were reflected from a 5.0‐fold increased caspase‐3‐like activity and a 10.0‐fold increased apoptosis in the 9‐O‐AcSA− cells when production of NO was lowered by adding competitive inhibitor of iNOS in reaction mixture. Therefore, it may be envisaged that a link exists between induction of this glycotope and their role in regulating viability of PBMCALL. Taken together, it is reasonable to hypothesise that O‐acetylation of sialic acids on PBMCALL may be an additional mechanism that promotes the survival of lymphoblasts by avoiding apoptosis via IFN‐γ‐induced NO production.

Increased interferon gamma production by peripheral blood mononuclear cells in response to stimulation of overexpressed disease-specific 9-O-acetylated sialoglycoconjugates in children suffering from acute lymphoblastic leukaemia

Disease‐specific over‐expression of 9‐O‐acetylated sialoglycoconjugates (9‐O‐AcSGs) on peripheral blood mononuclear cells (PBMC) of children with acute lymphoblastic leukaemia (ALL, PBMCALL) has been demonstrated using a lectin, Achatinin‐H, with specificity towards 9‐O‐AcSAα2‐6GalNAc. This study investigated the contributory role of 9‐O‐AcSGs induced on PBMCALL. Stimulation of PBMCALL with Achatinin‐H through 9‐O‐AcSGs led to a lymphoproliferative response with a significantly increased interferon‐γ (IFN‐γ) production when compared with unstimulated cells as demonstrated by enzyme‐linked immunosorbent assay and mRNA expression. Under identical conditions, PBMCALL ablated of O‐acetylations did not respond to such stimulation. In summary, it may be concluded that stimulation of over‐expressed 9‐O‐AcSGs regulate signalling for proliferation, leading to the release of IFN‐γ. Controlled expression of these molecules may be exploited as potential targets for therapy, promising beneficial effects to children with ALL.

Sialic acids: biomarkers in endocrinal cancers

Sialylations are post translational modification of proteins and lipids that play important role in recognition, signaling, immunological response and cell-cell interaction. Improper sialylations due to altered sialyl transferases, sialidases, gene structure and expression, sialic acid metabolism however lead to diseases and thus sialic acids form an important biomarker in disease. In the endocrinal biology such improper sialylations including altered expression of sialylated moieties have been shown to be associated with disorders. Cancer still remains to be the major cause of global death and the cancer of the endocrine organs suffer from the dearth of appropriate markers for disease prediction at the early stage and monitoring. This review is aimed at evaluating the role of sialic acids as markers in endocrinal disorders with special reference to cancer of the endocrine organs. The current study is summarized under the following headings of altered sialylations in endocrinal cancer of the (i) ovary (ii) pancreas (iii) thyroid (iv) adrenal and (v) pituitary gland. Studies in expression of sialic acid in testis cancer are limited. The future scope of this review remains in the targeting of endocrinal cancer by targeting altered sialylation which is a common expression associated with endocrinal cancer.

Scanning electron microscopic studies on antenna of Hemipyrellia ligurriens (Wiedemann, 1830) (Diptera: Calliphoridae)—A blow fly species of forensic importance

Blow flies (Diptera: Calliphoridae) are one of the foremost organisms amongst forensic insects to colonize corpses shortly after death, thus are of immense importance in the domain of forensic entomology. The blow fly Hemipyrellia ligurriens (Wiedemann, 1830) (Diptera: Calliphoridae) is considered as a forensically important fly species globally and is also known for its medical and veterinary importance. In the present study, we report for the first time scanning electron microscopic studies on the morphology of sensilla of antenna of adult male and female of H. ligurriens is with profound importance in better understanding of the insect morphology from forensic entomological perspective, and also could aid in proper identification of the species from other calliphorid flies. The structural peculiarities observed in the (i) antenna of H. ligurriens with three segments- scape, pedicel and flagellum with dorso-laterally placed arista (ii) densely covered microtrichia and most abundant trichoid sensilla identified on the antenna (iii) observation of only one type of sensilla, chaetic sensilla (ChI) on the scape (iv) two types of chaetic sensilla (ChI and ChII) and styloconic sensilla on the pedicel (v) the flagellum with three types of sensilla- trichoid, basiconic and coeloconic sensilla (vi) Basiconic sensilla with multiporous surfaces with characteristic olfactory function. Moderate sexual dimorphism in the width of the flagellum, the females with wider flagella than the males, bear significance to the fact that they bear more multi-porous sensilla than the males, thus suffice their need to detect oviposition sites. Significant difference was observed in the length and width of coeloconic sensilla between the two sexes, the females showed bigger coeloconic sensilla, suggesting their function in oviposition site detection and successful colonization in corpses.

Induction of apoptosis by Fe(salen)Cl through caspase-dependent pathway specifically in tumor cells.

Iron‐based compounds possess the capability of inducing cell death due to their reactivity with oxidant molecules, but their specificity towards cancer cells and the mechanism of action are hitherto less investigated. A Fe(salen)Cl derivative has been synthesized that remains active in monomer form. The efficacy of this compound as an anti‐tumor agent has been investigated in mouse and human leukemia cell lines. Fe(salen)Cl induces cell death specifically in tumor cells and not in primary cells. Mouse and human T‐cell leukemia cell lines, EL4 and Jurkat cells are found to be susceptible to Fe(salen)Cl and undergo apoptosis, but normal mouse spleen cells and human peripheral blood mononuclear cells (PBMC) remain largely unaffected by Fe(salen)Cl. Fe(salen)Cl treated tumor cells show significantly higher expression level of cytochrome c that might have triggered the cascade of reactions leading to apoptosis in cancer cells. A significant loss of mitochondrial membrane potential upon Fe(salen)Cl treatment suggests that Fe(salen)Cl induces apoptosis by disrupting mitochondrial membrane potential and homeostasis, leading to cytotoxity. We also established that apoptosis in the Fe(salen)Cl‐treated tumor cells is mediated through caspase‐dependent pathway. This is the first report demonstrating that Fe(salen)Cl can specifically target the tumor cells, leaving the primary cells least affected, indicating an excellent potential for this compound to emerge as a next‐generation anti‐tumor drug.

Environmental pollutants, pathogens and immune system in earthworms

Earthworms also known as farmer’s friends are natural tillers of soil. They belong to Phylum Annelida and class Oligochaeta. Acid soils with organic matter and surface humus maintain the largest fauna of worms and earthworms. Due to their habitat in soil, they are constantly exposed to microbes and pollution generated by anthropogenic sources. Studies have revealed that damage of the immune system of earthworms can lead to alterations of both morphological and cellular characteristics of worms, activation of signalling pathways and can strongly influence their survival. Therefore, the understanding of the robust immune system in earthworms has become very important from the point of view of understanding its role in combating pathogens and pollutants and its role in indicating the soil pollution. In this article, we have outlined the (i) components of the immune system and (ii) their function of immunological responses on exposure to pollutants and pathogens. This study finds importance from the point of view of ecotoxicology and monitoring of earthworm health and exploring the scope of earthworm immune system components as biomarkers of pollutants and environmental toxicity. The future scope of this review remains in understanding the earthworm immunobiology and indicating strong biomarkers for pollution.