Farhat Afrin

JISIASR · Centre for Interdisciplinary Sciences

Introduction: The current therapeutic armory for visceral leishmaniasis (VL) caused by Leishmania donovani complex is inadequate, coupled with serious limitations. Combination therapy has proved ineffective due to mounting resistance; however, the search for safe and effective drugs is desirable, in the absence of any vaccine. There is a growing i...

Background: There is a pressing need for drug discovery against visceral leishmaniasis, a life-threatening protozoal infection, as the available chemotherapy is antiquated and not bereft of side effects. Plants as alternate drug resources has rewarded mankind in the past and aimed in this direction, we investigated the antileishmanial potential of...

In continuance with earlier reported work, an extension has been carried out by the same research group. Mulling over the ongoing condition of resistance to existing antimalarial agents, we had reported synthesis and antimalarial activity of certain pyrazole-1,3,4-oxadiazole hybrid compounds. Bearing previous results in mind, our research group ide...

Leishmaniasis is one of the major neglected tropical diseases, for which no vaccines exist. Chemotherapy is hampered by limited efficacy coupled with development of resistance and other side effects. Leishmania parasites elude the host defensive mechanisms by modulating their surface proteins as well as dampening the host's immune responses. The pa...

Visceral leishmaniasis (VL) is a fatal, vector-borne disease caused by the intracellular protozoa of the genus Leishmania. Most of the therapeutics for VL are toxic, expensive, or ineffective. Sesquiterpenes are a new class of drugs with proven antimicrobial and antiviral activities. Artemisinin is a sesquiterpene lactone with potent antileishmania...

Background The therapy of visceral leishmaniasis (VL) is limited by resistance, toxicity and decreased bioavailability of the existing drugs coupled with dramatic increase in HIV-co-infection, non-availability of vaccines and down regulation of cell-mediated immunity (CMI). Thus, we envisaged combating the problem with plant-derived antileishmanial...

Development of new therapeutic approach to treat leishmaniasis has become a priority. In the present study, the antileishmanial effect of β-nitrostyrenes was investigated against in vitro promastigotes and amastigotes. A series of β-nitrostyrenes have been synthesized by using Henry reaction and were evaluated for their antimicrobial activities by...

[This corrects the article on p. 1368 in vol. 6, PMID: 26696979.].

Visceral leishmaniasis (VL) or kala-azar is a vector borne infectious disease caused by the protozoan parasites of the genus Leishmania. VL is endemic in more than 85 countries with an estimated 0.2–0.5 million people at risk, causing high morbidity and mortality across the globe. In the absence of effective vaccines, treatment solely relies on che...

Visceral leishmaniasis (VL) is a life-threatening protozoal infection chiefly impinging the rural and poor population in the tropical and sub-tropical countries. The deadly affliction is rapidly expanding after its association with AIDS, swiftly defying its status of a neglected disease. Despite successful formulation of vaccine against canine leishm...

Exploration of immunomodulatory antileishmanials of plant origin is now being strongly recommended to overcome the immune suppression evident during visceral leishmaniasis (VL) and high cost and toxicity associated with conventional chemotherapeutics. In accordance, we assessed the in vitro and in vivo antileishmanial and immunomodulatory potential...

In the absence of vaccines and limitations of currently available chemotherapy, development of safe and efficacious drugs is urgently needed for visceral leishmaniasis (VL) that is fatal, if left untreated. Earlier we reported in vitro apoptotic antileishmanial activity of n-hexane fractions of Artemisia annua leaves (AAL) and seeds (AAS) against L...

Visceral leishmaniasis (VL) or kala-azar is a vector borne infectious disease caused by the protozoan parasites of the genus Leishmania. VL is endemic in more than 85 countries with an estimated 0.2–0.5 million people at risk, causing high morbidity and mortality across the globe. In the absence of effective vaccines, treatment solely relies on che...

In the absence of vaccines and limitations of currently available chemotherapy, development of safe and efficacious drugs is urgently needed for visceral leishmaniasis (VL) that is fatal, if left untreated. Earlier we reported in vitro apoptotic antileishmanial activity of n-hexane fractions of Artemisia annua leaves (AAL) and seeds (AAS) against L...

Visceral leishmaniasis (VL) is a pestilent form of leishmaniasis that chiefly impinges the poorest sections of the society. The prototypical therapeutic interventions in vogue are handicapped due to toxicity and alarming increase in drug resistance. In the absence of vaccines, progressive emergence of HIV-VL co-infection and relapse in the form of...

Visceral leishmaniasis (VL), the second-most dreaded parasitic disease after malaria, is currently endemic in 88 countries. Dramatic increases in the rates of infection, drug resistance, and non-availability of safe vaccines have highlighted the need for identification of novel and inexpensive anti-leishmanial agents from natural sources. In this s...

Two-deoxy-D-glucose (2-DG), an inhibitor of glycolysis differentially enhances the radiation and chemotherapeutic drug induced cell death in cancer cells in vitro, while the local tumor control (tumor regression) following systemic administration of 2-DG and focal irradiation of the tumor results in both complete (cure) and partial response in a fr...

Single cell encapsulation technology is an emerging new approach for targeted delivery in tissue engineering and regenerative medicine. This technology provides an effective measure to deliver cells for transplantation in vivo for the treatment of several disorders. In this study, we have synthesized chitosan nanoparticles (size 149.73 nm and zeta...

Human malaria is a major parasitic infection, and the situation has worsened mainly due to the emergence of resistant malaria parasites to several anti-malarial drugs. Thus, an urgent need to find suitable drug targets has led to the development of newer classes of anti-malarial drugs. Helicases have been targeted to develop therapeutics for viral,...

Homing and engraftment, a determining factor in hematopoietic stem cell transplantation success is defined as a process through which hematopoietic stem/progenitor cells (HSPCs) lodge recipient bone marrow. SDF-1/CXCR4 axis acts as a principle regulator in homing and engraftment, however, CXCR4 signaling is dependent upon expression of CXCR4 and it...

Leishmaniasis is a pestilent affliction that importunately needs better therapeutics necessitated by the absence of effective vaccine, emergence as HIV co-infection, and the dread of debilitating chemotherapy. The Leishmania parasites incapacitate host macrophages by preventing the formation of phagolysosomes, impeding antigen presentation to T cel...

Fumaria parviflora Lam. (Fumaraceae) is widely used in traditional as well as folkloric system of medicine from ancient. It is commonly known as 'Pitpapra' or 'Shahtrah' in Indian traditional system of medicine and used for treating numerous ailments like diarrhea, fever, influenza, blood purifier and other complications. The object of the present...

Recently discovered R2TP complex is an important multiprotein complex involved in multiple cellular process like snoRNP biogenesis, PIKK signaling, RNA polymerase II assembly and apoptosis. Within R2TP complex, Pih1 tightly interacts with Rvb1/Rvb2 and with Tah1 to form R2TP macromolecular complex. R2TP complex further interacts with Hsp90 to form...

Leishmaniasis consists of a complex spectrum of infectious diseases with worldwide distribution of which visceral leishmaniasis or kala-azar caused by Leishmania donovani is the most devastating. In the absence of vaccines, chemotherapy remains the mainstay for the control of leishmaniasis. The drugs of choice are expensive and associated with mult...

Single living Jurkat cells have been encapsulated through polyelectrolytes nanoparticles poly(allyl amine hydrochloride) size 15.6 nm and poly(styrene-co-sulfonic acid sodium salt) size 30.2 nm, through layer by layer coating of oppositely charged plasma membrane. Confocal microscopy and scanning electron microscopy results showed complete shieldin...

SDF-1/CXCR4 axis plays a principle role in the homing and engraftment of hematopoietic stem/progenitor cells (HSPCs), a process that defines cells ability to reach and seed recipient bone marrow niche following their intravenous infusion. However, the proper functioning of CXCR4 downstream signaling depends upon consistent optimal expression of bot...

Human mesenchymal stem cells (hMSCs) present in the bone marrow are the precursors of osteoblasts, chondrocytes and adipocytes, and hold tremendous potential for osteoregenerative therapy. However, achieving directed differentiation into osteoblasts has been a major concern. The use of lithium for enhancing osteogenic differentiation has been docum...

Primer sequence for PCR. (DOC)

Signaling And Metabolic Pathways Represented By Differentially Regulated Genes. (DOC)

MSC characterization. (A) Flow cytometry analysis of mesenchymal markers CD44, CD105 and CD106, and hematopoietic marker CD34. Solid fill denotes isotype control and solid line represents MSC data. (B) Osteoblast and adipocyte differentiation of hMSCs assessed by Alizarin Red S, von Kossa staining and Oil Red-O staining. (TIF)

Primer sequence for Real time PCR. (DOC)

Biological Processes Classification of Significantly Regulated Genes. (DOC)

Complete list of differentially regulated genes. (DOC)

Leishmaniasis is one of the major tropical parasitic diseases that ranges in severity from the self-healing cutaneous lesions to fatal visceral manifestations. On one hand there is no vaccine available against visceral leishmaniasis (VL) (also known as Kala-azar in India) and on the other hand drug resistance, variable efficacy, toxicity and parent...

RuvB protein belongs to AAA+ family of enzymes involved in diverse cellular activities. In addition to the annotated two RuvB proteins in Plasmodium falciparum database, we report that a third RuvB protein is also present. The amino acid sequence analysis has revealed that P. falciparum RuvB3 (PfRuvB3) possesses Walker motif A, Walker motif B, sens...

This study was undertaken to investigate the synergistic interaction between amphotericin B (AmB) and acteoside, isolated from the aerial parts of the shrub Colebrookea oppositifolia (Lamiaceae). Acteoside alone exhibited no intrinsic antifungal activity but showed a potent synergism in combination with AmB against selected pathogenic species, with...

The efficacy of conventional radiation therapy, one of the most widely used treatment modalities of cancer, is limited by resistance of tumors as well as normal tissue toxicity. In the last decade, several studies have shown that protocols using low-dose radiation (LDR) are more effective in providing local tumor control with negligible normal tiss...

Despite significant advances in the treatment of visceral leishmaniasis (VL), conventional chemotherapy (CT) has considerable toxicities and relapses. Immunotherapeutic strategies, aimed to amplify Leishmania-specific immune response prior to or in synergy with CT may lower the required dose or duration of treatment and hence toxicity, improving ch...

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 rema...

Mesenchymal stem cells (MSCs) are gaining importance among clinicians following recent demonstration of safe allogeneic transplantation due to their ability to modulate the immune response. However,the molecular machinery regulating the expression of immunomodulatory factors in MSCs is unknown. We, therefore, inhibited glycogen synthase kinase-3 (G...

The prokaryotic ATP-dependent protease machineries such as ClpQY and ClpAP in the malaria parasite may represent potential drug targets. In the present study, we show that the orthologue of cyanobacterial ClpP protease in Plasmodium falciparum (PfClpP) is expressed in the asexual blood stages and possesses serine protease activity. The PfClpP was l...

Hydroxychavicol, isolated from the chloroform extraction of the aqueous leaf extract of Piper betle L., (Piperaceae) was investigated for its antifungal activity against 124 strains of selected fungi. The leaves of this plant have been long in use tropical countries for the preparation of traditional herbal remedies. The minimum inhibitory concentr...

Normal tissue toxicity is one of the major limiting factors in cancer therapy. Damage to normal tissues and critical organs restricts the use of higher therapeutic doses thereby compromising the efficacy. The glucose analog 2-deoxy-D-glucose (2-DG), an inhibitor of glycolytic ATP production has been shown to enhance radiation- and chemotherapeutic...

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 plastici...

Mesenchymal stem cells (MSCs) represent an adherent, fibroblast-like population present not only in the bone marrow, but in a number of tissues, including blood, adipose tissue, muscle, and dermis. Their extensive proliferation and transdifferentiation potential makes them best suited for tissue engineering applications. Identification of growth fa...

Hematopoietic stem cells (HSCs) possess a distinct ability to perpetuate through self-renewal and to generate progeny that differentiate into mature cells of myeloid and lymphoid lineages. A better understanding of the molecular mechanisms by which HSCs replicate and differentiate from the perspective of developing new approaches for HSC transplant...

High altitude pulmonary oedema (HAPE) is a severe form of altitude illness that develops in travellers on rapid ascent to or physical exertion at altitudes of >2500 m.1 The disease is characterised by pulmonary hypertension, uneven vasoconstriction, and overperfusion which is thought to cause stress failure of pulmonary capillaries leading to alveo...

Hippophae rhamnoides or seabuckthorn is used extensively in Indian and Tibetan traditional medicine for the treatment of circulatory disorders, ischemic heart disease, hepatic injury, and neoplasia. In the present study, we have evaluated the radioprotective potential of REC-1001, a fraction isolated from the berries of H. rhamnoides. Chemical anal...

CD8+ T cells are generated in response to Leishmania major (Lm) or Toxoplasma gondii parasitic infections, indicating that exogenously delivered Ag can be processed for presentation by MHC class I molecules. We show that presentation of Lm nucleotidase (NT)-OVA is TAP independent in vivo and in vitro, and is inhibited by chloroquine, but not by pro...

Sojourners visiting high-altitude (HA) (>2500 m) are susceptible to HA disorders; on the contrary, HA natives are well adapted to the extreme hypoxic environment. High aldosterone levels are believed to be involved in HA disorders, we, therefore, envisaged role of CYP11B2 gene variants in HA adaptation and therefore investigated the -344T/C, intron...

Present study was undertaken to evaluate the radioprotective ability of total polyphenols extracted from edible portion (epicarp and mesocarp) of apple. Prior administration of apple polyphenols to murine thymocytes significantly countered radiation induced DNA damage (evaluated by alkaline halo assay) and cell death (trypan blue exclusion method)...

Podophyllum hexandrum, a herb thriving in Himalayas has already been reported to exhibit antitumor and radioprotective properties. Present study was undertaken to unravel the possible mechanism responsible for the cytotoxic and radioprotective properties of REC-2001, a fraction isolated from the rhizome of P. hexandrum using murine peritoneal macro...

High-altitude natives are adapted to hypobaric hypoxia, suggestive of genetic basis of adaptation. Since endothelin-1 (ET-1) is of prime importance in high-altitude disorders in sojourners, we envisaged the role of allelic variants of ET-1 in high-altitude adaptation. Four ET-1 polymorphisms, viz., (CT)(n)-(CA)(n) repeat, -3A/-4A, G2288T, and Lys19...

CD4+ and CD8+ T-cell responses have been shown to be critical for the development and maintenance of acquired resistance to infections with the protozoan parasite Leishmania major. Monitoring the development of immunodominant or clonally restricted T-cell subsets in response to infection has been difficult, however, due to the paucity of known epit...

Numerous experimental vaccines have been developed with the goal of generating long-term cell-mediated immunity to the obligate intracellular parasite Leishmania major, yet inoculation with live, wild-type L. major remains the only successful vaccine in humans. We examined the expression of immunity at the site of secondary, low-dose challenge in t...

High salt intake is the main determinant of hypertension. The alleles, which once had adaptive value in the salt-poor environment, by promoting salt retention, now induce hypertension. It would be interesting to determine whether the variant alleles of the aldosterone synthase gene (CYP11B2), if related to exaggerated expression/altered activity, a...

High altitude pulmonary oedema (HAPE) is a severe form of altitude illness that may develop in individuals on rapid ascent to altitudes above 2500 m.1 The disease is characterised by hypoxia induced pulmonary vasoconstriction caused by endothelial dysfunction and intravascular fluid retention.2,3 While some families and individuals are at risk, tho...

Leishmania donovani promastigote membrane antigens (LAg) encapsulated in positively charged liposomes have been found to induce very significant levels of protection against experimental visceral leishmaniasis. The protectively immunized animals exhibited profound delayed-type hypersensitivity and antibody responses. The extent of protection induce...

Transformation of promastigotes of Leishmania donovani strain AG83 from amastigotes derived from an infected animal was studied in three media, Schneider's Drosophila medium (SDM), Medium 199 (M199), and biphasic M199 (B-M199) with 10% fetal bovine serum. The media, SDM and B-M199, both supported a more efficient transformation of promastigotes in...