2058 research outputs found
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Natural Products: Promising Resources for Cancer Drug Discovery
No full textNatural products are important sources of anti-cancer lead molecules. Many successful anti-cancer drugs are natural products
or their analogues. Many more are under clinical trials. The present review focuses on chemopreventive and anti-cancer activities of
polar and non-polar extracts, semi purified fractions and pure molecules from terrestrial plants of India reported between 2005 and 2010
emphasizing possible mechanisms of action of pure molecules
Mechanism of Cadmium Binding on the Cell Wall of an Acidophilic Bacterium
No full textUnder certain conditions bacteria can act as a good biosorbent for different toxic heavy metals. However,
no study on this aspect has been reported in case of acidophilic, heterotrophic, Gram-negative Acidiphilium
strains, which are mostly resistant to several heavy metals. FTIR, SEM, TEM along with sorption
experiments using bacterial cells of Acidiphilium symbioticum H8 were conducted to establish the mechanism
of Cd2+ ion sorption. The anionic functional groups present in the cell envelop were the components
primarily responsible for the metal-binding capability of the bacterium. Sorption experiment
further confirmed that 248.62 mg of cadmium was adsorbed per gram biomass at pH 6.0. The process
can better be explained by Langmuir–Freundlich dual isotherm model. Blocking of the functional groups
by chemical modification suggested that the binding of cadmium on the biomass occurs through electrostatic
reaction and complex formation. Accumulation of cadmium on the cell envelop was supported by
fine structure study
Design, Development and Implementation of Novel in silico Data Mining, Clustering and Visualization Tools for Comparative Genome and Proteome Analysis
No full textIf one recited the human genome sequence at the rate of 5 bases per second for 24 hours a day, it would take one about 19 years to recite the book of life. This is only taking into account 3 billion bases of the genome sequence itself, excluding data annotations and other information associated with sequence data. As of April 15, 2012, GenBank release 189.0 has 139,266,481,398 bases from 151,824,421 reported sequences - nearly 47 times the human
genome sequence content (GenBank release note - ftp://ftp.ncbi.nih.gov/genbank/gbrel.txt).
The number of sequenced genomes is presently growing at an unprecedented pace and there should be no reason to expect it to slow down in the future. On the contrary, the introduction of genomics at a massive scale with „second-generation sequencing technologies‟ such as
454, Solexa or Solid adds to this expectation (Mardis 2008), as illustrated by the recent genome sequencing of a single individual. Importantly, these new technologies promise to be very useful for genome analysis in non-model organisms (Ellegren 2008; Hudson 2008; Vera et al. 2008). Moreover, the 1000 genomes project will create a new map of genetic variation for our genome. Other projects are helping to catalogue genes involved in cancer, alternative splicing in different tissues and transcription
factor binding, for example. The evolution of „omic‟ science through microarray transcriptomics, metabolomics, proteomics, etc. is generating this huge data. This data have begun to revolutionize genomics and their effects are becoming increasingly widespread. There has been a vital need to warehouse, harness, disseminate, analyze and interpret this torrents of data, not only to quench the academic thirst of the researchers, but also for
medical diagnostic and therapeutic uses and several other biotechnological applications. For this, use of computational approaches was inevitable and thus emerged Bioinformatics – a new field of scientific enquiry that represents a confluence of biology, computer science and
information technology
A Facile Synthesis of PEG-Coated Magnetite (Fe3O4) Nanoparticles and Their Prevention of the Reduction of Cytochrome C
No full textWe report here a facile and green synthetic
approach to prepare magnetite (Fe3O4) nanoparticles (NPs)
with magnetic core and polyethylene glycol (PEG) surface
coating. The interaction of the bare and PEG-coated Fe3O4
NPs with cytochrome c (cyt c, an important protein with
direct role in the electron transfer chain) is also reported in
this study. With ultrasonication as the only peptization method
and water as the synthesis medium, this method is easy, fast,
and environmentally benign. The PEG coated NPs are highly
water dispersible and stable. The bare NPs have considerable
magnetism at room temperature; surface modification by PEG
has resulted in softening the magnetization. This approach can very well be applicable to prepare biocompatible, surface-modified
soft magnetic materials, which may offer enormous utility in the field of biomedical research. Detailed characterizations including
XRD, FTIR, TG/DTA, TEM, and VSM of the PEG-coated Fe3O4 NPs were carried out in order to ensure the future applicability
of this method. Although the interaction of bare NPs with cyt c shows reduction of the protein, efficient surface modification by
PEG prevents its reductio
Deciphering the Binding Mode of Zolpidem to GABAA α1 Receptor – Insights from Molecular Dynamics Simulation
No full textTo investigate the binding mode of Zolpidem to
GABAA and to delineate the conformational changes
induced upon agonist binding, we carried out atomistic
molecular dynamics simulation using the ligand binding
domain of GABAA α1 receptor. Comparative molecular
dynamics simulation of the apo and the holo form of
GABAA receptor revealed that γ2/α1 interface housing the
benzodiazepine binding site undergoes distinct conformational
changes upon Zolpidem binding. We notice that C
loop of the α1 subunit experiences an inward motion
toward the vestibule and the F loop of γ2 sways away from
the vestibule, an observation that rationalizes Zolpidem as
an alpha1 selective agonist. Energy decomposition analysis
carried out was able to highlight the important residues
implicated in Zolpidem binding, which were largely in
congruence with the experimental data. The simulation
study disclosed herein provides a meaningful insight into
Zolpidem-GABAAR interactions and helps to arrive at a
binding mode hypothesis with implications for drug design
Curcumin as Anti-Endometriotic Agent: Implication of MMP-3 and Intrinsic Apoptotic Pathway
No full textThe disease of reproductive women, endometriosis represents implantation of functional endometrial
glands outside uterine cavity. This invasive disorder is associated with dysregulation of matrix
metalloproteases (MMP)s and extracellular matrix (ECM) remodeling. In this study, we investigated the
role of MMP-3 on apoptosis during endometriosis. We also checked whether curcumin has potency to
regress endometriosis by modulating MMP-3 and apoptotic pathway. Mouse model of endometriosis
was designed by intraperitoneal inoculation of endometrial tissues to syngeneic female BALB/c. At 15th
day, stable endometriotic developments were observed with increased MMP-3 expression. TUNEL
positive cells were also found with endometriotic progression, which might resulted from destruction of
local immune cells. We speculate that increased MMP-3 activity might be involved in the Fas mediated
apoptosis. Curcumin treatment regressed endometriosis by inhibiting NFkB translocation and MMP-3
expression. It also accelerated apoptosis in endometriomas predominantly via cytochrome-c mediated
mitochondrial pathway. Involvement of mitochondria in apoptosis was further confirmed by atomic
force microscopy (AFM). These results were also supported by our therapeutic study, where curcumin
induced apoptosis both by p53 dependent and independent manner, while celecoxib followed only p53
independent pathway. Altogether, our study establishes the novel role of curcumin as a potent antiendometriotic
compound
Nanocapsulated Curcumin: Oral Chemopreventive Formulation against Diethylnitrosamine Induced Hepatocellular Carcinoma in Rat
No full textToxic outcome of chemical therapeutics as well as multidrug resistance are two serious phenomena for
their inacceptance in cancer chemotherapy. Antioxidants like curcumin (Cur) have gained immense
importance for their excellent anticarcinogenic activities and minimum toxic manifestations in biological
system. However, Cur is lipophilic and thus following oral administration hardly appears in blood indicating
its potential therapeutic challenge in cancer therapy. Nanocapsulated Cur has been used as a drug
delivery vector to focus the effectiveness of these vesicles against hepatocellular carcinoma. The theme of
work was to evaluate effectiveness in oral route of polylactide co-glycolide (PLGA) Nanocapsulated curcumin
(Nano Cur) against diethylnitrosamine (DEN) induced hepatocellular carcinoma (HCC) in rat.
Nano Cur of average diameter 14 nm and encapsulation efficiency of 78% were prepared. Fourier Transform
Infra Red (FTIR) analysis revealed that there is no chemical interaction between drug and the polymer.
Three i.p. injections of the chemical hepatocarcinogen DEN at 15 days interval causes hepatotoxicity,
the generation of reactive oxygen species (ROS), lipid peroxidation, decrease in plasma membrane microviscosity
and depletion of antioxidant enzyme levels in liver. Nano Cur (weekly oral treatment for
16 weeks at 20 mg/kg b.wt) in DEN induced HCC rats exerted significant protection against HCC and
restored redox homeostasis in liver cells. Nanocapsulated Cur caused cancer cell apoptosis as visualized
by ApoBrdU analysis. Histopathological analysis confirmed the pathological improvement in the liver.
Nano Cur was found to be a potential formulation in oral route in combating the oxidative damage of
hepatic cells and eliminating DEN induced hepatocellular cancer cells in rat whereas identical amount
of free Cur treatment was found almost ineffective
Radio-Attenuated Leishmanial Parasites as Immunoprophylactic Agent Against Experimental Murine Visceral Leishmaniasis
No full textThe present study intends to evaluate the role of radio-attenuated leishmania parasites as immunoprophylactic
agents for experimental murine visceral leishmaniasis. BALB/c mice were immunized with
gamma (c)-irradiated Leishmania donovani. A second immunization was given after 15 days of first
immunization. After two immunizations, mice were infected with virulent L. donovani promastigotes.
Protection against Kala-azar (KA) was estimated from spleen and liver parasitic burden along with the
measurement of nitrite and superoxide anion generation by isolation of splenocytes and also by T-lymphocyte
helper 1(Th1) and T-lymphocyte helper 2(Th2) cytokines release from the experimental groups.
It was observed that BALB/c mice having prior immunization with radio-attenuated parasites showed
protection against L. donovani infection through higher expression of Th1 cytokines and suppression of
Th2 cytokines along with the generation of protective free radicals. The group of mice without prior priming
with radio-attenuated parasites surrendered to the disease. Thus it can be concluded that radio-attenuated
L. donovani may be used for
Tryptamine-Gallic Acid Hybrid Prevents Non-steroidal Anti-inflammatory Drug-induced Gastropathy
No full textNon-steroidal anti-inflammatory drugs (NSAIDs) induce gastropathy by promoting mitochondrial pathology,
oxidative stress, and apoptosis in gastric mucosal cells.
We have synthesized SEGA (3a), a tryptamine-gallic acid hybrid, which prevents NSAID-induced gastropathy by
preventing mitochondrial oxidative stress, dysfunction, and apoptosis.
SEGA (3a) bears an immense therapeutic potential against NSAID-induced gastropathy.
This novel molecule is a significant addition in the discovery of gastroprotective drugs
Structural Diversity in Bacterial Ribosomes: Mycobacterial 70S Ribosome Structure Reveals Novel Features
No full textHere we present analysis of a 3D cryo-EM map of the 70S ribosome from Mycobacterium smegmatis, a saprophytic cousin of
the etiological agent of tuberculosis in humans, Mycobacterium tuberculosis. In comparison with the 3D structures of other
prokaryotic ribosomes, the density map of the M. smegmatis 70S ribosome reveals unique structural features and their
relative orientations in the ribosome. Dramatic changes in the periphery due to additional rRNA segments and extra
domains of some of the peripheral ribosomal proteins like S3, S5, S16, L17, L25, are evident. One of the most notable
features appears in the large subunit near L1 stalk as a long helical structure next to helix 54 of the 23S rRNA. The sharp
upper end of this structure is located in the vicinity of the mRNA exit channel. Although the M. smegmatis 70S ribosome
possesses conserved core structure of bacterial ribosome, the new structural features, unveiled in this study, demonstrates
diversity in the 3D architecture of bacterial ribosomes. We postulate that the prominent helical structure related to the 23S
rRNA actively participates in the mechanisms of translation in mycobacteri