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In vitro probiotic characterization of Lactobacillus casei isolated from marine samples
No full textThe present study evaluated probiotic potentials of marine bacteriocinogenic lactic acid bacteria (LAB).Three marine LAB isolates, designated SB71, SB73 and SB93, were characterized as Lactobacillus casei.They possessed features like high level of gastrointestinal survival, inability to form biogenic amines,adherence to Caco-2 cells and marked cholesterol assimilation. To the best of our knowledge, this is the first report about marine probiotic bacteria from the Indian subcontinent. Tolerance of the three isolates to NaCl, bile and low pH was noteworthy. EPS from SB93 markedly disrupted bacterial adherence and
promoted remediation of cadmium and lead. Broad-spectrum antimicrobial and antiadhesive activities were exhibited by the SB93 bacteriocin and the active principle survived autoclaving. All three bacteriocins exhibited antimicrobial activity against Vibrio cholerae as opposed to previous results. Earlier reports mentioned that the bacteriocinogenic isolates were cultivated for 24 h following which antimicrobial action of bacteriocins (in cell-free culture supernatants) was noted. However, in the present study, the test LAB isolates were cultivated for a period of up to 5 days and bacteriocins (in cell-free
supernatants collected daily from the cultures) continued to exhibit antimicrobial activity, thus advocating
for their potential lasting effect in diseased individuals
Monoamine oxidase B gene variants associated with attention deficit hyperactivity disorder in the Indo-Caucasoid population from West Bengal
Get PDFAttention deficit hyperactivity disorder (ADHD) is characterized by symptoms of inattention, excessive
motor activity and impulsivity detected mostly during childhood. These traits are known to be controlled by
monoamine neurotransmitters, chiefly dopamine, serotonin and norepinephrine. Monoamine oxidase A (MAOA)
and B (MAOB), two isoenzymes bound to the outer membrane of mitochondria, are involved in the degradation of
monoamines and were explored for association with ADHD in different ethnic groups. In the present study, few
exonic as well as intronic MAOB variants were analyzed in ADHD probands (N = 150) and ethnically matched
controls (N = 150) recruited following the Diagnostic and Statistical Manual for Mental Disorders-4th edition
(DSM-IV). Appropriate scales were used for measuring the behavioural attributes. Gene variants were analyzed by
amplification of target sites followed by DNA sequencing and data obtained were analyzed by population based
statistical methods.
Results: Out of 34 variants present in the analyzed sites, only seven functional variants, rs4824562, rs56220155,
rs2283728, rs2283727, rs3027441, rs6324 and rs3027440, were found to be polymorphic. rs2283728 ‘C’ (P = 3.45e-006)
and rs3027440 ‘T’ (P = 0.02) alleles showed higher frequencies in ADHD probands as compared to controls.
rs56220155 ‘A’ (P = 0.04) allele and ‘GA’ (P = 0.04) genotype showed higher frequencies in the male and female
ADHD probands respectively as compared to sex-matched controls. Analysis of pairwise linkage disequilibrium
revealed striking differences between probands and controls. Haplotype analysis revealed significantly higher
occurrence of different haplotypes in the ADHD probands while some haplotypes were detected in the controls
only. Higher scores for conduct problems were found to be associated with rs56220155 ‘A’ (P = 0.05) allele in the
male ADHD probands. Multifactor dimensionality reduction analysis showed independent as well as interactive
effects of polymorphic variants which were more robust in the male probands.
Conclusions: Since all the polymorphic variants analyzed were functional, it may be inferred that MAOB gene
variants are contributing to the etiology of ADHD in the Indo-Caucasoid population from eastern India which
merits further in depth analysis
A New DNA Methyltransferase-Histone Deacetylase-Kinase Axis in Innate Immunity
No full textRegulatory roles of protein and DNA modifications in gene expression during host defense have long been
appreciated. In a recent article published in Nature Immunology, Li et al. (2016) provide a unique glimpse of
yet another aspect of coordinated DNA methylation and protein acetylation in host response to pathogenic
stimuli. They elegantly demonstrate thatDNAmethylation and transcriptional activation at theHDAC9promoter
by DNMT3a, along with lysine deacetylation of TBK1 by HDAC9, are essential events during host defens
New Broad-spectrum Antibacterial Amphiphilic Aminoglycosides Active Against Resistant Bacteria: From Neamine Derivatives to Smaller Neosamine Analogues
No full textAminoglycosides (AGs) constitute a major family of potent and broad-spectrum antibiotics disturbing protein synthesis through binding to the A site of 16S rRNA. Decades of widespread clinical use of AGs strongly reduced their clinical efficacy through the selection
of resistant bacteria. Recently, conjugation of lipophilic groups to AGs generated a novel
class of potent antibacterial amphiphilic aminoglycosides (AAGs) with significant improved
activities against various sensitive and resistant bacterial strains. We have identified
amphiphilic 3’,6-dialkyl derivatives of the small aminoglycoside neamine as broad spectrum
antibacterial agents targeting bacterial membranes. Here, we report on the synthesis and the
activity against sensitive and resistant Gram-negative and/or Gram-positive bacteria of new
amphiphilic 3’,4’-dialkyl neamine derivatives and of their smaller analogues in the 6-
aminoglucosamine (neosamine) series prepared from N-acetylglucosamine
Structural and Functional Analysis of the Host Parasite Interaction Network Using Plasmodium as Case Study
No full textParasitic diseases caused by protozoan pathogens results into millions of deaths per year in addition to substantial suffering and socioeconomic decline worldwide. Active research for understanding host–parasite infection biology in order to develop improved therapeutics is of prime importance due to lack of effective vaccines coupled with the widespread emergence of drug-resistant parasites. Recent advances in next-generation sequencing and the rapid development of publicly accessible genomic databases for many human pathogens have facilitated the application of systems biology to the study of host–parasite interactions.
A top-down system analysis protocol has been developed to construct and analyze large scale protein-protein interaction network using various graph theoretical approaches to identify highly interacting hub and central proteins. Further, an in-silico knock-out (KO) approach is implemented to isolate important interacting proteins (IIPs), which in principle can elicit significant impact on the integrity of the interaction networks. This network biology protocol is applied on Plasmodium falciparum interactome to identify a small set of proteins as important interacting proteins (IIPs), which not only play crucial role in intra-pathogen network integrity, stage specificity but also interact with various human proteins involved in multiple metabolic pathways within the host cell. These IIPs could be used as potential drug targets in malarial research. Stage specific metabolic network was also constructed for P. falciparum followed by its analysis at intra-pathogen and host-pathogen condition.
Similar network analysis approach was used to study an interaction network of deregulated set of gene in mutant P53 condition in order to identify important hub proteins. Analysis of important interactions at the molecular level is also crucial. In a case study, an E3 ubiquitin ligase (COP1) mediated regulation of adipocyte triglyceride lipase (ATGL) protein was studied using molecular modeling and docking techniques. In another case study Inhibition of DNA topoisomerase by SQDG was studied. Origin and evolution of DNA-(C5)-methyltransferase was studied across the tree of life. This large scale phylogenetic study elucidated gradual complexity in the DNMT and other methyltransferase genes
Experimental evaluation of puerarin nanoparticle with reference to its contragestative potential
No full textUnintended pregnancy and population explosion are significant global problem with grave implications for the future. The recent census conducted by the United Nation dated 17 March 2015 estimated the world‘s human population to be over 7 billion, with India being
the second most populated country contributing 17.5% of the world‘s population with a number of approximately 1.27 billion (Zinkina J 2014). The growth in world human
population affects people through its impact on the economy and environment. This problem is much more severe in India because of the increasing pressure on the limited resources of the country. Unfortunately, the decreasing resources are making survivability of human
beings more and more competitive even for the basic necessities of life like food, clothing and shelter. People are experiencing crisis such as climate change, shortage of food and a severe shortage of energy that are contributing to the ever-increasing problems. The
phenomenal population growth also exerts immense pressure on the other basic necessities like education, health, housing, employment opportunities etc, affecting the standard of living. Our civilisation is being squeezed between the rising population densities, and if such
trends continue there will be a severe scarcity of food supply. Hence, time has come when all citizens must take measures to combat the population outburst (Haub & Sharma 2006). In order to find a solution to this conundrum or at the very least, curb the ill effects created by such a situation, contraceptives have emerged as a reasonable antidote. People have used birth control methods for thousands of years. There are numerous contraceptive
options available today. However, the currently available methods are considered inadequate to meet the varied and changing personal needs of couples at different times of their reproductive lives, and in the widely different geographical, cultural and religious settings
that exist around the world (Wang 1999).
The present dissertation is concerned with a plant-derived molecule, puerarin that has prospective anti-implantation effects and the future potential as the active constituent for the development of female contraceptive. And in this connection, I review briefly the female reproduction with a detailed note on the physiology of implantation, and the various methods
of contraception practiced by women worldwide
Novel Molecules for Neuroprotection in Experimental Parkinsonism
No full textNeurodegeneration of the substantia nigra (SN) particularly its pars compacta (SNpc) region disrupts control of motor function, as seen in Parkinson's disease (PD). Nigrostriatal dopaminergic denervation results in decreased dopamine levels in the striatum translating to inadequate dopaminergic signalling. Dopaminergic receptor signalling employs cAMP as a secondary messenger whose levels are regulated by cAMP degrading phosphodiesterase (PDE).
Differentiated SH-SY5Y neuronal cell-lines were used to check novel drug candidates against parkinsonian neurotoxin (1-Methyl 4-Phenylpyridinium (MPP+))-induced neuronal cell death. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treated mouse model of Parkinson's disease was used to assess the molecules’ effect on behavioural motor function using akinesia, catalepsy, swim, pole, open field and rotarod tests with ANY-maze software, cAMP levels in the striatum by spectrophotometric ELISA, PDE inhibitory activity by radiometric enzyme assay, striatal dopamine and serotonin neurochemistry as well as hydroxyl radical estimation by HPLC-electrochemistry and dopaminergic neuron survival in the SN by tyrosine hydroxylase immunohistochemistry.
Irsogladine was found to possess desirable characteristics such as: crossing of the blood brain barrier, PDE inhibitory property, radical scavenging ability, protection against striatal DA depletion, rescue SNpc dopaminergic neurons against degeneration and finally MPTP-induced behavioural dysfunctions. Four derivatives of Irsogladine; JVIR1, JVIR2, JVIR3 and PJD9 also show protection in the MPTP model demonstrating that shifting the Cl at position 5 to the 4th position of the dichlorophenyl ring of Irsogladine to aquire 6-(2,4-dichlorophenyl)-1,3,5-triazine-2,4-diamine (JVIR1) or removing both the Cl atoms on the dichlorophenyl ring of Irsogladine and replacing them with a single Br at the 2nd position of the phenyl ring to get 6-(2-bromophenyl)-1,3,5-triazine-2,4-diamine (JVIR2) or a single Br at the 4th position of the phenyl ring to yield 6-(4-bromophenyl)-1,3,5-triazine-2,4-diamine (JVIR3) or removal of all the halogens on the phenyl ring to get 6-phenyl-1,3,5-triazine-2,4-diamine (PJD9) does not interfere with the antiparkinsonian activity of the general structure or at least does not lead to loss of anti-parkinsonian activity. Removal of the phenyl ring and replacing it with either a methyl or methyl indolyl group to get PJD8 and PJD10 resulted in reduced antiparkinsonian activity. PJD8 and PJD10 probably do not influence striatal dopaminergic signalling via the elevation of cAMP and or DA. The two molecules do demonstrate marginal rescue from parkinsonian phenotype at the highest doses and further investigation on the underlying mechanism would help in lowering the doses or enhancing their activity
Molecular Basis of Neuroprotection Against Parkinsonism By Identified Ayurvedic Molecules
No full textParkinson’s disease (PD) is characterized by progressive and selective demise of mesencephalic substantia nigra pars compacta (SNpc) neurons with manifestation of motor
abnormalities including tremor, slowness in movement, rigidity and poor balance. Although L-3, 4- dihydroxy phenylalanine (L-DOPA) has been the mainstay of PD therapy,
which gives symptomatic relief in initial uses, yet it has severe side-effects on prolonged use, and causes on-off phenomenon, falls and L-DOPA-induced dyskinesia (Caillava-
Santos et al., 2015; Cenci, 2014; Metman et al., 1997; Sweet et al., 1975). Moreover, the drug does not show any beneficial effects on the natural progression of the disease
Carbon nanospheres mediated delivery of nuclear matrix protein SMAR 1 to direct experimental autoimmune encephalomyelitis in mice
Get PDFOwing to the suppression of immune responses and associated side effects, steroid based treatments for inflammatory encephalitis disease can be detrimental. Here, we demonstrate a novel carbon nanosphere (CNP) based treatment regime for encephalomyelitis in mice by exploiting the functional property of the nuclear matrix binding protein SMAR1. A truncated part of SMAR1 ie, the DNA binding domain was conjugated with hydrothermally synthesized CNPs. When administered intravenously, the conjugate suppressed experimental animal encephalomyelitis in T cell specific conditional SMAR1 knockout mice (SMAR-/-). Further, CNP-SMAR1 conjugate delayed the onset of the disease and reduced the demyelination significantly. There was a significant decrease in the production of IL-17 after re-stimulation with MOG. Altogether, our findings suggest a potential carbon nanomaterial based therapeutic intervention to combat Th17 mediated autoimmune diseases including experimental autoimmune encephalomyelitis
Design of a novel microtubule targeted peptide vesicle for delivering different anticancer drugs
No full textA microtubule targeted peptide-based delivery vehicle has been designed using two oppositely charged peptides, which targets tubulin/microtubules, delivers both hydrophilic and hydrophobic drugs into their target site through lysosome at acidic pH. Drug loaded vesicles show a significant anticancer effect compared to control drugs in a 2D monolayer and a 3D spheroid cell