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1.  Computational identification and binding analysis of orphan human cytochrome P450 4X1 enzyme with substrates 
BMC Research Notes  2015;8:9.
Background
Cytochrome P450s (CYPs) are important heme-containing proteins, well known for their monooxygenase reaction. The human cytochrome P450 4X1 (CYP4X1) is categorized as “orphan” CYP because of its unknown function. In recent studies it is found that this enzyme is expressed in neurovascular functions of the brain. Also, various studies have found the expression and activity of orphan human cytochrome P450 4X1 in cancer. It is found to be a potential drug target for cancer therapy. However, three-dimensional structure, the active site topology and substrate specificity of CYP4X1 remain unclear.
Methods
In the present study, the three-dimensional structure of orphan human cytochrome P450 4X1 was generated by homology modeling using Modeller 9v8. The generated structure was accessed for geometrical errors and energy stability using PROCHECK, VERFIY 3D and PROSA. A molecular docking analysis was carried out against substrates arachidonic acid and anandamide and the docked substrates were predicted for drug-likeness, ADME-Tox parameters and biological spectrum activity.
Results
The three-dimensional model of orphan human cytochrome P450 4X1 was generated and assessed with various structural validation programmes. Docking of orphan human cytochrome P450 4X1 with arachidonic acid revealed that TYR 112, ALA 126, ILE 222, ILE 223, THR 312, LEU 315, ALA 316, ASP 319, THR 320, PHE 491 and ILE 492 residues were actively participating in the interaction, while docking of CYP4X1 with anandamide showed that TYR 112, GLN 114, PRO 118, ALA 126, ILE 222, ILE 223, SER 251, LEU 315, ALA 316 and PHE 491 key residues were involved in strong interaction.
Conclusion
From this study, several key residues were identified to be responsible for the binding of arachidonic acid and anandamide with orphan human cytochrome P450 4X1. Both substrates obeyed Lipinski rule of five in drug-likeness test and biological spectrum prediction showed anticarcinogenic activity. Compared to anandamide, arachidonic acid showed strong interaction with cytochrome P450 4X1 and also less health effect in certain human system in ADME-Tox prediction. These findings provide useful information on the biological role and structure-based drug design of orphan human cytochrome P450 4X1.
doi:10.1186/s13104-015-0976-4
PMCID: PMC4322450  PMID: 25595103
Homology modeling; Human cytochrome; CYP4X1; Molecular docking; Arachidonic acid; Anandamide
2.  Thin-Film Microfabricated Nanofluidic Arrays for Size-Selective Protein Fractionation 
Lab on a chip  2013;13(23):4591-4598.
Size-selective fractionation and quantitation of biostructures in the sub-hundred nanometer size range is an important research area. Unfortunately, current methods for size fractionation are complex, time consuming, or offer poor resolution. Using standard microfabrication technology, we developed a nanofluidic sieving system to address these limitations. Our setup consists of an array of parallel nanochannels with a height step in each channel, an injection reservoir, and a waste reservoir. The height steps can size fractionate a protein mixture as a solution flows through the nanochannels via capillary action. We tested this system with different sizes and concentrations of five proteins to understand protein size and height step effects on trapping. Our results clearly show size dependent trapping of proteins at nanometer-scale height steps in nanochannels. We also developed a model that predicts the observed size-dependent trapping of proteins. This work is a key step towards scalable nanofluidic methods for molecular fractionation.
doi:10.1039/c3lc50869b
PMCID: PMC3864585  PMID: 24100699
3.  Recent Developments in β-Cell Differentiation of Pluripotent Stem Cells Induced by Small and Large Molecules 
Human pluripotent stem cells, including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), hold promise as novel therapeutic tools for diabetes treatment because of their self-renewal capacity and ability to differentiate into beta (β)-cells. Small and large molecules play important roles in each stage of β-cell differentiation from both hESCs and hiPSCs. The small and large molecules that are described in this review have significantly advanced efforts to cure diabetic disease. Lately, effective protocols have been implemented to induce hESCs and human mesenchymal stem cells (hMSCs) to differentiate into functional β-cells. Several small molecules, proteins, and growth factors promote pancreatic differentiation from hESCs and hMSCs. These small molecules (e.g., cyclopamine, wortmannin, retinoic acid, and sodium butyrate) and large molecules (e.g. activin A, betacellulin, bone morphogentic protein (BMP4), epidermal growth factor (EGF), fibroblast growth factor (FGF), keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), noggin, transforming growth factor (TGF-α), and WNT3A) are thought to contribute from the initial stages of definitive endoderm formation to the final stages of maturation of functional endocrine cells. We discuss the importance of such small and large molecules in uniquely optimized protocols of β-cell differentiation from stem cells. A global understanding of various small and large molecules and their functions will help to establish an efficient protocol for β-cell differentiation.
doi:10.3390/ijms151223418
PMCID: PMC4284775  PMID: 25526563
beta (β) cells; diabetes; differentiation; stem cells; pancreas
4.  The Synthetic Tryptanthrin Analogue Suppresses STAT3 Signaling and Induces Caspase Dependent Apoptosis via ERK Up Regulation in Human Leukemia HL-60 Cells 
PLoS ONE  2014;9(11):e110411.
Tryptanthrin is a natural product which has been reported to have several medicinal properties. In this study, we tried to investigate the detailed molecular mechanism of its bromo analogue (TBr), a potent cytotoxic agent in the induction of cancer cell death. It was found that TBr primarily targets STAT3 and ERK signaling during the induction of apoptosis in several human leukemia cell lines. In HL-60 cells, TBr treatment caused early down regulation of p-STAT3 with concomitant up regulation of p-ERK which led to the activation of intrinsic and extrinsic pathways of apoptosis. The mechanism of TBr mediated inhibition of p-STAT3 was found to be due to the activation of ubiquitin dependent degradation of tyrosine 705 and serine 727 p-STAT3. As IL-6 is the main driver of the STAT3 pathway, the effect of TBr on cell death was subdued when treated in the combination with IL-6 in HL60 cells. Interestingly, PD98059 significantly reduced the apoptotic effects of TBr, thus showing the direct involvement of p-ERK in TBr mediated cell death. It was further shown that apoptotic protein Bax silencing in HL-60 cells resists TBr mediated ERK dependent apoptosis. In summary, for the first time we report the mechanism of TBr mediated cell death in human leukemia cell lines by targeting STAT3 and ERK pathways.
doi:10.1371/journal.pone.0110411
PMCID: PMC4226462  PMID: 25383546
6.  Mandibulofacial dysostosis (Treacher Collins syndrome): A case report and review of literature 
Contemporary Clinical Dentistry  2014;5(4):532-534.
Treacher Collins syndrome (TCS) or Franceschetti syndrome is an autosomal dominant disorder of craniofacial development with variable phenotypic expression. It presents with characteristic facial appearance enabling it to be easily recognizable. A case of a 10-year-old girl having TCS is briefly described in this article. A review of the etiology, clinical features, differential diagnosis, and treatment options are also discussed.
doi:10.4103/0976-237X.142826
PMCID: PMC4229767  PMID: 25395774
Berry's syndrome; mandibulofacial dysostosis; Treacher Collins syndrome
7.  Mini review on tricyclic compounds as an inhibitor of trypanothione reductase 
Trypanosomiasis and leishmaniasis are two most ruinous parasitic infectious diseases caused by Trypanosoma and Leishmania species. The disease affects millions of people all over the world and associated with high morbidity and mortality rates. The review discuss briefly on current treatment of these parasitic diseases and trypanothione reductase (TryR) as potential targets for rational drug design. The enzyme trypanothione reductase (TryR) has been identified as unique among these parasites and has been proposed to be an effective target against for developing new drugs. The researchers have selected this enzyme as target is due to its substrate specificity in contrast to human analogous glutathione reductase and its absence from the host cell which makes this enzyme an ideal target for drug discovery. In this review we have tried to present an overview of the different tricyclic compounds which are potent inhibitors of TryR with their inhibitory activities against the parasites are briefly discussed.
doi:10.4103/0975-7406.142943
PMCID: PMC4231380  PMID: 25400403
Tricyclic; trypanosomiasis and leishmaniasis; trypanothione reductase
8.  3D-QSAR study of benzotriazol-1-yl carboxamide scaffold as monoacylglycerol lipase inhibitors 
Purpose:
The purpose of this study is to build up the 3D pharmacophore of Monoacylglycerol lipase (MAGL) inhibitor and to provide the basis to design the novel and potent MAGL inhibitors.
Material and Method:
A 3D-QSAR study on benztriazol-1-yl carboxamide derivatives as monoacylglycerol lipase (MAGL) inhibitors was successfully performed by means of pharmacophore mapping using PHASE 3.5 module of Schrφdinger-9.4.
Result:
The 3D-QSAR obtained from APRRR-105 hypothesis was found to be statistically good with r2 = 0.9228 and q2 = 0.871, taking PLS factor 4. The statistical significance of the model was also confirmed by a high value of Fisher's ratio of 82.8 and a very low value of root-mean-square error (RMSE) 0.2564. Another parameter which signifies the model predictivity is Pearson R. Its value of 0.9512 showed that the correlation between predicted and observed activities for the test set compounds is excellent.
Conclusion:
The study suggested that one H-bond acceptor, one positive center, and proper positioning of hydrophobic groups near the distal aromatic ring C are the crucial determinants for MAGL inhibition. Thus, it can be assumed that the present QSAR analysis is enough to demonstrate MAGL inhibition with the help of APRRR-105 hypothesis and will be helpful in designing novel and potent MAGL inhibitors.
doi:10.4103/0975-7406.142957
PMCID: PMC4231386  PMID: 25400409
3D-QSAR; benztriazol-1-yl carboxamides; monoacylglycerol lipase
9.  Author's reply 
Indian Journal of Orthopaedics  2014;48(5):536-537.
doi:10.4103/0019-5413.139894
PMCID: PMC4175875  PMID: 25298568
10.  Consensus & Evidence-based INOSA Guidelines 2014 (First edition) 
Obstructive sleep apnoea (OSA) and obstructive sleep apnoea syndrome (OSAS) are subsets of sleep-disordered breathing. Awareness about OSA and its consequences amongst the general public as well as the majority of primary care physcians across India is poor. This necessiated the development of the INdian initiative on Obstructive sleep apnoea (INOSA) guidelines under the auspices of Department of Health Research, Ministry of Health & Family Welfare, Government of India. OSA is the occurrence of an average five or more episodes of obstructive respiratory events per hour of sleep with either sleep related symptoms or co-morbidities or ≥ 15 such episodes without any sleep related symptoms or co-morbidities. OSAS is defined as OSA associated with daytime symptoms, most often excessive sleepiness. Patients undergoing routine health check-up with snoring, daytime sleepiness, obesity, hypertension, motor vehicular accidents and high risk cases should undergo a comprehensive sleep evaluation. Medical examiners evaluating drivers, air pilots, railway drivers and heavy machinery workers should be educated about OSA and should comprehensively evaluate applicants for OSA. Those suspected to have OSA on comprehensive sleep evaluation should be referred for a sleep study. Supervised overnight polysomnography (PSG) is the “gold standard” for evaluation of OSA. Positive airway pressure (PAP) therapy is the mainstay of treatment of OSA. Oral appliances are indicated for use in patients with mild to moderate OSA who prefer oral appliances to PAP, or who do not respond to PAP or who fail treatment attempts with PAP or behavioural measures. Surgical treatment is recommended in patients who have failed or are intolerant to PAP therapy.
PMCID: PMC4248396  PMID: 25366217
Bariatric surgery; CPAP; Indian guidelines; OSA; OSAS; polysomnography; sleep apnoea; sleep study; Syndrome Z
11.  Morel-Lavallee lesion in distal thigh: A case report 
It is a relatively rare condition involving a close degloving injury due to direct trauma with tangential force followed by the separation of the subcutaneous tissue from the underlying fascia. The rupture of small perforating vessels in this area, resulting in the formation of a cavity that filled with blood, lymph and fat foci, the latter being sometimes necrotic. Morel-Lavallée lesion was originally described in the lateral aspect of the proximal thigh, which is the most common site of this lesion; however other anatomic sites such as periscapular, lumbar and gluteal regions, ankles and knees have been described in the literature. Various methods of treatment has been described, but open debridement can result in a successful functional outcome.
doi:10.1016/j.jcot.2014.07.002
PMCID: PMC4223810
Trauma; Close degloving injury; Distal thigh; ACL
12.  Nontypeable Haemophilus influenzae inhibits autolysis and fratricide of Streptococcus pneumoniae in vitro 
Streptococcus pneumoniae (SP) and nontypeable Haemophilus influenzae (NTHi) are common commensals of the human airway and major bacterial pathogens of otitis media (OM) and other upper airway infections. The interaction between them may play an important role in the pathogenesis of polymicrobial infections. Although previous studies suggested NTHi could promote pneumococcal survival and biofilm formation, how NTHi affects pneumococcal activities has not been defined. Our data in the present studies indicated that the outcome of the interaction between SP and NTHi was in a cell-density-dependent manner and the enhancement of pneumococcal survival happened at the later stages of culturing. Using quantitative PCR, we found that the expression of pneumococcal genes regulating autolysis and fratricide, lytA and cbpD, were significantly down-regulated in co-culture with NTHi. We further observed that influence of NTHi was not on direct cell-to-cell contact, but that this contact may contribute to the interaction between these two microorganisms. These results suggest that pneumococcal survival and biofilm formation can be enhanced by down-regulating pneumococcal cell wall hydrolase production thereby inhibiting pneumococcal autolysis and fratricide in the presence of NTHi.
doi:10.1016/j.micinf.2013.11.006
PMCID: PMC4080417  PMID: 24269704
Streptococcus pneumoniae; nontypeable Haemophilus influenzae; survival; inhibit; autolysis; fratricide
13.  Generation of folliculogenic human epithelial stem cells from induced pluripotent stem cells 
Nature communications  2014;5:3071.
Epithelial stem cells (EpSCs) in the hair follicle bulge are required for hair follicle growth and cycling. The isolation and propagation of human EpSCs for tissue engineering purposes remains a challenge. Here we develop a strategy to differentiate human iPSCs (hiPSCs) into CD200+/ITGA6+ EpSCs that can reconstitute the epithelial components of the hair follicle and interfollicular epidermis. The hiPSC-derived CD200+/ITGA6+ cells show a similar gene expression signature as EpSCs directly isolated from human hair follicles. Human iPSC-derived CD200+/ITGA6+ cells are capable of generating all hair follicle lineages including the hair shaft, and the inner and outer root sheaths in skin reconstitution assays. The regenerated hair follicles possess a KRT15+ stem cell population and produce hair shafts expressing hair specific keratins. These results suggest an approach for generating large numbers of human EpSCs for tissue engineering and new treatments for hair loss, wound healing and other degenerative skin disorders.
doi:10.1038/ncomms4071
PMCID: PMC4049184  PMID: 24468981
14.  The Rational Design of Specific Peptide Inhibitor against p38α MAPK at Allosteric-Site: A Therapeutic Modality for HNSCC 
PLoS ONE  2014;9(7):e101525.
p38α is a significant target for drug designing against cancer. The overproduction of p38α MAPK promotes tumorigenesis in head and neck squamous cell carcinoma (HNSCC). The ATP binding and an allosteric site referred as DFG are the key sites of the p38α mitogen activated protein kinase (MAPK) exploited for the design of inhibitors. This study demonstrated design of peptide inhibitor on the basis of allosteric site using Glide molecular docking software and the biochemical analysis of the best modeled peptide. The best fitted tetrapeptide (FWCS) in the allosteric site inhibited the pure recombinant and serum p38α of HNSCC patients by 74 and 72%, respectively. The potency of the peptide was demonstrated by its IC50 (4.6 nM) and KD (3.41×10−10 M) values, determined by ELISA and by surface plasmon resonance (SPR) technology, respectively. The cell viability of oral cancer i.e. KB cell line was reduced in dose dependent manner by 60 and 97% by the treatment of peptide and the IC50 was 600 and 210 µM after 24 and 72 h incubation, respectively. Our result provides an insight for the development of a proficient small peptide as a promising anticancer agent targeting DFG site of p38α kinase.
doi:10.1371/journal.pone.0101525
PMCID: PMC4077802  PMID: 24983631
15.  Robotic assisted kidney transplantation 
Kidney transplantation is the standard of care for patients with end stage renal disease. While open surgery remains the gold standard, minimally invasive surgery has recently been introduced for the recipient undergoing kidney transplantation. We review the evolution of techniques of minimally invasive surgery for kidney transplantation with specific emphasis on technical aspects of robotic assisted kidney transplantation.
doi:10.4103/0970-1591.135669
PMCID: PMC4120216  PMID: 25097315
da Vinci surgical system; kidney recipient; laparoscopy; robotic assistance
16.  Clear cell carcinoma of minor salivary gland: A case of clinical dilemma 
Contemporary Clinical Dentistry  2014;5(3):389-392.
Clear cell tumor in oral cavity constitutes an assorted group of lesions, which may be odontogenic, metastatic or of salivary gland origin. Those associated with salivary glands accounts for less than 1% of total cases mainly seen in the major salivary gland. Occurrence of clear cell carcinoma in minor salivary gland is rare and uncommon. Hence, this case of intraoral clear cell carcinoma associated with minor salivary gland of palate in a 57-year-old male patient is being reported.
doi:10.4103/0976-237X.137965
PMCID: PMC4147820  PMID: 25191080
Clear cell carcinoma; immunohistochemistry; maxillary alveolus; minor salivary gland
17.  Study of Drug Utilization Pattern for Acute Exacerbation of Chronic Obstructive Pulmonary Disease in Patients Attending a Government Hospital in Kerala, India 
Objective:
Drug utilization studies are powerful exploratory tools to ascertain the role of drugs in society. This study was conducted to establish the drug utilization pattern and the common adverse drug reactions for the treatment of acute exacerbation of chronic obstructive pulmonary disease (COPD) in one of the government hospitals in Kerala, India.
Methods:
This was a prospective observational study aimed at recognizing the drug utilization pattern for the treatment of acute exacerbation of COPD for 7-day under nonexperimental settings. All information significant to the study was collected from the case records and discussions conducted with the inpatients and bystanders during ward rounds, with the support of a physician. Moreover, daily follow-ups were conducted to assemble data on amendment in therapy, add-on therapy, and clinical improvement until the patient was discharged from the hospital or to an upper limit of 7-day, whichever is earlier.
Results:
All the patients in this study received combination therapy. Among the inhalational β-agonists, salbutamol accounted for 74% use. Parenteral steroids were used in 78% of the patients and all of them received hydrocortisone. Steroid inhalers were used only in 25% of the patients. Anticholinergics were used in 77.5% of patients. Antibiotics were used in 86.7% patients. The main adverse effects noted were dry mouth (15%) and bad taste (10%) and these adverse effects were highly correlated with the use of anticholinergics (P < 0.05).
Conclusions:
Despite the use of drugs according to the availability and physician's preference, it was found in the analysis that majority were in accordance with Global Initiative for Chronic Obstructive Lung Disease criteria recommendations.
doi:10.4103/2249-4863.141622
PMCID: PMC4209682  PMID: 25374864
Acute exacerbation; chronic obstructive pulmonary disease; drug utilization
18.  Transcriptomic Analysis of Cultured Whale Skin Cells Exposed to Hexavalent Chromium [Cr(VI)] 
Hexavalent chromium Cr(VI) is known to produce cytotoxic effects in humans and is a highly toxic environmental contaminant. Interestingly, it has been shown that free ranging sperm whales (Phyester macrocephalus) may have exceedingly high levels of Cr in their skin. Also, it has been demonstrated that skin cells from whales appear more resistant to both cytotoxicity and clastogenicity upon Cr exposure compared to human cells. However, the molecular genetic mechanisms employed in whale skin cells that might lead to Cr tolerance are unknown.
In an effort to understand the underlying mechanisms of Cr(VI) tolerance and to illuminate global gene expression patterns modulated by Cr, we exposed whale skin cells in culture to varying levels of Cr(VI) (i.e., 0.0, 0.5, 1.0 and 5.0 μg/cm2) followed by short read (100 bp) next generation RNA sequencing (RNA-seq). RNA-seq reads from all exposures (≈280 million reads) were pooled to generate a de novo reference transcriptome assembly. The resulting whale reference assembly had 11K contigs and an N50 of 2,954 bp.
Using the reads from each dose (0.0, 0.5, 1.0 and 5.0 μg/cm2) we performed RNA-seq based gene expression analysis that identified 35 up-regulated genes and 19 down-regulated genes. The experimental results suggest that low dose exposure to Cr (1.0 μg/cm2) serves to induce up-regulation of oxidative stress response genes, DNA repair genes and cell cycle regulator genes. However, at higher doses (5.0 μg/cm2) the DNA repair genes appeared down-regulated while other genes that were induced suggest the initiation of cytotoxicity.
The set of genes identified that show regulatory modulation at different Cr doses provide specific candidates for further studies aimed at determination of how whales exhibit resistance to Cr toxicity and what role(s) reactive oxygen species (ROS) may play in this process.
doi:10.1016/j.aquatox.2013.03.003
PMCID: PMC3739694  PMID: 23584427
Sperm whale; Chromium; RNA-seq; Illumina HiSeq; ROS (reactive oxygen species); cytotoxicity
19.  Molecular Pathogenesis of Sporadic Melanoma and Melanoma-Initiating Cells 
Recent advances in molecular genetics and cancer stem cell biology have shed some light on the molecular basis of melanomagenesis. In this review, we will focus on major genetic alterations in the melanoma, particularly pathways involved in cell proliferation, apoptosis, and tumor suppression. The potential role of melanoma-initiating cells during melanomagenesis and progression will also be discussed. Understanding pathogenesis of melanoma may uncover new diagnostic clues and therapeutic targets for this increasingly prevalent disease.
doi:10.1043/2009-0418-RAR.1
PMCID: PMC4049155  PMID: 21128770
20.  Knowledge and Awareness of Diabetes and Diabetic Ketoacidosis (DKA) Among Medical Students in a Tertiary Teaching Hospital: An Observational Study 
Background: The management of Diabetes Mellitus and its important complication Diabetic Ketoacidosis is very crucial in today’s world where the prevalence of Diabetes is very high. Medical students are the pillars of our future healthcare system and it is important to evaluate and update their knowledge and awareness regarding these both conditions.
Materials and Methods: This study was a cross-sectional; Questionnaire based observational study conducted in a tertiary care hospital. The respondents were final year MBBS students of that college. Study instrument was a self developed, pre-validated, semi-structured questionnaire.
Results: A total of 73 questionnaires were considered for analysis, giving a response rate of 90.12% with 43.83% and 56.16% were male and female respondents respectively. About 81.25% and 90.24% of male and female respondents gave correct answer to question related to the best indicator of glycemic control. Lack of knowledge was seen regarding the world Diabetes day. Approximately 37% of the respondent’s parents were diabetic. Only 12 out of 73 respondents were aware about the factors leading to DKA.8 out of 73 were aware about investigations to be done in DKA. Around 43.84% of responders knew regarding the proper screening duration in person with risk of diabetes.
Conclusion: From the study it was concluded that most of the students have basic knowledge regarding diabetes mellitus, its clinical features and management etc but only 50 % of the respondent were aware about DKA and further teaching and post teaching evaluation are needed in future direction.
doi:10.7860/JCDR/2014/7917.4249
PMCID: PMC4064852  PMID: 24959462
Awareness; Diabetes mellitus; Diabetic Ketoacidosis; Knowledge; MBBS Students
21.  Antifungal and Antiproliferative Protein from Cicer arietinum: A Bioactive Compound against Emerging Pathogens 
BioMed Research International  2014;2014:387203.
The emergence of epidemic fungal pathogenic resistance to current antifungal drugs has increased the interest in developing alternative antibiotics from natural sources. Cicer arietinum is well known for its medicinal properties. The aim of this work was to isolate antimicrobial proteins from Cicer arietinum. An antifungal protein, C-25, was isolated from Cicer arietinum and purified by gel filtration. C-25 protein was tested using agar diffusion method against human pathogenic fungi of ATCC strains and against clinical isolates of Candida krusei, Candida tropicalis, and Candida parapsilosis, and MIC values determined were varied from 1.56 to 12.5 μg/mL. The SEM study demonstrated that C-25 induces the bleb-like surface changes, irregular cell surface, and cell wall disruption of the fungi at different time intervals. Cytotoxic activity was studied on oral cancer cells and normal cells. It also inhibits the growth of fungal strains which are resistant to fluconazole. It reduced the cell proliferation of human oral carcinoma cells at the concentration of 37.5 μg/mL (IC50) and no toxic effect was found on normal human peripheral blood mononuclear cells even at higher concentration of 600 μg/mL. It can be concluded that C-25 can be considered as an effective antimycotic as well as antiproliferative agent against human oral cancer cells.
doi:10.1155/2014/387203
PMCID: PMC4053179  PMID: 24963482
22.  Higher Caspase-like activity in symptomatic isolates of Blastocystis spp 
Parasites & Vectors  2014;7:219.
Background
Biochemical evidence of a caspase-like execution pathway has been demonstrated in a variety of protozoan parasites, including Blastocystis spp. The distinct differences in the phenotypic characterization reported previously have prompted us to compare the rate of apoptosis in Blastocystis spp. isolated from individuals who were symptomatic and asymptomatic. In the current study, we analysed the caspase activation involved in PCD mediated by a cytotoxic drug, (metronidazole) in both symptomatic & asymptomatic isolates.
Methods
Apoptosis was induced in Blastocystis spp. by treating cultures of symptomatic and asymptomatic isolates of 3 sub-types namely 1, 3 and 5 with two different concentrations, 0.1 and 0.0001 mg/ml of metronidazole (with and without pre-treatment with a pan-caspase inhibitor, zVAD.fmk). The experiment was repeated to assess the number of apoptotic cells in all the isolates of both conditions.
Results
Symptomatic isolates of subtype 3 (without pre-treatment with a pan-caspase inhibitor, zVAD.fmk) showed high fluorescence intensity for active caspase-like proteases [0.0001 mg/ml, 88% (p < 0.001) at 0.1 mg/ml, 70% (p < 0.001)] at the 72nd hour in vitro culture in comparison with asymptomatic isolates [0.0001 mg/ml, 65%, at 0.1 mg/ml, 55%]. The number of apoptotic cells was higher [0.0001 mg/ml, 89% (p < 0.001) and at 0.1 mg/ml, 70% (p < 0.001)] at the 72nd hour of in vitro culture in comparison with asymptomatic isolates [0.0001 mg/ml, 66% (p < 0.001) and at 0.1 mg/ml, 45% (p < 0.01)]. Cells treated with metronidazole in the presence of zVAD.fmk showed less than 10% caspase activation.
Conclusion
The high number of symptomatic cells expressing active caspase-like proteases and becoming apoptotic compared to asymptomatic cells clearly demonstrates that the response to metronidazole treatment is isolate dependent. Hence this justifies the conflicting reports on the curative success rates when treated with this drug. The study has also created a need to identify apoptosis effectors in Blastocystis spp of different isolates especially as it was shown that apoptosis was sub-typed related. These findings can be exploited for the development of diagnostic markers and novel therapeutic drugs to enhance the effectiveness of the diagnosis and treatment of the patients infected with Blastocystis spp.
doi:10.1186/1756-3305-7-219
PMCID: PMC4049410  PMID: 24886677
Blastocystis spp; Apoptosis; Symptomatic; Asymptomatic; Caspase-like proteases; Programmed cell death; Metronidazole
23.  Luteolin, a bioflavonoid inhibits azoxymethane-induced colon carcinogenesis: Involvement of iNOS and COX-2 
Pharmacognosy Magazine  2014;10(Suppl 2):S306-S310.
Colon cancer (CRC) is a serious health problem through worldwide. Development of novel drug without side effect for this cancer was crucial. Luteolin (LUT), a bioflavonoid has many beneficial effects such as antioxidant, anti-inflammatory, anti-proliferative properties. Azoxymethane (AOM), a derivative of 1, 2-Dimethyl hydrazine (DMH) was used for the induction of CRC in Balb/C mice. CRC was induced by intraperitoneal injection of AOM to mice at the dose of 15 mg/body kg weight for 3 weeks. Mouse was treated with LUT at the dose of 1.2 mg/body kg weight orally until end of the experiment. The expression of inducible nitric oxide synthase (iNOS) and cyclooxygense (COX)-2 were analyzed by RT-PCR and immunohistochemistry. The expressions of iNOS and COX-2 were increased in the case of AOM induction. Administration of LUT effectively reduced the expressions of iNOS and COX-2. The present study revealed that, LUT suppresses both iNOS and COX-2 expressions and act as an anti-inflammatory role against CRC.
doi:10.4103/0973-1296.133285
PMCID: PMC4078326  PMID: 24991108
Azoxymethane; colon cancer; COX-2; iNOS; Luteolin
24.  Fall in Vitamin D Levels during Hospitalization in Children 
Plasma levels of 25-hydroxyvitamin D [25(OH)D] were measured by competitive Electrochemiluminescence Immunoassay (ECLIA) in 92 children (67 boys, 25 girls) aged 3 months to 12 years at admission to hospital (timepoint 1, T1) and at discharge (timepoint 2, T2). There was a significant fall in the mean 25(OH)D from T1 (71.87 ± 27.25 nmol/L) to T2 (49.03 ± 22.25 nmol/L) (mean change = 22.84 nmol/L, P value = 0.0004). Proportion of patients having VDD (levels <50 nmol/L) at admission (25%, 23/92) increased significantly at the time of discharge (51.09%, 47/92) (P = 0.0004). There was a trend towards longer duration of hospital stay, requirement of ventilation and inotropes, development of healthcare-associated infection, and mortality in vitamin D deficient as compared to nondeficient patients though the difference was statistically insignificant. In conclusion, vitamin D levels fall significantly and should be monitored during hospital stay in children. Large clinical studies are needed to prospectively evaluate the effect of vitamin D supplementation in vitamin D deficient hospitalized children on various disease outcome parameters.
doi:10.1155/2014/291856
PMCID: PMC3985317  PMID: 24860607
25.  Primary amyloidoma of chest wall – a rare condition 
BMJ Case Reports  2012;2012:bcr0120125552.
Organ specific amyloidosis has been shown to be confined to various organs like liver, lung, spleen, urinary bladder and gastro-intestinal tract, but amyloidoma or tumoural amyloidosis of chest wall with no evidence of systemic amyloidosis is an extremely rare presentation and only two cases have been reported till now. The authors report a case of chest wall amyloidoma with review of literature.
doi:10.1136/bcr.01.2012.5552
PMCID: PMC3316792  PMID: 22605798

Results 1-25 (114)