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1.  Somatically expressed germ-granule components, PGL-1 and PGL-3, repress programmed cell death in C. elegans 
Scientific Reports  2016;6:33884.
We previously reported that germline apoptosis in C. elegans increased by loss of PGL-1 and PGL-3, members of a family of constitutive germ-granule components, from germ cells in adult hermaphrodite gonads. In this study, we found that somatic apoptosis was reduced in synthetic multivulva class B (synMuv B) mutants due to ectopic expression of PGL-1 and PGL-3 in the soma. In synMuv B-mutant somatic cells, CED-4 expression level was reduced due to ectopic expression of PGL-1. Furthermore, in contrast to wild type, somatic apoptosis in synMuv B mutants increased following DNA damage in a SIR-2.1-dependent manner. Intriguingly, somatic apoptosis was repressed not only in synMuv B mutants but also by ectopically expressing pgl-1 and/or pgl-3 transgenes in wild-type somatic cells. Our study demonstrates that germ-granule components, PGL-1 and PGL-3, can serve as negative regulators of apoptosis not only in the germline but also in the soma in C. elegans.
PMCID: PMC5030653  PMID: 27650246
2.  Cross-sectional study exploring barriers to adverse drug reactions reporting in community pharmacy settings in Dhaka, Bangladesh 
BMJ Open  2016;6(8):e010912.
To assess community pharmacists'/pharmacy technicians' knowledge and perceptions about adverse drug reactions (ADRs) and barriers towards the reporting of such reactions in Dhaka, Bangladesh.
A cross-sectional study was planned to approach potential respondents for the study. A self-administered questionnaire was delivered to community pharmacists/pharmacy technicians (N=292) practising in Dhaka, Bangladesh.
The overall response to the survey was 69.5% (n=203). The majority of the sample was comprised of pharmacy technicians (152, 74.9%) who possessed a diploma in pharmacy, followed by pharmacists (37, 18.2%) and others (12, 5.9%). Overall, 72 (35.5%) of the respondents disclosed that they had experienced an ADR at their pharmacy, yet more than half (105, 51.7%) were not familiar with the existence of an ADR reporting body in Bangladesh. Exploring the barriers to the reporting of ADRs, it was revealed that the top four barriers to ADR reporting were ‘I do not know how to report (Relative Importance Index (RII)=0.998)’, ‘reporting forms are not available (0.996)’, ‘I am not motivated to report (0.997)’ and ‘Unavailability of professional environment to discuss about ADR (RII=0.939)’. In addition to these, a majority (141, 69.46%) were not confident about the classification of ADRs (RII=0.889) and were afraid of legal liabilities associated with reporting ADRs (RII=0.806). Moreover, a lack of knowledge about pharmacotherapy and the detection of ADRs was another major factor hindering their reporting (RII=0.731).
The Directorate of Drug Administration in Bangladesh needs to consider the results of this study to help it improve and simplify ADR reporting in Bangladeshi community pharmacy settings.
PMCID: PMC4985923  PMID: 27489151
3.  Computational multiqubit tunnelling in programmable quantum annealers 
Nature Communications  2016;7:10327.
Quantum tunnelling is a phenomenon in which a quantum state traverses energy barriers higher than the energy of the state itself. Quantum tunnelling has been hypothesized as an advantageous physical resource for optimization in quantum annealing. However, computational multiqubit tunnelling has not yet been observed, and a theory of co-tunnelling under high- and low-frequency noises is lacking. Here we show that 8-qubit tunnelling plays a computational role in a currently available programmable quantum annealer. We devise a probe for tunnelling, a computational primitive where classical paths are trapped in a false minimum. In support of the design of quantum annealers we develop a nonperturbative theory of open quantum dynamics under realistic noise characteristics. This theory accurately predicts the rate of many-body dissipative quantum tunnelling subject to the polaron effect. Furthermore, we experimentally demonstrate that quantum tunnelling outperforms thermal hopping along classical paths for problems with up to 200 qubits containing the computational primitive.
Quantum tunnelling may be advantageous for quantum annealing, but multiqubit tunnelling has not yet been observed or characterized theoretically. Here, the authors demonstrate that 8-qubit tunnelling plays a role in a D-Wave Two device through a nonperturbative theory and experimental data.
PMCID: PMC4729842  PMID: 26739797
4.  Caffeine Induces the Stress Response and Up-Regulates Heat Shock Proteins in Caenorhabditis elegans 
Molecules and Cells  2016;39(2):163-168.
Caffeine has both positive and negative effects on physiological functions in a dose-dependent manner. C. elegans has been used as an animal model to investigate the effects of caffeine on development. Caffeine treatment at a high dose (30 mM) showed detrimental effects and caused early larval arrest. We performed a comparative proteomic analysis to investigate the mode of action of high-dose caffeine treatment in C. elegans and found that the stress response proteins, heat shock protein (HSP)-4 (endoplasmic reticulum [ER] chaperone), HSP-6 (mitochondrial chaperone), and HSP-16 (cytosolic chaperone), were induced and their expression was regulated at the transcriptional level. These findings suggest that high-dose caffeine intake causes a strong stress response and activates all three stress-response pathways in the worms, including the ER-, mitochondrial-, and cytosolic pathways. RNA interference of each hsp gene or in triple combination retarded growth. In addition, caffeine treatment stimulated a food-avoidance behavior (aversion phenotype), which was enhanced by RNAi depletion of the hsp-4 gene. Therefore, up-regulation of hsp genes after caffeine treatment appeared to be the major responses to alleviate stress and protect against developmental arrest.
PMCID: PMC4757805  PMID: 26743903
caffeine; C. elegans development; food-avoidance behavior; heat shock protein; proteomic analysis
5.  Reconstruction of post burn scalp alopecia by using expanded hair-bearing scalp flaps 
Pakistan Journal of Medical Sciences  2015;31(6):1405-1410.
Background and Objective:
Tissue expansion is a time-tested and frequently used procedure for utilizing local tissue to replace large defects. We aimed to assess the success & complications of tissue expansion in correction of post burn scalp alopecia.
In this study, 30 patients of scalp burn alopecia of 5 to 35 years age group were treated with tissue expansion of the scalp at Bahawal-Victoria Hospital from January 2013 to December 2014. The area of the scalp loss was within 1/5 to 2/5. Our technique employed an insertion site distal to the area needed to be expanded, attempting to minimize complication like extrusion & wound dehiscence. The patients were followed-up weekly during first month and then fortnightly for next four months.
Our study involved 8 male (26.67%) and 22 female subjects (73.33%) with a mean age of 21years. Flame burn accounted for the mostly 53.3% (n=16) of scalp burns & parieto-temporal region was most commonly affected in 33.4% (n=10) of subjects. Desired aesthetic results were achieved in all the patients without any major complication. Minor complication included mild infection in 8 (26.67%), seroma in 4 (13.33%) & wound dehiscence in 2 (6.67%) patients.
Tissue expansion is a simple, safe, & efficient technique for aesthetic scalp reconstruction. With a simple modification of distal incision and tunneling, we succeeded in minimizing complications. Versatile design of the expanded scalp flap can distribute the expanded hair-bearing scalp properly in the reconstructed recipient site.
PMCID: PMC4744290  PMID: 26870105
Tissue expansion; Scalp reconstruction; Burn
6.  The Gulf Implantable Cardioverter-defibrillator Registry: Rationale, Methodology, and Implementation 
The implantable cardioverter-defibrillator (ICD) is effective in the prevention of sudden cardiac death in high-risk patients. Little is known about ICD use in the Arabian Gulf. We designed a study to describe the characteristics and outcomes of patients receiving ICDs in the Arab Gulf region.
Gulf ICD is a prospective, multi-center, multinational, and observational study. All adult patients 18 years or older, receiving a de novo ICD implant and willing to sign a consent form will be eligible. Data on baseline characteristics, ICD indication, procedure and programing, in-hospital, and 1-year outcomes will be collected. Target enrollment is 1500 patients, which will provide adequate precision across a wide range of expected event rates.
Fifteen centers in six countries are enrolling patients (Saudi Arabia, United Arab Emirates, Kuwait, Oman, Bahrain, and Qatar). Two-thirds of the centers have dedicated electrophysiology laboratories, and in almost all centers ICDs are implanted exclusively by electrophysiologists. Nearly three-quarters of the centers reported annual ICD implant volumes of ≤150 devices, and pulse generator replacements constitute <30% of implants in the majority of centers. Enrollment started in December 2013, and accrual rate increased as more centers entered the study reaching an average of 98 patients per month.
Gulf ICD is the first prospective, observational, multi-center, and multinational study of the characteristics and, the outcomes of patients receiving ICDs in the Arab Gulf region. The study will provide valuable insights into the utilization of and outcomes related to ICD therapy in the Gulf region.
PMCID: PMC4738492  PMID: 26900416
Arabian Gulf; implantable defibrillator; registry
7.  Selectivity, Compatibility, Downstream Functionalization, and Silver Effect in the Gold and Palladium Dual-Catalytic Synthesis of Lactones 
Organometallics  2014;33(19):5448-5456.
The chemo- and regioselectivity and functional group compatibility in gold and palladium cooperatively catalyzed cross-coupling reactions were determined in the synthesis of lactones; the selectivity in the gold and palladium dual-metal catalysis system was distinct from that available for the same class of substrates in systems with only gold catalysis or only palladium catalysis rather than dual catalysis. The dual-catalytic rearrangement reaction selectively promoted oxidative addition at the C–O bond over the C–Br bond, providing a useful C–Br bond handle for downstream functionalization showcased via Suzuki–Miyaura and Sonogashira coupling reactions. Product classes were expanded from isocoumarins to three previously unpublished ring classes: pyrone, indolepyrone, and furopyrone.
PMCID: PMC4195511  PMID: 25328271
8.  Fucosyltransferase 1 mediates angiogenesis in rheumatoid arthritis 
The aim of this study was to determine the role of α(1,2)-linked fucosylation of proteins by fucosyltransferase1 (fut1) in rheumatoid arthritis (RA) angiogenesis.
Analysis of α(1,2)-linked fucosylated proteins in synovial tissues (STs) was performed by immunohistological staining. α(1,2)-linked fucosylated angiogenic chemokine expression in synovial fluids (SFs) was determined by immunoprecipitation and lectin blotting. To determine the angiogenic role of α(1,2)-linked fucosylated proteins in RA, we performed human dermal microvascular endothelial cell (HMVEC) chemotaxis and Matrigel assays using nondepleted and α(1,2)-linked fucosylated protein depleted RA SFs. To examine the production of proangiogenic chemokines by fucosyltransferase 1 (fut1) in HMVECs, cells were transfected with fut1 sense or antisense oligonucleotides, and enzyme-linked immunosorbent assay was performed. We then studied mouse lung endothelial cell (MLEC) chemotaxis using wild type and fut1 gene deficient MLECs.
α(1,2)-linked fucosylated proteins on RA ST endothelial cells (ECs) were highly expressed compared to normal ST. α(1,2)-linked fucosylated monocyte chemoattract protein-1 (MCP-1)/CCL2 was present in RA SFs, and was significantly elevated compared to osteoarthritis SFs. Depletion of α(1,2)-linked fucosylated proteins in RA SFs induced less HMVEC migration and tube formation compared to nondepleted RA SFs. We found that blocking fut1 expression in ECs resulted in decreased MCP-1/CCL2 and regulated upon activation and normal T cell expressed and secreted (RANTES)/CCL5 production. Finally, we showed that fut1 regulates EC migration in response to vascular endothelial cell growth factor.
α(1,2)-linked fucosylation by fut1 may be an important new target for angiogenic diseases like RA.
PMCID: PMC4426876  PMID: 24692243
α(1,2)-linked fucosylation; Fucosyltransferase 1; Rheumatoid Arthritis; Endothelial Cells; Angiogenesis
9.  Antinociceptive principle from Curcuma aeruginosa 
The rhizome of Curcuma aeruginosa Roxb (Zingiberaceae) has been used as a traditional folk medicine for the treatment of rheumatic disorders in Bangladesh. The aim of the current study was the bioassay-guided isolation and purification of an antinociceptive principle from the methanol extract of C. aeruginosa rhizomes.
The antinociceptive activity was determined using acetic acid induced writhing and formalin induced licking in the Swiss albino mice to investigate central and peripheral antinociceptive principle of C. aeruginosa rhizomes. Vacuum Liquid Chromatography (VLC) and open column chromatography were used for separation. Crystallization was used for the purification of the isolated compound germacrone (1). Diclofenac (10 mg/kg) and aspirin (100 mg/kg) were used as positive control and 5 % carboxymethyl cellulose (CMC) in distilled water (10 ml/kg) for negative control were used in the acetic acid induced writhing and formalin induced licking methods.
The methanol extract exhibited 37.50 and 45.31 % inhibition of writhing; 33.27 and 38.13 % inhibition of licking in the first phase and 69.72, 73.71 % inhibition of licking in the second phase at doses of 200 and 400 mg/kg, respectively. VLC of the extract yielded five fractions (Fr. 1 to Fr. 5). Fr. 1 exhibited 33.98 % inhibition that was comparably higher than other fractions (Fr. 2 to Fr. 5) at a dose of 100 mg/kg. Column chromatography of Fr. 1 generated five fractions (SF. 1 to SF. 5). Fraction SF.3 exhibited 46.88 % inhibition that was most potent among the other fractions at a dose of 50 mg/kg. Crystallization of the fraction SF.3 yielded germacrone (1), a cyclic sesquiterpene. Germacrone (1) showed 22.66, 34.77 and 51.17 % inhibition of writhing at doses of 10, 20 and 40 mg/kg, respectively; 30.43 and 37.53 % inhibition in the initial phase and 32.27 and 60.96 % inhibition in the second phase of licking at doses of 200 and 400 mg/kg, respectively.
Germacrone (1) showed a potent activity in both writhing and licking methods that indicates the compound as a central and peripheral antinociceptive principle of C. aeruginosa rhizomes with possible anti-inflammatory activity.
PMCID: PMC4474446  PMID: 26092132
Zingiberaceae; Antinociceptive activity; Germacrone (1); Cyclic sesquiterpene; Acetic acid; Formalin
10.  A novel role for inducible Fut2 in angiogenesis 
Angiogenesis  2012;16(1):195-205.
Angiogenesis plays an important role in wound healing and tumor growth. Fucosyltransferases synthesize fucosylated glycans and may play a major role in vascular biology.
To examine the role of an alpha(1,2) fucosyltransferase (Fut2) in angiogenesis.
Methods and results
We found that Fut2 mRNA and protein expression is inducible in human dermal micro-vascular endothelial cells (HMVECs). After finding that Fut2 is inducible in HMVECs, we examined if Fut2 contributes to angiogenesis. We found that Fut2 null endothelial cell (EC) migration and tube formation were significantly less compared to wild type (wt) ECs. Angio-genesis was impaired in Fut2 null compared to wt mice in the mouse Matrigel plug and the sponge granuloma angiogenesis assays. To assess the characteristics of Fut2 null ECs in vivo, we performed Matrigel plug angiogenesis assays in wt mice using Fut2 null and wt mouse ECs. We found a significant decrease in Fut2 null EC incorporation in neoangiogenesis compared to wt ECs. ERK1/2 activation, fibroblast growth factor receptor2, and vascular endothelial growth factor expression were less in Fut2 null ECs, suggesting a possible mechanism of impaired angio-genesis when Fut2 is lacking.
These data suggest a novel role for Fut2 as a regulator of angiogenesis.
PMCID: PMC4441274  PMID: 23065099
Angiogenesis; Fut2; Endothelial cells; VEGF; bFGF; ERK1/2 phosphorylation
11.  Association of geographical distribution of air quality index and type 2 diabetes mellitus in Isfahan, Iran 
Air pollution is a hazardous environmental problem with several adverse health effects including its impact on the development of chronic diseases as diabetes mellitus. This study aimed to investigate the association of geographical distribution of air quality index (AQI) and type 2 diabetes mellitus in an air-polluted city by using geographic information system (GIS).
This cross-sectional study was conducted in Isfahan, Iran. The records that have been registered from 2009 to 2012 in major referral public diabetes clinics were gathered; they included data of 1467 diabetic patients. Their living area was represented with spots in the city map. AQI data were also interpolated from monitoring stations spreading around the city. The GIS maps of air pollutants and diabetes were developed and the associations were determined.
The density of diabetic population was higher in highly polluted areas compared with areas with the lower levels of air pollution. No significant correlation was documented between the distribution of diabetic patients and air pollution level throughout the city.
Although the density of diabetic patients was higher in areas with higher air pollution, but the lack of association between AQI and the prevalence of diabetes might be because the air of different parts of the city was highly polluted, and we could not compare the prevalence of diabetes in areas with clean and polluted air.
PMCID: PMC4476344  PMID: 26101493
Air pollution; Diabetes mellitus; Geographic distribution
12.  The Relationship between Perchlorate in Drinking Water and Cord Blood Thyroid Hormones: First Experience from Iran 
Considering the controversial information regarding the effects of perchlorate on thyroid function of high risk population as neonates, and given the high prevalence rate of thyroid disorders specially congenital hypothyroidism in our region, this study aims to investigate for the first time in Iran, the relationship between drinking groundwater perchlorate and cord blood thyroid hormones level in an industrial region.
In this cross-sectional study, drinking groundwater perchlorate level of rural areas of Zarinshahr, Isfahan was measured. Simultaneously, cord blood level of thyroid hormones of neonates born in the studied region was measured. Thyroid function test of neonates in regions with low and high perchlorate level were compared.
In this study, 25 tap water samples were obtained for perchlorate measurement. Level of cord blood thyroid stimulating hormone (TSH), T4 and T3 of 25 neonates were measured. Mean (standard deviation) of perchlorate, TSH, T4 and T3 was 3.59 (5.10) μg/l, 7.81 (4.14) mIU/m, 6.06 (0.85) mg/dl, and 63.46 (17.53) mg/dl, respectively. Mean levels of thyroid function tests were not different in low (<5 μg/l) and high level of drinking ground water perchlorate (P > 0.05).
Perchlorate did not appear to be related to thyroid function of neonates in the studied industrial region. It seems that iodine status of the regions, as well as other environmental contaminants and genetic background, could impact on its relation with thyroid function of neonates.
PMCID: PMC4362289  PMID: 25789149
Environment; infant; perchlorate; thyroid gland
13.  Mechanistic Studies of Gold and Palladium Cooperative Dual-Catalytic Cross-Coupling Systems 
ACS catalysis  2014;4(2):622-629.
Double-label crossover, modified-substrate, and catalyst comparison experiments in the gold and palladium dual-catalytic rearrangement/cross-coupling of allenoates were performed in order to probe the mechanism of this reaction. The results are consistent with a cooperative catalysis mechanism whereby 1) gold activates the substrate prior to oxidative addition by palladium, 2) gold acts as a carbophilic rather than oxophilic Lewis acid, 3) competing olefin isomerization is avoided, 4) gold participates beyond the first turnover and therefore does not serve simply to generate the active palladium catalyst, and 5) single-electron transfer is not involved. These experiments further demonstrate that the cooperativity of both gold and palladium in the reaction is essential because significantly lower to zero conversion is achieved with either metal alone in comparison studies that examined multiple potential gold, palladium, and silver catalysts and precatalysts. Notably, employment of the optimized cocatalysts, PPh3AuOTf and Pd2dba3, separately (i.e., only Au or only Pd) results in zero conversion to product at all monitored time points compared to quantitative conversion to product when both are present in cocatalytic reactions.
PMCID: PMC3991925  PMID: 24757581
Gold and Palladium; Cooperative catalysis; Dual catalysis; Cross-coupling; Crossover; Mechanism; Intermediates
14.  Performance evaluation of a scoria-compost biofilter treating xylene vapors 
The removal of xylene vapors was studied in a biofilter packed with a new hybrid (scoria/compost) packing material at various inlet loads (IL) and empty bed residence times (EBRT) of 90, 60, and 40s. The best performance was observed for EBRT of 90s, where a removal efficiency of 98% was obtained under steady state condition for inlet xylene concentration of 1.34 g m−3, while a maximum elimination capacity of 97.5 g m−3 h−1 was observed for IL of 199.5 g m−3 h−1. Carbon dioxide production rates and the microbial counts for xylene-degraders followed xylene elimination capacities. Overall look to the results of this study indicates that the scoria/compost mixture could be considered as a potential biofilter carrier, with low pressure drop (here <4 mm H2O), to treat air streams containing VOCs.
PMCID: PMC4276096  PMID: 25587393
Xylene; Biofilter; Scoria; Compost; Elimination capacity
15.  First report on the association of drinking water hardness and endothelial function in children and adolescents 
Archives of Medical Science : AMS  2014;10(4):746-751.
This study aims to investigate the relationship of water hardness and its calcium and magnesium content with endothelial function in a population-based sample of healthy children and adolescents.
Material and methods
This case-control study was conducted in 2012 among 90 individuals living in two areas with moderate and high water hardness in Isfahan County, Iran. The flow-mediated dilatation (FMD) of the brachial artery and the serum levels of soluble adhesion molecules (sICAM-1, sVCAM-1) were measured as surrogate markers of endothelial function, and high-sensitivity C-reactive protein (hs-CRP), as a marker of inflammation.
Data of 89 participants (51% boys, mean age 14.75 (2.9) years) were complete. Those participants living in the area with high water hardness had higher FMD, hs-CRP, and soluble adhesion molecules (sICAM-1, sVCAM-1) than their counterparts living in the area with moderate water hardness. Multiple linear regression analysis showed that after adjustment for confounding factors of age, gender, body mass index, healthy eating index and physical activity level, total water hardness, as well as water content of calcium and magnesium, had a significant positive relationship with FMD. The corresponding associations were inverse and significant with soluble adhesion molecules (p < 0.05).
This study, which to the best of our knowledge is the first of its kind in the pediatric age group, suggests that water hardness, as well as its calcium and magnesium content, may have a protective role against early stages of atherosclerosis in children and adolescents.
PMCID: PMC4175776  PMID: 25276160
water hardness; endothelial function; calcium; magnesium; children and adolescents
16.  An in silico approach to design potential siRNA molecules for ICP22 (US1) gene silencing of different strains of human herpes simplex 1 
The herpes simplex virus (HSV-1) is a virus that manifests itself in viral infection with painful, watery blisters in the skin or on the genitals as well as mucous membrane such as the mouth or lips. During an outbreak, the disease is contagious particularly and is irredeemable with present technology. Genetic studies of HSV-1 have shown that ICP22 (US1) gene is an immediate early gene and is responsible for genome replication and also has contribution in viral infection.
For disease diagnosis, ICP22 (US1) gene may be suitable target. Viral activity can be controlled through RNA interference technology, a significant method for the post-transcriptional gene silencing. However, in different viral isolates there is a genetic variability; it is very challenging to design possible siRNA molecules which can silence the respective target genes. The work was done by using various computational tools as similarity search, target alignment, secondary structure prediction and RNA interaction evaluation.
In our study two effective siRNA molecules for ICP22 (US1) gene silencing of seven different strains of HSV-1 were rationally designed and authenticated using computational methods, which might lead to knockdown the viral activity.
siRNA molecules were foreseen against ICP22 (US1) gene of different strains of HSV-1 as effective aspirant using computational methods. Thus, the approach may deliver a vision for the chemical synthesis of antiviral RNA molecule for treatment of HSV-1, at genomic level.
PMCID: PMC3758079  PMID: 24023453
HSV-1; Antiviral; ICP22 (US1) gene; RNAi; siRNA
17.  Does Water Hardness Have Preventive Effect on Cardiovascular Disease? 
The aim of this study is to investigate the association of calcium and magnesium concentration of drinking water with cardiovascular disease (CVDs) in urban and rural areas of a city in Iran.
This case-control study was conducted in 2012 in Khansar County in Isfahan province, Iran. We used the official data of the Provincial health center regarding the chemical analysis data of urban and rural areas including the hardness, calcium and magnesium content of drinking water. Data of patients hospitalized for CVD in the only specialty hospital of the city was gathered for the years of 2010 and 2011.
In 2010, water calcium content above 72 mg/L was associated with reduced number of CVDs in 1000 population; whereas in 2011 this decrease in CVDs was observed for calcium levels of more than 75 mg/L. In 2010, the level of water Mg content ranged from 23 to 57 mg/L. By increasing Mg hardness level above 31 mg/L in 2010 and above 26 mg/L in 2011 were associated with decreased number of CVDs in 1000 people. decrease.
Our study suggests favorable protective effects of water hardness, mainly water magnesium content, on CVDs. Water hardness, as well as calcium and magnesium content of drinking water may have a protective role against CVDs. Further experimental studies are necessary to determine the underlying mechanisms and longitudinal studies are required to study the clinical impacts of the current findings.
PMCID: PMC3950737  PMID: 24627741
Calcium; cardiovascular disease; Iran; magnesium; water hardness
18.  Fucosyltransferase 1 mediates angiogenesis, cell adhesion and rheumatoid arthritis synovial tissue fibroblast proliferation 
We previously reported that sialyl Lewisy, synthesized by fucosyltransferases, is involved in angiogenesis. Fucosyltransferase 1 (fut1) is an α(1,2)-fucosyltransferase responsible for synthesis of the H blood group and Lewisy antigens. However, the angiogenic involvement of fut 1 in the pathogenesis of rheumatoid arthritis synovial tissue (RA ST) has not been clearly defined.
Assay of α(1,2)-linked fucosylated proteins in RA was performed by enzyme-linked lectin assay. Fut1 expression was determined in RA ST samples by immunohistological staining. We performed angiogenic Matrigel assays using a co-culture system of human dermal microvascular endothelial cells (HMVECs) and fut1 small interfering RNA (siRNA) transfected RA synovial fibroblasts. To determine if fut1 played a role in leukocyte retention and cell proliferation in the RA synovium, myeloid THP-1 cell adhesion assays and fut1 siRNA transfected RA synovial fibroblast proliferation assays were performed.
Total α(1,2)-linked fucosylated proteins in RA ST were significantly higher compared to normal (NL) ST. Fut1 expression on RA ST lining cells positively correlated with ST inflammation. HMVECs from a co-culture system with fut1 siRNA transfected RA synovial fibroblasts exhibited decreased endothelial cell tube formation compared to control siRNA transfected RA synovial fibroblasts. Fut1 siRNA also inhibited myeloid THP-1 adhesion to RA synovial fibroblasts and RA synovial fibroblast proliferation.
These data show that α(1,2)-linked fucosylated proteins are upregulated in RA ST compared to NL ST. We also show that fut1 in RA synovial fibroblasts is important in angiogenesis, leukocyte-synovial fibroblast adhesion, and synovial fibroblast proliferation, all key processes in the pathogenesis of RA.
PMCID: PMC3978694  PMID: 24467809
19.  Toluene Removal from Sandy Soils via In Situ Technologies with an Emphasis on Factors Influencing Soil Vapor Extraction 
The Scientific World Journal  2014;2014:416752.
The integration of bioventing (BV) and soil vapor extraction (SVE) appears to be an effective combination method for soil decontamination. This paper serves two main purposes: it evaluates the effects of soil water content (SWC) and air flow rate on SVE and it investigates the transition regime between BV and SVE for toluene removal from sandy soils. 96 hours after air injection, more than 97% removal efficiency was achieved in all five experiments (carried out for SVE) including 5, 10, and 15% for SWC and 250 and 500 mL/min for air flow rate on SVE. The highest removal efficiency (>99.5%) of toluene was obtained by the combination of BV and SVE (AIBV: Air Injection Bioventing) after 96 h of air injection at a constant flow rate of 250 mL/min. It was found that AIBV has the highest efficiency for toluene removal from sandy soils and can remediate the vadose zone effectively to meet the soil guideline values for protection of groundwater.
PMCID: PMC3920725  PMID: 24587723
20.  In Silico Molecular Characterization of Cysteine Protease YopT from Yersinia pestis by Homology Modeling and Binding Site Identification 
Drug Target Insights  2014;8:1-9.
Plague is a major health concern and Yersinia pestis plays the central causal role in this disease. Yersinia pestis has developed resistance against the commonly available drugs. So, it is now a key concern to find a new drug target. Cysteine protease YopT enzyme is an important factor used by Yersinia pestis for pathogenesis in its host and it has the anti-phagocytic function of removal of C-termini lipid modification. The 3D structure of cysteine protease YopT of Yersinia pestis was determined by means of homology modeling through multiple alignments followed by intensive optimization and validation. The modeling was done by Phyre 2 and refined by ModRefiner. The obtained model was verified with structure validation programs such as PROCHECK, verify 3D and ERRAT for reliability. Interacting partners and active sites were also determined. PROCHECK analysis showed that 93% of the residues are in the most favored region, 5.9% are in the additional allowed region and 1.1% are in the generously allowed region of the Ramachandran plot. The verify 3D value of 0.78 indicates that the environmental profile of the model is good. SOPMA is employed for calculation of the secondary structural features of cysteine protease YopT. Active site determination through CASTp proposes that this protein can be utilized as a potential drug target. However, these findings should further be confirmed by wet lab studies for a targeted therapeutic agent design against Yersinia pestis.
PMCID: PMC3921076  PMID: 24526834
plague; Yersinia pestis; homology modeling; active site; potential drug
21.  Comparative assessment on in vitro antioxidant activities of ethanol extracts of Averrhoa bilimbi, Gymnema sylvestre and Capsicum frutescens 
Pharmacognosy Research  2014;6(1):36-41.
Averrhoa bilimbi, Gymnema sylvestre and Capsicum frutescens are medicinal plants commonly used as traditional medicine for the treatment of various diseases. The present study was designed to investigate the antioxidant activities of Ethanolic extract of A. bilimbi, G. sylvestre and C. frutescens.
Materials and Methods:
The antioxidant activity of the extracts were evaluated using total phenolic and flavonoid contents, ferric reducing power and the free radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH).
Total phenolic and flavonoid contents were higher in G. sylvestre (53.63636 ± 0.454545 mg/g gallic acid equivalent) and C. frutescens (26.66667 ± 2.081666 mg/g quercetin equivalent) respectively. Reducing power of the crude ethanol extracts increased with the concentrations of the extracts and all the extracts showed moderate free radical scavenging activity against DPPH. The plant extract displayed moderate phenolic and flavonoid contents compared to gallic acid and quercetin equivalent respectively, whereas also exhibited significant scavenging of DPPH radical and reducing power compared with ascorbic acid as standard.
Our study suggests that G. sylvestre has significant antioxidant activity. The antioxidant compound of this plant might be a therapeutic candidate against oxidative stress related diseases. Different sub-fraction of A. bilimbi and C. frutescens should be studied further to assess the effect. Further study is necessary for isolation and characterization of the active antioxidant agents for better treatment.
PMCID: PMC3897006  PMID: 24497740
Antioxidant; G. sylvestre; ethanolic extract; free radical; oxidative stress
23.  Factors Associated with the Outcome of Open Tibial Fractures 
Although open tibial fractures are common in Malaysia, the outcomes for these patients have not been evaluated in the literature. This retrospective study was conducted to examine the factors associated with infection and non-union in open tibial fractures managed at Hospital Tengku Ampuan Afzan (HTAA), Kuantan, in 2009.
From 1 January until 31 December 2009, the Department of Orthopaedics of HTAA managed 58 patients with open tibial fracture who had a minimum of a one year follow-up period. The median age was 24.5 years (range: 4 to 72 years). The open tibial fractures were graded using the Gustilo open fracture classification as follows: 4 grade I, 21 grade II, 24 grade IIIA and 9 grade IIIB. All open fractures were subjected to a standard treatment protocol at HTAA, which includes the use of prophylactic antibiotics, emergency debridement, fracture stabilisation, wound coverage, and bone reconstruction when required. The mean time from injury to the initial debridement was 29.7 hours (range: 13 to 216 hours).
Seventeen (29%) cases were complicated by infection, and 10 patients (17%) developed non-union. The grade of the open fracture was significantly associated with infection, and age and the time interval between the injury and the initial wound debridement were significantly associated with non-union.
The high rates of infection and non-union, particularly in severe open fractures, indicate that there is a need to improve the management of open tibial fractures treated at HTAA. The time to initial debridement is an important factor that can be readily amended to improve the outcome. Further studies with larger sample sizes are likely needed to replicate and confirm our findings.
PMCID: PMC3957352  PMID: 24643115
assessment; case management; fractures; open; patient outcome; tibia
24.  Characterization of phytoconstituents and evaluation of total phenolic content, anthelmintic, and antimicrobial activities of Solanum violaceum Ortega  
Objective: The present study was conducted to detect possible chemicals (phytoconstituents), prove ethno-medicinal value of the plant, and investigate antimicrobial, anthelmintic, and total phenolic content of crude methanolic extract of the Solanum violaceum plant.
Materials and Methods: Phytochemical screening was carried out using different chemical group test methods. In anthelmintic activity test (using Pheretima posthuma model), five concentrations (10, 20, 30, 40, 50, and 80 mg/ml in distilled water) of extracts and albendazole as standard were used which involved the vermifuge and vermicidal activity on the worms. For the evaluation of in vitro antimicrobial activity, disc diffusion method, and to determine the total phenolic content, Folin-Ceocalteu method (gallic acid as standard) were used.
Results: The phytoconstituent analysis revealed presence of alkaloids, carbohydrate, glycoside, flavonoid, saponin, gum, diterpenes, phenol, protein, and tannin. The crude extract exhibited significant anthelmintic property comparing with the standard. The methanolic extract revealed broad-spectrum antimicrobial activity at the concentration of 400 µg/disc. The results were compared with that of the standard ciprofloxacin. The extract exhibited moderate amount of total phenolic compound (54.67±1.18 mg/gm of gallic acid equivalent).
Conclusion: Since S. violaceum have shown antimicrobial, antioxidant, and anthelmintic activities, more studies such as anti-inflammatory, analgesic, antipyretic, and other pharmacological activities should be carried out to justify its traditional use, as the plant is available and used broadly in the rural areas for folkloric remedies.
PMCID: PMC4075727  PMID: 25050288
Broad-spectrum; Phytoconstituents; Solanum violaceum; Total phenolic content; Vermicidal activity
25.  In vitro antioxidant, cytotoxic, thrombolytic activities and phytochemical evaluation of methanol extract of the A. philippense L. leaves 
To study the leaves of Adiantum philippense L. for their antioxidant, cytotoxicity and thrombolytic activities and to perform phytochemical evaluation.
In-vitro antioxidant activity of extract was studied using DPPH radical scavenging, reducing power, total phenol and total flavonoid content determination assays. The cytotoxic activity was determined using brine shrimp lethality bioassay, thrombolytic activity by clot disruption and phytochemical potential by qualitative analysis.
The antioxidant activity of the extracts was found promising. The reducing power of this crude extract increase with the increase of concentration; IC50 values of DPPH scavenging activity was (140.00±0.86) µg/mL as compared to ascorbic acid [IC50 (130.00±0.76) µg/mL]; Total phenol and total flavonoids content were (148.26±0.24) mg/mL and (163.06±0.56) mg/mL respectively. In cytotoxicity assay the LC50 values of the sample was (106.41±0.78) µg/mL where as for standard vincristin sulphate was (08.50±0.24) µg/mL as a positive control and the extract shows (12.86±1.02)% clot lytic whereas standard streptokinase shows (30.86±0.44% clot lytic activity in thrombolytic assay. The phytochemical evaluation indicates the presence of chemical constituents including carbohydrates, alkaloids, saponins, glycosides, flavonoids.
This study shows that the methanol extract of leaves of Adiantum philippense L. has bioactivity but further compound isolation is necessary to confirm the activities of individual compounds.
PMCID: PMC3644574  PMID: 23730559
Adiantum philippense L.; Antioxidant; Cytotoxicity; Phytochemical evaluation

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