Abstract: The concept of myocardial injury, although first recognized from animal studies, is now recognized as a clinical phenomenon that may result in microvascular damage, no-reflow phenomenon, myocardial stunning, myocardial hibernation and ischemic preconditioning. The final consequence of this event is left ventricular (LV) systolic dysfunction leading to increased morbidity and mortality. The typical clinical case of reperfusion injury occurs in acute myocardial infarction (MI) with ST segment elevation in which an occlusion of a major epicardial coronary artery is followed by recanalization of the artery. This may occur spontaneously or by means of thrombolysis and/or by primary percutaneous coronary intervention (PCI) with efficient platelet inhibition by aspirin (acetylsalicylic acid), clopidogrel and glycoprotein IIb/IIIa inhibitors. In recent years, percutaneous coronary intervention (PCI) has become a well-established technique for the treatment of coronary artery disease. PCI improves symptoms in patients with coronary artery disease and it has been increasing safety of procedures. However, peri- and post-procedural myocardial injury, including angiographical slow coronary flow, microvascular embolization, and elevated levels of cardiac enzyme, such as creatine kinase and troponin-T and -I, has also been reported even in elective cases. Furthermore, myocardial reperfusion injury at the beginning of myocardial reperfusion, which causes tissue damage and cardiac dysfunction, may occur in cases of acute coronary syndrome. Because patients with myocardial injury is related to larger myocardial infarction and have a worse long-term prognosis than those without myocardial injury, it is important to prevent myocardial injury during and/or after PCI in patients with coronary artery disease. To date, many studies have demonstrated that adjunctive pharmacological treatment suppresses myocardial injury and increases coronary blood flow during PCI procedures. In this review, we highlight the usefulness of pharmacological treatment in combination with PCI in attenuating myocardial injury in patients with coronary artery disease.
Abstract: A major goal in animal genetics is to understand the role of common genetic variants in diseases susceptibility and production traits. Sahiwal cattle can be considered as a global animal genetic resource due to its relatively high milk producing ability, resistance against tropical diseases and heat tolerant. CYP11B1 gene provides instructions for making a mitochondrial enzyme called steroid 11-beta-hydroxylase. It catalyzes the 11deoxy-cortisol to cortisol and 11deoxycorticosterone to corticosterone in cattle. The bovine CYP11B1 gene is positioned on BTA14q12 comprises of eight introns and nine exons and protein is associated with mitochondrial epithelium. The present study was aimed to identify the single-nucleotide polymorphisms in CYP11B1 gene in Sahiwal cattle breed of Pakistan. Four polymorphic sites were identified in exon one of CYP11B1 gene through sequencing approach. Significant finding was the incidence of the C→T polymorphism in 5'-UTR, causing amino acid substitution from alanine to valine (A30V) in Sahiwal cattle breed. That Ala/Val polymorphism may serve as a powerful genetic tool for the development of DNA markers that can be used for the particular traits for different local cattle breeds.
Abstract: Heme oxygenase-1 (HO-1), an enzyme degrading heme to carbon monoxide, iron, and biliverdin, has been recognized as playing a crucial role in cellular defense against stressful conditions, not only related to heme release. In the present study, the effects of TNF-a on the expression of heme oxygenase-1 (HO-1) in human aortic endothelial cells (HAECs) as well as the related mechanisms were investigated. 10 ng/mL TNF-α treatment significantly increased HO-1 expression after 6h, then a further increase at 12h and declined at 24h. Treatment with 2 ng/mL of TNF-a after 12 h resulted in a significant increase in HO-1 expression, which peaked at 10 ng/mL, then declined at 20 ng/mL. TNF-α induced HO-1 expression and then HO-1 expression reduced vascular cell adhesion molecule-1 (VCAM-1) expression. Phosphorylation studies of ERK1/2, JNK, and p38, three subgroups of mitogen-activated protein kinases (MAPKs) demonstrated TNF-α-induced ERK1/2, JNK, and p38 phosphorylation. The increase in HO-1 expression in response to TNF-α treatment was affected by pretreatment with SP600125 (a JNK inhibitor) and SB203580 (a p38 inhibitor), not with PD98059 (an ERK1/2 inhibitor). The expression of HO-1 was stronger in aortas of TNF-α-treated apo-E deficient mice when compared with control mice. These results suggest that low dose of TNF-α treatment notably induced HO-1 expression was mediated through JNK/p38 phosphorylation and may have a protective potential in cardiovascular diseases and inflammatory response through the regulation of HO-1 expression.
Abstract: Currently, mathematical and computer modeling are widely used in different biological studies to predict or assess behavior of such a complex systems as a biological are. This study deals with mathematical and computer modeling of bi-substrate enzymatic reactions, which play an important role in different biochemical pathways. The main objective of this study is to represent the results from in silico investigation of bi-substrate enzymatic reactions in the presence of uncompetitive inhibitors, as well as to describe in details the inhibition effects. Four models of uncompetitive inhibition were designed using different software packages. Particularly, uncompetitive inhibitor to the first [ES1] and the second ([ES1S2]; [FS2]) enzyme-substrate complexes have been studied. The simulation, using the same kinetic parameters for all models allowed investigating the behavior of reactions as well as determined some interesting aspects concerning influence of different cases of uncompetitive inhibition. Besides, it has been shown that uncompetitive inhibitors exhibit specific selectivity depending on mechanism of bi-substrate enzymatic reaction.
Abstract: Vetiver oil is secondary metabolite that accumulates in Vetiveria zizanioides roots. The aim of this study was to obtain best type of root culture which produce high amount of vetiver oil, and was similar to metabolites produce from its mother plant. Protein analysis was also conducted to detect protein, related to putative enzymes, which have a role in terpenoids synthesis in the root culture. The results showed that root culture derived from crown explant produced the best root growth. The root culture produced primary and lateral roots, ca. 40 branches. The vetiver oil produced from root culture was analyzed by using GC-MS., and the highest content of terpenoids from roots of crown explant attained 19.024%. The result of SDS PAGE showed proteins which were ±61 kD and ± 68 kD, each might be related to putative monoterpene synthase and sesquiterpenes complex, respectively.
Abstract: This study was conducted to evaluate the anti-diabetic
properties of ethanolic extract of two plants commonly used in folk
medicine, Mormodica charantia (bitter melon) and Trigonella
foenum-graecum (fenugreek). The study was performed on STZinduced
diabetic rats (DM type-I). Plant extracts of these two plants
were given to STZ diabetic rats at the concentration of 500 mg/kg
body weight ,50 mg/kg body weight respectively. Cidophage®
(metformin HCl) were administered to another group to support the
results at a dose of 500 mg/kg body weight, the ethanolic extracts and
Cidophage administered orally once a day for four weeks using a
stomach tube and; serum samples were obtained for biochemical
analysis. The extracts caused significant decreases in glucose levels
compared with diabetic control rats. Insulin secretions were increased
after 4 weeks of treatment with Cidophage® compared with the
control non-diabetic rats. Levels of AST and ALT liver enzymes were
normalized by all treatments. Decreases in liver cholesterol,
triglycerides, and LDL in diabetic rats were observed with all
treatments. HDL levels were increased by the treatments in the
following order: bitter melon, Cidophage®, and fenugreek. Creatinine
levels were reduced by all treatments. Serum nitric oxide and
malonaldehyde levels were reduced by all extracts. GSH levels were
increased by all extracts. Extravasation as measured by the Evans
Blue test increased significantly in STZ-induced diabetic animals.
This effect was reversed by ethanolic extracts of bitter melon or
fenugreek.
Abstract: Hepatitis B and hepatitis C are among the most
significant hepatic infections all around the world that may lead to
hepatocellular carcinoma. This study is first time performed at the
blood transfussion centre of Omar hospital, Lahore. It aims to
determine the sero-prevalence of these diseases by screening the
apparently healthy blood donors who might be the carriers of HBV or
HCV and pose a high risk in the transmission. It also aims the
comparison between the sensitivity of two diagnostic tests;
chromatographic immunoassay – one step test device and Enzyme
Linked Immuno Sorbant Assay (ELISA). Blood serum of 855
apparently healthy blood donors was screened for Hepatitis B surface
antigen (HBsAg) and for anti HCV antibodies. SPSS version 12.0
and X2 (Chi-square) test were used for statistical analysis. The seroprevalence
of HCV was 8.07% by the device method and by ELISA
9.12% and that of HBV was 5.6% by the device and 6.43% by
ELISA. The unavailability of vaccination against HCV makes it more
prevalent. Comparing the two diagnostic methods, ELISA proved to
be more sensitive.
Abstract: The activities of alkaline phosphatase and Ca2+ATPase in mud crab (Scylla serrata) collected from a soft-shell crab farm in Chantaburi Province, Thailand, in several stages of molting cycle were observed. The results showed that the activity of alkaline phosphatase in gill after molting was highly significant (p
Abstract: Enzymatic hydrolysis is one of the major steps involved in the conversion from sugarcane bagasse to yield ethanol. This process offers potential for yields and selectivity higher, lower energy costs and milder operating conditions than chemical processes. However, the presence of some factors such as lignin content, crystallinity degree of the cellulose, and particle sizes, limits the digestibility of the cellulose present in the lignocellulosic biomasses. Pretreatment aims to improve the access of the enzyme to the substrate. In this study sugarcane bagasse was submitted chemical pretreatment that consisted of two consecutive steps, the first with dilute sulfuric acid (1 % (v/v) H2SO4), and the second with alkaline solutions with different concentrations of NaOH (1, 2, 3 and 4 % (w/v)). Thermal Analysis (TG/ DTG and DTA) was used to evaluate hemicellulose, cellulose and lignin contents in the samples. Scanning Electron Microscopy (SEM) was used to evaluate the morphological structures of the in natura and chemically treated samples. Results showed that pretreatments were effective in chemical degradation of lignocellulosic materials of the samples, and also was possible to observe the morphological changes occurring in the biomasses after pretreatments.
Abstract: L-asparaginase was extracted from pathogenic
Escherichia coli which was isolated from urinary tract infection
patients. L-asparaginase was purified 96-fold by ultrafiltration, ion
exchange and gel filtration giving 39.19% yield with final specific
activity of 178.57 IU/mg. L-asparaginase showed 138,356±1,000
Dalton molecular weight with 31024±100 Dalton molecular mass.
Kinetic properties of enzyme resulting 1.25×10-5 mM Km and
2.5×10-3 M/min Vmax. L-asparaginase showed a maximum activity
at pH 7.5 when incubated at 37 ºC for 30 min and illustrated its full
activity (100%) after 15 min incubation at 20-37 ºC, while 70% of its
activity was lost when incubated at 60 ºC. L-asparaginase showed
cytotoxicity to U937 cell line with IC50 0.5±0.19 IU/ml, and
selectivity index (SI=7.6) about 8 time higher selectivity over the
lymphocyte cells. Therefore, the local pathogenic E. coli strains may
be used as a source of high yield of L-asparaginase to produce anti
cancer agent with high selectivity.
Abstract: Nano fibers produced by electrospinning are of industrial and scientific attention due to their special characteristics such as long length, small diameter and high surface area. Applications of electrospun structures in nanotechnology are included tissue scaffolds, fibers for drug delivery, composite reinforcement, chemical sensing, enzyme immobilization, membrane-based filtration, protective clothing, catalysis, solar cells, electronic devices and others. Many polymer and ceramic precursor nano fibers have been successfully electrospun with diameters in the range from 1 nm to several microns. The process is complex so that fiber diameter is influenced by various material, design and operating parameters. The objective of this work is to apply genetic algorithm on the parameters of electrospinning which have the most significant effect on the nano fiber diameter to determine the optimum parameter values before doing experimental set up. Effective factors including initial polymer concentration, initial jet radius, electrical potential, relaxation time, initial elongation, viscosity and distance between nozzle and collector are considered to determine finest diameter which is selected by user.
Abstract: This research was undertaken to study enzymatic activity in the shoots, roots, and rhizosphere of alfalfa (Medicago sativa L.) grown in quartz sand that was uncontaminated and
contaminated with phenanthrene at concentrations of 10 and 100 mg kg-1. The higher concentration of phehanthrene had a distinct
phytotoxic effect on alfalfa, inhibiting seed germination energy, plant survival, and biomass accumulation. The plant stress response to the
environmental pollution was an increase in peroxidase activity. Peroxidases were the predominant enzymes in the alfalfa shoots and
roots. The peroxidase profile in the shoots differed from that in the roots and had different isoenzyme numbers. 2,2'-Azinobis-(3-ethylbenzo-thiazoline-6-sulphonate) (ABTS) peroxidase was
predominant in the shoots, and 2,7-diaminofluorene (2,2-DAF)
peroxidase was predominant in the roots. Under the influence of
phenanthrene, the activity of 2,7-DAF peroxidase increased in the
shoots, and the activity of ABTS peroxidase increased in the roots.
Alfalfa root peroxidases were the prevalent enzyme systems in the
rhizosphere sand. Examination of the activity of alfalfa root
peroxidase toward phenanthrene revealed the possibility of
involvement of the plant enzyme in rhizosphere degradation of the
PAH.
Abstract: Studies were carried out on the comparative study of the production of Avicelase enzyme using sugarcane bagasse-SCB in two different statuses (i.e. treated and untreated SCB) by thermophilic Geobacillus stearothermophilus at 50ºC. Only four thermophilic bacterial isolates were isolated and assayed for Avicelase production using UntSCB and TSCB. Only one isolate selected as most potent and identified as G. stearothermophilus used in this study. A specific endo-β-1,4-D-glucanase (Avicelase EC 3.2.1.91) was partially purified from a thermophilic bacterial strain was isolated from different soil samples when grown on cellulose enrichment SCB substrate as the sole carbon source. Results shown that G. stearothermophilus was the better Avicelase producer strain. Avicelase had an optimum pH and temperature 7.0 and 50ºC for both UntSCB and TSCB and exhibited good pH stability between "5-8" and "4-9", however, good temperature stability between (30-80ºC) for UntSCB and TSCB, respectively. Other factors affecting the production of Avicelase were compared (i.e. SCB concentration, inoculum size and different incubation periods), all results observed and obtained were revealed that the TSCB was exhibited maximal enzyme activity in comparison with the results obtained from UntSCB, so, the TSCB was enhancing the Avicelase production.
Abstract: A statistical optimization of the saccharification
process of EFB was studied. The statistical analysis was done by
applying faced centered central composite design (FCCCD) under
response surface methodology (RSM). In this investigation, EFB
dose, enzyme dose and saccharification period was examined, and the
maximum 53.45% (w/w) yield of reducing sugar was found with 4%
(w/v) of EFB, 10% (v/v) of enzyme after 120 hours of incubation. It
can be calculated that the conversion rate of cellulose content of the
substrate is more than 75% (w/w) which can be considered as a
remarkable achievement. All the variables, linear, quadratic and
interaction coefficient, were found to be highly significant, other than
two coefficients, one quadratic and another interaction coefficient.
The coefficient of determination (R2) is 0.9898 that confirms a
satisfactory data and indicated that approximately 98.98% of the
variability in the dependent variable, saccharification of EFB, could
be explained by this model.
Abstract: A statistical optimization was studied to design a media composition to produce optimum cellulolytic enzyme where palm oil mill effluent (POME) as a basal medium and filamentous fungus, Trichoderma reesei RUT-C30 were used in the liquid state bioconversion(LSB). 2% (w/v) total suspended solid, TSS, of the POME supplemented with 1% (w/v) cellulose, 0.5%(w/v) peptone and 0.02% (v/v) Tween 80 was estimated to produce the optimum CMCase activity of 18.53 U/ml through the statistical analysis followed by the faced centered central composite design(FCCCD). The probability values of cellulose (
Abstract: In this work we report the recent progresses that have been achieved by our group in the last half decade on the field of computational proteomics. Specifically, we discuss the application of Molecular Dynamics Simulations and Electronic Structure Calculations in drug design, in the clarification of the structural and dynamic properties of proteins and enzymes and in the understanding of the catalytic and inhibition mechanism of cancer-related enzymes. A set of examples illustrate the concepts and help to introduce the reader into this important and fast moving field.
Abstract: Severe acute respiratory syndrome (SARS) is a respiratory disease in humans which is caused by the SARS coronavirus. The treatment of coronavirus-associated SARS has been evolving and so far there is no consensus on an optimal regimen. The mainstream therapeutic interventions for SARS involve broad-spectrum antibiotics and supportive care, as well as antiviral agents and immunomodulatory therapy. The Protein- Ligand interaction plays a significant role in structural based drug designing. In the present work we have taken the receptor Angiotensin converting enzyme 2 and identified the drugs that are commonly used against SARS. They are Lopinavir, Ritonavir, Ribavirin, and Oseltamivir. The receptor Angiotensin converting enzyme 2 (ACE-2) was docked with above said drugs and the energy value obtained are as follows, Lopinavir (-292.3), Ritonavir (-325.6), Oseltamivir (- 229.1), Ribavirin (-208.8). Depending on the least energy value we have chosen the best two drugs out of the four conventional drugs. We tried to improve the binding efficiency and steric compatibility of the two drugs namely Ritonavir and Lopinavir. Several modifications were made to the probable functional groups (phenylic, ketonic groups in case of Ritonavir and carboxylic groups in case of Lopinavir respectively) which were interacting with the receptor molecule. Analogs were prepared by Marvin Sketch software and were docked using HEX docking software. Lopinavir analog 8 and Ritonavir analog 11 were detected with significant energy values and are probable lead molecule. It infers that some of the modified drugs are better than the original drugs. Further work can be carried out to improve the steric compatibility of the drug based upon the work done above for a more energy efficient binding of the drugs to the receptor.
Abstract: The ability of agricultural and decorative plants to
absorb and detoxify TNT and RDX has been studied. All tested 8
plants, grown hydroponically, were able to absorb these explosives
from water solutions: Alfalfa > Soybean > Chickpea> Chikling vetch
>Ryegrass > Mung bean> China bean > Maize. Differently from
TNT, RDX did not exhibit negative influence on seed germination
and plant growth. Moreover, some plants, exposed to RDX
containing solution were increased in their biomass by 20%. Study of
the fate of absorbed [1-14ðí]-TNT revealed the label distribution in
low and high-molecular mass compounds, both in roots and above
ground parts of plants, prevailing in the later. Content of 14ðí in lowmolecular
compounds in plant roots are much higher than in above
ground parts. On the contrary, high-molecular compounds are more
intensively labeled in aboveground parts of soybean. Most part (up to
70%) of metabolites of TNT, formed either by enzymatic reduction
or oxidation, is found in high molecular insoluble conjugates.
Activation of enzymes, responsible for reduction, oxidation and
conjugation of TNT, such as nitroreductase, peroxidase,
phenoloxidase and glutathione S-transferase has been demonstrated.
Among these enzymes, only nitroreductase was shown to be induced
in alfalfa, exposed to RDX. The increase in malate dehydrogenase
activities in plants, exposed to both explosives, indicates
intensification of Tricarboxylic Acid Cycle, that generates reduced
equivalents of NAD(P)H, necessary for functioning of the
nitroreductase. The hypothetic scheme of TNT metabolism in plants
is proposed.
Abstract: Strain M was isolated from the latex of Hevea brasiliensis that grow in the rubber farm area of Malaysia Rubber Board. Strain M was tentatively identified as Bacillus sp. Strain M demonstrated high protease production at pH 9, and this was suitable to be applied in rubber processing that was in alkaline conditions. The right and suitable proportion to be used in applying supernatant into the latex was two parts of latex and one part of enzyme. In this proportion, the latex was stable throughout the 72 hours of treatment. The potential of strain M to degrade protein in the natural rubber latex was proven with the reduction of 79.3% nitrogen in 24 hours treatment. Centrifugation process of the latex before undergoing the treatment had increased the protein degradation in latex. Although the centrifugation process did not achieve zero nitrogen content, it had improved the performance of protein denaturing in the natural rubber.
Abstract: Camptothecin (CPT) is a cytotoxic quinoline alkaloid,
which inhibits the DNA enzyme topoisomerase I (topo I). It was
discovered in 1966 by M. E. Wall and M. C. Wani in systematic
screening of natural products for anticancer drugs. It was isolated
from the bark and stem of Camptotheca acuminata (Camptotheca,
Happy tree), a tree native in China. CPT showed remarkable
anticancer activity in preliminary clinical trials but also low
solubility and (high) adverse drug reaction. Because of these
disadvantages synthetic and medicinal chemists have developed
numerous syntheses of Camptothecine [1][2][3] and various
derivatives to increase the benefits of the chemical, with good results.
In our method CPT analogues has be six steps starting from available
material DL Malic acid.