S. M. Zahid Hosen

In silico-based vaccine design against Ebola virus glycoprotein

Ebola virus (EBOV) is one of the lethal viruses, causing more than 24 epidemic outbreaks to date. Despite having available molecular knowledge of this virus, no definite vaccine or other remedial agents have been developed yet for the management and avoidance of EBOV infections in humans. Disclosing this, the present study described an epitope-based peptide vaccine against EBOV, using a combination of B-cell and T-cell epitope predictions, followed by molecular docking and molecular dynamics simulation approach. Here, protein sequences of all glycoproteins of EBOV were collected and examined via in silico methods to determine the most immunogenic protein. From the identified antigenic protein, the peptide region ranging from 186 to 220 and the sequence HKEGAFFLY from the positions of 154–162 were considered the most potential B-cell and T-cell epitopes, correspondingly. Moreover, this peptide (HKEGAFFLY) interacted with HLA-A*32:15 with the highest binding energy and stability, and also a good conservancy of 83.85% with maximum population coverage. The results imply that the designed epitopes could manifest vigorous enduring defensive immunity against EBOV.

Antidiarrheal and antinociceptive activities of ethanol extract and its chloroform and pet ether fraction of Phrynium imbricatum (Roxb.) leaves in mice

Abstract Background: The objective of the study was to evaluate the antidiarrheal and antinociceptive activities of ethanol extract and its chloroform and pet ether fraction of Phrynium imbricatum (Roxb.) leaves in mice. Methods: In the present study, the dried leaves of P. imbricatum were subjected to extraction with ethanol, and then it was fractioned by chloroform and pet ether solvent. Antidiarrheal effects were tested by using castor oil-induced diarrhea, castor oil-induced enteropooling, and gastrointestinal transit test. Antinociceptive activity was evaluated by using the acetic acid-induced writhing test and formalin-induced paw licking test. Results: The standard drug loperamide (5 mg/kg) showed significant (p<0.001) inhibitory activity against castor oil-induced diarrhea, in which all the examined treatments decreased the frequency of defecation and were found to possess an anti-castor oil-induced enteropooling effect in mice by reducing both weight and volume of intestinal content significantly, and reducing the propulsive movement in castor oil-induced gastrointestinal transit using charcoal meal in mice. The results showed that the ethanol extract of P. imbricatum leaves has significant dose-dependent antinociceptive activity, and among its two different fractions, the pet ether fraction significantly inhibited the abdominal writhing induced by acetic acid and the licking times in formalin test at both phases. Conclusions: These findings suggest that the plant may be a potential source for the development of a new antinociceptive drug and slightly suitable for diarrhea, as it exhibited lower activity. Our observations resemble previously published data on P. imbricatum leaves.

Genomics and future of medicine

W have developed a proton magnetic resonance imaging and spectroscopy (MRI/MRS) protocol to quickly and noninvasively assess in vivo fat composition in human skeletal muscle. The protocol was applied to quantify gross adipose tissue depots and intramuscular lipid concentrations towards developing and substantiating the use of MRI/MRS to measure muscle quality in the thigh in three groups of older women varying in adiposity and habitual physical activity levels: obese (O); lean and sedentary (LS), and lean and active (LA). In the cross-sectional portion of the study, no significant differences in relative adipose tissue volumes or intramuscular lipid concentrations were found between the groups O and LS, revealing that the lipid distribution and storage were similar between obese and lean, sedentary subjects. However, group LA had 10% less relative fat volume and double the relative amount of lipids stored in a metabolically active state than O and LS. The longitudinal portion of the study involved two different four-month interventions on the thigh adipose composition of the O group: weight-loss diet (DI) and weight-stable exercise (EX). Group DI increased lipid concentrations without a change in distribution, due to loss of lean mass, whereas group EX had a favorable redistribution of intramuscular lipids without a loss of overall lipid concentration. In addition to other potential applications of our protocol in the area of analytical techniques for metabolomics, our results add to the growing literature regarding the importance of physical activity for the management of intramuscular lipids, even in individuals who are normal weight.Since the discovery of Agarwood (Incense tree), many studies reported its characteristic effects and variable benefits, as either to produce Arabian Incense or as a traditional medicine against many diseases. Laboratory experiments were carried out on the effect of different concentrations of Incense smoke inhalation on the lung weight and tissue in female mice. This research derives its importance from the fact that Incense is heavily used in Saudi Arabia in the absence of thorough studies of its effects on health. Eighty animals are used in this study, and are divided into four groups, each is 20 animals. Three groups are exposed to different concentrations (2, 4 and 6 gm) of Incense smoke daily for three months, and the fourth group is the control. At the end of each month, five animals from each group were dissected. Obtained data showed an increase but not significant in animal body and lung weight, this results return to natural increase as a result of normal growth of animals. Light microscope reveals some changes in the lung tissue, such as focal emphysema, rupture in the alveolar walls, hemorrhage, congestion, edema and few peri-bronchial lymphoid cells. After continuous exposure to Incense smoke focal necrosis and degradation are observed in some cells of epithelial bronchioles. Also, fibrosis of peri-bronchial, thickening in alveolar walls and aggregation of lymphoid cells are demonstrated in some lungs sections . Conclusion: according to the above manifestations it could be concluded that exposure to Incense smoke causes pulmonary harmful effects. Therefore, we can recommend that Incense smoke will be used only in open places to reduce its harms. [Samar Omar A. Rabah, Sahar Ragab El Hadad and Fatmah Albani. Histological changes of Mice lungs after daily exposure to different concentration of Incense smoke. Life Sci J 2013;10(1):552-560]. (ISSN: 1097-8135). http://www.lifesciencesite.com. 90T ultimate goal of this study is to understand how pathogenic mycobacteria utilize RNA modifications to control translation and survive the human innate immunity. Tuberculosis especially, a mycobacterial disease, is thought to latently infect a third of the world’s population in its dormant form. Yet, despite the availability of genomic and proteomic knowledge on how the invading pathogen responds to hostile host environments, our ability to understand the gene regulation system in these pathogens is hampered by the lack of understanding of gene expression controls during translation. We present preliminary evidence that the 27 tRNA modifications in mycobacteria undergo stress-induced reprogramming and play a major role in regulating gene expression by controlling selective translation key stress response genes as the organism enters and exits hypoxia-induced dormancy. We initiated these studies with a multidimensional HPLC platform to isolate, purify and quantify all major non-protein coding RNA species and systemically elucidated the complete set of RNA ribonucleoside modifications in Mycobacterium bovis BCG with LCMS/MS. When BCG cells were subjected to hypoxia, multivariate statistical analysis led to the discovery of signature changes in the spectrum of tRNA modifications that define each stage of entry into hypoxia-induced nonreplicative state and subsequent resuscitation upon exposure to oxygen. Correlative analysis of specific ribonucleosides altered during hypoxia with the proteins expressed at the same time will provide insights into the mechanisms controlling selective gene expression during the cellular response to the host environment, with implications for developing new pathogenesis-relevant functional biochemical assays, therapeutic biomarkers and drug targets.G Late Embryogenesis Abundant (LEA) proteins, also known as dehydrins, are claimed to stabilize macromolecules against damage caused by freezing, dehydration, ionic or osmotic stresses. However, their precise function remains unknown. We investigated the effect of wheat dehydrin (DHN-5) protein on the activity and thermostability of two distinct enzymes, β-glucosidase (bglG) and glucose oxidase/peroxidase (GOD/POD) in vitro. The purified DHN-5 protein had the capacity to preserve and stabilize the activity of bglG subjected to heat treatment. In addition, DHN-5 stabilized oxidizing enzymes, as it improved reliability in measuring glucose concentrations with a glucose oxidase/peroxidase (GOD/POD) kit while the temperature increased from 37 to 70°C. All together the data presented provide evidence that DHN-5 is a dehydrin able to preserve enzyme activities in vitro from adverse effects induced by heating. In order to understand the molecular mechanism by which DHN-5 exerts its protective function, we performed an approach to dissect the functional domains of DHN-5 responsible for this feature. In two distinct enzymatic assays, we found that the truncated forms of DHN-5 containing only one K-or two K-segments are able to protect albeit to less extent than the wild type protein, lactate dehydrogenase and β-glucosidase against damage induced by various stresses in vitro. However, the YS-and ф-segments alone have no protective effects on these enzymes. Therefore, our study provides the evidence that the protective function of DHN-5 seems to be directly linked to its K-segments which through their amphipatic α-helical structure, may act to prevent protein aggregation.R reports suggest that vitamin B1 (thiamine) participates in the processes underlying plant adaptations to certain types of biotic stress. However, mechanisms underlying vitamin-induced, especially thiamine-induced, disease resistance are largely unknown. Here, we show the ability of thiamine to induce resistance against Plasmopara viticola in a susceptible grapevine cv. Chardonnay by a dual mode of action involving direct antifungal activity and elicitation of host-defense responses including H2O2 generation, upregulation of PR genes, and hypersensitive cell death. In addition, we assessed whether thiamine could modulate phenylpropanoid pathway-derived phytoalexins in grapevine plants, as well as, the role of such secondary metabolites in this induced resistance process to P. viticola. We found that thiamine treatment elicited the expression of the phenylpropanoid pathway genes in grapevines. The expression of these genes correlated with an accumulation of stilbenes, phenolic compounds, flavonoids including a quercetin 3-O-glucoside, and lignin. Furthermore, the total antioxidant potential of thiamine-treated plants was 3.5-fold that of control plants. Four phenolic compounds corresponded to 97% of the total antioxidant potential of thiamine-treated plants. Among them, caftaric acid, which belongs to the hydroxy-cinnamic acids family, corresponded to 20% of the total antioxidant potential. Epifluorescence microscopic analysis revealed a concomitant presence of unbranched and altered pathogen mycelia and stilbenes production in the leaf mesophyll of thiamine-treated plants, suggesting a possible contribution of this phytoalexin family in thiamine-induced resistance to P. viticola in grapevine.Introduction and Objectives: Noise pollution is becoming increasingly more severe nowadays especially in industrial countries. Prevalence of noise is implicated in various illness of human and it is responsible for increased morbidity associated with modern life style. The present study was undertaken to evaluate the correlation between the changes in heart rate (HR) and blood glucose after exposure to acute and chronic high intensity noise using the Langendorff apparatus. Methods: The rats were divided into four groups and they include exposure to noise of intensity 80-100 dBA on duration of 12 hours exposure (acute effect), 8 hours daily for 20 days (chronic effect), 20 days into 3 days exposure and 2 days without 8 hours per day (intermittent effect) and the control group. Results: Noise of 80-100 dBA was found to cause a significant negative correlation between HR and blood glucose in acute noise exposure group (r=-0.091, p=0.01) and chronic continuous noise exposure group (r=-0.84, p =0.03). There was no correlation between the HR and blood glucose in chronic intermittent noise exposure study group. Conclusion: The present study determined that high intensity noise may have an adverse effect on cardiovascular functions and thus noise exposure should be well monitored.Today, throughout the world there is a considerable spread and growth of the population in different countries of the metabolic syndrome. In patients with metabolic disorders often have co-morbidities; often require urgent surgery to save their lives. The aim of our study was to evaluate the results of treatment of patients during their metabolic disorders. We investigated 94 patients with various surgical abdominal pathology at III-IV degree of obesity. The most frequently encountered in obesity were surgical diseases of the abdominal cavity and the abdominal wall, such as cholelithiasis, chronic and acute cholecystitis, ventral hernia, gastroesophageal reflux disease. Patients with metabolic disorders observed changes in many indicators of coagulation. Therefore, all patients underwent prophylactic low molecular weight heparin in the pre and postoperative period. Also before surgery, patients received a medical-prophylactic single intravenous broad-spectrum antibiotic. In most cases, the surgery performed laparoscopically, but in view of the severe subcutaneous fat and can not install the tracers, some patients underwent surgical treatment of open-wide excision of subcutaneous fat in the surgical approach. Local wound complications in the early postoperative period in patients with extreme forms of obesity were more common, which explains the severity of subcutaneous fat, deep wounds, and worse conditions of blood supply. When performing laparoscopy wound complications was significantly less than with open surgery. Thus, the presence of metabolic disorders complicates the treatment of concomitant surgical pathology. However, with careful preoperative planning, the prevention of life-threatening complications, the use of laparoscopic techniques allows to reduce the number of postoperative complications, as well as improve the quality of treatment.

In silico quest of selective naphthyl-based CREBBP bromodomain inhibitor

The reader proteins like bromodomains have recently gained increased attentions in the area of epigenetic drug discovery, as they are the potent regulators in gene transcription process. Among the other bromodomains, cAMP response element-binding protein (CREB) binding protein or CREBBP bomodomain involved in various cancer progressions and therefore, efforts to develop specific inhibitors of CREBBP bomodomain are of clinical value. In this study, we tried to identify selective CREBBP bromodomain inhibitor, which was accomplished by using molecular docking, free energy calculation and molecular dynamics (MD) simulation studies, considering a series of naphthyl based compounds. The docking procedure was validated by comparing root mean square deviations (RMSDs) of crystallographic complex to docked complex. Favorable electrostatic interactions with the Arg1173 side chain were considered to attain selectivity for CREBBP bromodomain over other human bromodomain subfamilies. We found that naphthyl-based compounds have greater binding affinities towards the CREBBP bromodomain, and formed non-bonded interactions with various side chain residues that are important for bromodomain inhibition. From detailed investigation by induced fit docking, compound 31 was found to have favorable electrostatic interactions with the Arg1173 side chain by forming conventional hydrogen bonds. This result was further confirmed by analyzing hydrogen bond occupancy and bonding distance during the molecular dynamics simulation. We believe that these findings offer useful insight for the designing of target specific new bromodomain inhibitor and also promote further structure guided synthesis of analogues for identification of potent CREBBP bromodomain inhibitors as well as detailed in vitro and in vivo analyses.

KEGG (Kyoto Encyclopedia of Genes and Genomes) for representation and analysis of molecular networks involving diseases and drugs

Many effective anti-glaucoma drugs, available for the treatment of ocular hypertension and open angle glaucoma are associated with rapid and extensive precorneal loss caused by drainage and high tear fluid turnover. The objective of this study involved the design of mucoadhesive nanoparticulate carrier system containing Timolol Maleate for ocular drug delivery to improve its corneal absorption. Nanoparticles were prepared by template polymerisation method and the process optimisation using different combination ratios of mucoadhesive polymers was carried out. The developed nanoparticle was checked for its particle size and zeta potential. The invitro release characteristics of the optimised nanoparticle were compared with the marketed formulation. The potential irritancy was evaluated using HET-CAM method. Transcorneal permeation data was performed using goat cornea. The study was carried out with an aim of giving a promising delivery system for management of glaucoma.T present work describes the pulmonary deposition and enhanced deaggregation behavior of multifunctional magnetic nano-aggregates. Magnetic dry powders for inhalation loaded with iron oxide nanoparticles were surface functionalized with variable concentrations of block copolymer, PPG-NH2. Increasing the concentration of PPG-NH2 showed controlled manipulation of the crystal size and morphology. Magnetic nanoparticles fabricated with 5 weight % of PPG-NH2 showed cubic crystal morphology. However, these nanoparticles exhibited rhombic dodecahedron crystal structure upon increasing the concentration to 25 weight %. Cubic phase magnetic nanoparticles demonstrated an enhanced in vitro aerosol deposition using magnetic field alignment. This enhancement can be accomplished at low inhalation flow rate (15 LPM). However, transformation to the rhombic dodecahedron crystallographic structure was observed to be associated with reduction in the powder geometric standard deviation (GSD), especially at 15 and 30 LPM. The approach presented in this paper showed significant enhancement in the deaggregation behavior of inhalation dry powders; that can be achieved with small amounts of magnetic nano-carriers relative to the active pharmaceutical ingredient. Aggregates of cubic nanoparticles showed promise for targeted pulmonary deposition of anticancer drugs.A simple, specific, selective and accurate stability-indicating reversed phase high performance liquid chromatographic method was developed for the simultaneous determination of Diclofenac potassium, Paracetamol and Methocarbamol. An isocratic RP-HPLC was achieved on younglin HPLC system using Varian C18 (250 Χ 4.6 mm i.d, 5 μm particle size) column with the mobile phase containing mixture of Methanol:water (80:20 v/v). The flow rate was 0.8 ml/min and the eluent was monitored at 272nm. The retention times of Diclofenac potassium(DIC), Paracetamol(PCM) and Methocarbamol(MET) were found to be 3.51, 6.42 and 9.90 min respectively. The linearity was established for DIC, PCM and MET in the range of 10-60μg/ml, 65-390μg/ ml, 100-600μg/ml respectively. The percentage recoveries of DIC, PCM and MET were found to be in the range of 99.73%±0.109, 99.59%±0.085 and 99.50%±0.16 respectively. The LOD for DIC, PCM and MET were found to be 1.10, 5.28 and 9.38μg/ml respectively, while LOQ were 3.42, 29.12 and 17.13 μg/ml respectively. All three drugs were subjected to acid, alkali, oxidation, and dry heat degradation. The degradation studies indicated DIC, PCM and MET showed degradation in acid, alkaline, H2O2, and in dry heat condition. The degradation products of DIC, PCM and MET were resolved well from the pure drug with significant differences in their retention time values. The developed method is stability indicating and separate degradants and can be used to determine the stability of samples. The proposed method was successfully applied to the determination of DIC, PCM and MET market formulation.Aim: Periodontal diseases are among the most prevalent infectious diseases. Due to biofilm structure of dental plaque, release of Chlorhexidine inside the crevice of the gingiva can be highly effective. Concerning the importance of designing, synthesis and application of efficient biocompatible systems for drug delivery with desired speed and appropriate time, in this study the ability of mineral porous nanostructural system with silicate and aluminosilicate network for carrying and releasing Chlorhexidine was investigated. Methods and Materials: The successful loading of drug in the mentioned holes was monitored by FT-IR, X-ray diffraction (XRD), Thermo gravimetric analysis (TGA), UV-Vis spectroscopy methods. Moreover, the drug delivery from mineral carrier was followed by UV-Vis spectroscopy. Results: According to the results, MCM-41 in comparison with other applied systems, due to its special specification including high surface area, large pore volume and more accessible silanol groups which result in better drug interaction illustrate beneficial merits in drug placement capacity and long-term drug release. Conclusions: MCM-41 was found as the best carrier by using MIC test and Disk diffusion test. As a conclusion this study showed that MCM the best candidate for carrying and delivering Chlorhexidine inside the gingival crevice.