Optimizing the extract yield of bioactive compounds in Valeriana officinalis root: a D-optimal design.

It is estimated that 80% of all synthetic drugs are derived from medicinal plants, and nowadays, many synthetic drugs are derived from medicinal plants. Valeriana officinalis can treat many diseases of the nervous system. A crucial aspect of valerian extract is that it inhibits the proliferation of breast cancer cells. To optimize the yield of bioactive compounds in the V. officinalis root extraction, a response surface methodology-based D-optimal design was used. To fulfill this aim, the effects of various factors such as solvent type and concentration, mixing temperature, ultrasound time, and drying method were examined. The optimal conditions for solvent percentages, mixing temperature, ultrasound time, solvent type, and drying methods were determined to be 94.88%, 25 °C, 48.95 min, methanol, and microwave, respectively, with a desirability of 0.921. The predicted valerenic acid, total phenols, total flavonoids, and antioxidant activity in V. officinalis extract were 1.19 (mg/g DW), 8.22 (mg/g DW), 5.27 (mg/g DW), and 92.64%, respectively. In optimal conditions, the extracted amounts of valerenic acid, total phenols, total flavonoids, and antioxidant activity were 2.07 mg/g DW, 7.96 mg/g DW, 5.52 mg/g DW, and 78.68%, respectively, which were consistent with the model predicted amounts (based on 95% prediction interval). This study could be useful as a model for demonstrating the efficacy of microwave drying to maximize the biochemical content of V. officinalis, as well as the antioxidant activity of the root extracts of V. officinalis on industrial scale.

Hydrophilic dangling chain interfacial segregation in polyurethane networks at aqueous interfaces and its underlying mechanisms: molecular dynamics simulations.

Polymer networks with hydrophilic dangling chains are ideal candidates for many submerged applications, e.g., protein non-adhesive coatings with non-fouling behavior. The dangling chains segregate from the polymer network towards the water and form a brush-like structure at the interface. Several factors such as the polymer network structure, dangling chain length, and water/dangling chain interaction may all affect the interfacial performance of the polymer. Therefore, we employed a Martini based coarse-grained (CG) molecular dynamics (MD) simulation to elucidate the influences of the abovementioned parameters on dangling chain interfacial segregation. We built up several polyurethane (PU) networks based on poly(tetra methylene glycol) (PTMG), as a macrodiol, and methoxy poly(ethylene glycol) (mPEG), as a dangling chain, with varying molecular weights. We found out that the macrodiol/dangling chain length ratio considerably smaller than one impedes the migration of dangling chains towards the water interface, while the dangling chain hydrophilicity and length determine the polymer interfacial layer density/thickness. Then, we artificially changed the dangling chain affinity to water from an intermediate to a very attractive water/dangling chain interaction. We justified that a brush-like structure forms in two consecutive steps: first, a longitudinal, and then a lateral migration of dangling chains in water. The latter step results in a uniform interfacial layer over the polymer interface that mainly occurs in the case of the attractive water/dangling chain interaction.

MARTINI-based simulation method for step-growth polymerization and its analysis by size exclusion characterization: a case study of cross-linked polyurethane.

Simulation studies of step-growth polymerization, e.g., polymerization of polyurethane systems, hold great promise due to having complete control over the reaction conditions and being able to perform an in-depth analysis of network structures. In this work, we developed a (completely automated) simulation method based on a coarse-grained (CG) methodology, i.e., the MARTINI model, to study the cross-linking reaction of a diol, a tri-isocyanate molecule and one-hydroxyl functional molecule to form a polyurethane network without and with dangling chains. This method is capable of simulating the cross-linking reactions not only up to very high conversions, but also under rather complicated reaction conditions, i.e., a non-stoichiometric ratio of the reactants, solvent evaporation and multi-step addition of the reactants. We introduced a novel network analysis, similar to size-exclusion chromatography based on graph theory, to study the growth of the network during the polymerization process. By combining the reaction simulations with these analysis methods, a set of correlations between the reaction conditions, reaction mechanisms and final network structure and properties is revealed. For instance, a two-step addition of materials for the reaction, i.e., first the dangling chain to the tri-isocyanate and then the diol, leads to the highest integrated network structure. We observed that different reaction conditions lead to different glass transition temperatures (Tg) of the network due to the distinct differences in the final network structures obtained. For example, by addition of dangling chains to the network, the Tg decreases as compared to the network without dangling chains, as also is commonly observed experimentally.

HybridRanker: Integrating network topology and biomedical knowledge to prioritize cancer candidate genes.

In the past few years, many researches have been conducted on identifying and prioritizing disease-related genes with the goal of achieving significant improvements in treatment and drug discovery. Both experimental and computational approaches have been exploited in recent studies to explore disease-susceptible genes. The experimental methods for identification of these genes are usually time-consuming and expensive. As a result, a substantial number of these studies have shown interest in utilizing computational techniques, commonly known as gene prioritization methods. From a conceptual point of view, these methods combine various sources of information about a particular disease of interest and then use it to discover and prioritize candidate disease genes. In this paper, we propose a gene prioritization method (HybridRanker), which exploits network topological features, as well as several biomedical data sources to identify candidate disease genes. In this approach, the genes are characterized using both local and global features of a protein-protein interaction (PPI) network. Furthermore, to obtain improved results for a particular disease of interest, HybridRanker incorporates data from diseases with similar symptoms and also from its comorbid diseases. We applied this new approach to identify and prioritize candidate disease genes of colorectal cancer (CRC) and the efficiency of HybridRanker was confirmed by leave-one-out cross-validation test. Moreover, in comparison with several well-known prioritization methods, HybridRanker shows higher performance in terms of different criteria.

Bioinspired pressure-sensitive adhesive: evaluation of the effect of dopamine methacrylamide comonomer as a general property modifier using molecular dynamics simulation.

The use of catechol-containing comonomers as a general property enhancer to achieve unique properties has received particular attention for designing bioinspired polymeric materials. In this study, molecular dynamics simulation was used to investigate the role of dopamine methacrylamide (DMA) and N-phenethyl methacrylamide (PMA) comonomers in chain conformation and their effects on the mechanical properties and adhesion of poly(n-butyl acrylate-co-acrylic acid) copolymer. Addition of 4% by weight of DMA comonomer in the terpolymer structure reduces the gyration radius of the poly(n-butyl acrylate-co-acrylic acid) copolymer. This reduction is due to the formation of intramolecular hydrogen bond interactions. A further increase in the DMA up to 12.2% by weight increases the radius of gyration by 5%. The effect of PMA on the gyration radius of the poly(n-butyl acrylate-co-acrylic acid) copolymer is more extensive, compared to DMA. While DMA enhances both van der Waals and electrostatic components of the cohesive energy density through increasing π-π interactions and hydrogen bond formations, PMA only improves the van der Waals component. Assessment of mechanical properties revealed that the addition of DMA comonomer resulted in a transition from brittle to tough behavior in poly(n-butyl acrylate-co-acrylic acid) pressure-sensitive adhesive. Ductility index improvement by DMA is higher than that by PMA. DMA comonomers accumulate on the silica surface resulting in the terpolymer chains approaching the dry silica surface from the hydroxyl groups of the catechol. Accumulation of DMA only enhances the cohesive energy and does not improve the adhesive energy.

A highly efficient microwave-assisted synthesis of an LED-curable methacrylated gelatin for bio applications.

This study deals with the development of an LED-curable methacrylated gelatin (GelMA) synthesis via microwave (MW) irradiation with a reaction and purification time-, energy-, and methacrylation reagent-saving approach. To investigate the efficiency of MW irradiation in GelMA synthesis, characteristics of the GelMAs prepared by using glycidyl methacrylate (GMA) or methacrylic anhydride (MA) via the MW-assisted (MWA) method were compared comprehensively with those synthesized via the conventional heating method. Moreover, MWA reaction conditions were optimized in terms of methacrylation reagent concentrations (C), reaction time (t), and MW power (P). Characterization and assessment of the GelMAs were conducted with 1H NMR, FT-IR, and Raman spectroscopy along with physical-mechanical, thermal, and hydrophilicity analysis. The results demonstrated that the MWA synthesized GMA-GelMA hydrogels were possessed of increased methacrylation degree (MD), gel fraction (GF), tensile strength (TS), elongation at break (EB), glass transition temperature (T g), and water contact angle (WCA) as well as decreased swelling degree (SD) values in comparison to those of MA-GelMA and GMA-GelMA hydrogels prepared via the MWA and conventional method, respectively. Enhanced properties of the MWA synthesized GMA-hydrogels suggested an effective methacryloyl conjugation leading to a greater amount of covalent crosslinking density justified by the dipolar moment calculations. Optimal GMA C, t, P, and purification time for a highly crosslinked GelMA hydrogel (MD: 96.1%, GF: 98.3%, SD: 10.11%, TS: 6.7 MPa, EB: 175.2%, T g: 75.34 °C, and WCA: 72.22°) were found to be a 5 times molar excess over the primary amine groups of gelatin, 5 min, 500 W, and 24 h, respectively. Thus, the optimized MW conditions offer a promising green method to prepare GelMAs for bio applications.

Association analysis and molecular tagging of phytochemicals in the endangered medicinal plant licorice (Glycyrrhiza glabra L.).

Licorice (Glycyrrhiza glabra L.) is a medicinal plant species valued in many countries in Asia and Europe for its phytochemical characteristics. Licorice biodiversity is becoming threatened nowadays in Iran due to increasing demand and a drastic decline of its natural habitats. Therefore, licorice domestication would be necessary in the near future, and molecular breeding would help to introduce genotypes suitable for cultivation. The present study was carried out with 170 individual licorice plants sampled in the wild in 59 localizations in 21 provinces of Iran. The association of 436 polymorphic AFLP markers, produced by 15 primer combinations (EcoRI/MseI), with six phenotypic phytochemical traits was studied. The AMOVA analysis show gene diversity among and within localizations. The population structure analysis identified two main sub-populations with significant genetic variation. Significant associations were identified between three markers (E3/M40-4, E34/M4-12 and E12/M31-15) and glycyrrhizin concentration, and between four markers (E11/M34-12, E11/M34-15, E9/M7-29, and E9/M7-30) and phenolic compounds contents. Markers detected can be useful in the domestication of licorice as well as in breeding programs. Licorice sampled in four localizations (KBA1, KBA2, SKh2 and Fa1) were found to be superior in terms of glycyrrhizin and antioxidants content, and therefore they can be considered as elite genotypes which could be included in the domestication process.

Subject: UV-B radiation and low temperature promoted hypericin biosynthesis in adventitious root culture of Hypericum perforatum.

The hypericin is assumed as a highly demanded and key bioactive compound, which has antiviral, antimicrobial, antioxidant, and antitumor properties isolated from Hypericum perforatum. Nowadays, increasing bioactive molecules' contents through generating novel compounds is one of the major research objectives of H. perforatum biotechnology; however, this plant remains recalcitrant and unmanageable to Agrobacterium mediated transformation and genetic improvement programs. In order to overcome these challenges, many researchers have focused on this unruly herb using biotic and abiotic eliciting strategies. Therefore, two experiments were separately designed for the evaluation of two types of abiotic elicitors, aiming at increasing the productivity of hypericin in the adventitious root suspension culture of H. perforatum. The first one was accomplished to evaluate the effect of UV-B light elicitors (the exposure time of 30, 60, and 90 min) and the recovery treatment (with or without) on hypericin content while the second one was assessed the effect of various temperatures (4°C, 8°C, 16°C, and 25°C) in three different exposure times (24 h, 72 h, and 7 d). Based on the results, UV-B (60 min) treatment followed by the recovery produced 0.430 µg/g DW hypericin and was distinguished as the most effective UV-B elicitation treatment. In addition, a temperature of 4°C for a period of 72 hours is required to get the highest amount of hypericin content. These findings indicate the fact that hypericin biosynthesis is notably affected by UV-B exposure time and Low-temperature. The data also clearly elucidate further mechanisms of hypericin production in H. perforatum adventitious root culture.

A new safranin based three-component photoinitiating system for high resolution and low shrinkage printed parts via digital light processing.

Additive manufacturing or 3D printing has attracted the interest of researchers in industry and academia because of its outstanding features. In this study, a new three-component photoinitiating system (PIS) consisting of safranin O (SFH+), thiol derivatives and diphenyl iodonium salt was used for the free radical photopolymerization of a diacrylate monomer (SR349) in DLP 3D printing. The photoinitiating characteristics of this PIS were evaluated and advantageously compared to those of a conventional PI (TPO) by using RT-FTIR. It is shown that the proposed PIS could be used as an efficient PIS for free radical photopolymerization. In addition, the resolution and shrinkage of printed parts in the presence of this three-component PIS were measured and compared to those printed using TPO as a photoinitiator. The resolution of printed parts was determined by using SEM and profilometry techniques. In addition, photorheometry was used to evaluate the linear shrinkage of samples. Moreover, the initiating mechanism of the three-component PIS was studied by using laser flash photolysis (LFP). A photocyclic mechanism was outlined for the three-component PIS which demonstrated this mechanism would be very beneficial for DLP 3D printing.

Factors affecting the properties of nitrocellulose emulsions: A comparative study.

In this study the influence of viscosity and chemical nature of dispersed phase, preparation conditions and storage temperature on the properties of nitrocellulose emulsions produced by gel emulsification (G) and direct mechanical emulsification (D) methods were examined. Chemical nature of dispersed phase had no effect on the drop size for both methods; however it had a significant effect on emulsion stability. Viscosity of dispersed phase did not considerably affect drop breakage process in route G, while strongly affected drop breakage in route D. Addition rate had no significant effect on the drop size produced by route D; while for route G high addition rate resulted in catastrophic phase inversion. The drop size produced by route D decreased dramatically by increasing stirring speed, whereas stirring speed had a minimal effect on the drop breakage process in route G. Finally, it was found that emulsion stability was greatly influenced by storage temperature.

Effect of drought stress on growth parameters, osmolyte contents, antioxidant enzymes and glycyrrhizin synthesis in licorice (Glycyrrhiza glabra L.) grown in the field.

Glycyrrhiza glabra L. (licorice) is a medicinal species rich in the specialised plant metabolite glycyrrhizin. It has been previously proposed that drought, which is increasing in importance due to the climatic change and scarcity of water resources, can promote the synthesis of glycyrrhizin. The effects of slight, moderate and intense drought (70, 35 and 23% of the regular irrigation, respectively) on growth parameters, osmolyte content, oxidative stress markers, antioxidant enzymes, glycyrrhizin biosynthesis genes and root glycyrrhizin concentration and contents, have been assessed in five Iranian licorice genotypes grown in the field. Drought decreased progressively biomass and leaf relative water contents, and increased progressively osmolyte (proline, glycine-betaine and soluble sugars) concentrations in leaves and roots. Drought caused oxidative stress in leaves, as indicated by lipid peroxidation and hydrogen peroxide concentrations, and increased the activities of antioxidant enzymes in leaf extracts (catalase, peroxidase, superoxide dismutase and pholyphenoloxidase). Drought promoted the synthesis of glycyrrhizin, as indicated by the increases in the expression of the glycyrrhizin biosynthesis pathway genes SQS1, SQS2, bAS, CYP88D6, CYP72A154 and UGT73, and increased the root concentrations of glycyrrhizin with drought in some genotypes. However, the large decreases in root biomass caused by drought led to general decreases in the amount of glycyrrhizin per plant with moderate and intense drought, whereas the slight drought treatment led to significant decreases in glycyrrhizin content in only one genotype. Under intense drought two of the genotypes were still capable to maintain half of the control glycyrrhizin yield, whereas in the other three genotypes glycyrrhizin yield was 22-33% of the control values. Results indicate that under intense drought, with only 23% of the normal water dose being applied, an appropriate choice of genotype can still lead to acceptable glycyrrhizin yields.

Comparison between the Outcomes of Intracoronary and Intravenous Administration of Eptifibatide during Primary Percutaneous Coronary Intervention in Patients with Acute ST-Elevation Myocardial Infarction.

AIM: To compare the outcomes of intracoronary (IC) and intravenous (IV) administration of eptifibatide during primary percutaneous coronary intervention (PPCI) in patients with ST-elevation myocardial infarction (STEMI). METHODS: In this prospective double-blind randomized clinical trial, 76 patients with STEMI selected for PPCI were randomly assigned in two groups to receive either IC or IV bolus of eptifibatide. The primary end point was coronary perfusion assessment by thrombolysis in myocardial infarction (TIMI) flow grade (TFG), TIMI perfusion grade (TPG), and corrected TIMI frame count (cTFC). Secondary end points were left ventricular ejection fraction (LVEF) restoration, ST-segment elevation resolution, and in-hospital major cardiovascular adverse events (MACEs) (including recurrent MI, need for target vessel revascularization (TVR), stroke, and death resulting from any cause) until discharge. RESULTS: Assessment revealed significantly better TFG (95% CI: 1.01-10.26, OR=3.224, P=0.042), more TFG 3 (65.79% vs. 86.11% in IV and IC groups, respectively), better TPG (P=0.024), more achieved TPG 3 and TPG 2＋3 (TPG 3: 44.74% vs. 72.22% and TPG 2＋3: 78.95% vs. 94.44% in the IV and IC groups, respectively) with better cTFC in the IC group (37.33±15.84 vs. 32.53± 20.71 in the IV and IC groups, respectively; P=0.034). LVEF was better restored in the IC group (6.21±8.61% vs. 14.72±5.34% in the IV and IC groups, respectively; P＜0.001) and the ST-segment elevation resolution was better achieved in the IC administration (95% CI: -22.55 to -6.23, P=0.001). There were no recurrent MI, stroke, or need for TVR among patients during the in-hospital stay. CONCLUSIONS: IC administration of eptifibatide during PPCI in patients with STEMI in comparison with IV administration of eptifibatide is associated with significantly better coronary reperfusion and improved clinical outcomes (IRCT2012090510751N1).

Biological Characteristic of Brachynema germari (Hemiptera: Pentatomidae): Comparative Study of Composite and Natural Diet.

This research was conducted to develop a composite diet and compare its effects on developmental time, fecundity, survival rate, and life table parameters of pistachio green stink bug, Brachynema germari Kolenati (Hemiptera: Pentatomidae) with a natural diet. The biological parameters of this pest were investigated using two-sex, age-stage life table theory on both composite and natural diets (25 ± 1°C, 50 ± 10% relative humidity, and a photoperiod of 16:8 [L:D] h). Based on the preliminary studies, the combination of the green beans ( Phaseolus vulgaris L.), sunflower seeds ( Helianthus annuus L.), and wild rue capsules ( Peganum harmala L.) was introduced into a composite diet. There was no significant difference between the longevity of each stage on diet treatments, but the mean fecundity of female fed on composite diet was about 196.48 ± 12.02 (eggs), which indicated a significant decrease than the fecundity of female fed on the natural diet (265.81 ± 11.67 eggs; P = 0.05, t -test). Also, main parameters of life table ( r , R 0 , T , and λ) for composite and natural diets were about 0.0863 ± 0.0031 d -1 , 89.03 ± 13.33 eggs, 51.987 ± 0.536 d, and 1.091 ± 0.0034 d -1 and 0.1023 ± 0.003 d -1 , 128.75 ± 17.56 eggs, 47.454 ± 0.439 d, and 1.1077 ± 0.0037 d -1 , respectively. There was a significant difference between these four parameters on both diets. Despite a significant decrease in fecundity with using composite diets, this diet can satisfy our needs now and the laboratory rearing of pistachio green stink bug did not stop over the year in the absence of host weeds and insect did not diapause.

Increased IL-17 and TGF-ß serum levels in peripheral blood of patients with ß-thalassemia major: implication for continual transfusions role in T helper17-mediated proinflammatory responses.

BACKGROUND/AIM: Recent studies have shown that IL-17-producing CD4+ T helper (Th17) cells play an important role in proinflammatory processes. In this report we analyzed IL-17, IL-21, and TGF-ß serum levels in the peripheral blood of Iranian beta-thalassemia major patients that clinically exhibited splenectomy and iron overload. MATERIALS AND METHODS: Blood samples were collected from 43 beta-thalassemia patients and 43 healthy individuals with no history of malignancies or autoimmune disorders. Then serum levels of IL-17, IL-21, and TGF-ß were measured by enzyme linked immunosorbent assay (ELISA). RESULTS: The levels of IL-17 (P = 0.005) and TGF-ß (P < 0.001) were significantly higher in the thalassemia patients compared to the healthy control. No significant differences in the level of serum IL-21 was observed between the patients and controls. There were no significant differences in serum levels of IL-17, IL-21, and TGF-ß between patients with high or low serum levels of ferritin. CONCLUSION: Multiple blood transfusions cause constant immune stimulation, as a result of repeated exposure to new alloantigens. This might have significant effects on the stimulation of cytokine producing cells in those patients and cytokine profile can be used as a related marker for assessing disease severity and consequently therapeutic intervention.