Search results for: acid resistant bacilli (ARB)

Authors: Yamina Boukari, Nashiru Billa, Andrew Morris, Stephen Doughty, Kevin Shakesheff

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Poly (lactic-co-glycolic) acid (PLGA) is a synthetic polymer that can be used in bone tissue engineering with the aim of creating a scaffold in order to support the growth of cells. The formation of microspheres from this polymer is an attractive strategy that would allow for the development of an injectable system, hence avoiding invasive surgical procedures. The aim of this study was to develop a microsphere delivery system for use as an injectable scaffold in bone tissue engineering and evaluate various formulation parameters on its properties. Porous and lysozyme-containing PLGA microspheres were prepared using the double emulsion solvent evaporation method from various molecular weights (MW). Scaffolds were formed by sintering to contain 1 -3mg of lysozyme per gram of scaffold. The mechanical and physical properties of the scaffolds were assessed along with the release of lysozyme, which was used as a model protein. The MW of PLGA was found to have an influence on microsphere size during fabrication, with increased MW leading to an increased microsphere diameter. An inversely proportional relationship was displayed between PLGA MW and mechanical strength of formed scaffolds across loadings for low, intermediate and high MW respectively. Lysozyme release from both microspheres and formed scaffolds showed an initial burst release phase, with both microspheres and scaffolds fabricated using high MW PLGA showing the lowest protein release. Following the initial burst phase, the profiles for each MW followed a similar slow release over 30 days. Overall, the results of this study demonstrate that lysozyme can be successfully incorporated into porous PLGA scaffolds and released over 30 days in vitro, and that varying the MW of the PLGA can be used as a method of altering the physical properties of the resulting scaffolds.

Keywords: bone, microspheres, PLGA, tissue engineering

Procedia PDF Downloads 417

Authors: Fahad Aljasass, Hamza Abu-Tarboush, Salah Aleid, Siddig Hamad

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The effects of different high hydrostatic pressure treatments on the shelf life of camel’s milk were studied. Treatments at 300 to 350 MPa for 5 minutes at 40°C reduced microbial contamination to levels that prolonged the shelf life of refrigerated (3° C) milk up to 28 days. The treatment resulted in a decrease in the proteolytic activity of the milk. The content of proteolytic enzymes in the untreated milk sample was 4.23 µM/ml. This content decreased significantly to 3.61 µM/ml when the sample was treated at 250 MPa. Treatment at 300 MPa decreased the content to 3.90 which was not significantly different from the content of the untreated sample. The content of the sample treated at 350 MPa dropped to 2.98 µM/ml which was significantly lower than the contents of all other treated and untreated samples. High pressure treatment caused a slight but statistically significant increase in the pH of camel’s milk. The pH of the untreated sample was 6.63, which increased significantly to 6.70, in the samples treated at 250 and 350 MPa, but insignificantly in the sample treated at 300 MPa. High pressure treatment resulted in some degree of milk fat oxidation. The thiobarbituric acid (TBA) value of the untreated sample was 0.86 mg malonaldehyde/kg milk. This value remained unchanged in the sample treated at 250 MPa, but then it increased significantly to 1.25 and 1.33 mg/kg in the samples treated at 300 and 350 MPa, respectively. High pressure treatment caused a small increase in the greenness (a* value) of camel’s milk. The value of a* was reduced from -1.17 for the untreated sample to -1.26, -1.21 and -1.30 for the samples treated at 250, 300 and 350 MPa, respectively. Δa* at the 250 MPa treatment was -0.09, which then decreased to -0.04 at the 300 MPa treatment to increase again to -0.13 at the 350 MPa treatment. The yellowness (b* value) of camel’s milk increased significantly as a result of high pressure treatment. The b* value of the untreated sample was 1.40, this value increased to 2.73, 2.31 and 2.18 after treatments at 250, 300 and 350 MPa, respectively. The Δb* value was +1.33 at the treatment 250 MPa, decreased to +0.91 at 300 MPa and further to +0.78 at 350 MPa. The pressure treatment caused slight effect on color, slight decrease in protease activity and a slight increase in the oxidation products of lipids.

Keywords: high hydrostatic pressure, camel’s milk, mesophilic aerobic bacteria, clotting, protease

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Authors: Sadegh Lotfieblisofla, Arash Khodabakhshi

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Tissue plasminogen activator (tPA) as a serine protease plays an important role in the fibrinolytic system and the dissolution of fibrin clots in human body. The production of this drug in plants such as tobacco could reduce its production costs. In this study, expression of tPA gene and protein targeting to different plant cell compartments, using various signal peptides has been investigated. For high level of expression, Kozak sequence was used after CaMV35S in the beginning of the gene. In order to design the final construction, Extensin, KDEL (amino acid sequence including Lys-Asp-Glu-Leu) and SP (γ-zein signal peptide coding sequence) were used as leader signals to conduct this protein into apoplast, endoplasmic reticulum and cytosol spaces, respectively. Cloned human tPA gene under the CaMV (Cauliflower mosaic virus) 35S promoter and NOS (Nopaline Synthase) terminator into pBI121 plasmid was transferred into tobacco explants by Agrobacterium tumefaciens strain LBA₄₄₀₄. The presence and copy number of genes in transgenic tobacco was proved by Southern blotting. Enzymatic activity of the rt-PA protein in transgenic plants compared to non-transgenic plants was confirmed by Zymography assay. The presence and amount of rt-PA recombinant protein in plants was estimated by ELISA analysis on crude protein extract of transgenic tobacco using a specific antibody. The yield of recombinant tPA in transgenic tobacco for SP, KDEL, Extensin signals were counted 0.50, 0.68, 0.69 microgram per milligram of total soluble proteins.

Keywords: tPA, recombinant, transgenic, tobacco

Procedia PDF Downloads 132

Authors: M. Gómez-Ramírez, A. Rivas-Castillo, I. Rodríguez-Pozos, R. A. Avalos-Zuñiga, N. G. Rojas-Avelizapa

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Among the diverse types of pollutants produced by anthropogenic activities, metals represent a serious threat, due to their accumulation in ecosystems and their elevated toxicity. The mine tailings of abandoned mines contain high levels of metals such as arsenic (As), zinc (Zn), copper (Cu), and lead (Pb), which do not suffer any degradation process, they are accumulated in environment. Abandoned mine tailings potentially could contaminate rivers and aquifers representing a risk for human health due to their high metal content. In an attempt to remove the metals and thereby mitigate the environmental pollution, an environmentally friendly and economical method of bioremediation has been introduced. Bioleaching has been actively studied over the last several years, and it is one of the bioremediation solutions used to treat heavy metals contained in sewage sludge, sediment and contaminated soil. Acidithiobacillus thiooxidans, an extremely acidophilic, chemolithoautotrophic, gram-negative, rod shaped microorganism, which is typically related to Cu mining operations (bioleaching), has been well studied for industrial applications. The sulfuric acid produced plays a major role in bioleaching. Specifically, Acidithiobacillus thiooxidans strain DSM 26636 has been able to leach Al, Ni, V, Fe, Mg, Si, and Ni contained in slags from coal combustion wastes. The present study reports the ability of A. thiooxidans DSM 26636 for the bioleaching of metals contained in two different mine tailing samples (MT1 and MT2). It was observed that Al, Fe, and Mn were removed in 36.3±1.7, 191.2±1.6, and 4.5±0.2 mg/kg for MT1, and in 74.5±0.3, 208.3±0.5, and 20.9±0.1 for MT2. Besides, < 1.5 mg/kg of Au and Ru were also bioleached from MT1; in MT2, bioleaching of Zn was observed at 55.7±1.3 mg/kg, besides removal of < 1.5 mg/kg was observed for As, Ir, Li, and 0.6 for Os in this residue. These results show the potential of strain DSM 26636 for the bioleaching of metals that came from different mine tailings.

Keywords: A. thiooxidans, bioleaching, metals, mine tailings

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Authors: Suraj Muke, Vikas Mankumare, Sadhana Sathaye

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Osteoporosis is the most common metabolic bone disease which affects an estimated 25 million people worldwide, leading to 1 million fractures, 40,000 annual deaths and health costs of billions of dollars. It is estimated that about 80% of total osteoporosis patients are women, amongst which majority are above the age of 45 years. Postmenopausal osteoporosis is associated with lack of intestinal calcium absorption, increasing pro-oxidant and inflammatory mediators. Lawsonia inermis is a biennial dicotyledonous herbaceous shrub is reported to possess a high flavonoid, high phenolic and Inhibitors of osteoclastogenesis like Daphneside and Daphnorin. The present study aimed to screen osteoprotective effect of methanolic extract of Lawsonia inermis (LIM) in rat model along with its antioxidant activity. LIM shows phenolic content 146.3Milligrams of Gallic acid equivalent present per gram of extract and 19.8 Milligrams of rutin per gram of extract of Total flavonoid content with IC50 value 42.99μg/ml. bilateral ovariectomized rat model in which Healthy female wistar rats were used for screening. Treatment with LIM was carried out using graded doses of 25mg/kg, 50mg/kg and 100mg/kg for period of 28 days. The negative control group comprised of ovariectomized rats along with saline treatment for four weeks whereas sham operated rats were used as positive control.LIM showed a decrease in bone turnover by preventing loss of urinary calcium and phosphorous moreover it decreased the alkaline phosphatase levels and loss of bone density is prevented by LIM suggesting decrease in osteoclast activity.

Keywords: antioxidant, osteoclast, osteoporosis, ovariectomized

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Authors: D. Mowla, N. Rasti, P. Keshavarz

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Reduction of fossil fuels sources, increasing of pollution gases emission, and global warming effects increase the demand of renewable fuels. One of the main candidates of alternative fuels is biodiesel. Biodiesel limits greenhouse gas effects due to the closed CO₂ cycle. Biodiesel has more biodegradability, lower combustion emissions such as CO, SO_x, HC, PM and lower toxicity than petro diesel. However, biodiesel has high production cost due to high price of plant oils as raw material. So, the utilization of waste cooking oils (WCOs) as feedstock, due to their low price and disposal problems reduce biodiesel production cost. In this study, production of biodiesel by transesterification of methanol and WCO using modified sodic potassic (SP) clinoptilolite zeolite and sodic potassic calcic (SPC) clinoptilolite zeolite as heterogeneous catalysts have been investigated. These natural clinoptilolite zeolites were modified by KOH solution to increase the site activity. The optimum biodiesel yields for SP clinoptilolite and SPC clinoptilolite were 95.8% and 94.8%, respectively. Produced biodiesel were analyzed and compared with petro diesel and ASTM limits. The properties of produced biodiesel confirm well with ASTM limits. The density, kinematic viscosity, cetane index, flash point, cloud point, and pour point of produced biodiesel were all higher than petro diesel but its acid value was lower than petro diesel. Finally, the reusability and regeneration of catalysts were investigated. The results indicated that the spent zeolites cannot be reused directly for the transesterification, but they can be regenerated easily and can obtain high activity.

Keywords: biodiesel, renewable fuel, transesterification, waste cooking oil

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Authors: Agnieszka Stempniewicz, Piotr Ceranowicz, Wojciech Macyk, Jakub Cieszkowski, Beata Kuśnierz-Cabała, Katarzyna Gałązka, Zygmunt Warzecha

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Objectives: There are numerous strategies for the prevention or treatment of oral mucositis. However, their effectiveness is limited and does not correspond to expectations. Recent studies have shown that obestatin exhibits a protective effect and accelerates the healing of gastrointestinal mucosa. The aim of the present study was to examine the influence of obestatin administration on oral ulcers in rats. Methods: lingual ulcers were induced by the use of acetic acid. Rats were treated twice a day intraperitoneally with saline or obestatin(4, 8, or 16 nmol/kg/dose) for five days. The study determined: lingual mucosa morphology, cell proliferation, mucosal blood flow, and mucosal pro-inflammatory interleukin-1β level(IL-1β). Results: In animals without induction of oral ulcers, treatment with obestatin was without any effect. Obestatin administration in rats with lingual ulcers increased the healing rate of these ulcers. Obestatin given at the dose of 8 or 16 nmol/kg/dose caused the strongest and similar therapeutic effect. This result was associated with a significant increase in blood flow and cell proliferation in gingival mucosa, as well as a significant decrease in IL-1β level. Conclusions: Obestatin accelerates the healing of lingual ulcers in rats. This therapeutic effect is well-correlated with an increase in blood flow and cell proliferation in oral mucosa, as well as a decrease in pro-inflammatory IL-1β levels. Obestatin is a potentially useful candidate for the prevention and treatment of oral mucositis. Acknowledgment: Agnieszka Stempniewicz acknowledges the support of InterDokMed project no. POWR.03.02.00- 00-I013/16.

Keywords: oral mucositis, ulcers, obestatin, lingual mucosa

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Authors: Ekaterina S. Marchenko, Gulsharat A. Baigonakova, Kirill M. Dubovikov, Igor A. Khlusov

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NiTi alloys combine biomechanical and biochemical properties. This makes them a perfect candidate for medical applications. However, there is a serious problem with these alloys, such as the release of Ni from the matrix. Ni ions are known to be toxic to living tissues and leach from the matrix into the surrounding implant tissues due to corrosion after prolonged use. To prevent the release of Ni ions, corrosive strong coatings are usually used. Titanium nitride-based coatings are perfect corrosion inhibitors and also have good bioactive properties. However, there is an opportunity to improve the biochemical compatibility of the surface by depositing another layer. This layer can consist of elements such as calcium and phosphorus. The Ca and P ions form different calcium phosphate phases, which are present in the mineral part of human bones. We therefore believe that these elements must promote osteogenesis and osteointegration. In view of the above, the aim of this study is to investigate the effect of crystallinity on the biocompatibility of a two-layer coating deposited on NiTi substrate by sputtering. The first step of the research, apart from the NiTi polishing, is the layer-by-layer deposition of Ti-Ni-Ti by magnetron sputtering and the subsequent synthesis of this composite in an N atmosphere at 900 °C. The total thickness of the corrosion resistant layer is 150 nm. Plasma assisted RF sputtering was then used to deposit a bioactive film on the titanium nitride layer. A Ca-P powder target was used to obtain such a film. We deposited three types of Ca-P layers with different crystallinity and compared them in terms of cytotoxicity. One group of samples had no Ca-P coating and was used as a control. We obtained different crystallinity by varying the sputtering parameters such as bias voltage, plasma source current and pressure. XRD analysis showed that all coatings are calcium phosphate, but the sample obtained at maximum bias and plasma source current and minimum pressure has the most intense peaks from the coating phase. SEM and EDS showed that all three coatings have a homogeneous and dense structure without cracks and consist of calcium, phosphorus and oxygen. Cytotoxic tests carried out on three types of samples with Ca-P coatings and a control group showed that the control sample and the sample with Ca-P coating obtained at maximum bias voltage and plasma source current and minimum pressure had the lowest number of dead cells on the surface, around 11 ± 4%. Two other types of samples with Ca-P coating have 40 ± 9% and 21 ± 7% dead cells on the surface. It can therefore be concluded that these two sputtering modes have a negative effect on the corrosion resistance of the whole samples. The third sputtering mode does not affect the corrosion resistance and has the same level of cytotoxicity as the control. It can be concluded that the most suitable sputtering mode is the third with maximum bias voltage and plasma source current and minimum pressure.

Keywords: calcium phosphate coating, cytotoxicity, NiTi alloy, two-layer coating

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Authors: Raana Babadi Fathipour

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Tea, a beverage widely cherished across the globe, has captured the interest of scholars with its recent acknowledgement for possessing noteworthy health advantages. Of particular significance is its proven ability to ward off ailments such as cancer and cardiovascular afflictions. Moreover, within the realm of culinary creations, lipid oxidation poses a significant challenge for food product development. In light of these aforementioned concerns, this present discourse turns its attention towards exploring diverse methodologies employed in extracting polyphenols from various types of tea leaves and examining their utility within the vast landscape of the ever-evolving food industry. Based on the discoveries unearthed in this comprehensive investigation, it has been determined that the fundamental constituents of tea are polyphenols possessed of intrinsic health-enhancing properties. This includes an assortment of catechins, namely epicatechin, epigallocatechin, epicatechin gallate, and epigallocatechin gallate. Moreover, gallic acid, flavonoids, flavonols and theaphlavins have also been detected within this aromatic beverage. Of these myriad components examined vigorously in this study's analysis, catechin emerges as particularly beneficial. Multiple techniques have emerged over time to successfully extract key compounds from tea plants, including solvent-based extraction methodologies, microwave-assisted water extraction approaches and ultrasound-assisted extraction techniques. In particular, consideration is given to microwave-assisted water extraction method as a viable scheme which effectively procures valuable polyphenols from tea extracts. This methodology appears adaptable for implementation within sectors such as dairy production along with meat and oil industries alike.

Keywords: camellia sinensis, extraction, food application, shelf life, tea

Procedia PDF Downloads 53

Authors: M. Cabral, A. Verdin, G. Garçon, A. Touré, C. Diop, M. Fall, S. Bouhsina, D. Dewaele, F.Cazier, A. Tall Dia, P. Shirali, A. Diouf

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This case-control study dealt with the health adverse effects within the population neighboring the Mbeubeuss waste dump, which is located near the district of Malika (Diamalaye II) in Dakar (Senegal). All the household and industrial waste arising from Dakar are stored in this open landfill without being covered and are therefore possible sources of Pb and Cd contaminated air emissions and lixiviates. The objective of this study is part of improving the health of the population neighboring Mbeubeuss by determining Pb and Cd concentrations both in environment and humans, and studying possible renal function alterations within the adults. Soil and air samples were collected in the control site (Darou Salam) and the waste dump neighboring site (Diamalaye II). Control and exposed adults were recruited as living in Darou Salam (n = 52) and in Diamalaye II (n = 77). Pb and Cd concentrations in soil, air and biological samples were determined. Moreover, we were interested in analyzing some impregnation (zinc protoporphyrin, d-aminolevulinic acid dehydratase) and oxidative stress biomarkers (malonedialdehyde, gluthatione status), in addition to several nephrotoxicity parameters (creatinuria, proteinuria, lactate dehydrogenase, CC16 protein, glutathione S-transferase-alpha and retinol binding protein) in blood and/or urine. The results showed the significant Pb and Cd contamination of the soil and air samples derived from the landfill, and therefore of the neighboring population of adults. This critical exposure to environmental Pb and Cd had some harmful consequences for their health, as shown by the reported oxidative stress and nephrotoxicity signs.

Keywords: Pb and Cd environmental exposure, impregnation markers, landfill, nephrotoxicity markers

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Authors: Mustafa Salman, Nurcan Cetinkaya, Zehra Selcuk, Bugra Genc

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The objectives of the present study were to estimate the microbial-N flow to the small intestine and to predict the digestible organic matter intake (DOMI) in grazing Karayaka sheep based on urinary excretion of purine derivatives (xanthine, hypoxanthine, uric acid, and allantoin) by the use of spot urine sampling under field conditions. In the trial, 10 Karayaka sheep from 2 to 3 years of age were used. The animals were grazed in a pasture for ten months and fed with concentrate and vetch plus oat hay for the other two months (January and February) indoors. Highly significant linear and cubic relationships (P<0.001) were found among months for purine derivatives index, purine derivatives excretion, purine derivatives absorption, microbial-N and DOMI. Through urine sampling and the determination of levels of excreted urinary PD and Purine Derivatives / Creatinine ratio (PDC index), microbial-N values were estimated and they indicated that the protein nutrition of the sheep was insufficient. In conclusion, the prediction of protein nutrition of sheep under the field conditions may be possible with the use of spot urine sampling, urinary excreted PD and PDC index. The mean purine derivative levels in spot urine samples from sheep were highest in June, July and October. Protein nutrition of pastured sheep may be affected by weather changes, including rainfall. Spot urine sampling may useful in modeling the feed consumption of pasturing sheep. However, further studies are required under different field conditions with different breeds of sheep to develop spot urine sampling as a model.

Keywords: Karayaka sheep, spot sampling, urinary purine derivatives, PDC index, microbial-N, feed intake

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Authors: Srinivasa Reddy Mallampati, Chi-Hyeon Lee, Nguyen Thanh Truc, Byeong-Kyu Lee

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Organic polymeric materials (plastics) are widely used in our daily life and various industrial fields. The separation of waste plastics is important for its feedstock and mechanical recycling. One of the major problems in incineration for thermal recycling or heat melting for material recycling is the polyvinyl chloride (PVC) contained in waste plastics. This is due to the production of hydrogen chloride, chlorine gas, dioxins, and furans originated from PVC. Therefore, the separation of PVC from waste plastics is necessary before recycling. The separation of heavy polymers (PVC 1.42, PMMA 1.12, PC 1.22 and PET 1.27 g/cm3 ) from light ones (PE and PP 0.99 g/cm3) can be achieved on the basis of their density. However it is difficult to separate PVC from other heavy polymers basis of density. There are no simple and inexpensive techniques to separate PVC from others. If hydrophobic the PVC surface is selectively changed into hydrophilic, where other polymers still have hydrophobic surface, flotation process can separate PVC from others. In the present study, the selective surface hydrophilization of polyvinyl chloride (PVC) by microwave treatment after alkaline/acid washing and with activated carbon was studied as the pre-treatment of its separation by the following froth flotation. In presence of activated carbon as absorbent, the microwave treatment could selectively increase the hydrophilicity of the PVC surface (i.e. PVC contact angle decreased about 19o) among other plastics mixture. At this stage, 100% PVC separation from other plastics could be achieved by the combination of the pre- microwave treatment with activated carbon and the following froth floatation. The hydrophilization of PVC by surface analysis would be due to the hydrophilic groups produced by microwave treatment with activated carbon. The effect of optimum condition and detailed mechanism onto separation efficiency in the froth floatation was also investigated.

Keywords: Hydrophilic, PVC, contact angle, additive, microwave, froth floatation, waste plastics

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Authors: Eric Beyegue, Boris Azantza, Judith Laure Ngondi, Julius E. Oben

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Background: It is clearly that phytochemical constituents of plants in relation exhibit free radical scavenging, antioxidant and glycosylation properties. This study investigated the in vitro antioxidant and free radical scavenging, inhibited activities against α-amylase and invertase enzymes of stem bark extracts C. edulis (Olacaceae). Methods: Four extracts (hexane, dichloromethane, ethanol and aqueous) from the barks of C. edulis were used in this study. Colorimetric in vitro methods were using for evaluate free radical scavenging activity DPPH, ABTS, NO, OH, antioxidant capacity, glycosylation activity, inhibition of α-amylase and invertase activities, phenolic, flavonoid and alkaloid contents. Results: C. edulis extracts (CEE) had a higher scavenging potential on the 2, 2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl (OH), nitrite oxide (NO), 2, 2-azinobis (3-ethylbenzthiazoline)-6-sulfonic acid (ABTS) radicals and glucose scavenging with the IC50 varied between 41.95 and 36694.43 µg/ml depending on the solvent of extraction. The ethanol extract of C. edulis stem bark (CE EtOH) showed the highest polyphenolic (289.10 + 30.32), flavonoid (1.12 + 0.09) and alkaloids (18.47 + 0.16) content. All the tested extracts demonstrated a relative high inhibition potential against α-amylase and invertase digestive enzymes activities. Conclusion: This study suggests that CEE exhibited higher antioxidant potential and significant inhibition potential against digestive enzymes.

Keywords: Coula edulis, antioxidant, scavenging activity, amylase, invertase

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Authors: Sudhir Kumar, V. R. Sinha

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Water in oil topical microemulsions of 5-FU were developed and optimized using face centered central composite design. Topical w/o microemulsion of 5-FU were prepared using sorbitan monooleate (Span 80), polysorbate 80 (Tween 80), with different oils such as oleic acid (OA), triacetin (TA), and isopropyl myristate (IPM). The ternary phase diagrams designated the microemulsion region and face centered central composite design helped in determining the effects of selected variables viz. type of oil, smix ratio and water concentration on responses like drug content, globule size and viscosity of microemulsions. The CCD design exhibited that the factors have statistically significant effects (p<0.01) on the selected responses. The actual responses showed excellent agreement with the predicted values as suggested by the CCD with lower residual standard error. Similarly, the optimized values were found within the range as predicted by the model. Furthermore, other characteristics of microemulsions like pH, conductivity were investigated. For the optimized microemulsion batch, ex-vivo skin flux, skin irritation and retention studies were performed and compared with marketed 5-FU formulation. In ex vivo skin permeation studies, higher skin retention of drug and minimal flux was achieved for optimized microemulsion batch then the marketed cream. Results confirmed the actual responses to be in agreement with predicted ones with least residual standard errors. Controlled release of drug was achieved for the optimized batch with higher skin retention of 5-FU, which can further be utilized for the treatment of many dermatological disorders.

Keywords: 5-FU, central composite design, microemulsion, ternanry phase diagram

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Authors: Syed Farooq Adil, Merajuddinkhan, Mujeeb Khan, Hamad Z. Alkhathlan

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Phytochemicals from plant extracts belong to an important source of natural products which have demonstrated excellent cytotoxic activities. However, plants of different origins exhibit diverse chemical compositions and bioactivities. Therefore, the discovery of plants based new anticancer agents from different parts of the world is always challenging. In this study, methanolic extracts of different parts of 11 plants from Saudi Arabia have been tested in vitro for their anticancer potential on human liver cancer cell line (HepG2). Particularly, for this study, plants from Asteraceae, Resedaceae, and Polygonaceae families were chosen on the basis of locally available ethnobotanical data and their medicinal properties. Among 12 tested extract samples, three samples obtained from Artemisia monosperma stem, Ochradenus baccatus aerial parts, and Pulicaria glutinosa stem have demonstrated interesting cytotoxic activities with a cell viability of 29.3%, 28.4% and 24.2%, respectively. Whereas, four plant extracts including Calendula arvensis aerial parts, Scorzonera musilii whole plant, A. monosperma leaves show moderate anticancer properties bearing a cell viability ranging from 11.9 to 16.7%. The remaining extracts have shown poor cytotoxic activities. Subsequently, GC-MS analysis of methanolic extracts of the four most active plants extracts such as C. comosum, O. baccatus, P. glutinosa and A. monosperma detected the presence of 41 phytomolecules. Among which 3-(4-hydroxyphenyl) propionitrile (1), 8,11-octadecadiynoic acid methyl ester (2), 6,7-dimethoxycoumarin (3), and 1-(2-hydroxyphenyl) ethenone (4) were found to be the lead compounds of C. comosum, O. baccatus P. glutinosa and A. monosperma, respectively.

Keywords: medicinal plants, asteraceae, polygonaceae, hepg2

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Authors: Faraidoon Rahmanzai, Mizuki Takigawa, Yu Bomura, Shigeyuki Date

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To obtain the high quality and essential workability of mortar, different types of superplasticizers are used. The superplasticizers are the chemical admixture used in the mix to improve the fluidity of mortar. Many factors influenced the superplasticizer to disperse the cement particle in the mortar. Nature and amount of replaced cement by slag, mixing procedure, delayed addition time, and heat stimulation technique of superplasticizer cause the varied effect on the fluidity of the cementitious material. In this experiment, the superplasticizers were heated for 1 hour under 60 °C in a thermostatic chamber. Furthermore, the effect of delayed addition time of heat stimulated superplasticizers (SP) was also analyzed. This method was applied to two types of polycarboxylic acid based ether SP (precast type superplasticizer (SP2) and ready-mix type superplasticizer (SP1)) in combination with a partial replacement of normal Portland cement with blast furnace slag (BFS) with 30% w/c ratio. On the other hands, the fluidity, air content, fresh density, and compressive strength for 7 and 28 days were studied. The results indicate that the addition time and heat stimulation technique improved the flow and air content, decreased the density, and slightly decreased the compressive strength of mortar. Moreover, the slag improved the flow of mortar by increasing the amount of slag, and the effect of external temperature of SP on the flow of mortar was decreased. In comparison, the flow of mortar was improved on 5-minute delay for both kinds of SP, but SP1 has improved the flow in all conditions. Most importantly, the transition points in both types of SP appear to be the same, at about 5±1 min.  In addition, the optimum addition time of SP to mortar should be in this period.

Keywords: combined effect, delay addition, heat stimulation, flow of mortar

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Authors: Nabiha Bouafia, Asma Ben Cheikh, Asma Ammar, Olfa Ezzi, Mohamed Mahjoub, Khaoula Meddeb, Imed Chouchene, Hamadi Boussarsar, Mansour Njah

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Background: Hospital acquired infections (HAI) cause significant morbidity, mortality, length of stay and hospital costs, especially in the intensive care unit (ICU), because of the debilitated immune systems of their patients and exposure to invasive devices. The aims of this study were to determine the rate and the risk factors of HAI in an ICU of a university hospital in Tunisia. Materials/Methods: A prospective study was conducted in the 8-bed adult medical ICU of a University Hospital (Sousse Tunisia) during 14 months from September 15th, 2015 to November 15th, 2016. Patients admitted for more than 48h were included. Their surveillance was stopped after the discharge from ICU or death. HAIs were defined according to standard Centers for Disease Control and Prevention criteria. Risk factors were analyzed by conditional stepwise logistic regression. The p-value of < 0.05 was considered significant. Results: During the study, 192 patients had admitted for more than 48 hours. Their mean age was 59.3± 18.20 years and 57.1% were male. Acute respiratory failure was the main reason of admission (72%). The mean SAPS II score calculated at admission was 32.5 ± 14 (range: 6 - 78). The exposure to the mechanical ventilation (MV) and the central venous catheter were observed in 169 (88 %) and 144 (75 %) patients, respectively. Seventy-three patients (38.02%) developed 94 HAIs. The incidence density of HAIs was 41.53 per 1000 patient day. Mortality rate in patients with HAIs was 65.8 %( n= 48). Regarding the type of infection, Ventilator Associated Pneumoniae (VAP) and central venous catheter Associated Infections (CVC AI) were the most frequent with Incidence density: 14.88/1000 days of MV for VAP and 20.02/1000 CVC days for CVC AI. There were 5 Peripheral Venous Catheter Associated Infections, 2 urinary tract infections, and 21 other HAIs. Gram-negative bacteria were the most common germs identified in HAIs: Multidrug resistant Acinetobacter Baumanii (45%) and Klebsiella pneumoniae (10.96%) were the most frequently isolated. Univariate analysis showed that transfer from another hospital department (p= 0.001), intubation (p < 10-4), tracheostomy (p < 10-4), age (p=0.028), grade of acute respiratory failure (p=0.01), duration of sedation (p < 10-4), number of CVC (p < 10-4), length of mechanical ventilation (p < 10-4) and length of stay (p < 10-4), were associated to high risk of HAIS in ICU. Multivariate analysis reveals that independent risk factors for HAIs are: transfer from another hospital department: OR=13.44, IC 95% [3.9, 44.2], p < 10-4, duration of sedation: OR= 1.18, IC 95% [1.049, 1.325], p=0.006, high number of CVC: OR=2.78, IC 95% [1.73, 4.487], p < 10-4, and length of stay in ICU: OR= 1.14, IC 95% [1.066,1.22], p < 10-4. Conclusion: Prevention of nosocomial infections in ICUs is a priority of health care systems all around the world. Yet, their control requires an understanding of epidemiological data collected in these units.

Keywords: healthcare associated infections, incidence, intensive care unit, risk factors

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Authors: Indu Barwal, Shloka Thakur, Subhash C. Yadav

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The plant virus capsid protein based nanoparticles are extensively studied for their application in biomedical research for development of nanomedicines and drug delivery systems. We have developed a chimeric drug delivery system by controlled in vitro assembly of separately bioconjugated fluorescent dye (as reporting molecule), folic acid (as receptor binding biomolecule for targeted delivery) and doxorubicin (as anticancer drug) using modified EDC NHS chemistry on heterologously overexpressed (E. coli) capsid proteins of cowpea chlorotic mottle virus (CCMV). This chimeric vehicle was further encapsidated on gold nanoparticles (20nm) coated with 5≠ thiolated DNA probe to neutralize the positive charge of capsid proteins. This facilitates the in vitro assembly of modified capsid subunits on the gold nanoparticles to develop chimeric GNPs encapsidated targeted drug delivery system. The bioconjugation of functionalities, number of functionality on capsid subunits as well as virus like nanoparticles, structural stability and in vitro assembly were confirmed by SDS PAGE, relative absorbance, MALDI TOF, ESI-MS, Circular dichroism, intrinsic tryptophan fluorescence, zeta particle size analyzer and TEM imaging. This vehicle was stable at pH 4.0 to 8.0 suitable for many organelles targeting. This in vitro assembled chimeric plant virus like particles could be suitable for ideal drug delivery vehicles for subcutaneous cancer treatment and could be further modified for other type of cancer treatment by conjugating other functionalities (targeting, drug) on capsids.

Keywords: chimeric drug delivery vehicles, bioconjugated plant, virus, capsid

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Authors: M. Szechynska-Hebda, M. Sobczak, E. Rozanska, J. Troczynska, Z. Banaszak, N. Hordyńska, M. Dyda, M. Wedzony

Abstract:

Chloroplasts, as essential organelles for photosynthesis, play a critical role in plant development. However, disturbances in the proper functioning of chloroplasts, in the extreme case manifesting as albinism of tissues and whole plants, are a phenomenon often occurring in conditions deviating from natural (e.g., in vitro cultures applied in breeding programs). Using whole-transcriptome analysis (RNA-Seq) together with light, fluorescent and electron microscopy, it was shown, that development of chloroplasts and formation of green or albino plants in the androgenesis process are genotype-dependent; however, they could be modulated by sub-optimal temperature treatment. The reprogramming of the microspore development from gametophytic to sporophytic, and then regeneration of green plant can be positively regulated by cold stress (4 ⁰C). A high temperature stress (32 ⁰C) can induce androgenesis, but it is a factor negatively influencing green plant regeneration (promoting albinism). A similar effect on microspores, androgenesis, and subsequent chloroplast formation, is elicited as a result of postponing the date of spike collection from spring to summer in field conditions (natural temperature rise). It is determined in both environmental or genotypic manner. The delay of the sowing date (environmental effect) or growing of late genotypes (genotypic effect) result in spike maturation at higher temperatures and significantly enhance albino plant formation in androgenesis process. Such a temperature system (4 ⁰C vs. 32 ⁰C) was used to study the chloroplast biogenesis process in wheat and triticale. It was shown, that efficiency of physiological processes differentiates microspore development during cold reprograming in genotypes susceptible and resistant to androgenesis. Moreover, a great variation in developmental stages of the microspores in one anther is observed for susceptible genotypes. Microspores that are more physiologically active under cold conditions can activate signaling pathways and processes, which provide an appropriate supply of metabolites to cell compartments. This, in turn, fully correlates with the genotype-dependent efficiency of chloroplast formation (or different types of plastid) at particular steps of androgenesis. The effect obtained after applying a high temperature stress is different. High temperature causes a significant acceleration of microspore development and less variation in developmental stages at the end of the treatment. Therefore, the developmental diversity of the microspores in one anther seems to be a critical factor for subsequent cell and chloroplast differentiation. The work was financed by Ministry of Agriculture and Rural Development within Program: 'Biological Progress in Plant Production', project no HOR.hn.802.15.2018

Keywords: androgenesis, chloroplast biogenesis, temperature stress, wheat

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Authors: Carolina V. Viegas, Monique Gonçalves, Gisel Chenard Diaz, Yordanka Reyes Cruz, Donato Alexandre Gomes Aranda

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To develop the massive cultivation of microalgae, it is necessary to isolate and characterize the species, improving genetic tools in search of specific characteristics. Therefore, the detection, identification and quantification of the compounds that compose the Scenedesmus sp. were prerequisites to verify the potential of these microalgae. The main objective of this work was to carry out the characterization of Scenedesmus sp. as to the content of ash, carbohydrates, proteins and lipids as well as the determination of the composition of their lipid classes and main fatty acids. The biomass of Scenedesmus sp, showed 15,29 ± 0,23 % of ash and CaO (36,17 %) was the main component of this fraction, The total protein and carbohydrate content of the biomass was 40,74 ± 1,01 % and 23,37 ± 0,95 %, respectively, proving to be a potential source of proteins as well as carbohydrates for the production of ethanol via fermentation, The lipid contents extracted via Bligh & Dyer and in situ saponification were 8,18 ± 0,13 % and 4,11 ± 0,11 %, respectively. In the lipid extracts obtained via Bligh & Dyer, approximately 50 % of the composition of this fraction consists of fatty compounds, while the other half is composed of an unsaponifiable fraction composed mainly of chlorophylls, phytosterols and carotenes. From the lowest yield, it was possible to obtain a selectivity of 92,14 % for fatty components (fatty acids and fatty esters) confirmed through the infrared spectroscopy technique. The presence of polyunsaturated acids (~45 %) in the lipid extracts indicated the potential of this fraction as a source of nutraceuticals. The results indicate that the biomass of Scenedesmus sp, can become a promising potential source for obtaining polyunsaturated fatty acids, carotenoids and proteins as well as the simultaneous obtainment of different compounds of high commercial value.

Keywords: microalgae, Desmodesmus, lipid classes, fatty acid profile, proteins, carbohydrates

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Authors: Naziema Begum Jappie

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Leadership and entrepreneurship in higher education have become critical components in navigating the evolving landscape of academia in the 21st century. This abstract explores the multifaceted relationship between leadership and entrepreneurship within the realm of higher education, emphasizing their roles in fostering innovation and sustainability. Higher education institutions, often characterized as slow-moving and resistant to change, are facing unprecedented challenges. Globalization, rapid technological advancements, changing student demographics, and financial constraints necessitate a reimagining of traditional models. Leadership in higher education must embrace entrepreneurial thinking to effectively address these challenges. Entrepreneurship in higher education involves cultivating a culture of innovation, risk-taking, and adaptability. Visionary leaders who promote entrepreneurship within their institutions empower faculty and staff to think creatively, seek new opportunities, and engage with external partners. These entrepreneurial efforts lead to the development of novel programs, research initiatives, and sustainable revenue streams. Innovation in curriculum and pedagogy is a central aspect of leadership and entrepreneurship in higher education. Forward-thinking leaders encourage faculty to experiment with teaching methods and technology, fostering a dynamic learning environment that prepares students for an ever-changing job market. Entrepreneurial leadership also facilitates the creation of interdisciplinary programs that address emerging fields and societal challenges. Collaboration is key to entrepreneurship in higher education. Leaders must establish partnerships with industry, government, and non-profit organizations to enhance research opportunities, secure funding, and provide real-world experiences for students. Entrepreneurial leaders leverage their institutions' resources to build networks that extend beyond campus boundaries, strengthening their positions in the global knowledge economy. Financial sustainability is a pressing concern for higher education institutions. Entrepreneurial leadership involves diversifying revenue streams through innovative fundraising campaigns, partnerships, and alternative educational models. Leaders who embrace entrepreneurship are better equipped to navigate budget constraints and ensure the long-term viability of their institutions. In conclusion, leadership and entrepreneurship are intertwined elements essential to the continued relevance and success of higher education institutions. Visionary leaders who champion entrepreneurship foster innovation, enhance the student experience, and secure the financial future of their institutions. As academia continues to evolve, leadership and entrepreneurship will remain indispensable tools in shaping the future of higher education. This abstract underscores the importance of these concepts and their potential to drive positive change within the higher education landscape.

Keywords: entrepreneurship, higher education, innovation, leadership

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Authors: Surbhi Aggarwal, Jaishree Paul

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Background: Role of GABA has been implicated in autoimmune diseases like multiple sclerosis, type1 diabetes and rheumatoid arthritis where they modulate the immune response but role in gut inflammation has not been defined. Ulcerative colitis (UC) and diarrhoeal predominant irritable bowel syndrome (IBS-D) both involve inflammation of gastrointestinal tract. UC is a chronic, relapsing and idiopathic inflammation of gut. IBS is a common functional gastrointestinal disorder characterised by abdominal pain, discomfort and alternating bowel habits. Mild inflammation is known to occur in IBS-D. Aim: Aim of this study was to investigate the role of GABA in UC as well as in IBS-D. Materials and methods: Blood and biopsy samples from UC, IBS-D and controls were collected. ELISA was used for measuring level of GABA in serum of UC, IBS-D and controls. RT-PCR analysis was done to determine GABAergic signal system in colon biopsy of UC, IBS-D and controls. RT-PCR was done to check the expression of proinflammatory cytokines. CurveExpert 1.4, Graphpad prism-6 software were used for data analysis. Statistical analysis was done by unpaired, two-way student`s t-test. All sets of data were represented as mean± SEM. A probability level of p < 0.05 was considered statistically significant. Results and conclusion: Significantly decreased level of GABA and altered GABAergic signal system was detected in UC and IBS-D as compared to controls. Significantly increased expression of proinflammatory cytokines was also determined in UC and IBS-D as compared to controls. Hence we conclude that insufficient level of GABA in UC and IBS-D leads to overproduction of proinflammatory cytokines which further contributes to inflammation. GABA may be used as a promising therapeutic target for treatment of gut inflammation or other inflammatory diseases.

Keywords: diarrheal predominant irritable bowel syndrome, γ-aminobutyric acid (GABA), inflammation, ulcerative colitis

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Authors: Zh. Saffari, A. Naeimi, M. S. Ekrami-Kakhki, F. Hamidi

Abstract:

Fe3O4 is one of the important magnetic oxides with spinel structure; it has exhibited unique electric and magnetic properties based on the electron transfer between Fe2+ and Fe3+ in the octahedral sites. Fe3O4 has received considerable attention in various areas such as cancer therapy, drug targeting, enzyme immobilization catalysis, magnetic cell separation, magnetic refrigeration systems and super-paramagnetic materials Fe3O4–TiO2 nanostructures were synthesized by simple, effective and new co-precipitation method assisted by ultrasonic reaction at room temperatures with organic surfactant. The effect of various parameters such as temperature, time, and power on the size and morphology of the product was investigated. Alternating gradient force magnetometer shows that Fe3O4 nanoparticles exhibit super-paramagnetic behaviour at room temperature. For preparation of nanocomposite, 1 g of TiO2 nanostructures were dispersed in 100 mL of ethanol. 0.25 g of Fe(NO3)2 and 2 mL of octanoic acid was added to the solution as a surfactant. Then, NaOH solution (1.5 M) was slowly added into the solution until the pH of the mixture was 7–8. After complete precipitation, the solution placed under the ultrasonic irradiation for 30 min. The product was centrifuged, washed with distilled water and dried in an oven at 100 °C for 3 h. The resulting red powder was calcinated at 800 °C for 3 h to remove any organic residue. The photocatalytic behaviour of Fe3O4–TiO2 nanoparticles was evaluated using the degradation of a Methyl Violet (MV) aqueous solution under ultraviolet light irradiation. As time increased, more and more MV was adsorbed on the nanoparticles catalyst, until the absorption peak vanish. The MV concentration decreased rapidly with increasing UV-irradiation time

Keywords: magnetic, methyl violet, nanocomposite, photocatalytic

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Authors: Sthephanie A. Colmenares, Fabio A. Rojas, Pablo A. Arbeláez, Johann F. Osma, Diana Narvaez

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The loss of functional tissue is a ubiquitous and expensive health care problem, with very limited treatment options for these patients. The golden standard for large bone damage is a cadaveric bone as an allograft with stainless steel support; however, this solution only applies to bones with simple morphologies (long bones), has a limited material supply and presents long term problems regarding mechanical strength, integration, differentiation and induction of native bone tissue. Therefore, the fabrication of a scaffold with biological, physical and chemical properties similar to the human bone with a fabrication method for morphology manipulation is the focus of this investigation. Towards this goal, an alginate and coral matrix was created using two production techniques; the coral was chosen because of its chemical composition and the alginate due to its compatibility and mechanical properties. In order to construct the coral alginate scaffold the following methodology was employed; cleaning of the coral, its pulverization, scaffold fabrication and finally the mechanical and biological characterization. The experimental design had: mill method and proportion of alginate and coral, as the two factors, with two and three levels each, using 5 replicates. The coral was cleaned with sodium hypochlorite and hydrogen peroxide in an ultrasonic bath. Then, it was milled with both a horizontal and a ball mill in order to evaluate the morphology of the particles obtained. After this, using a combination of alginate and coral powder and water as a binder, scaffolds of 1cm3 were printed with a SpectrumTM Z510 3D printer. This resulted in solid cubes that were resistant to small compression stress. Then, using a ESQUIM DP-143 silicon mold, constructs used for the mechanical and biological assays were made. An INSTRON 2267® was implemented for the compression tests; the density and porosity were calculated with an analytical balance and the biological tests were performed using cell cultures with VERO fibroblast, and Scanning Electron Microscope (SEM) as visualization tool. The Young’s moduli were dependent of the pulverization method, the proportion of coral and alginate and the interaction between these factors. The maximum value was 5,4MPa for the 50/50 proportion of alginate and horizontally milled coral. The biological assay showed more extracellular matrix in the scaffolds consisting of more alginate and less coral. The density and porosity were proportional to the amount of coral in the powder mix. These results showed that this composite has potential as a biomaterial, but its behavior is elastic with a small Young’s Modulus, which leads to the conclusion that the application may not be for long bones but for tissues similar to cartilage.

Keywords: alginate, biomaterial, bone engineering, coral, Porites asteroids, SEM

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Authors: Leila Najafian

Abstract:

Sarcoplasmic protein hydrolysates (SPHs) and myofibrillar protein hydrolysates (MPHs) from patin (Pangasius sutchi) were produced using two types of proteases: Papain and Alcalase. 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS) radical scavenging activities and metal chelating activity assays for antioxidant activities were carried out on the SPHs and MPHs. The hydrolysates were isolated and purified by ultrafiltration, gel filtration and reverse phase high-performance liquid chromatography (RP-HPLC) and liquid chromatography with tandem mass spectrometry detection (LC-MS/MS) was used in identifying peptide sequences. The results showed that when the DH of MPHs increased, the protein solubility increased, while the highest amount of the protein solubility of SPHs was after 60 min incubation. The effect of DH on antioxidant activities of SPHs and MPHs was investigated. Among the hydrolysates, papain-MPH and Alcalase-SPH, which had the highest antioxidant activities, were purified. The potent fractions obtained from RP-HPLC of sarcoplasmic (SI 3 fraction) and myofibrillar (MI 4 fraction) hydrolysates showed the highest DPPH radical scavenging activity. The FVNQPYLLYSVHMK peptide for MPH and the LVVDIPAALQHA peptide for SPH exhibited the highest antioxidant activity. The presence of hydrophobic and hydrophilic amino acids, namely leucine (L), valine (V), phenylalanine (F), histidine (H) and proline (P), in the peptide sequences of SPH and MPH are believed to contribute to high antioxidant activity. Hence, SPH and MPH from patin have the potential as a natural functional ingredient in food and pharmaceutical industry.

Keywords: patin (Pangasius sutchi), protein hydrolysates, antioxidative peptides, mass spectrometry

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Authors: Syed Asif Hassan, Tabrej Khan

Abstract:

Tuberculosis (TB) caused by bacillus Mycobacterium tuberculosis (Mtb) continues to take a disturbing toll on human life and healthcare facility worldwide. The global burden of TB remains enormous. The alarming rise of multi-drug resistant strains of Mycobacterium tuberculosis calls for an increase in research efforts towards the development of new target specific therapeutics against diverse strains of M. tuberculosis. Therefore, the discovery of new molecular scaffolds targeting new drug sites should be a priority for a workable plan for fighting resistance in Mycobacterium tuberculosis (Mtb). Mtb non-acylated lipoprotein LprG (Rv1411c) has a Toll-like receptor 2 (TLR2) agonist actions that depend on its association with triacylated glycolipids binding specifically with the hydrophobic pocket of Mtb LprG lipoprotein. The detection of a glycolipid carrier function has important implications for the role of LprG in Mycobacterial physiology and virulence. Therefore, considering the pivotal role of glycolipids in mycobacterial physiology and host-pathogen interactions, designing competitive antagonist (chemotherapeutics) ligands that competitively bind to glycolipid binding domain in LprG lipoprotein, will lead to inhibition of tuberculosis infection in humans. In this study, a unified approach involving ligand-based virtual screening protocol USRCAT (Ultra Shape Recognition) software and molecular docking studies using Auto Dock Vina 1.1.2 using the X-ray crystal structure of Mtb LprG protein was implemented. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the Ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has the higher hypothetical affinity, also has greater negative value. Based on the USRCAT, Lipinski’s values and molecular docking results, [(2R)-2,3-di(hexadecanoyl oxy)propyl][(2S,3S,5S,6R)-3,4,5-trihydroxy-2,6-bis[[(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6 (hydroxymethyl)tetrahydropyran-2-yl]oxy]cyclohexyl] phosphate (XPX) was confirmed as a promising drug-like lead compound (antagonist) binding specifically to the hydrophobic domain of LprG protein with affinity greater than that of PIM2 (agonist of LprG protein) with a free binding energy of -9.98e+006 Kcal/mol and binding affinity of -132 Kcal/mol, respectively. A further, in vitro assay of this compound is required to establish its potency in inhibiting molecular evasion mechanism of MTB within the infected host macrophages. These results will certainly be helpful in future anti-TB drug discovery efforts against Multidrug-Resistance Tuberculosis (MDR-TB).

Keywords: antagonist, agonist, binding affinity, chemotherapeutics, drug-like, multi drug resistance tuberculosis (MDR-TB), RV1411c protein, toll-like receptor (TLR2)

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Authors: Shadia Al-Bahlani, Khadija Al-Bulushi, Zuweina Al-Hadidi, Buthaina Al-Dhahl, Nadia Al-Abri

Abstract:

Breast cancer is the most common cancer in women worldwide. Triple-Negative Breast Cancer (TNBC) is an aggressive type of breast cancer, which is defined by the absence of Estrogen (ER), Progesterone (PR) and human epidermal growth factor (Her-2) receptors. The calpain system plays an important role in many cellular processes including apoptosis, necrosis, cell signaling and proliferation. However, the role of calpain in cisplatin (CDDP)-induced apoptosis in TNBC cells is not fully understood. Here, TNBC (MDA-MB231) cells were treated with different concentration of CDDP (0, 20 & 40 µM) and calpain activation and apoptosis were measured by western blot and Hoechst Stain respectively. In addition, calpain modulation by either activation and/or inhibition and its effect on CDDP-induced apoptosis were assessed by the same above approaches. Our findings showed that CDDP induced endoplasmic reticulum stress and thus Calcium release and subsequently activate calpain α-fodrin cleavage indicated by the increase in GRP78 and Calmodulin protein expression and respectively in MDA-MB231 cells. It also induced apoptosis as measured by Hoechst stain and caspase-12 cleavage. Calpain activation by both Cyclopiazonic acid and Thapsigargin showed similar effect and enhanced the sensitivity of these cells to CDDP treatment. On the other hand, calpain inhibition by either specific siRNA and/or exogenous inhibitor (Calpeptin) had an adverse effect where it attenuated calpain activation and thus CDDP- induced apoptosis in these cells. Altogether, these findings suggested that calpain activation play an essential role in sensitizing the TNBC cells to CDDP-induced apoptosis. This might lead to the discovery of novel treatment to over this aggressive type of breast cancer.

Keywords: calpain, cisplatin, apoptosis, breast cancer

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Authors: Khin Thanda Win, Chunying Zhang, Sanghyeob Lee

Abstract:

Mildew resistance locus o (Mlo), a plant-specific gene family with seven-transmembrane (TM), plays an important role in plant resistance to powdery mildew (PM). PM caused by Podosphaera xanthii is a widespread plant disease and probably represents the major fungal threat for many Cucurbits. The recent Cucurbita maxima genome sequence data provides an opportunity to identify and characterize the MLO gene family in this species. Total twenty genes (designated CmaMLO1 through CmaMLO20) have been identified by using an in silico cloning method with the MLO gene sequences of Cucumis sativus, Cucumis melo, Citrullus lanatus and Cucurbita pepo as probes. These CmaMLOs were evenly distributed on 15 chromosomes of 20 C. maxima chromosomes without any obvious clustering. Multiple sequence alignment showed that the common structural features of MLO gene family, such as TM domains, a calmodulin-binding domain and 30 important amino acid residues for MLO function, were well conserved. Phylogenetic analysis of the CmaMLO genes and other plant species reveals seven different clades (I through VII) and only clade IV is specific to monocots (rice, barley, and wheat). Phylogenetic and structural analyses provided preliminary evidence that five genes belonged to clade V could be the susceptibility genes which may play the importance role in PM resistance. This study is the first comprehensive report on MLO genes in C. maxima to our knowledge. These findings will facilitate the functional analysis of the MLOs related to PM susceptibility and are valuable resources for the development of disease resistance in pumpkin.

Keywords: Mildew resistance locus o (Mlo), powdery mildew, phylogenetic relationship, susceptibility genes

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Authors: Mumuni Sumaila, Viness Pillay, Yahya E. Choonara, Pradeep Kumar, Pierre P. Kondiah

Abstract:

Tuberculosis (TB) remains a serious challenge to public health globally, despite every effort put together to curb the disease. Current TB therapeutics available have proven to be inefficient due to a multitude of drawbacks that range from serious adverse effects/drug toxicity to inconsistent bioavailability, which ultimately contributes to the emergence of drug-resistant TB. An effective ‘cargo’ system designed to cleverly deliver therapeutic doses of anti-TB drugs to infection sites and in a sustained-release manner may provide a better therapeutic choice towards winning the war against TB. In the current study, we investigated mannose-functionalized lipopolysaccharide hybrid nanoparticles for safety and efficacy towards macrophage-targeted simultaneous delivery of the two first-line anti-TB drugs, rifampicin (RF) and isoniazid (IS). RF-IS-loaded lipopolysaccharide hybrid nanoparticles were fabricated using the solvent injection technique (SIT), incorporating soy lecithin (SL) and low molecular weight chitosan (CS) as the lipid and polysaccharide components, respectively. Surface-functionalized nanoparticles were obtained through the reaction of the aldehyde group of mannose with free amine functionality present at the surface of the nanoparticles. The functionalized nanocarriers were spherical with average particle size and surface charge of 107.83 nm and +21.77 mV, respectively, and entrapment efficiencies (EE) were 53.52% and 69.80% for RF and IS, respectively. FTIR spectrum revealed high-intensity bands between 1663 cm⁻¹ and 1408 cm⁻¹ wavenumbers (absent in non-functionalized nanoparticles), which could be attributed to the C=N stretching vibration produced by the formation of Schiff’s base (–N=CH–) during the mannosylation reaction. In vitro release studies showed a sustained-release profile for RF and IS, with less than half of the total payload released over a 48-hour period. The nanocarriers were biocompatible and safe, with more than 80% cell viability achieved when incubated with RAW 264.7 cells at concentrations 30 to 500 μg/mL over a 24-hour period. Cellular uptake studies (after a 24-hour incubation period with the murine macrophage cells, RAW 264.7) revealed a 13- and a 9-fold increase in intracellular accumulation of RF and IS, respectively, when compared with the unformulated RF+IS solution. A 6- and a 3-fold increase in intracellular accumulation of RF and IS, respectively, were observed when compared with the non-functionalized nanoparticles. Furthermore, fluorescent microscopy images showed nanoparticle internalization and accumulation within the RAW 264.7 cells, which was more significant in the mannose-functionalized system compared to the non-functionalized nanoparticles. The overall results suggested that the fabricated mannose-functionalized lipopolysaccharide nanoparticles are a safe and promising platform for macrophage-targeted delivery of anti-TB therapeutics. However, in vivo pharmacokinetic/pharmacodynamics studies are required to further substantiate the therapeutic efficacy of the nanosystem.

Keywords: anti-tuberculosis therapeutics, hybrid nanosystem, lipopolysaccharide nanoparticles, macrophage-targeted delivery

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Authors: Yang Yang, Luciana Magalhães Rebelo Alencar, Martha Sahylí Ortega Pijeira, Beatriz da Silva Batista, Alefe Roger Silva França, Erick Rafael Dias Rates, Ruana Cardoso Lima, Sara Gemini-Piperni, Ralph Santos-Oliveira

Abstract:

Radium-²²³ dichloride ([²²³Rₐ]RₐCl₂) is an alpha particle-emitting radiopharmaceutical currently approved for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases, and no known visceral metastatic disease. [²²³Rₐ]RₐCl₂ is bone-seeking calcium mimetic that bonds into the newly formed bone stroma, especially osteoblastic or sclerotic metastases, killing the tumor cells by inducing DNA breaks in a potent and localized manner. Nonetheless, the successful therapy of osteosarcoma as primary bone tumors is still a challenge. Nanomicelles are colloidal nanosystems widely used in drug development to improve blood circulation time, bioavailability, and specificity of therapeutic agents, among other applications. In addition, the enhanced permeability and retention effect of the nanosystems, and the renal excretion of the nanomicelles reported in most cases so far, are very attractive to achieve selective and increased accumulation in tumor site as well as to increase the safety of [²²³Rₐ]RₐCl₂ in the clinical routine. In the present work, [²²³Rₐ]RₐCl₂ nanomicelles were produced, characterized, in vitro evaluated, and compared with pure [²²³Rₐ]RₐCl2 solution using SAOS2 osteosarcoma cells. The [²²³Rₐ]RₐCl₂ nanomicelles were prepared using the amphiphilic copolymer Pluronic F127. The dynamic light scattering analysis of freshly produced [²²³Rₐ]RₐCl₂ nanomicelles demonstrated a mean size of 129.4 nm with a polydispersity index (PDI) of 0.303. After one week stored in the refrigerator, the mean size of the [²²³Rₐ]RₐCl₂ nanomicelles increased to 169.4 with a PDI of 0.381. Atomic force microscopy analysis of [223Rₐ]RₐCl₂ nanomicelles exhibited spherical structures whose heights reach 1 µm, suggesting the filling of 127-Pluronic nanomicelles with [²²³Rₐ]RₐCl₂. The viability assay with [²²³Rₐ]RₐCl₂ nanomicelles displayed a dose-dependent response as it was observed using pure [²²³Rₐ]RₐCl2. However, at the same dose, [²²³Rₐ]RₐCl₂ nanomicelles were 20% higher efficient in killing SAOS2 cells when compared with pure [²²³Rₐ]RₐCl₂. These findings demonstrated the effectiveness of the nanosystem validating the application of nanotechnology in targeted alpha therapy with [²²³Ra]RₐCl₂. In addition, the [²²³Rₐ]RaCl₂nanomicelles may be decorated and incorporated with a great variety of agents and compounds (e.g., monoclonal antibodies, aptamers, peptides) to overcome the limited use of [²²³Ra]RₐCl₂.

Keywords: nanomicelles, osteosarcoma, radium dichloride, targeted alpha therapy

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