Search results for: cysteine covalent binding

Authors: Sasan Talebnezhad, Saeed Pourmahdian, Naghi Assali

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Homogeneous α-diimine nickel (II) catalyst complexes, with and without amino para-aryl position functionality, were synthesized. These complexes were immobilized on carboxyl, hydroxyl and acyl chloride functionalized multi-walled carbon nanotubes to form five novel heterogeneous α diiminonickel catalysts. Immobilization was performed by covalent or electrostatic bonding via methylaluminoxane (MAO) linker or amide linkage. Both the nature of α-diimine ligands and the kind of interaction between anchored catalyst complexes and multi-walled carbon nanotube surface influenced the catalytic performance, microstructure, and morphology of obtained polyethylenes. The catalyst prepared by amide bonding showed lowest relative weight loss in thermogravimetry analysis and highest activities up to 5863 gr PE mmol-1Ni.hr-1. This catalyst produced polyethylene with dense botryoidal morphology.

Keywords: α-diimine nickel (II) complexes, immobilization, multi-walled carbon nanotubes, ethylene polymerization

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Authors: Rahul Shrivastava, Manish Tripathi, Mohmmad Yasir, Shailesh Singh

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Life style changes and depletion in atmospheric ozone layer in recent decades lead to increase in skin cancer including both melanoma and nonmelanomas. Natural products which were obtained from different plant species have the potential of anti skin cancer activity. In regard of this, present study focuses the potential effect of Glycosmis pentaphylla against anti skin cancer activity. Different Phytochemical constituents which were present in the roots of Glycosmis pentaphylla were identified and were used as ligands after sketching of their structures with the help of ACD/Chemsketch. These ligands are screened for their anticancer potential with proteins which are involved in skin cancer effects with the help of pyrx software. After performing docking studies, results reveal that Noracronycine secondary metabolite of Glycosmis pentaphylla shows strong affinity of their binding energy with Ribosomal S6 Kinase 2 (2QR8) protein. Ribosomal S6 Kinase 2 (2QR8) has an important role in the cell proliferation and transformation mediated through by N-terminal kinase domain and was induced by the tumour promoters such as epidermal growth factor. It also plays a key role in the neoplastic transformation of human skin cells and in skin cancer growth. Noracronycine interact with THR-493 and MET-496 residue of Ribosomal S6 Kinase 2 protein with binding energy ΔG = -8.68 kcal/mole. Thus on the basis of this study we can say that Noracronycine which present in roots of Glycosmis pentaphylla can be used as lead compound against skin cancer.

Keywords: glycosmis pentaphylla, pyrx, ribosomal s6 kinase, skin cancer

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Authors: Mohammadjavad Sotoudeheian

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Heart failure (HF) prevalence, as a global cardiovascular problem, is increasing gradually. A variety of molecular mechanisms contribute to HF. Proteins involved in cardiac contractility regulation, such as ion channels and calcium handling proteins, are altered. Additionally, epigenetic modifications and gene expression can lead to altered cardiac function. Moreover, inflammation and oxidative stress contribute to HF. The progression of HF can be attributed to mitochondrial dysfunction that impairs energy production and increases apoptosis. Molecular mechanisms such as these contribute to the development of cardiomyocyte defects and HF and can be therapeutically targeted. The heart's contractile function is controlled by cardiomyocytes. Calpain, and its related molecules, including Bax, VEGF, and AMPK, are among the proteins involved in regulating cardiomyocyte function. Apoptosis is facilitated by Bax. Cardiomyocyte apoptosis is regulated by this protein. Furthermore, cardiomyocyte survival, contractility, wound healing, and proliferation are all regulated by VEGF, which is produced by cardiomyocytes during inflammation and cytokine stress. Cardiomyocyte proliferation and survival are also influenced by AMPK, an enzyme that plays an active role in energy metabolism. They all play key roles in apoptosis, angiogenesis, hypertrophy, and metabolism during myocardial inflammation. The role of calpains has been linked to several molecular pathways. The calpain pathway plays an important role in signal transduction and apoptosis, as well as autophagy, endocytosis, and exocytosis. Cell death and survival are regulated by these calcium-dependent cysteine proteases that cleave proteins. As a result, protein fragments can be used for various cellular functions. By cleaving adhesion and motility proteins, calcium proteins also contribute to cell migration. HF may be brought about by calpain-mediated pathways. Many physiological processes are mediated by the calpain molecular pathways. Signal transduction, cell death, and cell migration are all regulated by these molecular pathways. Calpain is activated by calcium binding to calmodulin. In the presence of calcium, calmodulin activates calpain. Calpains are stimulated by calcium, which increases matrix metalloproteinases (MMPs). In order to develop novel treatments for these diseases, we must understand how this pathway works. A variety of myocardial remodeling processes involve calpains, including remodeling of the extracellular matrix and hypertrophy of cardiomyocytes. Calpains also play a role in maintaining cardiac homeostasis through apoptosis and autophagy. The development of HF may be in part due to calpain-mediated pathways promoting cardiomyocyte death. Numerous studies have suggested the importance of the Ca2+ -dependent protease calpain in cardiac physiology and pathology. Therefore, it is important to consider this pathway to develop and test therapeutic options in humans that targets calpain in HF. Apoptosis, autophagy, endocytosis, exocytosis, signal transduction, and disease progression all involve calpain molecular pathways. Therefore, it is conceivable that calpain inhibitors might have therapeutic potential as they have been investigated in preclinical models of several conditions in which the enzyme has been implicated that might be treated with them. Ca 2+ - dependent proteases and calpains contribute to adverse ventricular remodeling and HF in multiple experimental models. In this manuscript, we will discuss the calpain molecular pathway's important roles in HF development.

Keywords: calpain, heart failure, autophagy, apoptosis, cardiomyocyte

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Authors: Ghazala Yaqub, Zubi Sadiq, Almas Hamid, Saira Iqbal

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This paper is the very first report of three dual action hybrids synthesized by covalent linkage of carbazole based novel antibacterial compounds with efflux pump inhibitors i.e., indole acetic acid/gallic acid. Novel carbazole based antibacterial compounds were prepared first and then these were covalently linked with efflux pump inhibitors which leads to the successful formation of hybrids. All prepared compounds were evaluated for their bacterial cell killing capability against Escherichia coli, Staphylococcus aureus, Pasteurella multocida and Bacillus subtilis. Compound were effective against all tested bacterial strains at different concentrations. But when these compounds were linked with efflux pump inhibitors they showed dramatic enhancement in their bacterial cell killing potential and minimum inhibitory concentration of all hybrids ranges from 7.250 µg/mL to 0.0283 µg/mL.

Keywords: antimicrobial assay, carbazole, dual action hybrids, efflux pump inhibitors

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Authors: Lee Suan Chua

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This study investigated the effects of thermal treatment on Tualang honey sample in terms of honey colour and heat-induced small metabolites. The heating process was carried out in a temperature controlled water batch at 90 °C for 4 hours. The honey samples were put in cylinder tubes with the dimension of 1 cm diameter and 10 cm length for homogenous heat transfer. The results found that the thermal treatment produced not only hydroxylmethylfurfural, but also other harmful substances such as phthalic anhydride and radiolytic byproducts. The degradation of honey protein was reported due to the detection of free amino acids such as cysteine and phenylalanine in heat-treated honey samples. Sugar dehydration also occurred because fragmented di-galactose was identified based on the presence of characteristic ions in the mass fragmentation pattern. The honey colour was found getting darker as the heating duration was increased up to 4 hours. Approximately, 60 mm PFund of increment was noticed for the honey colour with the colour change rate of 14.8 mm PFund per hour. Based on the principal component analysis, the chemical profile of Tualang honey was significantly altered after 2 hours of heating at 90 °C.

Keywords: honey colour, hydroxylmethylfurfural, thermal treatment, tualang honey

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Authors: Tomasz Łęga, Marta Sosnowska, Mirosława Panasiuk, Lilit Hovhannisyan, Beata Gromadzka, Marcin Olszewski, Sabina Zoledowska, Dawid Nidzworski

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Toxic heavy metal ion contamination of industrial wastewater has recently become a significant environmental concern in many regions of the world. Although the majority of heavy metals are naturally occurring elements found on the earth's surface, anthropogenic activities such as mining and smelting, industrial production, and agricultural use of metals and metal-containing compounds are responsible for the majority of environmental contamination and human exposure. The permissible limits (ppm) for heavy metals in food, water and soil are frequently exceeded and considered hazardous to humans, other organisms, and the environment as a whole. Human exposure to highly nickel-polluted environments causes a variety of pathologic effects. In 2008, nickel received the shameful name of “Allergen of the Year” (GILLETTE 2008). According to the dermatologist, the frequency of nickel allergy is still growing, and it can’t be explained only by fashionable piercing and nickel devices used in medicine (like coronary stents and endoprostheses). Effective remediation methods for removing heavy metal ions from soil and water are becoming increasingly important. Among others, methods such as chemical precipitation, micro- and nanofiltration, membrane separation, conventional coagulation, electrodialysis, ion exchange, reverse and forward osmosis, photocatalysis and polymer or carbon nanocomposite absorbents have all been investigated so far. The importance of environmentally sustainable industrial production processes and the conservation of dwindling natural resources has highlighted the need for affordable, innovative biosorptive materials capable of recovering specific chemical elements from dilute aqueous solutions. The use of combinatorial phage display techniques for selecting and recognizing material-binding peptides with a selective affinity for any target, particularly inorganic materials, has gained considerable interest in the development of advanced bio- or nano-materials. However, due to the limitations of phage display libraries and the biopanning process, the accuracy of molecular recognition for inorganic materials remains a challenge. This study presents the isolation, identification and characterisation of metal binding phage clones that preferentially recover nickel.

Keywords: Heavy metal recovery, cleaning water, phage display, nickel

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Authors: M. Cynthya, V. Prabhawathi, D. Mukesh

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Food contamination occurs during post process handling. This leads to spoilage and growth of pathogenic microorganisms in the food, thereby reducing its shelf life or spreading of food borne diseases. Several methods are tried and one of which is use of antimicrobial packaging. Here, papain, a protease enzyme, is covalently immobilized with the help of glutarldehyde on polyurethane and used as a food wrap to protect food from microbial contamination. Covalent immobilization of papain was achieved at a pH of 7.4; temperature of 4°C; glutaraldehyde concentration of 0.5%; incubation time of 24 h; and 50 mg of papain. The formation of -C=N- observed in the Fourier transform infrared spectrum confirmed the immobilization of the enzyme on the polymer. Immobilized enzyme retained higher activity than the native free enzyme. The efficacy of this was studied by wrapping it over S. aureus contaminated cottage cheese (paneer) and cheese and stored at a temperature of 4°C for 7 days. The modified film reduced the bacterial contamination by eight folds when compared to the bare film. FTIR also indicates reduction in lipids, sugars and proteins in the biofilm.

Keywords: cheese, papain, polyurethane, Staphylococcus aureus

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Authors: Farzaneh Ziaee, Mohammad Ziaee

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N-acetyl-L-cysteine (NAC) is a well-known mucolytic agent, and recently its efficacy has been examined for the prevention and remediation of several diseases such as lung infections caused by Coronavirus. Also, it is administrated as the main antidote in paracetamol overdose and is effective for the treatment of idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD). This medicine is used as an antioxidant to prevent diabetic kidney disease (nephropathy). In this study, a method for the acylation of amino acids is employed to manufacture this drug in a height yield. Regarding this patented path, NAC can be made in a single batch step at ambient pressure and temperature. Moreover, this study offers a technique to make peptide bonds which is of interest for pharmaceutical and medicinal industries. The separation process was undertaken using appropriate solvents to achieve an excellent purification level. The synthesized drug was characterized via proton nuclear magnetic resonance (1H NMR), high-performance liquid chromatography (HPLC), Fourier transform infrared spectroscopy (FT-IR), elemental analysis, and melting point.

Keywords: N-acetylcysteine, synthesis, mucolytic medication, lung anti-inflammatory, COVID-19, antioxidant, pharmaceutical supplement, characterization

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Authors: Youjeong Hwang

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Purpose: Insulin-like growth factor-I (IGF-I) promotes B-cell development, immunoglobulin formation, and interleukin-6 (IL-6) production, then regulate the immune response and inflammation. As IGF-I and their receptor also exist in the periodontal tissue, they may affect the immune response caused by periodontal pathogens in aggressive periodontitis (AgP) patients. The function of IGF is regulated by IGF binding proteins (IGFBPs), and IGFBP-3 is known to most abundant in plasma. The aim of the present study was to assess the concentration of IGF-I and IGFBP-3 in plasma and gingival crevicular fluid (GCF) in AgP patients and to find out their association. Methods: Nine patients with AgP (test group) and nine healthy subjects (control group) were included in this study. None of the subjects had a history of systemic disease, smoking or steroids medication. GCF samples were collected by microcapillary pipettes and plasma samples were obtained by venipuncture. Probing pocket depth (PD), clinical attachment level (CAL) and bleeding on probing (BOP) were recorded. Samples were assayed for IGF-I and IGFBP-3 levels using ELISA. Results: Mean IGF-I level in GCF was higher in the test group than control. Mean IGF-I level in plasma and IGFBP-3 level in GCF and plasma in control group were higher than that of the test group. However, there was no statistical significance (p > 0.05). The mean level of IGF-I and IGFBP-3 in GCF was lower than those in plasma. Mean IGF-I level in plasma showed a negative correlation with PD and CAL (p < 0.05) in both groups. The levels of IGF-I and IGFBP-3 in GCF seemed to be negatively correlated with BOP in the test group (p < 0.05). Conclusions: The difference in the level of IGF-I and IGFBP-3 between AgP and healthy subjects was not significant. Further studies that explain the mechanism of the protective role of IGF-I with more samples are needed.

Keywords: aggressive periodontitis, pathogenesis, insulin-like growth factor, insulin-like growth factor binding protein

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Authors: Tej Varma Y, Debi D. Pant

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Photophysics and rotational dynamics of the fluorescent probe, 6-methoxyquinoline (6MQ) with cationic surfactant, alkyltrimethylammonium bromide (nTAB) micelle solutions have been investigated (n = 12, 14 and 16). Absorption and emission peaks of the dye have been observed to shift at concentrations around critical micellar concentration (cmc) of nTAB compared to that of bulk solutions suggesting probe is in a lower polar environment. The probe senses changes in polarity (ET (30)) brought about by variation of surfactant chain length concentration and is invariably solubilized in the aqueous interface or palisade layer. The order of change in polarity observed was DTAB > CTAB > TTAB. The binding constant study shows that the probe binds strongest with TTAB (is of the order TTAB > CTAB > DTAB) due to deeper penetration into the micelle. The anisotropy decay for the probe in all the nTAB micelles studied have been rationalized based on a two-step model consisting of fast-restricted rotation of the probe and slow lateral diffusion of the probe in the micelle that is coupled to the overall rotation of the micelle. Fluorescence lifetime measurements of probe in the cationic micelles demonstrate the close proximity of the 6MQ to the Br - counterions. The fluorescence lifetimes of TTAB and DTAB are much shorter than in CTAB. These results indicate that 6MQ resides to a substantial degree in the head group region of the micelles. All the changes observed in the steady state fluorescence, microenvironment, fluorescence lifetimes, fluorescence anisotropy, and other calculations are in agreement with each other suggesting binding of the cationic surfactant with the neutral dye molecule.

Keywords: photophysics, chain length, ntaB, micelles

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Authors: Patience Orobosa Olajide

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Five hydrocarbon degrading bacterial strains isolated from contaminated environment were investigated with respect to polyhydroxybutyrate (PHB) biosynthesis. Screening for bioplastic production was done on assay mineral salts agar medium containing 0.2% poly (3-hydroxybutyrate) as the sole carbon source. Two of the test bacteria were positive for PHB biosynthesis and were identified based on gram staining, biochemical tests, 16S rRNA gene sequence analysis as Pseudomonas aeruginosa and Bacillus licheniformis which grew at 37 and up to 65 °C respectively, thus suggesting the later to be thermotolerant. In this study, the effects of different carbon and nitrogen sources on PHB production in these strains were investigated. Maximum PHB production was obtained in 48 hr for the two strains and amounted to yields of 72.86 and 62.22 percentages for Bacillus licheniformis and Pseudomonas aeruginosa respectively. In these strains, glycine was the most efficient carbon sources for the production of PHB compared with other carbon (glucose, lactose, sucrose, Arabinose) and nitrogen (L- glycine, L-cysteine, DL-Tryptophan, and Potassium Nitrate) sources. The screening of microbial strains for industrial PHB production should be based on several factors including the cell’s capability to mineralize an inexpensive substrate, rate of growth and the extent of polymer accumulation.

Keywords: bacteria, poly-3-hydroxybutyrate (PHB), hydrocarbon, thermotolerant

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Authors: G. Fomo, O. J. Achadu, T. Nyokong

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Nanoconjugates of graphene quantum dots (GQDs) and 4-(tetrakis-5-(trifluoromethyl)-2-mercaptopyridinephthalocyanine (H₂Pc(OPyF₃)₄) or 4-(tetrakis-5-(trifluoromethyl)-2-mercaptopyridinephthalocyaninato) zinc (II) (ZnPc(OPyF₃)₄) were synthesized via a novel in situ one-step route. The bottom-up approach for the prepared conjugates could ensure the intercalation of the phthalocyanines (Pcs) directly onto the edges or surface of the GQDs and or non-covalent coordination using the π-electron systems of both materials. The as-synthesized GQDs and their Pcs conjugates were characterized using different spectroscopic techniques and their photophysicochemical properties evaluated. The singlet oxygen quantum yields of the Pcs in the presence of GQDs were enhanced due to Förster resonance energy transfer (FRET) occurrence within the conjugated hybrids. Hence, these nanoconjugates are potential materials for photodynamic therapy (PDT) and photocatalysis applications.

Keywords: graphene quantum dots, metal free fluorinated phthalocyanine, zinc fluorinated phthalocyanine, photophysicochemical properties

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Authors: Aikaterini Tsalampouni

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The European Union has long been the most developed model of economic and political integration that has brought a common market, a common currency and a standardization of national policies in certain areas in consistent with EU values and principles. To this direction, there is a parallel process of social integration that effect public policy decisions of member states. Even though social policy, i.e. social protection and moreover healthcare policy, still remains in state's responsibility to develop, EU applies different mechanisms in order to influence health policy systems, since from a more federalist point of view, EU ought to expand its regulatory and legislative roles in as many policy areas as possible. Recently, the pandemic has become a turning point for health care provision and at the same time has also highlighted the need to strengthen the EU’s role in coordinating health care. This paper analyses the EU health policy in general, as well as the response to COVID-19 pandemic with an attempt to identify indications of interaction between EU policies and the promotion of sustainable and resilient health systems. More analytically, the paper investigates the EU binding legal instruments, non-binding legal instruments, monitoring and assessment instruments and instruments for co-financing concerning health care provision in member states and records the evolution of health policies before and during the COVID-19 pandemic. The paper concludes by articulating some remarks regarding the improvement of health policy in EU. Since the ability to deal with a pandemic depends on continuous and increased investment in health systems, the involvement of the EU can lead to a policy convergence, necessary for the resilience of the systems, maintaining at the same time, a strong health policy framework in Europe.

Keywords: EU health policy, EU response to COVID-19, European Health Union, health systems in Europe

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Authors: Vatsal M. Patel, Navin B. Patel

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The present studies deal with the developing a series bearing a diphenyl ethers nucleus using structure-based drug design concept. A newer series of diphenyl ether based azetidinone namely N-(3-chloro-2-oxo-4-(3-phenoxyphenyl)azetidin-1-yl)-2-(substituted amino)acetamide (2a-j) have been synthesized by condensation of m-phenoxybenzaldehyde with 2-(substituted-phenylamino)acetohydrazide followed by the cyclisation of resulting Schiff base (1a-j) by conventional method as well as microwave heating approach as a part of an environmentally benign synthetic protocol. All the synthesized compounds were characterized by spectral analysis and were screened for in vitro antimicrobial, antitubercular and antiprotozoal activity. The compound 2f was found to be most active M. tuberculosis (6.25 µM) MIC value in the primary screening as well as this same derivative has been found potency against L. mexicana and T. cruzi with MIC value 2.09 and 6.69 µM comparable to the reference drug Miltefosina and Nifurtimox. To provide understandable evidence to predict binding mode and approximate binding energy of a compound to a target in the terms of ligand-protein interaction, all synthesized compounds were docked against an enoyl-[acyl-carrier-protein] reductase of M. tuberculosis (PDB ID: 4u0j). The computational studies revealed that azetidinone derivatives have a high affinity for the active site of enzyme which provides a strong platform for new structure-based design efforts. The Lipinski’s parameters showed good drug-like properties and can be developed as an oral drug candidate.

Keywords: antimycobacterial, antiprotozoal, azetidinone, diphenylether, docking, microwave

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Authors: Pouira Askary

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Indeed, in our globalized world which is facing with various international crises, the transnational corporations and other business enterprises have the capacity to foster economic well-being, development, technological improvement and wealth, as well as causing adverse impacts on human rights. The UN Human Rights Council declared that although the primary responsibility to protect human rights lie with the State but the transnational corporations and other business enterprises have also a responsibility to respect and protect human rights in the framework of corporate social responsibility. In 2011, the Human Rights Council endorsed the Guiding Principles on Business and Human Rights, a set of guidelines that define the key duties and responsibilities of States and business enterprises with regard to business-related human rights abuses. In UN’s view, the Guiding Principles do not create new legal obligations but constitute a clarification of the implications of existing standards, including under international human rights law. In 2014 the UN Human Rights Council decided to establish a working group on transnational corporations and other business enterprises whose mandate shall be to elaborate an international legally binding instrument to regulate, in international human rights law, the activities of transnational corporations and other business enterprises. Extremely difficult task for the working group to codify a legally binding document to regulate the behavior of corporations on the basis of the norms of international law! Concentration of this paper is on the origins of those human rights applicable on business enterprises. The research will discuss that the social and ethical roots of the CSR are much more institutionalized and elaborated than the legal roots. Therefore, the first step is to determine whether and to what extent corporations, do have an ethical responsibility to respect human rights and if so, by which means this ethical and social responsibility is convertible to legal commitments.

Keywords: CSR, ethics, international law, human rights, development, sustainable business

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Authors: Rasha Al-Saedi, Anthony Meijer

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The progress of new porous materials has increased rapidly over the past decade for use in applications such as catalysis, gas storage and removal of environmentally unfriendly species due to their high surface area and high thermal stability. In this work, a theoretical study of the zirconium-based metal organic framework (MOFs) were examined in order to determine their potential for gas adsorption of various guest molecules: CO2, N2, CH4 and H2. The zirconium cluster consists of an inner Zr6O4(OH)4 core in which the triangular faces of the Zr6- octahedron are alternatively capped by O and OH groups which bound to nine formate groups and three benzoate groups linkers. General formula is [Zr(μ-O)4(μ-OH)4(HCOO)9((phyO2C)3X))] where X= CH2OH, CH2NH2, CH2CONH2, n(NH2); (n = 1-3). Three types of adsorption sites on the Zr metal center have been studied, named according to capped chemical groups as the ‘−O site’; the H of (μ-OH) site removed and added to (μ-O) site, ‘–OH site’; (μ-OH) site removed, the ‘void site’ where H2O molecule removed; (μ-OH) from one site and H from other (μ-OH) site, in addition to no defect versions. A series of investigations have been performed aiming to address this important issue. First, density functional theory DFT-B3LYP method with 6-311G(d,p) basis set was employed using Gaussian 09 package in order to evaluate the gas adsorption performance of missing-linker defects in zirconium cluster. Next, study the gas adsorption behaviour on different functionalised zirconium clusters. Those functional groups as mentioned above include: amines, alcohol, amide, in comparison with non-substitution clusters. Then, dispersion-corrected density functional theory (DFT-D) calculations were performed to further understand the enhanced gas binding on zirconium clusters. Finally, study the water effect on CO2 and N2 adsorption. The small functionalized Zr clusters were found to result in good CO2 adsorption over N2, CH4, and H2 due to the quadrupole moment of CO2 while N2, CH4 and H2 weakly polar or non-polar. The adsorption efficiency was determined using the dispersion method where the adsorption binding improved as most of the interactions, for example, van der Waals interactions are missing with the conventional DFT method. The calculated gas binding strengths on the no defect site are higher than those on the −O site, −OH site and the void site, this difference is especially notable for CO2. It has been stated that the enhanced affinity of CO2 of no defect versions is most likely due to the electrostatic interactions between the negatively charged O of CO2 and the positively charged H of (μ-OH) metal site. The uptake of the gas molecule does not enhance in presence of water as the latter binds to Zr clusters more strongly than gas species which attributed to the competition on adsorption sites.

Keywords: density functional theory, gas adsorption, metal- organic frameworks, molecular simulation, porous materials, theoretical chemistry

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Authors: Hsiang-Ru Lin

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Cholesterol plays an essential role in the regulation of the progression of numerous important diseases including atherosclerosis and Alzheimer disease so the generation of suitable cholesterol-lowering reagents is urgent to develop. Liver X receptor (LXR) is a ligand-activated transcription factor whose natural ligands are cholesterols, oxysterols and glucose. Once being activated, LXR can transactivate the transcription action of various genes including CYP7A1, ABCA1, and SREBP1c, involved in the lipid metabolism, glucose metabolism and inflammatory pathway. Essentially, the upregulation of ABCA1 facilitates cholesterol efflux from the cells and attenuates the production of beta-amyloid (ABeta) 42 in brain so LXR is a promising target to develop the cholesterol-lowering reagents and preventative treatment of Alzheimer disease. Engelhardia roxburghiana is a deciduous tree growing in India, China, and Taiwan. However, its chemical composition is only reported to exhibit antitubercular and anti-inflammatory effects. In this study, four compounds, engelheptanoxides A, C, engelhardiol A, and B isolated from the root of Engelhardia roxburghiana were evaluated for their agonistic activity against LXR by the transient transfection reporter assays in the HepG2 cells. Furthermore, their interactive modes with LXR ligand binding pocket were generated by molecular modeling programs. By using the cell-based biological assays, engelheptanoxides A, C, engelhardiol A, and B showing no cytotoxic effect against the proliferation of HepG2 cells, exerted obvious LXR agonistic effects with similar activity as T0901317, a novel synthetic LXR agonist. Further modeling studies including docking and SAR (structure-activity relationship) showed that these compounds can locate in LXR ligand binding pocket in the similar manner as T0901317. Thus, LXR is one of nuclear receptors targeted by pharmaceutical industry for developing treatments of Alzheimer and atherosclerosis diseases. Importantly, the cell-based assays, together with molecular modeling studies suggesting a plausible binding mode, demonstrate that engelheptanoxides A, C, engelhardiol A, and B function as LXR agonists. This is the first report to demonstrate that the extract of Engelhardia roxburghiana contains LXR agonists. As such, these active components of Engelhardia roxburghiana or subsequent analogs may show important therapeutic effects through selective modulation of the LXR pathway.

Keywords: Liver X receptor (LXR), Engelhardia roxburghiana, CYP7A1, ABCA1, SREBP1c, HepG2 cells

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Authors: Farah Diab, Mohamad Khalil, Francesca Storace, Francesca Baldini, Piero Portincasaa, Giulio Lupidi, Laura Vergani

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Thymbra spicata is a thyme-like plant belonging to the Lamiaceae family that shows a global distribution, especially in the eastern Mediterranean region. Leaves of T. spicata contain large amounts of phenols such as phenolic acids (rosmarinic acid), phenolic monoterpenes (carvacrol), and flavonoids. In Lebanon, T. spicata is currently used as a culinary herb in salad and infusion, as well as for traditional medicinal purposes. Carvacrol (5-isopropyl-2-methyl phenol), the most abundant polyphenol in the organic extract and essential oils, has a great array of pharmacological properties. In fact, carvacrol is largely employed as a food additive and neutraceutical agent. Our aim is to investigate the beneficial effects of T. spicata ethanolic extract (TE) and its main component, carvacrol, using in vitro models of hepatic steatosis and endothelial dysfunction. As a further point, we focused on investigating if and how the binding of carvacrol to albumin, the physiological transporter for drugs in the blood, might be altered by the presence of high levels of fatty acids (FAs), thus impairing the carvacrol bio-distribution in vivo. For that reason, hepatic FaO cells treated with exogenous FAs such as oleate and palmitate mimic hepatosteatosis; endothelial HECV cells exposed to hydrogen peroxide are a model of endothelial dysfunction. In these models, we measured lipid accumulation, free radical production, lipoperoxidation, and nitric oxide release before and after treatment with carvacrol. The carvacrol binding to albumin with/without high levels of long-chain FAs was assessed by absorption and emission spectroscopies. Our findings show that both TE and carvacrol (i) counteracted lipid accumulation in hepatocytes by decreasing the intracellular and extracellular lipid contents in steatotic FaO cells; (ii) decreased oxidative stress in endothelial cells by significantly reducing lipoperoxidation and free radical production, as well as, attenuating the nitric oxide release; (ii) high levels of circulating FAs reduced the binding of carvacrol to albumin. The beneficial effects of TE and carvacrol on both hepatic and endothelial cells point to a nutraceutical potential. However, high levels of circulating FAs, such as those occurring in metabolic disorders, might hinder the carvacrol transport, bio-distribution, and pharmacodynamics.

Keywords: carvacrol, endothelial dysfunction, fatty acids, non-alcoholic fatty liver diseases, serum albumin

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Authors: Juliet Udoudom

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Inappropriate complement selection constitutes one of the major features of non-standard complementation in the Nigerian users of English output of sentence construction. This paper investigates complement clause choice in Written Educated Nigerian English (ENE) and offers some results. It aims at determining preferred and dispreferred patterns of complement clause selection in respect of verb heads in English by selected Nigerian users of English. The complementation data analyzed in this investigation were obtained from experimental tasks designed to elicit complement categories of Verb – Noun -, Adjective – and Prepositional – heads in English. Insights from the Government – Binding relations were employed in analyzing data, which comprised responses obtained from one hundred subjects to a picture elicitation exercise, a grammaticality judgement test, and a free composition task. The findings indicate a general tendency for clausal complements (CPs) introduced by the complementizer that to be preferred by the subjects studied. Of the 235 tokens of clausal complements which occurred in our corpus, 128 of them representing 54.46% were CPs headed by that, while whether – and if-clauses recorded 31.07% and 8.94%, respectively. The complement clause-type which recorded the lowest incidence of choice was the CP headed by the Complementiser, for with a 5.53% incident of occurrence. Further findings from the study indicate that semantic features of relevant embedding verb heads were not taken into consideration in the choice of complementisers which introduce the respective complement clauses, hence the that-clause was chosen to complement verbs like prefer. In addition, the dispreferred choice of the for-clause is explicable in terms of the fact that the respondents studied regard ‘for’ as a preposition, and not a complementiser.

Keywords: complement, complement clause complement selection, complementisers, government-binding

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Authors: Mina Rabipour, Elena Pallaske, Floyd Hassenrück, Rocio Rebollido-Rios

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Protein tyrosine kinases, including Lyn kinase of the Src family kinases (SFK), regulate cell proliferation, survival, and differentiation. Lyn kinase has been implicated in various cancers, positioning it as a promising therapeutic target. However, the conserved ATP-binding pocket across SFKs makes developing selective inhibitors challenging. This study aims to address this limitation by exploring the potential for allosteric modulation of Lyn kinase, focusing on how its structural dynamics and specific oncogenic mutations impact its conformation and function. To achieve this, we combined homology modeling, molecular dynamics simulations, and data science techniques to conduct microsecond-length simulations. Our approach allowed a detailed investigation into the interplay between Lyn’s catalytic and regulatory domains, identifying key conformational states involved in allosteric regulation. Additionally, we evaluated the structural effects of Dasatinib, a competitive inhibitor, and ATP binding on Lyn active conformation. Notably, our simulations show that cancer-related mutations, specifically I364L/N and E290D/K, shift Lyn toward an inactive conformation, contrasting with the active state of the wild-type protein. This may suggest how these mutations contribute to aberrant signaling in cancer cells. We conducted a dynamical network analysis to assess residue-residue interactions and the impact of mutations on the Lyn intramolecular network. This revealed significant disruptions due to mutations, especially in regions distant from the ATP-binding site. These disruptions suggest potential allosteric sites as therapeutic targets, offering an alternative strategy for Lyn inhibition with higher specificity and fewer off-target effects compared to ATP-competitive inhibitors. Our findings provide insights into Lyn kinase regulation and highlight allosteric sites as avenues for selective drug development. Targeting these sites may modulate Lyn activity in cancer cells, reducing toxicity and improving outcomes. Furthermore, our computational strategy offers a scalable approach for analyzing other SFK members or kinases with similar properties, facilitating the discovery of selective allosteric modulators and contributing to precise cancer therapies.

Keywords: lyn tyrosine kinase, mutation analysis, conformational changes, dynamic network analysis, allosteric modulation, targeted inhibition

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Authors: Matthew E. Potter, Daniel J. Stewart, Lindsay M. Armstrong, Pier J. A. Sazio, Robert R. Raja

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Rising CO₂ levels in the atmosphere means that CO₂ is a highly desirable feedstock. This requires specific catalysts to be designed to activate this inert molecule, combining a catalytic site tailored for CO₂ transformations with a support that can readily adsorb CO₂. Metal organic frameworks (MOFs) are regularly used as CO₂ sorbents. The organic nature of the linker molecules, connecting the metal nodes, offers many post-synthesis modifications to introduce catalytic active sites into the frameworks. However, the metal nodes may be coordinatively unsaturated, allowing them to bind to organic moieties. Imidazoles have shown promise catalyzing the formation of cyclic carbonates from epoxides with CO₂. Typically, this synthesis route employs toxic reagents such as phosgene, liberating HCl. Therefore an alternative route with CO₂ is highly appealing. In this work we design active sites for CO₂ activation, by tethering substituted-imidazole organocatalytic species to the available Cr3+ metal nodes of a Cr-MIL-101 MOF, for the first time, to create a tailored species for carbon capture utilization applications. Our tailored design strategy combining a CO₂ sorbent, Cr-MIL-101, with an anchored imidazole results in a highly active and selective multifunctional catalyst, achieving turnover frequencies of over 750 hr-1. These findings demonstrate the synergy between the MOF framework and imidazoles for CO₂ utilization applications. Further, the effect of substrate variation has been explored yielding mechanistic insights into this process. Through characterization, we show that the structural and compositional integrity of the Cr-MIL-101 has been preserved on functionalizing the imidazoles. Further, we show the binding of the imidazoles to the Cr3+ metal nodes. This can be seen through our EPR study, where the distortion of the Cr3+ on binding to the imidazole shows the CO₂ binding site is close to the active imidazole. This has a synergistic effect, improving catalytic performance. We believe the combination of MOF support and organocatalyst allows many possibilities to generate new multifunctional catalysts for CO₂ utilisation. In conclusion, we have validated our design procedure, combining a known CO₂ sorbent, with an active imidazole species to create a unique tailored multifunctional catalyst for CO₂ utilization. This species achieves high activity and selectivity for the formation of cyclic carbonates and offers a sustainable alternative to traditional synthesis methods. This work represents a unique design strategy for CO₂ utilization while offering exciting possibilities for further work in characterization, computational modelling, and post-synthesis modification.

Keywords: carbonate, catalysis, MOF, utilisation

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Authors: Leila Mosafa, Majid Moghadam, Mohammad Shahedi

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In this work, pectinase was immobilized on the surface of silica-coated magnetite nanoparticles via covalent attachment. The magnetite-immobilized enzyme was characterized by Fourier transform infrared spectroscopy, X-ray powder diffraction, scanning electron microscopy and vibrating sample magnetometry techniques. Response surface methodology using Minitab Software was applied for statistical designing of operating conditions in order to immobilize pectinase on magnetic nanoparticles. The optimal conditions were obtained at 30°C and pH 5.5 with 42.97 µl pectinase for 2 h. The immobilization yield was 50.6% at optimized conditions. Compared to the free pectinase, the immobilized pectinase was found to exhibit enhanced enzyme activity, better tolerance to the variation of pH and temperature, and improved storage stability. Both free and immobilized samples reduced the viscosity of apple juice from 1.12 to 0.88 and 0.92 mm2s-1, respectively, after 30 min at their optimum temperature. Furthermore, the immobilized enzyme could be reused six consecutive cycles and the efficiency loss in viscosity reduction was found to be only 8.16%.

Keywords: magnetite nanoparticles, pectinase enzyme, immobilization, juice clarification, enzyme activity

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Authors: Ahmad Abdi, M. Golzadeh Gangeraj, Alireza Barari, S. Shirali, S. Amini

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Aims: Diabetes is one of the common metabolic diseases in the world that has the dire adverse effects such as nephropathy, retinopathy and cardiovascular problems. Pharmaceutical and non-pharmaceutical strategies for control and treatment of diabetes are provided. Exercise and nutrition as non-drug strategies for the prevention and control of diabetes are considered. Exercises may increase oxidative stress and myocardium injury, thus it is necessary to take nutrition strategies to help diabetic athletes. Methods: This study was a semi-experimental research. Therefore, 24 men with type 2 diabetes were selected and randomly divided in four groups (1. control, 2. saffron extract, 3. aerobic exercises, 4. compound aerobic exercises and saffron extract). Saffron extract with 100 mg/day was used. Aerobic exercises, three days a week, for eight weeks, with 55-70% of maximum heart rate were performed. At the end, levels of Heart-type fatty acid-binding protein (HFABP) and Troponin T were measured. Data were analyzed by Paired t, One-way ANOVA and Tukey tests. Results: The serum Troponin T increased significantly in saffron extract, aerobic exercises and compound saffron extract -aerobic exercises in type 2 diabetic men(P=0.024, P =0.013, P=0.005 respectively). Saffron extract consumption (100 mg/day) and aerobic exercises did not significantly influence the serum HFABP (P =0.365, P =0.188 respectively). But serum HFABP decreased significantly in compound saffron extract -aerobic exercises group (P =0.003). Conclusions: Raised cardiac Troponin T and HFABP concentration accepted as the standard biochemical markers for the diagnosis of cardiac injury. Saffron intake may beneficially protect the myocardium from injuries. Compound saffron extract -aerobic exercises can decrease levels of Troponin T and HFABP in men with type 2 diabetes.

Keywords: Saffron, aerobic exercises, type 2 diabetes, HFABP, troponin T

Procedia PDF Downloads 267

Authors: Xiaolin Li, Terence Turney, John Forsythe, Bryce Feltis, Paul Wright, Vinh Truong, Will Gates

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Clay-hydrogel nanocomposites have attracted great attention recently, mainly because of their enhanced mechanical properties and ease of fabrication. Moreover, the unique platelet structure of clay nanoparticles enables the incorporation of bioactive molecules, such as proteins or drugs, through ion exchange, adsorption or intercalation. This study seeks to improve the mechanical and rheological properties of a novel hydrogel system, copolymerized from a tetrapodal polyethylene glycol (PEG) thiol and a linear, triblock PEG-PPG-PEG (PPG: polypropylene glycol) α,ω-bispropynoate polymer, with the simultaneous incorporation of various amounts of Na-saturated, montmorillonite clay (MMT) platelets (av. lateral dimension = 200 nm), to form a bioactive three-dimensional network. Although the parent hydrogel has controlled swelling ability and its PEG groups have good affinity for the clay platelets, it suffers from poor mechanical stability and is currently unsuitable for potential applications. Nanocomposite hydrogels containing 4wt% MMT showed a twelve-fold enhancement in compressive strength, reaching 0.75MPa, and also a three-fold acceleration in gelation time, when compared with the parent hydrogel. Interestingly, clay nanoplatelet incorporation into the hydrogel slowed down the rate of its dehydration in air. Preliminary results showed that protein binding by the MMT varied with the nature of the protein, as horseradish peroxidase (HRP) was more strongly bound than bovine serum albumin. The HRP was no longer active when bound, presumably as a result of extensive structural refolding. Further work is being undertaken to assess protein binding behaviour within the nanocomposite hydrogel for potential diabetic wound healing applications.

Keywords: hydrogel, nanocomposite, small molecule, wound healing

Procedia PDF Downloads 269

Authors: Alireza Jalalvand, Maryam Saleh, Somayeh Behjat Khatouni, Zahra Bahri Najafi, Foroozan Fatahinia, Narges Ismailzadeh, Behrokh Farahmand

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Object: In the last two decades, the recent outbreak of Coronavirus (SARS-CoV-2) imposed a global pandemic in the world. Despite the increasing prevalence of the disease, there are no effective drugs to treat it. A suitable and rapid way to afford an effective drug and treat the global pandemic is a computational drug study. This study used molecular docking methods to examine the potential inhibition of over 50 antiviral drugs against three fundamental proteins of SARS-CoV-2. METHODS: Through a literature review, three important proteins (a key protease, RNA-dependent RNA polymerase (RdRp), and spike) were selected as drug targets. Three-dimensional (3D) structures of protease, spike, and RdRP proteins were obtained from the Protein Data Bank. Protein had minimal energy. Over 50 antiviral drugs were considered candidates for protein inhibition and their 3D structures were obtained from drug banks. The Autodock 4.2 software was used to define the molecular docking settings and run the algorithm. RESULTS: Five drugs, including indinavir, lopinavir, saquinavir, nelfinavir, and remdesivir, exhibited the highest inhibitory potency against all three proteins based on the binding energies and drug binding positions deduced from docking and hydrogen-bonding analysis. Conclusions: According to the results, among the drugs mentioned, saquinavir and lopinavir showed the highest inhibitory potency against all three proteins compared to other drugs. It may enter laboratory phase studies as a dual-drug treatment to inhibit SARS-CoV-2.

Keywords: covid-19, drug repositioning, molecular docking, lopinavir, saquinavir

Procedia PDF Downloads 88

Authors: Shanna Swart, Caryn Fenner, Athanasios Kotsiopoulos, Susan Harrison

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Linear alkanes are produced as by-products from the increasing use of gas-to-liquid fuel technologies for synthetic fuel production and offer great potential for value addition. Their current use as low-value fuels and solvents do not maximize this potential. Therefore, attention has been drawn towards direct activation of these aliphatic alkanes to more useful products such as alcohols, aldehydes, carboxylic acids and derivatives. Cytochrome P450 monooxygenases (P450s) can be used for activation of these aliphatic alkanes using whole-cells or cell-free systems. Some limitations of whole-cell systems include reduced mass transfer, stability and possible side reactions. Since the P450 systems are little studied as cell-free systems, they form the focus of this study. Challenges of a cell-free system include co-factor regeneration, substrate availability and enzyme stability. Enzyme immobilization offers a positive outlook on this dilemma, as it may enhance stability of the enzyme. In the present study, 2 different P450s (CYP153A6 and CYP102A1) as well as the relevant accessory enzymes required for electron transfer (ferredoxin and ferredoxin reductase) and co-factor regeneration (glucose dehydrogenase) have been expressed in E. coli and purified by metal affinity chromatography. Glucose dehydrogenase (GDH), was used as a model enzyme to assess the potential of various enzyme immobilization strategies including; surface attachment on MagReSyn® microspheres with various functionalities and on electrospun nanofibers, using self-assembly based methods forming Cross Linked Enzymes (CLE), Cross Linked Enzyme Aggregates (CLEAs) and spherezymes as well as in a sol gel. The nanofibers were synthesized by electrospinning, which required the building of an electrospinning machine. The nanofiber morphology has been analyzed by SEM and binding will be further verified by FT-IR. Covalent attachment based methods showed limitations where only ferredoxin reductase and GDH retained activity after immobilization which were largely attributed to insufficient electron transfer and inactivation caused by the crosslinkers (60% and 90% relative activity loss for the free enzyme when using 0.5% glutaraldehyde and glutaraldehyde/ethylenediamine (1:1 v/v), respectively). So far, initial experiments with GDH have shown the most potential when immobilized via their His-tag onto the surface of MagReSyn® microspheres functionalized with Ni-NTA. It was found that Crude GDH could be simultaneously purified and immobilized with sufficient activity retention. Immobilized pure and crude GDH could be recycled 9 and 10 times, respectively, with approximately 10% activity remaining. The immobilized GDH was also more stable than the free enzyme after storage for 14 days at 4˚C. This immobilization strategy will also be applied to the P450s and optimized with regards to enzyme loading and immobilization time, as well as characterized and compared with the free enzymes. It is anticipated that the proposed immobilization set-up will offer enhanced enzyme stability (as well as reusability and easy recovery), minimal mass transfer limitation, with continuous co-factor regeneration and minimal enzyme leaching. All of which provide a positive outlook on this robust multi-enzyme system for efficient activation of linear alkanes as well as the potential for immobilization of various multiple enzymes, including multimeric enzymes for different bio-catalytic applications beyond alkane activation.

Keywords: alkane activation, cytochrome P450 monooxygenase, enzyme catalysis, enzyme immobilization

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Authors: Serap Durkut, A. Eser Elcin, Y. Murat Elcin

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Stimuli-sensitive polymeric hydrogels have received extensive attention in the biomedical field due to their sensitivity to physical and chemical stimuli (temperature, pH, ionic strength, light, etc.). This study describes the rheological properties of a novel thermoresponsive poly(N-vinylcaprolactam)-g-collagen hydrogel. In the study, we first synthesized a facile and novel synthetic carboxyl group-terminated thermo-responsive poly(N-vinylcaprolactam)-COOH (PNVCL-COOH) via free radical polymerization. Further, this compound was effectively grafted with native collagen, by utilizing the covalent bond between the carboxylic acid groups at the end of the chains and amine groups of the collagen using cross-linking agent (EDC/NHS), forming PNVCL-g-Col. Newly-formed hybrid hydrogel displayed novel properties, such as increased mechanical strength and thermoresponsive characteristics. PNVCL-g-Col showed low critical solution temperature (LCST) at 38ºC, which is very close to the body temperature. Rheological studies determine structural–mechanical properties of the materials and serve as a valuable tool for characterizing. The rheological properties of hydrogels are described in terms of two dynamic mechanical properties: the elastic modulus G′ (also known as dynamic rigidity) representing the reversible stored energy of the system, and the viscous modulus G″, representing the irreversible energy loss. In order to characterize the PNVCL-g-Col, the rheological properties were measured in terms of the function of temperature and time during phase transition. Below the LCST, favorable interactions allowed the dissolution of the polymer in water via hydrogen bonding. At temperatures above the LCST, PNVCL molecules within PNVCL-g-Col aggregated due to dehydration, causing the hydrogel structure to become dense. When the temperature reached ~36ºC, both the G′ and G″ values crossed over. This indicates that PNVCL-g-Col underwent a sol-gel transition, forming an elastic network. Following temperature plateau at 38ºC, near human body temperature the sample displayed stable elastic network characteristics. The G′ and G″ values of the PNVCL-g-Col solutions sharply increased at 6-9 minute interval, due to rapid transformation into gel-like state and formation of elastic networks. Copolymerization with collagen leads to an increase in G′, as collagen structure contains a flexible polymer chain, which bestows its elastic properties. Elasticity of the proposed structure correlates with the number of intermolecular cross-links in the hydrogel network, increasing viscosity. However, at 8 minutes, G′ and G″ values sharply decreased for pure collagen solutions due to the decomposition of the elastic and viscose network. Complex viscosity is related to the mechanical performance and resistance opposing deformation of the hydrogel. Complex viscosity of PNVCL-g-Col hydrogel was drastically changed with temperature and the mechanical performance of PNVCL-g-Col hydrogel network increased, exhibiting lesser deformation. Rheological assessment of the novel thermo-responsive PNVCL-g-Col hydrogel, exhibited that the network has stronger mechanical properties due to both permanent stable covalent bonds and physical interactions, such as hydrogen- and hydrophobic bonds depending on temperature.

Keywords: poly(N-vinylcaprolactam)-g-collagen, thermoresponsive polymer, rheology, elastic modulus, stimuli-sensitive

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Authors: Prabir Kumar Paul, Joyeeta Mitra

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Ergosterol, is an important fungal metabolite on phylloplane which is not synthesised by plants. However, the functional requirement of ergosterol to the plants is still an enigma. Being ubiquitously present in all plants except algae needs an insight into its physiological implication. The present study aimed at understanding if and how ergosterol influences the physiology of chloroplast particularly the activity of RuBisCo and carbonic anhydrase. The concept of the study was based on one of our earlier observation of enhanced Hills reaction in plants treated with fungal metabolites which contained ergosterol. The fungal metabolite treated plants had a significantly high concentration of photosynthetic pigments. Eight-week-old tomato plants raised under aseptic conditions at 25 + 10 C, 75 % relative humidity and 12 hour L/D photoperiod. Metabolites of Aspergillus niger and Fusarium oxysporum were sprayed on plants either singly or in a 1: 1 combination. A separate group of plants was also treated with 0.5, 1.0, 3.0, 5.0. 7.0 mg ergosterol / ml of n- heptane. Control plants were treated with sterile distilled water only. Plants were sampled at 24, 48, 72 and 96 hours of treatment. RuBisCo and carbonic anhydrase was estimated from sampled leaves. RuBisCo was separated on 1D SDS-PAGE and subjected to MALDI – TOF- TOF – MS analysis. The presence of ergosterol in fungal metabolites was confirmed. Fungal metabolites significantly enhanced the concentration and activity of RuBisCo and carbonic anhydrase. The Vmax activity of the enzymes was significantly high in metabolite treated plants. 1:1 mix of metabolite was more effective than when applied individually. Insilico analysis revealed, RuBisCo subunits had a binding site for ergosterol and in its presence affinity of Co2 to the enzyme increased by several folds. Invivo activity of RuBisCo was significantly elicited by ergosterol. Results of the present study indicate that ergosterol from phylloplane microfungi probably regulates the binding of Co2 to RuBisCo along with activity of carbonic anhydrase thereby modulating the physiology of choloroplast.

Keywords: carbonic anhydrase, ergosterol, phylloplane, RuBisCo

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Authors: Ngoc Quang Nguyen, Daewon Sohn

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Chitosan (CS) is a natural polycationic polysaccharide and pH-sensitive polymer with incomplete deacetylation from claiming chitin. It is also a guaranteeing material in terms of pharmaceutical, chemical, and sustenance industry due to its exceptional structure (reactive –OH and –NH2 groups). In this study, a catechol-functionalized chitosan (CCS, for an eminent level for substitution) was synthesized and propelled by marine mussel cuticles in place on research those intricate connections between Fe³⁺ and catechol under acidic conditions. The ratios of catechol, chitosan and other reagents decide the structure of the hydrogel. The gel formation is then well-maintained by dual cross-linking through electrostatic interactions between Fe³⁺ and CCS and covalent catechol-coupling-based coordinate bonds. The hydrogels showed enhanced cohesiveness and shock-absorbing properties with increasing pH due to coordinate bonds inspired by mussel byssal threads. Thus, the gelation time, rheological properties, UV-vis and ¹H-Nuclear Magnetic Resonance spectroscopy, and the morphologic aspects were elucidated to describe those crosslinking components and the physical properties of the chitosan backbones and hydrogel frameworks.

Keywords: catechol, chitosan, iron ion, gelation, hydrogel

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Authors: Driss Cherqaoui, Nouhaila Ait Lahcen, Ismail Hdoufane, Mehdi Oubahmane, Wissal Liman, Christelle Delaite, Mohammed M. Alanazi

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The Ebola virus is a highly contagious and deadly pathogen that causes Ebola virus disease. The Ebola virus glycoprotein (EBOV-GP) is a key factor in viral entry into host cells, making it a critical target for therapeutic intervention. Using a combination of computational approaches, this study focuses on the identification of natural compounds that could serve as potent inhibitors of EBOV-GP. The 3D structure of EBOV-GP was selected, with missing residues modeled, and this structure was minimized and equilibrated. Two large natural compound databases, COCONUT and NPASS, were chosen and filtered based on toxicity risks and Lipinski’s Rule of Five to ensure drug-likeness. Following this, a pharmacophore model, built from 22 reported active inhibitors, was employed to refine the selection of compounds with a focus on structural relevance to known Ebola inhibitors. The filtered compounds were subjected to virtual screening via molecular docking, which identified ten promising candidates (five from each database) with strong binding affinities to EBOV-GP. These compounds were then validated through molecular dynamics simulations to evaluate their binding stability and interactions with the target. The top three compounds from each database were further analyzed using ADMET profiling, confirming their favorable pharmacokinetic properties, stability, and safety. These results suggest that the selected compounds have the potential to inhibit EBOV-GP, offering new avenues for antiviral drug development against the Ebola virus.

Keywords: EBOV-GP, Ebola virus glycoprotein, high-throughput drug screening, molecular docking, molecular dynamics, natural compounds, pharmacophore modeling, virtual screening

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