Search results for: lysine synthesis pathway

Authors: Akintayo Emmanuel Temitope, Akintayo Cecilia Olufunke, Ziegler Thomas

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Bio-polyols are important components in polyurethane industries. The preliminary studies into the synthesis of bio-polyol products (epoxy-polyol and epoxyl-polyurethanes) from Jatropha curcas were investigated. The reactions were followed by both infrared and nuclear magnetic resonance. Physico-chemical characterisation of the samples for iodine value (IV), acid value (AV), saponification value (SV) and hydroxyl value (HV) were carried out. Thermal transitions of the products were studied by heating 5 mg of the sample from 20ºC to 800ºC and then cooling down to -500ºC on a differential scanning calorimeter (DSC). The preparation of epoxylpolyol and polyurethane from Jatropha curcas oil was smooth and efficient. Results of film and solubility properties revealed that coatings of Jatropha curcas epoxy-polyurethanes performed better with increased loading of toluylene 2, 4-diisocyanate (TDI) up to 2 wt% while their solvent resistance decreased beyond a TDI loading of 1.2 wt%. DSC analysis shows the epoxy-polyurethane to be less stable compared to the epoxy-polyol.

Keywords: synthesis, epoxy-polyol, epoxy-polyurethane, jatropha curcas oil

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Authors: Ali Bahri Lubis

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Tryptophan oxidation by Heme-dioxygenase enzyme is initial important stepTryptophan oxidation by Heme-dioxygenase enzyme is initial important step in kynurenine pathway implicating to several severe diseases such as Parkinson’s Disease, Huntington Disease, poliomyelitis and cataract. It is crucial to comprehend the oxidation mechanism with the hope to find decent treatment upon abovementioned diseases. The mechanism has been debatable since no one has been yet proved the mechanism obviously. In this research we have attempted to prove mechanistic steps of tryptophan oxidation via human indoleamine dioxygenase (h-IDO) using various substrates: L-tryptophan, L-tryptophan (indole-ring-2-13C), L-fully-labelled13C-tryptophan, L-N-methyl-tryptophan, L-tryptophan and 2-amino-3-(benzo(b)thiophene-3-yl) propanoic acid. All enzyme assay experiments were measured using a UV-Vis spectrophotometer, LC-MS, 1H-NMR, and HSQC. We also successfully synthesized enzyme products as our control in NMR measurements. The result exhibited that the distinct substrates produced N-formyl kynurenine (NFK) and hydroxypyrrolloindoleamine carboxylate acid (HPIC) in different concentrations and isomers, correlated to the proposal of considered mechanism reaction in kynurenine pathway implicating to several severe diseases such as Parkinson’s Disease, Huntington Disease, poliomyelitis and cataract. It is crucial to comprehend the oxidation mechanism with the hope to find decent treatment for the abovementioned diseases. The mechanism has been debatable since no one has yet proven the mechanism obviously. In this research we have attempted to prove mechanistic steps of tryptophan oxidation via human indoleamine dioxygenase (h-IDO) using various substrates: L-tryptophan, L-tryptophan (indole-ring-2-13C), L-fully-labelled13C-tryptophan, L-N-methyl-tryptophan, L-tryptophan and 2-amino-3-(benzo(b)thiophene-3-yl) propanoic acid. All enzyme assay experiments were measured using a UV-Vis spectrophotometer, LC-MS, 1H-NMR and HSQC. We also successfully synthesized enzyme products as our control in NMR measurements. The result exhibited that the distinct substrates produced N-formyl kynurenine (NFK) and hydroxypyrrolloindoleamine carboxylate acid (HPIC) in different concentrations and isomers, correlated to the proposal of considered mechanism reaction.

Keywords: heme-dioxygenase enzyme, tryptophan oxidation, kynurenine pathway, n-formyl kynurenine

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Authors: Agnieszka Fryźlewicz, Jowita Kras, Mikołaj Sadowski, Agnieszka Łapczuk-Krygier, Agnieszka Kącka-Zych Radomir Jasiński

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Nicotines are a group of compounds containing conjugated pyridine and pyrrolidine molecular segments. They are widely applied in medicine, pharmacy, and agriculture. Namely as researched treatment of Alzheimer, depression, Parkinson's, Tourette syndrome, general nervous and mental disorders. Furthermore, nicotine itself is used as a stimulant, animal repellent and was widely applied as an insecticide. In our work, we obtained nicotine analogues with possible applications in agriculture. The synthesis employed [3+2] cycloaddition (32CA) reactions, occurring between pirydyl-functionalised nitrones and conjugated nitroalkenes, that allowed us to fully regio- and stereoselectively obtain product. Moreover, cycloaddition reaction realizes rapidly in mild conditions with the full atomic economy, thus fitting into “green chemistry” trends.

Keywords: nicotine, isoxazolidine, 1-3-dipolar cycloaddition, green chemistry, biological and pharmacological activity

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Authors: Saeideh Lotfi Nikoo, Azadeh Ghaheri, Reza Omani Samani

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Context: In most cultures around the globe, infertility is recognized as a crisis and exposed infertile couples are under psychosocial pressure. Indeed, the quality of life (QoL) for infertile women is lower in comparison with fertile control. Objective, The purpose of this study, was to investigate the impact of social support and hope on QoL in women undergoing infertility treatment. Methods: A cross-sectional study. Patient(s): In this cross-sectional study, 350 infertile women were recruited who were referred to an infertility clinic for the first time and had no history of Assisted Reproductive Techniques (ART) failure. Intervention(s): Questionnaires on the Fertility Quality of Life (FertiQoL), Multi-dimensional Scale of Perceived Social Support (family and friends), and Snyder Hope Scale (pathway and agency) were used to collect data. Data analysis was done by univariate and multivariate analysis. P value <0.05 was considered statistically significant. Result(s): Multivariate analysis indicated that infertile women with a higher score of social support (by family & friends) (b= 0.59 (CI 95%: 0.03, 1.15) (P = 0.040), b= 0.61 (CI 95%: 0.17, 1.04) (P = 0.006)) and hope (pathway & agency) (b= 0.94 (CI 95%: 0.29, 1.59) (P = 0.005), b= 1.13 (CI 95%: 0.45, 1.82) (P = 0.001) respectively) have significantly better Core FertiQoL. The result revealed that social support and hope are significantly and positively associated with other subscales of FertiQoL as well. Conclusions: According to the results, lifestyle interventions such as receiving social support, building a sound family with effective communication, and providing appropriate health education are of crucial importance to address psychological distress and improve the fertility QoL of women experiencing fertility problems.

Keywords: inertility, social support, infertile women, hope

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Authors: R. Sarada Jayalakshmi Devi B. Bhaskar, S. Khayum Ahammed, T. N. V. K. V. Prasad

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Use of bioagents and biofungicides is safe to manage the plant diseases and to avoid human health hazards which improves food security. Myconanotechnology is the study of nanoparticles synthesis using fungi and their applications. The present work reports on preparation, characterization and antifungal activity of biogenic silver nanoparticles produced by the fungus Trichoderma sp. which was collected from groundnut rhizosphere. The culture filtrate of Trichoderma sp. was used for the reduction of silver ions (Ag+) in AgNO3 solution to the silver (Ag0) nanoparticles. The different ages (4 days, 6 days, 8 days, 12 days, and 15 days) of culture filtrates were screened for the synthesis of silver nanoparticles. Synthesized silver nanoparticles were characterized using UV-Vis spectrophotometer, particle size and zeta potential analyzer, Fourier Transform Infrared Spectrophotometer (FTIR) and Transmission Electron Microscopy. Among all the treatments the silver nitrate solution treated with six days aged culture filtrate of Trichoderma sp. showed the UV absorption peak at 440 nm with maximum intensity (0.59) after 24 hrs incubation. The TEM micrographs showed the spherical shaped silver nanoparticles with an average size of 30 nm. The antifungal activity of silver nanoparticles against Aspergillus niger causing collar rot disease in groundnut and aspergillosis in humans showed the highest per cent inhibition at 100 ppm concentration (74.8%). The results points to the usage of these mycogenic AgNPs in agriculture to control plant diseases.

Keywords: groundnut rhizosphere, Trichoderma sp., silver nanoparticles synthesis, antifungal activity

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Authors: Chang-Hui Shen, Michelle Esposito, Andrew J. Shen, Michael Adejokun, Diana Laterman

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The packaging of DNA into nucleosomes is critical to genomic compaction, yet it can leave gene promoters inaccessible to activator proteins or transcription machinery and thus prevents transcriptional initiation. Both chromatin remodelers and histone acetylases (HATs) are the two main transcription co-activators that can reconfigure chromatin structure for transcriptional activation. Ino80p is the core component of the INO80 remodeling complex. Recently, it was shown that Ino80p dissociates from the yeast INO1 promoter after induction. However, when certain HATs were deleted or mutated, Ino80p accumulated at the promoters during gene activation. This suggests a link between HATs’ presence and Ino80p’s dissociation. However, it has yet to be demonstrated that Ino80p can be acetylated. To determine if Ino80p can be acetylated, wild-type Saccharomyces cerevisiae cells carrying Ino80p engineered with a double FLAG tag (MATa INO80-FLAG his3∆200 leu2∆0 met15∆0 trp1∆63 ura3∆0) were grown to mid log phase, as were non-tagged wild type (WT) (MATa his3∆200 leu2∆0 met15∆0 trp1∆63 ura3∆0) and ino80∆ (MATa ino80∆::TRP1 his3∆200 leu2∆0 met15∆0 trp1∆63 ura3∆0) cells as controls. Cells were harvested, and the cell lysates were subjected to immunoprecipitation (IP) with α-FLAG resin to isolate Ino80p. These eluted IP samples were subjected to SDS-PAGE and Western blot analysis. Subsequently, the blots were probed with the α-FLAG and α-acetyl lysine antibodies, respectively. For the blot probed with α-FLAG, one prominent band was shown in the INO80-FLAG cells, but no band was detected in the IP samples from the WT and ino80∆ cells. For the blot probed with the α-acetyl lysine antibody, we detected acetylated Ino80p in the INO80-FLAG strain while no bands were observed in the control strains. As such, our results showed that Ino80p can be acetylated. This acetylation can explain the co-activator’s recruitment patterns observed in current gene activation models. In yeast INO1, it has been shown that Ino80p is recruited to the promoter during repression, and then dissociates from the promoter once de-repression begins. Histone acetylases, on the other hand, have the opposite pattern of recruitment, as they have an increased presence at the promoter as INO1 de-repression commences. This Ino80p recruitment pattern significantly changes when HAT mutant strains are studied. It was observed that instead of dissociating, Ino80p accumulates at the promoter in the absence of functional HATs, such as Gcn5p or Esa1p, under de-repressing processes. As such, Ino80p acetylation may be required for its proper dissociation from the promoters. The remodelers’ dissociation mechanism may also have a wide range of implications with respect to transcriptional initiation, elongation, or even repression as it allows for increased spatial access to the promoter for the various transcription factors and regulators that need to bind in that region. Our findings here suggest a previously uncharacterized interaction between Ino80p and other co-activators recruited to promoters. As such, further analysis of Ino80p acetylation not only will provide insight into the role of epigenetic modifications in transcriptional activation, but also gives insight into the interactions occurring between co-activators at gene promoters during gene regulation.

Keywords: acetylation, chromatin remodeler, epigenetic modification, Ino80p

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Authors: Yemane Tadesse Gebreslassie, Fisseha Guesh Gebremeskel

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Nanotechnology has made remarkable advancements in recent years, revolutionizing various scientific fields, industries, and research institutions through the utilization of metal and metal oxide nanoparticles. Among these nanoparticles, copper oxide nanoparticles (CuO NPs) have garnered significant attention due to their versatile properties and wide-range applications, particularly, as effective antimicrobial and anticancer agents. CuO NPs can be synthesized using different methods, including physical, chemical, and biological approaches. However, conventional chemical and physical approaches are expensive, resource-intensive, and involve the use of hazardous chemicals, which can pose risks to human health and the environment. In contrast, biological synthesis provides a sustainable and cost-effective alternative by eliminating chemical pollutants and allowing for the production of CuO NPs of tailored sizes and shapes. This comprehensive review focused on the green synthesis of CuO NPs using various biological resources, such as plants, microorganisms, and other biological derivatives. Current knowledge and recent trends in green synthesis methods for CuO NPs are discussed, with a specific emphasis on their biomedical applications, particularly in combating cancer and microbial infections. This review highlights the significant potential of CuO NPs in addressing these diseases. By capitalizing on the advantages of biological synthesis, such as environmental safety and the ability to customize nanoparticle characteristics, CuO NPs have emerged as promising therapeutic agents for a wide range of conditions. This review presents compelling findings, demonstrating the remarkable achievements of biologically synthesized CuO NPs as therapeutic agents. Their unique properties and mechanisms enable effective combating against cancer cells and various harmful microbial infections. CuO NPs exhibit potent anticancer activity through diverse mechanisms, including induction of apoptosis, inhibition of angiogenesis, and modulation of signaling pathways. Additionally, their antimicrobial activity manifests through various mechanisms, such as disrupting microbial membranes, generating reactive oxygen species, and interfering with microbial enzymes. This review offers valuable insights into the substantial potential of biologically synthesized CuO NPs as an alternative approach for future therapeutic interventions against cancer and microbial infections.

Keywords: biological synthesis, copper oxide nanoparticles, microbial infection, nanotechnology

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Authors: H. Benaldjia, N. Habib, F. Djefaflia, A. Nait-Merzoug, A. Harat, J. El-Haskouri, O. Guellati

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Currently, the technology has attracted knowledge of energy storage sources similar to batteries, capacitors and super-capacitors because of its very different applications in many fields with major social and economic challenges. Moreover, hydroxides have attracted much attention as a promising and active material choice in large-scale applications such as molecular adsorption/storage and separation for the environment, ion exchange, nanotechnology, supercapacitor for energy storage and conversion, electro-biosensing, and catalysts, due to their unique properties which are strongly influenced by their composition, microstructure, and synthesis method. In this context, we report in this study the synthesis of hydroxide-based nanomaterials precisely based on Ni and Fe using a simple hydrothermal method with mono and bi precursors at optimized growth conditions (6h-120°C). The obtained products were characterized using different techniques, such as XRD, FTIR, FESEM and BET, as well as electrochemical measurements.

Keywords: energy storage, Supercapacitors, nanocomposites, nanohybride, electro-active materials.

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Authors: T. Bielewicz, S. Dogan, C. Klinke

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Two-dimensional, solution-processable semiconductor materials are interesting for low-cost electronic applications [1]. We demonstrate the synthesis of lead sulfide nanosheets and how their size, shape and height can be tuned by varying concentrations of pre-cursors, ligands and by varying the reaction temperature. Especially, the charge carrier confinement in the nanosheets’ height adjustable from 2 to 20 nm has a decisive impact on their electronic properties. This is demonstrated by their use as conduction channel in a field effect transistor [2]. Recently we also showed that especially thin nanosheets show a high carrier multiplication (CM) efficiency [3] which could make them, through the confinement induced band gap and high photoconductivity, very attractive for application in photovoltaic devices. We are already able to manufacture photovoltaic devices out of single nanosheets which show promising results.

Keywords: physical sciences, chemistry, materials, chemistry, colloids, physics, condensed-matter physics, semiconductors, two-dimensional materials

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Authors: Amna J. Ghith, Khaled Abu Zid, Khairia Youssef, Nasser Saad

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Backgrounds: The multikinase and vascular endothelial growth factor (VEGF) receptor inhibitors interrupt the pathway by which angiogenesis becomes established and promulgated, resulting in the inadequate nourishment of metastatic disease. VEGFR-2 has been the principal target of anti-angiogenic therapies. We disclose the new thieno pyrimidines as inhibitors of VEGFR-2 designed by a molecular modeling approach with increased synergistic activity and decreased side effects. Purpose: 2-substituted thieno pyrimidines are designed and synthesized with anticipated anticancer activity based on its in silico molecular docking study that supports the initial pharmacophoric hypothesis with a same binding mode of interaction at the ATP-binding site of VEGFR-2 (PDB 2QU5) with high docking score. Methods: A series of compounds were designed using discovery studio 4.1/CDOCKER with a rational that mimic the pharmacophoric features present in the reported active compounds that targeted VEGFR-2. An in silico ADMET study was also performed to validate the bioavailability of the newly designed compounds. Results: The Compounds to be synthesized showed interaction energy comparable to or within the range of the benzimidazole inhibitor ligand when docked with VEGFR-2. ADMET study showed comparable results most of the compounds showed absorption within (95-99) zone varying according to different substitutions attached to thieno pyrimidine ring system. Conclusions: A series of 2-subsituted thienopyrimidines are to be synthesized with anticipated anticancer activity and according to docking study structure requirement for the design of VEGFR-2 inhibitors which can act as powerful anticancer agents.

Keywords: docking, discovery studio 4.1/CDOCKER, heterocycles based anticancer agents, 2-subsituted thienopyrimidines

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Authors: Anna Piasek, Anna Szymkiewicz, Gabriela Wiktor, Jolanta Pulit-Prociak, Marcin Banach

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Carbon dots (CDs) have great potential for application in many fields of science. They are characterized by fluorescent properties that can be manipulated. The nanomaterial has many advantages in addition to its unique properties. CDs may be obtained easily, and they undergo surface functionalization in a simple way. In addition, there is a wide range of raw materials that can be used for their synthesis. An interesting possibility is the use of numerous waste materials of natural origin. In the research presented here, the synthesis of CDs was carried out according to the principles of Green chemistry. Beet molasses was used as a natural raw material. It has a high sugar content. This makes it an excellent high-carbon precursor for obtaining CDs. To increase the fluorescence effect, we modified the surface of CDs with silver (Ag-CDs) nanoparticles. The process of obtaining CQD was based on the hydrothermal method by applying microwave radiation. Silver nanoparticles were formed via the chemical reduction method. The synthesis plans were performed on the Design of the Experimental method (DoE). Variable process parameters such as concentration of beet molasses, temperature and concentration of nanosilver were used in these syntheses. They affected the obtained properties and particle parameters. The Ag-CDs were analyzed by UV-vis spectroscopy. The fluorescence properties and selection of the appropriate excitation light wavelength were performed by spectrofluorimetry. Particle sizes were checked using the DLS method. The influence of the input parameters on the obtained results was also studied.

Keywords: fluorescence, modification, nanosilver, molasses, Green chemistry, carbon dots

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Authors: Chul Lee, Seoae Cho, Erich D. Jarvis, Heebal Kim

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Vocal learning, the ability to imitate vocalizations based on auditory experience, is a homoplastic character state observed in different independent lineages of animals such as songbirds, parrots, hummingbirds and human. It has now become possible to perform genome-wide molecular analyses across vocal learners and vocal non-learners with the recent expansion of avian genome data. It was analyzed the whole genomes of human and 48 avian species including those belonging to the three avian vocal learning lineages, to determine if behavior and neural convergence are associated with molecular convergence in divergent species of vocal learners. Analyses of 8295 orthologous genes across bird species revealed 141 genes with amino acid substitutions specific to vocal learners. Out of these, 25 genes have vocal learner specific genetic homoplasies, and their functions were enriched for learning. Several sites in these genes are estimated under convergent evolution and positive selection. A potential role for a subset of these genes in vocal learning was supported by associations with gene expression profiles in vocal learning brain regions of songbirds and human disease that cause language dysfunctions. The key candidate gene with multiple independent lines of the evidences specific to vocal learners was DRD5. Our findings suggest cAMP-based learning pathway in avian vocal learners, indicating molecular homoplastic changes associated with a complex behavioral trait, vocal learning.

Keywords: amino acid substitutions, convergent evolution, positive selection, vocal learning

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Authors: Bright Kwakye-Awuah, Elizabeth Von-Kiti, Isaac Nkrumah, Baah Sefa-Ntiri, Craig D. Williams

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Bauxite and kaolin from Ghana Bauxite Company mine site were used to synthesize zeolites. Bauxite served as the alumina source and kaolin the silica source. Synthesis variations include variation of aging time at constant crystallization time and variation of crystallization times at constant aging time. Characterization techniques such as X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive x-ray analysis (EDX) and Fourier transform infrared spectroscopy (FTIR) were employed in the characterization of the raw samples as well as the synthesized samples. The results obtained showed that the transformations that occurred and the phase of the resulting products were coordinated by the aging time, crystallization time, alkaline concentration and Si/Al ratio of the system. Zeolites A, X, Y, analcime, Sodalite, and ZK-14 were some of the phases achieved. Zeolite LTA was achieved with short crystallization times of 3, 5, 18 and 24 hours and a maximum aging of 24 hours. Zeolite LSX was synthesized with 24 hr aging followed with 24 hr hydrothermal treatment whilst zeolite Y crystallized after 48 hr of aging and 24 hr crystallization. Prolonged crystallization time produced a mixed phased product. Prolonged aging times, on the other hand, did not yield any zeolite as the sample was amorphous. Increasing the alkaline content of the reaction mixture above 5M introduced sodalite phase in the final product. The properties of the final products were comparable to zeolites synthesized from pure chemical reagents.

Keywords: bauxite, kaolin, aging, crystallization, zeolites

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Authors: Esther Friedlander, Philip Friedlander

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The use of immunotherapy that inhibits programmed death-1 (PD-1) or its ligand PD-L1 confers survival benefits in patients with non-small cell lung cancer (NSCLC). However, approximately 45% of patients experience primary treatment resistance, necessitating the development of strategies to improve efficacy. While the renin-angiotensin system (RAS) has systemic hemodynamic effects, tissue-specific regulation exists along with modulation of immune activity in part through regulation of myeloid cell activity, leading to the hypothesis that RAS inhibition may improve anti-PD-1/L-1 efficacy. A retrospective analysis was conducted that included 173 advanced solid tumor cancer patients treated at Valley Hospital, a community Hospital in New Jersey, USA, who were treated with a PD-1/L-1 inhibitor in a defined time period showing a statistically significant relationship between RAS pathway inhibition (RASi through concomitant treatment with an ACE inhibitor or angiotensin receptor blocker) and positive efficacy to the immunotherapy that was independent of age, gender and cancer type. Subset analysis revealed strong numerical benefit for efficacy in both patients with squamous and nonsquamous NSCLC as determined by documented clinician assessment of efficacy and by duration of therapy. A PUBMED literature search was now conducted to identify studies assessing the effect of RAS pathway inhibition on anti-PD-1/L1 efficacy in advanced solid tumor patients and compare these findings to those seen in the Valley Hospital retrospective study with a focus on NSCLC specifically. A total of 11 articles were identified assessing the effects of RAS pathway inhibition on the efficacy of checkpoint inhibitor immunotherapy in advanced cancer patients. Of the 11 studies, 10 assessed the effect on survival of RASi in the context of treatment with anti-PD-1/PD-L1, while one assessed the effect on CTLA-4 inhibition. Eight of the studies included patients with NSCLC, while the remaining 2 were specific to genitourinary malignancies. Of the 8 studies, two were specific to NSCLC patients, with the remaining 6 studies including a range of cancer types, of which NSCLC was one. Of these 6 studies, only 2 reported specific survival data for the NSCLC subpopulation. Patient characteristics, multivariate analysis data and efficacy data seen in the 2 NSLCLC specific studies and in the 2 basket studies, which provided data on the NSCLC subpopulation, were compared to that seen in the Valley Hospital retrospective study supporting a broader effect of RASi on anti-PD-1/L1 efficacy in advanced NSLCLC with the majority of studies showing statistically significant benefit or strong statistical trends but with one study demonstrating worsened outcomes. This comparison of studies extends published findings to the community hospital setting and supports prospective assessment through randomized clinical trials of efficacy in NSCLC patients with pharmacodynamic components to determine the effect on immune cell activity in tumors and on the composition of the tumor microenvironment.

Keywords: immunotherapy, cancer, angiotensin, efficacy, PD-1, lung cancer, NSCLC

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Authors: Sameh M. Osman, El-Refaie Kenawy, Zeid A. Al-Othman, Mohamed H. El-Newehy, El-Saied A. Aly, Sherine N. Khattab, Ayman El-Faham

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Recently, there has been a huge interest in using cyanuric chloride in a wide range of functional group transformations, as Cyanuric chloride has temperature-dependent differential reactivity for displacement of chlorides with various nucleophiles In the present work, some copolymers based on s-triazine Unit were prepared by microwave-assisted synthesis. For comparison study, the copolymers were synthesized by the conventional method. Synthesized Copolymers were characterized by MP, IR, TGA, DSC and GPC. The result indicated that copolymers are thermally stable and in good in composition and yield. Further studies that involve the test for selected removal of transition elements such as Cu (II), Zn (II) and Mn (II). Moreover, the effects of the polymeric triazine derivatives containing different functional groups which expected to have a good thermal stability and char formation ability on thermal degradation and flame retardancy.

Keywords: flame retardants, heavy metals, microwave-assisted synthesis, s-triazine

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Authors: Hani M. Alothaid, Louise Robson, Richmond Muimo

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Cystic fibrosis (CF) is a disease that affects respiratory function and in EU it affects about 1 in 2,500 live births with an average 40-year life expectancy. This disease caused by mutations within the gene encoding the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) chloride channel leading to dysregulation of epithelial fluid transport and chronic lung inflammation, suggesting functional alterations of immune cells. In airways, CFTR been found to form a functional complex with S100A10 and AnxA2 in a cAMP/PKA dependent manner. The multiprotein complex of AnxA2-S100A10 and CFTR is also regulated by calcineurin. The aim of this study was i) to investigate whether chloride ion (Cl−) channels are activated by Pseudomonas aeruginosa lipopolysaccharide (LPS from PA), ii) if this activation is regulated by cAMP/PKA/calcineurin pathway and iii) to investigate the role of LPS-activated Cl− channels in the release of pro-inflammatory cytokines by immune cells. Human peripheral blood monocytes were used in the study. Whole-cell patch records showed that LPS from PA can activate Cl− channels, including CFTR and outwardly-rectifying Cl− channel (ORCC). This activation appears to require an intact PKA/calcineurin signalling pathway. The Gout in the presence of LPS was significantly inhibited by diisothiocyanatostilbene-disulfonic acid (DIDS), an ORCC blocker (p<0.001). The Gout was further suppressed by CFTR(inh)-172, a specific inhibitor for CFTR channels (p<0.001). Monocytes pre-incubated with PKA inhibitor or calcineurin inhibitor before stimulated with LPS from PA that were resulted in DIDS and CFTR(inh)-172 insensitive currents. Activation of both ORCC and CFTR was however, observed in response to monocytes exposure to LPS. Additionally, ELISA showed that the CFTR and ORCC play a role in mediating the release of pro-inflammatory cytokines such as IL-1β upon exposure of monocytes to LPS. However, this secretion was significantly inhibited due to CFTR and ORCC inhibition. However, Cl− may play a role in IL-1β release independent of cAMP/PKA/calcineurin signalling due to the enhancement of IL-1β secretion even when cAMP/PKA/calcineurin pathway was inhibited. In conclusion, our data confirmed that LPS from PA activates Cl− channels in human peripheral blood monocytes. Our data also confirmed that Cl− channels were involved in IL-1β release in monocytes upon exposure to LPS. However, it has been found that PKA and calcineurin does not seem to influence the Cl− dependent cytokine release.

Keywords: cystic fibrosis, CFTR, Annexin A2, S100A10, PP2B, PKA, outwardly-rectifying Cl− channel, Pseudomonas aeruginosa

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Authors: Nasser R. El-Brollosy, Roberta Loddo

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6-Benzyl-1-(ethoxymethyl)-5-isopropyluracil (Emivirine) and its corresponding 1-benzyloxymethyl analogue (TNK-651) showed high activity against HIV-1. The present study describes synthesis of novel emivirine analogues by reaction of chloromethyl ethyl ether with uracils having 5-ethyl / isopropyl and 6-(3,5-dimethoxybenzyl) substituents. A series of new TNK-651 analogues substituted at N-1 with phenoxyethoxymethyl moiety was prepared on treatment of the corresponding uracils with bis(phenoxyethoxy) methane. The newly synthesized non-nucleosides were tested for biological activity against wild type HIV-1 IIIB as well as the resistant strains N119 (Y181C), A17 (K103N + Y181C), and the triple mutant EFVR (K103R + V179D + P225H) in MT-4 cells. Some of the tested compounds showed good activities. Among them 6-(3,5-dimethylbenzyl)-5-ethyl-1-[2-(phenoxyethyl) oxymethyl]uracil which showed inhibitory potency higher than emivirine against both wild type HIV-1 and the tested mutant strains.

Keywords: Emivirine, HIV, non-nucleoside reverse transcriptase, uracils

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Authors: Anas Al-Ali, Mohammed Suleiman, Ayman Hussein

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Sulfur is an important element has many practical applications in present as nanoparticles. Nanosize sulfur particles also have many important applications like in pharmaceuticals, medicine, syn-thesis of nano-composites for lithium batteries, modification of carbon nano tubes. Different methods were used for nano-sized particle synthesis; among those, chemical precipitation, electrochemical method, micro emulsion technique, composing of oil, surfactant, co-surfactant, aqueous phases with the specific compositions and ultrasonic treatment of sulfur-cystine solution. In this work Sulfur nanoparticles (S NPs) were prepared by a quick precipitation method with and without using a surfactant to stabilize the formed S NPs. The synthesized S NPs were characterized by XRD, SEM and TEM in order to confirm their sizes and structures.Application of nanotechnology is suggested for diag-nosis and treatment of cancer. The anticancer activity of the prepared S NPs has been tested on various types of cancer cell clones including leukemia, kidney and colon cancers.

Keywords: sulfur nanoparticles (S-NPs), TEM, SEM, XRD

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Authors: Fereshteh Chekin, Sepideh Sadeghi

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Nickel nanoparticles have attracted much attention because of applications in catalysis, medical diagnostics and magnetic applications. In this work, we reported a simple and low-cost procedure to synthesize nickel oxide nanoparticles (NiO-NPs) by using sodium dodecyl sulphate (SDS) and gelatin as stabilizer. The synthesized NiO-NPs were characterized by a variety of means such as transmission electron microscope (TEM), powder X-ray diffraction (XRD), scanning electron microscope (SEM) and UV-vis spectroscopy. The results show that the NiO nanoparticles with high crystalline can be obtained using this simple method. The grain size measured by TEM was 16 in presence of SDS, which agrees well with the XRD data. SDS plays an important role in the formation of the NiO nanoparticles. Moreover, the NiO nanoparticles have been used as a solid phase catalyst for the decomposition of hydrazine hydrate at room temperatures. The decomposition process has been monitored by UV–vis analysis. The present study showed that nanoparticles are not poisoned after their repeated use in decomposition of hydrazine.

Keywords: nickel oxide nanoparticles, sodium dodecyl sulphate, synthesis, stabilizer

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Authors: Li Lin Ong, Duc Thinh Khong, Zaher M. A. Judeh

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Phenylpropanoid sucrose esters (PSEs) are natural compounds found in various medicinal plants which exhibit important biological activities such as antiproliferation and α- and β-glucosidase inhibitory activities. Despite their potential as new therapeutics, total synthesis of PSEs has been very limited as their inherent structures contain one or more (substituted) cinnamoyl groups randomly allocated on the sucrose core via ester linkage. Since direct acylation of unprotected sucrose would be complex and tedious due to the presence of eight free hydroxyl groups, partially protected 2,1’:4,6-di-O-diisopropylidene sucrose was used as the starting material instead. However, similar reactivity between the remaining four hydroxyl groups still pose a challenge in the total synthesis of PSEs as the lack of selectivity can restrict customisation where acylation at specific OH is desired. To overcome this problem, a 4-step orthogonal protection scheme was developed. In this scheme, the remaining four hydroxyl groups on 2,1’:4,6-di-O-diisopropylidene sucrose, 6’-OH, 3’-OH, 4’-OH, and 3-OH, were protected with different protecting groups with an overall yield of > 40%. This orthogonally protected intermediate would provide a convenient and divergent access to a wider range of natural and synthetic PSEs as (substituted) cinnamoyl groups can be selectively introduced at desired positions. Using this scheme, three different series of monosubstituted PSEs were successfully synthesized where (substituted) cinnamoyl groups were introduced selectively at O-3, O-3’, and O-4’ positions, respectively. The expanded library of PSEs would aid in structural-activity relationship study of PSEs for identifying key components responsible for their biological activities.

Keywords: orthogonal protection, phenylpropanoid sucrose esters, selectivity, sucrose

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Authors: Molly Parker

Abstract:

Unintended pregnancy rates in Australia are amongst the highest in the developed world. Women with Substance Use Disorder often have riskier sexual behavior with nil contraceptive use and face disproportionately higher unintended pregnancies and Sexually Transmitted Infections, alongside Substance Use in Pregnancy (SUP) climbing at an alarming rate. In an inner-city Drug and Alcohol (D&A) service, significant barriers to sexual and reproductive health services have been identified, aligning with research. Rapid pathways were created for women seeking D&A treatment to be referred to Sexual and Reproductive Health services for the administration of Long-acting reversible contraception (LARC) and sexual health screening. For clients attending a D&A service, this is an opportunistic time to offer sexual and reproductive health services. Collaboration and multidisciplinary team input between D&A and sexual health and reproductive services are paramount, with rapid referral pathways being identified as the main strategy to improve access to sexual and reproductive health support for this population. With this evidence, a rapid referral pathway was created for women using the D&A service to access LARC, particularly in view of fertility often returning once stable on D&A treatment. A closed-ended survey was used for D&A staff to identify gaps in reproductive health knowledge and views of referral accessibility. Results demonstrated a lack of knowledge of contraception and appropriate referral processes. A closed-ended survey for clients was created to establish the need and access to services and to quantify data. A follow-up data collection will be reviewed to access uptake and satisfaction of the intervention from clients. Sexual health screening access was also identified as a deficit, particularly concerning due to the higher rates of STIs in this cohort. A rapid referral pathway will be undergoing implementation, reducing risks of untreated STIS both pre and post-conception. Similarly, pre and post-intervention structured surveys will be used to identify client satisfaction from the pathway. Although currently in progress, the research and pathway aim to be completed by December 2023. This research and implementation of sexual and reproductive health pathways from the D&A service have significant health and well-being benefits to clients and the wider community, including possible fetal/infancy outcomes. Women now have rapid access to sexual and reproductive health services, with the aim of reducing unplanned pregnancies, poor outcomes associated with SUP, client/staff trauma from termination of pregnancy, and client/staff trauma following the assumption of care of the child due to substance use, the financial cost for out of home care as required, the poor outcomes of untreated STIs to the fetus in pregnancy and the spread of STIs in the wider community. As evidence suggests, the implementation of a streamlined referral process is required between D&A and sexual and reproductive health services and has positive feedback from both clinicians and clients in improving care.

Keywords: substance use in pregnancy, drug and alcohol, substance use disorder, sexual health, reproductive health, contraception, long-acting reversible contraception, neonatal abstinence syndrome, FASD, sexually transmitted infections, sexually transmitted infections pregnancy

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Authors: Samy M. Shaban, Ismail Aiad, Mohamed M. El-Sukkary, E. A. Soliman, Moshira Y. El-Awady

Abstract:

In situ and green synthesis of cubic and spherical silver nanoparticles were developed using sun light as reducing agent in the presence of newly prepared cationic surfactant which acting as capping agents. The morphology of prepared silver nanoparticle was estimated by transmission electron microscope (TEM) and the size distribution determined by dynamic light scattering (DLS). The hydrophobic chain length of the prepared surfactant effect on the stability of the prepared silver nanoparticles as clear from zeta-potential values. Also by increasing chain length of the used capping agent the amount of formed nanoparticle increase as indicated by increasing the absorbance. Both prepared surfactants and surfactants capping silver nanoparticles showed high antimicrobial activity against gram positive and gram-negative bacteria.

Keywords: photosynthesis, hexaonal shapes, zetapotential, biological activity

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Authors: Gizaw Mamo Gebeyehu, Marianna Pap, Geza Makkai, Tibor Z. Janosi, Shima Rashidian, Tibor A. Rauch

Abstract:

Sepsis poses a significant global health threat, necessitating extensive exploration of indicators tied to its pathological mechanisms and multi-organ dysfunction. While murine studies have shed light on sepsis, the intricate cellular and molecular landscape in human sepsis remains enigmatic. Exploring the influence of activated monocyte-derived exosomes in sepsis sheds light on a promising pathway for understanding the intricate cellular and molecular mechanisms involved in this condition in humans. In sepsis, exosome-borne mRNA and miRNA orchestrate immune response gene expression in recipient cells. Yet, the specifics of exosome-mediated cell-to-cell communication, especially how mRNA cargoes modulate gene expression in recipient cells, remain poorly understood. This study aims to elucidate the precise molecular pathways through which exosomal mRNA cargo, particularly MAFB, contributes to the developing sepsis-induced molecular aberrations in liver tissues, employing rigorously defined cell culture conditions. THP-1 cells were treated with LPS to induce changes in exosomal RNA profiles. Exosomes were isolated and characterized using microscopy and mass spectrometry. RNA was extracted from exosomes and sequenced. The most abundant exosomal mRNAs were subjected to GO analysis for functional annotation analysis and KEGG database analysis to identify the involved enriched pathways. PCR (Polymerase Chain Reaction), RNA sequencing, and Western blotting were involved to analyze changes in gene expression, protein levels, and signaling pathways within the liver cells( HepG2) after exposure to exosomal MAFB. This study pinpoints exosomal MAFB as a potential key regulator linked to liver cell damage during sepsis, along with associated genes (miR155HG, H3F3A, and possibly JARD2) forming a crucial molecular pathway contributing to liver cell injury, Together, these elements indicate a vital molecular pathway that plays a significant role in the emergence of liver cell injury during sepsis.. These findings suggest the importance of further research on these components for potential therapeutic interventions in managing acute liver damage in sepsis.

Keywords: sepsis, exososome, exosomal MAFB, LPS-induced THP-1 cells, RNA profiles, sepsis-triggered liver injury

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Authors: Akanksha Agrawal, Richa Rathor, Geetha Suryakumar

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Muscle represents about ¾ of the body mass, and a healthy muscular system is required for human performance. A healthy muscular system is dynamically balanced via the catabolic and anabolic process. High altitude associated hypoxia altered this redox balance via producing reactive oxygen and nitrogen species that ultimately modulates protein structure and function, hence, disrupts proteostasis or protein homeostasis. The mechanism by which proteostasis is clinched includes regulated protein translation, protein folding, and protein degradation machinery. Perturbation in any of these mechanisms could increase proteome imbalance in the cellular processes. Altered proteostasis in skeletal muscle is likely to be responsible for contributing muscular atrophy in response to hypoxia. Therefore, we planned to elucidate the mechanism involving altered proteostasis leading to skeletal muscle atrophy under chronic hypobaric hypoxia. Material and Methods-Male Sprague Dawley rats weighing about 200-220 were divided into five groups - Control (Normoxic animals), 1d, 3d, 7d and 14d hypobaric hypoxia exposed animals. The animals were exposed to simulated hypoxia equivalent to 282 torr pressure (equivalent to an altitude of 7620m, 8% oxygen) at 25°C. On completion of chronic hypobaric hypoxia (CHH) exposure, rats were sacrificed, muscle was excised and biochemical, histopathological and protein synthesis signaling were studied. Results-A number of changes were observed with the CHH exposure time period. ROS was increased significantly on 07 and 14 days which were attributed to protein oxidation via damaging muscle protein structure by oxidation of amino acids moiety. The oxidative damage to the protein further enhanced the various protein degradation pathways. Calcium activated cysteine proteases and other intracellular proteases participate in protein turnover in muscles. Therefore, we analysed calpain and 20S proteosome activity which were noticeably increased at CHH exposure as compared to control group representing enhanced muscle protein catabolism. Since inflammatory markers (myokines) affect protein synthesis and triggers degradation machinery. So, we determined inflammatory pathway regulated under hypoxic environment. Other striking finding of the study was upregulation of Akt/PKB translational machinery that was increased on CHH exposure. Akt, p-Akt, p70 S6kinase, and GSK- 3β expression were upregulated till 7d of CHH exposure. Apoptosis related markers, caspase-3, caspase-9 and annexin V was also increased on CHH exposure. Conclusion: The present study provides evidence of disrupted proteostasis under chronic hypobaric hypoxia. A profound loss of muscle mass is accompanied by the muscle damage leading to apoptosis and cell death under CHH. These cellular stress response pathways may play a pivotal role in hypobaric hypoxia induced skeletal muscle atrophy. Further research in these signaling pathways will lead to development of therapeutic interventions for amelioration of hypoxia induced muscle atrophy.

Keywords: Akt/PKB translational machinery, chronic hypobaric hypoxia, muscle atrophy, protein degradation

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Authors: Siti Rahmah Shamsuri, Eiichiro Matsubara, Shohei Shiomi

Abstract:

The 1D nanomaterial is far surpassed the 0D nanomaterial. It does not just offer most of the benefit of the 0D nanomaterial such as the large surface area, a great number of active site and an efficient interfacial charge transfer but also can assemble into free-standing and flexible electrode due to their high aspect ratio. Thus, it is essential to develop a simple and ease synthesis of this 1D nanomaterial for the practical application. Here, nickel nanowire/cellulose hybrid has been successfully fabricated via a simple liquid-phase method with the assist of the magnetic field. A finer nickel nanowire was heterogeneously nucleated on the surface of the cellulose fiber, which demonstrated the effect of the hydroxyl group on the cellulose structure. The result of the nickel nanowire size was found to vary from 66-114 nm. A detailed discussion on the mechanism of the nickel nanowire/ cellulose hybrid formation is also shown in this paper.

Keywords: cellulose nanofiber, liquid-phase reduction, metal nanowire, nano hybrid material

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Authors: Ibrahim M. Labouta, Gina N. Tageldin, Salwa M. Fahmy, Hayam M. Ashour, Mounir A. Khalil, Tamer M. Ibrahim, Nefertiti A. El-Nikhely

Abstract:

Bruton’s tyrosine kinase (BTK) is a critical effector molecule in B cell antigen receptor (BCR) signaling transduction. It regulates B cell proliferation, development and survival. Since BTK is widely expressed in many B cell leukaemias and lymphomas, targeting BTK by small molecules inhibitors became an attractive idea as new treatment modalities for B cell mediated hematologic malignancies. Ibrutinib is the 1st generation BTK inhibitor, approved by FDA for treatment of relapsed mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL). It binds irreversibly to the unique cysteine (Cys481) within the ATP-binding pocket of BTK. Besides ibrutinib, many irreversible covalent BTK inhibitors comprising pyrimidine nucleus such as spebrutinib (phase IIb) showed high selectivity and potency when compared to it. In this study, the designed compounds were based on 5-cyano-2-methylsulfanyl pyrimidine core and decorated with electrophilic warheads which are essential for the optimal activity for targeted covalent inhibition (TCI). However, modifications at pyrimidine C4 or C6 were made by introduction of substituted amines which are provided to behave differently. The synthesized derivatives were evaluated for their anticancer activity in leukemia cell lines (e.g. THP-1). Results showed that, some derivatives exhibited antiproliferative activity with IC50 ranged from 5-50 μM, The in vitro enzymatic inhibitory assay for these compounds against BTK is still under investigation. Nevertheless, we could conclude from the initial biological screening that, the synthesized 4 or 6-subsitituted aminopyrimidines represent promising and novel antileukemic agents. Meanwhile, further studies are still needed to attribute this activity through targeting BTK enzyme and inhibition of BCR signaling pathway.

Keywords: BTK inhibitors, hematologic malignancies, structure based drug design (SBDD), targeted covalent inhibitors (TCI)

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Authors: Joanna Drzeżdżon

Abstract:

Polyvinyl alcohol and its derivatives such as 2-chloro-2-propen-1-ol have found application in many industries. They are mainly used for the production of adhesives, thickeners and stabilizers of emulsion paints, and surgical threads. Moreover, polyvinyl alcohol derivatives are indispensable reagents in the synthesis of hemiacetals. Polyolefins derived from polyvinyl alcohol are obtained by using catalysts belonging to complex compounds of transition metal ions. The aim of the studies is to the synthesis of a new complex, i.e. dipicolinate oxovanadium(IV) complex with 4,4’-dimethoxy-2,2’-bipyridyl, and to determine its catalytic activities. Moreover, the another aim of the studies was to set conditions for 2-chloro-2-propen-1-ol oligomerization. The catalytic system has been based on the dipicolinate complex of oxovanadium(IV) with 4,4’-dimethoxy-2,2’-bipyridyl and MMAO-12. The results of the studies showed that how a new oxovanadium(IV) complex compound effects on the 2-chloro-2-propen-1-ol oligomerization. Moreover, the results revealed that new catalytic material is a highly active catalyst for the investigated oligomerization.

Keywords: 2-chloro-2-propen-1-ol, oligomerization, dipicolinate, vanadium, methylaluminoxane

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Authors: Swastik Karmakar, Prasanta Das, Shital K. Chattopadhyay

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An efficient synthesis of symmetrical 2, 2′-Di-substituted 3, 3′-bisindolylarylmethanes (BIAMs) having different aryl and hetero-aryl moieties has been developed by Ag(I)-catalyzed indolyzation and a sequential deoxygenative addition involving o-alkynylanilines and aryl/hetero-aryl aldehydes as substrates. Alkyne and carbonyl units could be activated by Ag (I) simultaneously which results in a domino 5-endo-dig indole annulation, addition of C3 of this indole nucleus to the carbonyl carbon in addition to second indole annulation, and its dehydroxylative addition to the same carbonyl carbon to furnish BIAMs in excellent yield. As 3, 3′-bisindolylmethanes (BIMs) are biologically significant scaffolds, this moiety with further substitutions at the indole core could find some important use in medicinal chemistry. The methodology developed is atom-economic and involves more accessible silver salts, which could be useful for large-scale synthesis.

Keywords: alkyne, 3, 3′-Bisindolylarylmethanes, carbonyl, domino, 5-endo-dig indole annulation, silver catalyst

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Authors: Juan Huang, Nanqu Huang, Jingshan Shi, Yu Qiu

Abstract:

Objectives: There are pathophysiological connections between type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD), and research on drugs with hypoglycemic and beta-amyloid (Aβ)-clearing effects have great therapeutic potential for AD. Dendrobium nobile Lindl. Alkaloids (DNLA) as one of the active compounds of Dendrobium nobile Lindl. In this study, we attempted to verify the hypoglycemic effect and investigate the effects of DNLA on the amyloid precursor protein (APP) metabolic pathway of the hippocampus in db/db mice. Methods: 4-weeks-old male C57BL/KsJ mice were the control group. And the same age and sexuality db/db mice were: model, DNLA-L (20 mg/kg), DNLA-M (40 mg/kg), and DNLA-H (80 mg/kg). After, mice were treated with different concentrations of DNLA for 17 weeks. The fasting blood glucose (FBG) was detected by glucose oxidase assay every week from the 4th to last week. The protein expression of β-amyloid 1-42 (Aβ1-42), β-site amyloid precursor protein-cleaving enzyme 1 (BACE1), and APP were examined by Western blotting. Results: The concentration of FBG and the protein expression of Aβ1-42, BACE1, and APP were increased in the hippocampus of the model group. Moreover, DNLA not only significantly decreased the concentration of FBG but also reduced the protein expressions of Aβ1-42, BACE1 and APP in the hippocampus of db/db mice in a dose-dependent manner. Conclusions: DNLA can decrease the protein expressions of Aβ1-42 in the hippocampus of db/db mice, and the mechanism may be involved in the APP metabolic pathway.

Keywords: Alzheimer's disease, type 2 diabetes mellitus, β-site amyloid precursor protein-cleaving enzyme 1, traditional Chinese medicines, beta-amyloid

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Authors: Bokolombe Pitchou Ngoy, John Mack, Tebello Nyokong

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Synthesis and photochemical studies of BODIPY dyes have been investigated in this work in order to have a broad benchmark of this functionalized photosensitizer for biological applications such as photodynamic therapy or antimicrobial activity. The common acid catalyzed synthetic method was used, and BODIPY dyes were obtained in quite a good yield (25 %) followed by bromination and Knoevenagel condensation to afford the BODIPY dyes conjugated with maximum absorbance in the near-infrared region of the electromagnetic spectrum. The fluorescence lifetimes, fluorescence quantum yield, and Singlet oxygen quantum yield of the conjugated BODIPY dyes were determined in different solvents by using Time Correlation Single Photon Counting (TCSPC), fluorimeter, and Laser Flash Photolysis respectively. It was clearly shown that the singlet oxygen quantum yield was higher in THF followed by DMSO compared to another solvent. The same trend was observed for the fluorescence lifetimes.

Keywords: BODIPY, photodynamic therapy, photosensitizer, singlet oxygen

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