14 results on '"Abdullah S. Alawam"'
Search Results
2. Zingiber officinale-Mediated biosynthesis of bimetallic Gold/Silver (BAu/Ag) nanoalloys; an insight into antiviral and anticancer activities
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Khalid S. Alshallash, Ahmed M. Eid, Saad El-Din Hassan, Mohammed Ali Abdel-Rahman, Abdullah S. Alawam, Mohammed F. Hamza, and Amr Fouda
- Subjects
Green synthesis ,Nanoalloys ,Bimetallic ,Antiviral ,In-vitro cytotoxicity ,Science (General) ,Q1-390 - Abstract
Utilizing plant extracts in the green synthesis of bimetallic nanoalloys receives more attention due to its eco-friendly, cheap, single-step, easy-handling method, producing highly active and biocompatible nanoalloys. Therefore, the aqueous extract of ginger rhizome was used to form bimetallic gold/silver (Au/Ag) nanoalloys. There were 37.3 mg.g−1 of total soluble carbs, 0.75 mg.g−1 of proteins, and 0.03 mg.g−1 of phenolic compounds quantified in ginger rhizome. The production of BAu/Ag-NPs relies on these components. The as-formed BAu/Ag-NPs were characterized using UV–Vis spectroscopy. The results showed that the peak surface plasmon resonance (SPR) occurred between 440 and 545 nm. The existence of several functional groups involved in the reduction and stability of the generated nanoalloys was shown by Fourier-transform infrared (FT-IR). The nanoalloys, with an average size of 49.1 ± 16.2 nm, were observed to be spherical using transmission electron microscopy (TEM). Energy-dispersive X-ray (EDX) indicated that the synthesized nanoalloy mainly consisted of Au and Ag ions, which made up (31.2 % and 47.1 %) and (45.9 % and 28.6 %) of the sample’s atomic and weight percentages, respectively. The crystallography of the nanoalloys was confirmed using XRD analysis. When examined for their capacity to suppress viral replication, the synthesized nanoalloys showed remarkable results, with 78.2 % inhibition against HAV and 69.6 % against Cox-B4. In addition, the anticancer activity of nanoalloys against oral epithelial cells (OEC), MCF7 adenocarcinoma cells, and HepG2 hepatocarcinoma cells was investigated using the MTT assay method. While the nanoalloys exhibited moderate toxicity towards normal OEC (IC50: 502.5 ± 2.8 g.mL−1), they showed substantial cytotoxicity towards cancer cells, MCF7 and HepG2, with IC50 values of 212.6 ± 4.4 and 117.9 ± 6.6 µg.mL−1, respectively. According to these data, BAu/Ag nanoalloys show potential as antiviral and anticancer drugs that selectively kill cancer cells.
- Published
- 2024
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- View/download PDF
3. Insights into the identification and evolutionary conservation of key genes in the transcriptional circuits of meiosis initiation and commitment in budding yeast
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Deepyaman Das, Anis Ahmad Chaudhary, Mohamed A. M. Ali, Abdullah S. Alawam, Hironmoy Sarkar, and Soumita Podder
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evolutionary conservation ,gene regulatory network ,master regulator ,protein–protein interaction network ,Saccharomyces cerevisiae ,transcription factor ,Biology (General) ,QH301-705.5 - Abstract
Initiation of meiosis in budding yeast does not commit the cells for meiosis. Thus, two distinct signaling cascades may differentially regulate meiosis initiation and commitment in budding yeast. To distinguish between the role of these signaling cascades, we reconstructed protein–protein interaction networks and gene regulatory networks with upregulated genes in meiosis initiation and commitment. Analyzing the integrated networks, we identified four master regulators (MRs) [Ume6p, Msn2p, Met31p, Ino2p], three transcription factors (TFs), and 279 target genes (TGs) unique for meiosis initiation, and three MRs [Ndt80p, Aro80p, Rds2p], 11 TFs, and 948 TGs unique for meiosis commitment. Functional enrichment analysis of these distinct members from the transcriptional cascades for meiosis initiation and commitment revealed that nutritional cues rewire gene expression for initiating meiosis and chromosomal recombination commits cells to meiosis. As meiotic chromosomal recombination is highly conserved in eukaryotes, we compared the evolutionary rate of unique members in the transcriptional cascade of two meiotic phases of Saccharomyces cerevisiae with members of the phylum Ascomycota, revealing that the transcriptional cascade governing chromosomal recombination during meiosis commitment has experienced greater purifying selection pressure (P value = 0.0013, 0.0382, 0.0448, 0.0369, 0.02967, 0.04937, 0.03046, 0.03357 and
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- 2023
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- View/download PDF
4. Construction of an aerolysin-based multi-epitope vaccine against Aeromonas hydrophila: an in silico machine learning and artificial intelligence-supported approach
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Abdullah S. Alawam and Maher S. Alwethaynani
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immunoinformatics ,epitopes ,MD simulations ,systems biology ,vaccine ,A. hydrophila ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Aeromonas hydrophila, a gram-negative coccobacillus bacterium, can cause various infections in humans, including septic arthritis, diarrhea (traveler’s diarrhea), gastroenteritis, skin and wound infections, meningitis, fulminating septicemia, enterocolitis, peritonitis, and endocarditis. It frequently occurs in aquatic environments and readily contacts humans, leading to high infection rates. This bacterium has exhibited resistance to numerous commercial antibiotics, and no vaccine has yet been developed. Aiming to combat the alarmingly high infection rate, this study utilizes in silico techniques to design a multi-epitope vaccine (MEV) candidate against this bacterium based on its aerolysin toxin, which is the most toxic and highly conserved virulence factor among the Aeromonas species. After retrieval, aerolysin was processed for B-cell and T-cell epitope mapping. Once filtered for toxicity, antigenicity, allergenicity, and solubility, the chosen epitopes were combined with an adjuvant and specific linkers to create a vaccine construct. These linkers and the adjuvant enhance the MEV’s ability to elicit robust immune responses. Analyses of the predicted and improved vaccine structure revealed that 75.5%, 19.8%, and 1.3% of its amino acids occupy the most favored, additional allowed, and generously allowed regions, respectively, while its ERRAT score reached nearly 70%. Docking simulations showed the MEV exhibiting the highest interaction and binding energies (−1,023.4 kcal/mol, −923.2 kcal/mol, and −988.3 kcal/mol) with TLR-4, MHC-I, and MHC-II receptors. Further molecular dynamics simulations demonstrated the docked complexes’ remarkable stability and maximum interactions, i.e., uniform RMSD, fluctuated RMSF, and lowest binding net energy. In silico models also predict the vaccine will stimulate a variety of immunological pathways following administration. These analyses suggest the vaccine’s efficacy in inducing robust immune responses against A. hydrophila. With high solubility and no predicted allergic responses or toxicity, it appears safe for administration in both healthy and A. hydrophila-infected individuals.
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- 2024
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5. Antibiotic adjuvants: synergistic tool to combat multi-drug resistant pathogens
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Vikram Kumar, Nusrath Yasmeen, Aishwarya Pandey, Anis Ahmad Chaudhary, Abdullah S. Alawam, Hassan Ahmad Rudayni, Asimul Islam, Sudarshan S. Lakhawat, Pushpender K. Sharma, and Mohammad Shahid
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antibiotic resistant ,multi-drug resistant ,antibiotic adjuvants ,pathogens ,bacteria ,Microbiology ,QR1-502 - Abstract
The rise of multi-drug resistant (MDR) pathogens poses a significant challenge to the field of infectious disease treatment. To overcome this problem, novel strategies are being explored to enhance the effectiveness of antibiotics. Antibiotic adjuvants have emerged as a promising approach to combat MDR pathogens by acting synergistically with antibiotics. This review focuses on the role of antibiotic adjuvants as a synergistic tool in the fight against MDR pathogens. Adjuvants refer to compounds or agents that enhance the activity of antibiotics, either by potentiating their effects or by targeting the mechanisms of antibiotic resistance. The utilization of antibiotic adjuvants offers several advantages. Firstly, they can restore the effectiveness of existing antibiotics against resistant strains. Adjuvants can inhibit the mechanisms that confer resistance, making the pathogens susceptible to the action of antibiotics. Secondly, adjuvants can enhance the activity of antibiotics by improving their penetration into bacterial cells, increasing their stability, or inhibiting efflux pumps that expel antibiotics from bacterial cells. Various types of antibiotic adjuvants have been investigated, including efflux pump inhibitors, resistance-modifying agents, and compounds that disrupt bacterial biofilms. These adjuvants can act synergistically with antibiotics, resulting in increased antibacterial activity and overcoming resistance mechanisms. In conclusion, antibiotic adjuvants have the potential to revolutionize the treatment of MDR pathogens. By enhancing the efficacy of antibiotics, adjuvants offer a promising strategy to combat the growing threat of antibiotic resistance. Further research and development in this field are crucial to harness the full potential of antibiotic adjuvants and bring them closer to clinical application.
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- 2023
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6. Structural and Dynamical Basis of VP35-RBD Inhibition by Marine Fungi Compounds to Combat Marburg Virus Infection
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Abdullah S. Alawam, Hadil Sultan Alawam, Mohammed Merae Alshahrani, Maher S. Alwethaynani, Lina M. Alneghery, and Mubarak A. Alamri
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Marburg virus ,marine fungi ,VP35 ,RNA binding domain ,Biology (General) ,QH301-705.5 - Abstract
The Marburg virus (MBV), a deadly pathogen, poses a serious threat to world health due to the lack of effective treatments, calling for an immediate search for targeted and efficient treatments. In this study, we focused on compounds originating from marine fungi in order to identify possible inhibitory compounds against the Marburg virus (MBV) VP35-RNA binding domain (VP35-RBD) using a computational approach. We started with a virtual screening procedure using the Lipinski filter as a guide. Based on their docking scores, 42 potential candidates were found. Four of these compounds—CMNPD17596, CMNPD22144, CMNPD25994, and CMNPD17598—as well as myricetin, the control compound, were chosen for re-docking analysis. Re-docking revealed that these particular compounds had a higher affinity for MBV VP35-RBD in comparison to the control. Analyzing the chemical interactions revealed unique binding properties for every compound, identified by a range of Pi–cation interactions and hydrogen bond types. We were able to learn more about the dynamic behaviors and stability of the protein–ligand complexes through a 200-nanosecond molecular dynamics simulation, as demonstrated by the compounds’ consistent RMSD and RMSF values. The multidimensional nature of the data was clarified by the application of principal component analysis, which suggested stable conformations in the complexes with little modification. Further insight into the energy profiles and stability states of these complexes was also obtained by an examination of the free energy landscape. Our findings underscore the effectiveness of computational strategies in identifying and analyzing potential inhibitors for MBV VP35-RBD, offering promising paths for further experimental investigations and possible therapeutic development against the MBV.
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- 2024
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7. Specialized pro-resolving lipid mediators regulate inflammatory macrophages: A paradigm shift from antibiotics to immunotherapy for mitigating COVID-19 pandemic
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Vikram Kumar, Nusrath Yasmeen, Anis Ahmad Chaudhary, Abdullah S. Alawam, Mohammed Al-Zharani, Nosiba Suliman Basher, S. Harikrishnan, Muddapuram Deeksha Goud, Aishwarya Pandey, Sudarshan Singh Lakhawat, and Pushpender Kumar Sharma
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COVID-19 ,antimicrobial ,cytokine storm ,macrophages ,lipid mediators ,Biology (General) ,QH301-705.5 - Abstract
The most severe clinical manifestations of the horrifying COVID-19 disease, that claimed millions of lives during the pandemic time, were Acute respiratory distress syndrome (ARDS), Coagulopathies, septic shock leading eventually to death. ARDS was a consequence of Cytokine storm. The viral SARS-COV2infection lead to avalanche of cytokines and eicosanoids causing “cytokine storm” and “eicosanoid storm.” Cytokine storm is one of the macrophage-derived inflammatory responses triggered by binding of virus particles to ACE2 receptors of alveolar macrophages, arise mainly due to over production of various pro-inflammatory mediators like cytokines, e.g., interleukin (IL)-1, IL-2, and tumor necrosis factor (TNF)- α, causing pulmonary edema, acute respiratory distress, and multi-organ failure. Cytokine storm was regarded as the predictor of severity of the disease and was deemed one of the causes of the high mortality rates due to the COVID-19. The basis of cytokine storm is imbalanced switching between an inflammation increasing - pro-inflammatory (M1) and an inflammation regulating-anti-inflammatory (M2) forms of alveolar macrophages which further deteriorates if opportunistic secondary bacterial infections prevail in the lungs. Lack of sufficient knowledge regarding the virus and its influence on co-morbidities, clinical treatment of the diseases included exorbitant use of antibiotics to mitigate secondary bacterial infections, which led to the unwarranted development of multidrug resistance (MDR) among the population across the globe. Antimicrobial resistance (AMR) needs to be addressed from various perspectives as it may deprive future generations of the basic health immunity. Specialized pro-resolving mediators (SPMs) are generated from the stereoselective enzymatic conversions of essential fatty acids that serve as immune resolvents in controlling acute inflammatory responses. SPMs facilitate the clearance of injured tissue and cell debris, the removal of pathogens, and augment the concentration of anti-inflammatory lipid mediators. The SPMs, e.g., lipoxins, protectins, and resolvins have been implicated in exerting inhibitory influence on with cytokine storm. Experimental evidence suggests that SPMS lower antibiotic requirement. Therefore, in this review potential roles of SPMs in enhancing macrophage polarization, triggering immunological functions, hastening inflammation resolution, subsiding cytokine storm and decreasing antibiotic requirement that can reduce AMR load are discussed.
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- 2023
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8. Establishing the Role of Iridoids as Potential Kirsten Rat Sarcoma Viral Oncogene Homolog G12C Inhibitors Using Molecular Docking; Molecular Docking Simulation; Molecular Mechanics Poisson–Boltzmann Surface Area; Frontier Molecular Orbital Theory; Molecular Electrostatic Potential; and Absorption, Distribution, Metabolism, Excretion, and Toxicity Analysis
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Mubarak A. Alamri, Abdullah S. Alawam, Mohammed Merae Alshahrani, Sarkar M. A. Kawsar, Prinsa, and Supriyo Saha
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KRAS G12C ,Iridoids ,Sotorasib ,molecular docking ,MD simulation ,MM/PBSA ,Organic chemistry ,QD241-441 - Abstract
The RAS gene family is one of the most frequently mutated oncogenes in human cancers. In KRAS, mutations of G12D and G12C are common. Here, 52 iridoids were selected and docked against 8AFB (KRAS G12C receptor) using Sotorasib as the standard. As per the docking interaction data, 6-O-trans-p-coumaroyl-8-O-acetylshanzhiside methyl ester (dock score: −9.9 kcal/mol), 6′-O-trans-para-coumaroyl geniposidic acid (dock score: −9.6 kcal/mol), 6-O-trans-cinnamoyl-secologanoside (dock score: −9.5 kcal/mol), Loganic acid 6′-O-beta-d-glucoside (dock score: −9.5 kcal/mol), 10-O-succinoylgeniposide (dock score: −9.4), Loganic acid (dock score: −9.4 kcal/mol), and Amphicoside (dock score: −9.2 kcal/mol) showed higher dock scores than standard Sotorasib (dock score: −9.1 kcal/mol). These common amino acid residues between iridoids and complexed ligands confirmed that all the iridoids perfectly docked within the receptor’s active site. The 100 ns MD simulation data showed that RMSD, RMSF, radius of gyration, and SASA values were within range, with greater numbers of hydrogen bond donors and acceptors. MM/PBSA analysis showed maximum binding energy values of −7309 kJ/mol for 6-O-trans-p-coumaroyl-8-O-acetylshanzhiside methyl ester. FMO analysis showed that 6-O-trans-p-coumaroyl-8-O-acetylshanzhiside methyl ester was the most likely chemically reactive molecule. MEP analysis data highlighted the possible electrophilic and nucleophilic attack regions of the best-docked iridoids. Of all the best-docked iridoids, Loganic acid passed Lipinski, Pfizer, and GSK filters with a similar toxicity profile to Sotorasib. Thus, if we consider these iridoids to be KRAS G12C inhibitors, they will be a boon to mankind.
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- 2023
- Full Text
- View/download PDF
9. Molecular Basis of Methicillin and Vancomycin Resistance in Staphylococcus aureus from Cattle, Sheep Carcasses and Slaughterhouse Workers
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Hanan A. Zaher, Shimaa El Baz, Abdulaziz S. Alothaim, Sulaiman A. Alsalamah, Mohammed Ibrahim Alghonaim, Abdullah S. Alawam, and Mostafa M. Eraqi
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Staphylococcus aureus ,MRSA ,VRSA ,cattle ,sheep ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Staphylococcus aureus (S. aureus) is a serious infection-causing pathogen in humans and animal. In particular, methicillin-resistant S. aureus (MRSA) is considered one of the major life-threatening pathogens due to its rapid resistance to several antibiotics in clinical practice. MRSA strains have recently been isolated in a number of animals utilized in food production processes, and these species are thought to be the important sources of the spread of infection and disease in both humans and animals. The main objective of the current study was to assess the prevalence of drug-resistant S. aureus, particularly vancomycin-resistant S. aureus (VRSA) and MRSA, by molecular methods. To address this issue, a total of three hundred samples (200 meat samples from cattle and sheep carcasses (100 of each), 50 hand swabs, and 50 stool samples from abattoir workers) were obtained from slaughterhouses in Egypt provinces. In total, 19% S. aureus was isolated by standard culture techniques, and the antibiotic resistance was confirmed genotypically by amplification nucA gen. Characteristic resistance genes were identified by PCR with incidence of 31.5%, 19.3%, 8.7%, and 7% for the mecA, VanA, ermA, and tet L genes, respectively, while the aac6-aph gene was not found in any of the isolates. In this study, the virulence genes responsible for S. aureus’ resistance to antibiotics had the highest potential for infection or disease transmission to animal carcasses, slaughterhouse workers, and meat products.
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- 2023
- Full Text
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10. Generation and Regeneration of Thymic Epithelial Cells
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Abdullah S. Alawam, Graham Anderson, and Beth Lucas
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thymus ,thymic epithelial cell ,thymic atrophy ,regeneration ,bone marrow transplant ,immune reconstitution ,Immunologic diseases. Allergy ,RC581-607 - Abstract
The thymus is unique in its ability to support the maturation of phenotypically and functionally distinct T cell sub-lineages. Through its combined production of MHC-restricted conventional CD4+ and CD8+, and Foxp3+ regulatory T cells, as well as non-conventional CD1d-restricted iNKT cells and invariant γδT cells, the thymus represents an important orchestrator of immune system development and control. It is now clear that thymus function is largely determined by the availability of stromal microenvironments. These specialized areas emerge during thymus organogenesis and are maintained throughout life. They are formed from both epithelial and mesenchymal components, and collectively they support a stepwise program of thymocyte development. Of these stromal cells, cortical, and medullary thymic epithelial cells represent functional components of thymic microenvironments in both the cortex and medulla. Importantly, a key feature of thymus function is that levels of T cell production are not constant throughout life. Here, multiple physiological factors including aging, stress and pregnancy can have either short- or long-term detrimental impact on rates of thymus function. Here, we summarize our current understanding of the development and function of thymic epithelial cells, and relate this to strategies to protect and/or restore thymic epithelial cell function for therapeutic benefit.
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- 2020
- Full Text
- View/download PDF
11. Nanomedicine as potential cancer therapy via targeting dysregulated transcription factors
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Anas Ahmad, Summya Rashid, Anis Ahmad Chaudhary, Abdullah S. Alawam, Mohammad Ibrahim Alghonaim, Syed Shadab Raza, and Rehan Khan
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Cancer Research - Published
- 2023
12. Establishing the Role of Iridoids as Potential Kirsten Rat Sarcoma Viral Oncogene Homolog G12C Inhibitors Using Molecular Docking; Molecular Docking Simulation; Molecular Mechanics Poisson–Boltzmann Surface Area; Frontier Molecular Orbital Theory; Molecular Electrostatic Potential; and Absorption, Distribution, Metabolism, Excretion, and Toxicity Analysis
- Author
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Saha, Mubarak A. Alamri, Abdullah S. Alawam, Mohammed Merae Alshahrani, Sarkar M. A. Kawsar, Prinsa, and Supriyo
- Subjects
KRAS G12C ,Iridoids ,Sotorasib ,molecular docking ,MD simulation ,MM/PBSA ,FMO ,MEP ,ADMET - Abstract
The RAS gene family is one of the most frequently mutated oncogenes in human cancers. In KRAS, mutations of G12D and G12C are common. Here, 52 iridoids were selected and docked against 8AFB (KRAS G12C receptor) using Sotorasib as the standard. As per the docking interaction data, 6-O-trans-p-coumaroyl-8-O-acetylshanzhiside methyl ester (dock score: −9.9 kcal/mol), 6′-O-trans-para-coumaroyl geniposidic acid (dock score: −9.6 kcal/mol), 6-O-trans-cinnamoyl-secologanoside (dock score: −9.5 kcal/mol), Loganic acid 6′-O-beta-d-glucoside (dock score: −9.5 kcal/mol), 10-O-succinoylgeniposide (dock score: −9.4), Loganic acid (dock score: −9.4 kcal/mol), and Amphicoside (dock score: −9.2 kcal/mol) showed higher dock scores than standard Sotorasib (dock score: −9.1 kcal/mol). These common amino acid residues between iridoids and complexed ligands confirmed that all the iridoids perfectly docked within the receptor’s active site. The 100 ns MD simulation data showed that RMSD, RMSF, radius of gyration, and SASA values were within range, with greater numbers of hydrogen bond donors and acceptors. MM/PBSA analysis showed maximum binding energy values of −7309 kJ/mol for 6-O-trans-p-coumaroyl-8-O-acetylshanzhiside methyl ester. FMO analysis showed that 6-O-trans-p-coumaroyl-8-O-acetylshanzhiside methyl ester was the most likely chemically reactive molecule. MEP analysis data highlighted the possible electrophilic and nucleophilic attack regions of the best-docked iridoids. Of all the best-docked iridoids, Loganic acid passed Lipinski, Pfizer, and GSK filters with a similar toxicity profile to Sotorasib. Thus, if we consider these iridoids to be KRAS G12C inhibitors, they will be a boon to mankind.
- Published
- 2023
- Full Text
- View/download PDF
13. Failures in thymus medulla regeneration during immune recovery cause tolerance loss and prime recipients for auto-GVHD
- Author
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Abdullah S. Alawam, Emilie J. Cosway, Kieran D. James, Beth Lucas, Andrea Bacon, Sonia M. Parnell, Andrea J. White, William E. Jenkinson, and Graham Anderson
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T-Lymphocytes ,Immunology ,Brief Definitive Report ,Hematopoietic Stem Cell Transplantation ,Graft vs Host Disease ,Autoimmunity ,Mice, Transgenic ,T-Cell Antigen Receptor Specificity ,Epithelial Cells ,Dendritic Cells ,Thymus Gland ,Mice ,Immune Reconstitution ,Self Tolerance ,Cellular Microenvironment ,T-Lymphocyte Subsets ,Immune Tolerance ,Animals ,Immunology and Allergy ,Humans ,Female ,Tolerance ,Bone Marrow Transplantation - Abstract
The thymus ensures immune tolerance by synchronizing thymocyte development and selection. Alawam et al. show that a functional uncoupling of these events occurs after bone marrow transplantation, which results in post-transplant tolerance loss and autoimmunity caused by selective failures in thymus medulla regeneration., Bone marrow transplantation (BMT) is a widely used therapy for blood cancers and primary immunodeficiency. Following transplant, the thymus plays a key role in immune reconstitution by generating a naive αβT cell pool from transplant-derived progenitors. While donor-derived thymopoiesis during the early post-transplant period is well studied, the ability of the thymus to synchronize T cell development with essential tolerance mechanisms is poorly understood. Using a syngeneic mouse transplant model, we analyzed T cell recovery alongside the regeneration and function of intrathymic microenvironments. We report a specific and prolonged failure in the post-transplant recovery of medullary thymic epithelial cells (mTECs). This manifests as loss of medulla-dependent tolerance mechanisms, including failures in Foxp3+ regulatory T cell development and formation of the intrathymic dendritic cell pool. In addition, defective negative selection enables escape of self-reactive conventional αβT cells that promote autoimmunity. Collectively, we show that post-transplant T cell recovery involves an uncoupling of thymopoiesis from thymic tolerance, which results in autoimmune reconstitution caused by failures in thymic medulla regeneration., Graphical Abstract
- Published
- 2021
14. Generation and Regeneration of Thymic Epithelial Cells
- Author
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Beth Lucas, Abdullah S. Alawam, and Graham Anderson
- Subjects
lcsh:Immunologic diseases. Allergy ,0301 basic medicine ,Stromal cell ,T cell ,Immunology ,Thymus Gland ,Review ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,T-Lymphocyte Subsets ,thymus ,thymic atrophy ,medicine ,Animals ,Humans ,Immunology and Allergy ,Regeneration (biology) ,Mesenchymal stem cell ,FOXP3 ,Cell Differentiation ,Epithelial Cells ,bone marrow transplant ,immune reconstitution ,Cell biology ,Thymocyte ,030104 developmental biology ,medicine.anatomical_structure ,Cellular Microenvironment ,regeneration ,Stromal Cells ,thymic epithelial cell ,lcsh:RC581-607 ,CD8 ,030215 immunology - Abstract
The thymus is unique in its ability to support the maturation of phenotypically and functionally distinct T cell sub-lineages. Through its combined production of MHC-restricted conventional CD4+ and CD8+, and Foxp3+ regulatory T cells, as well as non-conventional CD1d-restricted iNKT cells and invariant γδT cells, the thymus represents an important orchestrator of immune system development and control. It is now clear that thymus function is largely determined by the availability of stromal microenvironments. These specialized areas emerge during thymus organogenesis and are maintained throughout life. They are formed from both epithelial and mesenchymal components, and collectively they support a stepwise program of thymocyte development. Of these stromal cells, cortical, and medullary thymic epithelial cells represent functional components of thymic microenvironments in both the cortex and medulla. Importantly, a key feature of thymus function is that levels of T cell production are not constant throughout life. Here, multiple physiological factors including aging, stress and pregnancy can have either short- or long-term detrimental impact on rates of thymus function. Here, we summarize our current understanding of the development and function of thymic epithelial cells, and relate this to strategies to protect and/or restore thymic epithelial cell function for therapeutic benefit.
- Published
- 2020
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