{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T22:43:40Z","timestamp":1788993820526,"version":"build-2803163510"},"reference-count":93,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T00:00:00Z","timestamp":1700265600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008809","name":"Scientific Research Deanship at University of Ha\u2019il-Saudi Arabia","doi-asserted-by":"publisher","award":["MDR-22027"],"award-info":[{"award-number":["MDR-22027"]}],"id":[{"id":"10.13039\/501100008809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Candidiasis, caused by opportunistic fungal pathogens of the Candida genus, poses a significant threat to immunocompromised individuals. Natural compounds derived from medicinal plants have gained attention as potential sources of anti-fungal agents. Ajwa dates (Phoenix dactylifera L.) have been recognized for their diverse phytochemical composition and therapeutic potential. In this study, we employed a multi-faceted approach to explore the anti-candidiasis potential of Ajwa dates\u2019 phytochemicals. Utilizing network pharmacology, we constructed an interaction network to elucidate the intricate relationships between Ajwa dates phytoconstituents and the Candida-associated molecular targets of humans. Our analysis revealed key nodes in the network (STAT3, IL-2, PTPRC, STAT1, CASP1, ALB, TP53, TLR4, TNF and PPARG), suggesting the potential modulation of several crucial processes (the regulation of the response to a cytokine stimulus, regulation of the inflammatory response, positive regulation of cytokine production, cellular response to external stimulus, etc.) and fungal pathways (Th17 cell differentiation, the Toll-like receptor signaling pathway, the C-type lectin receptor signaling pathway and necroptosis). To validate these findings, molecular docking studies were conducted, revealing the binding affinities of the phytochemicals towards selected Candida protein targets of humans (ALB\u2013rutin (\u22129.7 kJ\/mol), STAT1\u2013rutin (\u22129.2 kJ\/mol), STAT3\u2013isoquercetin (\u22128.7 kJ\/mol), IL2\u2013\u03b2-carotene (\u22128.5 kJ\/mol), CASP1\u2013\u03b2-carotene (\u22128.2 kJ\/mol), TP53\u2013isoquercetin (\u22128.8 kJ\/mol), PPARG\u2013luteolin (\u22128.3 kJ\/mol), TNF\u2013\u03b2carotene (\u22127.7 kJ\/mol), TLR4\u2013rutin (\u22127.4 kJ\/mol) and PTPRC\u2013rutin (\u22127.0 kJ\/mol)). Furthermore, molecular dynamics simulations of rutin\u2013ALB and rutin-STAT1 complex were performed to gain insights into the stability and dynamics of the identified ligand\u2013target complexes over time. Overall, the results not only contribute to the understanding of the molecular interactions underlying the anti-fungal potential of specific phytochemicals of Ajwa dates in humans but also provide a rational basis for the development of novel therapeutic strategies against candidiasis in humans. This study underscores the significance of network pharmacology, molecular docking and dynamics simulations in accelerating the discovery of natural products as effective anti-fungal agents. However, further experimental validation of the identified compounds is warranted to translate these findings into practical therapeutic applications.<\/jats:p>","DOI":"10.3390\/pathogens12111369","type":"journal-article","created":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T07:33:18Z","timestamp":1700292798000},"page":"1369","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation to Elucidate the Molecular Targets and Potential Mechanism of Phoenix dactylifera (Ajwa Dates) against Candidiasis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7080-6822","authenticated-orcid":false,"given":"Mohd","family":"Adnan","sequence":"first","affiliation":[{"name":"Department of Biology, College of Science, University of Ha\u2019il, Ha\u2019il 55473, Saudi Arabia"},{"name":"Medical and Diagnostic Research Centre, University of Ha\u2019il, Ha\u2019il 55473, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6236-0920","authenticated-orcid":false,"given":"Arif Jamal","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, University of Ha\u2019il, Ha\u2019il 55473, Saudi Arabia"},{"name":"Medical and Diagnostic Research Centre, University of Ha\u2019il, Ha\u2019il 55473, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5333-9505","authenticated-orcid":false,"given":"Syed Amir","family":"Ashraf","sequence":"additional","affiliation":[{"name":"Medical and Diagnostic Research Centre, University of Ha\u2019il, Ha\u2019il 55473, Saudi Arabia"},{"name":"Department of Clinical Nutrition, College of Applied Medial Sciences, University of Ha\u2019il, Ha\u2019il 55473, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3377-2763","authenticated-orcid":false,"given":"Fevzi","family":"Bardakci","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, University of Ha\u2019il, Ha\u2019il 55473, Saudi Arabia"},{"name":"Medical and Diagnostic Research Centre, University of Ha\u2019il, Ha\u2019il 55473, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3763-9698","authenticated-orcid":false,"given":"Mousa","family":"Alreshidi","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, University of Ha\u2019il, Ha\u2019il 55473, Saudi Arabia"},{"name":"Medical and Diagnostic Research Centre, University of Ha\u2019il, Ha\u2019il 55473, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9054-7744","authenticated-orcid":false,"given":"Riadh","family":"Badraoui","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, University of Ha\u2019il, Ha\u2019il 55473, Saudi Arabia"},{"name":"Medical and Diagnostic Research Centre, University of Ha\u2019il, Ha\u2019il 55473, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5919-1273","authenticated-orcid":false,"given":"Emira","family":"Noumi","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, University of Ha\u2019il, Ha\u2019il 55473, Saudi Arabia"},{"name":"Medical and Diagnostic Research Centre, University of Ha\u2019il, Ha\u2019il 55473, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bektas","family":"Tepe","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Faculty of Science and Literature, Kilis 7 Aralik University, Kilis TR-79000, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manojkumar","family":"Sachidanandan","sequence":"additional","affiliation":[{"name":"Medical and Diagnostic Research Centre, University of Ha\u2019il, Ha\u2019il 55473, Saudi Arabia"},{"name":"Department of Oral Radiology, College of Dentistry, University of Ha\u2019il, Ha\u2019il 55473, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9283-2124","authenticated-orcid":false,"given":"Mitesh","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Parul Institute of Applied Sciences and Centre of Research for Development, Parul University, Vadodara 391760, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Friedman, D.Z., and Schwartz, I.S. (2019). Emerging fungal infections: New patients, new patterns, and new pathogens. J. Fungi, 5.","DOI":"10.3390\/jof5030067"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"12","DOI":"10.14194\/ijitd.2.1.2","article-title":"Candidiasis: Past, present and future","volume":"2","author":"Saini","year":"2015","journal-title":"Int. J. Infect. Trop. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s12281-023-00455-3","article-title":"Candidiasis and Other Emerging Yeasts","volume":"17","author":"Sharma","year":"2023","journal-title":"Curr. Fungal Infect. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1080\/21505594.2021.2019950","article-title":"Pathogenesis and virulence of Candida albicans","volume":"13","author":"Lopes","year":"2022","journal-title":"Virulence"},{"key":"ref_5","first-page":"837","article-title":"Yeasts in the gut: From commensals to infectious agents","volume":"106","author":"Schulze","year":"2009","journal-title":"Dtsch. \u00c4rzteblatt Int."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Vila, T., Sultan, A.S., Montelongo-Jauregui, D., and Jabra-Rizk, M.A. (2020). Oral candidiasis: A disease of opportunity. J. Fungi, 6.","DOI":"10.3390\/jof6010015"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Du, H., Bing, J., Hu, T., Ennis, C.L., Nobile, C.J., and Huang, G. (2020). Candida auris: Epidemiology, biology, antifungal resistance, and virulence. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008921"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1016\/j.jmii.2022.12.002","article-title":"COVID-19-associated candidiasis and the emerging concern of Candida auris infections","volume":"56","author":"Tsai","year":"2022","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Jain, A., Jain, S., and Rawat, S. (2010). Emerging fungal infections among children: A review on its clinical manifestations, diagnosis, and prevention. J. Pharm. Bioallied Sci., 2.","DOI":"10.4103\/0975-7406.72131"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1046\/j.1529-8019.2002.01533.x","article-title":"Candidiasis and other fungal diseases of the mouth","volume":"15","author":"Samaranayake","year":"2002","journal-title":"Dermatol. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3201\/eid2301.161198","article-title":"Epidemiology of hospitalizations associated with invasive candidiasis, United States, 2002\u20132012","volume":"23","author":"Strollo","year":"2017","journal-title":"Emerg. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.18203\/2349-3291.ijcp20173803","article-title":"Clinical profile of Candidiasis in neonates","volume":"4","author":"Latha","year":"2017","journal-title":"Int. J. Contemp. Pediatr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1177\/0956462414548906","article-title":"Prevalence of oral candidiasis in HIV\/AIDS children in highly active antiretroviral therapy era. A literature analysis","volume":"26","author":"Castillo","year":"2015","journal-title":"Int. J. STD AIDS"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"15","DOI":"10.2165\/11315510-000000000-00000","article-title":"Clinical aspects of invasive candidiasis in solid organ transplant recipients","volume":"69","author":"Grossi","year":"2009","journal-title":"Drugs"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2429","DOI":"10.1007\/s00520-015-3035-8","article-title":"Influence of cancer treatment on the Candida albicans isolated from the oral cavities of cancer patients","volume":"24","author":"Ramla","year":"2016","journal-title":"Support. Care Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"i5","DOI":"10.1093\/jac\/dki218","article-title":"Changing patterns and trends in systemic fungal infections","volume":"56","author":"Richardson","year":"2005","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Kordalewska, M., and Perlin, D.S. (2019). Identification of drug resistant Candida auris. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.01918"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"155","DOI":"10.2147\/IDR.S116229","article-title":"Current perspective on emergence, diagnosis and drug resistance in Candida auris","volume":"10","author":"Sarma","year":"2017","journal-title":"Infect. Drug Resist."},{"key":"ref_19","unstructured":"Kumar, A. (2016). Anticandidal Agents, Academic Press."},{"key":"ref_20","first-page":"271","article-title":"Invasive fungal infection: New treatments to meet new challenges","volume":"116","author":"Wagener","year":"2019","journal-title":"Dtsch. \u00c4rzteblatt Int."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Awadelkareem, A.M., Siddiqui, A.J., Noumi, E., Ashraf, S.A., Hadi, S., Snoussi, M., Badraoui, R., Bardakci, F., Ashraf, M.S., and Danciu, C. (2023). Biosynthesized Silver Nanoparticles Derived from Probiotic Lactobacillus rhamnosus (AgNPs-LR) Targeting Biofilm Formation and Quorum Sensing-Mediated Virulence Factors. Antibiotics, 12.","DOI":"10.3390\/antibiotics12060986"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Bazaid, A.S., Alsolami, A., Patel, M., Khateb, A.M., Aldarhami, A., Snoussi, M., Almusheet, S.M., and Qanash, H. (2023). Antibiofilm, Antimicrobial, Anti-Quorum Sensing, and Antioxidant Activities of Saudi Sidr Honey: In Vitro and Molecular Docking Studies. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15092177"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Ranjutha, V., Chen, Y., Al-Keridis, L.A., Patel, M., Alshammari, N., Adnan, M., Sahreen, S., Gopinath, S.C., and Sasidharan, S. (2023). Synergistic Antimicrobial Activity of Ceftriaxone and Polyalthia longifolia Methanol (MEPL) Leaf Extract against Methicillin-Resistant Staphylococcus aureus and Modulation of mecA Gene Presence. Antibiotics, 12.","DOI":"10.3390\/antibiotics12030477"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"845","DOI":"10.3389\/fpls.2017.00845","article-title":"Date palm tree (Phoenix dactylifera L.): Natural products and therapeutic options","volume":"8","author":"Baqi","year":"2017","journal-title":"Front. Plant Sci."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Younas, A., Naqvi, S.A., Khan, M.R., Shabbir, M.A., Jatoi, M.A., Anwar, F., Inam-Ur-Raheem, M., Saari, N., and Aadil, R.M. (2020). Functional food and nutra-pharmaceutical perspectives of date (Phoenix dactylifera L.) fruit. J. Food Biochem., 44.","DOI":"10.1111\/jfbc.13332"},{"key":"ref_26","first-page":"2951","article-title":"In-vitro antibacterial activities of Ajwa dates fruit (Phoenix dactylifera L.) extract against selected gram-negative bacteria causing gastroenteritis","volume":"10","author":"Abdullah","year":"2019","journal-title":"Int. J. Pharm. Sci. Res."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Al-Shwyeh, H.A. (2019). Date palm (Phoenix dactylifera L.) fruit as potential antioxidant and antimicrobial agents. J. Pharm. Bioallied Sci., 11.","DOI":"10.4103\/JPBS.JPBS_168_18"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1016\/j.jiph.2021.10.006","article-title":"Antimicrobial and anti-biofilm activities of polyphenols extracted from different Saudi Arabian date cultivars against human pathogens","volume":"14","author":"Alfarhan","year":"2021","journal-title":"J. Infect. Public Health"},{"key":"ref_29","first-page":"1083","article-title":"In vitro inhibition potential of Phoenix dactylifera L. extracts on the growth of pathogenic fungi","volume":"6","author":"Bokhari","year":"2012","journal-title":"J. Med. Plants Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1080\/14786419.2010.536765","article-title":"Antifungal activity and phytochemical screening of extracts from Phoenix dactylifera L. cultivars","volume":"25","author":"Boulenouar","year":"2011","journal-title":"Nat. Prod. Res."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Elasbali, A.M., Al-Soud, W.A., Mousa Elayyan, A.E., Al-Oanzi, Z.H., Alhassan, H.H., Mohamed, B.M., Alanazi, H.H., Ashraf, M.S., Moiz, S., and Patel, M. (2023). Integrating network pharmacology approaches for the investigation of multi-target pharmacological mechanism of 6-shogaol against cervical cancer. J. Biomol. Struct. Dyn., 1\u201317.","DOI":"10.1080\/07391102.2023.2191719"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1039\/C5NP00005J","article-title":"Network pharmacology applications to map the unexplored target space and therapeutic potential of natural products","volume":"32","author":"Kibble","year":"2015","journal-title":"Nat. Prod. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1646905","DOI":"10.1155\/2020\/1646905","article-title":"Applications of network pharmacology in traditional Chinese medicine research","volume":"2020","author":"Zhou","year":"2020","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1002\/fsn3.3199","article-title":"Phytochemical analysis and nephroprotective potential of Ajwa dates in doxorubicin-induced nephrotoxicity rats: Biochemical and molecular docking approaches","volume":"11","author":"Baothman","year":"2023","journal-title":"Food Sci. Nutr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.tifs.2017.02.009","article-title":"A review on chemistry and pharmacology of Ajwa dates fruit and pit","volume":"63","author":"Khalid","year":"2017","journal-title":"Trends Food Sci. Technol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s13596-017-0257-y","article-title":"Phytochemical and GC-MS analysis of Saudi Arabian Ajwa variety of date seed oil and extracts obtained by the slow pyrolysis method","volume":"17","author":"Qadir","year":"2017","journal-title":"Orient. Pharm. Exp. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"W357","DOI":"10.1093\/nar\/gkz382","article-title":"SwissTargetPrediction: Updated data and new features for efficient prediction of protein targets of small molecules","volume":"47","author":"Daina","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3073","DOI":"10.1093\/bioinformatics\/btt540","article-title":"Shaping the interaction landscape of bioactive molecules","volume":"29","author":"Gfeller","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_39","first-page":"gkw943","article-title":"DisGeNET: A comprehensive platform integrating information on human disease-associated genes and variants","volume":"45","author":"Bravo","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_40","first-page":"D845","article-title":"The DisGeNET knowledge platform for disease genomics: 2019 update","volume":"48","author":"Ronzano","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"D204","DOI":"10.1093\/nar\/gku989","article-title":"UniProt: A hub for protein information","volume":"43","author":"Consortium","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2597","DOI":"10.1002\/pmic.201400515","article-title":"FunRich: An open access standalone functional enrichment and interaction network analysis tool","volume":"15","author":"Pathan","year":"2015","journal-title":"Proteomics"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"D605","DOI":"10.1093\/nar\/gkaa1074","article-title":"The STRING database in 2021: Customizable protein\u2013protein networks, and functional characterization of user-uploaded gene\/measurement sets","volume":"49","author":"Szklarczyk","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Dennis, G., Sherman, B.T., Hosack, D.A., Yang, J., Gao, W., Lane, H.C., and Lempicki, R.A. (2003). DAVID: Database for annotation, visualization, and integrated discovery. Genome Biol., 4.","DOI":"10.1186\/gb-2003-4-5-p3"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/0471250953.bi0814s24","article-title":"Using autodock for ligand-receptor docking","volume":"24","author":"Morris","year":"2008","journal-title":"Curr. Protoc. Bioinform."},{"key":"ref_47","unstructured":"Studio, D. (2023, February 15). Discovery studio. Accelrys [2.1]. Available online: https:\/\/discover.3ds.com\/discovery-studio-visualizer-download."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.ijbiomac.2022.10.115","article-title":"Targeting inhibition of microtubule affinity regulating kinase 4 by Harmaline: Strategy to combat Alzheimer\u2019s disease","volume":"224","author":"Adnan","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Adnan, M., Shamsi, A., Elasbali, A.M., Siddiqui, A.J., Patel, M., Alshammari, N., Alharethi, S.H., Alhassan, H.H., Bardakci, F., and Hassan, M.I. (2022). Structure-guided approach to discover tuberosin as a potent activator of pyruvate kinase M2, targeting cancer therapy. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232113172"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.1080\/07391102.2020.1751713","article-title":"Molecular docking and molecular dynamics simulations studies on \u03b2-glucosidase and xylanase Trichoderma asperellum to predict degradation order of cellulosic components in oil palm leaves for nanocellulose preparation","volume":"39","author":"Bahaman","year":"2021","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Bouali, N., Ahmad, I., Patel, H., Alhejaili, E.B., Hamadou, W.S., Badraoui, R., Hadj Lajimi, R., Alreshidi, M., Siddiqui, A.J., and Adnan, M. (2023). GC\u2013MS screening of the phytochemical composition of Ziziphus honey: ADME properties and in vitro\/in silico study of its antimicrobial activity. J. Biomol. Struct. Dyn., 1\u201313.","DOI":"10.1080\/07391102.2023.2205945"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"P\u00e1ll, S., Abraham, M.J., Kutzner, C., Hess, B., and Lindahl, E. (2014, January 2\u20133). Tackling exascale software challenges in molecular dynamics simulations with GROMACS. Proceedings of the Solving Software Challenges for Exascale: International Conference on Exascale Applications and Software, EASC 2014, Stockholm, Sweden.","DOI":"10.1007\/978-3-319-15976-8_1"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"6281","DOI":"10.1021\/acs.jctc.1c00645","article-title":"gmx_MMPBSA: A new tool to perform end-state free energy calculations with GROMACS","volume":"17","author":"Valiente","year":"2021","journal-title":"J. Chem. Theory Comput."},{"key":"ref_54","unstructured":"Altaf, M.M., Khan, M.S.A., and Ahmad, I. (2019). New Look to Phytomedicine, Elsevier."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1039\/b706296f","article-title":"Natural products as an inspiration in the diversity-oriented synthesis of bioactive compound libraries","volume":"25","author":"Cordier","year":"2008","journal-title":"Nat. Prod. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Bu, Q.-R., Bao, M.-Y., Yang, Y., Wang, T.-M., and Wang, C.-Z. (2022). Targeting Virulence Factors of Candida albicans with Natural Products. Foods, 11.","DOI":"10.3390\/foods11192951"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1021\/cb900243b","article-title":"Characterization of plant-derived saponin natural products against Candida albicans","volume":"5","author":"Coleman","year":"2010","journal-title":"ACS Chem. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mycmed.2016.10.002","article-title":"Anti-Candida albicans natural products, sources of new antifungal drugs: A review","volume":"27","author":"Zida","year":"2017","journal-title":"J. Mycol. Medicale"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/978-3-030-64872-5_16","article-title":"The effects of nutraceuticals and herbal medicine on candida albicans in oral candidiasis: A comprehensive review","volume":"1308","author":"Gharibpour","year":"2021","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"104","DOI":"10.4103\/phrev.phrev_8_17","article-title":"Plants\u2019 natural products as alternative promising anti-Candida drugs","volume":"11","author":"Soliman","year":"2017","journal-title":"Pharmacogn. Rev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.drudis.2013.07.016","article-title":"Traditional use of medicinal agents: A valid source of evidence","volume":"19","author":"Staiger","year":"2014","journal-title":"Drug Discov. Today"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Augostine, C.R., and Avery, S.V. (2022). Discovery of natural products with antifungal potential through combinatorial synergy. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.866840"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.copbio.2021.02.001","article-title":"Antifungal natural products","volume":"69","author":"Heard","year":"2021","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_64","first-page":"83","article-title":"Natural products and antifungal drug discovery","volume":"118","author":"Jacob","year":"2005","journal-title":"Methods Mol. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"497","DOI":"10.3390\/plants8110497","article-title":"Phenolic composition and antimicrobial activity of different Emirati Date (Phoenix dactylifera L.) pits: A comparative study","volume":"8","author":"Hussain","year":"2019","journal-title":"Plants"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"54","DOI":"10.3390\/agronomy12010054","article-title":"Pits of date palm: Bioactive composition, antibacterial activity and antimutagenicity potentials","volume":"12","author":"Selim","year":"2021","journal-title":"Agronomy"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Anwar, S., Raut, R., Alsahli, M.A., Almatroudi, A., Alfheeaid, H., Alzahrani, F.M., Khan, A.A., Allemailem, K.S., Almatroodi, S.A., and Rahmani, A.H. (2022). Role of Ajwa dates fruit pulp and seed in the management of diseases through in vitro and in silico analysis. Biology, 11.","DOI":"10.3390\/biology11010078"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1038\/ncomms2343","article-title":"Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans","volume":"4","author":"Smeekens","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e25790","DOI":"10.4161\/jkst.25790","article-title":"STAT2 phosphorylation and signaling","volume":"2","author":"Steen","year":"2013","journal-title":"Jak-Stat"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"960","DOI":"10.4049\/jimmunol.150.3.960","article-title":"Function associated with IL-2 receptor-beta on human neutrophils. Mechanism of activation of antifungal activity against Candida albicans by IL-2","volume":"150","author":"Djeu","year":"1993","journal-title":"J. Immunol. (Baltim. Md. 1950)"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"jcs249318","DOI":"10.1242\/jcs.249318","article-title":"Innate immune receptor clustering and its role in immune regulation","volume":"134","author":"Li","year":"2021","journal-title":"J. Cell Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"105677","DOI":"10.1016\/j.micpath.2022.105677","article-title":"Organ-specific host differential gene expression analysis in systemic candidiasis: A systems biology approach","volume":"169","author":"Miryala","year":"2022","journal-title":"Microb. Pathog."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1007\/s10875-020-00847-x","article-title":"Human STAT1 gain-of-function heterozygous mutations: Chronic mucocutaneous candidiasis and type I interferonopathy","volume":"40","author":"Okada","year":"2020","journal-title":"J. Clin. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/imr.12534","article-title":"Molecular mechanisms and functions of pyroptosis, inflammatory caspases and inflammasomes in infectious diseases","volume":"277","author":"Man","year":"2017","journal-title":"Immunol. Rev."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"7537649","DOI":"10.1155\/2019\/7537649","article-title":"Immune dysfunction and albumin-related immunity in liver cirrhosis","volume":"2019","author":"Wilde","year":"2019","journal-title":"Mediat. Inflamm."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"541","DOI":"10.3390\/ijms21020541","article-title":"P53 and the immune response: 40 years of exploration\u2014A plan for the future","volume":"21","author":"Levine","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.femsim.2004.12.005","article-title":"Biological importance of the two Toll-like receptors, TLR2 and TLR4, in macrophage response to infection with Candida albicans","volume":"44","author":"Blasi","year":"2005","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_78","first-page":"25","article-title":"Regulation of Candida albicans morphogenesis by tumor necrosis factor-alpha and potential for treatment of oral candidiasis","volume":"21","author":"Ohta","year":"2007","journal-title":"In Vivo"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Gal\u00e8s, A., Conduch\u00e9, A., Bernad, J., Lefevre, L., Olagnier, D., B\u00e9raud, M., Martin-Blondel, G., Linas, M.-D., Auwerx, J., and Coste, A. (2010). PPAR\u03b3 controls Dectin-1 expression required for host antifungal defense against Candida albicans. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000714"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.chom.2012.04.008","article-title":"Th17 cells in immunity to Candida albicans","volume":"11","author":"Gaffen","year":"2012","journal-title":"Cell Host Microbe"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"foy018","DOI":"10.1093\/femsyr\/foy018","article-title":"Th17 cells differentiated with mycelial membranes of Candida albicans prevent oral candidiasis","volume":"18","author":"Tasaki","year":"2018","journal-title":"FEMS Yeast Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"570","DOI":"10.2741\/3263","article-title":"Role of Toll-like receptors in systemic Candida albicans infections","volume":"14","author":"Gil","year":"2009","journal-title":"Front. Biosci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1574-695X.2008.00378.x","article-title":"Toll-like receptors and fungal infections: The role of TLR2, TLR4 and MyD88 in paracoccidioidomycosis","volume":"53","author":"Calich","year":"2008","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Dom\u00ednguez-Andr\u00e9s, J., Arts, R.J., Ter Horst, R., Gresnigt, M.S., Smeekens, S.P., Ratter, J.M., Lachmandas, E., Boutens, L., van de Veerdonk, F.L., and Joosten, L.A. (2017). Rewiring monocyte glucose metabolism via C-type lectin signaling protects against disseminated candidiasis. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006632"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1038\/ni.2369","article-title":"C-type lectin receptors orchestrate antifungal immunity","volume":"13","author":"Hardison","year":"2012","journal-title":"Nat. Immunol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"123","DOI":"10.3389\/fimmu.2018.00123","article-title":"Regulation of C-type lectin receptor-mediated antifungal immunity","volume":"9","author":"Tang","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/s10495-019-01589-x","article-title":"Necroptosis and its role in infectious diseases","volume":"25","author":"Xia","year":"2020","journal-title":"Apoptosis"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1007\/s10495-022-01755-8","article-title":"The regulation of necroptosis by ubiquitylation","volume":"27","author":"Chen","year":"2022","journal-title":"Apoptosis"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2622","DOI":"10.1038\/s41418-019-0323-8","article-title":"Dectin-1-induced RIPK1 and RIPK3 activation protects host against Candida albicans infection","volume":"26","author":"Cao","year":"2019","journal-title":"Cell Death Differ."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1160719","DOI":"10.3389\/fimmu.2023.1160719","article-title":"Advances in the role of STAT3 in macrophage polarization","volume":"14","author":"Xia","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.3389\/fimmu.2019.01448","article-title":"Fine-tuning of type I interferon response by STAT3","volume":"10","author":"Tsai","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.3389\/fimmu.2019.01253","article-title":"Signal integration of IFN-I and IFN-II with TLR4 involves sequential recruitment of STAT1-complexes and NF\u03baB to enhance pro-inflammatory transcription","volume":"10","author":"Csermely","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"e66014","DOI":"10.7554\/eLife.66014","article-title":"Competitive binding of STATs to receptor phospho-Tyr motifs accounts for altered cytokine responses","volume":"10","author":"Wilmes","year":"2021","journal-title":"eLife"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/12\/11\/1369\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:25:24Z","timestamp":1760131524000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/12\/11\/1369"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,18]]},"references-count":93,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["pathogens12111369"],"URL":"https:\/\/doi.org\/10.3390\/pathogens12111369","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,18]]}}}