Pub Date : 2026-01-24DOI: 10.1016/j.amolm.2026.100102
Jhashanath Adhikari Subin
Due to the effectiveness and relatively lower toxicity at high dose levels, natural products have been practiced in different medicine systems since ancient times. It plays a vital role in prophylactics and therapeutics of many maladies and has been an accessible and affordable choice to modern medicines. For a possible treatment option for the current pandemic caused by SARS-CoV-2, various chemical components of Swertia chirayita Roxb. ex Fleming plant were explored by computational methods. The phytochemicals present in the plant, amaroswerin, amarogentin, mangiferin, oleanolic acid, syringaresinol, swertiamarin, and sweroside were proposed as the top candidates with probable inhibition capabilities determined in terms of docking scores/binding affinities against non-structural protein 13 (PDB ID: 5RMM) calculated from flexible receptor molecular docking. The values calculated were −17.2, −15.7, −14.9, −13.0, −13.6, −13.0, and −13.3 kcal/mol, respectively and were better than those calculated for some FDA approved drugs and a native ligand which showed values from −12.9 to −8.9 kcal/mol. From the 200 ns long molecular dynamics simulations of different protein-ligand adducts, it was found that oleanolic acid RMSD was less than 5 Å and snapshots at multiple instances displayed that it nearly retained the docked position with moderately smooth nature of the curve. These geometrical results implied acceptable structural stability of the protein-ligand adduct. The binding free energy change of protein-oleanolic acid complex (−32.72 ± 4.65 kcal/mol) was the best among the test cases. This thermodynamic parameter hinted at the spontaneous nature of the reaction and its frame-by-frame analysis complemented the geometrical results. The ADMET prediction revealed lipophilic nature and some toxicity end-points of the hit molecule, oleanolic acid. The results point towards the need for further extensive characterization of it by in vitro and in vivo methods in the development of anti COVID-19 drug from readily available plant with ethnobotanical values.
{"title":"Computational assessment of the chemical components of Swertia chirayita Roxb. ex Fleming targeting NSP13 of SARS-CoV-2","authors":"Jhashanath Adhikari Subin","doi":"10.1016/j.amolm.2026.100102","DOIUrl":"10.1016/j.amolm.2026.100102","url":null,"abstract":"<div><div>Due to the effectiveness and relatively lower toxicity at high dose levels, natural products have been practiced in different medicine systems since ancient times. It plays a vital role in prophylactics and therapeutics of many maladies and has been an accessible and affordable choice to modern medicines. For a possible treatment option for the current pandemic caused by SARS-CoV-2, various chemical components of <em>Swertia chirayita</em> Roxb. ex Fleming plant were explored by computational methods. The phytochemicals present in the plant, amaroswerin, amarogentin, mangiferin, oleanolic acid, syringaresinol, swertiamarin, and sweroside were proposed as the top candidates with probable inhibition capabilities determined in terms of docking scores/binding affinities against non-structural protein 13 (PDB ID: 5RMM) calculated from flexible receptor molecular docking. The values calculated were −17.2, −15.7, −14.9, −13.0, −13.6, −13.0, and −13.3 kcal/mol, respectively and were better than those calculated for some FDA approved drugs and a native ligand which showed values from −12.9 to −8.9 kcal/mol. From the 200 ns long molecular dynamics simulations of different protein-ligand adducts, it was found that oleanolic acid RMSD was less than 5 Å and snapshots at multiple instances displayed that it nearly retained the docked position with moderately smooth nature of the curve. These geometrical results implied acceptable structural stability of the protein-ligand adduct. The binding free energy change of protein-oleanolic acid complex (−32.72 ± 4.65 kcal/mol) was the best among the test cases. This thermodynamic parameter hinted at the spontaneous nature of the reaction and its frame-by-frame analysis complemented the geometrical results. The ADMET prediction revealed lipophilic nature and some toxicity end-points of the hit molecule, oleanolic acid. The results point towards the need for further extensive characterization of it by <em>in vitro</em> and <em>in vivo</em> methods in the development of anti COVID-19 drug from readily available plant with ethnobotanical values.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"7 ","pages":"Article 100102"},"PeriodicalIF":0.0,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146081019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Current commercial methods of detection of high-risk human papilloma virus (hrHPV) rely mostly on the polymerase chain reaction (PCR) that use either 14 specific primer pairs or a single consensus primer pair (e.g., GP5+/GP6+). However, PCR requires the use of a thermal cycler (PCR machine) and electricity and therefore is not suitable for a low-cost Point of Care Test (PoCT). Moreover, PCR primers are often not suitable for isothermal amplification since at lower temperature they may anneal non-specifically leading to background amplification. We have developed an isothermal point of care method for the rapid detection of hrHPV that works at a constant temperature (<42°C) using recombinase polymerase amplification (RPA). A novel consensus primer pair was designed able to amplify all 14 hrHPV types. To enable the detection of the amplified double-stranded RPA products, one primer was labelled with a 5′-phosphate, and the other primer was labelled at the 5′-end with 6-carboxyfluorescein (FAM). Then, the double-stranded labelled RPA product was digested with Lambda exonuclease, which preferentially digests 5′-phosphorylated DNA ends whereas the 5′-FAM ends are protected, generating single-stranded 5′-FAM-labelled RPA products. These products can be detected by paper-based lateral flow assays (LFA) using biotinylated detection probes that detect all 14 hrHPV types at the same time (universal consensus detection probe). Lateral flow assay conditions were developed that allow these probes to detect all 14 hrHPV types. Using this novel isothermal rapid hrHPV detection method, amplification of all 14 hrHPV types at constant temperature (currently set at 37°C) within short time (<1h) was achieved.
{"title":"Development of an isothermal point of care method for detection of human papilloma virus (HPV)","authors":"Jean-Marc Zingg , Pratibha Joshi , Mercedes Lozano-Garcia , Erin Kobetz , Sapna Deo , Sylvia Daunert","doi":"10.1016/j.amolm.2026.100101","DOIUrl":"10.1016/j.amolm.2026.100101","url":null,"abstract":"<div><div>Current commercial methods of detection of high-risk human papilloma virus (hrHPV) rely mostly on the polymerase chain reaction (PCR) that use either 14 specific primer pairs or a single consensus primer pair (e.g., GP5+/GP6+). However, PCR requires the use of a thermal cycler (PCR machine) and electricity and therefore is not suitable for a low-cost Point of Care Test (PoCT). Moreover, PCR primers are often not suitable for isothermal amplification since at lower temperature they may anneal non-specifically leading to background amplification. We have developed an isothermal point of care method for the rapid detection of hrHPV that works at a constant temperature (<42°C) using recombinase polymerase amplification (RPA). A novel consensus primer pair was designed able to amplify all 14 hrHPV types. To enable the detection of the amplified double-stranded RPA products, one primer was labelled with a 5′-phosphate, and the other primer was labelled at the 5′-end with 6-carboxyfluorescein (FAM). Then, the double-stranded labelled RPA product was digested with Lambda exonuclease, which preferentially digests 5′-phosphorylated DNA ends whereas the 5′-FAM ends are protected, generating single-stranded 5′-FAM-labelled RPA products. These products can be detected by paper-based lateral flow assays (LFA) using biotinylated detection probes that detect all 14 hrHPV types at the same time (universal consensus detection probe). Lateral flow assay conditions were developed that allow these probes to detect all 14 hrHPV types. Using this novel isothermal rapid hrHPV detection method, amplification of all 14 hrHPV types at constant temperature (currently set at 37°C) within short time (<1h) was achieved.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"7 ","pages":"Article 100101"},"PeriodicalIF":0.0,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146081099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<div><h3>Background</h3><div>Snakebite envenomation Snakebite envenomation is a major public health problem, affecting an estimated 1.8–2.7 million people annually, predominantly in low- and middle-income countries. Despite its classification as a neglected tropical disease by the World Health Organization, snakebite envenomation continues to cause substantial morbidity and mortality, driven in part by limited access to effective antivenoms, delays in treatment, and the lack of widely available rapid diagnostic tools. The marked biological complexity and geographic variability of snake venom composition further complicate clinical management, underscoring the need for innovative and context-appropriate approaches to improve both therapeutic effectiveness and diagnostic accuracy. This review examines recent advancements in regionally informed antivenom strategies and next-generation diagnostic technologies, emphasizing their necessity for achieving more precise, timely, and context-appropriate snakebite management.</div></div><div><h3>Methods</h3><div>This review adopts a structured, critical narrative approach, synthesizing peer-reviewed literature and global health reports to evaluate recent innovations in antivenom development and snakebite diagnostics. Literature was identified using PubMed, Web of Science, and Scopus, with emphasis placed on studies published from 2010 onward, reflecting the period of rapid advances in venom omics, recombinant antivenoms, and diagnostic technologies. Searches were focused on terms directly relevant to the review's analytical scope, including <em>antivenom development</em>, <em>venom proteomics</em>, <em>transcriptomics</em>, and <em>snakebite diagnostics</em>. Rather than aiming for exhaustive coverage, studies were prioritized based on their relevance to therapeutic effectiveness, translational feasibility, scalability, and accessibility in snakebite-endemic settings. Findings were synthesized comparatively to identify key advances, persistent limitations, and barriers to clinical implementation.</div></div><div><h3>Findings</h3><div>Recent advances in antivenom research include the development of recombinant antibody platforms, immunoinformatics-guided design strategies, synthetic biology approaches, and the characterization of endogenous venom resistance mechanisms, all of which have contributed to improved understanding of how specificity and immunogenicity might be optimized beyond conventional antivenoms. At the same time, progress in diagnostic research, particularly involving lateral flow–based immunoassays and multi-omic venom profiling, has highlighted potential pathways for improving venom or toxin identification and supporting more informed clinical decision making. However, translation of these scientific advances into routine clinical practice remains limited. Persistent challenges related to large-scale manufacturing, regulatory approval, affordability, and implementation within resource-constr
蛇咬伤中毒是一个重大的公共卫生问题，每年影响约180万至270万人，主要发生在低收入和中等收入国家。尽管被世界卫生组织列为被忽视的热带病，但蛇咬伤中毒仍然造成大量发病率和死亡率，部分原因是获得有效抗蛇毒血清的机会有限、治疗延误以及缺乏广泛可用的快速诊断工具。蛇毒成分的显著生物学复杂性和地理变异性进一步复杂化了临床管理，强调需要创新和适合环境的方法来提高治疗效果和诊断准确性。本文综述了区域信息抗蛇毒血清策略和下一代诊断技术的最新进展，强调了实现更精确、及时和适合环境的蛇咬伤管理的必要性。方法本综述采用结构化、批判性的叙述方法，综合同行评议文献和全球卫生报告，评估抗蛇毒血清发展和蛇咬伤诊断的最新创新。文献通过PubMed、Web of Science和Scopus进行鉴定，重点是2010年以后发表的研究，反映了毒液组学、重组抗蛇毒血清和诊断技术的快速发展时期。搜索集中在与评论的分析范围直接相关的术语上，包括抗蛇毒血清的发展、蛇毒蛋白质组学、转录组学和蛇咬伤诊断。研究的目标不是详尽的覆盖，而是根据它们与蛇咬伤流行环境的治疗效果、转化可行性、可扩展性和可及性的相关性来优先考虑。对研究结果进行综合比较，以确定关键进展、持续限制和临床实施的障碍。抗蛇毒血清研究的最新进展包括重组抗体平台的开发、免疫信息学指导的设计策略、合成生物学方法和内源性蛇毒抗性机制的表征，所有这些都有助于提高对特异性和免疫原性如何在传统抗蛇毒血清之外优化的理解。与此同时，诊断研究的进展，特别是涉及基于侧流的免疫分析和多组毒液分析，突出了改进毒液或毒素识别和支持更明智的临床决策的潜在途径。然而，将这些科学进步转化为常规临床实践仍然有限。在资源有限的卫生系统内，与大规模生产、监管审批、可负担性和实施相关的持续挑战继续限制了下一代抗蛇毒血清和蛇咬流行地区诊断的实际影响。结论蛇咬伤管理的未来进展将取决于抗蛇毒血清开发、诊断创新和支持性全球卫生政策框架的协调进展。通过毒液分析和可扩展的模块化生产模型的支持，以及经过适当验证的快速诊断工具，区域知情的抗蛇毒血清策略代表了提高治疗有效性和可及性的可行途径。然而，要实现有意义的发病率和死亡率的降低，需要持续的跨学科合作，并明确关注转化、监管和卫生系统的限制，确保科学创新与高负担环境中的实际可行性和公平实施相匹配。
{"title":"Innovative approaches in snakebite treatment: the need for precision antivenoms and next-generation diagnostics","authors":"Emeka John Dingwoke , Umezuruike Linus Opara , Fatima Adis Adamude , Kingsley Onyekachi Moh , Gilbert Adzemye Nsadzetsen , Abdullahi Balarabe Sallau , Emmanuel Oluwadare Balogun , Amin Elsadig Eltayeb , Ikenna Ezeaku , John Wassagwa , Sunday Egba Omogo , Judith Chinelo Amailo , Maryann Chidimma Enemmuo , Okechukwu Kalu Iroha , Chukwuemeka Paul Nweje-Anyalowu , Chijioke Cyril Ilechukwu , Augustina Chinyere Amaefula","doi":"10.1016/j.amolm.2026.100100","DOIUrl":"10.1016/j.amolm.2026.100100","url":null,"abstract":"<div><h3>Background</h3><div>Snakebite envenomation Snakebite envenomation is a major public health problem, affecting an estimated 1.8–2.7 million people annually, predominantly in low- and middle-income countries. Despite its classification as a neglected tropical disease by the World Health Organization, snakebite envenomation continues to cause substantial morbidity and mortality, driven in part by limited access to effective antivenoms, delays in treatment, and the lack of widely available rapid diagnostic tools. The marked biological complexity and geographic variability of snake venom composition further complicate clinical management, underscoring the need for innovative and context-appropriate approaches to improve both therapeutic effectiveness and diagnostic accuracy. This review examines recent advancements in regionally informed antivenom strategies and next-generation diagnostic technologies, emphasizing their necessity for achieving more precise, timely, and context-appropriate snakebite management.</div></div><div><h3>Methods</h3><div>This review adopts a structured, critical narrative approach, synthesizing peer-reviewed literature and global health reports to evaluate recent innovations in antivenom development and snakebite diagnostics. Literature was identified using PubMed, Web of Science, and Scopus, with emphasis placed on studies published from 2010 onward, reflecting the period of rapid advances in venom omics, recombinant antivenoms, and diagnostic technologies. Searches were focused on terms directly relevant to the review's analytical scope, including <em>antivenom development</em>, <em>venom proteomics</em>, <em>transcriptomics</em>, and <em>snakebite diagnostics</em>. Rather than aiming for exhaustive coverage, studies were prioritized based on their relevance to therapeutic effectiveness, translational feasibility, scalability, and accessibility in snakebite-endemic settings. Findings were synthesized comparatively to identify key advances, persistent limitations, and barriers to clinical implementation.</div></div><div><h3>Findings</h3><div>Recent advances in antivenom research include the development of recombinant antibody platforms, immunoinformatics-guided design strategies, synthetic biology approaches, and the characterization of endogenous venom resistance mechanisms, all of which have contributed to improved understanding of how specificity and immunogenicity might be optimized beyond conventional antivenoms. At the same time, progress in diagnostic research, particularly involving lateral flow–based immunoassays and multi-omic venom profiling, has highlighted potential pathways for improving venom or toxin identification and supporting more informed clinical decision making. However, translation of these scientific advances into routine clinical practice remains limited. Persistent challenges related to large-scale manufacturing, regulatory approval, affordability, and implementation within resource-constr","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"7 ","pages":"Article 100100"},"PeriodicalIF":0.0,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146006722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.amolm.2025.100096
Lihle Mahamba, Mustafa Alhaji Isa, Abidemi Paul Kappo
{"title":"Corrigendum to “In silico identification of potential inhibitors for the universal stress G4LZI3 protein from Schistosoma mansoni using molecular docking and molecular dynamics simulation analyses” [Aspects of Molecular Medicine 5 (2025) 100084]","authors":"Lihle Mahamba, Mustafa Alhaji Isa, Abidemi Paul Kappo","doi":"10.1016/j.amolm.2025.100096","DOIUrl":"10.1016/j.amolm.2025.100096","url":null,"abstract":"","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"6 ","pages":"Article 100096"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145736697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-05DOI: 10.1016/j.amolm.2025.100098
Anel Sparks , Yolandi Swart , Craig J. Kinnear , Gian D. van der Spuy , Gerard Tromp , Brigitte Glanzmann , Marlo Möller
Despite ongoing efforts, the current human reference genome lacks diversity. Consequently, research using this resource might miss disease-causing variants in individuals whose ancestry does not correspond to that of the standard reference. Most individuals from South Africa are admixed to some extent, with ancestral contributions from several continental populations. This study set out to create a population-specific reference genome for admixed South Africans with the same coordinate system as the widely used GRCh38 reference. This approach was tested in diagnosing a South African individual with Mendelian susceptibility to mycobacterial disease (MSMD) using a novel approach that replaced portions of the reference genome with corresponding, but more variable portions of the population-specific sequences. We implemented the algorithm in a tool we named PopPatch. Short sequencing reads from two individuals were used for a rudimentary genome assembly which was then aligned to GRCh38p13. To test the algorithm and the generated reference genome, whole genome sequencing data from a TB-susceptible individual was aligned to SA_PopPatch and GRCh38, with variant call sets compared. The GRCh38p13 reference yielded no discoveries, while the SA_PopPatch reference identified a homozygous, non-synonymous single nucleotide variant in exon 20 of the JAK1 gene. This project introduces a novel method for creating population-specific reference genomes that align with the standard reference, ensuring congruency with databases based on the most widely used reference genome, GRCh38, while minimizing additional costs.
{"title":"De novo assembly of an admixed South African genome and its clinical application to genetic susceptibility to tuberculosis","authors":"Anel Sparks , Yolandi Swart , Craig J. Kinnear , Gian D. van der Spuy , Gerard Tromp , Brigitte Glanzmann , Marlo Möller","doi":"10.1016/j.amolm.2025.100098","DOIUrl":"10.1016/j.amolm.2025.100098","url":null,"abstract":"<div><div>Despite ongoing efforts, the current human reference genome lacks diversity. Consequently, research using this resource might miss disease-causing variants in individuals whose ancestry does not correspond to that of the standard reference. Most individuals from South Africa are admixed to some extent, with ancestral contributions from several continental populations. This study set out to create a population-specific reference genome for admixed South Africans with the same coordinate system as the widely used GRCh38 reference. This approach was tested in diagnosing a South African individual with Mendelian susceptibility to mycobacterial disease (MSMD) using a novel approach that replaced portions of the reference genome with corresponding, but more variable portions of the population-specific sequences. We implemented the algorithm in a tool we named PopPatch. Short sequencing reads from two individuals were used for a rudimentary genome assembly which was then aligned to GRCh38p13. To test the algorithm and the generated reference genome, whole genome sequencing data from a TB-susceptible individual was aligned to SA_PopPatch and GRCh38, with variant call sets compared. The GRCh38p13 reference yielded no discoveries, while the SA_PopPatch reference identified a homozygous, non-synonymous single nucleotide variant in exon 20 of the <em>JAK1</em> gene. This project introduces a novel method for creating population-specific reference genomes that align with the standard reference, ensuring congruency with databases based on the most widely used reference genome, GRCh38, while minimizing additional costs.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"6 ","pages":"Article 100098"},"PeriodicalIF":0.0,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145519715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-04DOI: 10.1016/j.amolm.2025.100097
Victoria A. Patten , Hocine Bendou , Denver T. Hendricks , Christopher G. Mathew , Wenlong Carl Chen , Joanna C. Fowler , Roshan K. Sood , Philip H. Jones , M. Iqbal Parker
Variant calling in complex genomic regions remains a critical challenge in cancer genomics, yet systematic evaluations of false positive rates in such regions are rarely reported. This investigative study examined somatic mutations in esophageal squamous cell carcinoma (ESCC) using Whole Genome Sequencing (WGS) data, that identified a high frequency of putative mutations in MUC3A, a gene with an inherently complex sequence architecture. Quantitative laboratory validation attempts failed to confirm any of these computationally predicted mutations, prompting systematic re-analysis. By assessing multiple variant calling algorithms and implementing a Panel of Normals (PON) filtering strategy, we demonstrate that standard bioinformatics pipelines generated extensive false positive calls in MUC3A, with false positive rates approaching 100 % for this gene. While previous studies have acknowledged limitations in variant calling for repetitive or homologous regions, our work provides evidence of complete analytical failure in the MUC3A gene, and establishes a reproducible framework for identifying such artefacts. These findings address a critical research gap by quantifying the magnitude of false discovery in complex genomic contexts and demonstrating that multi-tool consensus approaches combined with PON filtering are insufficient without accompanied experimental validation. We recommend mandatory quantitative confirmation for variants identified in sequence-complex genes and advocate for transparent reporting of validation rates in cancer genomic studies to prevent propagation of spurious findings in literature. This paper provides a cautionary warning to future research to take into consideration the limitations of alignment and variant calling tools and to employ a combination of tools to obtain robust and reliable results.
{"title":"A cautionary note on genomic complexity and bioinformatic analysis in cancer","authors":"Victoria A. Patten , Hocine Bendou , Denver T. Hendricks , Christopher G. Mathew , Wenlong Carl Chen , Joanna C. Fowler , Roshan K. Sood , Philip H. Jones , M. Iqbal Parker","doi":"10.1016/j.amolm.2025.100097","DOIUrl":"10.1016/j.amolm.2025.100097","url":null,"abstract":"<div><div>Variant calling in complex genomic regions remains a critical challenge in cancer genomics, yet systematic evaluations of false positive rates in such regions are rarely reported. This investigative study examined somatic mutations in esophageal squamous cell carcinoma (ESCC) using Whole Genome Sequencing (WGS) data, that identified a high frequency of putative mutations in <em>MUC3A</em>, a gene with an inherently complex sequence architecture. Quantitative laboratory validation attempts failed to confirm any of these computationally predicted mutations, prompting systematic re-analysis. By assessing multiple variant calling algorithms and implementing a Panel of Normals (PON) filtering strategy, we demonstrate that standard bioinformatics pipelines generated extensive false positive calls in <em>MUC3A</em>, with false positive rates approaching 100 % for this gene. While previous studies have acknowledged limitations in variant calling for repetitive or homologous regions, our work provides evidence of complete analytical failure in the <em>MUC3A</em> gene, and establishes a reproducible framework for identifying such artefacts. These findings address a critical research gap by quantifying the magnitude of false discovery in complex genomic contexts and demonstrating that multi-tool consensus approaches combined with PON filtering are insufficient without accompanied experimental validation. We recommend mandatory quantitative confirmation for variants identified in sequence-complex genes and advocate for transparent reporting of validation rates in cancer genomic studies to prevent propagation of spurious findings in literature. This paper provides a cautionary warning to future research to take into consideration the limitations of alignment and variant calling tools and to employ a combination of tools to obtain robust and reliable results.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"6 ","pages":"Article 100097"},"PeriodicalIF":0.0,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145465717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-11DOI: 10.1016/j.amolm.2025.100093
Dongsogo Julius , Larbie Christopher , Appiah-Oppong Regina , Emekpe Benjamin , Daniel Ataanya Abera , Yusif Mubarik , Iddrisu Abdul-Mumeen
Medicinal plants have become the option for management of liver diseases because of their availability, cost effectiveness and lesser side effects compared to pharmaceutical drugs. Various parts of plants including roots, leaves, stem, bark and seed have been reportedly used to treat liver diseases including jaundice, hepatitis, hepatosteatosis, hepatocellular carcinoma, hepatobillary disorders and hepatocellular carcinoma. Phytochemicals exhibit anti-oxidant and anti-inflammatory properties due to the presence of acidic polyhydroxyl groups in the phenols. These hydroxyl groups quench free radicals from oxygen, nitrogen and sulphur reactive species thereby inhibiting oxidative stress, inflammation and fibrogenic processes. The objective of the study was to determine the antioxidant, anti-inflammatory and cytotoxicity properties of medicinal plants for the purpose of selecting more efficacious raw materials for herbal products. Ethanolic and methanolic extracts of 13 medicinal plants were test for level of total phenols, flavonoids, 2, 2-diphenyl-1-picrylhydrazyl (DPPH) reducing potential, ferric reducing (FRAP), total antioxidant binding capacity (ABTS), red cell antihemolysis assay and 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) cytotoxicity. Except for DPPH scavenging activity, there was significance of difference between the methanolic and ethanolic extracts, total phenols (p = 0.03), flavonoids (p = 0.024), FRAP (p = 0.02), ABTS (p = 0.00) and red cell hemolysis (p = 0.010). There was correlation between phytochemicals, phenols and flavonoids and antioxidant markers, DPPH, FRAP, ABTS and red cell hemolysis (p < 0.05). Syzygium aromaticum, Curcuma longa, Taraxacum officinalis and Moringa oleifera exhibited the highest inhibitory anti-inflammatory and antioxidant properties. The study indicates that, phytochemical, antioxidant and inflammatory properties varied with the kind of plant, concentration of extract, extractant and polyphenol content. These properties should be evaluated in selecting materials for drug formulation.
{"title":"Antioxidant, anti-inflammatory and cytotoxicity properties of medicinal plants used for producing herbal products against hepatic diseases in Ghana","authors":"Dongsogo Julius , Larbie Christopher , Appiah-Oppong Regina , Emekpe Benjamin , Daniel Ataanya Abera , Yusif Mubarik , Iddrisu Abdul-Mumeen","doi":"10.1016/j.amolm.2025.100093","DOIUrl":"10.1016/j.amolm.2025.100093","url":null,"abstract":"<div><div>Medicinal plants have become the option for management of liver diseases because of their availability, cost effectiveness and lesser side effects compared to pharmaceutical drugs. Various parts of plants including roots, leaves, stem, bark and seed have been reportedly used to treat liver diseases including jaundice, hepatitis, hepatosteatosis, hepatocellular carcinoma, hepatobillary disorders and hepatocellular carcinoma. Phytochemicals exhibit anti-oxidant and anti-inflammatory properties due to the presence of acidic polyhydroxyl groups in the phenols. These hydroxyl groups quench free radicals from oxygen, nitrogen and sulphur reactive species thereby inhibiting oxidative stress, inflammation and fibrogenic processes. The objective of the study was to determine the antioxidant, anti-inflammatory and cytotoxicity properties of medicinal plants for the purpose of selecting more efficacious raw materials for herbal products. Ethanolic and methanolic extracts of 13 medicinal plants were test for level of total phenols, flavonoids, 2, 2-diphenyl-1-picrylhydrazyl (DPPH) reducing potential, ferric reducing (FRAP), total antioxidant binding capacity (ABTS), red cell antihemolysis assay and 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) cytotoxicity. Except for DPPH scavenging activity, there was significance of difference between the methanolic and ethanolic extracts, total phenols (p = 0.03), flavonoids (p = 0.024), FRAP (p = 0.02), ABTS (p = 0.00) and red cell hemolysis (p = 0.010). There was correlation between phytochemicals, phenols and flavonoids and antioxidant markers, DPPH, FRAP, ABTS and red cell hemolysis (p < 0.05). Syzygium <em>aromaticum, Curcuma longa, Taraxacum officinalis</em> and <em>Moringa oleifera</em> exhibited the highest inhibitory anti-inflammatory and antioxidant properties. The study indicates that, phytochemical, antioxidant and inflammatory properties varied with the kind of plant, concentration of extract, extractant and polyphenol content. These properties should be evaluated in selecting materials for drug formulation.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"6 ","pages":"Article 100093"},"PeriodicalIF":0.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144605604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemo-brain signifies the memory and cognitive challenges cancer patients encounter during and after chemotherapy. Lycopene (LP) is a naturally occurring carotenoid with potent anti-reactive oxygen species (ROS) characteristics. This study investigates the effect of Lycopene on Chemotherapy-induced cognitive dysfunction and hippocampal toxicity in rat models.
Method
Thirty Adult male Sprague-Dawley rats were divided into five groups of five (n = 6) rats each. Group A control received normal saline. Group B received a single dose of 10 mg/kg bwt cisplatin (CP, i.p.) on the first day. Group C received 100 mg/kg bwt of Lycopene (LP) (i.p) once daily. Group D received a single dose of 10 mg/kg CP (i.p.) on the first day, followed by 100 mg/kg bwt of LP (i.p) once daily. Group E was treated with 100 mg/kg bwt of LP (i.p) once daily, followed by a single dose of 10 mg/kg bwt CP (i.p.) on the last day. The experiment lasted for 28 days. Hippocampus histology, oxidative stress, neuro-inflammation, apoptotic markers, brain acetylcholinesterase (AChE) activity, and levels of dopamine (DA), gamma-aminobutyric acid GABA, and serotonin 5-HT were investigated.
Results
Lycopene attenuation of malondialdehyde and nitric oxide levels with elevated glutathione levels and intensified superoxide dismutase and catalase activities. Lycopene decreased the levels of inflammatory and apoptotic markers. In addition, LP reduced AChE activity, and elevated glial fibrillary acidic proteins increased neurotransmitter and brain-derived neurotrophic factors.
Conclusion
Lycopene protected chemobrain rats, decreasing inflammation and apoptosis, increasing antioxidant enzyme activities, and attenuating lipid peroxidation.
{"title":"Neurological mechanism of the dietary supplementations of lycopene on chemotherapy-induced cognitive dysfunction/chemobrain and hippocampal toxicity in the rat model","authors":"Sunday Aderemi Adelakun , Jacob Adewale Siyanbade , Akwu Bala Peter , Mistura Abisola Salami , Bisade Esther Adeyeluwa , Opeyemi Zainab Kaka","doi":"10.1016/j.amolm.2025.100094","DOIUrl":"10.1016/j.amolm.2025.100094","url":null,"abstract":"<div><h3>Background</h3><div>Chemo-brain signifies the memory and cognitive challenges cancer patients encounter during and after chemotherapy. Lycopene (LP) is a naturally occurring carotenoid with potent anti-reactive oxygen species (ROS) characteristics. This study investigates the effect of Lycopene on Chemotherapy-induced cognitive dysfunction and hippocampal toxicity in rat models.</div></div><div><h3>Method</h3><div>Thirty Adult male Sprague-Dawley rats were divided into five groups of five (n = 6) rats each. Group A control received normal saline. Group B received a single dose of 10 mg/kg bwt cisplatin (CP, i.p.) on the first day. Group C received 100 mg/kg bwt of Lycopene (LP) (i.p) once daily. Group D received a single dose of 10 mg/kg CP (i.p.) on the first day, followed by 100 mg/kg bwt of LP (i.p) once daily. Group E was treated with 100 mg/kg bwt of LP (i.p) once daily, followed by a single dose of 10 mg/kg bwt CP (i.p.) on the last day. The experiment lasted for 28 days. Hippocampus histology, oxidative stress, neuro-inflammation, apoptotic markers, brain acetylcholinesterase (AChE) activity, and levels of dopamine (DA), gamma-aminobutyric acid GABA, and serotonin 5-HT were investigated.</div></div><div><h3>Results</h3><div>Lycopene attenuation of malondialdehyde and nitric oxide levels with elevated glutathione levels and intensified superoxide dismutase and catalase activities. Lycopene decreased the levels of inflammatory and apoptotic markers. In addition, LP reduced AChE activity, and elevated glial fibrillary acidic proteins increased neurotransmitter and brain-derived neurotrophic factors.</div></div><div><h3>Conclusion</h3><div>Lycopene protected chemobrain rats, decreasing inflammation and apoptosis, increasing antioxidant enzyme activities, and attenuating lipid peroxidation.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"6 ","pages":"Article 100094"},"PeriodicalIF":0.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144670925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-18DOI: 10.1016/j.amolm.2025.100092
Damilare P. Dosunmu , Rachael Oluwakamiye Abolade , Mujeebat Bashiru , Adedoyin John-Joy Owolade , Muyiwa Kolawole Samuel , Ebunoluwa Omorilewa Boluwatife , Ayomadewa Mercy Olatunya , Precious O. Aribisala , Samuel Aduramurewa Osunnaya , Micheal Abimbola Oladosu , Ebenezer Ayomide Oni , Damilola Samuel Bodun
Background
Histone Deacetylase 3 (HDAC3) is an epigenetic enzyme that controls cell cycle progression, apoptosis, and gene expression. Overexpression of HDAC3 has been shown to be a potential contributing factor to the development and spread of breast cancer, and it has recently been identified as a promising target in breast cancer. As a result, repurposing currently approved drugs as novel HDAC3 inhibitors may reduce the labor-intensive and time-consuming process of developing new molecules.
Materials and methods
We sourced 4288 compounds from the ZINC15-approved drugs. We then employed both virtual and structure-based screening to identify and repurpose current drugs as selective inhibitors against the HDAC3 target protein. MD simulation was performed to assess the dynamic behavior and stability of the top ligand complexes for 100 ns.
Results
This computational screening obtained the top five compounds with docking scores of 10.96, 10.32, 9.83, 9.83, and 8.81 kcal/mol, respectively, in comparison with the reference ligand, BG45 (−4.18 kcal/mol), suggesting they may be more potent HDAC3 inhibitors. The MD simulation study of the top hit ligand-protein complex (HDAC3-ZINC000095618609 complex) revealed stable conformational changes. The results of pharmacokinetic and drug-likeness properties of the top-performing compounds reveal their potential to be considered viable HDAC3 inhibitors.
Conclusion
This study highlights the potential of drug repurposing as a cost-effective and faster approach to cancer treatment. here we have identified drugs have the potential to be repurposed as HDAC3 inhibitors; however, additional in vitro and in vivo studies are needed to confirm their efficacy.
{"title":"In silico identification of potential HDAC3 inhibitors through machine learning, molecular docking, and molecular dynamics simulations for drug repurposing","authors":"Damilare P. Dosunmu , Rachael Oluwakamiye Abolade , Mujeebat Bashiru , Adedoyin John-Joy Owolade , Muyiwa Kolawole Samuel , Ebunoluwa Omorilewa Boluwatife , Ayomadewa Mercy Olatunya , Precious O. Aribisala , Samuel Aduramurewa Osunnaya , Micheal Abimbola Oladosu , Ebenezer Ayomide Oni , Damilola Samuel Bodun","doi":"10.1016/j.amolm.2025.100092","DOIUrl":"10.1016/j.amolm.2025.100092","url":null,"abstract":"<div><h3>Background</h3><div>Histone Deacetylase 3 (HDAC3) is an epigenetic enzyme that controls cell cycle progression, apoptosis, and gene expression. Overexpression of HDAC3 has been shown to be a potential contributing factor to the development and spread of breast cancer, and it has recently been identified as a promising target in breast cancer. As a result, repurposing currently approved drugs as novel HDAC3 inhibitors may reduce the labor-intensive and time-consuming process of developing new molecules.</div></div><div><h3>Materials and methods</h3><div>We sourced 4288 compounds from the ZINC15-approved drugs. We then employed both virtual and structure-based screening to identify and repurpose current drugs as selective inhibitors against the HDAC3 target protein. MD simulation was performed to assess the dynamic behavior and stability of the top ligand complexes for 100 ns.</div></div><div><h3>Results</h3><div>This computational screening obtained the top five compounds with docking scores of <span><math><mrow><mo>−</mo></mrow></math></span> 10.96, <span><math><mrow><mo>−</mo></mrow></math></span> 10.32, <span><math><mrow><mo>−</mo></mrow></math></span> 9.83, <span><math><mrow><mo>−</mo></mrow></math></span> 9.83, and <span><math><mrow><mo>−</mo></mrow></math></span> 8.81 kcal/mol, respectively, in comparison with the reference ligand, BG45 (−4.18 kcal/mol), suggesting they may be more potent HDAC3 inhibitors. The MD simulation study of the top hit ligand-protein complex (HDAC3-ZINC000095618609 complex) revealed stable conformational changes. The results of pharmacokinetic and drug-likeness properties of the top-performing compounds reveal their potential to be considered viable HDAC3 inhibitors.</div></div><div><h3>Conclusion</h3><div>This study highlights the potential of drug repurposing as a cost-effective and faster approach to cancer treatment. here we have identified drugs have the potential to be repurposed as HDAC3 inhibitors; however, additional <em>in vitro</em> and <em>in vivo</em> studies are needed to confirm their efficacy.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"6 ","pages":"Article 100092"},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144470153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-01DOI: 10.1016/j.amolm.2025.100090
K. Narendra , Sonali K. Singh , C.K. Deepa , S. Meghana , K.R. Akanth , M. Manjushree , D. Raajasubramaniyan , S. Srinivasan , R. Murali , H.N. Sowbhagya
Dry Eye Disease (DED) significantly impacts quality of life through tear film instability and ocular surface inflammation. This review highlights advancements in treatments, mechanisms, and diagnostics. Emerging pharmacological therapies, including novel anti-inflammatory agents, secretagogues, corticosteroids, and autologous serum eye drops, alongside innovative devices like punctal plugs, thermal pulsation devices, and meibomian gland expression techniques. Lifestyle modifications and nutritional supplements, such as omega-3 fatty acids and antioxidants, are also explored.
Mechanistic insights cover tear film instability, inflammatory pathways, neuropathic pain, and meibomian gland dysfunction, emphasizing recent findings on the ocular surface microbiome, genetic and epigenetic factors, and chronic inflammation. Diagnostic innovations include AI and machine learning integration, advanced imaging techniques, tear film analysis, and functional tests, enhancing early detection and monitoring.
Emerging research on gene therapy, stem cell therapy, ocular surface microbiota, and gene editing technologies like CRISPR is examined for future treatment potential. Personalized medicine approaches, incorporating genomic and proteomic profiling and patient-reported outcomes, are emphasized for tailored therapies.
Environmental and lifestyle factors, including pollution, climate change, diet, and behavioral modifications, are considered for their impact on DED management. Integrating these advancements into clinical practice aims to improve patient outcomes and quality of life, highlighting the future potential of cutting-edge research and innovations.
{"title":"Exploring new Frontiers in dry eye Disease: Treatments, mechanisms, and diagnostic innovations a comprehensive review","authors":"K. Narendra , Sonali K. Singh , C.K. Deepa , S. Meghana , K.R. Akanth , M. Manjushree , D. Raajasubramaniyan , S. Srinivasan , R. Murali , H.N. Sowbhagya","doi":"10.1016/j.amolm.2025.100090","DOIUrl":"10.1016/j.amolm.2025.100090","url":null,"abstract":"<div><div>Dry Eye Disease (DED) significantly impacts quality of life through tear film instability and ocular surface inflammation. This review highlights advancements in treatments, mechanisms, and diagnostics. Emerging pharmacological therapies, including novel anti-inflammatory agents, secretagogues, corticosteroids, and autologous serum eye drops, alongside innovative devices like punctal plugs, thermal pulsation devices, and meibomian gland expression techniques. Lifestyle modifications and nutritional supplements, such as omega-3 fatty acids and antioxidants, are also explored.</div><div>Mechanistic insights cover tear film instability, inflammatory pathways, neuropathic pain, and meibomian gland dysfunction, emphasizing recent findings on the ocular surface microbiome, genetic and epigenetic factors, and chronic inflammation. Diagnostic innovations include AI and machine learning integration, advanced imaging techniques, tear film analysis, and functional tests, enhancing early detection and monitoring.</div><div>Emerging research on gene therapy, stem cell therapy, ocular surface microbiota, and gene editing technologies like CRISPR is examined for future treatment potential. Personalized medicine approaches, incorporating genomic and proteomic profiling and patient-reported outcomes, are emphasized for tailored therapies.</div><div>Environmental and lifestyle factors, including pollution, climate change, diet, and behavioral modifications, are considered for their impact on DED management. Integrating these advancements into clinical practice aims to improve patient outcomes and quality of life, highlighting the future potential of cutting-edge research and innovations.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100090"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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