Aspects of molecular medicine最新文献

{"title":"Potential antimicrobial properties of cytosine β-D-riboside derivatives through molecular dynamics and molecular docking exploration with bacterial and fungal proteins","authors":"Sarkar M.A. Kawsar , Rahnuma Tabassum , Nasrin Sultana Munia , Suraj N. Mali , Chin-Hung Lai , Jannatul Ferdous , Ferdausi Ali","doi":"10.1016/j.amolm.2025.100077","DOIUrl":"10.1016/j.amolm.2025.100077","url":null,"abstract":"<div><div>Nucleoside derivatives have contributed to the clinical and pharmaceutical fields as medicinal agents and approved drugs. The reaction of lauroyl chloride with cytosine β-D-riboside, i.e., cytidine (<strong>1</strong>) in DMF/Et<sub>3</sub>N, was the initiator step leading to 5′-<em>O</em>-(lauroyl)cytidine (<strong>2</strong>). Compound (<strong>2</strong>) was reacted with various acylating agents and penetrated to give 2′,3′-di-<em>O</em>-acyl derivatives (<strong>3</strong>–<strong>6</strong>). Physicochemical, spectroscopical, and elemental analysis methods were used to confirm the structure of the synthesized derivatives. <em>In vitro</em> antimicrobial tests, coupled with PASS prediction, revealed that these derivatives are highly effective against distinct pathogenic bacteria. Compared with the standard nystatin, compound <strong>5</strong> exhibited excellent antifungal efficacy against <em>Aspergillus flavus</em> and <em>Aspergillus niger</em>. Molecular docking analysis was performed to evaluate the binding interactions with the FimH lectin domain from <em>E. coli</em> K12 and urate oxidase (Uox) from <em>Aspergillus flavus</em>. For the FimH lectin domain, the binding affinities range from −2.35 to −9.32 kcal/mol (PyRx) and from −0.764 to 115.318 kcal/mol (iGEMDOCK), where compound <strong>2</strong> exhibited the highest binding affinity and outperformed the standard azithromycin, forming hydrogen bonds with ASN A:138, GLN A:133, ASP A:54, ASN A:46, PHE A:1, and ASP A:47, along with Pi-alkyl interactions with TYR A:48. Similarly, compound <strong>5</strong>, among the other synthesized compounds, strongly bound to Uox, with docking scores of −8.65 kcal/mol (PyRx) and −119.145 kcal/mol (iGEMDOCK), interacting with key residues such as THR A:173, LEU A:170, PHE A:258, and HIS A:256 through van der Waals forces, Pi‒Pi hydrophobic interactions, and hydrogen bonding. The RMSD, RMSF, and Rg analyses revealed that the docked complexes 4XO8:<strong>2</strong> and 1R4U:<strong>5</strong> exhibited stable protein‒ligand interactions, with no significant structural deviations observed during the 100 ns MD simulations. The hydrogen bonding and SASA results further support the stability of these complexes. According to DFT and FMO studies, compound <strong>5</strong> should exhibit the highest chemical reactivity because it has the smallest Egap (4.84 eV). In silico, ADMET and toxicity studies were used to evaluate the pharmacokinetic characteristics, drug-likeness, and toxicity parameters of the newly synthesized compounds. Finally, SAR study was performed to predict any subsequent changes in the antimicrobial activities of these compounds modified at various positions in their structure, especially those modified with [CH<sub>3</sub>(CH<sub>2</sub>)<sub>10</sub>CO] and {CH<sub>3</sub>(CH<sub>2</sub>)<sub>14</sub>CO}] groups. These results suggest that derivatives of lauroyl cytidine have great promise as antimicrobial agents for treat","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100077"},"PeriodicalIF":0.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143704154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibacterial potential of Trichoderma bioactive metabolites in managing Staphylococcus aureus infection: Integrated molecular modeling approaches","authors":"Gourav Choudhir ,&nbsp;Israil ,&nbsp;Faiza Iram ,&nbsp;Mohammad Shahid ,&nbsp;Anas Shamsi ,&nbsp;Md. Imtaiyaz Hassan ,&nbsp;Asimul Islam","doi":"10.1016/j.amolm.2025.100076","DOIUrl":"10.1016/j.amolm.2025.100076","url":null,"abstract":"<div><div><em>Staphylococcus aureus</em> is a primary hospital-acquired infection-causing bacteria that is becoming resistant to many antibiotics. Its infection sites <em>r</em>ange from skin to soft tissue. The development of drugs for managing <em>Staphylococcus aureus</em> infection is urgently required. Targeting the enzymes involved in bacteria maintaining the integrity of cell walls could provide advances compared to other targets. Integrating molecular modeling approaches with drug-likeness properties identified the metabolites with affinity and safety to use. Molecular docking results showed that three metabolites with promising binding affinities to FmtA and interactions with the vital amino acid residues are essential in catalytic activity. The drug likeliness analysis showed that selected metabolites do not have any violations of Lipinski rules. A molecular dynamics simulation study revealed that metabolites, bisorbibutenolide and Koninginin A, exhibited the most stable complexes with FmtA. Bisorbibutenolide and Koninginin A also formed hydrogen bonds with FmtA throughout the simulation. These findings suggest that bisorbibutenolide and Koninginin A have the potential for further development as an anti-<em>Staphylococcus aureus</em> agent via targeting FmtA. Moreover, comprehensive experimental studies are necessary to validate these computational findings.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100076"},"PeriodicalIF":0.0,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143686911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling potential antiviral phytochemicals from Molineria capitulata (Lour.) Herb. against varicella-zoster virus: Ethnomedicinal insights and computational analysis","authors":"Md. Nur Kabidul Azam ,&nbsp;Md Nasir Ahmed ,&nbsp;Partha Biswas ,&nbsp;Amia Kandker ,&nbsp;Md. Mohaimenul Islam Tareq ,&nbsp;Labib Shahriar Siam ,&nbsp;Md. Nazmul Hasan","doi":"10.1016/j.amolm.2025.100074","DOIUrl":"10.1016/j.amolm.2025.100074","url":null,"abstract":"<div><div>Varicella-Zoster Virus (VZV), causing chickenpox and potentially severe later-life complications, is traditionally treated by the Musahar tribe in Bangladesh using <em>Molineria capitulata</em> in a polyherbal formulation. This plant is also recognized in other regions for its anti-infective properties. This study aimed to evaluate the ethnomedicinal efficacy of <em>Molineria capitulata</em> against VZV using computational drug development approaches and to review its traditional medicinal uses. An ethnomedicinal survey was conducted, followed by QSAR, molecular docking, molecular dynamics simulation, ADMET and MM-GBSA analysis to assess potential treatments for VZV. Literature searches on PubMed and Google Scholar provided additional insights into the traditional antimicrobial uses of the plant. Twenty-four phytochemicals were screened against VZV thymidine kinase, revealing three with significant binding affinity (less than −10 kcal/mol): capituloside, curcapital, and pilosidine. These compounds showed strong protein interactions and stability in 100 ns simulations. Pilosidine had the highest docking score (−12.471 kcal/mol), followed by capituloside (−12.213 kcal/mol) and curcapital (−11.360 kcal/mol). Valacyclovir, the control, had a lower score (−5.807 kcal/mol). Pharmacokinetic profiles and QSAR analysis indicated their potential as lead compounds. Capituloside and pilosidine were effective against Herpes, Influenza, and Hepatitis B, while curcapital was effective against CMV, Herpes, Influenza, and Adenovirus. The physicochemical properties of these compounds highlight their significant potential as antiviral agents. The MM-GBSA evaluation indicated that among the complexes, the pilosidine-protein complex had the greatest free binding energy, with a value of −67.15 kcal/mol. <em>Molineria capitulata</em> holds promise for antiviral therapy development, and validating the therapeutic potential of capituloside, curcapital, and pilosidine against varicella-zoster virus requires comprehensive in-vitro and in-vivo studies.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100074"},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143686912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Personalized approaches to lung cancer treatment: A review of targeted therapies, pharmacogenomics, and combination strategies","authors":"Namini M,&nbsp;Bhagya G,&nbsp;Manjari Sharma","doi":"10.1016/j.amolm.2025.100073","DOIUrl":"10.1016/j.amolm.2025.100073","url":null,"abstract":"<div><div>Globally, lung cancer—more specifically, non-small cell lung cancer (NSCLC)—contributes significantly to the death toll from cancer. Recent advances in molecular research have identified key genetic mutations that drive tumor growth, including those in the EGFR, KRAS, ALK, and MET genes, accounting for around 80 % of lung cancers that are categorized as non-small cell lung cancer (NSCLC). The advent of targeted therapies such as Tyrosine kinase inhibitors (TKIs) and monoclonal antibodies, have revolutionized cancer treatment by specifically inhibiting oncogenic pathway. However, despite this advancements, treatment outcomes remain suboptimal due to intrinsic heterogeneity of cancers and the development of resistance mechanisms. The cancer treatment landscape is constantly changing to address these challenges and improve patient outcomes. Customization of cancer therapies through pharmacogenomics is hindered by tumor adapatability and resistance, limited prognostic biomarkers and suboptimal monotherapies, necessitating innovative research in adoptive therapies biomarker development and combination therapies. Ongoing trails aims to enhance treatment endurance via the advancement of combination regimens incorporating multiple targeted therapies or synergistic combination immunotherapy with chemotherapy. Ongoing research is focused on optimizing CRISPR-Cas9 delivery system, improving specificity and minimizing half target effect. Emphasizes the crucial role of molecular mutations, the advantages and disadvantages of targeted medicines, and the prospects for enhancing the effectiveness of lung cancer treatment results are all highlighted in this Review.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100073"},"PeriodicalIF":0.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143686910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of ultra-processed foods on cardiovascular diseases and cancer: Epidemiological and mechanistic insights","authors":"Olorunfemi Oyewole Babalola ,&nbsp;Ebenezer Akinnusi ,&nbsp;Paul Olamide Ottu ,&nbsp;Kpomah Bridget ,&nbsp;Godspower Oyubu ,&nbsp;Samuel Ayomikun Ajiboye ,&nbsp;Sakariyau Adio Waheed ,&nbsp;Amafili Chibuzo Collette ,&nbsp;Hameedah Oluwatoyin Adebimpe ,&nbsp;Chibuzo Valentine Nwokafor ,&nbsp;Ebenezer Ayomide Oni ,&nbsp;Precious Olayinka Aturamu ,&nbsp;Opeyemi Iwaloye","doi":"10.1016/j.amolm.2025.100072","DOIUrl":"10.1016/j.amolm.2025.100072","url":null,"abstract":"<div><div>Ultra-processed foods (UPFs) are increasingly recognized as contributors to the pathogenesis of cardiovascular diseases (CVDs) and cancer due to their adverse compositional and mechanistic effects. UPFs, distinguished by their high content of unhealthy fats, sodium, refined sugars, and synthetic additives, significantly increase dyslipidemia, hypertension, and obesity, which are key risk factors for CVDs. Chronic consumption leads to systemic inflammation, gut microbiota dysbiosis, endothelial dysfunction, and oxidative stress. Additives such as artificial sweeteners and sodium nitrites in UPFs are associated with carcinogenesis through mechanisms involving genotoxicity and promotion of inflammatory microenvironments. This review critically evaluates existing epidemiological, mechanistic, and clinical evidence linking UPFs consumption to CVDs and cancer, synthesizing insights into their underlying pathophysiological mechanisms and highlighting disparities in disease burden across diverse populations. Epidemiological evidence demonstrates that UPFs constitute over 50% of daily caloric intake in Western diets, with each 10% increase in UPF consumption associated with a 12% rise in CVDs risk and a comparable increase in cancer incidence. Addressing the global surge in UPF consumption through dietary guidelines, regulatory policies, and public health initiatives may mitigate these risks, improve metabolic and cardiovascular health, and reduce cancer prevalence.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100072"},"PeriodicalIF":0.0,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143600515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational framework for analyzing miRNA-mRNA interactions in sarcopenia: Insights into age-related muscular degeneration","authors":"Sarvesh Sabarathinam ,&nbsp;Akash Jayaraman ,&nbsp;Ramesh Venkatachalapathy ,&nbsp;Subhiksha Shekar","doi":"10.1016/j.amolm.2025.100070","DOIUrl":"10.1016/j.amolm.2025.100070","url":null,"abstract":"<div><h3>Background</h3><div>Sarcopenia, an age-related loss of skeletal muscle mass and function, impairs mobility, fragility, and quality of life. Despite progress in pathophysiology, molecular processes remain unknown. Recent research has investigated miRNAs as biomarkers for sarcopenia diagnosis and therapy. This work analyses differentially expressed genes (DEGs) and predicts miRNA-mRNA interactions using ML methods like XG-Boost and SHAP to find biomarkers.</div></div><div><h3>Objective</h3><div>This work evaluated the function of miRNA-mRNA interactions in sarcopenia pathogenesis and identified possible biomarkers by transcriptome analysis utilizing machine learning.</div></div><div><h3>Methods</h3><div>High-throughput mRNA sequencing datasets (GSE111006, GSE111010, and GSE111016) from GEO database were combined, pre-processed, and normalized using TPM and DESeq2 methods. XG-Boost regression analysis used 80/20 training and testing sets. SHAP analysis was used to evaluate model data and find significant DEGs. PPI networks were created using the STRING database, while miRNA-mRNA interactions were predicted using Encori and displayed with Cytoscape. The degree scores of miRNA-mRNA interactions were utilized to find biomarkers<strong>.</strong></div></div><div><h3>Results</h3><div>XG-Boost and SHAP analysis revealed 20 influential DEGs linked to sarcopenia. With 97% accuracy, the model predicted accurately. PPI network research identified six hub genes: NTRK2, PCK1, DSP, SCD, MMRN1, and EDIL3. MiRNA-mRNA interaction analysis found miR-186–5p as the highest-degree biomarker candidate (36). MiR-186–5p was linked to muscle metabolism, hypertrophy, and exercise response.</div></div><div><h3>Conclusion</h3><div>The study found miR-186–5p to be a promising biomarker for sarcopenia using an integrated machine learning technique. The findings show that miR-186–5p may be a diagnostic and therapeutic target for sarcopenia, revealing its pathogenesis and enabling tailored treatments. Experimental research is needed to prove its therapeutic value.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100070"},"PeriodicalIF":0.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143594037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kinetoplastid diseases: Insights into the mechanisms of drug action and resistance for novel drug discovery","authors":"Abdullah M. Tauheed ,&nbsp;Ammar U. Danazumi ,&nbsp;Oluwafemi A. Adepoju ,&nbsp;Patricia I. Kobo ,&nbsp;Auwal Adamu ,&nbsp;Emmanuel O. Balogun","doi":"10.1016/j.amolm.2025.100071","DOIUrl":"10.1016/j.amolm.2025.100071","url":null,"abstract":"<div><div><em>Trypanosoma</em> and <em>Leishmania</em> species are kinetoplastid protozoan parasites that cause diseases which result in significant disability-adjusted life years (DALYs) and agricultural losses in the developing world. Despite the progress recorded in understanding biology and chemotherapy of these pathogens of neglected diseases, treatment failure, due to drug resistance or toxicity-driven non-compliance remain major challenges. Advances in molecular parasitology have led to the identification of specific transport mechanisms, druggable targets and persister-like cells, which play distinct roles in the overall success of therapies. Transporters and other cellular transport mechanisms affect the internalisation of drugs and their intracellular availability which determine drug activity. Thus, we reviewed kinetoplastid drug transport mechanisms, molecular drug targets and persisters to highlight mechanisms of action and development of resistance for antikinetoplastid drugs, with the aim of providing novel insights for drug discovery programmes.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100071"},"PeriodicalIF":0.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel combination therapy of osimertinib and Tupichinol E in triple-negative breast cancer: Targeting EGFR and CDK4/6 pathways","authors":"Adyasa Samantaray,&nbsp;Debasish Pradhan","doi":"10.1016/j.amolm.2025.100069","DOIUrl":"10.1016/j.amolm.2025.100069","url":null,"abstract":"<div><div>Triple-Negative Breast Cancer (TNBC) is one of the most challenging form of breast cancer that lacks hormone receptors and HER2, limiting targeted treatment options. While a third-generation EGFR inhibitor, Osimertinib, has shown efficacy in various cancers, its role in TNBC is not well established. On the other hand, <em>Tupichinol E</em>, a novel compound, has shown promising anticancer potential in preclinical studies. This study investigates the combined effects of Osimertinib and <em>Tupichinol E</em> on TNBC cell lines, revealing a synergistic reduction in cell viability, increased apoptosis, and cell cycle arrest compared to individual treatments. Furthermore, cyclin-dependent kinases 4 and 6 (CDK4/6), important cell cycle regulators, are essential in transitioning cells from the G1 to S phase via retinoblastoma protein (RB) phosphorylation. Dysregulation of the CDK4/6-RB pathway is a hallmark in many cancers, including hormone receptor-positive breast cancers, and has become a focus of targeted therapies. Our findings not only emphasizes the therapeutic potential of combining Osimertinib with <em>Tupichinol E</em> in TNBC but also underscore the importance of CDK4/6 inhibitors in modulating cell cycle progression, offering a promising avenue for combination therapies in TNBC treatment.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100069"},"PeriodicalIF":0.0,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143518947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of Irisin in modulating hypoxia-related disorders: New insights and implications for cancer therapy","authors":"Ghazaleh Khalili-Tanha ,&nbsp;Alireza Shoari ,&nbsp;Elham Nazari","doi":"10.1016/j.amolm.2025.100068","DOIUrl":"10.1016/j.amolm.2025.100068","url":null,"abstract":"<div><div>Regular physical activity is well-known for its health benefits, including reducing the risk of chronic diseases like cancer. Irisin, a myokine released by skeletal muscles during exercise, has emerged as a key regulator in hypoxia-related disorders.Hypoxia, defined by reduced oxygen availability, is a hallmark of various pathological conditions, especially cancer, where it drives tumor growth, metastasis, and resistance to therapy. Recent studies suggest that irisin can modulate hypoxia-induced pathways, impacting processes such as angiogenesis, inflammation, and metabolic adaptation. By targeting these mechanisms, irisin may enhance the efficacy of cancer treatments, reduce tumor aggressiveness, and potentially overcome therapy resistance. Additionally, irisin's influence on the tumor microenvironment highlights its potential as a therapeutic agent to counteract hypoxia-driven cancer progression. This review summarizes current findings on irisin's role in hypoxia-related disorders, focusing on its molecular mechanisms and potential applications in oncology. Despite promising preclinical studies, further research is necessary to fully understand irisin's therapeutic potential, optimize delivery methods, and validate its safety and efficacy in clinical settings. Exploiting exercise-derived molecules such as irisin may enable novel strategies for cancer treatment and other hypoxia-related diseases.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100068"},"PeriodicalIF":0.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of pathogenic genetic variants associated with familial hypercholesterolemia in Ghanaian children","authors":"Philip Opoku-Agyeman ,&nbsp;Prince Ameyaw ,&nbsp;Selassie Bruku ,&nbsp;Gideon Ofori Addo ,&nbsp;Gideon Tetteh ,&nbsp;Esther Baafi ,&nbsp;Sandra Korkor Asare ,&nbsp;Abigail Foriwaah Frimpong ,&nbsp;Samuel Adu-Poku ,&nbsp;Sena Adzoa Matrevi ,&nbsp;Nancy Odurowah Duah-Quashie ,&nbsp;Kwesi Z. Tandoh","doi":"10.1016/j.amolm.2025.100067","DOIUrl":"10.1016/j.amolm.2025.100067","url":null,"abstract":"<div><div>Familial hypercholesterolemia (FH) is an important contributor to atherosclerotic cardiovascular disease (ASCVD) burden globally. FH disrupts cholesterol metabolism and causes lifelong elevation in low-density lipoprotein cholesterol (LDL-C). In sub-Saharan Africa (SSA), the increasing burden of ASCVD may be partly driven by genetic dyslipidemias of which FH is the commonest. However, there is absence of data on FH prevalence in SSA which delineates an important gap in the management of ASCVD. This study is the first to investigate the prevalence of pathogenic variants associated with FH in Ghana. We used 96 deidentified archived dried blood spot samples collected from a Ghanaian cohort, to determine the prevalence of pathogenic genetic variants associated with FH. These samples were collected from children under 9 years old as part of surveillance for antimalarial drug resistance in 2021. We searched the NCBI's ClinVar database and used <em>in silico</em> tools to identify 500–800 nucleotide base pair regions of interest in 3 genes known to harbor the commonest genetic variants associated with FH. We selected these regions of interest from the <em>LDLR</em> gene exons 4, 9 and 10, <em>APOB</em> exon 26 and <em>PCSK9</em> exon 2 loci. Next, we amplified these regions of interest using conventional polymerase chain reaction. Finally, we sequenced the amplicons using paired-end Sanger sequencing and called variants from the chromatogram files using an in-house custom built bash script utilizing the open access program Tracy. Subsequently, we did quality checks on all reported pathogenic variant calls manually using Benchling's sequence alignment tool. We identified one pathogenic variant V523 M in the <em>LDLR</em> exon 10 region and report an FH prevalence of 1% (1/96), 95% CI: [0%,3.07%], in our Ghanaian cohort. Our finding underscores the importance of FH in driving ASCVD burden in Ghana and advocates the need for implementation science-driven programs to manage this genetic dyslipidemia in Ghana and SSA.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100067"},"PeriodicalIF":0.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143465138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}