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Novel combination therapy of osimertinib and Tupichinol E in triple-negative breast cancer: Targeting EGFR and CDK4/6 pathways
Aspects of molecular medicine Pub Date : 2025-02-22 DOI: 10.1016/j.amolm.2025.100069
Adyasa Samantaray, Debasish Pradhan
{"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}
引用次数: 0
The role of Irisin in modulating hypoxia-related disorders: New insights and implications for cancer therapy
Aspects of molecular medicine Pub Date : 2025-02-21 DOI: 10.1016/j.amolm.2025.100068
Ghazaleh Khalili-Tanha , Alireza Shoari , Elham Nazari
{"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}
引用次数: 0
Prevalence of pathogenic genetic variants associated with familial hypercholesterolemia in Ghanaian children
Aspects of molecular medicine Pub Date : 2025-02-20 DOI: 10.1016/j.amolm.2025.100067
Philip Opoku-Agyeman , Prince Ameyaw , Selassie Bruku , Gideon Ofori Addo , Gideon Tetteh , Esther Baafi , Sandra Korkor Asare , Abigail Foriwaah Frimpong , Samuel Adu-Poku , Sena Adzoa Matrevi , Nancy Odurowah Duah-Quashie , Kwesi Z. Tandoh
{"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}
引用次数: 0
Molecular approaches based on investigating the therapeutic benefits of Moringa oleifera: Insights into biochemical and spermatological and metabolites studies
Aspects of molecular medicine Pub Date : 2025-02-16 DOI: 10.1016/j.amolm.2025.100065
Sudha Sankar , Subramaniam Umavathi , Ekambaram Gayathiri , Palanisamy Prakash
{"title":"Molecular approaches based on investigating the therapeutic benefits of Moringa oleifera: Insights into biochemical and spermatological and metabolites studies","authors":"Sudha Sankar ,&nbsp;Subramaniam Umavathi ,&nbsp;Ekambaram Gayathiri ,&nbsp;Palanisamy Prakash","doi":"10.1016/j.amolm.2025.100065","DOIUrl":"10.1016/j.amolm.2025.100065","url":null,"abstract":"<div><div>This study aimed to investigate the potential of Moringa oleifera extract, an herbal treatment known to support male reproductive function, in improving sperm motility. Adult male guinea pigs were divided into four groups (n = 5 per group). Group 1 served as the control, while Group 2 was induced with subfertility using Carbendazim. Group 3 consisted of subfertile guinea pigs treated with <em>Moringa oleifera</em> extract, and Group 4 included subfertile guinea pigs treated with clomiphene citrate. Sperm motility parameters, including sperm counts (sperm/ml), rapid and progressive motility (sperm/ml), and sperm agglutination (%), were assessed using standard methods. In control group, guinea pigs exhibited significantly higher sperm counts (44.0 ± 0.89 x 10^6 sperm/ml) and sperm motility (57.6 ± 1.45 x 10^6 sperm/ml, rapid, progressive) compared to the Carbendazim-induced subfertile group (p &lt; 0.05). Conversely, the subfertile group displayed significantly higher sperm agglutination (30 ± 1.26%) than the control group (p &lt; 0.05). Treatment with <em>Moringa oleifera</em> L extract and clomiphene citrate resulted in improved sperm motility parameters, with both groups showing higher sperm counts and rapid, progressive motility, and lower sperm agglutination compared to the sub-fertile group. These findings suggest that Moringa oleifera extract may enhance sperm motility in male guinea pigs with carbendazim-induced subfertility, positioning herbal remedies as potential alternatives for treating male infertility. Furthermore, the study highlights the potential of Moringa oleifera as a therapeutic agent for male infertility by demonstrating its effectiveness in improving sperm motility and reducing sperm agglutination. These results underscore the importance of exploring herbal remedies as safer, natural alternatives to conventional treatments for addressing the subfertility issue. Further research is needed to discover the underlying molecular mechanisms and assess the clinical significance of these outcomes in the context of human male fertility.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100065"},"PeriodicalIF":0.0,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534436","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}
引用次数: 0
Chalcone-related small molecules as potent antibacterial and antifungal agents: Design, synthesis, In vitro, and computational approaches
Aspects of molecular medicine Pub Date : 2025-02-15 DOI: 10.1016/j.amolm.2025.100066
Narmin Hamaamin Hussen , Larin Barzan Hussein , Aso Hameed Hasan , Shokhan Jamal Hamid , Chawan Othman Abdl , Bakhcha Sarkar , Kozhin Muhammed , Daroon Muhamad
{"title":"Chalcone-related small molecules as potent antibacterial and antifungal agents: Design, synthesis, In vitro, and computational approaches","authors":"Narmin Hamaamin Hussen ,&nbsp;Larin Barzan Hussein ,&nbsp;Aso Hameed Hasan ,&nbsp;Shokhan Jamal Hamid ,&nbsp;Chawan Othman Abdl ,&nbsp;Bakhcha Sarkar ,&nbsp;Kozhin Muhammed ,&nbsp;Daroon Muhamad","doi":"10.1016/j.amolm.2025.100066","DOIUrl":"10.1016/j.amolm.2025.100066","url":null,"abstract":"<div><div>Infectious diseases caused by bacteria and fungi are a global health concern due to resistance to traditional antimicrobial medications. A variety of chalcone-related small molecules have been designed, synthesized, and characterized small molecules using FTIR, NMR, and MS to find antimicrobial agents for treating these infections. These designed compounds (<strong>9, 11, 13</strong>) were evaluated for their potential inhibitory activity against five bacterial strains and one fungal strain using disc diffusion and MIC assays utilizing ampicillin and fluconazole as reference drugs. The MIC values ranged from 2.5 to 160 μg/mL, which can be attributed to improved membrane penetration and increased ligand-protein binding capability. Among them, molecule 9 exhibited a broad spectrum of antibacterial activity against gram-negative bacteria, with an MICs of 40 μg/mL against <em>P. aeruginosa</em> and 80 μg/mL against <em>E. coli</em>. Compound <strong>11</strong> showed potent activity against gram-positive bacteria and fungi, with a MICs of 40 μg/mL against <em>S. aureus</em> and 80 μg/mL against <em>C. albicans</em>. Furthermore, similar to <em>in vitro</em> study results, molecular docking demonstrated that compounds <strong>9</strong> and <strong>11</strong> had a better binding affinity against gram-positive and gram-negative bacteria and fungal species than reference drugs. Finally, physicochemical and drug-likeness results showed that all the compounds can pass Lipinski's rule of five, are absorbed through the GIT, and are suitable for oral administration.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100066"},"PeriodicalIF":0.0,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437554","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}
引用次数: 0
In vitro and in silico Anti-diabetes mechanism of phytochemicals from Curculigo pilosa and its pharmacokinetic profiling via α-amylase inhibition
Aspects of molecular medicine Pub Date : 2025-01-31 DOI: 10.1016/j.amolm.2025.100064
Damilola A. Omoboyowa , Temitope C. Aribigbola , Simbo T. Akinsulure , Damilola S. Bodun , Ezekiel A. Olugbogi , Ebenezer A. Oni
{"title":"In vitro and in silico Anti-diabetes mechanism of phytochemicals from Curculigo pilosa and its pharmacokinetic profiling via α-amylase inhibition","authors":"Damilola A. Omoboyowa ,&nbsp;Temitope C. Aribigbola ,&nbsp;Simbo T. Akinsulure ,&nbsp;Damilola S. Bodun ,&nbsp;Ezekiel A. Olugbogi ,&nbsp;Ebenezer A. Oni","doi":"10.1016/j.amolm.2025.100064","DOIUrl":"10.1016/j.amolm.2025.100064","url":null,"abstract":"<div><div>Diabetes mellitus is characterized by elevated blood glucose resulting from carbohydrate metabolism via glucose metabolizing enzymes such as α-amylase. <em>Curculigo pilosa</em> is traditionally used as herbal medication as anti-diabetes therapy but its mechanism of action is yet to be explored. This study investigates α-amylase inhibitory potential of <em>C. pilosa</em> using in vitro and in silico approaches. The ethylacetate, n-butanol and methanol extracts of <em>C. pilosa</em> were subjected to in vitro α-amylase inhibitory assay, followed by identification of the bioactive compounds from the most potent extract using HPLC. Integrated computational analyses were performed on ten (10) active compounds against α-amylase using Maestro Schrodinger (v2). The results of the in vitro α–amylase assay revealed n-butanol extract as the potent extract with IC<sub>50</sub> of 132.70 μg/mL, although the standard drug (acarbose IC<sub>50</sub> = 128.70 μg/mL) inhibits α-amylase better than the extracts. The HPLC result revealed the presence of ten (10) active compounds. Acarbose was observed to possess better binding affinity (−11.502 kcal/mol) than all the compounds but curculigoside was the hit compound with binding affinity of −8.797 kcal/mol. Some of the compounds showed appreciable inhibitory pIC<sub>50</sub> and fitness scores comparable to the standard drug. The pharmacokinetic profile revealed that none of the compounds violated more than one Lipinski's rule of five while the standard drug (acarbose) violated three (3) of the rules. The root mean square deviation shows reasonable level of stability within the simulation period for both curculigoside and acarbose. The result of in silico study showed significant inhibitory potential of the active compounds against α-amylase which was consistent with the in vitro inhibition of α amylase by the plant extract suggesting this as the possible mechanism of antidiabetes action of <em>C. pilosa</em>.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100064"},"PeriodicalIF":0.0,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143146624","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}
引用次数: 0
Stimuli-responsive supramolecular hydrogels for paclitaxel delivery: Progress and prospects
Aspects of molecular medicine Pub Date : 2025-01-04 DOI: 10.1016/j.amolm.2024.100062
Mohammad Qutub , Amol Tatode , Jayshree Taksande , Tanvi Premchandani , Milind Umekar , Ujban Md Hussain , Dinesh Biyani , Dadaso Mane
{"title":"Stimuli-responsive supramolecular hydrogels for paclitaxel delivery: Progress and prospects","authors":"Mohammad Qutub ,&nbsp;Amol Tatode ,&nbsp;Jayshree Taksande ,&nbsp;Tanvi Premchandani ,&nbsp;Milind Umekar ,&nbsp;Ujban Md Hussain ,&nbsp;Dinesh Biyani ,&nbsp;Dadaso Mane","doi":"10.1016/j.amolm.2024.100062","DOIUrl":"10.1016/j.amolm.2024.100062","url":null,"abstract":"<div><div>Cancer remains a leading cause of death worldwide, while chemotherapy playing a pivotal role in its management. However, traditional chemotherapy often encounters challenges such as non-specific drug delivery, systemic toxicity, and rapid clearance. Thermosensitive supramolecular hydrogels have emerged as an innovative platform for localized and sustained drug delivery, particularly for paclitaxel (PTX), a potent chemotherapeutic agent. These hydrogels exhibit unique sol-gel phase transitions at physiological temperatures, enabling minimally invasive administration and prolonged retention at tumor sites. Advances in hydrogel formulations, including dual stimuli-responsive systems and nanocrystal-loaded designs, enhance drug stability, controlled release, and therapeutic efficacy. Additionally, these hydrogels can incorporate multimodal therapeutic agents, such as immunomodulators and photosensitizers, achieving synergistic anticancer effects. Despite significant progress, challenges remain in optimizing tumor penetration, scaling production, and addressing tumor heterogeneity. Ongoing research into hydrogel composition, biocompatibility, and targeted delivery mechanisms aims to overcome these limitations, paving the way for their clinical translation. This review highlights recent advancements and future prospects of thermosensitive hydrogels for PTX delivery, emphasizing their potential to revolutionize cancer treatment by reducing systemic toxicity and improving localized therapeutic outcomes.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100062"},"PeriodicalIF":0.0,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143146631","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}
引用次数: 0
Role of antioxidants in skin aging and the molecular mechanism of ROS: A comprehensive review
Aspects of molecular medicine Pub Date : 2025-01-04 DOI: 10.1016/j.amolm.2025.100063
Narmin Hama amin Hussen , Sakar Karem Abdulla , Naza Mohammed Ali , Van Abdulqader Ahmed , Aso Hameed Hasan , Eman Erfan Qadir
{"title":"Role of antioxidants in skin aging and the molecular mechanism of ROS: A comprehensive review","authors":"Narmin Hama amin Hussen ,&nbsp;Sakar Karem Abdulla ,&nbsp;Naza Mohammed Ali ,&nbsp;Van Abdulqader Ahmed ,&nbsp;Aso Hameed Hasan ,&nbsp;Eman Erfan Qadir","doi":"10.1016/j.amolm.2025.100063","DOIUrl":"10.1016/j.amolm.2025.100063","url":null,"abstract":"<div><div>Skin aging is a multifaceted and gradual process influenced by both internal and external factors, including environmental stressors. These two mechanisms contribute to oxidative stress, triggered by ROS, which accelerates the aging of the skin. UV exposure increases the production of ROS in cells, which collectively contribute to the various skin changes linked to aging. However, the skin has a sophisticated antioxidant defense system that shields it from oxidative damage caused by both internal and external factors. The use of topical antioxidants have been shown to shield the skin from harmful free radicals generated intrinsically by regular cellular metabolism or as a result of UV light exposure. This review focuses on the assessment of the injury environmental factors cause to the skin, molecular mechanism of ROS in the skin aging, and the use of antioxidants to prevent that damaging and producing a protection against UV radiation from environmental factors. The systematic search was done for eligible articles which including in vivo and in vitro studies from studies between (1997 until 2024).</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100063"},"PeriodicalIF":0.0,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143146629","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}
引用次数: 0
Extracellular vesicles in thalassemia: Mechanisms, implications, and therapeutic potential
Aspects of molecular medicine Pub Date : 2024-12-30 DOI: 10.1016/j.amolm.2024.100061
Shahzad Ali Jiskani
{"title":"Extracellular vesicles in thalassemia: Mechanisms, implications, and therapeutic potential","authors":"Shahzad Ali Jiskani","doi":"10.1016/j.amolm.2024.100061","DOIUrl":"10.1016/j.amolm.2024.100061","url":null,"abstract":"<div><div>Thalassemia is one of the most common inherited disorders of erythrocytes, caused by abnormalities in the production of globin chains. The clinical spectrum of thalassemia is broad, ranging from severe and persistent anemia that necessitates consistent blood transfusions to mild, asymptomatic conditions. Key contributors to thalassemia complications, particularly, in patients with β-thalassemia major, are ineffective erythropoiesis and iron overload. These complications can lead to a variety of severe health issues, including chronic inflammation, organ dysfunction, thrombosis, vascular abnormalities, and systemic iron overload. Extracellular vesicles (EVs) are tiny membrane-bound particles secreted from the plasma membranes of various cells during activation and cell death. Research has indicated that EVs are involved in numerous physiological and pathological processes, including inflammatory responses, clot formation, and vascular injury. Recently, the role of EVs has garnered interest of their potential as biomarkers, providing diagnostic and prognostic value of various disorders. In the context of thalassemia, elevated levels of EVs have been observed, highlighting their significance in the disease's cellular activities. The current review aims to examine the role of EVs in the pathogenesis of thalassemia, their implications, and their potential clinical applications. By exploring the involvement of EVs in the inflammatory and vascular complications associated with thalassemia, this review provides insights into their potential as therapeutic targets and diagnostic tools, offering a new perspective on managing this complex and multifaceted disorder.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100061"},"PeriodicalIF":0.0,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143146630","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}
引用次数: 0
Unveiling the molecular mechanisms and clinical implications of maslinic acid in diabetes mellitus: Insights from network pharmacology
Aspects of molecular medicine Pub Date : 2024-12-10 DOI: 10.1016/j.amolm.2024.100060
Sarvesh Sabarathinam , Sanjana Satheesh
{"title":"Unveiling the molecular mechanisms and clinical implications of maslinic acid in diabetes mellitus: Insights from network pharmacology","authors":"Sarvesh Sabarathinam ,&nbsp;Sanjana Satheesh","doi":"10.1016/j.amolm.2024.100060","DOIUrl":"10.1016/j.amolm.2024.100060","url":null,"abstract":"<div><div>Maslinic acid(MA), a natural pentacyclic triterpene, has potent anti-tumor activity and exerts effects by various mechanisms, including apoptosis, cell cycle arrest, autophagy regulation, and angiogenesis alteration. We investigated the Network pharmacology and Molecular docking analysis of Maslinic Acid The network pharmacology report shows that 23 overlapping targets were identified with Maslinic Acid. Followed by the binding scores were found to be similar to the reference standard Rosiglitazone &amp; Pioglitazone. Maslinic Acid exerts its effect on insulin resistance via inhibition of peroxisome proliferator-activated receptor, α-amylase, and α-glucosidase inhibition, glycogen phosphorylase inhibition, reduction in ghrelin concentration, downregulation of SGLT1 and GLUT2 genes, NF-κB suppression, Nrf2 activation, and AMPK/SIRT 1 pathway activation. The Network analysis and docking score confirm the diabetic activity of Maslinic Acid. This study aims to study various targets of Maslinic Acid in correlation to Diabetes mellitus and analyze their mechanism in detail. Our investigation of MA as a potential treatment target for insulin resistance or diabetes mellitus using network pharmacology revealed that it has significant roles in producing glucose-lowering activity by regulating glucose homeostasis via several insulin signaling pathways discussed above.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100060"},"PeriodicalIF":0.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143146628","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}
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