Aspects of molecular medicine最新文献

{"title":"Linkage and association of rs3110045 and rs28499085 variants in the thyrotropin-releasing hormone receptor (TRHR) gene with the risk of familial type 2 diabetes","authors":"Rongling Wu ,&nbsp;Claudia Gragnoli","doi":"10.1016/j.amolm.2024.100037","DOIUrl":"https://doi.org/10.1016/j.amolm.2024.100037","url":null,"abstract":"<div><p>Type 2 diabetes (T2D) is a chronic and prevalent multisystemic disease that significantly increases morbidity and mortality. Dysfunction of the thyroid hormone system is common in patients with T2D, increasing their risk of both hyperthyroidism and hypothyroidism. Several components of the thyroid system are candidate risk genes for T2D. The thyrotropin-releasing hormone receptor (<em>TRHR</em>) gene encoding for TRHR is of particular interest since it is expressed by the dorsomedial hypothalamus neurons, which are known to regulate food intake. In humans, a variant in the <em>TRHR</em> gene has been previously reported in T2D patients in a population-based case-control study but not in familial T2D. We recruited 212 multigenerational families with T2D originated from the Italian peninsula with multiple cases of T2D and tested, via Pseudomarker 9 single nucleotide polymorphisms (SNPs) in the <em>TRHR</em> gene for linkage and linkage disequilibrium (i.e., linkage plus association) to/with T2D. We identified 2 novel risk variants (rs3110045 and rs28499085) significantly linked to and associated with the risk of T2D in the Italian families across several inheritance models. Our study is the first to confirm the previously reported association of <em>TRHR</em> gene with T2D and extends the risk to familial inheritance. However, functional and replication studies are still needed to confirm these results.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"3 ","pages":"Article 100037"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949688824000042/pdfft?md5=991c4d762c3e7d22a03c38d84b2e59ed&pid=1-s2.0-S2949688824000042-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139999854","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":"In silico drug discovery: Unveiling potential targets in Plasmodium falciparum","authors":"R. Murugesan,&nbsp;B. Kaleeswaran","doi":"10.1016/j.amolm.2024.100038","DOIUrl":"https://doi.org/10.1016/j.amolm.2024.100038","url":null,"abstract":"<div><h3>Objective</h3><p>Malaria, the plasmodium parasite, which causes and affects nearly half of the world's population, is the biggest human health issue. Malaria results in an annual death toll ranging from 1.2 to 2.7 million worldwide. Consequently, there is a pressing need for novel active ingredients with targeted effects to curb the worldwide spread of malaria.</p></div><div><h3>Methods</h3><p>This research is to explore innovative pharmacological molecules and employ bioinformatics methods (<em>in silico</em>) for the development of effective anti-malarial drugs. As part of the newest research into antimalarial chemicals, our study found seven drug combinations from different databases that showed drug-like properties and strong antimalarial activity <em>in silico</em>.</p></div><div><h3>Results</h3><p>The hexokinase-1 protein (PDB: <span>1CZA</span><svg><path></path></svg>) was docked with dioncophyllin-A, hugorosenone, marmesine, oxyprotostemonin, pachyrrhizin, plumbagin, and stemocurtisin. Among the pachyrrhizin compounds, the one with the highest docking score (−9.9 kcal/mol) was directed towards the 1CZA protein. Through superimposing the target and template structures, the active centres of the hexokinase I protein were identified, revealing structurally identical folds and undoubtedly conserved active sites. The SWISS-ADME tool was used to check how well the drug candidates were absorbed, distributed, broken down, and flushed out of the body (ADME).</p></div><div><h3>Conclusions</h3><p>In summary, our research identifies pachyrrhizin as a as a potential anti-malarial drug combination with strong <em>in silico</em> activity. We've elucidated their interaction with the hexokinase-1 protein and assessed their favourable pharmacokinetic properties. These findings represent a significant step toward developing effective treatments for malaria, emphasizing the importance of further experimental validation and clinical studies.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"3 ","pages":"Article 100038"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949688824000054/pdfft?md5=50376b42a51241b43eebef812cef9138&pid=1-s2.0-S2949688824000054-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140344688","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":"Human serum albumin binds spike protein and protects cells from SARS-CoV-2 infection by modulating the RAS pathway","authors":"Romualdo Varricchio ,&nbsp;Giovanna De Simone ,&nbsp;Gian Marco Vita ,&nbsp;Walter Nocera Cariola ,&nbsp;Maurizio Viscardi ,&nbsp;Sergio Brandi ,&nbsp;Gerardo Picazio ,&nbsp;Verena Zerbato ,&nbsp;Raffaella Koncan ,&nbsp;Ludovica Segat ,&nbsp;Stefano Di Bella ,&nbsp;Giovanna Fusco ,&nbsp;Paolo Ascenzi ,&nbsp;Alessandra di Masi","doi":"10.1016/j.amolm.2023.100033","DOIUrl":"10.1016/j.amolm.2023.100033","url":null,"abstract":"<div><p>Since the start of the pandemic, scientists have directed their research towards identifying COVID-19 risk factors and predictive elements. Numerous clinical studies have established a strong connection between hypoalbuminemia and an unfavorable prognosis for COVID-19. Here, we aim to explore the impact of human serum albumin (HSA) on SARS-CoV-2 infection. Our findings indicate that HSA plays a role in reducing the replication rate of SARS-CoV-2 in Vero E6 cells. This protective effect is due to HSA ability to bind to the S1 domain of the spike protein, effectively competing with ACE2. Moreover, we show that the protective role of HSA is dependent also on its ability to activate the protective axis within the RAS system pathway, which is responsible for inducing vasodilation and promoting anti-inflammatory, anti-fibrotic, and anti-apoptotic responses. In summary, the data presented in this study support the idea that reduced levels of circulating HSA in hypoalbuminemic patients may heighten their susceptibility to SARS-CoV-2 infection, as the spike protein is unhindered in its ability to bind to ACE2 and penetrate human cells. Besides, hypoalbuminemia exacerbates the imbalance of the RAS pathway towards the classical “detrimental” axis. This could potentially contribute to the increased severity and elevated mortality rate observed in individuals with low levels of circulating albumin.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"3 ","pages":"Article 100033"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949688823000333/pdfft?md5=0c53d54701d04e1e52bec07beb4f8e52&pid=1-s2.0-S2949688823000333-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139013329","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":"In silico study of the flavonoid compound of Sauropus androgynus leaves ON RNA-Dependent RNA polymerase (RdRp) SARS-CoV-2","authors":"Aghnia Nabila Ananda ,&nbsp;Triawanti Triawanti ,&nbsp;Bambang Setiawan ,&nbsp;Annisa Camellia Makati ,&nbsp;Jasmine Aisyah Putri ,&nbsp;Sentot Joko Raharjo","doi":"10.1016/j.amolm.2023.100032","DOIUrl":"10.1016/j.amolm.2023.100032","url":null,"abstract":"<div><h3>Objective</h3><p>RNA-dependent RNA polymerase (RdRp) is a protein that is essential in the replication and transcription processes of SARS-CoV-2. RdRp inhibitors must be sought, particularly in the identification of active substances in herbal or human dietary sources. The purpose of this study was to investigate the molecular docking of phytochemistry from the leaves of <em>Sauropus androgynus</em> against the RdRp protein.</p></div><div><h3>Methods</h3><p>This in silico study was performed using AutoDock Tools 1.5.7, AutoDock Vina v1.2.3 software, and BIOVIA Discovery Studio Visualizer 4.1.</p></div><div><h3>Results</h3><p>Afzelin, kaempferol, and trifolin were found as phytochemistry in Sauropus androgynus leaves. Among the three flavonoid molecules, afzelin has the lowest negative binding affinity (−7.677 kcal/mol), followed by trifolin (−6.906 kcal/mol) and kaempferol (−6.65 kcal/mol). All three flavonoid compounds have a binding affinity that is more negative than the three conventional drugs (favipiravir, remdesivir, ribavirin).</p></div><div><h3>Conclusions</h3><p>Flavonoid from the leaves of <em>Sauropus androgynus</em> leaves can be utilized as candidate for herbal or complementary medicine as an inhbitor of RdRp for COVID-19 treatment.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"3 ","pages":"Article 100032"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949688823000321/pdfft?md5=0d7af3c65653d94265a12879357adc18&pid=1-s2.0-S2949688823000321-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138615677","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":"Investigating the potential of natural compounds and known drugs against obstructive airway inflammation in inhibiting TRPC6","authors":"Uzma Saqib ,&nbsp;Isaac S. Demaree ,&nbsp;Alexander G. Obukhov ,&nbsp;Krishnan Hajela","doi":"10.1016/j.amolm.2024.100036","DOIUrl":"https://doi.org/10.1016/j.amolm.2024.100036","url":null,"abstract":"<div><p>The Transient Receptor Potential Canonical 6 (TRPC6) channel was implicated in the pathogenesis of pulmonary airway inflammation, chronic obstructive pulmonary disease, pulmonary edema, and pulmonary fibrosis. It was also proposed that Ca²⁺ influx through TRPC6 may contribute to triggering pulmonary inflammatory responses. The ChEMBL database lists 44 drugs that are clinically used to treat asthma, a type of obstructive airway inflammation (OAI). Since the mode of action and targets are not fully elucidated for many of these 44 drugs, we used computational approaches to determine the drugs’ potential to interact with the inhibitor binding site on the TRPC6 protein. We also screened a library of natural compounds to retrieve the phytochemicals with a potential to interact with TRPC6. The binding affinities of two well-known TRPC6 inhibitors, BTDM and 2-aminoethoxydiphenyl borate (2-APB), were compared with those of the screened compounds. We found that despite stable <em>in silico</em> binding and a well-defined three-dimensional molecular interaction pattern with the TRPC6 protein of the two top-scoring compounds, montelukast and solanesol, the molecules from the approved-drug and natural-compound libraries respectively, failed to show any significant efficacy in the <em>in vitro</em> assays.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"3 ","pages":"Article 100036"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949688824000030/pdfft?md5=b75db9a2af1a0785cfdb9500fcef112b&pid=1-s2.0-S2949688824000030-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139749606","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":"Hemostatic abnormalities for predicting and management of disease severity in COVID-19 affected patients: Review","authors":"Kovuri Umadevi ,&nbsp;Ruchira Clementina ,&nbsp;Dola Sundeep ,&nbsp;Mohd Imran Ali ,&nbsp;Rajarikam Nagarjuna Chary ,&nbsp;Arundhathi Shankaralingappa","doi":"10.1016/j.amolm.2024.100043","DOIUrl":"https://doi.org/10.1016/j.amolm.2024.100043","url":null,"abstract":"<div><p>The recent Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic has posed significant challenges to global healthcare, with a myriad of impacts on the human body, particularly noted in hemostatic abnormalities observed in COVID-19 patients. These abnormalities have been linked to an increased risk of serious thrombotic events like deep vein thrombosis, pulmonary embolism, and stroke. Unlike existing literature, this comprehensive review delves into the long-term implications of these abnormalities, providing invaluable guidance for ongoing patient care as we move into the post-pandemic era. We cover the entire spectrum of hemostatic abnormalities, including elevated levels of aPTT, D-dimer, PT, ferritin, INR, fibrinogen, fibrin, and FDP, all of which create a complex clinical scenario necessitating vigilant monitoring and targeted therapeutic interventions. With a focus on the heightened risk of thrombotic complications, we underscore the importance of timely anticoagulant therapy and other necessary interventions, tailored to the patient's unique clinical presentation. This review stands as a critical resource for clinicians, hematologists, and healthcare providers, equipping them to navigate the complexities of COVID-19 in both acute and long-term settings, ensuring optimal patient outcomes. As we collectively navigate the lasting impact of the pandemic, this targeted and in-depth analysis becomes an indispensable tool in advancing our understanding and management of COVID-19.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"3 ","pages":"Article 100043"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949688824000108/pdfft?md5=2371a4894ef87a159df30cf582741213&pid=1-s2.0-S2949688824000108-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140893543","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 interaction between ultra-processed foods and genetic risk score on body adiposity index (BAI), appendicular skeletal muscle mass index (ASM), and lipid profile in overweight and obese women","authors":"Fatemeh Gholami ,&nbsp;Azadeh Lesani ,&nbsp;Neda Soveid ,&nbsp;Niloufar Rasaei ,&nbsp;Mahsa Samadi ,&nbsp;Niki Bahrampour ,&nbsp;Gholamali Javdan ,&nbsp;Khadijeh Mirzaei","doi":"10.1016/j.amolm.2024.100044","DOIUrl":"10.1016/j.amolm.2024.100044","url":null,"abstract":"<div><h3>Background &amp; aims</h3><p>Ultra-processed foods (UPF) are formulations of ingredients, resulting from a series of industrial processes. Excess intake of UPF is associated with an increased risk of obesity and chronic disease. The present study investigates the interaction between the consumption of UPF and genetic risk score with body composition, body adiposity index (BAI), and appendicular skeletal muscle mass (ASM) in overweight and obese women.</p></div><div><h3>Method</h3><p>The study is cross-sectional with 376 overweight and obese women aged 18–65 years. The food consumption was obtained with 147-item food frequency (FFQ), and food items were grouped according to the level of processing as per the NOVA classification. Three single nucleotide polymorphisms (SNPs), including <em>Caveolin_1 (Cav_1), Melanocortin4 receptor (MC4R),</em> and <em>cryptochrome circadian regulator 1 (CRY1)</em>, were used to calculate GRS. The individual risk allele for each SNP was calculated using the incremental genetic model. Each SNP was recoded as 0, 1, or 2 based on the number of risk alleles associated with a higher body mass index (BMI). Subsequently, the unweighted GRS was computed by summing the number of risk alleles across the three SNPs. The GRS scale spans from 0 to 6, with each point representing a risk allele.Anthropometric measurements and some blood parameters were measured by standard protocols.</p></div><div><h3>Results</h3><p>After controlling for confounders such as age, energy intake, and BMI a significant interaction was found for appendicular skeletal muscle mass (β = −1.65, P = 0.04) and appendicular skeletal muscle mass index (β = −0.38, P = 0.07) on the NOVA classification system and GRS.</p></div><div><h3>Conclusions</h3><p>The findings of this study showed a significant interaction between GRS and the NOVA classification system on some body composition, including appendicular skeletal muscle mass. A higher intake of ultra-processed foods may be associated with lower appendicular skeletal muscle mass in people with high obesity-GRS.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"3 ","pages":"Article 100044"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S294968882400011X/pdfft?md5=b91b1fc46a2676788aea8ac2bae8948f&pid=1-s2.0-S294968882400011X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141044652","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":"Corrigendum to “Advances in RNA cancer therapeutics: New insight into exosomes as miRNA delivery” [Aspect. Mol. Med. 1 (2023) 100005]","authors":"Luca Volpini ,&nbsp;Federica Monaco ,&nbsp;Lory Santarelli ,&nbsp;Jiri Neuzil ,&nbsp;Marco Tomasetti","doi":"10.1016/j.amolm.2024.100041","DOIUrl":"https://doi.org/10.1016/j.amolm.2024.100041","url":null,"abstract":"","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"3 ","pages":"Article 100041"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S294968882400008X/pdfft?md5=f88de81285365cf1afb22ce153b03c0d&pid=1-s2.0-S294968882400008X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140619463","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":"Anti-hepatopathy and anti-nephropathy activities of Taraxacum officinale in a rat model of Streptozotocin diabetes-induced hepatorenal toxicity and dyslipidemia via attenuation of oxidative stress, inflammation, apoptosis, electrolyte imbalances, and mitochondrial dysfunction","authors":"Sunday Aderemi Adelakun ,&nbsp;Aniah Julius Akomaye ,&nbsp;Olusegun Dare Omotoso ,&nbsp;Olukayode Abimbola Arowosegbe","doi":"10.1016/j.amolm.2024.100034","DOIUrl":"10.1016/j.amolm.2024.100034","url":null,"abstract":"<div><p>Diabetes and chronic liver and kidney disease are common long-term conditions worldwide. <em>Taraxacum officinale</em> (TOE) has many medicinal properties, due to it phytochemicals constitutions. This study investigate activities of TOE in Streptozotocin diabetes-Induced Hepatorenal toxicity. Sixty rats were randomized into groups A, B, C, D, E, and F of ten rats each (n = 10). Group normal control, group B treated with TOE, group C diabetic (DM) negative control, group D DM rats treated with TOE, group E DM rats treated with metformin (MF)], group F treated with TOE follow by STZ-diabetic). Serum lipid profile, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), Gamma-glutamyl transferase (GGT), total proteins (TP), albumin (ALB), Urea, and creatinine, electrolyte, oxidative and antioxidant enzymes, caspase 3, inflammatory cytokines, tricarboxylic acid (TCA) cycle enzymes and mitochondrial membrane potential (ΔΨm), liver and kidney histology were investigated.</p><p>Treatment with TOE ameliorated all the electrolyte disruptions in DM rats. Treatment with TOE and TOE + MF recovered caspase 3, inflammatory makers, oxidative and antioxidant enzymes in DM rats. Moreover, an increase in lipid profile, hepatic and renal functional markers, ALT, AST, ALP, GGT, TP, ALB, Urea, TCA and renal mitochondrial respiratory-chain complexes (I-IV) and ΔΨm and a decrease in creatinine clearance was recovered in DM rats by TOE and TOE + MF treatment. TOE and TOE + MF protected against hepatic and renal histological damage in DM group.</p><p>Hepatorenal toxicity was effectively ameliorated by the TOE administration. TOE might be considered as a potential protective agent against hepatorenal toxicity.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"3 ","pages":"Article 100034"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949688824000017/pdfft?md5=fc7fa944b7cdfb215ed7cdfcbb1619a4&pid=1-s2.0-S2949688824000017-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139831807","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":"Curcumin and butyrate induce fibroblast senescence without the emergence of fibrosis biomarkers","authors":"Siwei Chu ,&nbsp;Natali Joma ,&nbsp;Hui Wen Yong ,&nbsp;Dusica Maysinger ,&nbsp;Ashok Kakkar ,&nbsp;Ursula Stochaj","doi":"10.1016/j.amolm.2023.100021","DOIUrl":"10.1016/j.amolm.2023.100021","url":null,"abstract":"<div><h3>Background</h3><p>Small molecules have emerged as valuable tools to modulate cellular homeostasis and the changes associated with aging. In particular, the phytochemical curcumin elicits cytoprotective effects that promote human health and longevity. The short-chain fatty acid butyrate provides anti-fibrotic activities, but can also induce cellular senescence.</p></div><div><h3>Rationale</h3><p>The impact of curcumin and butyrate on living cells are not fully understood. To obtain this information, our work focuses on fibroblasts. We selected fibroblasts as cellular model, because they (i) are present in different tissues and organs, (ii) contribute essential functions that derail during organismal aging, and (iii) are prime targets for therapeutic interventions that ameliorate aging-related pathologies.</p></div><div><h3>Methods and results</h3><p>A panel of quantitative assessments determines how curcumin and its nanoformulation (nano-curcumin), either alone or in combination with butyrate, modulate fibroblast physiology. Several experimental approaches and biomarkers demonstrate that curcumin (i) diminishes fibroblast viability, and (ii) promotes cellular senescence in a concentration-dependent fashion. Specifically, curcumin and nano-curcumin increase the activity of senescence-associated β-galactosidase and reduce the abundance of lamin B. When combined with butyrate, both curcumin and nano-curcumin enhance cell death and senescence. Free curcumin decreases the levels of Nrf2, a transcription factor that is upregulated upon oxidative stress. Neither curcumin nor nano-curcumin changes the abundance of the transcription factor NFκB, which is critical for inflammatory responses. Free curcumin, butyrate and nano-curcumin/butyrate combinations significantly diminish the abundance of the lysine deacetylase SIRT1, which is a key regulator of cellular senescence. Notably, none of the compounds or their combinations elevates biomarkers of fibrosis.</p></div><div><h3>Conclusions</h3><p>This study defines the cellular and molecular changes produced in fibroblasts by curcumin, nano-curcumin, alone or together with butyrate. Collectively, our results set the stage to explore curcumin/butyrate-based treatments to control the cellular activities that are contributed by fibroblasts.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"2 ","pages":"Article 100021"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42153356","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}