BioFactorsPub Date : 2023-12-26DOI: 10.1002/biof.2027
Mary Sonia Iheanacho, Ramji Kandel, Priti Roy, Kamaleshwar P. Singh
{"title":"Epigallocatechin-3-gallate attenuates arsenic-induced fibrogenic changes in human kidney epithelial cells through reversal of epigenetic aberrations and antioxidant activities","authors":"Mary Sonia Iheanacho, Ramji Kandel, Priti Roy, Kamaleshwar P. Singh","doi":"10.1002/biof.2027","DOIUrl":"10.1002/biof.2027","url":null,"abstract":"<p>Renal fibrosis is a pathogenic intermediate stage of chronic kidney disease (CKD). Nephrotoxicants including arsenic can cause kidney fibrosis through induction of oxidative stress and epigenetic aberrations. Epigallocatechin-3-gallate (EGCG), a green tea polyphenol, is known to have antioxidant and epigenetic modulation properties. Whether EGCG, through its antioxidant and epigenetic modulating activities, can attenuate fibrogenesis is not known. Therefore, the objective of this study was to determine whether EGCG can attenuate arsenic-induced acute injury and long-term exposure associated fibrogenicity in kidney epithelial cells. To address this question, two human kidney epithelial cell lines Caki-1 and HK-2 exposed to arsenic for both acute and long-term durations were treated with EGCG. The protective effect of EGCG on arsenic-induced cytotoxicity and fibrogenicity were evaluated by measuring the cell growth, reactive oxygen species (ROS) production, genes expression, and epigenetic changes in histone marks. Results revealed that EGCG has a protective effect in arsenic-induced acute cytotoxicity in these cells. EGCG scavenges the increased levels of ROS in arsenic exposed cells. Aberrant expression of fibrogenic genes in arsenic exposed cells were restored by EGCG. Abrogation of arsenic-induced fibrogenic changes was also associated with EGCG-mediated restoration of arsenic-induced aberrant expression of epigenetic regulatory proteins and histone marks. Novel findings of this study suggest that EGCG, through its antioxidant and epigenetic modulation capacities, has protective effects against arsenic-induced cytotoxicity and fibrogenic changes in kidney epithelial cells.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139037418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BioFactorsPub Date : 2023-12-22DOI: 10.1002/biof.2025
Francesca Diomede, Simone Guarnieri, Paola Lanuti, Fani Konstantinidou, Valentina Gatta, Thangavelu Soundara Rajan, Sante D. Pierdomenico, Oriana Trubiani, Guya Diletta Marconi, Jacopo Pizzicannella
{"title":"Extracellular vesicles (EVs): A promising therapeutic tool in the heart tissue regeneration","authors":"Francesca Diomede, Simone Guarnieri, Paola Lanuti, Fani Konstantinidou, Valentina Gatta, Thangavelu Soundara Rajan, Sante D. Pierdomenico, Oriana Trubiani, Guya Diletta Marconi, Jacopo Pizzicannella","doi":"10.1002/biof.2025","DOIUrl":"10.1002/biof.2025","url":null,"abstract":"<p>Mesenchymal stem cells (MSCs) treatment has been widely explored as a therapy for myocardial infarction, peripheral ischemic vascular diseases, dilated cardiomyopathy, and pulmonary hypertension. Latest in vitro studies suggest that MSCs can differentiate into contractile cardiomyocytes. One of the best-characterized MSCs products are MSCs-derived extracellular vesicles (EVs). EVs are crucial paracrine effectors of MSCs. Based on previous works, paracrine effects of MSCs play a primary role in the regenerative ability. Hence, in the current paper, we focused our attention on an alternative approach, exploiting products derived from human dental pulp stem cells (hDPSCs) rather than MSCs themselves, which may denote a cost-effective and safer approach. The focus has been on EVs and the bioactive molecules they contain to evaluate their ability to influence the differentiation process toward cardiomyogenic lineage. The expression of GATA4, ACTC1, CX43, and Nkx2.5 was evaluated using Immunofluorescence, real time-PCR, and Western blotting analyses. Furthermore, the expression profiling analysis of the microRNA hsa-miR-200c-3p, targeting the <i>GATA4</i> gene, was studied. The hsa-miR-200c-3p was found significantly down-regulated in both c-hDPSCs + EVs-hDPSCs and c-hDPSCs + EVs-HL-1 compared to untreated c-hDPSCs underlying a possible epigenetic mechanism behind the prevalent up-regulation of its targeted <i>GATA4</i> gene. The aim of the present work was to develop an in vitro model of hDPSCs able to differentiate into cardiomyocytes in order to investigate the role of EVs derived from hDPSCs and derived from HL-1 cardiomyocyte cell line in modulating the differentiation process toward cardiomyogenic lineage.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biof.2025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138828131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BioFactorsPub Date : 2023-12-22DOI: 10.1002/biof.2029
Rasha Ashkar, Ali Khattib, Sanaa Musa, Doron Goldberg, Soliman Khatib
{"title":"PON1 has palmitoyl-protein thioesterase (PPT) activity, and can affect the presence of SR-B1 on the endothelial cell membrane","authors":"Rasha Ashkar, Ali Khattib, Sanaa Musa, Doron Goldberg, Soliman Khatib","doi":"10.1002/biof.2029","DOIUrl":"10.1002/biof.2029","url":null,"abstract":"<p>The high-density lipoprotein (HDL)-associated enzyme paraoxonase 1 (PON1) is expressed almost exclusively in the liver and is then transported by HDL to the peripheral tissues. The lipophilic nature of PON1 enables its easy exchange between the lipoprotein and cell membranes in a process that is dependent on the HDL receptor scavenger receptor class B, type 1 (SR-B1). In endothelial cells, PON1 binding to the cell membrane leads to its internalization by endocytosis and subsequent lysosomal degradation. PON1 is a “promiscuous” enzyme with unusually broad substrate specificity in vitro, but its actual function and substrate are still unknown. The enzyme requires a lipid environment and becomes completely inactive upon delipidation. However, when PON1 binds HDL, its active site faces the lipoprotein's core and is inaccessible to external substrates. Hence, the HDL-bound PON1 is inactive toward substrates outside the particle's lipid core and is rapidly degraded and becomes inactive upon internalization. Consequently, the enzyme is only active in the cell membrane during its transit from HDL to the cytoplasm. To assign a function to PON1, we investigated whether it is a palmitoyl-protein thioesterase (PPT) that can hydrolyze the palmitoyl moieties of membrane proteins involved in HDL and cholesterol transport, such as SR-B1, ABCA1, or their neighboring caveola proteins to facilitate the release of HDL or trigger its endocytosis. This study shows that PON1 can hydrolyze palmitoyl-cysteine thioester bonds in vitro, has direct or indirect PPT activity in vivo, and can significantly decrease the presence of SR-B1 in the endothelial membrane.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biof.2029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138884132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BioFactorsPub Date : 2023-12-22DOI: 10.1002/biof.2026
{"title":"Correction to “Attenuative role of mangiferin in oxidative stress mediated liver dysfunction in arsenic intoxicated murines”","authors":"","doi":"10.1002/biof.2026","DOIUrl":"10.1002/biof.2026","url":null,"abstract":"<p>Saha S, Rashid K, Sadhukhan P, Agarwal N, Sil PC. Attenuative role of mangiferin in oxidative stress-mediated liver dysfunction in arsenic-intoxicated murines. Biofactors. 2016;42(5):515–532. https://doi.org/10.1002/biof.1276</p><p>The authors detected an editing error in Figure 5A. During the proofing stage of Figure 5A, the “Normal” liver subpanel was erroneously pasted twice, slightly overlapping. The correct Figure 5A is shown below. The authors confirm that all the experimental results and corresponding conclusions mentioned in the paper remain unaffected.</p><p>Phase contrast micrographs of rat liver (H & E) (200×) showing normal hepatic architecture, MAG-exposed group exhibiting normal architecture, arsenic-exposed disrupted hepatic architecture, indicating loss of hepatic integrity with altered membrane morphologies like vacuolated cytoplasm. Mangiferin post-treatment decreases this loss of hepatic architecture dose dependently comparable to the arsenic group. Mangiferin simultaneous treatment with the optimum dose showing marked improvement in the hepatic architecture altering morphological changes associated with arsenic intoxication.</p><p>We apologize for this error.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biof.2026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138884131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BioFactorsPub Date : 2023-12-18DOI: 10.1002/biof.1866
{"title":"Issue Information - Cover","authors":"","doi":"10.1002/biof.1866","DOIUrl":"https://doi.org/10.1002/biof.1866","url":null,"abstract":"","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://iubmb.onlinelibrary.wiley.com/doi/epdf/10.1002/biof.1866","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138739774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BioFactorsPub Date : 2023-12-14DOI: 10.1002/biof.2024
Alessia Remigante, Sara Spinelli, Paolo Zuccolini, Paola Gavazzo, Angela Marino, Michael Pusch, Rossana Morabito, Silvia Dossena
{"title":"Melatonin protects Kir2.1 function in an oxidative stress-related model of aging neuroglia","authors":"Alessia Remigante, Sara Spinelli, Paolo Zuccolini, Paola Gavazzo, Angela Marino, Michael Pusch, Rossana Morabito, Silvia Dossena","doi":"10.1002/biof.2024","DOIUrl":"10.1002/biof.2024","url":null,"abstract":"<p>Melatonin is a pleiotropic biofactor and an effective antioxidant and free radical scavenger and, as such, can be protective in oxidative stress-related brain conditions including epilepsy and aging. To test the potential protective effect of melatonin on brain homeostasis and identify the corresponding molecular targets, we established a new model of oxidative stress-related aging neuroglia represented by U-87 MG cells exposed to D-galactose (D-Gal). This model was characterized by a substantial elevation of markers of oxidative stress, lipid peroxidation, and protein oxidation. The function of the inward rectifying K<sup>+</sup> channel Kir2.1, which was identified as the main Kir channel endogenously expressed in these cells, was dramatically impaired. Kir2.1 was unlikely a direct target of oxidative stress, but the loss of function resulted from a reduction of protein abundance, with no alterations in transcript levels and trafficking to the cell surface. Importantly, melatonin reverted these changes. All findings, including the melatonin antioxidant effect, were reproduced in heterologous expression systems. We conclude that the glial Kir2.1 can be a target of oxidative stress and further suggest that inhibition of its function might alter the extracellular K<sup>+</sup> buffering in the brain, therefore contributing to neuronal hyperexcitability and epileptogenesis during aging. Melatonin can play a protective role in this context.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biof.2024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138686747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BioFactorsPub Date : 2023-12-08DOI: 10.1002/biof.2022
Bojan Stojnić, Sebastiá Galmés, Alba Serrano, Maria Sulli, Lana Sušak, Ndioba Seye, Andreu Palou, Gianfranco Diretto, M. Luisa Bonet, Joan Ribot
{"title":"Glycosaminoglycan dermatan sulfate supplementation decreases diet-induced obesity and metabolic dysfunction in mice","authors":"Bojan Stojnić, Sebastiá Galmés, Alba Serrano, Maria Sulli, Lana Sušak, Ndioba Seye, Andreu Palou, Gianfranco Diretto, M. Luisa Bonet, Joan Ribot","doi":"10.1002/biof.2022","DOIUrl":"10.1002/biof.2022","url":null,"abstract":"<p>Glycosaminoglycans are complex carbohydrates used as nutraceuticals for diverse applications. We studied the potential of the glycosaminoglycan dermatan sulfate (DS) to counteract the development of diet-induced obesity (DIO) using obesity-prone mice fed a high-fat diet (HFD) as a model. Oral DS supplementation protected the animals against HFD-induced increases in whole-body adiposity, visceral fat mass, adipocyte size, blood glucose levels, insulin resistance, and pro-inflammatory lipids levels in brown adipose tissue (BAT) and the liver, where it largely counteracted the HFD-induced changes in the nonpolar metabolome. Protection against DIO in the DS-supplemented mice occurred despite higher energy intake and appeared to be associated with increased energy expenditure, higher uncoupling protein 1 expression in BAT, decreased BAT “whitening,” and an enhanced channeling of fuel substrates toward skeletal muscle. This work is the first preclinical study to examine the anti-obesity activity of DS tested individually in vivo. The results support possible uses of DS as an active component in functional foods/supplements to manage obesity and associated metabolic diseases.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biof.2022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138555682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BioFactorsPub Date : 2023-12-08DOI: 10.1002/biof.2021
Jaime Santos, Irantzu Pallarès, Salvador Ventura
{"title":"A glimpse into the structural properties of α-synuclein oligomers","authors":"Jaime Santos, Irantzu Pallarès, Salvador Ventura","doi":"10.1002/biof.2021","DOIUrl":"10.1002/biof.2021","url":null,"abstract":"<p>α-Synuclein (αS) aggregation is the main neurological hallmark of a group of debilitating neurodegenerative disorders, collectively referred to as synucleinopathies, of which Parkinson's disease is the most prevalent. αS oligomers formed during the initial stages of aggregation are considered key pathogenic drivers of disease onset and progression, standing as privileged targets for therapeutic intervention and diagnosis. However, the structure of αS oligomers and the mechanistic basis of oligomer to fibril conversion are yet poorly understood, thereby precluding the rational formulation of strategies aimed at targeting oligomeric species. In this review, we delve into the recent advances in the structural and mechanistic characterization of αS oligomers. We also discuss how these advances are transforming our understanding of these elusive species and paving the way for oligomer-targeting therapeutics and diagnosis.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biof.2021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138557127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Endogenous chemicals guard health through inhibiting ferroptotic cell death","authors":"Yuan-Hao Song, Hong-Xu Lei, Dou Yu, Hao Zhu, Meng-Zhu Hao, Rong-Hua Cui, Xiang-Shuai Meng, Xie-Huang Sheng, Lei Zhang","doi":"10.1002/biof.2015","DOIUrl":"10.1002/biof.2015","url":null,"abstract":"<p>Ferroptosis is a new form of regulated cell death caused by iron-dependent accumulation of lethal polyunsaturated phospholipids peroxidation. It has received considerable attention owing to its putative involvement in a wide range of pathophysiological processes such as organ injury, cardiac ischemia/reperfusion, degenerative disease and its prevalence in plants, invertebrates, yeasts, bacteria, and archaea. To counter ferroptosis, living organisms have evolved a myriad of intrinsic efficient defense systems, such as cyst(e)ine-glutathione-glutathione peroxidase 4 system (cyst(e)ine-GPX4 system), guanosine triphosphate cyclohydrolase 1/tetrahydrobiopterin (BH<sub>4</sub>) system (GCH1/BH<sub>4</sub> system), ferroptosis suppressor protein 1/coenzyme Q<sub>10</sub> system (FSP1/CoQ<sub>10</sub> system), and so forth. Among these, GPX4 serves as the only enzymatic protection system through the reduction of lipid hydroperoxides, while other defense systems ultimately rely on small compounds to scavenge lipid radicals and prevent ferroptotic cell death. In this article, we systematically summarize the chemical biology of lipid radical trapping process by endogenous chemicals, such as coenzyme Q<sub>10</sub> (CoQ<sub>10</sub>), BH<sub>4</sub>, hydropersulfides, vitamin K, vitamin E, 7-dehydrocholesterol, with the aim of guiding the discovery of novel ferroptosis inhibitors.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138497746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BioFactorsPub Date : 2023-11-25DOI: 10.1002/biof.2020
Wisurumuni Arachchilage Hasitha Maduranga Karunarathne, Kyoung Tae Lee, Yung Hyun Choi, Chang-Hee Kang, Mi-Hwa Lee, Sang-Hun Kim, Gi-Young Kim
{"title":"Investigating rutin as a potential transforming growth factor-β type I receptor antagonist for the inhibition of bleomycin-induced lung fibrosis","authors":"Wisurumuni Arachchilage Hasitha Maduranga Karunarathne, Kyoung Tae Lee, Yung Hyun Choi, Chang-Hee Kang, Mi-Hwa Lee, Sang-Hun Kim, Gi-Young Kim","doi":"10.1002/biof.2020","DOIUrl":"10.1002/biof.2020","url":null,"abstract":"<p>Idiopathic pulmonary fibrosis (IPF) is a chronic lung condition characterized by the abnormal regulation of extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT). In this study, we investigated the potential of rutin, a natural flavonoid, in attenuating transforming growth factor-β (TGF-β)-induced ECM regulation and EMT through the inhibition of the TGF-β type I receptor (TβRI)-mediated suppressor of mothers against decapentaplegic (SMAD) signaling pathway. We found that non-toxic concentrations of rutin attenuated TGF-β-induced ECM-related genes, including fibronectin, elastin, collagen 1 type 1, and <i>TGF-β</i>, as well as myoblast differentiation from MRC-5 lung fibroblast cells accompanied by the downregulation of α-smooth muscle actin. Rutin also inhibited TGF-β-induced EMT processes, such as wound healing, migration, and invasion by regulating EMT-related gene expression. Additionally, rutin attenuated bleomycin-induced lung fibrosis in mice, thus providing a potential therapeutic option for IPF. The molecular docking analyses in this study predict that rutin occludes the active site of TβRI and inhibits SMAD-mediated fibrotic signaling pathways in lung fibrosis. These findings highlight the potential of rutin as a promising anti-fibrotic prodrug for lung fibrosis and other TGF-β-induced fibrotic and cancer-related diseases; however, further studies are required to validate its safety and effectiveness in other experimental models.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138440275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}