Pub Date : 2025-02-01DOI: 10.1016/j.biocel.2024.106724
Perihan Yagmur Guneri-Sozeri, Ogün Adebali
Bulky DNA adducts are mostly formed by external factors such as UV irradiation, smoking or treatment with DNA crosslinking agents. If such DNA adducts are not removed by nucleotide excision repair, they can lead to formation of driver mutations that contribute to cancer formation. Transcription factors (TFs) may critically affect both DNA adduct formation and repair efficiency at the binding site to DNA. For example, "hotspot" mutations in melanoma coincide with UV-induced accumulated cyclobutane pyrimidine dimer (CPD) adducts and/or inhibited repair at the binding sites of some TFs. Similarly, anticancer treatment with DNA cross-linkers may additionally generate DNA adducts leading to secondary mutations and the formation of malignant subclones. In addition, some TFs are overexpressed in response to UV irradiation or chemotherapeutic treatment, activating oncogenic and anti-oncogenic pathways independently of nucleotide excision repair itself. This review focuses on the interplay between TFs and nucleotide excision repair during cancer development and progression.
{"title":"Transcription factors, nucleotide excision repair, and cancer: A review of molecular interplay","authors":"Perihan Yagmur Guneri-Sozeri, Ogün Adebali","doi":"10.1016/j.biocel.2024.106724","DOIUrl":"10.1016/j.biocel.2024.106724","url":null,"abstract":"<div><div>Bulky DNA adducts are mostly formed by external factors such as UV irradiation, smoking or treatment with DNA crosslinking agents. If such DNA adducts are not removed by nucleotide excision repair, they can lead to formation of driver mutations that contribute to cancer formation. Transcription factors (TFs) may critically affect both DNA adduct formation and repair efficiency at the binding site to DNA. For example, \"hotspot\" mutations in melanoma coincide with UV-induced accumulated cyclobutane pyrimidine dimer (CPD) adducts and/or inhibited repair at the binding sites of some TFs. Similarly, anticancer treatment with DNA cross-linkers may additionally generate DNA adducts leading to secondary mutations and the formation of malignant subclones. In addition, some TFs are overexpressed in response to UV irradiation or chemotherapeutic treatment, activating oncogenic and anti-oncogenic pathways independently of nucleotide excision repair itself. This review focuses on the interplay between TFs and nucleotide excision repair during cancer development and progression.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"179 ","pages":"Article 106724"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822895","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}
Pub Date : 2025-02-01DOI: 10.1016/j.biocel.2024.106716
Hesham M. Hassan , Mahmoud El Safadi , Muhammad Faisal Hayat , Ahmed Al-Emam
Fenitrothion (FEN) is an organophosphate insecticidal agent that is considered as major source of organs toxicity. Saponarin (SAP) is a naturally occurring novel flavone that exhibits a wide range of medicinal properties. The current trial was conducted to evaluate the ameliorative potential of SAP against FEN instigated liver toxicity in rats. Thirty-two male albino rats were apportioned into four groups including control, FEN (10 mg/kg), FEN (10 mg/kg) + SAP (80 mg/kg), and SAP (80 mg/kg) alone treated group. It was revealed that FEN administration upregulated the gene expression of TNF-α, TLR4, IL-1β, MYD88, IL-6, TRAF6, COX-2, NF-κB, JAK1 and STAT3 while reducing the gene expression of IκB. Moreover, the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were increased while the activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), heme-oxygenase-1 (HO-1) and glutathione reductase (GSR) were decreased after FEN exposure. Furthermore, FEN administration notably escalated the levels of hepatic enzymes including alanine transaminase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) whereas reduced the levels of total proteins and albumin. Besides, FEN intake upregulated the levels of Caspase-9, Bax and Caspase-3 while reducing the levels of Bcl-2. Hepatic histology was impaired after FEN intoxication. Nonetheless, SAP treatment remarkably protected the normal state of liver via regulating abovementioned irregularities. Our in-silico analysis confirmed that SAP hold that potential to interact with binding pocket of these proteins, highlighting its ability as a therapeutic compound to alleviate FEN-induced liver damage.
{"title":"Prevention of fenitrothion induced hepatic toxicity by saponarin via modulating TLR4/MYD88, JAK1/STAT3 and NF-κB signaling pathways","authors":"Hesham M. Hassan , Mahmoud El Safadi , Muhammad Faisal Hayat , Ahmed Al-Emam","doi":"10.1016/j.biocel.2024.106716","DOIUrl":"10.1016/j.biocel.2024.106716","url":null,"abstract":"<div><div>Fenitrothion (FEN) is an organophosphate insecticidal agent that is considered as major source of organs toxicity. Saponarin (SAP) is a naturally occurring novel flavone that exhibits a wide range of medicinal properties. The current trial was conducted to evaluate the ameliorative potential of SAP against FEN instigated liver toxicity in rats. Thirty-two male albino rats were apportioned into four groups including control, FEN (10 mg/kg), FEN (10 mg/kg) + SAP (80 mg/kg), and SAP (80 mg/kg) alone treated group. It was revealed that FEN administration upregulated the gene expression of TNF-α, TLR4, IL-1β, MYD88, IL-6, TRAF6, COX-2, NF-κB, JAK1 and STAT3 while reducing the gene expression of IκB. Moreover, the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were increased while the activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), heme-oxygenase-1 (HO-1) and glutathione reductase (GSR) were decreased after FEN exposure. Furthermore, FEN administration notably escalated the levels of hepatic enzymes including alanine transaminase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) whereas reduced the levels of total proteins and albumin. Besides, FEN intake upregulated the levels of Caspase-9, Bax and Caspase-3 while reducing the levels of Bcl-2. Hepatic histology was impaired after FEN intoxication. Nonetheless, SAP treatment remarkably protected the normal state of liver via regulating abovementioned irregularities. Our <em>in-silico</em> analysis confirmed that SAP hold that potential to interact with binding pocket of these proteins, highlighting its ability as a therapeutic compound to alleviate FEN-induced liver damage.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"179 ","pages":"Article 106716"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792454","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}
Pub Date : 2025-02-01DOI: 10.1016/j.biocel.2025.106740
Bin Zhao , Bingfeng Zhang , Minhao Chenzhang , Kangxian Jiang , Dianyu Wang , Junyi Chen
Background
As a diuretic, ethacrynic acid (EA) has been shown to play a suppressive role in cancers, including prostate cancer (PC). However, its molecular regulatory mechanism is still unclear. Therefore, our study is centered on investigating the effect of EA on PC development and its mechanism.
Methods
To verify the binding relationship between EA and GSTP1, molecular docking and cellular thermal shift assay (CETSA) were conducted. To examine how EA affects PC cell proliferation, cell cycle, and apoptosis, cell function assays were performed. qRT-PCR was used to detect GSTP1 mRNA expression. The expression of GSTP1 protein and PI3K-AKT signaling pathway-related proteins in cells was detected by western blot (WB). To verify how EA and GSTP1 influence cell growth in PC, in vivo experiments were conducted.
Results
The binding relationship between GSTP1 and EA was confirmed by molecular docking and CETSA results. Cell experiments showed that EA could hinder PI3K/AKT pathway and PC cell proliferation, arrest the cell cycle in G0/G1 phase, and facilitate apoptosis by binding to GSTP1. In vivo experiments in nude mice verified that the interaction between EA and GSTP1 reduced PI3K and AKT phosphorylation and inhibited the growth of PC cells.
Conclusion
EA inhibits PC progression by binding to GSTP1 to downregulate the activity of PI3K/AKT pathway, and this result suggests the potential of EA to be an anticancer agent for PC therapy.
{"title":"Ethacrynic acid inhibits the growth and proliferation of prostate cancer cells by targeting GSTP1 and regulating the PI3K-AKT signaling pathway","authors":"Bin Zhao , Bingfeng Zhang , Minhao Chenzhang , Kangxian Jiang , Dianyu Wang , Junyi Chen","doi":"10.1016/j.biocel.2025.106740","DOIUrl":"10.1016/j.biocel.2025.106740","url":null,"abstract":"<div><h3>Background</h3><div>As a diuretic, ethacrynic acid (EA) has been shown to play a suppressive role in cancers, including prostate cancer (PC). However, its molecular regulatory mechanism is still unclear. Therefore, our study is centered on investigating the effect of EA on PC development and its mechanism.</div></div><div><h3>Methods</h3><div>To verify the binding relationship between EA and GSTP1, molecular docking and cellular thermal shift assay (CETSA) were conducted. To examine how EA affects PC cell proliferation, cell cycle, and apoptosis, cell function assays were performed. qRT-PCR was used to detect GSTP1 mRNA expression. The expression of GSTP1 protein and PI3K-AKT signaling pathway-related proteins in cells was detected by western blot (WB). To verify how EA and GSTP1 influence cell growth in PC, <em>in vivo</em> experiments were conducted.</div></div><div><h3>Results</h3><div>The binding relationship between GSTP1 and EA was confirmed by molecular docking and CETSA results. Cell experiments showed that EA could hinder PI3K/AKT pathway and PC cell proliferation, arrest the cell cycle in G0/G1 phase, and facilitate apoptosis by binding to GSTP1. <em>In vivo</em> experiments in nude mice verified that the interaction between EA and GSTP1 reduced PI3K and AKT phosphorylation and inhibited the growth of PC cells.</div></div><div><h3>Conclusion</h3><div>EA inhibits PC progression by binding to GSTP1 to downregulate the activity of PI3K/AKT pathway, and this result suggests the potential of EA to be an anticancer agent for PC therapy.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"180 ","pages":"Article 106740"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124095","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}
Pub Date : 2025-02-01DOI: 10.1016/j.biocel.2024.106731
Beini Sun , Yu Wang , Hongce Chen , Qialing Huang , Chunchun An , Qiuqiang Zhan , Xiaoping Wang , Tongsheng Chen
Disulfiram (DSF) and copper (Cu2 +) in combination exhibit powerful anti-cancer effect on a variety of cancer cell lines. Here, we found that DSF/Cu2+ facilitated the accumulation of intracellular reactive oxygen species (ROS), and induced ROS-dependent apoptosis accompanied by chromatin condensation and phosphatidylserine externalization in MCF-7 cells. DSF/Cu2+ caused caspase-independent apoptosis by promoting the AIF translocation from mitochondria to nucleus. Most importantly, the cytotoxicity of DSF/Cu2+ was markedly inhibited by knocking out AIF, suggesting the indispensability of AIF in DSF/Cu2+-induced apoptosis. The pro-apoptotic protein BAK instead of BAX was upregulated and activated upon DSF/Cu2+ treatment, and the BAK knockout cells exhibited high resistance to DSF/Cu2+, indicating the importance of BAK in DSF/Cu2+-induced apoptosis. Additionally, both co-immunoprecipitation and live-cell quantitative fluorescence resonance energy transfer (FRET) analysis revealed that DSF/Cu2+ unlocked the binding of MCL-1 to BAK, which resulted in subsequent BAK homo-oligomerization. Overall, our data demonstrate for the first time that DSF/Cu2+ unlocks the binding of MCL-1 to BAK, thus leading BAK oligomerization and subsequent AIF nucleus translocation to mediate caspase-independent apoptosis in MCF-7 cells.
{"title":"Disulfiram/copper induces BAK-mediated caspase-independent apoptosis in MCF-7 cells","authors":"Beini Sun , Yu Wang , Hongce Chen , Qialing Huang , Chunchun An , Qiuqiang Zhan , Xiaoping Wang , Tongsheng Chen","doi":"10.1016/j.biocel.2024.106731","DOIUrl":"10.1016/j.biocel.2024.106731","url":null,"abstract":"<div><div>Disulfiram (DSF) and copper (Cu<sup>2 +</sup>) in combination exhibit powerful anti-cancer effect on a variety of cancer cell lines. Here, we found that DSF/Cu<sup>2+</sup> facilitated the accumulation of intracellular reactive oxygen species (ROS), and induced ROS-dependent apoptosis accompanied by chromatin condensation and phosphatidylserine externalization in MCF-7 cells. DSF/Cu<sup>2+</sup> caused caspase-independent apoptosis by promoting the AIF translocation from mitochondria to nucleus. Most importantly, the cytotoxicity of DSF/Cu<sup>2+</sup> was markedly inhibited by knocking out AIF, suggesting the indispensability of AIF in DSF/Cu<sup>2+</sup>-induced apoptosis. The pro-apoptotic protein BAK instead of BAX was upregulated and activated upon DSF/Cu<sup>2+</sup> treatment, and the <em>BAK</em> knockout cells exhibited high resistance to DSF/Cu<sup>2+</sup>, indicating the importance of BAK in DSF/Cu<sup>2+</sup>-induced apoptosis. Additionally, both co-immunoprecipitation and live-cell quantitative fluorescence resonance energy transfer (FRET) analysis revealed that DSF/Cu<sup>2+</sup> unlocked the binding of MCL-1 to BAK, which resulted in subsequent BAK homo-oligomerization. Overall, our data demonstrate for the first time that DSF/Cu<sup>2+</sup> unlocks the binding of MCL-1 to BAK, thus leading BAK oligomerization and subsequent AIF nucleus translocation to mediate caspase-independent apoptosis in MCF-7 cells.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"179 ","pages":"Article 106731"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886399","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}
Pub Date : 2025-01-29DOI: 10.1016/j.biocel.2025.106741
Lei Zheng , Shuling Han , Olivia M Martinez , Sheri M Krams
Background and Aims
Liver ischemia-reperfusion injury (LIRI) profoundly affects liver function and survival largely through activation of the innate immune system. In this study we sought to elucidate the underlying mechanisms by which the innate immune system impacts liver function and survival in LIRI.
Approach and Results
RNA-seq analyses, from existing datasets of liver from mice with LIRI, was performed to identify differentially expressed genes (DEGs) associated with LIRI. Protein-protein interaction analysis revealed clusters involved in signaling pathways with a cluster anchored by Senp2, acting as a central modulator. Macrophages and monocytes were determined to be the source of Senp2 with monocyte-derived macrophages expressing the highest levels of Senp2. Experiments in a mouse model of LIRI further elucidated the expression, function, and mechanism of Senp2. Overexpression of Senp2 suppressed both the polarization of M1 macrophages and the production of inflammatory mediators. Further, Senp2-overexpressing macrophages significantly ameliorated LIRI.
Conclusions
Our study suggests that SENP2 plays an important role in regulating LIRI by influencing macrophage polarization through the Dvl2/GSK-3β/β-catenin axis. While further validation is needed, these findings indicate that targeting SENP2-mediated pathways could be a promising approach for mitigating LIRI and enhancing therapeutic strategies.
{"title":"SENP2 as a critical regulator in liver ischemia-reperfusion injury","authors":"Lei Zheng , Shuling Han , Olivia M Martinez , Sheri M Krams","doi":"10.1016/j.biocel.2025.106741","DOIUrl":"10.1016/j.biocel.2025.106741","url":null,"abstract":"<div><h3>Background and Aims</h3><div>Liver ischemia-reperfusion injury (LIRI) profoundly affects liver function and survival largely through activation of the innate immune system. In this study we sought to elucidate the underlying mechanisms by which the innate immune system impacts liver function and survival in LIRI.</div></div><div><h3>Approach and Results</h3><div>RNA-seq analyses, from existing datasets of liver from mice with LIRI, was performed to identify differentially expressed genes (DEGs) associated with LIRI. Protein-protein interaction analysis revealed clusters involved in signaling pathways with a cluster anchored by Senp2, acting as a central modulator. Macrophages and monocytes were determined to be the source of Senp2 with monocyte-derived macrophages expressing the highest levels of Senp2. Experiments in a mouse model of LIRI further elucidated the expression, function, and mechanism of Senp2. Overexpression of Senp2 suppressed both the polarization of M1 macrophages and the production of inflammatory mediators. Further, Senp2-overexpressing macrophages significantly ameliorated LIRI.</div></div><div><h3>Conclusions</h3><div>Our study suggests that SENP2 plays an important role in regulating LIRI by influencing macrophage polarization through the Dvl2/GSK-3β/β-catenin axis. While further validation is needed, these findings indicate that targeting SENP2-mediated pathways could be a promising approach for mitigating LIRI and enhancing therapeutic strategies.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"180 ","pages":"Article 106741"},"PeriodicalIF":3.4,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076204","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}
Pub Date : 2025-01-25DOI: 10.1016/j.biocel.2025.106738
Zihe Zheng , Wei Wang , Ming Huang , Bo Chen , Tao Wang , Zheng Xu , Xin Jiang , Xiaofu Dai
Background
Heart failure is linked to increased hospitalization and mortality. Mitochondrial permeability transition-driven necrosis is associated with cardiovascular diseases, but its role in heart failure is unclear. This study aimed to identify and validate genes related to mitochondrial permeability transition-driven necrosis in heart failure, potentially leading to new drug targets and signaling pathways.
Methods
We identified differentially expressed genes related to heart failure from the gene expression omnibus database and identified module genes related to mitochondrial permeability transition-driven necrosis from the gene set enrichment analysis database. Key genes were determined by intersecting these two gene groups using least absolute shrinkage and selection operator and support vector machine algorithms. Pathways, diagnostic efficacy, gene interactions, immune infiltration, and regulatory networks were analyzed. Small interfering RNAs were used for validation. Real-time-quantitative polymerase chain reaction, flow cytometry, and JC1 assays were performed in vitro.
Results
Forty-six differentially expressed genes, and 3439 module genes were identified. LYVE1, IL1RL1, and SERPINA3 were identified as significantly downregulated key genes, with IL1RL1 and SERPINA3 associated with heart failure risk. Benzo(a) pyrene, bisphenol A, estradiol, and particulate matter were found to simultaneously increase the expression of three key genes. In clinical samples, only LYVE1 and IL1RL1 were downregulated, as expected. Knockdown of these genes in cells led to increased necrosis and decreased mitochondrial membrane potential. Only estradiol reduced brain natriuretic peptide protein levels in hypertrophic cells.
Conclusions
LYVE1 and IL1RL1 were validated as key genes linked to mitochondrial permeability transition-driven necrosis in heart failure. Estradiol may have a therapeutic effect on heart failure.
{"title":"LYVE1 and IL1RL1 are mitochondrial permeability transition-driven necrosis-related genes in heart failure","authors":"Zihe Zheng , Wei Wang , Ming Huang , Bo Chen , Tao Wang , Zheng Xu , Xin Jiang , Xiaofu Dai","doi":"10.1016/j.biocel.2025.106738","DOIUrl":"10.1016/j.biocel.2025.106738","url":null,"abstract":"<div><h3>Background</h3><div>Heart failure is linked to increased hospitalization and mortality. Mitochondrial permeability transition-driven necrosis is associated with cardiovascular diseases, but its role in heart failure is unclear. This study aimed to identify and validate genes related to mitochondrial permeability transition-driven necrosis in heart failure, potentially leading to new drug targets and signaling pathways.</div></div><div><h3>Methods</h3><div>We identified differentially expressed genes related to heart failure from the gene expression omnibus database and identified module genes related to mitochondrial permeability transition-driven necrosis from the gene set enrichment analysis database. Key genes were determined by intersecting these two gene groups using least absolute shrinkage and selection operator and support vector machine algorithms. Pathways, diagnostic efficacy, gene interactions, immune infiltration, and regulatory networks were analyzed. Small interfering RNAs were used for validation. Real-time-quantitative polymerase chain reaction, flow cytometry, and JC<img>1 assays were performed <em>in vitro</em>.</div></div><div><h3>Results</h3><div>Forty-six differentially expressed genes, and 3439 module genes were identified. <em>LYVE1</em>, <em>IL1RL1</em>, and <em>SERPINA3</em> were identified as significantly downregulated key genes, with <em>IL1RL1</em> and <em>SERPINA3</em> associated with heart failure risk. Benzo(a) pyrene, bisphenol A, estradiol, and particulate matter were found to simultaneously increase the expression of three key genes. In clinical samples, only <em>LYVE1</em> and <em>IL1RL1</em> were downregulated, as expected. Knockdown of these genes in cells led to increased necrosis and decreased mitochondrial membrane potential. Only estradiol reduced brain natriuretic peptide protein levels in hypertrophic cells.</div></div><div><h3>Conclusions</h3><div><em>LYVE1</em> and <em>IL1RL1</em> were validated as key genes linked to mitochondrial permeability transition-driven necrosis in heart failure. Estradiol may have a therapeutic effect on heart failure.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"180 ","pages":"Article 106738"},"PeriodicalIF":3.4,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054100","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}
Pub Date : 2025-01-22DOI: 10.1016/j.biocel.2025.106735
Dietrich E. Lorke , Murat Oz
Acetylcholinesterase inhibition, the principal mechanism of acute organophosphorus compound toxicity, cannot explain neuropsychiatric symptoms occurring after exposure to low organophosphate concentrations causing no cholinergic symptoms. Organophosphate-triggered oxidative stress has increasingly come into focus, occurring when the action of reactive oxygen species, generated from free radicals, is not compensated by antioxidant free radical scavengers. Being nucleophilic, organophosphates can easily accept an electron, thereby generating free radicals. Organophosphates inhibit the antioxidant paraoxonase, and reactive oxygen species are produced during organophosphate metabolism. Organophosphates disrupt the function of mitochondria, the principal source of free radicals. Organophosphates also induce neuroinflammation, which generates reactive oxygen species, and reactive oxygen species in turn stimulate neuroinflammation. Markers of reactive oxygen species are elevated in vitro and in vivo after exposure to organophosphates and in individuals professionally exposed to organophosphates. This most probably contributes to the pathogenesis of the intermediate syndrome, chronic organophosphate-induced neuropsychiatric disorders and neurodegeneration occurring in patients after organophosphate exposure. Evidence for beneficial effects of antioxidants in organophosphate poisoning is discussed.
{"title":"A review on oxidative stress in organophosphate-induced neurotoxicity","authors":"Dietrich E. Lorke , Murat Oz","doi":"10.1016/j.biocel.2025.106735","DOIUrl":"10.1016/j.biocel.2025.106735","url":null,"abstract":"<div><div>Acetylcholinesterase inhibition, the principal mechanism of acute organophosphorus compound toxicity, cannot explain neuropsychiatric symptoms occurring after exposure to low organophosphate concentrations causing no cholinergic symptoms. Organophosphate-triggered oxidative stress has increasingly come into focus, occurring when the action of reactive oxygen species, generated from free radicals, is not compensated by antioxidant free radical scavengers. Being nucleophilic, organophosphates can easily accept an electron, thereby generating free radicals. Organophosphates inhibit the antioxidant paraoxonase, and reactive oxygen species are produced during organophosphate metabolism. Organophosphates disrupt the function of mitochondria, the principal source of free radicals. Organophosphates also induce neuroinflammation, which generates reactive oxygen species, and reactive oxygen species in turn stimulate neuroinflammation. Markers of reactive oxygen species are elevated <em>in vitro</em> and <em>in vivo</em> after exposure to organophosphates and in individuals professionally exposed to organophosphates. This most probably contributes to the pathogenesis of the intermediate syndrome, chronic organophosphate-induced neuropsychiatric disorders and neurodegeneration occurring in patients after organophosphate exposure. Evidence for beneficial effects of antioxidants in organophosphate poisoning is discussed.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"180 ","pages":"Article 106735"},"PeriodicalIF":3.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043083","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}
Pub Date : 2025-01-21DOI: 10.1016/j.biocel.2025.106739
Anita Valand , Poojitha Rajasekar , Louise V. Wain , Rachel L. Clifford
Lung fibrosis, including idiopathic pulmonary fibrosis (IPF), is a complex and devastating disease characterised by the progressive scarring of lung tissue leading to compromised respiratory function. Aberrantly activated fibroblasts deposit extracellular matrix components into the surrounding lung tissue, impairing lung function and capacity for gas exchange. Both genetic and epigenetic factors have been found to play a role in the pathogenesis of lung fibrosis, with emerging evidence highlighting the interplay between these two regulatory mechanisms. This review provides an overview of the current understanding of the interplay between genetics and epigenetics in lung fibrosis. We discuss the genetic variants associated with susceptibility to lung fibrosis and explore how epigenetic modifications such as DNA methylation, histone modifications, and non-coding RNA expression contribute to disease. Insights from genome-wide association studies (GWAS) and epigenome-wide association studies (EWAS) are integrated to explore the molecular mechanisms underlying lung fibrosis pathogenesis. We also discuss the potential clinical implications of genetics and epigenetics in lung fibrosis, including the development of novel therapeutic targets. Overall, this review highlights the importance of considering both genetic and epigenetic factors in the understanding and management of lung fibrosis.
{"title":"Interplay between genetics and epigenetics in lung fibrosis","authors":"Anita Valand , Poojitha Rajasekar , Louise V. Wain , Rachel L. Clifford","doi":"10.1016/j.biocel.2025.106739","DOIUrl":"10.1016/j.biocel.2025.106739","url":null,"abstract":"<div><div>Lung fibrosis, including idiopathic pulmonary fibrosis (IPF), is a complex and devastating disease characterised by the progressive scarring of lung tissue leading to compromised respiratory function. Aberrantly activated fibroblasts deposit extracellular matrix components into the surrounding lung tissue, impairing lung function and capacity for gas exchange. Both genetic and epigenetic factors have been found to play a role in the pathogenesis of lung fibrosis, with emerging evidence highlighting the interplay between these two regulatory mechanisms. This review provides an overview of the current understanding of the interplay between genetics and epigenetics in lung fibrosis. We discuss the genetic variants associated with susceptibility to lung fibrosis and explore how epigenetic modifications such as DNA methylation, histone modifications, and non-coding RNA expression contribute to disease. Insights from genome-wide association studies (GWAS) and epigenome-wide association studies (EWAS) are integrated to explore the molecular mechanisms underlying lung fibrosis pathogenesis. We also discuss the potential clinical implications of genetics and epigenetics in lung fibrosis, including the development of novel therapeutic targets. Overall, this review highlights the importance of considering both genetic and epigenetic factors in the understanding and management of lung fibrosis.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"180 ","pages":"Article 106739"},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030202","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}
Pub Date : 2025-01-20DOI: 10.1016/j.biocel.2025.106736
Ehsan Ahmadpour , Kimia Moradi , Reyhaneh Moghaddami , Rafieh Bagherifar , Arshad Ghaffari-Nasab , Mahdi Mahdipour , Azadeh Mizani , Mahdi Ahmadi , Monir Khordadmehr , Mohammad Hasan Kohansal
Cystic echinococcosis, caused by Echinococcus granulosus, is a zoonotic disease with immunomodulatory properties attributed to hydatid cyst fluid (HCF). Given the immune-modulating and anti-inflammatory properties of HCF observed in other contexts, its potential therapeutic effects in diabetes remain unexplored. This study aimed to investigate the potential therapeutic effects of HCF on glycemic control, inflammatory cytokines, and tissue histopathology in a streptozotocin (STZ)-induced model of type 1 diabetes. Twenty male rats were randomly divided into four groups (n = 5): a healthy control group, a hydatid cyst group that received three intraperitoneal injections of HCF at two-week intervals, a diabetic group that received a single intraperitoneal dose of STZ to induce diabetes, and a hydatid cyst + diabetic group (HCF + STZ) that received both HCF treatment and STZ administration. Serum glucose levels, inflammatory cytokines (TNF-α, IL-1β, and IL-10), and histopathological changes in pancreatic and renal tissues were analyzed. The HCF + STZ group demonstrated a significant reduction in serum glucose levels compared to the STZ-only group. Pro-inflammatory cytokines TNF-α and IL-1β were significantly decreased in HCF-treated diabetic rats, while the anti-inflammatory cytokine IL-10 was partially restored. Histopathological examination revealed severe pancreatic islet atrophy and renal degeneration in the diabetic group, which were markedly alleviated in the HCF + STZ group. These findings suggest that HCF’s immunomodulatory and anti-inflammatory properties may mitigate hyperglycemia and inflammatory responses in type 1 diabetes, warranting further investigation into its mechanisms and clinical applications.
{"title":"Protective effects of hydatid cyst fluid on inflammation and tissue damage in rat model of type 1 diabetes","authors":"Ehsan Ahmadpour , Kimia Moradi , Reyhaneh Moghaddami , Rafieh Bagherifar , Arshad Ghaffari-Nasab , Mahdi Mahdipour , Azadeh Mizani , Mahdi Ahmadi , Monir Khordadmehr , Mohammad Hasan Kohansal","doi":"10.1016/j.biocel.2025.106736","DOIUrl":"10.1016/j.biocel.2025.106736","url":null,"abstract":"<div><div>Cystic echinococcosis, caused by <em>Echinococcus granulosus</em>, is a zoonotic disease with immunomodulatory properties attributed to hydatid cyst fluid (HCF). Given the immune-modulating and anti-inflammatory properties of HCF observed in other contexts, its potential therapeutic effects in diabetes remain unexplored. This study aimed to investigate the potential therapeutic effects of HCF on glycemic control, inflammatory cytokines, and tissue histopathology in a streptozotocin (STZ)-induced model of type 1 diabetes. Twenty male rats were randomly divided into four groups (n = 5): a healthy control group, a hydatid cyst group that received three intraperitoneal injections of HCF at two-week intervals, a diabetic group that received a single intraperitoneal dose of STZ to induce diabetes, and a hydatid cyst + diabetic group (HCF + STZ) that received both HCF treatment and STZ administration. Serum glucose levels, inflammatory cytokines (TNF-α, IL-1β, and IL-10), and histopathological changes in pancreatic and renal tissues were analyzed. The HCF + STZ group demonstrated a significant reduction in serum glucose levels compared to the STZ-only group. Pro-inflammatory cytokines TNF-α and IL-1β were significantly decreased in HCF-treated diabetic rats, while the anti-inflammatory cytokine IL-10 was partially restored. Histopathological examination revealed severe pancreatic islet atrophy and renal degeneration in the diabetic group, which were markedly alleviated in the HCF + STZ group. These findings suggest that HCF’s immunomodulatory and anti-inflammatory properties may mitigate hyperglycemia and inflammatory responses in type 1 diabetes, warranting further investigation into its mechanisms and clinical applications.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"180 ","pages":"Article 106736"},"PeriodicalIF":3.4,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025726","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}
Non-healing wounds pose significant challenges and require effective therapeutic interventions. Extracellular vesicles (EVs) have emerged as promising cell-free therapeutic agents in tissue regeneration. However, the functional differences between different subpopulations of EVs in wound healing remain understudied. This study aimed to evaluate the effects of two distinct subpopulations of clonal mesenchymal stromal cells (cMSC)-derived EVs (cMSC-EVs), namely 20 K and 110K-cMSC-EVs, primarily on in vitro wound healing process, providing fast and cost-effective alternatives to animal models.
Methods
In vitro assays were conducted to compare the effects of 20 K and 110K-cMSC-EVs, isolated through high-speed centrifugation and differential ultracentrifugation, respectively. For evaluation the main mechanisms of wound healing, including cell proliferation, cell migration, angiogenesis, and contraction. Human dermal fibroblasts (HDF) were considered as the main cells for analysis of these procedures. Moreover, gene expression analysis was performed to assess the impact of these EV subpopulations on the related process of wound healing on HDF.
Results
The results demonstrated that both 20 K and 110K-cMSC-EVs exhibited beneficial effects on cell proliferation, cell migration, angiogenesis, and gel contraction. RT-qPCR revealed that both EV types downregulated interleukin 6 (IL6), induced proliferation by upregulating proliferating cell nuclear antigen (PCNA), and regulated remodeling by upregulating matrix metallopeptidase 1 (MMP1) and downregulating collagen type 1 (COL1).
Discussion
This study highlights the effects of both 20 K and 110K-cMSC-EVs on the potency of HDFs in wound healing-related process. As the notable finding, 20K-cMSC-EVs offer a more feasible and cost-effective subpopulation for isolation and follow the GMP standard, recommended to utilize this fraction for therapeutic application.
{"title":"Comparative effects of various extracellular vesicle subpopulations derived from clonal mesenchymal stromal cells on cultured fibroblasts in wound healing-related process","authors":"Hedie Poorkazem , Maryam Saber , Azadeh Moradmand , Saeed Yakhkeshi , Homeyra Seydi , Ensiyeh Hajizadeh-Saffar , Faezeh Shekari , Seyedeh-Nafiseh Hassani","doi":"10.1016/j.biocel.2025.106737","DOIUrl":"10.1016/j.biocel.2025.106737","url":null,"abstract":"<div><h3>Introduction</h3><div>Non-healing wounds pose significant challenges and require effective therapeutic interventions. Extracellular vesicles (EVs) have emerged as promising cell-free therapeutic agents in tissue regeneration. However, the functional differences between different subpopulations of EVs in wound healing remain understudied. This study aimed to evaluate the effects of two distinct subpopulations of clonal mesenchymal stromal cells (cMSC)-derived EVs (cMSC-EVs), namely 20 K and 110K-cMSC-EVs, primarily on <em>in vitro</em> wound healing process, providing fast and cost-effective alternatives to animal models.</div></div><div><h3>Methods</h3><div>In vitro assays were conducted to compare the effects of 20 K and 110K-cMSC-EVs, isolated through high-speed centrifugation and differential ultracentrifugation, respectively. For evaluation the main mechanisms of wound healing, including cell proliferation, cell migration, angiogenesis, and contraction. Human dermal fibroblasts (HDF) were considered as the main cells for analysis of these procedures. Moreover, gene expression analysis was performed to assess the impact of these EV subpopulations on the related process of wound healing on HDF.</div></div><div><h3>Results</h3><div>The results demonstrated that both 20 K and 110K-cMSC-EVs exhibited beneficial effects on cell proliferation, cell migration, angiogenesis, and gel contraction. RT-qPCR revealed that both EV types downregulated interleukin 6 (<em>IL6</em>), induced proliferation by upregulating proliferating cell nuclear antigen <em>(PCNA)</em>, and regulated remodeling by upregulating matrix metallopeptidase 1 (<em>MMP1</em>) and downregulating collagen type 1 (<em>COL1</em>).</div></div><div><h3>Discussion</h3><div>This study highlights the effects of both 20 K and 110K-cMSC-EVs on the potency of HDFs in wound healing-related process. As the notable finding, 20K-cMSC-EVs offer a more feasible and cost-effective subpopulation for isolation and follow the GMP standard, recommended to utilize this fraction for therapeutic application.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"180 ","pages":"Article 106737"},"PeriodicalIF":3.4,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015486","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}
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