Trifuhalol A (TFA), a phlorotannin derived from the edible brown seaweed Agarum cribrosum, has been reported to exert diverse physiological activities, yet its anti-diabetic mechanism remains unclear. This study systematically investigates the multi-targeted anti-diabetic effects of TFA, with a particular focus on enhancing glucose uptake and protecting pancreatic islets. In vitro enzyme inhibition assays demonstrated that TFA significantly inhibited the activities of α-glucosidase and α-amylase, indicating its potential to attenuate postprandial glycemic excursions by modulating carbohydrate hydrolysis. Additionally, TFA effectively suppressed the formation of advanced glycation end-products (AGEs), potentially reducing the risk of diabetes-associated complications. Mechanistically, TFA enhanced glucose uptake in C2C12 myotubes by activating the PI3K/Akt and AMPK signaling pathways, which in turn promoted the translocation of glucose transporter type 4 (GLUT4) to the plasma membrane, thereby facilitating cellular glucose utilization and insulin sensitivity. Furthermore, in vivo investigations using an alloxan-induced type 1 diabetic zebrafish further confirmed the bioefficacy of TFA, as evidenced by its capacity to reduce hyperglycemia, alleviate oxidative stress, and protect pancreatic islets, without eliciting observable systemic toxicity. Taken together, these findings provide both mechanistic and functional evidence supporting TFA as a safe and potent multi-target bioactive compound with promising applications in the development of functional foods and therapeutic strategies for diabetes management.
{"title":"Multi-Targeted Anti-Diabetic Effects of Trifuhalol A From Edible Seaweed via Glycation Inhibition, Glucose Uptake Enhancement and Pancreatic Islet Protection.","authors":"Dandan Xiao, Jia Fu, Aaron Taehwan Kim, Nisansala Madushani Liyanage, Fengqi Yang, You-Jin Jeon","doi":"10.1002/biof.70081","DOIUrl":"https://doi.org/10.1002/biof.70081","url":null,"abstract":"<p><p>Trifuhalol A (TFA), a phlorotannin derived from the edible brown seaweed Agarum cribrosum, has been reported to exert diverse physiological activities, yet its anti-diabetic mechanism remains unclear. This study systematically investigates the multi-targeted anti-diabetic effects of TFA, with a particular focus on enhancing glucose uptake and protecting pancreatic islets. In vitro enzyme inhibition assays demonstrated that TFA significantly inhibited the activities of α-glucosidase and α-amylase, indicating its potential to attenuate postprandial glycemic excursions by modulating carbohydrate hydrolysis. Additionally, TFA effectively suppressed the formation of advanced glycation end-products (AGEs), potentially reducing the risk of diabetes-associated complications. Mechanistically, TFA enhanced glucose uptake in C2C12 myotubes by activating the PI3K/Akt and AMPK signaling pathways, which in turn promoted the translocation of glucose transporter type 4 (GLUT4) to the plasma membrane, thereby facilitating cellular glucose utilization and insulin sensitivity. Furthermore, in vivo investigations using an alloxan-induced type 1 diabetic zebrafish further confirmed the bioefficacy of TFA, as evidenced by its capacity to reduce hyperglycemia, alleviate oxidative stress, and protect pancreatic islets, without eliciting observable systemic toxicity. Taken together, these findings provide both mechanistic and functional evidence supporting TFA as a safe and potent multi-target bioactive compound with promising applications in the development of functional foods and therapeutic strategies for diabetes management.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 1","pages":"e70081"},"PeriodicalIF":5.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146148795","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}
β-Secretase (BACE1) is the key enzyme responsible for generating amyloid-β (Aβ) peptides, whose aggregation and plaque formation are major hallmarks of Alzheimer's disease (AD). Owing to its central role in Aβ production, BACE1 has become a widely studied therapeutic target in the search for disease-modifying treatments for AD. However, evidence of numerous physiological substrates indicates that BACE1 participates in diverse biological processes, from the development and maintenance of the nervous system through control of neuronal differentiation and axonal myelination to immune response mediation by promotion of cell–cell interactions. These functions prompted research into the enzyme's role in other neurodegenerative disorders such as Parkinson's disease, Niemann–Pick type C disease, and Creutzfeldt–Jakob disease, whose pathophysiology includes aberrant protein aggregation and/or cognitive decline leading to dementia as seen in AD, as well as in neurological conditions such as schizophrenia and epilepsy, which are characterized by impaired neurotransmission and seizures, respectively. This review summarizes current knowledge on BACE1 substrates involved in nervous system regulation and immune response, highlights its roles at the molecular and genetic levels across aforementioned disorders, and outlines outcomes from clinical trials of BACE1 inhibitors.
{"title":"BACE1: Biological Functions and Involvement in the Pathophysiology of Alzheimer's Disease and Other Neurological Disorders","authors":"Marija Bartolić, Anita Bosak","doi":"10.1002/biof.70071","DOIUrl":"10.1002/biof.70071","url":null,"abstract":"<div>\u0000 \u0000 <p>β-Secretase (BACE1) is the key enzyme responsible for generating amyloid-β (Aβ) peptides, whose aggregation and plaque formation are major hallmarks of Alzheimer's disease (AD). Owing to its central role in Aβ production, BACE1 has become a widely studied therapeutic target in the search for disease-modifying treatments for AD. However, evidence of numerous physiological substrates indicates that BACE1 participates in diverse biological processes, from the development and maintenance of the nervous system through control of neuronal differentiation and axonal myelination to immune response mediation by promotion of cell–cell interactions. These functions prompted research into the enzyme's role in other neurodegenerative disorders such as Parkinson's disease, Niemann–Pick type C disease, and Creutzfeldt–Jakob disease, whose pathophysiology includes aberrant protein aggregation and/or cognitive decline leading to dementia as seen in AD, as well as in neurological conditions such as schizophrenia and epilepsy, which are characterized by impaired neurotransmission and seizures, respectively. This review summarizes current knowledge on BACE1 substrates involved in nervous system regulation and immune response, highlights its roles at the molecular and genetic levels across aforementioned disorders, and outlines outcomes from clinical trials of BACE1 inhibitors.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145802932","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}
J. Wang, J. Wang, Y. Liu, B, Ji, B. Ding, Y. Wang, et al., “Knockdown of Integrin β1 Inhibits Proliferation and Promotes Apoptosis in Bladder Cancer Cells,” BioFactors 51, no. 1 (2025): e2150, https://doi.org/10.1002/biof.2150.
In the originally published article, author Yang Liu's affiliation was incorrect. The correct affiliation is given below. This has been corrected in the online version of the article.
Incorrect:
Yang Liu1,2
1Department of Urology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
2Department of Urology, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China
Correct:
Yang Liu2
2Department of Urology, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China
{"title":"Correction to “Knockdown of Integrin β1 Inhibits Proliferation and Promotes Apoptosis in Bladder Cancer Cells”","authors":"","doi":"10.1002/biof.70068","DOIUrl":"10.1002/biof.70068","url":null,"abstract":"<p>J. Wang, J. Wang, Y. Liu, B, Ji, B. Ding, Y. Wang, et al., “Knockdown of Integrin β1 Inhibits Proliferation and Promotes Apoptosis in Bladder Cancer Cells,” <i>BioFactors</i> 51, no. 1 (2025): e2150, https://doi.org/10.1002/biof.2150.</p><p>In the originally published article, author Yang Liu's affiliation was incorrect. The correct affiliation is given below. This has been corrected in the online version of the article.</p><p>Incorrect:</p><p>Yang Liu<sup>1,2</sup></p><p><sup>1</sup>Department of Urology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China</p><p><sup>2</sup>Department of Urology, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China</p><p>Correct:</p><p>Yang Liu<sup>2</sup></p><p><sup>2</sup>Department of Urology, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China</p><p>We apologize for this error.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://iubmb.onlinelibrary.wiley.com/doi/epdf/10.1002/biof.70068","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145721079","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}
Gaia Giannitti, Kinga Kamińska, Sara Marchesi, Riccardo Garavaglia, Ivan Preosto, Małgorzata Grzesiak, Fabrizio Fontana
There is consistent evidence of an association between obesity and the risk of prostate cancer (PCa). A crosstalk between PCa and adipocytes has been highlighted; however, the role of extracellular vesicles (EVs) in this communication still needs to be elucidated. Herein, we demonstrated that PCa EVs can trigger lipolysis in 3T3-L1 adipose cells, by downregulating G0/G1 switch protein 2 (G0S2), inducing adipose triglyceride lipase (ATGL) expression and activating the cyclic AMP (cAMP)/protein kinase A (PKA)/hormone-sensitive lipase (HSL) signaling pathway. Interestingly, we showed that the free fatty acids (FFAs) released from the EV-treated adipocytes could increase PCa cell proliferation and clonogenic ability. Moreover, they promoted tumor cell migration and invasion, while parallelly reducing the induction of anoikis. Mechanistically, FFAs were found to trigger Akt activation, and pharmacological inhibition of this protein by BEZ235 could successfully counteract their cancer-promoting effects. Collectively, these results support the presence of an EV-driven bidirectional interplay between PCa cells and adipocytes, which reprograms the latter toward a lipolytic, tumor-promoting phenotype.
{"title":"Extracellular Vesicles Released From Prostate Cancer Cells Confer Pro-Tumor Properties to Adipocytes by Stimulating Lipolysis","authors":"Gaia Giannitti, Kinga Kamińska, Sara Marchesi, Riccardo Garavaglia, Ivan Preosto, Małgorzata Grzesiak, Fabrizio Fontana","doi":"10.1002/biof.70067","DOIUrl":"10.1002/biof.70067","url":null,"abstract":"<p>There is consistent evidence of an association between obesity and the risk of prostate cancer (PCa). A crosstalk between PCa and adipocytes has been highlighted; however, the role of extracellular vesicles (EVs) in this communication still needs to be elucidated. Herein, we demonstrated that PCa EVs can trigger lipolysis in 3T3-L1 adipose cells, by downregulating G0/G1 switch protein 2 (G0S2), inducing adipose triglyceride lipase (ATGL) expression and activating the cyclic AMP (cAMP)/protein kinase A (PKA)/hormone-sensitive lipase (HSL) signaling pathway. Interestingly, we showed that the free fatty acids (FFAs) released from the EV-treated adipocytes could increase PCa cell proliferation and clonogenic ability. Moreover, they promoted tumor cell migration and invasion, while parallelly reducing the induction of anoikis. Mechanistically, FFAs were found to trigger Akt activation, and pharmacological inhibition of this protein by BEZ235 could successfully counteract their cancer-promoting effects. Collectively, these results support the presence of an EV-driven bidirectional interplay between PCa cells and adipocytes, which reprograms the latter toward a lipolytic, tumor-promoting phenotype.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://iubmb.onlinelibrary.wiley.com/doi/epdf/10.1002/biof.70067","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145740910","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}
After Alzheimer's disease, Parkinson's disease (PD) is the second most common neuropathological condition. It is a progressive degenerative disease at superannuation that affects the central nervous system (CNS) and slowly disable patients doing regular activities like walking, speaking, and writing. Early diagnosis of this disease helps to manage the patients and provide them therapy effectively. From the past few years, gait, electroencephalogram (EEG) signals and speech signals have been inspected to detect this disease at an early stage, out of which the most frequently considered one is speech signal, as it is reported by the researchers that 90% of the PD patients suffer from speech disorders. Also, speech signal analysis is a non-invasive and cost-effective method to detect PD at an early stage, and it helps to build telediagnosis models for prediction. Classical speech signal processing methodologies adopted in PD detection sometimes suffer from inadequate understanding of the effect of PD speech generation models and how that is reflected on speech signals captured from the PD patients. Artificial intelligence (AI) based methods attempts to learn those models from the given data in the best possible way to distinguish PD patients from the healthy controls. This paper's primary goal is to survey AI methodologies to detect PD using speech signals as reported in the publications between 2020 and 2024. As deep learning (DL) is a subset of machine learning (ML) and ML is a subset of AI, we consider 55 research publications related to ML and DL methods adopted for speech signal-based PD diagnosis. All the articles were published by IEEE and we have considered key words like “Machine learning approaches in Parkinson's disease detection from speech signals,” “Application of Deep learning in Parkinson Disease detection from speech signals,” “Artificial Intelligence in Parkinson's disease detection”; to find the articles reviewed in this study. This comprehensive review article reveals that both ML and DL algorithms have demonstrated encouraging outcomes, and the need of focused effort on more explainable AI based methods that can be clinically interpreted and hence potentially can be trusted for early diagnosis of Parkinson's disease.
{"title":"Artificial Intelligence for Detection of Parkinson's Disease From Speech Signals—A Comprehensive Review","authors":"Dipdisha Bose, Anirban Mukherjee, Mrinal Acharya, Supriyo Choudhury, Nirmalya Ghosh","doi":"10.1002/biof.70065","DOIUrl":"10.1002/biof.70065","url":null,"abstract":"<div>\u0000 \u0000 <p>After Alzheimer's disease, Parkinson's disease (PD) is the second most common neuropathological condition. It is a progressive degenerative disease at superannuation that affects the central nervous system (CNS) and slowly disable patients doing regular activities like walking, speaking, and writing. Early diagnosis of this disease helps to manage the patients and provide them therapy effectively. From the past few years, gait, electroencephalogram (EEG) signals and speech signals have been inspected to detect this disease at an early stage, out of which the most frequently considered one is speech signal, as it is reported by the researchers that 90% of the PD patients suffer from speech disorders. Also, speech signal analysis is a non-invasive and cost-effective method to detect PD at an early stage, and it helps to build telediagnosis models for prediction. Classical speech signal processing methodologies adopted in PD detection sometimes suffer from inadequate understanding of the effect of PD speech generation models and how that is reflected on speech signals captured from the PD patients. Artificial intelligence (AI) based methods attempts to learn those models from the given data in the best possible way to distinguish PD patients from the healthy controls. This paper's primary goal is to survey AI methodologies to detect PD using speech signals as reported in the publications between 2020 and 2024. As deep learning (DL) is a subset of machine learning (ML) and ML is a subset of AI, we consider 55 research publications related to ML and DL methods adopted for speech signal-based PD diagnosis. All the articles were published by IEEE and we have considered key words like “Machine learning approaches in Parkinson's disease detection from speech signals,” “Application of Deep learning in Parkinson Disease detection from speech signals,” “Artificial Intelligence in Parkinson's disease detection”; to find the articles reviewed in this study. This comprehensive review article reveals that both ML and DL algorithms have demonstrated encouraging outcomes, and the need of focused effort on more explainable AI based methods that can be clinically interpreted and hence potentially can be trusted for early diagnosis of Parkinson's disease.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145666818","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}
I. T. Suryaningtyas, W. K. Jung, and J. Y. Je, “Fucosterol Promotes Browning in Mouse 3T3-L1 AdipocytesThrough HO-1/Nrf2 and AMPK Pathways,” BioFactors 51 (2025): e70035, https://doi.org/10.1002/biof.70035.
In the originally published version of this article, the Western blot panel presented in Figure 5c for the adipogenic and lipogenic markers PPARγ, C/EBPα, SREBP-1, and FAS was assembled using an incorrect image due to a file selection oversight during the final figure preparation stage.
Figure 5c. Western blot analysis of adipogenic and lipogenic markers, including PPARγ, C/EBPα, SREBP-1, and FAS.
We apologize for this error.
I. T. Suryaningtyas， W. K. Jung和J. Y. Je，“focusterol促进小鼠3T3-L1脂肪细胞通过HO-1/Nrf2和AMPK通路褐变”，BioFactors 51 (2025): e70035, https://doi.org/10.1002/biof.70035.In本文最初发表的版本，图5c中显示的脂肪生成和脂肪生成标记物PPARγ， C/EBPα， SREBP-1和FAS的Western blot面板由于在最后的图形准备阶段的文件选择疏忽，使用了不正确的图像。图5 c。脂肪生成和脂肪生成标记物的Western blot分析，包括PPARγ、C/EBPα、SREBP-1和FAS。我们为这个错误道歉。
{"title":"Corrigendum to “Fucosterol Promotes Browning in Mouse 3T3-L1 AdipocytesThrough HO-1/Nrf2 and AMPK Pathways”","authors":"","doi":"10.1002/biof.70060","DOIUrl":"10.1002/biof.70060","url":null,"abstract":"<p>I. T. Suryaningtyas, W. K. Jung, and J. Y. Je, “Fucosterol Promotes Browning in Mouse 3T3-L1 AdipocytesThrough HO-1/Nrf2 and AMPK Pathways,” <i>BioFactors</i> 51 (2025): e70035, https://doi.org/10.1002/biof.70035.</p><p>In the originally published version of this article, the Western blot panel presented in Figure 5c for the adipogenic and lipogenic markers PPARγ, C/EBPα, SREBP-1, and FAS was assembled using an incorrect image due to a file selection oversight during the final figure preparation stage.</p><p>Figure 5c. Western blot analysis of adipogenic and lipogenic markers, including PPARγ, C/EBPα, SREBP-1, and FAS.</p><p>We apologize for this error.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://iubmb.onlinelibrary.wiley.com/doi/epdf/10.1002/biof.70060","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676411","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}
Eunjeong Hong, Garam Yang, Sejong Oh, Eungseok Kim
Lactobacillus johnsonii JNU3402 (LJ3402) has previously been reported to ameliorate diet-induced hepatic steatosis. Because aging is tightly linked to metabolic disease, we hypothesized that LJ3402 might protect against age-related metabolic abnormalities in the liver. This study presents data demonstrating that LJ3402 administration reduces hepatic dysfunction in 24-month-old mice alongside the alleviation of general aging phenotypes. Furthermore, LJ3402 increased hepatic expression of genes involved in mitochondrial function and decreased senescence markers, thereby limiting age-related mitochondrial dysfunction and hepatocyte senescence, contributing to the attenuation of metabolic dysfunction-associated steatotic liver disease (MASLD) progression. Mechanistically, LJ3402 enhanced sirtuin 1 (SIRT1) expression in AML12 hepatocytes by stimulating the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) coactivation of peroxisome proliferator-activated receptor alpha (PPARα). Consequently, SIRT1 suppressed p53 acetylation and activity in senescent AML12 cells, reducing senescence markers and mitochondrial dysfunction. Thus, LJ3402 suppresses mitochondrial dysfunction and senescence of hepatocytes by stimulating the PGC-1α–SIRT1–p53 pathway, reducing age-related hepatic lipid accumulation.
{"title":"Lactobacillus johnsonii JNU3402 Ameliorates Age-Related Liver Dysfunction Through Stimulating PGC-1α-Mediated SIRT1 Expression","authors":"Eunjeong Hong, Garam Yang, Sejong Oh, Eungseok Kim","doi":"10.1002/biof.70069","DOIUrl":"10.1002/biof.70069","url":null,"abstract":"<p><i>Lactobacillus johnsonii</i> JNU3402 (LJ3402) has previously been reported to ameliorate diet-induced hepatic steatosis. Because aging is tightly linked to metabolic disease, we hypothesized that LJ3402 might protect against age-related metabolic abnormalities in the liver. This study presents data demonstrating that LJ3402 administration reduces hepatic dysfunction in 24-month-old mice alongside the alleviation of general aging phenotypes. Furthermore, LJ3402 increased hepatic expression of genes involved in mitochondrial function and decreased senescence markers, thereby limiting age-related mitochondrial dysfunction and hepatocyte senescence, contributing to the attenuation of metabolic dysfunction-associated steatotic liver disease (MASLD) progression. Mechanistically, LJ3402 enhanced sirtuin 1 (SIRT1) expression in AML12 hepatocytes by stimulating the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) coactivation of peroxisome proliferator-activated receptor alpha (PPARα). Consequently, SIRT1 suppressed p53 acetylation and activity in senescent AML12 cells, reducing senescence markers and mitochondrial dysfunction. Thus, LJ3402 suppresses mitochondrial dysfunction and senescence of hepatocytes by stimulating the PGC-1α–SIRT1–p53 pathway, reducing age-related hepatic lipid accumulation.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://iubmb.onlinelibrary.wiley.com/doi/epdf/10.1002/biof.70069","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676398","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}
Natural products are one of the pillars of the drug discovery process, as they provide various scaffolds and diverse biological activity. Cepharanthine (CEP), an alkaloid with a bisbenzyl-isoquinoline skeleton, was isolated from the Stephania genus. The research articles on this alkaloid invariably cite its usefulness due to its biological activity. The relevant keywords were searched in various databases, and two independent reviewers carefully removed the duplicates. The alkaloid exhibits multiple biological activities, such as anti-inflammatory, antioxidant, and anti-viral, apart from anti-cancer activities. It has been used to treat diverse medical conditions, including venomous snakebites. One of the key reactions of this alkaloid involves its ability to reverse multidrug resistance.
{"title":"Cepharanthine as a Biofactor: Molecular Functions, Signaling Pathway Modulation and Therapeutic Relevance in Cancer and Drug Resistance","authors":"Hector Hernández Parra, Héctor Adrián García-Gasca, Sheila Iraís Peña-Corona, Gerardo Leyva-Gómez, Harshada Manish Adhyapak, Nidhishree Adruguli Sudhakara, Nanjangud Venkatesh Anil Kumar, Daniela Calina, Javad Sharifi-Rad","doi":"10.1002/biof.70064","DOIUrl":"https://doi.org/10.1002/biof.70064","url":null,"abstract":"<div>\u0000 \u0000 <p>Natural products are one of the pillars of the drug discovery process, as they provide various scaffolds and diverse biological activity. Cepharanthine (CEP), an alkaloid with a bisbenzyl-isoquinoline skeleton, was isolated from the <i>Stephania</i> genus. The research articles on this alkaloid invariably cite its usefulness due to its biological activity. The relevant keywords were searched in various databases, and two independent reviewers carefully removed the duplicates. The alkaloid exhibits multiple biological activities, such as anti-inflammatory, antioxidant, and anti-viral, apart from anti-cancer activities. It has been used to treat diverse medical conditions, including venomous snakebites. One of the key reactions of this alkaloid involves its ability to reverse multidrug resistance.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145626732","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}
Beatriz Godinho Nascimento, Laís Leite Ferreira, Wagner Corsini, Marina Fiuza Silva, Flávia Pavani Teodoro, Alice Gabrielle Marques Santos, Wagner de Melo Fischer Macedo, Maurício Ariel Rostagno, Marcelo Jose Dias Silva, Carlos Vinicius Expedito de Souza, João Marcos Oliveira-Silva, Marcelo Aparecido da Silva, Angel Maurício Castro-Gamero, Túlio de Almeida Hermes
Soy isoflavones have been extensively studied for their beneficial effects in various diseases. Oxidative stress induces inflammation and myonecrosis in early disease stages in both mdx mice and human patients with Duchenne muscular dystrophy (DMD). This study aimed to investigate the effects of hydroethanolic soy extract (HSE) on dystrophic muscle in mdx mice (a mouse model of DMD), based on the estrogenic action of total soy isoflavones in reducing oxidative stress and inflammation. Phytochemical profiling of HSE was performed by UPLC-PDA-MS, and in silico molecular docking identified putative targets of the main isoflavones. Fourteen-day-old male mdx mice were treated orally with HSE (57 mg/kg/day, ~2 mg/kg genistein) for 45 days. Muscle function, biochemical markers, histopathology, and molecular indicators of inflammation and oxidative stress were evaluated. HSE contained multiple isoflavone classes, showing strong binding affinities for monoamine oxidase and estrogen receptors. The isoflavone-rich HSE showed no toxic effects in mdx mice and demonstrated a clear protective influence on skeletal muscle pathology. Treatment with HSE led to improved muscle integrity, as evidenced by increased muscle strength and a marked reduction in markers of muscle damage such as IgG-positive fibers and serum CK levels. Additionally, HSE effectively mitigated the inflammatory response, with significant downregulation of NF-κB, reduction of inflammatory and macrophage infiltration areas, and attenuation of oxidative stress markers. The antioxidant response was enhanced, reflected by lower ROS production, decreased lipid peroxidation (4-HNE and lipofuscin), and elevated levels of endogenous antioxidants (catalase and GSH). Moreover, HSE appeared to support muscle regeneration by increasing the proportion of centrally nucleated fibers while modulating myogenic regulatory pathways, as indicated by decreased MyoD expression. Isoflavone-rich HSE safely improved muscle integrity and function in mdx mice by attenuating oxidative stress and inflammation through modulation of the ROS/NF-κB pathway. These findings highlight the therapeutic potential of soy-derived isoflavones as a complementary approach for managing DMD.
{"title":"Hydroethanolic Soy Extract Rich in Isoflavones Protects Dystrophic Mutant Mice From Oxidative Stress and Inflammation via the ROS/NF-κB Feedback Pathway","authors":"Beatriz Godinho Nascimento, Laís Leite Ferreira, Wagner Corsini, Marina Fiuza Silva, Flávia Pavani Teodoro, Alice Gabrielle Marques Santos, Wagner de Melo Fischer Macedo, Maurício Ariel Rostagno, Marcelo Jose Dias Silva, Carlos Vinicius Expedito de Souza, João Marcos Oliveira-Silva, Marcelo Aparecido da Silva, Angel Maurício Castro-Gamero, Túlio de Almeida Hermes","doi":"10.1002/biof.70062","DOIUrl":"https://doi.org/10.1002/biof.70062","url":null,"abstract":"<div>\u0000 \u0000 <p>Soy isoflavones have been extensively studied for their beneficial effects in various diseases. Oxidative stress induces inflammation and myonecrosis in early disease stages in both mdx mice and human patients with Duchenne muscular dystrophy (DMD). This study aimed to investigate the effects of hydroethanolic soy extract (HSE) on dystrophic muscle in mdx mice (a mouse model of DMD), based on the estrogenic action of total soy isoflavones in reducing oxidative stress and inflammation. Phytochemical profiling of HSE was performed by UPLC-PDA-MS, and in silico molecular docking identified putative targets of the main isoflavones. Fourteen-day-old male mdx mice were treated orally with HSE (57 mg/kg/day, ~2 mg/kg genistein) for 45 days. Muscle function, biochemical markers, histopathology, and molecular indicators of inflammation and oxidative stress were evaluated. HSE contained multiple isoflavone classes, showing strong binding affinities for monoamine oxidase and estrogen receptors. The isoflavone-rich HSE showed no toxic effects in mdx mice and demonstrated a clear protective influence on skeletal muscle pathology. Treatment with HSE led to improved muscle integrity, as evidenced by increased muscle strength and a marked reduction in markers of muscle damage such as IgG-positive fibers and serum CK levels. Additionally, HSE effectively mitigated the inflammatory response, with significant downregulation of NF-κB, reduction of inflammatory and macrophage infiltration areas, and attenuation of oxidative stress markers. The antioxidant response was enhanced, reflected by lower ROS production, decreased lipid peroxidation (4-HNE and lipofuscin), and elevated levels of endogenous antioxidants (catalase and GSH). Moreover, HSE appeared to support muscle regeneration by increasing the proportion of centrally nucleated fibers while modulating myogenic regulatory pathways, as indicated by decreased MyoD expression. Isoflavone-rich HSE safely improved muscle integrity and function in mdx mice by attenuating oxidative stress and inflammation through modulation of the ROS/NF-κB pathway. These findings highlight the therapeutic potential of soy-derived isoflavones as a complementary approach for managing DMD.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145626671","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}
Age-related macular degeneration (AMD) is a common degenerative disease of the eye that ultimately leads to irreversible vision loss. Asparagine synthase (ASNS) is an aminotransferase, and its low expression is associated with retinal damage. The present study centered on the protective effect of ASNS on retinal epithelial cells. We found that in the AMD cell model, overexpression of ASNS reduced SA-β-gal staining and ROS production, and increased cell viability in H2O2-treated ARPE-19 cells. In addition, overexpression of ASNS increased glucose consumption, lactate production, extracellular acidification rate (ECAR), and oxygen consumption rate (OCR) and enhanced the expression of glycolytic markers. Molecular mechanistic studies revealed that ASNS was highly bound to USP13 protein and increased USP13 expression. Furthermore, ASNS protected the retinal epithelium from oxidative stress damage in an animal model of AMD. Taken together, these findings suggest that the ASNS/USP13 axis plays an important regulatory role in AMD development. Our findings not only emphasized the understanding of the role of glucose metabolism in AMD, but also identified a promising target for future AMD therapy.
{"title":"ASNS Regulates H2O2-Induced Senescence, Oxidative Stress, and Glucose Metabolism in ARPE-19 Cells by Modulating USP13 Expression","authors":"Xiangyang Xin, Xin Zhao, Xiaobo Han, Wenhan Pu","doi":"10.1002/biof.70057","DOIUrl":"10.1002/biof.70057","url":null,"abstract":"<p>Age-related macular degeneration (AMD) is a common degenerative disease of the eye that ultimately leads to irreversible vision loss. Asparagine synthase (ASNS) is an aminotransferase, and its low expression is associated with retinal damage. The present study centered on the protective effect of ASNS on retinal epithelial cells. We found that in the AMD cell model, overexpression of ASNS reduced SA-β-gal staining and ROS production, and increased cell viability in H<sub>2</sub>O<sub>2</sub>-treated ARPE-19 cells. In addition, overexpression of ASNS increased glucose consumption, lactate production, extracellular acidification rate (ECAR), and oxygen consumption rate (OCR) and enhanced the expression of glycolytic markers. Molecular mechanistic studies revealed that ASNS was highly bound to USP13 protein and increased USP13 expression. Furthermore, ASNS protected the retinal epithelium from oxidative stress damage in an animal model of AMD. Taken together, these findings suggest that the ASNS/USP13 axis plays an important regulatory role in AMD development. Our findings not only emphasized the understanding of the role of glucose metabolism in AMD, but also identified a promising target for future AMD therapy.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://iubmb.onlinelibrary.wiley.com/doi/epdf/10.1002/biof.70057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145602068","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}
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