BioFactors最新文献

{"title":"EPA and DHA acylcarnitines are less cardiotoxic than are saturated and monounsaturated long-chain acylcarnitines","authors":"Edgars Liepinsh,&nbsp;Baiba Gukalova,&nbsp;Kristaps Krims-Davis,&nbsp;Janis Kuka,&nbsp;Aiga Leduskrasta,&nbsp;Stanislava Korzh,&nbsp;Reinis Vilskersts,&nbsp;Marina Makrecka-Kuka,&nbsp;Ilze Konrade,&nbsp;Maija Dambrova","doi":"10.1002/biof.70014","DOIUrl":"10.1002/biof.70014","url":null,"abstract":"<p>Elevated levels of fatty acid-derived long-chain acylcarnitines are detrimental to cardiac health, primarily because of their adverse effects on mitochondrial function and key metabolic pathways in the heart. While trans-fatty acids are considered harmful and omega-3 polyunsaturated fatty acids (PUFAs) are considered beneficial, the specific properties of acylcarnitines derived from these types of fatty acids are not characterized. This study aimed to compare the effects of saturated palmitoylcarnitine (PC), monounsaturated cis-oleoylcarnitine (cis-OC), trans-elaidoylcarnitine (trans-EC), and polyunsaturated eicosapentaenoylcarnitine (EPAC) and docosahexaenoylcarnitine (DHAC) on heart function, cardiac cell viability, mitochondrial functionality, and insulin signaling pathways. Saturated and monounsaturated acylcarnitines, particularly trans-EC, significantly reduced cardiac contractility at concentrations of 8–12 μM, and trans-EC was identified as the most cardiotoxic acylcarnitine. Conversely, the presence of EPAC and DHAC in the perfusion buffer did not impair heart functionality. Saturated and monounsaturated acylcarnitines also drastically reduced H9C2 cell viability and suppressed mitochondrial OXPHOS by up to 70% at 25 μM, whereas PUFA-derived acylcarnitines caused only a 20%–25% reduction in OXPHOS and did not decrease cell viability. Furthermore, PC, cis-OC, and trans-EC significantly inhibited Akt phosphorylation, whereas EPAC and DHAC had a much weaker effect on insulin signaling. In conclusion, saturated and monounsaturated acylcarnitines, particularly trans-EC, exert significant cardiotoxic effects, primarily through the impairment of cardiac mitochondrial function. The omega-3 PUFA-derived acylcarnitines EPAC and DHAC are safe and less likely to damage cardiac mitochondria, cardiac cells, and the heart than other acylcarnitines. PUFA intake might be safer than other long-chain fatty acid-containing lipid sources in patients with FAODs and cardiometabolic diseases.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biof.70014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143793623","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":"Protective effect of melatonin against blue light-induced cell damage via the TRPV1–YAP pathway in cultured human epidermal keratinocytes","authors":"Seoyoung Choi,&nbsp;Eunbi Yu,&nbsp;See-Hyoung Park,&nbsp;Sae Woong Oh,&nbsp;Kitae Kwon,&nbsp;Gyeonghyeon Kim,&nbsp;Heejun Ha,&nbsp;Hee Seon Shin,&nbsp;Seokhyeon Min,&nbsp;Minkyung Song,&nbsp;Jae Youl Cho,&nbsp;Jongsung Lee","doi":"10.1002/biof.70015","DOIUrl":"10.1002/biof.70015","url":null,"abstract":"<p>Although blue light has been known to negatively affect skin cells, its detailed signaling mechanisms and anti-blue light agents have not been clearly elucidated. We investigated the involvement of Yes-associated protein (YAP)-mediated Hippo signaling in blue light-induced apoptosis, depending on the degree of blue light exposure. Additionally, we elucidated the effects of melatonin on blue light-irradiated keratinocytes and examined their action mechanisms. After blue light irradiation, its effects and antagonizing effects of melatonin on cell proliferation, apoptosis, DNA damage, and transient receptor potential vanilloid 1 (TRPV1)/YAP-mediated signaling were examined in HaCaT cells using western blots, image analysis, flow cytometric analysis, co-immunoprecipitation, and immunocytochemistry. We found that melatonin treatment attenuated the reduced cell viability and increased production of reactive oxygen species (ROS) in response to blue light irradiation. In the experiments to investigate the mechanism of action of blue light and melatonin, we found that YAP changed its binding protein, either p73 or TEAD, depending on the degree of blue light exposure. Melatonin treatment reduced blue light-induced phosphorylation of TRPV1 and MST1/2. Upon treatment with capsazepine, an antagonist of TRPV1, MST1/2 activation also reduced. Furthermore, we found that prolonged blue light irradiation induced DNA damage, which in turn induced YAP–p73 nuclear translocation. These effects were also notably attenuated by melatonin. These findings indicate that depending on the duration of blue light irradiation, two different YAP-mediated Hippo signaling pathways are activated. Additionally, these findings suggest that melatonin could be a potential therapeutic agent for blue light-induced skin damage.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biof.70015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770107","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":"Correction to “Zerumbone, a ginger sesquiterpene, inhibits migration, invasion, and metastatic behavior of human malignant glioblastoma multiforme in vitro”","authors":"","doi":"10.1002/biof.70010","DOIUrl":"10.1002/biof.70010","url":null,"abstract":"<p>Jalili-Nik M, Afshari AR, Sabri H, Bibak B, Mollazadeh H, Sahebkar A. Zerumbone, a ginger sesquiterpene, inhibits migration, invasion, and metastatic behavior of human malignant glioblastoma multiforme in vitro. BioFactors. 2021;47:729–39. https://doi.org/10.1002/biof.1756</p><p>The initial submission of this article presented Figure 4 derived from a scanned gel image that was cropped to focus on specific bands. This resulted in concerns regarding the verifiability of the original data. To rectify this issue, the authors have revised the figures in the article to include data from replicates for which source data is available. This updated analysis encompasses results from three independent experiments, which clearly demonstrate that the reduction in MMPs' activity with increasing dosages of Zerumbone is consistently replicated across these experiments. Importantly, the overall significance of the new reanalysis remains consistent with the initial findings, adequately addressing the editors' concerns. The authors ensure the integrity of their published work.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biof.70010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698923","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":"Induction of UBQLN1-mediated PGC1α stability by isoliensinine overcame hypoxia-induced resistance in liver cancer cells","authors":"Xuefen Xu,&nbsp;Wei Li,&nbsp;Ya Zhou,&nbsp;Meihui Wang,&nbsp;Shufan Ji,&nbsp;Siwei Xia,&nbsp;Yang Li,&nbsp;Xiaohan Guo,&nbsp;Sheng Huan,&nbsp;Feixia Wang,&nbsp;Feng Zhang,&nbsp;Haibo Cheng,&nbsp;Guoping Yin,&nbsp;Shizhong Zheng","doi":"10.1002/biof.70008","DOIUrl":"10.1002/biof.70008","url":null,"abstract":"<p>Hypoxia is a key reason for the failure of liver cancer therapy. Emerging evidences indicated that ROS played a crucial role in the sorafenib therapy, and overcoming the reduction in intracellular ROS levels was the first requirement for therapy resistance. Ubiquilin1 (UBQLN1) acted as an oncogene or suppressor gene involved in the protein degradation and abnormal protein aggregation. In this study, we proposed a novel strategy to reverse the hypoxia-induced resistance in liver cancer by isoliensinine (Iso), a significant bioactive compound derived from lotus seed. Based on preliminary screening, we found a significant elevation of UBQLN1 in liver cancer tissues obtained from the TCGA databases and in liver cancer cells under hypoxic model, which contributed to hypoxia-induced sorafenib resistance. Further data suggested that Iso significantly reversed the hypoxia-induced sorafenib resistance through directly targeting UBQLN1 and inducing ROS production. Notably, the ROS elevation induced by Iso could trigger IRP2-induced ferroptosis but remained below the threshold for mitochondrial damage in liver cancer cells. The related mechanism was that Iso reduced the binding between PGC1α and ubiquitin, promoting the stability of the PGC1α protein, which might accelerate mitochondrial energy metabolism. Taken together, our findings not only revealed that UBQLN1 played a critical role in ROS regulation, but also uncovered a previously unrecognized reversal mechanism of Iso in liver cancer, which promoted sensitization of sorafenib-induced ferroptosis by inhibition of UBQLN1/PGC1α pathway under hypoxia.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698924","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}

{"title":"Spatial and single-cell transcriptomic analysis reveals fibroblasts dependent immune environment in colorectal cancer","authors":"Hang Jia,&nbsp;Xianglin Liu,&nbsp;Guimin Wang,&nbsp;Yue Yu,&nbsp;Ning Wang,&nbsp;Tianshuai Zhang,&nbsp;Liqiang Hao,&nbsp;Wei Zhang,&nbsp;Guanyu Yu","doi":"10.1002/biof.70012","DOIUrl":"10.1002/biof.70012","url":null,"abstract":"<p>Colorectal cancer (CRC) exhibits a complex tumor microenvironment with significant cellular heterogeneity, particularly involving cancer-associated fibroblasts that influence tumor behavior and metastasis. This study integrated single-cell RNA sequencing and spatial transcriptomics to dissect fibroblast heterogeneity in CRC. Data processing employed Seurat for quality control, principal component analysis for dimensionality reduction, and t-Distributed Stochastic Neighbor Embedding for visualization. Differentially expressed genes were identified using DESeq2. Immune infiltration was assessed via Single-Sample Gene Set Enrichment Analysis, CIBERSORT, and xCell algorithms. Prognostic genes were identified through univariate Cox regression, followed by consensus clustering and survival analysis. Metabolic pathways were explored using scMetabolism. Experimental validation involved CCK8, scratch, and Transwell assays to evaluate the roles of key genes BGN and CERCAM in CRC cell proliferation and metastasis. Machine learning-driven analysis identified four fibroblast-associated genes (TRIP6, TIMP1, BGN, and CERCAM) demonstrating significant prognostic relevance in CRC. Consensus clustering based on these biomarkers stratified CRC patients into three distinct molecular subtypes (Clusters A–C). Notably, Cluster C exhibited the most unfavorable clinical outcomes coupled with marked upregulation of all four fibroblast-related genes. Comprehensive immune profiling revealed paradoxical features in Cluster C: heightened global immune activation (characterized by substantial leukocyte infiltration) coexisted with specific immunosuppressive elements, including significant enrichment of pro-tumorigenic M0 macrophages, depletion of anti-tumor plasma cells, and resting memory CD4+ T cells, along with coordinated upregulation of multiple immune checkpoint molecules. Computational prediction using the TIDE platform suggested enhanced immunotherapy responsiveness in Cluster C patients. Functional validation demonstrated that knockdown of BGN or CERCAM significantly impaired malignant phenotypes, reducing proliferative capacity, migration potential, and invasive ability. Fibroblasts demonstrate significant heterogeneity within the CRC immune microenvironment, impacting prognosis and therapeutic responses. Key genes BGN and CERCAM emerge as potential immunotherapeutic targets, offering new strategies for precision treatment of CRC.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143594951","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}

{"title":"Molecular and cell phenotype programs in oral epithelial cells directed by co-exposure to arsenic and smokeless tobacco","authors":"Samrat Das,&nbsp;Shefali Thakur,&nbsp;Vincent Cahais,&nbsp;François Virard,&nbsp;Liesel Claeys,&nbsp;Claire Renard,&nbsp;Cyrille Cuenin,&nbsp;Marie-Pierre Cros,&nbsp;Stéphane Keïta,&nbsp;Assunta Venuti,&nbsp;Cécilia Sirand,&nbsp;Akram Ghantous,&nbsp;Zdenko Herceg,&nbsp;Michael Korenjak,&nbsp;Jiri Zavadil","doi":"10.1002/biof.70011","DOIUrl":"10.1002/biof.70011","url":null,"abstract":"<p>Chronic exposure to arsenic can lead to various health issues, including cancer. Concerns have been mounting about the enhancement of arsenic toxicity through co-exposure to various prevalent lifestyle habits. Smokeless tobacco (SLT) products are commonly consumed in South Asian countries, where their use frequently co-occurs with exposure to arsenic from contaminated groundwater. To decipher the in vitro molecular and cellular responses to arsenic and/or smokeless tobacco, we performed temporal multi-omics analysis of the transcriptome and DNA methylome remodeling in exposed hTERT-immortalized human normal oral keratinocytes (NOK), as well as arsenic and/or smokeless tobacco genotoxicity and mutagenicity investigations in NOK cells and in human p53 knock-in murine embryonic fibroblasts (Hupki MEF). RNAseq results from acute exposures of NOK cell to arsenic alone and in combination with smokeless tobacco extract revealed upregulation of genes with roles in cell cycle changes, apoptosis and inflammatory responses. This was in keeping with global DNA hypomethylation affecting genes involved in the same processes after chronic treatment. At the phenotypic level, we observed a dose-dependent decrease in NOK cell viability, induction of DNA damage, cell cycle changes and increased apoptosis, with the most pronounced effects observed under arsenic and SLT co-exposure conditions. Live-cell imaging experiments indicated that the DNA damage likely resulted from induction of apoptosis, an observation validated by a lack of exome-wide mutagenesis in response to chronic exposure to arsenic and/or smokeless tobacco. In sum, our integrative omics study provides novel insights into the acute and chronic responses to arsenic and smokeless tobacco (co-)exposure, with both types of responses converging on several key mechanisms associated with cancer hallmark processes. The resulting rich catalogue of molecular programs in oral cells regulated by arsenic and smokeless tobacco (co-)exposure may provide bases for future development of biomarkers for use in molecular cancer epidemiology studies of exposed populations at risk.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571340","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}

{"title":"Effects of calciprotein particles on EMT induction in an in vitro 3D-cultured proximal tubule epithelial cell model of CKD","authors":"Yeo Min Yoon,&nbsp;Sang-Mi Woo,&nbsp;Hwanuk Guim,&nbsp;Jeong Ah Kim","doi":"10.1002/biof.70009","DOIUrl":"10.1002/biof.70009","url":null,"abstract":"<p>Calciprotein particles (CPPs) are blood-borne circulating nanoparticles composed of calcium phosphate and proteins that are known to exacerbate pathological processes such as chronic kidney disease-mineral bone disorder (CKD-MBD). Despite the significant interest in CKD-MBD pathogenesis, research directly addressing CPP-induced fibrosis in renal proximal tubules is rare, largely owing to the lack of suitable in vitro tissue models. Our study confirmed that 3D-cultured renal proximal tubule epithelial cells (PTECs) exhibited enhanced pathological characteristics compared to 2D-cultured PTECs when treated with CPPs, a key factor in CKD-MBD, and the uremic toxin. 3D-cultured PTECs under CKD-inducing conditions by CPPs were associated with epithelial–mesenchymal transition (EMT), mediated by transforming growth factor-β1 (TGF-β1), with notable changes in early EMT marker expression. Furthermore, this was attributed to increased expression of the calcium-sensing receptor (CASR), a receptor for CPPs, and activation of the downstream cell division control protein 42 (CDC42), leading to EMT progression. This study underscores the potential of PTEC-on-a-chip systems to serve as drug testing models, given the heightened sensitivity of these cells to external environments. This approach provides a better understanding of the pathological features of CKD and could contribute to the development of more effective in vitro models and therapeutics.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biof.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571339","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":"The effect of microbial metabolites from colonic protein fermentation on bacteria-induced cytokine production in dendritic cells","authors":"Zhuqing Xie,&nbsp;Danny Blichfeldt Eriksen,&nbsp;Peter Riber Johnsen,&nbsp;Dennis Sandris Nielsen,&nbsp;Hanne Frøkiær","doi":"10.1002/biof.70007","DOIUrl":"10.1002/biof.70007","url":null,"abstract":"<p>Compared to the well-defined immune-modulating effect of butyrate, the understanding of the effect of other protein fermentation metabolites is limited. This study aimed to investigate the impact of protein-derived metabolites (valerate, branched-chain fatty acids, ammonium, phenol, p-Cresol, indole, and hydrogen sulfide) on cytokine production in murine bone marrow-derived dendritic cells (BMDCs) stimulated with lipopolysaccharides (LPS), <i>Lactobacillus acidophilus</i> NCFM, or <i>Staphylococcus aureus</i> USA300. Some of the metabolites, but not the short-chain fatty acids (SCFAs), strongly affected cell viability. After short-term treatment and depending on the microbial stimulus, SCFAs affected the cytokine profile similarly but weaker than butyrate, as reflected by inhibition of IL-12p70 and IL-10 but enhanced IL-23 (LPS and <i>S. aureus</i> USA300) and IL-1β production. Compared to butyrate, valerate exhibited a weaker and slower effect on cytokine expression. Two-day treatment with valerate and butyrate resulted in similar effects, that is, LPS-induced IL-12 abrogation and IL-10 enhancement, increased aryl hydrocarbon receptor (<i>Ahr</i>) expression, and after LPS stimulation, increased expression of dual specificity phosphatase 1 (<i>Dusp1</i>). In conclusion, SCFAs exhibited low toxicity and modulated microbially stimulated BMDCs. Valerate and butyrate showed the strongest effect, which was dependent on the specific microbial stimulation and the course of the SCFA treatment. Our work adds knowledge regarding the role of protein-derived metabolites from gut bacterial fermentation on the immune system.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biof.70007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475749","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":"Investigating the impact of Ras-related protein RAB7A on colon adenocarcinoma behavior and its clinical significance","authors":"Zhili Shan,&nbsp;Xin Chen,&nbsp;Hong Chen,&nbsp;Xiaojun Zhou","doi":"10.1002/biof.70006","DOIUrl":"10.1002/biof.70006","url":null,"abstract":"<p>The Ras-related protein RAB7A has been implicated in the development and prognosis of various cancers. This study aims to investigate the prognostic significance of RAB7A in colon adenocarcinoma (COAD). We conducted a retrospective cohort study of COAD cases to assess RAB7A expression and its clinical relevance. The chi-square test was employed to establish associations between clinical features and RAB7A expression. Survival analyses, including Kaplan–Meier and Cox regression, were employed to evaluate the impact of RAB7A expression and clinical characteristics on COAD patient outcomes. Furthermore, we validated our clinical findings using The Cancer Genome Atlas (TCGA) dataset. To elucidate the tumor-related role of RAB7A in COAD, we conducted cellular assays and mouse models. Elevated RAB7A expression in COAD tissues exhibited significant associations with tumor size, invasion depth, and lymph node metastasis (all <i>p</i> &lt; 0.05). Univariate and multivariate analyses revealed that high RAB7A expression was significantly correlated with poorer overall survival. In vitro cellular assays, coupled with knockdown strategies, demonstrated that RAB7A promotes COAD tumor proliferation and invasion, a finding further substantiated by in vivo xenograft experiments. RAB7A may serve as a valuable biomarker and potential therapeutic target in the management of COAD.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380757","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}

{"title":"The in vitro and in vivo skin-whitening activity of Ectoine through enhanced autophagy in melanocytes and keratinocytes and zebrafish model","authors":"Wei-Chen Jane,&nbsp;Siang-Jyun Chen,&nbsp;Jhih-Hsuan Hseu,&nbsp;Xuan-Zao Chen,&nbsp;Sudhir Pandey,&nbsp;Hsueh-Wei Chang,&nbsp;Hsin-Ling Yang,&nbsp;You-Cheng Hseu,&nbsp;Yung-Luen Yu","doi":"10.1002/biof.70004","DOIUrl":"10.1002/biof.70004","url":null,"abstract":"<p>Ectoine, a natural bacterial osmolyte, suppressed UVA irradiated-α-melanocyte stimulating hormone (MSH) stimulated melanogenesis through antioxidant Nrf2 pathways in human keratinocytes; however, the underlying skin whitening mechanisms were not elucidated. The depigmenting efficiency of Ectoine (0–400 μM) through antimelanogenesis and melanin degradation by autophagy promotion was investigated in melanoma (B16F10) and melanin-feeding keratinocyte (HaCaT) cells and in vivo zebrafish model. MTT assay, Western blotting, GFP-LC3 puncta, AVO formation, melanin assay, immunofluorescence staining, TEM techniques, siLC3 transfection, and zebrafish model were utilized. Ectoine-induced autophagy in B16F10 and HaCaT cells was shown by enhanced LC3-II accumulation, autophagosome GFP-LC3 puncta, autolysosome AVOs formation, ATG4B downregulation, and Beclin-1/Bcl-2 dysregulation. The immunoprecipitation data revealed that Ectoine increased the association between LC3-II and p62 proteins in B16F10 and HaCaT cells. Importantly, antioxidant NAC pretreatment antagonized the Ectoine-induced ATG4B diminution in B16F10 and HaCaT cells. Ectoine inhibited melanogenesis by suppressing melanosome gp100, tyrosinase, TRP-1/-2, and/or melanin formation via autophagy in α-MSH-stimulated B16F10 and melanin-feeding HaCaT cells. TEM findings displayed that Ectoine increased melanosome-engulfing autophagosomes and autolysosomes in α-MSH-stimulated B16F10 and melanin-feeding HaCaT cells. Ectoine-inhibited melanogenesis in α-MSH-stimulated B16F10 cells and melanin-feeding HaCaT cells was reversed by pretreatment with the autophagy inhibitor 3-MA or LC3 silencing. In vivo study demonstrated that Ectoine (5 mM) suppressed endogenous body pigmentation by antimelanogenesis and melanin degradation through autophagy induction in a zebrafish model. The in vitro and in vivo study demonstrated that Ectoine inhibits melanogenesis and enhances melanin degradation by triggering autophagy. Ectoine could be utilized as a whitening ingredient in cosmetic formulations.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143186511","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}