BioFactors最新文献

{"title":"Optimizing Alternating Current Electrical Stimulation Parameters to Enhance Osteoblasts Differentiation","authors":"Jesús Bocio-Núñez,&nbsp;Mª. José Montoya-García,&nbsp;Mª. Ángeles Vázquez-Gámez,&nbsp;Daniel Martín,&nbsp;Pedro Chacón,&nbsp;Miguel Ángel Rico,&nbsp;Miguel Ángel Colmenero,&nbsp;Alberto Yufera,&nbsp;Mercè Giner","doi":"10.1002/biof.70097","DOIUrl":"10.1002/biof.70097","url":null,"abstract":"<p>Electrical stimulation (ES) has emerged as a promising technique in the field of bioengineering and biomedicine, particularly in bone regeneration and cell differentiation. ES using alternating current (AC) is based on the periodic reversal of current direction, which generates oscillating electric fields. The application of an electric field has effects on cell growth and differentiation, as well as on morphology and migration. This study aimed to explore the effect of applying AC electrostimulation within the proliferation, differentiation, and morphology process of osteoblastic cells. The electrical stimulation signals were daily applied for 3 h during 14 days. Different frequencies were tested (1 Hz, 10 Hz, 100 Hz, and 1 kHz), with amplitudes of 125, 250, 500, 750, 1000, and 1500 mV/mm. Cell viability was estimated using the AlamarBlue, and MC3T3-E1 differentiation levels were evaluated through alkaline phosphatase (ALP) activity. <i>RUNX2</i>, <i>OSX</i>, <i>ALP</i>, <i>OPG</i>, and <i>RANKL</i> gene expression was assessed by RT-PCR. Morphological analysis was performed through cell transfection followed by immunofluorescence. Statistical analysis was conducted by SPSS.23 and graphs generated through Graph-pad. Viability and ALP activity were optimal at 10 Hz. Once the frequency was defined, <i>RUNX2</i>, <i>OSX</i>, <i>ALP</i>, <i>OPG</i>, and <i>RANKL</i> gene expression revealed an increase in the differentiation and osteogenic activity levels at 10 Hz and 500–750 mV/mm. As well as, morphological studies showed an increase in the area, pseudopodia length, and numbers at 500 mV 10 Hz conditions. The optimal ES condition to differentiate MC3T3-E1 cells is 10 Hz 500–750 mV/mm. Electrostimulation has emerged as a promising technique in the field of bioengineering and biomedicine, particularly in bone regeneration and cell early maturation.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://iubmb.onlinelibrary.wiley.com/doi/epdf/10.1002/biof.70097","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147670106","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":"Eupatilin Ameliorates Sepsis-Induced Myocardial Injury by Targeting the KAT5-H3K27la Epigenetic Axis","authors":"Qianqian Du,&nbsp;Shuwan Hou,&nbsp;Minfu Liu,&nbsp;Jiaqin Wu,&nbsp;Huiming Yu,&nbsp;Fan Feng,&nbsp;Huaping Liang,&nbsp;Chunli Wang,&nbsp;Kang Xu,&nbsp;Qingjia Chi","doi":"10.1002/biof.70094","DOIUrl":"10.1002/biof.70094","url":null,"abstract":"<div>\u0000 \u0000 <p>Sepsis induced myocardial injury (SIMI) remains a life threatening complication with mortality rates exceeding 40% to 50%, yet effective therapies are lacking. This study investigates the cardioprotective effects of eupatilin (EUP), a bioactive flavonoid derived from Artemisia argyi, and reveals a previously unrecognized mechanism involving selective modulation of KAT5 mediated histone H3K27 lactylation (H3K27la). Using an LPS induced murine model and TNF-α stimulated human AC16 cardiomyocytes, we evaluated cardiac function, inflammatory responses, and apoptotic pathways through dose response analyses. Multi omics approaches including RNA seq, metabolomics, ChIP seq, and molecular docking were integrated to dissect the pharmacodynamic profile of EUP. EUP conferred concentration dependent cardioprotection with optimal effects at 25 μM. Compared with conventional glucocorticoid therapy, EUP showed enhanced target selectivity, markedly reducing pro inflammatory cytokines such as TNF-α, IL-1β, and IL-6 while improving cardiac function parameters including ejection fraction and fractional shortening. Mechanistically, EUP bound KAT5 with high affinity, suppressed its lactylation activity, and reduced H3K27la enrichment at the promoters of inflammatory genes. Metabolic flux analysis further indicated that EUP inhibited glycolytic lactate production and restored oxidative phosphorylation. Together, these findings identify EUP as a natural modulator of the KAT5-H3K27la axis, addressing both metabolic dysregulation and epigenetic reprogramming in SIMI. With a favorable pharmacokinetic profile and superior target specificity relative to standard immunosuppressive regimens, EUP holds promise for clinical translation in sepsis associated cardiac dysfunction.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580071","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148098405","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148097804","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":"Is There an Ace Up One's Sleeve in the Preanalytical Phase of the Circulating Tumor DNA Analysis?","authors":"Juscelino Carvalho de Azevedo Junior,&nbsp;Douglas Rafael da Cruz Carneiro,&nbsp;Fernanda Jardim da Silva,&nbsp;Ana Beatriz Lima Belicha,&nbsp;Anna Carolina Lima Rodrigues,&nbsp;Williams Fernandes Barra,&nbsp;Alessandro Leal,&nbsp;Danielle Queiroz Calcagno","doi":"10.1002/biof.70095","DOIUrl":"10.1002/biof.70095","url":null,"abstract":"<p>Circulating tumor DNA (ctDNA) analysis has emerged as a pivotal minimally invasive tool for early detection, monitoring, and treatment stratification in cancer patients. However, the accuracy and reliability of ctDNA assays are profoundly influenced by preanalytical variables. This review discusses the impact of biological features (circadian rhythm, age, and sex), lifestyle factors (diet, smoking, and physical activity), as well as technical aspects such as hemolysis, leukocyte lysis, and delayed plasma separation on ctDNA integrity and concentration. Fluctuations in ctDNA levels driven by these factors highlight the need for clear guidelines regarding precollection timing, dietary restrictions, and sample processing. Furthermore, the adoption of harmonized protocols is essential to reduce variability and improve reproducibility across clinical and research settings.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13033619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571991","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148093640","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":"L-Dopa Decarboxylase Mediates Apoptosis Through Regulation of PI3K/AKT Pathway in Response to DENV Infection","authors":"Evangelos Korakidis,&nbsp;Eirini Kyriakopoulou,&nbsp;Katerina I. Kalliampakou,&nbsp;George Mpekoulis,&nbsp;Iris Kolida,&nbsp;Eirini P. Kollia,&nbsp;Elli-Anna Stylianaki,&nbsp;Vassiliki Vassilaki,&nbsp;Konstantina Koukoutsi,&nbsp;Despoina P. Kiouri,&nbsp;Georgios C. Batsis,&nbsp;Sofia Marka,&nbsp;Dionysis Kefallinos,&nbsp;Despoina Smirlis,&nbsp;Evangelia Xingi,&nbsp;Marianna H. Antonelou,&nbsp;Diamantis Sideris,&nbsp;Christos T. Chasapis,&nbsp;Konstantinos Kambas,&nbsp;Dido Vassilacopoulou,&nbsp;Niki Vassilaki","doi":"10.1002/biof.70093","DOIUrl":"10.1002/biof.70093","url":null,"abstract":"<div>\u0000 \u0000 <p>L-dopa decarboxylase (DDC) is the biosynthetic enzyme of dopamine and serotonin. Although DDC has been originally studied for its role in neurotransmission, it has also been detected in peripheral organs, where it is implicated in cellular homeostasis. DDC has been identified by our research team as a negative regulator of dengue virus (DENV) replication in liver cells. The latter has been attributed, at least in part, to the physical interaction of DDC protein with phosphatidylinositol 3-kinase (PI3K), and its biosynthetic function. PI3K/AKT signaling and cell survival are manipulated by DENV to favor its replication. Based on the above, we investigated whether DDC exerts its antiviral activity against DENV propagation through modulation of DENV-induced cell death and especially apoptosis. Specifically, <i>DDC</i> silencing in Huh7.5 cells (shDDC) significantly reduced virus-induced cytopathic effect compared to the control cells (shControl). This finding was accompanied by suppression of both early and later stages of apoptosis in the silenced cells, as shown by Annexin V/PI staining and TUNEL assay, respectively. Accordingly, upon infection, shDDC cells showed suppressed activation of key caspases, BCL-2 family members and TRAIL-receptor genes that modulate the apoptotic cascade, compared to the control cells. Moreover, mitochondrial analysis in DENV-infected cells revealed that, upon <i>DDC</i> silencing, a less pronounced disruption of mitochondrial membrane potential and network integrity, higher respiratory capacity, lower ROS production, and reduced cytochrome c release were observed. As the PI3K/AKT pathway is known to be affected by both DENV and DDC, next we assessed whether DDC is involved in the virus-induced apoptosis through this axis. For this, we quantified the reduction of p-AKT and p-mTOR levels caused by DENV infection in the two cell lines, which was found greater in the shControl cells. Finally, chemical inhibition of AKT phosphorylation abolished the differences in cell viability and apoptosis between the two cell lines. In total, our findings highlight the suppressive role of DDC against DENV replication by modulating the PI3K/AKT-dependent apoptotic signaling.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147526096","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148084082","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":"ETV1 Promotes Glioma Progression via miR-3175/STEAP2 Axis","authors":"Zichen Liu,&nbsp;Wenshuai Deng,&nbsp;Zuoxiang Dong,&nbsp;Peng Sun","doi":"10.1002/biof.70090","DOIUrl":"10.1002/biof.70090","url":null,"abstract":"<div>\u0000 \u0000 <p>Glioblastoma is lethal brain tumor with dismal prognosis. ETV1, an ETS family transcription factor, has been implicated in multiple malignancies, yet its precise role and regulatory mechanisms in glioma progression remain incompletely defined. This study investigated the role of ETV1 in maintaining the malignant phenotype of high-grade gliomas through a novel regulatory axis involving microRNA-3175 (miR-3175) and STEAP2. ETV1 expression was analyzed in TCGA glioma datasets (<i>n</i> = 692) and 85 patient tissue specimens using bioinformatics, quantitative RT-PCR, Western blotting, and immunohistochemistry. ETV1 function was assessed through gain-of-function and loss-of-function studies in glioma cell lines (U251, A172) and validated in nude mouse xenografts with bioluminescence imaging. The ETV1-miR-3175-STEAP2 regulatory axis was characterized using chromatin immunoprecipitation, luciferase reporter assays, biotin-streptavidin pulldown, RNA immunoprecipitation, and rescue experiments. ETV1 was significantly upregulated in gliomas, with expression correlating to tumor grade and reduced overall patient survival. ETV1 overexpression promoted glioma cell proliferation, migration, and invasion in vitro and enhanced tumor growth while reducing survival in vivo, with elevated bioluminescence radiance indicating enhanced tumorigenicity, whereas ETV1 knockdown produced opposite effects and diminished bioluminescent signals. ETV1 transcriptionally activated miR-3175 through direct binding to its promoter. miR-3175 directly targeted and suppressed STEAP2 expression via conserved 3′UTR binding sites. STEAP2 functioned as a tumor suppressor; overexpression inhibited malignant phenotypes. Rescue experiments confirmed miR-3175 and STEAP2 mediate ETV1-driven glioma progression through a functional ETV1/miR-3175/STEAP2 regulatory axis. This study revealed a novel ETV1/miR-3175/STEAP2 regulatory axis driving glioma tumorigenesis and identified potential therapeutic targets for intervention.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147484330","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148082866","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}