Biomedicines最新文献

{"title":"Effect of Prostaglandin Analogues on Hyaluronan Production of Orbital Fibroblasts.","authors":"Sara Makhoul, Erika Galgoczi, Monika Katko, Janos K Aranyosi, Noémi Széll, Sandor Horvath, Istvan Orsos, Zsanett Molnar, Mariann Fodor, Endre V Nagy, Bernadett Ujhelyi","doi":"10.3390/biomedicines14092128","DOIUrl":"10.3390/biomedicines14092128","url":null,"abstract":"<p><p><b>Background:</b> In thyroid eye disease (TED) pathogenesis, a major contributor is hyaluronan (HA) overproduction by orbital fibroblasts (OF). TED patients often receive prostaglandin analogues (PGA) for elevated intraocular pressure. Their direct effects on OFs, however, remain unclear. <b>Methods:</b> OFs were established from connective tissues obtained from TED patients (<i>n</i> = 4) and non-TED controls (<i>n</i> = 4) during orbital surgeries. HA levels in primary OF culture media, and in the OFs' pericellular coat, were measured by ELISA. Cultures were performed with or without platelet-derived growth factor BB (PDGF-BB) stimulation, and treated for 72 h with 40 µM prostaglandin F2α (PGF2α), latanoprost, bimatoprost or tafluprost. mRNA expressions of HA synthases (HAS1, HAS2, HAS3) and HA-degrading enzymes (HYAL1, HYAL2, CEMIP) were quantified by RT-PCR. Proliferation and metabolic activity were analysed using BrdU incorporation and MTT assays. <b>Results:</b> PGF2α and each PGA reduced HA levels in the pericellular coat (<i>p</i> < 0.001), while only PGAs reduced HA concentration in the culture medium. Tafluprost and latanoprost suppressed PDGF-BB-stimulated HA synthesis to or below unstimulated levels, respectively (<i>p</i> < 0.001). Latanoprost markedly decreased <i>HAS2</i> mRNA expression (<i>p</i> < 0.001), even under PDGF-BB stimulation (<i>p</i> < 0.001). PGF2α and each PGA increased <i>CEMIP</i> mRNA expression (<i>p</i> < 0.001). Latanoprost decreased fibroblast proliferation and metabolic activity with and without PDGF-BB stimulation (<i>p</i> < 0.05). <b>Conclusions:</b> These in vitro findings suggest that PGAs modulate HA turnover in orbital fibroblasts through reduced HA synthesis and potentially enhanced degradation. While these observations are confined to cultured cells, they offer a hypothesis for potential clinical relevance in TED, which requires further in vivo validation.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network Pharmacology Identifies IKBKB as the Primary Target of Sinomenine in Osteoarthritis, with Accuracy Benchmarking and Orthogonal Validation.","authors":"Yifei Wei, Binglang Xiong, Peiwen Liang, Fuying Guo, Hongkai Peng, Guodong Qi, Xiao Xiao","doi":"10.3390/biomedicines14092131","DOIUrl":"10.3390/biomedicines14092131","url":null,"abstract":"<p><p><b>Background/Objective:</b> Osteoarthritis lacks disease-modifying therapy, and NF-κB signaling is among the best-supported intervention points in cartilage. Sinomenine suppresses this pathway in chondrocytes, but only its downstream consequences are known, and network pharmacology rarely measures its own accuracy. <b>Methods:</b> Targets from six prediction resources were intersected with osteoarthritis genes from five databases and with cartilage and synovial differentially expressed genes. Candidates underwent topological analysis and unrestricted enrichment; prioritized targets were examined by docking and triplicate 100 ns molecular dynamics. Benchmarking used a curated bioactivity reference set, with a variant correcting input-validation overlap. Predictions were tested by thermal shift, limited proteolysis, NMR, thermophoresis, and kinase and silencing assays in interleukin-1β-challenged chondrocytes and in mice after medial meniscus destabilization. <b>Results:</b> Integration yielded 96 candidates, 34 transcriptionally corroborated, giving a network of 78 nodes and 241 edges with 12 consensus hubs. NF-κB signaling ranked first among 74 enriched pathways (adjusted <i>p</i> = 2.7 × 10^-20), and convergent criteria prioritized IKBKB, RELA, TNF, PTGS2 and MMP9. Benchmarking gave an area under the curve that fell from 0.81 to 0.74 and sensitivity from 0.73 to 0.57 after correcting for circularity. Sinomenine raised the melting temperature of IKBKB by 4.3 °C, bound it at 8.7 μM and inhibited it ATP-competitively, whereas RELA and CHUK showed no engagement. Nuclear p65 fell from 71.3% to 34.8%, IKBKB silencing abolished most of the MMP13 response, and cartilage damage scores fell from 5.0 to 2.5 at 40 mg/kg. <b>Conclusions:</b> Sinomenine engages IKBKB directly and acts principally at the IKK-dependent activation step. The generating pipeline proved only moderately accurate once circularity was corrected, which argues for reporting such metrics routinely.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunogenic Cell Death in Melanoma Induced by Radiotherapy, Photodynamic Therapy, or Non-Thermal Plasma: The Role of Reactive Oxygen and Nitrogen Species.","authors":"Lisa Van der Heyden, Steve Vanlanduit, Evelien Smits, Annemie Bogaerts, Angela Privat-Maldonado","doi":"10.3390/biomedicines14092135","DOIUrl":"10.3390/biomedicines14092135","url":null,"abstract":"<p><p>Melanoma is characterised by profound immune evasion, and although immune checkpoint inhibitors (ICIs) have transformed clinical management, durable responses remain limited to a subset of patients. Therapies that induce immunogenic cell death (ICD) can enhance anti-tumour immunity by converting dying tumour cells into a source of tumour antigens and danger signals. Radiotherapy (RT), photodynamic therapy (PDT), and non-thermal plasma (NTP) are three pro-oxidant cancer therapies that induce ICD through the generation of reactive oxygen and nitrogen species (RONS), yet these modalities are rarely compared from the perspective of the characteristics of the RONS they produce. This review compares these modalities through a mechanistic framework in which RONS composition, site of generation, lifetime, and diffusion shape the intracellular compartments exposed to oxidative stress and the resulting immune-relevant responses. These characteristics influence which intracellular compartments sustain oxidative damage, thereby shaping endoplasmic reticulum (ER) stress, DNA-damage sensing, and mitochondrial dysfunction. The resulting stress responses can promote damage-associated molecular pattern emission and create conditions that support anti-tumour immune activation. Across the available literature, RT is commonly associated with cytosolic DNA sensing and type I interferon signalling, PDT frequently involves photosensitiser-localisation-dependent ER stress and calreticulin exposure, and NTP can engage several stress pathways in a treatment-parameter-dependent manner. These patterns are overlapping rather than exclusive and depend on the experimental variables of each treatment modality and the tumour biological context. By integrating these mechanistic differences, this review aims to provide a framework for understanding how RONS characteristics shape ICD and its associated anti-tumour immune effects, and how these pro-oxidant therapies may be combined with ICIs in melanoma. Because direct head-to-head comparisons using matched melanoma models and common immunological endpoints remain limited, the proposed modality-associated patterns should be interpreted as context-dependent tendencies rather than a fixed mechanistic hierarchy.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accelerated Wound Healing with a Bilayer Biodegradable Synthetic Matrix in Post-Surgical Diabetes-Related Foot Wounds: A Randomised Controlled Trial.","authors":"Frank P Guerriero, Robyn A Clark, Michelle Miller, Christopher L Delaney","doi":"10.3390/biomedicines14092130","DOIUrl":"10.3390/biomedicines14092130","url":null,"abstract":"<p><p><b>Objective:</b> Early case series using a synthetic bilayer biodegradable matrix (BTM) for diabetes-related neuropathic and neuroischemic foot wounds have shown encouraging outcomes. This study reports results from a single-centre randomised controlled trial evaluating its efficacy in a diabetes-related foot wound cohort. <b>Methods:</b> Participants with moderate-to-severe post-surgical diabetes-related foot wounds (Society of Vascular Surgery WIfI grade 3 or 4) were randomised to BTM plus usual standard of care (USOC) or USOC alone. Primary outcomes were complete wound healing and amputation rates at 12 months; secondary outcomes included time to healing, wound surface area reduction, and infection rates. (Ethics approval 2021/HRE00214, ACTRNNo. 12621001613897). <b>Results:</b> Between May 2022 and September 2024, 64 participants were enrolled (31 BTM + USOC, 30 USOC alone; three did not complete treatment). At 12 months, complete healing occurred in 64.5% of BTM-treated wounds versus 56.7% of USOC wounds (<i>p</i> = 0.53, non-significant), with no significant difference in amputation rates. Post hoc Kaplan-Meier analysis of wounds with a starting surface area greater than 10 cm² showed significantly faster healing in the BTM group (median 219 days) versus USOC alone (312 days, log-rank <i>p</i> = 0.037). A multivariate Cox proportional hazards regression, adjusting for WIfI score, age and starting wound area, confirmed this effect (HR 2.67, 95% CI 1.04-6.86, <i>p</i> = 0.04), with large BTM-treated wounds healed approximately 2.7 times faster than USOC alone. <b>Conclusions:</b> In this exploratory, post hoc analysis, BTM was associated with a reduction in time to complete healing in large post-surgical diabetes-related foot wounds compared with USOC. Given the post hoc nature of this finding, confirmation in a prospectively powered trial is warranted.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ubc9 Mediates SUMO2/3 Modification to Regulate Meiosis in Male Mice.","authors":"Peng Lv, Wenchao Xu, Bin Yang, Dengjianyi Xu, Tao Wang, Jihong Liu, Xiaming Liu","doi":"10.3390/biomedicines14092129","DOIUrl":"10.3390/biomedicines14092129","url":null,"abstract":"<p><p><b>Objective</b>: SUMOylation is a crucial protein modification that regulates various physiological and pathological processes. Ubc9 serves as a key ubiquitin-conjugating enzyme in the process of SUMOylation. However, the role of Ubc9 has yet to be elucidated during spermatogenesis in mammals. <b>Methods</b>: We analyzed the expression profile of Ubc9 in spermatogenesis via quantitative polymerase chain reaction, Western blotting, and meiotic chromosome spread assays. Stra8-EGFPCre mice were used to construct a germ cell-specific conditional Ubc9 knockout mouse model to explore the effects of Ubc9 on male fertility and testicular development. Histological and immunofluorescence staining were performed to observe the development of germ cells and the synaptonemal complex. Moreover, proteomics analysis of the testes was used to detect changes in the control and Ubc9-deficient mice at postnatal day 8. <b>Results</b>: Our results revealed that Ubc9 was highly expressed in the early stage of meiosis. Ubc9 was extensively distributed in the nucleus during meiosis I. Conditional Ubc9 knockout mice with Stra8-EGFPCre resulted in atrophy and reduced volume and mass of testes and complete loss of male fertility. Histological and immunofluorescence staining of testes revealed that the number of germ cells was significantly reduced in the seminiferous tubules in conditional Ubc9 knockout mice at postnatal day 9. Meiotic chromosome spread assays revealed that the synaptonemal complex was abnormally developed and arrested in meiosis I. Moreover, immunofluorescence staining with SUMO1 and SUMO2/3 revealed that Ubc9 regulated the development of the synaptonemal complex mainly via SUMO2/3 rather than SUMO1. The results of the proteomics analysis revealed that the levels of proteins related to the synaptonemal complex, including SYCE1, SYCE2, TEX12, SYCP1, DMC1, and Hormad1, were markedly decreased with Ubc9 deficiency. <b>Conclusions</b>: Taken together, our study demonstrated that Ubc9 influenced the development of the synaptonemal complex during meiosis I and is essential for male fertility in mammals.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhaler Devices as Potential Bacterial Reservoirs: A 30-Day Microbiota Analysis in Non-Cystic Fibrosis Bronchiectasis.","authors":"Jiyeon Baek, Ok Joo Sul, Hye Won Choi, Chaeyeong Jung, Sunju Lee, Jinkyeong Park, Harim Koo, Byungsuk Kwon, Fernando Sergio Leitao Filho, Seung Won Ra","doi":"10.3390/biomedicines14092132","DOIUrl":"10.3390/biomedicines14092132","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Handheld inhalers are essential for the management of bronchiectasis, yet their role as potential microbial reservoirs remains poorly understood. We aimed to characterize and compare the bacterial communities in pressurized metered-dose inhalers (pMDIs) and Respimat^® devices after 30 days of clinical use. <b>Methods:</b> In this 30-day prospective study of eight adults with non-cystic fibrosis bronchiectasis, inhaler devices (six pMDIs and four Respimat^® devices) were analyzed using 16S rRNA gene sequencing of the V4 region. Total bacterial loads (quantitative PCR), α- and β-diversity, differential taxon abundance (ANCOM-BC), and microbial source tracking (SourceTracker2) were compared between device types. <b>Results:</b> After 30 days, pMDIs showed significantly higher bacterial loads than negative controls (adjusted <i>p</i> < 0.05), whereas Respimat^® loads were indistinguishable from those of controls. Compared to Respimat^® devices, pMDIs showed a trend toward microbial simplification (α-diversity: Shannon index, <i>p</i> = 0.08). However, overall community structures did not differ significantly (β-diversity: PERMANOVA, adjusted <i>p</i> = 0.18). ANCOM-BC identified 12 amplicon sequence variants (ASVs) significantly enriched in pMDIs, including one belonging to the genus <i>Pseudomonas</i>, compared to only one ASV in Respimat^® devices. Paired device analyses between two participants who used both devices also revealed differences in the relative abundance of specific potentially pathogenic genera. For instance, in one participant, the pMDI was dominated by <i>Staphylococcus</i> (70.9% vs. 2.5% in the paired Respimat^®). <b>Conclusions:</b> After 30 days of use by patients with bronchiectasis, bacterial DNA was detected in the liquid contents of both inhaler types. Only pMDIs showed a significant increase in total bacterial load relative to negative controls, and pMDIs harboured more differentially abundant ASVs than Respimat^® devices, suggesting that pMDIs may be more susceptible to microbial contamination in patients with non-cystic fibrosis bronchiectasis.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Concurrent Inhibition of AKT and GLUT1 Reveals Endpoint-Specific Effects on Glucose Metabolism and Cell Death in HepG2 Hepatocyte-Derived Cells.","authors":"Abutaleb Asiri, Abeer Al Otaibi, Munazzah Tasleem, Sindiyan Al Shaikh Mubarak, Muwadah Al Said, Yara Al Mihmadi, Badr Al Subei, Abdulaziz Asiri, Ali Al Qarni, Ahmed Bakillah","doi":"10.3390/biomedicines14092133","DOIUrl":"10.3390/biomedicines14092133","url":null,"abstract":"<p><p><b>Background</b>: Glucose handling in hepatocyte-derived cells integrates insulin-responsive AKT signaling with GLUT1-mediated glucose transport, jointly regulating substrate trafficking, glycogen synthesis, and cell survival. MK-2206, a potent allosteric AKT inhibitor, and BAY-876, a highly selective GLUT1 inhibitor, represent targeted approaches to disrupt these processes. However, the consequences of simultaneous inhibition of both nodes in hepatocyte-derived cells remain incompletely understood. <b>Objective</b>: This study aims to evaluate the impact of simultaneous AKT inhibition and GLUT1 blockade on target engagement, cell viability, proliferation, cell death, glucose uptake, and glycogen storage in HepG2 cells. <b>Methods</b>: HepG2 cells were treated with MK-2206, BAY-876, or their combination under basal hyperglycemic and acute insulin-challenged conditions. Multi-model synergy, AKT/GLUT1 pharmacological effects, cell viability, proliferation, cell death, glucose uptake, and glycogen storage were assessed, alongside exploratory molecular docking analyses of both inhibitors against their respective targets. <b>Results</b>: Dual AKT and GLUT1 inhibition produced combination-specific reductions in cell viability and showed a pattern of concurrent antiproliferative effects and increased Annexin V/PI positivity without detectable caspase-3 activation under insulin-challenged conditions. Furthermore, the dual inhibition of AKT signaling and GLUT1-mediated glucose uptake produced combination-specific reductions in basal glycogen content, while glucose uptake reductions showed AKT-dominant patterns without significant combination superiority over MK-2206 alone under either metabolic state. Exploratory molecular docking of MK-2206 and BAY-876 against AKT1 and SLC2A1/GLUT1, respectively, generated computationally predicted binding poses consistent with the established binding modes of these inhibitors. <b>Conclusions</b>: Dual AKT/GLUT1 targeting produces endpoint-specific patterns of pharmacological interaction on insulin-responsive metabolism, proliferation, and cell death in HepG2 hepatocyte-derived cells, distinguishing combination-specific effects from AKT-driven effects. These findings support an endpoint-specific pharmacological framework in which AKT signaling and BAY-876-mediated GLUT1 pharmacological effects jointly influence glucose handling and cell fate in a hepatocyte-derived model.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endogenous Expression of HSP70 and Thioredoxin-1 During Methamphetamine-Induced Degeneration.","authors":"Michela Ferrucci, Gloria Lazzeri, Maria A Giambelluca, Paola Lenzi, Carla L Busceti, Francesco Fornai","doi":"10.3390/biomedicines14092134","DOIUrl":"10.3390/biomedicines14092134","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Although HSP70 and thioredoxin-1 (TRX1) are well known to counteract methamphetamine (METH)-induced neurodegeneration, no evidence on the effects of METH administration concerning the level, localization, and co-expression of HSP70 and/or TRX1 is available. Therefore, in the present study, carried out using methamphetamine-treated PC12 cells, we sought to analyze these effects along with the merging of specific markers for mitochondria, autophagy, lysosomes, and chaperone-mediated autophagy (CMA). <b>Methods</b>: The levels of specific proteins for specific cell compartments were assessed along with their merging. Thus, co-expression of HSP70 and TRX1 with lipidated LC3 (LC3-II), as well as lysosomal markers such as LAMP1 and LAMP2 (a specific marker for CMA), was assessed. Due to severe mitochondrial alterations produced by METH, both MitoTracker green and MitoTracker red were used in these experimental conditions. Light and electron microscopy, including in situ stoichiometry, were used in these experiments. <b>Results:</b> A moderate dose of METH, 100 µM, increases both TRX1 and HSP70; while HSP70 is preferentially co-expressed with the lysosome marker LAMP1, TRX1 is instead co-expressed with the marker LAMP2, which stains for CMA. Both chaperones increase along with cleaved caspase 3 and the autophagosome marker LC3-II. <b>Conclusions:</b> The outcome of the present study applies to METH-induced intoxication and is relevant in the fields of neurodegeneration, acute neuronal injury, and the domain of drug abuse. In fact, suppression of TRX1 enables METH-induced addiction, while overexpression of TRX1 or HSP70 produces the opposite effect.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Mesenchymal Stromal Cells from Bone Marrow and Neonatal Sources: A Comparative In Vitro Study of Their Myelopoietic and Lymphopoietic Supportive Capacity from Hematopoietic Progenitor Cells.","authors":"Ixel Luna-Cañedo, Guadalupe Rosario Fajardo-Orduña, Rosana Pelayo, Juan Carlos Balandrán, Héctor Mayani, Constantino López-Macías, Marco Alejandro Jimenez-Ochoa, Rodolfo Eduardo Pastelin-Ruiz, Juan José Montesinos, Víctor Adrián Cortés-Morales","doi":"10.3390/biomedicines14092124","DOIUrl":"10.3390/biomedicines14092124","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Mesenchymal stromal cells (MSCs) isolated from neonatal sources have been proposed in clinical cell therapy to enhance hematopoietic stem cell transplantation due to their hematopoietic support capacity. Here we evaluated this capacity, particularly the lymphopoietic potential that remains poorly understood. <b>Methods</b>: In this in vitro study, MSCs obtained from bone marrow (BM), and neonatal sources such as placenta (PL), umbilical cord blood (UCB), and Wharton's jelly (WJ) were cultured under the same conditions to compare their abilities to support the formation of myeloid (dendritic cell-like/non-classical monocyte-like) and lymphoid (NK and B cells) lineages from hematopoietic progenitor cells (HPCs). MSCs were co-cultured with CD34⁺CD38^- Lin^- HPCs in the presence or absence of exogenous cytokines; cell lineages obtained were evaluated through flow cytometry. <b>Results</b>: Our results demonstrate that similarly to BM-MSCs, MSCs from neonatal sources have potential to support the formation of dendritic cells, non-classical monocytes, NK, and B cells. However, in contrast to BM-MSCs, neonatal sources favor the generation of lymphoid populations of advanced stages of differentiation. <b>Conclusions</b>: These results indicate that MSCs from neonatal sources have increased lymphopoietic potential compared to BM-MSCs, a finding with significant implications for the selection of MSC sources in clinical trial design.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Echinacoside Alleviates Cisplatin-Induced Acute Kidney Injury by Regulating Bap1 to Inhibit Ferroptosis.","authors":"Lijia Chen, Mingjie Zhang, Miao Chi, Zehua Ye, Bojun Li, Songyuan Yang, Miao Zhang, Wei Dong, Haoyong Li, Xiangjun Zhou","doi":"10.3390/biomedicines14092127","DOIUrl":"10.3390/biomedicines14092127","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Cisplatin-induced acute kidney injury (AKI) is a major adverse complication restricting cisplatin-based chemotherapy. Ferroptosis contributes substantially to proximal tubular epithelial injury during AKI. This work aimed to explore the renoprotective effect of echinacoside (ECH) and its underlying molecular mechanism against cisplatin-provoked AKI. <b>Methods:</b> Eight-week-old male C57BL/6 cisplatin-AKI mice models and HK-2 tubular epithelial cells were used for in vivo and in vitro experiments. Public single-cell transcriptome data and 4D-DIA proteomics were applied to screen key ferroptosis-associated molecules. Functional validation, Western blotting, and molecular docking simulations were performed to characterize the regulatory axis of ECH. <b>Results:</b> ECH ameliorated renal dysfunction, inflammation, and tubular damage in cisplatin-induced AKI. Omics analyses nominated Bap1 as a critical ferroptosis-related differential protein. ECH restored the Slc7a11/GPX4 pathway to restrain lipid peroxidation and mitochondrial ferroptotic damage. Molecular docking predicted a potential interaction between ECH and Bap1. ECH downregulated Bap1 protein expression, and Bap1 overexpression largely abrogated ECH-mediated anti-ferroptosis and renoprotective effects. <b>Conclusions:</b> ECH mitigates cisplatin-triggered AKI, which is associated with Bap1 downregulation, Slc7a11/GPX4 axis restoration, and ferroptosis suppression. The ECH-Bap1-ferroptosis regulatory relationship offers a candidate therapeutic target and natural agent for the preventive treatment of cisplatin-related nephrotoxicity.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}