Frontiers in bioscience (Landmark edition)最新文献

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Dapagliflozin Attenuates Myocardial Inflammation and Apoptosis after Coronary Microembolization in Rats by Regulating the SIRT1/NF-κB Signaling Pathway.
IF 3.3
Frontiers in bioscience (Landmark edition) Pub Date : 2025-03-18 DOI: 10.31083/FBL27082
Tao Li, Chang-Jun Luo, Ze-Qiang Yi, Lang Li
{"title":"Dapagliflozin Attenuates Myocardial Inflammation and Apoptosis after Coronary Microembolization in Rats by Regulating the SIRT1/NF-κB Signaling Pathway.","authors":"Tao Li, Chang-Jun Luo, Ze-Qiang Yi, Lang Li","doi":"10.31083/FBL27082","DOIUrl":"https://doi.org/10.31083/FBL27082","url":null,"abstract":"<p><strong>Background: </strong>Coronary microembolization (CME) often occurs as a serious complication during or after percutaneous coronary intervention (PCI), leading to an impairment in heart function, inflammation, and cell death. Dapagliflozin (DAPA) has been shown to have cardioprotective effects. However, its role and exact mechanism in CME remains unclear.</p><p><strong>Methods: </strong>A preclinical CME model was developed via the administration of microspheres into the left ventricle. In an in vitro model, the CME-created microenvironment was observed by using lipopolysaccharide (LPS) with hypoxic induction on H9C2 cardiomyocytes. Before developing both experimental models, DAPA or the sirtuin 1 (SIRT1) inhibitor \"EX-527\" was administered. Echocardiography, histological examination, and molecular and immunological assays were carried out to assess the levels of cardiac tissue or cardiomyocyte damage, inflammation, and apoptosis.</p><p><strong>Results: </strong>Heart dysfunction and tissue damage caused by CME can be alleviated by pre-treatment with DAPA, which also reduces myocardial inflammation and apoptosis. Moreover, both experimental studies have depicted that DAPA can upregulate the SIRT1 level and downregulate the acetylation and phosphorylation levels of nuclear factor kappa-B (NF-κB) p65. This effect inhibits the induction of NF-κB signaling and mitigates cardiomyocyte damage. However, DAPA's cardioprotective effect was reversed when co-treated with EX-527.</p><p><strong>Conclusions: </strong>DAPA reduces myocardial damage caused by CME by suppressing myocarditis and apoptosis via the SIRT1/NF-κB axis.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 3","pages":"27082"},"PeriodicalIF":3.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Growth Arrest-specific 1 Inhibits Keap1/Nrf2 Signaling Transduction in the Activation of the Ferroptosis Program in Retinal Müller Cells.
IF 3.3
Frontiers in bioscience (Landmark edition) Pub Date : 2025-03-18 DOI: 10.31083/FBL27954
Rongfeng Dai, Yu Qian, Siqi Liu, Xi Zou, Shanshan Sun, Zhuo Sun
{"title":"Growth Arrest-specific 1 Inhibits Keap1/Nrf2 Signaling Transduction in the Activation of the Ferroptosis Program in Retinal Müller Cells.","authors":"Rongfeng Dai, Yu Qian, Siqi Liu, Xi Zou, Shanshan Sun, Zhuo Sun","doi":"10.31083/FBL27954","DOIUrl":"https://doi.org/10.31083/FBL27954","url":null,"abstract":"<p><strong>Background: </strong>Diabetes retinopathy (DR) represents a microvascular disease in diabetes. Growth arrest-specific 1 (GAS1) is differentially expressed in rat retinal Müller cells under high glucose (HG) conditions, and its promotion of ferroptosis contributes to retinal cell death. However, the influence of GAS1 in DR is elusive. Herein, we aimed to investigate the effect and potential mechanism based on GAS1-mediated ferroptosis on DR.</p><p><strong>Methods: </strong>After HG treatment, the differentially expressed genes in rat retinal Müller cells were analyzed by transcriptome sequencing followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses; finally, GAS1 was selected. The effects of GAS1 knockdown/overexpression and nuclear factor erythroid 2-related factor (Nrf2) silencing on viability, apoptosis, lipid peroxidation, Fe<sup>2+</sup>, and oxidative stress levels in HG-induced/transfected Müller cells were measured by Cell Counting Kit-8 (CCK-8) assay, flow cytometry, and commercial reagent kits. The potential effects of GAS1 and Nrf2, especially on GAS1, Nrf2, and Kelch-like ECH-associated protein 1 (Keap1) expressions in cells, were determined by quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot.</p><p><strong>Results: </strong>HG treatment decreased cell viability and glutathione (GSH) levels and increased apoptosis, lipid reactive oxygen species (ROS), glutathione disulfide (GSSG), malondialdehyde (MDA), oxidative stress, and Fe<sup>2+</sup> levels in Müller cells (<i>p</i> < 0.01). HG treatment also upregulated GAS1, Keap1, and total Nrf2 expressions while downregulating nuclear Nrf2 in Müller cells (<i>p</i> < 0.001). GAS1 downregulation enhanced cell viability, GSH levels, and nuclear Nrf2 expression while reducing the levels of apoptosis, lipid ROS, GSSG, MDA, Fe<sup>2+</sup>, Keap1, and total Nrf2 in HG-treated Müller cells (<i>p</i> < 0.001), whereas GAS1 overexpression had the opposite effects. Additionally, Nrf2 silencing reversed the impact of GAS1 overexpression in HG-treated Müller cells (<i>p</i> < 0.05).</p><p><strong>Conclusion: </strong>GAS1 inhibits Keap1/Nrf2 signaling transduction in activating ferroptosis in retinal Müller cells; thus, this study can aid in setting the stage for novel treatment methods against DR.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 3","pages":"27954"},"PeriodicalIF":3.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparative Study of Structural and Functional Rearrangements in Skeletal Muscle Mitochondria of SOD1-G93A Transgenic Mice at Pre-, Early-, and Late-Symptomatic Stages of ALS Progression. SOD1-G93A转基因小鼠骨骼肌线粒体在渐冻症进展前期、早期和晚期的结构和功能重排比较研究
IF 3.3
Frontiers in bioscience (Landmark edition) Pub Date : 2025-03-18 DOI: 10.31083/FBL28260
Natalia V Belosludtseva, Anna I Ilzorkina, Mikhail V Dubinin, Irina B Mikheeva, Konstantin N Belosludtsev
{"title":"Comparative Study of Structural and Functional Rearrangements in Skeletal Muscle Mitochondria of SOD1-G93A Transgenic Mice at Pre-, Early-, and Late-Symptomatic Stages of ALS Progression.","authors":"Natalia V Belosludtseva, Anna I Ilzorkina, Mikhail V Dubinin, Irina B Mikheeva, Konstantin N Belosludtsev","doi":"10.31083/FBL28260","DOIUrl":"https://doi.org/10.31083/FBL28260","url":null,"abstract":"<p><strong>Background: </strong>Amyotrophic lateral sclerosis (ALS) is a progressive multisystem disease characterized by limb and trunk muscle weakness that is attributed, in part, to abnormalities in mitochondrial ultrastructure and impaired mitochondrial functions. This study investigated the time course of structural and functional rearrangements in skeletal muscle mitochondria in combination with motor impairments in Tg (copper-zinc superoxide dismutase enzyme (SOD1) G93A) dl1/GurJ (referred to as SOD1-G93A/low) male mice, a familial ALS model, as compared with non-transgenic littermates.</p><p><strong>Methods: </strong>The neurological status and motor functions were assessed weekly using the paw grip endurance method and the grid suspension test with two-limb and four-limb suspension tasks. Transmission electron microscopy followed by quantitative analysis was performed to study ultrastructural alterations in the quadriceps femoris. Functional analysis of skeletal muscle mitochondria was performed using high-resolution Oxygraph-2k (O2K) respirometry and methods for assessing the calcium retention capacity index and the content of lipid peroxidation products in freshly isolated preparations.</p><p><strong>Results: </strong>Based on the behavioral phenotyping data, specific age groups were identified: postnatal day 56 (P56) (<i>n</i> = 10-11), 84 (P84) (<i>n</i> = 10-11), and 156 (P154) (<i>n</i> = 10-12), representing the pre-symptomatic, early-symptomatic and late-symptomatic stages of ALS progression in SOD1-G93A/low mice, respectively. Electron microscopy showed mosaic destructive changes in subsarcolemmal mitochondria in fibers of the quadriceps femoris from 84-day-old SOD1-G93A/low mice. Morphometric analysis revealed an elevation in the mean size of the mitochondria in SOD1-G93A mice at P84 and P154. In addition, the P154 transgenic group demonstrated a decrease in sarcomere width and the number of mitochondria per unit area. At the symptomatic stage, SOD1-G93A mice exhibited a decreased respiratory control ratio, ADP-stimulated, and uncoupled respiration rates of mitochondria isolated from the quadriceps femoris muscle, as measured by high-resolution respirometry. In parallel, the mitochondria showed lower calcium retention capacity and increased levels of lipid peroxidation products compared with the control.</p><p><strong>Conclusions: </strong>Taken together, these results indicate stage-dependent changes in skeletal muscle mitochondrial ultrastructure and functions associated with defective oxidative phosphorylation, impaired calcium homeostasis, and oxidative damage in the SOD1-G93A/low mouse model, which appears to be a promising direction for the development of combination therapies for ALS.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 3","pages":"28260"},"PeriodicalIF":3.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
3D Bioprinting of Cultivated Meat Followed by the Development of a Fine-Tuned YOLO Model for the Detection and Counting of Lipoblasts, Fibroblasts, and Myogenic Cells.
IF 3.3
Frontiers in bioscience (Landmark edition) Pub Date : 2025-03-18 DOI: 10.31083/FBL36266
Rozaliia Nabiullina, Sergey Golovin, Evgeniya Kirichenko, Mikhail Petrushan, Alexander Logvinov, Marya Kaplya, Darya Sedova, Stanislav Rodkin
{"title":"3D Bioprinting of Cultivated Meat Followed by the Development of a Fine-Tuned YOLO Model for the Detection and Counting of Lipoblasts, Fibroblasts, and Myogenic Cells.","authors":"Rozaliia Nabiullina, Sergey Golovin, Evgeniya Kirichenko, Mikhail Petrushan, Alexander Logvinov, Marya Kaplya, Darya Sedova, Stanislav Rodkin","doi":"10.31083/FBL36266","DOIUrl":"https://doi.org/10.31083/FBL36266","url":null,"abstract":"<p><strong>Background: </strong>Cultured meat holds significant potential as a pivotal solution for producing safe, sustainable, and high-quality protein to meet the growing demands of the global population. However, scaling this technology requires innovative bioengineering approaches integrated with software methods to assess the growth of cell cultures. This study aims to develop a technology for 3D printing a hybrid meat product and subsequently design a finely tuned You Only Look Once (YOLO) model for detecting and counting lipoblasts, fibroblasts, and myogenic cells.</p><p><strong>Methods: </strong>Cultures of multipotent mesenchymal stem cells (MMSCs) and fibroblasts were obtained from the domestic rabbit <i>Oryctolagus cuniculus domesticus</i>. Standard protocols were employed to induce adipogenic and myogenic differentiation from MMSCs. Fibroblasts were isolated from skin biopsy samples. The 3D printing process utilized bioinks. The engineering approach involved the development of a unique print head integrated into a 3D printer. Confocal and transmission electron microscopy of the cells within the construct was performed. A dataset of digital images of lipoblasts, myogenic cells, and fibroblasts was created. Four models based on the YOLOv8-seg architecture were trained on annotated images, implemented in the Telegram bot.</p><p><strong>Results: </strong>Stable cultures of lipoblasts, myogenic cells, and fibroblasts were obtained. 3D-printed tissue constructs composed of rabbit cells, sodium alginate, and sunflower protein were successfully fabricated. A unique print head for a 3D printer was assembled. Confocal microscopy confirmed cell viability within the tissue construct. Ultrastructural analysis revealed dense intercellular contacts and high metabolic activity. The resulting product replicated the organoleptic and structural properties of natural meat. In the IT segment, the single-class model trained on lipoblasts achieved metrics of recall 85%, precision 77%, and mean Average Precision at IoU threshold 0.50 (mAP50) 79%, which improved in the multiclass model to recall 92%, precision 92%, and mAP50 81%. The IT solution was implemented in a Telegram bot capable of detecting and counting different cell types.</p><p><strong>Conclusions: </strong>A 3D tissue construct was achieved. Detailed microscopic analysis demonstrated cell viability and high metabolic activity within the polymerized alginate hydrogel. The engineered tissue product presents a potential alternative to natural meat. Additionally, the trained neural network models, implemented in a Telegram bot, proved effective in monitoring culture growth and identifying cell types in digital images across three cell cultures. As a result, we developed four YOLOv8 models and demonstrated that the multiclass model outperforms the single-class model. However, all models exhibited reduced accuracy in high-density cultures, where overlapping cells led to undercounting.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 3","pages":"36266"},"PeriodicalIF":3.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Chronic Inflammation to Cancer: The Impact of Oxidative Stress on DNA Methylation.
IF 3.3
Frontiers in bioscience (Landmark edition) Pub Date : 2025-03-18 DOI: 10.31083/FBL26142
Olivia M Damiano, Aaron J Stevens, Diane N Kenwright, Annika R Seddon
{"title":"Chronic Inflammation to Cancer: The Impact of Oxidative Stress on DNA Methylation.","authors":"Olivia M Damiano, Aaron J Stevens, Diane N Kenwright, Annika R Seddon","doi":"10.31083/FBL26142","DOIUrl":"https://doi.org/10.31083/FBL26142","url":null,"abstract":"<p><p>The genomic landscape of cancer cells is complex and heterogeneous, with aberrant DNA methylation being a common observation. Growing evidence indicates that oxidants produced from immune cells may interact with epigenetic processes, and this may represent a mechanism for the initiation of altered epigenetic patterns observed in both precancerous and cancerous cells. Around 20% of cancers are linked to chronic inflammatory conditions, yet the precise mechanisms connecting inflammation with cancer progression remain unclear. During chronic inflammation, immune cells release oxidants in response to stimuli, which, in high concentrations, can cause cytotoxic effects. Oxidants are known to damage DNA and proteins and disrupt normal signalling pathways, potentially initiating a sequence of events that drives carcinogenesis. While research on the impact of immune cell-derived oxidants on DNA methylation remains limited, this mechanism may represent a crucial link between chronic inflammation and cancer development. This review examines current evidence on inflammation-associated DNA methylation changes in cancers related to chronic inflammation.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 3","pages":"26142"},"PeriodicalIF":3.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Potential Genetic Approach to Specific Primary Immunodeficiencies: Which Perspectives?
IF 3.3
Frontiers in bioscience (Landmark edition) Pub Date : 2025-03-17 DOI: 10.31083/FBL36795
Giuseppe Murdaca, Francesca Paladin, Sebastiano Gangemi
{"title":"Potential Genetic Approach to Specific Primary Immunodeficiencies: Which Perspectives?","authors":"Giuseppe Murdaca, Francesca Paladin, Sebastiano Gangemi","doi":"10.31083/FBL36795","DOIUrl":"https://doi.org/10.31083/FBL36795","url":null,"abstract":"","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 3","pages":"36795"},"PeriodicalIF":3.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Revisiting the Role of Platelet-Activating Factor in COVID-19-Induced Cardiovascular Complications.
IF 3.3
Frontiers in bioscience (Landmark edition) Pub Date : 2025-03-17 DOI: 10.31083/FBL36981
Smaragdi Antonopoulou
{"title":"Revisiting the Role of Platelet-Activating Factor in COVID-19-Induced Cardiovascular Complications.","authors":"Smaragdi Antonopoulou","doi":"10.31083/FBL36981","DOIUrl":"https://doi.org/10.31083/FBL36981","url":null,"abstract":"","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 3","pages":"36981"},"PeriodicalIF":3.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Possible Role of Platelets in the Development and Progression of Non-Alcoholic Fatty Liver Disease.
IF 3.3
Frontiers in bioscience (Landmark edition) Pub Date : 2025-03-17 DOI: 10.31083/FBL26748
Anna F Sheptulina, Ekaterina O Liusina, Olga A Zlobovskaya, Anton R Kiselev, Oxana M Drapkina
{"title":"Possible Role of Platelets in the Development and Progression of Non-Alcoholic Fatty Liver Disease.","authors":"Anna F Sheptulina, Ekaterina O Liusina, Olga A Zlobovskaya, Anton R Kiselev, Oxana M Drapkina","doi":"10.31083/FBL26748","DOIUrl":"https://doi.org/10.31083/FBL26748","url":null,"abstract":"<p><p>To date, an increasing body of evidence supports the potential role of activated platelets in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). This is likely due to their ability to secrete biologically active substances that regulate liver regeneration processes, ensure hemostasis, and participate in the immune response. Additionally, several studies have demonstrated the efficacy of antiplatelet agents in reducing inflammation, the severity of liver fibrosis, and the progression of fibrosis in non-alcoholic steatohepatitis (NASH). Since NAFLD is not an independent indication for antiplatelet therapy, the primary evidence regarding their efficacy in NAFLD has been derived from studies using animal models of NAFLD or in patients with concomitant cardiovascular diseases. This narrative review will discuss the main functions of platelets, their unique interactions with liver cells, and the outcomes of these interactions, as well as the results of studies evaluating the efficacy and safety of antiplatelet therapy in patients with NAFLD.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 3","pages":"26748"},"PeriodicalIF":3.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
NO Pain! No Cancer? The Crosstalk Between Nociception, ROS, and Cancer Development.
IF 3.3
Frontiers in bioscience (Landmark edition) Pub Date : 2025-03-13 DOI: 10.31083/FBL31328
Tzu-Yin Chen, Tohru Yoshioka, Wen-Li Hsu
{"title":"NO Pain! No Cancer? The Crosstalk Between Nociception, ROS, and Cancer Development.","authors":"Tzu-Yin Chen, Tohru Yoshioka, Wen-Li Hsu","doi":"10.31083/FBL31328","DOIUrl":"https://doi.org/10.31083/FBL31328","url":null,"abstract":"<p><p>Transient receptor potential (TRP) channels, particularly those involved in nociception (nociceptive TRP channels), are implicated in both pain and cancer development. Activation of these channels by diverse stimuli triggers calcium influx, leading to mitochondrial oxidative stress and reactive oxygen species (ROS) accumulation. This ROS production contributes to both nociceptive signaling (causing pain) and aging processes, including genomic instability, a key driver of carcinogenesis. Although a direct causal link between pain and cancer onset remains elusive, the shared involvement of nociceptive TRP channels strongly suggests a correlation. This opinion article proposes targeting the crosstalk between nociceptive TRP channels and ROS as a promising therapeutic strategy to mitigate cancer and cancer-associated pain simultaneously. While further research is needed to definitively establish a causal relationship between pain and cancer risk, the available evidence suggests that inhibiting this pathway may offer significant benefits for both cancer prevention and treatment.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 3","pages":"31328"},"PeriodicalIF":3.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Quality by Design (QbD) Project of Human Dermal Fibroblast and its Therapeutic Effects on Managing Degenerative Intervertebral Disc Fibrosis in Rabbit and Cynomolgus Monkey. 人真皮成纤维细胞的质量源于设计(QbD)项目及其对兔和猴退行性椎间盘纤维化的治疗效果。
IF 3.3
Frontiers in bioscience (Landmark edition) Pub Date : 2025-03-12 DOI: 10.31083/FBL28062
Li Zhou, Hongsheng Li, Chen Chen, Hao Yang, Guicheng Zhang, Qin Zhang, Mengnan Wen, Lei Shi, Tong Xing, Ming Fan, An Qin, Jie Zhao, Shen'ao Zhou
{"title":"A Quality by Design (QbD) Project of Human Dermal Fibroblast and its Therapeutic Effects on Managing Degenerative Intervertebral Disc Fibrosis in Rabbit and Cynomolgus Monkey.","authors":"Li Zhou, Hongsheng Li, Chen Chen, Hao Yang, Guicheng Zhang, Qin Zhang, Mengnan Wen, Lei Shi, Tong Xing, Ming Fan, An Qin, Jie Zhao, Shen'ao Zhou","doi":"10.31083/FBL28062","DOIUrl":"https://doi.org/10.31083/FBL28062","url":null,"abstract":"<p><strong>Background: </strong>Low back pain (LBP) is the leading cause of disability among the elderly, placing significant social and economic burdens on societies globally. A common cause of chronic LBP is lumbar disc degeneration. Previously, we reported that autologous or allogenic fibroblast injections could treat intervertebral disc degeneration (IVDD) in preclinical studies by maintaining disc height and stability through fibrosis. However, the pathway to successful drug development remains unclear.</p><p><strong>Methods: </strong>To develop a novel human allogenic fibroblast injection, we launched a quality-by-design (QbD) project focusing on human dermal fibroblasts (HDFs).</p><p><strong>Results: </strong>We developed a tissue separation process, HDF culture process, and HDF cryopreservation process. The tissue disinfection method used 5% povidone-iodine solution and 75% alcohol for 3-5 min each; the tissue digestion conditions used neutral protease AF followed by overnight soaking plus collagenase NB6 digestion for 2-3 h; the non-animal component medium contained high glucose dulbecco's modified eagle medium (DMEM) + 7.5% human platelet lysate (hPL); A cell density of 14,000-18,000 cells/cm<sup>2</sup> was used; the cell cryopreservation solution contained 75% CS10 + 10% human serum albumin (HSA) + 15% saline (NaCl). Finally, we explored its therapeutic effects by treating IVDD in rabbits.</p><p><strong>Conclusions: </strong>The model of lumbar disc degeneration in rabbits was induced by acupuncture, and HDF was injected into the intervertebral disc. The therapeutic effect of HDF was observed by imaging and histopathology at 1, 3, and 6 months after administration. HDF treatment significantly improved the water content of degenerative intervertebral discs and maintained the height and stability of intervertebral discs. Signal pathway analysis in cynomolgus monkeys suggested that the primary mechanism involves promoting disc fibrosis. Therefore, this study demonstrated the feasibility and cost-effectiveness of manufacturing FibroCell<sup>TM</sup>, a foreskin-derived human dermal fibroblast injection. FibroCell<sup>TM</sup> shows promise as a cell-based therapy for IVDD treatment.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 3","pages":"28062"},"PeriodicalIF":3.3,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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