Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03846-6
Background Ferroptosis is associated with the pathological progression of hemorrhagic injury and ischemia–reperfusion injury. According to our previous study, exosomes formed through bone marrow mesenchymal stem cells modified with miR-340-3p (MB-exos) can restore damaged endometrium. However, the involvement of ferroptosis in endometrial injury and the effect of MB-exos on ferroptosis remain elusive. Methods The endometrial injury rat model was developed. Exosomes were obtained from the supernatants of bone marrow mesenchymal stromal cells (BMSCs) and miR-340/BMSCs through differential centrifugation. We conducted RNA-seq analysis on endometrial tissues obtained from the PBS and MB-exos groups. Ferroptosis was induced in endometrial stromal cells (ESCs) by treating them with erastin or RSL3, followed by treatment with B-exos or MB-exos. We assessed the endometrial total m6A modification level after injury and subsequent treatment with B-exos or MB-exos by methylation quantification assay. We performed meRIP-qPCR to analyze m6A modification-regulated endogenous mRNAs. Results We reveal that MB-exos facilitate the injured endometrium to recover by suppressing ferroptosis in endometrial stromal cells. The injured endometrium showed significantly upregulated N6-methyladenosine (m6A) modification levels; these levels were attenuated by MB-exos through downregulation of the methylase METTL3. Intriguingly, METTL3 downregulation appears to repress ferroptosis by stabilizing HMOX1 mRNA, thereby potentially elucidating the mechanism through which MB-exos inhibit ferroptosis in ESCs. We identified YTHDF2 as a critical m6A reader protein that contributes to HMOX1 mRNA degradation. YTHDF2 facilitates HMOX1 mRNA degradation by identifying the m6A binding site in the 3′-untranslated regions of HMOX1. In a rat model, treatment with MB-exos ameliorated endometrial injury-induced fibrosis by inhibiting ferroptosis in ESCs. Moreover, METTL3 short hairpin RNA-mediated inhibition of m6A modification enhanced the inhibitory effect of MB-exos on ferroptosis in endometrial injury. Conclusions Thus, these observations provide new insights regarding the molecular mechanisms responsible for endometrial recovery promotion by MB-exos and highlight m6A modification-dependent ferroptosis inhibition as a prospective therapeutic target to attenuate endometrial injury.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025141
Colorectal cancer (CRC) is a common type of gastrointestinal malignancy, and it has a close connection with long noncoding RNAs (lncRNAs). This study aims to examine the involvement of long noncoding RNA LINC00114, which targets heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) in regulating glutamine metabolism and angiogenesis in the metastasis of colorectal cancer (CRC). LINC00114 and HNRNPA1 levels are measured in CRC tissues and cells to determine their expression levels. Then, siRNA targeting LINC00114 (si-LINC00114) is used to transfect CRC cells, and cell proliferation and metastasis are detected. The influence of exogenous glucose and glutamine supplementation on angiogenesis induced by LINC00114 in CRC is investigated in HUVECs. Glutamine metabolism in CRC cells is also detected. Furthermore, the role of LINC00114 in CRC xenograft tumors is studied in vivo. LINC00114 and HNRNPA1 are highly expressed in CRC and positively correlate with CD31. si-LINC00114 significantly inhibits proliferation, metastasis and HNRNPA1 expression in CRC cells. An RNA-binding-protein immunoprecipitation (RIP) assay confirms that LINC00114 can bind to HNRNPA1 and positively regulate its expression. Further experiments confirm that si-LINC00114 significantly inhibits cell proliferation and tubule formation in HUVECs. Exogenous glucose and glutamine supplementation significantly promotes the levels of LINC00114 and HNRNPA1 in CRC cells and promotes tubule formation in HUVECs. In addition, transfection of CRC cells with si-LINC00114 and/or oe-HNRNPA1 regulates glutamine metabolism in CRC cells. Animal studies confirm that intervention with LINC00114 represses the progression and vascular normalization of CRC and regulates glutamine metabolism. In conclusion, LINC00114 promotes CRC metastasis by targeting HNRNPA1 to regulate glutamine metabolic reprogramming and angiogenesis.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025065
Stem cell fate is profoundly influenced by a complex interplay of biochemical and biophysical cues, with the latter increasingly recognized for its roles in cellular processes, yet the mechanisms are unclear. Since chromatin accessibility is a critical determinant in the processes of osteogenesis and bone repair, investigating the contributions of open chromatin regions (OCRs) to the intracellular signaling pathways triggered by topographical cues, which lead to osteogenic differentiation is highly valuable. This study explores the impact of the nanotopography of biomaterials on the osteogenic differentiation of human bone marrow stem cells (hBMSCs). By utilizing electrospun poly-L-lactide (PLLA) membranes with random fiber arrangements, we mimic the natural extracellular matrix (ECM) topography to study its effects on hBMSCs, contrasting them with flat PLLA controls. Through high-throughput Assay for Transposase-Accessible Chromatin with sequencing (ATAC-seq) and RNA sequencing (RNA-seq), we reveal that the nanotopography of electrospun surfaces promotes osteogenic differentiation by modulating the chromatin accessibility of the YBX1 gene promoter, leading to its upregulation. Lentiviral knockdown experiments further confirm the crucial role of YBX1, revealing a reversal of the osteogenic effects induced by nanotopography. This study emphasizes the importance of YBX1 in the osteogenic response to the surface topography of biomaterials and suggests that nanotopographical cues could be harnessed to direct stem cell fate. These findings are important for developing biomaterials that promote specific stem cell outcomes in regenerative medicine. Our results further contribute to a deeper understanding of the mechanisms underlying stem cell differentiation in response to environmental cues and pave the way for the rational design of biomaterials with enhanced osteogenic potential. By elucidating the role of chromatin accessibility and specific transcription factors such as YBX1, this study highlights the intricate interplay between cell-material interactions and the intracellular signaling pathways that govern stem cell fate.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024076
Rheumatoid arthritis (RA) is an idiopathic and chronic autoimmune disease for which there are currently no effective treatments. Oxypeucedanin hydrate (OXH) is a natural coumarin known for its potent anti-inflammatory properties. However, further investigations are needed to determine its therapeutic efficacy in treating RA. In this study, we evaluate the anti-inflammatory activity of OXH by treating LPS-induced RAW264.7 macrophages. Our results show that OXH treatment reverses the changes in iNOS, COX-2, IL-1β, IL-6, and TNF-α levels. Additionally, OXH reduces ROS production. Further analysis reveals that OXH suppresses the activation of the NF-κB/MAPK pathway. CETSA results show that OXH competes with LPS for binding to the TLR4/MD2 complex. MST experiments demonstrate the specific affinity of OXH for the TLR4/MD2 complex, with a Kd value of 33.7 μM. Molecular docking analysis suggests that OXH binds to the pocket of the TLR4/MD2 complex and interacts with specific amino acids, such as GLY-343, LYS-388, and PHE-345. Molecular dynamics simulations further confirm this conclusion. Finally, we investigate the potential of OXH in treating RA using a collagen-induced arthritis (CIA) model in rats. OXH effectively ameliorates the symptoms of CIA, including improving body weight, reducing swelling and redness, increasing talus volume, and decreasing bone erosion. OXH also decreases the mRNA levels of pro-inflammatory factors in synovial tissue. Transcriptome enrichment analysis and western blot analysis confirm that OXH suppresses the NF-κB/MAPK pathway, which is consistent with our in vitro findings.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03985-w
The original article erroneously presents an overlapping artefact in Fig. 2H; the corrected figure can be viewed ahead in this Correction article.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21505
BACKGROUND: The Affiliated Hospital of Jiangxi University of Chinese Medicine has used traditional Chinese medicine (TCM) to treat children with cerebral palsy (CP) for over 20 years, but no analysis of medication patterns has been conducted. OBJECTIVE: To analyze TCM syndrome types and explore medication patterns for CP in children based on medical records and literature. METHODS: An evidence-based retrieval strategy was used to search and manage literature and medical records on TCM treatment for CP in children. Bibliometric methods were applied to mine and analyze data characteristics. VOSviewer software was used to create visual knowledge maps. IBM SPSS Modeler software was used for association rule analysis of TCM drugs. Radar chart method was used to analyze the four natures and five flavors of drugs. RESULTS AND CONCLUSION: A total of 503 medical records and 90 articles were included. Syndrome analysis showed that the main TCM syndrome type of CP in children was liver-kidney deficiency. Intervention analysis showed that external therapy was most frequently used, and among oral medications, drugs for nourishing liver and kidney were most common. Medication pattern analysis showed that among the top 20 drugs by frequency in both medical records and literature, 12 (60%) were the same. The drug pairs Shanyao (Rhizoma Dioscoreae) and Fuling (Poria), and Shudi (Radix Rehmanniae Preparata) and Fuling (Poria) had high support and confidence above 82.50%, indicating significant association. Among all TCM drugs for CP in children, the nature was mainly warm, followed by neutral and cold; the flavor was mainly sweet, followed by bitter and pungent; the meridian tropism was mainly liver and kidney meridians, followed by spleen, heart, and lung meridians. Most drugs in these formulas were non-toxic. The results indicate that CP in children is mainly characterized by liver-kidney deficiency, and the formulas used in clinical practice and related clinical research are mostly for nourishing liver and kidney, among which Liuwei Dihuang Pill and its derivative formulas appear most frequently. The drug pairs with the highest frequency and reliability are Shudi and Fuling, and Shanyao and Fuling. The nature and flavor of drugs are mainly warm, sweet, and attributed to liver and kidney meridians.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21538
BACKGROUND: In recent years, high-intensity interval exercise has been widely used and gained attention due to its short duration. However, its safety has been seriously questioned because of its high intensity and the controversial effects on the heart. Therefore, exploring time-efficient, intensity-controllable exercise interventions with good compliance has become a research hotspot in the field of exercise science. OBJECTIVE: To investigate the effects of blood flow restriction combined with aerobic exercise on energy expenditure. METHODS: Fifteen male college students were recruited. A repeated-measures crossover design was used to design two exercise protocols: low-intensity aerobic exercise (non-blood flow restriction group) and blood flow restriction training combined with low-intensity aerobic exercise (blood flow restriction group). Both protocols were performed at 40% maximal oxygen uptake, with 10 minutes of running per session, 1 minute rest between sessions, for a total of five sessions and an exercise duration of 54 minutes. In the blood flow restriction group, a cuff was placed at the most proximal end of both lower limbs and pressurized to 50% of the arterial occlusion pressure before exercise, and the pressure was released during each exercise interval. The interval between the two protocols was at least 72 hours. Blood lactate, energy expenditure during exercise, excess post-exercise oxygen consumption, ratings of perceived exertion, heart rate, and blood pressure were measured. RESULTS AND CONCLUSION: (1) Total energy expenditure in the blood flow restriction group was significantly greater than that in the non-blood flow restriction group (P < 0.05). (2) There was no significant difference in the proportional contribution of the three energy systems (aerobic, anaerobic lactic, and anaerobic alactic) between the two exercise modes (P > 0.05). (3) The total excess post-exercise oxygen consumption within 40 minutes of recovery was significantly greater in the blood flow restriction group than in the non-blood flow restriction group (P < 0.05). At 1 minute of recovery, heart rate was significantly higher in the blood flow restriction group than in the non-blood flow restriction group (P < 0.05). At other time points, there were no significant differences in ratings of perceived exertion, heart rate, or blood pressure between the two groups. (4) These findings suggest that blood flow restriction training combined with low-intensity aerobic exercise can increase energy expenditure and excess post-exercise oxygen consumption without additional increases in ratings of perceived exertion, providing an additional training option for individuals seeking to increase physical activity levels, but attention should be paid to the elevated heart rate during recovery.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026068
Chemotherapy-induced neurotoxicity (CIN) is a prevalent and debilitating side effect of cancer treatment, with paclitaxel being a classic anticancer drug that often causes significant neurotoxicity. However, effective interventions are lacking. This study aimed to elucidate the mechanisms underlying paclitaxel-induced neurotoxicity. We confirmed that paclitaxel exerts cytotoxic effects on SH-SY5Y and HT-22 neuronal cells. RNA-seq analysis revealed that ferroptosis is among the top enriched pathways in paclitaxel-treated neurons, and gene set enrichment analysis (GSEA) confirmed the enrichment of ferroptosis-related pathways. Transmission electron microscopy showed fragmented mitochondria with decreased cristae and increased membrane density, characteristic of ferroptosis. Paclitaxel dose-dependently increased intracellular reactive oxygen species (ROS) and iron levels while decreasing glutathione (GSH) levels. Mechanistically, paclitaxel suppressed the expression of Nrf2, SLC7A11, and GPX4, key components of the Nrf2/SLC7A11/GSH/GPX4 signaling pathway that protects against ferroptosis. Rescue experiments with ferroptosis inhibitors (liproxstatin-1) further confirmed the involvement of ferroptosis. These findings demonstrate that paclitaxel induces neurotoxicity by activating ferroptosis via suppression of the Nrf2/SLC7A11/GSH/GPX4 axis, providing potential therapeutic targets for preventing and treating paclitaxel-induced neurotoxicity.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025141
Colorectal cancer (CRC) remains the third most common malignancy and second leading cause of cancer-related mortality, with metastasis accounting for the majority of deaths. Long noncoding RNAs (lncRNAs) have emerged as critical regulators of tumor progression, yet the mechanistic basis of their involvement in CRC metabolic reprogramming and angiogenesis is incompletely defined. This study investigates the role of LINC00114 in CRC metastasis, focusing on its interaction with heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) and downstream effects on glutamine metabolism and angiogenesis. LINC00114 and HNRNPA1 were found to be highly expressed in CRC tissues and cells, positively correlating with CD31. siRNA-mediated silencing of LINC00114 (si-LINC00114) significantly inhibited CRC cell proliferation, metastasis, and HNRNPA1 expression. RNA-binding protein immunoprecipitation confirmed direct binding of LINC00114 to HNRNPA1, with positive regulation of HNRNPA1 expression. In HUVECs, si-LINC00114 suppressed proliferation and tubule formation. Exogenous glucose and glutamine supplementation promoted LINC00114 and HNRNPA1 levels in CRC cells and enhanced HUVEC tubule formation, with glutamine exerting a greater effect than glucose. Transfection with si-LINC00114 and/or oe-HNRNPA1 modulated glutamine metabolism in CRC cells. In vivo, LINC00114 intervention repressed tumor progression, vascular normalization, and glutamine metabolism. These findings establish LINC00114 as a promoter of CRC metastasis through HNRNPA1-mediated glutamine metabolic reprogramming and angiogenesis, suggesting potential therapeutic targets.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025065
Stem cell fate is profoundly influenced by a complex interplay of biochemical and biophysical cues, with the latter increasingly recognized for its roles in cellular processes, yet the mechanisms are unclear. Since chromatin accessibility is a critical determinant in the processes of osteogenesis and bone repair, investigating the contributions of open chromatin regions (OCRs) to the intracellular signaling pathways triggered by topographical cues, which lead to osteogenic differentiation is highly valuable. This study explores the impact of the nanotopography of biomaterials on the osteogenic differentiation of human bone marrow stem cells (hBMSCs). By utilizing electrospun poly-L-lactide (PLLA) membranes with random fiber arrangements, we mimic the natural extracellular matrix (ECM) topography to study its effects on hBMSCs, contrasting them with flat PLLA controls. Through high-throughput Assay for Transposase-Accessible Chromatin with sequencing (ATAC-seq) and RNA sequencing (RNA-seq), we reveal that the nanotopography of electrospun surfaces promotes osteogenic differentiation by modulating the chromatin accessibility of the YBX1 gene promoter, leading to its upregulation. Lentiviral knockdown experiments further confirm the crucial role of YBX1, revealing a reversal of the osteogenic effects induced by nanotopography. This study emphasizes the importance of YBX1 in the osteogenic response to the surface topography of biomaterials and suggests that nanotopographical cues could be harnessed to direct stem cell fate. These findings are important for developing biomaterials that promote specific stem cell outcomes in regenerative medicine. Our results further contribute to a deeper understanding of the mechanisms underlying stem cell differentiation in response to environmental cues and pave the way for the rational design of biomaterials with enhanced osteogenic potential. By elucidating the role of chromatin accessibility and specific transcription factors such as YBX1, this study highlights the intricate interplay between cell-material interactions and the intracellular signaling pathways that govern stem cell fate.