Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05059-5
Background Mitochondrial dysfunction contributes to poor embryo quality and recurrent assisted reproductive technology (ART) failure. Mitochondrial transplantation (MIT), which involves supplementing oocytes with exogenous mitochondria, has been proposed as a novel strategy to improve ART outcomes. However, both its clinical efficacy and safety remain unclear.
Methods In this single-center trial, 151 patients with a history of ≥ 2 failed ART cycles provided 1178 metaphase II (MII) oocytes. Sibling oocytes were randomized 1:1 to receive autologous bone marrow mesenchymal stem cells (BMSCs) mitochondria co-injection during intracytoplasmic sperm injection (ICSI) or standard ICSI. The primary outcome was the rate of day-3 good-quality embryos.
Results MIT significantly accelerated early embryonic cleavage at the 3-cell stage and 5-cell stage, but this morphokinetic alteration did not translate into improvements in good-quality embryo rate, clinical pregnancy rate, or live birth rate. Long-term follow-up of 23 live births revealed no adverse effects, with all offspring exhibiting normal growth and development. Exploratory analysis revealed that oocytes yielding ≥ 70% transferable embryos after MIT harbored an elevated higher burden of medium frequency (0.05–0.5) mtDNA point mutations.
Conclusions While autologous BMSCs-MIT transiently alters early cleavage kinetics, it does not demonstrate a clinical advantage in unselected patients with recurrent ART failure. Nevertheless, its observed safety profile and the identification of mtDNA mutation burden as a potential predictive biomarker provide a foundation for shifting future MIT research from a universal approach toward precision application in molecularly stratified populations.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024157
The biomolecular assemblies (condensates or aggregates) formed by mutant proteins are a pathological hallmark of neurodegenerative diseases. Some RNA-binding proteins (RBPs) are typically prone to aggregation that is closely associated with disease pathologies. These RBPs include numerous well-recognized pathogenic proteins, such as TAR DNA binding protein of 43 kDa (TDP-43), fused in sarcoma (FUS), ataxin-2 (Atx2), and poly(A)-binding protein nuclear 1 (PABPN1). Recent studies have revealed that liquid-liquid phase separation (LLPS), as a mechanism, underlies the highly dynamic and reversible granule formation of RBPs, and highlighted that multivalent RNA molecules play crucial roles in this process. These granules are necessary for diverse physiological functions, such as RNA splicing, trafficking, and even RNA storage, during stress. However, the aberrant phase transition of these mutant RBPs usually results in the formation of solid-like aggregates or inclusions within both the cytoplasm and nucleus. More importantly, aggregates formed by RBPs can sequester specific proteins, RNAs or other interacting partners, consequently contributing to RBP-related pathologies. For example, wild-type PABPN1 forms dynamic nuclear speckles with the assistance of poly(A) RNAs, whereas Ala expansion of PABPN1 results in the formation of aggregates, which are involved in the disease progression of oculopharyngeal muscular dystrophy (OPMD). Although the biological importance of various RBP granules is realized in either the cytoplasm or nucleus, how RNA regulates the formation of granules and the transition to aberrant RBP aggregates remains largely unknown. The interaction of a protein with other biomolecules (proteins, nucleic acids, etc.) is the prerequisite for the protein executing its normal biological function in cells. Identifying protein-protein and protein-RNA interactions is fundamental for the biochemical investigation of an individual protein and for attempts to understand the functional role of the protein. To date, many methods for studying protein-protein interactions have been developed on the basis of various principles, but it is still difficult to clarify whether the interactions between proteins, especially the RBPs involved, are direct or indirect, since RBPs generally bind to diverse RNAs closely and are incorporated into macromolecular ribonucleoprotein (RNP) complexes. We have taken several pairs of RBPs as examples, including TDP-35 (C-terminal 35-kDa fragment of TDP-43) with TDP-43 or TIA1, PABPN1 with a 25-kDa component of the mammalian cleavage factor I complex (CFIm25) and Atx2 with DEAD-box RNA helicase 6 (DDX6), and applied modified co-immunoprecipitation (Co-IP) and supernatant/pellet (S/P) fractionation experiments to characterize the association and sequestration of RBPs by using single-stranded DNA (ssDNA) chimera under ribonuclease (RNase) treatment. We designed several pieces of ssDNA oligonucleotides to mimic particular RNAs in cells that may mediate the association and sequestration of RBPs. The association of RBP proteins generally requires binding with multivalent RNA chains, since the bound RNAs tend to incorporate into a large protein-RNA complex with the help of RNA molecules. In Co-IP assay, especially for RBPs, RNase is often utilized to digest RNA in cell lysates to characterize whether the association of different RBPs is direct or indirect. It is important for us to demonstrate the active role of particular RNAs in the association or interaction of RBPs. Therefore, we designed and synthesized ssDNA chimeras to mimic the corresponding RNA that specifically bind to both RBPs simultaneously. In this case, ssDNA is used for rescuing the association of RBPs under the condition of RNase treatment, since the ssDNA oligonucleotide is resistant to nuclease activity. To design ssDNA chimeras for the RBPs of interest, first, the RNA sequences that bind to the two RPBs should be defined. The ssDNA should contain at least two portions (motifs) that specifically bind to each RBP, and each ssDNA portion may include 2–3 repeats of the binding sequence, so that the ssDNA can be recognized and bound efficiently by each RBP. Notably, the T base in ssDNA may sometimes be replaced with the U base (dU) for some more specific-binding RBPs, such as PABPN1. In the case of TDP-43 with Atx2, the binding specificities of the RNA sequences for TDP-43 and Atx2 are UG-rich and AUUUUU (AU5), respectively; then, the TG repeat portion is designed to bind to TDP-43, and the AT5 repeat is to bind to Atx2. Thus, an integrated method of co-IP and S/P fractionation was applied to characterize the association and sequestration of RBPs by combining ribonuclease (RNase) and ssDNA treatments.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024035
Acute lung injury (ALI) is a serious condition characterized by damage to the lungs. Recent research has revealed that activation of the NLRP3 inflammasome in alveolar macrophages, a type of immune cell in the lungs, plays a key role in the development of ALI. This process, known as pyroptosis, contributes significantly to ALI pathogenesis. Researchers have conducted comprehensive bioinformatics analyses and identified 15 key genes associated with alveolar macrophage pyroptosis in ALI. Among these, NLRP3 has emerged as a crucial regulator. This study further reveal that the ULK1 protein diminishes the expression of NLRP3, thereby reducing the immune response of alveolar macrophages and mitigating ALI. Conversely, TRAF3, another protein, is found to inhibit ULK1 through a process called ubiquitination, leading to increased activation of the NLRP3 inflammasome and exacerbation of ALI. This TRAF3-mediated suppression of ULK1 and subsequent activation of NLRP3 are confirmed through various in vitro and in vivo experiments. The presence of abundant M0 and M1 alveolar macrophages in the ALI tissue samples further support these findings. This research highlights the TRAF3-ULK1-NLRP3 regulatory axis as a pivotal pathway in ALI development and suggests that targeting this axis could be an effective therapeutic strategy for ALI treatment.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261634
The toxicity of traditional Chinese medicines (TCMs) constitutes a core component of pharmacological theory, alongside the four natures and five flavors, ascending-descending-floating-sinking, and channel tropism, collectively guiding clinical TCM practice. Highly toxic medicinal materials present formidable challenges: their complex compositions impede full elucidation of toxic constituents and mechanisms, while diverse clinical regimens and significant individual variability further complicate research. This review systematically examines highly toxic medicinal materials listed in the 2025 edition of the Chinese Pharmacopoeia. Integrating herbal textual research with modern pharmacological investigations, it analyzes common toxic components and pathways, the bidirectional toxicity-efficacy relationship, and strategies for reducing toxicity while preserving efficacy. The application of modern analytical detection techniques in quality control is reviewed, and other potentially toxic substances and risk management strategies are discussed. The 2025 Pharmacopoeia classifies highly toxic materials primarily as plant-derived, imposing strict regulations on dosage forms, pregnancy contraindications, compatibility contraindications, usage, and special population restrictions. Historical toxicity grading has evolved; for instance, Chuanwu (Aconiti Lateralis Radix Praeparata) was recorded as 'toxic' in Wupu Bencao but as 'highly toxic' in Mingyi Bielu and Yaoxing Lun. Advanced analytical tools such as HPLC-MS have enabled fingerprinting and identification of over 50 highly toxic compounds, including aconitine-type alkaloids and brucine. Mechanistic studies based on apoptotic signaling pathways and metabolomics have revealed complex 'biphasic toxicity effects.' Traditional processing detoxification and compatibility antagonism have been scientifically validated and optimized. However, challenges persist, particularly the incomplete 'component-toxicity' association, which restricts clinical dosage ranges and elevates potential risks, constraining further clinical application. This review aims to provide a scientific reference for deepening quality standard research and promoting safe, rational clinical use of highly toxic medicinal materials.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05059-5
Background: Mitochondrial dysfunction contributes to poor embryo quality and recurrent assisted reproductive technology (ART) failure. Mitochondrial transplantation (MIT) has been proposed to improve ART outcomes, but its efficacy and safety remain unclear. Methods: In this single-center trial, 151 patients with ≥2 failed ART cycles provided 1178 metaphase II (MII) oocytes. Sibling oocytes were randomized 1:1 to receive autologous bone marrow mesenchymal stem cell (BMSC) mitochondria co-injection during intracytoplasmic sperm injection (ICSI) or standard ICSI. The primary outcome was day-3 good-quality embryo rate. Results: MIT significantly accelerated early cleavage at the 3-cell and 5-cell stages, but this did not translate into improved good-quality embryo rate, clinical pregnancy rate, or live birth rate. Long-term follow-up of 23 live births revealed no adverse effects, with normal growth and development. Exploratory analysis showed that oocytes yielding ≥70% transferable embryos after MIT harbored a higher burden of medium-frequency (0.05–0.5) mtDNA point mutations. Conclusions: Autologous BMSC-MIT transiently alters early cleavage kinetics but does not demonstrate clinical advantage in unselected patients with recurrent ART failure. Its safety profile and the identification of mtDNA mutation burden as a potential predictive biomarker support shifting future research toward precision application in molecularly stratified populations.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21336
BACKGROUND: High-altitude hypoxia has been reported to damage the male reproductive system, but whether stem cells can protect against male reproductive damage caused by high-altitude hypoxia has not been reported. OBJECTIVE: To investigate the preventive effect of human umbilical cord mesenchymal stem cell transplantation on reproductive damage in hypoxia-exposed male mice. METHODS: Human umbilical cord mesenchymal stem cells were isolated and cultured, and three-lineage differentiation and flow cytometry identification were performed. Twenty-one C57BL/6 male mice were randomly divided into control, hypoxia, and stem cell groups (n=7). The hypoxia and stem cell groups were exposed to a chronic intermittent hypoxia model simulating an altitude of 5,000 m (11.1% oxygen). In the stem cell group, 1×10^6 human umbilical cord mesenchymal stem cells were injected via the tail vein once a week for 6 weeks, while the other groups received PBS. Body mass, food intake, and water intake were monitored. After hypoxia exposure, testicular tissue was analyzed for morphology, ultrastructure, reactive oxygen species levels, and mitochondrial membrane potential; epididymal tissue was analyzed by hematoxylin-eosin staining and sperm motility; and the homing ability of stem cells was observed by DiL fluorescence tracing. RESULTS AND CONCLUSION: Human umbilical cord mesenchymal stem cell transplantation significantly improved water and food intake in hypoxic mice but had no significant effect on body mass. Morphological analysis showed that hypoxia caused edema of the testis and epididymis and shedding of spermatogenic cells, while stem cell transplantation alleviated these structural damages and reversed mitochondrial swelling and atrophy in germ cells. Additionally, stem cell transplantation significantly inhibited hypoxia-induced increase in reactive oxygen species, restored mitochondrial membrane potential, and improved sperm motility. Tracing experiments showed that after entering the mice, stem cells mainly accumulated in lung tissue, with low homing to the testis. In conclusion, human umbilical cord mesenchymal stem cell transplantation can protect the structure and function of germ cell mitochondria, reduce hypoxia-induced testicular and epididymal edema, and thereby restore spermatogenesis and sperm motility.
Chinese Journal of New Drugs•2025•DOI: cast_zgxyzz_1236731781232251260
Background: Iron deficiency anemia (IDA) is a global health concern, and intravenous iron preparations are increasingly used. Ferric derisomaltose (FDI) is a newer formulation with potential advantages. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of FDI compared with other iron therapies or placebo in treating IDA. Methods: We searched PubMed, Embase, Cochrane Library, and CNKI up to October 2023 for randomized controlled trials (RCTs) comparing FDI with active comparators or placebo in patients with IDA. The primary outcomes were change in hemoglobin (Hb) from baseline, and safety outcomes included adverse events (AEs), serious adverse events (SAEs), and hypersensitivity reactions. Data were pooled using random-effects models. Results: A total of 15 RCTs involving 3,452 patients were included. FDI significantly increased Hb levels compared with placebo (mean difference [MD] 1.2 g/dL, 95% CI 0.8-1.6) and was non-inferior to other intravenous iron formulations (MD 0.1 g/dL, 95% CI -0.2 to 0.4). FDI was associated with fewer hypersensitivity reactions compared with ferric carboxymaltose (risk ratio [RR] 0.3, 95% CI 0.1-0.9). The incidence of AEs was similar between FDI and other iron preparations. Subgroup analyses showed consistent results across different etiologies of IDA. Conclusion: Ferric derisomaltose is effective and safe for treating IDA, with a lower risk of hypersensitivity reactions compared with some other intravenous iron formulations. These findings support its use in clinical practice.