Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04350-1
Hematopoietic stem cells (HSCs) are the primitive cells that give rise to common precursors for all blood cell lineages. Abnormalities in their number and/or function are important factors leading to the decline of immune function and the occurrence of various systemic diseases. Phase separation refers to a physicochemical mechanism in which intracellular liquid-liquid phase separation (LLPS) forms membrane-less organelles. It participates in various physiological activities and is related to the occurrence of diseases. Studies have shown that the functional activity of HSCs is regulated by complex mechanisms, and phase separation is closely related to these complex mechanisms such as genetic regulation, epigenetic regulation, microenvironment regulation, gene expression, autophagy degradation, and cell proliferation. With the deepening of research, the importance of phase separation in the pathogenesis and treatment of diseases such as leukemia and tumors has gradually emerged, but the deep mechanism of its regulation of HSCs genetic regulation still lacks exploration, and the direction of clinical targeted therapy is not yet clear. Here, we will summarize and elaborate the genetic regulation mechanism of HSCs, discuss the relationship between phase separation and the functional regulation of HSCs, and analyze the possibility of phase separation participating in the genetic regulation of HSCs to treat diseases, in order to provide help for the clinical implementation of targeted therapy for HSCs regulation.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04396-1
Background One major factor contributing to infertility in women of childbearing age is premature ovarian insufficiency (POI). Exosomes produced from human umbilical cord mesenchymal stem cells (hUMSC-Exos) have drawn a lot of attention lately as a potential treatment for ovarian dysfunction brought on by POI. However, its therapeutic mechanism is still unclear and needs further exploration.
Methods POI model was established by intraperitoneal injection of cyclophosphamide (CTX) in female Wistar rats. These POI rats were treated with hUMSC-Exos for one week. In addition to in vivo experiments, in vitro POI models were also established. In vitro experiments, theca interstitial cells (TICs) treated with CTX were exposed to normal as well as let-7a-5p inhibitory hUMSC-Exos. The ovary structure, morphology, endocrine function, and reproductive ability of POI rats were observed by H&E staining and ELISA. Western blot, immunofluorescence staining (IF), and quantitative real-time polymerase chain reaction (qRT-PCR) were used to evaluate the autophagy-related indexes in ovary and TICs of POI rats in each group.
Results CTX induced abnormalities of ovarian morphology, structure, endocrine, and reproductive function in rats, and accompanied by autophagy of TICs. Notably, hUMSC-Exos diminishes ovarian structural and functional damage in POI rats and TICs autophagy via targeting the AMPK/mTOR pathway. Furthermore, downregulating let-7a-5p in hUMSC-Exos weakened their ability to prevent TICs autophagy.
Conclusions Overall, the findings suggested that hUMSC-Exos improves ovarian function in POI rats by inhibiting TICs autophagy via the let-7a-5p/AMPK/mTOR pathway. Our study provided further evidence that POI patients can benefit from hUMSC-Exos-mediated therapy.
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•2026•DOI: 10.3724/abbs.2025195
Chronic psychosocial stress is increasingly recognized as a key risk factor for dry eye disease, potentially because of its disruption of the circadian transcriptome and lacrimal gland function, which impacts eye health. In this study, we test this hypothesis by using two mouse models (high platform and restraint experiments) of psychological stress and report that both models uniquely alter the circadian transcriptome and signaling pathways of the lacrimal gland. Psychosocial stress significantly affects the normal rhythmic oscillations of extraorbital lacrimal gland (ELG) immune cell trafficking, secretion response, and lipid deposition. Both models significantly reduce the volume of stimulated lacrimal secretions as well as the recruitment of immune cells to the lacrimal gland. Importantly, treatment with beta-adrenergic receptor blockers or glucocorticoid synthesis inhibitors significantly improves these secretory functions and histopathological changes. Collectively, these findings demonstrate the detrimental effects of chronic psychosocial stress on lacrimal gland circadian transcriptome homeostasis and suggest potential clinical applications for patients with both psychological stress and dry eye disease.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2023268
MicroRNAs (miRNAs) are small noncoding RNAs (ncRNAs) that play their roles in the regulation of physiological and pathological processes. Originally, it was assumed that miRNAs only modulate gene expression post-transcriptionally in the cytoplasm by inducing target mRNA degradation. However, with further research, evidence shows that mature miRNAs also exist in the cell nucleus, where they can impact gene transcription and ncRNA maturation in several ways. This review provides an overview of novel models of nuclear miRNA functions. Some of the models remain to be verified by experimental evidence, and more details of the miRNA regulation network remain to be discovered in the future.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024132
Through genome-wide association studies (GWAS) and integrated expression quantitative trait locus (eQTL) analyses, numerous susceptibility genes (“eGenes”, whose expressions are significantly associated with common variants) associated with systemic lupus erythematosus (SLE) have been identified. Notably, a subset of these eGenes is correlated with disease activity. However, the precise mechanisms through which these genes contribute to the initiation and progression of the disease remain to be fully elucidated. In this investigation, we initially identify SPATS2L as an SLE eGene correlated with disease activity. eSignaling and transcriptomic analyses suggest its involvement in the type I interferon (IFN) pathway. We observe a significant increase in SPATS2L expression following type I IFN stimulation, and the expression levels are dependent on both the concentration and duration of stimulation. Furthermore, through dual-luciferase reporter assays, western blot analysis, and imaging flow cytometry, we confirm that SPATS2L positively modulates the type I IFN pathway, acting as a positive feedback regulator. Notably, siRNA-mediated intervention targeting SPATS2L, an interferon-inducible gene, in peripheral blood mononuclear cells (PBMCs) from patients with SLE reverses the activation of the interferon pathway. In conclusion, our research highlights the pivotal role of SPATS2L as a positive-feedback regulatory molecule within the type I IFN pathway. Our findings suggest that SPATS2L plays a critical role in the onset and progression of SLE and may serve as a promising target for disease activity assessment and intervention strategies.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.15.20261502
Methicillin-resistant Staphylococcus aureus (MRSA) accounts for over 30% of clinical S. aureus isolates globally, with bacteremia mortality reaching 27.3%—approximately threefold that of methicillin-sensitive infections. Existing antibiotics face cross-resistance across β-lactams, macrolides, quinolones, and sulfonamides. This study isolated five compounds from the ethyl acetate fraction of Callicarpa nudiflora dried leaf ethanol extract via silica gel, Sephadex LH-20, and ODS column chromatography. Structures were elucidated by IR, HR-ESI-MS, 1H-NMR, 13C-NMR, HSQC, HMBC, and COSY. Compound 1, a new monoterpene named callinuene A, is (Z)-2-methyl-6-methyleneocta-2,7-dien-1-yl (E)-3-(4-hydroxyphenyl)acrylate. Compounds 2–5 were identified as monasuslunin, (1S,5R,9R)-10,10-dimethyl-2,6-dimethylenebicyclo[7.2.0]undecan-5-ol, 7-epi-eudesm-4(15)-ene-1β,6β-diol, and sclareolide, respectively; compounds 3–5 are first isolates within this species. Minimum inhibitory concentrations (MICs) were determined by nutrient broth dilution. Compound 1 exhibited MICs of 8 μg/mL against S. aureus ATCC29213 and MRSA T144, while MICs against E. coli ATCC25922 and multidrug-resistant E. coli B2 exceeded 128 μg/mL. Compounds 2–5 showed no meaningful activity (MIC ≥ 64 μg/mL). Oxacillin MICs were <0.25, 16, 32, and 32 μg/mL for the same strains; meropenem MICs were <0.25, 2, <0.25, and <0.25 μg/mL. Compound 1 demonstrates selective anti-staphylococcal activity, warranting further development as a lead scaffold against MRSA.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21461
BACKGROUND: The increasing prevalence of minimally invasive surgery has placed higher demands on high-frequency electrosurgical equipment. Imported minimally invasive tungsten alloy electrodes offer high cutting precision, low tissue adhesion, and good biocompatibility, but their high cost limits their widespread application. Therefore, conducting biocompatibility and preclinical animal studies on Chinese-made 3D-printed minimally invasive tungsten alloy needle electrodes can provide a scientific basis for the research and development of Chinese-made minimally invasive electrodes. OBJECTIVE: To evaluate the biocompatibility and preclinical safety of Chinese-made 3D-printed tungsten alloy needle-shaped electrodes. METHODS: (1) Biocompatibility: L-929 cells were co-cultured with extracts from Chinese-made 3D-printed minimally invasive tungsten alloy needle electrodes at different concentrations (100%, 50%, 25%, and 12.5%), and the cytotoxicity of the materials was assessed using the MTT assay. Intradermal stimulation experiments were performed on New Zealand white rabbits to evaluate the skin irritation of the Chinese-made 3D-printed minimally invasive tungsten alloy needle electrodes. Skin sensitization was evaluated in albino guinea pigs. (2) Preclinical animal experiments: 36 SD rats were randomly divided into three groups (n=12 per group): 304 stainless steel electrode group, imported minimally invasive tungsten alloy needle electrode group, and Chinese-made 3D-printed minimally invasive tungsten alloy needle electrode group. The corresponding electrodes were used to cut subcutaneous tissue and abdominal wall muscle, and the incisions were sutured. The amount of adherent material on the electrode surface, intraoperative blood loss, and smoke formation were recorded. At 14 days postoperatively, wound healing, fat liquefaction, and histological morphology of the incision were observed. RESULTS AND CONCLUSION: (1) MTT assay showed that the cell survival rate in the extract group of Chinese-made 3D-printed minimally invasive tungsten alloy needle electrodes was higher than 80%, indicating no obvious cytotoxicity. Intradermal stimulation and sensitization tests showed no significant skin irritation or sensitization reaction. (2) Compared with the 304 stainless steel electrode group, the Chinese-made 3D-printed minimally invasive tungsten alloy needle electrode group had reduced electrode surface adhesion, increased intraoperative blood loss and smoke formation (P < 0.05). There were no significant differences between the Chinese-made and imported tungsten alloy needle electrode groups in terms of electrode surface adhesion, intraoperative blood loss, and smoke formation (P > 0.05). There were no significant differences among the three groups in wound healing, fat liquefaction, and incision adverse reactions (P > 0.05). Hematoxylin-eosin staining showed mild inflammatory cell infiltration in all three groups, consistent with normal wound repair pathology, with no abnormal immune reaction or delayed healing. (3) The results indicate that Chinese-made 3D-printed minimally invasive tungsten alloy needle electrodes have good biocompatibility and safety, with overall performance comparable to imported tungsten needle electrodes.
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.