This study aimed to produce a high-quality mesenchymal stem cell-derived secretome (MSC-sec) using a three-dimensional culture system to enhance its therapeutic potential for skin wounds. Human umbilical cord-derived MSCs were cultured on optimally modified gelatin sponge (GS) scaffolds (ethanol-plus-polylysine), which maintained high cell viability. The secretome from these GS-cultured MSCs (GS-MSC-sec) contained significantly higher concentrations of key growth factors (KGF, VEGF, PDGF) compared to conventional 2D culture. In vitro, GS-MSC-sec enhanced fibroblast proliferation, migration, and angiogenesis. In a rat full-thickness skin wound model, concentrated GS-MSC-Section (5 ×) not only accelerated wound healing but also promoted wound-induced hair neogenesis. This enhanced regeneration was associated with upregulation of Wnt/β-catenin and TLR3/STAT3 signaling and downregulation of BMP/Smad signaling. These findings demonstrate that GS-MSC-sec possesses significant therapeutic potential for promoting skin wound healing and regeneration, with implications for treating alopecia.

To investigate the key research hotspots and trends related to exosomes in premature ovarian insufficiency (POI) using bibliometric visualization analysis, and to provide a data-driven framework for future scientific and clinical development.

Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor, characterized by poor prognosis, high intratumoral heterogeneity, and pronounced therapy resistance, primarily driven by glioma stem cells (GSCs). SUMOylation, a reversible post-translational modification, has emerged as a critical regulator of GBM progression and therapeutic response. By modifying transcription factors, SUMOylation enhances oncogenic transcriptional programs, contributing to chemoresistance and retinoid resistance. RNA-binding proteins are also affected, influencing exosomal microRNA sorting, invasion, and vasculogenic mimicry. Additionally, SUMOylation of metabolic and cell cycle regulators supports glycolysis, proliferation, and GSC maintenance, highlighting its role in metabolic rewiring. Dysregulation of tumor suppressors through small ubiquitin-like modifier (SUMO)-mediated mechanisms, such as SENP1-dependent deSUMOylation of HIF-1α and β-catenin, promotes stemness and immune evasion. SUMOylation further intersects with angiogenesis, immune regulation, and epigenetic modifiers, including histone deacetylases and zeste homolog 2, shaping tumor plasticity and therapy resistance. Preclinical studies indicate that pharmacological inhibition of SUMOylation with agents like TAK-981, topotecan, or Paromomycin reduces tumor growth, reverses therapy resistance, and enhances radiosensitivity. Moreover, SUMO-related enzymes, such as UBA2, SENP1, and SUMO2/3, may serve as prognostic biomarkers. Understanding SUMOylation in GBM offers insights into tumor biology and identifies potential therapeutic targets to improve patient outcomes.

The interfacial mechanisms governing stem cell adhesion on wettability-patterned microstructures remain insufficiently understood, particularly regarding how initial fluid dynamics dictate subsequent protein distribution and cellular organization. Herein, we fabricate three distinct laser-textured surface architectures on Ti6Al4V─periodic microgrooves, microdimple arrays, and disordered porous structures─and investigate their physicochemical properties, protein adsorption behavior, and mesenchymal stem cell responses. Surface characterization reveals that laser texturing induces complete surface oxidation and generates pronounced time-dependent, anisotropic wettability, driven by capillary infiltration and plastron destabilization. Notably, cell adhesion exhibits strong topographical dependency: on deep microgrooves (depth > 20 μm), mesenchymal stem cells predominantly anchor at groove-ridge junctions rather than spreading within grooves, displaying either "spanning" or "guided" cytoskeletal architectures. Protein adsorption experiments demonstrate a consistent "high-seeking, low-avoiding" distribution pattern, where fetal bovine serum preferentially enriches on ridges and planar regions while being virtually excluded from pits and porous interiors. Using phase-field simulations of droplet dynamics on topology-mimetic models, we reveal that hydrophilic ridges generate moderate, positive interfacial pressure, serving as fluid-anchoring points, whereas grooves produce repulsive, high-pressure zones. This interfacial pressure gradient provides a physical rationale for the spatially selective fluid retention that precedes and likely directs protein patterning and subsequent cell adhesion.

Idiopathic nephrotic syndrome is the most common glomerulopathy in children, and minimal change disease (MCD) is the most common histological pattern. First-line treatment involves glucocorticosteroids, but frequent relapses and steroid dependence may lead to steroid-related complications. Rituximab (RTX) is recommended in cases of lack of response or treatment side effects, reducing relapse rates and limiting the need for other medications. The mechanism of RTX involves B-cell depletion through various cytotoxic mechanisms. Its efficacy in nephrotic syndrome (NS) may stem from its influence on cytokines produced by B cells and a further effect on the podocyte cytoskeleton has been postulated. The present case describes a 19-year-old male with NS resulting from MCD, with a frequently relapsing, steroid-dependent, multidrug-resistant disease. He experienced a hypersensitivity reaction to RTX after the third dose, which contraindicated therapy continuation with traditional infusion. Due to the limited therapeutic options, a 12-step RTX desensitization protocol was adopted, allowing for safe administration of subsequent doses, achievement of remission, and gradual discontinuation of glucocorticosteroids.

Osteoarthritis is fundamentally a whole-joint disease, and a critical pathological feature is the limited capacity of articular cartilage for self-regeneration, leading to accelerated joint degeneration once breakdown begins. Current therapeutic strategies are primarily palliative, and conventional marrow stimulation procedures such as microfracture often yield suboptimal, short-lived outcomes. Stem cell-based biologic augmentation using mesenchymal stem cells has emerged as a promising approach through direct chondrocyte differentiation, paracrine stimulation, and immunomodulation. Umbilical cord-derived mesenchymal stem cells offer robust proliferative capacity, enhanced biological potency, and lower immunogenicity than adult mesenchymal stem cells, and can be obtained with minimal ethical concerns. Clinical trials of human umbilical cord blood-derived mesenchymal stem cells combined with hyaluronic acid hydrogel (CARTISTEM®) have demonstrated excellent safety, improved patient-reported outcomes, and durable hyaline-like cartilage regeneration. Emerging evidence further suggests that combining high tibial osteotomy with human umbilical cord blood-derived mesenchymal stem cells-based cartilage regeneration for medial compartment osteoarthritis with varus malalignment creates a synergistic biological and mechanical environment that promotes structural cartilage repair. In conclusion, surgically transplanted human umbilical cord blood-derived mesenchymal stem cells show therapeutic potential in arthritic knees, although the role of intra-articular injections and the optimal indications for combined high tibial osteotomy remain to be clarified.

The hepatitis E virus (HEV) is a leading cause of acute hepatitis worldwide. Although most infections are self-limiting, zoonotic genotypes can persist in immunocompromised individuals. Transmitted via the fecal-oral route, HEV has been suggested to directly infect the intestinal epithelium, a tissue with high regenerative capacity. Here, we demonstrate that HEV predominantly infects proliferative transit-amplifying and intestinal stem cells within the crypts of human pluripotent stem cell-derived intestinal organoids (hIOs). Supporting this, we detected HEV RNA in the intestinal crypts of an HEV-infected patient. We further found that HEV infection spreads through cell division and is maintained in hIOs for more than 40 days, contrasting with acute hepatitis A virus, whose infections are rapidly cleared from hIOs. Given the self-renewal ability and metabolic constraints of proliferative intestinal progenitor cells, our findings suggest that intestinal crypts could serve as reservoirs for chronic HEV infection and highlight the intestinal crypt as a primary target for viral infection in the gastrointestinal tract.

Patients with myelodysplastic syndrome (MDS) harboring SRSF2 (serine and arginine rich splicing factor 2) mutations exhibit poor prognosis and aberrant inflammatory activation, underscoring an urgent need for therapies. Here, we reveal that low messenger RNA expression of SETD2 (SET domain containing 2) in hematopoietic stem and progenitor cells (HSPCs) from patients with MDS carrying SRSF2P95 mutations (SRSF2P95-Mut MDS) correlates with adverse outcomes and increased inflammation. Multivariate analysis confirmed the correlation between low SETD2 expression and poor prognosis in patients with SRSF2P95-Mut MDS. Furthermore, Setd2 loss in the Srsf2P95H/+ mouse model resulted in lethal MDS with hyperinflammation and expansion of myeloid-derived suppressor cells (MDSCs). Mechanistically, SETD2 methylates SRSF2P95H at lysine-17 and lysine-65 to inhibit aberrant splicing of CEACAM1-4 (isoforms of carcinoembryonic antigen cell adhesion molecule), which enhances interleukin-1β (IL-1β) signaling through Slc7a11 (solute carrier family 7 member 11)-mediated cystine uptake, thereby promoting HSPC differentiation into MDSCs, establishing an IL-1β-driven immunosuppressive microenvironment. These findings identify the SRSF2P95HK17me1K65me2-CEACAM1-4 signaling axis as a promising therapeutic target in SRSF2P95-Mut MDS.

Synucleinopathies is an umbrella term for multiple neurological disorders, including Parkinson's disease (PD), Lewy body dementia (LBD), and multiple system atrophy (MSA). A central pathological hallmark of synucleinopathies is the aggregation of α-synuclein (αS, a neuronal protein) and its prion-like spread. Therefore, inhibition of αS aggregation and spread is considered a viable therapeutic approach for the treatment of synucleinopathies. Foldamers are synthetic ligands that mimic the secondary structure of proteins. Using an oligoquinoline (OQ) scaffold-based foldamer approach, we have previously identified a foldamer (SK-129) that potently inhibits αS aggregation. Here, using a wide range of biophysical, cellular, and in vivo methods, we showed that SK-129 rescued synucleinopathy phenotypes in cellular, Caenorhabditis elegans, and human induced pluripotent stem cell (iPSC)-derived neuron models. SK-129 specifically bound to neurotoxic αS oligomers with ~6-fold higher affinity (Kd = 221 ± 29 nM) than to physiological αS monomer, validating αS oligomers as a therapeutic target. Furthermore, SK-129 efficiently crossed the blood-brain barrier (BBB) and exhibited favorable pharmaceutical properties in mice. Treatment with SK-129 prevented brain histopathology and increased survival in a mouse model expressing human A53T mutant αS without showing any apparent cytotoxicity. SK-129 inhibited αS aggregation mediated by exosomes derived from C. elegans or patients with PD in HEK293T reporter cells. SK-129 completely inhibited the coaggregation of αS-tau, a pathological biomarker for LBD in both cellular and mouse models. Overall, we report a potent foldamer with therapeutic potential for PD and LBD.

Vaccination is the best way to combat annual influenza epidemics, yet the breadth of vaccine-induced humoral immunity toward decades of future differentially evolving influenza A (IAV) and influenza B (IBV) viruses is unclear. Using historic 1994 influenza vaccination cohorts of young and older adults, we defined antibody responses elicited by 1994 vaccination against future influenza strains spanning three decades of differentially evolving IAV and IBV strains. Quality of antibody responses and vaccine-induced and cross-reactive B cell memory responses were investigated. Vaccination increased antibody titers against all 1994 vaccine components in younger and older adults. Antibodies to future H1N1 strains were also detected across younger and older adults, including nonneutralizing hemagglutinin (HA) stem responses. Prominent boosting against earlier B/Yamagata/16/1988 and future Yamagata lineage strains was also observed, but antibody responses toward future rapidly evolving H3N2 strains were minimal. Systems serology revealed divergent antibody signatures between younger and older adults against future antigens. However, postvaccination responses were of high quality in both age groups. Cross-reactive HA-specific memory B cells induced by 1994 vaccination bound to vaccine and future H1 and IBV strains but exhibited minimal responses against H3. Group 1 cross-reactive H1/H5 stalk-specific responses also contributed to the overall H1 future response, whereas cross-reactive H3/H7 stalk-specific B cells were not detected. Our study provides insights into the breadth of vaccine-induced humoral immunity toward future influenza viruses over 30 years of influenza virus evolution, including newly emerging pandemic strains, and highlights the unmet need to optimize future vaccines strategies, especially for H3N2.

Dengue virus infection is a major global health problem with clinical outcomes ranging from mild febrile illness to severe disease. Although a reduction in platelet counts is a common feature of dengue, the mechanisms underlying the presence of viral antigens in circulating platelets remain incompletely understood. In this study, we investigated whether infection of megakaryocytic precursors contributes to the generation of platelets carrying dengue virus proteins. Using the human megakaryocytic precursor cell lines K562 and MEG-01 cell lines as in vitro models, we show that reference strains and clinical isolates of dengue virus infect megakaryocytic precursors and modulate their differentiation, as evidenced by increased expression of the differentiation marker CD41 and the production of platelet-like particles. Flow cytometry analysis demonstrated that PLPs released from infected precursors contained precursor-derived PLP-associated dengue virus envelope protein. Correlation analyses revealed significant associations between the extent of precursor infection and both differentiation markers and PLP-associated E protein levels at early time points. Consistent with these findings, dengue virus E protein was detected in platelets from dengue patients, while no statistically significant differences were observed between clinical severity groups, a trend toward higher proportions of E+ platelets were observed in patients with dengue with warning signs or severe dengue. Spearman correlation analyses further supported an association between in vitro precursor infection and the generation of E-positive PLPs. In contrast, platelets from healthy donors incubated ex vivo with dengue virus did not acquire E protein, indicating that direct uptake or infection of circulating platelets is inefficient. Together, these results support a model in which infection of megakaryocytic precursors contributes to the generation of platelets carrying dengue virus antigens, suggesting that platelet-associated E protein may reflect bone marrow involvement during dengue infection.

Transition from a pluripotent to a differentiated cell state is accompanied by significant changes in genome organization. Activity dependent neuroprotective protein (ADNP) is a chromatin regulator with critical roles in neurodevelopment and limits the genomic occupancy of CTCF, a master architectural protein in genome organization, in embryonic stem cells. However, ADNP localization, function, and relationship with CTCF in differentiated neural lineages are not well studied. Here we develop a dual degron model which allows us to acutely deplete ADNP in neural progenitor cells (NPCs). We find that ADNP depletion does not impact NPC survival in the short term, but results in a genome organization switch, which favors the formation of short-range chromatin looping interactions coinciding with CTCF accumulation. Furthermore, ADNP localizes to active gene promoters in NPCs that are unoccupied by CTCF, where it prevents over-expression of genes that are activated upon neurodifferentiation and represses those involved in commitment to other lineages. Our findings uncover CTCF-dependent as well as CTCF-independent regulatory mechanisms of ADNP in NPC-specific chromatin organization and gene expression programs that may underlie its essential function in neurodevelopment.

Against the backdrop of an aging global population, cognitive decline poses significant challenges to individuals' quality of life. Currently, therapeutic interventions for cognitive impairment, particularly in neurological disorders such as Alzheimer's Disease (AD), remain limited. DHCR24 (3β-dehydrocholesterol-Δ24-reductase), a cholesterol synthase, has been shown to exert neuroprotective effects in AD by mitigating oxidative stress. This study aims to delineate the specific molecular mechanisms through which DHCR24 influences cognitive learning function.

PD-1+TCF1+ stem-like CD8 T cells are a progenitor population that provides a proliferative burst of effector CD8 T cells upon PD-1 blockade therapy, making them a key therapeutic target in antiviral and anticancer immunotherapy. Here, we show that IL-7 therapy preferentially expands these stem-like CD8 T cells, using NT-I7, a long-acting Fc-fused recombinant human IL-7 (efineptakin alfa). Gene profile analysis showed that a proliferating stem-like cluster induced by NT-I7 exhibited enrichment of genes related to lymphocyte migration. After NT-I7 treatment, proliferation of stem-like cells in the spleen was initiated within the white pulp, followed by egress into the red pulp. NT-I7 treatment led to an increase in stem-like CD8 T cells in circulation and peripheral tissues, contrasting with their resident property in lymphoid organs. These findings suggest NT-I7 as a promising strategy to expand and mobilize stem-like CD8 T cells to enhance antiviral and anticancer immunotherapies.

High recurrence rates, significant metastatic potential, and limited overall survival make triple-negative breast cancer (TNBC) the most challenging subtype among breast cancers. Previous studies have indicated that the downregulation of TGFB2-AS1 can enhance the stem-like properties of tumor cells, thereby promoting TNBC progression. Bioinformatics analysis has revealed the regulatory role of GATA6 in TGFB2-AS1 transcription, providing insights into the transcriptional regulation of TGFB2-AS1 by GATA6 and offering potential prognostic biomarkers and therapeutic strategies for TNBC.

Fanconi anemia (FA) is a rare inherited disorder characterized by genomic instability, bone marrow failure, and a markedly increased risk of developing acute myeloid leukemia (AML). The intrinsic hypersensitivity of FA cells to DNA-damaging agents renders conventional chemotherapy particularly toxic and often ineffective.

The prognosis of relapsed or refractory T-cell and NK-cell lymphoid proliferations and lymphomas (R/R T/NK-LPD/LYM) remains poor. Modified dendritic cell–cytokine-induced killer (DC–CIK) cells loaded with tumour stem cell (TSC) membrane microparticles (MMPs) can improve the targeted killing activity against tumours. However, the use of this treatment has not been reported for R/R T/NK-LPD/LYM. Herein, we report 3 cases. Case 1 involved an 8-year-old male who presented with bilateral cervical painless lymphadenopathy and a left elbow mass. Case 2 involved a 44-year-old man with recurrent nasal congestion and a runny nose. Case 3 involved a 49-year-old man whose bilateral cervical, axillary, and inguinal lymph nodes were enlarged. The biopsy results revealed T-lymphoblastic leukaemia/lymphoma, not otherwise specified (NOS); extranodal NK/T-cell lymphoma, nasal type; and nodal T follicular helper (TFH) cell lymphoma, angioimmunoblastic type (nTFHL-AI) for Patients 1, 2, and 3, respectively. All three patients ultimately underwent modified dendritic cell–cytokine-induced killer cell therapy loaded with tumour stem cell membrane microparticles following disease progression, relapse, and chemotherapy-associated complications after first-line therapy and multiple lines of salvage therapy. Following treatment with modified dendritic cell–cytokine-induced killer cells loaded with tumour stem cell membrane microparticles, two of these three patients achieved complete and durable remission, whereas the third patient achieved a partial response, with no treatment-related adverse events reported. At the most recent follow-up, two patients maintained stable disease (SD) with preserved quality of life, while one patient experienced progressive disease (PD) and died because of multiple organ dysfunction syndrome secondary to transplantation-associated colitis. To our knowledge, this is the first report of the use of modified dendritic cell–cytokine-induced killer cells loaded with tumour stem cell membrane microparticles for the treatment of R/R T/NK-LPD/LYM. Our findings warrant further evaluation of this novel targeted immunotherapy in future prospective clinical trials.

We have reported that trabecular meshwork stem cells (TMSCs) are effective for trabecular meshwork (TM) regeneration. This study aims to investigate different responses of TMSCs and TM cells to TGF-β2 and protective factors in TMSCs.

Stem cell-derived insulin-producing cells (Ins-PCs) hold great promise for diabetes treatment. Placenta-derived multipotent stem cells (PMSCs) are considered an ideal source of Ins-PC generation due to their immunomodulatory and differentiation properties. However, the cellular and molecular pathways underlying PMSC differentiation to Ins-PCs have not been fully elucidated. In this study, PMSCs were isolated from human placenta and successfully differentiated into Ins-PCs using miRNA-181a mimics. Differentiated Ins-PCs produced a significant amount of insulin and upregulation of C-peptide, insulin, and MAFA expression, compared to undifferentiated control PMSCs. RNA sequencing and LC-MS/MS were performed to uncover the pathways involved in the Ins-PC differentiation process. RNA sequencing revealed the transcriptional landscape of PMSC-derived Ins-PC differentiation. Pathway analysis identified important pathways involved in the differentiation process, including Notch and Wnt/ß-catenin, and so forth. Proteomics analysis further affirmed the presence of key insulin pathway-related proteins involved in the differentiation of PMSCs into Ins-PCs, including LEPR, STC2, MAP2K2, and so forth. Moreover, integrated transcriptomic and proteomic analyses further highlighted LEPR as a potential key regulator for Ins-PC differentiation. These findings demonstrated the feasibility of generating Ins-PCs from PMSCs and identified potential signaling pathways and regulators underlying Ins-PC differentiation, supporting PMSCs as a promising stem cell source of cell-based therapy for diabetes treatment.

Steroid-refractory acute graft-versus-host disease (SR-aGVHD), a severe complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) lacking standard second-line therapy, was studied in a retrospective analysis of 95 patients (2019-2024) at Third Hospital of Shanxi Medical University. We compared umbilical cord mesenchymal stem cells (UC-MSCs) plus standard care (n = 44) vs. standard care alone (n = 51). UC-MSCs were infused intravenously at 1-3 × 106 cells/kg with three infusions per patient. The MSC group had higher complete response (CR) rates than non-MSC group: 84.1% vs. 58.8% for grade II-IV SR-aGVHD (p = 0.007) and 54.5% vs. 31.4% for grade III-IV SR-aGVHD (p = 0.034) at week 4. Liver and gut CR rates improved by 31.8% and 28.1%, respectively. Multivariate analysis identified age ≥35 years, grade IV aGVHD, and hemoglobin ≤90 g/L as independent adverse prognostic factors. After median follow-up of 27 months, overall survival (OS) did not differ (HR = 1.04, p = 0.911). UC-MSCs improve early SR-aGVHD remission; prognostic factors enable risk stratification.