To investigate the therapeutic potential of an interleukin-21-expressing recombinant oncolytic influenza virus (rOV-IL-21) in pancreatic cancer.
Methods
Viral replication, IL-21 expression, and cytotoxicity of rOV-IL-21 in pancreatic cancer cells were evaluated by hemagglutination assay and CCK-8 assay. A subcutaneous pancreatic cancer model was established in C57BL/6 mice, and tumor growth was monitored. Flow cytometry was used to assess intratumoral immune activation. In vivo safety was evaluated by monitoring body weight, serum ALT/AST levels, and histopathological changes in major organs. ANOVA analysis was used for comparisons among multiple groups, and Tukey multiple comparison test was used for pairwise comparisons between groups. Two-factor repeated measures analysis of variance (ANOVA) was used for comparisons involving time and treatment doses.
Results
rOV-IL-21 can stably replicate and efficiently express IL-21 in pancreatic cancer cells, exhibiting a pronounced dose-dependent cytotoxic effect. In the syngeneic subcutaneous tumor model established with KPC pancreatic cancer cells, rOV-IL-21 significantly inhibited tumor growth (P < 0.001) and prolonged the survival of mice (P = 0.001 8) . Flow cytometric analysis of tumor-infiltrating immune cells showed that rOV-IL-21 enhanced the cytotoxic function of CD8+ T cells, with significantly increased proportions of GzmB+ CD8+ T cells [ (19.23 ± 1.46) % vs (7.53 ± 2.28) %, P < 0.05] and reduced proportions of exhausted CD8+ T cells [ (3.47 ± 0.52) % vs (14.54 ± 5.91) %, P < 0.05]when compared with control groups. There were no significant differences in serum ALT or AST levels between the rOV-IL-21 and control groups (P > 0.05) .
Conclusion
rOV-IL-21 demonstrates favorable safety and potent antitumor efficacy in pancreatic cancer models, which is associated with enhanced cytotoxic function of intratumoral CD8+ T cells. These findings support rOV-IL-21 as a promising oncolytic virus-based immunotherapeutic strategy for pancreatic cancer.
To explore the effects and mechanisms of bone marrow mesenchymal stem cell exosomes (BMSC-exo) on endometriosis (EMS) in mice.
Methods
Mouse endometrial epithelial cells (mEECs) were divided into the BMSC-exo group (co-cultured with 25 μg/mL) and phosphate buffer saline (PBS) group (co-cultured with equal volume of PBS) . The EdU method was used to detect cell proliferation rate. Cell scratch and Transwell assays were employed to assess cell migration ability. RT-qPCR was used to detect the relative expression levels of Interleukin-1β (IL-1β) , interleukin-6 (IL-6) , chemokine 2 (Ccl-2) , and tumor necrosis factor alpha (TNF-α) in mEECs. BALB/c mice were divided into sham-operated, EMS model, and BMSC-exo groups (n = 7) . EMS and BMSC-exo groups were used to construct EMS models. Mice in the BMSC-exo group received weekly tail vein injections of BMSC-exo at a dose of 3 μg/g for 4 weeks. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of EMS lesion tissue in mice. Enzyme-linked immunosorbent assay (ELISA) was used to detect inflammatory factors IL-1β, IL-6, Ccl-2, and TNF-α in serum and cell supernatants. Western blot was used to detect the expression of TLR4 and NF-κB p65 in endometrial tissue. Comparisons between two groups were performed using the independent sample t-test. Comparisons among multiple groups were performed using one-way analysis of variance (ANOVA) , with post-hoc pairwise comparisons conducted using Dunnett's t-test. For data not following a normal distribution, comparisons between two groups were performed using the Wilcoxon signed-rank test. For the analysis of repeated measures factors between two groups, the two-way repeated measures ANOVA was used.
Results
Compared with PBS group, the proliferation rates[ (41.00 ± 3.61) % vs (59.67 ± 2.52) %], cell scratch healing rates [ (22.00 ± 3.00) %vs (65.33 ± 5.51) %], the number of migration cells (82.00 ± 19.31 vs 145.00 ± 9.85) of mEECs, the expression of IL-1β mRNA (0.18 ± 0.05 vs 1.00 ± 0.01) , IL-6 mRNA (0.30 ± 0.09 vs 0.99 ± 0.01) , Ccl-2 mRNA (0.27 ± 0.08 vs 1.00 ± 0.02) , TNF-α mRNA (0.33 ± 0.08 vs 1.00 ± 0.06) and the concentrations of IL-1β[ (1 083.00 ± 67.68) vs (1 507.00 ± 131.10) pg/mL], IL-6[ (878.70 ± 19.50) vs (1 127.00 ± 75.59) pg/mL], Ccl-2 [ (1 046.00 ± 56.72) vs (1 298.00 ± 52.52) pg/mL] and TNF-α[ (1 069.00 ± 114.80) vs (1 470.00 ± 165.90) pg/mL] in cell supernatants in the BMSC-exo group were significantly decreased (P < 0.05) , were significantly decreased (all P < 0.05) . Compared with the sham-operated group, the pathological damageof endometrium in EMS group was significantly, with increased concentrations of serum inflammatory factors IL-1β [ (2 034.00 ± 165.50) vs (1 083.00 ± 125.80) pg/mL], IL-6 [ (3 292.00 ± 232.30) vs (1 505.00 ± 126.20) pg/mL], Ccl-2 [ (1 300.00 ± 64.50) vs (939.30 ± 56.45) pg/mL] and TNF-α [ (545.00 ± 34.70) vs (344.00 ± 41.33) pg/mL] (all P < 0.01) , as well as a significantly upregulated expression of TLR4 (1.44 ± 0.06 vs 0.38 ± 0.06) and NF-κB p65 (1.18 ± 0.03 vs 0.29 ± 0.04) (all P < 0.001) . Compared with the EMS group, the BMSC-exo group showed a reduction in EMS tissue lesions, with a decrease in the expression of serum inflammatory factors IL-1β [ (1 488.00 ± 202.50) vs (2 034.00 ± 165.50) pg/mL], IL-6 [ (2 543.00 ± 317.20) vs (3 292.00 ± 232.30) pg/mL], Ccl-2 [ (1 058.00 ± 57.95) vs (1 300.00 ± 64.50) pg/mL], TNF-α [ (415.00 ± 13.00) vs (545.00 ± 34.70) pg/mL] (all P < 0.05) , and TLR4 (0.81 ± 0.03 vs 1.44 ± 0.06) , NF-κB p65 (0.81 ± 0.06 vs 1.18 ± 0.03) expression (all P < 0.001) .
Conclusion
BMSC-exo inhibits TLR4/NF-κB signaling pathway to alleviate EMS in mice.
Induced pluripotent stem cells (iPSCs) , with their unlimited proliferative capacity and multi-lineage differentiation potential, hold great promise in vascular research. This study aimed to systematically analyze the global trends, research hotspots, and future directions of iPSC-related vascular research using bibliometric methods.
Methods
Publications on iPSCs and vascular research were retrieved from the Web of Science Core Collection. Bibliometric and visualization analyses were conducted using Bibliometrix, VOSviewer, and CiteSpace, focusing on annual publication trends, country and institutional collaboration networks, keyword clustering and burst detection, as well as co-citation analysis.
Results
The number of publications on iPSCs in vascular research has steadily increased. The United States and China lead this field and have established extensive international collaboration networks. Research hotspots have shifted from basic differentiation mechanisms to vascular regeneration, disease modeling, and translational applications. Keyword burst analysis highlighted endothelial differentiation, vascular regenerative medicine, and personalized therapy as emerging focal points.
Conclusion
Research on iPSCs in the vascular field is rapidly expanding, characterized by strong international collaboration and interdisciplinary integration. Future studies should emphasize clinical translation by integrating multi-omics and intelligent analytical approaches, thereby advancing the application of iPSCs in vascular graft development and novel therapeutic strategies.
Lipocalin 2 (LCN2) , also known as neutrophil gelatinase-associated lipocalin (NGAL) , is an essential innate immune protein that critically contributes to the pathogenesis of sepsis. Recent studies show that LCN2 affects sepsis onset and progression through multiple mechanisms, including the regulation of iron metabolism, inflammatory response, oxidative stress, and antibacterial immune response. The expression level of LCN2 was correlated with disease severity and patient prognosis, indicating its application value as a potential biomarker and therapeutic target. LCN2 also plays a significant role in sepsis-associated multi-organ injury, encompassing acute kidney injury, intestinal damage, encephalopathy, hepatic injury, myocardial damage, and lung injury. Future investigations should further elucidate its precise mechanisms and clinical utility to offer novel strategies for the early intervention and therapy of sepsis.
Stem cell therapy demonstrates significant potential in addressing major refractory diseases. As a key infrastructure for advancing the clinical translation of stem cells and the development of related industries, the establishment and operation of stem cell banks are of crucial importance. This review systematically summarizes the main types, current status, and applications of stem cell banks at home and abroad, focusing on identifying the core challenges confronting the system, and proposes systematic development countermeasures from the aspects of policy supervision, resource sharing, technological innovation and ethical supervision, aiming to provide references for the construction and development of stem cell resource banks in China.
Stem cells possess unique capabilities for self-renewal, differentiation, and homing, which could regenerate and repair damaged tissues, regulate immune function, and maintain tissue microenvironment homeostasis, confering distinct advantages in the treatment of various refractory diseases and providing new ideas and potential strategies for the management of age-related disorders. This article reviews Phase Ⅰ-Ⅲ clinical trials related to stem cells and their derivatives published between 2023 and 2025 via Pubmed databases, with a particular focus on collecting and summarizing 34 age-related studies, that are systemically organized and analysed across five core dimensions: indication types, stem cell types, routes of administration, safety, and efficacy. The findings indicate that stem cell therapy holds broad promise; but still faces numerous challenges, including incomplete elucidation of the underlying mechanisms of action, an insufficient number of Phase Ⅲ clinical trials, the urgent need to improve standardization and normalization within the industry, and the necessity for continued long-term monitoring of efficacy and safety.
Human pluripotent and totipotent-like stem cells serve as crucial in vitro models for investigating early embryonic development. Stem cells with distinct developmental potentials exhibit unique advantages in simulating embryonic development, constructing embryo-like models, and exploring the differentiation of embryonic and extraembryonic lineages. This review summarizes recent research advances in the fields of pluripotent and totipotent stem cells, outlining progress in converting stem cell models from pluripotency toward totipotency in vitro, ranging from the successive establishment of stem cell lines with different pluripotent states to the successful capture of totipotency-related cell models possessing both embryonic and extraembryonic developmental potentials. Furthermore, it compares the similarities and differences among stem cells in various states from three dimensions: establishment methodologies, molecular characteristics, and developmental potentials, and discusses the application value of blastoids and post-implantation embryo-like structures derived from these models in simulating early developmental processes.